ICU Manual Prem Kumar, TA Naufal Rizwan, Sushma Vijay Pingale, G Ninoo George, Marun Raj
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ICU MANUAL
ICU MANUAL
Editor-in-Chief Prem Kumar MD DA DNB Assistant Professor Department of Anesthesiology Critical Care and Pain Medicine Saveetha Medical College and Hospital Chennai, Tamil Nadu, India Editors TA Naufal Rizwan MD CCEBDM (Diabetology) Assistant Professor Department of Internal Medicine Saveetha Medical College and Hospital Chennai, Tamil Nadu, India Sushma Vijay Pingale MD DA Assistant Professor Department of Anesthesiology Critical Care and Pain Medicine Saveetha Medical College and Hospital Chennai, Tamil Nadu, India G Ninoo George MD DM Consultant Department of Nephrology Billroth Hospitals Chennai, Tamil Nadu, India Marun Raj MS MCh Assistant Professor Department of Vascular Surgery Saveetha Medical College and Hospital Chennai, Tamil Nadu, India
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ICU Manual
First Edition: 2017
9789352700301
_FM5Dedicated to
My Lord Jesus Christ, whom I love more for His grace and mercy towards me and He is the reason for all the exaltation in my life.
My dear wife Vero, and my loving son Sammy, who are my greatest joy.
My dear parents, sister and in-laws, especially Dr Joseph, who encouraged me to write this book.
All my teachers, especially to my mentor Professor Naheed Azhar, who inspired me to become anesthesiologist and intensivist.
_FM7CONTRIBUTORS
A Meenakshi Sundaram MS DNB Assistant Professor Department of Otorhinolaryngology Saveetha Medical College and Hospital Chennai, Tamil Nadu, India
Deepalakshmi MBBS Postgraduate Department of Biochemistry KAPV Medical College Trichy, Tamil Nadu, India
Dianitta Devapriya Veronica MBBS Postgraduate Department of Otorhinolaryngology Kilpauk Medical College and Hospital Chennai, Tamil Nadu, India
G Ninoo George MD DM Consultant Department of Nephrology Billroth Hospitals Chennai, Tamil Nadu, India
Jenu Santhosh MD Assistant Professor Department of Internal Medicine Thoothukudi Medical College and Hospital Thoothukudi, Tamil Nadu, India
K Gunalan MS Assistant Professor Department of Orthopedics Saveetha Medical College and Hospital Chennai, Tamil Nadu, India
Marun Raj MS MCh Assistant Professor Department of Vascular Surgery Saveetha Medical College and Hospital Chennai, Tamil Nadu, India
Prem Kumar MD DA DNB Assistant Professor Department of Anesthesiology Critical Care and Pain Medicine Saveetha Medical College and Hospital Chennai, Tamil Nadu, India
Sumathy MD Assistant Professor Institute of Anesthesiology and Critical Care Madras Medical College and Hospital Chennai, Tamil Nadu, India
Surendran GD MD Assistant Professor Department of Cardiology Kilpauk Medical College and Hospital Chennai, Tamil Nadu, India
Sushma Vijay Pingale MD DA Assistant Professor Department of Anesthesiology Critical Care and Pain Medicine Saveetha Medical College and Hospital Chennai, Tamil Nadu, India
S Yuvaraj MBBS DA Consultant Intensivist Raghavendra Multispeciality Hospital Madurai, Tamil Nadu, India
TA Naufal Rizwan MD CCEBDM (Diabetology) Assistant Professor Department of Internal Medicine Saveetha Medical College and Hospital Chennai, Tamil Nadu, India
Vinoj MBBS DA PGDHS (Diabetology) Postgraduate Department of Internal Medicine Tirunelveli Medical College and Hospital Tirunelveli, Tamil Nadu, India
V Thanga Thirupathi Rajan MS MCh Associate Professor Department of Neurosurgery Saveetha Medical College and Hospital Chennai, Tamil Nadu, India
PREFACE
Critical care medicine is relatively new but increasingly important medical specialty, which has become fully established in the current decade. ICU Manual focuses on the basic principles of intensive care which every practicing intensivist and postgraduate should be aware of. The concept of conditions commonly prevalent in intensive care has been dealt with in detail making it useful for the reader to gain a thorough knowledge of the intensive care. The scientific content is streamlined so that it would be of immense use for practicing intensivists in developing countries.
Flow charts, tables, algorithms and pictures have also been added to facilitate easy understanding of the subject. Many authors from various specialties have contributed for this book. It covers extensively on all the essentials—from the basics and system-specific topics to the recent advances—thereby making it comprehensive for intensive care. The recent articles and the current guidelines of sepsis and deep vein thrombosis (DVT) have also been included. The special feature of this book is the inclusion of the chapter ‘Role of Ultrasound in Critical Care’, since the use of ultrasound in critical care has tremendously increased in the past five years and has totally changed the practice of intensive care in certain areas.
We hope that this book will be a good resource to all the readers and help in intensive care practice and would be of immense use in treating the critically ill patients.
Prem Kumar
ACKNOWLEDGMENTS
I offer my gratitude to all the contributors and editors of this book, without whom, this book would have not been possible. I thank our respected Chancellor of Saveetha University, Dr NM Veeraiyan; and, our Director, Dr Saveetha Rajesh, for their constant motivation in writing this book. To my professors, colleagues, postgraduates, illustrators and all the supporting staff, who helped me in bringing this book to its present shape. Finally, I thank Mr Jayanandan, Mrs Samina Khan, Ms Saima Rashid, and all the supporting staff of M/s Jaypee Brothers Medical Publishers (P) Ltd., New Delhi, India, for their support in bringing up this ICU Manual, which would be of immense help to the readers.
1Intensive care unit
Chapter 1 Setting Up an ICU Prem Kumar2

SETTING UP AN ICUCHAPTER 1

Prem Kumar
Intensive care unit (ICU) is a specified area in a hospital designed to manage critically ill patients. It is an emerging specialty and all specialties merge to give a comprehensive care to the patient. Currently, it is managed by either the anesthesiologists or critical care physicians. Team consists of physicians, nursing staff and other paramedical staff trained in critical care.
 
INITIAL PLANNING
Initial planning includes formation of a team consisting of team leader along with nursing and paramedical personnel. Allocation of budget is based on the resources and infrastructure.
 
INFRASTRUCTURE
Planning of infrastructure is based on the level of ICU which would fit the resources. Number of ICUs and beds, design of each bed along with layout, space and ventilation. The next important planning for any ICU is the requirement of equipment. Equipment required for ICU are basic and advanced monitors (7 lead ECG, SpO2 (oxygen saturation), noninvasive and invasive blood pressure, EtCO2 (end tidal carbon dioxide analysis), stroke volume variation, pulse pressure variation, central venous pressure, pulmonary artery pressure monitoring, transthoracic echocardiography), ventilators–containing basic and advanced modes of ventilation, wall mount with oxygen and suction outlet. Environmental planning includes plan for (ceiling—height, color, lighting), flooring, ICU infection control program, air conditioning and ventilation, biomedical waste management, visitors timing and entry dress protocol. Data management—entry and storage of data by computers for medical records and intra- and inter-hospital communication. Internet should be available for hospital staff. Library for doctors with all the latest edition books for ICU management should be arranged. Adequate space should be allocated for central nursing station with data storage and central monitoring. Rooms for doctors, nursing and paramedical staff should be included in the plan. Waiting room for relatives should be planned outside the ICU.4
 
INDIAN SOCIETY OF CRITICAL CARE MEDICINE (ISCCM) PROVIDE GUIDELINES FOR EACH LEVEL ICU PLANNING IN INDIA
 
Level I (Table 1.1)
Level I ICU is recommended for small hospitals. ICU bed strength should be 6–8 and the set-up should be equipped to put a patient on mechanical ventilation for at least 1–2 days. Noninvasive monitors (ECG, SpO2, NIBP) along with blood gas analysis should be available. ICU personnel (nursing and paramedical staff) should be trained in providing basic life support to patients admitted in ICU. The intensivist should be able to provide basic and advanced cardiac life support and should be a trained person in critical care. The hospital should have a clinical laboratory doing complete blood count, blood sugar, electrolyte, liver and renal function test, X-ray and ultrasonography (USG) along with microbiology support. Blood bank should be available round the clock and at least one critical care book should be available for reference.
 
Level II (Table 1.2)
The recommendations for level II ICU include all the recommendations of level I ICU plus the following recommendations:
Table 1.1   ICU staffing
Personnel
Comments
Intensivist
He is the team leader and should be a qualified, experienced and full time intensivist who should lead the whole team
Senior registrars and resident doctors
They can be postgraduates from anesthesia, general medicine or respiratory medicine or allied surgical specialties. Recommendation is one doctor for ≤5 patients who are critically ill (on ventilator and/or undergoing invasive monitoring with Multiorgan failure). One postgraduate resident with one graduate resident for an ICU of 10 to 14 beds
Nursing staff
1/1—patient/nurse ratio for ventilated patients or in multiorgan failure (MOF). Ratio should not be <2 nurses for 3 patients. The most important factor for success in any ICU is the quality of care given by nursing staff trained in critical care
Respiratory therapist
Physiotherapy and ventilator management of mechanically ventilated patients
Nutritionist
They play a vital role in feeding and calorie calculation in ICU patients
Class IV workers and security
They play a role in the prevention of nosocomial infections by keeping the ICU clean. They also protect the ICU from overcrowding
Clinical lab staff, microbiology, imaging staff and biomedical engineer
5
Table 1.2   ICU bed and space recommendations
ICU bed recommendation
1 to 4 per 100 hospital beds
Total bed strength in ICU should be between 8 to 12 and should not be <6 or not >24
ICU space recommendation
Space per bed should be 125–150 sq ft area per bed.
1–2 rooms are kept designated for isolation.
There should be 100–150% extra space to accommodate nursing station, storage, patient movement area, equipment area, doctors and nurses rooms and toilet
Level II ICU is recommended for larger hospitals where the ICU bed strength can be 6–12. ICU should have a qualified intensivist along with junior doctors and nursing staff trained in critical care. The ICU staff should attend Continuing Medical Education (CME's) and workshops in critical care every year to update themselves. Advanced monitoring such as invasive blood pressure, EtCO2, stroke volume variation, pulse pressure variation, central venous pressure, pulmonary artery pressure monitoring, transthoracic echocardiography (TTE) should be available. ICU should be equipped to deliver long-term mechanical ventilation with advanced modes of ventilation along with organ support system. Access to clinical laboratory, microbiology support for diagnosis including fungus identification, blood bank, imaging (CT, MRI) should be available for 24 hours. Other specialty support such as neurology, cardiology, etc. should be available in case of requirement (e.g. Transvenous pacing). There should be an integrated HDU (high dependency unit) for stepping down patients from ICU. Institution protocols should be formulated for ICU along with ethical clinical research.
 
Level III
The recommendations for level III ICU includes all the recommendations of level I and II ICU plus the following recommendations:
Level III ICU is recommended for tertiary care hospitals where the ICU bed strength can be 10 to 16 with one or multiple ICUs as per requirement and the ICU is preferably a closed one with multidisciplinary unit headed by a qualified intensivist along with senior registrar, junior residents and nursing staff trained in critical are. ICU should be able to deliver care at the highest standard along with a very good transport facility available both for inter-hospital and intra-hospital transport. All the multisystem care should be available round the clock with referrals being taken from all the other hospitals. Apart from the advanced monitoring, bedside X-ray, USG, 2D-Echo, Fibreoptic bronchoscopy, bedside dialysis and renal replacement therapy (RRT) should be available. Optimum patient/nurse ratio is maintained with 1/1 patient/nurse ratio in ventilated patients and the patient area should not be <100 sq ft per patient. Hospital should train doctors for fellowship courses and conduct research in critical care and actively participate in national and international research programs. Institution should have infection control and ethical committee.6
 
OTHER ISSUES
  • Keep bed 2 feet away from the bed wall to access the head end in case of emergency.
  • Two beds should be especially designated for RRT.
  • An alarm bell which has both sound and light indicators must be provided to each patient.
  • The International Noise Council recommends that the noise level in an ICU be under 45 dB in the daytime, 40 dB in the evening and 20 dB at night.
  • Natural light is recommended in the ICU.
  • Vitrified nonslippery tiles for the floors, wall height of 4–5 feet, ceiling design enhanced by soft colors and decorating with patterns make it patient friendly.
  • It is mandatory to have four covered pans (Yellow, blue, red, black) provided for each patient.
  • Each bed must have alcohol-based handwash solution which is used before caregiver handles the patient. There should be at least two barriers to the entry of ICU.
  • There should be only one entry and exit to ICU to allow free access to machines and 2 barriers before entering ICU.
  • Proper fire-fighting/extinguishing machines should be there.
 
Heating, Ventilation and Air-conditioning (HVAC) System of ICU
The ICU should be fully air-conditioned which allows control of temperature, humidity and air change. It is recommended to have a minimum of six total air changes per room per hour, with two air changes per hour composed of outside air. The dirty utility and laboratory need five changes per hour. It is recommended that all air should be filtered to 99% efficiency down to 5 microns. Smoking should not be allowed in the ICU complex. For critical care units, temperatures from 16oC to 25oC is desirable. A few cubicles may have a choice of positive or negative operating pressures. Power back up in ICU should be available.
 
BIBLIOGRAPHY
  1. American College of Critical Care Medicine's Task Force on Guidelines: Guidelines for Intensive Care Unit Design. SCCM and AACN; 1993.
  2. Flynn J, Segil A, Steffy G. Architectural Interior Systents Lighting/Acoustics/Air Conditioning. 2nd edn. New York. Van Norstrand Reinhold; 1988.
  3. Integration of the Professional Nurse and the Technical Nurse in Critical Care; 1987.
  4. Intensive Care Unit Planning and Designing in India Guidelines 2010. Guidelines Committee ISCCM; 2010.
7Physiology of critically ill patient
Chapter 2 Critically Ill Patient and Oxygenation Prem Kumar8

CRITICALLY ILL PATIENT AND OXYGENATIONCHAPTER 2

Prem Kumar
The fight of the body is to ensure tissue oxygenation in critically ill patients.
Oxygen transport, delivery and utilization are complex process and its understanding is especially useful in critically ill patient since both oxygen transport and delivery are disturbed due to various factors. In this chapter, we deal with the basics of O2 transport and delivery and the various factors which affect them.
 
OXYGEN CASCADE
 
Definition
Oxygen cascade is transfer of O2 from atmosphere to mitochondria of cells.
The steps of oxygen cascade are:
  • Inspired oxygen
  • Alveolar oxygen
  • Arterial blood
  • Microcirculation
  • Interstitium
  • Mitochondria.
 
Inspired Oxygen
Partial pressure gradient for O2 is the key to gas movement. O2 flows downhill from the air through the alveoli and blood into the tissues. At sea level, the atmospheric pressure is 760 mm Hg and O2 makes up to 21% of inspired air.
  PiO2  = FiO2 × (Pb – PH2O)
  PiO2  = 0.21 × (760 – 47)
  PiO2  = 149 mm Hg
where Pb-Barometric pressure, PH2O-Water vapor pressure10
 
Alveolar Oxygen
As the O2 reaches the alveoli CO2 is present in large amounts, the alveolar CO2 level (PACO2) is usually the same as PaCO2.
Now the partial pressure of alveolar O2,
  PAO2  = PiO2 – PACO2/R.
R is respiratory quotient, which is the amount of CO2 excreted for the amount of O2 utilized.
R is 0.8, then PAO2 will be 149 – 40/0.8 = 99 mm Hg.
 
Arterial Oxygen
The next step is movement of O2 from alveolus to artery, there is significant gradient usually 5–10 mm Hg explained by V/Q mismatch, diffusion gradient and physiologic shunt.
Four factors influence transmission of O2 from alveoli to capillaries. They are:
  1. V/Q mismatch
  2. R – L shunt
  3. Cardiac output
  4. Diffusion defect.
 
Microcirculation and Interstitium
As the blood saturated with O2 from the alveolus reaches the pulmonary artery, the systemic circulation transports this oxygenated blood to the tissues. The steps of this transport and the further drop in partial pressure of O2 are explained here:
Oxygen content (CaO2) = (Hb × SaO2 × 1.39) + (0.003 × PaO2)
Approximately, CaO2 is 20.8 mL per 100 mL of blood
(Where SaO2 is arterial O2 saturation,
1.39-Amount of O2 per gram of normal hemoglobin,
PaO2-Partial pressure of arterial oxygen,
0.003-Dissolved oxygen)
Oxygen dissociation curve guides in understanding the oxygen content of blood. Each molecule of hemoglobin binds 4 molecules of O2 and binding of 1 oxygen molecule to hemoglobin binding site favors binding of another oxygen molecule to other binding sites on hemoglobin which is the reason for the S-shape of ODC curve. This property is called cooperativity. The affinity of hemoglobin to PO2 is not consistent at all levels of PO2 which can be seen in the Figure 2.1.
Oxygen flux or delivery (DO2) is defined as the quantity of oxygen made available to the tissues in one minute.
Delivery of oxygen (DO2) = CaO2 × Q, where Q is cardiac output.
  DO2  = 20.8/100 × 5000
    = 1000 mL (Approx)
Amount of O2 consumption per minute is VO2
  VO2  = Q × (CaO2 – CvO2)11
Fig. 2.1: Oxygen dissociation curve
where CaO2=Content of O2 in arterial blood = 20 mL, CvO2=Content of O2 in venous blood = 15 mL).
Difference is 5 mL per 100 mL
Now VO2 is 5000 × 5/100 = 250 mL/minute
Therefore, the oxygen extraction ratio (VO2/DO2) is approximately 25%.
 
Mitochondrial Level
At tissue level, PO2 is 3–4 mm Hg. This PO2 keeps the mitochondria of the cell to do aerobic metabolism. When this PO2 falls below 1 mm Hg the mitochondria switches to anaerobic metabolism, this point of switching is called Pasteur point (Fig. 2.2).
 
Indices of Pulmonary O2 Transfer
  • A-a gradient
  • PaO2/FiO2 ratio
  • Qs/Qt (venous admixture)
  • Estimated shunt fraction.
 
Indices of Oxygen Dynamics
  • Oxygen delivery index
  • Oxygen consumption index—methods to measure this index is by reverse Fick method and indirect colorimetry
  • Mixed venous oxygen tension (SVO2)
  • Mixed central venous oxygen saturation (ScvO2).12
Fig. 2.2: Oxygen cascade
 
Regional Oxygen Indices
  • CO2 gap–normal = 8–10 mm Hg
  • Gastric intramucosal pH
  • Tissue PO2.
 
TISSUE OXYGENATION
Adequacy of tissue oxygenation is based on the balance between oxygen supply (DO2) to O2 demand or the amount of O2 required to maintain aerobic metabolism. When there is disruption or imbalance, tissue hypoxia ensues, which without treatment would lead to dysoxia (shock). Under physiological conditions, O2 demand equals VO2 (2.5 mL/kg/minute) for a DO2 of 12 mL/kg/minute with an Oxygen extraction ratio (OER) of 20%. During severe hypoxemia or shock, DO2 decreases consequent to a decrease in cardiac output which is compensated by increase in OER.
  Critical DO2  = 4 mL/kg/minute
  Critical OER  = 60%
Increase in OER due to increased sympathetic drive causes vasoconstriction and redistribution of blood flow.13
 
VO2
VO2 is used as a measure of tissue O2 consumption. It can be calculated by Fick's equation but it is not reliable since it can vary with many factors (e.g. Lung disease). VO2 can be calculated indirectly by measures of PA catheter but metabolic cart is required to directly measure VO2. Hence, VO2 of <100 mL/min/m2 can be used as a measure of reduced tissue oxygenation. As VO2 falls, lactate level starts increasing.
VO2 is not a good parameter to reflect tissue oxygenation in sepsis since O2 is consumed for the inflammatory process in sepsis, thereby showing a falsely elevated VO2. But in sepsis, the problem is not tissue oxygenation but O2 utilization at tissues which on increased severity leads to multiorgan failure. Thus, VO2 is not a good indicator of tissue oxygenation in sepsis. This VO2 deficit is called O2 debt which is treated by increasing cardiac output in case of poor ventricular function, increasing FiO2 in case of decrease in SaO2, correcting anemia, if it is present. Although correction of all these parameters is done based on early goal directed therapy in sepsis, still the outcome is very poor.
 
Mixed Venous O2 Tension (SvO2)
SvO2 can be used as a surrogate indicator for assessing the adequacy of global tissue oxygenation (VO2 – DO2 balance).
Normal SvO2 = 65 – 70%. Increased SvO2 indicates significant fall in DO2 with or without an increase in O2 demand. 40% SvO2 is the critical value for the patient resulting in dysoxia/shock (Table 2.1).
 
Measures of O2 Exchange
  • P(A – a)O2
  • PaO2/FiO2 (P/F) ratio
  • PaO2/PAO2 (a/A) ratio.
Measures to indicate the severity of disease based on interventions (e.g. PEEP) is assessed by a parameter called oxygen index (OI).
Table 2.1   Causes of increased and decreased SvO2
Causes of ↑ SvO2
Causes of ↓ SvO2
High cardiac output
Impaired tissue oxygenation
Sepsis
Hypothermia
Left-to-right shunting
Hypoxia
Anemia
Reduced cardiac output
Thyroid storm
Malignant hyperthermia
14
 
ScvO2 (Mixed Venous O2 Saturation)
ScvO2 >70% is used as an end point in early goal directed therapy. It is also used as a surrogate marker for SvO2 but differs from SvO2 by ± 5%.
 
Lactate
By large, it is the most commonly used parameter to evaluate O2 supply and demand imbalance. And 2 mEq/L is abnormal which occurs due to switch over form aerobic to anaerobic metabolism. Just checking a single value is not reliable but evaluating the trend of serum lactate is a good method to indicate tissue oxygenation. Survival rate decreases as lactate level increases.
 
BIBLIOGRAPHY
  1. Bakker J, Coffernils M, Leon M, et al. Blood lactate levels are superior to oxygen-derived variables in predicting outcome in septic shock. Chest. 1991;99:956-62.
  2. Dellinger, et al. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock (2012). Crit Care Med. 2013;41:580-637.
  3. Dunham CM, Seigel JH, Weireter L, et al. Oxygen debt and metabolic acidemia as quantitative predictors of mortality and the severity of the ischemic insult in hemorrhagic shock. Crit Care Med. 1991;19:231-43.
  4. Fink MP. Impaired cellular use of oxygen in critically ill patients. J Crit Illness. 2001; 16(suppl):S28-32.
  5. Guyton and Hall. Textbook of medical physiology, 11th edn. Elsevier publications. 2006.
  6. Hameed SM, Aird WC, Cohn SM. Oxygen delivery. Crit Care Med. 2003;31(suppl). S658-67.
  7. Leach RM, Treacher DF. The relationship between oxygen delivery and consumption. Dis Mon. 1994;30:301-68.
  8. Nunn JF. Nonrespiratory functions of the lung. In: Nunn JF (Ed). Applied Respiratory Physiology. London: Butterworths. 1993:306-17.
  9. Shoemaker WC. Oxygen transport and oxygen metabolism in shock and critical illness. Crit Care Clin. 1996;12:939-69.
  10. William F Ganong. Review of medical physiology, 21st edn. McGraw-Hill publications, 2003.
15Vascular access and hemodynamic monitoring
Chapter 3 Peripheral Arterial Catheterization Prem Kumar
Chapter 4 Peripheral Venous Catheterization Prem Kumar
Chapter 5 Central Venous Catheterization Prem Kumar
Chapter 6 Pulmonary Artery Catheterization Prem Kumar
Chapter 7 Hemodynamic Monitoring Prem Kumar16

PERIPHERAL ARTERIAL CATHETERIZATIONCHAPTER 3

Prem Kumar
Peripheral arterial catheterization is one of the common invasive procedures done in ICU after central venous catheterization. It is performed in patients where beat-to-beat arterial blood pressure monitoring is required and where severe blood loss and major cardiovascular changes are expected. Also indicated when frequent arterial blood sampling is required and when cardiac output is indirectly measured using pulse contour analysis.
 
INDICATIONS
  • Continuous beat-to-beat blood pressure monitoring—hemodynamic monitoring
  • Frequent blood sampling
  • Arterial drug administration—thrombolytics
  • Intra-aortic balloon pump (IABP)
  • Assessing volume responsiveness from pulse pressure variation (PPV) or systolic pressure variation (SPV)
  • Determination of cardiac output by pulse contour analysis.
 
EQUIPMENT
  • Arterial cannula
  • Pressure transducer
  • Monitor
  • Heparinized saline-filled noncompliant tubing
  • Stopcocks.
 
MONITORING SITES
  • Radial artery—most common
  • Femoral artery
  • Axillary artery
  • Dorsalis pedis artery
  • Brachial artery
  • Ulnar artery
  • Posterior tibial artery.
18
 
Safer Arteries for Cannulation in Chronological Order
Radial > femoral > dorsalis pedis > axillary > brachial artery
 
TECHNIQUE
 
Pre-requisites
  • Modified Allen test—done to assess the adequacy of collateral flow to the hand. The intensivist compresses the radial and ulnar arteries and the palm is exsanguinated by making a tight fist. Then the patient should open the fist and the occlusion of the ulnar artery is released, then there is flushing of the palm within a few seconds with normal collaterals, severely reduced collateral flow is present when the palm remains pale for more than 10 seconds. The other artery is also checked with the same procedure. Disadvantage is that the sensitivity of modified Allen test is 80%.
  • Doppler
Arterial cannulation can be done by various techniques:
  • Seldinger's technique
  • Transfixion technique
  • Ultrasound-guided Seldinger's technique.
 
Seldinger's Technique
Radial artery: Position of the hand is 40–60° dorsiflexion and wrist is prepared and given local anesthesia with 0.5 mL of 1% lignocaine on both sides of the radial artery (to reduce vasospasm and produce local anesthesia). A 20-gauge catheter-over-needle apparatus is used for puncture and the needle is entered at 30–60° angle to the skin 3 cm proximal to the distal wrist crease. The cannula is advanced until there is return of blood and the guidewire is passed into the artery after viewing the pulsatile blood flow and thereafter the cannula is guided over the guidewire.
In the transfixion technique, the anterior and the posterior walls of the artery are punctured intentionally and after the needle is removed from the catheter, the catheter is pushed into the vessel lumen.
Ultrasound-guided percutaneous technique can be done but the learning curve is little steep.
Brachial artery: Although brachial artery does not have collateral circulation. Many studies have proven the safety of its use.
Femoral artery: Its waveform closely resembles aorta. Risk of distal ischemia is less due to its large size.
Axillary artery: It is used for long-term monitoring catheterization and the left side is preferred over the right because the tip of catheter will lie distal to the aortic arch and great vessels.19
 
Complications
  • Distal ischemia
  • Hematoma
  • Hemorrhage
  • Arterio–venous fistula
  • Pseudoaneurysm
  • Thrombosis
  • Embolization
  • Local infection
  • Nerve damage
  • Peripheral neuropathy
  • Cerebral embolization— in case of cannulation of central arteries.
Continuous flush devices used with arterial cannulas are designed to release 3 mL/hour of heparinized saline from an infusion bag pressurized to 300 mm Hg. Air embolism can be prevented by clearing all the air bubbles in the tubing and not putting flush valve for more than 2–3 seconds.
 
Arterial Waveform (Figs 3.1 and 3.2)
  • Systole—ejection of blood from the left ventricle into the aorta
  • Diastole—peripheral arterial run off of this stroke volume
  • Mean arterial pressure—diastolic pressure plus one third times pulse pressure. It can be calculated by adding the area under the waveform divided by the duration of cardiac cycle.
The duration of time taken for the electrical events of depolarization through the ventricle and ejection of left ventricle and transmission to aorta with resultant change in the pressure transducer ending up in a arterial waveform is 120–180 msec after the R wave of an ECG. As the arterial pressure wave travels from the aorta to the periphery, changes noticed in the waveform are a steeper arterial upstroke, higher systolic peak and the dicrotic notch appears later, prominent diastolic wave and lower end-diastolic pressure. So in comparison with the aorta, peripheral arterial waveforms have higher systolic pressure, lower diastolic pressure, and wider pulse pressure. Though the systolic pressure rises towards the periphery, mean arterial pressure changes very little because of the narrowing of the systolic wave. Hence, mean arterial pressure is a better measure of central arterial pressure (Fig. 3.3).
Fig. 3.1: Arterial pressure waveforms
20
Fig. 3.2: Phases of arterial waveform
  1 – systolic upstroke;   2 – systolic peak
  3 – systolic decline;   4 – dicrotic notch (corresponds with closure of aortic valve)
  5 – diastolic runoff;   6 – end-diastolic pressure
Fig. 3.3: Waveform of central and peripheral arteries
21
 
Recent Advances in Arterial Pressure Monitoring
The following parameters are used as dynamic parameters in assessing volume responsiveness:
  • Systolic pressure variation (SPV).
  • Pulse pressure variation (PPV).
  • Stroke volume variation (SVV).
 
Artifacts of the Monitoring System
The operating characteristics of the system depends on natural frequency, frequency response and damping coefficient. The fluid-filled tubing measures the blood pressure through the transducers. This system can produce artifacts by oscillating spontaneously and distorting the arterial waveform. To get an accurate frequency response, the resonant frequency of the system should be at least 5 times more than the highest frequency in the input signal. Resonant frequency of the system should be more than 20 Hz.
To ensure a flat frequency response (accurate recording across a spectrum of frequencies), the resonant frequency of a monitoring system should be at least 5 times higher than the highest frequency in the input signal. Physiologic peripheral arterial waveforms have a fundamental frequency of 3–5 Hz, and therefore the resonant frequency of a system used to monitor arterial pressure should ideally be greater than 20 Hz to avoid ringing and systolic overshoot. The damping coefficient is a measure of the system's ability to cause attenuation of the incoming signal. The catheter-transducer systems are designed to be underdamped but with an acceptable resonant frequency (> 12 Hz). If the system's resonant frequency is lower than 7.5 Hz, the pressure waveform becomes distorted.
  • Hence, higher the resonant frequency, damping will have very less effect on the waveform
  • Lower the resonant frequency (e.g. 10–15 Hz), damping coefficient should be very low (0.4–0.6) to achieve an accurate waveform
  • Very low resonant frequency (< 7.5 Hz) will distort the waveform irrespective of the damping factor.
Despite whether the system becomes underdamped or overdamped, mean arterial pressure remains unchanged (Fig. 3.4 and Table 3.1).
 
Fast-flush Test (Square Wave Test)
Fast-flush test is a method of determining the dynamic response of the monitoring system to assess the amount of distortion existing in the system. The fast-flush valve is opened for a short time and the resulting flush artifact is examined (Fig. 3.5).
An optimal fast-flush test results in one undershoot followed by small overshoot, then followed by the waveform. An adequate fast-flush test usually corresponds to a resonant frequency of 10–20 Hz with a damping coefficient of 0.5–0.7 for peripheral arterial pressure monitoring. 22
Fig. 3.4: Dampening of arterial waveforms
Fig. 3.5: Effects of fast flush test on dampening
Table 3.1   Causes of dampening
Overdampening
Underdampening
Air bubbles
Clot
Kink
Deflated pressure bag
Over compliant tubing
Poor connections of stopcock
Excessive tubing length
Patient on inotropes
 
When is Fast Flush Test Done?
  • Every 8 hours
  • If significant change appears in patient hemodynamic status
  • After zeroing and sampling
  • Change in tubing
  • Damped waveform seen in monitor.23
 
BIBLIOGRAPHY
  1. Bazaral MG, Welch M, Golding LAR, Badhwar K. Comparison of brachial and radial arterial pressure monitoring in patients undergoing coronary artery bypass surgery. Anesthesiology. 1990;73:38-45.
  2. Darovic GO, Vanriper S, Vanriper J. Fluid-filled monitoring systems. In: Darovic GO, ed. Hemodynamic monitoring, 2nd ed. Philadelphia: WB Saunders; 1995.pp.149-75.
  3. Gardner R: Direct arterial pressure monitoring. Curr Anaesth Crit Care. 1990;1:239–46.
  4. Gardner RM. Direct blood pressure measurement—dynamic response requirements. Anesthesiology. 1981;54:227-36.
  5. Kleinman B, Powell S, Kumar P, Gardner RM. The fast flush test measures the dynamic response of the entire blood pressure monitoring system. Anesthesiology. 1992;77: 1215-22.
  6. Levin PD, Sheinin O, Gozal Y. Use of ultrasound guidance in the insertion of radial artery catheters. Crit Care Med. 2003;31:481-4.
  7. Mark JB. Technical requirements for direct blood pressure measurement. In: Mark JB, ed. Atlas of Cardiovascular Monitoring, New York: Churchill Livingstone. 1998:99-126.
  8. O'Rourke MF, Yaginuma T. Wave reflections and the arterial pulse. Arch Intern Med. 1984;144(2):366-71.
  9. Pauca AL, Wallenhaupt SL, Kon ND, et al. Does radial artery pressure accurately reflect aortic pressure? Chest. 1992;102(4):1193-8.

PERIPHERAL VENOUS CATHETERIZATIONCHAPTER 4

Prem Kumar
One of the most common procedures done in ICU and the catheter which almost all the patients have in the ICU is a peripheral venous catheter.
 
INSERTION TECHNIQUES (FIGS 4.1A TO F)
  • Catheter over needle technique
  • Ultrasound-guided technique.
 
PRECAUTIONS
  • Handwashing with disinfectant before doing the procedure
  • Non-sterile gloves is used for peripheral venous cannulation
  • Skin around the insertion site should be disinfected before inserting the catheter. CDC recommends chlorhexidine. Other agents which can be used are povidone-iodine. The disinfectant should not be wiped rather it is allowed to dry to obtain its full anti-infective effect.
 
EQUIPMENT
The catheter is made of polymers and short-term catheters are made of polyurethane and long-term catheters are made of silicone polymers. The size of catheters are expressed in gauge. The gauge size was actually introduced for solid wires and gauge size tells the information about the number of wires that can be placed side-by-side in a given space. The gauge size varies inversely with the diameter of the catheter.
 
PRINCIPLE
Hagen-Poiseuille formula is the principle by which venous catheter's flow rate is determined. Hence according to this equation, radius of the catheter is the primary determinant of flow. So according to this principle, rapid infusion of fluids are better obtained with short catheters with large diameters.
Q  = ΔP(πr4/8µL)
Where, Q – flow; P – pressure gradient; r – radius; µ – viscosity; L– length of catheter.25
Figs 4.1A to F: Steps of peripheral venous cannulation. (A) Tourniquet application over the forearm to make veins prominent and cleaning the site of cannulation with antiseptic solution; (B) Insertion of the IV cannula over the vein; (C) Backflow of blood seen on the back of stylet indicating the presence of cannula inside the vein; (D) Slight withdrawal of the stylet; (E) The cannula is pushed into the vein gently; (F) The IV cannula is secured with tapes
Hence, because of the low resistance in a short catheter, a well placed 2-wide bore peripheral cannula is far more superior for rapid infusion than central venous catheter. This is well seen in clinical scenarios such as trauma, gastrointestinal bleeding, obstetric hemorrhage, etc. Large catheters (7 fr) can be inserted in an antecubital vein and used for this purpose. This is well located by ultrasound in case of obese patients or when there is difficulty in identifying the peripheral veins.
 
Advantages
  • Ease of insertion
  • Ability to infuse fastly in emergency
  • Low risk of infection
  • Cost-effective.26
 
Disadvantages
  • Difficult to cannulate in critically ill patients since most of their veins are either thrombosed or they are edematous
  • Hypertonic agents (e.g. Hypertonic saline) and vasoactive agents cannot be administered into a peripheral vein
  • Need to replace every 3–4 days due to the risk of thrombophlebitis.
 
MIDLINE CATHETERS
It is devoid of the limitations of peripheral vein catheter such as the risk of phlebitis is low, need not be replaced early. They are usually 4–8 inches long and thereby inserted into a large peripheral vein either by vision or ultrasound.
 
BIBLIOGRAPHY
  1. Centers for Disease Control and Prevention. Guidelines for the prevention of intravascular catheter-related infections. MMWR. 2002;51(No.RR-10):1-30.
  2. Paul N Lanken, et al. The intensive care unit manual. 2nd edn, PA. Elsevier Publications; 2014.

CENTRAL VENOUS CATHETERIZATIONCHAPTER 5

Prem Kumar
Central venous pressure (CVP) is a clinical measure of right ventricular filling pressure and it identifies the ventricular filling volume which is the preload by Frank-Starling law. CVP placement remains one of the most commonly done procedures in intensive care unit (ICU) for many clinical uses, but the procedure is not without complications. Hence, the applied anatomy of major veins namely internal jugular vein, subclavian vein and femoral vein will be highlighted. Also the indications (Tables 5.1 and 5.2), techniques, and complications of central venous catheterization along with catheter management will be discussed in this chapter.
Table 5.1   Indications of central venous catheterization
Central venous pressure monitoring
Pulmonary artery catheterization
Total parenteral nutrition
Acute hemodialysis
Transvenous cardiac pacing
Plasmapheresis
Inability to achieve peripheral venous catheterization
Perioperative—aspiration of air emboli, vasopressor/inotrope administration, cardiac surgeries, major surgeries with major fluid shifts
Drug administration—chemotherapy, vasoactive agents, prolonged antibiotic therapy, drugs irritable to peripheral veins
Cardiopulmonary arrest
Table 5.2   Site selection and its indications
Internal jugular vein
Subclavian vein
Femoral vein
  • Acute hemodialysis
  • Emergency transvenous pacemakers
  • Pulmonary artery catheters
  • Patients with coagulopathy
  • Low-risk of pneumothorax compared with subclavian vein
  • Shock
  • Long-term total parenteral nutrition
  • Neurosurgery (e.g. Posterior fossa tumors)
  • Trauma
  • Acute hemodialysis/plasmapheresis
  • Trauma
  • Severe lung disease
  • Angioplasty
  • Cardiopulmonary arrest
28
Fig. 5.1: Anatomy of right internal jugular vein
 
APPLIED ANATOMY
 
Internal Jugular Vein (Fig. 5.1)
The internal jugular vein (IJV) originates at the jugular foramen from the sigmoid sinus in the skull and the internal jugular vein lies in the groove between the sternal and clavicular heads of the sternocleidomastoid muscle, lateral and slightly anterior to the carotid artery and terminates behind the sternal end of clavicle, where it joins the subclavian vein to form the brachiocephalic vein although the relationship between the IJV and the carotid artery can vary in a group of population. The vagus lies between and rather behind the artery and vein. The junction of the right IJV (averages 2–3 cm in diameter) with the right subclavian vein forming the innominate vein follows a straight path to the superior vena cava (SVC). In contrast, a catheter passed through the left IJV must enter a sharp turn at the left IJV—subclavian junction, which results in a greater percentage of catheter malpositions.
The external jugular vein crosses the sternocleidomastoid in the superficial fascia traversing the roof of the posterior triangle of the neck and then enters the deep fascia 2.5 cm above the clavicle to drain into the subclavian vein.
 
Subclavian Vein (Fig. 5.2)
The subclavian vein (SV) is the continuation of the axillary vein and extends from the outer border of the 1st rib to the medial border of scalenus anterior extending 3–4 cm along the undersurface of the clavicle and becomes the brachiocephalic vein where it joins the ipsilateral IJV at Pirogoff's confluence behind the sternoclavicular articulation. The vein is 1–2 cm in diameter, posteriorly, the SV is separated from the subclavian artery and brachial plexus by the scalenus anterior. Inferiorly, the vein rests on the first rib, Sibson's fascia, dome of the pleura. On the left side, it receives the termination of the thoracic duct.29
Fig. 5.2: Anatomy of right subclavian vein
Fig. 5.3: Anatomy of right femoral vein
 
Femoral Vein (Fig. 5.3)
The femoral vein is continuation of the popliteal vein and becomes the external iliac vein at the inguinal ligament. At the inguinal ligament, femoral vein lies within the femoral sheath and lies medial to the femoral artery, which in turn lies medial to the femoral branch of the genitofemoral nerve (famously called by the mnemonic—Vein, artery and nerve (VAN). 30
 
TECHNIQUES
 
Internal Jugular Vein
There are three approaches:
  1. Central—most commonly used approach.
  2. Anterior
  3. Posterior.
 
Central Approach (Fig. 5.4)
Positioning of right IJV cannulation: This was demonstrated by Daily and colleagues and right IJV cannulation is most commonly catheterized. The patient is placed in the supine position with 15° Trendelenburg position to distend the vein and minimize the risk of air embolism with the head slightly turned to the left to expose the right side of the neck. Pillows that cause the neck to be flexed should be removed and excessive neck extension or left-sided rotation of the head should be avoided because this may cause the internal jugular vein to collapse over the carotid artery, hence increasing the risk for carotid arterial puncture.
Landmarks: Sternal notch, clavicle, and sternocleidomastoid muscle (lateral and medial head).
Monitoring and sedation: The patient should be sedated, receiving supplemental oxygen, and monitored with an electrocardiogram (ECG), blood pressure monitor, and pulse oximeter.
Fig. 5.4: Technique of catheterizing right internal jugular vein—central approach
31Aseptic technique: The skin is cleaned from earlobe to clavicle to sternal notch, preferably with 2% chlorhexidine and draped.
Equipment: Standard triple-lumen catheter kits include the equivalent of a 7-French triple-lumen catheter with 15 (recommended), 20, or 30 cm of catheter length, a 0.032-inch diameter guidewire with J tip, an 18-gauge needle, an 18-gauge catheter-over-needle, a 7-Fr vessel dilator, and appropriate syringes and suture material. All lumens of the catheter should be flushed with heparinized saline and the cap to the distal lumen removed. Heparinized saline is prepared by adding 1000 IU to 100 mL of saline.
Technique: The pulsation of the carotid artery can be felt medial to the medial border of the sternomastoid muscle. The vein lies lateral to the artery, often beneath the belly of the muscle itself. Lower in the neck, it passes deep to the groove between the sternal and clavicular heads of the muscle. For the central approach, skin puncture is done at the apex of the triangle formed by the two muscle heads of the sternomastoid and the clavicle after the skin is anesthetized by subcutaneous infiltration of 1% lignocaine with a 25-gauge needle. Before puncture, a finder needle is introduced. At an angle of 30° to skin, the needle is advanced steadily with constant negative pressure in the syringe, and usually the vein is punctured within 1–5 cm. If the first attempt is unsuccessful, the operator should reassess patient position, landmarks, and techniques. Subsequent attempts may be directed slightly laterally or medially to the initial site of puncture, as long as the plane of the internal carotid artery (ICA) is not violated. Once the vein is punctured, the syringe is removed after ensuring that the blood flow is not pulsatile and the hub is then occluded with a finger to prevent air embolism or excessive bleeding. The guidewire, with the J-tip oriented correctly, is then inserted and should pass freely up to 20 cm. Guidewire insertion beyond 20 cm should be avoided since it may cause ventricular arrhythmias or cardiac perforation. The guidewire should pass easily, if resistance is still encountered, rotation of the guidewire during insertion often allows passage, but forceful insertion only leads to complications. With the guidewire in place, a scalpel is used for making incision at the skin entry site to facilitate passage of the 7-Fr vessel dilator. The dilator is inserted down the wire to a depth while maintaining control and sterility of the guidewire. The triple-lumen catheter is then inserted over the guidewire, ensuring that the operator has control of the guidewire, proximal to the catheter to avoid intravascular loss of the wire. The catheter is then advanced 15–17 cm (17–19 cm for left IJV) into the vein, the guidewire withdrawn, and the distal lumen capped. The catheter is sutured securely to limit tip migration and bandaged properly. A chest radiograph should be obtained to detect complications and the location of the catheter tip.
 
Anterior Approach (Fig. 5.5)
Anatomical landmark for anterior approach is the midpoint on the sterna head of sternomastoid. Carotid artery can be palpated 1 cm medial to the lateral border of the sternal head. Fingers are kept to palpate the artery and the needle is introduced just lateral to the pulsation at an angle of 45° and directed downwards towards the ipsilateral nipple. Usually, the IJV is punctured within 3 cm. If IJV is not punctured, the needle is directed 5° laterally. 32
Fig. 5.5: Technique of catheterizing right internal jugular vein—anterior approach
Fig. 5.6: Technique of catheterizing right internal jugular vein—posterior approach
 
Posterior Approach (Fig. 5.6)
In the posterior approach, external jugular vein is used as a landmark. The needle is introduced 1 cm anterior to the point where the external jujular vein (EJV) crosses the posterior border of the sternomastoid or 5 cm upward from 33the clavicle along the lateral head of the sternomastoid. The needle is directed caudally and posteriorly toward the suprasternal notch at an angle of 45° with the sagittal plane, with a 15° upward angulation. IJV is usually punctured within 6 cm. If the attempt is not successful, the needle should be directed slightly more cephalad on the next attempt.
Complications: Operator's inexperience appears to increase the number of complications. Overall incidence of complications in IJV catheterization is 0.1–4%. Coagulopathy is a relative contraindication to IJV catheterization.
  • Internal carotid artery (ICA) puncture—most common complication
  • Pneumothorax
  • Thrombosis
  • Infection
  • Vascular erosions
  • Air embolism
  • Cardiac perforation
  • Cardiac arrhythmias.
Subclavian vein cannulation
There are two approaches:
  1. Infraclavicular approach—most common.
  2. Supraclavicular approach.
Position: The patient is put in 30° Trendelenburg position with a folded roll between the shoulder blades. The head is turned towards the opposite side of cannulation and both the arms are adducted.
 
Infraclavicular Approach (Figs 5.7A and B)
Landmarks—clavicle, 2 heads of sternomastoid, suprasternal notch.
Technique
The intensivist stands on the side of the patient's shoulder where the vein is to be cannulated. Right subclavian vein is preferred. The skin is punctured 2–3 cm caudal to the midpoint of the clavicle or in the junction of medial 1/3rd or lateral 2/3 just inferior to the clavicle and needle is inserted just beneath the posterior surface of the clavicle. The needle tip is directed toward the suprasternal notch which is identified by the intensivist's other hand. If the subclavian vein is not punctured in the first attempt, the needle is withdrawn and a second attempt is done in a slightly more cephalad direction. In order to avoid pneumothorax, the needle should stay parallel to the base and not angle down toward the chest. Subclavian vein catheterization should not be the first choice for patients with high-risk pulmonary disease or coagulopathy.
 
Advantages
  • Lower risk of infection compared with internal jugular vein or femoral vein catheterization
  • Ease of cannulation in trauma patients or patients with cervical collar
  • Better for long term maintenance especially for chemotherapy and total parenteral nutrition (TPN)
  • Patient comfort.34
Figs 5.7A and B: Technique of catheterizing right subclavian—vein infraclavicular approach
Complications
  • Pneumothorax incidence is high compared with IJV cannulation
  • Subclavian artery puncture
  • Catheter tip malposition.
 
Supraclavicular Approach (Figs 5.8A and B)
Position of the intensivist—Intensivist stands on the head end of the patient on the side of cannulation.
Landmarks—clavicular head of sternomastoid, sternoclavicular joint.35
Figs 5.8A and B: Technique of catheterizing right subclavian vein—supraclavicular approach
36
Technique
The site of puncture is just lateral to the clavicular head of sternomastoid above the clavicle. The needle is advanced toward or just caudal to the contralateral nipple just under the clavicle. The needle is angled at 45° at sagittal plane and directed towards a dividing line between the sternoclavicular joint and clavicular head of the sternomastoid. The depth of insertion is just beneath the clavicular head of sternomastoid at an angle of 15° below the coronal plane. The needle should enter the subclavian jugular junction after 1–4 cm, and after the vein is punctured, catheterization is done.
 
Femoral Vein Cannulation
Position—supine position with the leg extended and slightly abducted at the hip.
 
Technique (Figs 5.9A and B)
Femoral vein puncture is done 3 cm below the inguinal ligament just medial to the palpated femoral artery at an angle of 45° and with tip angulated in cephalad and medial direction. Either a long (40–70 cm) catheter or short (15–20 cm) is used. Long catheter is positioned under ECG or fluoroscopic guidance. Short catheter can be kept in the common iliac vein. Femoral vein cannulation is the easiest among all the 3 veins.
Advantages
  • Burns or trauma
  • Surgical procedures involving the head, neck, and upper part of the thorax
  • Cardiopulmonary resuscitation
  • Can be used in patients with severe lung disease since reduced incidence of pulmonary complications.
Complications
  • Arterial puncture
  • Thromboembolism
  • Infection
  • Scrotal hemorrhage
  • Intestinal perforation.
 
Peripherally Inserted Central Venous Catheters
Peripherally inserted central venous catheters (PICC) has become a popular alternative to centrally inserted catheters in patients requiring long-term intravenous therapy. Venous access for a PICC is obtained either through an antecubital vein, preferably the basilic vein, which can be catheterized easily than the cephalic vein because of its more linear course. Most PICC catheters are flexible and nonthrombogenic silicone catheters.
Advantages
  • Used for long-term intravenous therapy—chemotherapy or total parenteral nutrition (TPN)
  • Can be done in bedside by even less trained personnel
  • Low risk catheter related complications—pneumothorax, infection
  • Cost-effective.37
Figs 5.9A and B: Technique of catheterizing right femoral vein
Disadvantages
  • Central venous pressure (CVP) recorded via PICCs is slightly higher than the pressure measured with centrally inserted catheters
  • Increased risk of cardiac perforation and arrhythmias.38
 
ULTRASOUND-GUIDED TECHNIQUES
The use of ultrasound for central venous cannulation has revolutionized anesthesia and critical care because of the reduction in the complications hence enhancing the safety profile of the invasive technique.
There are two techniques for using 2D ultrasound:
  1. Static approach.
  2. Real time approach.
Static approach: A mark is placed on the skin indicating the placement of insertion of needle with the help of ultrasound and cannulation is done thereafter without ultrasound.
Real time approach: Needle insertion is visualized while performing the procedure.
All the three veins—internal jugular, subclavian or femoral vein can be cannulated with ultrasound technique (Figs 5.10 to 5.13).
Figs 5.10A and B: Ultrasound image of left internal jugular vein—short-axis view
Fig. 5.11: Ultrasound image of right internal jugular vein—long-axis view
39
Fig. 5.12: Ultrasound image of right femoral vein—short-axis view
Fig. 5.13: Ultrasound image of right subclavian vein—infraclavicular region
 
 
Advantages of Ultrasound Over Landmark Technique
  • Increased success rate in first attempt
  • Reduction in complications—reduced carotid artery puncture, pneumothorax, hemothorax, hematoma, catheter tip malpositions
  • Reduced number of attempts
  • Reduced duration of cannulation
  • Reduction in central venous catheter-associated blood stream infection
  • 40  Improved identification of preexisting thrombus formation and anatomical variations in the IJV location thus facilitating safer and more successful cannulation of the vessel
  • Visualization of both transverse and longitudinal axis in ultrasound prevents the double wall puncture during the needle insertion.
 
Confirming Catheter Tip Position
  • Radiological identification is done and the tip of the catheter should lie within the superior vena cava and positioned below the inferior border of the clavicles and above the level of the third rib, the T4 to T5 interspace, the tracheal carina, or at the branching of the right mainstem bronchus. The right tracheobronchial angle is the most reliable landmark on plain chest radiograph for the upper margin of the SVC and is mostly at least 3 cm above the caval—atrial junction. The tip of the catheter should lie about 1 cm below this landmark.
  • The ideal location for the catheter tip is the proximal superior vena cava 3 to 5 cm proximal to the caval-atrial junction. Positioning of the catheter tip within the right atrium or right ventricle should be avoided.
  • The use of ECG electrode in the central venous catheter can be used as a method of confirming the catheter tip. It is based on the P-wave. This technique is based on the CVP catheter being used as an exploring electrode. The P wave would be increasing in negativity as it moves away from the right atrium and increasing positivity as it moves into right atrium (Fig. 5.14).
 
Management of Catheter
 
Catheter-related Infection
Catheter-related blood stream infection is defined as at least two blood cultures positive with the same organism, obtained from at least two separate sites at different times. An exit site infection presents with erythema, tenderness. A tunnel infection is characterized by pain and induration along the track of the catheter. Catheters can become infected from four potential sources: the skin insertion site, the catheter hub, hematogenous seeding, and infusate contamination.
 
Protocol for Catheter Management
Chlorhexidine is a better disinfectant and should be used instead of iodine-based solutions for site preparation before catheter insertion. Replacement of fluid administration sets every 72–96 hours is safe. Transparent polyurethane dressings are better than gauzes and tapes. It is recommended that gauze be changed every 2 days and transparent dressing changed every 7 days. Chlorhexidine impregnated gauze has been shown to reduce infection. Subcutaneous tunneling of catheters reduces the incidence of infection. Avoid guidewire exchanges since it has been shown to increase the infection rate.41
Fig. 5.14: ECG electrode method of confirming the position of catheter tip
 
BIBLIOGRAPHY
  1. Daily PO, Griepp RB, Shumway NE. Percutaneous internal jugular vein cannulation. Arch Surg. 1970; 101:534-6.
  2. Eerola R, Kaukinen L, Kaukinen S. Analysis of 13,800 subclavian vein catheterizations. Acta Anaesthesiol Scand. 1985;29:193.
  3. Hayashi H, Amano M. Does ultrasound imaging before puncture facilitate internal jugular vein cannulation? Prospective randomized comparison with landmark-guided puncture in ventilated patients. J Cardiothorac Vasc Anesth. 2002;16:572-5.
  4. Karakitsos D, Labropoulos N, De Groot E, et al. Real-time ultrasound-guided catheterization of the internal jugular vein: a prospective comparison with the landmark technique in critical care patients. Crit Care. 2006;10(6):R162.
  5. Maki DG, Botticelli JT, LeRoy ML, et al. Prospective study of replacing administration sets for intravenous therapy at 48- vs. 72-hour intervals. 72 hours is safe and cost-effective. JAMA. 1987;258:1777.
  6. Maki DG, Ringer M, Alvarado CJ. Prospective randomised trial of povidone-iodine, alcohol, and chlorhexidine for prevention of infection associated with central venous and arterial catheters. Lancet. 1991;338(8763):339-43.
  7. 42Malloy DL, McGee WT, Shawker TH, Brenner M, Bailey KR, Evans RG, Parker MM, Farmer JC, Parillo JE. Ultrasound guidance improves the success rate of internal jugular vein cannulation: a prospective, randomized trial. Chest. 1990;98:157-60.
  8. McDonnell JE, Perez H, Pitts SR, et al. Supraclavicular subclavian vein catheterization: modified landmarks for needle insertion. Ann Emerg Med. 1992;21:421.
  9. Merrer J, De Jonghe B, Golliot R, et al. Complications of femoral and subcalvian venous catheterization in critically ill patients. A randomized controlled trial. JAMA. 2001;286:700-7.
  10. Milling TJ, Jr Rose J, Briggs WM, et al. Randomized, controlled clinical trial of point-of-care limited ultrasonography assistance of central venous cannulation: the Third Sonography Outcomes Assessment Program (SOAP-3) Trial. Crit Care Med. 2005; 33(8):1764-9.
  11. Mimoz O, Pieroni L, Lawrence C, et al. Prospective, randomized trial of two antiseptic solutions for prevention of central venous or arterial catheter colonization and infection in intensive care unit patients. Crit Care Med. 1996;24(11):1818-23.
  12. Moosman DA. The anatomy of infraclavicular subclavian vein catheterization and its complications. Surg Gynecol Obstet. 1973;136:71.
  13. Netter FH. Atlas of human anatomy. Summit, NJ, Cibn-Geigy, 1989.
  14. O'Grady NP, Alexander M, Dellionger EP, et al. Guidelines for prevention of intravascular catheter–related infections. Centers for Disease Control and Prevention. MMWR Recomm Rep. 2002;51(RR-10):1-29.
  15. Parras F, Ena J, Bouza E, et al. Impact of an educational program for the prevention of colonization of intravascular catheters. Infect Control Hosp Epidemiol. 1994;15:239.
  16. Pinsky MR. Hemodynamic monitoring in the intensive care unit. Clin Chest Med. 2003;24:549-60.
  17. Randolph AG, Cook DJ, Gonzales CA, Pribble CG. Ultrasound guidance for placement of central venous catheters: a meta-analysis of the literature. Crit Care Med. 1996;24: 2053-8.
  18. Williams PL, Warwick R. Gray's Anatomy, 8th ed. Philadelphia, WB Saunders, 1980.

PULMONARY ARTERY CATHETERIZATIONCHAPTER 6

Prem Kumar  
HISTORY
In 1970, Swan and Ganz introduced pulmonary artery catheterization (PAC) into clinical practice for hemodynamic assessment of patients with acute myocardial infarction and from then, its use in clinical practice has increased because of the measurement of various physiologic variables in critical care.
 
Pulmonary Artery Catheter
Pulmonary artery catheter (PAC) has a 7.0- to 9.0-Fr circumference (1 Fr = 0.0335 mm) and the length is 110 cm marked at 10-cm intervals, and contains four internal lumens (Fig. 6.1). The catheter is made of polyvinylchloride coated with heparin to prevent thrombosis. PAC is passed through a sterile sheath that attaches to the hub of the introducer and allows sterile manipulation of PAC position during use. The balloon is tested by filling it completely with 1.5 mL of air from a volume-limited syringe to ensure symmetry of expansion and patency. The function of the air-filled balloon at the catheter tip is to float the catheter forward with blood flow through the right heart chambers and into the pulmonary artery. Pacing PA catheters has two groups of electrodes on the catheter surface, enabling intracardiac electrocardiographic (ECG) recording or can be used also for temporary cardiac pacing.
Fig. 6.1: Patient with pulmonary artery catheter with different lumens
44The distal port at the catheter tip is used for monitoring of pulmonary artery pressure, whereas the proximal lumen second is 30 cm proximal and is used for monitoring of CVP. The third lumen leads to a balloon near the tip, and the fourth lumen is for a temperature thermistor. The end of the thermistor lies just proximal to the balloon.
 
PA Catheter Lumens
  • Distal lumen: Connected to pressure monitoring system to monitor pressures in the pulmonary artery. It is used for withdrawing blood mixed venous saturation samples and it is not used for continuous fluid/drug administration.
  • Proximal injectate lumen: It is used to monitor CVP and inject solution to intermittently assess cardiac output through thermodilution.
  • Proximal infusion lumen: For administration of fluids/drugs.
  • Inflation valve lumen and syringe: It connects to balloon to inflate air (typically 1.5 mL) into the balloon for wedging.
  • Thermistor connector lumen: PA blood temperature and allows thermodilution CO measurements.
 
Indications
According to the ACCF/AHA guidelines, pulmonary artery catheterization is appropriate in the following settings.
  • Cardiogenic shock during supportive therapy
  • Severe chronic heart failure requiring inotropic, vasopressor, and vasodilator therapy
  • Suspected “pseudosepsis” (high cardiac output, low systemic vascular resistance, elevated right atrial and pulmonary capillary wedge pressures)
  • Potentially reversible systolic heart failure such as fulminant myocarditis and peripartum cardiomyopathy
  • Discordant right and left ventricular failure
  • Transplantation work-up
  • Not indicated as routine in high-risk cardiac and noncardiac patients
  • To detect hemodynamic differential diagnosis of pulmonary hypertension
  • To assess response to therapy in patients with precapillary and mixed types of pulmonary hypertension
  • Aspiration of air emboli.
 
PERIOPERATIVE INDICATIONS
 
CLASS I
Placement of a pulmonary artery catheter is indicated, preferably before the induction of anesthesia or surgical incision, in patients in cardiogenic shock undergoing CABG (Level of Evidence: C).45
 
CLASS IIa
Placement of a pulmonary artery catheter can be useful in the intraoperative or early postoperative period in patients with acute hemodynamic instability (Level of Evidence: B).
 
CLASS IIb
Placement of a pulmonary artery catheter may be reasonable in clinically stable patients undergoing CABG after consideration of baseline patient risk, the planned surgical procedure, and the practice setting (Level of Evidence: B).
 
Technique
  • After checking for the balloon integrity, deflate it and check the pressure tubing, transducers and stopcocks.
  • Right internal jugular veins is cannulated and with the guidewire in place, enlarge the puncture site using a scalpel and a vessel dilator sheath apparatus is introduced through the guidewire using a twisting motion. The guidewire and vessel dilator are removed, leaving the introducer sheath in the vessel and the sheath is sutured.
  • Stopcocks are attached to the right atrium and PA ports of the PA catheter and the proximal and distal catheter lumens are filled with flush solution. Close the stopcocks to keep flush solution within the lumens and to avoid introduction of air into the circulation.
  • After the PA catheter is introduced into a right internal jugular vein, the right atrium is reached when the PAC is inserted 20–25 cm, the right ventricle at 30–35 cm, the pulmonary artery at 40–45 cm, and the wedge position at 45 to 55 cm. RA length indication—35–40 cm from the left antecubital fossa, 10 to 15 cm from the internal jugular vein, 10 cm from the subclavian vein, and 35–40 cm from the femoral vein.
  • The distances are rough guided and waveform morphology is used as a guide for catheter placement and catheter position confirmed with a chest radiograph. The tip of the PAC should be within 2 cm of the cardiac silhouette on a chest radiograph.
  • Once the catheter is in right atrium, measure the pressure, waveform and inflate the balloon with the recommended amount of air anticipating the catheter is in the right atrium. Inflation of the balloon should be associated with a slight feeling of resistance.
  • With the balloon inflated, advance the catheter until a RV pressure tracing is seen on the monitor. Record the right ventricle pressure. This is the time when cardiac arrhythmias are encountered. If there is difficulty in reaching the right ventricle, elevation of head to 5° and a right-tilt position will facilitate the entry of the catheter into the right ventricle.
  • The catheter is advanced further until there is rise in diastolic pressure tracing which indicates PA placement. If a RV trace appears even after the catheter is advanced 15 cm, suspect coiling in the right ventricle, then deflate the balloon and withdraw it to the right atrium, then reinflate it and repeat the same steps again.46
    Fig. 6.2: Zones of lung and the placement of PA catheter
  • As the catheter is advanced, there is fall on the pressure tracing from the levels of systolic pressure noted in the RV and PA which indicates that PA catheter is in the pulmonary artery occlusion pressure position. A typical pulmonary artery occlusion pressure tracing should be noted with a and v waves. Deflate the balloon, a phasic PA pressure should appear on the pressure tracing. A PAC positioned in both zone 1 and 2 will be susceptible to alveolar pressure, and the measurements will reflect alveolar or airway pressure rather than left ventricular filling pressure. Hence, the tip of the PAC must lie in zone 3 for PAWP to be accurate (Fig. 6.2).
  • Secure the catheter in the correct PA position by suturing it to the skin.
  • Take a chest radiograph to confirm catheter tip position.
 
Special Situations of Difficulty in PA Catheterization
After successful internal jugular vein (IJV) cannulation, if attempts to advance the PAC to the right ventricle prove difficult, the physician should consider the possibility of abnormal venous anatomy. Among the abnormalities, the most common abnormality of the systemic veins is persistence of the left superior vena cava and a rare form of atrial septal defect called as unroofed coronary sinus, can also be seen in some patients where there is a potential for the PAC to enter the left atrium and systemic circulation. These abnormalities can be detected by waveform characteristics which show a downstream right atrial pressure and a transmitted dampened left ventricular pressure waveform.
 
PHYSIOLOGICAL VARIABLES WITH PA CATHETERIZATION (TABLES 6.1 TO 6.3)
Pulmonary artery (PA) catheter can measure hemodynamic parameters such as cardiac output, pulmonary artery diastolic and wedge pressure and indirectly 47measure ventricular filling pressures. It can also measure mixed venous oxygen saturation. With the PA catheter in position and the balloon deflated, the distal lumen transmits PA pressure and the PA waveform is characterized by a systolic peak and diastolic trough with a dicrotic notch due to closure of the pulmonary valve (Fig. 6.3). The peak PA systolic pressure corresponds to the T wave of an ECG.
Table 6.1   Oxygen saturation at various chambers and vessels
Sampling chamber or vessel
Oxygen saturation (in %)
SVC
70
IVC
80
RA
75
RV
75
Pulmonary artery
75
Table 6.2   Parameters measured by PA catheter
Variable
Normal range (units)
Central venous pressure (CVP)
0–8 mm Hg
Right ventricular systolic pressure (RVSP)
15–30 mm Hg
Right ventricular end-diastolic pressure (RVEDP)
0–8 mm Hg
Pulmonary artery systolic pressure (PAP)
15–30 mm Hg
Pulmonary artery diastolic pressure (PADP)
4–12 mm Hg
Pulmonary artery occlusion pressure (PAOP)
2–12 mm Hg
Mean pulmonary artery pressure
10–18 mm Hg
Pulmonary artery occlusion pressure (PAOP) reflects left atrial pressure, and is an indirect indicator of left ventricular filling pressure. To confirm the PA catheter position is in zone 3, the catheter tip should be below the level of the left atrium in a chest X-ray in supine position and also by withdrawing a blood specimen from the distal lumen and measuring oxygen saturation which should be >95%. With the patient having a normal mitral valve and normal left ventricular function, the mean PAOP correlates well with left ventricular end-diastolic pressure (LVEDP).
 
Measuring Cardiac Output
  • It can be measured by thermodilution principle
  • It can be approximately measured merely by mixed venous oxygen saturation. Normal mixed venous oxygen saturation (SvO2) is 70–75%. Reduced SvO2 occurs in patients with shock, heart failure. Fiberoptic reflectance oximetry can continuously measure SvO2 and indicate cardiac output indirectly. This is used as a derived measure of oxygen consumption and oxygen delivery to guide the treatment of critically ill patients. Currently used as a guide for septic shock in goal-directed therapy.48
Table 6.3   Derived parameters obtained with data from PA catheter
Variable
Formula
Normal range
Arterial oxygen content (CaO2)
SaO2 × Hb × 1.39 + PaO2 (mm Hg) × 0.003
180 mL liter–1
Mixed venous oxygen content (CvO2)
SvO2 × Hb × 1.39 + PvO2 (mm Hg) × 0.003
130 mL liter–1
Oxygen delivery (DO2)
× CaO2
800–1000 mL min–1
Oxygen consumption (VO2)
/(CaO2/CvO2)
180–300 mL min–1
Oxygen delivery index (DO2I)
Do2/BSA
500–650 mL min–1 m–2
Oxygen consumption (VO2I)
Vo2/BSA
100–180 mL min–1 m–2
Cardiac index (CI)
/BSA
2.5–4.0 liter min–1 m–2
Stroke volume (SV)
/HR
60–80 mL
Stroke index (SI)
SV/BSA
30–65 mL m–2
Left ventricular stroke work index (LVSWI)
CI × (MAP–PAOP) × 0.0136
40–60 g m–1 m–2
Systemic vascular resistance (SVR)
(MAP–CVP) × 80/
900–1200 dyns cm–5 m–2
Systemic vascular resistance index (SVRI)
(MAP–CVP)×80/CI
1500–2500 dyns cm–5 m–2
Mean pulmonary artery pressure (mPAP)
[PASP + (2×PADP)]/3
10–20 mm Hg
Right ventricular stroke work index (RVSWI)
Cl × (MPAP–CVP) × 0.0136
6–12 g m–1 m–2
Pulmonary vascular resistance (PVR)
(MPAP–PAOP) × 80/
50–150 dyns cm–5 m–2
Pulmonary vascular resistance index (PVRI)
(MPAP–PAOP) × 80/CI
250–350 dyns cm–1 m–2
Body surface area (BSA) = Weight (Kg)0.425 × height (cm)0.725 × 0.007184;
, cardiac output
Fig. 6.3: Waveforms showing the position of PA catheter
49
Table 6.4   Effects of various conditions on the pulmonary parameters
Condition
Abnormality
Positive end-expiratory pressure
Mean PAWP > mean LAP
Mitral stenosis
Mean LAP > LVEDP
Mitral regurgitation
Mean LAP > LVEDP
Aortic regurgitation
LAP < LVEDP
Pulmonary arterial hypertension
PADP > mean PAWP
Pulmonary veno-occlusive disease
Mean PAWP > mean LAP
Postpneumonectomy
PAWP < LAP or LVEDP
 
Pulmonary Artery Occlusion Pressure (Table 6.4)
  • It is mostly interchanged with pulmonary artery wedge pressure
  • Pathophysiologic conditions involving the left-sided cardiac chambers or valves produce characteristic changes in the pulmonary artery and wedge pressure waveforms. One among the following is the tall v wave of mitral regurgitation.
  • In mitral regurgitation, distortion of the systolic portion of the wedge pressure waveform is present whereas in mitral stenosis, distortion in diastolic portion is present.
  • Constrictive pericarditis—rapid early diastolic ventricular filling resulting in square root sign.
  • During positive-pressure ventilation, inspiration increases pulmonary artery and wedge pressure. These effects are minimized, if the PAP and PAWP are measured at the end of expiration.
  • PAWP and PADP can be used as surrogate measures of left ventricular filling.
  • Alteration in PAWP alters pulmonary capillary pressure though both are not the same, which in turn reflects the hydrostatic pressure (important factor for development of pulmonary edema).
  • The end-diastolic wedge pressure after atrial contraction best predicts left ventricular end-diastolic filling pressure or preload.
 
Factors Causing Variability of PAOP in Measuring Preload
 
Complications
  • All the complications associated with central vein catheterization
  • Pulmonary thrombosis
  • Pulmonary infarction
  • Pulmonary artery perforation
  • 50Cardiac arrhythmias
  • Balloon rupture
  • Catheter coiling and knotting
  • Infection
  • Intracardiac damage to walls, valve, endocardial disruption.
 
BIBLIOGRAPHY
  1. 2011 ACCF/AHA guideline for coronary artery bypass graft surgery: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2011;58:2584-614.
  2. Azocar RJ, Narang P, Talmor D, et al. Persistent left superior vena cava identified after cannulation of the right subclavian vein. Anesth Analg. 2002;95:305-7.
  3. Barash PG, Nardi D, Hammond G, et al. Catheter-induced pulmonary artery perforation: mechanisms, management and modifications. J Thorac Cardiovasc Surg. 1981;82:5.
  4. Chatterjee K, Swan JHC, Ganz W, et al. Use of a balloon-tipped flotation electrode catheter for cardiac monitoring. Am J Cardiol. 1975;36:56.
  5. Foote GA, Schabel SI, Hodges M. Pulmonary complications of the flow-directed balloon-tipped catheter. N Engl J Med. 1974;290:927.
  6. JM Gore, JS Alpert, JR Benotti, et al. Handbook of Hemodynamic Monitoring. Boston: Little Brown; 1984.
  7. Lange HW, Galliani CA, Edwards JE. Local complications associated with indwelling Swan-Ganz catheters. Am J Cardiol. 1983;52:1108.
  8. Lange RA, Moore DM, Cigarroa RG, et al. Use of pulmonary capillary occlusion pressure to assess severity of mitral stenosis: is true left atrial pressure needed in this condition? J Am Coll Cardiol. 1989;13:825.
  9. Meister SG, Furr CM, Engel TR, et al. Knotting of a flow-directed catheter about a cardiac structure. Cathet Cardiovasc Diagn. 1977;3:171.
  10. Pace NL, Horton W. Indwelling pulmonary artery catheters: their relationship to aseptic thrombotic endocardial vegetations. JAMA. 1975;233:893.
  11. Pearson KS, Gomez MN, Moyers JR, et al. A cost/benefit analysis of randomized invasive monitoring for patients undergoing cardiac surgery. Anesth Analg. 1989;69: 336-41.
  12. Practice Guidelines For Pulmonary Artery Catheterization: an Updated Report by the American Society of Anesthesiologists Task Force on Pulmonary Artery Catheterization. Anesthesiology. 2003;99:988-1014.
  13. Resano FG, Kapetanakis EI, Hill PC, et al. Clinical outcomes of low-risk patients undergoing beating-heart surgery with or without pulmonary artery catheterization. J Cardiothorac Vasc Anesth. 2006;20:300-6.
  14. Roizen MF, Berger DL, Gabel RA, et al. Practice guidelines for pulmonary artery catheterization. An updated report by the American Society of Anesthesiologists Task Force on Pulmonary Artery Catheterization. Anesthesiology. 2003;99:988-1014.
  15. Schwann TA, Zacharias A, Riordan CJ, et al. Safe, highly selective use of pulmonary artery catheters in coronary artery bypass grafting: an objective patient selection method. Ann Thorac Surg. 2002;73:1394-401.
  16. Stewart RD, Psyhojos T, Lahey SJ, et al. Central venous catheter use in low-risk coronary artery bypass grafting. Ann Thorac Surg. 1998;66:1306-11.
  17. Swan HJC, Ganz W, Forrester J, et al. Catheterization of the heart in man with use of a flow-directed balloon-tipped catheter. N Engl J Med. 1970;283:447.
  18. Sweitzer BJ, Hoffman WJ, Allyn JW, Daggett WJ. Diagnosis of a left-sided superior vena cava during placement of a pulmonary artery catheter. J Clin Anesth. 1993;5:500-4.

HEMODYNAMIC MONITORINGCHAPTER 7

Prem Kumar
Critically ill patients require hemodynamic monitoring not only for diagnostic purpose but also for intervention aimed for supporting organs and it can be used as a guide to therapy. Although vital signs are still used widely in ICU, they are poor predictors of the hemodynamic state. Recently, fluid responsiveness by noninvasive methods have become better predictors of preload rather than static measures like central venous pressure. Now there are methods of assessing cardiac output by noninvasive methods rather than thermodilution method. With the recent evidence about hemodynamic monitoring, we will discuss the various methods and parameters of hemodynamic monitoring and its clinical significance (Table 7.1).
Hemodynamic variables can be either measured or calculated. Using direct arterial blood pressure monitoring and PA catheter monitoring, hemodynamic variables of both systemic and pulmonary circulation can be measured or calculated.
 
THORACIC BIOIMPEDANCE PLETHYSMOGRAPHY
Electrodes are placed in the neck and thorax region and the fluctuations in electrical impedance are measured. The change in aortic flow is measured by the change in the thoracic bioimpedance through the cardiac cycle.
 
ESOPHAGEAL AND TRANSCUTANEOUS DOPPLER MONITORING
It measures blood flow velocity in the descending aorta by a Doppler probe kept in the esophagus 40 cm from the mouth. It is a useful monitor for measuring cardiac output. It has been used for high-risk surgical patients but its use in critical care is yet to be validated. Transcutaneous Doppler monitoring by an external probe can measure transpulmonary and transaortic cardiac output.
 
Capnography
 
Uses of Capnography in ICU
  • Detection of return of spontaneous circulation after cardiac arrest
  • Detection of esophageal intubation and accidental extubation52
Table 7.1   Parameters of hemodynamic monitoring
Noninvasive methods
Transthoracic echocardiography
Thoracic Bioimpedance Plethysmography
Esophageal Doppler
Transcutaneous Doppler Ultrasonography
End tidal CO2 monitoring
Pulse oximetry
Mucosal tonometry
Static measures
Invasive arterial blood pressure
Central venous pressure
IVC diameter by ultrasound
Hemodynamic measures with PA catheter
Cardiac output by thermodilution method
Left ventricular end-diastolic area index (LVEDAI)
Dynamic parameters
Pulse pressure variation
Stroke volume variation
Systolic pressure variation
Pleth variability index (PVI)
Distensibility index of IVC
Collapsibility index of the superior vena cava
End-expiratory occlusion test
Preload responsiveness by passive leg raising test
Pulse contour cardiac output analysis—PiCCO, NICOM system
Abbreviations: PiCCO, pulse index contour continuous cardiac output; NICOM, noninvasive cardiac output Monfoss
  • Diagnosing air and pulmonary embolism
  • Indirect indicator of cardiac output.
 
Pulse Oximetry
It is considered as an essential monitor for all ICU patients receiving supplemental oxygen. It is useful in trauma patients to detect pulmonary embolism. A sudden drop in saturation in the presence of a normal chest X-ray in trauma patients is highly predictive of pulmonary embolism.53
 
MUCOSAL TONOMETRY
A tube with balloon tip is inserted into the stomach and gastric tonometry monitors gastric circulation and is an early indicator of splanchnic hypoperfusion. Intermittently, the saline or air is aspirated and the CO2 level is measured. The CO2 from the mucosa diffuses to the gastric lumen and is detected by the tonometry. Gastric mucosal CO2 and pH are good predictors of trauma or perioperative complications.
CVP/RAP→Can indirectly measure RVEDP→RV preload
PAWP→can indirectly measure LVEDP→LV preload
 
Mean Arterial Pressure
Mean arterial pressure (MAP) is a better indicator of tissue perfusion pressure than systolic and diastolic pressure because it is least dependent on the technique and the site of measurement. The normal MAP is 60–70 mm Hg. Though it is a useful parameter for tissue perfusion, still its reliability is low because MAP does not adequately reflect perfusion at tissue level in critically ill patients. There can be normal MAP yet the patient may have impaired tissue perfusion. Tissue autoregulation is also disturbed in severely ill patients.
 
Invasive Arterial Blood Pressure Monitoring
The character of the arterial waveform depends upon two factors:
  1. Stroke volume.
  2. Compliance of arteries and arterioles.
 
Clinical Applications of IBP Monitoring
  • In case of hypotension, if the arterial waveform shows spike pattern with prominent dicrotic notch, it indicates hypovolemia.
  • Continuous beat-to-beat blood pressure monitoring which would be useful in critically ill patients.
  • Pulse contour analysis—estimation of stroke volume and cardiac output can be done by analysis of invasive blood pressure (IBP) waveform. It calculates stroke volume from the area under the systolic portion of the waveform. Cardiac output (CO) is derived by stroke volume and heart rate and both these parameters can be monitored continuously on a beat-to-beat basis. This analysis is reliable even in patients with hemodynamic instability but its reliability and validity with arrhythmias is yet to be ascertained. This analysis has been shown to have good comparability with thermodilution method.
  • Systolic time interval can provide information about the ventricular contractile function.
 
Central Venous Pressure Monitoring (Fig. 7.1)
Normal central venous pressure (CVP) is 0–5 mm Hg and with positive pressure ventilation it can be up to 10 mm Hg. 54
Fig. 7.1: Waveforms of central venous monitoring
Fig. 7.2: Effect of systolic dysfunction on the pressure-volume loop of the left ventricle. The isovolumic pressure-volume curve is shifted to the right, decreasing the stroke volume
Dynamic change in CVP in response to volume challenge or respiratory cycle can help in evaluation of volume status. Monitoring of cardiac filling pressures are done to estimate cardiac-filling volumes, which in turn determine the stroke volumes of both the left and right ventricles. According to the Frank-Starling law, the force of contraction is proportional to end-diastolic muscle fiber length at any given level of intrinsic contractility or inotropy. This muscle fiber length (preload) is proportional to end-diastolic volume. The relationship between ventricular stroke volume and end-diastolic volume is called the Frank-Starling curve. Increase in CVP in response to fluid challenge suggests that the heart is in the plateau portion of the frank starling curve (Figs 7.2 and 7.3).
 
ScvO2
The sample is obtained from the superior vena cava. This parameter can be used as an outcome measure in patients with sepsis and high-risk surgical patients treated in ICU. The difference between ScvO2 and SvO2 is that ScvO2 is 3–5% lower than SvO2. It can be used as an alternative to SvO2 in managing septic shock patients. 55
Fig. 7.3: Diastolic dysfunction increases end-diastolic volume and shifts the diastolic pressure-volume relationship upward and to the left. This reduces the stroke volume
Table 7.2   Measured parameters from PA catheter
Variable
Normal range (units)
Central venous pressure (CVP)
0–8 mm Hg
Right ventricular systolic pressure (RVSP)
15–30 mm Hg
Right ventricular end-diastolic pressure (RVEDP)
0–8 mm Hg
Pulmonary artery systolic pressure (PAP)
15–30 mm Hg
Pulmonary artery diastolic pressure (PADP)
4–12 mm Hg
Pulmonary artery occlusion pressure (PAOP)
2–12 mm Hg
Mean pulmonary artery pressure
10–18 mm Hg
 
Monitoring with PA Catheter
PA catheter measures various hemodynamic variables both measured and calculated which is shown in Table 7.2.
Apart from these variables, mixed venous oxygen saturation and cardiac output are also measured. This information derived from the PA catheter directly 56or indirectly will estimate left ventricular filling pressure and will guide the administration of fluids and inotrope/vasopressor agents. These parameters are measured at end-expiration to minimize the effect of inspiratory increase in intrathoracic pressure which can produce confounding results. The tip of the PA catheter should be in west zone 3 (Table 7.3). The following criteria suggest that the tip of PA catheter is in zone 3:
Table 7.3   Derived parameters obtained with data from PA catheter
Variable
Formula
Normal range
Cardiac index (CI)
/BSA
2.5–4.0 litre min–1 m–2
Stroke volume (SV)
/HR
60–80 mL
Stroke index (SI)
SV/BSA
30–65 mL m–2
Left ventricular stroke work index (LVSWI)
CI × (MAP – PAOP) × 0.0136
40–60 g m–1 m–2
Systemic vascular resistance (SVR)
(MAP–CVP) × 80/
900–1200 dyn s cm–5 m–2
Systemic vascular resistance index(SVRI)
(MAP – CVP) × 80/CI
1500–2500 dyn s cm–5 m–2
Mean Pulmonary Artery Pressure (MPAP)
[PASP + (2 × PADP)]/3
10–20 mm Hg
Right ventricular stroke work index (RVSWI)
Cl × (MPAP – CVP)× 0.0136
6–12 g m–1 m–2
Pulmonary Vascular resistance (PVR)
(MPAP–PAOP) × 80/
50–150 dyn s cm–5 m–2
Pulmonary vascular resistance index (PVRI)
(MPAP – PAOP) × 80/CI
250–350 dyn s cm–1 m–2
Arterial oxygen content (CaO2)
SaO2 × Hb × 1.39 + PaO2 (mm Hg) × 0.003
180 mL litre–1
Mixed venous oxygen content (CVO2)
SvO2 × Hb × 1.39 + PvO2 (mm Hg) × 0.003
130 mL litre–1
Oxygen delivery (DO2)
× CaO2
800–1000 mL min–1
Oxygen consumption (VO2)
/(CaO2/CvO2)
180–300 mL min–1
Oxygen delivery index (DO2I)
DO2/BSA
500–650 mL min–1 m–2
Oxygen consumption (VO2 I)
VO2/BSA
100–180 mL min–1 m–2
Body surface area (BSA) = Weight (Kg)0.425 × height(cm)0.725 × 0.007184;
, cardiac output
  • Application of PEEP causes < 50% alteration in PAOP
  • Atrial waveforms
  • In chest radiography—tip should be below the left atrium.
 
Measures of Left Ventricular Preload
  • PADP
  • PAWP
  • Intrathoracic blood volume index (ITBI)
  • CVP.57
 
Mixed Venous Oxygen Saturation (SvO2)
Sampling is done by aspirating blood from the distal port of PA catheter. Thus, the blood collected here is from SVC, IVC and coronary sinus. It can be monitored even continuously with fiberoptic reflectance oximetry. It utilizes the concept of Fick's method. It indicates the balance between oxygen delivery and oxygen consumption at the tissues. Normal ScvO2 is ≥70%. This parameter is useful in guiding therapy of septic shock (River's protocol—early goal directed therapy). Hence, it is an indirect indicator of cardiac output and tissue hypoxia. An arbitrary calculation is that, a SvO2 of 0.5 corresponds to venous PO2 of 25 mm Hg.
Measurement of cardiac output in critically ill patients provides a global assessment of the circulation, and with other hemodynamic measurements (heart rate, arterial blood pressure, CVP, PAP, and PAWP), it can derive circulatory variables such as systemic vascular resistance (SVR), pulmonary vascular resistance (PVR) and ventricular stroke work. Reduced CO increases mortality and thermodilution method is used. Commonly used injectate is cold normal saline (alternative is lithium) and is injected in superior vena cava and by detecting the blood temperature by a thermistor near the distal tip, the device estimates the flow.
Transpulmonary dilution technique is an alternative to PAC where a tracer is injected through a CVP line and detected in an arterial line (e.g. radial artery).
 
Echocardiography
Transesophageal echo can visualize cardiac chambers by which the volumetric changes between systole and diastole are measured. With this information, stroke volume and cardiac output can be estimated. Left ventricular end-diastolic area index (LVEDAI) is a static measure of LV preload.
 
Ultrasonography
58
Figs 7.4A and B: Ultrasound-guided IVC imaging showing collapsibility in the second image
 
Interpretations
  • Spontaneous breathing patients—fluid responsive, if
    • IVC measuring < 2 cm in diameter coupled with IVC collapse >50% with each breath or
    • IVC collapsibility >12%
  • Mechanically ventilated patiens—fluid responsive, if IVC distensibility >18%.
  • IVC collapsibility = (Max diameter – min diameter)/(mean diameter) × 100
  IVC distensibility = (Max diameter – min diameter)/(min diameter) × 100
  • Caval index (the fractional change in the IVC diameter during respiration).
  • A greater than 50% decrease in IVC diameter is associated with a CVP <8 mm Hg in management of sepsis.
Doppler ultrasound can be used to measure blood velocity in descending aorta and can be used for estimating cardiac output (Figs 7.4A and B).
 
Dynamic Parameters of Fluid Responsiveness
Dynamic parameters can predict increased cardiac output from volume challenge even when volume expansion is not done, and hence they are better predictors of fluid responsiveness than static measures. The first idea of conception of fluid responsiveness was the variation in arterial blood pressure observed during positive-pressure mechanical ventilation. These are measured using invasive arterial pressure monitoring, and these parameters result from the changes in intrathoracic pressure and lung volume that occur during the respiratory cycle (Flow chart 7.1).
 
SYSTOLIC PRESSURE VARIATION
Systolic pressure variation (SPV) is divided into inspiratory and expiratory components by measuring the increase (ΔP) and decrease (ΔD) in systolic pressure in relation to the end-expiratory and apneic baseline pressure.
 
Interpretation of SPV
  • During positive pressure ventilation, normal SPV = 7–10 mm Hg
  • Hypovolemia—increase in SPV especially the ΔD component.59
Flow chart 7.1: Cyclical variation of systemic arterial pressure
Studies have proven that SPV is a better indicator of LV preload than PAOP, CVP.
 
Pulse Pressure Variation
The maximum difference in arterial pulse pressure measured during a respiratory cycle in a patient on mechanical ventilation divided by the mean of maximal and minimal pulse pressure. Normal pulse pressure variation (PPV) is <13%. It is a better indicator for fluid responsiveness than most static measures of preload.
 
Stroke Volume Variation
Recent methods of cardiac output measurement based on pulse contour analysis like stroke volume variation (SVV) is a good indicator of volume responsiveness. Normal SVV is 10% and patients with increased variability will be fluid responsive.
 
LIMITATIONS OF DYNAMIC PARAMETERS
  • They can vary with tidal volume, peak inspiratory pressure and lung dynamics
  • Can vary with cardiac arrhythmias
  • Only validated in mechanically ventilated patients
  • Their validation in spontaneously breathing patients is yet to be proved.
 
Preload Responsiveness by Passive Leg Raising Test
Passive leg raising (PLR) is a simple maneuver that can resemble a rapid volume expansion of approximately 300–500 mL. Passive leg raising induces a gravitational transfer of blood from the lower limb to the right side of the heart. A 45° elevation is given to legs for 3 minutes and it has been found to have a good test of preload responsiveness in critically ill patients. Advantage of this technique is that it can 60be used for spontaneously breathing patients and patients with arrhythmias unlike PPV, SVV which can be used only in mechanically ventilated patients.
 
PiCCO/NiCOM System
It uses the transpulmonary dilution method to measure cardiac output and an increase in pulse contour cardiac output by more than 10% in response to PLR has been shown to predict volume responsiveness in mechanically ventilated patients with spontaneous breathing activity.
 
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  12. Monnet X, Rienzo M, Osman D, Anguel N, Richard C, Pinsky MR, Teboul JL. Passive leg raising predicts fluid responsiveness in the critically ill. Crit Care Med. 2006,34: 1402-7.
  13. Nagdev AD, Merchant RC, Tirado-Gonzalez A, Sisson CA, Murphy MC. Emergency department bedside ultrasonographic measurement of the caval index for noninvasive determination of low central venous pressure.” Annals of Emergency Medicine. 2010;55(3):290-5.
  14. Preisman S, Kogan S, Berkenstadt H, Perel H. Predicting fluid responsiveness in patients undergoing cardiac surgery: Functional hemodynamic parameters including the respiratory systolic variation test and static preload indicators. Br J Anaesth. 2005;95:746-55.
  15. Pölönen P, Ruokonen E, Hippeläinen M, et al. A prospective, randomized study of goal-oriented hemodynamic therapy in cardiac surgical patients. Anesth Analg. 2000; 90:1052-9.
  16. 61Reuter DA, Kirchner A, Felbinger TW, et al. Usefulness of left ventricular stroke volume variation to assess fluid responsiveness in patients with reduced cardiac function. Crit Care Med. 2003;31:1399-404.
  17. Rex S, et al. Prediction of fluid responsiveness in patients during cardiac surgery. British Journal of Anaesthesia. 2004;93(6):782-8.
  18. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368-77.
  19. Rooke GA. Systolic pressure variation as an indicator of hypovolemia. Curr Opin Anaesthesiol. 1995;8:511-5.
  20. Tavernier B, Makhotine O, Lebuffe G, et al. Systolic pressure variation as a guide to fluid therapy in patients with sepsis-induced hypotension. Anesthesiology. 1998;89: 1313-21.
62Shock
Chapter 8 An Overview of Shock Prem Kumar
Chapter 9 Hypovolemic Shock Prem Kumar
Chapter 10 Obstructive Shock Prem Kumar
Chapter 11 Cardiogenic Shock TA Naufal Rizwan
Chapter 12 Multiple Organ Dysfunction Syndrome Prem Kumar63

AN OVERVIEW OF SHOCKCHAPTER 8

Prem Kumar
Shock is one of the common problem prevalent in intensive care unit (ICU) and the mortality and morbidity due to shock is high. It can be due to various causes like hypovolemia, cardiac causes, sepsis and medical disorders like pulmonary vascular disease. In this chapter, we will discuss the pathophysiology, clinical features, diagnosis, hemodynamic monitoring and management.
 
DEFINITION
It is an acute clinical syndrome resulting in cellular dysoxia ultimately resulting in organ dysfunction and failure. Cellular hypoxia due to reduced tissue perfusion is the primary pathophysiology of shock.
 
CLASSIFICATION (TABLE 8.1)
It can be classified into four types:
  1. Hypovolemic shock.
  2. Cardiogenic shock.
  3. Distributive shock—septic, anaphylactic, neurogenic, adrenal, drug-induced.
  4. Obstructive shock.
Table 8.1   Hemodynamic variations in various types of shock
Type of shock
CVP
Cardiac output (CO)
PCWP
SVR
Mixed venous oxygen saturation (SvO2)
Hypovolemic
↓↓
Cardiogenic
↓↓
Distributive
Normal or ↑
Normal or ↓
↓ or ↑
Normal or ↑
Obstructive
↓↓
Normal or ↓
Abbreviations: CVP, central venous pressure; PCWP, pulmonary capillary wedge pressure; SVR, systemic vascular resistance
66
 
CLINICAL FEATURES
Hypotension as such is not an exclusive feature of shock. Clinical manifestations of organ dysfunction is good indicator of shock. Tachycardia, hypotension, tachypnea and irritability, if the cause of shock is not corrected are all early manifestations of shock. Reduced organ perfusion as indicated by reduced urine output, lactic acidosis, hepatic dysfunction are all late features if shock is uncorrected or is refractory to treatment. In case of cardiogenic shock, patient may have elevated jugular venous pressure, arrhythmias, pulmonary edema.
 
Diagnosis (Table 8.2 and Flow chart 8.1)
It is based on the history, physical examination, lab investigations and hemodynamic monitoring. Arterial blood gas analysis to see lactate level, acidosis. Hemoglobin, urea, creatinine, cortisol level can be used for diagnosis. central venous pressure (CVP), PAWP, CO, EtCO2, and echocardiogram will help in diagnosis and management.
 
Management
Primary goals of management in shock are:
  • Early recognition
  • Diagnosis of etiology
  • Improving tissue perfusion to prevent cellular injury
  • Primary treatment of etiology
  • Prevention of end-organ failure.
Table 8.2   Clinical manifestations of shock
Organ
Clinical features
Etiology
Heart
Tachycardia, arrhythmias
Myocardial depression
CCF
MI, coronary ischemia, sympathetic stimulation
Peripheral circulation
Hypotension, ↑ JVP
Hyponatremia
↓ SVR
CCF
CNS
Irritable, confused, somnolent
↓ cerebral perfusion
RS
Tachypnea, crepitation
Pulmonary edema sepsis
Kidney
Oliguria
AKI
↓ renal perfusion
Liver
Jaundice (late)
↑ liver enzymes
↓ hepatic perfusion
Skin
Cold, clammy, cyanosis
Vasoconstriction hypoxemia
Metabolic
Lactic acidosis, fever
↓ tissue perfusion infection
67
Flow chart 8.1: Diagnosis of shock based on history
68
 
End Points of Resuscitation
  • Normal tissue perfusion—primary tissue perfusion
  • Normal vital signs
  • Normal end-organ perfusion—adequate urine output, improved mental status
  • Normal serum lactate and base deficit
  • Hemodynamic variable-based end points:
    • SvO2 >70%
    • Oxygen delivery
    • CVP = 8–10 mm Hg
    • PAWP >12 mm Hg
    • Cardiac output
    • EtCO2 = 35–45 mm Hg
    • Dynamic parameters of fluid responsiveness—PPV (<13%), SVV (<10%), etc.
Apart from the specific therapies for each type of shock which would be discussed in the respective chapters, the overall management of resuscitation in shock are:
  • Fluid resuscitation and blood component transfusion
  • Administration of vasopressors/inotropes
  • Use of mechanical support if necessary like IABP
  • Adjunctive therapies.
 
Fluid Management
The initial management of all the types of shock is fluid administration. The goal is to restore the lost volume and improve the tissue perfusion in terms of oxygen transport to optimize the perfusion of end-organ and cellular oxygenation. Initial fluid of administration should be a balanced salt solution with a volume of 20 mL/kg given intravenously. In hemodynamically unstable patients, invasive monitoring would help in guiding therapy. Goals of resuscitation are given above.
 
Crystalloid vs Colloid (Table 8.3)
There has been long-term debate about which fluid is superior. Till date the current evidence shows that colloids are not superior to crystalloids in terms of survival, hence isotonic crystalloids are the preferred fluid for initial resuscitation although colloids can be used for specific indications. Normal saline and ringer lactate are the crystalloids used although recently certain isotonic fluids like plasmalyte is more isotonic than normal saline and ringer lactate.
Table 8.3   Points of mention about crystalloids
Normal saline
Ringer lactate
  • Osmolality – 308
  • Hypernatremia and hyperchloremic metabolic acidosis are complications that can occur on large volume administration
  • Osmolality – 273
  • Considered to be more physiologic than normal saline
  • Lactate in RL buffers metabolic acidosis
  • Higher lactate produces CO2 causing respiratory acidosis
69Recently, the management of hypovolemic shock has shifted towards hypotensive resuscitation. This is an emerging idea in hypovolemic shock and is applicable in mechanical causes of bleeding where the cause of bleeding is not achieved.
 
Vasopressors/Inotropes (Table 8.4)
The balance obtained between fluid volume and vasopressor/inotrope administration according to the cause of shock is the main component of resuscitation in shock. Vasopressors are started in patients where fluid bolus had failed in attaining the end point of resuscitation. Vasopressors reduce the need of large volume resuscitation, but it causes adverse effects due to end organ damage (due to peripheral vasoconstriction).
Table 8.4   Commonly used vasopressors/inotropes for shock
Drug
Dose
Comments
Adverse effects
Dopamine
1–20 µg/kg/minute
Renal 1–5 µg/kg/min
Beta action 5–10 µg/kg/min
Alpha action >10 µg/kg/min
Initial drug of choice for any type of shock
Tachycardia, tissue necrosis
Dobutamine
2–20 µg/kg/minute
Beta agonistic used in cardiogenic shock
Beta-2 action may cause hypotension hence cautious use in patients with hypotension
Epinephrine
0.01–0.1 µg/kg/minute
Used in cardiac arrest and in severe hypotension with bradycardia
Tachycardia, arrhythmias, splanchnic and renal vasoconstriction, myocardial ischemia
Norepinephrine
0.01–1 µg/kg/minute
Vasopressor of choice for septic shock
Myocardial ischemia, tissue hypoxia
Vasopressin
0.01–0.04 U/minute
Alternative drug for cardiac arrest, used in the treatment of catecholamine resistant shock, has a role in septic shock
Splanchnic hypoperfusion, hyponatremia
Milrinone
50 µg/kg bolus infusion—0.375– 0.75 µg/kg/minute
Congestive cardiac failure with cardiogenic shock
Thrombocytopenia
Phenylephrine
0.5–10 µg/kg/minute
Pure alpha 1 agonist
Reduced cardiac output
70
 
BIBLIOGRAPHY
  1. Blair SD, Janvrin SB, McCollum CN, et al. Effect of early blood transfusion on gastrointestinal hemorrhage. Brit J Surg. 1986;73:783.
  2. Choi PTL, Yip G, Quinonez LG, et al. Crystalloids vs. colloids in fluid resuscitation: a systematic review. Crit Care Med. 1999;27:200.
  3. Civetta JM, Taylor RW, Kirby RR. Critical Care, 4th edn. Philadelphia: Lippincott-Raven; 2009.
  4. Cochrane Injuries Group Albumin Reviewers: Human albumin administration in critically ill patients: systematic review of randomized controlled trials. BMJ. 1998; 317:235.
  5. Dellinger, et al. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012. Crit Care Med. 2013;41:580-637.
  6. Dutton RP, MacKenzie CF, Scalea TM. Hypotensive resuscitation during active hemorrhage: impact on in-hospital mortality. J Trauma. 2002;52:1141.
  7. Roberts K, Revell M, Youssef H, Bradbury AW, Adam DJ. Hypotensive resuscitation in patients with ruptured abdominal aortic aneurysm. Eur J Vasc Endovasc Surg. 2006;31:339-44.
  8. Schierhout G, Roberts I. Fluid resuscitation with colloid or crystalloid solutions in critically ill patients: a systematic review of randomized trials. BMJ. 1998;316:961.
  9. Vermeulen LC Jr, Ratko TA, Erstad BL, et al. A paradigm for consensus. The University Hospital Consortium guidelines for the use of albumin, nonprotein colloid, and crystalloid solutions. Arch Intern Med. 1995;155:373.
  10. Viega C, Mello PM, Sharma VK, et al. Shock overview. Semin Respir Crit Care Med. 2004;25:619.

HYPOVOLEMIC SHOCKCHAPTER 9

Prem Kumar
Hypovolemic shock can be due to hemorrhage or nonhemorrhagic causes but it is commonly caused by hemorrhage. Hemorrhagic shock results in hypovolemia and causes tissue hypoperfusion due to blood loss. It is a fact that other types of shock also have a component of hypovolemia during its course.
 
ETIOLOGY
  • Hemorrhage
  • GI loss—diarrhea, vomiting, fistula
  • Pancreatitis
  • Burns
  • Renal loss—trauma-induced diabetes insipidus, postobstructive diuresis
  • Major abdominal surgery
  • Retroperitoneal—ruptured abdominal aortic aneurysm.
 
PATHOPHYSIOLOGY (Flow chart 9.1)
The lethal triad of traumatic hemorrhagic shock are:
  • Metabolic acidosis
  • Hypothermia
  • Coagulopathy.
 
Diagnosis
 
Management
The initial management of any patient with post-shock cardiac arrest is based on advanced cardiac life support (ACLS) where circulation, airway, breathing (CAB) is followed. Circulation, airway and breathing is initiated until the patient has return of spontaneous circulation and postcardiac arrest care is given. If the patient comes to the emergency department (ED) with hypovolemic shock, advanced trauma life support (ATLS) guidelines are followed (Table 9.3). 74
Table 9.3   Primary survey
Airway
Breathing
Circulation
Disability
Exposure
Diagnosis
Auscultation
Pulse oximetry, arterial blood gas analysis (ABG), chest X-ray
Vital signs, e-FAST, typing and cross matching, coagulation parameters, complete blood count, pelvic X-ray
Glassgow coma scale (GCS) score, neurological examination, cervical spine films, CT-brain
Full physical examination, Detailed history, Other lab studies to support diagnosis
Management
Triple maneuver, oxygen, intubation
Mechanical ventilation, intercostal drainage
IV access, fluid infusion, pressure on wounds, O –ve blood, thoracotomy, surgery, pelvic binder
Cervical collar, emergency surgery, intracranial pressure (ICP) monitoring
Removal of clothes and thorough examination surgery, detailed review
Primary survey is done to identify and treat life and limb threatening injuries and the focus should be on the injuries which needs immediate management and is based on the golden hour. Once the patient is stabilized, secondary survey is done with further diagnostic studies to diagnose the missed injuries. ATLS emphasizes the ABCDE mnemonic: airway, breathing, circulation, disability, and exposure.
 
KEY ELEMENTS OF MANAGING HEMORRHAGIC SHOCK
  • Recognition of hemorrhagic shock and the need of rapid initiation of damage control operative treatment.
  • Maintaining hypotensive resuscitation during active bleeding by infusing limited volume of crystalloid and blood components.
  • Airway management plan with rapid-sequence induction of anesthesia accompanied by cricoid pressure (Sellick's maneuver) and in-line cervical stabilization, followed by direct laryngoscopy.
  • Wide bore peripheral cannula is better for rapid infusion than a central venous catheter in hemorrhagic shock.
  • Isotonic crystalloids (ringer lactate, normal saline) are administered and any visible hemorrhage is controlled with direct pressure.
  • Hemodynamics should be monitored with heart rate, ECG and noninvasive or invasive blood pressure monitoring. Although the parameters of cardiac preload like central venous pressure, pulmonary artery wedge pressure (PAWP) are useful in guiding fluid therapy in hemorrhagic shock, still its reliability is less and better methods of volume responsiveness are pulse pressure variation where the measurements are more reliable than static preload parameters.
  • 75Urinary catheter is placed soon to assess the renal perfusion
  • Initial administration of 20 mL/kg of crystalloid is done and if the source of hemorrhage is not identified and the vitals are not stabilized with the initial infusion of crystalloids, crystalloid infusion is minimized and packed RBC is given.
  • There is no specific transfusion trigger in trauma patients with hemorrhagic shock but Hb of 7 g/dL is a generally accepted value.
  • Current evidence recommends the application of hypotensive resuscitation [or Damage Control Resuscitation (DCR)] in patients with hemorrhagic shock with active bleeding where the source of bleeding is unknown and the definitive control of bleeding is not done although this approach has not been shown to improve mortality. DCR is a strategy combining hemostatic resuscitation, permissive hypotension and damage control surgery. The goals of this strategy are initial stabilization of the patient, reducing metabolic acidosis, hypothermia, hypocalcemia and coagulopathy.
  • This hypotensive resuscitation strategy reduces transfusion requirement and severe postoperative coagulopathy in trauma patients with hemorrhagic shock. Mean arterial pressure of 65 mm Hg is the goal for this resuscitation.
  • Thromoboelastometry (TEG) is used as a guide for transfusion of procoagulant blood components in patients with traumatic hemorrhagic shock.
  • Current evidence recommends the administration of PRBC: Fresh Frozen Plasma: Platelets in a ratio of 1:1:1 in patients with massive blood loss. This approach has been shown to improve survival due its impact on the early intervention in preventing trauma induced coagulopathy.
  • The use of tranexamic acid and rFVIIa should be considered in patients with uncontrolled hemorrhage following trauma even after optimization of acidosis, platelet count and procoagulant factors.
 
BIBLIOGRAPHY
  1. Committee on Trauma. Advanced Trauma Life Support Manual. Chicago: American College of Surgeons; 1997.pp.103-12.
  2. Duchesne JC, McSwain NE, Jr, Cotton BA, Hunt JP, Dellavolpe J, Lafaro K, et al. Damage control resuscitation: The new face of damage control. J Trauma. 2010;69:976-90.
  3. Holcomb JB, Jenkins D, Rhee P, Johannigman J, Mahoney P, Mehta S, et al. Damage control resuscitation: Directly addressing the early coagulopathy of trauma. J Trauma. 2007;62:307-10.
  4. Morrison CA, Carrick MM, Norman MA, Scott BG, Welsh FJ, Tsai P, Liscum KR, Wall MJ Jr, Mattox KL. Hypotensive resuscitation strategy reduces transfusion requirements and severe postoperative coagulopathy in trauma patients with hemorrhagic shock: preliminary results of a randomized controlled trial. J Trauma. 2011;70(3):652-63.
  5. Rugeri L, Levrat A, David JS, Delecroix E, Floccard B, Gros A, et al. Diagnosis of early coagulation abnormalities in trauma patients by rotation thrombelastography. J Thromb Haemost. 2007;5:289-95.
  6. Schöchl H, Nienaber U, Hofer G, Voelckel W, Jambor C, Scharbert G, et al. Goal-directed coagulation management of major trauma patients using thromboelastometry (ROTEM)-guided administration of fibrinogen concentrate and prothrombin complex concentrate. Crit Care. 2010;14:R55.
  7. 76Shakur H, Roberts I, Bautista R, Caballero J, Coats T, Dewan Y, et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): A randomised, placebo-controlled trial. Lancet. 2010;376:23-32.
  8. Spinella PC, Perkins JG, McLaughlin DF, Niles SE, Grathwohl KW, Beekley AC, et al. The effect of recombinant activated factor VII on mortality in combat-related casualties with severe trauma and massive transfusion. J Trauma. 2008;64:286.

OBSTRUCTIVE SHOCKCHAPTER 10

Prem Kumar
Obstructive shock is also called as mechanical shock and they are a group of conditions which cause acute increase in pulmonary vascular resistance either through direct obstruction of pulmonary vessels or through release of mediators which cause pulmonary vasoconstriction (Table 10.1).
 
CAUSES
  • Pulmonary embolism—most common cause
  • Cardiac tamponade
  • Air or fat or amniotic fluid embolism.
 
PATHOPHYSIOLOGY
Flow chart 10.1 shows pathophysiology of obstructive shock.
 
CLINICAL FEATURES
Without any preexisting cardiopulmonary disease, acute increase in mean pulmonary artery pressure results in acute increase in right ventricle (RV) afterload results in RV failure resulting in reduced cardiac output and shock. Tachycardia, tachypnea, hypotension are signs of tissue hypoperfusion. Hypoxemia results due to ventilation perfusion mismatching. If RV failure is present, patient presents with hepatojugular reflux, Kussmaul sign, and jugular venous distension with tricuspid regurgitation. If the embolism is very massive, patient may end up with cardiac arrest.
Table 10.1   Etiology and mechanism of obstructive shock
Type
Mechanism
Etiology
Obstructive
Mechanical interference with ventricular filling
Cardiac tamponade, inferior vena cava compression, atrial tumor or clot
Interference with ventricular emptying
Pulmonary or air or fat or amniotic fluid embolism
78
Flow chart 10.1: Pathophysiology of obstructive shock
Abbreviations: PVR, pulmonary vascular resistance; RV, right ventricle; RVEDV, right ventricle end diastolic volume; RVEDP, right ventricle end diastolic pressure; RAP, right atrial pressure; LV, left ventricle; CO, cardiac output
 
Diagnosis
Electrocardiography shows sinus tachycardia and ST-T wave changes in anterolateral chest leads. Signs of myocardial ischemia may be present in case of reduced coronary perfusion. Transthoracic echo shows hypokinesia of RV, tricuspid regurgitation, flattening of interventricular septum (Table 10.2).
Pulmonary embolism, fat embolism, amniotic fluid embolism and pericardial tamponade are discussed in the respective chapters in detail. Hence a brief outline of clinical features and management of all these conditions would be discussed in this chapter. Air embolism would be discussed in detail in this chapter.
 
AIR EMBOLISM
Air embolism occurs when air entrains the venous or arterial circulation through peripheral or central venous veins and if air embolism is large, it can cause hemodynamic instability, cardiac failure and even cardiac arrest. In the intraoperative period, the rate of occurrence of venous air embolism varies 79according to the procedure, the intraoperative position, and the detection method used. The incidence is more in posterior fossa procedures done in sitting position. Other causes are during CO2 insufflation during laparoscopic procedures and it can occur during administration of pulmonary vasodilators. The severity of hemodynamic changes are based upon the rate at which air enters the pulmonary circulation, preexisting cardiopulmonary disease, volume and the inflammatory response triggered by the embolism.
Table 10.2   Risk factors associated with the conditions
Condition
Risk factors
Cardiac Tamponade
Post MI, trauma, infectious, carcinoma, postcatheter complications, postcardiothoracic surgery, postradiation, idiopathic
Pulmonary embolism
Immobilization, previous history of thromboembolism, major surgery within 3 months, obesity, trauma, hypercoagulable states
Fat embolism
Long bone and pelvic fractures within 48–72 hours, orthopedic procedures, burns, diabetes mellitus, postliposuction, acute pancreatitis
Amniotic fluid embolism
Peripartum period, use of labor induction agents like oxytocin, difficult labor, amniocentesis, trauma
Air embolism
Craniotomy especially for posterior fossa procedures in sitting position, laparoscopy, barotraumas, airway procedures, large air entrainment into central or peripheral venous catheters, trauma
Arterial embolism is more dangerous than venous embolism because of the fact that it can result in cardiogenic shock by entering the coronary circulation. Significant volume of venous air embolism that can cause clinical effect was found to be around 100 mL but clinical effects with even 50 mL has been recorded. Cardiac arrest secondary to massive pulmonary embolism was found to be 300–500 mL. The clinical features resemble that of massive pulmonary embolism and there is chance of paradoxical embolism in case of anatomic septal defects. In sitting craniotomy, the common sources of venous air embolism are the transverse, the sigmoid, and the sagittal sinus.
 
Diagnosis
  • Transesophageal echocardiography (TEE)—most sensitive
  • Precordial Doppler
  • Expired nitrogen analysis
  • End tidal CO2 analysis.
The combination of precordial Doppler and EtCO2 is the standard of care for detecting venous air embolism in patients undergoing sitting craniotomy. Doppler probe is placed in a left or right parasternal location between the second and third or third and fourth ribs has a high sensitivity level of detection rate for air embolism.
 
Management
The mainstay of therapy for air embolism is supportive. Therapy consists of:
  • Terminating the route of air entry80
Table 10.3   Specific conditions causing obstructive shock and its management
Condition
Management
Cardiac tamponade
Nontraumatic—immediate pericardiocentesis
Traumatic—surgical decompression
Pulmonary embolism
Anticoagulation
Thrombolysis
Surgical thrombolectomy
Hemodynamic support in case of cardiac failure and hypotension
Fat embolism
Supportive corticosteroids
Amniotic fluid embolism
Supportive blood component therapy
CPR
  • Treating the intravascular air embolism
  • Maintaining hemodynamic stability.
Steps of managing air embolism during sitting craniotomy in the intraoperative period:
  • Flood the surgical site with saline
  • Jugular compression
  • Lowering the head
  • Place the patient in left lateral decubitus position
  • Aspirate the central venous catheter
  • Keep FiO2 of 100%
  • Discontinue nitrous oxide
  • Start vasopressors/inotropes in case of hemodynamic instability (Table 10.3).
 
BIBLIOGRAPHY
  1. Black S, Muzzi DA, Nishimura RA, et al. Preoperative and intraoperative echocardiography to detect right-to-left shunt in patients undergoing neurosurgical procedures in the sitting position. Anesthesiology. 1990;72:436-8.
  2. Cucchiara RF, Seward JB, Nishimura RA, et al. Identification of patent foramen ovale during sitting position craniotomy by transesophageal echocardiography with positive airway pressure. Anesthesiology. 1985;63:107-9.
  3. Mammoto T, Hayashi Y, Ohnishi Y, et al. Incidence of venous and paradoxical air embolism in neurosurgical patients in the sitting position: Detection by transesophageal echocardiography. Acta Anaesthesiol Scand. 1998;42:643-7.
  4. Mellor A, Soni N. Review article: Fat embolism. Anaesthesia. 2001;56:145-60.
  5. Michenfelder JD, Miller RH, Gronert GA. Evaluation of an ultrasonic device (Doppler) for the diagnosis of venous air embolism. Anesthesiology. 1972;36:164-7.
  6. Mirski MA, Lele AV, Fitzsimmons L, et al. Diagnosis and treatment of vascular air embolism. Anesthesiology. 2007;106:164-77.
  7. Papadopoulos G, Kuhly P, Brock M, et al. Venous and paradoxical air embolism in the sitting position: A prospective study with transesophageal echocardiography. Acta Neurochir. 1994;126:140-3.
  8. Schubert A, Deogaonkar A, Drummond JC. Precordial Doppler probe placement for optimal detection of venous air embolism during craniotomy. Anesth Analg. 2006; 102:1543-7.

CARDIOGENIC SHOCKCHAPTER 11

TA Naufal Rizwan  
DEFINITION
Cardiogenic shock is a condition characterized by reduction in the cardiac output resulting in tissue hypoxia which leads on to various functional and structural disturbances in vital organs. Etiology is given in Table 11.1.
 
CHARACTERISTICS
Cardiogenic shock is characterized by:
  • Cardiac index <2.2 L/min/m2
  • Systolic BP <90 mm Hg
  • Pulmonary capillary wedge pressure (PCWP) >18 mm Hg.
Table 11.1   Etiology
Common causes
Coronary artery disease—Acute myocardial infarction (MI) is the most common cause (90%)
Causes of cardiogenic shock in MI
LV failure (85%)
Acquired VSD
Mitral regurgitation
Arrhythmias—refractory sustained tachy and bradyarrhythmias
Valvular heart disease, e.g. severe MS, AR
Cardiomyopathies/myocarditis
Postcardiopulmonary bypass/prosthetic valve dysfunction
Uncommon causes
Pulmonary embolism, acute cor pulmonale
Pericardial tamponade
Severe metabolic acidosis
Abbreviations: VSD, ventricular septal defect; LV failure, left ventricular failure; MS, mitral stenosis; AR, aortic regurgitation
82
 
PATHOGENESIS (Flow chart 11.1)
Pathogenesis of cardiogenic shock is given in Flow chart 11.1.
Flow chart 11.1: Pathogenesis of cardiogenic shock
 
CLINICAL FEATURES
Cardiogenic shock may or may not be associated with acute pulmonary edema. The usual presenting complaints are chest pain and breathlessness. The affected patients are confused, drowsy, diaphoretic and apprehensive.
On examination, the pulse is weak and rapid (although in severe heart block, bradycardia is noted). Hypotension with reduced systolic and narrow pulse pressure is seen. Jugular venous distension is usually present. Cardiovascular auscultation may demonstrate S3 gallop and pansystolic murmur of ventricular septal defect (VSD) and mitral regurgitation (MR). Rales are seen in left ventricular (LV) failure producing cardiogenic shock. Metabolic acidosis and oliguria (urine output < 30 mL/hr) are also present in a few patients.
 
HIGH-RISK PATIENTS FOR CARDIOGENIC SHOCK
  • Acute MI (more common with anterior wall MI)
  • Reinfarction
  • Old age and female sex
  • Diabetes mellitus.83
 
Investigations
  • Renal function tests—elevated urea, creatinine due to renal hypoperfusion
  • Liver function tests—elevated liver enzymes due to liver hypoperfusion
  • ABG—metabolic acidosis/hypoxemia.
 
Electrocardiogram
Electrocardiogram (ECG) changes seen in cardiogenic shock are usually consistent with a massive acute infarct or severe and diffuse ischemia or prior myocardial damage. A relative lack of ECG abnormalities in contrast to the severity of the hemodynamic status should alert one to consider another cause of cardiogenic shock such as aortic dissection or rupture of the myocardium (i.e. free wall, ventricular septum, papillary muscle, or chordae).
 
Chest X-ray
Pulmonary venous congestion and pulmonary edema may be noted.
 
Echocardiography with Color Flow Doppler
Echocardiography is helpful in determining the following:
  • LV and RV function
  • Cardiac output estimation
  • Detection of MR and ventricular septal rupture
  • Pericardial tamponade
  • Proximal aortic dissection with aortic insufficiency.
 
Pulmonary Artery Catheterization
The advantages of doing pulmonary artery catheterization are:
  • Estimation of filling pressures and cardiac output
  • Optimizing the use of IV fluids, inotropic agents and vasopressors.
 
LEFT HEART CATHETERIZATION AND ANGIOGRAPHY
It is indicated when immediate coronary intervention is required or when a definite diagnosis has not been made.
 
Treatment
84
 
General Measures
Patients in cardiogenic shock are usually hypotensive and this should be managed with IV fluids and if necessary, blood transfusions. Positive pressure ventilation plays a great role in the correction of hypoxemia and metabolic acidosis. Pacing, preferably dual chamber is recommended for AV block and bradycardia. Tachyarrhythmias (VT/AF) are corrected by cardioversion or drugs.
 
Pharmacotherapy
The management of cardiogenic shock is outlined based on the three different scenarios:
  1. Cardiogenic shock with hypovolemia
  2. Cardiogenic shock with low cardiac output
  3. Cardiogenic shock with pulmonary edema
Cardiogenic shock with hypovolemia: Managed with IV fluids, blood transfusions and vasopressors
Cardiogenic shock with low cardiac output
  • If SBP > 100 mm Hg, Inj. nitroglycerin IV infusion 10–20 µg/min
  • If SBP is 70–100 mm Hg and no signs of shock—Inj. dobutamine IV infusion 2–20 µg/kg/minute
  • If SBP is <100 mm Hg and signs of shock present—Inj. norepinephrine IV infusion 0.5–30 µg/min or Inj. dopamine 5–15 µg/kg/min
Cardiogenic shock with pulmonary edema: General measures like oxygen therapy, positive pressure ventilation.
Specific measures for cardiogenic shock with pulmonary edema
  • Morphine IV 2–4 mg
  • Furosemide IV 0.5–1 mg/kg
    It is not necessary to continue the diuretics in pulmonary congestion even after the patient has improved because it may lead to volume depletion, thereby worsening the ischemia and pulmonary edema
  • Nitroglycerin-sublingual or Inj. nitroglycerin IV infusion 10–20 µg/minute if SBP >100 mm Hg)
  • If SBP is <100 mm Hg and signs of shock present—Inj. Norepinephrine IV infusion
      0.5–30 µg/minute or Inj. dopamine 5–15 µg/kg/minute
  • If SBP is 70–100 mm Hg and no signs of shock—Inj. dobutamine IV infusion 2–20 µg/kg/minute
 
INVASIVE PROCEDURES IN CARDIOGENIC SHOCK
 
Aortic Counter Pulsation
It is a procedure which improves hemodynamic status temporarily in cardiogenic shock patients, till the patient is taken up for coronary intervention or urgent surgery. Intra-aortic balloon pump (IABP) is contraindicated in aortic regurgitation and aortic dissection.85
 
Procedure
A sausage-shaped balloon is placed into the aorta via the femoral artery. This balloon inflates automatically during diastole and collapses during systole. Thus, the afterload during systole is reduced and coronary blood flow during diastole is increased, thereby myocardial oxygen demand and ischemia are reduced.
 
Ventricular Assist Devices
It can be used as a stop-gap procedure in patients with refractory shock until the patients are planned for cardiac transplantation.
 
Reperfusion-revascularization
Percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) should be considered for coronary artery disease.
 
VASOPRESSORS
Vasopressors play an important role in the management of cardiogenic shock as they cause an increase in the blood pressure and thus the cardiac output.
Following are the vasopressors used in the management of cardiogenic shock:
  • Norepinephrine
    Action: Potent vasoconstrictor and positive inotropic
    Dose: Start with 2–4 µg/minute—can be increased up to 30 µg/minute
  • Dopamine
    Action: Renal vasodilatation, positive inotropic, positive chronotropic, vasoconstriction
    Dose: <2 µg/kg/minute—dilates renal vascular bed (dopamine receptors)
      2–10 µg/kg/minute—+ve inotropic and +ve chronotropic (beta adrenergic stimulation)
      >10 µg/kg/min—vasoconstrictor effects (alpha receptor stimulation)
  • Dobutamine
    Action: Positive inotropic and chronotropic effect
      Dose: 2–20 µg/kg/minute
 
BIBLIOGRAPHY
  1. Bates ER, Moscucci M. Post-myocardial infarction cardiogenic shock. In: Brown DL (Ed). Cardiac Intensive Care. Philadelphia: Pa: Saunders; 1998.pp.215-27.
  2. Dan L Longo, Dennis L Kasper, J Larry Jameson, Anthony S Fauci, Stephen L Hauser, Joseph Loscalzo. Harrison's principles of internal medicine. 18th ed. 2012. McGraw Hill publications. pp.3896-4006.
  3. David Hasai, Peter B Berger, Alexander Battler, David R Holmes Jr. Cardiogenic Shock: Diagnosis and Treatment. Br J Anaesth. 2002;89(4):665-6.
  4. Fincke R, Hochman JS, Lowe AM, et al. SHOCK investigators. Cardiac power is the strongest hemodynamic correlate of mortality in cardiogenic shock: a report from the SHOCK trial registry. J Am Coll Cardiol. 2004;44:340-8.
  5. Hochman J. Annual Scientific Sessions. Dallas, TX: In: Cardiogenic shock. American Heart Association; 1998.
  6. 86Hochman JS, Buller CE, Sleeper LA, et al. Cardiogenic shock complicating acute myocardial infarction: etiologies, management and outcome: a report from the SHOCK trial registry. J Am Coll Cardiol. 2000;36:1063-70.
  7. Khalid L, Dhakam SH. A review of cardiogenic shock in acute myocardial infarction; Curr Cardiol Rev. 2008;4(1):34-40.
  8. Leslie M. Cardiogenic shock in acute myocardial infarction: The era of mechanical support. J Am Coll Cardiol. 2016;67(16):1881-4.
  9. Lindholm MG, Boesgaard S, Torp-Pedersen C, Kober L. TRACE registry study group. Diabetes mellitus and cardiogenic shock in acute myocardial infarction. Eur J Heart Fail. 2005;7:834-9.
  10. Lindholm MG, Kober L, Boesgaard S, Torp-Pedersen C, Aldershvile J. Cardiogenic shock complicating acute myocardial infarction; prognostic impact of early and late shock development. Eur Heart J. 2003;24:258-5.
  11. Mann DL, Zipes DP, Libby P, Bonow RO. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 2-Volume Set, 10th ed.
  12. Maxine AP, Stephen JM, Michael WR. Acute heart failure and pulmonary edema. 54th edn. Current Medical Diagnosis and Treatment. 2015.pp.398-412.
  13. Souhami RL, Moxham J. Cardiogenic shock. Textbook of medicine. 4th edn, pp.493-4.
  14. St Tone GW, Ohman EM, Miller MF, Joseph DL, Christenson JT, Cohen M, Urban PM, Reddy RC, Freedman RJ, Staman KL, Ferguson JJ. Contemporary utilization and outcomes of intra-aortic balloon counterpulsation in acute myocardial infarction: the benchmark registry. J Am Coll Cardiol. 2003;41:1940-5.
  15. Valentin Fuster, Richard Walsh Robert Harrington. Hurst's the Heart, 13th Edn. 2011. McGraw-Hill publications.
  16. Williams SG, Wright DJ, Tan LB. Management of cardiogenic shock complicating acute myocardial infarction: towards evidence based medical practice; Heart. 2000;83: 621-6.

MULTIPLE ORGAN DYSFUNCTION SYNDROMECHAPTER 12

Prem Kumar
Multiple organ dysfunction syndrome (MODS) is one of the common consequences seen in a critically ill patient. It is the end point of sepsis and pronounces increased incidence of mortality. The mortality increases as the number of organs dysfunctioned increases.
 
DEFINITION
It is the presence of simultaneous or sequential dysfunction or failure of two or more organs (or) altered organ function in an acutely ill patient such that homeostasis could not be maintained without intervention.
 
ETIOLOGY
  • Sepsis—most common
  • Congestive cardiac failure
  • Postcardiac arrest
  • Gastrointestinal bleeding
  • End-stage liver disease.
 
PATHOPHYSIOLOGY
The organ failure occurs in a particular sequence in patients who are more prone for MODS (Flow charts 12.1 and 12.2). They are as follows:
Although the pathophysiology is less understood, there are theories regarding its mechanisms.
More important among them are:
  • Gut hypothesis
  • Two hit hypothesis
  • Tissue hypoxia hypothesis
  • Endotoxin hypothesis
  • Theory of apoptosis
Zeng et al. found that the receptor for advanced glycation end products (RAGE) [transmembrane receptor of the immunoglobulin family] plays a role in 88innate immune response and its activation along with polymorphism has been found to release proinflammatory cytokines which in turn causes cellular injury thus can predispose to MODS.
Flow chart 12.1: Sequence of organ failure in MODS
Abbreviation GI, gastrointestinal
Flow chart 12.2: Pathophysiology of MODS
Abbreviations ROS, reactive oxygen species; TNF, tumor necrosis factor; IL, interleukin; TXA2, thromboxane A2; NO, nitric oxide
89
 
CLINICAL SYNDROMES
The clinical syndromes associated with MODS are:
  • Cardiovascular system—congestive cardiac failure, shock
  • Respiratory system—ARDS
  • Central nervous system—encephalopathy
  • Kidney—acute tubular necrosis
  • GIT—paralytic ileus, intestinal ischemia, upper GI bleeding
  • Hematology—DIC, thrombocytopenia, leukopenia
  • Neuromuscular—polyneuropathy
  • Hepatic dysfunction resulting in hepatic failure
  • Endocrine—hyperglycemia from insulin resistance, hypertriglyceridemia, hypoalbuminemia, weight loss, and hypercatabolism
  • Immune—pyrexia, nosocomial pneumonia.
 
SCORING SYSTEMS
There are different scoring systems which can assess the severity of MODS and predict the mortality rate of patients with MODS (Table 12.1). The most commonly used scoring systems in ICU's are SOFA (sequential organ failure assessment) score (Table 12.2) and MODS (multiple organ dysfunction score). These scores have the advantage of being measured daily and usually done at the time of ICU admission and predict the clinical course of the patient in ICU unlike the APACHE (Acute Physiology and Chronic Health Evaluation) II score (Table 12.3). Another advantage is the ability to know the impact of a therapeutic intervention. Cardiovascular dysfunction is better related to outcome with the SOFA score than with the MODS score.
Table 12.1   MODS scoring system
MODS scoring system
Variable
0
1
2
3
4
PaO2/FiO2
>300
226–300
151–225
76–150
≤5
Platelet count (103/mm3)
>120
80–120
50–80
21–50
≤20
Bilirubin (mg/dL)
≤1.2
1.2–3.5
3.5–7.0
7.0–14
≥14
HR × CVP/MAP
≤10
10.1–15
15.1–20
20.1–30
>30
Glasgow Coma Scale score
15
13–14
10–12
7–9
≤6
Creatinine
(mg/dL)
≤1.1
1.1–2.3
2.3–4
4.0–5.7
5.7
Abbreviation: HR, heart rate; CVP, central venous pressure; MAP, mean arterial pressure; PaO2, arterial oxygenation; FiO2, inspired concentration of oxygen
90
Table 12.2   SOFA scoring system
Variable
1
2
3
4
Pao2 (mm Hg)
<400 ± MV
<300 ± MV
<200 + MV
<100 + MV
Platelet count (103/mm3)
<150
<100
<50
<20
Cardiovascular system
MAP <70 mm Hg
Dopa/dobutamine ≤ 5 μg/kg min
Dopa > 5 μg/kg/min,
adr/NA ≤ 0.1 μg/min
Dopa > 15 μg/kg min, adr/NA > 0.1 μg/min
Glasgow Coma Scale
13–15
10–12
6–9
<6
Bilirubin (mg/dL)
1.2–1.9
2–5.9
6–11.9
>12
Cr (mg/dL) or Urine output
1.2–1.9
2–3.4
3.5–4.9 or
<500 mL/day
>5 or
<200 mL/day
Abbreviations: MV, mechanical ventilation; MAP, mean arterial pressure; NA, noradrenaline
 
Prevention
Till date the current strategy followed for management of MODS is prevention.
The steps taken care in critically ill patients for preventing MODS are:
 
Management
  • The treatment is primarily supportive and treatment of the underlying cause.
  • Sepsis is a common condition predisposing to MODS and hence appropriate treatment to mitigate the infection by antimicrobial therapy is done.
  • Maintenance of adequate tissue oxygen delivery with fluid, blood component transfusion and inotropes/vasopressors.
  • Supporting ventilation and oxygenation.
  • Nutritional support.
  • To add H2 blockers for preventing stress related GI bleeding.
  • Deep vein thrombosis (DVT) prophylaxis with low molecular weight heparin.
  • Avoiding neuromuscular blocking agents which can precipitate polyneuropathy.
  • Correction of electrolyte disturbances.
 
Prognosis
MODS has a very high mortality rate varying from 30% to 100% depending on the number of organ systems involved and the duration of dysfunction. The mortality rate increases as the number of organ system involved increases. The pathogenesis is complex and combination of factors is responsible for the development of MODS. The mortality rate is increased if brain, liver, lung, and kidney are involved. MODS score is used as a prognostic indicator.
 
BIBLIOGRAPHY
  1. Baue AE. Multiple organ failure, multiple organ dysfunction syndrome, and systemic inflammatory response syndrome: why no magic bullets? Arch Surg. 1997; 132(7):703-7.
  2. Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. Chest. 1992;101:1644-55.
  3. Carrico CJ, Meakins JL, Marshall JC. Multiple organ failure syndrome. Arch Surg. 1986; 121:196-202.
  4. Cerra FB. Metabolic manifestations of multiple systems organ failure. Crit Care Clin. 1989;5:119-31.
  5. Fink MP. Adequacy of gut oxygenation in endotoxemia and sepsis. Crit Care Med. 1993;21:S4-S8.
  6. Kale IT, Kuzu MA, Berkem H, et al. The presence of hemorrhagic shock increases the rate of bacterial translocation in blunt abdominal trauma. J Trauma. 1998;44:171-4.
  7. Marshall JC, Cook DJ, Christou NV, et al. Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome. Crit Care Med. 1995;23:1638-52.
  8. Mavrommatis AC, Theodoridis T, Orfanidou A, et al. Coagulation system and platelets are fully activated in uncomplicated sepsis. Crit Care Med. 2000;28:451-7.
  9. Moore FA, Moore EE. Evolving concepts in the pathogenesis of postinjury multiple organ failure. Surg Clin North Am. 1995;75:257-77.
  10. 93Morrison DC, Ryan JL. Endotoxins and disease mechanisms. Annu Rev Med. 1987; 38:417-32.
  11. Pastores SM, Katz DP, Kvetan V. Splanchnic ischemia and gut mucosal injury in sepsis and the multiple organ dysfunction syndrome. Am J Gastroenterol. 1996;91:1697-10.
  12. Peres Bota D, Melot C, Lopes Ferreira F, Nguyen Ba V, Vincent JL. The Multiple Organ Dysfunction Score (MODS) versus the Sequential Organ Failure Assessment (SOFA) score in outcome prediction. Intensive Care Med. 2002;28(11):1619-24.
  13. Terregino CA, Lopez BL, Karras DJ, et al. Endogenous mediators in emergency department patients with presumed sepsis: are levels associated with progression to severe sepsis and death? Ann Emerg Med. 2000;35:26-34.
  14. Unno N, Wang H, Menconi MJ, et al. Inhibition of inducible nitric oxide synthase ameliorates endotoxin-induced gut mucosal barrier dysfunction in rats. Gastroenterology. 1997;113:1246-57.
  15. Vincent JL, Angus DC, Artigas A, et al. Effects of drotrecogin alfa (activated) on organ dysfunction in the PROWESS trial. Crit Care Med. 2003;31:834-40.
  16. Vincent JL, Moreno R, Takala J, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22:707-10.
  17. Zeng L, Du J, Gu W, Zhang AQ, Wang HY, Wen DL, Qiu L, Yang XT, Sun JH, Zhang M, Hao J, Jiang JX. Rs 1800625 in the receptor for advanced glycation end products gene predisposes to sepsis and multiple organ dysfunction syndrome in patients with major trauma. Crit Care. 2015;19(1):6.
94Infection and immune disorders in ICU
Chapter 13 Approach to Nosocomial Infections Prem Kumar
Chapter 14 Urinary Tract Infections Prem Kumar
Chapter 15 Sepsis and Septic Shock Prem Kumar
Chapter 16 Principles of Antibiotic Use in ICU Prem Kumar
Chapter 17 Tropical Infections Jenu Santhosh
Chapter 18 Anaphylaxis Prem Kumar95

APPROACH TO NOSOCOMIAL INFECTIONSCHAPTER 13

Prem Kumar
Nosocomial infections or hospital acquired infections are one of the major problems in the hospital because it carries economic burden on the patient. Intensive care (ICU) is responsible for one-fourth of all the hospital-based infections. The prevalence according to centers for disease control and prevention (CDC) is 5–10% and the mortality due to nosocomial infections is 10–25%. The most common ICU infections are urinary tract infection (UTI), pneumonia, and blood stream infections (BSI) and most infections are usually device related. The combined factor of the ease of transmission and organism resistance to antibiotics makes intensive care unit a vulnerable place for nosocomial infections.
 
RISK FACTORS
The three important factors which increase the risk of infection are device, patient factors and cross infection.
  • Invasive devices
  • Severity of the underlying condition
  • Prolonged ICU stay
  • Mechanical ventilation
  • Poor nutrition
  • Poor hand hygiene of the health care providers
  • Pathogenicity of the organism
  • Resistance of the organism to antibiotics
  • Immunosuppression.
Host becomes vulnerable to nosocomial infections if they have associated chronic diseases like diabetes, chronic steroid intake, breach of natural defence in certain group of patients (e.g. burns, invasive devices like endotracheal tube, central venous catheter) and misuse of broad spectrum antibiotics (e.g. invasive candidiasis).
 
Common Causes of Nosocomial Infection in ICU
  • Catheter-associated urinary tract infection (CAUTI)
  • Catheter-related bloodstream infection—arterial and central venous catheters
  • Ventilator-associated pneumonia (VAP)
  • 98Surgical wound infections—necrotizing fasciitis
  • Abdominal infections—intra-abdominal sepsis, postsplenectomy sepsis
  • Central nervous system infection—meningitis
  • Device infection—replacement prosthesis infections.
 
Timeline of Evolution of Organisms Causing Nosocomial Infections in ICU
(Stenotrophomonas, Acinetobacter)
 
MECHANISMS OF DRUG RESISTANCE
  • Beta-lactamase and extended spectrum beta-lactamase (ESBL) produces cross resistance to multiple antibiotics like beta-lactams, fluoroquinolones and aminoglycosides.
  • Methicillin-resistant staphylococcus aureus (MRSA) methicillin-resistant staphylococcus aureus it occurs due to altered penicillin binding protein which is linked to Mec A gene.
  • Pneumococcal resistance—penicillin resistance is acquired due to low-affinity penicillin-binding proteins. Resistance to macrolides, lincosamides, and streptogramin B type antibiotics is acquired due to target-site modification caused by ribosomal methylation in 23S rRNA encoded by the ermB gene and efflux mechanism encoded by the mef gene. Resistance to fluoroquinolones is due to mutations in the gyrA and parC genes. The most important risk factor for antibiotic-resistant pneumococcal infection is use of a specific antibiotic within the previous three months.
  • Among the gram –ve bacilli, E. coli is developing resistance to fluoroquinolones and Enterobacter has become resistant to cephalosporins.
 
NOSOCOMIAL PNEUMONIA
Hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and healthcare-associated pneumonia (HCAP) are all part of the spectrum of nosocomial pneumonia. They are all important causes of morbidity and mortality in ICU patients. The prevalence rate of VAP in mechanically ventilated patients in ICU is around 20%.
 
Definitions
HAP: Pneumonia that occurs 48 hours or more after admission, which was not incubating at the time of admission.
VAP: Pneumonia that occurs more than 48–72 hours after endotracheal intubation.
99HCAP: Condition where the patient was hospitalized in hospital for ≥ 2 days within 90 days of the infection; admitted in a nursing home resided or long-term care facility; received recent intravenous antibiotic therapy, or wound care within the past 30 days of the current infection; or attended a hospital or hemodialysis clinic.
 
Microbiology of HAP/VAP (Tables 13.1 and 13.2)
Among the nonmultidrug resistant strains—S. pneumoniae, S. aureus, H. influenza, Legionella, Gram–ve bacilli, serratia. Among the MDR strains - P. aeruginosa, methicillin-resistant staphylococcus aureus (MRSA), Antibiotic-resistant enterobacteriaceae, Acinetobacter, Klebsiella, Legionella, extended-spectrum beta-lactamase (ESBL) positive strains. Polymicrobial infection is common in patients with acute respiratory distress syndrome (ARDS). Influenza (most common), parainfluenza, adenovirus, and respiratory syncytial virus account for 70% of the nosocomial viral infections.
Table 13.1   Common organisms causing nosocomial infections
Site of infection
Common bacteria
Nosocomial pneumonia
Streptococcus pneumoniae
Staphylococcus aureus
Haemophilus Influenzae
Legionella
Gram –ve bacilli
Multidrug resistance (MDR):
Pseuolomonas Aeruginosa
Meticillin-reristant Staphylococcus aureus (MRSA)
Antibiotic-resistant Enterobacteriaceae
Acinetobacter
Klebsiella
Legionella
Extended spectrum beta-lactamase (ESBL) positive
Intra-abdominal sepsis
E. coli
P. aeruginosa
Enterococcus species
Bacteroides species
Catheter-related blood stream infection
Staphylococcus species
Enterobacteriaceae
P. aeruginosa
Surgical-wound infections
Streptococcus species
Staphylococcus species
Gram-negative bacilli
Urinary tract infections
Gram negative enteric bacilli (E. coli–most common), Klebsiella, Enterobacter, Citrobacter, Proteus, Morganella, Staphylococcus aureus, Enterococcus
Nosocomial diarrhea
Clostridium difficile-associated diarrhea
100
Table 13.2   Common organisms causing nosocomial infections
Organism
Comment
Pseudomonas aeruginosa
Opportunistic pathogen causing pneumonia in critically ill patient and has resistance to many broad spectrum antibiotics. Combination therapy is currently used for its treatment
Klebsiella
Resistance to antibiotics due to extended-spectrum beta-lactamase (ESBL)
Staphylococcus aureus
Methicillin-resistant staphylococcus aureus (MRSA) is widely seen in ICU but is treated with glycopeptides like vancomycin. Recently glycopeptides resistant strains have been identified
Enterobacter
It produces ESBL and thus developing resistance to antibiotics. Implicated in cross colonization
Enterococcus
These organisms emerged with the increased use of cephalosporins. It has developed resistance to penicillin, aminoglycosides and recently vancomycin resistant enterococcus (VRE)
Tuberculosis
Multidrug-resistant tuberculosis (MDR-TB)
Clostridium difficile
This emerged after the use of broad spectrum antibiotics especially clindamycin. Organism releases toxin which causes pseudomembranous colitis.
Candida
C. glabrata and C. krusei strains are seen in ICU. They develop due to antibiotic effect
Acinetobacter
Its incidence is increasing in ICU and has high incidence of cross infection. They are multidrug resistant. Previously they were sensitive to carbapenems but resistance to carbapenems has developed recently making the infection with this organism extremely difficult to treat
Stenotrophomonas maltophilia
This organism is multidrug resistant and is resistant to beta-lactams, aminoglycosides, fluoroquinolones and because it produces carbapenemase, it has developed resistance to carbapenems. That's why this agent is called super-resistant organism
 
Risk Factors for MDR Pathogens
  • Antimicrobial therapy in the preceding 3 months
  • Current hospitalization of ≥5 days
  • High frequency of antibiotic resistance in the community or in the specific hospital unit
  • Immunosuppressive disease and/or therapy
  • Presence of risk factors for HCAP:
    • Hospitalization for ≥2 days in the preceding 3 months
    • Resided in a nursing home
    • Received recent intravenous antibiotic therapy
    • Chronic dialysis within 30 days
    • Wound care.
101
 
Pathogenesis
The critical factors associated with VAP are:
  • Oropharyngeal colonization with pathogenic microorganisms
  • Aspiration of oropharyngeal organisms during intubation or leakage of secretions containing bacteria after intubation through microaspiration around the tube into the lower respiratory tract
  • Abnormal host defense mechanisms.
Other factors for pathogenesis:
  • Source of infection are healthcare devices and health care personnel
  • Host and treatment related colonization factors—severity of the patient's underlying disease, prior surgery, exposure to antibiotics and exposure to invasive respiratory devices.
  • Bacterial translocation from the gastrointestinal tract.
  • The stomach and sinuses can be potential reservoirs of nosocomial pathogens and may cause nosocomial infections.
HAP requires the entry of microbial pathogens into the lower respiratory tract, followed by colonization, which has to overcome the host's defence mechanisms to establish infection.
 
Clinical Features
All the features of pneumonia like fever, leukocytosis, tachypnea, tachycardia, hypoxemia, pulmonary consolidation on physical examination, increase in respiratory secretions. Chest radiography shows new or evolving lung infiltrates.
 
Diagnosis
The presence of clinical features of pneumonia (fever, leukocytosis, or purulent tracheal secretions) and radiographic infiltrate point towards the diagnosis of HAP/VAP. In the presence of clinical suspicion of VAP, samples of lower respiratory tract secretions (endotracheal aspirate, bronchoalveolar lavage sample, or protected specimen brush sample) should be obtained from all patients with suspected HAP, and is collected before administration of antibiotics. The purpose of the quantitative-culture approach is to differentiate between colonization and true infection. A sterile culture in the absence of antibiotics in the past 72 hours though rules out bacterial pneumonia, still a possibility of viral or legionella infection is present. Arterial oxygenation saturation should be measured in all patients to determine the need for supplemental oxygen and it can point towards the diagnosis of multiple organ dysfunction syndrome (MODS) or acute respiratory dysfunctions syndrome (ARDS) if it is associated. Unnecessary use of antibiotics and duration of antibiotic use was reduced in patients who were done quantitative culture methods and it also reduced the mortality in patients with HAP/VAP. Clinical features carry high sensitivity but has low specificity. Quantitative culture methods has high specificity. Hence in patients suspected with VAP, both clinical criteria and diagnostic culture methods will point towards the diagnosis of HAP/VAP.
102Pugin et al. developed a surrogate clinical criteria for increasing the specificity of clinical diagnosis of VAP. The criteria is named clinical pulmonary infection score (CPIS). CPIS combines clinical, radiographic, physiological, and microbiologic data into a score (Table 13.3). The maximal score is 12. CPIS score >6 correlates well with VAP. Singh et al. demonstrated that patients with a low suspicion of VAP (CPIS of 6 or less) can have antibiotics safely discontinued after 3 days.
Table 13.3   Clinical pulmonary infection score
Criteria
Score
Temperature (°C)
38.5–38.9
≥39.0 and ≤36.0
1
2
Leukocytosis
< 4000 or >11,000/µL
Bands >50%
1
2
Oxygenation (mm Hg)
PaO2/FIO2 <250 and no ARDS
2
Tracheal aspirate
Pathogenic bacteria cultured ≤1 or no growth
Pathogenic bacteria cultured >1+
Plus same pathogenic bacteria on Gram stain >1+
0
1
2
Chest radiography
No infiltrate
Diffuse or patchy infiltrate
Localized infiltrate
0
1
2
Tracheal secretions
≥14+
Plus purulence
1
2
 
Management (Flow chart 13.1 and Table 13.4)
Table 13.4   Initial empiric therapy for HAP/VAP
Risk factor
Pathogens
Antimicrobial therapy
Patients with no known risk factors for MDR pathogens, early onset and no disease severity
Antibiotic sensitive
Ceftriaxone
Or
Levofloxacin, moxifloxacin, or ciprofloxacin
Or
Ampicillin/sulbactam
Or
Ertapenem103
Patients with known risk factors for MDR pathogens, late onset and disease severity
Pseudomonas aeruginosa
Klebsiella pneumoniae, Extended-spectrum beta-lactamase (ESBL)
Acinetobacter species
Methicillin-resistant Staphylococcus aureus (MRSA)
Legionella pneumophila
Antipseudomonal cephalosporin (cefepime, ceftazidime)
Or
Beta-lactam/Beta lactamase inhibitor (piperacillin–tazobactam)
Or
Antipseudomonal carbepenem (imipenem or meropenem) plus
Antipseudomonal fluoroquinolone (ciprofloxacin or levofloxacin)
Or
Aminoglycoside (amikacin, gentamicin, or tobramycin) plus
Linezolid or vancomycin
For Legionella – macrolide + fluoroquinolone is used
Key recommendations for MDR pathogens
  • If ESBL positive Enterobacteriaceae are isolated—carbapenem is preferred
  • P. aeruginosa—combination therapy
  • Acinetobacter—carbapenems, sulbactam, colistin, and polymyxin are preferred
  • MRSA VAP—linezolid is an alternative to vancomycin in case of renal insufficiency and if patients is receiving nephrotoxic agents.
  • Restricting the duration of antibiotic therapy and antibiotic cycling is done to limit antibiotic resistance
A negative tracheal-aspirate culture or if the growth is below the threshold for quantitative cultures, and if the sample was taken before any antibiotic change, strongly suggests that antibiotics should be discontinued. If CPIS reduces over 2–3 days, then the antibiotic course should stopped after 8 days. 7–8 days course is associated with less incidence of antibiotic resistance. There is high failure rate of therapy with MRSA and other MDR pathogens and hence regular CPIS assessment and quantitative culture is done to see the response to therapy.
 
Prevention
Surveillance for nosocomial infections is the mainstay for prevention and control of nosocomial infections. It is very clear from the prospective studies that the use of evidence-based guidelines through bundled interventions in ICU reduce the rate of nosocomial infections (Table 13.5). The success of any guideline is increased by following the specific, measurable, achievable, relevant, and time bound (SMART) approach.
 
SMART Approach
 
Guidelines for Prevention of Catheter-associated of Urinary Tract Infection (CAUTI)
Effective interventions
  • Catheterization done only when there are proper indications
  • Maintain good hand hygiene
  • Use of aseptic technique and sterile equipment for catheter insertion
  • Proper securing of catheter
  • Maintenance of closed sterile drainage
  • Aseptic methods for obtaining urine samples
  • Maintenance of unobstructed urine flow
  • Educating healthcare providers to perform correct techniques of catheter insertion and maintenance.
Interventions to be avoided
  • Regular bacteriologic monitoring
  • Routine use of prophylactic antibiotics.
 
Guidelines for Prevention of Catheter-related Bloodstream Infections
Effective interventions
  • Educating healthcare providers to perform correct techniques of catheter insertion and maintenance and only trained designated personnel to perform the procedure with strict adherence to guidelines
  • Maintaining proper hand hygiene before performing procedure
  • Performing with aseptic technique during catheter insertion and care—clean gloves for peripheral catheters and sterile gloves for invasive lines, sterile barrier precautions for central line insertion.
  • 106Care of catheter site—skin disinfection with 2% chlorhexidine or 70% alcohol, use of sterile transparent, semipermeable dressing, replacement of soiled dressing
  • Prompt removal of catheter that is not necessary
  • Selection of catheter, insertion technique, and site with lowest complication risk
  • Cleansing of injection port with 70% alcohol or iodophor before access
  • Replacement of administration sets not more frequently than every 72 hours
  • Appropriate preparation and quality control of intravenous admixtures
  • Surveillance to determine infection rates, trends, and lapses in infection control.
Interventions to be avoided
  • Routine antibiotic prophylaxis—topical, intranasal, and systemic formulations
  • Routine use of antibiotic lock solution
  • Routine use of arterial or venous cut-down for catheter insertion
  • Routine use of in-line filters for infection control.
 
Guidelines for Preventing Surgical Site Infections
Effective interventions
  • Preoperative preparation of patient
  • Hand and forearm antisepsis of surgical personnel
  • Administration of antimicrobial prophylaxis only when indicated, with dosing to maintain bactericidal levels throughout surgery
  • Intraoperative ventilation, cleaning and disinfection of environmental surfaces, sterilization of surgical instruments, and use of surgical attire and drapes
  • Intraoperative asepsis
  • Aseptic surgical technique
  • Protecting incision site postoperatively with sterile dressing for 24–48 hours
  • Doing handwash before and after any contact with surgical site
  • Surveillance to identify infection.
Interventions to be avoided
  • Routine antibiotic prophylaxis with vancomycin
  • Routine environmental sampling of operating room.
 
BIBLIOGRAPHY
  1. Arya SC, Agarwal N, Agarwal S, George S, Singh K. Nosocomial infection: hospital infection surveillance and control. J Hosp Infect 2004;58:242-3.
  2. Bersten AD, Soni N, TE Oh. Oh's Intensive Care Manual, 5th edn. 2009. Butterworth-Heinemann publications, Philadelphia.
  3. Chastre J, Fagon JY. Ventilator-associated pneumonia. Am J Respir Crit Care Med. 2002;165:867-903.
  4. Craven DE, Kunches LM, Kilinsky V, Lichtenberg DA, Make BJ, McCabe WR. Risk factors for pneumonia and fatality in patients receiving continuous mechanical ventilation. Am Rev Respir Dis. 1986;133:792-6.
  5. 107Drucker P. The practice of management. New York. NY: Harper and Row, 1954.
  6. Fartoukh M, Maitre B, Honore S, Cerf C, Zahar JR, Brun-Buisson C. Diagnosing pneumonia during mechanical ventilation: the clinical pulmonary infection score revisited. Am J Respir Crit Care Med. 2003;168:173-9.
  7. Fink MP, Snydman DR, Niederman MS, Leeper KVJ, Johnson RH, Heard SO, Wunderink RG, Caldwell JW, Schentag JJ, Siami GA, et al. Severe Pneumonia Study Group. Treatment of severe pneumonia in hospitalized patients: results of a multicenter, randomized, doubleblind trial comparing intravenous ciprofloxacin with imipenem– cilastatin. Antimicrob Agents Chemother. 1994;38:547-57.
  8. Gruson D, Hilbert G, Vargas F, Valentino R, Bui N, Pereyre S, Bebear C, Bebear CM, Gbikpi-Benissan G. Strategy of antibiotic rotation: long-term effect on incidence and susceptibilities of gram-negative bacilli responsible for ventilator-associated pneumonia. Crit Care Med. 2003;31:1908-14.
  9. Hutt E, Kramer AM. Evidence-based guidelines for management of nursing home-acquired pneumonia. J Fam Pract. 2002;51:709-16.
  10. Kollef MH, Ward S, Sherman G, Prentice D, Schaiff R, Huey W, Fraser VJ. Inadequate treatment of nosocomial infections is associated with certain empiric antibiotic choices. Crit Care Med. 2000;28:3456-64.
  11. Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscalzo J. Harrison's principles of internal medicine, 18th edn. 2012. McGraw Hill Publications.
  12. Loveday HP, et al. National evidence-based guidelines for preventing healthcare-associated Infections in NHS Hospitals in England. Journal of Hospital Infection. 2014;86S1:S1-S70.
  13. Niederman MS, et al. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171:388-416.
  14. Niederman MS. Guidelines for the management of respiratory infection: why do we need them, how should they be developed, and can they be useful? Curr Opin Pulm Med. 1996;2:161-5.
  15. Pugin J, Auckenthaler R, Mili N, et al. Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic “blind” bronchoalveolar lavage fluid. Am Rev Respir Dis. 1991;143:1121-9.
  16. Sarink MS, et al. Antimicrobial therapy in the intensive care unit. Indian Journal of Clinical Practice, 2013;23(10).
  17. Singh N, Rogers P, Atwood CW, Wagener MM, Yu VL. Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit: a proposed solution for indiscriminate antibiotic prescription. Am J Respir Crit Care Med. 2000; 162:505-11.
  18. Tablan OC, Anderson LJ, Besser R, Bridges C, Hajjeh R. Healthcare Infection Control Practices Advisory Committee, Centers for Disease Control and Prevention. Guidelines for preventing healthcare–associated pneumonia, 2003: recommendations of the CDC and the Healthcare Infection Control Practices Advisory Committee. MMWR Recomm Rep. 2004;53(RR-3):1-36.
  19. Yehia Aly AN, et al. Nosocomial infections in a medical-surgical intensive care unit. Med Princ Pract. 2008;17:373-7.

URINARY TRACT INFECTIONSCHAPTER 14

Prem Kumar
Urinary tract infection (UTI) is the most common nosocomial infection prevalent in intensive care unit (ICU). It is the most common source of gram –ve sepsis present in ICU causing morbidity and mortality. Predominant number of patients who had UTI had an indwelling urinary catheter. Urinary tract infections associated with indwelling catheter is called catheter-associated UTI (CAUTI). We will discuss the diagnosis, management and methods of prevention in this chapter.
 
DEFINITIONS
  • UTI—symptomatic infection of bladder and kidneys. Cystitis and pyelonephritis.
  • Uncomplicated UTI—acute cystitis or pyelonephritis in nonpregnant women without anatomic abnormalities or instrumentation of the urinary tract.
  • Complicated UTI—symptomatic cystitis or pyelonephritis with structural or functional abnormalities of the urinary tract or with a foreign body or with delayed response to therapy.
Urinary tract infections (UTIs) are defined using symptomatic urinary tract infection (SUTI) criteria, asymptomatic bacteremic UTI (ABUTI), or urinary system infection (USI) criteria.
Catheter-associated UTI (CAUTI): UTI where an indwelling urinary catheter was in place for >2 days on the date of event or the day before. If an indwelling urinary catheter was in place for >2 calendar days and then removed, the date of event for the UTI must be the day of discontinuation or the next day for the UTI to be catheter-associated.
 
RISKS (TABLE 14.1)
Most of the organisms are colonized from perineum, rectum, vagina and distal urethra. The catheter and the growth in the urine bag can also cause infection. Incomplete emptying of the bladder while the catheter is in place can also cause UTI. 109
Table 14.1   Risk factors associated with urinary tract infection (UTI)
Use of urinary catheter
Duration of catheterization
Urinary drainage bag colonization
Diabetes mellitus
Female patient
Old age
Elevated renal parameters
Unsterile techniques of catheter insertion and catheter care
Patients with structural or functional abnormalities of urinary system
Neurological disease—neurogenic bladder, CVA, etc.
Patients with urological diseases like benign prostatic hyperplasia, bladder or ureteric stone, epididymo-orchitis, etc.
Abbreviation: CVA, cerebrovascular accident
 
COMMON ORGANISMS CAUSING URINARY TRACT INFECTION
UTI is commonly caused by Gram-negative enteric bacilli. E. coli is the most common organism among the Gram-negative bacteria. Specific type of E. coli which has P-pili has the ability to adhere the uroepithelial membranes and cause UTI. Patients receiving antibiotics or anatomical defects in urinary system are colonized with Klebsiella, Enterobacter, Citrobacter, Proteus, Morganella. Less common organisms causing UTI are gram +ve organisms like Staphylococcus aureus, Enterococcus. Enterococcus are resistant to antibiotics. Candida-associated UTI occurs with hematological dissemination and is the common organism among fungal organisms.
 
Diagnosis (Flow chart 14.1 and Tables 14.2 and 14.3)
Patients may complain of increased frequency and urgency, nocturia, dysuria, hematuria. Loin pain and fever should preclude the diagnosis to pyelonephritis. Perineal pain may indicate prostatitis. Hence, urinary frequency, urgency, loin tenderness and fever should point the diagnosis towards upper urinary tract infection. The absence of pyuria and significant bacteriuria does not exclude the diagnosis of UTI.
 
Urine Analysis
  • Increased leukocytes
  • Dipstick test for leukocyte esterase and nitrate
  • Increased number of bacteria with absence of contamination by epithelial cells110
    Flow chart 14.1: Diagnostic algorithm of UTI
    Abbreviations: UTI, urinary tract infection; CFU, colony-forming unit; CAUTI, catheter-associated urinary tract infection; ABUTI, asymptomatic bacteremic
  • Urinary gram stain
  • >1 organism/high-powered field is indicative of greater than 105 colony-forming units (CFUs) per mL.
Patients with clinical diagnosis of UTI should be done quantitative urinary culture before initiation of antibiotics. In patients with severe sepsis suspected due to UTI should have blood culture done in case of a negative urinary culture. Some complicated UTIs may require radiological methods for diagnosis.
 
Management (Table 14.4)
Antimicrobial therapy is instituted for symptomatic UTI. The choice of the antibiotic and the dose and duration of therapy depends on the infection site and the complicating conditions. Asymptomatic bacteriuria in the absence of pyuria 111does not require treatment with antibiotics except in pregnancy, neutropenic patients, renal transplant recipients and patients undergoing urology procedures.
Table 14.2   Diagnostic criteria
CAUTI
Non-CAUTI
Must meet at least one of the following criteria (A or B):
Criteria A
  • Patient has an indwelling urinary catheter in place for the entire day on the date of event and such catheter had been in place for >2 calendar days, on that date (day of device placement = Day 1)
  • Patient has at least one of the following signs or symptoms.
    • Fever (>38.0°C)
    • Suprapubic tenderness
    • Costovertebral angle pain or tenderness
  • Patient has a urine culture with no more than two species of organisms, at least one of which is a bacteria of ≥105 CFU/mL.
OR
Criteria B
  • Patient had an indwelling urinary catheter in place for >2 calendar days which was removed on the day of, or day before the date of event
  • Patient has at least one of the following signs or symptoms.
    • Fever (>38.0°C)
    • Suprapubic tenderness
    • Costovertebral angle pain or tenderness
    • Urinary urgency
    • Urinary frequency
    • Dysuria
  • Patient has a urine culture with no more than two species of organisms, at least one of which is a bacteria of ≥105 CFU/mL.
Patient must meet all the criteria given below:
  • One of the following is true.
    • Patient has/had an indwelling urinary catheter but it has/had not been in place >2 calendar days, (OR)
    • Patient did not have a urinary catheter in place on the date of event nor the day before the date of event
  • Patient has at least one of the following signs or symptoms.
    • Fever (>38°C)
    • Suprapubic tenderness
    • Costovertebral angle pain or tenderness
    • Urinary frequency
    • Urinary urgency
    • Dysuria
  • Patient has a urine culture with no more than two species of organisms, at least one of which is a bacteria of ≥105 CFU/mL.
Table 14.3   Diagnostic criteria of ABUTI
Asymptomatic bacteremic urinary tract infection
Patient must meet all the criteria given below:
  • Patient with or without an indwelling urinary catheter has no signs or symptoms of symptomatic urinary tract infection.
  • Patient has a urine culture with no more than two species of organisms, at least one of which is a bacteria of ≥105 CFU/mL.
  • Patient has a positive blood culture with at least one matching bacteria to the urine culture and matching common commensals in the urine.
112
Table 14.4   Management of uncomplicated UTI
Men
Women
Pregnant women
  • Trimethoprim sulfamethoxazole for 14 days
  • Fluoroquinolones (ofloxacin–200 mg 12th hourly, ciprofloxacin 500 mg 12th hourly, and levofloxacin) for 14 days
  • With urine culture results, antibiotic continued for 2–4 weeks
Comment–a prolonged course of antibiotics is given in male to prevent chronic prostatitis
1st line
  • Trimethoprim sulfamethoxazole– 1 DS tab 12th hourly for 3 days Double strength (DS: 160 mg/800 mg = TMP/SMX)
  • Nitrofurantoin 100 mg twice daily for 5–7 days
2nd line
  • Fluoroquinolones (ofloxacin, ciprofloxacin, and levofloxacin) for 3 days
  • Beta lactams for 7 days
  • Ampicillin, cephalosporins and nitrofurantoin are safe in pregnancy
  • Ampicillin and cephalosporins are the drugs of choice for the treatment of asymptomatic or symptomatic UTI
  • Sulphonamides and fluoroquinolones are contraindicated due to its teratogenic effects
 
Complicated UTI
  • Antibiotics are guided by urine culture or empirically started with prior urinary culture results until new culture results.
  • Nephrectomy is done in case of Xanthogranulomatous pyelonephritis.
  • Emphysematous pyelonephritis—percutaneous drainage can be used as the initial therapy followed by elective nephrectomy.
 
Pyelonephritis
  • Fluoroquinolones (500 mg 12th hourly) are the first-line therapy for acute uncomplicated pyelonephritis. Its given for 7 days orally or parenterally.
  • Initially, 2 g of IV ceftriaxone is given if trimethoprim/sulfamethoxazole is started and the culture results are awaited.
  • Generally pyelonephritis is best treated by urine culture results.
 
Treatment of CAUTI
The formation of biofilm on the urinary catheter is the prime cause for the pathogenesis of CAUTI and it affects both therapeutic and preventive management. Change of catheter can be done during the treatment of CAUTI. Ampicillin with beta-lactamase inhibitor, cephalosporins, aminoglycosides are started initially. In case of poor response to therapy in 2–3 days or in severe cases, anti-pseudomonal antibiotics (fluoroquinolone, carbapenem with aminoglycoside, cephalosporin with antipseudomonal activity) are started. In case of Candida, fluconazole and amphotericin B are used.113
 
Treatment of Urosepsis
Fluoroquinolones and cephalosporins are used and if secondary to urological procedures, antipseudomonal antibiotics are started like ampicillin with beta lactamase inhibitor, carbapenem, aminoglycosides.
 
PREVENTION OF CAUTI—RECOMMENDATIONS BY HICPAC (HEALTHCARE INFECTION CONTROL PRACTICES ADVISORY COMMITTEE) 2009 GUIDELINES
The best way of preventing CAUTI in ICU is its use for appropriate indications:
  • Acute urinary retention or bladder outlet obstruction
  • For accurate measurements of urinary output in critically ill patients
  • For selected surgical procedures:
    • Patients undergoing urologic surgery or other surgery on contiguous structures of the genitourinary tract
    • Anticipated prolonged duration of surgery. Catheters inserted for this reason should be removed in PACU.
    • Patients anticipated to receive large-volume infusions or diuretics during surgery
    • Need for intraoperative monitoring of urinary output.
  • Patient requiring prolonged immobilization
  • To assist in healing of open sacral or perineal wounds in incontinent patients
  • For terminally ill patients.
 
Key Recommendations for Prevention of CAUTI
  • Insert catheters only for appropriate indications and leave in place only as long as needed.
  • Avoid use of urinary catheters in patients and nursing home residents for management of incontinence.
  • Use urinary catheters in operative patients only as necessary, rather than routinely.
  • For operative patients who have an indication for an indwelling catheter, remove the catheter as soon as possible postoperatively, preferably within 24 hours, unless there are appropriate indications for continued use.
  • Consider using alternatives to indwelling urethral catheterization in selected patients when appropriate.
  • Perform hand hygiene immediately before and after insertion or any manipulation of the catheter device or site.
  • Ensure that only properly trained persons perform the technique.
  • In the acute care hospital setting, insert urinary catheters using aseptic technique and sterile equipment. Use sterile gloves, drape, sponges, an appropriate antiseptic or sterile solution for periurethral cleaning, and a single-use packet of lubricant jelly for insertion.
  • In the nonacute care setting, clean (i.e. nonsterile) technique for intermittent catheterization is an acceptable and more practical alternative to sterile technique for patients requiring chronic intermittent catheterization.
  • 114Properly secure indwelling catheters after insertion to prevent movement and urethral traction.
  • If intermittent catheterization is used, perform it at regular intervals to prevent bladder overdistension.
Recommendations for urinary catheter maintenance:
  • Following aseptic insertion of the urinary catheter, maintain a closed drainage system.
  • Maintain unobstructed urine flow after inserting a urinary catheter.
  • Use standard precautions, including the use of gloves and gown as appropriate, during any manipulation of the catheter or collecting system.
  • Unless clinical indications exist, do not use systemic antimicrobials routinely to prevent CAUTI in patients requiring either short or long-term catheterization.
  • Do not clean the periurethral area with antiseptics to prevent CAUTI while the catheter is in place. Routine hygiene is appropriate.
  • Routine irrigation of the bladder with antimicrobials is not recommended.
  • Clamping indwelling catheters prior to removal is not necessary.
 
BIBLIOGRAPHY
  1. Carolyn v. Gould, et al. Guideline for prevention of catheter-associated urinary tract infections. Healthcare infection control practices advisory committee. 2009.
  2. Dolin SJ, Cashman JN. Tolerability of acute postoperative pain management: nausea, vomiting, sedation, pruritus, and urinary retention. Evidence from published data. Br J Anaesth. 2005;95(5):584-91.
  3. Dudeck MA, Horan TC, Peterson KD. National Healthcare Safety Network (NHSN) Report, Data Summary for 2009, “Device-associated Module”. Am J Infect Control. 2011;39:349-67.
  4. Garner JS, Jarvis WR, Emori TG, et al. CDC definitions for nosocomial infections, 1988. Am J Infect Control. 1988;16:128-40.
  5. Lo E, Nicolle L, Classen D, et al. Strategies to prevent catheter-associated urinary tract infections in acute care hospitals. Infect Control Hosp Epidemiol. 2008;29:S41-S50.
  6. Stephan F, Sax H, Wachsmuth M, Hoffmeyer P, Clergue F, Pittet D. Reduction of urinary tract infection and antibiotic use after surgery: a controlled, prospective, before-after intervention study. Clin Infect Dis. 2006;42(11):1544-51.
  7. Wong ES. Guideline for prevention of catheter-associated urinary tract infections. Am J Infect Control. 1983;11(1):28-36.

SEPSIS AND SEPTIC SHOCKCHAPTER 15

Prem Kumar
Sepsis is a major health problem in intensive care unit (ICU) and it accounts for a predominant cause of morbidity and mortality in ICU and it varies from 10% to 30% and it increases if the patient ends up with multiple organ dysfunction syndrome (MODS). Although the understanding of the pathophysiology and management of sepsis and septic shock has improved in the past decade, the mortality has still not improved despite antimicrobial therapy and hemodynamic support. This chapter discusses the clinical spectrum of sepsis and septic shock from the latest update of surviving sepsis campaign guidelines, 2012.
 
DEFINITIONS
SIRS: Presence of signs of systemic inflammation is called SIRS (systemic inflammatory response syndrome).
Sepsis: Presence of infection along with systemic manifestations.
Severe sepsis: Sepsis accompanied with sepsis-induced organ dysfunction or tissue hypoperfusion.
Septic shock: Severe sepsis-induced hypotension which is persistent inspite of adequate fluid resuscitation.
Sepsis-induced hypotension: Systolic blood pressure (SBP) <90 mm Hg or mean arterial pressure (MAP) <70 mm Hg or a SBP decrease >40 mm Hg or <2 SD below normal for age in the absence of other causes of hypotension.
MODS: It is the presence of simultaneous or sequential dysfunction or failure of two or more organs (or) altered organ function in an acutely ill patient such that homeostasis could not be maintained without intervention.
 
PATHOGENESIS
Pathogenesis of septic shock is shown in Flow chart 15.1. Venn diagram depicting spectrum of sepsis is shown in Figure 15.1.
Clinical syndromes associated with sepsis:
  • Cardiovascular system—congestive cardiac failure, shock due to reduced intravascular volume. Peripheral vasodilatation resulting in reduced systemic 116vascular resistance and vasopressor resistance due to release of nitric oxide (NO). Myocardial depression with systolic and diastolic dysfunction.
    Flow chart 15.1: Pathogenesis of septic shock
    Abbreviations: IL, interleukin; TNF, tumor necrosis factor; ROS, reactive oxygen species; IFN, interferon; CARS, compensatory anti-inflammatory response syndrome; MOF, multiple organ failure
    Fig. 15.1: Venn diagram depicting spectrum of sepsis
    Abbreviation: SIRS, systemic inflammatory response syndrome
  • Respiratory system—ARDS
  • Central nervous system—septic encephalopathy
  • Kidney—acute tubular necrosis
  • 117GIT—paralytic ileus, intestinal ischemia, upper GI bleeding, gastric stress ulcers, intestinal mucosal injury
  • Hematology—DIC, thrombocytopenia, leukopenia
  • Neuromuscular—critical illness polyneuropathy, myopathy
  • Hepatic—intrahepatic cholestasis, hepatic failure
  • Endocrine—hyperglycemia from insulin resistance, hypertriglyceridemia, hypoalbuminemia, weight loss, and hypercatabolism
  • Immune—pyrexia, nosocomial pneumonia, neutrophil dysfunction.
 
Diagnosis
Sepsis can present initially with tachycardia, hypotension, tachypnea, fever. Altered mental status, hypothermia, organ dysfunction, leukopenia indicates poor prognosis. Hypoxemia, thrombocytopenia, consumptive coagulopathy, acute tubular necrosis, elevated transaminases, hyperglycemia, pneumonia and intra-abdominal infection are the other manifestations. Previously Gram –ve infections were common in patients with sepsis but trend of infection is hanging towards Gram +ve and fungal infections. Abdomen and lung are major sources of infection.
 
Diagnostic Criteria
SIRS: SIRS is the systemic inflammatory response to any insult—infection or non-infection. The current sepsis guidelines have removed this terminology but still the term is being used by many authors.
It is characterized by two or more of the following:
  1. Temperature <36°C or > 38°C
  2. Heart rate >90/min
  3. Respiratory rate >20 breaths/minute or PaCO2 <32 mm Hg
  4. White blood cell count <4000/µL or >12,000/µL or 10% immature band forms.
 
SEPSIS
Documented or suspected infection and some of the following variables are given in Table 15.1.
 
SEVERE SEPSIS
 
Management of Severe Sepsis and Septic Shock
The three areas to be optimized in severe sepsis and septic shock are:
  1. Trigger
  2. Amplification cascade
  3. Organ dysfunction.
Trigger is usually infection and it is treated by antimicrobial therapy. Amplification is managed by administering activated protein C which exerts anti-inflammatory and antithrombotic effects and reduces the progression of sepsis. 119Organ dysfunction is treated by supportive measures like fluid resuscitation, vasopressors/inotropes.
The management of severe sepsis and septic shock is done by the following protocol.
  • Initial resuscitation and infection issues
    • Initial resuscitation
    • Screening and diagnosis of sepsis
    • Antimicrobial therapy
    • Source control
    • Infection prevention
  • Hemodynamic support
    • Fluid resuscitation
    • Vasopressors/inotropes
  • Adjunctive therapy
    • Corticosteroids
  • Supportive therapy
    • Blood component administration
    • Immunoglobulins
    • Selenium
    • Recombinant activated protein C (APC)
    • Ventilatory management of ARDS
    • Sedation, analgesia and neuromuscular blockade
    • Glycemic control
    • Renal replacement therapy
    • Bicarbonate therapy
    • DVT prophylaxis
    • Stress ulcer prophylaxis
    • Nutrition.
 
Initial Resuscitation
Sepsis-induced tissue hypoperfusion should be resuscitated with the following guidelines. This resuscitation protocol was demonstrated by Rivers et al., and it is called early goal directed therapy (Table 15.2 and Flow chart 15.2). Target of resuscitation is normalizing lactate level.
But recently 3 trials (Protocolized Care for Early Septic Shock [ProCESS] trial), (Australasian Resuscitation in Sepsis Evaluation [ARISE] trial), and (Protocolized Management in Sepsis [ProMISe] trial) has challenged early goal directed therapy demonstrating that early goal-directed therapy (EGDT) did not lead to an improvement in outcome. These studies demonstrated that there was no significant difference in mortality at 90 days among those receiving 6 hours of EGDT and those receiving usual resuscitation.
Table 15.2   Goals of initial resuscitation in septic shock
During the first 6 hours of resuscitation, the goals of initial resuscitation are:
  • CVP 8–12 mm Hg. In mechanically ventilated patients or decreased ventricular compliance, CVP of 12–15 mm Hg is maintained
  • MAP ≥65 mm Hg
  • Urine output ≥0.5 mL/kg/hour
  • Superior vena cava oxygenation saturation (ScvO2) or mixed venous oxygen saturation (SvO2) 70% or 65%, respectively.
120
Flow chart 15.2: Early goal-directed therapy
Abbreviations: CVP, central venous pressure; MAP, mean arterial pressure; ScvO2, mixed venous oxygen saturation in central vein
 
Screening and Diagnosis of Sepsis
The critical component in reducing mortality from sepsis-related multiple organ dysfunction is the time taken to diagnose severe sepsis. Hence, early diagnosis of sepsis and early intervention is recommended. A sample of blood should be sent for blood culture early before administering empirical antibiotics. Cultures of other sites such as urine, CSF, wounds, respiratory secretions, or other body fluids that may be the source of infection, should also be obtained before antimicrobial therapy. Early lab studies and imaging studies should be done to support or confirm the diagnosis.
Surviving sepsis campaign (SSC) bundles (Table 15.3) have reduced the mortality rate in ICU and are recommended for resuscitation and early management of sepsis patients as they are admitted in the hospital. 121
Table 15.3   Surviving sepsis campaign bundles
To be completed within 3 hours:
  • Measure lactate level
  • Obtain blood cultures prior to administration of antibiotics
  • Administer broad spectrum antibiotics
  • Administer 30 mL/kg crystalloid for hypotension or lactate 4 mmol/L
To be completed within 6 hours:
  • Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation) to maintain a mean arterial pressure (MAP) ≥65 mm Hg
  • In the event of persistent arterial hypotension despite volume resuscitation (septic shock) or initial lactate ≥4 mmol/L:
    • Measure central venous pressure (CVP)
    • Measure central venous oxygen saturation (ScvO2)
    *Targets for quantitative resuscitation included in the guidelines are CVP of ≥8 mm Hg, ScvO2 of ≥70%, and normalization of lactate.
  • Remeasure lactate if initial lactate was elevated.
 
ANTIMICROBIAL THERAPY
Recommendation is to administer intravenous antibiotics within the 1st hour of recognition of severe sepsis and septic shock. Initial empirical antimicrobial therapy should include 1 or more drugs which have activity against bacterial, viral and fungal organisms presumed to be the source of infection. The most common pathogens causing septic shock in hospitalized patients are Gram-positive bacteria, followed by Gram-negative and mixed bacterial microorganisms. Candidiasis and toxic shock syndromes though uncommon should be suspected in certain patients (immunosuppressed or neutropenic state, prior intense antibiotic therapy, or colonization in multiple sites). Low procalcitonin level can be used as a guide to discontinue empiric antibiotics but the evidence is very less for its routine use in patients with severe sepsis. Empiric antibiotic therapy should not be administered for more than 3–5 days and de-escalation should be done as soon as possible. Typical duration of therapy is 7–10 days but may be needed longer in patients with neutropenia, viral or fungal infections. Antimicrobial therapy should not be used for patients with severe inflammatory states of noninfectious cause.
  • Severe sepsis with neutropenia and multidrug resistant organisms like Acinetobacter and Pseudomonas—combination empirical therapy
  • Severe infection with respiratory failure and septic shock—combination therapy with an extended spectrum beta-lactam and aminoglycoside/fluoroquinolone for P. aeruginosa bacteremia
  • Streptococcus pneumoniae with septic shockcombination of beta-lactam and macrolide
  • IV drug abusers—vancomycin
  • In case of neutropenic patients, empirical antifungal agents can be started empirically if neutropenia persists for more than 5 days
  • Empirical antifungal drugs—amphotericin B is used for all life-threatening fungal infections. Fluconazole or echinocandins is recommended by recent Infectious Diseases Society of America (IDSA) guidelines for severe 122candidiasis. Echinocandins is used for severe illness or when the patient is recently treated with antifungal agents.
  • Severe sepsis with neutropenia with suspected pseudomonas infection— ceftazidime or piperacillin – tazobactam or meropenem + aminoglycoside.
 
Source Control
A specific diagnosis of local infection is sought or diagnosed or excluded early and intervention is started within first 12 hours after diagnosis to control the source. Vascular access sites thought to be a source of infection should be removed and the intervention as far as possible should be less invasive. Surgical control or percutaneous drainage of the infection is essential in patients with severe intra-abdominal infections.
 
Prevention of Infection
Selective oral decontamination (SOD) and selective digestive decontamination (SDD) can be given to reduce the incidence of ventilator-associated pneumonia (VAP). Oral chlorhexidine is used for oropharyngeal decontamination in ICU patients with severe sepsis.
 
HEMODYNAMIC SUPPORT
 
Fluid Therapy
Crystalloids are the initial fluid of choice to be used in the resuscitation of severe sepsis and septic shock. Colloids are not advised. Albumin has a role when patients require substantial amounts of crystalloids. Initial fluid challenge of 30 mL/kg of crystalloids is administered in patients with septic shock when there is suspicion of hypovolemia and the fluid challenge is continued until the patient has improvement in hemodynamics as indicated by dynamic parameters like PPV, SVV or static parameters like arterial blood pressure, CVP, heart rate.
 
Vasopressors/Inotropes
All patients requiring vasopressors or inotropes should have an invasive arterial blood pressure monitoring. Norepinephrine is the first choice vasopressor in septic shock and the target mean arterial pressure is 65 mm Hg. Dopamine is an alternative to norepinephrine. Epinephrine can be added if an additional vasopressor is required and low dose dopamine for renal vasodilatation is not recommended. Vasopressin and phenylephrine are not recommended as the first choice but can be used for refractory cases of septic shock. Vasopressin dose is 0.03 U/minute. Phenylephrine is used when norepinephrine is associated with serious arrhythmias, persistently low blood pressure with high cardiac output, or as salvage therapy when combined inotrope/vasopressor drugs and low dose vasopressin have failed to achieve the target MAP. In the presence of myocardial dysfunction and low cardiac output or ongoing signs of hypoperfusion despite 123achieving adequate intravascular volume and adequate MAP, dobutamine infusion of 20 µg/kg/minute is started.
 
Adjunctive Therapy
Intravenous hydrocortisone is not routinely used to treat patients with septic shock if hemodynamic stability is achieved with fluids and vasopressors. If this is not possible, intravenous hydrocortisone is used as a continuous infusion of 200 mg/day. Corticosteroids should not be administered for the treatment of sepsis in the absence of shock and adrenocorticotropic hormone (ACTH)stimulation test is done to identify patients who require steroids. Hydrocortisone infusion is tapered when vasopressors are not required.
 
Supportive Therapy
 
Blood Component Administration
After resolution of tissue hypoperfusion packed RBC transfusion is recommended when Hb is <7 g/dL in the absence of cardiac disease, acute hemorrhage and the target Hb concentration is 7–9 g/dL. The use of erythropoietin and antithrombin is not recommended in severe sepsis and septic shock. Fresh frozen plasma is not used in clotting disorders in the absence of bleeding. In patients with severe sepsis, prophylactic platelet are administered when counts are <10,000/mm3 (10 × 109/L) in the absence of apparent bleeding. Prophylactic platelet transfusion when counts are <20,000/mm3 (20 × 109/L) if the patient has a significant risk of bleeding. Higher platelet counts (≥50,000/mm3 [50 × 109/L]) are taken as cut off for active bleeding, surgery, or invasive procedures.
 
Immunoglobulins and Selenium
They are not recommended in severe sepsis and septic shock.
 
Recombinant Activated Protein C (rhAPC)
The first ever trial showing the role of rhAPC in severe sepsis was PROWESS (Recombinant Human-activated Protein C Worldwide Evaluation in Severe Sepsis) trial in 2001 which demonstrated reduction in mortality but the PROWESS SHOCK trial done in 2011, showed no benefit of rhAPC in patients with septic shock and hence not recommended in severe sepsis and septic shock.
 
Mechanical Ventilation of Sepsis-induced Acute Respiratory Distress Syndrome
A tidal volume of 6 mL/kg predicted body weight is initiated in acute respiratory distress syndrome (ARDS) and the plateau pressure is limited to ≤30 cm H2O. positive end-expiratory pressure (PEEP) is applied to prevent alveolar collapse at end expiration and higher PEEP is required in case of hypoxemia not responding to low PEEP. Head end elevation of head of 30–45° is given to prevent aspiration 124and the development of ventilator-associated pneumonia (VAP). Recruitment maneuver and prone positioning is used in severe refractory hypoxemia and when PaO2/FiO2 ratio is ≤100 mm Hg. A weaning protocol is recommended with frequent spontaneous breath trials in patients who meet weaning criteria and extubated if fit for extubation. Noninvasive ventilation can be considered in specific group of ARDS patients. SSC guidelines does not recommend the routine use of pulmonary artery catheter (PAC) and beta-2 agonists in ARDS patients unless there are specific indications. A conservative fluid strategy is used for patients who do not have tissue hypoperfusion.
 
Sedation, Analgesia, and Neuromuscular Blockade
Sedation is minimized in patients put on mechanical ventilation and neuromuscular blocking agents are avoided in patients without ARDS and if used, it should be used with train-of-four monitoring. In patients with ARDS, neuromuscular blocking agents are not used >48 hours.
 
Glycemic Control
Blood glucose should be managed by a protocol in patients with severe sepsis and insulin is started when two consecutive blood glucose levels are >180 mg/dL. The target for upper limit should be ≤180 mg/dL and blood glucose should be monitored every 1–2 hours until glucose values and insulin infusion rates are stable and then every 4 hours thereafter. Point of care monitors should be interpreted with caution because of its unreliability. Treatment should avoid hyperglycemia (>180 mg/dL), hypoglycemia, and wide swings in glucose levels. Many studies have shown that the variability in glucose levels over time is an important determinant of mortality.
 
Renal Replacement Therapy
There is no mortality benefit between continuous renal replacement therapy (CRRT) and intermittent hemodialysis in patients with severe sepsis and acute renal failure. CRRT is used in hemodynamically unstable sepsis patients for fluid balance.
 
Bicarbonate Therapy
Sodium bicarbonate therapy is not recommended for improving hemodynamics or reducing vasopressor requirements in patients with tissue hypoperfusion-induced lactic acidosis with pH ≥7.15.
 
DVT Prophylaxis
ICU patients are at risk for deep vein thrombosis and hence patients with severe sepsis are recommended daily pharmacoprophylaxis against venous thromboembolism (VTE). Daily subcutaneous low-molecular weight heparin (LMWH) which is preferred or twice daily unfractionated heparin (UFH) or 125thrice daily UFH. If creatinine clearance is <30 mL/min, dalteparin or UFH is used. Combination of heparin and intermittent pneumatic compression device is better than heparin alone. In patients where heparin is contraindicated, graduated compression stockings or intermittent compression devices is used.
 
Stress Ulcer Prophylaxis
H2 blocker or proton pump inhibitor is given to patients with severe sepsis/septic shock who have risk factors for bleeding. Patients without risk factors for bleeding are not given prophylaxis routinely.
 
Nutrition
Once the patient is diagnosed with severe sepsis or septic shock, oral or enteral feeding are started within 48 hours in low dose feeding rather than full caloric feeding in the first week and the patient should not be left with fasting or only given intravenous glucose. Underfeeding (60−70% of target) or trophic feeding (upper limit of 500 kcal) is probably a better nutritional strategy in the first week of severe sepsis/septic shock. The recommendation is to use intravenous glucose and enteral nutrition rather than total parenteral nutrition (TPN) alone or parenteral nutrition in conjunction with enteral feeding in the first week. The use of immunomodulators like arginine, glutamine or omega-3 fatty acids supplementation with enteral nutrition is not advised by the SSC 2012 guidelines.
 
BIBLIOGRAPHY
  1. Antonelli M, Conti G, Rocco M, et al. A comparison of noninvasive positive-pressure ventilation and conventional mechanical ventilation in patients with acute respiratory failure. N Engl J Med. 1998;339:429-35.
  2. Basso N, Bagarani M, Materia A, et al. Cimetidine and antacid prophylaxis of acute upper gastrointestinal bleeding in high risk patients. Controlled, randomized trial. Am J Surg. 1981;141:339-41.
  3. Beale RJ, Bryg DJ, Bihari DJ. Immunonutrition in the critically ill: a systematic review of clinical outcome. Crit Care Med. 1999;27:2799-805.
  4. Chuntrasakul C, Siltharm S, Chinswangwatanakul V, et al. Early nutritional support in severe traumatic patients. J Med Assoc Thai. 1996;79:21-6.
  5. Cooper DJ, Walley KR, Wiggs BR, et al. Bicarbonate does not improve hemodynamics in critically ill patients who have lactic acidosis: A prospective, controlled clinical study. Ann Intern Med. 1990;112:492-8.
  6. Dellinger, et al. Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41:580-637.
  7. Drakulovic MB, Torres A, Bauer TT, et al. Supine body position as a risk factor for nosocomial pneumonia in mechanically ventilated patients: A randomized trial. Lancet. 1999;354:1851-8.
  8. Egi M, Bellomo R, Stachowski E, et al. Variability of blood glucose concentration and short-term mortality in critically ill patients. Anesthesiology. 2006;105:244-52.
  9. Gao Smith F, Perkins GD, Gates S, et al. BALTI-2 study investigators: Effect of intravenous ß-2 agonist treatment on clinical outcomes in acute respiratory distress syndrome (BALTI-2): A multicenter, randomized controlled trial. Lancet. 2012; 379:229-35.
  10. 126Geerts W, Cook D, Selby R, et al. Venous thromboembolism and its prevention in critical care. J Crit Care. 2002;17:95-104.
  11. Krinsley JS. Glycemic variability: a strong independent predictor of mortality in critically ill patients. Crit Care Med. 2008;36:3008-13.
  12. Mackenzie IM, Whitehouse T, Nightingale PG. The metrics of glycaemic control in critical care. Intensive Care Med. 2011;37:435-43.
  13. Marx WH, DeMaintenon NL, Mooney KF, et al. Cost reduction and outcome improvement in the intensive care unit. J Trauma. 1999;46:625-9.
  14. National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network; Wiedemann HP, Wheeler AP, Bernard GR, et al. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006;354:2564-75.
  15. Ranieri VM, Rubenfeld GD, Thompson BT, et al. Acute respiratory distress syndrome: The Berlin definition. JAMA. 2012;307:25226-33.
  16. Rhodes A, Bennett ED. Early goal-directed therapy: an evidence-based review. Crit Care Med. 2004;32:S448-S450.
  17. Rice TW, Mogan S, Hays MA, et al. Randomized trial of initial trophic versus full-energy enteral nutrition in mechanically ventilated patients with acute respiratory failure. Crit Care Med. 2011;39:967-74.
  18. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368-77.
  19. Rudis MI, Sikora CA, Angus E, et al. A prospective, randomized, controlled evaluation of peripheral nerve stimulation versus standard clinical dosing of neuromuscular blocking agents in critically ill patients. Crit Care Med. 1997;25:575-83.
  20. Sandham JD, Hull RD, Brant RF, et al. Canadian Critical Care Clinical Trials Group: A randomized, controlled trial of the use of pulmonary artery catheters in high-risk surgical patients. N Engl J Med. 2003;348:5-14.
  21. Stocker R, Neff T, Stein S, et al. Prone positioning and low-volume pressure-limited ventilation improve survival in patients with severe ARDS. Chest. 1997;111:1008-17.
  22. The ARISE Investigators and the ANZICS Clinical Trials Group. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014;371:1496-506.
  23. The NICE-SUGAR Study Investigators: Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009;360:1283-97.
  24. The Process Investigators, Yearly DM, Kellum JA, Huang DT, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370:1683-93.
  25. Vinsonneau C, Camus C, Combes A, et al. Hemodiafe Study Group: Continuous venovenous haemodiafiltration versus intermittent haemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: a multicenter randomized trial. Lancet. 2006;368:379-85.

PRINCIPLES OF ANTIBIOTIC USE IN ICUCHAPTER 16

Prem Kumar
Due to the increasing incidence of new infections in the last two decades and the development of drug-resistant bacteria, use of antibiotics has drastically changed in ICU. The major cause of drug-resistant microorganism are due to wrong initiation and combination of antibiotics. Prevention of infection is the best step in preventing antibiotic use in ICU patients. This chapter deals with the principles of antibiotic use in ICU with the recent guidelines.
 
PRINCIPLES OF ANTIBIOTIC PRESCRIPTION
  • Appropriate investigations required for diagnosis and culture should be sent.
  • Risk stratification of patient and the condition is done.
  • Culture should be sent before initiating antibiotics.
  • An institutional antibiotic policy for prescribing antibiotics for various infections should be formulated.
  • Before prescribing antibiotics, review of various clinical factors interacting with the antibiotics should be done such as renal, hepatic function, allergy and drug interaction.
  • Antibiotic stewardship is a strategy followed to limit antibiotic resistance. It involves the selection of an appropriate drug with optimal dose and duration while minimizing toxicity.
  • Initiation of empirical antibiotics should be done based on clinical severity and should be de-escalated according to culture results (e.g. Severe sepsis).
  • To check whether the appropriate dose is advocated for that illness.
  • The need for antibiotics should be reviewed daily.
  • Parenteral administration is usually reserved for patients who cannot take oral medications and in seriously ill patients.
  • With the opinion of ID physicians, investigations such as antibiotic assay, minimum inhibitory concentration (MIC) of the antibiotic, serum bactericidal activity is done which would be useful in severe nosocomial infections.
  • In case of failure of response to antibiotics, opinion is obtained from a microbiologist/clinical pharmacologist/infectious disease physician regarding change of antibiotics.
  • The usual prescription of 2-week course of antibiotics is unnecessary and the duration of antibiotic course should be shorter.
  • 128Switching of one combination of antibiotics to another—antibiotic surfing. It should not be done in case of poor response to therapy without properly investigating the cause of the persistent infection (Table 16.1).
 
COMMON CAUSES OF INFECTION IN ICU
Nosocomial infections are common in ICU. The most common causes of infections are:
  • Catheter-associated urinary tract infection (CAUTI)
  • Catheter-related bloodstream infection
  • Ventilator-associated pneumonia (VAP)
  • Surgical wound infections—necrotizing fasciitis
  • Abdominal infections—intra-abdominal sepsis, postsplenectomy sepsis
  • Central nervous system infection—meningitis
  • Device infection—replacement prosthesis infection.
 
PHARMACOKINETIC PRINCIPLES (TABLE 16.2)
The success of the therapy depends on the drug concentration achieved to inhibit or kill bacteria at the site of infection. The location of the infection points towards the choice of drug and the route of administration. The minimal drug concentration achieved at the infected site should be approximately equal to the MIC for the infecting organism, and in fact multiples of MIC is required in certain severe infections. Most of the antibiotics are excreted through the kidneys, hence the dosage is altered according to the creatinine clearance in patients with renal dysfunction. The pharmacokinetics is changed in ICU patients due to body fluid alteration, hypoalbuminemia, alteration in volume of distribution, clearance and elimination.
Table 16.1   Antibiotics and their site of action
Bactericidal
Bacteriostatic
Cell wall—beta-lactams (e.g. penicillins, cephalosporins, and carbapenems)
Cell membrane—polymyxin, daptomycin
Bacterial DNA—fluoroquinolones
Alteration of protein synthesis—aminoglycosides
Inhibition of protein synthesis—sulfonamides, tetracyclines, macrolides, chloramphenicol, streptogramins, and linezolid
Table 16.2   Pharmacodynamic characteristics of certain antibiotics in ICU
Characteristic
Antibiotic
Time dependent
Beta-lactams, carbapenems, glycopeptides
Concentration dependent
Aminoglycosides
Both concentration and time dependent
Fluorquinolones
129
 
Empirical Therapy for Sepsis without an Obvious Focus of Primary Infection
The choice of empirical antimicrobial therapy depends on the following factors:
  • History
  • Physical examination
  • Recent antibiotic treatment in the past 3 months
  • Drug allergy
  • Clinical condition
  • Drug susceptibility pattern for various pathogens in the ICU.
In patients with severe sepsis or septic shock, antibiotic therapy should be initiated within an hour of therapy according to surviving sepsis 2012 guidelines. Sufficient evidence exists that delay or failure to initiate antimicrobial therapy is associated with increased morbidity and mortality in patients with severe sepsis or septic shock. Every hour of delay in initiating antibiotics in severe sepsis will decrease the survival by 7% approximately. Recommendation is to administer broadspectrum intravenous antibiotics within the 1st hour of recognition of severe sepsis and septic shock. Initial empirical antimicrobial therapy should include one or more drugs which have activity against bacterial, viral and fungal organisms presumed to be the source of infection.
The most common pathogens causing septic shock in hospitalized patients are Gram-positive bacteria, followed by Gram-negative and mixed bacterial microorganisms. Candidiasis and toxic shock syndromes though uncommon should be suspected in certain patients (immunosuppressed or neutropenic state, prior intense antibiotic therapy, or colonization in multiple sites). Low procalcitonin level can be used as a guide to discontinue empiric antibiotics but the evidence is very less for its routine use in patients with severe sepsis. Empiric antibiotic therapy should not be administered for more than 3–5 days and de-escalation should be done as soon as possible. Typical duration of therapy is 7–10 days but may needed longer in patients with neutropenia, viral or fungal infections. Antimicrobial therapy should not be used for patients with severe inflammatory states of noninfectious cause.
  • Severe sepsis with neutropenia and multidrug resistant organisms such as Acinetobacter and Pseudomonas—combination empirical therapy with Piperacillin—Tazobactam/Meropenem/Cefepime + Aminoglycoside ± Vancomycin
  • Severe infection with respiratory failure and septic shock—combination therapy with an extended spectrum beta-lactam and aminoglycoside/fluoroquinolone for P. aeruginosa bacteremia
  • Streptococcus pneumoniae with septic shock—combination of beta-lactam and macrolide
  • IV drug abusers—vancomycin
  • In case of neutropenic patients, empirical antifungal agents can be started empirically, if neutropenia persists for more than 5 days.
  • Empirical antifungal drugs—amphotericin B is used for all life-threatening fungal infections. Fluconazole or Echinocandins is recommended by recent Infectious Diseases Society of America (IDSA) guidelines for severe 130candidiasis. Echinocandins is used for severe illness or when the patient is recently treated with antifungal agents.
  • Severe sepsis with neutropenia with suspected Pseudomonas infection-ceftazidime or piperacillin—tazobactam or meropenem + aminoglycoside.
 
Empirical Antibiotic Therapy Based on Infection Site (Table 16.3)
Catheter-associated urinary tract infections (CAUTI) are discussed in detail under the chapter urinary tract infections.
Table 16.3   Empirical antibiotic therapy based on infection site
Site of infection
Common bacteria
Appropriate antibiotic
Nosocomial pneumonia
S. pneumonia
S. aureus
H. Influenzae
Legionella
Gram-negative Bacilli
MDR
P. aeruginosa
MRSA
Antibiotic-resistant Enterobacteriaceae
Acinetobacter
Klebsiella
Legionella
ESBL-positive
Ceftriaxone (2 g IV OD)
Or
Ciprofloxacin (400 Mg IV 8th hourly), Or Levofloxacin (750 mg IV OD)
Or
Ampicillin/Sulbactam (3 g IV 6th hourly)
Or
Ertapenem (1 g IV OD)
MDR
Ceftazidime (2 g IV 8th hourly)
Or
Cefepime (2 g IV 12th hourly)
Or
Piperacillin/Tazobactam (4.5 g IV 6th hourly), Imipenem (1 g IV 8th hourly), Or Meropenem (1 g IV 8th hourly)
Plus
Gentamicin (7 mg/kg IV OD) Or Amikacin (20 mg/kg IV OD)
Or
Ciprofloxacin (400 mg IV 8th hourly), Or Levofloxacin (750 mg IV OD)
Plus
Linezolid (600 mg IV 12th hourly) Or Vancomycin (15 mg/kg, up To 1 g IV, 12th hourly
Intra-abdominal sepsis
E. coli
P. aeruginosa
Enterococcus species
Bacteroides species
Ertapenem
Or
Piperacillin-Tazobactam (4.5 gm IV every 6 hours)
Or
Third- or Fourth-generation Cephalosporin (Active Against P. aeruginosa)131
Or
Cefepime 2 g IV Every 8 hours PLUS Metronidazole
500 mg IV every 6 hours
Or
In case of penicillin allergy, Aztreonam 2 gm IV every 8 hours
Plus
Metronidazole 500 mg IV every 6 hours
Plus
Vancomycin
In case of Vancomycin-resistant Enterococci, Add Linezolid/Daptomycin/Tigecycline.
Antifungal therapy with micafungin may be considered in critically ill patients. Antifungal therapy should be used in patients where fungi are isolated in culture.
Catheter-related blood stream infection
Staphylococcus species
Enterobacteriaceae
P. aeruginosa
B-lactam with activity against
P. aeruginosa
Plus
Vancomycin
Surgical—wound Infections
Streptococcus species
Staphylococcus species
Gram-negative bacilli
B-lactam + B-lactamase inhibitor (Clavulanic Acid)
Piperacillin-Tazobactam
Meropenem
 
STEPS TAKEN TO PREVENT ANTIBIOTIC RESISTANCE
Multidrug resistant pathogen (MDR): Isolates resistant to drugs from three or more antimicrobial classes with different mechanisms of action are considered MDR.
The incidence of multidrug resistant pathogens (Table 16.4) in ICU is increasing and the reason for this is due to the improper use of antibiotics with relation to condition, dose, duration, interval of dosage.
Common scenarios where antibiotics are misused:
  • Excessive use of certain antibiotics (e.g. fluoroquinolones)
  • Prolonged empiric antibiotic treatment without clear evidence of infection
  • Treatment of positive culture in absence of active clinical infection
  • Prolonged prophylaxis
  • Failure to narrow antibiotic therapy after the causative organism is identified.
 
Presurgery Antibiotic Prophylaxis
A single dose of antibiotic administered within 1 hour before the incision is appropriate for most surgical procedures. Duration of prophylaxis for surgical site infection should not exceed 24 hours in most cases. This prophylaxis ensures to target the skin bacterial flora while avoiding broadspectrum activity.
 
BIBLIOGRAPHY
  1. Barie PS, Hydo LJ, Shou J, et al. Influence of antibiotic therapy on mortality of critical surgical illness caused or complicated by infection. Surg Infect (Larchmt). 2005;6:41-54.
  2. Bennett JW, Murray CK, Holmes RL, Patterson JE, Jorgensen JH. Diminished vancomycin and daptomycin susceptibility during prolonged bacteremia with methicillin-resistant Staphylococcus aureus. Diagn Microbiol Infect Dis. 2008;60(4): 437-40.
  3. 133Bratzler DW, Houck PM. Antimicrobial prophylaxis for surgery: an advisory statement from the National Surgical Infection Prevention Project. Clin Infect Dis. 2004;38(12): 1706-15.
  4. Henry F. Chambers, General Principles of Antimicrobial Therapy. Goodman and Gilman's The Pharmacological Basis of Therapeutics, 11th edn. McGraw-Hill Publications, 2006.
  5. Ibrahim EH, Sherman G, Ward S, et al. The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting. Chest. 2000;118:146-55.
  6. Kanj SS, Kanafani ZA. Current concepts in antimicrobial therapy against resistant gram-negative organisms: extended-spectrum beta-lactamase producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and multidrug-resistant Pseudomonas aeruginosa. Mayo Clin Proc. 2011;86(3):250-9.
  7. Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006;34:1589-96.
  8. Leibovici L, Shraga I, Drucker M, et al. The benefit of appropriate empirical antibiotic treatment in patients with bloodstream infection. J Intern Med. 1998;244:379-86.
  9. Levine OS, Farley M, Harrison LH, Lefkowitz L, McGeer A, Schwartz B. Risk factors for invasive pneumococcal disease in children: a population-based case-control study in North America. Pediatrics. 1999;103(3):E28.
  10. Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscalzo J. Harrison's Principles of Internal Medicine, 18th edn. McGraw Hill Publications; 2012.
  11. MS Krishna Sarin, et al. Antimicrobial Therapy in the Intensive Care Unit. Indian Journal of Clinical Practice. 2013;23(10).
  12. Schuetz P, Albrich W, Mueller B. Procalcitonin for diagnosis of infection and guide to antibiotic decisions: past, present and future. BMC Med. 2011;9:107.

TROPICAL INFECTIONSCHAPTER 17

Jenu Santhosh  
SEVERE MALARIA
Management of severe malaria comprises four main areas: assessment of the patient, specific antimalarial treatment, adjunctive therapy, and supportive care. Vital organ dysfunction or increase in the infected total proportion of erythrocytes infected >2% (a level corresponding to >1012 parasites in an adult) is an indicator of increased mortality.
 
Diagnosis
Severe malaria is a medical emergency. The airway should be secured in unconscious patients and breathing and circulation assessed. The patient should be weighed or weight estimated—to give correct dosage of drugs and immediate measurements of blood glucose (stick test), hematocrit, parasitemia (parasite count, stage of malaria parasite development, and proportion of neutrophils-containing malaria pigment), and in adults, renal function (blood urea or creatinine) should be taken. The degree of acidosis is an important determinant of outcome; indicators of poor prognosis is given in Table 17.1 The plasma bicarbonate or venous lactate should be measured, if possible. If facilities are available, arterial or capillary blood pH and gases should be measured in patients who are unconscious, hyperventilating, or in shock. Blood should be taken for cross-match, and (if possible) full blood count, platelet count, clotting studies, bacterial culture, and full biochemistry (Table 17.2).
The assessment of fluid balance is critical in severe malaria. Acidotic breathing or respiratory distress, particularly in severely anemic children, often indicates hypovolemia and requires prompt but careful rehydration. Careful and frequent evaluations of the jugular venous pressure, peripheral perfusion, venous filling, skin turgor, and urine output should be made. Reduced hydration causes acidosis and over hydration causes pulmonary edema.
In uncertainty, central venous catheter should be inserted and the pressure (CVP) measured directly. Unconscious patients must have a diagnostic lumbar puncture to exclude bacterial meningitis. The opening pressure should be recorded and the rise and fall with respiration noted.
 
Management
Currently, four commonly used parenteral drug treatments are recommended for severe malaria—artesunate, artemether, quinine, and quinidine (Table 17.3).135
Table 17.1   Indicators of poor prognosis
Clinical
Lab parameters
  • Hemodynamic instability/shock
  • Temperature <36°C
  • Respiratory distress
  • Renal failure
  • Marked agitation, coma
  • Seizures
  • Bleeding
  • Metabolic acidosis (arterial pH <7.3, serum HCO3 <15 mmol/L)
  • ↑ serum bilirubin (>3 mg/dL), creatinine (>3 mg/dL), liver enzymes, urate, CPK, lactate (>5 mmol/L).
  • Hypoglycemia (<40 mg/dL)
  • Leukocytosis
  • Severe anemia (PCV <15%)
  • Decreased fibrinogen (<200 mg/dL)
  • Platelet count (<50,000/µL)
  • Prolonged PT, aPTT
  • Hyperparasitemia (>20% of parasites identified as pigment-containing trophozoites and schizonts, >5% of neutrophils with visible pigment, parasitemia level >1,00,000/µL)
Abbreviations: CPK, creative phosphokinase; PCN, packed cell volume; PT, prothrombin time; PTT, partial thromboplastin time
Table 17.2   Manifestations of severe malaria
Abbreviations: ARDS, acute respiratory distress syndrome; DIC, disseminated intravascular coagulation
Among these drugs, parenteral artesunate is the drug of choice for severe malaria for all patients. Most of the severe malaria are commonly caused by falciparum. Even in a patient considered to need parenteral treatment for P. vivax, P. ovale, or P. malariae infection, it is best to treat for falciparum malaria because there may be a mixed infection. Severe malaria requires ICU admission and care.
The pharmacokinetic properties of artesunate are superior to those of artemether and arteether because it is water soluble and can be given either by intravenous or intramuscular injection. Quinidine is more toxic than quinine and should be used only when none of the other effective parenteral drugs are available.136
Table 17.3   Dosages of antimalarial drugs
Drugs and dosages
Artesunate IV: 2.4 mg/kg stat, at 12 and 24 hours, then daily
or
Artemether IM: Initial dose of 3.2 mg/kg followed by 1.6 mg/kg every 24 hours until oral medication is tolerated
or
Quinine IV: Loading dose 20 mg/kg given over 4 hours, then 10 mg/kg given 8 hours after the loading dose was started, followed by 10 mg/kg every 8 hours
or
Quinine IM: Loading dose of 20 mg/kg is given as two simultaneous injections in the anterior thigh (10 mg/kg in each) after dilution of quinine in sterile water to a concentration of 60–100 mg/mL, maintenance dose of 10 mg/kg is given as one IM injection every 8 hours using the same dilution
or
Quinidine IV: 10 mg/kg infused over 1–2 hours followed by 1.2 mg/kg per hour by constant infusion.
Total plasma concentrations of 8–15 mg/L
For Quinine and 3.5–8.0 mg/L for quinidine are effective and don't cause toxicity.
Electrocardiographic monitoring is necessary especially for patients on quinidine. Total treatment duration for all regimens is 7 days. Once the patient has recovered sufficiently to tolerate oral medication reliably, the parenteral treatment can be discontinued and a second drug should be added, such as doxycyline 3 mg/kg for 7 days, clindamycin 10 mg/kg bid for 7 days, or atovaquone 20 mg/kg/day proguanil 8 mg/kg/day for 3 days.
 
Supportive Care
These should include recording of vital signs, with an accurate assessment of respiratory rate and pattern, assessment of the coma score, and urine output. The blood glucose should be checked, with rapid stick tests every 4 hours, if possible. Convulsions should be treated promptly with anticonvulsants such as intravenous or rectal diazepam. Physician treads a narrow path between underhydration, and thus worsening renal impairment, and overhydration, with the risk of precipitating pulmonary edema. So monitoring the hydration status is essential.
If the patient becomes oliguric (< 0.4 mL/kg/hr) despite adequate rehydration and the blood urea or creatinine are rising or already high, fluids should be restricted to replace insensible losses only. In acute renal failure or severe metabolic acidosis, hemofiltration or hemodialysis should be initiated as early as possible. Hypoglycemia should be suspected in any patient who deteriorates suddenly and treated with 10% dextrose.
Patients with acute pulmonary edema should be nursed upright and given oxygen, and the right-sided filling pressures should be reduced with whichever treatments are available (loop diuretics, opiates, venodilators, hemofiltration, dialysis). Positive pressure ventilation should be started if indicated. In case of DIC, fresh-frozen plasma or platelets can be given according to clinical features. 137
 
Severe Malaria in Pregnancy
Pregnant women in the second and third trimesters are more likely to develop severe malaria than other adults often complicated by pulmonary edema and hypoglycemia. Hypoglycemia should be expected and is often recurrent, if the patient is receiving quinine. The antimalarial drugs should be given in full doses. Postpartum bacterial infection is a common complication in these cases. Artemisinin derivatives should not be used in the first trimester of pregnancy. In the second and third trimesters of pregnancy, artesunate (2 mg/kg/day for 7 days) may be given with one of the other drugs. When the patient with severe malaria has recovered sufficiently, oral medication should be substituted.
 
DENGUE
Dengue is a viral hemorrhagic fever transmitted by Aedes aegypti mosquito and there are 4 distinct viruses which can cause this infection. Dengue patients gets admitted to ICU for dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). It is also known by the name breakbone fever. This disease is common in children although it can occur in any age group. Macrophage or monocyte infection is the main pathogenesis of DHF/DSS.
 
Clinical Features
The clinical features of DHF-DSS are hemorrhagic phenomena and hypovolemic shock which are caused by increased vascular permeability and plasma leakage. The early features in patients who ultimately develop DHF-DSS are indistinguishable from those of ordinary dengue fever, namely, fever, malaise, headache, musculoskeletal pain, facial flushing, anorexia, nausea, and vomiting. Fever has a biphasic curve with initial phase of 3–7 days, remission of few hours to 2 days and second phase with 1–2 days. Macular rash appears on the first day along with adenopathy, palatal vesicles, and scleral injection. It has a biphasic rash with evanescent maculopapular, scarlatiniform, morbilliform, or petechial changes which proceeds from extremities to the torso. However, with the defervescence of fever 2–7 days later, reduced perfusion and early signs of shock are manifested by central cyanosis, restlessness, diaphoresis, and cool, clammy skin and extremities.
Abdominal pain is a common complaint. A rapid and weak pulse, narrowing of the pulse pressure to less than 20 mm Hg, and, in the most extreme cases, an unrecordable blood pressure establish the shock syndrome. The platelet count declines and petechiae appear with spontaneous ecchymoses. Bleeding occurs at mucosal surfaces from the gastrointestinal tract and at venipuncture sites. The liver is palpably enlarged in up to 75% of patients, with variable splenomegaly. Increased amylase levels and sonographic evidence of pancreatic enlargement may be seen in 40% of patients. Pleural effusions can be detected in more than 80% of cases, if a decubitus film is taken. The presence of pleural and peritoneal effusions is associated with severe disease. Capillary-alveolar leakage may cause ARDS.
In untreated patients, hypoperfusion due to myocardial dysfunction and reduced ejection fraction results in metabolic acidosis and organ failure. With adequate support, spontaneous resolution of vasculopathy and circulatory failure 138usually can be expected within 2–3 days, with complete recovery afterward. The duration of illness ranges from 7 to 10 days in most cases. Fatality rates have reached 50% in underserved populations, but in experienced centers, fewer than 1% of cases are fatal. Encephalopathy (often reflecting CNS hemorrhage), prolonged shock, and hepatic or renal failure are rare but if present, they are associated with a poor prognosis. Concurrent infection with bacteria, parasites, and other viral pathogens occurs frequently in areas with high transmission. Dual infections, principally Gram-negative sepsis, have been reported in patients hospitalized with dengue, resulting in prolonged fever and hospitalization. In two thirds of patients with DHF, reactivation of herpesvirus-6 infection may be seen.
 
Differential Diagnosis
It is difficult to clinically diagnose dengue from other febrile illness. But the diagnosis is aided, if laboratory examination indicates leukopenia, neutropenia, thrombocytopenia, or mildly elevated AST levels. Specificity of tourniquet test, a requirement in the DHF case definition is also low. In comparison with chikungunya, another epidemic A. aegypti–borne infection, dengue patients are less likely to have conjunctivitis, rash, and musculoskeletal pain. The difficulty of differentiating dengue from rubella, measles, and even influenza has been underscored by the early misrecognition of entire epidemics. The clinical differentiation of DHF from YF and other viral hemorrhagic fevers is also difficult, and diagnosis requires laboratory confirmation.
 
Investigations
Clinical or laboratory differentiation, at the time of first presentation, of patients who can develop DHF would facilitate intervention before the sudden onset of shock. AST elevations greater than 60 U/mL, leukocyte counts less than 5000/mm3 (characteristic), and absolute neutrophil counts less than 3000/mm3, thrombocytopenia (<1,00,000/µL) are features which can be present in DHF/DSS. Tourniquet test can be done for differentiating dengue from other febrile illnesses. Increased IL-8 levels may have prognostic value. Studies to discover the pathogenic roles of other cytokines are in progress. Other findings are elevated hematocrit, hypoalbuminemia, hemoconcentration. Ultrasonography has been more sensitive in detecting pleural effusions, ascites, and gallbladder edema in more than 95% of severe cases, and pararenal and perirenal effusions in 77%, as well as hepatic and splenic subcapsular and pericardial effusions. IgM and IgG enzyme-linked immunosorbent assays (ELISAs) after the febrile phase is done for diagnosis, PCR or detection of the specific viral protein NS1 by ELISA can be diagnostic during the first few days of infection.
 
Management of Dengue and Dengue Hemorrhagic Fever
Antipyretics may help to relieve the symptoms of dengue fever. Aspirin should not be used as it may cause Reye's syndrome. Oral rehydration is indicated to replace losses from vomiting and high fever. Attentive clinical monitoring of patients with suspected DHF-DSS is necessary. Careful monitoring of circulation and vascular leakage by serial clinical assessments of pulse, blood pressure, skin perfusion, 139urine output, and hematocrit, to trigger intravenous fluid therapy is essential. An increase in hematocrit of greater than 20% indicates a significant loss of intravascular volume and the urgent need for fluid resuscitation. Normal saline is administered to maintain circulation and, under continued monitoring, for recurrent shock. Shock necessitates rapid intervention with isotonic crystalloid or colloid solutions, or, if needed, plasma or whole-blood transfusions.
Vascular integrity is usually restored spontaneously in 48 hours. Hence overhydration resulting in pulmonary edema is a risk, and positive-pressure ventilation with positive end-expiratory pressure may be needed. Whole blood, platelet, and fresh-frozen plasma transfusions may be needed, if there is significant hemorrhage, but caution is indicated in the administration of heparin except in patients with clear signs of disseminated intravascular coagulopathy. Platelet transfusions can be considered for patients with severe thrombocytopenia (<10,000/µL) or when there is evidence of bleeding.
Preventive transfusions may be harmful and should be avoided, and invasive procedures should be minimized to avoid hemorrhagic complications. Treatment to end virus replication could be beneficial, although viremia levels are already decreasing dramatically at the time of presentation to healthcare providers. In some locations, intravenous gamma-globulin has been used empirically, but no benefit has been established in a controlled evaluation. Neither high-dose methylprednisolone (30 mg/kg) nor AC-17 (carbazochrome sodium sulfonate), which is believed to reduce vascular permeability, was beneficial in controlled trials. Treatment with anti-TNF antibody has increased survivability in a lethal mouse model of dengue. Secondary and concurrent infections should be investigated and treated.
 
BIBLIOGRAPHY
  1. Centers for Disease Control and Prevention: Treatment of Malaria (guidelines for clinicians). Atlanta, Department of Health and Human Services, 2010.
  2. Centers for Disease Control and Prevention: Update: Management of patients with suspected viral hemorrhagic fever—United States. MMWR Morb Mortal Wkly Rep. 1995;44:475.
  3. Dondorp A, et al. Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): An open-label randomized trial. Lancet. 2010;376(9753):1647-57.
  4. Lee IK, et al. Clinical characteristics, risk factors, and outcomes in adults experiencing dengue hemorrhagic fever complicated with acute renal failure. Am J Trop Med Hyg. 2009;80(4):651-5.
  5. Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscalzo J. Harrison's Principles of Internal Medicine. 18th edn. McGraw Hill Publications, 2012.
  6. Pasvol G. Management of severe malaria: interventions and controversies. Infect Dis Clinic North Am. 2005;19(1):211-40.
  7. Potts JA, et al. Clinical and laboratory features that distinguish dengue from other febrile illnesses in endemic populations. Trop Med Int Health. 2008;13(11):1328-40.
  8. Rosenthal PJ. Artesunate for the treatment of severe falciparum malaria. N Engl J Med. 2008;358(17):1829-36.
  9. World Health Organization: Guidelines for the Treatment of Malaria, 2nd ed. Geneva, World Health Organization, 2010.
  10. Yadav SP, et al. Control of massive bleeding in dengue hemorrhagic fever with severe thrombocytopenia by use of intravenous anti-D globulin. Pediatr Blood Cancer. 2008; 51(6):812-3.

ANAPHYLAXISCHAPTER 18

Prem Kumar  
INTRODUCTION
Anaphylaxis is a severe, life-threatening, generalized or systemic hypersensitivity reaction. It is characterized by rapidly developing, life-threatening problems involving the airway, breathing and circulation. Classically, anaphylaxis comes under systemic immediate type 1 hypersensitivity. Incidence is 8:1,00,000 persons/year for general population. It is between 1:3500 and 1:13,000 during anesthesia.
 
DEFINITIONS
Anaphylaxis—rapid, severe life-threatening generalized immunologically mediated events involving an antigen-specific IgE-mediated mechanism that occur after exposure to foreign substances in previously sensitized persons.
Anaphylactoid reaction is clinically indistinguishable from anaphylaxis and is coined when the mechanism of the reaction is not immunologically mediated and prior exposure of the antigen is not required. They are due to mast cell degranulation which can occur due to drug like nonsteroidal anti-inflammatory drugs (NSAIDs).
Recent consensus is to avoid the term anaphylactoid reaction. Anaphylaxis is divided into immune, nonimmune or idiopathic.
 
ETIOLOGY AND PREDISPOSING FACTORS
  • Insect venoms, foods (e.g. peanuts), drugs, latex are common factors causing immune-mediated anaphylactic reaction. Certain drugs can also cause non-immune mediated reactions. A small number of patients have clinical effects of allergic reactions, but not identifiable cause which are classified under the idiopathic type.
  • Causes of nonimmune-mediated reactions are complement activation due to blood transfusion, NSAIDs, colloids (dextran, starch), local anesthetics, protamine, opioids, chemotherapeutic agents.
  • Other causes of anaphylactic reactions are antibiotics (penicillin group of drugs), anesthetic drugs [neuromuscular blocking drugs—vecuronium, atracurium, succinyl choline, pancuronium, rocuronium, mivacurium and 141gallamine in that order, hypnotics, colloids, opioids, local anesthetics], contrast media, blood products, cosmetic products, hormones, enzymes, pollen extracts.
  • Common causes of mortality are due to antibiotics, radiocontrast dye, foods, insect stings in that order. Food is a common triggering agent in children.
  • Patients with asthma are more prone to have severe bronchospasm.
  • Patients on beta blockers tend to have severe reactions.
  • Previously it was thought that patients with history of atopy had high risk of developing anaphylaxis, but according to recent studies, it is clear that atopy does not increase the risk of anaphylaxis.
 
Pathophysiology
  • Specific IgE cross-linked by allergen (drug)
  • Complement activation by specific IgG or IgM binding to antigen (drug)
  • Direct complement activation by way of the alternate pathway
  • Direct activation of mast cells or basophils.
The angioedema and urticarial manifestations of anaphylactic reactions are due to the release of histamine. Chemical mediators in anaphylaxis are cysteinyl leukotrienes (LTC4, LTD4, and LTE4), PAF, and bradykinin. Leukotrienes cause bronchiolar constriction. Hemodynamic collapse is due to release of prostaglandin D2 and histamine. Other factors which play a role in anaphylactic reaction are platelet activating factor, eosinophil and neutrophil chemotactic factor. The microscopic findings in the bronchi shows luminal secretions, submucosal edema, and eosinophilic infiltration, and intractable bronchospasm. Laryngeal angioedema cause airway obstruction. Nonimmune-mediated reaction is caused by NSAIDs, radiocontrast media which are mediated by mast cell degranulation.
 
CLINICAL MANIFESTATIONS
The hallmark of anaphylactic reaction is its onset within seconds to few minutes.
  • Respiratory system—hoarseness of voice, stridor due to laryngeal edema, bronchospasm.
  • Cardiovascular system—tachycardia, bradycardia, hypotension, and cardiac arrest.
  • Gastrointestinal system—nausea, vomiting, diarrhea, abdominal pain.
  • Skin manifestations—erythema, urticaria, angioneurotic edema, pale, cyanosis, conjunctival congestion. Characteristic feature is the eruption of well-circumscribed, erythematous wheals with raised serpiginous borders and blanched centers.
  • Central nervous system—confused, anxious, choking sensation, seizures, loss of consciousness.
Anaphylactic reactions are most likely if these three criterias are fulfilled:
  1. Sudden onset and rapid progression of symptoms
  2. Life-threatening ABC problems
  3. Skin and/or mucosal changes.142
Table 18.1   ABCDE approach for diagnosing anaphylactic reaction
Airway
  • Airway swelling
  • Difficulty in breathing and swallowing
  • Sensation that throat is ‘closing up’
  • Hoarse voice
  • Stridor
Breathing
  • Shortness of breath, increased respiratory rate
  • Wheeze, cyanosis, confusion due to hypoxia
  • Respiratory arrest
Circulation
  • Signs of shock
  • Tachycardia, hypotension
  • Myocardial ischemia/angina
  • Cardiac arrest
Disability
  • Sense of impending doom
  • Anxiety
  • Decreased conscious level
Exposure
  • Skin and mucosal changes
  • Erythema
  • Urticaria, angioedema
 
Diagnosis
Initial blood sampling is not useful but sample collected during the episode and assayed later for histamine and tryptase is helpful for diagnosing anaphylaxis. The basal tryptase concentration is 0.8–1.5 ng/mL and the normal value usually <1 ng/mL. The half-life of tryptase is approximately 2.5 hours and maximum concentrations occur rapidly within 1 hour, serum tryptase concentrations of >20 ng/mL may be seen after anaphylactic reactions.
Measurement of specific IgE antibodies by a radioallergosorbent test (RAST) can be helpful for diagnosis. Intracutaneous skin testing can be helpful to find the instigating agent causing the reaction but should not be done within 6 weeks of the reaction. Serum tryptase level is elevated within 4 hours of a reaction and it is helpful in reactions occurring under general anesthesia. Diagnosis can be done by the ABCDE approach (Table 18.1).
 
Treatment (Flow chart 18.1)
Early recognition and treatment is vital in the management of anaphylaxis. Once there is anaphylactic reaction, cardiopulmonary resuscitation is critical. Adequate intravenous access with two 18-gauge or larger peripheral catheters should be 143secured soon. Fluid administration, aggressive use of vasopressors, epinephrine are mainstay of treatment. Monitoring heart rhythm, blood pressure, oxygenation is important. Mild symptoms of anaphylaxis like skin rashes and pruritus can be managed by administering 0.3–0.5 mL of 1:1000 (1 mg/mL) epinephrine SC or IM and repeated at 5–10 minute intervals. In case of hypotension, crystalloids and vasopressors (dopamine).
Flow chart 18.1: Algorithm for management of anaphylaxis
144
 
ROLE OF EPINEPHRINE IN ANAPHYLAXIS
  • Receptor action—alpha and beta adrenergic effects
  • Causes vasoconstriction (α1) and bronchial smooth-muscle relaxation (β2)
  • Delays antigen absorption when infiltrated locally into an injection or sting site
  • Attenuation of increased venous permeability.
In case of desaturation, oxygen is administered through face mask. If patient goes for respiratory arrest, bag and mask ventilation and endotracheal intubation may be necessary. In case of large tongue edema, laryngeal or vocal cord edema where oropharyngeal intubation is difficult, cricothyroidotomy or tracheotomy may be needed. Cricothyroidotomy is preferred to tracheotomy in an emergency, as the cricothyroidotomy is easier to perform and is usually safer. In case of bronchospasm, inhaled β2 agonists such as albuterol would be useful.
Other drugs which would be useful for anaphylaxis are:
  • Antihistamine—diphenhydramine, 50–100 mg or 1–2 mg per kg IM or IV. Antihistamines are more effective in prevention than in treatment of anaphylaxis. Hence, it should never be used as the primary therapy for anaphylactic shock.
  • Intravenous glucocorticoids—initial dose of hydrocortisone is 5 mg/kg to a maximum of 200 mg given intravenously, followed by 2.5 mg/kg to 200 mg given intravenously every 4–6 hours for 24–48 hours. Steroids are not useful for acute episodes but prevents recurrence of bronchospasm, hypotension, or urticaria.
  • Aminophylline, 0.25–0.5 g IV.
 
Prevention
  • Eliciting history carefully about the precipitants causing anaphylactic reactions.
  • Awareness of cross reacting agents (e.g. penicillin and cephalosporins)
  • If there is a history of a previous anaphylactic reaction to an agent/drug, it is advisable to select a structurally unrelated agent.
  • Penicillin cause the highest incidence of anaphylactic reactions and hence positive skin tests to benzylpenicillin products is indicate that anaphylactic reactions can occur with treatment.
  • Desensitization can be done with the drug if an alternative is not available for that drug and that the drug is necessary for treatment.
  • Agents or drugs with preservatives like metabisulfite and methylparaben are associated with reactions (e.g. local anesthetics).
  • 145Patients with history of anaphylaxis should wear a Medic-Alert bracelet or necklace which details precipitating agents and potential cross-reacting agents.
  • Patient should be well educated about the agents causing reactions and advised to avoid it.
  • Consultation with the allergist is done and proper evaluation and planning of the management of the patients prone for anaphylactic agents are done.
 
BIBLIOGRAPHY
  1. Boyd AD, Romita MC, Conlan AA, et al. A clinical evaluation of cricothyroidotomy. Surg Gynecol Obstet. 1979;149:365-8.
  2. Fisher MM, Baldo BA. Anaphylaxis during anaesthesia; current aspects of diagnosis and prevention. Eur J Anaesthesiol. 1994;11:263-84.
  3. Lieberman P. Anaphylactic reactions during surgical and medical procedures. J Allergy Clin Immunol. 2002;110:S64-S9.
  4. McGrath K, Patterson R, Grammer LC, Greenberger PA (Eds). Allergic Diseases. In: Anaphylaxis Diagnosis and Management. Philadelphia: Lippincott-Raven; 1997.pp.439-58.
  5. Schwartz LB, Metcalfe DD, Miller JS, et al. Tryptase levels as an indicator of mast-cell activation in systemic anaphylaxis and mastocytosis. N Engl J Med. 1987;316:1622-6.
  6. Sheffer AL. Anaphylaxis. J Allergy Clin Immunol. 1985;75:227-33.
  7. Soar J, Pumphrey R, Cant A, et al. Working group of the resuscitation Council (UK). Emergency treatment of anaphylactic reactions–guidelines for healthcare providers. Resuscitation. 2008;77(2):157-69.
  8. The diagnosis and management of anaphylaxis: an updated practice parameter. J Allergy Clin Immunol. 2005;115:S483-S523.
  9. Valentine MD. Anaphylaxis and stinging insect hypersensitivity. JAMA. 1992;268: 2830-3.
  10. Whittington T, Fisher MM. Anaphylactic and Anaphylactoid Reactions in Bailliére's Clinical Anesthesiology. 1998.pp.301-21.
146Poisoning and envenomation
Chapter 19 General Principles of Poisoning Jenu Santhosh
Chapter 20 Poisoning Jenu Santhosh, TA Naufal Rizwan
Chapter 21 Drug Overdose Jenu Santhosh, TA Naufal Rizwan
Chapter 22 Envenomation Jenu Santhosh147

GENERAL PRINCIPLES OF POISONINGCHAPTER 19

Jenu Santhosh
Poison is defined as the substance producing harmful effects in living things. In humans, clinical features of poisoning may be seen within a period of three hours for most poisons except for a few where the manifestations are delayed (e.g. aspirin, paracetamol, iron, TCAs).
 
MANIFESTATIONS
Clinical manifestations vary with each poison. Always consider poisoning in any patient who presents with bizarre clinical manifestations. Since the history is usually unreliable, it is always better to ask the relatives regarding certain evidences of poisoning such as presence of containers, missing pills, etc.
Following are to be examined:
  • Vitals: Heart rate, respiration, blood pressure, temperature
  • Odor: Alcohol, solvents, insecticides
  • Skin:
    • Color change: blue-methemoglobinemia, flushed—serotonin syndrome
    • Sweating—organophosphorous poisoning, sympathomimetics
    • Bruising—anticoagulants
    • Blisters—pressure related, barbiturates (if associated with unconsciousness for >6 hours)
  • Neurological
  • Cardiovascular system
  • Systemic examination.
 
NEUROLOGICAL EXAMINATION
Coma: If coma is associated with localizing signs, it is unlikely due to poisoning. But transient localizing signs may be associated with barbiturates and dilantin (phenytoin). Coma is seen with alcohol, sedatives and antipsychotics.
Pupils: It may be constricted or dilated but sometimes may be unequal. It is the size of the pupil that is more important than the reflexes.
  • Miosis: Organophosphate, cholinergics, opiates, barbiturates.
  • Mydriasis: Atropine, dhatura, ephedrine, amphetamine, cyanide, cocaine.
150Seizures: Seizures may be caused by tricyclic antidepressants, theophylline, serotonin syndrome, alcohol withdrawal or sedatives, insecticides, antihistaminics.
 
Temperature
  • Decreased: Opiates, barbiturates, carbon monoxide
  • Increased: Anticholinergics, antihistaminics, phenothiazines, amphetamine, neuroleptic malignant syndrome.
 
CARDIOVASCULAR
  • Tachycardia: Atropine, dhatura, alcohol, sympathomimetics
  • Bradycardia: Organophosphates, carbamates, digoxin, beta-blockers. If bradycardia is associated with hypertension, think of intracranial bleed (Cushing's reflex), clonidine, cocaine.
  • Hypertension: Sympathomimetics
  • Hypotension: Antihypertensives, sedatives.
 
METABOLIC
  • Metabolic acidosis: Aspirin, methanol, ferrous sulphate
  • Hypoglycemia: Insulin, oral hypoglycemic agents, quinine, hepatotoxic agents
  • Hypokalemia: Diuretics, Cleistanthus collinus (odduvanthalai-local name in South India)
  • Hepatotoxic: Paracetamol, copper, antituberculous agents (ATT).
 
MANAGEMENT
Criteria for ICU admission:
  • Respiratory failure, inability to protect airway
  • GCS < 8, seizures
  • Metabolic abnormalities such as hypoglycemia, electrolyte abnormalities, metabolic acidosis, coagulopathy, hepatic failure
  • Sinus tachycardia (HR >110), arrhythmias, SBP <90 mm Hg, heart block, QRS >0.12 second.
 
Assessment
  • Ensure clear airway and suction the secretions, look for cough and gag reflex, consider endotracheal intubation.
  • Check SpO2 and give oxygen, if necessary, observe the breathing and its pattern, ventilate if necessary.
  • Monitor heart rate and rhythm; check blood pressure.
  • Check GCS; control seizures and agitation; observe for muscle spasm and rigidity; look for pupil size and reaction.
  • 151Look for odor, skin color, temperature. Search for rashes, skin lesions, cyanosis, jaundice.
  • Look for abdominal guarding and rigidity, UGI or LGI bleed.
  • Monitor for adequacy of urine output. Look for urine color.
 
Specific Treatment
  • Reduce absorption
  • Increase elimination
  • Specific antidotes.
 
Reduce Absorption
  • Surface decontamination—washing the skin and eye
  • Gastrointestinal-induced vomiting, stomach wash, activated charcoal, catharsis, whole bowel irrigation.
Induced vomiting
It is contraindicated in comatose patients and in those who are convulsing and in those who have consumed corrosives.
Gastric lavage
It is safer than induced vomiting. It is more effective, if it is given within 60 minutes of poison ingestion. It can be also given late in poisons with delayed gastric emptying, viz. salicylates and anticholinergics. It can be done in comatose patients after securing the airway.
Activated charcoal
It is effective for most poisons except alcohol, ethylene glycol, mineral acids, alkali, lithium, fluoride, iron. Multidose-activated charcoal (MDAC) is useful than single dose charcoal. Dose is 12.5 g hourly to 50 g 4th hourly. If the quantity of the substance ingested is not known, 10 times the ingested dose by weight should be given.
Cathartics
There is a controversy regarding the use of cathartics to hasten the elimination of charcoal/poison complex. Commonly used cathartics are sorbitol and magnesium citrate.
 
Increase Elimination
It is possible only if the drug is distributed predominantly in the extracellular space and low protein bound. It is better to maintain urinary output of all patients with poisoning to 150–200 mL per hour. Urinary alkalinization is recommended for salicylate poisoning.
Other modes are hemodialysis (barbiturates), charcoal/resin hemoperfusion (theophylline), hemofiltration, peritoneal dialysis. Albumin dialysis (MARS) is used for protein-bound drugs.152
 
Specific Antidotes
Specific antidotes are shown in Table 19.1.
Table 19.1   Specific antidotes
Drug
Antidote
Dose
Acetaminophen
N-acetyl cysteine
Oral: 140 mg/kg loading dose followed by 70 mg/kg every 4 hourly for 17 doses
Intravenous:150 mg/kg in 200 mL 5% dextrose over 15 minutes; then 50 mg/kg diluted in 500 mL over 4 hours; then 100 mg/kg diluted in 1000 mL over 16 hours
Benzodiazepines
Flumazenil
0.2–0.3 mg bolus; Infusion: 0.2–1 mg/hourly
Carbon monoxide
100% Oxygen
Digoxin
Digoxin specific antibodies
Ethylene glycol, methanol
Ethanol
750 mg/kg as loading dose followed by 100–250 mg/kg per hour infusion
Fomipezole
15 mg/kg up to 1 g over 30 minutes as a loading dose
10–15 mg/kg every 12 hours as maintenance
Copper
Penicillamine
20–30 mg/kg/day; max 2 g/day
Iron
Desferrioxamine
15 mg/kg per hour up to max of 6 g
Methemoglobinia
Methylene blue
1–2 mg/kg slow intravenous over 5 minutes; repeat in 60 minutes
Opiates
Naloxone
0.4–2 mg every 2–3 minutes as bolus
Infusion: 0.4–0.8 mg/hour
Organophosphorous
Atropine
Bolus: 0.6–3 g every 5 minutes till atropinization occurs. Oximes should also be given
Glycopyrrolate
Bolus: 0.4–1 mg
 
BIBLIOGRAPHY
  1. Eddleston M, Juszczak E, Buckley NA, Senarathna L, Mohamed F, Dissanayake W, et al. Multiple-dose activated charcoal in acute self-poisoning: A randomised controlled trial. Lancet. 2008;371:579-87.
  2. In: Critical Care Toxicology, Diagnosis and Management of the Critically Poisoned Patient, 1st edn. Brent, Wallace, Burkhart, Phillips, Donovan (Eds), 2005.
  3. Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscalzo J. Harrison's Principles of Internal Medicine. 18th edn. McGraw Hill-publications, 2012
  4. Olson KR. Poisoning and Drug Overdose, 5th edn. McGraw Hill Publications, 2006.
  5. Parikh CK. Parikh Textbook of Medical Jurisprudence and Toxicology, 4th edn. Mumbai: Medical Publication; 1989.pp.912-4.

POISONINGCHAPTER 20

Jenu Santhosh, TA Naufal Rizwan
Pesticides include:
  • Organophosphorus
  • Carbamate
  • Organochlorine
  • Pyrethroids.
 
ORGANOPHOSPHORUS AND CARBAMATE POISONING (TABLE 20.1)
Organophosphorus pesticides inhibit acetylcholinesterase in synapses and on red-cell membranes, and butyrylcholinesterase in plasma. Acute acetylcholinesterase inhibition results in accumulation of acetylcholine and stimulation of acetylcholine receptors in synapses of the neuromuscular junctions, autonomic nervous system.
 
Clinical Features
Although both organophosphorus compound (OPC) and carbamate poisoning produce cholinergic and nicotinic symptoms, the symptoms in carbamates are less severe.
Table 20.1   Organophosphorus compounds and carbamates
Organophosphorus compounds
  • Parathion
  • Monocrotophos
  • Chlorpyrifos
  • Diazinon
  • Fenthion
Carbamates
  • Aldicarb
  • Bendiocarb
  • Carbofuran
154
 
Cholinergic Symptoms
These include increased secretions like salivation, lacrimation, urination, defecation, bronchial secretions, etc. Patients can also have confusion, seizures, miosis and bradycardia.
 
Nicotinic Symptoms
These include muscle twitching, fasciculations, muscle weakness and respiratory paralysis.
 
Intermediate Syndrome
This develops 12 hours–4 days after the consumption of poison and is characterized by weakness of ocular muscles, neck, bulbar, proximal limb and respiratory muscles. This is due to prolonged action of acetylcholine on the nicotinic receptors.
 
Delayed Polyneuropathy
This occurs many months after the consumption of poison and is characterized by weakness of the distal muscles of the legs (foot drop) and small muscles of the hands.
 
Investigations
  • Serum cholinesterase and RBC cholinesterase
  • Gastric aspirate and blood samples for toxicological analysis
  • Complete blood count, electrolytes
  • Renal and liver function test
  • ECG may show ST-T wave changes and arrhythmias
  • Nerve conduction studies.
 
Management
 
General Measures
  • Maintain airway, breathing and circulation
  • Body should be washed thoroughly as OPC can get absorbed through skin also
  • Gastric lavage using normal saline
  • Activated charcoal can be given (1g/kg every 6th hourly for 1–2 days).
 
Specific Measures
  • Atropine: It is the antidote of choice. It should be given at a dose of 1–2 mg every 3–5 minutes till the signs of atropinization occurs which include dry 155axilla, clear lungs, heart rate >80/minute, absent pinpoint pupils and systolic blood pressure >90 mm Hg. But high dose can cause delirium.
  • Pralidoxime: It is a cholinesterase reactivator and is given at a dose of 30 mg/kg bolus infusion (in 100 mL normal saline over a period of 1 hour) followed by 8 mg/kg/hour for next 2 days and 1–2 g IV tds for next 5 days. Certain studies showed lack of benefit when given in low dose but still World Helath Organization (WHO) recommends use of oximes in patients with organophosphorus poisoning who is on atropine. It is not indicated in carbamate poisoning.
  • Benzodiazepines: It is indicated if seizures are present or if the patient develops atropine delirium.
 
ORGANOCHLORINE AND PYRETHROID POISONING (TABLE 20.2)
Table 20.2   Organochlorine compounds and pyrethroids
Organochlorine compounds
  • Endosulfan
  • Aldrin
  • Dieldrin
  • Chlordane
  • Endrin, etc.
Pyrethroids
  • Cypermethrin
  • Cyclothrin
  • Deltamethrin, etc.
 
Clinical Features
Organochlorine toxicity produces nausea, vomiting, diarrhea, paraesthesias, confusion, seizures and coma. The other complications include respiratory failure and liver cell failure. Pyrethroids usually causes only sensory disturbances like burning, tingling sensation and numbness.
 
Management
This includes the general measures that have been outlined under organophosphorus poisoning. There is no specific antidote for these poisons.
Commonly seen plant poisoning include:
  • Oleander
  • Cleistanthus collinus (oduvanthalai).
 
Oleander Poisoning
The common plants are Nerium oleander and Thevetia peruviana. All parts of the plants are poisonous.
156Clinical features
Patients usually present with nausea, vomiting, abdominal pain and numbness in the mouth. Oleander poisoning can affect the heart and in fact, the cardiac involvement is the most common cause of death in this poisoning. The various cardiac effects are bradyarrhythmias, conduction block, myocarditis and cardiac arrest. Hyperkalemia and metabolic acidosis are also seen with this poison.
Management
General measures as outlined above should be followed. If the patient has bradycardia, Inj. atropine 0.6–1.2 mg IV should be given. Oral orciprenaline 10 mg tds can also be given. Temporary pacing should be done in case of significant conduction block.
 
Oduvanthalai Poisoning
It belongs to Cleistanthus collinus and the toxic constituents are dyphyllin, cleistanthin and collinusin. This poison acts by inhibiting Na-K ATPase, cholinesterase and DNA synthesis.
Clinical features
Patient usually presents with nausea, vomiting, diarrhea and abdominal pain. The complications include cardiotoxicity (VT, VF, asystole), renal tubular acidosis, renal failure, coagulopathy, neuromuscular blockade, respiratory failure and hypokalemia (due to renal loss of potassium).
Investigations
These include serum electrolytes, ABG, renal and liver function test, coagulation profile. The ECG changes of this poisoning are QT prolongation, ST depression, VPCs, etc.
Treatment
Apart from the general measures in the management, hypokalemia should be corrected by potassium chloride (KCL) infusion at a rate of around 20 mEq/hr. Serum potassium should be monitored every 4th hourly till it is corrected and then twice a day for the next 5 days. Bradycardia should be managed with Inj. atropine/tab. Orciprenaline/temporary pacing. Ventilatory support and dialysis are indicated in appropriate cases.
 
Rodenticide Poisoning
Rodenticides are used to kill mice, rats and other small rodents. It contain various constituents such as aluminum phosphide, zinc phosphide, warfarin, strychnine, etc.
Clinical features
The clinical features and complications depend on the constituent present in it. Phosphides present as chest pain, pulmonary edema, renal failure and liver failure. Arsenic content cause diarrhea, shock and delirium whereas warfarin causes bleeding diathesis. Stiffness of the limbs is noted in strychnine.
157Treatment
General measures as outlined previously. Specific measures include Inj. vitamin K (1 amp IV for 3 days) and fresh frozen plasma are given for bleeding diathesis and benzodiazepines (diazepam/midazolam) are given if fits occur. Hemodialysis is indicated if renal failure is present.
 
Corrosive Poisoning
Corrosives include acids or alkali or both. Alkalis are more dangerous than the acids as it has the tendency to cause liquefactive necrosis. Common corrosives which are used as poisons are household bleaches and toilet cleaners.
Clinical features
Corrosives cause damage to the skin and produce redness, edema and charring. Consumption of corrosives also cause serious damage to the oral cavity, respiratory tract and gastrointestinal (GIT) resulting in complications like GIT perforation, bronchospasm, pulmonary edema, mediastinitis and shock.
Treatment
Maintain airway, breathing and circulation. Nasogastric tube, neutralization with milk and activated charcoal are contraindicated. Adequate hydration through IV fluids is a must and signs of peritonitis or mediastinitis has to be looked for. Upper GI scopy should be done within 48 hours to assess the severity of the injury.
 
Kerosene Poisoning
Kerosene is a hydrocarbon and accidental ingestion is common in children. It predominantly affects the respiratory system as this volatile chemical may displace alveolar oxygen and also cause damage to the alveolar membranes.
Clinical features
Patient usually presents with cough, fever, nausea, vomiting, abdominal pain, lethargy, etc. On examination, patient may have cyanosis, tachypnea, wheeze and crackles. The complications include seizures, coma, ARDS, myocarditis and arrhythmias.
 
Investigations
 
Chest X-ray
Chest X-ray should be taken for all symptomatic patients. Positive findings are usually seen only after few hours of ingestion and these include perihilar opacities, bibasal infiltrates, atelectasis and rarely pneumothorax or pneumomediastinum.
Treatment
The priority is given to airway stabilization and if necessary, intubation and mechanical ventilation with PEEP should be provided. Routine prophylactic use of corticosteroids or antibiotics is not warranted.158
 
BIBLIOGRAPHY
  1. Aaron CK. Organophosphates and carbamates. In: Ford MD, Delaney KA, Ling LJ, Erickson T, (Eds) Clinical toxicology. WB Saunders Company; Philadelphia; 2001. pp. 819-28.
  2. Aggarwal R, Diddee S. Organophosphate or organochlorines or something else….? Indian J Crit Care Med. 2009;13(1):31-3.
  3. Cannon RD, Ruha AM. Insecticides, herbicides, and rodenticides. In: Adams JG (Ed). Emergency Medicine Clinical Essentials, 2nd edn. Philadelphia, PA: Elsevier Saunder; 2013.
  4. Cherian AM, Peter JV, Samuel J. Effectiveness of P2AM (PAM-pralidoxime) in the treatment of organophosphorus poisoning. A randomized, double blind placebo controlled trial. J Assoc Physicians India. 1997;45:22-4.
  5. Eade NR, Taussig LM, Marks MI. Hydrocarbon pneumonitis. Pediatrics. 1974;54:351-7.
  6. Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet. 2008;371(9612):597-607.
  7. Eddleston M, Singh S, Buckley N. Organophosphorus poisoning (acute). Clin Evid. 2005;13:1744-55.
  8. Fengsheng He. Synthetic pyrethroids. Toxicology. 1994;91:43-9.
  9. He F, Wang S, Liu L, Chen S, Zhang Z, Sun J. Clinical manifestations and diagnosis of acute pyrethroid poisoning. Arch Toxicol. 1989;63:54-8.
  10. Jeyaratnam J. Acute pesticide poisoning: a major global health problem. World Health Stat Q. 1990;43:139-44.
  11. Johnson MK, Jacobsen D, Meredith TJ. Evaluation of antidotes for poisoning by organophosphorus pesticides. Emerg Med. 2000;12:22-37.
  12. Johnson S, Peter JV, Thomas K, Jeyaseelan L, Cherian AM. Evaluation of two treatment regimens of pralidoxime (1 gm single bolus dose vs 12 gm infusion) in the management of organophosphorus poisoning. J Assoc Physicians India. 1996;44:529-31.
  13. Langford SD, Boor PJ. Oleander toxicity: an examination of the human and animal toxic exposures. Toxicology. 1996;109:1-13.
  14. Lotti M. Clinical toxicology of anticholinesterase agents in humans. In: Krieger R (Ed). Handbook of Pesticide Toxicology. 2nd edn. Academic Press; San Diego. 2001;2:1043-85.
  15. McConnell R, Hruska AJ. An epidemic of pesticide poisoning in Nicaragua: implications for prevention in developing countries. Am J Public Health.1993;83:1559-62.
  16. Namba T, Hiraki K. PAM (pyridine-2-aldoxime methiodide) therapy of alkylphosphate poisoning. JAMA. 1958;166:1834-9.
  17. Parikh CK. Parikh Textbook of Medical Jurisprudence and Toxicology, 4th edn. Bombay, Medical Publication; 1989.pp.912-4.
  18. Raghu R, Naik R, Vadivelan M. Corrosive poisoning. Indian J Clini Practice. 2012;23(3).
  19. Thomas K, Dayal AK, Gijsbers A, Seshadri MS. Oduvanthalai leaf poisoning. J Assoc Physicians India. 1987;35:769-71.

DRUG OVERDOSECHAPTER 21

Jenu Santhosh, TA Naufal Rizwan  
SEDATIVES AND HYPNOTICS
These drugs are used in the treatment of insomnia and anxiety disorders. Barbiturates and benzodiazepines are the most important drugs of this group.
 
Clinical Features
The symptoms common to overdose of both these drugs include decreased mentation, hypotension, dysarthria, slurred speech, bradycardia and loss of reflexes. Respiratory depression is seen with overdose of both the drugs, although more severe with the barbiturates. Extensor plantar response, coma and blisters over pressure spots and dorsum of the fingers are seen with barbiturates overdose.
 
Treatment
  • General measures, as previously explained under the chapter of general principles, have to be followed.
  • Forced alkaline diuresis and hemoperfusion are indicated in severe barbiturate poisoning (they are not useful in benzodiazepine poisoning)
  • Flumazenil is the antidote for benzodiazepine poisoning. The dose is 0.2 mg over 30 seconds followed by 0.3 mg at 1 minute intervals to a total dose of 3 mg.
 
ANTIDEPRESSANTS
The commonly used antidepressants are tricyclic antidepressants and SSRIs. Newer drugs such as mirtazepine and venlafaxine are usually less toxic than the tricyclics.
 
Clinical Features
Patients usually present with anticholinergic features such as dilated pupils, urinary retention, dryness of mouth and fever. The two important complications of this poisoning are cardiotoxicity and neurotoxicity. Cardiac involvement is manifested by supraventricular tachycardia, ventricular tachycardia (predicted by QRS duration of limb leads >160 msec), conduction blocks and pulmonary edema whereas CNS involvement is manifested as agitation, confusion, seizures and coma.160
 
Treatment
In addition to the general measures, the cardiotoxic effects of antidepressants are treated by forced alkaline diuresis, hyperventilating the intubated patient (to keep PCO2 no lower than 25 mm Hg) and temporary pacing for conduction blocks. Seizures are treated with benzodiazepines and the CNS depression can be reversed with Inj. Physostigmine (2 mg IV over 1 min).
 
ACETAMINOPHEN POISONING
Acetaminophen poisoning is very common since the drug is freely available over the counter. It mainly affects the liver and the toxicity dose is 140 mg/kg or at least 7.5 g. The mechanism involved in hepatic toxicity is due to the depletion of hepatic glutathione and the subsequent accumulation of a metabolite, N-acetyl-p-benzoquinoneimine.
 
Clinical Features
The usual initial complaints are nausea, vomiting and loss of appetite. Patient will have elevated liver enzymes that can even reach 1000 U/L. Other manifestations are encephalopathy, renal failure, hypoglycemia, metabolic acidosis. Death may be due to fulminant hepatic failure, ARDS, multiorgan failure, sepsis and cerebral edema.
 
Treatment
General measures as discussed under the chapter of general principles have to be followed. Charcoal is not effective when it is given 30 min after drug ingestion. N-acetyl cysteine is the specific antidote and it can be given either IV or oral. The oral dose is 140 mg/kg followed by 70 mg/kg for a total of 17 doses. The IV dose is 150 mg/kg in 200 mL of 5% dextrose over 1 hour followed by 50 mg/kg over 4 hours and 100 mg/kg over 16 hours. N-acetyl cysteine (NAC) prevents the severity of hepatic necrosis in patients who have high acetaminophen levels (>200 µg/mL measured at 4 hour or >50 µg/mL at 12 hour after ingestion). NAC is most effective if it is given within 8 hours of drug ingestion but can be given even till 36 hours of ingestion. Liver transplantation is the treatment in case of fulfillment of the below criteria (Table 21.1).
Table 21.1   Criteria for orthotopic liver transplantation in acetaminophen toxicity
  • Acute hepatic failure (e.g. mental confusion, jaundice, coagulation disturbances)
  • Metabolic acidosis despite fluid resuscitation (pH <7.3, lactate levels >3.5 mmol/L)
  • PT >100 sec, INR >6.5
  • Serum creatinine >3.3 mg/dL or 300 µmol/L
  • Encephalopathy grade ≥III within 24 hour period.
 
OPIOIDS
Opioids cause sedation and respiratory depression at high doses and the peak effect of most opioids occurs within 3 hours but the elimination half-life differs 161with most opioids. Clinical features include pinpoint pupils, bradycardia, hypotension, lethargy, respiratory depression, seizures. Proper history along with lab investigations—serum electrolytes, glucose, arterial blood gases or oximetry, chest X-ray, routine toxic screening is done. Treatment includes usual general measures. Specific treatment includes administration of opioid antagonist— naloxone, nalmefene. Naloxone 0.4–2 mg IV and doses are repeated every 2–3 minutes and upto a total dose of 10–20 mg can be given. Duration of naloxone is 1–2 hours and patient is not discharged until 3–4 hours since the last dose of naloxone. It is better to observe for 6–12 hours. Intubation and mechanical ventilation may be required in case of respiratory failure.
 
BETA-BLOCKERS
Beta-blockers are widely used for the treatment of hypertension, angina pectoris, cardiac arrhythmias, heart failure, glaucoma, etc. Beta-blockers overdose can occur and complications are more with those with cardiac disease. Clinical features include hypotension, bradycardia, prolonged PR interval, heart block, pulmonary edema, cardiac arrest, hyperkalemia. Bronchospasm, seizures, hypoglycemia and coma are not uncommon. Atropine is not effective in these patients although it is commonly used by most physicians. Glucagon is given at a dose of 5–10 mg and followed by infusion of 1–5 mg/hour. Alternatively, adrenaline infusion can be given at a dose of 1–4 µg/minute. Cardiac pacing is done in case of severe bradycardia not responding to medical management. Torsades de pointes can result from Sotalol which can be treated with isoproterenol and magnesium. Correction of hypokalemia may be necessary.
 
BIBLIOGRAPHY
  1. Barnett R, Grace M, Boothe P, et al. Flumazenil in drug overdose: randomized, placebo-controlled study to assess cost effectiveness. Crit Care Med. 1999;27(1):78-81.
  2. Blackford MG, Felter T, Gothard MD, Reed MD. Assessment of the clinical use of intravenous and oral N-acetylcysteine in the treatment of acute acetaminophen poisoning in children: a retrospective review. Clin Ther. 2011;33(9):1322-30.
  3. Jay SJ, Johanson WG Jr, Pierce AK. Respiratory complications of overdose with sedative drugs. Am Rev Respir Dis. 1975;112(5):591-8.
  4. Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscalzo J. Harrison's Principles of Internal Medicine, 18th edn. McGraw Hill publications; 2012.
  5. Mindikoglu AL, et al. Outcome of liver transplantation for drug-induced acute liver failure in the United States: Analysis of the United Network for Organ Sharing database. Liver Transpl. 2009;15:719.
  6. Navarro VJ, Senior JR. Drug-related hepatotoxicity. N Engl J Med. 2006;354:731.
  7. Olson KR. Poisoning and Drug Overdose, 5th edn. McGraw Hill-Publications; 2006.
  8. Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985). N Engl J Med. 1988;319(24):1557-62.
  9. Spiller HA, Krenzelok EP, Grande GA, Safir EF, Diamond JJ. A prospective evaluation of the effect of activated charcoal before oral N-acetylcysteine in acetaminophen overdose. Ann Emerg Med. 1994;23(3):519-23.
  10. Worthley LI. Clinical toxicology: part I. Diagnosis and management of common drug overdosage. Crit Care Resusc. 2002;4(3):192-215.

ENVENOMATIONCHAPTER 22

Jenu Santhosh  
SCORPIONS (SCORPIONIDAE)
Scorpions are found in many parts of the world. Toxic species of scorpions are found in India also. They are generally nocturnal and capable of stinging humans. They have paired venom glands in a bulbous segment called the telson.
 
Clinical Features
C. exilicauda venom causes prolonged depolarization due to opening of neuronal sodium channels. Somatic and autonomic nerves can be affected. Cranial nerve palsy can occur in severe cases causing abnormal eye movements, blurred vision and respiratory failure. Motor dysfunction can present with jerking of limbs mimicking like seizures. Symptoms like nausea, vomiting, agitation and tachycardia can be severe due to the sting especially in children. Pain, paresthesias in the area of sting are the initial symptoms which later may become generalized. Symptoms can last for 24–48 hours without antivenom treatment. The complications of scorpion sting include pulmonary edema, cardiac dysfunction, pancreatitis, bleeding diathesis, skin necrosis and occasionally death. Diagnosis of scorpion sting is primarily clinical since it can be confused with other conditions causing local pain.
 
Treatment
Initial treatment is mainly supportive with analgesics. Scorpion antivenom can be used if available. Local toxic agency help should be sought for dosage and use of antivenom. Both immediate and delayed allergic reactions including serum sickness can occur with the use of antivenom and hence antivenom administration should be reserved for cases of severe systemic toxicity. Some studies have demonstrated lack of benefit in the routine administration of antivenom for scorpion stings although antivenom produces rapid resolution of symptoms in severe toxicity. Usually 1–2 vials are sufficient for severe cases.
 
CATERPILLARS AND MOTHS (LEPIDOPTERA)
The adverse effects resulting from contact with caterpillars, butterflies and moths are called lepidopterism.163
 
Clinical Features
Caterpillars are the larval stage of moths and have either spines or hairs for protection. The spines and hairs may cause mechanical irritation, whereas the venom can produce additional symptoms. Most of the caterpillars are harmless to humans. Pruritus from localized caterpillar dermatitis and diffuse urticaria are the predominant symptoms with exposure to the hairs and venom. With certain species, intense local burning pain rather than pruritus is typical. A grid like pattern of hemorrhagic papules may be seen within 2–3 hours of exposure and may last for several days. Regional lymphadenopathy is common, and the affected limb can swell considerably. Other symptoms include headaches, fever, hypotension, and convulsions. Mortality due to caterpillar contact is rare.
 
Treatment
No antivenom is available till date and the treatment is mainly symptomatic and supportive. Spines of caterpillars can be removed by adhesive tape. Antihistamines and steroids may be administered for pruritus. Intravenous fluids and subcutaneous epinephrine may be needed if hypotension arises.
 
REPTILE BITES
 
Introduction
Snake bite is very common in India since most of the population resides in the rural areas which is a home for many species of snakes. Mortality due to snake bite is quite high in India due to superstitions and delay in the administration of antivenom. The major venomous snakes can be divided into the following groups.
  • Viperidae (vipers)
  • Elapidae
  • Hydrophinae (sea snakes).
 
Crotalinae (Pit Viper) Bites
Crotaline snakes are also called as pit vipers and they are distinguished from other snakes by the presence of two fangs that fold against the roof of the mouth, in contrast to the coral snakes, which have shorter, fixed, and erect fangs and bilateral pits present midway below and between the eye and the nostril.
 
Pathophysiology
The venom of these species contains a complex enzyme which can cause systemic and local tissue injury. Hemolysis, fibrinolysis, increased vascular permeability, hypovolemia and dysfunction of the neuromuscular junction are the manifestations. Coagulopathy is due to activation and consumption of fibrinogen and platelets. Ptosis due to cranial nerve palsy, respiratory failure and mental confusion are other features. 164
 
Clinical Features
Clinical manifestations of snake bite depend on the following:
  • Age of the victim
  • Species of snake
  • Characteristics of the bite (location, depth, and number, the amount of venom injected)
  • Time elapsed since the bite.
About 1/4th of the snake bites are dry and do not result in any manifestations. Usually fang marks are seen, localized pain, edema on the site of bite which can be progressive, oral numbness, tingling sensation, tachycardia, muscle fasciculation, altered consciousness can be seen. Usually local edema occurs within 30 minutes but in severe cases, edema can be very severe and that too can progress very fast to the entire limb. Airway edema can occur which in turn causes upper airway obstruction. Ecchymosis and coagulopathy are other clinical manifestations.
 
Diagnosis
It is based on eliciting history and the presence of fang marks. Snake bite can manifest with the features given in Flow chart 22.1.
The absence of any of these manifestations for a period of 8–12 hours following the bite indicates a dry bite.
 
Treatment
First aid
First aid measures should never substitute or delay the definitive treatment for snake bite (administration of antivenom). All patients bitten by a pit viper should be taken to a hospital (Table 22.1). Suction of the bite site, ice application, application of electric shock, tourniquet application and incision of the site of bite are dangerous and should not be performed. Application of tourniquet obstructs arterial flow and can cause ischemia, hence is contraindicated.
Flow chart 22.1: Manifestations of snake bite
Table 22.1   Recommended first aid measures for snake bite
  • Evacuate the patient from the danger zone to prevent another bite
  • Immobilization of the bitten limb in a neutral position to prevent absorption of venom
  • Minimize physical activity
  • Transfer the patient to hospital where antivenom is available.
165
 
Emergency Management
As an emergency measure, an intravenous access, administration of oxygen and limb immobilization can be done before transfer to a health facility where antivenom is available. Tourniquets and constriction bands if present should not be removed until intravenous access is established and in case of hypotension, rapid intravenous isotonic fluid infusion is given.
Antivenom is the mainstay of therapy for poisonous snakebite. Composition of antivenom is antibodies derived from the serum of animals injected and immunized with snake venom. Patients who show progressive signs and symptoms (local signs, coagulopathy and hypotension) after snake bites with pit vipers should be given antivenom immediately. Recent trials have shown that FabAV is more effective and safe than polyvalent antivenom. FabAV does not require local skin testing and administered as a single large initial dose followed by three maintenance doses. Initial dose is 4–6 vials which can be repeated if necessary based on initial control (cessation of progression of local signs, systemic effects, and coagulopathy). After initial control has been achieved, 2 vials are given as maintenance doses. Antivenom should be administered only in ICU with all the resuscitative drugs for anaphylactic reaction kept ready. Dilution of antivenom is done with 250 mL of crystalloid and intravenously infused slowly over 10 minutes initially to watch for anaphylaxis followed by total infusion within 1 hour. Intramuscular route is not recommended. In case of any anaphylactic/anaphylactoid reaction, infusion is terminated immediately and antihistaminics, corticosteroids are given. Adrenaline is administered in case of severe allergic reactions. In case of hypotension, isotonic fluids like normal saline or ringer lactate is used, if hypotension sustains after fluid administration, then vasopressors are given. Antivenom administration itself corrects coagulopathy but in case of active bleeding despite antivenom may require plasma. Monitoring limb circumference every 30 minutes is one of the guides for antivenom effectiveness. Lab parameters are done every 4 hours.
Compartment syndrome is one of the complications which occurs due to increased compartment pressure due to venom spread into the muscle compartment which manifests as severe pain. The use of fasciotomy in compartment syndrome due to snake bite is controversial (Table 22.2).
Table 22.2   Management of compartment syndrome
  • Determine intracompartmental pressure
  • If not elevated, continue the usual management
  • If signs of compartment syndrome are present and compartment pressure is >30 mm Hg:
    • Elevate limb
    • Mannitol is given at a dose of 1–2 g/kg IV over 30 minutes
    • Simultaneously administer additional antivenom, 4–6 vials IV over 60 minutes
    • Consider fasciotomy in case of elevation in compartment pressure which is persistent for another 1 hour.
166Tetanus immunization is done and antibiotic therapy should be started only if there is presence of infection. The use of steroids is controversial. Delayed serum sickness can present with fever, rash, and arthralgias and should be treated with oral prednisone 60 mg/day and tapered over 1–2 weeks.
 
Discharge Criteria
Patients can be discharged once the swelling begins to subside, coagulopathy is reversed, and patient is ambulatory. Patients with dry bites should be observed for at least 8 hours. Follow-up is required.
 
Coral Snake (Elapid) Bite
Elapids are found throughout the world in tropical and warm climates. Cobras (Naja), kraits and mambas belong to this group. Elapid bites produce primarily neurologic effects like diplopia, dysarthria, ptosis along with bulbar paralysis, dysphagia, dyspnea, contracted pupils, tremors, salivation, respiratory failure and rarely seizures. The usual immediate cause of death is paralysis of respiratory muscles although the clinical manifestations can be delayed up to 12 hours.
Respiratory failure results from the effects of neurotoxin, hence measuring maximal inspiratory pressure and vital capacity can be useful in these patients. Patient needs to be observed for signs of respiratory muscle weakness and reduced ventilation. Local swelling is monitored every hour after snake bite by measuring limb circumference, the presence and extent of local ecchymosis, and assessment of circulation.
 
Treatment
First aid measure
Aim of initial first aid measure is to delay absorption of venom till the patient is shifted to hospital where antivenom is available. Patients with elapid snake bites should have their limb wrapped in an elastic bandage applied initially over the bite site and then covering the entire limb. The limb is then splinted to prevent movement. The principles behind these measures are to prevent systemic absorption of the venom. Application of tourniquet obstructs arterial flow and can cause ischemia, hence is contraindicated.
 
Emergency Management
History of snakebite or suspected cases should prompt the initiation of investigation and observation. The pressure bandage should be kept in place until the patient receives antivenom. If there is immediate deterioration of the patient after bandage removal, the bandage can be reapplied while antivenom is given.
Antivenom should be administered only in patients who have clinical or laboratory evidence of envenomation. Investigations include complete blood count, serum electrolytes, renal and liver function test, coagulation profile, creatine kinase, and urine testing for hematuria or myoglobinuria. Abnormal renal 167or coagulation parameters should warn the physician of imminent neurological effects since systemic envenomation has occurred. In case of increased PT, aPTT, serum fibrinogen and FDP degradation products are done (Table 22.3).
Table 22.3   Indications of antivenom
  • Neurological effects such as diplopia, dysarthria, ptosis along with bulbar paralysis, dysphagia, dyspnea, contracted pupils, tremors
  • Vomiting and severe headache
  • Progressive muscle weakness with diaphragmatic involvement
  • Coagulopathy
It is recommended that 3–5 vials of antivenom be administered to patients who have been bitten if there is evidence of the above indications. If there is no clinical or laboratory evidence of venom effect, the elastic bandage should be removed and the patient observed for 12 hours. Coagulation profile should be repeated every 2 hours after bandage removal. When indicated, antivenom should be given immediately and there is no difference in dosage between an adult and children. Pregnancy is not a contraindication to antivenom therapy.
Skin testing before antivenom administration is not recommended as it may sensitize the patient to future antivenom use and delays definitive therapy. Anaphylaxis is a rare complication of antivenom therapy, hence administration of a small subcutaneous dose of 0.3 mL of 1:1000 epinephrine (adrenaline) in an adult or 0.1 mL in a child along with a parenteral antihistamine is the author's suggestion. A 5-day course of oral prednisolone can be prescribed to reduce the incidence of serum sickness in those patients who receive large doses of antivenom.
 
Cobra Bite
Cobras are mostly found in southern Asia and very commonly seen in India and also in Africa. Nearly ½ of the bites are dry. Certain species of cobras have the ability to spit jets of venom toward the victim's eyes.
Cobra venom contains a mixture of toxins.
  • Neurotoxin is the predominant effect of cobra snakes. They bind to postsynaptic acetylcholine receptors and produce depolarizing neuromuscular blockade.
  • Cell membrane toxins produce cardiac arrhythmias and impaired contractility.
  • Enzymes can breakdown protein and connective tissue.
 
Clinical Features
Pain at the bite site, local swelling, cranial nerve dysfunction (ptosis, diplopia, dysphagia), generalized muscle weakness followed by paralysis, respiratory failure, altered sensorium, hemodynamic instability and parasympathetic stimulation (salivation and bronchorrhea) are all clinical manifestations. Victims injured in the eye of venom present with pain, burning sensation, and blurred vision. Skin reaction around the bite site may develop over 48 hours with local 168hemorrhage and necrosis. Coagulopathy is rare following a cobra bite with exception of spitting cobra.
 
Treatment
First aid
The pressure-immobilization technique used for common snakes has not been found to be useful with cobra bites. The constricting elastic bandage can be used although still not recommended. In case of venom exposure to the eyes, irrigation of eyes is useful.
Emergency treatment
The mainstay of treatment found to be effective for cobra bite is administration of polyvalent antivenom. Antivenom is obtained by antibodies derived from the serum of animals injected and immunized with snake venom obtained from several cobra species in that region but there is high incidence of allergic reactions with this antivenom. Antivenom is started before releasing the bandage in patients with evidence of systemic toxicity but antivenom is effective only for reducing systemic toxicity and not for reducing local tissue injury. For patients with significant muscle weakness or paralysis, anticholinesterases like neostigmine can produce short-term benefit till antivenom are available. Hypotension is treated with fluids and vasopressors. In case of respiratory failure, intubation and mechanical ventilation is started.
Disposition
Patients without signs of envenomation should be observed in ICU for 24 hours since signs of systemic toxicity usually occur in 2–6 hours and mortality is common during this period. Patient may take 1 week to recovery in case of antivenom administration and supportive treatment.
 
BIBLIOGRAPHY
  1. Burgess JL, Dart RC, Egen NB, Mayersohn M. The effects of constriction bands on rattlesnake venom absorption: A pharmacokinetic study. Ann Emerg Med. 1992; 21:1086.
  2. Bush SP, Hegewald K, Green SM, et al. Effects of a negative pressure venom extraction device (Extractor) on local tissue injury after artificial rattlesnake envenomation in a porcine model. Wilderness Environ Med. 2000;11:180.
  3. Dart RC, McNally J. Efficacy, safety, and use of snake antivenoms in the United States. Ann Emerg Med. 2001;37:181.
  4. Dart RC, Stark Y, Fulton B, et al. Insufficient stocking of poisoning antidotes in hospital emergency departments. JAMA. 1996;276:1508.
  5. Davidson TM, Schafer S, Killfoil J. Cobras. Wilderness Environ Med. 1995;6:203.
  6. Gold BS, Dart RC, Barish RA. Bites of venomous snakes. New Engl J Med. 2002;347:347.
  7. Gold BS. Neostigmine for the treatment of neurotoxicity following envenomation by the Asiatic cobra. Ann Emerg Med. 1996;28:87.
  8. Hawdon GM, Winkel KD. Could this be snakebite? Aust Fam Physician. 1997;26:1386-94.
  9. Howath DM, Southee AE, Whyte IM. Lymphatic flow rates and first-aid in simulated peripheral snake or spider envenomation. Med J Aust. 1994;161:695.
  10. 169Kent R Olson. Poisoning and Drug Overdose, 5th edn. 2006. McGraw Hill Publications.
  11. Kitchens CS, Van Mierop LHS. Envenomation by the eastern coral snake (Micrurus fulvius fulvius): A study of 39 victims. JAMA. 1987;258:1615.
  12. Langley RL, Morrow WE. Deaths resulting from animal attacks in the United States. Wilderness Environ Med. 1997;8:8.
  13. Lee C, Ryan M, Arnold T. Local manifestations of Agkistrodon contortrix (copperhead) envenomation treated successfully with Crotalidae polyvalent immune Fab (ovine) Crofab [abstract 214]. J Toxicol Clin Toxicol. 2001;39:559.
  14. Offerman SR, Bush SP, Moynihan JA, Clark RF. Crotaline Fab antivenom for the treatment of children with rattle snake envenomation. Pediatrics. 2002;110:968.
  15. Pochanugool C, Limthongkul S, Wilde H. Management of Thai cobra bites with a single bolus of antivenin. Wilderness Environ Med. 1997;8:20.
  16. Ruha AM, Curry SC, Beuhler M. Initial postmarketing experience with Crotalidae Polyvalent Immune Fab for treatment of rattlesnake envenomation. Ann Emerg Med. 2002;39:609.
  17. Sutherland SK. Antivenom use in Australia. Premedication, adverse reactions and the use of venom detection kits. Med J Aust. 1992;157:734.
  18. Sutherland SK. Deaths from snake bite in Australia, 1981–1991. Med J Aust. 1992;157: 740.
  19. Tagwireyi DD, Ball DE, Nhachi CF. Routine prophylactic antibiotic use in the management of snakebite. BMC Clin Pharmacol. 2001;1:4.
  20. Tibballs J. Premedication for snake antivenom. Med J Aust. 1994;160:4.
  21. White J. Bites and stings from venomous animals: A global overview. Ther Drug Monit. 2000;22:65.
  22. White J. CSL Antivenom Handbook. Melbourne, Australia, CSL Ltd, 2001.
  23. White J. Envenoming and antivenom use in Australia. Toxicon. 1998;36:1483.
170Burns
Chapter 23 Classification and Evaluation of Burns Prem Kumar
Chapter 24 Management of Burns Prem Kumar171

CLASSIFICATION AND EVALUATION OF BURNSCHAPTER 23

Prem Kumar
The incidence of burns in India is 6–7 million per year. About 10% of these are life-threatening and require hospitalization, and they require multiple surgeries and prolonged rehabilitation.
 
CLASSIFICATION
There are 3 zones, 5 depths and 5 causative types of burns injury.
 
Three Zones
  1. Zone of coagulation
  2. Zone of stasis
  3. Zone of hyperemia.
 
Five Depths (Fig. 23.1)
  1. First degree—superficial two epidermal
  2. Second degree—it has two types: Superficial and deep partial thickness
  3. Third degree—full thickness
  4. Fourth degree—involvement of deep structures such as muscle and bone.
 
Five Causative Types
  1. Hot liquids
  2. Fire—flame
  3. Contact with hot objects
  4. Chemical
  5. Electrical conduction.
 
PHYSIOLOGICAL DISTURBANCES (TABLE 23.1 AND Flow chart 23.1)
Burns can affect all systems but it depends on the type of burns, depth of involvement and the timing of postinjury.174
Fig. 23.1: Layers of skin and depth of burns
Table 23.1   Physiological disturbances due to burns on various systems
  • Respiratory system:
    • Early phase—Inhalational injury causing airway obstruction, CO poisoning.
    • Delayed phase–After few days, patient may develop ARDS, pulmonary embolism, pneumonia, respiratory failure.
    • Presence of inhalational injury is an indication for endotracheal intubation.
  • Cardiovascular system: Hypovolemia causing reduced tissue perfusion and lactic acidosis. Myocardial depression and venous thromboembolism.
  • Central nervous system: Seizures due to hyponatremia, peripheral nerve injury.
  • Gastrointestinal system: Curling's ulcer, acute necrotizing enterocolitis, acalculous cholecystitis, pancreatitis, hepatic dysfunction due to reduced hepatic blood flow.
  • Renal system: Acute renal failure occur due to reduced renal blood flow.
  • Endocrine system: Acute adrenal insufficiency can occur due to necrosis.
  • Hematology: Anemia, platelet dysfunction, thrombocytopenia, DIC.
  • Eye: Corneal ulcer, ectopia.
 
BURNS ASSESSMENT
History: Ample history is asked and the cause and duration of burns is elicited.
Clinical assessment of burns is based on:
  • Burns surface area estimation—rule of Nines, Lund and Browder chart, hand method (Figs 23.2 and 23.3).
  • Depth of burns (Table 23.2)
  • Presence or absence of circumferential burns.175
Flow chart 23.1: Pathophysiology of burns
Abbreviations: ROS, reactive O2 species; SIRS, systemic inflammatory response syndrome
Fig. 23.2: Rule of Nine chart
176
Fig. 23.3: Lund and Browder chart
Table 23.2   Depth of burns and its features
Depth of burns
Skin color
Sensory
Blisters
Wound healing
1st degree (Figs 23.4A and B)
Red and blanch to touch
Painful
Absent
  • Within 1 week
  • No scarring
2nd degree—superficial partial (Figs 23.5A to C)
Pink, may blanch to touch
Painful
Present
  • Within 2 weeks
  • May need skin grafting
  • Heals with scarring
2nd degree—deep partial (Figs 23.6A to C)
Red/white
Painful
Variable
  • Within 2–3 weeks
  • Needs skin grafting
  • Heals with scarring
3rd degree—full thickness (Figs 23.7A to C)
Black or cherry red
Painless
Absent
  • Needs skin grafting
  • Heals with scarring
Figs 23.4A and B: I Degree: Burns
177
Figs 23.5A to C: II Degree: Superficial burns
Figs 23.6A to C: II Degree: Deep burns
In the hand method of burns assessment, 1% of total body surface area equals palm and fingers of the patient's hand.
Patient with burns requires complete initial evaluation similar to evaluation of a trauma patient but with some differences. Once the initial evaluation is over, burn specific secondary survey should be done to recognize the insults on various systems.178
Figs 23.7A to C: III Degree, burns (Courtesy: Dr Surya C Rao MS, MCH, Plastic Surgeon)
 
Initial Evaluation
Airway compromise can occur due to pharyngeal edema/laryngeal edema which can cause airway obstruction. Hence, the decision to intubate the patient should be done at the earliest with clinical judgment. Securing the airway in burns patient is quite challenging due to airway edema. Endotracheal tube is secured with a tie over the back of neck.
 
Indications of Endotracheal Intubation
  • Airway obstruction due to pharyngeal or laryngeal edema
  • Depressed level of consciousness
  • Hypoxemia not responding to treatment with oxygen
  • Circumferential full thickness nasolabial burns.
 
Modes of Securing the Airway
  • Nasal/oral intubation—blind or fiberoptic bronchoscopy guided
  • Laryngeal mask airway
  • Needle/surgical cricothyroidotomy
  • Surgical tracheostomy
Intravenous access is initially done with peripheral vein for initial resuscitation followed by central venous access for fluid management. 179
 
SECONDARY SURVEY
  • History of injury
  • Head and face evaluation: Look for eye globe injury (clouded appearance over cornea), signs of inhalational injury (singed hairs, carbonaceous debris), any pressure point over injured areas, whether endotracheal tube is secured with tie.
  • Central nervous system evaluation: Look for neurologic injury, order for CT-brain and spine, if needed, pain and sedation management should be started as early as possible (narcotics, benzodiazepines), determine CO-Hb level to avoid CO toxicity.
  • Look for chest wall movement and examine neck: If there is deep circumferential burns, patient may require escharotomy to increase ventilation and increase venous drainage.
  • Evaluation of volume status: Most of the patients are hypovolemic. Start resuscitation according to calculated fluid volumes with various formulas.
  • Evaluation of extremities: In case of fracture, external splinting is done. Doppler is done to determine blood flow so that escharotomy or fasciotomy can be done, if there is vascular compromise.
  • Look for lab investigations: Do arterial blood gas analysis, CO-Hb level, serum urea, creatinine to rule out renal involvement, chest radiography is done to rule out rib injury, pneumothorax, placement of central venous catheter.
 
BIBLIOGRAPHY
  1. C Brunicardi F. Schwartz's Principles of Surgery, 8th edn. McGraw-Hill Publications; 2004.
  2. Civetta JM, Taylor RW, Kirby RR. Critical Care, 4th edn. Philadelphia: Lippincott-Raven; 2009.
  3. Gupta JL, et al. National Programme for Prevention of Burn Injuries. Indian J Plast Surg. 2010;43(Suppl):S6-10.
  4. Hettiaratchy S, Papini R. Initial management of a major burn: Overview. BMJ. 2004; 328(7455):1555-7.
  5. Irwin, Richard S Rippe, James M Irwin, Rippe's Intensive Care Medicine, 6th edn. Lippincott Williams and Wilkins Publications; 2008.
  6. Stabilization, transfer and transport, in Advanced Burn Life Support Course Instructor Manual. Chicago, American Burn Association. 2005.pp.73-8.

MANAGEMENT OF BURNSCHAPTER 24

Prem Kumar
Burns are managed in three phases:
  1. Early resuscitative phase
  2. Wound management phase
  3. Rehabilitative and reconstructive phase.
Gupta et al. proposed a strategy for management of patient with burns— maintain circulation and blood pressure (shock management), maintain airway, increase body resistance, avoid bacterial toxemia, avoid autotoxemia, watch for renal complications and multiple organ dysfunctions, maintain nutrition, abide by principles of biomechanical physiotherapy and rehabilitation and analyze factors for reducing mortality. Burns referral criteria is given in Table 24.1 and priorities in managing burns patient is given in Table 24.2.
 
EARLY RESUSCITATIVE PHASE
Massive capillary leak leading to increased capillary permeability ending up in hypovolemia is the major alteration in this phase. Other reasons for fluid loss are decreased reflection coefficient to proteins, increased evaporation of fluid from wound surface, increased metabolic rate. Hence, fluid resuscitation plays a major role in the management of this phase. Burns >15% requires calculation of fluid infusion. There are many formulas for calculating volume requirements but repeated re-evaluation is necessary. Currently, crystalloids are the recommended fluid for burns patient. Although the role of colloid has been conflicting, still it is used in some certain European countries.
Table 24.1   Burn center referral criteria
The American Burn Association (ABA) criteria for referral
  • Partial-thickness burns involving more than 10% of the total body surface area
  • Full-thickness burns involving 1% or more of the total body surface area
  • Less-extensive burns involving face, hands, feet, genitalia, perineum, or major joints
  • Significant electric burns (including lightning injury), significant chemical burns, significant inhalation injury
  • Lesser burns in patients with preexisting medical conditions that can complicate management, prolong recovery, or affect mortality
  • Lesser burns in association with concomitant trauma sufficient to influence outcome
  • Any size burn in a child in a hospital without qualified personnel or the equipment needed for the care of children
  • Any size burn in a patient who will require special social or psychiatric intervention or long-term rehabilitation
181
Table 24.2   Priorities in managing burns patient
A
Airway management
B
Breathing
C
Circulation
D
Drugs-analgesics/vasopressors/inotropes/antibiotics/sedatives
E
Escharotomy
F
Fluid management
G
General supportive care—physiotherapy/nutrition
Table 24.3   Formulas for fluid calculation in burns
Formula
Initial 24 hours
Next 24 hours
Parkland
Ringer's lactated (RL) solution 4 mL/kg/% burn, of which 50 % should be administered over 1st 8 hours
Colloids given as 20–60% of calculated plasma volume. Glucose in water (5%) is added in amounts required to maintain a urinary output of 0.5–1 mL/hour
Modified Parkland
RL 4 mL/kg/% burn
Begin colloid infusion of 5% albumin 0.3–1 mL/kg/% burn/per hour
Brooke
RL solution 1.5 mL/kg/% burn plus colloids 0.5 mL/kg/% burn plus 2000 mL glucose in water (5%)
RL 0.5 mL/kg/% burn, colloids 0.25 mL/kg/% burn and the same amount of glucose in water (5%) as in the first 24 hours
Modified Brooke
RL solution 2 mL/kg/% burn
Colloids at 0.3–0.5 mL/kg/% burn. Glucose in water (5%) is added in the amounts required to maintain good urinary output (0.5–1 mL/hour).
Evan's
Crystalloids 1 mL/kg/% burn plus colloids at 1 mL/kg/% burn plus 2000 mL glucose in water (5%).
Crystalloids at 0.5 mL/kg/% burn, colloids at 0.5 mL/kg/% burn and the same amount of glucose in water (5%) as in the first 24 hours
Monafo
Recommends using a solution containing 250 mEq Na, 150 mEq lactate and 100 mEq Cl. The amount is adjusted according to the urine output.
Solution is titrated with 1/3 normal saline according to urinary output
Formulas used for fluid volume calculation (Table 24.3) are:
  • Parkland formula
  • Modified Parkland formula
  • Brooke formula
  • Modified Brooke formula
  • 182Muir and Barclay formula
  • Evan's formula
  • Monafo formula.
These formulas take body surface area and body weight into account for fluid volume calculation in adults.
 
End Points of Fluid Resuscitation
  • Clinical—peripheral pulses felt and consciousness not obtunded
  • Urine output >0.5 mL/kg/hour
  • Base deficit <2
  • Systolic blood pressure >90 mm Hg.
 
WOUND MANAGEMENT PHASE
After 18–24 hours of burns injury, patient goes into a hypermetabolic phase (Table 24.4). In case of full thickness burns, excision and grafting is required unless they are less than 1 cm in diameter. Grafting is done within three weeks to minimize scarring. Determination of immunization status is done for tetanus.
 
Perioperative Care of Burns Patient
Burns patient often come to OT for wound excision, closure, fasciotomy/escharotomy. Hence proper perioperative management should be done with the pathophysiological understanding. Airway assessment and management is the key in managing burns patient. Difficult airway guidelines should be followed in case of anticipated difficult airway with all the alternative airway equipment such as fiberoptic bronchoscope, laryngeal mask airway, cricothyroidotomy in place. Use of depolarizing muscle relaxants (succinylcholine) is usually avoided after the 24 hours of burns until 1 year due to the risk of hyperkalemia (extrajunctional receptors).
Table 24.4   Issues to be addressed in the hypermetabolic phase
Fluid management
Nutritional support
Temperature control
Infection control
Analgesia
Adequate fluid management should be done according to the formulas given above.
  • Enteral nutrition through nasogastric tube
  • If there is ileus, hemodynamic instability— start parenteral nutrition
Calorie = 1.5 × BMR (REE)
Protein = 2.5 g/kg/day
  • Avoid hypothermia since hypothermia increases fluid loss
  • Maintain high ambient temperature and humidity
  • Topical agents (0.5% silver nitrate, mafenide acetate, silver sulfadiazine)
  • Excision of deep burn tissue is the best method to prevent sepsis
  • If there is suspected infection, start empirical antibiotics until culture report is awaited
  • As such prophylactic antibiotics are not recommended
Can be based on whether patients are intubated or nonintubated:
  • Intravenous opioids are the mainstay of analgesia in burns patient. (e.g. morphine, fentanyl)
  • Ketamine can be used in low doses (0.5–1 mg/kg) in case of opioid tolerant patients or burns dressing
183
 
REHABILITATIVE PHASE
Occupational therapy is done by using range of motion exercises and splinting to avoid contracture at various sites. Multidisciplinary team should help the patient return to the community but it is time consuming.
 
Carbon Monoxide Poisoning
Those who have history of structural fires have increased risk of carbon monoxide (CO) poisoning. CO-Hb because of its higher affinity to O2 causes inhibition of cytochrome enzymes and causes ODC curve to be shifted to the left which in turn leads to tissue hypoxia. CO-Hb > 50% can obtund consciousness and cause cardiovascular depression.
 
MANAGEMENT OF CARBON MONOXIDE POISONING
100% normobaric O2/HBO (Hyperbaric O2) can be given. Though there are conflicting evidence in the usage of HBO for CO poisoning, still it is imperative to use HBO in patients who are comatose and with high CO-Hb levels. Recommendation is to use 2–3 atm for 90 minutes with three 10 minutes airbreak.
 
Chemical Burns
Most agents can be irrigated with tap water for half an hour. Litmus paper can be used as a guide for irrigation until we get neutral pH. Hydrofluoric acid cause chemical injury to skin and it binds calcium and cause severe hypocalcemia, hence 10% calcium gluconate is used. Deep burns require immediate wound debridement.
 
Electric Injury
It can cause both local and systemic effects. Voltage up to 1000 volts have local wounds which may need debridement and closure with skin grafts and flaps. High voltage electric injury (>1000 volts) cause systemic effects such as myocardial injury, fractures, compartment syndrome, rhabdomyolysis. Hence, monitoring should be done for at least 2–3 days. Compartment syndrome will require decompression if diagnosed over serial examination. Fluid resuscitation may be tricky in these patients since the percentage of burns does not correlate well with tissue injury.184
 
COMPLICATIONS
  • Fluid loss, hypovolemia and shock
  • Respiratory distress due to inhalational injury
  • Infection
  • Increased plasma viscosity and thrombosis
  • Distal ischemia due to circumferential burns
  • Severe muscle damage leading to rhabdomyolysis which in-turn may cause renal failure
  • Hemoglobinuria and renal damage
  • Cyanide poisoning
  • Hypertrophic scarring.
 
BIBLIOGRAPHY
  1. Barret JP. In: Principles and practice of burn surgery. Barret-Nerin JP, Herndon DN, Eds. New York: Marsel Dekker; 2005. pp. 1-32.
  2. Baxter C. Fluid volume and electrolyte changes in the early post-burn period. Clin Plastic Surg. 1974;1:693-703.
  3. Baxter CR. Fluid resuscitation, burn percentage, and physiologic age. J Trauma. 1979;19:864-6.
  4. Fodor L, Fodor A, Ramon Y, Shoshani O, Rissin Y, Ullman Y. Controversies in fluid resuscitation for burn management: Literature review and our experience. Injury Int J Care injured. 2006;37:374-9.
  5. Gupta JL. Ten commandments of burn management. Indian J Burns. 2012;20:7-10.
  6. Haberal M, Sakallioglu Abali AE, Karakayali H. Fluid management in major burn injuries. Indian J Plast Surg. 2010;43(Suppl):S29-36.
  7. Kucan JO. Thermal burns: resuscitation and management. In: Cohen M, Goldwyn RM, eds. Mastery of plastic and reconstructive surgery. New York: Little Brown; 1994. pp. 400-6.
  8. Monafo WW. Treatment of burn shock by intravenous and oral administration of hypertonic lactated saline solution. J Trauma. 1970;10:575-86.
  9. Scheulen JJ, Munster AM. The Parkland formula in patients with burns and inhalation injury. J Trauma.1982;22:869-71.
  10. Warden GD. Burn shock resuscitation. World J Surg. 1992;16:16-23.
185Respiratory Diseases in Intensive care unit
Chapter 25 Approach to Acute Respiratory Failure Prem Kumar
Chapter 26 Acute Lung Injury and Acute Respiratory Distress Syndrome Prem Kumar
Chapter 27 Acute Exacerbation of Chonic Obstructive Pulmonary Disease Prem Kumar
Chapter 28 Acute Severe Asthma Prem Kumar
Chapter 29 Deep Venous Thrombosis and Pulmonary Embolism Prem Kumar, Marun Raj
Chapter 30 Obstructive Sleep Apnea and Obesity Hypoventilation Syndrome Prem Kumar186

APPROACH TO ACUTE RESPIRATORY FAILURECHAPTER 25

Prem Kumar
Respiratory failure is a common problem in intensive care unit (ICU) and its management is vital to any intensivist. Respiratory failure is broadly divided into four broad categories (Tables 25.1 and 25.2).
  1. Hypoxemic (Type 1)
  2. Hypercapnic (Type 2)
  3. Perioperative (Type 3)
  4. Shock (Type 4).
  • Hypoxemic respiratory failure is defined as a partial pressure of oxygen in arterial blood (PaO2) of less than 60 mm Hg when the fraction of inspired oxygen (FiO2) is 0.60 or more.
  • Hypercapnic respiratory failure is defined as a partial pressure of carbon dioxide in arterial blood (PaCO2) of more than 45 mm Hg.
  • Type 3 respiratory failure is perioperative respiratory failure usually due to atelectasis and shunting.
  • Type 4 respiratory failure is due to shock and hypoperfusion of respiratory muscles.
Table 25.1   Causes of acute respiratory failure
  • Central causes: Trauma, cerebrovascular accident, central nervous system infections, raised intracranial tension, drugs like opioids, intravenous anesthetics (e.g. thiopentone), sedative agents (e.g. midazolam)
  • Neuromuscular disorders and drugs: Myasthenia gravis, Guillain Barré syndrome, drugs like organophosphates, neuromuscular blockers, botulism
  • Electrolyte disturbances: Hypokalemia, hypophosphatemia
  • Airway disorders: Bronchial asthma, acute exacerbation of chronic bronchitis or emphysema, obstruction of airway by foreign body, edema or mass
  • Lung parenchymal diseases: Pneumonia, aspiration, lung contusion, pulmonary edema
  • Circulation: Pulmonary embolism, heart failure
  • Chest wall: Rib fracture, flail chest
  • Pleural disorders: Pneumothorax, pleural effusion
188
Table 25.2   Etiology of various types of respiratory failure
Type 1
Type 2
Type 3
Type 4
Pulmonary edema
Lung infection
Aspiration
Near drowning
Alveolar hemorrhage
ARDS
Pulmonary embolism
Fat embolism
COPD
Bronchial asthma
Myasthenia gravis
GBS
Phrenic nerve injury
Myopathy
Electrolyte disturbances
Drug overdose
Cervical cord injury
Obstructive sleep apnea syndrome, Alveolar hypoventilation
ARDS
Laryngeal edema
Obstruction of airway by edema, foreign body, mass
Atelectasis in the perioperative period after general anesthesia
Hypoperfusion of respiratory muscles in shock
Abbreviations: ARDS, acute respiratory distress syndrome; COPD, chronic obstructive pulmonary disease; GBS, Guillain-Barrré syndrome
 
PATHOPHYSIOLOGY
Type 1: The above mentioned conditions affect the parenchyma, interstitium and alveoli of the lung and cause V/Q mismatch and in turn cause hypoxemia.Ventilation increases as compensatory mechanism to combat hypoxia and causes normal or low PaCO2.
Type 2: Most common causes causing type 2 failure are those conditions causing obstructive lung disease which ends up with alveolar hypoventilation causing rise in PaCO2. Central causes like trauma or opioids reduces the respiratory drive hence causing hypercarbia whereas impaired ventilation due to neuromuscular disorders like myasthenia gravis is due to reduced strength of respiratory muscles to wash out CO2.
Type 3: This type of respiratory failure caused by atelectasis occurs primarily in the perioperative period after general anesthesia. This atelectasis causes reduction in the functional residual capacity in the dependent regions of lung which in turn causes V/Q mismatch and hypoxemia.
 
CLINICAL PRESENTATION
Signs and symptoms are based upon the cause of respiratory failure. The primary symptom of hypoxemia is dyspnea. Other signs and symptoms of hypoxemia includes restlessness, clouding of consciousness, tachypnea, cyanosis, bradycardia, tachycardia, hypertension and later followed by hypotension, cardiac arrhythmias. Hypercarbia can produce somnolence, tremors, seizures and coma. But in patients with chronic obstructive pulmonary disease (COPD) symptoms manifest later because the level of PaCO2 causing symptoms and signs are higher in COPD patients.
189Signs of hypoxemia include cyanosis, restlessness, confusion, anxiety, delirium, tachypnea, bradycardia or tachycardia, hypertension, cardiac dysrhythmias, and tremor. Dyspnea and headache are the cardinal symptoms of hypercapnia. Signs of hypercapnia include peripheral and conjunctival hyperemia, hypertension, tachycardia, tachypnea, impaired consciousness, papilledema, and asterixis. The symptoms and signs of acute respiratory failure are both insensitive and nonspecific; therefore, the physician must maintain a high index of suspicion and obtain arterial blood gas analysis if respiratory failure is suspected.
Analysis of arterial blood gas will show widened alveolar arterial gradient, hypoxia, hypercarbia and PaO2/FiO2 ratio. Chest radiography will be useful in diagnosing conditions like pneumothorax, rib fracture and pulmonary pathology. Bilateral infiltrates will point towards pulmonary edema. CT scan may be taken if needed for specific conditions.
 
TREATMENT (Flow chart 25.1)
Management aims towards two things:
  1. Therapy directed towards the cause.
  2. Respiratory care to ensure adequate gas exchange.
 
Respiratory Care
It can be done in the following ways:
  • Nonventilator therapies
  • Noninvasive positive-pressure ventilation (NIPPV) therapy
  • Invasive mechanical ventilation with tracheal intubation.
 
Nonventilator Therapy
Mainstay of nonventilator management is administration through nasal prongs or venturi mask to increase oxygenation. In conditions where lung parenchymal pathology is present (e.g. pneumonia) and ARDS, oxygen inhalation improves oxygenation. Oxygen therapy should be given even to COPD patients in respiratory failure in a lower flow (1–3 L/min) in order to maintain the hypoxic drive in these patients. In patients with type 1 failure, the goal of oxygen therapy is to improve oxygenation and the PaO2 >65 mm Hg and SpO2 >90%. Oxygen therapy with mask is of little benefit if the alveolar arterial gradient is very wide. Venturi mask can provide FiO2 of up to 0.4 and if more concentration of FiO2 is needed, mask with reservoir bag is used.
 
Noninvasive Ventilation
The NIPPV is the current first-line of therapy for COPD patients with type 2 respiratory failure since it reduces the need for tracheal intubation and invasive ventilation and reduces the length of ICU stay. BiPAP (bilevel positive airway pressure ventilation) is preferred for such patients. In patients with COPD, inhaled bronchodilators are administered. Prerequisites for using NIPPV is given in Table 25.3. If not responding to bronchodilators, corticosteroids (intravenous methylprednisolone 40–100 mg 6th hourly) should be given. A course of antibiotics is given if infection is suspected or if associated with sputum.190
Flow chart 25.1: Algorithm for approaching a patient with respiratory failure
Abbreviations: NIPPV, noninvasive positive-pressure ventilation
Table 25.3   Prerequisites for using NIPPV
  • Patients able to maintain a patent airway
  • Patients with ability to clear secretions
  • Hemodynamically stable
  • Intact consciousness
  • Tolerant to face mask
191Factors associated with NIPPV failure:
  • GCS < 11
  • Respiratory rate ≥30/minute
  • pH <7.25 at admission or 2 hours after therapy
  • APACHE II ≥9.
Patients with acute respiratory distress syndrome (ARDS) or severe hypoxemia benefit less with noninvasive ventilation. Hence, in patients with ARDS, invasive mechanical ventilation is preferred.
 
Intubation and Mechanical Ventilation (Table 25.4)
The ARDS needs low tidal volume ventilation (6 mL/kg predicted body weight) and the goals and ventilation strategy is discussed in the chapter ALI/ARDS. Any mode of ventilation which controls the ventilation and produces less ventilator patient dyssynchrony can be used. Traditional modes of ventilation such as assist control (A/C) mode and synchronized intermittent mandatory ventilation (SIMV) can be used. On weaning the patient, pressure support ventilation (PSV) or CPAP, BiPAP can be used.
The goals of mechanical ventilation in these patients are to improve PaO2, optimize PaCO2 according to the underlying cause and giving rest to respiratory muscles which enables the patient to revert back to spontaneous breathing once the underlying cause is corrected and the lung dynamics and gas exchange returns back to normal. Nutrition support is required to bring back the respiratory muscle function and hence, nutritional support is recommended for all ICU patients on invasive ventilation.
These goals of mechanical ventilation to improve oxygenation are primarily achieved by increasing mean airway pressure (using PEEP) and the FiO2. But positive end-expiratory pressure (PEEP) should be cautiously used in patients with hypotension and patients prone for barotrauma like lung parenchymal disease. PEEP reduces intrapulmonary shunting and thus, improves oxygenation. This increase in PaO2 can be achieved with lower inspired concentration of oxygen. There is a possibility of auto–PEEP or intrinsic PEEP developing in patients with obstructive lung disease. This intrinsic PEEP develops due to air trapping. Tidal volume and ventilator rate are adjusted to normalize pH, PaO2, PaCO2 and base deficit. Weaning and extubation can be challenging but daily reassessment and periodic spontaneous breath trial will help the intensivist to wean off these patients.
Table 25.4   Indications of intubation and mechanical ventilation
  • Apnea
  • Severe hypoxemia despite supplemental oxygen with high FiO2
  • Acute hypercarbia resulting in respiratory acidosis not responding to drugs
  • Altered mental status
  • Inability to clear secretions
  • Inability to protect airway
  • Increased work of breathing (RR >35/min)
192
 
BIBLIOGRAPHY
  1. Bardsley PA, Howard P, DeBacker W, et al. Two years treatment with almitrine bismesylate in patients with hypoxic chronic obstructive airways disease. Eur Respir J. 1991;4:308.
  2. Bone RC, Pierce AK, Johnson RL Jr. Controlled oxygen administration in acute respiratory failure in chronic obstructive pulmonary disease: a reappraisal. Am J Med. 1978;65:896.
  3. Cohen CA, Zagelbaum G, Gross D, et al. Clinical manifestations of inspiratory muscle fatigue. Am J Med. 1982;73:308.
  4. Conti G, Antonelli M, Navalesi P, et al. Noninvasive vs. conventional mechanical ventilation in patients with chronic obstructive pulmonary disease after failure of medical treatment in the ward: a randomized trial. Intensive Care Med. 2002;28:1701.
  5. Driver AG, LeBrun M. Iatrogenic malnutrition in patients receiving ventilatory support. JAMA. 1980;244:2195.
  6. Falke KJ, Pontoppidon H, Kumar A, et al. Ventilation with end-expiratory pressure in acute lung disease. J Clin Invest. 1972;51:2315-23.
  7. Marini JJ, Copps JS, Culver BH. The inspiratory work of breathing during assisted mechanical ventilation. Chest. 1985;87:612.
  8. Schumaker GL, Epstein SK. Managing acute respiratory failure during exacerbation of chronic obstructive pulmonary disease. Respir Care. 2004;49:766-82.
  9. The ARDS network ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342:1301-8.

ACUTE LUNG INJURY AND ACUTE RESPIRATORY DISTRESS SYNDROMECHAPTER 26

Prem Kumar
Acute lung injury and acute respiratory distress syndrome are common occurrences in the intensive care unit (ICU). Sepsis is the most common cause and the morbidity and mortality caused by this problem is quite high (30–60%). Indirect causes contribute to almost 50% cases of ARDS. In recent years because of the new developments in the ventilation strategy, the mortality has improved. Incidence of ARDS annually is 79/100,000 person-years. Predisposing risk factors is given in Table 26.1.
 
DEFINITION
ALI/ARDS is defined by the following criteria:
  • Acute onset
  • PaO2/FiO2 (P/F) ratio <300 in ALI and <200 in ARDS
  • Non-cardiogenic pulmonary edema by clinical evidence of normal left atrial pressure or pulmonary artery occlusion pressure <18 mm Hg
  • Bilateral diffuse infiltrates on chest radiograph.
Table 26.1   Predisposing risk factors
Indirect lung injury
  • Sepsis
  • Polytrauma
  • Acute pancreatitis
  • Transfusion reaction (TRALI)
  • Drug overdose
  • Cardiopulmonary bypass
Direct lung injury
  • Pneumonia
  • Pulmonary contusion
  • Aspiration pneumonitis
  • Burns causing inhalational injury
  • Near drowning
  • Fat embolism syndrome
Low serum albumin has been found to be a risk factor for development of ARDS
194
 
PATHOPHYSIOLOGY
The pathophysiology of acute lung injury is incompletely understood. The hallmark of ALI is diffuse alveolar damage. The disease process goes into three phases:
  1. Exudative phase
  2. Proliferative phase
  3. Fibrotic phase.
 
 
Pathophysiology of ALI/ARDS
It is given in Flow chart 26.1.
 
Diagnosis
American European consensus clinical definition of ALI/ARDS is as follows:
The diagnostic criteria should be that ARDS should be of acute onset, PaO2/FiO2 (P/F) ratio <300 in ALI and <200 in ARDS, non-cardiogenic pulmonary edema by evidence of normal left atrial pressure or pulmonary artery occlusion pressure <18 mm Hg and bilateral diffuse infiltrates on chest radiograph.
Apart from the diagnostic criteria, other methods to support the diagnosis, although not specific are pulmonary edema fluid to plasma protein ratio, brain natriuretic peptide level <100 pg/mL, bronchoalveolar lavage (BAL) fluid showing neutrophils.
Flow chart 26.1: Pathophysiology of ALI/ARDS
195
 
Radiographic Findings
Chest X-ray shows bilateral diffuse infiltrates, vascular pedicle width <70 mm and absence of Kerley B lines and CT scan will show heterogeneous opacities and ground-glass opacities concentrated more over the lower regions of lung.
 
MANAGEMENT
  • Treatment of the cause is the primary aim for ARDS. Sepsis is the common cause for indirect lung injury, hence appropriate management should be done with antibiotics.
  • Ventilator management.
In the older methods of treatment, higher tidal volume (12 mL/kg) was used which is not recommended nowadays. The current recommendation for ARDS includes lung protective strategy with low tidal volume ventilation. ARDS network has recommended a protocol for managing ALI/ARDS patients. This low tidal volume ventilation has drastically reduced the mortality by 20%.
 
Initial Ventilator Settings
  • Calculate predicted body weight (PBW)
Males = 50 + 2.3 [height (inches) – 60]
Females = 45.5 + 2.3 [height (inches) – 60]
 
Goals
  • pH goal: 7.30–7.45
  • Oxygenation goal: PaO2 55–80 mm Hg or SpO2 88–95%
  • Plateau pressure goal: ≤30 cm H2O
  • I:E ratio goal: 1:1–1:3.196
 
WEANING PROTOCOL FOR ARDS
Criteria for conducting spontaneous breathing trial (SBT) daily
  • FiO2 0.40 and PEEP ≤ 8
  • PEEP and FiO2 ≤ values of previous day
  • Patient has good spontaneous breathing efforts
  • Systolic blood pressure ≥90 mm Hg without vasopressor support
  • Patient not on muscle relaxants.
  ↓
With all the above criteria being met and if the patient tolerates weaning with CPAP/PS < 5 cm H2O for > 2 hours, FiO2 0.5, PEEP ≤ 5, start unassisted breathing trial
  ↓
  Place the patient on T-piece or CPAP ≤5 cm H2O. Assess for tolerance up to two hours by the following criteria
  ↓
  • SpO2 ≥90 and/or PaO2 ≥60 mm Hg
  • Spontaneous tidal volume (VT) ≥4 mL/kg PBW
  • RR ≤35/minute
  • pH ≥7.3
  • HR <120/minute
  • No respiratory distress
  ↓
  If tolerated for at least 30 minutes, consider extubation, If not tolerated, resume to SBT settings
  ↓
  • Oxygenation goal: PaO2 55–80 mm Hg or SpO2 88–95%
Use a minimum PEEP of 5 cm H2O. Use the combination to achieve the goal.
PEEP/FiO2 combination
FiO2
0.3
0.4
0.4
0.5
0.5
0.6
0.7
0.7
PEEP
5
5
8
8
10
10
10
12
FiO2
0.7
0.8
0.9
0.9
0.9
1.0
PEEP
14
14
14
16
18
18–24
  • Plateau pressure goal (Pplat): ≤30 cm H2O
  Check plat of 0.5 second inspiratory pause for at least 4th hourly and after each change in PEEP or VT.
If Pplat > 30 cm H2O: decrease VT by 1 mL/kg steps (minimum = 4 mL/kg)
If Pplat <25 cm H2O and VT <6 mL/kg, increase VT by 1 mL/kg until plat >25 cm H2O or
  VT = 6 mL/kg.
  • pH goal: 7.30–7.45
  Acidosis management (pH<7.30), if pH 7.15-7.30:
Increase RR until pH >7.30 or PaCO2 <25 (Maximum set RR = 35)
If pH <7.15: Increase RR to 35.
  If pH remains <7.15, VT may be increased in 1 mL/kg steps until
197  pH > 7.15 (Pplat target of 30 may be exceeded).
  Consider giving NaHCO3
Alkalosis management: (pH>7.45) Decrease ventilator rate if possible.
  • I:E ratio goal: 1:1–1:3.
Adjunctive therapies
Criteria for adjunctive therapy:
  Adjunctive therapies are indicated when PaO2 <55 mm Hg or SpO2 <88% with FiO2 ≥0.7 and plateau pressure >30 cm H2O.
  • Inhaled nitric oxide: It improves ventilator perfusion mismatching. It is not recommended routinely for patients with ARDS rather it can be used as a rescue therapy to improve oxygenation in patients with ARDS with severe hypoxemia and increased pulmonary artery pressure. Dose is 2.5–5 µg inhaled 6–9 times.
  • Glucocorticoids: The use of glucocorticoids is not routinely recommended. They can be used in the late fibroproliferative phase of ARDS to improve oxygenation but their use has not shown to improve mortality.
  • Prone positioning: Prone positioning improves ventilator perfusion mismatch and improves lung compliance, increases functional residual capacity and oxygenation. The Proning Severe ARDS Patients (PROSEVA) study group evaluated the effect of early application of prone positioning on outcomes in patients with severe ARDS (PaO2/FiO2 ratio <150 mm Hg, FiO2 >0.6 and PEEP >5 cm H2O) and found that early application of prolonged prone-positioning in severe ARDS decreased 28-day and 90-day mortality than the supine group.
  • Lung recruitment maneuver: It is defined as sustained deep inflation of the lung with the aim of opening up collapsed distal airway of the dependent regions of lung. Usual method of performing recruitment maneuver is sustained peak inflation pressure of 40 cm H2O for 40 seconds. But its result on improved survival is questionable. It has to be done cautiously since it can cause hemodynamic instability.
  • High frequency oscillatory ventilation (HFOV)
  • ECMO.
 
FLUID MANAGEMENT
There were two trials to indicate that pulmonary artery catheter was associated with increased mortality. They were: Study to Understand Prognosis and Preferences for Outcomes and Risks of Treatments (SUPPORT) and the Fluids and Catheters Treatment Trial (FACTT). The conservative fluid management is the current recommended fluid strategy because it improves central nervous system function and lung function with reduced length of ICU stay.
 
NUTRITIONAL SUPPORT
Early enteral nutrition support with trophic calorie supplementation of 10 mL/hr is the standard of care for ARDS patients. Omega-3 fatty acid and antioxidant supplementation is not recommended since it has been found to increase mortality. 198
 
BIBLIOGRAPHY
  1. Claude Guérin, et al. Prone Positioning in Severe Acute Respiratory Distress Syndrome. N Engl J Med. 2013;368:2159-68.
  2. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368-77.
  3. Rubenfeld GD, Herridge MS. Epidemiology and outcomes of acute lung injury. Chest. 2007;131:554-62.
  4. Ryan A, Hearty A, Prichard R, Cunningham A, Rowley S, Reynolds J. Association of hypoalbuminemia on the first postoperative day and complications following esophagectomy. J Gastrointest Surg. 2007;11:1355-60.
  5. The National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network,: Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med. 2006;354:1671.
  6. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000;342:1301-8.
  7. Wiedemann HP, Wheeler AP, Bernard GR, et al. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006;354:2564-75.

ACUTE EXACERBATION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASECHAPTER 27

Prem Kumar  
INTRODUCTION
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality among patients ending up with respiratory failure. Exacerbation of COPD is also a common cause for intensive care unit (ICU) admission. Global initiative for Chronic Obstructive Lung Disease (GOLD) defines COPD as a disease state characterized by airflow limitation that is not fully reversible. It includes chronic bronchitis and emphysema. Chronic bronchitis is associated with obstruction of small airways which is common in smokers; emphysema is associated with enlargement of air sacs, loss of elasticity, and closure of small airways and small airway disease where there is narrowing of small bronchioles. In this chapter, we will discuss about the risk factors, pathophysiology, diagnosis and treatment of chronic obstructive lung disease and its exacerbation in particular.
 
RISK FACTORS
  • Cigarette smoking
  • Respiratory infections—they are an important cause for exacerbation of COPD
  • Genetic— α1-antitrypsin deficiency
  • Occupational exposure—coal mining, gold mining, and cotton textile dust.
 
PATHOPHYSIOLOGY (Flow chart 27.1)
Progressive expiratory airflow obstruction is the most common finding of COPD. Due to some precipitating factors, inflammatory edema, glandular hypertrophy and excessive secretion of mucus occurs which cause expiratory airway obstruction which in turn occurs due to loss of distension forces on the airways resulting in structural and functional narrowing of airway. Due to the risk factors mentioned above, there is destruction of alveolar walls resulting in loss of elastic recoil and expiratory airway obstruction. 200
Flow chart 27.1: Pathophysiology of acute exacerbation of COPD
The effects of severe airflow obstruction include:
  • Ventilation maldistribution resulting in V/Q mismatch and impaired gas exchange
  • Increased work of breathing due to increased airway resistance
  • Reduced minute ventilation due to reduced peak expiratory flow rate
  • Air trapping resulting in dynamic hyperinflation.
 
DIAGNOSIS
 
Clinical Presentation
The cardinal symptoms of COPD are cough with sputum production and exertional dyspnea. Patients with severe disease or exacerbation can have expiratory wheeze, usage of accessory respiratory muscles and the classic tripod sign. Cyanosis can be seen if hypoxemia is very severe. The traditional way of classifying pink puffers for emphysema and blue bloaters for chronic bronchitis has been challenged recently since the current literature points clinical features towards the combination of pathophysiological changes of both chronic bronchitis and emphysema. Signs of right heart failure can be present if there is associated pulmonary hypertension.
 
Pulmonary Function Test (Fig. 27.1)
Pulmonary function test (PFT) shows obstructive pattern and there is reduction in FEV1 and FEV1/FVC . There is increase in total lung capacity, functional residual capacity, and residual volume when the severity of disease increases. 201
Fig. 27.1: Flow volume loops show decrease in the expiratory flow rate and the expiratory curve is concave upward indicating obstructive pattern
Abbreviations: PEF, peak expiratory flow; PIF, peak inspiratory flow
Table 27.1   GOLD criteria for grading severity of COPD
GOLD stage—severity
Spirometry
0–At risk
Normal
I–Mild
FEV1/FVC <0.7 and FEV1 ≥80% predicted
II–Moderate
FEV1/FVC <0.7 and 50% ≤FEV1 <80% predicted
III–Severe
FEV1/FVC <0.7 and 30% ≤FEV1 <50% predicted
IV–Very Severe
FEV1/FVC <0.7 and FEV1<30% predicted
or
FEV1 <50% predicted with respiratory failure or signs of right heart failure
Global initiative for chronic obstructive lung disease (GOLD) staging for severity of the disease is shown in Table 27.1. Chest radiography shows hyperlucency, bullae and flattening of diaphragm. Arterial blood gas analysis depicts hypoxemia, hypercarbia and respiratory acidosis and aids in the management.
 
Acute Exacerbation
By definition, exacerbation is worsening of cough/sputum production and dyspnea which could be due to precipitating factors or increase in the severity of the airflow obstruction and requires a change in regular medication. Sputum production usually has a change in the character during exacerbation. Acute exacerbation is one of the cause for respiratory failure thus, necessitating ICU admission. Patients with moderate to severe obstruction tend to have more exacerbations. During an exacerbation, precipitating factor should be identified and based on the severity, treatment should be initiated.
202Usual precipitating factor is a respiratory infection or an intercurrent illness. Usually the respiratory infections are bacterial (Streptococcus pneumoniae, haemophilus influenzae) or viral, postabdominal surgery.
 
CLINICAL ASSESSMENT
History: The current and the previous symptoms, history of previous exacerbations and treatment, severity of breathlessness, fever.
Physical examination: Grading of dyspnea, cyanosis, signs of heart failure, use of accessory muscles, central nervous system examination. Presence of wheezing and paradoxical motion of abdomen.
Investigations: Chest radiography to view any patchy shadows, pneumothorax, Kerley lines for pulmonary edema. Arterial blood gas analysis for detecting hypoxemia, hypercarbia and respiratory acidosis.
 
Treatment (Table 27.2)
  • Supplemental oxygen therapy
  • Inhaled bronchodilators
  • Corticosteroids
  • Antibiotics.
 
Supplemental Oxygen Therapy
Usually exacerbations respond to oxygen therapy. Venturi face mask is advised since it delivers known oxygen concentration. The concentration of 25–30% is sufficient to maintain adequate oxygenation but at the cost of hypercarbia. Hypercarbia can cause ventilation perfusion mismatch and worsen the patient. Saturation of >90% is sufficient for COPD patients. The use of oxygen at higher flow rate and concentration is not advised in patients with COPD in exacerbation. Ventilation perfusion mismatching and impaired gas exchange results in hypoxemia. Intrapulmonary shunting is minimal in COPD. Hence, COPD patients respond to supplemental oxygen therapy with low flow rate (1–3 L/min), if hypoxemia does not respond to oxygen therapy, then other causes need to be suspected. Patients with hemodynamic instability and heart failure require higher oxygen concentration, hence they require ventilator support.
Table 27.2   Dosages of various drugs useful in acute exacerbation of COPD
Drug
Dose
Anticholinergic: Ipratropium bromide
17 µg/puff, 2–3 puffs every 6 hours
Inhaled β2 agonists: albuterol
90 µg/puff, 2 puffs every 4–6 hours
Azithromycin
Ciprofloxacin
500 mg followed by 250 mg daily for 5 days
500 mg every 12 hours for 7 days
203
 
Inhaled Bronchodilators
Bronchodilators offer symptomatic relief by reducing airway resistance but these agents do not improve the lung function or do not prevent the progression of the disease. Anticholinergic agents like Ipratropium bromide is preferred to β2 agonists since it does not cause tachycardia. But β2 agonists have a more rapid onset of action and improves symptoms abruptly. The combination of anticholinergics and inhaled bronchodilators are effective in most of the patients with exacerbation rather than sole therapy.
 
Corticosteroids
Glucocorticoids prevent relapses, reduces the length of ICU stay and improves the postbronchodilator FEV1. According to current evidence, glucocorticoids should not be used in high dose or for longer duration instead the recommended dose is 30–40 mg of oral prednisolone or its equivalent for a period of 10–14 days. Hyperglycemia and myopathy can be a complication in ICU patients.
 
Antibiotics
Patients with exacerbation are mostly infected with either bacterial or viral infections. Usual bacterial pathogens are Streptococcus pneumoniae, Haemophilus influenzae. Antibiotics can be chosen after culture sensitivity or in case of severe infection, intravenous penicillin or cephalosporins along with macrolides/respiratory fluoroquinolones can be started empirically. Antibiotics given early have been found to reduce the incidence of intubation and mortality according to recent studies.
Indications for mechanical ventilation are also the causes for ICU admission too. Mechanical ventilation can be given by noninvasive positive-pressure ventilation (NIPPV) or invasive mechanical ventilation through endotracheal tube.
 
Indications for ICU Admission
  • Acute onset of respiratory acidosis and hypercarbia
  • Severe hypoxemia (PaO2 <40 mm Hg)
  • Severe dyspnea culminating in respiratory failure
  • Severe underlying disease not amenable for conservative management without ICU admission.
 
Indications of Mechanical Ventilation
  • Severe hypoxemia (PaO2 <40 mm Hg)
  • Hypercarbia (PaCO2 >60 mm Hg)
  • Severe respiratory acidosis (pH <7.2)
  • Severe dyspnea
  • Clouding of consciousness
  • Respiratory failure with hemodynamic instability.
204
 
Ventilation Strategy
  • Reduce tidal volume to 8 mL/kg
  • Keep low ventilator respiratory rate— less than 12 breaths/minute
  • Prolong expiratory time—1:2.5–1:3.
Most of the current ventilator strategies for COPD advocate pressure controlled ventilation initially with heavy sedation or paralysis to optimize gas exchange and patient machine synchrony. Once the gas exchange is optimized and the lung dynamics is near normalized, the patient is weaned from the ventilator usually with CPAP or BiPAP or PSV. By increasing the peak inspiratory flow rate, the inspiratory time is shortened hence reducing the work of breathing. Dynamic hyperinflation occurs in COPD patients during mechanical ventilation due to air trapping which in turn increases the work of breathing. Dynamic hyperinflation can be expressed in terms of intrinsic PEEP or auto PEEP. Intrinsic PEEP is the difference between the alveolar pressure and the proximal airway pressure measured at the end of expiration.
 
Detecting Intrinsic PEEP
This occurs in case of increased respiratory rate, significant airway obstruction, reduced expiratory time or inadequate inspiratory flow rate. Before measuring intrinsic positive end-expiratory pressure (PEEP), the patient should be sedated or paralyzed. It can be measured by visualizing the ventilator graphics and by measuring plateau pressure or by measuring the intrinsic PEEP itself. Plateau pressure can be measured by applying end-inspiratory pause and if it is more than 25 cm H2O, it indicates presence of intrinsic PEEP. Intrinsic PEEP is measured by prolonged end-expiratory pause. If intrinsic PEEP exceeds 10 cm H2O, then it is prudent to prolong the expiratory time or increase the inspiratory flow rate.
 
Application of External PEEP
Intrinsic PEEP can be overcome by applying external PEEP equivalent to or slightly less than auto-PEEP. The level of PEEP necessary to overcome intrinsic PEEP should be kept below 85% of measured intrinsic PEEP.
 
Weaning from Mechanical Ventilation
Pressure support ventilation or continuous positive airway pressure (CPAP) with daily spontaneous breath trial is effective for weaning patients with COPD.
 
Parameters Indicating Weaning Success
  • Simplified weaning index <9/minute
  • CROP index ≥13 mL/breaths/minute
  • Respiratory rate/tidal volume in liters (rapid shallow breathing index) <100 breaths/min/L.
205
 
Prognosis
BODE index is a useful predictor for survival in COPD patients.
B – Body mass index
O – Airflow obstruction
D – Severity of dyspnea
E – Exercise tolerance.
 
BIBLIOGRAPHY
  1. Chang DW. Clinical application of mechanical ventilation, 3rd edn. India: Cengage Learning, 2006.
  2. Guerin C, Milic-Emili, Fournier G. Effect of PEEP on work of breathing in mechanically ventilated COPD patients. Intensive Care Med. 2000;26:1207.
  3. Marini JJ. Should PEEP be used in airflow obstruction? Am Rev Respir Dis. 1989;140:1.
  4. Menitove SM, Goldring RM. Combined ventilator and bicarbonate strategy in the management of status asthmaticus. Am J Med. 1983;74:898.
  5. Pauwels RA, Buist AS, Calverley PM, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. Am J Respir Crit Care Med. 2001;163:1256.
  6. Pingleton SK. Nutritional support in the mechanically ventilated patient. Clin Chest Med. 1988;9:101.
  7. Smith TC, Marini JJ. Impact of PEEP on lung mechanics and work of breathing in severe airflow obstruction. J Appl Physiol. 1988;65:1488.
  8. Vitacca M, Vianello A, Colombo D, et al. Comparison of two methods for weaning patients with chronic obstructive pulmonary disease requiring mechanical ventilation for more than 15 days. Am J Respir Crit Care Med. 2001;164:225.
  9. Wilkins RL, et al. Egan's fundamentals of respiratory care, 8th edn. St. Louis, MO: Mosby; 2003.

ACUTE SEVERE ASTHMACHAPTER 28

Prem Kumar
Asthma is an inflammatory disease of the airways characterized by reversible airway obstruction which makes the airway more responsive than nonasthmatics to various stimuli leading to airway wall thickening and edema which in turn leads to excessive narrowing with subsequent airflow obstruction and symptomatic wheezing and dyspnea. Most of the asthmatics have one or more exacerbations in a year. Recently, the term status asthmaticus has been replaced by acute severe asthma or exacerbation.
Upper respiratory tract virus infections such as rhinovirus, respiratory syncytial virus, and coronavirus are the most common triggers of acute severe exacerbations. Other triggers are beta blockers, certain foods. Exercise is a triggering factor in children. Pathophysiology of acute severe asthma is given in Flow chart 28.1.
 
CLINICAL FEATURES
Cough, dyspnea, wheeze are cardinal symptoms. The symptoms may become worse at night. The patient may experience chest tightness. The patients are so breathless that they cannot speak a complete sentence. They may become cyanotic due to severe hypoxemia. On physical examination, tachycardia, tachypnea, accessory muscle use are all features of severe airway obstruction. Expiratory wheeze is heard throughout the lung. Pulsus parodoxus occurs due to large swings in intrathoracic pressure and there is accentuated fall in systolic blood pressure during inspiration. All wheezing is not due to asthma. It can be due to other causes like pulmonary edema, chronic obstructive pulmonary disease (COPD), etc. Severe exacerbations can cause right ventricular strain, acute reversible left ventricular dysfunction and myocardial ischemia. History of coronary artery disease is important because the patient may be taking beta-blockers and may be more prone for respiratory complications. The intensivist should elicit history about the time of onset of the exacerbation and what triggered the attack.
 
DIAGNOSIS
 
Pulmonary Function Tests
Clinical assessment of the severity of airflow obstruction is misleading, hence objective assessment of airflow is required (Table 28.1). The PEFR and FEV1 have 207limitations in assessing airway function since both the parameters are sensitive to obstruction of central airways and obstruction of small peripheral airways is less reflected by these parameters. Peak flow measurement is deferred in patients with severe exacerbation since it worsens bronchospasm. But in other patients without severe exacerbations, PEFR or FEV1 predicts the requirement of hospitalization. If the expiratory flow does not improve 60 minutes after initial therapy, then the patient would required hospital admission. The normal range of PEFR is 500–700 L/minute for men and 380–500 L/minute for women. Exacerbations are characterized by decreases in expiratory airflow that can be documented and quantified by simple measurement of lung function (spirometry or PEFR) (Table 28.2).
Flow chart 28.1: Pathophysiology of acute severe asthma
Abbreviations: PEEP, positive end-expiratory pressure
Table 28.1   Objective assessment of obstruction after initial therapy
PEFR or FEV1
Interpretation
>70% predicted or >15% increase
Good response
50–70% predicted or 10–15% increase
Equivocal response
<50% predicted or <10% increase
Poor response
Abbreviations: PEEP, positive end expiratory pressure; PEFR, peak expiratory flow rate
208
Table 28.2   Classification of severity of asthma exacerbation
Symptoms and signs
Initial PEFR
(or FEV1)
Clinical course
Mild
Dyspnea only with activity
PEFR >70% predicted
Home therapy
Good relief with inhaled SABA may need short course of oral corticosteroids
Moderate
Dyspnea interferes with or limits usual activity
PEFR 40–69% predicted
Usually requires hospital visit
Relief with frequent inhaled SABA
Oral systemic corticosteroids; some symptoms last for 1–2 days after treatment is begun
Severe
Dyspnea at rest; interferes with conversation
PEFR <40% predicted
May require hospitalization
Partial relief from frequent inhaled SABA
Oral systemic corticosteroids; some symptoms last for >3 days after treatment is begun
Adjunctive therapies are helpful
Life threatening
Too dyspneic to speak; perspiring
PEFR <25% predicted
Requires hospitalization and ICU
Admission
Minimal or no relief from frequent inhaled SABA
Intravenous corticosteroids
Adjunctive therapies are helpful
Abbreviations: SABA, short-acting beta-2 agonist; PEFR, peak expiratory flow rate
 
Risk Factors Associated with Mortality due to Asthma
  • History of severe exacerbation with intubation and ventilatory support
  • Use of >2 canisters of short-acting beta-2 agonist (SABA) per month
  • Two or more hospitalizations in the past year
  • Difficulty in recognizing the severity of worsening asthma
  • Low socioeconomic status
  • Drug abuse
  • Patient with comorbid illness—chronic pulmonary disease, cardiovascular disease.
 
Arterial Blood Gas Analysis
Arterial blood gases shows hypoxemia and reduced PCO2 due to hyperventilation in mild-to-moderate exacerbation. A normal or rising PCO2 is an indication of 209severe exacerbation and impending respiratory failure and requires immediate monitoring and therapy. There can be compensatory hypocapnic metabolic acidosis in response to acute respiratory alkalosis.
 
Chest X-ray
A chest roentgenogram may show pneumonia or pneumothorax.
 
MANAGEMENT (TABLE 28.3 AND Flow chart 28.2)
  • Administer supplemental oxygen in moderate-to-severe exacerbations to correct hypoxemia.
  • Administer frequent SABA to reverse airflow obstruction.
  • Administer oral corticosteroids to reduce airway inflammation in moderate to severe exacerbations or in patients who have failure of response to SABA.
  • Monitor response to treatment
    • Repeated lung function measures (FEV1 or PEFR) after 1 hour is the single best predictor of hospitalization.
    • The presence of drowsiness is an indicator for impending respiratory failure and patient requires ICU admission and ventilatory support.
  • Consider adjunctive treatments with intravenous magnesium sulfate or heliox, in severe exacerbations, if patients are unresponsive to the initial therapy.
  • Consider inhaled corticosteroids for preventing relapse.
  • Review the inhaler technique.
 
 
Treatments not Recommended for Exacerbation of Asthma
  • Antibiotics unless there is documented evidence of infection
  • Mucolytics
  • Methylxanthines
  • Sedation.
 
Adjunctive Therapies
  • Magnesium sulfate is useful only in severe exacerbations. It may increase airflow rates by reducing airflow obstruction. Dose—2 g intravenously over 20 minutes
  • Heliox
  • Aminophylline—not recommended for exacerbations but can play some role in refractory cases.
 
Noninvasive Ventilation
Studies have suggested the combination of noninvasive ventilation and albuterol nebulization to be superior than SABA alone. The prerequisites and contraindications are discussed in the chapter of noninvasive ventilation. Continuous positive airway 210pressure (CPAP) or preferably bi-level positive airway pressure (BiPAP) is started in asthmatic patients with exacerbations who require noninvasive positive pressure ventilation (NIPPV). Start CPAP of 5–10 cm H2O or BiPAP with inspiratory positive airway pressure (IPAP) of 8 cm H2O and titrate according to need up to 15 cm H2O. expiratory positive airway pressure (EPAP) – 5 cm H2O. the pressures are adjusted so that the patient has respiratory rate below 25/minute, tidal volume >7 mL/kg and comfort.
Table 28.3   Dosages of drugs used in exacerbation of asthma
Drug
Dose
Comments
Albuterol
Nebulizer solution
(0.63 mg/3 mL,
1.25 mg/3 mL,
2.5 mg/3 mL,
5.0 mg/mL)
MDI
(90 µg/puff)
2.5–5 mg in 3 mL normal saline every 15–20 minutes for 3 doses, then 2.5–10 mg every 1–4 hours as needed
4–8 puffs every 20 minutes up to 4 hours, then every 1–4 hours as needed
Only selective beta 2 agonists are recommended
For intubated patients, titrate to physiologic effects
Levalbuterol
Nebulizer solution
(0.63 mg/3 mL,
1.25 mg/0.5 mL,
1.25 mg/3 mL)
MDI
(45 µg/puff)
1.25–2.5 mg every 20 minutes for 3 doses, then 1.25–5 mg every 1–4 hours as needed
4–8 puffs every 20 minutes up to 4 hours, then every 1–4 hours as needed
Levalbuterol administered in one-half the mg dose of albuterol provides comparable efficacy and safety
Ipratropium bromide
Nebulizer solution
(0.25 mg/mL)
MDI
(18 µg/puff)
0.5 mg every 20 minutes for 3 doses, then as needed
8 puffs every 20 minutes as needed up to 3 hours
Should not be used as first-line therapy;
Should be added to
SABA therapy for severe exacerbations
Can mix in same nebulizer with albuterol
Epinephrine
1:1,000 (1 mg/mL)
0.3–0.5 mg every 20 minutes for 3 doses Given subcutaneously
Terbutaline
(1 mg/mL)
0.25 mg every 20 minutes for 3 doses
Terbutaline is preferred in pregnancy if parenteral therapy is indicated. It is used with caution in coronary artery disease
Methylprednisolone
Oral or IV
40–80 mg/day in 1 or 2 divided doses until PEFR reaches 70% of predicted or personal best
Total course of corticosteroids for asthma exacerbation may require 3–10 days
Course <1 week, there is no need to taper the dose
Course >1 week, there is no need to taper if the patient is on inhaled steroids
Inhaled steroids can be started anytime in the treatment of an asthma exacerbation
Abbreviations: MDI, metered-dose inhaler; IV, intravenous; SABA, short-acting beta-2 agonist
211
Flow chart 28.2: Management of asthma exacerbation
Abbreviations: PEFR, peak expiratory flow rate; SABA, short-acting beta-2 agonist; PEF, peak expiratory flow
212
Table 28.4   Indications of endotracheal intubation and mechanical ventilation
  • Progressive hypercapnia
  • Obtunded mental status
  • Silent chest
  • Exhaustion of breathing—impending respiratory failure
  • Hemodynamic instability
  • Increased production of secretions
  • Inability to protect airway
 
Endotracheal Intubation and Mechanical Ventilation (Table 28.4)
Administration of a short- and rapid-acting intravenous benzodiazepine facilitates intubation. Oral intubation is preferred rather than nasal since nasal polyps and sinusitis are common in asthma and a larger endotracheal tube is placed through oral route thus reducing the airway resistance. A large endotracheal tube facilitates the option of therapeutic bronchoscopy later.
 
Initial Ventilator Settings
To avoid dynamic hyperinflation, the following settings are set in the ventilator:
  • Tidal volume: 7–8 mL/kg
  • Ventilator respiratory rate: 12–14/minute
  • Inspiratory flow rate: 60 L/minute
  • Minute ventilation: 7–8 L/minute
  • PEEP: 5 cm H2O.
Either volume control or synchronized intermittent mandatory (SIMV) can be used. Pressure-controlled ventilation (PCV) has the advantage of limiting the peak inspiratory pressure. The current strategy for mechanical ventilation in status asthmaticus is controlled hypoventilation with permissive hypercapnia. This strategy does not establish a normal PaCO2 as long as the minute ventilation and fraction of inspired oxygen maintain adequate tissue oxygenation, in other words hypercapnia is accepted–permissive hypercapnia.
 
Dynamic Hyperinflation
To measure auto–PEEP, the patient ventilator asynchrony should be absent or there should not be any patient effort. Single breath plateau pressure and auto–PEEP can measure dynamic hyperinflation. Plateau pressure can be measured by end-inspiratory hold maneuver. Auto–PEEP is obtained by measuring airway opening pressure during an end-expiratory hold maneuver. Persistence of 213expiratory flow at the start of inspiration also suggests auto–PEEP. Auto–PEEP < 30 cm H2O can be tolerated.
 
Extubation Criteria
  • No hypercapnia
  • No significant dynamic hyperinflation
  • Airway resistance <20 cm H2O
  • PEEP <5 cm H2O
  • Hemodynamically stable
  • Patient able to protect airway
  • Mental status not obtunded
  • No excessive secretions.
 
BIBLIOGRAPHY
  1. Bellomo R, McLaughlin P, Tai E, et al. Asthma requiring mechanical ventilation: a low morbidity approach. Chest. 1994;105:891.
  2. Feihl F, Perret C. Permissive hypercapnia. Am J Respir Crit Care Med. 1994;150:1722.
  3. Global Initiative for Asthma: NHLBI/WHO Workshop Report. Publication No. 95-3659, Bethesda, MD, National Heart, Lung, and Blood Institute, 1995.
  4. Global strategy for asthma management and prevention. NIH Publication 02-3659, 2002.
  5. Hankinson J, Odencrantz J, Ferdan K. Spirometric reference values from a sample of the general U.S. population. Am Rev Respir Crit Care Med. 1999;159:179-87.
  6. Harrison BDW, Hart GJ, Ali NJ, et al. Need for intravenous hydrocortisone in addition to oral prednisolone in patients admitted to hospital with severe asthma without ventilatory failure. Lancet. 1986;1:181.
  7. Manthous CA, Hall JB, Caputo MA, et al. Heliox improves pulsus paradoxus and peak expiratory flow in nonintubated patients with severe asthma. Am J Respir Crit Care Med. 1995;151:310.
  8. National Asthma Education and Prevention Program. Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma. Publication No. 55-4051. Bethesda, MD, National Institutes of Health, 1997.
  9. National Asthma Education and Prevention Program Expert Panel Report. Guidelines for the diagnosis and management of asthma. The Expert Panel Report 3, Summary Report. 2007.
  10. National Asthma Education and Prevention Program Expert Panel Report. Guidelines for the diagnosis and management of asthma. Update on selected topics, 2002. NIH Publication No. 02-5074,2003.
  11. Ratto D, Alfaro C, Sipsey J, et al. Are intravenous corticosteroids required in status asthmaticus? JAMA. 1988;260:527.
  12. Wilmoth DF, Carpenter RM. Preventing complications of mechanical ventilation: permissive hypercapnia. AACN Clin Issues. 1996;7:473.

DEEP VENOUS THROMBOSIS AND PULMONARY EMBOLISMCHAPTER 29

Prem Kumar, Marun Raj
Deep venous thrombosis (DVT) and pulmonary embolism (PE) are spectrum of venous thromboembolism. DVT and PE can occur in any ICU patient and more so in patients with risk factors. Hence, prophylaxis against DVT is more effective in preventing mortality due to pulmonary embolism (Table 29.1).
Table 29.1   Risk factors associated with DVT and PE
Risk factors associated with venous thromboembolism
  • Trauma
  • Prolonged Immobilization
  • Prolonged ventilation
  • Previous history of DVT/PE
  • Obesity
  • Coronary artery disease
  • Diabetes mellitus
  • Congestive cardiac failure
  • Postpartum period
  • Malignancy
  • Age >40
  • Central venous catheters
  • Hip or leg fracture
Inherited conditions
  • Factor V Leiden deficiency
  • Antiphospholipid antibody syndrome
  • Heparin-induced thrombocytopenia
  • Anti-thrombin deficiency
  • Protein C, S deficiency
Major surgeries
  • Orthopedic surgeries—total knee replacement, total hip replacement
  • Laparoscopic surgeries
  • Vascular surgeries
  • Major general surgery
 
PATHOPHYSIOLOGY (Flow chart 29.1)
Most common sites of origin of pulmonary embolism are:
  • Calf and popliteal veins of leg
  • Pelvic veins
  • Inferior vena cava.
 
CLINICAL FEATURES AND DIAGNOSIS
Most of the patients with PE have detectable DVT of legs. Most of the emboli are asymptomatic and the clinical presentation depends on the size of emboli, location, number of emboli (single/multiple) and the cardiorespiratory status 215of the patient. Symptoms include breathlessness, leg pain, edema of limbs, discoloration. Signs include dyspnea, tachypnea and tachycardia. Pain on forced dorsiflexion of the foot (Homan's sign) can be seen in DVT. Hemoptysis and pleuritic chest pain is due to pulmonary infarction. Worsening of dyspnea and hemodynamic instability can be due to right ventricular failure. Massive pulmonary embolism can lead to circulatory collapse and cardiac arrest. More than 50% obstruction of pulmonary circulation is required to cause increase in mean pulmonary artery pressure. Other causes of embolism can be fat, air, amniotic fluid, cement and bone fragment while reaming.
Flow chart 29.1: Pathophysiology of venous thromboembolism
Noninvasive imaging is used in patients, where there is high clinical suspicion of DVT or PE (Flow chart 29.2).
 
Electrocardiogram
The most common finding is sinus tachycardia and the more specific to PE is the SIQ3T3 sign - S wave in lead I, a Q wave in lead III, and an inverted T wave in lead III. Other findings are T-wave inversion in leads V1 to V4.
 
Lab Investigations
Plasma d-dimer is used to rule out DVT, as it has got high negative predictive value. Serum troponin and plasma heart-type fatty acid–binding protein levels can be elevated due to RV microinfarction. Elevated BNP or NT-BNP can also be seen. D-dimer can be falsely elevated in severe systemic illness (Table 29.2).
Table 29.2   Features of different sizes of embolism
Pulmonary embolus
Hypotension
Echocardiography
Prognosis
Small
No
No findings
Excellent
Moderate-to-large
No
RV hypokinesia
Borderline
Massive
Yes
RV failure
Poor
216
Flow chart 29.2: Algorithms for PE and DVT diagnosis
Fig. 29.1: Loss of vein compressibility in DVT (Popliteal vessels)
 
Venous Ultrasonography
The primary criteria for diagnosing DVT is loss of vein compressibility. Other diagnostic features are loss of phasic variability and loss of distal augmentation (Fig. 29.1). 217
Fig. 29.2: Right pulmonary infarct due to pulmonary embolus
 
Chest X-ray
Usually, a normal chest X-ray is common in PE. Other findings are a peripheral wedged-shaped density above the diaphragm (Hampton's hump), focal oligemia (Westermark's sign), and an enlarged right descending pulmonary artery (Palla's sign).
 
CT–Chest
CT with contrast is the main imaging modality used for diagnosis of PE. Cardiac chambers along with proximal and distal veins can be imaged for thrombus (Fig. 29.2).
 
MRI
Used along with gadolinium, it can detect DVT in cases where ultrasound is equivocal. It is useful for detecting large proximal PE rather than distal PE.
 
V/Q Scan
It is used in patients who cannot tolerate intravenous contrast. High probability is defined as two or more segmental perfusion defects in the presence of normal ventilation.
 
Echocardiography
Although it is sensitive to detect only main pulmonary artery PE, it does help to rule out other conditions (Figs 29.3 and 29.4).218
Fig. 29.3: Pulmonary embolus present in pulmonary artery indicated by arrow
Fig. 29.4: Thrombus occupying the entire IVC
 
PREVENTION (TABLES 29.3 TO 29.6)
The following methods are used for prevention of thromboembolism:
  • Intermittent pneumatic compression
  • Compression stockings
  • Administration of heparin—unfractionated or low molecular weight heparin
  • Fondaparinux
  • Warfarin.219
Table 29.3   ACCP guidelines for prevention of thrombosis in nonsurgical patients
Clinical condition/situation
Recommended prophylaxis
Hospitalized acutely ill medical patients
Risk for thrombosis
Increased risk of thrombosis who are bleeding or at high risk for major bleeding
LDUH or LMWH bid, or fondaparinux
Mechanical thromboprophylaxis with graduated compression stockings or intermittent pneumatic compression
Critically ill patients
Increased risk of thrombosis who are bleeding or at high risk for major bleeding
Routine ultrasound screening is not advised.
LMWH or LDUH thromboprophylaxis is recommended.
Mechanical thromboprophylaxis with graduated compression stockings or intermittent pneumatic compression
Abbreviations: LDUH, low dose unfractionated heparin; LMWH, low molecular weight heparin; ACCP, American College of Chest Physicians
Table 29.4   ACCP guidelines for prevention of thrombosis in nonorthopedic surgical patients
Clinical condition/situation
Recommended prophylaxis
Patients undergoing general, GI, urological, gynecologic, bariatric, vascular, plastic, or reconstructive surgery
Very low risk for VTE
Low risk for VTE
Moderate risk for VTE with no high risk of bleeding complications
Moderate risk for VTE with high risk of bleeding complications
High risk for VTE with no high risk of bleeding complications
High risk for VTE in patients who undergo surgery for cancer with no high risk of bleeding complications
High risk for VTE with high risk of bleeding complications
High risk for VTE in whom both LMWH and unfractionated heparin are contraindicated or unavailable and who are not at high risk for major bleeding complications
No pharmacologic or mechanical prophylaxis.
Mechanical prophylaxis, preferably with intermittent pneumatic compression (IPC)
LMWH, LDUH, or mechanical prophylaxis, preferably with IPC
Mechanical prophylaxis, preferably with IPC
LMWH or LDUH plus mechanical prophylaxis with elastic stockings or IPC
Extended-duration pharmacologic prophylaxis (4 weeks) with LMWH
Mechanical prophylaxis, preferably with IPC
Low-dose aspirin, fondaparinux, or mechanical prophylaxis, preferably with IPC
220Patients undergoing cardiac surgery
Uncomplicated postoperative course
Hospital course prolonged by one or more nonhemorrhagic surgical complications
Mechanical prophylaxis, preferably with optimally applied IPC or pharmacologic prophylaxis
Add pharmacologic prophylaxis with LDUH
or LMWH to mechanical prophylaxis
Patients undergoing thoracic surgery
Moderate risk for VTE who are not at high risk for perioperative bleeding
High risk for VTE who are not at high risk for perioperative bleeding
High risk for major bleeding
LDUH, LMWH, or mechanical prophylaxis with optimally applied IPC
LDUH, LMWH, plus mechanical prophylaxis with optimally applied IPC
Mechanical prophylaxis with optimally applied IPC.
Patients undergoing craniotomy
With no risk
Very high risk for VTE
Mechanical prophylaxis with IPC.
Mechanical prophylaxis with IPC plus pharmacologic prophylaxis once adequate hemostasis is established and the risk of bleeding decreases.
Patients undergoing spinal surgery
No risk
High risk for VTE (malignant disease or those undergoing surgery with combined anterior-posterior approach)
Mechanical prophylaxis with IPC, unfractionated heparin, or LMWH
Mechanical prophylaxis with IPC plus pharmacologic prophylaxis once adequate hemostasis is established and the risk of bleeding decreases.
Patients with major trauma: Traumatic brain injury, acute spinal injury, and traumatic spine injury
Major trauma with no risk
High risk for VTE
Major trauma patients in whom LMWH and LDUH are contraindicated
LDUH, LMWH, or mechanical prophylaxis, preferably with IPC.
Add mechanical prophylaxis to pharmacologic prophylaxis when not contraindicated by lower extremity injury.
Mechanical prophylaxis with IPC when not contraindicated by lower-extremity injury. Add pharmacologic prophylaxis with either LMWH or LDUH when the risk of bleeding diminishes or the contraindication to heparin resolves.
Abbreviation: VTE, venous thromboembolism
221
Table 29.5   ACCP guidelines for prevention of thrombosis in orthopedic surgical patients
Clinical condition/situation
Recommended prophylaxis
Patients undergoing major orthopedic surgery: Total hip arthroplasty (THA), total knee arthroplasty (TKA), hip fracture surgery (HFS)
Patients undergoing THA or TKA
Patients undergoing HFS
Patients undergoing major orthopedic surgery (THA, TKA, HFS) and receiving LMWH as thromboprophylaxis
Thromboprophylaxis for patients undergoing major orthopedic surgery in the outpatient period
Patients undergoing major orthopedic surgery and increased risk of bleeding
LMWH, fondaparinux, apixaban, dabigatran, rivaroxaban, LDUH, adjusted-dose VKA, aspirin, or an intermittent pneumatic compression device (IPCD) for minimum of 10–14 days
LMWH, fondaparinux, LDUH, adjusted-dose VKA, aspirin, or an IPCD for minimum of 10–14 days
Start LMWH preferably in these patients and start LMWH ≥12 hour before surgery or ≥12 hour after surgery. It is recommended to use dual prophylaxis with an antithrombotic agent and an IPCD during the hospital stay
Thromboprophylaxis for up to 35 days from the day of surgery
IPCD
Abbreviations: VKA, vitamin K antagonist; IPCD, intermittent pneumatic compression device
Table 29.6   Dose of anticoagulants for prophylaxis of VTE
Drug
Dose
Unfractionated heparin
80 units/kg bolus and 18 units/kg/hour infusion Or bolus of 5,000 U every 8–12 hours
LMWH
Enoxaparin
Dalteparin
1 mg/kg 12th hourly or 40 mg SC once daily or 12th hourly
100 U/kg 12th hourly or 2500–5000 U SC once daily
Fondaparinux
2.5 mg SC once daily
Warfarin
5 mg initially and titrate the dose to get INR of 2.0–3.0
222
 
TREATMENT (Flow chart 29.3)
Flow chart 29.3: DVT treatment
 
Algorithm for PE Management
It is based on hemodynamic instability and right ventricular function.
 
Anticoagulation (Table 29.7)
Table 29.7   Dose of anticoagulants for treatment of VTE
Drug
Dose
aPTT
Unfractionated heparin
80 units/kg bolus and 18 units/kg/hour infusion
Maintain 2–3 times the normal
LMWH
Enoxaparin
Dalteparin
1 mg/kg SC 12th hourly
200 U/kg SC once a day
100 U/kg SC 12th hourly
Monitoring not required
FONDAPARINUX
(Anti–Xa pentasaccharide)
<50 kg—5 mg
50–100 kg—7.5 mg
>100 kg—10 mg
Monitoring not required
WARFARIN
(3–5 days of bridging with parenteral anticoagulants is required)
5 mg initially
INR titration to 2.0–3.0
223
 
New Oral Anticoagulants
  • Rivaroxaban—Xa inhibitor
  • Dabigatran—direct thrombin inhibitor.
 
Duration of Anticoagulation
  • DVT restricted to calf veins or upper extremity, proximal leg DVT, or PE, cancer patients with DVT/PE—3 to 6 months
  • Idiopathic DVT/PE—2 to 3 months.
 
IVC Filters
 
Indications
  • Presence of acute PE with contraindication to anticoagulation
  • Recurrent venous thrombosis inspite of adequate anticoagulation.
In patients with acute PE who are treated with anticoagulants, use of an IVC filter is not recommended.
 
Treatment of RV Dysfunction
  • Intravenous fluid is administered judiciously in case of right ventricular dysfunction.
  • Dopamine/dobutamine are the first line vasopressors used in case of hemodynamic instability.
 
Thrombolysis
  • rtPA—100 mg over 2 hours. Contraindications are recent surgery, intracranial disease. Indication is massive PE.
  • Successful thrombolysis can reverse right heart failure and prevent recurrence.
 
BIBLIOGRAPHY
  1. Anderson FA Jr, Spencer FA. Risk factors for venous thromboembolism. Circulation. 2003;107(23 Suppl 1):I9.
  2. Benotti JR, Dalen JE. The natural history of pulmonary embolism. Clin Chest Med. 1984;5:403.
  3. Chastre J, Cornud F, Bouchama A, et al. Thrombosis as a complication of pulmonary-artery catheterization via the internal jugular vein: prospective evaluation by phlebography. N Engl J Med. 1982;306:278.
  4. Cranley JJ, Canos AJ, Sull WJ. The diagnosis of deep venous thrombosis. Fallibility of clinical symptoms and signs. Arch Surg. 1976;111:34.
  5. Geerts WH, et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-based Clinical Practice Guidelines, 8th edn. Chest. 2008;133: 381S.
  6. Guyatt GH, et al. Antithrombotic Therapy and Prevention of Thrombosis. American College of Chest Physicians Evidence-based Clinical Practice Guidelines, 9th edn. Chest. 2012;141(2)(Suppl):7S-47S.
  7. 224Kucher N, Goldhaber SZ. Management of massive pulmonary embolism. Circulation. 2005;112:e28.
  8. Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscalzo J. Harrison's Principles of Internal Medicine, 18th edn. McGraw-Hill Publications; 2012.
  9. McIntyre KM, Sasahara AA. The hemodynamic response to pulmonary embolism in patients without prior cardiopulmonary disease. Am J Cardiol. 1971;28:288.
  10. Paul M L. The ICU Book, 3rd edn. Lippincott Williams and Wilkins, 2007.
  11. Torbicki A, et al. Guidelines on the diagnosis and management of acute pulmonary embolism: The Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J. 2008;29:2276.

OBSTRUCTIVE SLEEP APNEA AND OBESITY HYPOVENTILATION SYNDROMECHAPTER 30

Prem Kumar  
HISTORY
President Howard Taft stated, “I have lost that tendency to sleepiness which made me think of the fat boy in Pickwick. My color is very much better and my ability to work is greater”. Joe the “Fat Boy,” the character in Dickens's The Posthumous Papers of the Pickwick Club, was from where the term “Pickwickian syndrome” got derived.
 
INTRODUCTION
Obesity can be defined as a “disease” since it is physiologic dysfunction with environmental, genetic, and endocrinologic causes. Common diseases associated with obesity include insulin resistance, type 2 diabetes mellitus, obstructive sleep apnea (OSA), obesity hypoventilation syndrome, coronary artery disease, hypertension and osteoarthritis. The OSA is seen in increased incidence as an etiology for intermittent functional upper airway obstruction. Obesity is a known risk factor although OSA can occur in patients without obesity too (Tables 30.1 and 30.2).
Table 30.1   Levels of risk associated with increasing body mass index
Classification
BMI (kg/m2)
Risk of developing health problems
Underweight
Normal weight
Overweight
<18.5
18.5–24.9
25.0–29.9
Increased
Least
Increased
Obese
Class 1
Class 2
Class 3
Superobese
30.0–34.9
35.0–39.9
40.0–49.9
≥50
High
Very high
Extremely high
Exceedingly high
226
Table 30.2   Waist circumference and risk
Waist circumference
Body mass index (kg/m2)
Normal weight
Overweight
Obese class 1
<102 cm (♂)
Least risk
Increased risk
High risk
<88 cm (♀)
≥102 cm (♂)
Increased risk
High risk
Very high risk
≥88 cm (♀)
Spectrum of sleep disorders
Snoring→hypopnea→apnea→OSA→OHS.
 
OBSTRUCTIVE SLEEP APNEA
Obstructive sleep apnea (OSA) is a condition characterized by functional upper airway obstruction which is associated with recurrent episodes of cessation of breathing (apnea), reduction in airflow (hypopnea) during sleep resulting in sleep deprivation and reduction in oxygen saturation inspite of respiratory effort.
  • Apnea—no airflow >10 seconds
  • Hypopnea—reduction in airflow >50% for 10 seconds and with at least 4% reduction in SpO2 and arousal in EEG.
Causes of apnea can be either obstructive or central.
 
Diagnosis
Obstructive sleep apnea (OSA) can be suspected in patients having complaints of snoring, apnea, daytime somnolence with exclusion of all other possible causes which can cause or exacerbate OSA—adenotonsillar enlargement, macroglossia, hypothyroidism, drug addiction with sedatives, opioids. Diagnosis is done with polysomnography which calculates AHI (apnea/hypopnea index) which should be >5 events/hour of sleep (Table 30.3).
AHI can be also calculated with the following formula:
AHI = Total number of apneas + hypopneas ÷ total sleep time × 60
Table 30.3   Recent classification for severity of obstructive sleep apnea
  • Mild—AHI of 5–15 events/hour
  • Moderate—AHI of 15–30 events/hour
  • Severe—AHI of >30 events/hour
Oropharyngeal examination can be useful in patients with OSA. Modified Mallampati score 3 or 4, macorglossia, retroganthia, tonsillar enlargement, narrow oropharyngeal cavity can all point towards OSA. Large neck circumference of 17 inches in men, >16 inches in women, or >60 cm in anyone is also a risk factor. 227
 
Pathophysiology of OSA
Anatomic narrowing of upper airway plays a major role in the pathophysiology of OSA. Apart from anatomic changes, there is decrease in respiratory center output which causes loss of pharyngeal muscle tone during sleep casuing obstruction. Frequent apneic episodes result in arousal, daytime somnolence, change in sleep pattern (from deep sleep to wakeful ness indicated by the alpha pattern in EEG) and sleep deprivation. Fall in oxygen saturation causes hypoxemia which causes pulmonary vasoconstriction and on chronic stimulation may lead to pulmonary hypertension and cardiac failure (cor pulmonale). 10% to 20% of patients with OSA have chronic alveolar hypoventilation with elevation in PaCO2 and can also develop cardiac arrhythmias. OSA plays an important role in metabolic syndrome.
 
Central Sleep Apnea
Recurrent episodes of apnea during sleep in the absence of respiratory effort. Mostly, it is idiopathic but the most common cause of central sleep apnea (CSA) in ICU is congestive cardiac failure, neuromuscular disorder, cardiac failure, opioid sedation and brainstem disorder. CSA is due to loss of respiratory drive to respiratory muscles. CPAP or adaptive support ventilation (ASV) is useful in these patients.
 
OBESITY HYPOVENTILATION SYNDROME
Obesity hypoventilation syndrome (OHS) is also known by the name—pickwickian syndrome. The diagnostic criteria for OHS developed by the American Academy of sleep Medicine are given in Table 30.4. The OHS is associated with awake chronic hypoxemia (PaO2 <65 mm Hg) without the presence of any other cause (COPD, lung disease). These patients have impaired central ventilatory drive. OHS patients have daytime hypercarbia which is absent in OSA. But the diagnsosis of OHS in ICU is challenging because of other factors associated with hypoxia and hypercarbia.
Table 30.4   Diagnostic criteria for obesity hypoventilation syndrome
  • BMI>30 kg/m2
  • Awake arterial hypercapnia (PaCO2 >45 mm Hg)
  • Rule out other causes of hypoventilation
  • Polysomnography reveals sleep hypoventilation with nocturnal hypercapnia with or without obstructive apnea/hypopnea events
Obesity hypoventilation syndrome (OHS) is associated with daytime hypercarbia with nocturnal increase in PaCO2 (>10 mm Hg from baseline). Pulmonary function test and chest radiography are done to exclude COPD or any other obstructive lung disease. FEV1/FVC ratio is normal in OHS whereas it is reduced in obstructive lung disease. Electrocardiography and echocardiogram can reveal features of right ventricular enlargement and pulmonary hypertension (‘p’ pulmonale). Factors associated with hypoxemia in OHS are atelectasis, alveolar hypoventilation, V/Q mismatch and pulmonary hypertension with heart failure. 228
 
 
Treatment
Supplemental oxygen is ineffective in patients with OHS. BiPAP is started, if the patient is intolerant to CPAP of ≥15 cm H2O, persistent hypoxemia inspite of resolved obstruction, and if PaCO2 does not normalize after 3 months of therapy with CPAP. Patients with type 2 respiratory failure should be considered for early initiation of noninvasive ventilation. Early initiation of NIV will reduce the need for intubation and invasive ventilation. NIV with facemask is preferred in ICU patients rather than nasal mask.
 
Goals for NIV in OHS
  • Improvement of signs and symptoms
  • Improving PaO2
  • Normalizing the nocturnal and daytime PaCO2 and pH
  • Daytime PaCO2 of 40–50 mm Hg.
After achieving the goals, the patient can be transferred from ICU. Failure of improvement with NIV should be considered as indication for invasive ventilation. Failure of all strategies should point towards consultation with bariatric surgeon.
 
Indications of Tracheostomy in OHS
  • It is considered as a last option in patients where all treatments have failed
  • Daytime hypercapnia inspite of all treatments.
Tracheostomy can improve hypercapnia and nocturnal obstructive events.
 
Respiratory Stimulants
  • Acetazolamide
  • Medroxy progesterone.
Their role is questionable but may be used in combination with CPAP/BiPAP (Flow chart 30.1).
Flow chart 30.1: Algorithm for management of OHS in an obese patient
229
Fig. 30.1: RAMP position for intubating a morbidly obese patient
 
Perioperative Management
It includes a careful preoperative assessment of airway and all other systems involved with obesity. Large neck circumference (>17 inches in males, >15 inches in females) and increased amount of pretracheal soft tissue measured ultrasonically were found to be positive predictors of difficult intubation with laryngoscopy performed with patients in the sniffing position. Collins et al. did a study on two different positions for intubation in obese patients. They found that there was a favorable laryngoscopic view with RAMP position rather than sniffing position (Fig. 30.1). Intubating these morbidly obese patients is challenging, and hence an experienced anesthesiologist is required to intubate these patients. Intubation using fiberoptic bronchoscopy is used, and if ventilation is difficult to maintain, a proseal or intubating Laryngeal mask airway can be used as an alternative. Postoperative management of airway is done with CPAP or BiPAP machines in PACU with monitoring of EtCO2 and pulse oximetry to prevent atelectasis and small airway closure.
 
BIBLIOGRAPHY
  1. Alam K, Lewis JW, Stephens JN, et al. Obesity, metabolic syndrome and sleep apnoea: All pro-inflammatory states. Obes Rev. 2007;8:119-27.
  2. Al Dabal L, Bahammam AS. Obesity hypoventilation syndrome. Annals of Thoracic Medicine 2009;4(2):41-9. doi:10.4103/1817-1737.49411.
  3. Collins JS, Lemmens HJ, Brodsky JB, et al. Laryngoscopy and morbid obesity: A comparison of the “sniff” and “ramped” positions. Obes Surg. 2004;14:1171-5.
  4. Conway B, Rene A. Obesity as a disease: No lightweight matter. Obes Rev. 2004;5: 145-51.
  5. Ezri T, Gewurtz G, Sessler DI, et al. Prediction of difficult laryngoscopy in obese patients by ultrasound quantification of anterior neck soft tissue. Anaesthesia. 2003; 58:1111-4.
  6. 230Guilleminault C. Clinical features and evaluation of obstructive sleep apnea. Kryger MH, Roth T, Dement WC (Eds). Principles and Practice of Sleep Medicine, 2nd edn. Philadelphia: WB Saunders; 1994.p 667.
  7. Kushida CA, Chediak A, Berry RB, Brown LK, Gozal D, Iber C, et al. Clinical guidelines for the manual titration of positive airway pressure in patients with obstructive sleep apnea. J Clin Sleep Med. 2008;4(2):157-71.
  8. Miller WP. Cardiac arrhythmias and conduction disturbances in the sleep apnea syndrome. Am J Med. 1982;73:317.
  9. Onal E, Lopata M, O'Connor T. Pathogenesis of apneas in hypersomnia: sleep apnea syndrome. Am Rev Respir Dis. 1982;125:167.
  10. Orr WC, Martin RJ. Obstructive sleep apnea associated with tonsillar hypertrophy in adults. Arch Intern Med. 1981;141:990.
  11. Rajagopal KR, Abbrecht PH, Derderian SS, et al. Obstructive sleep apnea in hypothyroidism. Ann Intern Med. 1984;101:491.
  12. Shepard JW Jr, Garrison MW, Grither DA, et al. Relationship of ventricular ectopy to oxyhemoglobin desaturation in patients with obstructive sleep apnea. Chest. 1985; 88:335.
  13. Walsh RE, Michaelson ED, Harkleroad LE, et al. Upper airway obstruction in obese patients with sleep disturbance and somnolence. Ann Intern Med. 1972;76:185.
231Approach to mechanical ventilation
Chapter 31 Basics of Mechanical Ventilation Prem Kumar, S Yuvaraj
Chapter 32 Initiation of Ventilation Prem Kumar
Chapter 33 Modes of Ventilation Prem Kumar
Chapter 34 Weaning from Mechanical Ventilation Prem Kumar
Chapter 35 Patient Ventilator Asynchrony Prem Kumar
Chapter 36 Noninvasive Ventilation Prem Kumar, S Yuvaraj232

BASICS OF MECHANICAL VENTILATIONCHAPTER 31

Prem Kumar, S Yuvaraj
Mechanical ventilation is a type of breathing in which an external machine augments or controls the breathing of a patient when the ventilatory requirements are not met. The goal of mechanical ventilation is to reduce the work of breathing in the patient and to improve gas exchange.
There are two types of mechanical ventilation:
  1. Negative pressure ventilation
  2. Positive pressure ventilation.
Another classification of mechanical ventilation is:
  • Noninvasive ventilation
  • Invasive ventilation.
 
NEGATIVE PRESSURE VENTILATION
Till the mid 20th century, ventilators used for the patients were only negative pressure ventilators popularly called as iron lung. Flow of oxygen was driven into the patient's lung by creating a subatmospheric pressure around the chest. But it was difficult to nurse and access the patients especially when the patient was hemodynamically unstable. Later negative pressure ventilators lost its popularity and positive pressure ventilators replaced them.
 
POSITIVE PRESSURE VENTILATION
Positive-pressure ventilation is a type of ventilation where pressure above the atmospheric pressure is driven either through a face mask or nasal mask (non-invasive) or through an endotracheal tube (invasive). In an ICU, either non-invasive or invasive ventilation is given according to the clinical conditions. On delivery of the ventilation, airway pressure is more than the alveolar pressure.
 
VENTILATOR DESIGN
Current ventilators use bellows system using oxygen as driving gas. Recently piston driven ventilators and microprocessor controlled pneumatic drive mechanism are being used. The ventilators are designed to trigger, limit and cycle the breath according to set parameters. Mode controller is either pneumatic-or 234microprocessor-based system which enables the breath delivery according to algorithm and feedback (closed loop) from the patient. Recently closed loop system has become very popular since it allows continuous adjustment in algorithms according to patient's lung dynamics. Flow and pressure transducers are installed in the ventilator which will act as sensors for breath effort. Humidifiers also are part of the system which humidifies the gases delivered to the patient. Ventilator circuit with known compliance is used.
 
NOMENCLATURES AND THEIR SIGNIFICANCE
Any mode of ventilation has four components (Table 31.1):
  1. Breath type
  2. Control
  3. Phase variables
  4. Conditional variable.
Table 31.1   Components of ventilation
Breath type
Control variable
Phase variables
Conditional variable
  • Mandatory
  • Assisted
  • Spontaneous-assisted
  • Pressure
  • Time
  • Flow
  • Volume
  • Trigger
  • Limit
  • Cycling
  • Expiration
  • PEEP
 
BREATH TYPE (Figs 31.1 to 31.4)
Mandatory: The breath is initiated and terminated by the machine.
Assisted: The breath is initiated by the patient but terminated by the machine.
Spontaneous: The breath is initiated and terminated by the patient.
Fig. 31.1: Volume control mode with mandatory breaths
235
Fig. 31.2: SIMV (volume control) with pressure support showing assisted breaths
Fig. 31.3: Pressure support ventilation with spontaneous breaths
Fig. 31.4: Spontaneous and supported breaths in pressure waveform
236
 
Control
Usually volume or pressure controlled ventilation modes are seen in most ventilators. Control indicates preset parameter which assures the set limit, e.g. volume-controlled ventilation assures set tidal volume (Figs 31.5 and 31.6).
 
Trigger
It is a physical change that initiates a breath. Four types of trigger are—time, pressure, flow, volume.
Fig. 31.5: Volume control ventilation shown by waveform (indicated by arrow)
Fig. 31.6: Pressure control ventilation shown by waveform (indicated by arrow)
237
 
Limit
After triggering is on, limit is the mechanism that provides a mode of ventilation within a parameter such as time, pressure, volume, flow. Volume-limited breaths are flow controlled. Pressure-limited ventilation are pressure controlled. Time and volume control is seen infrequently.
 
Cycling
Cycling is defined as the transition point where there is change from inspiratory phase to expiratory phase in a mechanically ventilated breath. It can be time cycled which is most commonly seen in most pressure-controlled breaths. This can be seen when inspiratory time lapses (Ti) in pressure-controlled ventilation. It can also be:
Time cycled—seen in PCV
Pressure cycled—seen in intermittent mandatory breaths
Flow cycled—seen in PSV
Volume cycled—seen in volume assist modes.
 
Expiration
Expiration can be prolonged in conditions like COPD where air trapping is common.
 
Effects of Positive Pressure Ventilation and PEEP
Lung dynamics—pressures in airways, alveoli are increased. Especially the peak inspiratory pressure and mean airway pressure are related to tidal volume, peak inspiratory flow rate and compliance. In lungs where compliance is decreased (e.g. ARDS), higher peak inspiratory pressure (PIP) and PEEP is required to ventilate the lung.
PEEP: It is an airway pressure strategy which increases the end-expiratory pressure above the atmospheric pressure. PEEP increases mean airway pressure and results in reduced cardiac output and increase in PEEP may cause hypotension. It causes increase in PAP (pulmonary artery pressure) and hence increased central venous pressure. The goal of PEEP in patients with airway obstruction is to minimize inspiratory work.
Cardiovascular effects: Positive pressure ventilation causes increase in intrathoracic pressure which in turn causes compression of great vessels and ends in reduction of cardiac output. Positive pressure ventilation as such causes fall in central venous pressure (CVP) due to reduced venous return.
 
BIBLIOGRAPHY
  1. Chang DW. Clinical application of mechanical ventilation, 3rd edn. 2006.
  2. Gay PC, Rodarte JR, Hubmayr RD. The effects of positive expiratory pressure on isovolume flow and dynamic hyperinflation in patients receiving mechanical ventilation. Am Rev Respir Dis. 1989;139:621.
  3. 238Hill NS. Clinical applications of body ventilators. Chest. 1986;90:897.
  4. Irwin RS, Rippe JM. Irwin and rippe's intensive care medicine, 6th edn. Lippincott Williams and Wilkins, 2008.
  5. Petrof BJ, Legare M, Goldberg P, et al. Continuous positive airway pressure reduces work of breathing and dyspnea during weaning from mechanical ventilation in severe chronic obstructive pulmonary disease. Am Rev Respir Dis. 1990;141:281.
  6. Tobin MJ, Jubran A, Laghi F. Patient-ventilator interaction. Am J Respir Crit Care Med. 2001;163:1059.

INITIATION OF VENTILATIONCHAPTER 32

Prem Kumar
Mechanical ventilation is indicated in patients who are not able to maintain the ventilation or on loss of spontaneous ventilation. Mechanical ventilators either give partial or complete support depending upon the condition and status of the patient (Tables 32.1 and 32.2).
Table 32.1   Indications for initiation of mechanical ventilation
Indications
  • Severe hypoxemia—PaO2 <50 mm Hg with FiO2 of >0.5
  • PaCO2 >50 mm Hg
  • Severe metabolic (lactic) acidosis pH <7.2
  • SpO2 <85%
  • Impending ventilatory failure as indicated by the following criteria:
    • Tidal volume <5 mL/kg
    • Respiratory rate >35/minute
    • Vital capacity <10 mL/kg
    • Minute ventilation >10 L/minute
    • Maximal inspiratory pressure < –20 cm H2O
  • Alveolar arterial gradient >450 mm Hg with 100% oxygen
  • Head injury with GCS (Glassgow coma scale) <8
  • Severe hemodynamic instability with hypoxemia
  • Apnea due to other causes (e.g. Drug toxicity, myasthenia gravis)
  • Vd/Vt ratio >0.6
Table 32.2   Types of respiratory failure—conditions which require mechanical ventilation
Type 1 respiratory failure
Type 2 respiratory failure
Type 3 respiratory failure
Type 4 respiratory failure
Conditions with increased shunting
  • ARDS
  • Pulmonary edema
  • Pneumonia
  • Intrapulmonary shunting
Obstructive lung disease
  • Asthma
  • COPD
Perioperative failure
  • Atelectasis
Occurs due to shock where there is decreased perfusion to respiratory muscles
240Once mechanical ventilation is initiated, the goals of mechanical ventilation are:
  • Reducing the work of breathing
  • Improving the gas exchange
  • Reversion of the pathological condition to normal
  • Correction of lung dynamics
  • Avoiding complications due to mechanical ventilation (e.g. barotrauma, nosocomial pneumonia, oxygen toxicity).
 
INITIAL VENTILATOR SETTINGS
Initial ventilator settings should be based upon the patient's status, pathophysiology of the condition and its relation to the respiratory system. The following ventilatory settings must be selected:
  • Mode
  • Tidal volume
  • Inspired oxygen concentration (FiO2)
  • Respiratory rate (mandatory)
  • Inspiratory to expiratory ratio (I:E ratio) or inspiratory time (Ti)
  • PEEP
  • Trigger sensitivity
  • Inspiratory flow pattern
  • Pressure support
  • Alarm settings.
 
Mode
The initial step in initiating ventilation is selection of mode and the decision of selecting the mode depends on whether the patient requires total or partial ventilatory support. Most of the ICU patients may require complete support initially followed by partial support on weaning (Table 32.3).
But nowadays combined modes or dual control modes are available in modern ventilators. (e.g. SIMV can be combined with pressure support which fastens the weaning process).
Table 32.3   Traditional modes and its uses in ICU
Modes
Comments
Assist control (A/C) mode/volume control (VCV) mode
Usually started with this mode for complete ventilatory support
Synchronized intermittent
Mandatory ventilation (SIMV)
Can give partial or complete ventilatory support
Continuous positive airway pressure (CPAP)/bilevel positive airway pressure (BiPAP)/pressure support ventilation (PSV)
Gives partial support and can be used only in spontaneously breathing patients
241
 
Tidal Volume
Initial tidal volume is usually 10–12 mL/kg based on the predicted body weight. But in conditions like ARDS lower tidal volumes of 6 mL/kg is recommended since lower tidal volume with higher respiratory rate is preferred to reduce the lung injury caused by higher tidal volume. Reduced tidal volume is also used in COPD patients with prolonged expiratory time to avoid air trapping. Tidal volume is preferable to be guided with expired tidal volume and capnography since the circuit compliance is another factor which has to be borne in mind while calculating the tidal volume. This volume lost due to circuit compliance is called circuit compression volume.
 
FiO2
The initial concentration can be set at 100% but after stabilizing the patient, the least possible FiO2 (usually 0.3–0.4) to obtain better PaO2 (>90 mm Hg) is kept. Higher concentration of oxygen can cause atelectasis, oxygen toxicity and further increase the lung damage. It can be increased if other settings like PEEP and pressure support does not improve oxygenation.
 
Respiratory Rate
The initial respiratory rate to attain normal PaCO2 is usually 10–12 breaths/minute increased respiratory rates can be associated with air trapping causing intrinsic PEEP. Once the patient is put on an initial ventilator setting, blood gas analysis is done after 1 hour to titrate the respiratory rate and other settings to optimize oxygenation and ventilation.
 
I:E Ratio
Usually, the normal I:E ratio kept in ventilator settings is 1:2–1:3. Expiratory phase is prolonged in patients with COPD to avoid air trapping and thus to prevent auto-PEEP. Auto-PEEP is an unintended end expiratory pressure which develops due to inadequate alveolar air emptying resulting in air trapping. Inverse I:E ratio is used in ARDS patients who have severe hypoxemia refractory to the usual treatment. Inverse ventilation requires high sedation or paralysis. Increasing the flow rate or reducing the tidal volume or reducing the respiratory rate or reducing the inspiratory time (Ti%) will increase the I:E ratio or prolong the expiratory phase.
 
PEEP
It is an airway pressure strategy which increases the end-expiratory pressure above the atmospheric pressure. PEEP increases the functional residual capacity by alveolar recruitment and improves the oxygenation and reduces the work of breathing. It is also indicated for patients having refractory hypoxemia due to intrapulmonary shunting. Usually, PEEP of 5 cm H2O is kept normally for ventilated patients. In patients with ARDS (reduced lung compliance), higher PEEP is required to improve oxygenation.242
 
Trigger Sensitivity
The change required in the patient to deliver the ventilator breath is trigger sensitivity. It is usually set at –2 cm H2O which means the patient just needs to generate a pressure of –2 cm H2O at airway opening to initiate the ventilator breath. Increasing the trigger (e.g. –4 cm H2O) means that the patient needs to put more inspiratory effort to trigger the ventilator. It can be either pressure or flow trigger.
 
Inspiratory Flow Pattern
It can be square flow pattern and sine wave pattern. Ascending and descending flow patterns can be seen in patients with obstructive lung disease. Usually, square flow pattern is used initially after keeping the setting in the ventilator.
 
Pressure Support
Nowadays modern ventilators have dual modes (e.g. SIMV with pressure support [PS]). This pressure support augments the tidal volume in the spontaneous breath which occurs in between the mandatory breaths thus reducing the work of breathing and thereby fastening the weaning period.
 
Ventilator Alarms
Ventilator alarms are kept to avoid the hazards and complications due to ventilator or due to the patient's condition. The alarm setting parameters are the following:
  • High and low airway pressure alarm
  • High and low minute ventilation alarm
  • Low-expiratory tidal volume alarm
  • Apnea alarm
  • High and low FiO2 alarm
  • High respiratory rate alarm.
 
High and Low Airway Pressure Alarm
It is usually set at 40 cm H2O as empirical value in adults or 30 cm H2O in children. But the usual way of setting the high pressure alarm is 10–15 cm H2O above the peak-inspiratory pressure in the patient. In the same way, low pressure alarm is set at 10–15 cm H2O below the peak-inspiratory pressure.
 
High and Low Minute Ventilation Alarm
The threshold limit for both high and low alarm is 10–15% above and below the patients baseline minute ventilation.
 
Low-expired Tidal Volume Alarm
It is set at 100 mL below the average expired tidal volume in the patient.243
 
Apnea Alarm
Apnea alarm should be set with 20 second delay and in most of the current ventilators there is a back up mode in case if the apnea alarm is activated.
 
High and Low FiO2 Alarm
The threshold limit for FiO2 alarm is 5–10% above or below the analysed value in the patient.
 
High Respiratory Rate Alarm
The alarm is usually kept 10–15 breaths above or below the observed the respiratory rate (Flow charts 32.1 and 32.2).
Flow chart 32.1: Trouble shooting the ventilator alarms
Flow chart 32.2: Trouble shooting the PEEP alarms
244
 
BIBLIOGRAPHY
  1. Chang DW. Clinical application of mechanical ventilation, 3rd edn. 2006.
  2. Hill NS. Clinical applications of body ventilators. Chest. 1986;90:897.
  3. Hubmayr RD, Gay PC, Tayyab M. Respiratory system mechanics in ventilated patients: techniques and indications. Mayo Clin Proc. 1987;62:358.
  4. Irwin RS, Rippe JM. Irwin and Rippe's intensive care medicine, 6th edn. Lippincott Williams and Wilkins; 2008.
  5. MacIntyre N (Ed). Controversies in Mechanical Ventilation. Clinics in Chest Medicine. Philadelphia: Elsevier Saunders; 2008.
  6. Stroetz RW, Hubmayr RD. Patient-ventilator interactions. Monaldi Arch Chest Dis. 1998;53:331.
  7. Tobin MJ, Jubran A, Laghi F. Patient-ventilator interaction. Am J Respir Crit Care Med. 2001;163:1059.

MODES OF VENTILATIONCHAPTER 33

Prem Kumar
There are different modes of ventilation with different operating characteristics each having an advantage and disadvantage of its own. Hence choosing a mode of ventilation is solely based on the clinical condition of the patient, lung dynamics and goal of ventilation. Although newer modes of ventilation have come into clinical practice, traditional modes of ventilation always find their importance in day to day practice in ICU.
Basic modes of ventilation
  • Volume-controlled ventilation (VCV)
  • Assist control mode (A/C)
  • Pressure-controlled ventilation (PCV)
  • Synchronized intermittent mandatory ventilation (SIMV)
  • Continuous positive airway pressure (CPAP)
  • Bilevel positive airway pressure (BiPAP)
  • Pressure support ventilation (PSV).
Newer modes of ventilation
  • Pressure-regulated volume control (PRVC)
  • Airway pressure release ventilation (APRV)
  • Inverse ratio ventilation (IRV)
  • Biphasic positive airway pressure (BIPAP)
  • Adaptive support ventilation (ASV)
  • Proportional assist ventilation (PAV)
  • Neurally adjusted ventilatory assist (NAVA)
  • Liquid ventilation
  • High frequency ventilation.
 
BASIC MODES OF VENTILATION
 
Volume-controlled Ventilation/Assist Control
Volume control mode delivers breath irrespective of patient's pattern of breathing whereas assist control allows the patient to initiate the machine delivered breath although the tidal volume is controlled by the machine. Nowadays volume control mode is not present in most ICU ventilators because of ventilator patient dyssynchrony caused by this mode and excessive need of sedation or paralysis with neuromuscular muscle relaxants. It provides rest to the respiratory muscles.246
 
Initial Settings
Respiratory rate, tidal volume, FiO2 are set in the ventilator and if the mode is VCV, the tidal volume delivered is assured provided the patient is fully sedated or paralysed. Most of the ventilators are volume-cycled. In assist control mode, the patient's inspiratory effort is detected by the demand valve in the ventilator and the breath completed by the ventilator and the patient can inspire through the ventilator demand valve. If the peak inspiratory pressure exceeds the safe limit, then the remaining tidal volume above the PIP is not delivered. The assist control mode will not allow the patient to take intermittent spontaneous breaths.
 
Advantages
  • Patient receives assured tidal volume
  • Offers complete ventilatory rest to respiratory muscles.
 
Disadvantages
  • Patient ventilator dyssynchrony
  • Respiratory alkalosis in case of spontaneous ventilation.
 
Indications
  • It is used as an initial mode of ventilation in patients who are paralyzed or patients with no spontaneous ventilation or postoperative patients who are ventilated electively.
  • To reduce the work of breathing
  • Absent central respiratory drive (e.g. opioid overdose)
  • Tetanus
  • Assist control mode can be used in patients with intact respiratory drive who needs complete respiratory support. If the patient does not trigger, then the breath is time triggered.
  • VCV characteristics—time-triggered, volume-cycled
  • A/C—patient- or time-triggered, volume- or pressure-cycled
    Waveforms —See Figure 33.1.
 
Pressure Control Ventilation
In PCV, the pressure-controlled breaths are time-triggered to the set respiratory rate and after the mandatory breath is initiated, a plateau pressure is initiated and maintained by the ventilator. The advantage of PCV is it can reduce the peak inspiratory pressure since the mandatory breath is pressure limited and ensure adequate ventilation and oxygenation. Hence, the incidence of barotrauma is reduced.
 
Initial Settings
Pressure limit, respiratory rate, FiO2 is set but the tidal volume is not assured in this mode. Another disadvantage is that it requires high sedation or paralysis.247
Fig. 33.1: Volume control mode with mandatory breaths
 
Advantages
It limits the peak inspiratory pressure and plateau pressure and minimizes lung injury.
 
Disadvantages
  • Tidal volume is not assured
  • It requires high sedation or paralysis.
 
Indications
  • Conditions which require a low airway pressure to maintain oxygenation and ventilation (e.g. Severe ARDS)
  • Lung damage prone patients (e.g. One lung ventilation)
    PCV characteristics-time-triggered, pressure-limited, time-cycled
    Waveforms —See Figure 33.2.
 
Synchronized Intermittent Mandatory Ventilation
It is a mode in which the ventilator delivers mandatory breaths during a spontaneous inspiratory effort or is time-triggered in the absence of spontaneous breath. Because of the synchronization, breath stacking is avoided. Breath stacking is defined as the occurrence of spontaneous breath during a machine delivered mandatory breath. Breath stacking occurs in intermittent mandatory ventilation which can result in patient ventilator dyssynchrony which in turn would increase the work of breathing. In SIMV, the demand valve opens in response to the patient's inspiratory effort. If at the time of mandatory breath, there is a spontaneous effort, then the machine delivers an assisted breath. SIMV allows spontaneous breath of any tidal volume in between the mandatory breaths. If SIMV has dual control mode with pressure support, then the spontaneous breath is pressure-supported allowing reduced work of breathing during spontaneous breathing and hastens weaning. 248
Fig. 33.2: Pressure control mode with mandatory breaths
 
Initial Settings
Complete ventilatory support—keep usual respiratory rate of 10–12 breaths/minute.
In case of partial ventilatory support, the respiratory rate is reduced in decrements adjusted to the minute ventilation in accordance with the spontaneous breaths.
 
Merits
  • Facilitates weaning by supporting spontaneous breaths and reducing work of breathing
  • Reduces ventilation perfusion mismatch by reducing alveolar dead space ventilation
  • Reduces airway pressure
  • Maintains respiratory muscle power.
 
Demerits
  • It cannot completely control the I:E ratio in the presence of spontaneous breaths
  • High incidence of weaning failure.
 
Indications
  • It is usually used as a weaning mode for patients who need partial ventilatory support who are taken off from the control mode (volume or pressure).
    SIMV characteristics: Type of breath-mandatory, spontaneous and assisted breath, time or patient-triggered, volume-cycled.
    Waveforms —See Figures 33.3 and 33.4.
249
Fig. 33.3: SIMV (pressure control ventilation) with pressure support shown by waveform (indicated by arrow)
Fig. 33.4: SIMV (volume control) with pressure support showing assisted breaths
 
PRESSURE SUPPORT VENTILATION (FIG. 33.5)
 
Pressure-regulated Volume Control
It has different names in various ventilators like autoflow, adaptive pressure ventilation. It is present in the Siemens ventilator. It is present as a dual control mode with control mode and SIMV. PRVC gives volume support with the lowest peak inspiratory pressure by altering flow rate and inspiratory time in response to change in lung compliance and airway pressure. This mode prolongs the inspiratory time to deliver the target volume to compensate for lower inspiratory flow. The ventilator gives test breath. Certain ventilators have automode which 250combines PRVC and volume support where in case of absence of spontaneous ventilation, PRVC is initiated and if spontaneous effort is present, automode switches to volume support.
Fig. 33.5: Pressure support ventilation with spontaneous breaths
  Pressure change  = tidal volume/compliance
In response to target pressure, the ventilator switches to pressure control ventilation and assures tidal volume with least peak inspiratory pressure.
 
Initial Settings
Tidal volume, ventilator rate, trigger sensitivity, inspiratory time. It determines lung dynamics by giving test breaths.
 
Indications
Useful in patients where adequate tidal volume is required with low peak inspiratory pressure. (e.g. ARDS) but many studies have indicated that there is no benefit with this mode compared with PCV.
PRVC characteristics—control or synchronized intermittent breath, time or patient-triggered, volume-cycled.
 
Airway Pressure Release Ventilation
This is a mode of ventilation in which spontaneous ventilation are allowed like CPAP maintaining a long period of high pressure followed by a short period of low pressure where there is release of PEEP valve. The long period constitutes the inspiratory phase and short phase constitutes the expiratory phase resulting in an I:E ratio of 7-9:1. It resembles a pressure-controlled ventilation with inverse I:E ratio. The only difference being that in APRV, the patient is allowed to breathe 251spontaneously during any point of a mandatory breath. APRV mandatory breaths are pressure limited. The patient's tidal volume will vary according to the lung dynamics and the pressure gradient.
 
Initial Settings
Phigh, Plow, Thigh, Tlow.
 
Advantages
  • Decreases the frequency of opening and closing the alveoli, in other words APRV maintains alveolar recruitment throughout the ventilatory cycle.
  • Reduces lung injury due to the lower peak airway pressure generated by this mode.
 
Disadvantage
Pneumothorax.
 
Indications
To improve oxygenation in patients with severe ARDS since it can provide partial ventilatory support with lower peak airway pressure.
APRV characteristics—time-triggered, pressure-limited, time-cycled. Allows spontaneous breathing during any point of mandatory breath.
 
Inverse Ratio Ventilation
There have been attempts in increasing the inspiratory time to increase oxygenation in ARDS. Often an I:E ratio of 2:1–4:1 is used in IRV. Pressure control ventilation is used in IRV. IRV improves oxygenation by reducing alveolar dead space ventilation and intrapulmonary shunting. This improvement in oxygenation is due to increase in mean airway pressure.
 
Initial Settings
Pressure preset, FiO2, I:E ratio.
 
Advantage
Improves oxygenation in ARDS.
 
Disadvantages
  • Auto–PEEP due to shortened expiratory time
  • Barotrauma
  • Because of the prolonged the inspiratory duration, ventilation requires sedation and peripheral muscle relaxants.252
 
Indication
Acute respiratory distress syndrome (ARDS).
 
Biphasic Positive Airway Pressure
Biphasic positive airway pressure (BIPAP) can be described as pressure-controlled ventilation with pressure support ventilation in a system allowing time-cycled mandatory breaths and allows unrestricted spontaneous breathing at any moment of the ventilatory cycle. It uses the same principle as APRV. Baum et al. described biphasic positive airway pressure ventilation as a mode in which spontaneous ventilation could be achieved at any point in the mechanical ventilation cycle (inspiration or exhalation). This mode allows unrestricted spontaneous breathing to reduce sedation and promote weaning. BIPAP and APRV are conceptually the same, the main difference being that the time spent in low pressure (Tlow) is less than 1.5 seconds for APRV. Otherwise, they have identical characteristics, thus allowing any ventilator with the capability of delivering APRV to deliver biphasic positive airway pressure, and vice versa. Since it enables progressive transition from controlled to all levels of augmented mechanical ventilation, BIPAP appears to be a suitable mode for the entire period of mechanical ventilation of the patient.
 
Initial Settings
As with a pressure-controlled, time-cycled mode, the duration of each phase (T(high), T(low)) as well as the corresponding pressure levels (P(high), P(low)) can be adjusted independently. BIPAP system delivers two different positive pressure levels—an inspiratory positive airway pressure, or IPAP, and an expiratory positive airway pressure, or EPAP. The difference between these two pressure levels is commonly referred to as the pressure support.
 
Indications
  • It can be used for both initiation of ventilation and weaning
  • ARDS improves lung compliance, venous admixture, and arterial oxygen tension without causing cardiovascular impairment in ARDS.
 
Advantages
  • Improves oxygenation, reduces venous admixture.
  • Recruits collapsed alveoli
  • Hastens weaning since this mode allows spontaneous breathing at any point of ventilatory cycle.
 
Liquid Ventilation
It is a technique where perfluorocarbons are used as oxygen delivery agents. The solubility of oxygen and carbon dioxide is 20 times higher in PFC's. the higher solubility of oxygen with PFC's increases the oxygen delivery to the lung.
253There are two types of liquid ventilation:
  1. Total
  2. Partial
 
Total Liquid Ventilation
Only PFC is used as oxygen delivery agent, it requires special equipment. The lungs are filled with PFC with a volume equal to FRC and a liquid ventilator is used to generate tidal volume. CO2 clearance is achieved with a rate of 4–5 breaths/minute. Distribution of PFC within the lungs is more uniform with total type.
 
Partial Type
PFC and gases like inhaled nitric oxide are used as oxygen delivery agents. Partial liquid ventilation can be done with usual ventilator. Partial liquid ventilation is also called PAGE (PFC-associated gas exchange). PFC may act as artificial surfactant for neonatal respiratory distress syndrome (RDS) or as a lavage for certain types of pulmonary dysfunction.
 
Indications
  • Used in severe respiratory distress syndrome (hyaline membrane disease) in neonates who do not meet the criteria for ECMO.
  • Meconium aspiration syndrome with respiratory failure
  • ARDS
  • Nonventilatory indication—can be used as a medium for delivery of antibiotics, anesthetic agents, vasoactive agents.
 
Advantages
  • PFC is inert
  • Keeps alveoli open at end expiration, increases functional residual capacity and acts as PEEP.
  • Improvement of oxygenation in acute lung injury
  • Improvement in lung compliance
  • Causes lavage effect by which the alveolar debris can be suctioned.
  • Reduces the production of inflammatory cytokines
 
Disadvantages
  • Equipment is costly especially with total liquid ventilation
  • Pneumothorax
  • Hemodynamic instability especially with total liquid ventilation.
 
High Frequency Ventilation
High frequency ventilation is a newer mode of ventilation where the ventilator delivers small tidal volumes of high respiratory rates (>60 breaths/minute). 1 hz equals 60 breaths/minute.254
 
Types (Tables 33.1 and 33.2)
  • High frequency positive pressure ventilation (HFPPV)
  • High frequency jet ventilation (HFJV)
  • High frequency oscillatory ventilation (HFOV).
Table 33.1   Frequencies of various types of high frequency ventilation
Type of ventilator
Frequency
High frequency positive pressure ventilation (HFPPV)
60–150 breaths/minute
High frequency jet ventilation (HFJV)
100–150 breaths/minute
High frequency oscillatory ventilation (HFOV)
180–900 breaths/minute
Table 33.2   Differences between HFPPV and HFJV
HFPPV
HFJV
Principle
Tidal volume is delivered by convective air current
High frequency jet ventilator delivers high pressure pulsed gas to the patient via an adaptor attached to ET tube
Clinical indications
ARDS patients who do not respond or worsening with routine ventilation
  • Severe pulmonary hypoplasia
  • Severe restrictive lung disease
  • Postpulmonary disease induced pulmonary hypertension
Complications
  • Barotrauma
  • Hemodynamic instability
  • Intracranial hemorrhage in neonates
These complications are due to the increased mean airway pressure seen with this mode.
  • Necrotizing tracheobronchitis due to lack of humidification
  • Hyperinflation due to gas trapping
  • Hemodynamic instability
  • Unpredictable tidal volume delivery, hence PaO2 and PaCO2 should be monitored.
 
High Frequency Oscillatory Ventilation
This mode has been in use for neonates and children for hyaline membrane disease and severe pulmonary disease but is recently in use for adult patients too but with limited indications. High frequency oscillatory ventilation (HFOV) in current literature is only indicated as a rescue therapy.
 
Principle
A piston pump produces oscillatory waves which deliver the gas to the lungs. The oscillator attached to the ET tube assists both inspiration and expiration.
 
Indications
  • Hyaline membrane disease—most common indication for HFOV. Usually preterm neonates are considered for HFOV
  • Congenital diaphragmatic hernia
  • 255Pulmonary hypoplasia
  • Failure of response to conventional ventilation in neonates
  • Pulmonary hypertension
  • Increasing FiO2 requirement, PIP >20 cm H2O, infants <1 kg
  • For clinical use in adults, a trial of HFOV can be considered when:
    • FiO2 >60%
    • Mean airway pressure >20 cm H2O
    • PEEP >15 cm H2O.
 
Advantages
  • Allows decoupling of oxygenation and ventilation
  • Humidification is not an issue unlike other types
  • Better CO2 elimination
  • Oxygenation is proportional to mean airway pressure and tidal volume
  • Prevents release of inflammatory mediators in lung.
 
Disadvantages
  • Requires high PEEP
  • Hyperinflation and barotrauma
  • Hemodynamic instability.
 
Closed Loop Ventilation
  • Adaptive support ventilation (ASV)
  • Proportional assist ventilation (PAV)
  • Neurally adjusted ventilatory assist (NAVA).
 
Adaptive Support Ventilation
It a closed loop ventilation which changes the ventilatory parameters according to patient's breathing pattern. It alters the mandatory breaths and pressure support level according to the feedback the ventilator gets from the lung dynamics of the patient. This mode is present in Hamilton medical ventilator. The ventilator gives a test breath and measures airway resistance (Paw), compliance and auto –PEEP. Based on the above feedback gathered breath to breath, the ventilator selects respiratory rate, tidal volume, inspiratory time, I:E ratio, pressure support for mandatory and spontaneous breaths. In case there is no spontaneous effort, the ventilator provides mandatory breaths according to the preselected values. If there is spontaneous breaths, then the mandatory breath rate reduces and the spontaneous breaths are supported with pressure support.
 
Initial Settings
Body weight (for calculation of dead space – 2.2 mL/kg), percentage of minute volume (20–200% of predetermined setting). Predetermined setting of minute volume in adults–100 mL/min/kg and children– 20 mL/min/kg (e.g. 120% means 120 mL/min/kg). 256
 
Advantages
  • Since it employs lung protective strategies, it is useful in ARDS, COPD patients in minimizing lung injury.
  • Better patient ventilator synchrony
  • Reduced need of sedation
  • Reduced work of breathing and length of ICU stay.
 
ASV Characteristics
Mandatory breaths—pressure limited, time cycled, dual controlled (SIMV + PSV) on breath by breath basis
Spontaneous breaths—PSV with variable pressure.
 
Proportional Assist Ventilation
Proportional assist ventilation (PAV) delivers gas with a feedback mechanism which it gets on a breath-to-breath basis. This mode is available in puritan Bennett ventilator. With the test breath, the ventilator calculates resistance, elastance and auto–PEEP. With these calculations, the ventilator generates inspiratory flow rate and volume and provides support in proportion to the pulmonary characteristics and demand of the patient. In other words, PAV is a novel mode of partial ventilatory support in which the ventilator generates an inspiratory pressure in proportion to the respiratory effort of the patient. Unlike PSV where the pressure support is constant, PAV alters pressure support according to the patient's demand. The respiratory drive has to be intact in this mode.
 
Initial Settings
Cycle (3 L/min), trigger, percent support (% of work of breathing). Percent support usually started at 70% and decreased in intervals.
 
Indications
  • Restrictive lung disease
  • Improves ventilation and reduces the work of breathing in ventilator dependent patients with COPD.
 
Advantages
  • Patient ventilator synchrony
  • Provides uniform breathing pattern.
 
Disadvantages
  • Cannot be used in patients with reduced respiratory drive.
  • PAV support will be inadequate to relieve the patient's symptoms if the elastance and resistance are overestimated, a positive feedback will develop 257and the ventilator will continue to deliver flow and volume while the patient stops inspiratory effort (the “run-away” phenomenon).
 
Characteristics
Assisted breaths, pressure- or flow-triggered, volume or flow cycling.
 
Neutrally Adjusted Ventilatory Assist
Neutrally adjusted ventilatory assist (NAVA) is a novel mode of ventilation in which the system has the ability to measure the electrical activity of the diaphragm and convert the ventilatory drive into ventilatory output. This is called neuroventilatory coupling. Microprocessor-based technology obtains signals and the signal from the diaphragm triggers the ventilator and assists the patient's inspiratory effort in proportion to the diaphragmatic electrical activity. This ventilator support occurs within a breath and between breaths. This mode is yet to come into clinical practice.
 
Prerequisites
  • Intact diaphragmatic function
  • Intact phrenic nerve
  • Intact neuromuscular junction.
 
BIBLIOGRAPHY
  1. Arnal JM, Wysocki M, Nafati C, Donati S, Granier I, Corno G, Durand-Gasselin J. Automatic selection of breathing pattern using adaptive support ventilation. Intensive Care Med. 2008;34(1):75-81.
  2. Chang DW. Clinical application of mechanical ventilation, 3rd edn, 2006.
  3. Derdak S. High-frequency oscillatory ventilation for acute respiratory distress syndrome in adult patients. Crit Care Med. 2003;31(4 Suppl):S317-23.
  4. Fedora M, Nekvasil R, Deda M, Klimovic, Dominik P. Partial liquid ventilation: first experience in children with acute respiratory distress syndrome. Scripta Medica (Brno). 2000;73(4):229-36.
  5. Kaisers U, Kelly KP, Busch T. Liquid ventilation. New Concepts in Respiratory Function: Br J Anaesth. 2003;91(1):143-51.
  6. Kimless-Garber DB, Wolfson MR, Carlsson C, Shaffer TH. Halothane administration during liquid ventilation. Respir Med. 1997;91:255-62.
  7. Susan P. Mechanical ventilation. Physiological and clinical applications. Mosby publications.
  8. Thomas HS, Wolfson MR, Greens Pan JS. Liquid ventilation: Current status. Pediatr Rev. 1999;20:134-42.
  9. Valls I, Soler A, Wauer RR, Vallis-I-Soler A 2nd. European symposium on liquid ventilation. Eur J Med Res. 2001;6(3):115-38.
  10. Verbrugge SJ, Lachmann B. Partial liquid ventilation. Eur Respir J. 1997;10(9):1937-9.
  11. Zelinka MA, Wolfson MR, Calligaro I, et al. A comparison of intratracheal and intravenous administration of gentamicin during liquid ventilation. Eur J Pediatr. 1997;156: 401-4.

WEANING FROM MECHANICAL VENTILATIONCHAPTER 34

Prem Kumar  
DEFINITION OF WEANING
The process of gradual discontinuation of mechanical ventilatory support from the patient (Flow chart 34.1).
 
WEANING CRITERIA
  • Adequate oxygenation
    • spO2 >92%,
    • PaO2 >60 mm Hg with FiO2 of <0.4,
    • PaCO2 <50 mm Hg
      Flow chart 34.1: Weaning process
      Abbreviations: NIV, noninvasive ventilation; SBT, spontaneous breath trial
    • 259P[A-a]O2 <350 mm Hg,
    • PaO2/FiO2 >200 mm Hg
  • Adequate ventilation
    • Tolerates SBT for 1–2 hours,
    • Vt (tidal volume) >5 mL/kg,
    • Vital capacity >10 mL/kg
    • RR <30/minute
    • EtCO2 <50 mm Hg
    • Minute ventilation <10 L/minute
  • Lung dynamics and reserve
    • Maximal inspiratory pressure > –25 cm H2O
    • Static compliance > 30 mL/cm H2O
    • Vd/Vt <0.6
    • RSBI<100
    • Qs/Qt (an indicator of pulmonary shunting) <20%
  • Neuromuscular criteria
    • P0.1 >5 cm H2O (indicator of neuromuscular inspiratory drive)
  • Clinical criteria
    • Hemodynamically stable
    • Normal mental status
    • Normotheramic
    • No or minimal sedation.
 
Measuring Parameters for Weaning (Figs 34.1 to 34.3)
Fig. 34.1: Measurement of static compliance, resistance, plateau pressure
260
Fig. 34.2: Measurement of maximal inspiratory pressure (MIP)
Fig. 34.3: Measurement of P0.1
 
Weaning Indices
  • Simplified weaning index <9/minute
  • Compliance rate oxygenation and pressure index (CROP) >13 mL/breaths/minute
  • Rapid shallow breathing index (RSBI)—respiratory rate/tidal volume in liters <100.
Among all these indices, rapid shallow breathing index is more accurate in predicting weaning success. Patient is taken from the ventilator, and the expired tidal volume and spontaneous respiratory rate is measured for 1 minute.
Simplified weaning index evaluates gas exchange and ventilator endurance. CROP index indicates pulmonary gas exchange and the adequacy of respiratory neuromuscular drive to the patient demand. 261
 
Weaning Techniques
  • Synchronized intermittent mandatory ventilation (SIMV)
  • Pressure support ventilation (PSV)
  • Continuous positve airway pressure (CPAP) bilevel positive airway pressure (BiPAP)
  • T-tube trial.
 
Weaning Trial
When predictors of weaning are favorable, spontaneous breathing trial (SBT) is indeed done with any of the above weaning modes.
 
Weaning Protocol of Synchronized Intermittent Mandatory Ventilation (SIMV) (Flow chart 34.2)
Flow chart 34.2: Weaning protocol of SIMV
 
Weaning Protocol of PSV (Flow chart 34.3)
Flow chart 34.3: Weaning protocol of PSV
262
 
Weaning Protocol of T Tube
This is a traditional technique of weaning the patient. It is done in between mechanical ventilation. Initially it is done for 5–10 minutes and later the duration of T tube trial is increased to 30 minutes. But studies (Esteban, et al.) have found that a single trial for a day is as effective as multiple trials and a single trial of 30 minutes duration with T tube is effective in identifying patients for safe extubation. Though the technique of T tube weaning trial has become unpopular, still it is being used by some intensivists.
 
Weaning with CPAP/BiPAP
Noninvasive/invasive ventilation with CPAP/BiPAP is used in patients with COPD and type 2 respiratory failure and it has been shown that it facilitates extubation and reduces the duration of mechanical ventilation. It can be done with either face mask or through an endotracheal tube. The pressure support can be reduced by 2–4 cm H2O over hours. Weaning with spontaneous breathing modes has definitely a role in type 2 respiratory failure patients who have failed T tube trials.
 
Weaning Success
Effective spontaneous breathing without any ventilatory assistance for more than 24 hours.
 
Weaning Failure
  • Abdominal distension causing increased work of breathing
  • Subglottic stenosis, laryngeal edema
  • Acute respiratory distress syndrome (ARDS)
  • Respiratory muscle fatigue
  • Poor neurological status
  • Inadequate ability to protect airway
  • Poor lung reserve and dynamics.
 
Extubation
A good clinician takes care of extubation in a meticulous way since the clinical judgement should be correct in picking up the time of extubation to avoid post-extubation respiratory distress.
 
Prerequisites for Extubation
  • Head-end elevation by 30–60°
  • Withholding enteral feeding for at least 4–6 hours
  • Adequately suctioned upper airway and endotracheal tube
  • Alveolar recruitment with AMBU bag (optional)
  • Good airway reflexes
  • Good respiratory drive
  • No laryngeal edema identified by cuff leak test or ultrasound.
  • Favorable weaning predictor tests.263
 
Our Institutional Protocol for Extubation
  • Give 1.5 mg/kg of 2% xylocard intravenously to abolish sympathetic stimulation.
  • Give good oropharyngeal suction
  • Deflate the cuff
  • Occlude the tube
  • Observe and hear whether patient can breath around the tube
  • Introduce cook's airway exchange catheter into the endotracheal tube
  • Extubate the endotracheal tube with the airway exchange catheter (AEC) in position
  • Give O2 of 6 L/minute through AEC for 5–10 minute
  • If SpO2 > 92%, AEC can be removed
  • Place venturi mask and give O2 with 4–6 L/minute.
 
Indications for Paralyzing a Patient in Mechanical Ventilation
  • Paralysis with muscle relaxants should be kept as a last option
  • Weaning Failure
  • Severe hemodynamic instability
  • Neurosurgeries to prevent increased ICP
  • Poor lung compliance
  • Synchronization with modes of ventilation with inverse I:E ratio (e.g. APRV, IRV).
 
BIBLIOGRAPHY
  1. Adderley RJ, et al. When to extubate the croup patient: the “leak” test. Can J Anaesth. 1987;34(3(Pt 1)):304-6.
  2. Deem S. Limited value of the cuff-leak test. Respir Care. 2005;50(12):1617-8.
  3. Epstein SK, Ciubotaru RL. Independent effects of etiology of failure and time to reintubation on outcome for patients failing extubation. Am J Respir Crit Care Med. 1998;158:489-93.
  4. Esteban A, Alia I, Tobin MJ, et al. Effect of spontaneous breathing trial duration on outcome of attempts to discontinue mechanical ventilation. Spanish Lung Failure Collaborative Group. Am J Respir Crit Care Med. 1999;159:512.
  5. Institute of Anesthesiology and Critical Care, Madras Medical College Institutional Protocol for mechanical ventilation.
  6. Meade M, Guyatt G, Cook D, et al. Predicting success in weaning from mechanical ventilation. Chest. 2001;120(6 Suppl):400S-24S
  7. Meade M, Guyatt G, Stinuff T, et al. Trials comparing alternative weaning modes and discontinuation assessments. Chest. 2001;120(6 Suppl):425S-37S.
  8. Nava S, Ceriana P. Causes of failure of noninvasive mechanical ventilation. Respir Care. 2004;49(3):295-303.
  9. Nava S, Gregoretti C, Fanfulla F, et al. Noninvasive ventilation to prevent respiratory failure after extubation in high-risk patients. Crit Care Med. 2005;33:2465.
  10. Tobin MJ, Jubran A. Principles and practice of mechanical ventilation. 2nd edn. New York, NY: Mcgraw hill; 2006. pp.1185-1220.
  11. Yang KL, Tobin MJ. A prospective study of indexes predicting the outcome of trials of weaning from mechanical ventilation. N Engl J Med. 1991;324:1445.

PATIENT VENTILATOR ASYNCHRONYCHAPTER 35

Prem Kumar
Patient ventilator asynchrony is a common problem in intensive care unit (ICU) patients put on ventilator. The basic mechanism that causes patient ventilator asynchrony is the mismatch between neural inspiratory and mechanical inspiratory time. It is often undetected and improperly treated. Optimal mode selection and settings, understanding patient's clinical condition, lung dynamics and ventilator graphics will prevent, detect and treat this condition thus, avoiding the consequences of patient ventilator asynchrony such as increased work of breathing and myocardial oxygen consumption. Other consequences of patient ventilator asynchrony are increased duration of ICU stay, mechanical ventilation, and increased incidence of weaning failure.
Patient ventilator interaction depends on four variables (Fig. 35.1 and Table 35.1):
  1. Neural function (central)
  2. Diaphragmatic contraction
  3. Clinical condition or input
  4. Respiratory mechanics of the lung and chest wall.
Let's discuss the key features of patient ventilator asynchrony—variables contributing to asynchrony, physiological effects, detection and treatment.
Fig. 35.1: Design features of an automated control system in ventilator
Table 35.1   Variables contributing to patient ventilator interaction
Patient variables
Ventilator variables
  • Respiratory drive
  • Ratio of inspiratory time to total breath cycle
  • Inspiratory flow demand (spontaneous)
  • Triggering mechanism
  • Cycling
  • Flow delivery
265
Flow chart 35.1: Causes of patient ventilator asynchrony
 
VARIABLES CONTRIBUTING TO ASYNCHRONY (Flow chart 35.1)
  • Ventilatory requirement—flow and volume demand of the patient
  • Ventilatory drive
  • Patient's inspiratory flow
  • Ratio of inspiratory time to breath cycle duration
  • Trigger mechanism
  • Cycling criteria
  • Gas delivery asynchrony.
Gas delivery asynchrony can occur when the flow, pressure and volume delivered by the ventilator is inadequate to meet the demand of the patient. In this perspective, pressure-limited ventilatory breaths will cause less asynchrony since flow is adjusted to maintain constant pressure.
Inspiratory phase asynchrony is due to the ineffective triggering inspite of patient's inspiratory effort. Certain causes of ineffective triggering are intrinsic positive end-expiratory pressure (PEEP), low elastance and increased airway resistance. Administering external PEEP to a patient with auto-PEEP can reduce the patient's inspiratory effort to trigger the ventilator. Other interventions which can be used for overcoming auto-PEEP are prolongation of expiratory time, reducing respiratory rate, reducing tidal volume, administration of bronchodilators. Increased application of pressure support can reduce the respiratory drive and hence causing ineffective triggering.
Patient ventilator asynchrony can be prevented by having a continuous interaction between the following parameters—trigger, cycling, ventilatory drive of the patient, flow delivery, inspiratory flow demand, ratio of inspiratory time to total breath duration. If these parameters constantly change itself according to the demand of the patient based on the patient's lung dynamic variables, patient ventilator interaction would be better. For achieving this synchrony, there has to be a closed loop system between the patient and ventilator. So based on the patient variables, the ventilator alters the parameters for the demand of the patient. Newer modes of ventilation like proportional assist ventilation, adaptive support ventilation and neurally adjusted ventilatory assist are modes of closed loop system.
One of the causes for patient ventilator asynchrony in assist control ventilation (volume-cycled) is the set inspiratory flow rate in the post-trigger phase. For pressure support ventilation, the initial pressure rise time, flow-threshold for 266inspiratory cycling, pressure support level are factors which can influence patient ventilator synchrony. Optimization of the patient ventilator can be obtained with continuous matching of the following variables in the patient and the ventilator.
Continuous measurement of the following parameters and manual or automated (preferable) adaptation of the ventilator to the changes in the patient's variable in the above variables or respiratory mechanics (e.g. compliance, resistance, airway pressure, etc.) can reduce patient ventilator asynchrony.
 
Physiologic Effects of Patient Ventilator Asynchrony
  • Effects of inadequate ventilatory support: Tachypnea due to increased respiratory workload, agitation, paradoxical breathing, hypercarbia, use of accessory muscles of respiration.
  • Effects of excessive support: Delayed cycling causing inadequate expiratory time causing dynamic hyperinflation resulting in auto–PEEP.
 
Diagnosis of Patient Ventilator Asynchrony (Figs 35.2 to 35.4)
Optimal synchrony is based on three factors:
  1. Patient effort
  2. Graphic waveforms of mechanical ventilator
  3. Flow cycling.
Hence, in case of suspicion of patient ventilator asynchrony, the intensivist has to observe the patient effort, tidal volume and ventilator waveform. It is best done by putting the patient in pressure support ventilation (PSV) mode, and based on signs of asynchrony, the flow cycle setting is adjusted so that excessive pressure is avoided at end exhalation and triggering is optimal to avoid delayed, ineffective and double triggering.
Premature cycling occurs when the ventilator terminates the breath while the patient goes into a longer inspiratory period. During premature cycling, the ventilator senses the second breath and results in stacking of breaths or double triggering. The end result of this type of asynchrony is reduced tidal volume and increased inspiratory load. Studies have indicated that higher flow cycling percentages of peak inspiratory flow results in premature cycling.
Fig. 35.2: Patient ventilator asynchrony seen in square pattern. Dotted lines represent normal pressure waveform. Arrow shows asynchrony
267
Fig. 35.3: Patient ventilator asynchrony seen in descending ramp pattern. Dotted lines represent normal pressure waveform. Arrow shows asynchrony
Fig. 35.4: Patient ventilator asynchrony seen in descending ramp pattern. Arrow shows Breath with inadequate flow rate (upper picture) and excessive patient trigger in pressure waveform (lower picture)
Delayed cycling is defined as the presence of active expiratory effort before the cycle criterion is met. This typically occurs in COPD. Delayed cycling results in dynamic hyperinflation and intrinsic PEEP and hence increased respiratory workload and delayed triggering.
 
Management of Patient Ventilator Asynchrony (Table 35.2)
Recent modes of ventilation like proportional assist ventilation, NAVA, adaptive support ventilation reduces the incidence of patient ventilator asynchrony by 268adapting itself to the ventilator demands of the patient like airway pressure, flow and volume. NAVA has a technology of neuroventilatory coupling which senses the neural activity in the diaphragm and starts triggering the ventilator. These newer modes of ventilation are is discussed in detail under the chapter modes of ventilation.
Table 35.2   Causes and management of patient ventilator asynchrony
Etiology
Management
Delayed cycling—high resistance and low elastic recoil (COPD)
Decrease inspiratory time. Decrease tidal volume in case of CMV mode. Increase expiratory trigger sensitivity in case of PSV mode
Ineffective triggering—poor inspiratory effort, auto-PEEP
Reduce trigger sensitivity
Start interventions for reducing iPEEP – application of external PEEP, reduce tidal volume, prolong expiratory time
Delayed triggering—reduced trigger sensitivity or increased trigger inspiratory time
This is possible to be rectified only with new modes like NAVA. Increase trigger sensitivity
Double triggering—increased ventilatory demand, reduced inspiratory time
Decrease expiratory cycling criteria, decrease ventilatory demand by adjusting tidal volume and inspiratory time and flow
Autotriggering—leak in circuit, water in circuit, cardiac oscillations
Increase trigger sensitivity
Avoid hyperventilation
Switch over from flow to pressure triggering
Abbreviations: COPD, chronic obstructive pulmonary disease; PEEP, positive end-expiratory pressure; CMV, continuous mandatory ventilation; NAVA, neurally adjusted ventilatory assist
 
BIBLIOGRAPHY
  1. Calderini E, Confalonieri M, Puccio PG, et al. Patient Ventilator asynchrony during noninvasive ventilation: The role of the expiratory trigger. Intensive Care Med. 1999; 25:662-7.
  2. Nilsestuen JO, Hargett KD. Using ventilator graphics to identify patient-ventilator asynchrony. Respir Care. 2005;50(2):202-34.
  3. Parthasarathy S, Jubran A, Tobin MJ. Cycling of inspiratory and expiratory muscle groups with the ventilator in airflow limitation. Am J Respir Crit Care Med. 1998;158: 1471-8.
  4. Prinianakis G, Kondili E, Georgopoulos D. Effects of the flow waveform method of triggering and cycling on patient-ventilator interaction during pressure support. Intensive Care Med. 2003;29(11):1950-9.
  5. Ranieri VM, Grasso S, Fiore T, Giuliani R. Auto-positive end-expiratory pressure and dynamic hyperinflation. Clin Chest Med. 1996;17:379-94.
  6. Sassoon CS, Foster GT. Patient-ventilator asynchrony. Curr Opin Crit Care. 2001;7(1): 28-33.
  7. Thille AW, Rodriguez P, Cabello B, et al. Patient-ventilator asynchrony during assisted mechanical ventilation. Intensive Care Med. 2006;32:1515-22.
  8. Tokioka H, Tanaka T, Ishizu T, Fukushima T, Iwaki T, Nakamura Y, Kosogabe Y. The effect of breath termination criterion on breathing patterns and the work of breathing during pressure support ventilation. Anesth Analg. 2001;92(1):161-5.

NONINVASIVE VENTILATIONCHAPTER 36

Prem Kumar, S Yuvaraj  
DEFINITION
Noninvasive positive pressure ventilation (NIPPV) is a technique of assisting ventilation without the use of endotracheal tube.
 
EQUIPMENT (INTERFACE)
Nasal, face mask, helmet, mouthpiece can be used for delivering NIPPV. These interfaces should be tied on the back of the head or nape of neck with a strap for tight fit to minimize leaks.
 
PROTOCOL FOR MANAGING PATIENTS PLANNED FOR NIPPV
  • Evaluation: history, diagnosis, level of respiratory distress, see whether the patient fulfils all the prerequisites for NIPPV.
  • Monitoring:
Clinical parameters—patient comfort, consciousness level, chest wall movement, patient ventilator asynchrony
Vitals—blood pressure, heart rate, ECG, respiratory rate, pulse oximetry.
Pulmonary gas exchange—arterial blood gas analysis.
Ventilatory parameters—expired tidal volume, lung dynamics measurements.
  • Settings:
Contnuous positive airway pressure (CPAP)—set pressure support of 10–15 cm H2O and positive end-expiratory pressure (PEEP) of 5 cm H2O
BiPAP – Set IPAP of 10–15 cm H2O and expiratory psoitive airway pressure (EPAP) of 5 cm H2O and titrate according to clinical condition. Alter flow rate, sensitivity, and inspiratory time to optimize synchrony.
  • Proper selection of patients for NIPPV would avoid failure of noninvasive ventilation and unnecessary need for invasive ventilation. Patients with hypoxic, hypercapnic or mixed respiratory failure, tachypnea and respiratory distress are able candidates for NIPPV.
 
Prerequisites for Using NIPPV
  • Patients able to maintain a patent airway
  • Patients with ability to clear secretions
  • 270Hemodynamically stable
  • Intact consciousness
  • Tolerant to face mask
  • No gastrointestinal bleeding or recent gastroesophageal surgery
  • No recent facial trauma or burns
  • No fixed upper airway obstruction.
 
Factors Associated with NIPPV Failure
  • GCS <11
  • Respiratory rate ≥ 30/minute
  • Ph <7.25 at admission or 2 hours after therapy
  • Severe hypercarbia (>80 mm Hg)
  • APACHE II ≥9
  • ARDS with SAPS (simplified acute physiology score) >34
  • ARDS with failure of PaO2/FiO2 improvement over 175 after 1 hour of NIPPV
  • Patient ventilator asynchrony
  • Poor dentition
  • Severe air leakage.
 
Noninvasive Ventilatory Modes
  • Continuous positive airway pressure (CPAP)
  • Bilevel positive airway pressure (BiPAP)
  • Pressure support ventilation (PSV)
  • Proportional assist ventilation (PAV).
 
Continuous Positive Airway Pressure
It delivers constant pressure in both cycles of respiration in a spontaneous breathing patient. It does not deliver any mandatory breaths, hence can only be used in a spontaneously breathing patient. This mode needs adequate alveolar ventilation and respiratory drive. It can be administered by demand flow or continuous flow system.
 
Initial Settings
  • It is initially started with pressure support of 5–10 cm H2O and increased in increments of 2–3 cm H2O according to patient comfort and blood gas analysis
  • It can be used for alveolar recruitment in ARDS (40 cm H2O PEEP for 40 sec).
Advantages
  • It reduces the work of breathing by unloading inspiratory muscles and improves dyspnea in COPD patients
  • Increases functional residual capacity and improves oxygenation by reducing intrapulmonary shunting
  • Reduces left ventricular after load in cardiac failure patients thus improving cardiac output and symptoms.271
 
Bilevel Positive Airway Pressure
Bilevel positive airway pressure (BiPAP) differs from CPAP in that it has 2 pressure levels—IPAP (inspiratory positive airway pressure) and EPAP (expiratory positive airway pressure). This mode delivers either mandatory breaths or patient triggered spontaneous supported breaths. It has a spontaneous/timed mode. IPAP improves ventilation by augmenting tidal volume and EPAP which is nothing but the PEEP, increases oxygenation and relieves upper airway obstruction. The difference between IPAP and EPAP is the pressure support which augments tidal volume. The BiPAP device can be driven by air or supplemental oxygen which can be added to the circuit to increase the FiO2.
 
Initial Settings
  • Set the mode—spontaneous/timed
  • Set IPAP of 10–15 cm H2O and EPAP of 5 cm H2O and titrate according to clinical condition. Alter flow rate, sensitivity, and inspiratory time to optimize synchrony.
  • On weaning the patient, IPAP is reduced in decrements of 2–3 cm H2O until 5 cm H2O and EPAP to 5 cm H2O. When IPAP pressure equals EPAP, this mode becomes like CPAP.
  • Set IPAP maximum time 0.25 seconds longer than the inspiratory time of the patient.
 
Pressure Support Ventilation
This mode is used to reduce the work of breathing and augment the tidal volume of a spontaneous breathing patient. It applies a preset plateau pressure to the patient's airway throughout the duration of the spontaneous inspiratory effort. The tidal volume varies with the patient's flow demand and the ventilator cycles to expiration when there is a reduction in the inspiratory flow.
 
Initial Settings
Pressure support—start with 8–10 cm H2O and increase till the expiratory tidal volume is 7–8 mL/kg, spontaneous respiratory rate <25/minute and there is patient comfort.
PEEP—start with 5 cm H2O and increase if PaO2 is reduced.
Advantages
  • Augments the spontaneous tidal volume.
  • Reduces the work of breathing.
PSV characteristics—spontaneous mode, pressure-limited, pressure-triggered, flow-cycled.
 
Indications
  • Asthma
  • Acute exacerbation of COPD
  • Cardiogenic pulmonary edema
  • 272Negative pressure pulmonary edema (postobstructive)
  • Pneumonia
  • Type 1 respiratory failure
  • Obstructive sleep apnea
  • Trauma patients without contraindications for NIPPV
  • Postoperative patients
  • Facilitating weaning in mechanically ventilated patients.
 
ASTHMA
Noninvasive positive pressure ventilation (NIPPV) can be considered as an alternative for patients who are at risk of endotracheal intubation since invasive mechanical ventilation worsens lung dynamics by causing hyperinflation and hence barotrauma.
 
Acute Exacerbation of COPD
NIPPV is the current first-line of therapy for COPD patients with type 2 respiratory failure since it reduces the need for tracheal intubation and invasive ventilation, reduces the length of ICU stay, improves gas exchange and hemodynamics, reduces severity of dyspnea. Early institution of NIPPV has been found to reduce complications. NIPPV with PSV and external PEEP reduces the work of breathing and ameliorates the auto–PEEP level.
 
Cardiogenic Pulmonary Edema
Administration of positive pressure ventilation reduces the work of breathing and left ventricular after load thus, maintaining cardiac output. It should be combined with medical treatment for pulmonary edema. For cardiogenic pulmonary edema, BiPAP has been found to produce better results than CPAP in terms of dyspnea alleviation and gas exchange. Hence, early administration of NIPPV is considered in patients with cardiogenic pulmonary edema.
 
Negative Pressure Pulmonary Edema (Postobstructive)
Postobstructive pulmonary edema after anesthesia is due to laryngospasm or due to any cause of obstruction to the upper airway. Postairway obstruction causes increase in the negative intrapleural pressure due to vigorous coughing against closed airway which increases venous return and causes increased left ventricular after load and increased transcapillary gradient which causes pulmonary edema. This is usually treated by maintaining a patent airway and institution of positive pressure ventilation.
 
PNEUMONIA
The definitive role of NIPPV has been found in patients with COPD with community-acquired pneumonia. 273
 
Type 1 Respiratory Failure
NIPPV has questionable role in patients with hypoxemic respiratory failure. But there are studies which show that NIPPV reduces the work of breathing and the incidence of endotracheal intubation. The role of NIPPV in hemodynamically stable ARDS patients has been traditionally minimal. But recent studies showed that NIPPV has improved dyspnea, gas exchange and lowered neuromuscular drive when used for hemodynamically stable ARDS patients. A study by L'Her et al. has shown that PSV combined with PEEP improved the lung dynamics and pulmonary gas exchange in ARDS patients.
 
Obstructive Sleep Apnea
CPAP/BiPAP is effective in treating the respiratory and sleep problems associated with OSA. It splints the upper airway by increasing the positive pressure thus, overcoming the obstruction and hence, prevents alveolar collapse during sleep.
 
Goals for NIV in Obstructive Hypoventilation Syndrome
  • Improvement of signs and symptoms
  • Improving PaO2
  • Normalizing the nocturnal and daytime PaCO2 and pH
  • Daytime PaCO2 of 40–50 mm Hg.
 
Postoperative Patients
Atelectasis is common after thoracic and upper abdominal surgeries. This can cause reduction in functional residual capacity, vital capacity and thus reduction in PaO2. There is good evidence that early NIPPV improves gas exchange and reduces the incidence of reintubation in postoperative patients.
 
BIBLIOGRAPHY
  1. Bott J, Carroll MP, Conway JH, et al. Randomized controlled trial of nasal ventilation in acute respiratory failure due to COPD. Lancet. 1993;341:1555-7.
  2. Brochard L, Mancebo J, Wysocki M, Lofaso F, Conti G, Rauss A, et al. Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med. 1995;333:817-22.
  3. Craig DB. Postoperative recovery of pulmonary function. Anesth Analg. 1981;60(1): 46-52.
  4. Ferrer M, Valencia M, Nicolas JM, Bernadich O, Badia JR, Torres A. Early noninvasive ventilation averts extubation failure in patients at risk: a randomized trial. Am J Respir Crit Care Med. 2006;173:164-70.
  5. Hines and Marschall. Stoelting's Anesthesia and Co-Existing Disease, 5th edn. Elsevier publications, 2008.
  6. Jolliet P, Abajo B, Pasquina P, Chevrolet JC. Non-invasive pressure support ventilation in severe community-acquired pneumonia. Intensive Care Med. 2001;27(5):812-21.
  7. Katz JA, Marks JD. Inspiratory work with and without continuous positive airway pressure in patients with acute respiratory failure. Anesthesiology. 1985;63(6):598-607.
  8. 274Lindner KH, Lotz P, Ahnefeld FW. Continuous positive airway pressure effect on functional residual capacity, vital capacity and its subdivisions. Chest. 1987;92(1):66-70.
  9. Naughton MT, Benard DC, Liu PP, Rutherford R, Rankin F, Bradley TD. Effects of nasal CPAP on sympathetic activity in patients with heart failure and central sleep apnea. Am J Respir Crit Care Med. 1995;152:473-9.
  10. Plant J, Owen J, Elliot M. Early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: a multicenter randomized controlled trial. Lancet. 2000;355:1931-5.
  11. Rocker GM, Mackenzie MG, Williams B, Logan PM. Noninvasive positive pressure ventilation: successful outcome in patients with acute lung injury/ARDS. Chest. 1999;115:173-7.
275Cardiovascular Diseases in ICU
Chapter 37 Cardiac Arrhythmias Surendran GD
Chapter 38 Acute Heart Failure Surendran GD
Chapter 39 Approach to Acute Myocardial Infarction Surendran GD
Chapter 40 Hypertensive Crisis Surendran GD
Chapter 41 Cardiac Tamponade Surendran GD276

CARDIAC ARRHYTHMIASCHAPTER 37

Surendran GD  
SUPRAVENTRICULAR ARRHYTHMIAS
 
Atrial Fibrillation
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia encountered in clinical practice. It is a supraventricular arrhythmia characterized by low-amplitude baseline oscillations (fibrillatory or ‘f’ waves) and an irregularly irregular ventricular rhythm. It is due to disorganized atrial electrical activation and uncoordinated atrial contraction. AF is associated with an increased risk of stroke and heart failure.
 
Classification
  • Paroxysmal—AF that terminates spontaneously within 7 days
  • Persistent—AF that is present for >7 days but less than a year and requires cardioversion
  • Permanent—AF lasting greater than 1 year and refractory to cardioversion
Paroxysmal AF can be classified into vagotonic, adrenergic or mixed AF.
Lone AF refers to AF that occurs in patients younger than 60 years who do not have hypertension or any evidence of structural heart disease.
 
Mechanism
There are two electrophysiologic mechanisms of AF:
  1. Automatic, triggered, or micro-reentrant foci, so-called drivers, which fire at rapid rates.
  2. Multiple re-entrant circuits.
 
Etiology
The causes of AF can be broadly classified into cardiac and noncardiac causes.
 
Cardiac Causes
  • Hypertensive heart disease
  • Ischemic heart disease
  • 278Valvular heart disease (especially mitral valve)
  • Cardiomyopathies
  • Constrictive pericarditis
  • Cardiac tumors and cardiac surgery
  • Pericarditis, myocarditis
  • Tachycardia-induced AF (Wolff-Parkinson-White syndrome).
 
Noncardiac Causes
  • Severe pulmonary hypertension and pulmonary embolism
  • Obesity and obstructive sleep apnea
  • Excessive alcohol intake (holiday heart syndrome)
  • Hyperthyroidism (the most common correctable cause).
 
Clinical Features
Signs and symptoms
The symptoms of AF vary widely. The most common symptom is palpitation, other symptoms are fatigue, dyspnea, effort intolerance and lightheadedness. Syncope is an uncommon symptom. Polyuria can occur because of the release of atrial natriuretic peptide. Clinical examination should concentrate on identifying AF and its causes as well the effects, viz. hemodynamic instability, signs of peripheral thromboembolism, etc. The most important clinical finding of AF is irregularly irregular pulse. Pulse deficit >10 is another notable finding and it is due to short R-R intervals. Examination of JVP shows irregular pulsations with absent ‘a’ waveforms. Variable intensity of S1 and associated murmurs are seen if AF is associated with valvular heart disease.
 
Investigations
The various blood investigations to be done in a case of AF are thyroid function tests, liver function tests, and renal function tests.
ECG
Low-amplitude baseline oscillations (fibrillatory or f waves) and an irregularly irregular ventricular rhythm is diagnostic. The f waves have a rate of 300 to 600/min and are variable in amplitude, shape, and timing. The ventricular rate is typically 100 to 160/min. In patients with Wolff-Parkinson-White syndrome, the ventricular rate in AF can exceed 250/minute because of conduction over the accessory pathway.
Echo
ECHO helps to diagnose any underlying structural heart disease.
Chest X-ray
Chest X-ray is done to diagnose underlying lung pathology or cardiac lesions (Fig. 37.1).279
Fig. 37.1: Absent P waves with irregular RR interval indicating atrial fibrillation
 
Management
Patients who go to the emergency department because of AF generally have a rapid ventricular rate. Control of the ventricular rate is most rapidly achieved with intravenous diltiazem or esmolol. If the patient is hemodynamically unstable, immediate transthoracic cardioversion is done.
Cardioversion should be preceded by transesophageal echocardiography to rule out a left atrial thrombus, if:
  • AF has been present for more than 48 hours, or
  • The duration is unclear and the patient is not already receiving an anticoagulant.
In hemodynamically stable patients, cardioversion is done for patients with symptomatic AF who are seen with a first episode of AF or who have had long intervals of sinus rhythm between previous episodes.
Early cardioversion
It is done if onset of AF <48 hours. The chances of thrombus formation and recurrence is less here and anticoagulation is not needed.
Delayed cardioversion
It is done if duration of AF >48 hours. Similarly, one has to go for delayed cardioversion only if TEE is unavailable or TTE shows LA thrombus.
Pharmacologic cardioversion
Although sedation is not required, the disadvantages of pharmacologic cardioversion are that the efficacy is lower than electrical cardioversion and it is very unlikely to be effective if the duration of AF >7 days.280
Table 37.1   Dosages of common antiarrhythmic agents
Drug
Loading
Maintenance
Adenosine
6–12 mg (rapid bolus)
Quinidine
6–10 mg/kg at 0.3–0.5 mg/kg per minute
Digoxin
0.25 mg 2nd hourly until 1 mg total
0.125–0.25 mg/d
Ibutilide
1 mg over 10 minute if over 60 kg
Amiodarone
15 mg/minute for 10 minute, 1 mg/minute for 6 hours
0.5–1 mg/minute
Lidocaine
1–3 mg/kg at 20–50 mg/minute
1–4 mg/minute
Procainamide
15 mg/kg over 60 minute
1–4 mg/minute
Diltiazem
0.25 mg/kg over 3–5 minute (max 20 mg)
5–15 mg/hour
Verapamil
5–10 mg over 3–5 minute
2.5–10 mg/hour
Esmolol
500 µg/kg over 1 minute
50 µg/kg/minute
Intravenous: Ibutilide, procainamide and amiodarone. Dosages of common anti-arrhythmic agents is given in Table 37.1.
Oral: Propafenone (300–600 mg) and flecainide (100–200 mg).
Electrical cardioversion (Transthoracic)
Biphasic shock is preferred as it is more efficacious and produces less tissue damage). To begin with, 150–200 J is given to begin and increased if required. Ibutilide infusion preceding shock can reduce energy requirement and increases efficacy.
Role of anticoagulation
If the AF duration >48 hours or unclear, anticoagulation should be given 3 weeks prior to cardioversion and 4 weeks postcardioversion (electrical or chemical). An alternative to 3 weeks of therapeutic anticoagulation before cardioversion is anticoagulation with heparin and transesophageal echocardiography. If no thrombi are seen, the patient can safely be cardioverted but requires 4 weeks of therapeutic anticoagulation after cardioversion.
Long-term management
The two key components in the management of AF are rate control and rhythm control.
Rate control
Rate-control strategy is preferable to a rhythm-control strategy in asymptomatic or minimally symptomatic patients > 65 years. In younger patients and in patients >65 years or older whose AF is symptomatic despite adequate heart rate control, cardioversion can be tried. Drugs for rate control are digitalis, beta-blockers, calcium channel antagonists, and amiodarone. Of these drugs, beta-blockers and calcium channel antagonists are the 1st line drugs. Digitalis is ideal for patients with heart failure and AF whereas amiodarone is appropriate choice if the other agents are not tolerated or are ineffective. Antithrombotic therapy to prevent thromboembolism is recommended for all patients with AF, except those with lone AF or contraindications.
281Special scenarios
  • Postoperative atrial fibrillation: It is common after open heart surgery (25–40%) and commonly occurs due to hypomagnesemia. Beta-blockers, sotalol, and amiodarone reduce risk of AF.
  • AF in Wolff-Parkinson-White syndrome: These patients have an accessory pathway with a short refractory period and can experience a very rapid ventricular rate during AF (>250 to 300 beats/minute) and can result in loss of consciousness or precipitate ventricular fibrillation and cardiac arrest. Transthoracic cardioversion is done if hemodynamically unstable. If hemodynamically stable, intravenous procainamide may be preferable to ibutilide because it blocks accessory pathway conduction.
    Digitalis and calcium channel antagonists are contraindicated as they selectively block conduction in the AV node and can result in increased conduction through the accessory pathway. The preferred therapy is catheter ablation of the accessory pathway.
  • AF in heart failure: Rate-control drugs used are digitalis and beta-blockers or amiodarone. Only amiodarone and dofetilide are the safe rhythm control drugs.
  • Acute myocardial infarction: Electrical cardioversion is recommended for patients with hemodynamic compromise or ongoing ischemia or when adequate rate control cannot be achieved with drug therapy. Intravenous amiodarone or digitalis to slow the ventricular rate is recommended. If not contraindicated, intravenous beta-blocker or nondihydropyridine CCBs are recommended for rate control.
  • Hyperthyroidism: Beta-blocker is first-line therapy. If a beta-blocker cannot be used, verapamil or diltiazem should be used for rate control.
  • Atrial fibrillation during pregnancy: For Rate control-Digoxin/beta-blocker/nondihydropyridine CCB is given. If hemodynamically stable, pharmacologic cardioversion with quinidine or procainamide and direct electrical cardioversion is recommended in hemodynamically unstable patients.
  • AF in pulmonary disease: The primary therapy for is correction of hypoxemia and acidosis. Verapamil or diltiazem is recommended for rate control. Theophylline and beta-adrenergic agonists are avoided.
  • AF in hypertrophic cardiomyopathy: Disopyramide plus a beta-blocker, verapamil, or diltiazem (or) amiodarone is given.
 
Atrial Flutter
It is a macrore-entrant atrial rhythm involving the cavotricuspid isthmus.
 
ECG Findings (Fig. 37.2)
The typical ECG findings are identically recurring, regular, sawtooth flutter waves with uniform morphology due to fixed circuit, best seen in leads II, III, aVF, or V1. Atrial rate is usually 250 to 350 beats/minute and ventricular rhythm will be regular and have a fixed relationship with the flutter waves (except in case of varying AV block).282
Fig. 37.2: Flutter waves with tachycardia indicating atrial flutter
 
Treatment
Cardioversion with 50 J DC is the preferred treatment or intravenous ibutilide, procainamide or amiodarone can also be given. Anticoagulation regimen is the same as in AF. Catheter ablation is also very effective in recurrent cases.
 
Focal Atrial Tachycardias
Here the atrial rates vary from 150 to 200 beats/minute with a P-wave contour different from that of the sinus P-wave with isoelectric intervals in between. It occurs commonly in patients with significant structural heart disease and digitalis toxicity. Beta-blocker or a calcium channel blocker class IA, IC, or III drugs can be given. Catheter ablation indicated in incessant tachycardia.
 
Chaotic Atrial Tachycardia (Multifocal Atrial Tachycardia)
It is characterized by:
  • Atrial rates between 100 and 130 beats/minute
  • At least 3 different P-wave morphologies
  • At least 3 different PR intervals
  • Isoelectric line in between P waves.
ECG of multifocal atrial tachycardia is shown in Figures 37.3 and 37.4. Occurs commonly in COPD and CCF. Management is directed primarily toward the underlying disease.
 
Supraventricular Reentrant Tachycardias
It can be due to:
  • Atrioventricular nodal reentrant tachycardia (AVNRT)
  • Atrioventricular reentrant tachycardia (AVRT).283
 
Atrioventricular Nodal Reentrant Tachycardia
Electrophysiology
A slow pathway with short refractory period and fast pathway with long refractory period are present within the AV node. Premature atrial complex blocks conduction in the fast pathway anterogradely, travels to the ventricle through the slow pathway and returns to atrium via the fast pathway causing circus movement and thereby precipitating tachycardia (Fig. 37.5).
Symptoms
Patients may complain of palpitations, dyspnea or rarely syncope.
Treatment
Vagal maneuvers (carotid sinus massage, the Valsalva and Müller maneuvers,
Fig. 37.3: Multifocal atrial tachycardia
284
Fig. 37.4: Multifocal atrial tachycardia showing P wave of different morphologies and different PR intervals
Fig. 37.5: Atrioventricular nodal reentrant tachycardia
 
Atrioventricular Reentrant Tachycardia
Accessory pathways are fibers that connect the atrium or AV node to the ventricle outside the normal AV nodal–His-Purkinje conduction system. When anterograde conduction is present, it produces pre-excitation of the ventricle and delta waves. If only retrograde conduction is present, there is neither pre-excitation nor delta wave. AVRT without pre-excitation presents with narrow complex tachycardia and is managed in the same way as AVNRT (Fig. 37.6).
Treatment
Vagal maneuvers and drugs such as intravenous adenosine, verapamil, or diltiazem and beta-blockers (AV node blockade) can be given. These drugs are contraindicated in SVT with pre-excitation. Instead, drugs that prolong the refractory period in the accessory pathway should be used, such as class IA and IC drugs.
Electrocardiographic clues that permit differentiation among the various SVTs (Flow chart 37.1):
  • P waves identical to sinus P waves and occur with a long RP interval and a short PR interval are most likely caused by sinus nodal reentry, sinus tachycardia, or an atrial tachycardia arising from the right atrium near the sinus node.285
    Fig. 37.6: AVRT with left side accessory pathway
    Flow chart 37.1: Diagnosis of narrow QRS complex tachycardia
  • 286Retrograde (inverted in leads II, III, and aVF) P waves
    Reentry involving the AV junction, either AV nodal reentry or reciprocating tachycardia using a paraseptal accessory pathway.
  • ST segment depression in narrow-complex tachycardia
    AV reentrant tachycardia by an accessory pathway.
  • Tachycardia without P waves
    AV nodal reentry (retrograde P waves buried in the QRS complex)
  • Tachycardia with an RP interval >90 ms
Accessory pathway.
 
VENTRICULAR ARRHYTHMIAS
 
Ventricular Premature Complex
Origin of premature ventricular beats which arise from sites distal from the Purkinje fibers produces slow ventricular activation and a wide QRS complex which is >140 ms in duration. Ventricular premature complexes (VPCs) are common and increase with age and the presence of structural heart disease. VPC can occur as bigeminy, trigeminy, couplets. Three or more consecutive VPCs are termed as VT when the rate is >100 beats per minute (Fig. 37.7). VPCs are associated with full compensatory pause. Treatment is based on the presence of associated severe symptoms and structural heart disease. VPCs are benign and need not be treated in the absence of structural heart disease.
 
Ventricular Tachycardia
Its origin is distal to the bifurcation of the His bundle. It can occur due to disorder in impulse formation (enhanced automaticity or triggered activity) or conduction (reentry). The QRS complex during VT may be uniform (monomorphic) or may vary from beat to beat (polymorphic). Algorithm for diagnosis of wide QRS complex tachycardia is given in Flow chart 37.2.
Fig. 37.7: Ventricular premature complex
287
Fig. 37.8: Monomorphic VT
Fig. 37.9: Polymorphic VT showing capture and fusion beats
 
ECG Findings (Figs 37.8 to 37.10)
  • Occurrence of 3 or more consecutive VPCs whose duration is >120 ms, with the ST-T vector pointing opposite the major QRS deflection.
  • The RR interval is usually regular and rate ranges from 70 to 250 (depending on VT type).
Duration of 30 seconds is taken for differentiating sustained and non-sustained VT. Sustained VT requires termination of VT within 30 seconds 288because of hemodynamic collapse or VT that is terminated by therapy from an implantable defibrillator.
Flow chart 37.2: Diagnosis of wide QRS complex tachycardia
 
Supports SVT with Aberrancy
  • Onset with premature P wave and RP interval ≤100 msec
  • P and QRS rate and rhythm linked to suggest that ventricular activation depends on atrial discharge
  • Long-short cycle sequence and slowing or termination by vagal tone.289
Fig. 37.10: Nonsustained VT with AV dissociation and capture beats
 
Supports VT
  • Presence of Fusion beats, capture beats and AV dissociation—but not always present
  • P and QRS rate and rhythm linked to suggest that atrial activation depends on ventricular discharge, e.g. 2:1 VA block
  • “Compensatory” pause
  • Left-axis deviation; QRS duration >140 msec.
 
Management
  • VT without hemodynamic compromise—medical management.
  • VT with hemodynamic compromise/unresponsive to medical treatment— DC cardioversion.
Medical management
Intravenous administration of amiodarone, lidocaine or procainamide followed by an infusion is used.
Amiodarone
Loading dose of 15 mg/minute is given over 10 minutes
Infusion of 1 mg/minute for 6 hours
Maintenance dose of 0.5 mg/minute for the next 18 hours
This can be continued for next few days as necessary. Hypotension does not occur with newer preparations and can be used in renal and liver failure.
 
Long-term Prevention
ICD is the treatment of choice for patients who have survived cardiac arrest or who have sustained VT resulting in hemodynamic compromise and poor LV 290function. In patients who refuse an ICD, empiric amiodarone may be the next best therapy.
 
Specific Types/Scenarios
VT in acute MI
  • Acute phase (2–30 minute)—mainly occurs due to reentrant mechanisms/increased automaticity.
  • Delayed phase (30 minute–72 hours) due to abnormal automaticity in surviving cells.
  • Chronic phase (>72 hours) due to reentry.
VT in old MI
It is usually from scar tissue and is usually monomorphic. Polymorphic VT in MI occurs in acute in active ischemia and requires no QT prolongation.
Treatment of sustained VT in MI
  • 1st line in normal LV function—intravenous procainamide or sotalol
  • 1st line in impaired LV function—intravenous amiodarone or lidocaine
  • Peri-infarct polymorphic VT —more responsive to amiodarone.
 
Arrhythmogenic Right Ventricular Cardiomyopathy
It is an inherited disease that results in fibrofatty infiltration of predominantly the right ventricle due to mutation in proteins of the desmosome and is manifested by RVOT VT.
 
ECG
May show complete or incomplete RBBB and T wave inversion in V1 to V3.
Epsilon wave—Terminal notch in QRS.
Treatment
  • ICDs are generally preferable to pharmacologic approaches.
  • RF epicardial catheter ablation can be tried.
 
Catecholaminergic Polymorphic Ventricular Tachycardia
It occurs in the absence of overt structural heart disease and normal QT intervals and presents with stress-induced VT that is often bidirectional. The treatment of choice is beta-blockers and an ICD. Sympathectomy is effective in some cases.
 
Brugada Syndrome
Brugada syndrome presents as an idiopathic VF in which patient has RBBB and ST-segment elevation in the anterior precordial leads without any evidence of structural heart disease (Fig. 37.11). It occurs due to mutations in genes responsible for the sodium channel (SCN5A) and calcium channel. Drug of choice is quinidine. ICDs are required for treatment to prevent sudden death.291
Fig. 37.11: Type 1 Brugada syndrome
Fig. 37.12: Torsades de Pointes
 
Torsades de Pointes
VT characterized by QRS complexes of changing amplitude that appear to twist around the isoelectric line and occur at rates of 200 to 250/minute and QT intervals generally >500 ms. Polymorphic VT in the absence of QT prolongation is not considered as Torsades de Pointes (Fig. 37.12).
 
Causes
Congenital severe bradycardia, Congenital long QT syndrome, potassium depletion, and use of QT-prolonging medications (such as class IA or III anti-arrhythmic drugs).
 
Treatment
The precipitating cause of the long QT should be corrected. Intravenous magnesium is the DOC followed by temporary ventricular or atrial pacing. Isoprenaline, lidocaine, mexiletine or phenytoin can also be tried. Class IA, class IC, and class III antiarrhythmic agents (e.g. amiodarone, dofetilide, sotalol) are contraindicated.292
Fig. 37.13: Ventricular fibrillation
Torsades de pointes resulting from congenital long-QT syndrome is treated with beta-blocker, pacing, and ICDs. The other less common VTs are bidirectional VT, bundle branch reentrant VT, fascicular VT and outflow VT.
 
Ventricular Flutter and Fibrillation
Ventricular flutter is manifested as a sine wave in appearance—regular large oscillations occurring at a rate of 150 to 300/minute. VF is recognized by the presence of irregular undulations of varying contour and amplitude (Fig. 37.13). It is seen most commonly in association with coronary artery disease. Immediate nonsynchronized DC electrical shock using 200–360 J is mandatory therapy for VF.
 
Sinus Bradycardia
Here the sinus node discharges at a rate <60 beats/minute. Sinus bradycardia needs treatment only when symptomatic or when associated with hemodynamic compromise. It usually responds to atropine. If persistent, pacing should be done.
 
Sinus Pause or Sinus Arrest
Sinus pause or sinus arrest is recognized by a pause in the sinus rhythm. The P-P interval of the pause is not a multiple of the basic P-P interval. Pacing is indicated if the pause is >3 seconds.
 
Sinoatrial Exit Block
It is a benign condition where the sinus node fires normally but an impulse formed within the sinus node fails to depolarize the atria or does so with delay. The duration of the pause is a multiple of the basic P-P interval.293
Table 37.2   Characteristics of Mobitz type I and II block
Mobitz type I (Wenckebach)
Mobitz type II
It is characterized by progressive lengthening of the conduction time until an impulse is not conducted
Occasional or repetitive sudden block of conduction of an impulse, without prior measurable lengthening of conduction time
Fig. 37.14: Prolonged interval indicating 1st degree heart block
Fig. 37.15: Progressive lengthening of PR interval followed by a dropped beat indicating 2nd degree Mobitz type 1 AV block
 
AV Block
An AV block exists if the atrial impulse is conducted with delay or is not conducted at all to the ventricle when the AV junction is not physiologically refractory. The three types are:
  1. First-degree heart block—PR interval is prolonged but all impulses are conducted (Fig. 37.14).
  2. Second-degree heart block occurs in two forms (Table 37.2):
    1. i.  Mobitz type I (Wenckebach) (Fig. 37.15)
    2. ii.  Mobitz type II (Fig. 37.16)
  3. Third-degree block—No impulses are conducted (Fig. 37.17).
294
Fig. 37.16: Regular PR interval with intermittent nonconducting P wave indicating Mobitz type 2 block
Fig. 37.17: Complete heart block in a patient with inferior wall myocardial infarction
When the block is at the AV nodal level, the escape complexes are narrow in morphology and have rate of 40–60/minute. When it is below the AV level, the escape complexes are broad and have a slow rate of about 40/minute.
AV block is quite common in inferior wall MI and is usually due to vagotonia as well as Bezold Jarisch reflex and is usually transient. But high degree AV block in anterior wall MI is usually associated with extensive myocardial damage and pump failure and indicates poor prognosis.
 
Management
Intravenous atropine, isoprenaline. Pacing is done in significant cases.
 
BIBLIOGRAPHY
  1. Barra SNC, Providência R, Paiva L, et al. A review on advanced atrioventricular block in young or middle-aged adults. Pacing Clin Electrophysiol. 2012;35:1395.
  2. 295Fuster V, Ryden LE, Cannom DS, et al. 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011; 123:e269.
  3. Lee KW, Badhwar N, Scheinman MM. Supraventricular tachycardia—part I. Curr Probl Cardiol. 2008;33:467.
  4. Márquez MF, Bonny A, Hernández-Castillo E, et al. Long-term efficacy of low doses of quinidine on malignant arrhythmias in Brugada syndrome with an implantable cardioverter defibrillator: A case series and literature review. Heart Rhythm. 2012;9: 1955.
  5. Nademanee K, Veerakul G, Chandanamattha P, et al. Prevention of ventricular fibrillation episodes in Brugada syndrome by catheter ablation over the anterior right ventricular outflow tract epicardium. Circulation. 2011;123:1270.
  6. Narayan SM, Krummen DE, Shivkumar K, et al. Treatment of atrial fibrillation by the ablation of localized sources: CONFIRM (Conventional Ablation for Atrial Fibrillation with or without Focal Impulse and Rotor Modulation) trial. J Am Coll Cardiol. 2012; 60:628.
  7. Pellegrini CN, Scheinman MM. Clinical management of ventricular tachycardia. Curr Probl Cardiol. 2010;35:453.
  8. Pflaumer A, Davis AM. Guidelines for the diagnosis and management of catecholaminergic polymorphic ventricular tachycardia. Heart Lung Circ. 2012;21:96.
  9. Prystowsky EN, Padanilam BJ, Joshi S, Fogel RI. Ventricular arrhythmias in the absence of structural heart disease. J Am Coll Cardiol. 2012;59:1733.
  10. Teh AW, Kistler PM, Kalman JM. Using the 12-lead ECG to localize the origin of ventricular and atrial tachycardias: Part 1. Focal atrial tachycardia. J Cardiovasc Electrophysiol. 2009;20:706.

ACUTE HEART FAILURECHAPTER 38

Surendran GD  
DEFINITION
Acute heart failure is the term used to describe the rapid onset of signs and symptoms of pulmonary congestion and/or peripheral hypoperfusion due to cardiac and/or vascular dysfunction requiring hospital admission and immediate treatment.
 
CLASSIFICATION
 
Simplified Classification Based on ESC Guidelines
  • Decompensated heart failure: It is characterized by worsening signs and symptoms of congestion on a background of chronic heart failure. It may be acute, subacute or indolent. The cardiac output generally is preserved to some extent, and they are hemodynamically stable.
  • Acute hypertensive heart failure: In this type of heart failure, hypertension can be the cause or the effect or both. It is usually acute in onset and the patients have preserved ejection fraction.
  • Cardiogenic shock: It is a condition characterized by reduction in cardiac output resulting in tissue hypoxia which leads on to various functional and structural disturbances in vital organs.
 
PATHOPHYSIOLOGY
Acute heart failure (AHF) is an extremely complex and heterogeneous syndrome with varying presentation. In short, it occurs due to one or more of triggering factors upon a previously normal or compensated heart disease or a chronically failing heart that leads to interplay of myocardial/renal/vascular/neurohumoral factors leading to symptomatic congestion and/or end-organ dysfunction (Flow chart 38.1).
 
CLINICAL FEATURES
The symptoms of heart failure can generally be classified into:
  • Those due to congestion
  • Those due to hypoperfusion.297
Flow chart 38.1: Pathophysiology of acute heart failure
 
Symptoms
Dyspnea is the most common symptom and is present in 90% cases. Dyspnea typically is present at rest or with minimal exertion. Patients also may present with signs and symptoms related to systemic venous congestion such as peripheral edema. In elderly patients, atypical manifestations such as fatigue, depression, altered mental status or sleep disruptions can occur.
 
Signs
Despite advances in diagnostics technology and imaging, heart failure remains a clinical diagnosis, and physical examination is of utmost importance.
  • The JVP is elevated in cardiac failure. It reflects the right atrial pressure and is an indirect measure of LV filling pressures and the single most useful physical examination finding in the assessment of patients with AHF. S3 gallops generally indicate an ejection fraction of <30% (severe LV systolic dysfunction).
  • Rales or inspiratory crackles are the most common physical examination finding but may not be heard in chronic failure due to pulmonary hypertension and increased lymphatic drainage. Cool peripheries and Peripheral edema (in about 65% cases) are common findings of acute heart failure. Hypotension and low pulse pressure indicate poor outcomes.
 
BIOMARKERS
Natriuretic peptide testing in the diagnosis of acute dyspnea is currently the only class I indication for a biomarker test in heart failure. NT-proBNP has similar diagnostic value as BNP. BNP <30 rules out AHF; BNP > 100 confirms AHF.298
 
Renal Function Tests
Blood urea nitrogen (BUN) is more directly related to the severity of AHF than creatinine. It is proportional to neurohormonal activation in AHF.
 
Chest Radiography
Evidence of congestion is found in more than 80% of these patients.
 
Electrocardiography
It may show findings suggestive of ischemia, MI or arrhythmias.
 
Echocardiography
It is the single most useful test in the investigation of AHF. Echocardiography can assess global systolic and diastolic function, regional wall motion abnormalities, valvular function, hemodynamics including estimates of filling pressures and cardiac output and pericardial disease.
 
Management
 
Emergency Care
This consists of rapidly relieving symptoms and identifying precipitating causes and triggers and giving specific therapy to deal with them.
  • Nasal O2 therapy: Indicated in patients with severe hypoxemia (SaO2 <90%)
  • NIPPV: In patients with cardiogenic pulmonary edema, continuous positive airway pressure (CPAP) or noninvasive intermittent positive-pressure ventilation (NIPPV) helps alleviate symptoms, and reduces the need for invasive ventilation and reduces mortality.
  • Morphine: Morphine may be useful in patients with severe anxiety or distress but should be avoided, especially in the presence of hypotension, bradycardia, advanced atrioventricular block or CO2 retention.
  • Loop diuretics: These drugs helps in relieving the volume overload and thus provide immediate symptom relief. The intravenous route increases the bioavailability and allows for rapid onset of action (typically within 30–60 minutes).
  • Vasodilators play an important role in the initial therapy of patients with pulmonary edema.
 
Management of Acute Heart Failure
 
Based on Initial Clinical Status
Drugs/Interventions
Indications
  • Intravenous bolus of loop diuretic
Initially given in heart failure
  • Oxygen
During hypoxemia
  • Intravenous opioid
For reducing anxiety and distress
299
 
Based on Systolic Blood Pressure
Drugs/Interventions
Indications
  • Add nonvasodilating inotrope
SBP <85 mm Hg or shock
  • No additional therapy
SBP of 85–110 mm Hg
  • Consider vasodilators (e.g. nitroglycerine)
SBP >110 mm Hg
Systolic blood pressure (SBP): Based upon the response to treatment to the initial treatment based on clinical status and systolic blood pressure, the follow-up treatment is planned. If there is response to treatment by the above measures, the above treatment is continued. If there is no response to the above treatment, the patient is re-evaluated based on systolic blood pressure, oxygen saturation and urine output.
 
Based on Re-evaluation of Patient's Clinical Status
Drugs/Interventions
Indications
O2/NIV/Invasive mechanical ventilation
Oxygen saturation (SaO2) <90%
Consider vasopressors/Nonvasodilating inotrope/right heart catheterization/Mechanical circulatory support (e.g. IABP, ventricular assist device)
SBP <85 mm Hg
Diuretics consider low dose dopamine/right heart catheterization/ultrafiltration
Urine output <20 mL/hour
 
SPECIFIC THERAPIES FOR ACUTE HEART FAILURE
 
Diuretics
With significant volume overload (>5–10 liters) or diuretic resistance, a continuous intravenous infusion can be considered (though DOSE trial showed no added advantage). For diuretic resistance, thiazide-like diuretic that blocks the distal tubule-intravenous chlorothiazide (500–1000 mg) or oral metolazone (2.5–10 mg) is given before the loop diuretic. If hypokalemia is a persistent problem, potassium-sparing diuretic such as spironolactone or eplerenone should be considered (Table 38.1).
 
VASODILATORS
Patients admitted with AHF and treated with diuretics plus vasodilators had significantly better survival.
 
Classification
  • Predominantly venous dilators (reduction in preload)
  • Arterial dilators (decrease in afterload)
  • Balanced vasodilators (combined effect).300
Table 38.1   Therapeutic approaches for volume management in acute heart failure
Severity of volume overload
Diuretic/device
Dose (mg)
Comments
Moderate
Furosemide
or
Torsemide
20–40 mg
10–20 mg
Titrate dose according to clinical response
Monitor Na, K, creatinine
Severe
Furosemide
or
Torsemide
ultrafiltration
40–160 mg or 5–40 mg/hour infusion
20–100 mg or 5–20 mg/hour
200–500 mL/hour
Adjust ultrafiltration rate to clinical response, monitor for hypotension
Refractory to loop diuretics
Add Hydrochlorothiazide
or
Metolazone
25–50 mg twice daily
2.5–10 mg once daily
Combination with loop diuretic may be better than very high dose of loop diuretics alone
 
Nitrates
They are potent venodilators and they decrease ventricular filling pressures and cause improvement in pulmonary congestion, dyspnea and myocardial oxygen demand at low doses. At higher doses, they act as arteriolar vasodilators also, reducing afterload and increasing cardiac output. They are relatively selective for epicardial coronary arteries resulting in increased coronary blood flow and making them useful for patients with concomitant active myocardial ischemia.
The major limitation of organic nitrates is tolerance (develops within 24 hours). Headache is the most common adverse effect. The recent use of PDE-5 inhibitors (sildenafil, tadalafil, and vardenafil) should be ruled out before administration of nitrates as this deadly combination can lead to catastrophic hypotension. Nitrates should be discontinued, if SBP is below 90 mm Hg.
 
Sodium Nitroprusside
Nitroprusside is a prodrug that is rapidly metabolized to nitric oxide and cyanide. The cyanide metabolite causes nausea, abdominal discomfort and dysphoria. Cyanide accumulation is seen mainly in hepatic dysfunction patients only. This drug produces balanced reduction in afterload and preload. Because of very short life (seconds to a few minutes), it is accurately titratable. Tapering the dose is important as it can cause rebound hypertension. Sodium nitroprusside is particularly effective in the setting of markedly elevated afterload (e.g. hypertensive AHF) and moderate to severe mitral regurgitation. However, due to coronary steal phenomenon not recommended in active myocardial ischemia.
 
Nesiritide
It is a recombinant human B-type [brain] natriuretic peptide. It produces potent vasodilation and mild increases in cardiac output through cGMP-mediated 301vasodilation. Nesiritide causes hypotension in volume-depleted patients and so used only in congestive patients (Table 38.2).
Table 38.2   Dosages of various vasodilators used for heart failure
Vasodilators
Initial dose
Infusion range
Comments
Nitroglycerin;
Glyceryl trinitrate
20 μg/minute
40–200 μg/minute
Hypotension
Isosorbide dinitrate
1 mg/hour
2–10 mg/hour
Hypotension
Nitroprusside
0.3 μg/kg/minute
0.3– 5 μg/kg/minute (usually <4 μg/kg/minute)
Caution in patients with active myocardial ischemia; can cause hypotension; cyanide toxicity; thiocyanate toxicity; light sensitivity
Nesiritide
2 μg/kg bolus with 0.01–0.03 μg/kg/minute infusion
0.010–0.030 μg/kg/minute
 
Inotropes and Inodilators
These are used in hypoperfusion when other interventions have failed.
 
Dobutamine
Dobutamine is an agonist of both beta 1- and beta 2-adrenergic receptors with variable effects on the alpha-receptors. Tachyphylaxis may occur, if used for longer than 24–48 hours. Concomitant beta-blocker therapy will result in competitive antagonism and higher doses of dobutamine (10–20 μg/kg/minute) are required.
 
Mechanism
Beta-receptor stimulation results in increased inotropy and chronotropy. At low doses, stimulation of beta 2- and alpha-receptors causes vasodilation, reduction in afterload and indirect increases in cardiac output. However at higher doses, vasoconstriction occurs.
 
Adverse Effects
Tachyarrhythmias and myocardial ischemia (contraindicated in active ischemia).
 
Dopamine
Dopamine is an agonist of both adrenergic and dopaminergic receptors and an inhibitor of norepinephrine uptake. The effects of this drug varies with the dose.
  • Low-dose dopamine (≤2 μg/kg/minute): Proposed to cause selective dilation of renal, splanchnic and cerebral arteries but it is still an unsettled concept. It can be tried but to be discontinued in case of no response.
  • 302Intermediate-dose dopamine (2–10 μg/kg/minute): At this dose, it causes increased inotropy but this effect depends on myocardial catecholamine stores which unfortunately are often depleted in patients with advanced heart failure. Hence, dopamine is a poor inotrope in patients with severe systolic dysfunction.
  • High-dose dopamine (10–20 μg/kg/minute): It causes peripheral and pulmonary artery vasoconstriction, by alpha-1 agonism. This can lead to end-organ ischemia and should be used cautiously.
 
Epinephrine
Epinephrine is a full beta-receptor agonist. Its increasing inotropic effect is independent of myocardial catecholamine stores, and hence, is an useful agent in the treatment of transplant recipients with denervated hearts.
 
Phosphodiesterase (PDE IIIa) Inhibitors (Milrinone, Enoximone)
These drugs have positive inotropic effect without causing tachycardia or tachyphyaxis. Similarly, antagonism by beta-blockers is not a problem and can be used with dobutamine for synergic effects. It causes significant peripheral and pulmonary vasodilation and can be used in LV dysfunction with pulmonary hypertension or in transplant recipients. However, caution is required in both renal and hepatic insufficiency. Side effects these drugs include hypotension and arrhythmias.
 
Levosimendan
It is a novel inodilator which acts by cardiac myofilament calcium sensitization (inotropic) and activation of vascular smooth muscle potassium channels (vasodilator). It significantly increase cardiac output, reduces PCWP and afterload and decrease dyspnea. Hypotension and tachyarrhythmias are the common side effects (Table 38.3).
 
OTHER DRUGS USED IN THE TREATMENT OF ACUTE HEART FAILURE
 
Digoxin
Digoxin acts by increasing the myocardial contractility without increasing the heart rate or decreasing the BP. Initial slow bolus 0.5 mg (rapid bolus causes vasoconstriction) followed by 0.25 mg oral/intravenous 12 hours later as maintenance is given. It has a narrow therapeutic window therapeutic window and should be avoided in active ischemia, advanced renal failure and AV blocks.
 
Arginine Vasopressin Antagonists
These drugs are given only in symptomatic hyponatremia (as Vasopressin causes hypervolemic hyponatremia of heart failure). Tolvaptan (oral) and conivaptan (IV) are the available drugs but without improved long-term outcomes.303
Table 38.3   Dosages of various inotropes used for heart failure— milrinone dose to be altered
Inotropes
Initial dose
Maximal dose
Comments
Dobutamine
1–2 μg/kg/minute
2–20 μg/kg/minute
Inotropy
Dopamine
1–2 μg/kg/minute
2–4 μg/kg/minute
Inotropy
Milrinone
25–75 μg/kg bolus over 10–20 minute followed by 0.375–0.75 µg/kg/minute
0.10–0.75 μg/kg/minute
Inodilator
Enoximone
0.5–1 mg/kg
5–20 μg/kg/minute
Inodilator
Levosimendan
12 μg/kg bolus over 10 minute followed by infusion
0.1–0.2 μg/kg/minute
Inodilator
Epinephrine
0.05–0.5 μg/kg/minute
For vasoconstriction and inotropy. Causes tachycardia, arrhythmias and end-organ hypoperfusion
Norepinephrine
0.2–1.0 μg/kg/minute
For vasoconstriction and inotropy, causes reflex bradycardia, cardiac arrhythmias and end-organ hypoperfusion
 
Calcium-channel Blockers
Calcium-channel blockers (CCBs) without significant myocardial depressant effects, such as nicardipine and clevidipine, are useful in patients with AHF with severe hypertension refractory to other therapies.
 
Istaroxime
It causes increased cytosolic calcium accumulation during systole, with positive inotropic effects and rapid sequestration of cytosolic calcium into the sarcoplasmic reticulum during diastole. Trials have shown that the addition of istaroxime to standard therapy lowered PCWP and heart rate and increased SBP.
 
Nonpharmacologic Therapies
 
Ultrafiltration
Ultrafiltration involves removal of isotonic fluid, in a more effective way potentially without the neurohormonal activation seen with diuretics. However, derangement of renal function and high in-hospital mortality are associated with this procedure.304
 
Hypertonic Saline
Administration of hypertonic saline (HSS) (3%), along with high-dose furosemide and sodium and fluid restriction, may be associated with greater diuretic and clinical response as shown by the SMAC-HF study, however, further studies are needed.
 
Novel Agents/Drugs Under Study
Serelaxin, Urodilatin [a modified version of pro–atrial natriuretic peptide (pro-ANP)].
Ularitide, (a synthetically-produced urodilatin), Cenderitide (CD-NP), Aliskiren (Direct renin inhibitor), Tezosentan (Endothelin receptor antagonists) etc.
 
Cardiorenal Syndrome in Hospitalized Patients
It is defined as increase in serum creatinine above 0.3 mg/dL (or 25% decreases in GFR) despite hemodynamic congestion. It should not be confused with changes in renal function during successful decongestion therapy which is usually are transient. ACE inhibitors and spironolactone should be stopped in this patient. Higher doses of diuretics and vasodilators are used to treat this condition.
 
Criteria for Discharge
  • Precipitating factors treated
  • Volume status optimized
  • Change over from intravenous diuretic to oral diuretic therapy
  • Pharmacologic therapy optimized
  • LV ejection fraction documented
  • Counseling regarding risk factor modification done
  • Discharge instructions and family education
  • Review clinic visit scheduled.
 
BIBLIOGRAPHY
  1. Binanay C, Califf RM, Hasselblad V, O'Connor CM, Shah MR, Sopko G, Stevenson LW, Francis GS, Leier CV, Miller LW; ESCAPE investigators and ESCAPE study coordinators. Evaluation study of congestive heart failure and pulmonary artery catheterization effectiveness: the ESCAPE trial. JAMA. 2005;294(13):1625-33.
  2. Dickstein, et al. 2008; Filippatos and Zannad 2007.
  3. Dupont M, Mullens W, Finucan M, Taylor DO, Starling RC, Tang WH. Determinants of dynamic changes in serum creatinine in acute decompensated heart failure: the importance of blood pressure reduction during treatment. Eur J Heart Fail. 2013;15(4):433-40.
  4. Felker GM, Lee KL, Bull DA, et al. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011;364:797.
  5. Gray A, Goodacre S, Newby DE, et al. Noninvasive ventilation in acute cardiogenic pulmonary edema. N Engl J Med. 2008;359:142.
  6. 305Hasenfuss G, Teerlink JR. Cardiac inotropes: Current agents and future directions. Eur Heart J. 2011;32:1838.
  7. Lee DS, Stitt A, Austin PC, et al. Prediction of heart failure mortality in emergent care: A cohort study. Ann Intern Med. 2012;156:767.
  8. Maisel AS, Krishnaswamy P, Nowak RM, et al. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med. 2002;347:161.
  9. McMurray JJ, Adamopoulos S, Anker SD, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2012;33:1787.
  10. Metra M, Teerlink JR, Voors AA, et al. Vasodilators in the treatment of acute heart failure: What we know, what we don't. Heart Fail Rev. 2009;14:299.
  11. Pang PS, Cleland JG, Teerlink JR, et al. A proposal to standardize dyspnoea measurement in clinical trials of acute heart failure syndromes: The need for a uniform approach. Eur Heart J. 2008;29:816.
  12. Park JH, Balmain S, Berry C, et al. Potentially detrimental cardiovascular effects of oxygen in patients with chronic left ventricular systolic dysfunction. Heart. 2010;96: 533.
  13. Vital FM, Saconato H, Ladeira MT, et al. Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary edema. Cochrane Database Syst Rev. 2008;(3):CD005351.
  14. West RL, Hernandez AF, O'Connor CM, et al. A review of dyspnea in acute heart failure syndromes. Am Heart J. 2010;160:209.
  15. Zile MR, Bennett TD, St John Sutton M, et al. Transition from chronic compensated to acute decompensated heart failure: Pathophysiological insights obtained from continuous monitoring of intracardiac pressures. Circulation. 2008;118:1433.

APPROACH TO ACUTE MYOCARDIAL INFARCTIONCHAPTER 39

Surendran GD  
DEFINITION
Acute myocardial infarction is a syndrome of myocardial ischemia with evidence of myocardial necrosis on biochemical tests or electrocardiography or imaging.
 
UNIVERSAL DEFINITION OF MYOCARDIAL INFARCTION
There should be an evidence of myocardial necrosis in a clinical-setting consistent with acute myocardial ischemia (Table 39.1).
Table 39.1   Universal definition of myocardial infarction
Detection of a rise and/or fall in cardiac biomarker values (preferably cTroponin), with at least one of the following:
  • Presence of ischemic symptoms
  • Significant and new ST-T changes or new LBBB
  • Presence of new pathologic Q waves on ECG
  • Evidence of new regional wall motion abnormality or new loss of viable myocardium in imaging
  • Angiography demonstrating thrombus in coronary arteries
 
UNIVERSAL MYOCARDIAL INFARCTION CLASSIFICATION OF TYPE
Type 1: Spontaneous myocardial infarction related to atherosclerotic plaque rupture.
Type 2: Myocardial infarction secondary to ischemic imbalance.
Type 3: Myocardial infarction resulting in death when biomarker values are unavailable.
Type 4a: Myocardial infarction related to percutaneous coronary intervention.
Type 4b: Myocardial infarction related to stent thrombosis.
Type 5: Myocardial infarction related to coronary artery bypass grafting.307
 
Pathophysiology (Flow chart 39.1)
Flow chart 39.1: Pathophysiology of acute MI
Table 39.2   Clinical features associated with myocardial dysfunction
  • >15% myocardial involvement—Reduced EF
  • >25% myocardial involvement—Clinical heart failure
  • >40% myocardial involvement—Cardiogenic shock
 
CLINICAL FEATURES
Contrary to assumption that clinical examination is less important these days, it is very important in deciding treatment strategy, risk stratification and follow-up as well as identification of complications (Table 39.2 and Fig. 39.1).
 
Symptomatology (Table 39.3)
The precipitating factors are unusual heavy exercise (particularly in fatigued or habitually inactive patients) and emotional stress. The peak incidence of STEMI usually occurs in the morning due to circadian periodicity of increased secretion of catecholamines and cortisol. The most common symptom is chest discomfort resembling classic angina pectoris and it is of crushing, oppressing or compressing in nature. Pain is felt predominantly retrosternal in location with radiation to the ulnar aspect of left upper limb or jaw. It generally lasts for more than 30 minutes, and is not relieved by rest or nitrates. Inferior wall MI can present with nausea,vomiting and epigastric pain due to vagal reflex.
The patients can also present with atypical features such as symptoms of heart failure, CNS symptoms, syncope, Psychosis and overwhelming weakness, etc.308
Fig. 39.1: Insufficiency of coronary flow may take place by any of the above-mentioned mechanisms
Table 39.3   Causes of myocardial infarction without coronary atherosclerosis
  • Arteritis
  • Trauma (Physical/Radiation/Iatrogenic)
  • Coronary mural thickening due to metabolic disease
  • Luminal narrowing (Spasm/Dissection)
  • Emboli to coronary arteries
  • Congenital coronary artery anomalies
 
Signs
Patients are anxious and restless and describe their pain with a clenched fist held against the sternum (Levine sign). Those presenting with failure may have cold and clammy extremities. Small volume pulse is seen in LVF whereas brisk upstroke is seen in mitral regurgitation or ventricular septal rupture. Inferior wall MI patients usually have bradycardia and hypotension (due to Bezold Jarisch reflex) whereas in anterior wall MI, tachycardia and hypertension are observed as a result of excess sympathetic drive. JVP is elevated in patients with CCF and RV-MI. On auscultation, S4 is almost always present but is less specific for MI whereas the presence of S3 signifies severe LV dysfunction. Systolic murmur of 309mitral regurgitation can be heard at the apex due to papillary muscle rupture or dysfunction. Pericardial rubs are usually common on the 2nd or 3rd day are seen usually at the left parasternal border and are usually triphasic (Tables 39.4 and 39.5).
Table 39.4   Killip's prognostic classification
Killip's class
I  No congestive heart failure
II  Mild congestive heart failure, rales, S3, congestion on chest X-ray
III  Pulmonary edema
IV  Cardiogenic shock
Table 39.5   TIMI score for STEMI
Thrombolysis in myocardial infarction (TIMI) score for ST elevation
Acute myocardial infarction
  • DM, history of HTN or history of angina (1 point)
  • Systolic blood pressure less than 100 mm Hg (3 points)
  • Heart rate greater than 100 (2 points)
  • Killip's class II–IV (2 points)
  • Body weight less than 150 Ib or 67 kg (1 point)
  • Anterior lead ST elevation or left BBB (1 point)
  • Time to treat more than 4 hours (1 point)
Age
  • ≥=75 years old (3 points)
  • 65–75 years old (2 points)
  • Less than 65 (0 points)
TIMI risk score predicts 30-day mortality after an MI
  • 0 point: 0.8%
  • 1 point: 1.6 %
  • 2 points: 2.2%
  • 3 points: 4.4%
  • 4 points: 7.3%
  • 5 points: 12%
  • 6 points: 16%
  • 7 points: 23%
  • 8 points: 27%
  • 9–14 points: 36%
Abbreviations: DM, diabetes mellilus; HTN, hypertension; BPM, beats per minute; BBB, bundle branch block
 
Investigations
Even though the criteria for MI give importance to cardiac biomarkers, the physician should NOT wait for the results to start treatment. Treatment should be started as soon as possible based on history, clinical examination and ECG (Table 39.6 and Fig. 39.2).310
Table 39.6   ECG criteria for STEMI
ST elevation
New ST elevation at the J point in two contiguous leads with the following criteria:
≥0.2 mV in men or ≥0.15 mV in women in V2–V3 and/or ≥0.1 mV in all leads (except V2–V3)
Fig. 39.2: Anterior wall MI—ST elevation in anterior wall leads (V1–4)
Table 39.7   ECG criteria for acute MI in the presence of LBBB (Sgarbossa criteria)
Electrocardiographic criterion
Points
Concordant ST segment elevation ≥1 mm in leads with a positive QRS complex
5
Concordant ST segment depression ≥1 mm in leads V1–V3
3
ST segment elevation ≥5 mm and discordant with the QRS complex
2
A score of ≥3 is more specific for acute MI
 
Posterior MI
Abnormal R wave in V1 (0.04 second in duration and/or R/S ratio ≥1 in the absence of pre-excitation or RV hypertrophy) with ST depression in ≥2 precordial leads (V1–V4).
 
ECG MANIFESTATIONS OF ISCHEMIA IN THE SETTING OF LBBB
New or presumably new LBBB at presentation previously considered as a STEMI equivalent should not be considered diagnostic of acute myocardial infarction (MI) in isolation. Following are the criteria for determining MI in the presence of LBBB (Tables 39.7 and 39.8, Fig. 39.3)311
Table 39.8   ECG changes associated with previous MI in the absence of LVH and LBBB (based on ESC and ACC guidelines)
  • Any Q wave in leads V2–V3 ≥0.02 sec or a QS complex in leads V2 and V3
  • Q wave ≥0.03 sec and ≥0.1 mV deep or QS complex in leads I, II, aVL, aVF, or V4–V5 in any 2 leads of a contiguous lead grouping (I, aVL; V1–V6; II, III, aVF)
  • R wave ≥0.04 sec in V1–V2 and R/S ≥1 with a concordant positive T-wave in absence of a conduction defect
Fig. 39.3: Inferior wall MI showing ST elevation in leads II, III, aVF
Fig. 39.4: Global ST depression and characteristic ST elevation of aVR suggests critical LMCA lesion with high-risk of sudden cardiac arrest
 
Serum Markers of Cardiac Damage
Myocardial injury can be detected by the presence of circulating proteins released from damaged myocardial cells. But they usually do not provide clues to the cause of damage. For example, myocarditis and hence should always be interpreted in the appropriate context (Fig. 39.4).312
 
Cardiac Troponins (Troponin T and I)
They are the preferred biomarkers in MI. In patients with MI, troponins first begin to rise by approximately 3 hours after the onset of chest pain and cTnI may persist for 7–10 days after MI; whereas elevations in cTnT may persist for up to 10–14 days. Troponin T assays have greater uniformity in testing and are preferred. All patients with suspected MI should undergo testing of Troponin T at admission and 3–6 hours later. Further testing is needed only in doubtful cases.
 
CK-MB
It is considered to be less specific than troponin T and is of use only when troponin T is not available and to detect reinfarction within 10 days.
 
Echocardiography
It is useful as a diagnostic tool when the clinical picture indicates an MI but ECG is nondiagnostic. ECHO helps in evaluating the extent of jeopardized myocardium as well as complications. In the Post-MI phase, it helps in viability testing for revascularization (Flow chart 39.2).
 
Management
The central goal is to salvage the involved myocardium within the time window by restoring perfusion by pharmacologic means or by catheter-based/surgical therapy.
 
ANTIPLATELET THERAPY
 
Aspirin
The loading dose of Aspirin is 162–325 mg and it should be given to all patients. Enteric-coated preparations should not be given for loading dose. Patient should chew the drug for buccal absorption.
 
Clopidogrel
Despite inhibition of cyclo-oxygenase (COX) by aspirin, platelet activation continues through thromboxane A2–independent pathways. So platelet P2Y12 receptor antagonists such as clopidogrel are given in all patients along with aspirin with STEMI. The loading dose of clopidogrel is 300 mg. However in patients planned for PCI, the loading dose of clopidogrel is 600 mg followed by 75 mg daily is given.
 
Prasugrel
The loading dose of prasugrel is 60 mg followed by 10 mg daily. Prasugrel should not be given in patients with history of TIA or stroke.313
Flow chart 39.2: Management of patient with STEMI
Abbreviation: FMC, first medical contact
 
Ticagrelor
The loading dose of Ticagrelor is 180 mg followed by 90 mg twice. When using Ticagrelor, the recommended maintenance dose of Aspirin is 81 mg daily.
 
PAIN CONTROL
Morphine is the drug of choice as it decreases sympathetic overdrive in addition to providing analgesia. It also reduces cardiac workload and produce peripheral arterial and venous dilatation.
 
Nitrates
They enhance coronary blood flow by coronary vasodilation and also decrease ventricular preload by venodilatation. They are contraindicated in those with suspected right ventricular infarction or marked hypotension (e.g. systolic pressure <90 mm Hg), especially if accompanied by bradycardia. If hypotension 314and bradycardia occurs as a side effect, reversal can be done with intravenous atropine. Long-acting preparations should be avoided in acute MI. They are useful only in patients with persistent or recurrent angina, heart failure or hypertension
 
Beta-blockers
Beta-adrenergic blockade diminishes circulating levels of free-fatty acids and thereby maintain the balance between myocardial oxygen supply and demand. All patients without contraindication should receive oral beta-blockers within the first 24 hours. They reduce the need for analgesics in many patients and reduce infarct size and life-threatening arrhythmias. Beta-blockers are avoided in hypotension (SBP<90 mm Hg), bradycardia, acute exacerbation of COPD and AV block.
 
Dosage
  • Metaprolol 5 mg IV is given thrice at 5 minute intervals.
  • Oral metaprolol tartrate 25–50 mg 6th hourly for 2–3 days followed by 100 mg bid.
 
ACE Inhibitors/ARB
ACE inhibitors reduce the rate of mortality from STEMI accompanied by significant reductions in the development of heart failure. They also reduce the incidence of ischemic events including recurrent infarction and the need for coronary revascularization. They should be given to all STEMI patients within 24 hours even in the absence of heart failure unless contraindicated. ARBs are equally effective in ACEI intolerant patients.
 
Aldosterone Antagonists
Eplerenone also reduces cardiovascular mortality.
 
Calcium-channel Blockers
They are not helpful in the acute phase of MI. Verapamil and Diltiazem can be given to control rapid ventricular rate in MI with atrial fibrillation without LVF when the rate is not adequately controlled by beta-blockers.
 
Magnesium
Patients with STEMI should have their serum magnesium measured on admission as hypomagnesemia can cause arrhythmias.Magnesium correction is given only if levels are below 2 mEq/L or if Torsades des Pointes is present.
 
Glucose Control
Blood glucose levels should be maintained <180 mg/dL while avoiding hypoglycemia.315
Table 39.9   Contraindications and cautions in the use of fibrinolytics for treating STEMI
Absolute contraindications
  • Previous intracranial hemorrhage
  • Known structural cerebral vascular disease
  • Ischemic stroke within 3 months except acute ischemic stroke within 4.5 hours
  • Intracranial or intraspinal surgery within 2 months
  • Severe uncontrolled hypertension (unresponsive to emergency therapy)
  • Active bleeding or bleeding diathesis
  • Significant closed head or facial trauma with in 3 months
  • For streptokinase, previous treatment within the previous 6 months
  • Known malignant intracranial neoplasm (primary or metastatic)
  • Suspected aortic dissection
 
Oxygen
Oxygen should be given only if hypoxemia is present as routine use increase SVR.
 
LIMITATIONS OF INFARCT SIZE
Time is myocardium is the key in the management of acute MI. Each 30-minute delay from symptom to PCI increases risk for 1-year mortality by 8%. Various trials have shown a trend toward a lower mortality rate in patients with STEMI, especially if they were treated within 2 hours of the onset of symptoms even before reaching hospital (Pre-hospital fibrinolysis). It is especially useful when the anticipated transportation time is more than 60–90 minutes but needs expert crew (Table 39.9).
 
Fibrinolysis
The maximal efficacy of fibrinolytics is achieved, if it is administered within 2–3 hours of MI. Between 6 and 12 hours, fibrinolysis does show reduction in mortality. However, fibrinolytics after 12 hours show no mortality benefit. Nevertheless they can be tried in patients <65 years with TW >12 hours with symptoms of ongoing ischemia especially in large anterior wall infarcts.
Platelet rich thrombi are more resistant to fibrinolysis than are fibrin and erythrocyte-rich thrombi and have an increased tendency for reocclusion after initial successful reperfusion. In a PCI-capable facility, primary PCI is the preferred mode of reperfusion therapy. If delay from first medical contact to performing primary PCI is anticipated to exceed 120 minutes, fibrinolytic therapy is indicated.
 
Fibrinolytics and Their Dosages
 
Alteplase
15 mg IV bolus followed by 0.75 mg/kg (up to 50 mg) IV over 30 minutes and then 0.5 mg/kg (up to 35 mg) IV over 60 minutes. The maximum total dose is 100 mg for patients weighing more than 67 kg. This is the most common alteplase infusion parameter used for AMI.316
 
Tenecteplase
Tenecteplase is administered in a 30–50 mg IV bolus over 5 seconds. The dosage is calculated on the basis of the patient's weight as follows: <60 kg—30 mg, 60 to 69 kg—35 mg, 70 to 79 kg—40 mg, 80 to 89 kg—45 mg.
 
Streptokinase
1.5 million U in 100 mL of NS given IV over 60 minutes.
 
Reteplase
Two 10-U vials is first reconstituted with sterile water (10 mL) to 1 U/mL. The adult dose of reteplase for AMI consists of 2 IV boluses of 10 units each; there is no weight adjustment. The first 10 U IV bolus is given over 2 minutes; 30 minutes later, a second 10 U IV bolus is given over 2 minutes. Administer normal saline (NS) flush before and after each bolus.
 
PERCUTANEOUS CORONARY INTERVENTION
 
Primary PCI
When PCI is used as primary reperfusion therapy in patients with STEMI, it is referred to as direct or primary PCI.
 
Rescue PCI
PCI done when fibrinolysis has failed to reperfuse the infarct vessel or a severe stenosis is present in the infarct vessel, it is called rescue PCI. Routine delayed angiography and PCI after successful fibrinolytic therapy may also be considered and this is known as secondary PCI.
 
Advantages of PCI Over Fibrinolysis
Following are the conditions where only PCI can be considered and fibrinolysis is contraindicated:
  • Patients who present late, especially >12 hours after symptom onset
  • Patients in cardiogenic shock
  • Patients with increased risk for bleeding.
Referral to a PCI center can be superior to fibrinolysis, if the anticipated time delay is <1–2 hours. But if not, it is always better to start fibrinolysis rather than wasting precious time window in the process of transporting to a PCI facility expecting better results.
 
Indications for Delayed Coronary Angiography with PCI
  • Cardiogenic shock or acute severe HF that develops after initial evaluation
  • Intermediate or high-risk findings on predischarge noninvasive ischemia testing
  • 317Spontaneous or easily provoked myocardial ischemia
  • Failed reperfusion or reocclusion after fibrinolytic therapy
  • Stable patients after successful fibrinolysis—before discharge and between 3 and 24 hour.
 
Anticoagulants
 
Benefits of Anticoagulation
  • Establishing and maintaining patency of the infarct-related artery
  • Prevent deep venous thrombosis and pulmonary embolism
  • Prevent ventricular thrombus formation and cerebral embolization.
 
Unfractionated Heparin Dose (Table 39.10)
Bolus dose of 60 units/kg (maximum of 4000 units)
      ↓
Initial infusion at 12 units/kg/hour (maximum of 1000 units/hour for 48 hours)
Heparin should be given for at least 48 hours after fibrinolytic therapy. aPTT to be maintained at 1.5–2 times control (≈50 to 70 seconds). Alternative anticoagulant regimens are preferred, if administered for longer than 48 hours to prevent heparin-induced thrombocytopenia.
 
Low-Molecular-Weight Heparin
They provide a stable, reliable anticoagulant effect, high bioavailability permitting administration via the subcutaneous route, and a high anti-Xa–to–anti-IIa ratio resulting in a marked decrement in thrombin generation. LMWH clearly reduced recurrent MI but with a pattern of increased bleeding.
 
Parenteral Factor Xa Antagonists
Although Fondaparinux reduced the risk of death or reinfarction in patients receiving fibrinolytic therapy, it also increased the risk of catheter thrombosis in PCI group.
Table 39.10   Key points about the use of heparin
  • Patients undergoing pharmacologic reperfusion therapy should receive anticoagulant therapy for a minimum of 48 hours and preferably for the duration of hospitalization after STEMI, up to 8 days
  • Enoxaparin or fondaparinux is preferred when administration of an anticoagulant for longer than 48 hours is planned
  • In patients with history of heparin-induced thrombocytopenia, bivalirudin in conjunction with streptokinase is the choice
  • For patients planned for CABG, unfractionated heparin is preferred due to rapid reversal.
318
 
Direct Thrombin Inhibitors
In patients undergoing fibrinolysis, direct thrombin inhibitors such as hirudin or bivalirudin reduces the incidence of recurrent MI but with higher risk of bleeding. When administered for a short period as an adjunct to primary PCI, it reduced 30–day rate of major bleeding or major adverse cardiovascular events. Nevertheless bivalirudin is associated with an increased early risk for stent thrombosis.
 
Complications of Acute Myocardial Infarction
A search for complications of MI should always be done in patients with sudden deterioration despite routine treatment. Complications of MI can be classified as:
  • Mechanical
  • Arrhythmic
  • Embolic
  • Inflammatory.
 
Mechanical Complications
The various mechanical complications of acute coronary syndrome are:
  • Ventricular septal rupture (VSR)
  • Acute mitral regurgitation (MR)
  • Ventricular free wall rupture
  • Ventricular pseudoaneurysm
  • Ventricular aneurysm
  • Cardiogenic shock
  • LV and RV failure
  • Dynamic LVOT obstruction.
 
Ventricular Septal Rupture
This complication is usually seen 2–5 days after MI. Elderly patients, female sex, hypertension, first MI and delayed perfusion are the usual precipitating factors. The patient presents with sudden worsening of clinical features and a new onset pansystolic murmur is heard at left parasternal border.
Treatment
All VSR should be taken for surgical repair irrespective of the shunt fraction. IV vasodilators (nitroprusside) and IABP can be used as bridge therapy for surgery. Despite surgery, mortality is usually higher.
 
Acute Mitral Regurgitation
Mitral regurgitation occurs as a result of LV dilatation, papillary muscle ischemia or rupture of papillary muscle. Clinically, it is diagnosed by the presence of pansystolic murmur that radiates to axilla (in anterior rupture) and to the base or parasternal region (in posterior rupture). It is more common in IWMI because posterior papillary muscle has single blood supply by PDA whereas the anterior muscle is supplied by both LAD and LCx.319
Treatment
Surgical repair is the definitive treatment. Vasodilators (IV nitroprusside) and respiratory support act as a bridge therapy to surgical repair.
 
Ventricular Free Wall Rupture
Although the incidence of ventricular free wall rupture is <1%, it has got a very high mortality (>60%). It is more common in the first 5 days of MI. The patient presents with sudden onset of chest pain with coughing or straining and leading on to rapid hemodynamic compromise. Features of cardiac tamponade dominate the clinical picture.
Treatment
In severe hemodynamic instability, pericardiocentesis can be done followed by emergency thoracotomy with surgical repair.
 
Ventricular Pseudoaneurysm
It is more commonly seen in inferior wall MI. Ventriculography is the most reliable method of diagnosis and surgical resection is the treatment of choice.
 
Ventricular Aneurysm
It is more common with anterior wall MI than with inferior wall MI or posterior wall MI. Aneurysms can be acute or chronic. Acute aneurysms lead to severe LV dysfunction and cardiogenic shock whereas chronic aneurysms are usually clinically silent but may lodge mural thrombi and result in embolic manifestations. Persistent ST elevation in ECG inspite of reperfusion and alleviation of pain is an important finding.
Treatment
Management is with vasodilators, ACEI and IABP and surgical aneurysmectomy in refractory cases. Anticoagulation needed for at least three months, if mural thrombus is present. LV failure and cardiogenic shock has been dealt extensively in acute heart failure management.
 
Intra-aortic Balloon Counterpulsation
It is used for the treatment of STEMI in three groups of patients:
  1. Hemodynamically unstable patients and in whom support of the circulation is required for the performance of cardiac catheterization and angiography.
  2. Cardiogenic shock that is unresponsive to medical management.
  3. Patients with refractory ischemia that is unresponsive to other treatments or who are waiting for definitive revascularization.
Temporary mechanical support with left ventricular assist devices may allow time for recovery of stunned or hibernating myocardium. Hemodynamic improvement is greater with the percutaneous left ventricular assist device.320
 
RV Failure
It is common in acute inferior wall MI or Inferoposterior MI. It is usually transient and improves with reperfusion.
The combination of JVP >8 cm H2O and Kussmaul's sign is sensitive and specific. Cardiac auscultation may reveal RVS3 and RVS4. ECG shows ST elevation in V4R and sometimes in V1 in addition to inferior lead changes.
Treatment
Rushing of IV fluids to maintain CVP >15 mm Hg is the mainstay of treatment. If still not responsive, dobutamine infusion can be helpful. RV assist device is indicated in resistant cases.
 
Dynamic LVOT Obstruction
It is a very uncommon complication seen in AWMI and occurs due to compensatory hyperkinesias of inferobasal segments of LV leading to dynamic LVOT obstruction. Eventhough these patients present with shock, they improve with intravenous fluids and beta-blockers. However before giving fluids, this condition should be confirmed by TTE.
 
Arrhythmic Complications
The various arrhythmias associated with ventricular premature complex, ventricular tachycardia, VF, atrial fibrillation, PSVT, sinus bradycardia, junctional rhythm and AV block.
 
Embolic Complications
Embolic complications are more common in large AWMI (10%). Embolism mostly occur in the first 2 weeks after MI and TTE is the test of choice to find out LV mural thrombus.
 
Inflammatory Complications
 
Early Pericarditis
Early pericarditis usually occurs 1–3 days after MI and is more common with trans mural MI. Patients presents with pain which is worse in supine position and relieved by bending forwards and the pain also radiates to the trapezius ridge (pathognomonic). Triphasic rub may also be heard.321
ECG findings (has to be differentiated from MI)
  • ST segment elevation (generalized) with concavity upwards
  • PR segment depression
  • T wave inversion is seen only after ST becomes isoelectric.
This typical picture is usually not seen in MI.
Treatment
Aspirin 650 mg QID is the first-line drug for pericarditis. Nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids are to be avoided in acute MI as it interferes with myocardial healing.
 
Late Pericarditis (Dressler's Syndrome)
It usually occurs 1–8 weeks after MI and is due to autoimmune reaction to necrotic tissue. The patient presents with fever and leukocytosis and raised ESR. Steroids and NSAIDs can be used if it occurs 4 weeks after MI.
 
BIBLIOGRAPHY
  1. Bodis J, Boncz I, Kriszbacher I. Permanent stress may be the trigger of an acute myocardial infarction on the first work-day of the week. Int J Cardiol. 2009;144:423.
  2. Cantor WJ, Fitchett D, Borgundvaag B, et al. Routine early angioplasty after fibrinolysis for acute myocardial infarction. N Engl J Med. 2009;360:2705.
  3. Dracup K, McKinley S, Riegel B, et al. A randomized clinical trial to reduce patient prehospital delay to treatment in acute coronary syndrome. Circ Cardiovasc Qual Outcomes. 2009;2:524.
  4. Falk E, Nakano M, Bentzon JF, et al. Update on acute coronary syndromes: The pathologists’ view. Eur Heart J. 2013;34:719.
  5. Mehta RH, Starr AZ, Lopes RD, et al. Incidence of and outcomes associated with ventricular tachycardia or fibrillation in patients undergoing primary percutaneous coronary intervention. JAMA. 2009;301:1779.
  6. Nabel EG, Braunwald E. A tale of coronary artery disease and myocardial infarction. N Engl J Med. 2012;366:54.
  7. Oldgren J, Wallentin L, Afzal R, et al. Effects of fondaparinux in patients with ST-segment elevation acute myocardial infarction not receiving reperfusion treatment. Eur Heart J. 2008;29:315.
  8. O'Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127:e362.
  9. O'Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;61:e78.
  10. Reynolds HR, Hochman JS. Cardiogenic shock: Current concepts and improving outcomes. Circulation. 2008;117:686.
  11. Steg PG, James SK, Atar D, et al. ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2012;33:2569.
  12. Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. J Am Coll Cardiol. 2012;60:1581.
  13. Van de Werf FJ, Topol EJ, Sobel BE. The impact of fibrinolytic therapy for ST-segment elevation acute myocardial infarction. J Thromb Haemost. 2009;7:14.

HYPERTENSIVE CRISISCHAPTER 40

Surendran GD  
DEFINITION
Hypertensive crises are a heterogeneous group of disorders characterized by severe hypertension and acute target organ damage. Severe hypertension is defined as systolic BP >180 mm Hg and diastolic BP >120 mm Hg.
 
HYPERTENSIVE EMERGENCY (PREVIOUSLY MALIGNANT HYPERTENSION)
Hypertensive emergency is defined as severe hypertension with evidence of acute target organ damage, manifested by a variety of symptoms and typically BP is > 220/130 mm Hg. Severe hypertension with chronic target organ damage without acute manifestations does not constitute an emergency. Hypertensive emergency needs ICU admission and immediate lowering of BP with intravenous antihypertensive (Table 40.1).
Table 40.1   Definition of hypertensive emergency
Severe hypertension (>180/120) plus any of the following:
  • Hypertensive encephalopathy
  • Acute stroke, intracranial hemorrhage, cerebral infarction
  • Acute congestive heart failure
  • Acute coronary syndrome
  • Acute renal insufficiency
  • Acute aortic dissection
  • Eclampsia
  • Retinopathy, papilledema
  • Postoperative bleeding from vascular suture lines
  • Postcoronary artery bypass grafting (CABG)
323
 
HYPERTENSIVE URGENCY
Hypertensive urgency is defined as severe hypertension without acute end organ damage. BP can be lowered over a period of days to weeks. Patients can be treated on an outpatient basis with oral medications. BP in this scenario can be as high as 220/130 mm Hg but without target organ damage. They require follow-up within 24–72 hours.
There is no absolute BP cut-off value to differentiate HT emergency from urgency. It is the presence or absence of acute target organ damage which differentiates the two scenarios.
 
Pseudo Emergencies
These are acute rises in blood pressure due to a physiologic factor leading to a massive sympathetic drive. For example, pain, hypoxia, hypercarbia, hypoglycemia, anxiety, etc. Usually, it does not need medications to lower BP.
 
Pathophysiology
Autoregulation is the cornerstone in the pathogenesis as well as management. The vital organs possess autoregulatory mechanisms to maintain constant blood flow despite fluctuations in BP. This protects them from both hypoperfusion and hyperperfusion, both of which can be detrimental.
In normotensives and patients with adequately controlled BP, the range of autoregulation is mean arterial pressure of 60–120 mm Hg. So even a slight increase beyond this level will lead to target organ damage. But in chronic hypertensive patients arteriolar smooth muscle hypertrophy prevents direct transmission of pressure to the tissues and autoregulation is shifted to higher levels. Hence, these patients tolerate elevated BP without target organ damage.
Elevated levels of circulating catecholamine's cause arteriolar fibrinoid necrosis and endothelial damage which releases vasoactive amines and leads to a vicious cycle which results in hypertensive emergency.
 
Precipitating Factors of Hypertensive Crisis
  • Undiagnosed or poorly controlled essential hypertension
  • Nonadherence to drug regimen
  • Renovascular disease/renal parenchymal disease
  • Actue CNS insults, e.g. stroke
  • Drug-induced, e.g. sympathomimetic, nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Collagen vascular diseases, e.g. scleroderma
  • Pre-eclampsia
  • Phenochromocytoma
  • Obstructive sleep apnea.
 
Diagnosis
History: Symptomatology suggestive of target organ damage such as dyspnea, chest pain, headache, confusion, altered sensorium, vomiting, oliguria, 324hematuria, visual disturbances should be elicited. History of hypertension, its precipitating factors and treatment history should be obtained
Physical examination: BP measurement should be taken at 15–20 minute intervals from both upper and lower extremities. A thorough examination should be done for vascular bruits especially renal bruits and all pulses should be checked. Presence of S3 and S4, murmurs, pulmonary edema and any focal deficits should be searched for meticulously.
 
INVESTIGATIONS
 
Blood Tests
  • Complete blood count and peripheral smear
  • Urea, creatinine and electrolytes: For renal failure and endocrine abnormalities
  • Urine routine analysis: Hematuria and proteinurea indicate glomerular damage
  • Cardiac enzymes: Slightly elevated in hypertensive crisis.
Evaluation of secondary causes of hypertension is usually done after the crisis settles down except measurement of renin, aldosterone and metanephrenine levels in clinically relevant scenarios as most antihypertensives alter these values once therapy is started.
 
Electrocardiography (ECG)
Left ventricular hypertrophy (LVH) indicates chronic hypertension, ST segment and T wave changes may indicate changes secondary to LVH or ischemia/infarction.
 
Chest X-ray
May show cardiomegaly, pulmonary edema or enlarged aortic shadow suggestive of aortic aneurysm or discussion.
 
CT/MRI Brain
It is done to rule out stroke in cases presenting with altered sensoruim.
 
Management
Hypertensive emergencies are treated in ICU and the goal is to minimize or reverse end organ damage. While reducing the BP, one should keep in mind that mean arterial pressure (MAP) should not be lowered more than 25% of baseline blood pressure. However, this does not apply to all situations and an aggressive BP lowering should be done in the following three conditions.
  1. Aortic dissection
  2. Acute pulmonary edema
  3. Postoperative bleeding.
325The various drugs used in the management of hypertensive crisis are:
 
Sodium Nitroprusside
It is the drug of choice in many conditions as it has a rapid onset of action, rapid reversal and predictable homodynamic response. It decreases both afterload and preload. It does not raise intracranial pressure (ICP) unlike nitroglycerin (NTG) and hence can be safely given in neurologic conditions.
However, this causes cyanide and thiocyanate toxicity in patients with liver and renal failure. Similarly, it should be avoided in acute coronary syndrome as it can cause coronary steal phenomenon.
 
Labetolol
It is an α + β-blocker with β to α blocking ratio of 7:1. It has a rapid onset of action (<5 min) and the effects also last longer (1–3 hours). Heart rate, SVR and MAP all fall. All contraindications to β-blockers apply to labetalol also.
 
Nitroglycerin
It is primarily a venodilator with some degree of after load reduction as well. It is the best drug in acute coronary syndromes due to favorable redistribution of coronary blood flow and dilation of epicardial coronary arteries. Not situated in raised ICP as it increases cerebral blood flow.
Other drugs
  • Urapidil: New central sympatholytic which acts on central serotinogergic pathways and also as a peripheral and adrenergic blocker.
  • Fenoldopam: It is a selective peripheral dopamine-1-receptor agonist. It is primarily an arterial vasodilator with rapid action. It is highly useful in the intraoperative period especially for renal transplantation and in renal insufficiency.
  • Nicardipine: It is a dihydropyridine calcium-channel blockers (CCB). Useful in postoperative setting and neurologic crisis (does not raise ICP) but contraindicated in acute coronary syndrome. It is given as a continous IV infusion.
  • Clevidipine: It is a short acting CCB without reflex tachycardia.
  • Enalaprilat: It is a short acting intravenous angiotensin-converting-enzyme inhibiter (ACEI) that is preferred especially in scleroderma renal crisis.
  • Intravenous hydralazine: Its use should be limited to pre-eclampsia and eclampsia. It is contraindicated in active ischemia and raised intracranial pressure (ICP).
Once BP is controlled adequately, switch over to oral again. At least two anti-hypertensive drugs are started.
 
Management of Specific Hypertensive Crises
  • Hypertensive crisis with encephalopathy: This can manifest into two forms.
    1. Diffuse cerebral edema and encephalopathy: This manifests as altered sensorium, irritability and rarely seizures. It reverses completely once BP is lowered. Nitroprusside is the preferred agent in this setting.
    2. 326Posterior reversible leukoencephalopathy syndrome: It is usually seen in post cardiac transplant recipients on cyclosporine or tacrolimus. MRI is required for the diagnosis and it resolves completely with BP lowering.
  • Ischemic stroke: Elevated blood pressure protects the peri-ischemic areas which are already maximally dilated from hypoperfusion. Hence, blood pressure should not be lowered unless it is >220/120 mm Hg or when thrombolytic therapy is considered (require BP <185/110 mm Hg) as it may increase the extension of the infarct. Infarct, reducing BP by 15% in the first 24 hours is sufficient
  • Hemorrhagic stroke: Labetolol is the preferred drug in this setting and lowering SBP <140 mm Hg has showed better results than usual recommended goal of 180 mm Hg
  • Advanced retinopathy: This is usually associated with BP >220/130 mm Hg with evidence of multiple end-organ damage and Grade III or IV retinopathy. The prognosis of these cases is poor and hence examining the fundus is of utmost importance in HT crisis.
  • Aortic dissection: BP should be lowered immediately in type A dissection as it requires immediate surgery. Type B requires antihypertensives to decrease shear force on vessel wall. Sodium nitroprusside with intravenous metoprolol is the treatment of choice.
  • Acute cardiogenic pulmonary edema (due to hypertension): Here pulmonary edema is not due to volume over load but due to acute pressure overload and afterload mismatch. Hence, instead of overzealous treatment with intravenous loop diuretics (which may actually worsen the picture), treatment to reduce afterload should be given and IV nitrates are the treatment of choice. Once BP is lowered, pulmonary edema will be reduced.
  • Myocardial ischemia: Elevated BP can induce demand supply mismatch and also rupture coronary plaques. Intravenous nitroglycerin is the treatment of choice.
 
Other Special Scenarios
Post-CABG: Nitroglycerine is the drug of choice.
Postoperative bleeding: Nitroprusside/Nicardipine/Labetolol can be used.
Pregnancy
  • Magnesium prevents progression from pre-eclampsia to eclampsia.
  • Labetolol is the drug of choice to lower the BP.
Pheochromocytoma: Phentolamine is the drug of choice.
 
Hypertensive Urgencies
These are usually seen in chronic hypertensives who are nonadherent to treatment. They present with severe SHT but without acute target organ damage. Here the goal is to reduce blood pressure over days without causing hypoperfusion. Outpatient treatment with oral agents is enough.327
The various drugs available for treatment are:
  • Captopril: It is the fastest acting oral ACE inhibitor (acts within 15–30 min) and can be given safely. It is started with 6.25 mg and gradually increased to 12.5 mg/25 mg TID.
  • Nifedipine: Long acting can be given (30 mg daily with up titration).
  • Labetdilol: It is also an effective agent (Start with 100 mg BID with up titration according to response).
 
BIBLIOGRAPHY
  1. Civetta JM, Taylor RW, Kirby RR. Critical Care, 4th edn. Philadelphia: Lippincott-Raven; 2009.
  2. Irwin RS, Rippe JM, Irwin Rippe's. Intensive Care Medicine, 6th edn. Lippincott: Williams and Wilkins Publications; 2008.
  3. Longo DL, Kasper DL, Jameson JL, Fauci AS, Stephen LH, Loscalzo J. Harrison's principles of internal medicine, 18th edn McGraw Hill Publications; 2012.
  4. Paul NL. The intensive care unit manual, 2nd edn PA: Elsevier Publications; 2014.

CARDIAC TAMPONADECHAPTER 41

Surendran GD  
DEFINITION
Accumulation of large amount of fluid in the pericardial space leading on to compromised ventricular function, ultimately resulting in reduction of circulation is known as pericardial tamponade.
Cardiac tamponade comprises a continuum ranging from mild (pericardial pressure <10 mm Hg) to severe (pericardial pressure >15–20 mm Hg). This condition is characterized by equal elevation of atrial and pericardial pressures, an exaggerated inspiratory decrease in arterial systolic pressure (pulsus paradoxus), and arterial hypotension.
 
PATHOPHYSIOLOGY
Although pericardial tamponade is usually caused by large effusions (>500 mL), sometimes rapidly accumulating small effusion of about 100–150 mL can also cause tamponade. The high pericardial pressure impedes the filling of the right side of the heart; effects on the left side of the heart are largely secondary to underfilling. Pericardial pressure and right atrial pressure are elevated above normal and are equal to each other.
 
PRECIPITATING FACTORS
Drugs (cyclosporine, anticoagulants, thrombolytics), recent cardiac surgery, indwelling instrumentation, blunt chest trauma, malignancies, connective tissue disease, renal failure and septicemia, etc.
 
CLINICAL FEATURES
The most common symptom of tamponade is dyspnea, which is usually relieved by sitting forward. Pericardial pain may be seen in some patients. Patients with tamponade almost always appear uncomfortable, with signs reflecting varying degrees of reduced cardiac output and shock, including tachypnea, diaphoresis, cool extremities, cyanosis and depressed sensorium.329
 
BECKS TRIAD (USEFUL CLUE FOR DIAGNOSIS OF TAMPONADE)
  • Hypotension
  • Elevated jugular venous pressure (JVP)
  • Muffled heart sounds.
The other signs of tamponade are tachycardia, hypotension with reduced pulse pressure (late stages), Kussmauls sign, pulsus paradoxus, Loss of ‘y’ descent in JVP and clear lungs
 
DIFFERENTIAL DIAGNOSIS
The differential diagnoses of tamponade are:
  • Myocardial failure
  • Right-sided heart failure due to pulmonary embolus or pulmonary hypertension
  • Right ventricular MI.
 
INVESTIGATIONS
 
Electrocardiography
The characteristic ECG changes of pericardial tamponade are reduced voltage and electrical alternans. Reduced voltage is nonspecific as it is seen in other conditions like emphysema, pneumothorax, etc. Electrical alternans is highly specific but relatively insensitive for large effusions.
 
Chest X-ray
In moderate to large effusions, the cardiac silhouette is enlarged giving a rounded, flask like appearance. Lateral views may reveal pericardial fat sign. The lungs are oligemic.
 
M Mode/2D Echocardiogram
Early diastolic collapse of the anterior RV free wall is the most specific finding whereas late diastolic RA collapse is the more sensitive finding. Rarely, left ventricular collapse and left atrial collapse occur with loculated effusions after cardiac surgery. The cardiac chambers are small in tamponade and the heart may swing anteroposteriorly within the effusion.
 
Doppler Echocardiography
Tricuspid flow increases and mitral flow decreases during inspiration (reverse in expiration). Decrease in transmitral E velocity >25% on inspiration and decrease in tricuspid E velocity >40% on expiration is noted.330
 
Cardiac Catheterization
It helps in confirmation of the diagnosis and quantification of the hemodynamic compromise. RA pressure and intrapericardial pressures are elevated and are almost identical to each other. Pulmonary capillary wedge pressure (PC-WP), pulmonary artery (PA) diastolic pressure and RV mid diastolic pressure is also elevated. LV systolic and aortic pressures are normal.
Cardiac catheterization also helps in detecting other cardiac abnormalties (cardiomyopathies, coronary artery disease (CAD), etc.) and hemodynamic abnormalties (LV faiure, pulmonary hypertension (PHT), etc.).
Coronary angiography, LV/RV angiography and CT are the other available tests.
 
MANAGEMENT
Not all patients with echocardiographic signs of tamponade require pericardiocentesis. In case of low pressure tamponade (seen in hemodialysis and when diuretics are administered to patients with effusions), peicardiocentesis is not needed whereas hyperacute tamponade (usually resulting from cardiac trauma)necessitates immediate pericardiocentesis. Majority of patients falls between these two extremes and will require pericardial drainage.
 
Pericardiocentesis
Needle pericardiocentesis is usually done by the subxiphoid approach with continuous monitoring. As soon as fluid is drained a J-tipped guidewire is inserted and a drainage catheter is introduced. After rapid aspiration of about 100–150 mL to rapidly reduce symptoms, a pig-tail catheter is left in situ for continuous drainage.
Drainage of the pericardial fluid using a catheter minimizes trauma, allows measurement of pericardial pressure and instillation of drugs into the pericardium, and helps prevent re-accumulation of pericardial fluid. Extended (3 ± 2 days) catheter drainage is associated with a trend toward lower recurrence. Drainage should continue until the volume of the aspirated volume is less than 25 mL/d.
 
Surgical Drainage
Open surgical drainage offers several advantages, including complete drainage, access to pericardial tissue for histopathologic and microbiologic diagnoses, the ability to drain loculated effusions and the absence of traumatic injury resulting from blind placement of a needle into the pericardial sac. The collected pericardial fluid should be sent for necessary investigations.
 
Recurrent Effusions
Recurrent effusions may be treated by repeat pericardiocentesis, sclerotherapy with tetracycline, surgical creation of a pericardial window or pericardiectomy. 331Pleuropericardial window is usually created in patients with malignant effusions. Pericardiectomy may be required for recurrent effusions in dialysis patients.
 
BIBLIOGRAPHY
  1. Chen EP, Miller JI. Modern approaches and use of surgical treatment for pericardial disease.
  2. Fejka M, Dixon SR, Safian RD, et al. Diagnosis, management, and clinical outcome of cardiac tamponade complicating percutaneous coronary intervention. Am J Cardiol. 2002;90:1183-6.
  3. Hoit BD. Pericarditis. In: Antman E (Ed). Cardiovascular Therapeutics, 2nd edn. Philadelphia, PA: WB Saunders; 2002.pp.1113-22.
  4. Sagrista-Sauleda J, Angel J, Sambola A, et al. Low-pressure cardiac tamponade: clinical and hemodynamic profile. Circulation. 2006;114:945-52.
  5. Tsang TS, Seward JB, Barnes ME, et al. Outcomes of primary and secondary treatment of pericardial effusion in patients with malignancy. Mayo Clin Proc. 2000;75:248-53.
  6. Tsang TS, Barnes ME, Gersh BJ, et al. Outcomes of clinically significant idiopathic pericardial effusion requiring intervention. Am J Cardiol. 2003;91:704-7.
332Renal and electrolyte disturbances in ICU
Chapter 42 Acute Kidney Injury Jenu Santhosh, Prem Kumar
Chapter 43 Renal Replacement Therapy G Ninoo George
Chapter 44 Hyponatremia TA Naufal Rizwan
Chapter 45 Potassium Prem Kumar, Sushma Vijay Pingale
Chapter 46 Calcium TA Naufal Rizwan
Chapter 47 Phosphorus TA Naufal Rizwan
Chapter 48 Magnesium TA Naufal Rizwan333

ACUTE KIDNEY INJURYCHAPTER 42

Jenu Santhosh, Prem Kumar  
INTRODUCTION
Kidneys receive major cardiac output (25%). Renal cortex receives almost 90% of the total renal blood flow. Local myogenic reflex maintains the renal blood flow and filtration, viz. increasing perfusion pressure causes contraction of the afferent arteriole causing reduction in filtration pressure. Low pressure dilates the afferent arteriole and constricts the efferent arteriole thus maintaining filtration. Acute kidney injury (AKI) occurs in 20% of patients with sepsis and 50% of those with septic shock.
 
CHARACTERISTICS
Acute kidney injury (AKI) is characterized by the sudden deterioration of kidney function resulting in the retention of nitrogenous and other waste products usually cleared by the kidneys (Table 42.1).
 
CATEGORIES
 
Prerenal Azotemia
It is the most common type of AKI. Most common causes are hypovolemia causing reduced renal perfusion, reduced cardiac output, nephrotoxic drugs like NSAIDs which leads to rise in creatinine and blood urea nitrogen levels. This condition is reversible if the cause is corrected but if it gets prolonged, it may lead to acute tubular necrosis. Failure of renal autoregulation occurs when the systolic blood pressure falls below 80 mm Hg or when the mean arterial blood pressure falls below 60 mm Hg. ACE inhibitors and angiotensin receptor blockers (ARBs) reduce efferent arteriolar vasoconstriction which is a cause of concern in pre-existing renal disease patients, bilateral renal artery stenosis since efferent arteriolar vasoconstriction is required to maintain GFR due to low renal perfusion. Another risk for the development of prerenal azotemia is cirrhosis of liver where renal perfusion is reduced inspite of volume overload—hepatorenal syndrome. 336
Table 42.1   Etiology of acute kidney injury
Causes
Abbreviations: NSAID, nonsteroidal anti inflammatory drugs; ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker
 
Intrinsic Acute Kidney Injury
Most common causes are ischemia, sepsis, drug induced. Outer medulla is more prone for damage during ischemia. Pathophysiology is persistent glomerular vasoconstriction in response to ischemia, endothelial and vascular smooth muscle damage, and tubular obstruction causing reduced GFR. Ischemia can be a cause of AKI in postoperative patients also especially in patients who undergo major surgeries of prolonged duration with prolonged intraoperative hypotension and major blood loss. (e.g. Cardiothoracic surgery with cardiopulmonary bypass, aortic cross clamping for vascular procedures, abdominal procedures). Risk factors for postoperative AKI are diabetes mellitus, pre-existing renal disease, heart failure, contrast agents.
 
Postrenal AKI
This occurs due to partial or complete obstruction either one or both the ureters or with bladder neck obstruction due to benign prostatic hyperplasia causing 337retrograde increase in hydrostatic pressure due to backflow which in turn causes reduced glomerular filtration. Causes are obstruction of ureters by calculi, blood clots or stricture or an obstructed Foley's catheter can sometimes be a cause.
Effects of decreased renal function in critically ill
  • Electrolyte disturbances
  • Volume overload
  • Acidosis
  • Decreased immunity
  • Increased infection
  • Dysregulated inflammatory response
  • Altered half-life of medications
  • Immune, endocrine, cardiovascular, pulmonary, hematological, CNS, neuromuscular dysfunction (Tables 42.2 and 42.3).
 
DIAGNOSIS
 
Current Definition of AKI
 
MARKERS FOR RENAL DYSFUNCTION IN AKI
 
Urine Output
It is more of a marker for renal blood flow than for solute clearance. It is not an ideal marker for renal dysfunction since oliguria may be seen with intact tubular function and elevated vasopressin whereas normal urine output may be seen with injured tubules (nonoliguric renal failure) but with poor urine quality (inadequate waste removal).
 
Serum Creatinine
It is an amino acid formed from skeletal muscle. It is freely filtered and not reabsorbed or metabolized by the kidney. There are certain pitfalls in its measurement.
  • The amount of creatinine depends upon age, sex, diet, muscle mass, and muscle disease. It takes time to accumulate. Hence, it does not detect renal dysfunction in real time.
  • 10% to 40% of creatinine is cleared by tubular secretion. Hence, it can mask significant fall in GFR
  • Drugs can alter the values (blood taken through the intravenous line where N-acetylcysteine (NAC) is administered will show low creatinine values if estimated by enzymatic method).
 
Serum Urea
Levels are altered by various factors like volume status (increased levels in volume depletion) catabolic state, GI bleed, steroid use, metabolic acidosis (causes muscle proteolysis) and liver disease (decreased synthesis).
 
Urine Abnormalities
Only situation where it is used is systemic vasculitis or glomerulonephritis where presence of dysmorphic RBCs and casts is useful diagnostically therapeutically and prognostically.
 
New Biomarkers
Plasma panel—Neutrophil gelatinase-associated lipocalcin (NGAL), cystatin C
Urine panel—NGAL, cystatin C, IL-18, KIM-1.
 
Cystatin C
Presence in urine detects and quantifies renal tubular injury. Serum levels are more sensitive to early and mild changes in kidney function than serum creatinine.339
 
NGAL
It is one of the earliest protein released from kidneys after renal injury and is detectable in blood and urine. It rises within 1–3 hours of insult and peaks at 6 hours (for creatinine only 3rd day). It is been identified as a powerful predictor of AKI.
 
IL-18
Urine level increases at 6 hours and peak at 12 hours after insult.
 
KIM-1
It is specific for nephrotoxic and ischemic renal injury. Rises only after 12–24 hours after the insult.
 
Prevention
  • Hydration and volume expansion
    • Intravenous route is preferred route to oral route in preventing AKI
    • Use isotonic to hypotonic fluids (avoid hydroxy ethyl starch (HES) and other high molecular weight preparations).
  • Maintain perfusion pressure
    • Target pressure is individualized. Maintain higher mean arterial pressure (MAP) in chronic hypertensives who become hypotensive.
    • Keep PaO2 >60 mm Hg and hemoglobin 8–10 gm%
    • Use vasopressors only after volume repletion. This is because if vascular volume is low, and vasopressors are used they reduce renal perfusion in the process of maintaining MAP. The recommended MAP is 60–65 mm Hg.
    • Nor adrenaline may be used. This is useful in septic shock as it constricts efferent arteriole preferably.
    • Look for intra-abdominal hypertension.
  • Avoid nephrotoxic substances
    • Use single daily dose of aminoglycosides if they cannot be avoided.
    • Use minimal volume of nonionic, iso-osmolar contrast with adequate isotonic fluids to prevent contrast nephropathy.
    • Avoid NSAIDs, antibiotics with nephrotoxicity and ACE inhibitors.
 
Pharmacological
  • Furosemide: They do not prevent kidney injury but may produce harm. They may be needed in volume overloaded patients with renal failure, if there is no adequate response they should be stopped.
  • Dopamine agonists: They have been tried as renoprotective agents but there is no evidence to prove its effectivity.
  • Natriuretic peptides: ANP has been tried in AKI. Studies demonstrated that there is no reduction in mortality rates either in low dose or high dose group. But low dose ANP (50 ng/kg/min) reduced the need for RRT.
  • 340Calcium channel blockers: There is no benefit with calcium channel blockers.
  • Adenosine antagonists: Theophylline needs further study for usage in AKI.
  • Contrast nephropathy: It is defined as rise in creatinine > 0.5 mg% or > 25% above baseline after exposure to contrast. Contrast nephropathy leads to a rise in serum creatinine within 24–48 hours, peak within 3–5 days, and resolves within 5–7 days. Adequate hydration with 0.45% normal saline at 1 mL/kg/hour for 12 hours, use of N-acetylcysteine (NAC) and the choice of contrast agent may prevent contrast nephropathy. Standard dosage of NAC- 600 mg intravenously before the procedure and 600 mg orally twice daily for 48 hours after the procedure.
  • Mannitol: Its use in prevention of oliguric renal failure is not well established. Its use may be even detrimental.
If there is no response inspite of maintaining adequate MAP, PaO2 and hemoglobin (8–10 gm %), the patient is said to have established intrinsic renal failure.
 
Treatment for Established Renal Failure
  • Volume resuscitation and use of vasopressors to optimize systemic and renal hemodynamics.
  • Elimination of nephrotoxic agents
  • Initiation of renal replacement therapy when indicated
  • Correct electrolytes and acid base abnormalities (hyponatremia, hyperkalemia, metabolic acidosis, hypocalcemia, hyperphosphatemia)
  • Adjust drug doses
  • Nutritional support—Sufficient protein and calorie intake is given to avoid negative nitrogen balance
  • Infection control
  • Discontinue magnesium containing antacids to avoid hypermagnesemia.
  • Rhabdomyolysis is treated with aggressive fluid resuscitation. Alkaline solutions like sodium bicarbonate can be beneficial in preventing tubular injury. In case of reduced urine flow, diuretics can be used after volume repletion.
  • Postrenal AKI is treated by relieving the obstruction by suprapubic cystostomy in case of bladder neck obstruction, percutaneous nephrostomy or ureteral stent placement in case of ureteral obstruction. After relieving the obstruction, diuresis can persist for few days.
 
Indications of Dialysis in AKI
  • Volume overload despite diuretic therapy
  • Hyperkalemia
  • Acidosis refractory to medical therapy
  • Creatinine clearance or estimated glomerular filtration rate (GFR) <10 mL/min/1.73 m2
  • BUN >100 mg/dL in patients without clinical signs of recovery of kidney function
  • Bleeding diathesis
  • 341Presence of uremic symptoms (asterixis, encephalopathy, pericardial rub or effusion, uremic bleeding).
 
Complications of AKI
  • Metabolic acidosis
  • Hyperkalemia
  • Volume overload
  • Electrolyte disturbances— hyponatremia, hypocalcemia, hyperphosphatemia
  • Uremia
  • Altered drug metabolism.
 
BIBLIOGRAPHY
  1. Allgren RL, Marbury TC, Rahman SN, et al. Anaritide in acute tubular necrosis. N Engl J Med. 1997;336:828.
  2. Battle DC, Arruda JAL, Kurtzman NA. Hyperkalemic distal renal tubular acidosis associated with obstructive uropathy. N Engl J Med. 1981;304:373.
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  7. Dan LL, Dennis LK, Jameson JL, et al. Harrison's principles of internal medicine, 18th edn. McGraw Hill publications; 2012.
  8. Heyman SN, Brezis M, Reubinoff CA, et al. Acute renal failure with selective medullary injury in the rat. J Clin Invest. 1988;82:401.
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  12. Rahman SN, Kim GE, Mathew AS, et al. Effects of atrial natriuretic peptide in clinical acute renal failure. Kidney Int. 1994;45:1731.
  13. Ronco C. Continuous renal replacement therapies for the treatment of acute renal failure in intensive care patients. Clin Nephrol. 1993;40:187.
  14. Rose BD. Acute renal failure. In: Rose BD (ed): Pathophysiology of Renal Disease. New York: McGraw-Hill; 1981.p.55.

RENAL REPLACEMENT THERAPYCHAPTER 43

G Ninoo George  
INTRODUCTION
Acute kidney injury (AKI) is extremely common in critically ill patients. The incidence of AKI in critically ill patients is increasing due to various factors like increasing patient age, multiple comorbidities, use of nephrotoxic agents, invasive vascular procedures using iodinated contrast agents, etc. Not only is the incidence increasing, so also is the severity of AKI, often necessitating the need for renal replacement therapy.
Kidney is one of the few vital organs whose physiological function can be replaced using extracorporeal treatment. Renal replacement therapy (RRT) refers to any modality that can replace the function of the kidney using artificial means. To qualify as renal replacement, the treatment should be able to control fluid balance, electrolyte balance and acid-base balance. To this date, we have three forms of RRT, viz. hemodialysis, peritoneal dialysis and renal transplantation. Different modalities of renal replacement therapy is given in Table 43.1 and terminologies used in AKI is given in Table 43.2. Of these, renal transplantation is practiced only in chronic kidney disease and therefore will not be discussed further.
Table 43.1   Different modalities of renal replacement therapy
Modalities of renal replacement therapy in current clinical practice:
  • Intermittent
    • Intermittent hemodialysis (IHD)
    • Sustained low efficiency dialysis (SLED); extended daily dialysis (EDD)
  • Continuous
    • Peritoneal dialysis (PD)
    • Continuous renal replacement therapy (CRRT)
    • slow continuous ultrafiltration (SCUF)
    • CAVH/CVVH
    • CAVHD/CVVHD
    • CAVHDF/CVVHDF
Abbreviations: CAVH, continuous arteriovenous hemofiltration; CVVH, continuous venovenous hemofiltration; CAVHD, continuous arteriovenous hemodiafiltration; CVVHD, continuous venovenous hemodiafiltration; CAVHDF, continuous arteriovenous hemodiafiltration; CVVHDF, continuous venovenous hemodiafiltration
343
Table 43.2   Terminologies used in AKI
  • I: Intermittent
  • AV: Arteriovenous (here the driving force for blood to move around the circuit is heart)
  • VV: Venovenous (here the driving force is external pump)
  • HF: Hemofiltration (fluid removal)
  • HD: Hemodialysis (solute removal)
  • HDF: Hemodiafiltration (fluid and solute removal)
  • Detoxification: Hemoperfusion/hemodialysis
  • SCUF: Slow continuous ultrafiltration
  • SCD: Slow continuous dialysis
  • SLED: Slow low efficiency dialysis.
 
Indications of Renal Replacement Therapy
The classical indications of RRT in the ICU are:
  • Refractory fluid overload
  • Refractory hyperkalemia
  • Metabolic acidosis
  • Uremic complications.
Apart from these classical indications, there are several other situations where renal replacement therapy can be beneficial. These include different types of poisonings (methanol, lithium, etc.), removal of cytokines by hemofiltration in sepsis, refractory hypercalcemia, refractory congestive cardiac failure, etc.
 
ACCESS
Safe and secure access to the patient's blood is of paramount importance in hemodialysis. For this, several types of dialysis catheters are available. The catheters currently used in practice have two lumens of the venovenous type. Arterial access is not required in acute hemodialysis since most machines have a blood pump that can suck blood out of the venous system.
The most common site of insertion of the dialysis catheter is the right internal jugular vein. The next preferred site is left internal jugular vein, followed by the femoral vein. The use of subclavian vein for dialysis access should be avoided as much as possible for the risk of creating central vein stenosis, which precludes future creation of AV fistula on that side of the upper limb, if need arises in future. The use of femoral vein carries the highest risk of infection among the various dialysis access sites and hence the dialysis catheter should not be kept for more than 1 week in the femoral site. On the other hand, the internal jugular dialysis catheter can be kept for a maximum of 4 weeks without high risk of infection. Notwithstanding this, any unnecessary prolongation of dialysis catheter carries risk of infection, sepsis and thrombosis.
344In peritoneal dialysis (PD), various acute and chronic type PD catheters are available. The PD catheters are inserted in the infraumbilical position directed to one of the iliac fossae.
 
HEMODIALYSIS VERSUS PERITONEAL DIALYSIS
Acute PD is not commonly practised nowadays in most countries due to risk of peritonitis and lack of efficacy compared to HD. However in resource-constrained settings where HD facility is lacking, acute PD can be life-saving. On the other hand, chronic PD using Tenckhoff silicone catheters are as effective as chronic HD and are commonly practised worldwide. However, chronic PD is not suitable for acute usage in the ICU. Thus, in the ICU, the preferred modality is HD rather than PD. If at all, acute PD is practised, it has to be carried out in strict aseptic precautions and the catheter should not be kept in situ for more than 5 days due to increased risk of infection.
 
INTERMITTENT HEMODIALYSIS VERSUS SLOW LOW EFFICIENCY DIALYSIS
In patients who are hemodynamically unstable, conventional intermittent HD can cause further hemodynamic instability. Therefore, in patients who are on inotropic support, sustained low-efficiency dialysis called SLED is preferred. In this modality, the blood pump speed is reduced to around 100 mL/minute and dialysate flow is reduced to around 300 mL/minute and carried out for extended periods of time ranging from 6 to 12 hours.
 
SLOW LOW EFFICIENCY DIALYSIS VERSUS CONTINUOUS RENAL REPLACEMENT THERAPY
In hemodynamically unstable patients, another modality of dialysis called continuous renal replacement therapy (CRRT) is gaining popularity, especially in affluent countries like US, Australia and Europe. CRRT is of various types like CAVHD, CAVHF, CAVHDF, CVVHD, CVVHF and CVVHDF. Of these, CVVHD, CVVHF and CVVHDF are commonly practised. CRRT is carried out almost 18–24 hours daily using commercially available dialysate and replacement solutions. CRRT carries several advantages over SLED like better hemodynamic stability, lack of sudden fluctuations in fluid balance, better nutritional support, lack of fluid restrictions and better recovery of AKI. However, there is no mortality advantage over SLED and it is quite expensive. Thus in resource constrained settings, SLED is commonly used, whereas in affordable patients with hemodynamic instability, CRRT is preferred.
 
ADVERSE EFFECTS OF RENAL REPLACEMENT THERAPY
The RRT is an invasive therapeutic modality and therefore can produce various complications. Some of the most commonly encountered complications are given in Table 43.3.345
Table 43.3   Complications of RRT
Access-related
Dialysis-related
Catheter-induced sepsis
Catheter-induced thrombosis
Catheter displacement
Poor catheter flow (fibrin sheath)
Intradialytic hypotension
Sudden changes in electrolyte balance
Risks of anticoagulation, etc.
 
CONCLUSION
Renal replacement therapy is a life-saving therapeutic modality in critically ill patients. CRRT and SLED are suitable modalities in hemodynamically unstable patients, whereas intermittent HD is preferred in other patients. In resource-constrained settings where HD facilities do not exist, PD can be life-saving.
 
BIBLIOGRAPHY
  1. Abraham G, Varughese S, Mathew M, Vijayan M. A review of acute and chronic peritoneal dialysis in developing countries. Clin Kidney J. 2015;8(3):310-7.
  2. Ansari N. Peritoneal dialysis in renal replacement therapy for patients with acute kidney injury. Int J Nephrol. 2011.pp.739-94.
  3. Cho KC, Himmelfarb J, Paganini E, Ikizler TA, Soroko SH, Mehta RL, Chertow GM. Survival by dialysis modality in critically ill patients with acute kidney injury. J Am Soc Nephrol. 2006;17(11):3132-8.
  4. Ghahramani N, Shadrou S, Hollenbeak C. A systematic review of continuous renal replacement therapy and intermittent haemodialysis in management of patients with acute renal failure. Nephrology (Carlton). 2008;13(7):570-8.
  5. Kellum JA. Renal replacement therapy in critically ill patients with acute renal failure: does a greater dose improve survival? Nature Clinical Practice Nephrology. 2007;3:128-9.
  6. Liu KD, Himmelfarb J, Paganini E, Ikizler TA, Soroko SH, Mehta RL, Chertow GM. Timing of initiation of dialysis in critically ill patients with acute kidney injury.Clin J Am Soc Nephrol. 2006;1(5):915-9.
  7. Mehta RL. Continuous renal replacement therapy in the critically ill patient. Kidney International. 2005;67:781-95.
  8. Ostermann M, Dickie H, Barrett NA. Renal replacement therapy in critically ill patients with acute kidney injury—when to start. Nephrol Dial Transplant. 2012;27(6):2242-8.
  9. Ronco C, Bellomo R, Ricci Z. Continuous renal replacement therapy in critically ill patients. Nephrol Dial Transplant. 2001;16(Suppl 5):67-72.

HYPONATREMIACHAPTER 44

TA Naufal Rizwan
Hyponatremia is a condition where the serum sodium is less than 135 mEq/L. It usually results from retention of water secondary to impairment in free water excretion. When the serum sodium falls slowly over a period of days or weeks, our body compensates by extruding solutes into the extracellular space. However, in case of rapid fall in sodium, compensatory mechanisms do not occur resulting in various complications.
 
CAUSES
Most cases of hyponatremia are associated with low osmolality. However, in some patients the osmolality may not be low, indicating the presence of significant concentration of other osmotically active solutes in the plasma. Etiology of hyponatremia based on urine sodium level is given in Table 44.1.
Table 44.1   Etiology of hyponatremia based on urine sodium level
Urine sodium level
Etiology
>20 mEq/L
  • Renal causes of hypovolemic hyponatremia
  • SIADH, renal failure, postoperative states, hypothyroidism, pain
<10 mEq/L
  • GI and skin causes of hypovolemic hyponatremia
  • Hypervolemic causes like CCF, cirrhosis, nephrotic syndrome (except CRF)
Abbreviations: SIADH, syndrome of inappropriae antidiuretic hormone; GI, gastrointestinal; CCF, congestive cardiac failure; CRF, chronic renal failure
347
 
PSEUDOHYPONATREMIA
  • Increased plasma osmolality (>290 mOsm/kg)
    • Hyperglycemia, mannitol, glycerol
  • Normal plasma osmolality (275–290 mOsm/kg)
    • Hyperlipidemia, hyperproteinemia, post-TURP.
 
TRUE HYPONATREMIA (< 275 MOSM/KG)
  • Hypovolemic
    • Renal loss (diuretics, salt wasting nephropathy, hypoaldosteronism)
    • GI loss (vomiting, diarrhea, tube drainage, fistula)
    • Skin loss (sweating, burns, cystic fibrosis)
  • Euvolemic
    • Syndrome of inappropriate antidiuretic hormone (SIADH), postoperative states (TURP), pain (due to AVP release)
    • Hypothyroidism, glucocorticoid deficiency, primary polydipsia
  • Hypervolemic
    • Congestive cardiac failure (CCF), nephrotic syndrome, cirrhosis liver, chronic renal failure.
 
Clinical Features
The symptoms of hyponatremia not only correlates with the serum sodium concentration, but also with the rapidity of onset. Hence, acute hyponatremia is more dangerous than the chronic one. The clinical features are predominantly neurologic and these include nausea, vomiting, confusion, difficulty in concentration, lethargy, agitation, headache, etc. Seizures, stupor and coma usually occur only when plasma sodium is <120 mEq/L or when it decreases rapidly.
In addition to the neurologic findings, patient may also have muscle weakness, muscle cramps, rhabdomyolysis, signs of hypovolemia (dry mucous membrane, tachycardia) or hypervolemia (pedal edema, ascites, etc.).
 
Investigations
  • Serum sodium
  • Serum osmolality
  • Urine sodium level
  • Urine osmolality
    • In most cases of hyponatremia, urine osmolality is >200 mOsm/kg
    • One important exception is primary polydipsia where it is <100 mOsm/kg.
 
Treatment
Treatment of hyponatremia depends on:
  • Symptoms
  • Volume status of the patient
  • Acute or chronic.348
 
Cardinal Rules of Correction of Hyponatremia
  • In asymptomatic hyponatremia, the serum sodium should not be raised by more than 0.5–1 mEq/L/hour and in the first 24 hours, the rise should not be more than 12 mEq/L
  • In acute or severe symptomatic hyponatremia, it can be increased by 1–2 meq/L/hour for first 4 hours but again not more than 12 mEq/L in the first 24 hours.
 
ASYMPTOMATIC HYPONATREMIA
The objective should be to find out the underlying cause and correction of the same.
  • Hypovolemic hyponatremia
    • Normal saline should be infused.
  • Hypervolemic hyponatremia
    • Salt and water restriction + Loop diuretics
    • Water restriction should be less than the urine output
    • Vasopressin antagonists (conivaptan, tolvaptan) can also be tried.
  • Euvolemic hyponatremia
    • Water restriction + treatment of the underlying cause
    • Vasopressin antagonists (conivaptan, tolvaptan) can also be tried.
 
SYMPTOMATIC HYPONATREMIA
In case of symptomatic hyponatremia, rapid correction (but not more than 12 mEq/L in the first 24 hours) using hypertonic saline (3% or 5%) can be done.
 
Steps in Correcting Hyponatremia
 
Step 1: Expected Change in Sodium
Total body water is 0.6 × body weight (men) and 0.5 × body weight (women)
For example, in a 50 kg man with a serum sodium of 120 mmol/L, and if corrected with 3% Nacl,
The expected change in sodium =
= 12.68
This means 1 liter of 3% Nacl will produce 12.68 mmol/L change in serum sodium level.
 
Step 2 : Liters Infusate and Hours to Correct (Table 44.2)
349
Table 44.2   Sodium level in various infusate
Infusate
Sodium level (mmol/L)
5% NaCl
855
3% NaCl
513
0.9% NaCl
154
Ringer lactate
130
0.45% NaCl
77
Hours to correct = (Target sodium–serum sodium) × 0.5
i.e. (135–120) × 0.5 = 30 hours.
 
Step 3: Rate of Infusion
So, the final answer is, 3% Nacl should be given at a rate of 39.4 mL/hour for a period of 30 hours for correcting the hyponatremia in this patient.
 
OSMOTIC DEMYELINATION SYNDROME
This syndrome is seen as a result of rapid correction of hyponatremia. It occurs due to sudden osmotic shrinkage of brain cells and is more commonly seen in correction of chronic hyponatremia since their brain volume has returned to near normal as a result of osmotic adaptive mechanisms. It is characterized by dysphasia, spastic quadriparesis, pseudobulbar palsy, mutism, delirium, coma, etc. The risk of osmotic demyelination syndrome (ODS) is high in alcoholics, malnutrition and hypokalemia. There is no specific treatment for this condition.
 
HYPERNATREMIA
It is a condition where the serum sodium is greater than 145 mEq/L. More commonly, it is the result of combined water and electrolyte deficit, with losses of water in excess of sodium. Persons with diminished thirst (elderly) and diminished access to fluids are at the highest risk of developing hypernatremia.
 
Causes
The causes of hypernatremia are classified as follows.
 
Hypovolemic
  • Renal losses
    • Osmotic diuresis secondary to hyperglycemia, urea, mannitol
    • Postobstructive diuresis
  • 350Gastrointestinal losses
    • Diarrhea
  • Skin losses
    • Fever, exercise, severe burns, heat exposure.
 
Euvolemic
It occurs due to diabetes insipidus (DI) and the three types of DI are:
  1. Central
    • Tumor, hydrocephalus, ACA occlusion, trauma, inflammation
  2. Nephrogenic
    • Genetic—mutations in aquaporins channels
    • Acquired—Hypokalemia, hypercalcemia, lithium, ifosfamide, antivirals
  3. Gestational
    • Due to reduced circulating AVP.
 
Hypervolemic
  • Administration of hypertonic saline, sodium bicarbonate
  • Primary hyperaldosteronism.
 
Clinical Features
The symptoms are seen predominantly in acute hypernatremia. Most of the symptoms are neurologic and these include confusion, lethargy, altered mental status, stupor and deep coma. They occur as a result of sudden shrinkage of brain cells. Patients with acute hypernatremia are also at risk of developing various vascular complications like parenchymal hemorrhage, Subarachnoid hemorrhage and subdural hematomas. Rhabdomyolysis is another complication which occurs due to osmotic damage of the muscle membranes.
 
Investigations
  • Serum sodium
  • Serum osmolality
  • Urine osmolality
    • If >800 mOsm/kg and low urine volume—GI loss and insensible water loss
    • If >800 mOsm/day and adequate urine volume—diuretics, osmotic diuresis
  • Serum AVP and the response to DDAVP—to differentiate central from nephrogenic DI
  • Urine electrolytes and urine volume.
 
Treatment
The therapeutic goals are to:
  • Stop the ongoing water loss
  • Correct the water deficit.351
 
Step 1: Calculate the Water Deficit
In hypernatremia, the total body water is 50% of weight in men and 40% in women.
For example, in a 60 kg man with a plasma sodium of 160 mmol/L,
 
Step 2: Correction of Water Deficit
Half of the water deficit can be corrected in the first 24 hours (in case of acute hypernatremia) and the remaining half over the next 24–48 hours. The rate of sodium fall should not be more than 0.5 mmol/L/hour and definitely should not be more than 12 mmol/L in the first 24 hours. Rapid correction of hypernatremia can result in swelling of the brain cells leading to seizures and permanent neurologic damage.
The safest route of administration of water is by mouth or via a nasogastric tube. Alternatively, 5% D or ½ NS can also be given intravenously.
 
MANAGEMENT OF DIABETES INSIPIDUS
 
Central Diabetes Insipidus (DI)
  • Desmopressin—intranasal or 4 µg/day IV or SC in divided doses
  • Low salt diet + low dose thiazides diuretics.
 
Partial Central DI
  • Chlorpropamide, clofibrate, carbamazepine
These drugs stimulate AVP secretion or its action on kidney.
  • NSAIDs—they impair prostaglandin synthesis and potentiate AVP action.
 
Nephrogenic DI
  • Treatment of underlying disorder and removal of offending drug
  • Low salt diet + low dose thiazides diuretics
  • NSAIDs and amiloride.
 
BIBLIOGRAPHY
  1. Adeleye O, Faulkner M, Adeola T, ShuTangyie G. Hypernatremia in the elderly. J Nation Med Assoc. 2002;94(8):701-5.
  2. Adrogué HJ, Madias NE. The challenge of hyponatremia. J Am Soc Nephrol. 2012;23(7):1140-8.
  3. Alshayeb HM, Showkat A, Babar F, Mangold T, Wall BM. Severe hypernatremia correction rate and mortality in hospitalized patients. Am J Med Sci. 2011;341(5):356-60.
  4. 352Bagshaw SM, Townsend DR, McDermid RC. Disorders of sodium and water balance in hospitalized patients. Cana J Anesth. 2009;56(2):151-67.
  5. Bhave G, Neilson EG. Body fluid dynamics: back to the future. J Am Soc Nephrol. 2011;22:2166-81.
  6. Chua M, Hoyle GE, Soiza RL. Prognostic implications of hyponatremia in elderly hospitalized patients. Arch Gerontol Geriatr. 2007;45(3):253-8.
  7. Clayton JA, Le Jeune IR, Hall IP. Severe hyponatremia in medical in-patients: etiology, assessment and outcome. QJM. 2006;99(8):505-11.
  8. Lien YH, Shapiro JI. Hyponatremia: clinical diagnosis and management. Am J Med. 2007;120(8):653-8.
  9. Lima EQ, Aguiar FC, Barbosa DM, Burdmann EA. Severe hypernatremia (221 mEq/l), rhabdomyolysis and acute renal failure after cerebral aneurysm surgery. Nephrol Dial Transplant. 2004;19(8):2126-9.
  10. Lobo DN, Stanga Z, Alastair J, Simpson D, Anderson JA, Rowlands BJ, Allison SP. Dilution and redistribution effects of rapid 2-liter infusions of 0.9% (w/v) saline and 5% (w/v) dextrose on haematological parameters and serum biochemistry in normal subjects: a double-blind crossover study. Clin Sci. 2001;101:173-9.
  11. Miller M, Morley JE, Rubenstein LZ. Hyponatremia in a nursing home population. J Am Geriatr Soc. 1995;43(12):1410-3.
  12. Miller M. Hyponatremia in the elderly: risk factors, clinical consequences, and management. Clin Geriatr. 2009;17(9):34-9.
  13. Michael MB, Craig HB, Natasha JP. Diagnosis and management of sodium disorders: Hyponatremia and hypernatremia. Am Fam Physician. 2015;91(5):299-307.
  14. Nguyen MK, Kurtz I. Correction of hypervolemic hypernatremia by inducing negative Na+ and K+ balance in excess of negative water balance: a new quantitative approach. Nephrol Dial Transplant. 2008;23:2223-7.
  15. Nguyen MK, Kurtz I. New insights into the pathophysiology of the dysnatremias: a qualitative analysis. Am J Physiol Renal Physiol. 2004;287:F172-F80.
  16. Ofran Y, Lavi D, Opher D, Weiss TA, Elinav E. Fatal voluntary salt intake resulting in the highest ever-documented sodium plasma level in adults (255 mmol L-1): a disorder linked to female gender and psychiatric disorders. J Intern Med. 2004;256(6):525-8.
  17. Park YJ, Kim YC, Kim MO, Ryu JH, Han SW, Kim HJ. Successful treatment in the patient with serum sodium level greater than 200 mEq/L. J Korean Med Sci. 2000;15(6):701-3.
  18. Pfennig CL, Slovis CM. Sodium disorders in the emergency department: a review of hyponatremia and hypernatremia. Emerg Med Pract. 2012;14(10):1-26.
  19. Sam R, Hart P, Haghighat R, Ing TS. Hypervolemic hypernatremia in patients recovering from acute renal failure in the intensive care unit. Clin Exp Nephrol. 2012;16:136-46.
  20. Schlanger LE, Bailey JL, Sands JM. Electrolytes in the aging. Adv Chronic Kidney Dis. 2010;17(4):308-19.
  21. Schrier RW, Bansal S. Diagnosis and management of hyponatremia in acute illness. Curr Opin Crit Care. 2008;14(6):627-34.
  22. Snyder NA, Feigal DW, Arieff AI. Hypernatremia in elderly patients. A heterogeneous morbid and iatrogenic entity. Ann Intern Med. 1997;107:309-19.
  23. Takamata A, Yoshida T, Nishida N, Morimoto T. Relationship of osmotic inhibition in thermoregulatory responses and sweat sodium concentration in humans. Am J Physiol Regul Integr Comp Physiol. 2001;280:R623-R9.
  24. Vaidya C, Ho W, Freda BJ. Management of hyponatremia: providing treatment and avoiding harm. Cleve Clin J Med. 2010;77(10):715-26.
  25. Verbalis JG, Goldsmith SR, Greenberg A, et al. Hyponatremia treatment guidelines 2007: expert panel recommendations. Am J Med. 2007;120(11 suppl 1):S1-S21.
  26. Verbalis JG. Hyponatremia and hypo-osmolar disorders. In: Greenberg A, Cheung AK (Eds). Primer on kidney diseases, 5th edn. Philadelphia, PA: WB Saunders Co; 2009. pp.52-9.

POTASSIUMCHAPTER 45

Prem Kumar, Sushma Vijay Pingale
The human body, in normal condition, contains total body potassium of approximately 50 mEq/kg. Majority of the potassium is intracellular and only 2% of the total potassium stores are found extracellularly. This extracellular potassium reflects the balance between potassium intake and excretion.
 
POTASSIUM BALANCE IN HEALTH AND DISEASE
Average daily dietary [K+] intake in adults is 80 mEq/day out of which 70 mEq is excreted in urine and remaining 10 mEq through the stools. The cell membrane Na+ K+ ATPase regulates the extracellular K+ concentration. Na+ K+ ATPase pump actively transports sodium out of, and potassium into, most cells. The activity of this pump is enhanced by insulin and catecholamines, thereby causing a decrease in plasma potassium levels.
In acidosis, extracellular H+ ions enter cells and this movement results in the intracellular K+ ions moving out to maintain the electrical balance. This causes an increase in plasma potassium levels. The reverse effect is seen in alkalosis where the extracellular K+ ions move into the cells to balance the movement of H+ ions out of cells. This results in decrease in plasma potassium levels. The plasma K+ concentration changes approximately 0.6 mEq/L per 0.1 U in arterial pH (range 0.2–1.2 mEq/L).
The normal serum potassium levels are 3.5–5.5 mEq/L.
 
HYPOKALEMIA
Hypokalemia is defined as a serum potassium concentration less than 3.5 mEq/L. The relationship between changes in total body potassium and changes in serum potassium is curvilinear and hence plasma potassium concentration correlates poorly with the total potassium deficit. A decrease in plasma [K+] from 4 mEq/L to 3 mEq/L usually represents a 100–200 mEq deficit, whereas plasma [K+] below 3 mEq/L can represent a deficit anywhere between 200 mEq and 400 mEq.
 
Causes
Hypokalemia can arise due to excessive loss through renal, gastrointestinal route or due to transcellular shifts and rarely due to inadequate intake (Table 45.1).354
Table 45.1   Causes of hypokalemia
Transcellular shift
  • Metabolic alkalosis
  • Hypokalemic periodic paralysis
  • Insulin administration
  • Head injury
  • β-2 agonists
  • Total parenteral nutrition
  • Hypothermia
Decreased intake
Gastrointestinal loss
  • Severe diarrhea
  • Nasogastric suctioning
  • Intestinal fistulas
Renal loss
  • Diuretic administration
  • Osmotic diuresis
  • Salt wasting nephropathies
  • Renal tubular acidosis
 
Renal Loss
The most common cause for excessive renal loss of potassium is either diuretic therapy or increased mineralocorticoid activity. The other causes are renal tubular acidosis, ketoacidosis, hypomagnesemia, salt wasting nephropathies and drugs. The urinary Cl-concentration is high (>25 mEq/L) in renal cause of hypokalemia and low (<15 mEq/L) in extrarenal cause (nasogastric suction, alkalosis) of hypokalemia.
 
Gastrointestinal Loss
The main gastrointestinal (GI) causes of loss of potassium are diarrhea and nasogastric suction. The normal stool volume is approximately 200 mL and contains 75 mEq/L of K+. But in diarrhea, the daily volume of stool can rise up to 10 liters. Thus, significant amount of potassium is lost in severe diarrhea and hence can result in hypokalemia if not replenished adequately. The other GI causes are fistulae, laxative abuse, villous adenomas and pancreatic tumors secreting vasoactive intestinal peptide.
 
Transcellular Shifts
The movement of potassium from extracellular compartment to intracellular compartment is seen in alkalosis, hypokalemic periodic paralysis, beta-2 agonists and insulin therapy and in hypothermia.
 
Clinical Features
Mild hypokalemia (K+ 2.5–3.5 mEq/L) is often asymptomatic and may manifest only in the form of ECG changes like flattening and inversion of T wave, ST depression, prominent U waves (>1 mm in height) and prolongation of the 355QT interval. Cardiac toxicity may be manifested by serious arrhythmias due to hyperpolarization of the myocardial cell membrane, leading to a prolonged refractory period and increased susceptibility to reentrant arrhythmias. Severe hypokalemia (K+ <2.5 mEq/L) results in skeletal muscle weakness especially the quadriceps, muscle cramps, tetany and ileus. Polyuria due to stimulation of thirst and resistance to the action of ADH are the primary renal manifestations of hypokalemia. Severe hypokalemia can also result in rhabdomyolysis.
 
Management
The first step in management of hypokalemia is to treat any condition that promotes transcellular potassium shifts (e.g. alkalosis, hypothermia etc.). If the cause of hypokalemia is potassium depletion then potassium replacement should be done. Oral or intravenous potassium chloride generally is the preferred treatment for hypokalemia.
Oral route for replacement is generally safest (60–80 mEq/d) and preferred in mild hypokalemia. Oral potassium chloride can be given in crystalline form (salt substitutes), as liquid, or in a slow-release tablet or capsule. Salt substitutes contain 50 to 65 mEq per teaspoon. They are safe, cheap and better tolerated than the other preparations. The liquid preparations of potassium chloride are often unpalatable, and the slow-release preparations can, in rare cases, cause ulcerative or stenotic lesions in the gastrointestinal tract as a result of the local accumulation of high concentrations of potassium.
Severe hypokalemia should be managed by intravenous replacement with potassium chloride, which is available as a concentrated solution in ampoules containing 10, 20, 30, and 40 mEq of potassium. These solutions are extremely hyperosmotic (2 mEq/L solution has an osmolality of 4000 mOsm/L H2O) and hence must be diluted. The maximum rate of intravenous potassium replacement should not exceed 20 mEq/hour. The infusion should be given through a central vein because of the irritating properties of the hyperosmotic potassium solutions. Life-threatening arrhythmias where serum K+ is <1.5 mEq/L may necessitate an infusion rate of up to 40 mEq/l. In such cases infusion through a central line can pose a theoretical risk of transient hyperkalemia in the right heart chambers, which can predispose to a sudden cardiac standstill and hence must be avoided. Femoral line or 2 large bore peripheral venous lines are preferred in such circumstances. Intravenous replacement should generally not exceed 240 mEq/d. ECG monitoring should be done in patients with significant ECG changes and monitoring of muscle strength in patients with muscle weakness during the replacement therapy. Replacement of the potassium deficit usually requires several days. When hypokalemia is refractory to replacement with potassium chloride, then magnesium levels should be assessed and a magnesium deficiency if observed should be corrected.
 
HYPERKALEMIA
Hyperkalemia is defined as serum potassium level >5.5 mEq/L. It is a common electrolyte abnormality in intensive care unit (ICU) patients (e.g. renal failure). The most common cause of hyperkalemia is reduced renal excretion of K+. Other causes are given in Table 45.2.356
Table 45.2   Causes of hyperkalemia
  • Transcellular shift: Metabolic acidosis, burns, prolonged immobilization, tumor lysis, neuromuscular disease, arginine, hyperosmolality
  • Acute or chronic renal failure
  • Adrenal insufficiency: Addison's disease, infections (tuberculosis, human immunodeficiency virus (HIV), heparin, congenital adrenal hyperplasia
  • Hyporeninemic hypoaldosteronism: Diabetes, tubulointerstitial disease
  • Hyperkalemic periodic paralysis
  • Drug-induced: Succinylcholine, digoxin, nonsteroidal anti-inflammatory drugs (NSAIDs), β-blockers, cyclosporine, angiotensin-converting-enzyme (ACE) inhibitors, angiotensin receptor blocke (ARB), rennin inhibitor, spironolactone, amiloride.
  • Congestive heart failure
  • Hypovolemia
  • Pseudohyperkalemia
 
Pseudohyperkalemia
It is increase in serum K+ due to the release of K+ during or after venipuncture, thrombocytosis, erythrocytosis, leukocytosis. There is elevation in measured plasma potassium concentration due to potassium movement out of the cells during or after the blood specimen has been drawn.
 
Metabolic Acidosis
Buffering of excess hydrogen ions in the cells causes transcellular shift of potassium to extracellular fluid to maintain electroneutrality.
 
Renal Disease
Hyperkalemia occurs due to impaired intake of K+ into cells, reduced Na+/K+ ATPase activity, high potassium intake, hypoaldosteronism.
 
Critical Illness
Hypoaldosteronism due to reduced adrenal production occurs in critically ill patients.
 
Clinical Features
Resting membrane potential depends on potassium. Hyperkalemia causes partial depolarization of the cell membrane, decrease in the membrane excitability and affects the repolarization phase of cardiac action potential resulting in impaired cardiac conduction, weakness of the muscles, hence hyperkalemia causes cardiac conduction disturbances. Cardiac arrhythmias associated with hyperkalemia are peaked T waves (earliest sign), widening of PR interval and QRS complexes, loss of 357p wave, sine wave pattern, ventricular tachycardia, ventricular fibrillation, heart block, asystole. Electrocardiogram (ECG) findings associated with hyperkalemia is based on serum potassium level—tall peaked T waves (5.5–6.5 mEq/L), loss of P waves (6.5–7.5 mEq/L), widened QRS complex (7–8 mEq/L), and ultimately to a sine wave pattern (8 mEq/L). Neuromuscular manifestations are paresthesias, weakness and paralysis of respiratory muscles. Hyperkalemia causes reduction in the excretion of acid load which causes metabolic acidosis (retention of NH4+).
 
Diagnosis
History, physical examination should be focus on diet, medications, blood pressure, history of renal failure, volume status. Laboratory investigations include serum sodium, potassium, magnesium, calcium, urea, creatinine, serum osmolality, complete blood count, and urinary pH.
Table 45.3   Treatment of hyperkalemia
Management
Comment
10 mL of 10% calcium gluconate (3–4 mL of calcium chloride) intravenously over 2 to 3 minutes Onset starts in 1–3 minutes and lasts for 30–60 minutes Can be repeated
Calcium raises the action potential threshold and reduces excitability without change in the resting membrane potential (RMP). Calcium reverses the depolarization blockade caused by hyperkalemia by restoring the difference between the resting and threshold potentials
10 units of IV regular insulin along with 50 mL of 50% dextrose. Onset starts in 10–20 min, peaks at 30–60 minutes, and lasts 4 to 6 hours. This is followed by infusion of 10% dextrose at 50 to 75 mL/hour to avoid hypoglykemia. Hyperkalemia with glucose concentrations >200–250 mg/dL, insulin should be administered without glucose
Rapid transcellular shift of K+ into cells. Administering glucose for hyperkalemia has the risk of worsening hyperkalemia due to the osmotic effect of hypertonic glucose
Inhaled β2-agonists—inhaled albuterol of 10–20 mg inhaled over 10 minutes, onset starts in 30 minutes, peaks at about 90 minutes, and lasts for 2–6 hours
It should be used along with insulin. Renal failure patients are resistant to the effects of β2-agonists. Hyperglycemia, tachycardia are adverse effects
Soda bicarbonate (40–80 mEq)
As such it has no therapeutic effect for hyperkalemia. Can be used for hyperkalemia along with severe metabolic acidosis
Potassium excretion—loop and thiazide diuretics
Can be given in hypervolemic patients with preserved renal function
Potassium removal—dialysis
Most effective method to reduce potassium
Potassium binders—sodium polystyrene sulfonate. Dose is 15–30 g in 50 mL of 33% sorbitol to avoid constipation
Sodium polystyrene sulfonate (Kayexalate) is a cation exchange resin that enhances K+ excretion in gastrointestinal tract and increases the fecal excretion of K+. Full effect can take up to 24 hours. Complication of kayexalate is intestinal necrosis
358
 
Management (Table 45.3)
The first initial step in managing hyperkalemia is whether the patient needs emergency treatment or not. Once the patient develops cardiac manifestations due to hyperkalemia or when serum K+ is >6.5 mEq/L, it is a medical emergency and requires immediate treatment. Management requires ICU admission, continuous cardiac monitoring.
 
BIBLIOGRAPHY
  1. Adrogue H, Madias N. Changes in plasma potassium concentration during acute acid-base disturbances. Am J Med. 1981;71:456.
  2. Allon M, Copkney C. Albuterol and insulin for treatment of hyperkalemia in hemodialysis patients. Kidney Int. 1990;38:869.
  3. Allon M. Hyperkalemia in end-stage renal disease: mechanisms and management. J Am Soc Nephrol. 1995;6:1134.
  4. Charytan D, Goldfarb DS. Indications for hospitalization of patients with hyperkalemia. Arch Intern Med. 2000;160:1605.
  5. Don B, Schambelan M. Hyperkalemia in acute glomerulonephritis due to transient hyporeninemic hypoaldosteronism. Kidney Int. 1990;38:1159.
  6. Don BR, Sebastian A, Cheitlin M, et al. Pseudohyperkalemia caused by fist clenching during phlebotomy. N Engl J Med. 1990;322:1290-2.
  7. Emmett M, Hootkins RE, Fine KD, et al. Effect of three laxatives and a cation exchange resin on fecal sodium and potassium excretion. Gastroenterology. 1995;108:752.
  8. Evans KJ, Greenberg A. Hyperkalemia: A review. J Intensive Care Med. 2005;20:272-90.
  9. Kunin A, Surawicz B, Sims E. Decrease in serum potassium concentration and appearance of cardiac arrhythmias during infusion of potassium with glucose in potassium-depleted patients. N Engl J Med. 1962;266:228.
  10. Longo DL, Kasper DL, Jameson JL. et al. Harrison's principles of internal medicine. 18th edn. McGraw Hill publications. 2012.
  11. Oster JR, Singer I, Fishman LM. Heparin-induced aldosterone suppression and hyperkalemia. Am J Med. 1995;98:575.
  12. Sterns RH, et al. Ion-exchange resins for the treatment of hyperkalemia: Are they safe and effective? J Am Soc Nephrol. 2010;21:733.
  13. Whang R, Whang D, Ryan M. Refractory potassium depletion. A consequence of magnesium deficiency. Arch Intern Med. 1992;152:40.

CALCIUMCHAPTER 46

TA Naufal Rizwan  
CALCIUM METABOLISM
The adult human body contains approximately 1100 g of calcium, of which approximately 99% is located in the bones. The normal serum calcium level is 8.9–10.1 mg/dL, of which 50% is free ionized calcium, 40% is bound to proteins and remaining 10% is combined with various anions. The extracellular calcium level is maintained in a narrow range by various feedback mechanisms that operate between the parathyroid glands, kidney, intestine and bone.
 
Functions of Calcium
  • Excitation contraction coupling in all muscles
  • Neurotransmitter release at nerve terminals
  • Coagulation cascade
  • Complement cascade
  • Cofactor for numerous enzymes
  • Bone and teeth formation
  • Salivary and aldosterone secretion.
 
HYPOCALCEMIA
Hypocalcemia is said to be present if:
Total corrected calcium is <2.1 mmol/L (<8.4 mg/dL)
and/or
Ionized Calcium is <1.2–1.3 mmol/L (4.8–5.2 mg/dL)
(Conversion: 1 mmol/L = 4 mg/dL)
Corrected calcium (mg/dL): Measured total calcium (mg/dL) + 0.8 (4.4–serum albumin{g/dL})
Hypocalcemia is an electrolyte abnormality commonly seen in intensive care unit (ICU) patients. Hypoalbuminemia is one of the most common cause of hypocalcemia in ICU. Other common cause is renal failure.360
 
Causes (Table 46.1)
Table 46.1   Causes of hypocalcemia based on the parathyroid hormone levels
  • Low parathyroid hormone levels
    • Parathyroid agenesis: Isolated/Digeorge syndrome (patient also has cleft lip/palate, congenital heart diseases)
    • Parathyroid destruction: Surgical/radiation/infiltrative diseases/autoimmune diseases
    • Parathyroid dysfunction: Hypomagnesemia
  • High parathyroid hormone levels
    • Vitamin D deficiency or impaired 1,25(OH)2 production/action: Nutritional/Renal insufficiency/vit D resistance
    • Parathyroid hormone resistance syndromes: Pseudohypoparathyroidism/PTH receptor mutations
    • Drugs: Calcium chelators/bisphosphonates/phenytoin/ketoconazole
    • Miscellaneous causes: Acute pancreatitis/acute rhabdomyolysis/osteoblastic metastases
 
Clinical Features
The clinical features of hypocalcemia vary from being asymptomatic (in mild and chronic) to life-threatening complications (in severe). The clinical features are predominantly neuromuscular and cardiopulmonary.
 
Cardiopulmonary Manifestations
The cardiopulmonary manifestations of hypocalcemia are wheezing, stridor due to laryngeal spasm, bradycardia, dysphagia, arrhythmias, etc. Negative chronotropy and reduced myocardial contractility may lead to hypotension, angina and heart failure.
 
Neuromuscular Manifestations
Focal numbness and paresthesias of the fingers, toes and perioral regions are the usual symptoms in moderate to severe hypocalcemia. Seizures and carpopedal spasm are seen in severe hypocalcemia. Irritability, confusion, hallucinations, dementia and extrapyramidal manifestations are the other manifestations of hypocalcemia.
 
CHVOSTEK'S SIGN
Gentle tapping of the facial nerve, just 2 cm anterior to the tragus of the ear, results in twitching of the circumoral muscles.
 
TROUSSEAU SIGN
Carpal spasm induced by keeping the inflated blood pressure cuff 20 mm Hg above the systolic BP for 3 minutes.
The other manifestations of hypocalcemia include dystonias, papilloedema, choreathetosis, hemiballismus and oculogyric crisis.361
 
Investigations
  • Serum calcium (ionized), magnesium, phosphate
  • Serum albumin to rule out factitious hypocalcemia
  • Serum PTH level
  • Liver function tests
  • Vitamin D metabolites
  • ECG–QT prolongation in hypocalcemia
  • Skeletal X-ray—to rule out rickets, osteomalacia, osteoblastic metastases, etc.
 
Treatment
The treatment depends on the severity of hypocalcemia, rapidity at which it develops and the presence of complications. Hypomagnesemia, if associated, should be corrected.
 
Severe Symptomatic Hypocalcemia
10 mL of 10% calcium gluconate (90 mg) given IV over 5 minutes.
(diluted in 50 mL of 5% dextrose or 0.9% Nacl)
↓ If hypocalcemia still persists
10 ampoules of calcium gluconate in 1 L of 5% dextrose or 0.9% Nacl (administered over 24 h).
 
Chronic Hypocalcemia (Mostly Seen with Hypoparathyroidism)
Calcium supplements (1000–1500 mg/d elemental calcium in divided doses) and either vitamin D2 or D3 (25,000–100,000 U daily) or calcitriol [1,25(OH)2D, 0.25–2 g/d] should be given. Nutritional vitamin D deficiency is treated with low doses of vitamin D (50,000 U, 2–3 times per week for several months) while vitamin D deficiency due to malabsorption require much higher doses (100,000 U/d or more).
 
HYPERCALCEMIA
Hypercalcemia is a condition where the serum calcium level is >10.5 mg/dL. More than 90% of cases are due to primary hyperparathyroidism and malignancy. Excess calcium ingestion can also cause hypercalcemia as in the case of milk-alkali syndrome. Causes are given in Table 46.2
 
Clinical Features
The clinical features of hypercalcemia depend on the serum level of calcium and the rapidity of the development of hypercalcemia. The symptoms are predominantly renal, neuropsychiatric and gastrointestinal. Mild hypercalcemia (10.5–11.5 mg/dL) is usually asymptomatic whereas severe hypercalcemia (>12 mg/dL) produces serious symptoms.362
Table 46.2   Causes of hypercalcemia
Abbreviations: PTH, parathyroid hormone; TPN, total parenteral nutrition
 
Neuropsychiatric
Impaired concentration, lethargy, personality changes, stupor, depression, coma, etc.
 
Gastrointestinal
Nausea, vomiting, anorexia, constipation, peptic ulcer, pancreatitis.
 
Renal
Polyuria, hematuria, nephrolithiasis,renal colic, AKI, etc.
 
DIAGNOSTIC WORKUP
 
Blood Investigations
 
Serum Albumin
Since ionized calcium estimation is influenced by numerous artifacts and collection methods, measurement of total calcium is a better option. However, it has to be corrected (as previously explained) based on the serum albumin level.
 
Serum PTH, Serum Phosphorus
Elevated PTH and calcium with low phosphorus—primary hyperparathyroidism.
 
PTHrP
Elevated in malignancy.363
 
Urine Calcium
Hypocalciuria is <100 mg/d—seen in milk-alkali syndrome, thiazide diuretic use, and familial hypocalciuric hypercalcemia.
Hypercalciuria is >300 mg/d—malignancy or those receiving oral active vitamin D therapy.
 
Chest X-ray
May be helpful in malignancy, sarcoidosis and tuberculosis.
 
ECG
ECG changes include shortened QT interval, AV block, idioventricular rhythm, etc.
 
Treatment
The treatment of hypercalcemia depends on the underlying cause. Mild hypercalcemia usually do not require any treatment. The various treatment options available for the management of hypercalcemia are as follows:
 
Hydration
Hypercalcemia invariably produces dehydration. Hence, volume expansion should be the initial line of management. 4–6 L of IV saline may be required to restore the volume status. Care should be taken when restoring the volume in patients with congestive cardiac failure (CCF) and renal failure.
 
Diuretics
Loop diuretics (Furosemide) are the diuretics of choice. However, they should be given only after dehydration is corrected. Thiazides worsen hypercalcemia and are contraindicated.
 
Bisphosphonates
Although they are safe, effective and normalizes calcium level in more than 70% of cases, they require 48–72 hours before reaching full therapeutic effect. They act by inhibiting the calcium resorption from bone which is the cause of hypercalcemia in malignancy and severe hyperparathyroidism. The commonly used bisphosphonates are:
  • Zoledronic acid (4 mg intravenously over 30 min)
  • Pamidronate (60–90 mg intravenously over 2–4 h)
  • Etidronate (7.5 mg/kg day for 3–7 consecutive days).
 
Steroids
Steroids are the preferred therapy in 1,25 (OH)2 D-mediated hypercalcemia as they reduce the levels of 1,25 (OH)2D. The commonly used steroids are 364IV hydrocortisone (100–300 mg/d) or oral prednisone (40–60 mg daily) for 3–7 days.
Other drugs such as ketoconazole, chloroquine, and hydroxychloroquine may also decrease 1,25 (OH)2D production and are used occasionally.
 
Other Drugs
The other drugs used rarely in the management of hypercalcemia are calcitonin, gallium nitrate, plicamycin, IV phosphate (can cause serious tissue damage) and calcimimetic agent cinacalcet hydrochloride (a new agent that suppresses PTH).
Calcitonin
Calcitonin reduces calcium resorption from bone by inhibiting osteoclasts and increases renal excretion of calcium, sodium, potassium, magnesium, and phosphate. Advantages of calcitonin are its rapid onset, effect within 24 hours, analgesic effect, and low toxicity. It can be used safely in patients with renal failure. Dose is 8 IU per kg every 6 hours for 5 days.
Gallium Nitrate
Gallium nitrate inhibits resorption of bone and causes hypocalcemia. Dose is 200 mg/BSA for 5 days by continuous IV infusion. Adverse effect is renal toxicity and should not be used in patients with hypotension. It should not be coadministered with aminoglycosides within 48 hours before or after treatment with gallium nitrate. Adequate urine output is maintained during therapy. It is given in patients where calcitonin and bisphosphonate therapy have failed.
 
Dialysis
It is rarely required.
 
BIBLIOGRAPHY
  1. Adhikaree J, Newby Y, Sundar S. Denosumab should be the treatment of choice for bisphosphonate refractory hypercalcemia of malignancy. BMJ Case Rep. 2014;2014.
  2. Bastepe M, Juppner H. Pseudohypoparathyroidism and mechanisms of resistance toward multiple hormones: molecular evidence to clinical presentation. J Clin Endocrinol Metab. 2003;88:4055-8.
  3. Bech A, de Boer H. Denosumab for tumor-induced hypercalcemia complicated by renal failure. Ann Intern Med. 2012;156:906.
  4. Binstock ML, Mundy GR. Effect of calcitonin and glucocorticoids in combination on the hypercalemia of malignancy. Ann Intern Med. 1980;93:269-72.
  5. Burkhardt E, Kistler HJ. Hypercalciämie bei hospitalisierten Patienten. Schweiz Med Wschr. 1981;111:2017 -23.
  6. Chernow B, Zaloga G, McFadden E, et al. Hypocalcemia in critically ill patients. Crit Care Med. 1982;10:848.
  7. Cicci JD, Buie L, Bates J, van Deventer H. Denosumab for the management of hypercalcemia of malignancy in patients with multiple myeloma and renal dysfunction. Clin Lymphoma Myeloma Leuk. 2014;14:e207.
  8. Connor TB, Rosen BL, Blaustein MP, et al. Hypocalcemia precipitating congestive heart failure. N Engl J Med. 1982;307(14):869-72.
  9. Connor TB, Rosen BL, Blaustein MP, et al. Hypocalcemia precipitating congestive heart failure. N Engl J Med. 1982;307:869.
  10. 365Davenport A, Goel S, Mackenzie JC. Treatment of hypercalcemia with pamidronate in patients with end stage renal failure. Scand J Urol Nephrol. 1993;27:447.
  11. Dietzek A, Connelly K, Cotugno M, et al. Denosumab in hypercalcemia of malignancy: a case series. J Oncol Pharm Pract. 2015;21:143.
  12. Gennari C. Calcium and vitamin D nutrition and bone disease of the elderly. Public Health Nutrition. 1988;4(2B):547-59.
  13. Halterman JS, Smith SA. Hypocalcemia and stridor: an unusual presentation of vitamin D-deficient rickets, J Emerge Med. 1998;16(1):41-3.
  14. Hasling C, Charles P, Mosekilde L. Etidronate disodium in the management of malignancy-related hypercalcemia. Am J Med. 1987;82(Suppl 2A):51.
  15. Hastbacka J, Pettila V. Prevalence and predictive value of ionized hypocalcemia among critically ill patients. Acta Anaesthesiol Scand. 2003;47:1264-9.
  16. Henrich D, Hoffmann M, Uppenkamp M, Bergner R. Ibandronate for the treatment of hypercalcemia or nephrocalcinosis in patients with multiple myeloma and acute renal failure: Case reports. Acta Haematol. 2006;116:165.
  17. Hu MI, Glezerman IG, Leboulleux S, et al. Denosumab for treatment of hypercalcemia of malignancy. J Clin Endocrinol Metab. 2014;99:3144.
  18. Karuppiah D, Thanabalasingham G, Shine B, et al. Refractory hypercalcaemia secondary to parathyroid carcinoma: response to high-dose denosumab. Eur J Endocrinol. 2014;171:K1.
  19. Lienhardt A, Bai M, Lagarde JP, Rigaud M, Zhang Z, Jiang Y, et al. Activating mutations of the calcium-sensing receptor: management of hypocalcemia. J Clin Endocrinol Metab. 2001;86:5313-23.
  20. Marx SJ. Familial hypocalciuric hypercalcemia. Primer on the metabolic bone disease and disorders of mineral metabolism, In: Favus MJ (Ed). Philadelphia, Lippincott Williams & Wilkins. 1999.pp.195-8.
  21. Marx SJ. Hyperparathyroid and hypoparathyroid disorders. N Engl J Med. 2000;343: 1863-75.
  22. Minambres I, Chico A, Perez A. Severe hypocalcemia due to vitamin D deficiency after extended Roux-en-Y gastric bypass. Journal of Obesity. 2011;2011 (Article ID 141024):3.
  23. Mosekilde L. Vitamin D and the elderly. Clin Endocrin. 2005;62(3):265-81.
  24. Mundy GR, Guise TA. Hypercalcemia of malignancy. Am J Med. 1997;103:134-5.
  25. Noto H, Heller H. Vitamin D deficiency as an ignored cause of hypocalcemia in acute illness: report of 2 cases and review of the literature. The Open Endocrinology Journal. 2009;3:1-4.
  26. Slomp J, van der Voort PH, Gerritsen RT, Berk JA, Bakker AJ. Albumin-adjusted calcium is not suitable for diagnosis of hyper- and hypocalcemia in the critically ill. Crit Care Med. 2003;31:1389-93.
  27. Trimarchi H, Lombi F, Forrester M, et al. Disodium pamidronate for treating severe hypercalcemia in a hemodialysis patient. Nat Clin Pract Nephrol. 2006;2:459.
  28. Warrell RP Jr, Israel R, Frisone M, et al. Gallium nitrate for acute treatment of cancer-related hypercalcemia. Ann Intern Med. 1988;108:669.
  29. Wisneski LA. Salmon calcitonin in the acute management of hypercalcemia. Calcif Tissue Int. 1990;46:S26.
  30. Zivin JR, Gooley T, Zager RA, et al. Hypocalcemia: a pervasive metabolic abnormality in the critically ill. Am J Kidney Dis. 2001;37:689.

PHOSPHORUSCHAPTER 47

TA Naufal Rizwan  
INTRODUCTION
The normal serum level of phosphate is 2.5–4.5 mg/dL. About 85% of total body phosphorus is present in the bone with extracellular fluid (ECF) and intracellular fluid (ICF) concentrations almost the same. Serum phosphate levels vary by as much as 50% on a normal day and hence, the estimation should be ideally done in the basal, fasting state.
 
METABOLISM
The small intestine and the kidneys play a major role in maintaining the phosphate level. The phosphate absorption from the small intestine is increased by 1, 25(OH)2D whereas the absorption is decreased by calcium salts, aluminum hydroxide (present in antacids) and sevelamer hydrochloride.
The proximal tubule is the principal site of renal phosphate reabsorption. Parathyroid hormone (PTH) and FGF23 (new hormone) impairs the phosphate reabsorption. Similarly, the presence of hypocalcemia, hypomagnesemia and volume expansion reduces the reabsorption whereas volume depletion increases it.
 
HYPOPHOSPHATEMIA
Hypophosphatemia can be acute or chronic. Although the causes can be inherited or acquired, the three principal mechanisms that can cause low phosphate levels are increased renal phosphate excretion, diminished intestinal phosphate absorption and redistribution.
 
Increased Renal Phosphate Excretion
 
PTH/PTHrP Dependent
Primary hyperparathyroidism, secondary hyperparathyroidism (Vit D deficiency, calcium starvation), hypercalcemia of malignancy (PTHrP) and familial hypocalciuric hypercalcemia.367
 
PTH/PTHrP Independent
Genetic causes
X-linked hypophosphatemic (XLH) rickets, autosomal dominant hypophosphatemic rickets (ADHR), Dent disease, Fanconi's syndrome, Wilson disease, etc.
Acquired causes
Tumor-induced osteomalacia (TIO), alcoholism, hyperaldosteronism, uncontrolled DM, hypomagnesemia, drugs (acetazolamide, diuretics, cisplatin, calcitonin, steroids, estrogens) and toxins (alcohol, lead).
 
Impaired Intestinal Phosphate Absorption
Aluminum containing antacids and sevalamer.
 
Redistribution of ECF Phosphate into Cells
IV glucose, insulin therapy for diabetic ketoacidosis (DKA) or prolonged hyperglycemia, catecholamines (epinephrine, dopamine), Gram-negative sepsis, respiratory alkalosis, leukemic blast crisis, etc.
 
Accelerated Net Bone Formation
Following parathyroidectomy,treatment of vitamin D deficiency, Pagets disease, etc
 
Clinical Features
Symptoms of hypophosphatemia are nonspecific and highly dependent on cause, duration and severity.
 
Mild Hypophosphatemia (2–2.5 mg/dL)
It is usually asymptomatic although some patients complain of weakness. Chronic hypophosphatemia also tends to be less severe with the predominant complaints being proximal muscle weakness, pseudofractures and bone pain in adults. In children, they manifest as short stature and rickets.
 
Severe Hypophosphatemia (<2 mg/dL)
The clinical features of severe hypophosphatemia are as follows.
  • Neuromuscular: Weakness, lethargy, confusion, hallucinations, disorientation, dysarthria, dysphagia, anisocoria, nystagmus, ataxia, cerebellar tremor, hyperreflexia, sensory deficits, paraesthesia, impaired bladder control, seizures, coma and death.
  • Cardiorespiratory: Cardiac dysfunction, ventricular arrhythmias and respiratory failure.
  • 368Rhabdomyolysis: Occurs as a result of adenosine triphosphate (ATP) depletion and altered membrane integrity. It is more common in acute alcohol withdrawal patient.
  • Hematological (due to ATP depletion): Hemolysis, diminished leukocyte chemotaxis, platelet dysfunction and impaired phagocytosis.
 
Investigations
 
Biochemistry
  • Serum phosphate, magnesium, calcium and potassium level
  • Arterial blood gas analysis, urinalysis, serum uric acid.
 
Radiology
X-ray, bone densitometry, Technetium Tc99 sestamibi scan (in selected cases).
 
Treatment
The various treatment options available for treating hypophosphatemia are:
  • Dietary phosphate
  • Oral phosphate preparations
  • IV phosphate.
 
Mild-to-Moderate Hypophosphatemia
Oral phosphate supplements are useful, especially in the genetic disorders of phosphate wasting and oncogenic osteomalacia. It is given as sodium or potassium phosphorus preparations and the usual dose is 2–3 g/day. The side effects include osmotic diarrhea, volume overload and hyperkalemia.
 
Severe Hypophosphatemia
Presence of severe hypophosphatemia (<2 mg/dL) and neuromuscular and cardiorespiratory manifestations warrants the need of IV phosphate supplementation. Intravenous phosphate is given as sodium or potassium phosphate. The initial dose is 1–3 mmol/h given for 6 hours. If hypocalcemia is present, it has to be corrected first before correcting the phosphate level. IV phosphate should be given cautiously in patients with renal failure or metabolic alkalosis.
 
Other Measures
 
Calcimimetic Drugs (Cinacalcet)
These drugs act by activating the calcium sensing receptor on parathyroid gland cells and thus, reducing the PTH release. The dose of cinacalcet is 30 mg PO qid initially.369
 
Vitamin D Preparations
It acts by increasing the intestinal and renal absorption of phosphate. They are highly useful in hypophosphatemia occurring as a result of secondary hypoparathyroidism (due to vitamin D deficiency). The various formulations available are:
  • Ergocalciferol (vitamin D2) at doses of 10000–80000 U/day
  • Calcitriol (active vitamin D3) at doses 0.25 µg/d PO
  • Paracalcitol—vitamin D analog.
 
Surgery
It is useful in patients with primary hypoparathyroidism and tumor-induced osteomalacia.
 
HYPERPHOSPHATEMIA
Hyperphosphatemia is a condition where the serum phosphate level is greater than 5.5 mg/dL. It is a major cause of secondary hyperparathyroidism, especially in chronic renal insufficiency, as it stimulates the production of parathyroid hormone (PTH). Etiology of hyperphosphatemia is given in Table 47.1.
 
Clinical Features
The signs and symptoms of hyperphosphatemia are due to the following factors.
  • Acute effects of hypocalcemia
  • Deposition of abnormal calcium phosphate complexes in various tissues
  • Hyperphosphatemia-induced resistance to PTH.
 
Neuromuscular
Altered mental status, delirium, seizures, coma, muscle cramps, paraesthesias, Chvostek sign, Trousseau sign, tetany.
Table 47.1   Causes of hyperphosphatemia
The causes can be broadly classified as follows.
• Impaired renal phosphate excretion
- Autoimmune, postsurgical, postradiation
- Vitamin D intoxication, milk-alkali syndrome, sarcoidosis, hypomagnesemia
• Massive ECF phosphate loads
• Excessive intake of phosphate (uncommon cause)
Abbreviation: ECF, extracellular fluid
370
 
Cardiovascular
Hypotension, heart failure, prolonged QT interval, arrhythmias.
 
Metastatic Calcification
  • Vascular calcification (capillaries, small arterioles)
  • Aortic valve calcification
  • Nephrocalcinosis
  • Calciphylaxis (calcific uremic arteriolopathy)—can cause gangrene and ulcers.
 
Investigations
  • Serum phosphate, calcium, potassium, magnesium
  • Blood urea nitrogen (BUN) and serum creatinine
  • ECG changes of hypocalcemia like prolonged QT interval may be present
  • Radiographs may show evidence of metastatic calcification (e.g., basal ganglia).
 
Treatment
The various treatment options available are:
  • Volume expansion—This enhances renal phosphate clearance
  • Hypocalcemia correction (described in detail under hypocalcemia)
  • Oral phosphate binders.
They act by decreasing the gastrointestinal absorption of phosphorus. Binders containing calcium may cause hypercalcemia and similarly, binders containing aluminum are contraindicated in renal failure because of aluminium toxicity.
The commonly used phosphate binders are:
 
Sevelamer Hydrochloride
It does not affect calcium and has been found to decrease the incidence of vascular calcium deposition in patients with renal failure. The dose is 2.4–4.8 g PO divided tid with meals.
 
Lanthanum Carbonate
It is a noncalcium, nonaluminum phosphate binder. It is highly useful in ESRD patients. The dose is 250–500 mg PO tid as chewable tabs.
 
Binders-containing Aluminum
Antacids containing aluminum can also be used as a phosphate binder but it is avoided in renal failure patients because of the risk of developing aluminum toxicity.371
 
Hemodialysis
It is indicated for refractory cases and for patients with renal failure.
 
BIBLIOGRAPHY
  1. Adeney KL, Siscovick DS, Ix JH. Association of serum phosphate with vascular and valvular calcification in moderate CKD. J Am Soc Nephrol. 2009;20:381-7.
  2. Ahmed S, O'Neill KD, Hood AF. Calciphylaxis is associated with hyperphosphatemia and increased osteopontin expression by vascular smooth muscle cells. Am J Kidney Dis. 2001;37:1267-76.
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  6. De Boer IH, Rue TC, Kestenbaum B. Serum phosphorus concentrations in the third National Health and Nutrition Examination Survey (NHANES III). Am J Kidney Dis. 2009;53:399-407.
  7. Dhingra R, Sullivan LM, Fox CS. Relations of serum phosphorus and calcium levels to the incidence of cardiovascular disease in the community. Arch Intern Med. 2007;167:879-85.
  8. DiMeglio LA, White KE, Econs MJ. Disorders of phosphate metabolism. Endocrinol Metab Clin North Am. 2000;29:591-609.
  9. Faroqui S, Levi M, Soleimani M, Amlal H. Estrogen downregulates the proximal tubule type IIa sodium phosphate cotransporter causing phosphate wasting and hypophosphatemia. Kidney Int. 2008;73:1141-50.
  10. Gaasbeek A, Meinders AE. Hypophosphatemia: an update on its etiology and treatment. Am J Med. 2005;118:1094-101.
  11. Knochel JP. The clinical status of hypophosphatemia: an update. N Engl J Med. 1985;313:447-9.
  12. Knochel JP. The pathophysiology and clinical characteristics of severe hypophosphatemia. Arch Intern Med. 1977;137:203-20.
  13. Krajisnik T, Olauson H, Mirza MA. Parathyroid Klotho and FGF-receptor 1 expression decline with renal function in hyperparathyroid patients with chronic kidney disease and kidney transplant recipients. Kidney Int. 2010;78:1024-32.
  14. Moe SM. Disorders involving calcium, phosphorus, and magnesium. Prim Care. 2008; 35:215-37:v–vi.
  15. Murer H, Hernando N, Forster I, Biber J. Proximal tubular phosphate reabsorption: molecular mechanisms. Physiol Rev. 2000;80:1373-409.
  16. Roman-Garcia P, Carrillo-Lopez N, Cannata-Andia JB. Pathogenesis of bone and mineral related disorders in chronic kidney disease: Key role of hyperphosphatemia. J Ren Care. 2009;35(Suppl 1):34-8.
  17. Shimizu Y, Tada Y, Yamauchi M. Hypophosphatemia induced by intravenous administration of saccharated ferric oxide: another form of FGF23-related hypophosphatemia. Bone. 2009;45:814-6.
  18. Takeda E, Taketani Y, Sawada N. The regulation and function of phosphate in the human body. Biofactors. 2004;21:345-55.
  19. Tenenhouse H. Phosphate transport: molecular basis, regulation and pathophysiology. J Steroid Biochem Mol Biol. 2007;103:572-7.
  20. Wolf M. Fibroblast growth factor 23 and the future of phosphorus management. Curr Opin Nephrol Hypertens. 2009;18:463-8.

MAGNESIUMCHAPTER 48

TA Naufal Rizwan  
HYPOMAGNESEMIA
Magnesium is an important divalent cation. It plays a major role in cellular function, replication and energy metabolism by acting as a cofactor in various enzymes, nucleic acids and transporters. Around 50% of the total body magnesium is in the bones. Among the extraskeletal magnesium, only 1% is confined to the extracellular fluid (ECF) whereas the remaining 99% extraskeletal magnesium is present within the cells (Table 48.1).
The normal level of magnesium is 1.7–2.4 mg/dL (1.5–2 mEq/L). Intestinal absorption of magnesium is stimulated by 1,25(OH)2 and regulation of serum magnesium concentration is achieved mainly through renal reabsorption (predominantly in cTAL).
 
Clinical Features
The clinical features of hypomagnesemia are predominantly neuromuscular and cardiovascular. Severity of symptoms, at times, may not correlate with the serum magnesium level.
Table 48.1   Causes of hypomagnesemia
Extrarenal causes
Renal causes
  • Impaired intestinal absorption: Malabsorption syndromes, proton pumpinhibition (PPI) drugs, vit D deficiency, TRPM6 mutations (Hypomagnesemia with secondary hypocalcemia seen)
  • Increased intestinal losses: Vomiting, diarrhea, fistulas, intestinal drainage
  • Cutaneous losses: Intense exertion, burns
  • Redistribution
    • To bone: Postparathyroidectomy, Osteoblastic metastases, treatment of vit D deficiency
    • Intracellular: Recovery from DKA, correction of respiratory acidosis
  • Genetic causes: Magnesium wasting syndromes, Barter's syndrome, Gitelman's syndrome
  • Acquired causes: ATN, tubulointerstitial disease, renal transplantation
  • Drugs: Diuretics, cisplatin, aminoglycosides, amphotericin B, cyclosporine
  • Others: SIADH, DM, hypercalcemia, hyperaldosteronism, hyperthyroidism
373
 
Neuromuscular
Symptoms and signs of neuromuscular irritability such as tremors, muscle twitching, muscle weakness, vertigo, frank tetany, Trousseau's and Chvostek's signs are seen in hypomagnesemic patients. Seizures (sometimes triggered by loud noises) and vertical nystagmus are also present. Depression, psychosis and irritability are some of the psychiatric manifestations of this disorder.
 
Cardiovascular
Patients with hypomagnesemia are more prone to develop cardiac arrhythmias such as supraventricular tachycardias and ventricular arrhythmias (like monomorphic VT, torsades de pointes, VF, etc). ECG abnormalities of hypomagnesemia are prolonged PR or QT intervals, ST straightening and T-inversion.
 
Electrolyte Homeostasis
Hypokalemia and hypocalcemia are commonly associated with hypomagnesemia
 
Skeletal System
Increased osteoclastic activity coupled with decreased osteoblastic activity results in increased skeletal fragility and impaired skeletal growth.
 
Treatment
 
Mild Cases
In mild and asymptomatic cases, oral salts are preferred. The various oral formulations available are Magnesium chloride, hydroxide, oxide, etc. They are usually given at 40–60 meq/d in divided doses. Large doses can produce diarrhea.
 
Severe Cases
In severe cases, intravenous route is the preferred route of administration for magnesium. Both MgCl2 and MgSO4 can be given. However, the sulfate ions in MgSO4 can bind with calcium, thereby worsening hypocalcemia. The usual dose is 100 mEq/d given as a continuous infusion (1g contains 8 mEq). The dose should be reduced to 75% in case of reduced GFR. Intracellular Mg store takes longer time to replenish, so magnesium administration should continue for 1–2 days even after the serum Mg level is normalized. Intramuscular route should be avoided.
Serum magnesium should be monitored at 12–24 hours intervals as excessive administration of magnesium can result in hypermagnesemia, which is detected by facial flushing, loss of deep tendon reflexes, hypotension and atrioventricular block. In patients with inappropriate renal magnesium wasting, potassium sparing diuretics such as amiloride and triamterene should be given. They act by blocking the distal tubule epithelial sodium channel.374
 
HYPERMAGNESEMIA
Hypermagnesemia is a condition where the serum magnesium level is greater than 2.5 mg/dL. It is a rare electrolyte abnormality as the kidneys are highly effective in excreting excess magnesium. Intestinal pathology like paralytic ileus, obstruction and perforation can cause prolonged retention of even normal amount of Mg containing cathartics resulting in hypermagnesemia.
 
Clinical Features
The most prominent clinical features are vasodilation and neuromuscular blockade. The signs and symptoms vary according to the level of serum magnesium. Platelet clumping and delayed thrombin formation are seen at higher levels of serum magnesium (Tables 48.2 and 48.3).
 
Investigations
  • Serum magnesium, potassium and calcium
  • Serum BUN and creatinine
  • Serum CPK and urine myoglobin if rhabdomyolysis is suspected
  • ABG, thyroid function test
  • ECG—Intraventricular conduction delay, PR, QRS and QT-prolongation.
 
Treatment
The various treatment options available are:
Table 48.2   Causes of hypermagnesemia
  • Impaired magnesium excretion: Renal failure, familial hypocalciuric hypercalcaemia
  • Excessive intake: Mg-containing vitamins, cathartics, antacids and IV Mg infusions
  • Endocrine causes: Adrenal insufficiency, hypothyroidism
  • Rapid mobilization from soft tissues: Trauma, burns, shock, sepsis
Table 48.3   Clinical manifestations of hypermagnesemia based on serum magnesium level
Serum magnesium
Clinical features
2.5–4 mg/dL
Nausea, vomiting, skin flushing, weakness, sedation
4–5.5 mg/dL
Disappearance of deep tendon reflexes and increase in PR and QRS duration
5.5–7.5 mg/dL
Hypotension, vasodilation and respiratory depression
7.5–10 mg/dL
Arrhythmias and intraventricular conduction block
Greater than 10 mg/dL
Asystole, heart block, respiratory failure, coma
375
 
Hydration and Diuretics
Vigorous IV hydration should be done using Ringer lactate or normal saline. Careful monitoring of the cardiovascular function is a must. Following hydration, loop diuretics (such as furosemide) should be given to increase the excretion of magnesium.
 
Calcium
IV calcium gluconate, given at a dose of 100–200 mg over 1–2 hours, offers temporary benefit by antagonizing the neuromuscular and cardiovascular toxicity of hypermagnesemia.
 
Hemodialysis
It is the treatment of choice in patients with severe hypermagnesemia and in patients with renal failure.
 
BIBLIOGRAPHY
  1. Ali A, Walentik C, Mantych GJ, et al. Iatrogenic acute hypermagnesemia after total parenteral nutrition infusion mimicking septic shock syndrome: two case reports.Pediatrics. 2003;112:e70-e2.
  2. Bairaktari E, Kalaitzidis R. Hypomagnesemia in alcoholic patients. Alcohol Clin Exp Res. 1998;22:134.
  3. Birrer RB, Shallash AJ, Totten V. Hypermagnesemia-induced fatality following epsom salt gargles, Journal of Emergency Medicine. 2002;22(2):185-8.
  4. Cao Z, Bideau R, Valdes RJ, et al. Acute hypermagnesemia and respiratory arrest following infusion of MgSO4 for tocolysis. Clin Chim Acta. 1999;285:191-3.
  5. Chernow B, Bamberger S, Stoiko M, et al. Hypomagnesemia in patients in postoperative intensive care. Chest. 1989;95:391-7.
  6. Cohen L, Laor. A correlation between bone magnesium concentration and magnesium retention in the intravenous magnesium load test. Magnes Res. 1990;3:271-4.
  7. Dai LJ, Quamme GA. Intracellular Mg2+ and magnesium depletion in isolated renal thick ascending limb cells, Journal of Clinical Investigation. 1991;88(4):1255-64.
  8. Deheinzelin D, Negri EM, Tucci MR, et al. Hypomagnesemia in critically ill cancer patients: A prospective study of predictive factors. Braz J Med Biol Res. 2000;33:1443-8.
  9. Escuela MP, Guerra M, Anon JM, et al. Total and ionized serum magnesium in critically ill patients. Intensive Care Med. 2005;31:151-6.
  10. Huey CG, Chan KM, Wong ET, et al. Los Angeles County-University of Southern California Medical Center clinical pathology case conference: extreme hypermagnesemia in a neonate. Clin Chem. 1995;41:615-8.
  11. Jhang WK, Lee YJ, Kim AY, Park JS, Park SY. Severe hypermagnesemia presenting with abnormal electrocardiographic findings similar to those of hyperkalemia in a child undergoing peritoneal dialysis, Korean Journal of Pediatrics. 2013;56(7):308-11.
  12. Kroll MH, Elin RJ. Relationships between magnesium and protein concentrations in serum. Clin Chem. 1985;31:244-6.
  13. Lote CJ, Thewles A, Wood JA, et al. The hypomagnesemic action of FK506: urinary excretion of magnesium and calcium and the role of parathyroid hormone. Clin Sci (Lond). 2000;99:285-92.
  14. 376Mathers TW, Beckstrand RL. Oral magnesium supplementation in adults with coronary heart disease or coronary heart disease risk. J Am Acad Nurse Pract. 2009; 21:651-7.
  15. Quamme GA. Renal magnesium handling: new insights in understanding old problems. Kidney Int. 1997;52:1180-95.
  16. Ryzen E, Wagers PW, Singer FR, Rude RK. Magnesium deficiency in a medical ICU population. Crit Care Med. 1985;13:19-21.
  17. Schelling JR. Fatal hypermagnesemia. Clin Nephrol. 2000;53:61.
  18. Spiegel DM. Magnesium in chronic kidney disease: unanswered questions. Blood Purif. 2011;31:172-6.
  19. Walser M. Ion association VI. Interactions between calcium, magnesium, inorganic phosphate, citrate and protein in normal human plasma. J Clin Invest, 1961;40:723-30.
  20. Wong ET, Rude RK, Singer FR, Shaw ST Jr. A high prevalence of hypomagnesemia and hypermagnesemia in hospitalized patients. Am J Clin Pathol. 1983;79:348-52.
377Gastrointestinal Diseases in ICU
Chapter 49 Upper Gastrointestinal Bleeding TA Naufal Rizwan
Chapter 50 Lower Gastrointestinal Bleeding TA Naufal Rizwan
Chapter 51 Acute Pancreatitis TA Naufal Rizwan
Chapter 52 Acute Liver Failure TA Naufal Rizwan
Chapter 53 Abdominal Infections in ICU TA Naufal Rizwan378

UPPER GASTROINTESTINAL BLEEDINGCHAPTER 49

TA Naufal Rizwan
Acute gastrointestinal bleeding is a common problem necessitating admission in ICU. Due to advent of noninvasive methods of treatment, the mortality has reduced. Upper gastrointestinal bleeding usually presents as hematemesis or melena. Vomiting of blood is known as hematemesis. It may be either bright red or brown coffee grounds material. Passage of black tarry stools is called melena, which can develop with as little as 50 mL blood loss. Rarely, if the upper gastro-intestinal bleeding is severe, it can also manifest as hematochezia (Table 49.1).
 
PEPTIC ULCER
This is the most common cause for UGI bleed, accounting for nearly 50% of all cases. However, the incidence has declined in the recent past, possibly due to the better management of H. pylori infection and prophylaxis with proton pump inhibitors in high-risk patients.
 
VARICEAL BLEED
This accounts for 10–20% of all UGI bleed. Esophageal varices are more common than the gastric or duodenal varices.
Table 49.1   Causes of upper GI bleeding
  • Esophagogastric (Mallory-Weiss) mucosal tear
  • Esophageal rupture (Boerhaave's syndrome)
  • Inflammation and erosions (esophagitis, gastritis, duodenitis)
  • Varices of esophagus, stomach or duodenum
  • Neoplasm (carcinoma, lymphoma, leiomyoma, leiomyosarcoma, polyps)
  • Hemobilia
  • Vascular-enteric fistula (usually from aortic aneurysm or graft)
  • Vascular anomalies
380
 
MALLORY-WEISS TEAR
It is a nontransmural tear at the gastroesophageal junction, occuring as a result of vomiting, retching or vigorous coughing. It is commonly associated with heavy alcohol use. About 5% of UGI bleeding is due to Mallory-Weiss tear.
 
BOERHAAVE'S SYNDROME
Spontaneous rupture at the gastroesophageal junction as a result of forceful vomiting or retching is called as Boerhaave syndrome.
 
VASCULAR ANOMALIES
  • Angioectasias (angiodysplasias): These are aberrant submucosal vessels, which are 1–10 mm in size caused by chronic obstruction of submucosal veins.
  • Telangiectasias: These are small, cherry red lesions caused by dilation of venules. They are also seen in CREST syndrome.
  • Dieulafoy lesion: This is an aberrant, large submucosal artery situated mostly in the proximal stomach.
Risk factors associated with mortality in upper GI bleeding:
  • Age >60 years
  • Shock on admission
  • Incidence of rebleeding in 3 days
  • Failure to clear red nasogastric aspirate.
 
MANAGEMENT
Because patients vary in the severity of bleeding, the orderly sequence of history taking, physical examination, diagnostic evaluation, and treatment may have to be altered to meet the immediate demands.
 
History
  • Ingestion of gastric mucosal irritants: The recent ingestion of aspirin, other nonsteroidal anti-inflammatory drugs, or alcohol raises the possibility that erosive gastritis or other mucosal injury has developed. Aspirin not only causes direct mucosal injury, but also interferes with platelet adhesion and worsens the prognosis of acutely bleeding patients.
  • Associated medical conditions: The number of associated medical conditions directly increases the risk of mortality in acute gastrointestinal bleeding. Mortality in patients with no accompanying medical conditions is about 1%, whereas the risk of dying in patients with four or more associated illnesses is more than 70%.381
 
Hemodynamic Assessment
Coolness of the extremities and pallor of the conjunctivae, mucous membranes, and nail beds may be evident as a result of blood loss and peripheral vasoconstriction. The presence of postural signs (when the patient sits up from a supine position, the pulse rate increases more than 20 beats per minute and the systolic blood pressure drops more than 10 mm Hg) indicate that blood loss has exceeded 1 L.
  • SBP <100 mm Hg and HR >100–Severe acute blood loss
  • SBP >100 mm Hg and HR >100–Moderate acute blood loss
  • SBP >100 mm Hg and HR <100–Minor blood loss
 
Fluid, Electrolyte, and Blood Replacement
  • Large-bore intravenous catheter should be inserted promptly into a peripheral vein. Blood can be drawn at this time for laboratory studies. If the bleeding is profuse, two or more intravenous catheters may be required. In case a peripheral vein is not available, venous access should be established via a jugular, subclavian, or femoral vein.
  • Infusion of fluids: Normal saline is infused rapidly until blood for transfusion is available. If the patient is bleeding profusely and blood for transfusion is not yet available, saline should be infused even if the patient has ascites and edema. If bleeding is less severe, hypotonic sodium solutions may be infused until blood for transfusion arrives.
 
Blood Replacement
  • Packed cells should be transfused to maintain Hb > 7 g/dL. One unit of FFP should be given for each 5 units of packed RBC transfused. Platelets should be transfused if platelet count is <50000/mm3. In uremic patients with active bleeding, desmopressin (DDAVP) may be given (3 doses, 0.3 µ/kg IV, twice daily).
  • A central venous pressure catheter or Swan-Ganz catheter may be necessary to evaluate the effects of volume replacement and the need for continued infusion of blood, particularly in elderly patients or patients with cardiovascular disease. Urine output should be monitored to know about the perfusion of vital organs.
 
Nasogastric Intubation and Gastric Lavage
A nasogastric (NG) tube should be passed in all patients with acute gastrointestinal bleeding unless the source is obviously the lower gastrointestinal tract. If the aspirate is clear, NG tube can be removed.
 
Benefits of NG Intubation
It helps to document the presence of blood and to monitor the rate of bleeding. It can also be used for gastric lavage and to decompress the stomach, thus facilitating hemostasis.382
 
Disadvantages of NG Intubation
In addition to causing discomfort to the patient, it also causes irritation of the esophageal and gastric mucosae, creating mucosal artifacts and aggravating existing lesions. NG intubation also predisposes to gastroesophageal reflux and pulmonary aspiration.
 
PHARMACOLOGIC THERAPY
  • Proton pump inhibitors
If high, IV PPI—Pantoprazole or esomeprazole 80 mg IV bolus followed by 8 mg/h continuous infusion for 72 hours—Rebleeding risk.
If low, oral PPI—esomeprazole or pantoprazole 40 mg OD or bid
  • Octreotide: It is indicated in UGI bleed, related to liver disease or portal hypertension. The usual dose is 100 µg IV bolus followed by 50–100 µ/hour continuous infusion. Terlipressin may also be used instead of octreotide.
  • Nonselective beta-blockers: Beta-blockers are indicated to reduce the risk of variceal rebleeding.
    • Propranolol: Starting dose 20 mg BID—maintenance dose 40 mg BID
    • Nadolol: Starting dose 40 mg OD—maintenance dose 80 mg OD.
 
ENDOSCOPY
Once the hemostasis is achieved, endoscopy should be done to identify the source of bleeding and to know the risk of rebleeding. It can also be used to render endoscopic therapy.
The choice of various treatment options available in endoscopy are:
  • Thermocoagulation
  • Laser photocoagulation
  • Banding
  • Sclerotherapy
  • Endoclip application
  • Endoscopic injection of epinephrine (1:10000).
 
SPECIFIC CONDITIONS
 
Endoscopic Therapy for Peptic Ulcer
 
Indication
The ulcer with a nonbleeding visible vessel as it has got a 50% chance of rebleeding or continued bleeding.
Endoscopic treatment options available are:
  • Endoscopic therapy with thermocoagulation (bipolar or heater probes)
  • Endoscopic clips
  • Endoscopic injection of epinephrine383
 
Endoscopic Therapy for Varices
  • Endoscopic banding: This is the endoscopic treatment of choice for variceal bleed. The advantages of this procedure are less complications and less rebleeding compared to sclerotherapy.
However, repeat sessions are required at every 2–4 weeks intervals until the varices are obliterated or reduced to small sizes.
  • Sclerotherapy: Sclerotherapy is a procedure in which sclerosants (ethanolamine, tetradecyl sulfate) are injected into the variceal trunks. It is indicated in whom the visualization for banding is difficult. The complications of sclerotherapy are esophageal ulceration, stricture and perforation.
 
Nonendoscopic Treatment Options for Varices
Apart from endoscopy, the various other treatment options available for varices are:
  • Balloon tube tamponade
  • Transvenous intrahepatic portosystemic shunts
  • Surgical portosystemic shunts.
 
Balloon Tube Tamponade (Sengstaken-Blakemore or Minnesota Tube)
The triple-lumen Sengstaken-Blakemore (SB) tube is representative of several tubes that can compress gastroesophageal varices by balloon tamponade. One lumen is used to evacuate the stomach. The second and third lumens lead to the gastric and esophageal balloons, respectively.
Indications: Balloon tamponade is indicated only in variceal bleeding that is not controlled by pharmacological or endoscopic measures. It should be used only as a temporary procedure.
Complications
  • Esophageal ulceration,
  • Aspiration
  • Airway obstruction.
 
Transvenous Intrahepatic Portosystemic Shunts (TIPSS)
It is a procedure in which an expandible wire mesh stent is passed into the liver parenchyma through a catheter inserted in the jugular vein, thus creating a portosystemic shunt between hepatic vein and portal vein.
Indications
  • Bleeding from gastric varices and portal hypertensive gastropathy (Banding cannot be done for gastric varices)
  • Recurrent esophageal variceal bleed, not responding to endoscopic techniques.
Complications
Stent thrombosis } Hence, periodic monitoring with Doppler
stent stenosis } ultrasonography or hepatic venography is required.
384
 
Surgical Portosystemic Shunts
With the advent of TIPSS, surgical portosystemic shunts are rarely performed.
 
BIBLIOGRAPHY
  1. Al-Dhahab H, Barkun A. The acute management of nonvariceal upper gastrointestinal bleeding. Ulcers Vol. 2012, Article ID 361425.
  2. Avunduk, Canan. Manual of Gastroenterology: Diagnosis and Therapy, 4th edn.
  3. Baradarian R, Ramdhaney S, Chapalamadugu R, et al. Early intensive resuscitation of patients with upper gastrointestinal bleeding decreases mortality. Am J Gastroenterol. 2004;99:619.
  4. Branicki FJ, Boey J, Fok PJ, et al. Bleeding duodenal ulcer: a prospective evaluation of risk factors for rebleeding and death. Ann Surg. 1989;211:411.
  5. Huang ES, Karsan S, Kanwal F, et al. Impact of nasogastric lavage on outcomes in acute GI bleeding. Gastrointest Endosc. 2011;74:971.
  6. Hwang JH, Fisher DA, Ben-Menachem T, et al. The role of endoscopy in the management of acute non-variceal upper GI bleeding. Gastrointest Endosc. 2012; 75:1132.
  7. Laine L, Jensen DM. Management of patients with ulcer bleeding. Am J Gastroenterol. 2012;107:345.
  8. Leontiadis G, Barkun A. Commentary: what is the optimal PPI dosing following endoscopic haemostasis in acute ulcer bleeding? Alimentary Pharmacology & Therapeutics. 2012;35(11):1351-2.
  9. Leontiadis GI, Howden CW. The role of proton pump inhibitors in the management of upper gastrointestinal bleeding. Gastroenterol Clin North Am. 2009;38:199-213.
  10. Leontiadis GI, Sharma VK, Howden CW. Proton pump inhibitor treatment for acute peptic ulcer bleeding. Cochrane Database of Systematic Reviews, no. 1, p. CD002094, 2006.
  11. Longo DL, Fauci AS, Kasper DL, et al. Principles of Internal Medicine, 18th edn.
  12. Papadakis MA, McPhee SJ, Rabow MW. Current Medical Diagnosis & Treatment 2015, 54th edn.
  13. Ramsoekh D, van Leerdam ME, Rauws EA, et al. Outcome of peptic ulcer bleeding, nonsteroidal anti-inflammatory drug use, and Helicobacter pylori infection. Clin Gastroenterol Hepatol. 2005;3:859-64.
  14. Sung JJ, Barkun A, Kuipers EJ. Peptic Ulcer Bleed Study Group. Intravenous esomeprazole for prevention of recurrent peptic ulcer bleeding: a randomized trial. Ann Intern Med. 2009;150:455-64.
  15. Upper GI bleeding–associated mortality: Challenges to improving a resistant outcome. Am J Gastroenterol. 2010;105:90-2.
  16. Vergara M, Calvet X, Gisbert JP. Epinephrine injection versus epinephrine injection and a second endoscopic method in high-risk bleeding ulcers. Cochrane Database Syst Rev. 2007;18:CD005584.

LOWER GASTROINTESTINAL BLEEDINGCHAPTER 50

TA Naufal Rizwan
Bleeding that arises from a source below the ligament of Treitz is known as lower gastrointestinal bleed. In about 95% of cases, it is from the small intestine or the colon. Spontaneous cessation of bleeding occurs in more than 2/3rd of patients.
 
ETIOLOGY
  • Hemorrhoids
  • Anal fissure
  • Inflammatory bowel disease (proctitis or colitis)
  • Neoplasm (carcinoma or polyps)
  • Diverticulosis
  • Ischemic enteritis or colitis
  • Angiodysplasia
  • Antibiotic-associated colitis
  • Radiation colitis
  • Amyloidosis
  • Meckel's diverticulum
  • Vascular-enteric fistula
 
Diverticulosis
It is the most common cause for lower gastrointestinal bleed, accounting for nearly one half of all the cases. The risk is increased in patients using NSAIDs. However, bleeding stops spontaneously in about 80% of cases.
 
Anorectal Disease
The common anorectal diseases producing lower gastrointestinal bleed are fissure in ano, hemorrhoids and rectal ulcers. It usually presents as small amounts of bright red blood seen in the toilet bowl.
 
Angioectasias
They are flat, red lesions (2–10 mm) with ectatic peripheral vessels radiating from a central vessel. They are commonly seen in patients over 70 years of age and usually manifest as painless bleeding melena or hematochezia.386
 
Neoplasms
Both benign polyps and carcinomas present as lower GI bleed in the form of hematochezia or occult blood.
 
Inflammatory Bowel Disease
In addition to hematochezia or occult blood loss, patients with inflammatory bowel disease also present with diarrhea, constipation and abdominal pain.
 
INVESTIGATIONS
The most important thing in a lower GI bleed is to rule out the upper GI source of bleeding. If the aspirate from the nasogastric tube has coffee ground appearance, it indicates UGI bleed. The other specific investigations available are:
 
Anoscopy and Sigmoidoscopy
If the bleeding is not severe, anoscopy and sigmoidoscopy should be performed initially to rule out anorectal diseases, inflammatory bowel diseases, etc.
 
Colonoscopy
In case of large volume bleeding, colonoscopy becomes the preferred investigation. Before doing the colonoscopy, bowel should always be purged to remove the blood clots.
 
Nuclear Scintigraphy (Technetium-labeled Red Blood Cell)
The advantages of doing a radionuclide scan are to localize the source of bleeding and to know if angiography is required or not.
 
Arteriography
Angiograms are usually done only when the Technetium scans are positive for active, significant bleeding. However, when the bleeding is very severe causing hemodynamic compromise, it should be performed without attempt at colonoscopy or scintigraphy.
 
Push Enteroscopy and Capsule Endoscopy
These help in localizing the small intestinal source of bleeding.
 
TREATMENT
 
Hemodynamic Assessment
Hemodynamic assessment is the first step in the management of lower gastrointestinal bleed. Coolness of the extremities and pallor of the conjunctivae, 387mucous membranes and nail beds may be evident as a result of blood loss and peripheral vasoconstriction.
  • Systolic BP (SBP) <100 mm Hg and HR (Heart rate) >100–severe acute blood loss
  • SBP >100 mm Hg and HR >100–moderate acute blood loss
  • SBP >100 mm Hg and HR <100–minor blood loss.
 
Volume Resuscitation
Large-bore intravenous catheter should be inserted promptly into a peripheral vein. Blood loss should be adequately managed by infusion of fluids and blood replacement. Urine output should be monitored to know about the perfusion of vital organs.
 
SPECIFIC MEASURES
The treatment options available are:
  • Colonoscopy
  • Intra-arterial embolization
  • Surgical treatment.
 
Colonoscopy
Various modalities of treatment that can be done with the help of colonoscopy are:
  • Epinephrine injection
  • Cautery (bipolar or heater probe)
  • Application of endoclips or bands
 
Intra-arterial Embolization
It is a procedure in which an autologous clot or small pieces of gelatin sponge are injected into the artery, thereby occluding the bleeding vessel and achieving hemostasis. However, this can be done only if the bleeding vessel is identified. Complications like ischemic colitis occur in a minority of patients.
 
Surgical Treatment
With the advent of colonoscopic and angiographic procedures, the need for surgical treatment has greatly come down. However, if the bleeding is severe (requiring more than 6 units of blood in 24 hours) as in the case of diverticulosis and angiodysplasia, surgery is indicated.
 
BIBLIOGRAPHY
  1. Arroja B, Cremers I, Ramos R, Cardoso C, Rego AC, Caldeira A, et al. Acute lower gastrointestinal bleeding management in Portugal: a multicentric prospective 1-year survey. Eur J Gastroenterol Hepatol. 2011;23:317-22.
  2. Avunduk, Canan. Manual of Gastroenterology: Diagnosis and Therapy, 4th edn. Lippincott William & Wilkin; 2008.
  3. 388Brackman MR, Gushchin VV, Smith L, Demory M, Kirkpatrick JR, Stahl T. Acute lower gastroenteric bleeding retrospective analysis (the ALGEBRA study): an analysis of the triage, management and outcomes of patients with acute lower gastrointestinal bleeding. Am Surg. 2003;69:145-9.
  4. Chaudhry V, Hyser MJ, Gracias VH, Gau FC. Colonoscopy: the initial test for acute lower gastrointestinal bleeding. Am J Surg. 1998;64:723-8.
  5. Dutta G, Panda M. Case Report: An uncommon cause of lower gastrointestinal bleeding: a case report. Cases Journal. 2008;1:235.
  6. D'Othée BJ, Surapaneni P, Rabkin D, Nasser I, Clouse M. Microcoil embolization for acute lower gastrointestinal bleeding. Cardiovasc Intervent Radiol. 2006;29(1):49-58.
  7. Gayer C, Chino A, Lucas C, Tokioka S, Yamasaki T, Edelman DA, et al. Acute lower gastrointestinal bleeding in 1112 patients admitted to an urban emergency medical center. Surgery. 2009;146:600-6 discussion 606-7.
  8. Green BT, Rockey DC, Portwood G, Tarnasky PR, Guarisco S, Branch MS, et al. Urgent colonoscopy for evaluation and management of acute lower gastrointestinal hemorrhage: a randomized controlled trial. Am J Gastroenterol. 2005;100:2395-402.
  9. Hreinsson, Gumundsson JP, Kalaitzakis S, Björnsson E, Einar S. Lower gastrointestinal bleeding: incidence, etiology, and outcomes in a population-based setting. European Journal of Gastroenterology & Hepatology. 2013;25(1):37-43.
  10. Koh DC, Luchtefeld MA, Kim DG, et al. Efficacy of transarterial embolization as definitive treatment in lower gastrointestinal bleeding. Colorectal Dis. 2009;11(1):53-9.
  11. Lanas A, et al. Time trends and impact of upper and lower gastrointestinal bleeding and perforation in clinical practice. Am J Gastroenterol. 2009;104:1633-41.
  12. Longo DL, Fauci AS, Kasper DL, et al. Harrison's Principles of Internal Medicine, 18 ed. McGraw-Hill; 2012.
  13. Makela JT, Kiviniemi H, Laitinen S, Kairaluoma MI. Diagnosis and treatment of acute lower gastrointestinal bleeding. Scand J Gastroenterol. 1993;28:1062-6.
  14. Navuluri R, Kang L, Patel J, Ha T. Acute lower gastrointestinal bleeding; Semin Intervent Radiol. 2012;29(3):178-86.
  15. Papadakis MA, McPhee SJ, Rabow MW. Current medical diagnosis & treatment, 54th edn., 2015.

ACUTE PANCREATITISCHAPTER 51

TA Naufal Rizwan  
GENERAL CONSIDERATIONS
Acute inflammation of the pancreas is known as acute pancreatitis. Gall-stones and alcohol account for the majority of the cases. It can range from a mild, self-limiting disorder to a more serious necrotic pancreatitis.
 
ETIOLOGY
It is given in Table 51.1.
Table 51.1   Causes of acute pancreatitis
Common causes:
  • Gallstones
  • Alcohol
  • Hypertriglyceridemia
  • ERCP
  • Postoperative
  • Trauma
Uncommon causes:
  • Vasculitis, connective tissue disorders
  • Infections (Mumps, coxsackie virus, CMV)
  • Pancreas divisum, cystic fibrosis, renal failure
  • Pancreatic cancer, hypercalcemia
Drugs:
  • Azathioprine
  • Sulfonamides
  • Estrogens
  • Valproic acid
  • Tetracyclines, pentamidine, thiazides, furosemide
 
PATHOGENESIS
The pathogenesis largely remains unclear. The postulated mechanisms are:
  • Autodigestion: Toxins, infections, increased intracellular calcium lead onto the activation of the pancreatic proteases that, in turn, results in the digestion of pancreatic and peripancreatic tissues.
  • 390Pancreatic ductular hypertension due to the obstruction of the pancreatic drainage at the level of ampulla.
 
CLINICAL FEATURES
Abdominal pain is the most common presenting symptom. It can be mild or severe, mostly located in the epigastrium and periumbilical region with occasional radiation to the back and chest. The pain is characteristically reduced when the patient sits with the trunk flexed and knees drawn up. Nausea, vomiting and abdominal distension may also be present. Low-grade fever, hypotension and tachycardia are seen in more severe disease. Jaundice is seen if the underlying etiology is a gallstone.
Abdominal examination may reveal epigastric tenderness, guarding, and reduced bowel sounds. The signs of severe necrotizing pancreatitis are Grey Turners sign (blue-red-purple or green-brown discoloration of the flanks due to tissue metabolism of hemoglobin) and Cullen's sign (Faint blue discoloration around the umbilicus due to hemoperitoneum).
 
INVESTIGATIONS
 
Elevated Serum Amylase and Lipase
More than threefold elevation of serum amylase and lipase is almost diagnostic of acute pancreatitis, if the other causes are ruled out. There is no correlation between the severity of pancreatitis and the degree of elevation of these enzymes. Serum amylase returns to baseline values in 3–5 days whereas lipase may remain elevated even up to 2 weeks (Table 51.2).
Table 51.2   Markers of severity of acute pancreatitis
Markers of severity within 24 hours
  • SIRS
  • Hemoconcentration (Hct>44%)
  • BISAP
    (B) Blood urea nitrogen >22 mg%
    (I) Impaired mental status
    (S) SIRS
    (A) Age >60 years
    (P) Pleural effusion
  • Organ failure
    • Cardiovascular: BP <90 mm Hg, Heart rate >130
    • Pulmonary: PAO2 <60 mm Hg
    • Serum Creatinine >2.0 mgs%
Markers of severity during hospitalization
  • Persistent organ failure
  • Pancreatic necrosis
  • Hospital-acquired infection
391
 
Nonpancreatic Causes for Increased Serum Amylase
  •   Upper gastrointestinal perforation
  •   Biliary peritonitis
  •   Intestinal infarction
  •   Macroamylasemia.
 
Other Blood Investigations
  •   Leukocytosis
  •   Hematocrit >44% (hemoconcentration)
  •   BUN >22 mg/dL (loss of plasma into peritoneal cavity)
  •   Hyperglycemia (↓ insulin and ↑ glucagon, glucocorticoids)
  •   Hypocalcemia (saponification of calcium by fatty acids in fat necrosis areas)
  •   Hyperbilirubinemia, increased SGOT, SGPT, ALP—seen in 10% patients
  •   Hypertriglyceridemia—seen in 5–10% patients
  •   Elevated serum LDH (>500 U/dL)—carries a poor prognosis
  •   Hypoxemia (PO2 <60 mm Hg)—may herald the onset of ARDS.
 
RADIOLOGY
  •   Chest X-ray—to rule out gastrointestinal perforation
  •   X-ray abdomen—may show gall stones and pancreatic calcification
  •   USG Abdomen—helps in detection of gallstones and demonstration of pancreatic swelling and necrosis.
  •   CT abdomen—helps in assessing the severity of acute pancreatitis and evaluating the complications (Table 51.3).
Table 51.3   CT severity index
Grade
Findings
Score
A
Normal pancreas
0
B
  • Enlarged pancreas with irregular contour
  • No peripancreatic inflammation
1
C
Peripancreatic inflammation present
2
D
Intrapancreatic or extrapancreatic fluid collections
3
E
Two or more collections or gas in pancreas
4
Necrosis %
Score
0
0
<33%
2
33–50%
4
>50%
6
CT severity index equals unenhanced CT score plus necrosis score
Maximum = 10 ≥6 = severe disease
392
 
DIFFERENTIAL DIAGNOSIS
  •   Perforated viscous
  •   Acute cholecystitis
  •   Acute intestinal obstruction
  •   Mesenteric ischemia
  •   Myocardial infarction
  •   Dissecting aortic aneurysm
  •   Diabetic ketoacidosis
  •   Pneumonia
Ranson's criteria and APACHE II are not very useful as they are cumbersome, require large data and do not have acceptable predictive values.
 
MANAGEMENT
 
General Measures
Patient should be kept nil per oral and enteral nutrition is supported by either nasogastric or nasojejunal tubes. Patients with pancreatitis have severe abdominal pain and this is relieved by giving analgesics. There is no role for prophylactic antibiotics. However if the patient appears septic, antibiotics may be started awaiting culture reports. If the cultures are negative, antibiotics should be discontinued. Other drugs that have been found to be useful are octreotide (somatostatin analogue) and gabexate mesylate (antiprotease).
 
Specific Measures
 
Necrosectomy
It is indicated in necrotizing pancreatitis with ongoing signs of pancreatic infection such as fever, leukocytosis, etc. The various techniques available for necrosectomy are endoscopic, retroperitoneal and percutaneous catheter (Table 51.4).
Table 51.4   Complications of acute pancreatitis
Local
  • Pancreatic necrosis
  • Pancreatic abscess
  • Pancreatic pseudocyst
  • Pancreatic ascites
  • Thrombosis of blood vessels (splenic and portal vein)
  • Obstructive jaundice
Systemic
  • Renal: Oliguria, renal vessel thrombosis
  • Cardiovascular: Hypotension, pericardial effusion
  • Pulmonary: Pleural effusion, pneumonitis, ARDS
  • CNS: Psychosis, fat embolism
  • Others: Purtscher's retinopathy (sudden blindness), DIC
393
 
ERCP
  •   Urgent ERCP—done in acute biliary peritonitis associated with cholangitis or organ failure
  •   Elective ERCP—done in recurrent biliary obstruction
  •   ERCP with sphincterotomy—done in pancreatic duct disruptions.
 
BIBLIOGRAPHY
  1. Akeda K, Takada T, Kawarada Y, et al. JPN guidelines for the management of acute pancreatitis: medical management of acute pancreatitis. J Hepatobiliary Pancreat Surg. 2006;13:42-7.
  2. Avunduk, Canan. Manual of Gastroenterology: Diagnosis and Therapy, 4th edn. Lippincott Williams & Wilkin; 2008.
  3. Cruz-Santamaría DM, Taxonera C, Giner M. Update on pathogenesis and clinical management of acute pancreatitis. World J Gastrointest Pathophysiol. 2012;3(3):60-70.
  4. David C, Whitcomb. Acute pancreatitis. N Engl J Med. 2006;354:2142-50.
  5. Dellinger EP, Tellado JM, Soto NE, et al. Early antibiotic treatment for severe acute necrotizing pancreatitis: a randomized, double-blind, placebo-controlled study. Ann Surg. 2007;245:674-83.
  6. Eatock FC, Chong P, Menezes N, et al. A randomized study of early nasogastric versus nasojejunal feeding in severe acute pancreatitis. Am J Gastroenterol. 2005;100:432-9.
  7. Johnson CD, Besselink MG, Carter R. Acute pancreatitis. BMJ. 2014;349.
  8. Longo DL, Kasper DL, Jameson JL, et al. Harrison's principles of internal medicine, 18th edn. McGraw Hill publications; 2012.
  9. Olsch UR, Nitsche R, Ludtke R, et al. Early ERCP and papillotomy compared with conservative treatment for acute biliary pancreatitis (The German Study Group on Acute Biliary Pancreatitis). N Engl J Med. 1997;336:237-42.
  10. Papachristou GI, Muddana V, Yadav D, et al. Comparison of BISAP, Ranson's, APACHE-II, and CTSI scores in predicting organ failure, complications, and mortality in acute pancreatitis. Am J Gastroenterol. 2010;105:435-41.
  11. Papadakis MA, McPhee SJ, Rabow MW. Current medical diagnosis & treatment. 54th edition. 2015.
  12. Petrov MS, Shanbhag S, Chakraborty M, et al. Organ failure and infection of pancreatic necrosis as determinants of mortality in patients with acute pancreatitis. Gastroenterology. 2010;139:813-20.
  13. Singh VK, Bollen TL, Wu BU, et al. An assessment of the severity of interstitial pancreatitis. Clin Gastroenterol Hepatol. 2011;9:1098-103.
  14. Steer ML, Perides G. Pathogenesis: How does acute pancreatitis develop? In: Domínguez-Muñoz E, (Ed). Clinical pancreatology for practicing gastroenterologists and surgeons. Oxford: Blackwell Publishing Ltd; 2005.pp.10-26.
  15. Talukdar R, Vege SS. Classification of the severity of acute pancreatitis. Am J Gastroenterol. 2011;106:1169-70.
  16. Van Santvoort HC, Bakker OJ, Bollen TL, et al. A conservative and minimally invasive approach to necrotizing pancreatitis improves outcome. Gastroenterology. 2011; 141:1254-63.

ACUTE LIVER FAILURECHAPTER 52

TA Naufal Rizwan  
INTRODUCTION
Fulminant hepatic failure (FHF), acute hepatic failure and fulminant hepatitis all refer to acute severe impairment of liver function accompanied by encephalopathy and coma in patients who have had liver disease for less than 8 weeks.
 
CLASSIFICATION
The classification of acute liver failure is based on the time interval between the development of jaundice and hepatic encephalopathy. There are two types of classification available for acute liver failure (Tables 52.1 and 52.2).
Table 52.1   First classification
Stage
Time from jaundice to hepatic encephalopathy
Hyper acute
Acute
Subacute
<7 days
8–28 days
29 days–12 weeks
Table 52.2   Second classification
Stage
Time from jaundice to hepatic encephalopathy
Fulminant
Subfulminant
<2 weeks
>2 weeks
 
CAUSES OF ACUTE LIVER FAILURE (TABLE 52.3)
Table 52.3   Etiology of acute liver failure
Infective
Hepatitis virus A, B, C, D, E
Herpes simplex
CMV
Ischemic
Ischemic hepatitis
Acute Budd-Chiari syndrome
Surgical shock
Drug reactions and toxins
Acetaminophen (paracetamol) overdose
Antidepressants
Halothane
Isoniazid, rifampicin
Non-steroidal anti-inflammatory drugs
Mushroom poisoning
Metabolic
Wilsons disease
Reyes syndrome
Fatty liver of pregnancy
395
 
Viral Hepatitis
The most common cause for acute liver failure worldwide is acute viral hepatitis, Hepatitis A infection being the most common. Infection with hepatitis B virus, herpes simplex virus (HSV) and rarely hepatitis C virus (HCV) may also lead to FHF. Fulminant liver failure due to HSV and CMV responds to acyclovir and ganciclovir, respectively.
 
Acetaminophen Poisoning
The characteristic picture is of very high serum aspartate transaminase levels, usually accompanied by a lower level of alanine transaminase. N-acetyl cysteine, if administered within 15 hours, prevents the development of fulminant hepatic failure in the majority of cases.
 
PATHOPHYSIOLOGY
Acute liver failure is characterized by liver cell death which can occur due to apoptosis or necrosis.
 
CLINICAL FEATURES
Although acute liver failure patients have nonspecific symptoms such as nausea, malaise and vomiting in the earlier stages, they rapidly develop jaundice and hepatic encephalopathy, which can lead on to coma.
 
ASSOCIATIONS OF ACUTE HEPATIC FAILURE
Following are associated with acute hepatic failure:
  •   Hepatic encephalopathy
  •   Cerebral edema
  •   Coagulopathy
  •   Electrolyte and metabolic disturbances
  •   Infections
  •   Renal complications
  •   Pulmonary complications.
 
Hepatic Encephalopathy
Neuropsychiatric manifestations occurring secondary to liver dysfunction is known as hepatic encephalopathy. Although the exact mechanism of hepatic encephalopathy is still not fully known, the postulated mechanism is as follows:396
Table 52.4   Hepatic encephalopathy scale
Grade
Neurologic status
0
No abnormality detected
1
Mild lack of awareness, shortened attention span
2
Lethargy, disorientation in time, clear personality change
3
Very drowsy but responsive to stimuli, confused, gross disorientation in time or space
4
Comatose, unresponsive to painful stimuli with or without abnormal movements (decorticate or decerebrate posturing)
 
Clinical Features (Table 52.4)
The onset of encephalopathy is often sudden and the affected patients are usually agitated and they exhibit violent behavior. They are restless with a few patients showing personality changes too. Delusions, delirium and mania are also noted in majority of the patients. Other features of acute liver failure include nightmares, seizures, flapping tremor and fetor hepaticus.
 
Cerebral Edema
Cerebral edema with subsequent raised intracranial tension is the most common cause of death in patients with acute liver failure.
 
Mechanism
  • Cytotoxic hypothesis:
397
  • Vasogenic hypothesis: Cerebral edema occurs due to changes in cerebral blood flow and blood brain barrier.
 
Clinical Features
The clinical features of cerebral edema include systolic hypertension, bradycardia and dysconjugate eye movements. Increased muscle tone and myoclonus are also seen in a few patients. Patients with cerebral edema exhibit decerebrate posturing and slow oculovestibular reflexes. The pupillary reaction is usually sluggish; however, papilloedema is uncommon.
 
Coagulopathy
Coagulopathy predisposes to bleeding, which if severe (involving the GIT and brain can even lead on to death. The reasons for coagulopathy in acute liver failure are depletion of clotting factors (except factor VIII all others are produced by the liver), increased fibrinolytic activity and diminished platelet function.
 
Infections
More than 90% of patients with acute liver failure have clinical or bacteriological evidence of infection. Most of the infections are respiratory and caused by Gram +ve organisms. Fungal infections are also common. Poor host defences, poor respiratory effort, suppressed protective mechanisms like cough reflex and the presence of endotracheal tubes, venous lines and urinary catheters are the predisposing factors for infections.
 
Metabolic and Electrolyte Disturbances
The common metabolic abnormalities seen in acute liver failure are hypokalemia, hypophosphatemia, hypocalcemia and hypomagnesemia. Hypoglycemia is seen due to increased insulin levels and diminished gluconeogenesis. Respiratory alkalosis due to hyperventilation and respiratory acidosis due to elevated ICP and respiratory depression are also noted.
 
Renal Abnormalities
Renal failure is common in fulminant hepatic failure and the causes are hepato-renal syndrome (functional renal failure occurring secondary to liver failure), acute tubular necrosis and sepsis.
 
Pulmonary Complications
The various pulmonary complications associated with acute liver failure are atelectasis, ARDS and pulmonary edema.398
Investigations of acute liver failure
Hemoglobin, platelets, WBC, prothrombin time, blood group
Blood glucose, liver function tests, renal function tests, electrolytes
Microbiology, viral markers for hepatitis, blood culture-aerobic and anaerobic, sputum, urine, stool culture
ABG
Chest X-ray, ECG, EEG, USG abdomen, CT abdomen, CT brain
Plasma FDP, hepatic scan, liver biopsy
 
PROGNOSIS
Prognosis in acute hepatic failure depends on the age of the patient, cause of the acute liver failure, clinical course, occurrence of secondary complications, and duration and severity of the coma.
Prothrombin time greater than 100 seconds regardless of the stage of encephalopathy or the presence of any three of the following findings indicates a poor prognosis in FHF caused by viral hepatitis or drug toxicity excluding acetaminophen toxicity:
  •   Arterial pH <7.3
  •   Age <10 or >40 years
  •   Jaundice >7 days before the onset of encephalopathy
  •   Prothrombin time >50 seconds
  •   Serum bilirubin >18 mg/DL.
 
Causes of Death in Fulminant Hepatic Failure
  •   Neurologic complications (67%),
  •   Gastrointestinal hemorrhage (13%)
  •   Bacterial infection and sepsis (13%)
  •   Hemodynamic complications (8%).
 
TREATMENT
 
General Measures
Vitals like blood pressure, pulse rate and respiratory rate should be monitored. Nasogastric tube, urinary catheter and intravenous catheter should be placed. For patients who are in respiratory distress, endotracheal intubation and ventilation should be considered. Blood samples for various investigations must be sent periodically.
 
Specific Measures
 
Hepatic Encephalopathy
Hepatic encephalopathy is managed by protein-restricted diet, phosphate enema twice daily, lactulose 30 mL twice or thrice daily and oral antibiotics (Metronidazole, rifaximin). Sedatives should be avoided.399
 
Cerebral Edema
The foremost thing in the management of cerebral edema is measurement of ICP using epidural, subdural or extradural catheters. Osmotic diuretics like IV mannitol (20%) should be used to reduce the edema. In resistant cases, surgical decompression like craniectomy should be performed.
 
Hypoglycemia and Electrolyte Abormalities
Hypoglycemia is corrected by giving 100 mL of 50% glucose followed by continuous infusion of 5% or 10% dextrose. The other electrolyte abnormalities like hypokalemia and hypocalcemia should also be corrected appropriately
 
Renal Failure
Continuous arteriovenous or venovenous hemofiltration is the preferred option if serum creatinine is >4.5 mg/d. It is better to avoid intermittent hemodialysis.
 
Respiratory Failure
Intubation and ventilation required to maintain normal blood gases and prevent aspiration.
 
Hypotension
Hypotension is usually corrected with albumin and crystalloid. In cases not responding to the above, vasopressors are added.
 
Infection
Frequent cultures should be sent to determine the bacterial growth. Prophylactic antibiotics are usually not indicated. However, if the cultures are positive, specific antibiotics and antifungals must be added later.
 
Bleeding
Gastrointestinal bleeding is managed by H2 blocker, proton pump inhibitors, sucralfate and transfusion of fresh frozen plasma and platelets. Arterial puncture is usually avoided.
  • Artificial liver support
    MARS—Molecular adsorbent recirculating system
      This uses an albumin impregnated dialysis membrane and a dialysate containing 5% human albumin. The dialysate is perfused over charcoal and resin adsorbents and finally dialyzed to remove water-soluble toxins including ammonia.
  • Bioartificial liver support
    Here, bioreactors containing viable hepatocytes in culture are used.
400The various bioartificial liver support systems are:
  •   ‘Bioartificial Liver’ (BAL)
  •   ‘Extracorporeal Liver Assist Device’ (ELAD)
  •   ‘Berlin Extracorporeal Liver Support System’ (BELS).
 
LIVER TRANSPLANTATION
Liver transplantation may be a lifesaving procedure for patients with acute liver failure and delay in implementing this therapy can be fatal.
In most centers, worsening hepatic encephalopathy, clinical evidence of cerebral edema, and increasing prolongation of the prothrombin time after 24 to 48 hours of intensive medical treatment are used as the key factors for recommending liver transplantation.
King's College Hospital criteria for liver transplantation in acute liver failure
Acetaminophen (paracetamol)
    or
Nonacetaminophen patients
    or
Any three of the following variables (irrespective of grade of encephalopathy)
 
Contraindications
The contraindications for liver transplantation are:
  •   Active ongoing infection
  •   ARDS
  •   Fixed dilated pupils for prolonged periods of time (1 hour or more)
  •   Cerebral perfusion pressure <40 mm Hg or ICP >35 mm Hg for >1 hour.
The outcome of liver transplantation also depends on graft quality, because grafts from incompatible blood groups, steatotic grafts, or partial or reduced-size grafts do not produce favorable results.
 
Auxiliary Liver Transplantation
It is a procedure in which the native liver, which is left in place, may recover if a transplanted auxiliary liver provides temporary support. The advantage over conventional transplantation is the temporary need for immunosuppression.401
 
BIBLIOGRAPHY
  1. Agarwal B, Wright G, Gatt A, et al. Evaluation of coagulation abnormalities in acute liver failure. J Hepatol. 2012;57:780.
  2. Avunduk, Canan. Manual of Gastroenterology: Diagnosis and Therapy, 4th edn. Lippincott William & Wilkin.
  3. Bernal W, Hyyrylainen A, Gera A, et al. Lessons from look-back in acute liver failure? A single centre experience of 3300 patients. J Hepatol. 2013;59:74-80.
  4. Bernal W, Wendon J. Acute liver failure. N Engl J Med. 2013;369:2525-34.
  5. Caraceni P, van Thiel DH. Acute liver failure. Lancet. 1995;345:163.
  6. Chai P, Samuel D. Etiology and prognosis of fulminant hepatitis in adults. Liver Transpl. 2008;14(Suppl 2):S67-S79.
  7. Dooley JS, Lok A, Burroughs AK, Heathcote J. Sherlock's Diseases of the Liver and Biliary System, 12th edn.
  8. Lee WM, Recent Developments in acute liver failure. Best Pract Res Clin Gastroenterol. 2012;26(1):3-16.
  9. Lee WM. Etiologies of acute liver failure. Semin Liver Dis. 2008;28:142.
  10. Longo DL, Kasper DL, Jameson JL, et al. Harrison's principles of internal medicine, 18th edn. McGraw Hill publications; 2012.
  11. Mochida S, Takikawa Y, Nakayama N, et al. Diagnostic criteria of acute liver failure: A report by the Intractable Hepato-biliary Diseases Study Group of Japan. Hepatol Res. 2011;41:805.
  12. Papadakis MA, McPhee SJ, Rabow MW. Current Medical Diagnosis & Treatment, 54th edn. 2015.
  13. Richardson P, O'Grady J. Diseases of the liver: Acute liver disease. The Pharmaceutical Journal. 2009.
  14. Schiff ER, Maddrey WC, Sorrell MF. Schiff's Diseases of the Liver, 11th Edition.
  15. Stravitz RT, Kramer DJ. Management of acute liver failure. Nat Rev Gastroenterol Hepatol. 2009;6:542-53.

ABDOMINAL INFECTIONS IN ICUCHAPTER 53

TA Naufal Rizwan  
INTRODUCTION
It is broadly defined as the inflammation of the peritoneum secondary to microorganisms, resulting in purulence in the peritoneal cavity. They are the second most common cause of severe sepsis in the ICU and their mortality rate is very high. Most of them are associated with an inflammation or perforation process of the gastrointestinal tract.
 
CLASSIFICATION
 
Uncomplicated IAI (Intra-abdominal Infection)
Inflammation confined to the GIT without anatomic disruption—peritoneum not involved.
 
Complicated IAI (Table 53.1)
Anatomic disruption present—Inflammation involves the peritoneal space too.
 
Localized Peritonitis
Manifest as an abscess with tissue debris, bacteria, inflammatory cells and exudative fluid contained in a fibrous capsule.403
Table 53.1   Organisms according to source
Source
Expected organism
Primary peritonitis
Young healthy female cirrhotic CAPD
Streptococcus enteric gram negatives Staphylococcus aureus
Secondary peritonitis
Stomach and duodenum
Biliary system
Small Intestine
Distal ileum and colon
Lactobacillus, Streptococcus
E. coli, Klebsiella, Enterococcus
E.coli, Klebsiella, Lactobacillus, Enterococci, Streptococci, Diptheroids
Bacteroides fragilis, Clostridium spp. E.coli, Klebsiella, Enterobacter spp.
Tertiary peritonitis
Immunocompromised
Enterococcus, Candida, Enterobacter
Staphylococcus epidermidis
 
Primary Peritonitis
Here, gut wall is intact (so bacteria reach via translocation across the intact gut wall) and infection is predominantly monomicrobial.
 
Secondary Peritonitis
In secondary peritonitis, gut wall is not intact—perforation, laceration or necrotic segment of the GI tract are present and infection is usually polymicrobial.
 
Tertiary Peritonitis
It is an infection that is persistent or recurrent at least 48 hours after appropriate management of primary or secondary peritonitis. They are usually seen in immunocompromised patients.
 
PATHOPHYSIOLOGY
Pathophysiology of abdominal infections are shown in Figure 53.1.
 
CLINICAL FEATURES
The clinical features depend on whether the intra-abdominal infection is complicated or not and also on the type of peritonitis. Fever, nausea, vomiting and abdominal pain (increased by coughing or sneezing) are the usual presenting complaints. Examination of the abdomen shows guarding, rigidity, abdominal tenderness and rebound tenderness. Patient lies motionless with flexed knees. Bowel sounds are usually sluggish or absent and jaundice may be present. Tachycardia, tachypnea and oliguria are seen if the patient develops sepsis.404
Fig. 53.1: Pathophysiology of abdominal infections
 
INVESTIGATIONS
  •   Complete blood count, electrolytes, blood sugar
  •   Urea, creatinine, liver function tests
  •   ABG, serum lactate
  •   X-ray abdomen
  •   USG abdomen, CT abdomen
  •   Peritoneal fluid analysis—useful in spontaneous bacterial peritonitis
  •   Blood culture
 
MANAGEMENT
The three key components in the management of intra-abdominal infections are:
  1. Resuscitation
  2. Source control
  3. Antimicrobial treatment.
 
Resuscitation
Patients with IAI have volume depletion as a result of vomiting, diarrhea, fever, diminished oral intake and third space loss (due to ileus). Intravenous fluids, blood replacement and vasopressors are required to restore the volume. Target for volume replacement should be to achieve a mean arterial pressure (MAP) > 65 mm Hg and a central venous pressure (CVP) of 12–15 mm Hg within the first 6 hours.
 
Source Control
Elimination or control of the source of infection is critical in the management of the infection. The various procedures available for controlling the source of infection are:405
  •   Establishing bowel continuity
 
Drainage
The two types of drainage procedures available are percutaneous and open drainage.
  1. Percutaneous drainage: It is usually done under imaging guidance. It is less invasive and more affordable. It is useful in patients who are poor surgical candidates. However, in cases of frank bowel perforation or if there is a significant amount of necrotic tissue present, percutaneous drainage will not be of use.
  2. Open drainage: It is indicated if generalized peritonitis or bowel necrosis is present.
 
Debridement
It is a procedure wherein foreign bodies, fecal matter, hematoma, and infected or necrotic tissues are removed.
 
Establishing Bowel Continuity
It is a definitive procedure in which both the anatomy and the function of the gastrointestinal tract is restored. Single stage procedures with primary anastomoses are the treatment of choice. The type of procedure depends on the underlying surgical illness.
 
Antimicrobial Treatment (Table 53.2)
Although surgery is the mainstay of treatment in complicated IAI, systemic antibiotics have got its own merits. They play a great role in the prevention as well as treatment of the infection, in addition to reducing the complications. The choice of antimicrobial regimen and duration of treatment is guided by patient risk, which in this context, is intended to describe the risk for failure of treatment.
The conditions associated with high risk of treatment failure are health care-associated infections, APACHE II score >15, advanced age, organ dysfunction, immunosuppression and malignancy.
Table 53.2   Empirical management of abdominal infections
Risk of the patient
Treatment
High-risk patients
Piperacillin/tazobactam 3.375 g IV q6h
(or)
Cefepime 2 gm IV bid + Metronidazole 500 mg IV every 6 hours
Low-risk patients
Tigecycline 100 mg IV stat followed by 50 mg IV every 12 hours
(or)
Ceftriaxone 1–2 gm IV od + Metronidazole 500 mg IV q6h
406
If Enterococcus is suspected, vancomycin should be added. In case of vancomycin resistant enterococci, Daptomycin/linezolid/tigecycline should be used. Micafungin is added if fungal cultures are positive.
 
DURATION OF TREATMENT
The usual duration of treatment is 5–7 days. Once patients are able to tolerate oral intake, antibiotic therapy can be transitioned to oral dosing for the remainder of their treatment. The commonly used oral antibiotics are either amoxycillin-clavulanic acid or metronidazole with moxifloxacin/ciprofloxacin.
 
GI Colonization
Gastrointestinal tract is one of the major sources of sepsis due to the translocation of pathogenic bacteria and this gets precipitated by the administration of antibiotics and acid suppressants. The use of antibiotics which are nonabsorbable can prevent colonization and recently selective decontamination is also useful for this purpose.
 
Acalculous Cholecystitis
Though it is uncommon in ICU, still it typically develops in critically ill patients. It is an acute inflammation of the gallbladder which occurs without gallstones.
 
Risk Factors
  •   Sepsis
  •   Major abdominal surgery
  •   Multiple trauma
  •   Patients on parenteral nutrition with extensive burns
  •   Prolonged illness with multiple organ system failure.
 
Pathophysiology
Since the etiology is unknown, it is thought to be due to gallbladder distention with bile stasis and ischemia. There is edema of the serosa and muscular layers, with patchy thrombosis of arterioles and venules.
 
Clinical Features and Diagnosis
In the conscious patient, right upper quadrant pain and tenderness, fever, and leukocytosis are present. In the unconscious patient, fever, leukocytosis and elevated alkaline phospatase are all features requiring further evaluation. Ultrasonography is the diagnostic imaging of choice and it can demonstrate abscess, biliary sludge, fluid collection around the gallbladder, distended gallbladder with thickened wall, biliary sludge, pericholecystic fluid, and the presence or absence of abscess formation. CT scan can also be done in case if inconclusive with ultrasound but there is strong suspicion of the diagnosis. 407
 
Management
Acalculous cholecystitis requires immediate intervention to prevent gall-bladder rupture. Percutaneous cholecystostomy by ultrasound or CT guidance is the treatment of choice for these patients since most of these patients are hemodynamically unstable. In case of an inconclusive diagnosis, percutaneous cholecystostomy is done both for diagnosis and treatment. If patients don't improve with cholecystostomy, open cholecystectomy is done after the patient is stabilized.
 
BIBLIOGRAPHY
  1. Barie PS, Hydo LJ, Eachempati SR. Longitudinal outcomes of intra-abdominal infection complicated by critical illness. Surg Infect (Larchmt). 2004;5(4):365-73.
  2. Ben-Ami R, Rodriguez-Bano J, Arsian H, et al. A multinational survey of risk factors for infection with extended-spectrum β-lactamase-producing Enterobacteriaceae in nonhospitalized patients. Clin Infect Dis. 2009;49:682-90.
  3. Evans HL, Raymond DP, Pelletier SJ, et al. Diagnosis of intra-abdominal infection in the critically ill patient. Curr Opin Crit Care. 2001;7(2):117-21.
  4. Leaper D. Nosocomial infection. Br J Surg. 2004;91(5):526-7.
  5. Lopez N, Kobayashi L, Coimbra R. A Comprehensive review of abdominal infections. World J Emerg Surg. 2011;6:7.
  6. Mazuski JE, Sawyer RG, Nathens AB, et al. The Surgical Infection Society guidelines on antimicrobial therapy for intra-abdominal infections: an executive summary. Surgical Infection Society, 3rd edn. 2002.pp.161-74.
  7. Menichetti F, Sganga G. Definition and classification of intra-abdominal infections. J Chemother. 2009;21(Suppl 1):3-4.
  8. Pieracci FM, Barie PS. Management of severe sepsis of abdominal origin. Scand J Surg. 2007;96(3):184-96.
  9. Sartelli M, Catena F, Ansaloni L, Coccolini F. Complicated intra-abdominal infections worldwide: the definitive data of the CIAOW study. World Journal of Emergency Surgery. 2014;9:37.
  10. Solomkin JS, Mazuski JE, Baron EJ, et al. Guidelines for the selection of anti-infective agents for complicated intra-abdominal infections. Clin Infect Dis. 2003;37:997-1005.
  11. Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Surg Infect (Larchmt). 2010, 11(1):79-109.
  12. Solomkin JS, Mazuski JE, Bradley JS, Rodvold KA. Diagnosis and management of complicated intra-abdominal infection in adults and children: Guidelines by the Surgical Infection Society and the Infectious Diseases Society of America; Oxford Journals, Medicine & Health, Clinical Infectious Diseases. 2010;50(2):133-64.
  13. Swenson BR, Metzger R, Hedrick TL, et al. Choosing antibiotics for intra-abdominal infections: what do we mean by “high risk”? Surg Infect (Larchmt). 2009;10:29-39.
  14. T Herzog, AM Chromik, W UhL. Treatment of complicated intra-abdominal infections in the era of multidrug resistant bacteria. European Journal of Medical Research. 2010;15:525-32.
408Hematological disorders in Intensive Care Unit
Chapter 54 Hemolytic Anemia and Sickle Cell Crisis Vinoj
Chapter 55 Disseminated Intravascular Coagulation and Heparin-induced Thrombocytopenia Vinoj
Chapter 56 Immune Thrombocytopenic Purpura Vinoj409

HEMOLYTIC ANEMIA AND SICKLE CELL CRISISCHAPTER 54

Vinoj  
HEMOLYTIC ANEMIA
Hemolytic anemia is a group of blood disorders where the lifespan of red blood cells is reduced to less than 120 days. Hemolysis can occur extravascularly or intravascularly among which extravascular hemolysis is the most common, which occurs due to RBC deformability. Intravascular hemolysis occurs due to mechanical trauma to RBC or due to complement fixation or toxic factors against RBC. The principal clinical manifestations of hemolytic anemia are anemia and jaundice. Along with these features splenomegaly is specifically seen in extravascular hemolysis due to hyperplasia of phagocytes. Whereas hemoglobinemia, hemoglobinuria, hemosideremia are more commonly seen in intravascular hemolysis. Hemolytic anemias can be episodical or continuous. The hemolytic anemias can be classified into intrinsic RBC defect or due to external factor.
 
Intrinsic RBC Defect
  • Inherited genetic defect
  •   Membrane disorders
    •   Hereditary spherocytosis
    •   Hereditary elliptocytosis
  •   Enzyme deficiency
    •   HMP shunt—G6PD deficiency
    •   Glutathione synthetase deficiency
    •   Glycolytic—pyruvate kinase deficiency
    •   Hexokinase deficiency
  •   Hemoglobinopathies
    •   Sickle cell anemia
    •   Thalassemia
    •   Unstable hemoglobinemia
    •   Methemoglobinemia
  •   Membrane lipid abnormalities
    •   Abetalipoproteinemia
  •   Acquired genetic defect
  •   Paroxysmal nocturnal hemoglobinuria
412
 
Extrinsic Factors
  •   Immune-mediated destruction
    •   Hemolytic disease of newborn
    •   Transfusion reactions
    •   Drug-induced—dapsone, nalidixic acid, nitrofurantoin, primaquine, sulfonamides, penicillins, cephalosporins, procainamide, α methyl dopa, NSAIDs.
    •   Autoimmune disorders.
  •   Mechanical trauma
    •   HUS/TTP
    •   DIC
    •   Defective cardiac valves
    •   Repetitive physical trauma like Marathon running, etc.
  •   Infections
    •   Malaria
    •   Babesiosis.
  •   Toxic injury
    •   Clostridial sepsis
    •   Snake venom
    •   Lead poisoning.
  •   Sequestration
  •   Hypersplenism.
 
Diagnosis
Hemolytic anemia can be severe in ICU due to various causes such as aplastic crisis in patient with chronic hemolytic anemia, DIC, sepsis with bacteria releasing hemolytic toxin, autoimmune cause. Hemolytic anemia should be suspected in case of failure of rise in hematocrit in spite of blood transfusion, increased LDH and raised indirect bilirubin, hemoglobinuria. Patients are pale, jaundiced, have hepatosplenomegaly due to extramedullary erythropoiesis. Haptoglobin binds free intravascular hemoglobin and is cleared through the liver, resulting in a low serum haptoglobin level. Differences between intravascular and extravascular hemolysis is shown in Table 54.1.
Table 54.1   Differences between intravascular and extravascular hemolysis
Investigation
Intravascular hemolysis
Extravascular hemolysis
Hemoglobin/hematocrit
Lactate dehydrogenase
Indirect bilirubin
Reticulocyte count
Osmotic fragility
-
Present
Coombs’ test (direct antiglobulin test)
Positive
Positive
DIC screen (includes FDP, D dimer and others)
Positive
Positive
Flow cytometry CD55, CD59
Positive
Negative
413
 
Complications
Anemia, jaundice, acute kidney injury, acute lung injury, acute heart failure, shock, DIC, thromboembolic episodes, electrolyte disturbances, predispose infections, aplastic crisis, iron overload are common in patients with hemolytic anemias since they are on frequent red cell transfusions. Iron overload can cause liver and cardiac dysfunction.
 
Treatment
Folic acid supplementation is given for all patients with hemolytic anemia at a dose of 5 mg for acute hemolytic crisis and 1 mg for chronic hemolytic anemia. Packed red cells transfusion may be needed during exacerbation and hemodynamic instability. Post-splenectomy patients are more prone for infections, hence in case of suspected infections, antibiotics should be started. Iron chelating agents like parenteral deferoxamine remove 10–20 mg/day or oral deferasirox. In patients with chronic hemolytic anemia who has aplastic crisis due to parvovirus infection will require red cell transfusion support for a week. Serial reticulocyte count can be done to monitor recovery.
 
SICKLE CELL CRISIS
Sickle cell anemia is an autosomal recessive disorder in which abnormal hemoglobin leads to chronic hemolytic anemia. A single DNA base change leads to amino acid substitution of valine for glutamine in sixth position on beta globin chain.
 
Pathophysiology
HbS on deoxygenation polymerizes reversibly to form gelatinous polymers that stiffen the RBC membrane, increase viscosity and cause dehydration due to ionic leak. These changes produce sickle-shaped cell that loses the ability to traverse the small capillaries. These altered sticky cells abnormally adhere to the endothelium of venues and cause microvascular obstruction leading to tissue ischemia, acute pain, and end-organ damage.
 
Clinical Manifestation
Patients with sickle cell crisis present with hemolytic anemia, reticulocytosis and granulocytosis also occur. Patients are pale, jaundiced and can have hepatosplenomegaly. Vaso-occlusion can be triggered by fever, changes in temperature, hypoxia or infections. This causes ischemia in musculoskeletal and connective structures which is manifested by acute pain, tenderness, fever, and tachycardia. When these occur recurrently, it is called as painful crises. Pain can last for a few hours to weeks. Repeated crises requiring hospitalization (>3 per year) is associated with decreased survival in adult life. Acute chest syndrome is due to in situ sickling in lung which, in turn, causes chest pain, tachypnea, fever, cough, arterial oxygen desaturation. Bone ischemia can occur due to aseptic necrosis of femoral and humeral heads. Other manifestations are chronic 414arthropathy, salmonella osteomyelitis, hand-foot syndrome—painful infarcts of digits and dactylitis, retinal hemorrhage, neovascularization and detachments, renal papillary necrosis—isosthenuria, stroke, increased susceptibility to pneumococcal infection—autosplenectomy, priapism.
 
Lab Findings
Hematocrit 15–30%, granulocytosis, sickle cells constituting 5–50% RBC, reticulcytosis, Howel jolly bodies, hemoglobin electrophoresis—HbS 85–98% of Hb, reactive thrombocytosis, rise in indirect bilirubin levels.
 
Management of Crisis
Acute painful crisis is managed with vigorous hydration and evaluation of the precipitating cause and analgesia with patient controlled analgesia (PCA). PCA is given with morphine. Morphine is given at a dose of 0.1–0.15 mg/kg every 3–4 hour for severe pain. Skeletal pain is treated with Ketorolac 30–60 mg initially followed by 15–30 mg every 6–8 hour. Short-term pain relief can be given with nitrous oxide but it has the adverse effect of causing diffusion hypoxia, hence should be given only after consultation with anesthesiologist. It is given along with oxygen to prevent hypoxia. NSAIDs are given for arthropathy.
Mainstay of treating sickle cell anemia is administration of hydroxyurea. Hydroxyurea is indicated for patients with repeated episodes of acute chest syndrome or with more than three crises per year requiring hospital admission. It increases fetal Hb and causes suppression of the granulocyte and reticulocyte count (WBC and reticulocytes play a major role in the pathogenesis of crisis). It is given at a dose of 10–30 mg/kg per day and dose is titrated to keep white cell count between 5000 and 8000/µL. Hydroxyurea improves survival. Azacytidine and decitabine can also be used for this purpose but there is increased incidence of complications. Bone marrow transplantation is the most effective way to treat sickle cell anemia but more commonly used in children.
Acute chest syndrome is an emergency which requires ICU admission. Oxygen therapy is given to treat hypoxemia and steps are taken to evaluate and treat pneumonia and pulmonary embolism since they are common in sickle cell crisis. Red cell transfusion is given to maintain Hb >10 g/dL and exchange transfusion is done in case of arterial desaturation. Complications like pulmonary hypertension, cardiomyopathy, and renal failure are causes of mortality in sickle cell disease patients.
 
BIBLIOGRAPHY
  1. Colledge NR, Walker BR, Ralston S, Davidson S. Davidson's Principles and Practice of Medicine, 22nd edn. Edinburgh. Churchill Livingstone/Elsevier. 2005.
  2. Dacie J. The Hemolytic Anemias. London: Churchill Livingstone; 1985-95.
  3. Johnson CS. The acute chest syndrome. Hematol Oncol Clin North Am. 2005;19:857-79.
  4. Longo DL, Kasper DL, Jameson JL, Fauci AS, et al. Harrison's principles of internal medicine, 18th edn. McGraw Hill publications; 2012. 
  5. 415Ohene-Frempong K. Indications for red cell transfusion in sickle cell disease. Sem Hematol. 2001;38[Suppl 1]:5-13.
  6. Steinberg MH. Management of sickle cell disease. N Engl J Med. 1999;340:1021-30.
  7. Steinberg MH. Pathophysiologically based drug treatment of sickle cell disease. Trends Pharmacol Sci. 2006;27:204.
  8. Switzer JA, et al. Pathophysiology and treatment of stroke in sickle-cell disease: Present and future. Lancet Neurol. 2006;5:501.
  9. Vichinsky Ep, Neumayr Ld, Earles An, Williams R, Lennette Et, Dean D, et al. Causes and outcomes of the acute chest syndrome. In: Sickle cell disease. N Engl J Med. 2000;342(25):1855-65.
  10. Yale Sh, Nagib N, Guthrie T. Acute chest syndrome. In: Sickle cell disease. Crucial considerations in adolescents and adults. Postgraduate Medicine. 2000;107(1):215-8,221-2.

DISSEMINATED INTRAVASCULAR COAGULATION AND HEPARIN-INDUCED THROMBOCYTOPENIACHAPTER 55

Vinoj  
DISSEMINATED INTRAVASCULAR COAGULATION
Disseminated intravascular coagulation (DIC) is a syndrome where there is inappropriate thrombin activation leading to excessive blood protease activity resulting in widespread intravascular fibrin formation which overcomes anticoagulant mechanisms. Causes of DIC is given in Table 55.1.
 
Pathophysiology
The activation of thrombin leads to the following:
  •   Fibrinogen conversion to fibrin
  •   Platelet activation and consumption
  •   Factors V and VIII activation
  •   Protein C activation
  •   Endothelial cell activation
  •   Fibrinolysis.
Table 55.1   Causes of DIC
Common clinical causes of disseminated intravascular coagulation
  • Infections—bacterial, viral, mycotic
  • Trauma
  • Tissue injury—fat embolism, rhabdomyolysis, extensive burns
  • Immunological disorders—acute hemolytic transfusion reaction, organ or tissue transplant rejection, Graft-versus-host disease
  • Obstetric complications—Abruptio placenta, amniotic-fluid embolism, septic abortion, intrauterine death
  • Snakebite, insect bite
  • Liver disease—fatty liver of pregnancy, cirrhosis, fulminate hepatic failure
  • Carcinomas
  • Massive transfusion
  • Severe shock
  • ARDS
  • Drugs—warfarin, fibrinolytic agents, prothrombin concentrate, aprotinin
417Uncontrolled thrombin activation leads to consumption of coagulation factors and platelets along with fibrin deposition in microcirculation. This causes red cell damage, hemolysis and organ damage due to ischemia. Secondary fibrinolysis leads to release of D-dimer. Diffuse bleeding occurs due to consumption of coagulation factors and thrombocytopenia.
 
Clinical Features
The patients with DIC can have varied spectrum of clinical manifestations from thrombosis to bleeding according to the imbalance of hemostasis present in the patient. Patients can be asymptomatic with laboratory evidence of DIC but no bleeding or thrombosis which is usually seen in carcinomas or sepsis. Bleeding can occur from venipuncture sites or from GIT, liver, lung, can present with petechiae, ecchymosis. Bleeding is due to a combination of coagulation factor depletion, platelet dysfunction, thrombocytopenia, and excessive fibrinolysis. These patients may present with diffuse bleeding from multiple sites. Thrombosis can occur due to activation of clotting process leading to venous thrombosis.
 
Lab Findings
It is based on the finding the cause of DIC. Platelet count, RBC count, coagulation profile—aPTT, PT, thrombin time (TT) and markers of fibrin degradation products (FDPs) and analysis of the bloodsmear. These investigations should be repeated every 8 hours. In DIC, PT/aPTT are prolonged. Thrombocytopenia is present with the elevated FDP levels. FDP level is the most sensitive test for DIC. The D-dimer test is more specific for detection of fibrin and it indicates that the cross-linked fibrin is dissolved by plasmin. Levels of AT-III and plasminogen are reduced.
 
Treatment
Treatment of the underlying cause is the primary mode of management and management of complications is based in the result of coagulation tests. Most of the patients with DIC are critically ill and hence they may need respiratory and hemodynamic support.
Patients with thrombocytopenia and reduced coagulation factors require replacement therapy with FFP or cryoprecipitate or platelets. PT is a good indicator for assessing severity of clotting factors consumption. In case of low fibrinogen level or fibrinolysis, 10 U of cryoprecipitate is given for every 2–3 U of FFP to correct the hemostasis. In case of severe thrombocytopenia, platelet transfusion is done at a dose of 1–2 units for every 10 kg body weight.
Heparin, antifibrinolytics, AT-III can be given to control coagulation. Continuous heparin infusion at a dose of 5–10 U/kg/hour can be given for patients with known thrombosis or with carcinomas known to cause thrombosis. Heparin is also given for patients with intrauterine fetal death although these agents have not been to improve mortality. Antifibrinolytic drugs like epsilon-aminocaproic acid (EACA), or tranexamic acid prevents fibrin degradation by plasmin which in turn may reduce bleeding episodes in patients with DIC and hyperfibrinolysis although there is always a risk of thrombosis. Purpura fulminans associated with acquired protein C deficiency can be treated with protein C.418
 
HEPARIN-INDUCED THROMBOCYTOPENIA
Heparin-induced thrombocytopenia (HIT) is caused by antibodies directed against antigens on platelet factor 4. IgG antibodies mediate this process by binding to heparin-PF4 and Fc receptors. This causes generation of platelet microparticles which are prothrombotic due to binding of clotting factors and thrombin.
Type I — it is reversible and has effects on the pulmonary vasculature.
Type II—progressive and severe thrombocytopenia associated with thrombosis mostly fatal.
 
Clinical Features
Heparin-induced thrombocytopenia (HIT) is more common in females and patients who are in unfractionated heparin than low-molecular-weight heparin. Patients have thrombocytopenia and it usually begins 3–14 days after commencing heparin infusion or it can occur within hours in a patient previously exposed to heparin. It is unusual for the platelet count to fall below 1,00,000/µL and 50% decrease of platelet count from the baseline value should raise the suspicion of HIT. It is more common in post surgery patients. HIT is associated with arterial or venous thrombosis but more commonly venous thrombosis.
 
Investigations
Heparin-induced thrombocytopenia (HIT) can be diagnosed by enzyme-linked immunosorbent assay (ELISA) for antibodies against heparin-PF4 complex. More specific test is serotonin release assay.
 
Management
Heparin should be discontinued and an alternative anticoagulant should be initiated to prevent or to treat thrombosis. Alternative anticoagulants are lepirudin, argatroban, bivalirudin, or fondaparinux. Platelet transfusions are not indicated and should be avoided since it may even initiate or worsen thrombosis. Patients with HIT have to be treated with parenteral anticoagulants till the platelet count returns to normal after which warfarin can be started. In case of patients with HIT who require urgent surgery may receive heparin once platelet activation has been blocked with antiplatelet drugs like aspirin or ticlopidine. LMWHs can be tested in the laboratory using serotonin release before patient administration although they also can cause HIT.
 
Platelet Dysfunction
Critically ill patients develop platelet dysfunction due to uremia or it is drug-induced. Clinical manifestations are bleeding. Qualitative platelet dysfunction 419can be treated with desmopressin 0.3 μg/kg IV every 12 hours which increases von Willebrand's Factor (vWF) levels and improves platelet aggregation. Conjugated estrogens 0.6 mg/kg IV every day for 5 days are also effective but peak action takes several days. Dialysis is the treatment of choice for patients with platelet dysfunction resulting in bleeding.
 
BIBLIOGRAPHY
  1. Colledge NR, Walker BR, Ralston S, Davidson S. Davidson's Principles and Practice of Medicine, 22nd edn. Edinburgh: Churchill Livingstone/Elsevier; 2005.
  2. Levi M, Cate HT. Disseminated intravascular coagulation. N Engl J Med. 1999;341:586.
  3. Levi M. Disseminated intravascular coagulation: what's new. Crit Care Clin. 2005;21:449.
  4. Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscalzo J. Harrison's Principles of Internal Medicine, 18th edn. McGraw Hill publications; 2012.
  5. Osterud B, Bjorklid E. The tissue factor pathway in disseminated intravascular coagulation. Semin Thromb Hemost. 2001;27:605.
  6. Pixley RA, De La Cadena R, Page JD, et al. The contact system contributes to hypotension but not disseminated intravascular coagulation in lethal bacteremia. J Clin Invest. 1993;91:61.
  7. Wada H. Disseminated intravascular coagulation. Clinica Chimica Acta. 2004;344:13.
  8. Warkentin TE, Kelton JB. A 14-year study of heparin-induced thrombocytopenia. Am J Med. 1996;101:502.
  9. Warkentin TE, Levine MN, Hirsh J, et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Eng J Med. 1995;332:1330.
  10. Weiner CP. The obstetric patient and disseminated intravascular coagulation. Clin Perinatol. 1986;13:705.

IMMUNE THROMBOCYTOPENIC PURPURACHAPTER 56

Vinoj
Immune thrombocytopenia (ITP) is an autoimmune-mediated hematological disorder affecting platelets. Here the immune system produces antibodies directed against platelet antigens, resulting in platelet destruction and suppression of platelet production in the bone marrow. ITP is estimated to affect approximately 3.3/100,000 adults per year and 6.4/100,000 children/year. The incidence of ITP increases with age and, among adults between the ages of 18 and 65 years, is slightly higher in women than in men.
 
PATHOGENESIS
Evidence is now convincing that the syndrome of ITP is caused by platelet destruction as the result of an immunologic process. Platelet survival is greatly shortened and thrombocytopenia in ITP appears to result from the action of a platelet antibody. The responsible factor is an immunoglobulin of the IgG class that is species specific. As acute ITP associated with antecedent viral infection, a viral antigen-antibody complex, may be responsible for platelet sensitization and destruction in ITP. Spleen also is important in ITP as a site of production of platelet antibodies. In chronic ITP, an immunoglobulin has been demonstrated on the surface of the megakaryocytes producing impaired thrombopoises. Patients with ITP can develop additional antibodies to other tissues and organs. For example, thyroid tissue.
 
CLASSIFICATION OF IMMUNE THROMBOCYTOPENIC PURPURA
Immune thrombocytopenia purpura (ITP) is defined as isolated thrombocytopenia (platelet count < 100 × 109/L) with no associated causes or disorders.
Traditionally, ITP has been classified as:
  • Acute: Sudden onset, lasting less than 6 months
  • Chronic: Persisting more than 6 months
  • Refractory: Persistently low platelet counts despite appropriate treatment or splenectomy.421
 
CLINICAL FEATURES
Immune thrombocytopenia purpura (ITP) is a diagnosis of exclusion and history is elicited for any drug intake and infection (HIV and hepatitis C). Isolated thrombocytopenia is present.
 
Acute ITP
Acute ITP occurs most frequently in children 2–6 years, it rarely affects adults and has no gender predilection. The onset of the disorder usually is sudden. A history of infection preceding the onset of bleeding may be present. Acute ITP usually is self-limited. Spontaneous remissions occur in as many as 90% of patients. The duration of the disease ranges from a few days to a few months.
 
Chronic ITP
Chronic ITP affects persons of all ages, but it is relatively more common between puberty and 50 years of age. It occurs more frequently in women than in men, a ratio of approximately 3:1 has been found. The onset of the chronic form of the disorder usually is insidious. Patients usually have a fluctuating clinical course. Episodes of bleeding may last a few days or a few weeks, and may be intermittent or even cyclic. Spontaneous remissions are uncommon.
 
Bleeding Manifestations
  •   Petechiae or purpura
  •   Unusual or easy bruising
  •   Persistent bleeding symptoms from cuts or other injuries
  •   Mucosal bleeding
  •   Frequent or heavy nasal bleeding
  •   Hemorrhage from any site (usually gingival or menorrhagia in women).
 
LABORATORY FINDING
 
Blood
  •   Isolated thrombocytopenia is the essential abnormality
  •   Abnormalities in platelet size and morphologic appearance are common
  •   Prolonged bleeding time
  •   Absent or deficient clot retraction
  •   A positive reaction to the tourniquet test
  •   Deficient prothrombin consumption.
Prothrombin time, partial thromboplastin time, and coagulation time, are normal in patients with uncomplicated thrombocytopenia.422
 
The Marrow
Increased marrow megakaryocytes with a shift to younger, less polyploid megakaryocytes and fewer mature, platelet-producing megakaryocytes has been commonly reported.
 
Tests for Platelet Antibodies
Assays of PAIgG represent the first sensitive and reproducible method for demonstrating antibodies in ITP.
 
TREATMENT
 
1st Line Therapy
 
Corticosteroids
Corticosteroids are the standard initial treatment for patients with ITP. Corticosteroids prevent the destruction of platelets by macrophages within the spleen and liver thereby increasing platelet levels. The first-line treatment option is prednisone 0.5–2 mg/kg/day until the platelet count increases to over 30–50 × 109/L. Corticosteroids are usually prescribed as a short-term treatment (3–4 weeks). On stopping treatment, dose should always be tapered.
 
Immunoglobulins
Immunoglobulins are used to desensitize the immune system. Usually a dose of 1 g/kg body weight is given for 2–3 days. IVIg is indicated for patients at high risk of bleeding or before surgery to increase platelet counts. The response to IVIg is rapid but generally transient lasting between 2 and 4 weeks. Repeat infusions of IVIg at regular intervals can be done to maintain the platelet count at a safe level. Concomitant use with corticosteroids can attenuate the response.
 
2nd Line Therapy
 
Immunosuppressants
In patients with severe symptomatic ITP, more intensive immunosuppression may be required. Azathioprine response rates can be slow and patients should receive continuous treatment for at least 4 months before being considered unresponsive. Cyclosporin A can be used alone or in combination with prednisone. Mycophenolate mofetil is an antiproliferative immunosuppressant that has been used in a limited manner.
 
Corticosteroid-sparing Agents
Danazol is an attenuated androgen originally developed to treat endometriosis. The response rate is around 60%, with older patients appearing to respond better. 423Dapsone has anti-inflammatory and immunomodulatory effects. Response rates of around 50% have been reported. Dapsone may be particularly useful in elderly patients or if splenectomy is contraindicated.
 
Monoclonal Antibodies
Rituximab is a chimeric monoclonal antibody that binds to the CD20 surface antigen present on B-cells and acts as an immunosuppressant. Rituximab is widely used even though it is not indicated for ITP and the optimal dose has not been established.
 
Splenectomy
Splenectomy is indicated for patients who are refractory or intolerant to corticosteroids and have severe thrombocytopenia, bleeding or both. It is recommended to wait at least 6 months from diagnosis before performing a splenectomy in case of spontaneous remission.
 
Thrombopoietin Receptor Agonists
Thrombopoietin receptor agonists mimic the action of the body's endogenous thrombopoietin to stimulate the production of platelets in bone marrow. Unlike other available therapies they are not immunosuppressive. Two thrombopoietin receptor agonists are currently available—eltrombopag, a daily oral medication, and romiplostim, a once-weekly subcutaneous injection. Both are indicated for adult splenectomized patients who have ITP refractory to other treatments such as corticosteroids and immunoglobulins, and as second-line therapy for nonsplenectomized patients in whom surgery is contraindicated. A response (increase in platelet count) is usually seen within 1–2 weeks of treatment initiation in both splenectomized and nonsplenectomized patients. If there is no response to the highest dose after 4 weeks, the patient can be considered unresponsive.
 
Vinca Alkaloids
Vinca alkaloids, such as vincristine and vinblastine, are used in cancer to inhibit tumor cell growth. In ITP, vinca alkaloids may inhibit phagocytic cell function through binding to platelet microtubules, which may help localize treatment to the platelet-destroying phagocytic cells.
 
EMERGENCY TREATMENT OF ACUTE BLEEDING
In patients with severe bleeding, in addition to conventional critical care measures, appropriate treatment includes platelet transfusions, high-dose parenteral glucocorticoids, and IVIg. Platelet transfusions may produce some increase in platelet numbers in many patients, often diminish bleeding for a time, and can be effective in the management of serious complications, e.g. subarachnoid hemorrhage. They should be reserved for such life-threatening emergencies or for the immediate preoperative treatment of patients with serious hemorrhage 424before splenectomy. Dose of intravenous immunoglobulin is 1 g/kg/day for 2–3 days. Methylprednisolone is given at a dose of 1 g/day for 3 days.
 
BIBLIOGRAPHY
  1. Arnold DM, et al. Systematic review: efficacy and safety of rituximab for adults with idiopathic thrombocytopenic purpura. Ann Intern Med. 2007;146(1):25-33.
  2. British Committee for Standards in Haematology General Haematology Task Force. Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy. Br J Haematol. 2003;120(4):574-96.
  3. Bussel JB, et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med. 2007;357(22):2237-47.
  4. Civetta JM, Taylor RW, Kirby RR. Critical care, 4th edn. Philadelphia: Lippincott-Raven; 2009.
  5. Dutta TK, et al. Dapsone in treatment of chronic idiopathic thrombocytopenic purpura in adults. J Assoc Physicians India. 2001;49:421-5.
  6. Kaushansky K. Thrombopoietin. N Engl J Med. 1998;339(11):746-54.
  7. Kuter DJ, et al. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomized controlled trial. Lancet. 2008;371 (9610):395-403.
  8. Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscalzo J. Harrison's Principles of Internal Medicine, 18th edn. McGraw Hill publications; 2012.
  9. Maloisel F, et al. Danazol therapy in patients with chronic idiopathic thrombocytopenic purpura: long-term results. Am J Med. 2004;116(9):590-4.
  10. Provan D. Characteristics of immune thrombocytopenic purpura: a guide for clinical practice. Eur J Haematol. 2009;82(Suppl 71):8-12.
  11. Provan D, et al. International consensus report on the investigation and management of primary immune thrombocytopenia, Blood, 2009.
425Endocrine disorders in Intensive Care Unit
Chapter 57 Diabetic Ketoacidosis Vinoj, G Ninoo George
Chapter 58 Hyperosmolar Hyperglycemic State Vinoj, Ninoo George
Chapter 59 Diabetes I nsipidus Vinoj, Ninoo George
Chapter 60 Syndrome of Inappropriate Secretion of Antidiuretic Hormone Vinoj, Ninoo George
Chapter 61 Thyroid Emergencies Vinoj, Ninoo George
Chapter 62 Adrenal Emergencies Vinoj, Ninoo George426

DIABETIC KETOACIDOSISCHAPTER 57

Vinoj, G Ninoo George
Diabetic ketoacidosis (DKA) is a life-threatening metabolic disorder resulting from decreased effective circulating insulin, insulin resistance and increased production of counter-regulatory hormones. The frequency of DKA ranges from 16% to 80% of children newly diagnosed with diabetes, depending on geographic location. It is the leading cause of morbidity and is the most common cause of diabetes-related deaths in children and adolescents with type 1 diabetes. Mortality is predominantly due to cerebral edema. While it occurs predominantly in type 1 diabetic patients at the time of diagnosis, it can also happen in type 2 diabetes when medications are inadequately managed. DKA and HHS (hyperosmolar hyperglycemic hyperosmolar state) are present along a spectrum of hyperglycemia, with or without ketosis. DKA constitutes a triad of hyperglycemia, ketonemia and high anion gap metabolic acidosis which is given in Figure 57.1.
It is characterized by
Fig. 57.1: Triad of diabetic ketoacidosis
Laboratory parameters observed in diabetic ketoacidosis are as follows. Blood glucose concentration is usually around 250–600 mg/dL, plasma ketones are >3 mmol/L, serum bicarbonate is <15 mEq/L and arterial pH is in the range of 6.8 – 7.3 with increased anion gap. DKA and HHS are differentiated by the following parameters (Table 57.1).428
Table 57.1   DKA and HHS should be differentiated based on lab parameters
DKA
HHS
Glucose, mmol/L (mg/dL)
13.9–33.3 (250–600)
33.3–66.6 (600–1200)
Osmolality (mOsm/mL)
300–320
330 -380
Plasma ketones
++++
+/–
Arterial pH
6.8–7.3
>7.3
Arterial PCO2, mm Hg
20–30
Normal
Anion gap [Na–(Cl + HCO3)]
Normal to mild ↑
Serum bicarbonate, mEq/L
<15 mEq/L
Normal to mild ↓
Creatinine
Mild ↑
Moderate ↑
Sodium, mEq/L
125–135
135–145
Potassium
Normal to ↑
Normal
Abbreviations: DKA, diabetic ketoacidosis, HHS, hyperosmolar hyperglycemic
 
PRECIPITATING FACTORS
Several factors are known to precipitate ketoacidosis. The predominant ones are as follows.
  • Inadequate insulin therapy
  • New onset diabetes (20–25%)
  • Infections (30–45%)
  • Cerebrovascular accident, myocardial infarction, acute pancreatitis
  • Drugs: Clozapine, olanzapine (atypical antipsychotics)
  • Trauma, surgery
  • Pregnancy.
 
BASIC PATHOPHYSIOLOGY OF DIABETIC KETOACIDOSIS (Flow chart 57.1)
  • Absolute or relative insulin deficiency
  • Increased counter regulatory hormones
  • Decreased insulin/glucagon ratio promotes
    • Gluconeogenesis
    • Glycogenolysis
    • Ketone body formation
      • β-hydroxybutyrate is the major constituent
      • Acetone produces the fruity breath odor
      • Acetoacetate is commonly detected by sodium nitroprusside test.
 
CLINICAL FEATURES
 
Symptoms
  •   Nausea, vomiting (induced by β hydroxybutyrate)
  •   Thirst/polyuria429
    Flow chart 57.1: Pathogenesis of diabetic ketoacidosis
  •   Abdominal pain
  •   Shortness of breath.
 
Signs
  •   Tachycardia
  •   Dehydration/hypotension
  •   Tachypnea/respiratory distress/Kussmaul's respiration
  •   Acetone smell breath
  •   Abdominal tenderness
  •   Lethargy/loss of consciousness.
 
MANAGEMENT GOALS
430
 
ASSESSMENT AND MONITORING
  • Find out the factors which precipitated the event
  • Measure capillary glucose every 1–2 hour during treatment
  • Serum electrolytes: K+, Na+, Mg+, Cl, bicarbonate, phosphate and anion gap every 4 hours for the first 24 hours.
  • Acid base status: pH, HCO3, PCO2, β hydroxybutyrate
  • Renal function: Creatinine, Urine Output
  • Monitor blood pressure, pulse, respirations, mental status, fluid intake and output every 1–4 hour.
 
FLUID REPLACEMENT
  • Average fluid loss will be around 3–5 L
    • 3 L extracellular—replace with saline
    • 3 L intracellular—replace with dextrose
  •   Administer 2–3 L of 0.9% saline over first 1–3 hours (15–20 mL/kg/hour)
  •   Switch over to 0.45% saline at 250–500 mL/hour (when hemodynamic stability and adequate urine output are achieved).
  •   Change to 5% glucose in 0.45% saline when plasma glucose reaches 200 mg/dL.
 
INSULIN THERAPY
Short-acting regular insulin is preferred. Administer bolus dose of 0.1 U/kg IV. Start insulin infusion 0.1 U/kg/hour and increase the dose to 2-3 times if there is no response in 2–3 hours. If the initial serum potassium is <3.3 mmol/L (3.3 mEq/L), do not administer insulin until the potassium is corrected. If the initial serum potassium is >5.2 mmol/L (5.2 mEq/L), do not supplement K+ until the potassium is corrected. IV insulin should be continued until the acidosis resolves (when serum bicarbonate is >18 mEq/L). Once acidosis resolves, taper the dose of insulin to 0.5 U/kg/hour. Hyperglycemia usually improves at a rate of 75–100 mg/dL. Plasma glucose should be maintained at 150–200 mg/dL complications of DKA are given in detail in Table 57.2.
 
ELECTROLYTE CORRECTION
Replace potassium of 10 mEq/hour when plasma K+ <5.0–5.2 mEq/L (or 20–30 mEq/L of infusion fluid) and ECG is normal, and there is documented normal urine flow and normal creatinine. Administer 40–80 mEq/h when plasma K+ < 3.5 mEq/L or if bicarbonate is given. The goal is to maintain the serum potassium at >3.5 mmol/L (3.5 mEq/L).
Despite a bicarbonate deficit bicarbonate replacement is not usually necessary. However, in case of severe acidosis where arterial pH <6.9, sodium bicarbonate of 50 mEq/L is added in 200 mL of sterile water with 10 mEq/L KCl per hour for 2 hours until the pH is >7.0. Phosphate replacement is beneficial when serum phosphate is <1 mg/dL. Hypomagnesemia may develop during 431therapy and which may require supplementation. Patient is shifted to long-acting insulin once the patient is started on oral diet.
Table 57.2   Complications of DKA
Cerebral edema
It is the leading cause of mortality in children and is caused due to idiogenic osmoles which stabilizes brain cells from shrinking while DKA is developing
Hypokalemia
  • Precipitated by failing to correct the potassium deficit
  • This is caused by rehydration and insulin therapy which not only corrects acidosis but also facilitates potassium reentry into the cell
Hypoglycemia
Due to inadequate monitoring
Acute pulmonary edema
Due to excessive fluid therapy
Other complications
Cortical vein thrombosis, myocardial infarction, acute gastric dilatation, erosive gastritis, late hypoglycemia, respiratory distress, infections, hypophosphatemia
Abbreviations: DKA, diabetic ketoacidosis
 
BIBLIOGRAPHY
  1. American Diabetes Association. Clinical practice recommendations, 2002. Diabetes Care. 2002;25(Suppl)1:S1-147.
  2. Atkin SH, et al. Fingerstick glucose determination in shock. Ann Intern Med. 1991; 114(12):1020-4.
  3. Colledge NR, Walker BR, Ralston S, Davidson S. Davidson's Principles and Practice of Medicine, 22nd edn. Edinburgh: Churchill Livingstone/Elsevier publications.
  4. Emergency Nurses Association. Medical emergencies. In: ENPC provider manual, 2nd edn. Park Ridge (IL): The Association. 1999.p.273-301.
  5. Jabbour SA, Miller JL. Uncontrolled diabetes mellitus. Clin Lab Med. 2001;21(1):99-110.
  6. Kearney T, et al. Diabetic and endocrine emergencies. Postgrad Med J. 2007;83(976):79-86.
  7. Kitabchi AE, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32:1335.
  8. Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscalzo J. Harrison's Principles of Internal Medicine. McGraw Hill publications; 2012(18).
  9. National Center for Chronic Disease Prevention and Health Promotion. Diabetic ketoacidosis. In: Diabetes surveillance, Atlanta (GA): Centers for Disease Control and Prevention; 1999.
  10. Westphal SA. The occurrence of diabetic ketoacidosis in noninsulin-dependent diabetes and newly diagnosed diabetic adults. Am J Med. 1996;101(1):19-24.

HYPEROSMOLAR HYPERGLYCEMIC STATECHAPTER 58

Vinoj, G Ninoo George
Hyperosmolar hyperglycemic state (HHS) is a life-threatening emergency manifested by marked elevation of blood glucose, hyperosmolarity, and little or no ketosis. It is reported in all age groups, but it most frequently affects older patients with type 2 diabetes. The hallmark of hyperosmolar hyperglycemic state is profound dehydration, marked hyperglycemia, and often some degree of neurologic impairment with mild or no ketosis. The mortality rate of hyperosmolar hyperglycemic state ranges from 10% to 50%. Precipitating factors of HHS is given in Table 58.1.
 
PATHOPHYSIOLOGY
The initiating event in hyperosmolar hyperglycemic state is glucosuric diuresis. Glucosuria impairs the concentrating capacity of the kidney, further exacerbating water loss. Under normal conditions, the kidneys act as a safety valve to eliminate glucose above a certain threshold and prevent further accumulation. However, decreased intravascular volume or underlying renal disease decreases the glomerular filtration rate, causing the glucose level to increase. The loss of more water than sodium leads to hyperosmolarity. Although insulin is present, it is not adequate to reduce blood glucose levels, particularly in the presence of significant insulin resistance.
Table 58.1   Precipitating factors in hyperosmolar hyperglycemic state
  • Acute myocardial infarction
  • Cerebrovascular accident
  • Cushing's syndrome
  • Hyperthermia/Hypothermia
  • Pancreatitis
  • Renal failure
  • Infection
  • Medications like calcium channel blocker, chlorpromazine, glucocorticoids, phenytoin
  • Total parenteral nutrition
  • Noncompliance
  • Substance abuse
  • Undiagnosed diabetes
433
 
CLINICAL FEATURES
Patients typically present with weakness, visual disturbance, or leg cramps. Nausea and vomiting may occur, but are much less frequent than in patients with diabetic ketoacidosis. Eventually, patients develop neurologic symptoms of lethargy, confusion, hemiparesis or seizures. Physical findings reveal profound dehydration that is manifested by poor tissue turgor, dry buccal mucosa membranes; soft, sunken eyeballs; cool extremities; and a rapid, thready pulse. A low-grade fever often is present. Abdominal distention may occur because of gastroparesis induced by hypertonicity. Various changes in mental status may manifest, ranging from complete lucidity to disorientation to lethargy to coma.
 
Laboratory Findings
Typical laboratory findings in hyperosmolar hyperglycemic state include blood glucose levels greater than 600 mg per dL, serum osmolarity greater than 320 mOsm/kg, pH levels greater than 7.30, and mild or absent ketonemia. DKA and HHS are differentiated by the following parameters (Table 58.2).
 
Management
  •   IV 0.9% saline
  •   Correction of any hypokalemia
  •   IV insulin (as long as serum K is ≥3.3 mEq/L)
Fluid loss is more pronounced in HHS than DKA. Treatment is 0.9% saline solution 1–3 liter intravenously over the first 2–3 hours, then at 1 L/hour to raise blood pressure and improve circulation and urine output. If the serum sodium >150 mmol/L (150 mEq/L), 0.45% saline should be used. It can be replaced by 0.45% saline when blood pressure becomes normal and plasma glucose reaches 300 mg/dL. The rate of infusion of IV fluids should be adjusted depending on blood pressure, cardiac status, and the balance between fluid input and output. The average water deficit in HHS patients is 8–10 liters and fluid infusion should be done over 1–2 days at 200–300 mL/hour. Insulin is given at 0.1 U/kg IV bolus followed by a 0.1 unit/kg/hour infusion after the first liter of saline has been infused.
Table 58.2   Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemia state (HHS) should be differentiated based on lab parameters
DKA
HHS
Glucose, mmol/L (mg/dL)
13.9–33.3 (250–600)
33.3–66.6 (600–1200)
Osmolality (mOsm/mL)
300–320
330–380
Plasma ketones
++++
+/–
Arterial pH
6.8–7.3
>7.3
Arterial PCO2, mm Hg
20–30
Normal
Anion gap [Na – (Cl + HCO3)]
Normal to mild ↑
Serum bicarbonate, mEq/L
<15 mEq/L
Normal to mild ↓
Creatinine
Mild ↑
Moderate ↑
Sodium, mEq/L
125–135
135–145
Potassium
Normal to ↑
Normal
434Hydration alone can sometimes precipitously decrease plasma glucose, so insulin dose may need to be reduced. A too-quick reduction in osmolality can lead to cerebral edema. Once plasma glucose reaches 300 mg/dL, insulin infusion should be reduced to basal levels (1–2 units/h) until rehydration is complete and the patient is able to eat. Target plasma glucose is between 250 and 300 mg/dL. Addition of 5% dextrose infusion may occasionally be needed to avoid hypoglycemia. After recovery from the acute episode, patients are usually switched to adjusted doses of subcutaneous insulin. Most patients can resume using oral hypoglycemic drugs once their condition is stable.
Potassium replacement is similar to DKA
  •   40 mEq/h for serum K <3.3 mEq/L
  •   20 to 30 mEq/h for serum K between 3.3 and 4.9 mEq/L
  •   None for serum K ≥5 mEq/L.
 
BIBLIOGRAPHY
  1. American Diabetes Association. Clinical practice recommendations. Diabetes Care 2002;25(Suppl 1):S1–147.
  2. Colledge NR, Walker BR, Ralston S, Davidson S. Davidson's Principles and Practice of Medicine, 22nd edn. Edinburgh: Churchill Livingstone/Elsevier publications.
  3. Emergency Nurses Association. Medical emergencies. In: ENPC provider manual. 2nd edn. Park Ridge (IL): The Association; 1999.pp.273–301.
  4. Kearney T, et al. Diabetic and endocrine emergencies. Postgrad Med J. 2007;83(976): 79–86.
  5. Kitabchi AE, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32:1335.
  6. Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscalzo J. Harrison's Principles of Internal Medicine. 18th edn. McGraw Hill publications; 2012.

DIABETES INSIPIDUSCHAPTER 59

Vinoj, G Ninoo George
Diabetes insipidus is a rare syndrome characterized by the excretion of abnormal large volumes of dilute urine (polyuria) and a concomitant increase in fluid intake (polydipsia). Types of diabetes insipidus is given in Table 59.1.
 
VASOPRESSIN: NEURAL HORMONE
  •   Synthesis of the arginine vasopressin (AVP) and oxytocin precursors occurs in the cell bodies of magnocellular neurosecretory neurons within the supraoptic nucleus and paraventricular nucleus of the hypothalamus
  •   They migrate along the axons and get stored in secretory granules within the terminals of the magnocellular neurons in the posterior pituitary
  •   Vasopressin exerts its antidiuretic effect via V2 receptors in kidney and involves insertion of protein water channels called aquaporin.
  •   Vasopressin-responsive water channel in the collecting ducts is aquaporin-2
Table 59.1   Types of diabetes insipidus
Type of DI
Causes
Underlying mechanism
Nephrogenic diabetes insipidus
Acquired or genetic
Lack of renal sensitivity to circulating AVP
Primary polydipsia
Compulsive/habitual excessive intake of fluids
Excessive fluid intake despite normal AVP levels and sensitivity to the hormone
Gestational diabetes insipidus
Pregnancy
Lack of AVP due to increased metabolism of vasopressin by the enzyme vasopressinase, produced by the placenta
Central diabetes insipidus (pituitary/neurohypophyseal/cranial)
Disease, trauma, genetic mutation
Lack of production of AVP
436
 
ETIOLOGY
 
Nephrogenic Diabetic Insipidus
Nephrogenic diabetes insipidus (NDI), which can be congenital or acquired, results from failure of the kidney to respond to vasopressin.
 
Congenital Nephrogenic DI
  •   X-linked (90-95%) caused by mutation of V2 receptor gene (AVPR2) is located at chromosome region Xq28
  •   Autosomal dominant or autosomal recessive present in 5–10 % of patients caused by mutation of Aquaporin 2 gene (AQP2) located at chromosome region 12q13
  •   Sporadic nephrogenic DI with mental retardation and intracerebral calcification
 
Acquired Nephrogenic DI
  •   Acquired metabolic abnormalities—Hypokalemia, hypercalcemia
  •   Drugs—lithium, amphotericin b, diphenylhydantoin, foscarnet, cidofovir
  •   Medullary Damage—chronic pyelonephritis, cystinosis, sickle cell disease chronic renal failure, obstructive nephropathy, infiltrative disease (leukemia, lymphoma, amyloidosis).
 
Central Diabetic Insipidus
Central diabetes insipidus is caused due to decreased vasopressin production.
 
Acquired
  •   Idiopathic
  •   Tumors—Craniopharyngioma, germinoma, hypothalamic metastases (especially breast carcinoma), hypothalamic glioma, large pituitary tumors with suprasellar extension, lymphoma
  •   Intracranial surgery
  •   Head injury
  •   Granulomata — sarcoidosis, tuberculosis (TB), wegener's, histiocytosis
  •   Infections—encephalitis, meningitis, cerebral abscess
  •   Vascular disorders—hemorrhage/thrombosis, aneurysms, sickle cell disease, sheehans syndrome (postpartum pituitary necrosis)
  •   Postradiotherapy.
 
Inherited
  •   Autosomal recessive combination of diabetes insipidus, diabetes mellitus, optic atrophy, deafness (DIDMOAD)—Wolfram syndrome
  •   Autosomal dominant mutations of vasopressin gene.437
 
Gestational Diabetes Insipidus
This condition results from degradation of vasopressin by placental vasopressinase. Gestational diabetes insipidus may be associated with increased complications of pregnancy, including pre-eclampsia. Treatment for most cases of gestational diabetes insipidus is with the synthetic hormone desmopressin.
 
Primary Polydipsia (Dipsogenic Diabetes Insipidus)
It is caused by a primary defect in osmoregulation of thirst. Dipsogenic diabetes insipidus has been reported in tuberculous meningitis, multiple sclerosis, and neurosarcoidosis.
 
Clinical Manifestations of Diabetes Insipidus
The most common symptom in people with diabetes insipidus is passing large volumes of urine (Polyuria). This usually means that there is a need to go to the toilet frequently, often during the night, which results in disturbed sleep. Bladder control usually remains normal.
Large losses of water from the body results in a great increase in thirst (Polydipsia), to make up for the lost fluid. Therefore in individuals with diabetes insipidus, thirst becomes the regulator of water balance in the body. A person with diabetes insipidus may drink 6–20 liters of water per day, although in partial diabetes insipidus the amounts may be less.
Other signs may include needing to get up at night to urinate (nocturia) and bed-wetting (enuresis). Patient may also present with:
  •   Hypernatremic dehydration
  •   Anorexia, constipation
  •   Hyperthermia and lack of sweating
  •   Symptoms of underlying cause
Infants and young children who have diabetes insipidus may have the following signs and symptoms:
  •   Unexplained fussiness or inconsolable crying
  •   Unusually wet diapers
  •   Fever, vomiting or diarrhea
  •   Dry skin with cool extremities
  •   Delayed growth
  •   Weight loss.
 
Lab Investigations
  •   Biochemistry
    •   Plasma glucose, urea and electrolytes
    •   Plasma and urine osmolality
  •   Water deprivation test and response to desmopressin (Table 59.2). The patient is deprived of fluids for up to 8 hours or 5% loss of body weight, following which desmopressin (DDAVP) 2 µg (IM) is given. Plasma vasopressin levels and osmolality in response to infusion of 5% hypertonic saline at 0.05 mL/kg/minute for two hours may be measured in cases of diagnostic difficulty.438
    Table 59.2   Classification of causes of diabetes insipidus (DI) on basis of water deprivation and DDAVP response
    Urine osmolality after fluid deprivation (mOsm/kg)
    Urine osmolality after DDAVP (mOsm/kg)
    Likely diagnosis
    <300
    >800
    Central DI
    <300
    <300
    Nephrogenic DI
    >800
    >800
    Primary/psychogenic polydipsia
    <300
    >800
    Partial central DI or nephrogenic DI or primary/psychogenic polydipsia or diuretic abuse
  •   A therapeutic trial of low-dose desmopressin is another option, with careful monitoring of plasma osmolality or serum sodium. Central DI patients improve, and those with nephrogenic DI are unaffected. Those with psychogenic polydipsia develop hyponatremia and may stop drinking.
  •   MRI of the pituitary, hypothalamus and surrounding tissues, including the pineal gland, may be contributory in helping to determine the underlying cause.
  •   Renal tract ultrasound or intravenous pyelogram (IVP) may be used to assess for obstructive complications caused by the high urinary back-pressure.
 
Treatment of Central Diabetes Insipidus
  •   Since the primary problem is hormone deficiency, physiological replacement with desmopressin is usually effective. Criteria for desmopressin administration is given in Table 59.3.
  •   Desmopressin (DDAVP) acts on the distal tubules and collecting ducts of the kidney to increase water reabsorption, as a long-acting analog of anti-diuretic hormone (ADH).
 
Available Formulations
  •   Intranasal solution—100 µg/mL
  •   Intranasal spray (10 µg/spray)
  •   Parenteral (IM/IM)—4 µg/mL used rarely
  •   Oral—200 µg/tablet (roughly 10 µg intranasal dose is approximately equivalent to 200 µg orally).
Table 59.3   Criteria for desmopressin administration
Desmopressin should be administered only after the below criteria are fulfilled:
  • Serum sodium is >145 mmol/L
  • Urine output exceeds 4 mL/kg/hr (calculated 6 hourly)
  • Urine specific gravity is 1.005 or less (dilute urine output)
439
 
Administration—Principles
  •   Under 2 years, dose is usually 2–5 µg intranasally
  •   ≥2 years, dose is similar to adult dose (5–10 µg/day)
  •   Dosage effect is based on all or nothing principle—in general, the dose determines the duration of action and not the degree of response
  •   Oral dose has slower onset/offset of action, therefore not useful in acute situation
  •   Nasal administration is operator dependent—also need to consider effectiveness, if problems with nasal mucosa such as intercurrent upper respiratory infection, hayfever, etc.
  •   Careful fluid balance needs to be maintained to prevent fluid overload/hyponatremia.
Mild cases of DI (urine output 3-4 liters/24 hours) can be managed by ingestion of water to quench thirst. It is essential to avoid chronic overdosage with desmopressin since it will cause hyponatremia.
 
Long-term Management
Because of the risk of hyponatremia, occasional (1 to 3 monthly) measurements of serum sodium are advised. Some endocrinologists recommend skipping desmopressin administration for one day each week to avoid the development of hyponatremia.
 
Treatment of Nephrogenic Diabetes Insipidus
If daily urine volume is < 4 liters for 24 hours and the patient is not suffering from severe dehydration, then definitive therapy is not always necessary. It is essential to drink water and to drink enough to satiate their thirst. Any metabolic disturbance is corrected and in case of any suspicion of any drug causing the condition, it should be stopped. High-dose DDAVP can be used with success in mild-to-moderate cases of nephrogenic DI. Combination treatment with a thiazide diuretic and/or amiloride in combination with prostaglandin synthesis inhibitor and low-sodium diet may be effective in reducing polyuria and polydipsia. Patients with nephrogenic DI undergoing surgery need careful multidisciplinary management with close attention to fluid regimens and DDAVP administration. Patients with genetic causes or severe nephrogenic DI may need to practice clean, intermittent catheterization to reduce urinary tract back-pressure complications.
 
COMPLICATIONS
DDAVP can worsen myocardial ischemia in susceptible patients. There may be a need for nitrates/other antianginal medications. Patients with genetic causes of nephrogenic DI are prone to bladder dysfunction and hydroureter/hydronephrosis if the condition is undiagnosed or untreated for an appreciable period of time.440
 
BIBLIOGRAPHY
  1. Bichet D. Vasopressin receptor mutations in nephrogenic diabetes insipidus. Semin Nephrol. 2008;28:245.
  2. Cooperman M. Diabetes insipidus. http://emedicine.medscape.com/article/117648. Updated June 17, 2011. Accessed January 9, 2012.
  3. Loh JA, et al. Disorders of water and salt metabolism associated with pituitary disease. Endocrinol Metab Clin North Am. 2008;37(1):213–34.
  4. Makaryus AN, et al. Diabetes insipidus: diagnosis and treatment of a complex disease. Cleve Clin J Med. 2006;73(1):65–71.
  5. Sands JM, Layton HE. Urine concentrating mechanism and its regulation. In: Seldin DW, Giebisch G (Eds). The Kidney: Physiology and Pathophysiology, 3rd edn. Philadelphia: Lippincott Williams and Wilkins; 2000.pp.1175-216.
  6. Zerbe RL, Robertson GL. A comparison of plasma vasopressin measurements with a standard indirect test in the differential diagnosis of polyuria. N Engl J Med. 1981;305:1539-46.

SYNDROME OF INAPPROPRIATE SECRETION OF ANTIDIURETIC HORMONECHAPTER 60

Vinoj, G Ninoo George  
INTRODUCTION
The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a disorder of impaired water excretion caused by the inability to suppress the secretion of antidiuretic hormone (ADH). It is one of the most common causes of hyponatremia in critically-ill patients. It is commonly under-diagnosed and often mismanaged due to poor understanding of its pathophysiology. SIADH is one of the medical conditions where the treatment, if inappropriate, can be more damaging than the disease itself. However, if diagnosed and treated appropriately, the condition is easily reversible and one can avoid unnecessary disease or treatment-related morbidity and mortality.
 
PATHOPHYSIOLOGY
The knee-jerk reaction of many physicians on seeing hyponatremia in a patient is to initiate normal saline, with the presumption that hyponatremia always occurs due to loss of sodium from the body. While this is true in depletional hyponatremia (e.g. diarrhea), in most other cases of hyponatremia, this concept is fundamentally wrong. It is imperative to understand that hyponatremia is more of a disorder of water metabolism than sodium metabolism, with ADH being a key-player in initiation and maintenance of hyponatremia. Hence, any disturbance in ADH secretion will manifest itself as changes in serum sodium concentration.
Before moving into the pathophysiology of SIADH, let us understand normal water metabolism in our body. Water metabolism in humans is synonymous with ADH metabolism. The prime function of ADH is to maintain serum osmolality in the normal range of 285–295 mOsm/kg.
Serum osmolality >295 mOsm/kg causes stimulation of thirst and ADH release (ADH acts on the kidney leading to conservation of water, which reflects in production of concentrated urine). When serum osmolality <285 mOsm/kg, ADH secretion stops, thereby leading to production of dilute urine. This dilute urine excretes the excess free water restoring serum osmolality to normal.
Majority of cases of hyponatremia (>99%) which are clinically encountered are of the hypoosmolar type, since serum sodium is the principal determinant 442of serum osmolality. So extrapolating from our previous discussion, when hyponatremia occurs (i.e. serum osmolality <285 mOsm/kg), ADH secretion should stop and urine should become dilute. If this compensation occurs, then the water gain will be excreted and serum sodium (i.e. serum osmolality) will be restored to normal.
Apart from serum osmolality, another major stimulus for ADH release is effective arterial blood volume (EABV). When a person becomes volume depleted (e.g. diarrhea, dehydration, etc.) or EABV is low (e.g. CCF, cirrhosis, nephrotic syndrome), irrespective of his serum osmolality. ADH will be released (because the body is programmed in such a way to think that effective circulating blood volume is more important than serum osmolality).
From Table 60.1, one can understand that in any type of hyponatremia, ADH is elevated. Volume status should be identified in case of ↑ADH. If patient has effective volume depletion, then ADH is getting released appropriately. If patient does not have effective volume depletion, then ADH is released inappropriately as in SIADH (Flow chart 60.1).
 
Causes of SIADH
The usual causes of SIADH are malignancies, pulmonary and neurologic diseases. However, even severe pain, nausea and stress can lead to inappropriate ADH release. Postoperative patient suffering from pain, nausea and stress is prone to SIADH supported by the fact that they are put on intravenous dextrose infusions for nutritional support. The various causes of SIADH are summarized in Table 60.2.
Table 60.1   Differential diagnosis of SIADH
S. No.
Cause
Serum osmolality and sodium
ADH level
1.
Depletional Hyponatremia
(Diarrhea, vomiting, burns, renal loss, etc.)
Serum osmolality low
Serum sodium low
ADH elevated
Although according to serum osmolality, ADH should be suppressed, but since patient is volume depleted, ADH will be released. Thus, there is water gain causing hyponatremia in these conditions
2.
Hypervolemic hyponatremia (CCF, cirrhosis, nephrotic)
Serum osmolality low
Serum sodium low
ADH elevated
Although patient is fluid overloaded, but since patient's EABV is depleted, ADH will be released. Thus, there is water gain causing hyponatremia in these conditions
3.
SIADH (nausea, pain, stress, CNS, pulmonary disorders, etc.)
Serum osmolality low
Serum sodium low
ADH elevated
There is no physiologic stimulus for ADH release like osmolality or volume depletion. However, due to certain nonphysiologic stimulus, ADH is inappropriately released leading to water gain and hyponatremia
443
Flow chart 60.1: Pathogenesis of hyponatremia
444
Table 60.2   Causes of SIADH
Carcinomas
Pulmonary disorders
Nervous system disorders
Other
Bronchogenic and duodenal carcinoma
Bacterial and viral pneumonia
Encephalitis (viral or bacterial)
AIDS - HIV
Carcinoma of the pancreas
Tuberculosis
Meningitis (viral, bacterial, tuberculous, and fungal)
Idiopathic (elderly)
Gastric carcinoma
Pulmonary abscess
Head trauma
Prolonged exercise
Thymoma
Positive pressure ventilation
Brain abscess an tumors
Carcinoma of the bladder
Asthma
Subarachnoid hemorrhage or subdural hematoma
Lymphoma
Mesothelioma
Cerebellar and cerebral atrophy
Ewing's sarcoma
Cystic fibrosis
Cavernous sinus thrombosis
Carcinoma of the prostate
Pneumothorax
Guillain-Barré syndrome
Carcinoma of the ureter
Acute intermittent porphyria
Oropharyngeal carcinoma
445
Table 60.3   Diagnostic criteria of SIADH
Diagnostic criteria of SIADH
  •   Hyponatremia <135 mmol/liter together with decreased effective serum osmolality < 275 mOsm/kg
  •   Urinary osmolality >100 mOsm/kg
  •   Absence of heart, kidney and liver disease
  •   Urinary sodium concentration >40 mmol/liter, unless taking diuretics or on a severe salt restriction
  •   Normal adrenal and thyroid function
  •   Failure to correct hyponatremia by infusion of 0.9% NaCl
  •   Successful correction of hyponatremia by fluid restriction/vaptans
 
Clinical Features of SIADH
The clinical features of SIADH are secondary to the effects of hyponatremia. Thus the symptoms can vary from giddiness, gait disturbance, frequent falls, memory disturbance and cognitive defects in mild hyponatremia to altered sensorium, drowsiness, seizures and coma in extreme cases. More importantly, one should try to find out the presence of any underlying condition like malignancy, lung or neurologic diseases, which adds credence to the diagnosis of SIADH.
 
Diagnosis of SIADH (Table 60.3)
A rare differential diagnosis is cerebral salt-wasting syndrome. Its laboratory parameters resemble SIADH, although the spot urinary sodium concentration is usually much greater than 30–40 mmol/liter, sometimes exceeding 150 mmol/liter. Clinically, patients with cerebral salt-wasting syndrome cannot be subjected to fluid restriction since it would lead to hypovolemia and hypotension and they may require infusion of 0.9% or 3% NaCl to maintain blood pressure.
In clinical practice, the distinction between euvolemia and hypovolemia is difficult, thereby in such situations it would be helpful to infuse 0.9% NaCl of about 500–1000 mL over 12 hours and observe any alterations of serum sodium and the urinary sodium. In euvolemic SIADH, serum sodium will not change appreciably in response to 0.9% NaCl, but the urinary sodium will increase. Conversely, in hypovolemic hyponatremia the saline infusion will improve the serum sodium, leaving the urinary sodium more or less unchanged. A different type of clinical problem may arise from the combined occurrence of two etiologies of hyponatremia at the same time (Flow chart 60.2).
 
Treatment of SIADH
Various modalities have been tried in the treatment of SIADH. A brief discussion of the various modalities is mentioned here.
 
Free Water Restriction
Since the primary pathology in SIADH in retention of free water. Free water restriction is of prime importance to prevent further worsening of hyponatremia 446and may in some instances to correct hyponatremia. The normal osmolar load of a person's diet that needs to be excreted in urine daily is ~ 600 mOsm. Free water intake from oral intake and intravenous fluids should generally be < 1–1.5 liters/day and total intake of all liquids should be at least 500 mL less than urinary output. Thus, the amount of free water restriction that needs to be done depends on the urine osmolality. If the urine osmolality is very high (say more than 600 mOsm/L), then free water restriction less than 500 mL daily is required.
Flow chart 60.2: Differential diagnosis of hyponatremia
 
Increasing Osmolar Load in Diet
If the osmolar load is increased in the diet, then more free water is required to excrete the load, thus increasing free water clearance. This was previously one of 447the mainstays of treatment before vaptans became available. One can increase the osmolar load in diet by using salt tablets, urea, protein, etc. Urea in dosages of 10–40 g/day results in osmotic diuresis and enhanced water excretion. The drawback of urea is its taste; not all patients will accept it.
 
Overcoming ADH Action
Demeclocycline, an antibiotic (600–1200 mg/day), and lithium carbonate, an antidepressant (600–900 mg/day), may both cause nephrogenic diabetes insipidus, thus overcoming the action of ADH. This effect has been used to treat the hyponatremia of SIADH. However, nephrogenic diabetes insipidus takes 2–4 days to come about, does not occur in all patients receiving these agents, may be associated with renal toxicity (in the case of lithium), and corrects hyponatremia rather slowly by 2–4 mmol/liter/day. These drugs are not currently used very often to correct hyponatremia.
Role of Vaptans
The recent introduction of parenteral (conivaptan) and orally available (tolvaptan) antagonists to the renal V-2 vasopressin receptor—collectively called vaptans— has been considered a breakthrough. Conivaptan was originally developed as an oral preparation but is now available on the market as intravenous parenteral conivaptan. Eligible patients are treated in hospital. An initial loading dose of 20 mg over 30 minutes is recommended. This is followed by a continuous infusion at a rate of 20 mg/day for up to 4 days. In a study by Velez et al. this regimen increased the serum sodium from 121.7 to 129.2 mmol/liter within the first 24 hour of treatment. Lower serum sodium, lower blood urea nitrogen, and higher estimated glomerular filtration rate (eGFR) at baseline were correlated with a larger absolute increase in serum sodium at 24 hour. The following adverse events have been noted—infusion site reactions, including thrombophlebitis, postural hypotension, hypotension, mild-to-moderate increases in blood urea nitrogen or creatinine, and significantly increased thirst. Four of 42 patients corrected their hyponatremia too fast (Zeltser et al. 2007). No osmotic demyelination was noted.
Tolvaptan is available as a tablet, usually taken once a day in the morning. The recommended dosage for SIADH is 15–30 mg/day. Patients receiving tolvaptan should discontinue any previous fluid restriction and drink fluids freely though not excessively. The treatment should be initiated under close supervision by the hospital (as an outpatient or an inpatient). When given in this way, tolvaptan increased serum sodium from approximately 128–136 mmol/liter within 4 days in one study.
When vaptans are used, it is critical to monitor levels for the first 24 hour– exclude a too rapid correction rate. Any fluid restriction should be discontinued and drinking encouraged. Any increase in serum sodium of >6 mmol/liter by 6th hour of treatment is likely to result in a rise of >10 mmol/liter at 24 hours. In such cases, water should be given orally or intravenously [(by infusion, e.g. of 5% dextrose in water (D5W)] at hour 6 of treatment to slow the rate of correction. There is the possibility of a too rapid correction rate in cases of severe hyponatremia (<<120 mmol/liter) and in those with a high eGFR at baseline. It may not be always necessary to continue treatment until a serum sodium concentration of 136 mmol/liter or higher has been achieved; in some patients, symptoms will disappear at a serum sodium concentration of 130 mmol/liter.448
 
Use of Hypertonic Saline
One of the common errors in clinical practice is to initiate normal saline (0.9%) for SIADH. This is potentially dangerous and can lead to worsening of hyponatremia. However, with use of 3% saline, hyponatremia can be corrected in SIADH. One method to calculate the rate of correction is provided by the Adrogué–Madias formula (see formula). The formula calculates the change in the serum sodium concentration that is expected to result from an infusion of saline solution. By comparing this total change in the serum sodium with the desired rate of correction per hour, it is then possible to derive the hourly infusion rate. The formula may underestimate the change in serum sodium actually achieved and this applies to severe hyponatremia (<120 mmol/liter) in particular. Therefore, it is advisable to follow the actual serum sodium closely, for example, every 3 hour when infusing various concentrations of saline.
where
NaSerum  =  Calculated change in serum sodium
Volinf  =  Volume of infused saline
Nainf  =  Sodium concentration of saline infusion
TBW  =  Total body water (approx 50% of body weight in women, 60% of body weight in men)
 
Risk of Osmotic Demyelination Syndrome
Osmotic demyelination syndrome is a pathological condition that occurs due to over-rapid correction of serum sodium. A correction rate of <8–10 mmol/L per day should be strictly followed while treating SIADH. Causes of over-correction include sudden amelioration of stimulus of ADH release, use of loop diuretics, simultaneous correction of potassium, etc. To avoid risk of over-correction, close monitoring of sodium every 4 hours is mandatory especially while correcting severe hyponatremia.
 
BIBLIOGRAPHY
  1. Adrogué HJ, Madias NE. Hyponatremia. N Engl J Med. 2000;342:1581-9.
  2. Annane D, Decaux G, Smith N. Efficacy and safety of oral conivaptan, a vasopressin-receptor antagonist, evaluated in a randomized, controlled trial in patients with euvolemic or hypervolemic hyponatremia. Am J Med Sci. 2009;337:28-36.
  3. Berl T, Quittnat-Pelletier F, Verbalis G, Schrier RW, Bichet DG, Ouyang J, et al. Oral tolvaptan is safe and effective in chronic hyponatremia. J Am Soc Nephrol. 2010;21: 705–12.
  4. Berl T. The Adrogué–Madias formula revisited. Clin J Am Soc Nephrol. 2007;2:1098-9.
  5. Decaux G, Waterlot Y, Genette F, Mockel J. Treatment of the syndrome of inappropriate secretion of antidiuretic hormone with furosemide. N Engl J Med. 1981;304:329-30.
  6. Decaux G. Is asymptomatic hyponatremia really asymptomatic? Am J Med. 2006;119(7 Suppl 1):S79-82.
  7. 449Ellison DH, Berl T. The syndrome of inappropriate antidiuresis. N Engl J Med. 2007;356: 2064-72.
  8. Gross P. Clinical management of SIADH. Ther Adv Endocrinol Metab. 2012;3(2):61-73.
  9. Schrier RW, Gross P, Gheorghiade M, Berl T, Verbalis JG, Czerwiec FS, et al. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med. 2006;355:2099–12.
  10. Velez JCQ, Dopson SJ, Sanders DS, Delay TA, Arthur JM. Intravenous conivaptan for the treatment of hyponatremia caused by the syndrome of inappropriate secretion of antidiuretic hormone in hospitalized patients: a single-centre experience. Nephrol Dial Transplant. 2010;25:1524–31. 

THYROID EMERGENCIESCHAPTER 61

Vinoj, G Ninoo George  
INTRODUCTION
Thyroid emergencies are rare, life-threatening conditions resulting from either severe deficiency of thyroid hormones (myxedema coma) or, by contrast, decompensated thyrotoxicosis with the increased action of thyroxine (T4) and triiodothyronine (T3) exceeding metabolic demands of the organism (thyrotoxic storm). Another emergency condition is the thyroid ophthalmopathy.
The understanding of the pathogenesis of these conditions, appropriate recognition of the clinical signs and symptoms, and their prompt and accurate diagnosis and treatment are crucial in optimizing survival.
 
THYROID STORM
It is a dreaded fortunately rare complication of a very common disorder. It is a life-threatening exacerbation of hyperthyroidism. It is also called thyrotoxic crisis. It has a mortality rate up to 30%. The mortality is mainly due to cardiac failure, arrhythmia or hyperthermia.
 
Clinical Features
The clinical diagnosis is based on the identification of signs and symptoms that suggest decompensation of several organ systems. Some of these cardinal manifestations include fever out of proportion to an apparent infection and dramatic diaphoresis.
The other key components of thyrotoxic storm include tachycardia out of proportion to the fever, and gastrointestinal dysfunction, which can include nausea, vomiting, diarrhea and, in severe cases, jaundice. As the storm progresses, symptoms of central nervous system dysfunction simulating an encephalopathic picture will appear, which may include increasing agitation and emotional lability, confusion, paranoia, psychosis, and coma. In older patients, thyrotoxic storm may present as so-called masked or apathetic thyrotoxicosis.
 
Precipitating Factors
  •   Stroke
  •   Injection
  • 451  Trauma
  •   Diabetic ketoacidosis
  •   Surgery especially on the thyroid
  •   Radioiodine therapy.
 
Scoring (Table 61.1)
  •   >45 = Highly suggestive of thyroid storm
  •   25–44 = Suggestive of impending storm
  •   <25 = Unlikely to represent storm.
Table 61.1   Burch and Wartofsky diagnostic criteria
Diagnostic parameters
Scoring points
Thermoregulatory dysfunction
Temperature °F (°C)
  • 99–99.9 (37.2-37.7)
  • 100–100.9 (37.8–38.2)
  • 101–101.9 (38.3–38.8)
  • 102–102.9 (38.9–39.2)
  • 103–103.9 (39.3–39.9)
  • >/= 104.0 (>/= 40.0)
5
10
15
20
25
30
Central nervous system effects
  • Absent
  • Mild (agitation)
  • Moderate (delirium, psychosis, extreme lethargy)
  • Severe (seizures, coma)
0
10
20
30
Gastrointestinal-hepatic dysfunction
  • Absent
  • Moderate (diarrhea, nausea/vomiting, abdominal pain)
  • Severe (unexplained jaundice)
0 10 20
Cardiovascular dysfunction
Tachycardia (beats/minute)
  • 90–109
  • 101–119
  • 120–129
  • 130–139
  • >/= 140
5
10
15
20
25
Congestive heart failure
  • Absent
  • Mild (pedal edema)
  • Moderate (bibasilar crepitations)
  • Severe (pulmonary edema)
0
5
10
15
Atrial fibrillation
  • Absent
  • Present
Precipitating event
  • Absent
  • Present
0
10
0
10
 
Management
Requires a multifaceted approach:
  1. Intensive monitoring and supportive care
  2. Identification and treatment of the precipitating cause
  3. Measures-reducing thyroid hormone synthesis.
The mainstay of treatment is to ward-off the hyperthyroidism. This requires administration of antithyroid drugs, SSKI (5% Super Saturated Potassium Iodide), beta-blocker—propranolol, steroids.
 
Pharmacologic Therapy
  • Propylthiouracil is the drug of choice. It inhibits thyroid hormone synthesis by inhibiting thyroid peroxidase enzyme as well as blocks peripheral conversion of T3 to T4. A loading dose of 600 mg is given IV followed by 200–300 mg 6th hourly via oral or through nasogastric tube or rectally.
  • One hour after the loading dose of propylthiouracil give 5% Super Saturated Potassium Iodide (SSKI) 6th hourly which blocks thyroid hormone synthesis via the Wolff-Chaikoff effect. Iopanoic acid or sodium iodide may be used as an alternative.
  • Next drug to be given is the non selective β-blocker propranolol which acts by inhibiting the peripheral conversion of T4 to T3. It controls the tachycardia. A dose of 40–60 mg per oral 4th hourly or 2 mg IV 4th hourly can be given.
  • Other supporting measures include dexamethasone 2 mg IV 6th hourly. Antibiotics, if infection is present, cooling, administration of O2 and IV fluids.
 
Thyroid Ophthalmopathy
Severe thyroid ophthalmopathy with optic nerve involvement or chemosis resulting in corneal damage is a medical emergency. A short-term high-dose steroid is the treatment of choice.
  •   Prednisolone 40–80 mg daily can be combined with cyclosporine. Dose should be tapered by 5 mg every 2 weeks.
  •   Pulse therapy with IV methyl prednisolone of 500–1000 mg in 250 mL normal saline infused over 2 hour daily for 1 week followed by oral regimen.
  •   In case of failure of medical management, orbital decompression can be tried.
 
MYXEDEMA COMA
It is an uncommon but life-threatening form of untreated hypothyroidism with physiological decompensation. This complication occurs following cessation of thyroid replacement medication due to poor compliance or in an undiagnosed patient. The most common presentation of the syndrome is in hospitalized elderly women with long-standing hypothyroidism, with 80% of cases occurring in women older than 60 years. However, myxedema coma occurs in younger patients as well (Table 61.2).452
Table 61.2   Precipitating factors of myxedema coma
Hypothermia
Congestive cardiac failure
Cerebrovascular accidents
Myocardial infarction
Gastrointestinal bleeding
Infection
  • Pneumonia
  • Urinary tract infection
  • Cellulitis
  • Sepsis
Drugs
  • Amiodarone
  • Lithium
  • Respiratory depressants—sedatives, antidepressants, anesthetic agents
 
PATHOGENESIS
Hypoventilation, leading to hypoxia and hypercapnia, plays a major role in pathogenesis. Hypoglycemia and dilutional hyponatremia also contribute to the development of myxedema coma. Hypothermia produces cardiac depression which results in diminished cardiac output and that causes a reflex peripheral vasoconstriction. This leads to a mild diastolic hypertension and diminished blood volume.
 
Clinical Features (Fig. 61.1)
Hypothermia (often profound to 26.7°C and unconsciousness constitute two of the cardinal features of myxedema coma. Of importance is the coincident infection may be masked by hypothyroidism, with a patient presenting as afebrile despite an underlying severe infection. Although coma is the predominant clinical presentation, a history of disorientation, depression, paranoia, or hallucinations (myxedema madness) may often be elicited.
The neurologic findings may also include cerebellar signs (poorly coordinated purposeful movements of the hands and feet, ataxia, adiadochokinesia), poor memory and recall, or even frank amnesia, and abnormal findings on electroencephalography (low amplitude and a decreased rate of α-wave activity). Status epilepticus has been also described and up to 25% of patients may experience seizures possibly related to hyponatremia, hypoglycemia, or hypoxemia.
 
Diagnosis
  •   Serum T4 and intracellular T3 levels will be low
  •   Serum TSH level is high
  •   Serum TSH level is low in central hypothyroidism which is a very rare entity
  •   Other investigations
    •   Serum electrolytes453
      Fig. 61.1: Clinical manifestations of myxedema coma
    •   ECG
    •   Central venous pressure monitoring
    •   Arterial blood gas analysis
 
Treatment Goals (Fig. 61.2)
Fig. 61.2: Management modalities of myxedema coma
454
 
General Measures in Management
  •   Airway protection from aspiration in patients with poor consciousness level should be given utmost priority.
  •   It is better to avoid sedatives.
  •   Correction of hyponatremia.
  •   It may be prudent to administer 3% sodium chloride along with furosemide so that serum sodium may be elevated by 3–4 mEq/L to tide over the immediate crisis.
 
Hormone Replacement
  •   Thyroid hormone therapy is the backbone of treatment of patients with myxedema coma.
  •   At present, oral and intravenous T4 and T3 are used.
  •   T4 (levothyroxine) therapy provides steady, smooth and slow onset action. It avoids major peaks and troughs in the body. It is also easily available. It can be given as a single bolus of 500 µg. Though repeat dose is not required for few days, it is usually continued at a dose of 50–100 µg/day. T4 level rises acutely to levels above normal and slowly get converted to T3. If IV preparation is not available, levothyroxine can be given through nasogastric tube by the same initial dose.
  •   Advantages of liothyronine (T3) therapy:
    •   Early onset of action
    •   Beneficial effect on neuropsychiatric symptoms.
    •   Dose = T3 is given at a dose of 10–20 µg bolus either IV or through nasogastric tube followed by 10 µg which is given after 24 hours and thereafter 10 µg every 4 hourly for the next few days till patient is able to take orally.
    •   Liothyronine in excessive can cause arrhythmias.
  •   Another option is to combine levothyroxine 200 µg and liothyronine 25 µg as single bolus dose IV followed by daily treatment with levothyroxine 50–100 µg/day and liothyronine 10 µg/8th hourly.
 
Predictors of Mortality
  •   Hypotension, bradycardia at presentation.
  •   Need for mechanical ventilation
  •   Hypothermia unresponsiveness to treatment
  •   Sepsis
  •   Low Glasgow coma score (GCS), high APACHE II and sequential organ failure assessment (SOFA) score>6.
 
BIBLIOGRAPHY
  1. Colledge NR, Walker BR, Ralston S, Davidson S. Davidson's Principles and Practice of Medicine, 22nd edn. Edinburgh: Churchill Livingstone/Elsevier.
  2. Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscalzo J. Harrison's Principles of Internal Medicine, 18th edn. McGraw Hill Publications; 2012.
  3. Wartofsky L. Myxoedema coma, endocrinology metabolism. Clinics of North America, 2006;35:687-98.
  4. Yamamoto T, Fukuyama J, Fujiyoshi A. Factors associated with mortality of myxedema coma: report of eight cases and literature survey. Thyroid. 1999;9(12):1167-74.

ADRENAL EMERGENCIESCHAPTER 62

Vinoj, G Ninoo George  
ADRENAL CRISIS
Glucocorticoids (mainly cortisol) and mineralocorticoids (mainly aldosterone) are important for life and its production by the adrenal glands is especially important at times when the body experiences intense ‘stress’, such as surgery, trauma or serious infection. If the adrenal glands cannot produce enough cortisol, the body might not be able to cope with this kind of major stress, which can be life-threatening.
  •   This situation is called adrenal crisis and is a medical emergency.
  •   Any patient with unexplained hypotension in the intensive care unit, think of Adrenal crisis.
It is also known as Addisonian crisis or acute adrenal insufficiency.
 
Pathophysiology
The basic pathology is insufficient levels of cortisol and aldosterone. Crisis occurs when the physiological demand for the hormones exceeds the ability of adrenal glands to produce cortisol. This scenario usually occurs in a patient with chronic adrenal insufficiency when subjected to an intercurrent stress or illness.
 
Etiology of Adrenal Insufficiency
Adrenal insufficiency arises if the adrenal glands are destroyed, absent or cannot function. Failure of the adrenal glands themselves is called primary adrenal insufficiency or Addison's disease (most common) (Table 62.1).
Serum ACTH level is used to differentiate between primary and secondary adrenal insufficiency.
 
PRIMARY (↑ ACTH)
Addison's disease is most often caused by autoimmune disease where the body's immune system mounts an attack against its own adrenal cells. However, it can also be caused by infection, most importantly by tuberculosis.
Sometimes both adrenal glands are surgically removed for various reasons. This is called a bilateral adrenalectomy and is another cause of primary adrenal 456insufficiency. Suppression of HPA axis can occur only after 5 days of treatment with glucocorticoids. Patients who were on glucocorticoids for at least 1 month and patients who discontinued glucocorticoids within the last year are candidates who have the highest risk for adrenal suppression.
Table 62.1   Etiology of adrenal insufficiency—primary and secondary causes
Primary causes
Addison's disease
Common causes
  • Autoimmune
  •   Sepsis
  • Hemorrhage secondary to trauma
  • Tuberculosis
  • HIV/AIDS
  • Metastatic carcinoma
  • Bilateral adrenalectomy
  • Drug induced
  • Critical illness
Rare causes
  • Lymphoma
  • Intra-adrenal hemorrhage (Waterhouse Friedrichsen syndrome following meningococcal septicemia)
  • Amyloidosis
  • Hemochromatosis
Corticosteroid biosynthetic enzyme defects
Congenital adrenal hyperplasia
Drugs
  • Metyrapone
  • Ketoconazole
  • Etomidate
Secondary (↓ ACTH)
Withdrawal of suppressive glucocorticoid therapy
Hypothalamic or pituitary disease
Loss of the pituitary gland ability to produce ACTH is most often caused by a tumor in that area. Secondary adrenal insufficiency results due to the loss of production and control of ACTH by pituitary gland.
 
Precipitating Factors
  •   Gastrointestinal infection
  •   Fever
  •   Surgery
  •   Burns
  •   General anesthesia
457
Table 62.2   Clinical manifestations of adrenal insufficiency
Signs and symptoms caused by glucocorticoid deficiency
Fatigue, weight loss, joint pain, myalgia
Fever, anemia, lymphocytosis, eosinophilia
Hypoglycemia, hyponatremia
Hypotension especially postural
Signs and symptoms caused by mineralocorticoid deficiency
Abdominal pain, nausea, vomiting
Dizziness
Salt craving
Low blood pressure, postural hypotension
Increased serum creatinine (due to volume depletion)
Hyponatremia
Hyperkalemia
 
Clinical Features
Clinical signs and symptoms of adrenal insufficiency usually develop gradually and can include severe fatigue and weakness, loss of weight, increased pigmentation of the skin, faintness and low blood pressure, often with a particular drop in blood pressure shortly after standing up (postural hypotension). Other symptoms include nausea, vomiting, salt craving and painful muscles and joints. Hyperpigmentation occurs due to excess of pro-opiomelanocortin (POMC)-derived peptides (Table 62.2).
 
Investigations
  • Fasting blood sugar
  • ACTH stimulation test: To establish the diagnosis of adrenal insufficiency with confidence, a short synacthen test (SST) needs to be performed. This test is also known as an ACTH stimulation test or a cosyntropin test. The short synacthen test measures the ability of the adrenal glands to produce cortisol in response to ACTH, the pituitary hormone that regulates adrenal cortisol production. When carrying out this test, a baseline blood sample is drawn before injecting a dose of ACTH, followed by drawing of a second blood sample 30–60 minutes after the ACTH injection. If the adrenal glands are healthy, cortisol production in the second sample will exceed commonly 500–550 nmol/L. By contrast, failing adrenal glands will not be able to produce this amount of cortisol. The term critical illness-related corticosteroid insufficiency is used for considering adrenal function.
  • Serum cortisol level: Serum-free cortisol <10 µg/dL is used as a threshold for glucocorticoid therapy.
  • Serum sodium and potassium estimation.
458
 
Treatment Goals
 
Volume Correction
  •   IV normal saline 500–100 mL for adults, 10–20 mL/kg for child.
  •   In severe hyponatremia (<125 mmol/L), avoid increase of plasma sodium >10 mmol/L/day to prevent pontine demyelination.
  •   Fludrocortisone is not required during the acute phase of treatment.
 
Glucocorticoids Replacement for Primary Insufficiency
  •   IV hydrocortisone succinate 100 mg stat
  •   Continue parenteral hydrocortisone 50–100 mg IV over 24 hours and after initial stabilization of the patient, hydrocortisone is decreased by 50% each day.
  •   Maintenance dose of hydrocortisone is 20–30 mg/day.
  •   According to current SSC guidelines, recommendation for use of steroids in sepsis is that intravenous hydrocortisone not routinely used to treat patients with septic shock if hemodynamic stability is achieved with fluids and vasopressors. If this is not possible, intravenous hydrocortisone is used as a continuous infusion of 200 mg/day. Corticosteroids should not be administered for the treatment of sepsis in the absence of shock and ACTH stimulation test is done to identify patients who require steroids. Hydrocortisone is tapered when vasopressors are not required.
  •   Perioperative replacement—For minor surgeries, a single supplemental dose of 25 mg of hydrocortisone or its equivalent is given. For major surgeries, dose of glucocorticoids is increased from 50 to 75 mg/day of hydrocortisone or its equivalent up to 2 days.
 
Correction of Metabolic Abnormalities
  •   Acute hypoglycemia—IV 10% glucose
  •   Correction of hyperkalemia
    •   Stabilize cell membrane potential
      • IV calcium gluconate (10 mL of 10% solution)
    •   Shift K+ into cells
      • Inhaled β2 agonist, e.g. Salbutamol
      • IV glucose (50 mL of 50% solution) and 5U insulin
      • Intravenous sodium bicarbonate
    •   Remove K+ from body
      • IV furosemide and normal saline
      • Ion exchange resin orally or rectally
      • Dialysis
459
 
Treatment of Underlying Cause
  •   Consider acute infection.
  •   Consider adrenal or pituitary pathology.
 
BIBLIOGRAPHY
  1. Arlt W, Allolio B. Adrenal insufficiency. Lancet. 2003;361:1881-93.
  2. Arlt W, et al. Dehydroepiandrosterone replacement in women with adrenal insufficiency. New England Medical Journal. 2003;341(14):1013-20.
  3. Colledge NR, Walker BR, Ralston S, Davidson S. Davidson's Principles and Practice of Medicine, 22nd edn. Edinburgh, Churchill Livingstone/Elsevier publications.
  4. Longo DL, Kasper DL, Jameson JL, et al. Harrison's principles of internal medicine, 18th ed. McGraw Hill publications; 2012.
  5. Guinot M, Duclos M, Idres N, Souberbielle Jc, Megret A, Bouc Y. Value of basal serum cortisol to detect corticosteroid-induced adrenal insufficiency. In: Elite Cyclists. European Journal Applied Physiology. 2007;99:205-16.
  6. Gurnell EM, et al. Long-term replacement. In: Primary adrenal insufficiency: A randomized, controlled trial. The Journal of Clinical Endocrinology & Metabolism. 2008;93(2):400-09.
  7. Hahner S, Allolio B. Management of adrenal insufficiency. In different clinical settings. Expert Opinions in Pharmacotherapy. 2005;6(14):2407-17.
460Obstetric emergencies
Chapter 63 Obstetric Hemorrhage Prem Kumar
Chapter 64 Hypertensive Disorders of Pregnancy Prem Kumar
Chapter 65 Acute Fatty Liver of Pregnancy Prem Kumar
Chapter 66 Amniotic Fluid Embolism Prem Kumar461

OBSTETRIC HEMORRHAGECHAPTER 63

Prem Kumar
Obstetric hemorrhage still remains a major cause of maternal morbidity and mortality. In fact, postpartum hemorrhage is still the leading cause of death in developing countries. There is a normal physiologic blood loss at the time of delivery. In an average vaginal delivery, the patient loses on an average of 300 to 500 mL and it is 1,000 to 1,500 mL with cesarean section. The increased blood volume in pregnant patients compensates this loss. In case of severe hemorrhage, medical and surgical intervention is needed. The obstetrician, intensivist and the anesthesiologist is involved in most of the obstetric emergencies related to hemorrhage.
 
CAUSES OF OBSTETRIC HEMORRHAGE
Antepartum hemorrhage
Postpartum hemorrhage
Abruption of placenta
Atonicity of uterus
Placenta previa
Retained placenta
Vasa previa
Placenta accreta
Rupture of uterus
Uterine inversion
Genital trauma
 
CLASSIFICATION
It is shown in Table 63.1
Table 63.1   Classification of blood loss in obstetric hemorrhage
Blood low
Clinical features
Severity
<15%
Minimal on none
15–25%
Tachycardia (<100/min) mild hypotension
Mild
25–35%
Tachycardia (>100/min), hypotension, oliguria, confused, tachypnea
Moderate
>35%
Tachycardia (>120/min), severe hypotension, anuria, tachypnea, obtunded consciousness
Severe
464
 
ANTEPARTUM HEMORRHAGE
Most of the causes of antepartum hemorrhage is due to either abruption of placenta or placenta previa. These causes of placental hemorrhage produce more adverse effects on the fetus than the mother. First and second trimester conditions such as spontaneous abortion and ectopic pregnancy can lead to blood loss and if it is significant, then the patient is monitored in the ICU continuous hemodynamic monitoring. Fluid management and blood transfusion is required to prevent hypovolemic shock. Third trimester bleeding causes are usually placental (e.g. Placenta previa, abruption of placenta).
 
Placenta Previa
Placenta previa is when the placenta covers the cervical os. It can be total or partial. Total type—placenta covers the entire cervical os. Partial type—placenta covers a part of cervical os. They present with painless vaginal bleeding. The absence of abdominal pain and abnormal uterine tone distinguishes placenta previa from placental abruption. Diagnosis is usually made with ultrasound. Vaginal examinations are best avoided. Once the condition is diagnosed, bedrest and monitoring of mother and fetus is done. Expectant management mandates access to a higher center with 24-hour obstetric and anesthesia services and a neonatal intensive care unit.
 
Criteria for Terminating Expectant Management
  •   Patient has active labor
  •   Gestational age reaches 37 weeks
  •   Fetus attains lung maturity
  •   Presence of excessive bleeding occurs.
Tocolytic therapy is not advised for patients with anticipated placental abruption or uncontrolled hemorrhage. If the patient is taken for cesarean section, at least 4 packed red cells are kept on table and 2 wide bore cannulas are started preinduction with anticipation of severe intraoperative hemorrhage. Anesthesia can be quite challenging in these patients, hence a senior person should be available to manage these cases. Sometimes, the patient may have placental abnormalities (accreta abutting the myometrium, increta invading partially into the myometrium, and percreta invading through the myometrium). These conditions may require hysterectomy during cesarean section in case of uncontrolled bleeding.
 
Abruption of Placenta
Placental abruption is premature separation of placenta from the uterine wall usually from the decidua basalis. Clinical features are vaginal bleeding or concealed bleeding within the uterus, abdominal tenderness and increased uterine activity. The risk of abruption is fetal hypoxia and it can lead to fetal distress or intrauterine death. Abruption also causes a decrease in the placental surface available for exchange of oxygen and hence fetal distress. Abruption is 465the most common cause of disseminated intravascular coagulation (DIC) in pregnancy.
 
Common Complications Associated with Placental Abruption
  •   Hypovolemic shock
  •   Coagulopathy
  •   Fetal distress or death
  •   Acute renal failure.
Diagnosis is by clinical presentation and ultrasound which may show the presence of retroplacental hematoma. Fetal heart rate monitoring and maternal hemodynamics should be monitored. Wide bore cannula is started and blood sent for cross-matching. Hemoglobin and coagulation studies are done. Initial management is done with fluid therapy and blood transfusion. The presence of fetal blood in maternal circulation is found by Kleihauer-Betke test.
 
Criteria for Conservative Management
  •   Maternal hemodynamics stable
  •   Fetus stable
  •   Abruption not severe
  •   Mother not at term.
If bleeding does not arrest during delivery, considering the risk of the mother's life, uterine artery ligation or hysterectomy may be necessary. If there is coagulopathy, fresh frozen plasma or cryoprecipitate may be required.
 
Vasa Previa
Velamentous insertion of the cord where fetal vessels traverse the fetal membranes ahead of the fetal presenting part is called vasa previa. Membrane rupture can be associated with fetal vessel rupture leading to fetal demise. This condition is associated with high fetal mortality (50–70%). The treatment of vasa previa is directed solely toward ensuring fetal survival. Ruptured vasa previa is an obstetric emergency which needs immediate delivery by cesarean section. Attention should be given for neonatal volume replacement during resuscitation.
 
POSTPARTUM HEMORRHAGE
Postpartum hemorrhage (PPH) is defined as blood loss more than 500 mL in vaginal delivery, and it is more than 1,000 mL with cesarean section. Though this definition is arbitrary, still this can be used as a guide for management.
  •   Primary PPH—occurs first 24 hours after delivery
  •   Secondary PPH—occurs between 24 hours and 6 weeks postpartum.
The most common cause of PPH is uterine atony and it occurs in the immediate postpartum period. Other causes are retained placenta, coagulopathy, genital trauma (lacerations of the cervix and vagina). Delayed hemorrhage occurs due to retained placenta. Soft uterus and vaginal bleeding are clinical features of uterine atony. In case of uterine atony, bimanual compression, uterine massage 466and uterotonic agents are given. Blood typing and cross-matching should be done along with complete blood count and coagulation studies. The goal of treatment is early restoration of blood pressure and hematocrit. Placenta accreta is defined as an abnormally adherent placenta. There are three types:
Table 63.2   Pharmacologic therapy for uterine atony
Drug
Dose
Adverse effects
Oxytocin
20–60 IU/L intravenous infusion
Hypotension, cardiac arrhythmias
Methylergonovine
0.2 mg intramuscular
Contraindicated in cardiac disease and hypertension since it causes arteriolar constriction and causes rise in blood pressure
15-methylprostaglandin F2α
250 µg intramuscular or intramyometrially
Bronchoconstriction, contraindicated in pulmonary hypertension
  1. Placenta accreta vera—adherence to the myometrium without invasion of or passage through uterine muscle.
  2. Placenta increta—invasion of the myometrium.
  3. Placenta percreta—invasion of the uterine serosa or other pelvic structures.
 
 
Role of Intensivist or Anesthesiologist in Uterine Atony (Table 63.2)
  •   Wide-bore cannula
  •   Supplemental oxygen
  •   Adequate fluid resuscitation based on hemodynamics
  •   Administration of uterotonic agents.
 
Management of Severe Blood Loss (Flow chart 63.1)
  •   Cross-match blood
  •   Warm the blood if the infusion rate is higher (>100 mL/min) or if there is massive blood transfusion.
  •   Give 6–8 units of fresh frozen plasma for every 10 units of packed red cells
  •   Give 10 units of platelets if platelet count is <50,000 mm3
  •   Consider recombinant factor VIIa. Dose—60–100 µg/kg
  •   Add cryoprecipitate to replace fibrinogen.467
Flow chart 63.1: Management options in PPH
468
 
BIBLIOGRAPHY
  1. Brenner WE, Edelmar DA, Hendricks CA. Characteristics of patients with placenta previa and results of expectant management. Am J Obstet Gynecol. 1978;132:180.
  2. Clark S. Placenta previa accreta and prior cesarean section. Obstet Gynecol. 1985;66:89.
  3. Ferguson JE II, Bourgesis FJ, Underwood P. B-Lynch suture for postpartum hemorrhage. Obstet Gynecol. 2000;95:1020.
  4. Hurd WW, Meodornik M, Hertzberg V, et al. Selective management of abruptio placentae: a prospective study. Obstet Gynecol. 1983;61:467.
  5. Pais SO, Glickman M, Schwartz, et al. Embolization of pelvic arteries for control of postpartum hemorrhage. Obstet Gynecol.1980;53:754.
  6. Pozaic S. Hemorrhagic complications in pregnancy. In: Harvey CJ (Ed). Critical Care Obstetrical Nursing. Gaithersburg, Md: Aspen Publications; 1991;115-46.
  7. Pritchard JA, Rowland RC. Blood volume changes in pregnancy and the puerperium. Am J Obstet Gynecol. 1964;88:391.
  8. Schwartz PE. The surgical approach to severe postpartum hemorrhage. In: Bereowitz RL (Ed). Critical Care of the Obstetric Patient. New York: Churchill Livingstone; 1983.p.285.
  9. Ueland K. Maternal cardiovascular dynamics. VII. Intrapartum blood volume changes. Am J Obstet Gynecol. 1976;126:671-7.

HYPERTENSIVE DISORDERS OF PREGNANCYCHAPTER 64

Prem Kumar
Hypertension is the most common medical disorder in pregnancy. It is one of the major causes for maternal morbidity and mortality. In this chapter, we will be discussing pre-eclampsia and eclampsia in detail. These patients are referred to ICU for uncontrolled hypertension, seizures, pulmonary edema, coagulopathy, renal failure or cerebral complications.
 
CLASSIFICATION OF HYPERTENSIVE DISORDERS IN PREGNANCY
  •   Gestational hypertension
  •   Pre-eclampsia—mild, severe
  •   Chronic hypertension
  •   Chronic hypertension with superimposed pre-eclampsia.
 
DEFINITIONS
  •   Pre-eclampsia—new onset of hypertension and proteinuria after 20 weeks of gestation.
  •   Eclampsia—occurrence of new onset seizure in a pregnant woman with pre-eclampsia not attributable to other causes.
 
PRE-ECLAMPSIA
 
Risk Factors
  •   Nulliparity
  •   Multiple gestation
  •   Hydatidiform mole
  •   Obesity
  •   History of pre-eclampsia in previous pregnancy
  •   Advanced maternal age
  •   History of placental abruption
  •   History of pre existing hypertension.470
Flow chart 64.1: Pathogenesis of pre-eclampsia
 
Pathogenesis (Flow chart 64.1)
  •   Failure of trophoblastic invasion into spiral arteries resulting in change only in the decidual segments. The myometrial segments remain constricted and are hyper-responsive to stimuli.
  •   Angiotensin 1 receptor antibodies may release oxygen radicals and block trophoblastic invasion.
 
Clinical Features
Women present with hypertension and early onset have worse outcome. The condition usually regresses after delivery usually within 2 days. Features of severe pre-eclampsia is given in Table 64.1.
 
Diagnostic Criteria
  •   A sustained systolic blood pressure of at least 140 mm Hg, or a sustained diastolic blood pressure of at least 90 mm Hg, that occurs after 20 weeks’ gestation in a woman with previously normal blood pressure.
  •   Proteinuria of ≥300 mg in a 24-hour urine collection.
Table 64.1   Features of severe pre-eclampsia
Hemoconcentration is an indicator of disease severity. Increased serum uric acid level is found in pre-eclampsia.
Abbreviation: HELLP syndrome, hemolysis, elevated liver enzyme levels, and low platelet level syndrome
471
 
Management
 
Lab Investigations
  •   Complete blood count, liver function test, platelet count, 24-hour urine protein, serum creatinine.
  •   Doppler ultrasound to estimate the blood flow velocity of uteroplacental circulation.
  •   Nonstress test.
 
Treatment
  •   The ultimate treatment of pre-eclampsia is delivery of the placenta and the fetus.
  •   The goals of management are control of blood pressure, maintenance of placental perfusion, prevention of seizures, prevention of complications. Most of these cases are managed in the ICU till 72 hours after delivery.
  •   Prophylactic steroids are administered if the gestation is less than 34 weeks (betamethasone, 12 mg intramuscularly [IM] every 24 hours for two doses or dexamethasone, 6 mg IM every 12 hours for four doses).
  •   Monitoring with ECG, noninvasive blood pressure, SpO2, urine output is done.
 
Antihypertensive Therapy (Table 64.2)
The goal of antihypertensive therapy is to reduce maternal complications (e.g. placental abruption, cerebral hemorrhage, congestive cardiac failure). The goal of therapy is to lower the mean arterial pressure by not more than 15–25% and with a target diastolic pressure of 100–105 mm Hg or the systolic blood pressure should be reduced by 20–30 mm Hg and diastolic pressure by 10–15 mm Hg. Most commonly used antihypertensives are hydralazine, labetalol, sodium nitroprusside and nifedipine.
Table 64.2   Drugs used for PIH
Drug
Dose
Onset of action
Adverse effects
Points of special mention
Hydralazine
5 mg IV followed by 5–10 mg every 20 minutes to a maximum of 40 mg
10–20 minutes
Duration— 6–8 hours
Tachycardia, headache, neonatal thrombocytopenia
Drug of choice for severe pre-eclampsia
Labetalol
20–40 mg IV every 10 minutes to a maximum of 220 mg
5–10 minutes
Contraindicated in patients with asthma, congestive cardiac failure
Now considered as 1st line therapy
Sodium nitroprusside
0.25–5 µg/kg/min IV
0.5–1 minutes
Fetal cyanide toxicity
Used as a bridge to delivery
Nifedipine
10 mg orally and repeated after 30 minutes if required
Headache, flushing, risk of PPH
Hypotension and potentiation of neuromuscular blockade in patients taking magnesium sulfate
Abbreviations: PIH, pregnancy-induced hypertension; PPH, postpartum hemorrhage
472
 
Other Agents
  •   Nitroglycerine
  •   Diazoxide
  •   Ketanserin
  •   Magnesium
  •   Nimodipine
  •   Methyldopa—only for mild cases.
 
Seizure Prophylaxis
Anticonvulsants are given to prevent seizures in pre-eclampsia and prevent recurrent seizures in eclampsia. Magnesium sulfate is the drug of choice. Current literature implies that seizures are not due to cerebral vasospasm but due to abrupt sustained blood pressure elevation causing cerebral vasodilation and cerebral edema. There is still controversy about the use of magnesium sulfate in pre-eclampsia. Still it is been started for severe pre-eclampsia by many obstetricians and intensivists.
 
Magnesium Sulfate
Mechanism of action—not clearly understood. Proposed mechanisms are antagonism of calcium at membrane causing reduction in cerebral vasospasm, inhibits platelet aggregation and causes vasodilatation by release of prostacyclin from the vascular endothelium, blocks NMDA receptors. The infusion is initiated with the onset of labor and continued till 24 hours postpartum. Serum concentration and adverse effects of magnesium is given in Table 64.3.
 
Actions
  •   Anticonvulsant effect
  •   Antihypertensive effect
  •   Tocolytic effect.
 
Dosage Regimens
  • Loading dose: 4–6 g given over 20–30 minutes
  • Maintenance infusion: 1–2 g/hour.
 
Pharmacokinetics
It is eliminated by kidneys. Half life is 4 hours in patients with normal renal function.473
Table 64.3   Serum concentration and adverse effects of magnesium
Serum concentration of magnesium
Interpretation
1.7–2.4 mg/dL
Normal serum concentration
5–9 mg/dL
Therapeutic concentration
12 mg/dL
Lost patellar reflexes
15–20 mg/dL
Respiratory depression
>25 mg/dL
Cardiac arrest
 
Cardiac Effects of Hypermagnesemia
  •   Prolonged PR and QT interval causing A-V block if serum concentration >18 mg/dL
  •   Cardiac arrest if serum concentration >25 mg/dL.
Magnesium toxicity may be reversed with the administration of IV calcium (10 mL of a 10% solution of calcium gluconate given slowly IV over 10 minutes).
 
Complications of Severe Pre-eclampsia
  •   Reversible cerebral edema, stroke
  •   Renal failure—most cases are prerenal or intrarenal and it resolves completely after delivery. Bilateral renal cortical necrosis is a serious rare complication
  •   Pulmonary edema—usually occurs postpartum
  •   HELLP syndrome
  •   Placental abruption.
 
HELLP SYNDROME
HELLP syndrome is a high risk variant of severe pre-eclampsia characterised by hepatic, renal and cerebral complications. This is associated with high maternal mortality. Hemolysis is the hallmark of HELLP syndrome. Other findings are periportal hepatic necrosis and hemorrhage, DIC, abruption of placenta, pulmonary edema, and renal failure. Predominantly it occurs in the postpartum period.
 
Diagnostic Criteria
  • Hemolysis—serum bilirubin >1.2 mg/dL, peripheral smear showing features of hemolysis.
  • Elevated liver enzymes—lactate dehydrogenase >600 IU/L, SGOT >70 IU/L
  • Platelet count <1,00,000/mm3.
 
Clinical Features
  • Nausea and vomiting
  • Epigastric pain
  • 474Hypertension
  • Headache.
 
Diagnosis
Complete blood count, platelet count, liver function test. In case of hepatic bleeding, ultrasonography and CT scan is useful for diagnosis.
 
Management
The diagnosis of HELLP syndrome is considered an indication for immediate delivery. The treatment is same as that of severe pre-eclampsia-controlling hypertension, correcting coagulation abnormalities. The use of high dose corticosteroid (dexamethasone 10 mg 6th hourly) has been found to raise platelet count. Hepatic hemorrhage without rupture with hemodynamic stability can be managed conservatively. In case of rupture of subscapular hematoma of liver which is a life-threatening complication of HELLP syndrome, the patient presents with hypovolemic shock. The condition is a surgical emergency, hence it requires fluid and blood resuscitation with emergency laparotomy.
 
ECLAMPSIA
It is defined as new onset seizure during pregnancy or postpartum period in a woman who has clinical features of pre-eclampsia without previous seizure disorder. Seizures can occur in intrapartum period or within 48 hours after delivery. Eclampsia is associated with high maternal and perinatal mortality. Complications which can occur in mother are cerebrovascular event, pulmonary aspiration, cardiac arrest.
 
Management
The goals of management of eclampsia are ABCs of resuscitation. Protect the airway by giving jaw thrust and oxygen, breathing is supported by bag and mask ventilation with oxygen. Circulation is supported by IV access and blood pressure monitoring. Termination and prevention of seizures by magnesium sulfate is done. If seizure is not controlled with magnesium, diazepam 5–10 mg is given. If there are refractory seizures, patient is given thiopentone sodium and succinylcholine and the patient is intubated and given ventilatory support. Antihypertensive therapy is given with intravenous labetalol or hydralazine. Delivery of the fetus is considered once the mother is stabilized preferably by vaginal route.
 
BIBLIOGRAPHY
  1. American College of Obstetricians and Gynecologists. Diagnosis and Management of Preeclampsia and Eclampsia. ACOG Practice Bulletin No. 33, January 2002. Obstet Gynecol. 2002;99:159-67.
  2. Chestnut DH. Chestnut's Obstetric Anesthesia: Principles and Practice, 4th edn. Philadelphia: Elsevier Publishers; 2009.
  3. 475Lucas MJ, Leveno KJ, Cunningham FG. A comparison of magnesium sulfate with phenytoin for the prevention of eclampsia. N Engl J Med. 1995;333:201.
  4. Mabie W, Gonzalez AR, Sibas BM, et al. A comprehensive trial of labetalol and hydralizene in the acute management of severe hypertension complicating pregnancy. Obstet Gynecol. 1987;70:328.
  5. Report on the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol. 2000;183:S1-22.
  6. Sibai B. Diagnosis, prevention, and management of eclampsia. Obstet Gynecol. 2005; 105:402.
  7. The Magpie Trial Collaborative Group: Do women with pre-eclampsia, and their babies, benefit from magnesium sulfate? The Magpie Trial: a randomized placebo-controlled trial. Lancet. 2002;359:1877.
  8. Witlin AG, Sibai B. Magnesium sulfate therapy in preeclampsia and eclampsia. Obstet Gynecol. 1998;92:883.
  9. Working Group Report on High Blood Pressure in Pregnancy. Washington, DC, National Institutes of Health, 2000.

ACUTE FATTY LIVER OF PREGNANCYCHAPTER 65

Prem Kumar
Acute fatty liver of pregnancy (AFLP) is an uncommon disorder of pregnancy. Incidence is 1 in 1,00,000 pregnancies. It is characterized by impaired hepatic function leading to liver failure.
 
PATHOPHYSIOLOGY
  • Acute fatty liver of pregnancy is common in women with multiple gestation. More than 50% of cases are associated with pre-eclampsia.
  • There is documented evidence of the presence of AFLP in mothers whose fetus had long chain hydroxyacyl coenzyme dehydrogenase deficiency.
  • Another study showed that mitochondrial dysfunction in fetal liver as another etiology. But none of these evidences have proved to be the causative factor for AFLP, still the etiology for AFLP is unknown.
 
CLINICAL PRESENTATION
Diagnosis of AFLP is considered in a woman of late gestation presenting with impaired hepatic function. They may complain of vomiting, gastrointestinal bleeding and right upper abdominal pain. Patients may have jaundice, headache and malaise.
 
LAB INVESTIGATIONS
Elevated liver enzymes, prolonged prothrombin time and reduced antithrombin III level. Hypoglycemia is common and it occurs due to impaired glycogenolysis. Fatty infiltration can be seen in ultrasonography. Patients may end up with hepatorenal syndrome.
 
DIFFERENTIAL DIAGNOSIS (TABLE 65.1)
Acute fatty liver of pregnancy has to be differentiated from viral hepatitis, intrahepatic cholestasis and HELLP syndrome.477
Table 65.1   Differential diagnosis of acute fatty liver of pregnancy
Disorder
Serum bilirubin (mg/dL)
Liver enzymes (IU/L)
Specific features
AFLP
<5
<500
Fatty infiltration
Hypoglycemia
Hepatorenal syndrome
Intrahepatic cholestasis
<5
<300
Pruritus, dilated canaliculi
Viral hepatitis
>5
>1000
Jaundice
HELLP syndrome
<5
>500
Hemolysis
Thrombocytopenia
Abbreviations: AFLP, acute fatty liver of pregnancy; HELLP, hemolysis, elevated liver enzymes and low platelets
 
COMPLICATIONS
  • Profound hypoglycemia
  • Acute renal failure
  • DIC
  • Hepatic encephalopathy
  • Hepatic rupture
  • Coagulopathy
  • Gastrointestinal bleeding
  • Fetal effects—uteroplacental insufficiency leading to fetal distress.
 
MANAGEMENT
Acute fatty liver of pregnancy is a medical emergency and the mainstay is supportive treatment. Goals of the management are:
  • Maintaining oxygenation
  • Maintaining renal and neurological function
  • Correction of metabolic disorders and electrolyte disturbances
  • Correction of hypoglycemia
  • Correction of coagulation abnormalities
  • Delivery of the fetus once the mother is stabilized.
Intravenous infusion with 10% dextrose is given to prevent hypoglycemia and blood glucose level maintained >60 mg/dL. In case there is hepatic encephalopathy, low protein diet and enteral lactulose is given to reduce serum ammonia level. AFLP is a reversible form of peripartum liver failure hence all forms of invasive treatment should be planned carefully. Orthotopic liver transplantation can be considered for patients who have no signs of recovery even after 72 hours of postpartum period.
478
 
BIBLIOGRAPHY
  1. Amon E, Allen SR, Petrie RH, Belew JE. Acute fatty liver of pregnancy associated with pre-eclampsia: management of hepatic failure with postpartum liver transplantation. Am J Perinatol. 1991;8:278-9.
  2. Castro MA, Fassett MJ, Reynolds TB, et al. Reversible peripartum liver failure: a new perspective on the diagnosis, treatment, and cause of acute fatty liver of pregnancy, based on 28 consecutive cases. Am J Obstet Gynecol. 1999;181:389-95.
  3. Davidson KM, Simpson LL, Knox TA, D'Alton ME. Acute fatty liver of pregnancy in triplet gestation. Obstet Gynecol. 1998;91:806-8.
  4. Franco J, Newcomer J, Adams M, Saeian K. Auxiliary liver transplant in acute fatty liver of pregnancy. Obstet Gynecol. 2000;95:1042.
  5. Haemmerli UP. Jaundice during pregnancy: with special emphasis on recurrent jaundice during pregnancy and its differential diagnosis. Acta Med Scand. 1966; 4444:1-111.
  6. Kaplan MM. Acute fatty liver of pregnancy. N Engl J Med. 1985;313:367-70.
  7. Rinaldo P, Treem WR, Riely CA. Liver disease in pregnancy. N Engl J Med. 1997; 336:377-8.

AMNIOTIC FLUID EMBOLISMCHAPTER 66

Prem Kumar
Amniotic fluid embolism (AFE) is a devastating condition which is largely unpreventable without any cause. It is a diagnosis of exclusion and the maternal mortality rate is very high (30–80%). Most of these deaths occur in the first few hours. The incidence is 1 in 80,000 deliveries.
 
PATHOPHYSIOLOGY
  • Some studies have suggested that leukotrienes are responsible for the pathological features of AFE.
  • Immune-mediated complement activation is another hypothesis.
  • Disturbance of the clotting mechanism by released trophoblast has been suggested by some investigators.
  • Amniotic fluid contains prostaglandin, leukotrienes, fetal debris which can get released into maternal circulation through uterine veins or placental abruption. These factors causes complement activation and pulmonary vasoconstriction resulting in pulmonary hypertension.
  • This syndrome or pathophysiology more likely resembles anaphylaxis. Hence, AFE constituting hemodynamic instability, coagulopathy and hypoxia is suggested by many as anaphylactoid syndrome of pregnancy.
  • There is a biphasic response to the effects of AFE—early and second phase.
  • Early phase constitutes pulmonary vasoconstriction and pulmonary hypertension resulting in right heart failure. This phase occurs within 30 minutes.
  • Second phase consists of left ventricular failure resulting in pulmonary edema.
 
CLINICAL FEATURES
The diagnosis of AFE is that of exclusion. Patients present with breathlessness, cyanosis, sudden hemodynamic collapse, seizures during labor or cesarean section or even in the postpartum period. Coagulopathy is also another feature of AFE in patients who survive the insult. There has been an increased incidence of AFE in patients where pharmacologic induction of labor was done or when membranes are ruptured artificially.480
 
LAB INVESTIGATIONS
  • Maternal plasma concentration of zinc coproporphyrin which is a component of meconium is thought to be a sensitive test for diagnosing AFE.
  • Monoclonal antibody test for detection of fetal mucin in maternal circulation.
 
MANAGEMENT
  • Supportive management is the mainstay in the management of AFE.
  • Start CPR if required. The use of perimortem cesarean section has resulted in maternal and neonatal survival.
  • Resuscitative measures should be aggressive by starting a wide bore IV cannula for rapid infusion of fluids, inotropic support is given if required.
  • Pulmonary artery catheterization is useful in these patients to measure the pulmonary artery occlusion pressure and in diagnosing left ventricular failure and hence is used as a guide for fluid and inotropic support.
  • Most of these patients would require tracheal intubation and ventilatory support.
  • Blood component therapy is given to manage the coagulopathy.
  • Neurological assessment is done frequently since the patient may have neurologic sequelae.
 
BIBLIOGRAPHY
  1. Clark SL, Hankins GDV, Dudley DA, et al. Amniotic fluid embolism: Analysis of the national registry. Am J Obstet Gynecol. 1995;172:1158-69.
  2. Clark SL. New concepts of amniotic fluid embolism: A review. Obstet Gynecol Surv. 1990;45:360-8.
  3. Davies S. Amniotic fluid embolism and isolated disseminated intravascular coagulation. Can J Anaesth. 1999;46:456.
  4. Gilbert WM, Danielson B. Amniotic fluid embolism: decreased mortality in a population-based study. Obstet Gynecol. 1999;93973-77.
  5. Gilmore DA, Wakins J, Secrest J, et al. Anaphylactoid syndrome of pregnancy: a review of the literature with latest management and outcome data. AANA J. 2003;71:120.
  6. Kobayashi H, Ohi H, Terao T. A simple, noninvasive, sensitive method for diagnosis of amniotic fluid embolism by monoclonal antibody TKH-2 that recognizes NeuAcα2–6GalNAc. Am J Obstet Gynecol. 1993;168:848-53.
  7. Lee W, Gensberg KA, Cotton DB, et al. Squamous and trophoblastic cells in the maternal pulmonary circulation identified by invasive hemodynamic monitoring during the postpartum period. Am J Obstet Gynecol. 1986;155:159.
  8. Margarson MP. Delayed amniotic fluid embolism following cesarean section under spinal anaesthesia. Anaesthesia. 1995;50:804-6.
  9. Quinn A, Barrett T. Delayed onset of coagulopathy following amniotic fluid embolism: Two case reports. Internat J Obstet Anesth. 1993;2:177-80.
  10. Stehr SN, Liebich I, Kamin G, Koch T, Litz RJ. Closing the gap between decision and delivery: amniotic fluid embolism with severe cardiopulmonary and haemostatic complications with a good outcome. Resuscitation. 2007;74:377-81.
481NEUROLOGICAL DISORDERS IN INTENSIVE CARE UNIT
Chapter 67 Cerebrovascular Diseases TA Naufal Rizwan
Chapter 68 Status Epilepticus TA Naufal Rizwan
Chapter 69 Meningitis and Encephalitis TA Naufal Rizwan
Chapter 70 Alcohol Withdrawal Syndrome TA Naufal Rizwan
Chapter 71 Delirium in ICU TA Naufal Rizwan482

CEREBROVASCULAR DISEASESCHAPTER 67

TA Naufal Rizwan
Cerebrovascular diseases comprises heterogeneous group of disorders that herald their presence by producing symptoms and signs resulting from either ischemia or hemorrhage within central nervous system (CNS) (Fig. 67.1).
Fig. 67.1: Classification of cerebrovascular disease
Abbreviation: TIA, transient ischemic attack
 
TRANSIENT ISCHEMIC ATTACK
 
Definition
It is characterized by an acute loss of focal cerebral or monocular function with symptoms lasting <24 hours and which is thought to be due to inadequate cerebral or ocular blood supply as a result of low blood flow, thrombosis or embolism associated with disease of the arteries, heart or blood.
 
Features of Transient Ischemic Attacks
Transient ischemic attacks (TIA) is sudden in onset. The symptoms are maximal at onset and resolve within 24 hours. Brain imaging may or may not show a relevant focal ischemic lesion in the brain.
 
Management of Transient Ischemic Attacks
Patients with TIA or those with stroke, who have made a good immediate recovery, should be assessed and investigated for cause as soon as possible. Patients likely to have a diagnosis of TIA should be prescribed aspirin 300 mg daily immediately and risk factors for cerebrovascular disease such as severe hypertension should be treated appropriately.484
 
STROKE
 
Definition
A clinical syndrome characterized by an acute loss of focal cerebral function due to a vascular event with symptoms lasting >24 hours or leading to death.
 
Types
•  Hemorrhagic stroke: Spontaneous hemorrhage into the brain substance.
•  Ischemic stroke: Inadequate blood supply to a part of the brain as a result of low blood flow, thrombosis or embolism associated with diseases of the blood vessels, heart or blood.
 
ISCHEMIC STROKE (80%)
 
Pathophysiology
Around 80% of ischemic strokes occur in the carotid or anterior circulation and 20% occur in vertebrobasilar or posterior circulation.
 
Large Artery Atherosclerotic Disease
Atherosclerosis mainly affects larger extracranial or intracranial vessels. The mechanism is mainly artery to artery embolization or in situ thrombosis in areas of preexisting arterial stenosis.
 
Small Vessel or Penetrating Artery Disease (Lacunes)
Long standing hypertension induces changes in the small penetrating vessels of brain in the form of medial hypertrophy and fibrinoid necrosis leading to occlusion. Lacunes are small ischemic infarcts from 0.5 mm to 15 mm in the deep region of brain or brainstem caused by lipohyalinosis of penetrating arteries of brain.
 
Embolic Stroke (Box 67.1)
485
 
CLINICAL FEATURES
 
Focal Neurological and Ocular Symptoms
 
Motor Symptoms
The predominant motor symptoms include weakness or clumsiness of one side of the body, in whole or in part (hemiparesis, monoparesis and sometimes only the hand). Some patients may develop also simultaneous bilateral weakness and difficulty in swallowing.
 
Speech/Language Disturbances
Patients have difficulty in understanding or expressing spoken language (aphasia, dysarthria). They may also have difficulty in reading (dyslexia), writing (dysgraphia) and calculating (dyscalculia).
 
Sensory Symptoms
Altered feeling on one side of the body, in whole or in part.
 
Visual Symptoms
The visual symptoms seen in stroke are loss of vision in one eye (in whole or in part) or loss of vision in half or quarter of the visual field. Bilateral blindness and double vision (diplopia) are also seen in some patients.
 
Vestibular Symptoms
Patient may experience disturbances in balance, giddiness, etc.
 
Behavioral/Cognitive Symptoms
Difficulty in dressing, combing hair, cleaning teeth, geographical disorientation (visuospatial–perceptual dysfunction) and forgetfulness.
 
Nonfocal Neurological Symptoms
  •   Generalized weakness and/or sensory disturbance
  •   Light-headedness, faintness
  •   ‘Blackouts’ with altered or loss of consciousness with or without impaired vision in eyes
  •   Incontinence of urine or feces
  •   Confusion, ringing in the ears (tinnitus).
486
 
HEMORRHAGIC STROKE
 
Pathophysiology
 
Intracerebral and Cerebellar Hemorrhage
Hemorrhagic stroke is mostly due to rupture of microaneurysms (Charcot Bouchard aneurysms). They are usually massive and often fatal. The common sites of bleed are basal ganglia, pons, cerebellum and subcortical white matter. In normotensive patients, particularly over 60 years, lobar intracerebral hemorrhage occurs in the frontal, temporal, parietal or occipital cortex.
 
Subarachnoid Hemorrhage
The common causes for subarachnoid hemorrhage are:
  •   Saccular (berry) aneurysms (70%)
  •   Arteriovenous malformation (AVM) 10%
  •   No arterial lesion found in 15% of cases.
 
Subdural and Extradural Hemorrhage/Hematoma
Mostly traumatic.
 
CLINICAL FEATURES OF HEMORRHAGIC STROKE
Hemorrhagic stroke is usually a sudden, dramatic event. Intense headache usually described as “worst headache of my life”. Seizures may be present. Headache with loss of consciousness along with photophobia, phonophobia, nuchal rigidity should alert the possibility of subarachnoid hemorrage (SAH). Loss of consciousness is common with major lobar hemorrhages. Focal neurological signs like contralateral hemiparesis, hemisensory loss suggesting basal ganglia hemorrhage are common.
 
Assessment of Acute Stroke
Brain imaging (CT brain) should be taken as soon as possible in all patients, at least within 24 hours of onset. This is very important, especially in a patient who has the following:
  •   On anticoagulants
  •   Known bleeding tendency
  •   Depressed level of consciousness
  •   Unexplained progressive or fluctuating symptoms
  •   Papilledema
  •   Neck stiffness or fever.
If the underlying pathology is uncertain or the diagnosis of stroke is in doubt even after the CT scan, magnetic resonance imaging (MRI) should be considered.487
 
Early Interventions
Blood glucose, arterial oxygen concentration, hydration and temperature should be maintained within normal limits. Blood pressure should only be lowered in the acute phase where there are likely to be complications from hypertension, e.g. hypertensive encephalopathy, aortic aneurysm or acute kidney injury or if systolic BP >210 mm Hg in ischemic stroke and >180 mm Hg in hemorrhagic stroke. Aspirin (300 mg) orally or rectally should be given as soon as possible after the onset of stroke symptoms if a hemorrhagic stroke is ruled out. Patients should also be mobilized as soon as possible.
 
Thrombolytics in Ischemic Stroke
Intravenous recombinant tissue plasminogen activator (tPA) alteplase (0.9 mg/kg to a 90 mg max; 10% as a bolus, then the remainder over 60 minutes) is given in patients with confirmed ischemic stroke within 3 hours of onset symptoms. Contraindications for thrombolytic therapy is given in Box 67.2.
Table 67.2   Contraindications for thrombolytic therapy
  • Sustained BP >185/110 mm Hg despite treatment
  • Platelets <100,000; HCT <25%
  • Use of heparin within 48 hours and prolonged PTT, or elevated INR
  • Rapidly improving symptoms/minor stroke symptoms
  • Prior stroke or head injury within 3 months; prior intracranial hemorrhage
  • Major surgery in preceding 14 days/gastrointestinal bleeding in preceding 21 days
  • Recent myocardial infarction
  • Coma or stupor
 
MANAGEMENT OF CEREBRAL EDEMA
Five to ten percent of patients develop cerebral edema leading to obtundation or brain herniation. Edema peaks on the 2nd or 3rd day but can cause mass effect for approximately 10 days. Larger the infarct, greater the significance of clinical edema. Water restriction and IV mannitol (1.5 to 2 g/kg IV over 30 minutes) may be used to raise the serum osmolarity.
 
Rehabilitation
All patients should be referred to a specialist rehabilitation team involving treating doctor, physiotherapist, speech therapist, psychologist (to assess depression). All members of the healthcare team should work together with the patient, caregiver and family using a shared philosophy and common goals. The team should promote integrating the practice of skills gained in therapy into the patient's daily routine in a consistent manner.
 
General Management
Patients with dysphagia should be managed by a trained specialist and receive advice on safe swallowing techniques. Nutritional and hydration support should 488be considered for any patient with malnutrition or difficulties in feeding. Bowel and bladder function should be monitored and actively managed. The patient's cognitive status should be considered when planning and delivering treatment.
 
Secondary Prevention
Advice on lifestyle factors.
 
Blood Pressure Control
High blood pressure persisting for over two weeks should be treated (non-diabetics <140/85 mm Hg; diabetics <130/80 mm Hg). The drugs preferred are Thiazide diuretics (indapamide or bendrofluazide) or an angiotensin-converting enzyme (ACE) inhibitor (e.g. perindopril or ramipril) or preferably combination of both, unless there are contraindications.
 
For Ischemic Stroke/TIA
 
Antiplatelets
Aspirin (75–300 mg) daily or clopidogrel or a combination of low dose aspirin and dipyridamole modified release (MR). For aspirin intolerant patients, clopidogrel (75 mg daily or dipyridamole MR 200 mg twice daily) should be used.
 
Anticoagulants
Anticoagulation should be started in every patient with persistent or paroxysmal atrial fibrillation (valvular or nonvalvular) unless contraindicated. Anticoagulants should not be started until brain imaging has excluded hemorrhage, and usually not until 14 days have passed from the onset of an ischemic stroke.
 
Statins
Treatment with a statin (e.g. 40 mg simvastatin) should be given to patients with ischemic stroke or TIA unless contraindicated. Any patient with a carotid artery territory stroke, without severe disability, should be considered for carotid endarterectomy. Carotid endarterectomy should be performed as soon as the patient is fit for surgery.
 
BIBLIOGRAPHY
  1. Adams RJ, Albers G, Alberts MJ. Update to the AHA/ASA recommendations for the prevention of stroke in patients with stroke and transient ischemic attack. Stroke. 2008;39:1647-52.
  2. Allan H Ropper, Martin A Samuels, Joshua Klein. Adams and Victor's Principles of Neurology, 10th edition.
  3. Amarenco P, Labreuche J, Lavallee P, Touboul PJ. Statins in stroke prevention and carotid atherosclerosis: systematic review and up-to-date meta-analysis. Stroke. 2004;35:2902-9.
  4. 489Asaithambi G, Tong X, George MG, Tsai AW, Peacock JM, Luepker RV, Lakshminarayan K. Acute stroke reperfusion therapy trends in the expanded treatment window era. J Stroke Cerebrovasc Dis. 2014;23(9):2316-21.
  5. Berkhemer OA, Puck SS, Fransen, Beumer D, Lucie A van den Berg, Hester FL, Albert JY, Wouter JS. A randomized trial of intra-arterial treatment for acute ischemic stroke. N Engl J Med. 2015;372:11-20.
  6. Campbell BCV, Mitchell PJ, Kleinig TJ, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015;372:1009-18.
  7. Chaturvedi S, Bruno A, Feasby T. Carotid endarterectomy—an evidence-based review: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2005;65:794-801.
  8. Kato Y, Hayashi T, Tanahashi N, Kobayashi S, Cardioembolic Stroke is the Most Serious Problem in the Aging Society: Japan Standard Stroke Registry Study; Japan Standard Stroke Registry Study Group.
  9. Lewis PR, Timothy AP. Merritt's Neurology, 12th edition.
  10. Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscalzo J. Harrison's principles of internal medicine, 18th edition. McGraw Hill Publications; 2012.
  11. Maxine AP, Stephen J, Michael WR. Current Medical Diagnosis & Treatment, 54th edition, 2015.
  12. Nassief A, Marsh JD. Statin therapy for stroke prevention. Stroke. 2008;39.
  13. Toby B. Cumming, Marshall RS, Ronald ML. Stroke, cognitive deficits, and rehabilitation: still an incomplete picture. Int J Stroke. 2013;8(1).
  14. Tong X, George MG, Yang Q, Gillespie C. Predictors of in-hospital death and symptomatic intracranial hemorrhage in patients with acute ischemic stroke treated with thrombolytic therapy: Paul Coverdell Acute Stroke Registry 2008-2012. Int J Stroke. 2014;9(6):728-34.
  15. Zhang Y, Reilly KH, Tong W. Blood pressure and clinical outcome among patients with acute stroke in inner Mongolia, China. J Hypertens. 2008;26:1446-52.

STATUS EPILEPTICUSCHAPTER 68

TA Naufal Rizwan  
DEFINITION
Status epilepticus is characterized by continuous seizures or repetitive seizures with the patient not regaining consciousness in between the seizure episodes (in repetitive seizures) and that usually lasts for >15–30 minutes.
 
ETIOLOGY
  •   Anticonvulsants drug withdrawal or noncompliance
  •   CNS infections
  •   Trauma
  •   Brain tumors
  •   Metabolic derangements.
 
TYPES
At a simplified level, status may be classified into generalized convulsive status epilepticus, nonconvulsive status epilepticus (including complex partial and absence status), and simple partial status.
 
CONVULSIVE
Generalized tonic clonic movements seen.491
 
Nonconvulsive (Including Complex Partial and Absence Status)
Here there are no tonic clonic movements. The typical picture is of a twilight state with varying degrees of confusion. The usual automatisms of complex partial seizures may or may not be seen.
 
SIMPLE PARTIAL STATUS EPILEPTICUS
It is probably even rarer and commonly takes a somatomotor form.
 
COMPLICATIONS
The complications of status epilepticus are:
  •   Acidosis
  •   Hyperthermia, hypotension
  •   Renal failure (due to myoglobinuria)
  •   Cardiorespiratory dysfunction
  •   Neurological sequelae-epileptic encephalopathy (Usually in seizures lasting >30 minute).
 
INVESTIGATIONS
  •   Blood tests for metabolic parameters
  •   Imaging of the brain
  •   Electroencephalogram (EEG)—measures the electrical activity of the cortex
  •   MEG (Magnetoencephalography)—measures the magnetic fields generated by the cortical activity-done in interictal period.
 
Importance of EEG
The importance of EEG lies in the fact that it is the only way of diagnosing nonconvulsive status epilepticus. It is also helpful in generalized convulsive status epilepticus patients who are paralyzed with neuromuscular blockade for airway protection. Similarly if the patient remains comatose for a long time even after the seizure stopped, EEG must be done to detect ongoing seizures.
 
TREATMENT
 
General Measures
Airway maintenance is of great importance as it may prevent cerebral hypoxia as well as aspiration pneumonitis. Any underlying metabolic derangements, if present, must be appropriately corrected. Care must be taken to prevent injuries to the patient.492
 
Specific Measures
 
Advantages of Fosphenytoin Over Phenytoin
  • Can be mixed with all common intravenous solutions
  • Less reactions at the infusion site
  • Can be administered at a faster rate (150 mg/min).
 
BIBLIOGRAPHY
  1. Beran RG. An alternative perspective on the management of status epilepticus. Epilepsy Behav. 2008;12(3):349-53.
  2. Chapman MG, Smith M, Hirsch NP. Status epilepticus. Anaesthesia. 2001;56:648-59.
  3. Chen JWY, Wasterlain CG. Status epilepticus: pathophysiology and management in adults. Lancet Neurol. 2006;5(3):246-56.
  4. 493Cherian A, Thomas SV. Status epilepticus. Ann Indian Acad Neurol. 2009;12(3): 140-53.
  5. Husain AM, Horn GJ, Jacobson MP. Non-convulsive status epilepticus: Usefulness of clinical features in selecting patients for urgent EEG. J Neurol Neurosurg Psychiatry. 2003;74:189-91.
  6. Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscalzo J. Harrison's Principles of Internal Medicine. 18th edition McGraw Hill Publications; 2012.
  7. Lothman E. The biochemical basis and pathophysiology of status epilepticus. Neurology. 2003;40:13-23.
  8. Maxine AP, Stephen JM, Michael WR. Current Medical Diagnosis and Treatment. 5th edition 2015. pp.168-70.
  9. Meierkord H, Boon P, Engelsen B, Gocke K, Shorvon S, Tinuper P, Holtkamp M. EFNS guideline on the management of status epilepticus. Eur J Neurol. 2006;13(5):445-50.
  10. Misra UK, Kalita J, Patel R. Sodium valproate versus phenytoin in status epilepticus: A pilot study. Neurology. 2006;67:340-2.
  11. Mark M, Heinrich M. Fundamentals of neurology. 2006. pp.161-71.
  12. John PB, Daniel HL. Status epilepticus in adults. The Lancet Neurology. 2015;14(6): 615-24.
  13. Rossetti AO, Lowenstein DH. Management of refractory status epilepticus in adults: still more questions than answers. Lancet Neurol. 2011;10(10):922-30.
  14. Seif-Eddeine H, Treiman DM. Problems and controversies in status epilepticus: a review and recommendations. Expert Rev Neurother. 2011;11(12):1747-58.
  15. Towne AR, Waterhouse EJ, Boggs JG, Garnett LK, Brown AJ, Smith JR, Jr, et al. Prevalence of nonconvulsive status epilepticus in comatose patients. Neurology. 2000;54:340-5.
  16. Ulate-Campas, Caughlin F, Gainza-Lein M, Sanches IF, Pearl PL, et al. Automated seizure detection systems and their effectiveness for each type of seizure. Euro J Epilepsy. 2016. pp.88-101.

MENINGITIS AND ENCEPHALITISCHAPTER 69

TA Naufal Rizwan  
DEFINITION
Infection of the meninges (generally the arachnoid and piamater) and the subarachnoid space is known as meningitis. If the inflammation also involves the brain parenchyma, it is called meningoencephalitis.
 
CLASSIFICATION
Acute, subacute, and chronic.
 
ACUTE BACTERIAL MENINGITIS
Causes of acute bacterial meningitis is given in Table 69.1.
 
Routes of Spread
  • Hematogenous spread (infected thrombi, bacteria)
  • Direct extension from the adjacent septic foci (ear, paranasal sinuses)
  • Iatrogenic (spinal surgery, cerebral surgery, etc.).
Table 69.1   Common causes of acute bacterial meningitis
Organisms
The common causes of acute bacterial meningitis and their risk factors are:
  • Streptococcus pneumoniae—otitis, sinusitis, alcoholism, postsplenectomy and diabetes
  • Neisseria meningitidis—complement deficiencies
  • Group B streptococcus (S. agalactiae)—Neonates and older age groups
  • Listeria monocytogenes—neonates, pregnancy, older persons
  • S. aureus and CoNS—neurosurgical procedures
  • Gram-negative bacilli (Klebsiella, E. coli, Proteus)—cirrhosis, alcoholism, diabetes
  • Haemophilus influenzae—children
Abbreviation: CoNS, coagulase
495
 
PATHOGENESIS (Flow chart 69.1)
Flow chart 69.1: Pathogenesis of bacterial meningitis
Abbreviations: LPS, Lipopolysaccharide; TNF, tumor necrosis factor; IL, interleukin; ICP, intracranial pressure.
These cytokines and chemokines produce the following consequences:
  • Alters the blood brain barrier leading to vasogenic edema
  • Stimulate the production of reactive oxygen and nitrogen species, resulting in cell death
  • Stimulate the adherence of neutrophils to vascular endothelial cells, thus producing cytotoxic edema, cell injury and cell death
  • Helps in the formation of subarachnoid exudates which in turn obstructs the flow of cerebrospinal fluid resulting in obstructive hydrocephalus
  • Infiltration of the blood vessels (vasculitis) which will in turn result in cerebral ischemia, infarction, cortical vein thrombosis, etc.
 
CLINICAL FEATURES
 
Classic Triad
  • Headache
  • Fever
  • Neck stiffness (Nuchal rigidity).
The other symptoms and signs of meningitis are nausea, vomiting, photophobia, irritability, lethargy, confusion, stupor or coma. Seizures are seen in around 30% cases and may be due to ischemia, hypoxia or cerebral edema. Hypotension (in severe cases), tachycardia and tachypnea are also seen in some patients. On examination, the deep tendon reflexes are depressed. Kernig sign and Brudzinski sign are present. Petechiae, purpura or ecchymoses (mostly in lower half of body) are seen in meningococcal meningitis. Cranial nerve palsies and focal neurologic signs are uncommon and usually do not develop until several days after the onset of the infection.496
 
Features of Raised ICP
Features of increased ICP are deteriorating or reduced level of consciousness, papilledema, dilated and poorly reactive pupils, sixth nerve palsies, decerebrate posturing and the Cushing reflex (bradycardia, hypertension and irregular respiration).
 
INVESTIGATIONS
 
CSF Analysis
Lumbar puncture and cerebrospinal fluid (CSF) analysis is the most important investigation in the management of meningitis. It should be done in all the patients unless contraindicated because of increased intracranial tension. Antibiotics given within 4 hours before obtaining the cerebrospinal fluid probably do not affect the CSF culture results.
Latex agglutination: May be positive in patients with meningitis due to S. pneumoniae, N. meningitidis, H. influenzae type b, E. coli, group B streptococci.
Limulus lysates: Positive in cases of gram-negative meningitis.
PCR, CIE, ELISA, RIA-costly but highly effective.
  • Complete blood count—leucocytosis present
  • Blood culture is positive in about 50% cases
  • Culture of the oropharynx, nasopharynx and petechial skin rash in selected cases
  • Urine routine
  • Liver function tests and renal function tests
  • Serum electrolytes and blood glucose CSF for analysis (Table 69.2).
 
IMAGING
Before doing a lumbar puncture, imaging of the brain is mandatory in the following conditions:
The radiological investigations to be done in a case of meningitis are X-ray chest (may disclose an abscess or pneumonitis), X-ray of paranasal sinuses, CT brain and MRI brain.
 
DIFFERENTIAL DIAGNOSIS
  • Viral meningitis
  • Tuberculous, leptospiral and fungal meningitis
  • Chemical meningitis (following lumbar puncture, spinal anesthesia, etc.)
  • Sarcoid meningitis.
In case of recurrent meningitis, the following disorders must be considered:
  • BehÇet disease (recurrent oropharyngeal ulcers, uveitis, orchitis and meningitis)
  • Mollaret meningitis (recurrent fever and headache—HSV-induced)
  • Vogt-Koyanagi-Harada syndrome (Meningitis with iridocyclitis and depigmentation of the hair and skin)
  • Carcinomatous and lymphomatous meningitis.
 
TREATMENT
 
Antibiotics
As bacterial meningitis is a medical emergency, antibiotics should be started within 60 minutes of a patient's arrival in the emergency room. Empirical antimicrobial therapy is initiated in patients with suspected bacterial meningitis (before the results of CSF Gram's stain and culture) as per the following recommendations (Tables 69.3 and 69.4).
 
ANTIBIOTICS BASED ON ORGANISMS
Once the CSF culture reports come, antibiotics can be changed based on the organisms as follows (Tables 69.5 and 69.6).
Table 69.3   Empirical antimicrobial therapy
Age of patient
Antimicrobial therapy
  • 0–4 weeks
  • 4–12 weeks
  • 3 months–18 years
  • 18–50 years
  • >50 years
Cefotaxime plus ampicillin
Third-generation cephalosporin plus ampicillin
Third-generation cephalosporin plus vancomycin
Third-generation cephalosporin plus vancomycin
Third-generation cephalosporin plus vancomycin plus ampicillin
498
Table 69.4   Empirical antimicrobial therapy for special conditions
Special conditions
  • Immunocompromised
Vancomycin plus ampicillin and ceftazidime
  • Basilar skull fracture
Third-generation cephalosporin plus vancomycin
  • Head trauma/neurosurgery
Vancomycin plus ceftazidime
  • CSF shunt
Vancomycin plus ceftazidime
For severe penicillin allergy, consider vancomycin and chloramphenicol (for meningococcus) and trimethoprim/sulfamethoxazole (for Listeria).
Abbreviation: CSF, cerebrospinal fluid
Table 69.5   Choice of antibiotics based on organism
Organism
Antibiotic
Haemophilus influenzae
B-lactamase-negative
B-lactamase-positive
Ampicillin or Third-generation cephalosporins or chloramphenicol
Third-generation cephalosporins or chloramphenicol or cefepime
Neisseria meningitidis
Penicillin G or ampicillin or Third-generation cephalosporins or chloramphenicol
Streptococcus pneumoniae
Penicillin MIC <0.1 g/mL
Penicillin MIC 0.1–1.0 g/mL
Penicillin MIC >2.0 g/mL
Penicillin G or ampicillin or Third-generation cephalosporins, Chloramphenicol or vancomycin plus rifampin
Third-generation cephalosporins or vancomycin or meropenem
Vancomycin plus third-generation cephalosporins or meropenem
Enterobacteriaceae
Third-generation cephalosporins or meropenem or fluoroquinolone or trimethoprim/sulfamethoxazole or cefepime
Pseudomonas aeruginosa
Ceftazidime or cefepime or meropenem or fluoroquinolone or piperacillin
Listeria monocytogenes
Ampicillin or penicillin G or Trimethoprim/sulfamethoxazole
Streptococcus agalactiae
Ampicillin or penicillin G or third-generation cephalosporins or vancomycin
Staphylococcus aureus
Methicillin-sensitive
Methicillin-resistant
Nafcillin or oxacillin or vancomycin
Vancomycin or linezolid, quinupristin-dalfopristin, daptomycin
Staphylococcus epidermidis
Vancomycin
Abbreviation: MIC, minimum inhibitory concentration
The usual duration of antibiotics is between 10 and 14 days. Prolongation of fever or the late appearance of drowsiness, hemiparesis or seizures should raise the suspicion of subdural effusion, mastoiditis, sinus thrombosis, cortical vein thrombosis or brain abscess; all require that therapy be continued for a longer period.499
Table 69.6   Antibiotics dosage
Antimicrobial agent
Adult
Ampicillin
12 g/day, q4h
Cefepime
6 g/day, q8h
Cefotaxime
12 g/day, q4h
Ceftriaxone
4 g/day, q12h
Ceftazidime
6 g/day, q8h
Gentamicin
7.5 (mg/kg)/day, q8h
Meropenem
3 g/day, q8h
Metronidazole
1500–2000 mg/day, q6h
Penicillin G
G 20–24 million U/d, q4h
Vancomycin
2 g/day, q12h
 
Corticosteroids
Corticosteroids have been found to be effective in the management of acute bacterial meningitis. The incidence of seizures and coma were reduced in patients who received corticosteroids. However, there was no change in the incidence of neurologic sequelae such as hearing loss. The usual dose of dexamethasone is 10 mg IV q6h for 4 days. The first dose of steroid should ideally be given 20 minutes prior or at least along with the first dose of antibiotics.
 
Other Measures
Head-end elevation, hyperventilation, mannitol and other neurosurgical interventions are adopted if cerebral edema is present. Anticonvulsants should be added if seizures occur.
 
Prognosis
The poor prognostic factors for acute bacterial meningitis are onset of seizures within 24 hours of admission, diminished level of consciousness, infancy, old age, presence of comorbid conditions and increased intracranial tension.
 
Sequelae
The neurological sequelae of acute bacterial meningitis are diminished intelligence, memory disturbances, seizures, hearing loss and gait disturbances.
 
VIRAL MENINGITIS
 
Etiology
The common viruses responsible for acute meningitis are enteroviruses (echoviruses, coxsackieviruses), herpes simplex, Varicella zoster, Epstein-Barr virus, HIV and arthropod-borne viruses.500
 
Routes of Entry
  • Respiratory passages—e.g. measles, mumps, VZV
  • Gastrointestinal route—e.g. enteroviruses
  • Genital route—e.g. HSV
  • Inoculation by mosquitoes or animal bites—e.g. rabies.
 
Clinical Features
The symptoms of viral meningitis are more or less similar to the acute bacterial meningitis described above but with reduced severity. However, the presence of seizures, focal neurologic signs, stupor and coma are highly uncommon in viral meningitis and their presence usually indicates viral encephalitis or another CNS infectious process.
 
INVESTIGATIONS
 
CSF Analysis
The usual CSF picture in acute viral meningitis is as follows:
  • Opening pressure—normal or mildly elevated
  • Glucose—normal
  • Protein—normal or slightly elevated (20–80 mg/dL)
  • Cell count 25–500/mm3 with lymphocytic pleocytosis.
 
Exceptions
In some cases of meningitis due to mumps, CSF glucose may be reduced. Similarly, neutrophilic predominance is seen in meningitis due to ECHO virus infection.
 
Other Investigations
Apart from the routine investigations mentioned in the management of acute bacterial meningitis, other important investigations are:
  • Serologic studies: Helps in documenting the antibodies and is useful in arboviruses like West nile virus.
  • PCR amplification of viral nucleic acid: This test is costly but highly sensitive and is very useful in CMV, EBV, VZV, HHV-6, etc.
  • Viral culture: It has poor sensitivity and not routinely done.
 
Differential Diagnosis
  • Partially treated bacterial meningitis
  • Mycobacterial/fungal meningitis
  • Neoplastic and noninfectious meningitis.501
 
Treatment
General measures like maintaining the fluid and electrolyte balance should be taken care. Analgesics, antipyretics and antiemetics should be given for appropriate patients. Antivirals are usually indicated only in severe viral meningitis.
 
For Severe HSV, EBV, VZV
Acyclovir IV 20–30 mg/day in 3 divided doses followed by oral acyclovir 800 mg 5 times/day or famciclovir 500 mg tid or valacyclovir 1000 mg tid for 1–2 weeks. For less severe patients, oral drugs alone are sufficient.
 
For HIV Meningitis
HAART should be given. Pleconaril is a newer drug that can be used for enteroviral meningitis.
 
Prognosis
The prognosis is an excellent with neurologic sequelae reported in only a very few cases.
 
TUBERCULAR MENINGITIS
 
Etiology
Mycobacterium tuberculosis.
 
Pathogenesis
Tubercles are formed in the brain parenchyma due to the hematogenous spread of the tubercle bacilli during the primary infection. These tubercles later enlarge, become caseous and may discharge the bacilli and antigens into the subarachnoid space producing meningitis.
 
Clinical Features
 
Prodromal Stage (2 weeks–2 months)
Low-grade fever, headache, night sweats, neck stiffness, loss of appetite, loss of weight, lethargy, vomiting, abdominal pain, etc.
 
Later Stage
Stupor, focal neurologic signs, seizures, cranial nerve palsies and hydrocephalus.502
Table 69.7   Lab investigations
Abbreviations: CSF, cerebrospinal fluid; AFB, acid-fast bacilli; PCR, polymerase chain reaction; DNA, deoxyribonuceleic acid; CT, computed tomography; MRI, magnetic resonance imaging
 
Sequelae
Minor or major sequelae occur in about 25% of the patients who recover. These include deafness, convulsive seizures, blindness, hemiplegia, paraplegia and intellectual impairment.
 
Investigations
It is given in Table 69.7.
 
Treatment
 
Antituberculous Therapy
 
Steroids
Dexamethasone is indicated if evidence of hydrocephalus is present.
 
FUNGAL MENINGITIS
Organisms: Cryptococcal neoformans, Histoplasma capsulatum, C. immitis, etc. They are acquired by the inhalation of fungal spores.503
 
Investigations
  • CSF analysis: Increased protein, reduced glucose and lymphocytic pleocytosis
  • PCR.
 
Treatment
  • Cryptococcus neoformans
      Amphotericin B (0.7 mg/kg/day IV) + flucytosine 100 mg/kg/day for 2 weeks
      ↓
      Flucanozole PO 400 mg/day for 2 months
        ↓
      Fluconazole PO 200 mg/day for 12 months
  • Histoplasma capsulatum
      Amphotericin B (0.7 mg/kg/day IV) for 4 weeks
        ↓
      Itraconazole PO 200 mg/day for 6 months.
 
VIRAL ENCEPHALITIS
 
Definition
Inflammation of the brain parenchyma is called as encephalitis. Encephalitis is usually associated with meningitis (Meningoencephalitis), spinal cord or nerve roots (encephalomyelitis, encephalomyeloradiculitis).
 
Etiology
Herpes simplex virus, VZV, EBV, arthropod-borne virus, CMV, enterovirus, etc.
 
Clinical Features
The clinical features of acute viral encephalitis are fever, confusion, behavioral changes, personality changes and hallucinations, etc. Some patients may also have focal neurologic signs like aphasia, ataxia, involuntary movements and cranial nerve deficits. Seizures, weakness, diabetes insipidus and SIADH are also seen in some patients.
 
Investigations
 
CSF Analysis
CSF picture in viral encephalitis is similar to viral meningitis with:
  • Mildly increased protein
  • Normal glucose
  • Lymphocytic pleocytosis
  • PCR-highly sensitive for CMV, EBV, HHV-6, enteroviruses
  • 504Culture—poor sensitive
  • Serology—IgM antibodies—west nile virus.
 
MRI, CT, EEG
Presence of focal findings is highly suggestive of HSV encephalitis. Examples of focal findings include:
  • Increased signal intensity in the frontotemporal region on MRI
  • Focal areas of mass effect and contrast enhancement on CT
  • Periodic focal temporal lobe spikes on EEG.
 
Brain Biopsy
Brain biopsy is indicated in patients in whom PCR fail to lead to a specific diagnosis, if focal abnormalities are present in MRI and if there is no response to treatment with antivirals.
 
TREATMENT
 
General Measures
Monitoring of vitals like respiration, blood pressure and ICP should be done. Fluid and electrolyte balance should be maintained. Antipyretics and anticonvulsants are given for appropriate patients. Precautions should be taken to prevent the development of DVT, pressure sores and aspiration pneumonia.
 
Specific Measures (Table 69.8)
Table 69.8   Pharmacologic management of viral encephalitis
For HSV, EBV, VZV
For CMV
Other newer drugs for viral encephalitis
Abbreviations: HSV, herpes simplex virus; EBV, Espstein-Barr virus; VZV, varicella zoster virus; CMV, cytomegalovirus
505
 
Sequelae
The sequelae of acute viral encephalitis include movement disorders, weakness, seizure disorder and cognitive impairment.
 
BIBLIOGRAPHY
  1. Abdulkareem M Al Bekairy, Shmeylan Al Harbi, Abdulmalik M Alkatheri, Saleh Al Dekhail, Lolowa Al Swaidan, Nabil Khalidi. Bacterial meningitis: An update review. Afr. J. Pharm. Pharmacol. 2018(18).pp.469-78.
  2. Baringer JR. Herpes simplex virus encephalitis. In: Davis LE, Kennedy PGE (Eds).Infectious diseases of the nervous system, 1st edition, Butterworth-Heinemann; 2002.pp.139-64.
  3. Broued MC, Tunked AR, Van de Break D. Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. Clin Microbiol. Rev. 2010;23(3):467-92.
  4. Dorothee H, Nguyen DB, Nguyen T, Mai H, et al. Intensified antituberculosis therapy in adults with tuberculous meningitis. N Engl J Med. 2016;374:124-34.
  5. Galimi R. “Extrapulmonary Tuberculosis: Tuberculous Meningitis New Developments,” European Review for Medical and Pharmacological Sciences. 2011;15(4).pp. 365-86.
  6. Haldar S, Sharma N, Gupta VK, Tyagi JS. “Efficient Diagnosis of Tuberculous Meningitis by Detection of Mycobacterium tuberculosis DNA in Cerebrospinal Fluid Filtrates Using PCR.” J Med Micro. 2009;58(5).pp.616-24.
  7. Kennedy PGE. Viral encephalitis-causes, differential diagnosis and management. Neurol Neurosurg Psychiatry. 2004;75:i10-i15.
  8. Lamelas A, Harris SR, Roltgen K, et al. Emergence of a new epidemic Neisseria meningitidis serogroup A Clone in the African meningitis belt: high-resolution picture of genomic changes that mediate immune evasion, MBio. 2014;5:e01974–e0201.
  9. Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscalzo J. Harrison's Principles of Internal Medicine, 18th edition, McGraw Hill Publications; 2012.
  10. Mei-Ling Sharon Tai. Tuberculous Meningitis: Diagnostic and Radiological Features, Pathogenesis and Biomarkers; NM. 2013;4(2).
  11. Mustapha MM, Lee HH. Insights into seasonal dynamics of bacterial meningitis; The Lancet Global Health. 2016;4(6):e345-16.
  12. Mustapha MM, Marsh JW, Krauland MG, et al. Genomic epidemiology of hypervirulent serogroup W, ST-11 Neisseria meningitidis. EBioMedicine. 2015;2:1447-55.
  13. Olaf Hoffman, Weber RJ. Pathophysiology and Treatment of Bacterial Meningitis. Ther Adv Neurol Disord. 2009;2(6):1-7.
  14. Paireau J, Chen A, Broutin H, Grenfell B, Basta NE. Global trends in seasonal dynamics of bacterial meningitis: a time-series analysis. Lancet Glob Health. 2016;4: e370-e7.
  15. Papadakis MA, Mcphee SJ, Rasovo MW. Current Medical Diagnosis and Treatment, 54th edition, 2015.
  16. Sili U, Kaya A. Herpes simplex virus encephalitis: Clinical manifestations, diagnosis and outcome in 106 adult patients Mert. 2014;60(2):112-8.
  17. Van de Beek, D. Progress and challenges in bacterial meningitis. Lancet. 2012;380: 1623-4.

ALCOHOL WITHDRAWAL SYNDROMECHAPTER 70

TA Naufal Rizwan
Symptoms that occur in established alcoholics when they are starved of alcohol for more than a few hours are known as alcohol withdrawal syndrome. It is usually seen in a binge or periodic drinker rather than the steady drinker. It is also called as alcohol abstinence syndrome.
 
SYMPTOMS
Symptoms of alcohol withdrawal syndrome are tabulated in Table 70.1.
Table 70.1   Symptoms of alcohol withdrawal syndrome
Early
Late
  • Tremulousness
Delirium tremens
  • Hallucinosis
  • Seizures
 
Tremulousness
This is the most common withdrawal symptom. The patients usually describe it as ‘jitters’ or ‘shakes’. Initially tremulousness begins in the morning and once the patient takes alcohol, the symptoms disappear. However, the symptoms return on successive mornings with increasing severity. Generalized tremor is the most important feature of this illness. This tremor is more when the patient is in emotional stress and is mild when he/she is in quiet surroundings. The tremor may even interfere with his speech and eating. The other associated symptoms are facial flushing, over alertness, easy startling, nausea, vomiting, abdominal pain, etc. The patients may also have tachycardia, tachypnea and systolic hypertension.
 
Hallucinosis
Hallucinosis is a disturbance of perception and is seen in around 25% of alcohol withdrawal patients. The most common hallucinations are visual, although auditory, olfactory or tactile hallucinations are noted in a few patients. Visual hallucinations, if present, usually involve the persons or animals.507
 
“Alcoholic Mania” (Also Called as Hallucinatory Insanity of Drunkards)
It is a special type of alcoholic psychosis, consisting of more or less pure auditory hallucinosis, prominent at the night time. Most auditory hallucinations are human voices, belonging to their friends or relatives. Ringing, buzzing or clicking sounds are also noted in some patients. These hallucinations appear so real to the patient that he may even call the police or commit suicide if the hallucinations are threatening. Following treatment, the patient realizes the voices were indeed imaginary.
 
Seizures (Rum Fits or Whiskey Fits)
Seizures are usually seen 8–48 hours after the cessation of alcohol. Most of them are GTCS and usually 2–6 episodes are seen in a day. More than 25% of patients with seizures go on to develop delirium tremens. Focal seizures and status epilepticus are uncommon with alcohol withdrawal.
 
DELIRIUM TREMENS
Delirium tremens is an acute organic psychosis that usually manifests 2–3 days after the last alcohol drink. Delirium tremens is the most dangerous alcohol withdrawal symptom. It may follow withdrawal seizures either before the postictal period has cleared or after 1 or 2 asymptomatic days. It is usually seen in a patient who has been admitted for some other illness, accident or operation.
 
Clinical Features
Patients with delirium tremens are confused, agitated and restless. They may exhibit sleeplessness, tremors and sensory hyperacuity. Visual hallucinations (often snakes) and delusions are also seen in some patients. Signs and symptoms of autonomic hyperactivity like fever, diaphoresis, dehydration, tachycardia, arrhythmias and dilated pupils are present.
 
Pathogenesis
The exact pathogenesis of alcohol withdrawal symptoms is still unclear. However, the increase of excitatory neurotransmitters (Glutamate) and a decrease in inhibitory neurotransmitters (GABA) plays an important role in the pathogenesis of this disorder. Hypomagnesemia and increased arterial pH also contribute to the disorder.
 
Investigations
  • Blood investigations—complete blood count, liver function tests, renal function tests
  • ABG analysis, serum electrolytes (potassium, calcium, magnesium)
  • CSF study
  • CT brain, MRI brain
  • EEG.508
 
Management
 
Management of Withdrawal Symptoms
  • Benzodiazepines (drug of choice): Benzodiazepines like diazepam, lorazepam and chlordiazepoxide are the usual drugs used in the management of delirium tremens.
    • Oral (mild withdrawal symptoms): Diazepam 20 mg/day, decreasing at 5 mg/day
    • IV (moderate to severe symptoms): Lorazepam 2 mg/diazepam 10 mg slow IV repeated at 30 minute intervals until the patient is calm
  • Beta-blockers: Atenolol 50 mg od or bid—to reduce the autonomic symptoms
  • Alpha-2 agonists: Clonidine 5 µg/kg orally every 2 hours—for cardiovascular withdrawal symptoms
  • Carbamazepine—400–800 mg daily orally may also be given
  • Thiamine 100 mg/d and other vitamin supplements
  • Phenytoin has no role in preventing seizures during alcoholic withdrawal
  • If hallucinations are the only symptoms, antipsychotics like haloperidol or phenothiazines may be considered (these drugs can increase the risk of seizures).
 
MANAGEMENT OF DELIRIUM TREMENS
Treatment of the patient with delirium tremens can be difficult, and the condition is likely to run a course of 3–5 days regardless of the therapy employed.
  • Parenteral benzodiazepines: Diazepam, 10 mg IV, or lorazepam 2 mg IV or IM, repeated every 15 minutes until calming. Maintenance doses are given every 2–4 hourly depending on the patients response
  • Dehydration—corrected by IV fluids
  • Hyperthermia—corrected by cooling mattresses or evaporative cooling
  • Hypotension—corrected by IV fluids and vasopressors
  • Infections—treated by antibiotics
  • Hypoglycemia—corrected by 25% dextrose
  • Correction of electrolyte abnormalities
  • Thiamine 100 mg IV od, pyridoxine 100 mg/day, folic acid 1 mg/day.
 
BIBLIOGRAPHY
  1. Amato L, Minozzi S, Vecchi S, Davoli M. Benzodiazepines for alcohol withdrawal. Cochrane Database Syst Rev. 2010; CD005063.
  2. Bayard M, Mcintyre J, Hill KR, Woodside JJ. Alcohol withdrawal Syndrome. Am Fam Physician. 2004;69(6):1443-1450.
  3. Benjamin J Sadock, Virginia Alcott Sadock and Pedro Ruiz. Kaplan and Sadock's Comprehensive Textbook of Psychiatry, 9th edition.
  4. Dennis DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscalzo J. Harrison's Principles of Internal Medicine, 18th edition. McGraw Hill Publications; 2012.
  5. Esel E. Neurobiology of alcohol withdrawal: inhibitory and excitatory neurotransmitters. Turkish J Psychiatry. 2006; 17(2):129-37.
  6. Ferguson JA, Suelzer CJ, Eckert GJ, et al. Risk factors for delirium tremens development. J Gen Intern Med. 1996;11:410.
  7. 509Hall W, Zador D. The alcohol withdrawal syndrome. Lancet. 1997;349(9069):1897-1900.
  8. Kosten TR, O'Connor PG. Management of drug and alcohol withdrawal. N Engl J Med. 2003;348:1786.
  9. Malcolm R, Myrick H, Roberts J, Wang W, Anton RF, Ballenger JC. The effects of carbamazepine and lorazepam on single versus multiple previous alcohol withdrawals in an outpatient randomized trial. J Gen Intern Med. 2002;17:349-55.
  10. Mayo-Smith MF. Pharmacological management of alcohol withdrawal. A meta-analysis and evidence-based practice guideline. American Society of Addiction Medicine Working Group on Pharmacological Management of Alcohol Withdrawal. JAMA. 1997;278:144-51.
  11. McKeon A, Frye MA, Delanty N. The alcohol withdrawal syndrome. J Neurol Neurosurg Psychiatry. 2008;79:854-62.
  12. McKinley MG. Alcohol withdrawal syndrome overlooked and mismanaged? Crit Care Nurs. 2005; 25(3):40-9.
  13. Papadakis MA, Mcphee SJ, Raboue MW. Current Medical Diagnosis & Treatment, 54th edition; 2015.
  14. Ropper AH, Samuels MA, Klein J. Adams and Victor's Principles of Neurology, 10th edition.
  15. Rowland LP, Pedley TA. Merritt's Neurology, 12th edition.
  16. Wright T, Myrick H, Henderson S, Peters H, Malcolm R. Risk factors for delirium tremens: a retrospective chart review. Am J Addict. 2006;16:213-9.

DELIRIUM IN INTENSIVE CARE UNITCHAPTER 71

TA Naufal Rizwan  
DEFINITION
Delirium is an acute confusional state characterized by the presence of hallucinations, delusions, illusions along with psychomotor and autonomic overactivity.
 
CLINICAL FEATURES
The symptoms of delirium usually develop over a period of 2–3 days. The earliest symptoms are impaired concentration and restlessness. The other associated features are disruption of the sleep-wake cycle, drowsiness, incoherence, irritability and inattention. Emotional lability, impairment of language and memory are also present. In some patients, autonomic disturbances like tremors, tachycardia, sweating, dilated pupils, facial flushing is seen. These symptoms usually disappear in 2–3 days, although in exceptional cases they may persist for several weeks, and recovery is usually complete.
 
TERMINAL DELIRIUM
Delirium occurring at the end of life. It is usually due to multiple medical causes and may even be unrecognized.
 
Sundowning
Mild-to-moderate delirium occurring at the night, mostly seen in patients with pre-existing dementia, is called as sundowning.
 
Etiology
 
Non-neurologic Causes
  • Pneumonia, enteric fever, malaria, etc.
  • Septicemia and bacteremia (septic encephalopathy)
  • Postoperative states
  • Endocrine causes—Increased thyroid and cortisol levels.511
 
Neurologic Causes
  • Vascular, neoplastic or other diseases involving the temporal lobes and brainstem
  • Concussion and contusion (traumatic delirium)
  • Meningitis, encephalitis
  • Subarachnoid hemorrhage.
 
Toxic/Withdrawal States
  • Alcohol and drugs withdrawal
  • Drug intoxications—cocaine, amphetamine, opiates, benzodiazepines, etc.
  • Postconvulsive delirium.
 
Pathology and Pathophysiology
It has been found that certain specific areas of the brain are responsible for some of the symptoms that are seen in delirium. For example, temporal lobes play a role in auditory and olfactory hallucinations while the midbrain and hypothalamus are concerned with visual hallucinations and autonomic symptoms of delirium, respectively.
The postulated mechanisms of delirium are:
  • Delirium seen in withdrawal states: Some drugs have a depressant action on certain parts of the brain. Withdrawal of these drugs may result in overactivity of those parts of the brain, resulting in delirium.
  • Delirium seen in infections: It is due to the direct toxic effect of the infections on the brain.
 
Differential Diagnosis
Delirium has to be differentiated from:
  • Acute confusional state with psychomotor underactivity
  • Beclouded dementia
  • Acute confusional state secondary to focal cerebral disease.
 
Investigations
The investigations that are needed to be done in a patient with delirium depend on the following three different scenarios of presentation:
  1. Patient is afebrile and no focal neurologic signs
    • Endogenous metabolic disorders: Glucose, urea, creatinine, electrolytes, ABG, thyroid tests, LFT, autoantibody screen, cardiac enzymes, etc.
    • Exogenous toxic state: Toxicologic screening of blood and urine.
  2. Patient is febrile or signs of meningeal irritation present
    • Systemic infection: CBC, chest X-ray, urine routine, urine and blood culture
    • Meningitis and encephalitis: Lumbar puncture.
  3. Focal neurologic signs or seizures present CT or mri scan, eeg.
512
 
Treatment
Four key steps in the management of delirium include:
  1. Identifying the cause
  2. Controlling the behavior
  3. Preventing complications
  4. Supporting functional needs.
 
General Measures
Identifying the underlying medical cause and withdrawal of all the offending drugs must be carried out. Proper environment is mandatory in the management of delirium such as a room with adequate natural lighting will reduce the incidence of ‘sun downing’. A family member or a nurse should be with the patient at all times preferably. An agitated patient should not be tied to the bed, rather he should be allowed to walk about the room as this may reduce his excitement and fright. Warm baths, mentally stimulating activities and frequent reorientation to the surroundings have been found to be effective in reducing the delirium. The physician should explain every procedure (including simple ones like recording the temperature) to the patient as this will allay the fear and reduce the risk of hallucination.
 
Specific Measures (Medications)
Most of the delirious patients can be managed by the general measures described above. However, medications are required in some patients. The two indications for medication in delirious states are behavioral control (e.g. pulling out IV lines) and subjective distress (e.g. pronounced fear due to hallucinations). Haloperidol, quetiapine and risperidone are the commonly used drugs. Benzodiazepines (diazepam or lorazepam) are useful in alcohol withdrawal syndrome.
 
Electroconvulsive Therapy
It has been used as a last resort for delirious patients with severe agitation who are not responsive to pharmacotherapy, such as high doses of IV haloperidol.
 
BIBLIOGRAPHY
  1. Barr J, Fraser GL, Puntillo K, et al. Clinical Practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Critical Care Medicine. 2012
  2. Cavallazzi R, Mohamed Saad, Paul E Marik. Delirium in the ICU. An overview. Annals of Intensive Care. 2012,2:49.
  3. Dan LL, Dennis LK, Larry J, Anthony SF, Stephen LH, Joseph L. Harrison's Principles of Internal Medicine. 18th edition 2012. pp.515-6.
  4. Dubois MJ, Bergeron N, Dumont M, Dial S, Skrobik Y. Delirium in an intensive care unit: a study of risk factors. Intensive Care Med. 2001;27(8):1297-304.
  5. Immers HE, Schuurmans MJ, van de Bijl JJ. Recognition of delirium in ICU patients: a diagnostic study of the NEECHAM confusion scale in ICU patients. BMC Nurs. 2005; 4:7.
  6. 513Jeremy SP, Ryan DH, Li W, Benjamin H, Michael NY, et al. Delirium in survivors of cardiac arrest treated with mild therapeutic hypothermia. Am J Crit Care.2016;25(4):e81-e9.
  7. Mark VB, Peter P, Lisette S. Assessment of delirium in ICU patients. Neth J Crit Care. 2010;14(1).
  8. Maxine AP, Stephen JM, Michael WR. Delirium. Current Medical Diagnosis and Treatment. 54th edition 2015.pp.64-5.
  9. Ouimet S, Kavanagh BP, Gottfried SB, Skrobik Y. Incidence, risk factors and consequences of ICU delirium.Intensive Care Med. 2007;33(1):66-73.
  10. Peterson JF, Pun BT, Dittus RS, Thomason JW, Jackson JC, Shintani AK, Ely EW. Delirium and its motoric subtypes: study of 614 critically ill patients. Am Geriatr Soc. 2006,54(3):479-84.
  11. Reade MC, Finger S. Sedation and delirium in the intensive care unit. N Engl J Med. 2014;370:444-54.
  12. Roberts B, Rickard CM, Rajbhandari D, Turner G, Clarke J, et al. Multicentre study of delirium in ICU patients using a simple screening tool. Aust Crit Care. 2005;18(1): 8-14.
  13. Ryosuke T, Yasutaka O. A clinical perspective of sepsis-associated delirium. Journal of Intensive Care. 2016;4:18.
  14. Sadock BJ, Sadock VA, Ruiz P. Kaplan and Sadock's Comprehensive Textbook of Psychiatry, 9th edition Wolters Kluwer; 2009.
  15. van Eijk MMJ, Slooter AJC. Delirium in intensive care unit patients. Semin Cardoithorac Vasc Anesth. 2010;14:141-47.
514Neuromuscular disorders
Chapter 72 Guillain-Barré Syndrome TA Naufal Rizwan
Chapter 73 Myasthenia Gravis TA Naufal Rizwan
Chapter 74 Periodic Paralysis TA Naufal Rizwan
Chapter 75 Critical Illness Polyneuropathy TA Naufal Rizwan515

GUILLAIN-BARRÉ SYNDROMECHAPTER 72

TA Naufal Rizwan  
GENERAL CONSIDERATIONS
Guillain-Barré syndrome (GBS) is an acute or subacute polyradiculoneuropathy that is autoimmune in nature. Males are frequently affected and adults are at higher risk than children. Subtypes of Guillain-Barré syndrome is given in Table 72.1.
 
ETIOLOGY
In more than 2/3rd of cases, it usually occur 2–3 weeks following an acute respiratory or gastrointestinal infection. Organisms commonly associated with GBS are Campylobacter jejuni, CMV, EBV, human herpes virus, Mycoplasma pneumoniae and HIV. GBS is also frequently seen in patients suffering from SLE and non-Hodgkins lymphoma.
 
PATHOGENESIS
The exact mechanism still remains unclear. However, various evidences show that autoimmunity play an important role in the pathogenesis of GBS. Gangliosides, which are glycosphingolipids are involved in cell-cell interaction and regulation of growth. In GBS, antibodies are directed against these gangliosides resulting in nerve conduction block. Both humoral and cell-mediated immunity contribute to the pathogenesis of the disease.
Table 72.1   Subtypes of Guillain-Barré syndrome
Subtype
Features
Electrodiagnosis
Acute inflammatory demyelinating polyneuropathy (AIDP)
Rapid recovery
Anti-GM1 antibodies
Demyelinating
Acute motor axonal neuropathy (AMAN)
Rapid recovery
Anti-GD1a antibodies
Axonal
Acute motor sensory axonal neuropathy (AMSAN)
Slow recovery
Axonal
Miller-Fisher syndrome (MFS)
Ataxia, areflexia, ophthalmoplegia
anti-GQ1b antibodies
Demyelinating
518
 
CLINICAL FEATURES
The symptoms of Guillain-Barré syndrome are predominantly motor in nature, although sensory and autonomic involvement is noted in some patients.
 
Motor
The most characteristic feature of GBS is symmetrical weakness, which often begin in the legs and then later involve the upper limbs (ascending paralysis). Weakness evolves over hours to few days and leg weakness is more than the arm. Deep tendon reflexes are absent.
 
Sensory
In early GBS, tingling sensation in the legs and pain in the shoulder may be present. Proprioception is greatly affected whereas pain and temperature are usually intact.
 
Cranial Nerves
Bilateral LMN facial palsy, which is asymmetric, is seen in 50% cases. Lower cranial nerves (9–12) involvement, though not very common, can result in bulbar weakness. Rarely 3, 4, 6 nerves are affected.
 
Autonomic Involvement
Autonomic involvement is manifested by facial flushing, sweating and postural hypotension. In serious cases, patient can also develop cardiac arrhythmias, bladder dysfunction and pulmonary dysfunction.
 
Findings which Help in Diagnosis
 
Clinical
  • Progressive, symmetric motor weakness that usually ceases by 4 weeks
  • Hyporeflexia or areflexia
  • Cranial nerve involvement (most common-facial nerve)
  • Mild-to-moderate sensory signs
  • Autonomic involvement—tachycardia, postural hypotension, etc.
  • Recovery starts in 2–4 weeks
  • Preceding GI or respiratory infection.
 
Laboratory
The CSF albumino cytological dissociation [(Elevated CSF protein 1–10 g/L (100–1000 mg/dL) without accompanying pleocytosis)].519
 
Electrodiagnostic
  • Nerve conduction velocity slowing or conduction block (80%)
  • Absence of H and F responses
  • NCV normal in about 20% patients.
 
Findings Reducing the Possibility of GBS
  • Asymmetric weakness
  • Severe bladder/bowel involvement
  • Definite sensory level
  • CSF mononuclear cells >50/mm3.
 
Differential Diagnosis
 
Infections
  • Diphtheria, Lyme disease, tick-borne diseases
  • Poliomyelitis, CMV.
 
Noninfectious
  • Botulism
  • Vasculitis
  • OPC poisoning, arsenic poisoning
  • Myasthenia gravis
  • Porphyria.
 
Treatment
 
General Measures
The general measures include analgesics for pain, frequent turning to prevent pressure sores and exercises to prevent joint contractures.
 
Specific Measures
Steroids have no role in the treatment of GBS. The various treatment options available are:
  • IVIg-administered at a dose of 400 mg/kg/day for 5 days—this neutralizes the GBS autoantibodies
  • Plasmapheresis—40–50 mL/kg plasma exchange, 4–5 times a week.
Treatment is usually not indicated if the patient has reached the plateau phase, unless the motor weakness is very severe. With the above treatment, most patients show improvement at the end of first week. Severe GBS presenting with bulbar dysfunction may require intubation and mechanical ventilation. 520
 
Prognosis
Full recovery is seen in 80–85% of patients, although persisting areflexia may be present. Recovery is delayed and incomplete in GBS with axonal damage. About 5% of patients develop one or more relapses; such cases are designated as chronic inflammatory demyelinating polyneuropathy (CIDP). Advanced age, delay in the onset of treatment and severe GBS indicate poor prognosis.
 
BIBLIOGRAPHY
  1. Bianca van den Berg, Christa Walgaard, Judith Drenthen, Christiaan Fokke, Bart C Jacobs, Pieter A van Doorn. Guillain–Barré syndrome: pathogenesis, diagnosis, treatment and prognosis. Nature Reviews Neurology. 2014;10:469-82.
  2. Colls BM. “Guillain-Barré syndrome and hyponatraemia.” Internal Medicine Journal; 2004.p.218.
  3. Dan LL, Dennis LK, Larry J, Anthony SF, Stephen LH, Joseph L. Harrison's Principles of Internal Medicine, 18th edn; 2012.pp.515-30.
  4. Hadden RD, et al. Preceding infections, immune factors, and outcome in Guillain–Barré syndrome. Neurology. 2001;56:758-65.
  5. Hiraga A, et al. Recovery patterns and long term prognosis for axonal Guillain–Barré syndrome. J Neurol Neurosurg. Psychiatry. 2005;76:719-22.
  6. Hugh JW, Bart CJ, Pieter AV. Guillain-Barrés yndrome. Lancet. 2016;388:717-27.
  7. Hughes RA, et al. Immunotherapy for Guillain–Barré syndrome: a systematic review. Brain. 2007;130:2245-57.
  8. Inés GS, Irene SG, Francisco JR, Javier A. Guillain-Barré Syndrome: Natural history and prognostic factors: a retrospective review of 106 cases. BMC Neurology. 2013;13:95.
  9. Kaida K, Kusunoki S. Antibodies to gangliosides and ganglioside complexes in Guillain–Barré syndrome and Fisher syndrome: mini-review. J Neuroimmunol. 2010; 223:5-12.
  10. Kuwabara S, Yuki N Axonal. Guillain–Barré syndrome: concepts and controversies. Lancet Neurol. 2013;12:1180-8.
  11. Mark M, Heinrich M. Fundamentals of Neurology. 1st edn; 2006. pp.173-4.
  12. Maxine AP, Stephen JM, Michael WR Delirium. Current Medical Diagnosis and Treatment, 54th edn; 2015.pp.1023-6.
  13. Nobuhiro Yuki, et al. Guillain–Barré Syndrome. N Engl J Med. 2012;366:2294-304.
  14. Udaya Seneviratne. Guillain-Barré syndrome; Postgrad Med J. 2000;76:774-82.

MYASTHENIA GRAVISCHAPTER 73

TA Naufal Rizwan
Myasthenia gravis is a neuromuscular junction disorder characterized by fluctuating weakness of certain voluntary muscles. Weakness during continued activity and improvement following rest and anticholinesterases are the important features of this disease.
 
ETIOLOGY
Although exact etiology still remains unclear, autoimmune mechanisms play an important role in the disease process. This is supported by the presence of thymic abnormalities in most of the myasthenia patients.
 
PATHOGENESIS
 
Normal
 
Myasthenia Gravis
In myasthenia gravis, repeated activity reduces the release of ACh at the neuromuscular (NM) junction (presynaptic rundown). Also, there is destruction of the ACh receptor by the anti-AChR antibodies.522
 
Relationship between Thymus Gland and Myasthenia Gravis
About 75% of myasthenia gravies (MG) patients have hyperplastic thymus and 10% have thymomas. Myoid cells (muscle-like cells) in the thymus have AChRs on their surface and may act as an autoantigen, eliciting autoimmune response.
 
CLINICAL FEATURES
Myasthenia gravis affects women more than the men. Peak incidence in women is in their 20s and in men in their 30s. The two cardinal features of MG are weakness and fatigability. Weakness increases on repeated usage and is relieved by rest and drugs. Drugs causing exacerbation of myasthenia gravis is given in Box 73.1. Infections can lead to increased weakness resulting in crisis.
 
 
Eye Signs and Symptoms
Involvement of the eyes is one of the most characteristic and early manifestations of MG.
Ptosis
It occurs due to weakness of levator palpebrae superiors. It can be unilateral or bilateral. Fluctuating ptosis is also seen in some patients. Sunlight worsens the ptosis and ice pack over the eyes relieves it.
Diplopia
It is due to involvement of other extraocular muscles.
Lid twitch sign
Twitching of the upper eyelid that appears a moment after the patient moves the eyes from a downward to the primary position.
 
Other Signs and Symptoms
  • Snarling expression—involvement of facial muscles results in the natural smile being transformed in to snarl
  • Mushy speech—weakness of the tongue
  • Myasthenic hand—weakness of the distal extremity muscles
  • Weakness of neck muscles result in difficulty in holding up the head
  • Chewing, especially tough food like meat, becomes difficult.
In more than 2/3rd of patients, weakness becomes generalized involving the limb muscles. Limb weakness is often proximal and asymmetric. In severe 523cases, weakness of the diaphragm, abdominal muscles, intercostals and even the external sphincters of the bladder and bowel can occur.
Table 73.1   Difference between myasthenia gravis and LEMS
Myasthenia gravis
LEMS
Type
Postsynaptic disorder
Presynaptic disorder
Antibodies against
ACh Receptor
P/Q-type calcium channels
Predominant involvement
Extraocular muscles
Proximal muscles of lower limbs
Deep tendon reflexes
Preserved
Depressed or absent
Repetitive nerve stimulation (Higher rates-50 HZ)
Decremental response
Incremental response
Ocular Myasthenia Gravis
If weakness remains restricted to the ocular muscles for 3 years, it is likely that it will not become generalized and these patients are said to have ocular MG.
Not seen in myasthenia gravis
  • Deep Tendon reflexes are not altered
  • Pain is seldom an important complaint
  • Demonstrable sensory loss is never seen
  • Muscle atrophy is usually not seen.
 
Differential Diagnosis
  • Lambert-Eaton myasthenic syndrome (LEMS) (Table 73.1)
  • Botulism
  • Neurasthenia
  • Hyperthyroidism
  • Congenital myasthenic syndromes (genetic abnormality).
 
Disorders Associated with MG
Rheumatoid arthritis, systemic lupus crythematosus (SLE), Graves’ disease, thymoma, Hashimotos thyroiditis, etc.
 
INVESTIGATIONS
 
Antibodies Assay
  • Anti-ACh receptor antibodies: These are the most important antibodies and are seen in 85% of generalized MG and 50% of ocular MG patients. However, the absence of these antibodies does not rule out MG. Similarly, no correlation has been found between the antibody level and severity of the disease. The antibody level decrease with the treatment and exacerbations increase it.
  • 524Anti-musk (muscle specific kinase) antibodies: These are seen in around 40% generalized MG patients, in whom AChR antibody is negative. They are not seen in AChR antibody positive or ocular MG patients.
 
Electrodiagnostic Testing
 
Prerequisites
Anti-AChE medications should be stopped at least 6 hours before the test. Weak muscles or proximal muscles should be tested preferably. Electric shock should be delivered at a rate of 2–3/second and muscle action potentials recorded.
 
Impression
Normal persons: Repetitive nerve stimulation does not change the evoked responses.
Myasthenia gravis: Rapid reduction of >10–15% in the amplitude of the evoked responses.
 
Anticholinesterase Test
Edrophonium (Tensilon) 2 mg IV given—if weakness improves, it is suggestive of MG. Edrophonium is preferred because it is both short as well as rapid acting. Since edrophonium can produce side effects such as nausea, diarrhea, salivation, etc. atropine should be kept ready. Neostigmine 15 PO can also be used for the test.
 
Imaging
  • CT or MRI of the brain to rule out intracranial lesions in ocular or cranial MG
  • CT mediastinum to rule out thymoma.
 
TREATMENT
Various treatment options available are as follows:
  • Anticholinesterase medications
  • Immunosuppressive agents
  • Intravenous immunoglobulin (IVIg)
  • Plasmapheresis
  • Thymectomy.
 
Anticholinesterase Medications
Pyridostigmine is the most commonly used drug and the usual dose is 30–60 mg given 3–4 times daily. Action starts in 15 minutes and last up to 3–4 hours. Nausea, salivation and diarrhea are the common side effects which can be managed with atropine/diphenoxylate or loperamide.525
 
Glucocorticoids
 
Prednisolone
 
Other Immunosuppressive Drugs
  • Azathioprine: The usual starting dose is 50 mg/d which is then gradually increased to 2–3 mg/kg. However, beneficial effect is seen only after 3–6 months. Idiosyncratic reactions such as flulike symptoms, bonemarrow suppression are seen in 10% of patients. Allopurinol should not be used to treat hyperuricemia in patients receiving azathioprine.
  • Mycophenolate mofetil: This drug acts by inhibiting the purine synthesis of the denovo pathway. The dose is 1–1.5 g, given twice a day. Beneficial effect is seen only after many months. The adverse effects are rare with a very small risk of malignancy.
  • Calcineurin inhibitors: The calcineurin inhibitors used in the treatment of MG are Cylosporine (4–5 mg/kg/d) and Tacrolimus (0.07–0.1 mg/kg/d). Nephrotoxicity and hypertension are important adverse effects.
  • Cyclophosphamide: Indicated in MG refractory to other treatment.
  • Rituximab: It is an antibody against CD20 B cells and is preferably used in MG with anti-MuSK (muscle-specific tyrosine kinase) antibody.
 
Plasmapheresis
It is a procedure where the pathogenic antibodies are mechanically removed from the blood. Usually, 5 exchanges are done over 2 weeks period (3–4 L/exchange). It is used as a temporary procedure in serious patients.
 
IV Immunoglobulin
The usual dose of IVIg is 400 mg/kg/d given for 5 days. It should not be used as a long-term management. Mild side effects like headache, fluid overload are noted in some patients.
 
Thymectomy
Following thymectomy, improvement is seen in up to 85% patients. Removal of thymoma, if present, also reduces the risk of local tumor spread. All patients 526with generalized MG, between puberty and 55 years of age, should undergo thymectomy (even if thymoma is not present).
 
EVALUATING THE EFFECTIVENESS OF TREATMENT
  • Range of eye movements
  • Forced vital capacity
  • Time taken for the ptosis to develop following an upward gaze
  • Forward arm abduction time (for 5 min).
 
MYASTHENIC CRISIS
 
Definition
Exacerbation of weakness in a myasthenic patient which is serious enough to endanger the life is known as myasthenic crisis.
 
Causes
Infection (most common cause) and excessive anticholinesterase drugs (cholinergic drugs).
 
Treatment
  • Antibiotic therapy
  • Respiratory assistance
  • Fluid and electrolyte balance to be maintained
  • Plasmapheresis or IVIg
  • Stop AChE drugs if their excessive use is the cause for crisis.
 
BIBLIOGRAPHY
  1. Allan H Ropper, Martin A Samuels, Joshua Klein. Adams and Victor's Principles of Neurology, 10th edn.
  2. Andrew G Engel, Michael Benatar. Myasthenia gravis and myasthenic disorders. Neurology. 2013;81(1)99.
  3. Annapurni Jayam Trouth, Alok Dabi, Noha Solieman, Mohankumar Kurukumbi, Janaki Kalyanam. Myasthenia gravis: A review. Autoimmune Dis. 2012; 2012:874680.
  4. Barth D, Nabavi Nouri M, Ng E, Nwe P, Bril V. Comparison of IVIg and PLEX in patients with myasthenia gravis. Neurology. 2011;76(23)2017-23.
  5. Batocchi AP, Evoli A, Schino CD, Tonali P. Therapeutic apheresis in myasthenia gravis. Therapeutic Apheresis. 2000;4(4):275-9.
  6. Chaudhry V, Cornblath DR, Griffin JW, O'Brien R, Drachman DB. Mycophenolate mofetil: a safe and promising immunosuppressant in neuromuscular diseases. Neurology. 2001;56(1):94-6.
  7. Dan L Longo, Dennis L Kasper, J Larry Jameson, Anthony S Fauci, Stephen L Hauser, Joseph Loscalzo. Harrison's Principles of Internal Medicine, 18th edn. 2012. McGraw Hill publications.
  8. 527Gold R, Schneider-Gold C. Current and future standards in treatment of myasthenia gravis. Neurotherapeutics. 2008;5(4):535-41.
  9. Hellmann MA, Mosberg-Galili R, Lotan I, Steiner I. Maintenance IVIg therapy in myasthenia gravis does not affect disease activity. 2014;338(Issues 1-2):39-42.
  10. Keesey JC. Clinical evaluation and management of myasthenia gravis. Muscle and Nerve. 2004;29(4):484-505.
  11. Lewis P Rowland, Timothy A Pedley. Merritt's Neurology, 12th edn.
  12. Maxine A Papadakis, Stephen J McPhee, Michael W Rabow. Current Medical Diagnosis and Treatment, 54th edn. 2015.
  13. Pascuzzi RM. The edrophonium test, Seminars in Neurology. 2003;23(1):83-8.
  14. Pescovitz MD. Rituximab, an anti-CD20 monoclonal antibody: history and mechanism of action. American Journal of Transplantation. 2006;6(5):859-66.
  15. Vern C Juel, Janice M Massey. Myasthenia gravis. Orphanet Journal of Rare Diseases. 2007;2:44.

PERIODIC PARALYSISCHAPTER 74

TA Naufal Rizwan
Familial periodic paralysis comprises diseases characterized by recurrent episodes of limb weakness. The three main types are:
  1. Hypokalemic periodic paralysis (HypoKPP)
  2. Hyperkalemic periodic paralysis (HyperKPP)
  3. Anderson's syndrome or periodic paralysis with cardiac arrhythmia.
 
HYPOKALEMIC PERIODIC PARALYSIS
This disorder occurs due to a mutation in the CALCL1A3 or SCN4A.
 
Types
 
HypoKPP Type 1 (90%)
It is the most common type and it is inherited as an autosomal dominant disorder. It occurs due to mutation in the skeletal muscle calcium channel gene CALCL1A3.
 
HypoKPP Type 2 (10%)
It is due to mutations in the voltage-sensitive sodium channel gene (SCN4A).
Clinical features
Diet rich in carbohydrate and sodium, and rest following prolonged exercise are the usual predisposing factors for hypokalemic periodic paralysis. Weakness affects the proximal muscles more than the distal muscles. Ocular and bulbar muscles are less commonly involved while the respiratory muscles are usually spared. Weakness usually resolves in 24–48 hours. Only in severe attacks, tendon and cutaneous reflexes are absent. Cutaneous sensation is not disturbed. Repeated attacks of HypoKPP have been found to occur in patients with hyperthyroidism. However, the paralytic attacks cease when the thyroid disorder has been successfully treated.
Complications
Immediate: Life-threatening cardiac arrhythmias-due to hypokalemia.
Delayed: Severe proximal weakness.529
Investigations
  • Documentation of low potassium and increased sodium level during attacks.
  • Interattack muscle biopsies show the presence of single or multiple centrally placed vacuoles or tubular aggregates.
  • Motor conduction studies may demonstrate reduced amplitudes.
  • EMG may show electrical silence in severely weak muscles. In between attacks, EMG and NCS are usually normal.
Treatment
During attacks: Oral KCl 0.2–0.4 mmol/kg every 30 minutes until serum potassium becomes normal. However, if patient has vomiting or diarrhea or cannot take oral potassium, it should be given as intravenous infusion (preferably in mannitol since dextrose containing solution are contraindicated).
Prophylactic treatment:
  • Acetazolamide 125–1000 mg/d in divided doses (only in hypoKPP type 1)
        Although acetazolamide paradoxically lowers the potassium level, this is offset by the beneficial effect of metabolic acidosis
  • Triamterene or spironolactone 25–100 mg/d
  • Low carbohydrate, low sodium diet.
 
HYPERKALEMIC PERIODIC PARALYSIS
This disorder occurs due to a mutation in sodium channel SCN4A gene.
 
Description
Weakness is usually mild, often affects the proximal muscles and usually lasts less than 4 hours. Attacks are precipitated by rest following exercise and fasting.
 
Investigations
Serum potassium: Potassium values are usually elevated, although in a significant proportion of cases, it is within normal limits.
Nerve conduction study: Reduced motor amplitudes.
EMG: Myotonic discharges during and between attacks.
Muscle biopsy: Vacuoles that are smaller, less numerous, and more peripheral compared to the hypokalemic form or tubular aggregates are seen.
 
Treatment
  • Acetazolamide 125–1000 mg/d in divided doses.530
  • Thiazides or fludrocortisone.
 
Potassium-aggravated Myotonia
It is a variant of hyperkalemic periodic paralysis in which weakness is not seen, instead myotonia is present.
 
ANDERSON'S SYNDROME
Five diagnostic criteria for Anderson's syndrome are:
  1. Dysmorphism
  2. Periodic paralysis
  3. Potassium sensitivity
  4. Myotonia (usually mild)
  5. Cardiac arrhythmia.
Spontaneous attacks have been associated with high, low, or normal potassium levels.
 
BIBLIOGRAPHY
  1. Allan H Ropper, Martin A Samuels, Joshua Klein. Adams and Victor's Principles of Neurology, 10th edn.
  2. Bendahhou S, Cummins TR, Tawil R, Waxman SG, Ptacek LJ. Activation and inactivation of the voltage-gated sodium channel: role of segment S5 revealed by a novel hyperkalaemic periodic paralysis mutation. J Neurosci. 1999b;19:4762-71.
  3. Benjamin R Soule, Nicole L Simone. Hypokalemic periodic paralysis: a case report and review of the literature. Cases Journal. 2008;1:256.
  4. Dan L Longo, Dennis L Kasper, J Larry Jameson, Anthony S Fauci, Stephen L Hauser, Joseph Loscalzo. Harrison's Principles of Internal Medicine. 18th edn. 2012. McGraw Hill publications.
  5. Donaldson MR, Jensen JL, Tristani-Firouzi M, Tawil R, Bendahhou S, Suarez WA, et al. PIP2 binding residues of Kir 2.1 are common targets of mutations causing Andersen syndrome. Neurology. 2003;60:1811-6.
  6. Haider Abbas, Nikhil Kothari, Jaishri Bogra. Hypokalemic periodic paralysis. Natl J Maxillofac Surg. 2012;3(2):220-1.
  7. Heine R, Pika U, Lehmann-Horn F. A novel SCN4A mutation causing myotonia aggravated by cold and potassium. Hum Mol Genet. 1993;2:1349-53.
  8. Jurkat-Rott K, Lerche H, Lehmann-Horn F. Skeletal muscle channelopathies. J Neurol. 2002;249(11):1493-1502.
  9. Lewis P Rowland, Timothy A Pedley. Merritt's Neurology,12th edition.
  10. Maxine A Papadakis, Stephen J McPhee, Michael W Rabow. Current Medical Diagnosis and Treatment, 54th edn. 2015.
  11. Okinaka S, Shizume K, Iino S, Watanabe A, Irie M, Noguchi A, The association of periodic paralysis and hyperthyroidism in Japan.J Clin Endocrinol Metab. 1957; 17(12):1454-9.
  12. Periodic Paralyses Treatment and Management: Naganand Sripathi, MD; Nicholas Lorenzo, MD, CPE.
  13. Phillip Wong. Hypokalemic thyrotoxic periodic paralysis: Case Reports; CJEM. 2003; 5(5):353-5.
  14. Sushil K Ahlawat, Anita Sachdev. Hypokalaemic paralysis. Postgrad Med J. 1999;75:193-7.

CRITICAL ILLNESS POLYNEUROPATHYCHAPTER 75

TA Naufal Rizwan
Critical illness polyneuropathy (CIP) is a sensorimotor polyneuropathy which is characterized by flaccid weakness and sensory loss and is seen in patients who are critically ill. It was first described by Bolton and colleagues in 1984.
 
PREDISPOSING FACTORS
It is seen in critically-ill patients who are suffering from sepsis and multiorgan failure. Although the exact incidence is not known, it has been estimated that more than 50% of patients in ICU with sepsis/systemic inflammatory response syndrome (SIRS) develop CIP. Additional risk factors for developing CIP are female gender, high blood sugar, low serum albumin, immobility, multi-organ dysfunction, renal failure, renal replacement therapy, duration of organ dysfunction and ICU stay, low albumin and central neurologic failure.
 
PATHOLOGY
Critical illness polyneuropathy is primarily a distal axonopathy in which distal degeneration of both motor and sensory axons occur without any inflammation. The underlying cause of the axonal degeneration may relate to a lack of vascular autoregulation and increased microvascular permeability resulting in endoneural edema and capillary occlusion.
 
PATHOGENESIS
Although the exact pathogenesis is still unclear, microcirculatory changes have been postulated to be the leading factor involved in the disease process (Flow chart 75.1).
 
CLINICAL FEATURES
Critical illness polyneuropathy often overlaps with critical illness myopathy. The clinical features of CIP are:
  • Tetraparesis or tetraplegia is the hallmark of this disease. Weakness is generalized, flaccid, symmetric and progressive. Lower limbs are involved 532more commonly than the upper limbs. Weakness of the distal muscles is more than the proximal muscles. Phrenic nerve, if involved, can result in respiratory difficulties. In fact, most of the times, CPI is identified only when the patient is unable to be successfully weaned from the mechanical ventilator.
    Flow chart 75.1: Pathogenesis of critical illness polyneuropathy
  • Deep tendon reflexes are diminished or lost. Abnormalities of the touch, pain, temperature and vibration sensation (which is more in the distal parts) is also noted in patients with CPI.
 
Screening
Initial screening for CIP/CIM may be performed using the Medical Research Council (MRC) score. The MRC score involves assessing strength in 3 muscle groups in the right and left sides of both the upper and lower extremities. Each muscle tested is given a score of 0–5, giving a total possible score of 60. An MRC score less than 48 is suggestive of CIP/CIM. However, it can be done only in patients who are awake and cooperative, which unfortunately is not usually seen in ICU patients. Also, the screening tool is nonspecific, because it does not identify the cause a person's muscle weakness. If weakness is detected, this evaluation should be done repeatedly. In the case of weakness being persistent, nerve conduction study should be performed.
 
Diagnosis
Nerve conduction study is the best diagnostic test to confirm critical illness polyneuropathy. Electrophysiological studies show reduction or absence of both compound muscle and sensory nerve action potentials, fibrillations and loss of motor unit potentials with a maximal effort. Significant slowing of nerve conduction or nerve conduction blocks are not seen and if present, the possibility of Guillain-Barré syndrome should be considered. The presence of tissue edema, inadequate voluntary contraction and electrical interference often makes this test difficult to perform.533
 
Differential Diagnosis
The differential diagnosis for CIP are Guillain-Barré syndrome, acute porphyria, botulism, prolonged effect of nondepolarizing neuromuscular blocking agents and myasthenic crisis.
 
TREATMENT
No specific treatment is available. Supportive treatment includes proper attention to the pulmonary hygiene and prevention of bed sores, deep vein thrombosis, skin breakdown and compressive neuropathies. Hyperglycemia and hypoalbuminemia should be corrected. Intensive insulin therapy is found beneficial in the management of CIP. Insulin itself has some potential beneficial effects, including anti-inflammatory effects, endothelial protection, improvement of dyslipidmia and is also an anabolic hormone.
Rehabilitation is another important component in the management of CIP. The various physiotherapy options available are exercises, early mobilization and percutaneous neuromuscular electrical stimulation (NMES). NMES is a method to induce skeletal muscle growth as well as to enhance capacity for patients who are not able to perform active exercises preventing loss of muscle mass. Since patient cooperation is not required, it is considered an alternative for active exercises. NMES has been found to increase muscle strength, regional vascularization (helps in pressure sores) and tissue healing. Recovery from critical illness polyneuropathy takes months to years and is often incomplete.
 
BIBLIOGRAPHY
  1. Bednarík J, Vondracek P, Dusek L, Moravcova E, Cundrle I. Risk factors for critical illness polyneuromyopathy. J Neurol. 2005;252:343-51.
  2. Bolton CF, Gilbert JJ, Hahn AF, Sibbald W. Ployneuropathy in critical ill patients. J Neurol Neurosurg Psychiatry. 1984;47:1223-31.
  3. Bolton CF. Neuromuscular complications of sepsis. Int Care Med. 1993;19:S58-63.
  4. Coakley JH, Nagendran K, Yarwood GD, Honavar M, Hinds CJ. Patterns of neurophysiological abnormality in prolonged critical illness. Intensive Care Med. 1998;24: 801-7.
  5. De Letter MA, Schmidtz PI, Visser FA, Verheul FA, Schellens RL, Op de Coul DA, et al. Risk factors for development of polyneuropathy and myopathy in critically ill patients.Crit Care Med. 2001;29:2281-6.
  6. Garnacho-Montero-J, Madrazo-Osuna J, Garcia-Garmendia JL. Critical illness polyneuropathy: Risk factors and clinical consequences—A cohort study in septic patients. Int Care Med. 1993;27:1288-96.
  7. Gerovasili V, Stefanidis K, Vitzilaios K, Karalzanos E, Politis P, Koroneos A. Electrical muscle stimulation preserves the muscle mass of critical ill patients: A randomized study. Crit Care. 2009;13:161.
  8. Johnson KL. Neuromuscular complications in the intensive care unit-critical illness polyneuromyopathy. AACN Advanced Crit Care. 2007;18:167-82.
  9. Latronico N, Bertolini G, Guarneri B, Botteri M, Peli E, Andreoletti S, et al. Simplified electrophysiological evaluation of peripheral nerves in critically ill patients:The Italian multicenter rimynestudy. Crit Care. 2007;11:R11.
  10. Latronico N, Fenzi F, Recupero D, Guarneri B, Tomelleri G, Tonin P, et al. Critical illness myopathy and neuropathy. Lancet. 1996;347:1579-82.
  11. 534Lefaucheur JP, Nordine T, Rodriguez P, Brochard L. Origin of ICU acquired paresis determined by direct muscle stimulation. J Neurol Neurosurg Psychiatry. 2006;77: 500-6.
  12. Leijten FS, de Weerd AW, Poortveit DC, De Ridder VA, Ulrich C. Critical illness polyneuropathy in multiorgan dysfunction syndrome and weaning from ventilator. Int Care Med. 1996;22:856-61.
  13. Routsi C, Gerovasili V, Vasileiadis I, Karalzanos E, Pitsolis J, Tripodaki E. Electrical stimulation prevents critical illness polyneuromyopathy: A randomized parallel intervention trial. Crit Care. 2010;14:274.
  14. Stevens RD, Dowdy DW, Michaels RK, Mendez–Tellez PA, Pronovost PJ, Needham DM. Nueromuscular dysfunction acquired in critical care illness. Int Care Med. 2007;33:1876-91.
  15. Tepper M, Rakic S, Haas JA, Woittiez AJ. Incidence and onset of critical illness polyneuropathy in patients with septic shock. Neth J Med. 2000;56:211-4.
  16. Witt NJ, Zochodne DW, Bolton CF, Grand Maison F, Wells G, Young GB, et al. Peripheral nerve function in sepsis and multiple organ failure. Chest. 1991;99:176-84.
535Approach to a trauma patient
Chapter 76 Advanced Trauma Life Support Prem Kumar
Chapter 77 Open Fractures K Gunalan
Chapter 78 Pelvic Fractures K Gunalan
Chapter 79 Fat Embolism Syndrome Sushma Vijay Pingale
Chapter 80 Abdominal Trauma Marun Raj
Chapter 81 Vascular Trauma of Extremities Marun Raj
Chapter 82 Traumatic Head Injury Sushma Vijay Pingale, V Thanga Thirupathi Rajan
Chapter 83 Thoracic Trauma Sushma Vijay Pingale, Marun Raj536

ADVANCED TRAUMA LIFE SUPPORTCHAPTER 76

Prem Kumar  
INTRODUCTION
The advanced trauma life support (ATLS) guidelines recommend that any trauma evaluation should first include a “primary survey” which includes the identification and treatment of life and limb threatening injuries beginning with the treatment of the injury which requires immediate attention (Table 76.1). The focus should be on urgent problems which should be captured in the “golden hour”. Once these urgent needs are taken care of, a meticulous “secondary survey” is done with further diagnostic studies to reduce the incidence of missed injuries. Faster the diagnosis, faster the initiation of treatment and better the outcome. ATLS emphasizes the ABCDE mnemonic: airway, breathing, circulation, disability, and exposure.
 
AIRWAY
Verifying for an open airway is of prime importance since hypoxia is the immediate threat to the patient if airway is involved in trauma. Causes of airway obstruction in trauma patients is given in Table 76.2. Hypoxia can lead to permanent brain damage and if airway is not protected, patient may end up in death due to hypoxia in 5–10 minutes.
Table 76.1   Primary survey
Airway
Breathing
Circulation
Disability
Exposure
Diagnosis
Auscultation
Pulse oximetry, ABG, chest X-ray
  • Vital signs, e-FAST, typing and cross matching,
  • Coagulation parameters,
  • Complete blood count, pelvic X-ray
  • GCS score, neurological examination,
  • Cervical spine films, CT-brain
  • Full physical examination,
  • Detailed history, other lab studies to support diagnosis.
Management
Triple maneuver, oxygen, intubation
  • Mechanical ventilation
  • Intercostal drainage
  • IV access
  • Fluid infusion
  • Pressure on wounds
  • O-ve blood Thoracotomy
  • Surgery
  • Pelvic binder
  • Cervical collar
  • Emergency surgery, ICP monitoring
  • Removal of clothes and thorough examination
  • Surgery
  • Detailed review
538The airway is best managed by endotracheal intubation in comatose patients. Rapid sequence induction is done with thiopentone (3–5 mg/kg), fentanyl (3–5 µg/kg) followed by a short acting neuromuscular blocking agent like succinylcholine (1–2 mg/kg). Succinylcholine can increase the intracranial pressure transiently but its use will lead to faster intubation, its benefits may outweigh its risks. Hence, one must weigh the use of succinylcholine in each individual situation based on the acuity of CNS injury, the anticipated speed with which intubation should be accomplished, and the likelihood that hypoxia will develop. Alternative to succinylcholine are rocuronium (0.9–1.2 mg/kg). But rocuronium has longer duration of action compared to succinylcholine. The use of thiopentone may result in hypotension in volume depleted patients hence etomidate would be a better choice in these patients. The patient should be adequately preoxygenated by giving 100% oxygen for 5 minutes or 4 vital capacity breaths if it is an emergency. The patient should be intubated in neutral head position with a manual-in line cervical spine immobilization in case of suspected cervical spine injury which is discussed in the chapter under airway management. Indications of endotracheal intubation in trauma patients is given in Table 76.3. The placement of the endotracheal tube should be confirmed by auscultation in prehospital setup and by a capnometer in hospital setup. The endotracheal tube not only helps in establishing good oxygenation and ventilation but also protects against aspiration. When oral intubation is difficult, as seen in severe maxillofacial trauma or difficult airway, then urgent surgical airway should be established by a cricothyrotomy or tracheostomy.
Table 76.2   Causes of airway obstruction in trauma patients
Causes of airway obstruction or inadequate ventilation in trauma patients
  • Hemorrhage in the upper airway
  • Poor consciousness (GCS <8) leading to airway obstruction due to tongue
  • Aspiration of gastric contents
  • Cervical spine injury
  • Pneumothorax
  • Direct injury to tracheobronchial tree
  • Shock
  • Traumatic brain injury
Table 76.3   Indications of endotracheal intubation in trauma patients
Acute airway obstruction
  • Traumatic airway injury
  • Burns causing smoke inhalation
  • Laryngeal edema
  • Laryngospasm
    • Head injury with GCS ≤8
    • Cardiac arrest
    • Trauma patients with respiratory failure
    • Risk of aspiration (bleeding, vomiting)
539
 
BREATHING
Breathing if found to be shallow and inadequate mandates mechanical ventilation. Injuries which must be made out are tension pneumothorax, flail chest, pulmonary contusion. Inspect the head and neck, look for symmetrical chest movements, subcutaneous emphysema, tracheal deviation or use of accessory muscles of respiration. Surgical or interventional procedure may be required and has high priority if it is the cause of cardiac arrest (e.g. Cricothroidotomy, tracheostomy for upper airway obstruction, tube thoracostomy, or open thoracotomy).
 
CIRCULATION
Hemorrhage is the next priority in any trauma patient since it can be fatal if it is ongoing and untreated. Prompt identification and assessment of hemorrhage, identifying the cause of hemodynamic instability and faster initiation of management while resuscitation is ongoing will improve the outcome in a trauma patient presenting with hypovolemic shock. Assessment of shock includes an early phase which focuses on the diagnosis of the common sites of bleeding followed by immediate intervention in ED or OT if the condition requires immediate intervention. This is followed by a late phase which begins after hemostasis is achieved until restoration of the normal physiology. The sites of bleeding in a trauma patient are assessed by FAST scan which is discussed in detail under the chapter role of ultrasound in critical care. In case of active hemorrhage requiring surgical intervention, damage control surgery is done for anatomic control of hemorrhage. Goals of early and late resuscitation is given in Table 76.4.
Resuscitation of hemorrhage is based upon three goals:
  1. Restoration of blood volume
  2. Restoration of peripheral vascular resistance
  3. Restoration of tissue perfusion.
Resuscitation of hemorrhagic shock is divided into two phases:
  1. Early phase—ongoing active bleeding
  2. Late phase—all the sources of bleeding are controlled.
Table 76.4   Goals of early and late resuscitation
Goals of early resuscitation
Goals of late resuscitation
Systolic blood pressure of 80–90 mm Hg
Normal coagulation parameters
Hematocrit of 25–30%
Platelet count >50,000/mm3
Maintain core temperature >35°C
Prevent worsening of acidosis and increase in lactate
Adequate analgesia
Systolic blood pressure >100 mm Hg
Normal coagulation parameters
Hematocrit of >25%
Maintain normal body temperature
Maintain normal electrolytes, urine output
Reverse systemic acidosis and document the trend of serum lactate
Optimize cardiac output
540
 
Early Resuscitation
Administration of fluids is the mainstay of management in early phase. The goal of resuscitation is to restore cardiac output and blood pressure. Initial administration of 20 mL/kg of warmed isotonic crystalloids is recommended by guidelines. Isotonic crystalloids (ringer lactate, normal saline, Plasma-Lyte A) are administered and any visible hemorrhage is controlled with direct pressure. Current evidence recommends the application of hypotensive resuscitation [or damage control resuscitation (DCR)] in patients with hemorrhagic shock with active bleeding where the source of bleeding is unknown and the definitive control of bleeding is not done although this approach has not been shown to improve mortality. DCR is a strategy combining hemostatic resuscitation, permissive hypotension and damage control surgery. Goals of this strategy are initial stabilization of the patient, reducing metabolic acidosis, hypothermia, hypocalcemia and coagulopathy. This hypotensive resuscitation strategy reduces transfusion requirement and severe postoperative coagulopathy in trauma patients with hemorrhagic shock. Mean arterial pressure of 65 mm Hg is the goal for this resuscitation.
Aggressive fluid resuscitation can cause increased blood pressure thereby leading onto increased bleeding, dilutional anemia resulting in reduced tissue perfusion, reduced clotting factors, immune suppression, hypothermia, electrolyte disturbances. Blood sample is sent for grouping, cross-matching, complete blood count, lactate. Blood gas analysis is also done.
 
Late Resuscitation
It starts after control of bleeding by surgery or by other methods. The goal of late resuscitation is to restore tissue perfusion along with vital organ support. Prolonged tissue and organ hypoperfusion can lead onto multiorgan failure.
 
Resuscitation Fluids
 
Isotonic Crystalloids
Initial fluid of choice for trauma patients with hemorrhagic shock are isotonic crystalloids (ringer lactate, normal saline, Plasma-Lyte A). Advantages —they are cost-effective, nonallergic, noninfectious, can be administered with medications, easy for administration and can be easily warmed to room temperature. Disadvantages are absence of coagulation capacity, reduced half-life in the intravascular compartment, absence of O2 carrying capacity, can trigger cellular apoptosis due to reperfusion injury.
 
Hypertonic Saline
It is not recommended for routine use in trauma patients but the advantage of hypertonic saline is its faster ability to restore intravascular volume than crystalloids. It can be used for fluid resuscitation in war conditions. It can be used as an osmotic agent in patients with traumatic brain injury with raised intracranial pressure.541
 
Colloids
Colloids though has the theoretical advantage of rapidly restoring intravascular volume than crystalloids, it has been found by studies that colloids have no better advantage over crystalloids in terms of tissue perfusion and mortality. It can be used when the IV access is limited. Disadvantages are the lack of O2 carrying capacity and clotting.
 
Packed RBCs
They are the most important blood component for the treatment of traumatic hemorrhagic shock. Advantages are O2 carrying capacity, better expansion of intravascular volume compared to other fluids. In case of emergency when there is no time for cross-matching, O negative blood is given. Disadvantages are transfusion reactions, infections, hypothermia, etc.
 
Plasma
It may be required in conditions when there is expected massive transfusion or in patients with coagulopathy. Plasma requires blood typing and not cross-matching.
 
Platelets
Current evidence recommends the administration of PRBC: Fresh frozen plasma: platelets in a ratio of 1:1:1 in patients with massive blood loss. This approach has been shown to improve survival due its impact on the early intervention in preventing trauma-induced coagulopathy. Platelet transfusion is indicated for coagulopathic patients with active bleeding. Platelets should not be administered through warmers or rapid infusors since it can adhere to the surfaces of these devices.
 
MASSIVE TRANSFUSION
 
Definition
Transfusion of blood more than patient's blood volume in 24 hours or transfusion of >10% blood volume in <10 minutes or >50% of blood volume in 4 hours in an adult.
Massive transfusion can occur in clinical scenarios like trauma, surgical complications, ruptured aortic aneurysm, etc. mortality is high after massive transfusion due to acidosis, coagulopathy, etc.
 
Criteria for Activation of Massive Transfusion Protocol (Flow chart 76.1)
  • Major surgical bleeding
  • Severe trauma of thorax, abdomen or long bones resulting in severe blood loss542
    Flow chart 76.1: Massive transfusion protocol (MTP)
  • Actual or anticipated transfusion of 4 units of packed RBCs in <4 hours
  • Unstable hemodynamics with active ongoing bleeding.
 
Goals of Massive Transfusion Protocol (Table 76.5)
Optimization of tissue perfusion, oxygenation and cardiac output are goals of massive transfusion protocol (MTP). Lab studies are done every 30–60 minutes to monitor the electrolyte, coagulation, metabolic and acid base status. Complete blood count, serum-ionized calcium, ABG, coagulation studies are done every hour to monitor status.
 
COMPLICATIONS
Hypocalcemia due to citrate, hypothermia, hyperkalemia due to release of potassium on cell lysis, metabolic alkalosis occurs due to conversion of citrate to lactate and in turn to bicarbonate. Other complications are ARDS, DIC. The most common cause of bleeding following massive blood transfusion is dilutional thrombocytopenia.543
Table 76.5   Goals of resuscitation in MTP
  • pH >7.2
  • Base excess < –5
  • Serum lactate <4 mmol/L
  • Platelet count >50,000/mm3
  • Coagulation studies—PT/aPTT <1.5 times the normal, INR ≤1.5, serum fibrinogen >100 mg/dL
  • Serum ionized calcium >1.1 mmol/L
  • Core temperature >35°C
 
Disability
Level of consciousness is assessed using AVPU scale—alert, voice, pain, unresponsiveness (GCS, pupil size, reaction to light, equality). If required, intubate the patient, start intravenous mannitol 1 g/kg in case of increased ICP and prepare to shift the patient for CT-brain and cervical spine film. If the patient is hemodynamically unstable, stabilize the patient and shift for imaging. Put cervical collar in case of suspected cervical spine injury, push for emergency surgery in case of any need for surgical intervention.
 
Exposure
Complete physical examination is done after undressing the patient. Prevent hypothermia by removing the source causing hypothermia. Lab investigations are done for support of diagnosis followed by complete review of the patient.
 
Secondary Survey
Once the primary survey is over and the primary resuscitation efforts are over along with optimization of vital function, secondary survey is started with head to toe evaluation. Complete history and physical examination including neurological examination are done to review the patient. Vital signs are reevaluated, lab studies and imaging are done to confirm the clinical diagnosis. Additional studies which can be done after stabilization of the patient to diagnose the suspected condition are CT-chest, abdomen, spine, angiography, bronchoscopy, esophagoscopy, urography, etc. Patients with trauma are frequently reevaluated with monitoring of vital signs, ABG, central venous pressure, pulse oximetry, urine output. Pain relief is given with regional nerve blocks and IV opioids.
Head trauma, thoracic trauma and abdominal trauma are discussed in detail in their respective chapters.
 
BIBLIOGRAPHY
  1. Advanced Trauma Life Support Course for Physicians. The American College of Surgeons; 1993.
  2. Crosby ET. Tracheal intubation in the cervical spine-injured patient-Editorial. Can J Anaesth. 1992;39(2):105-9.
  3. 544Doyle JA, Davis DP, Hoyt DB. The use of hypertonic saline in the treatment of traumatic brain injury. J Trauma. 2001;50:367-83.
  4. Dutton RP, McCunn M, Hyder M, et al. Factor VIIa for correction of traumatic coagulopathy. J Trauma. 2004;57:709-18.
  5. Majernick TG, Bieniek R, Houston JB, et al. Cervical spine movement during orotracheal intubation. Ann Emerg Med. 1986;15:417-20.
  6. Podolsky S, Baraff LJ, Simon RR, Hoffman JR, Larmon B, Ablon W. Efficacy of cervical spine immobilization methods. J Trauma. 1983;23(6):461-5.
  7. Rhee P, Burris D, Kaufmann C, et al. Lactated Ringer's solution resuscitation causes neutrophil activation after hemorrhagic shock. J Trauma. 1998;44:313-9.
  8. Sellick BA. Cricoid pressure to control regurgitation of stomach contents during induction of anaesthesia. Lancet. 1961;2:404-6.
  9. Stern SA, Dronen SC, Birrer P, et al. Effect of blood pressure on hemorrhage volume and survival in a near-fatal hemorrhage model incorporating a vascular injury. Ann Emerg Med. 1993;22:155-63.
  10. Velanovich V. Crystalloid versus colloid fluid resuscitation: A meta-analysis of mortality. Surgery. 1989;105:65-71.

OPEN FRACTURESCHAPTER 77

K Gunalan  
INTRODUCTION
Open fractures are usually the result of high-energy trauma and should alert the treating physician to the possibility of associated injuries. Therefore, detailed evaluation and appropriate resuscitation of the patient is necessary. The neurovascular status of the injured extremity should be carefully assessed, and the development of compartment syndrome should not be overlooked. The soft-tissue injury should be evaluated to determine the size and location of the wound, the degree of muscle damage, and the presence of contamination.
 
CLASSIFICATION
The Gustilo and Anderson classification system (Table 77.1) which was subsequently modified by Gustilo et al. is used widely to grade open fractures. In this system, type I indicates a puncture wound of ≤1 cm with minimal contamination or muscle crushing. Type II indicates a laceration of >1 cm in length with moderate soft-tissue damage and crushing; bone coverage is adequate and comminution is minimal. A type-IIIA open fracture involves extensive soft-tissue damage, often due to a high-energy injury with a severe crushing component. Massively contaminated wounds and severely comminuted or segmental fractures are included in this subtype. Soft-tissue coverage of the bone is adequate. Type IIIB indicates extensive soft-tissue damage with periosteal stripping and bone exposure, usually with severe contamination and bone comminution. A type-IIIC fracture is associated with an arterial injury requiring repair.
Table 77.1   Gustilo open fracture classification
Type
Definition
I
Open fracture with clean wound and wound <1 cm in length
II
Open fracture with extensive soft tissue damage and crushing. Wound is >1 cm
IIIA
IIIB
IIIC
Open fracture with extensive soft tissue damage and crushing. Fractures are severely comminuted or segmental and wounds are contaminated. May require vascular repair
Open fractures with extensive soft-tissue damage with periosteal stripping and bone exposure, usually with severe contamination and bone comminution
Open fractures associated with arterial injury requiring repair
546
 
ANTIBIOTIC COVER
As most open fractures are contaminated with microorganisms, antibiotics are used not for prophylaxis but rather to treat wound contamination. To prevent a clinical infection, immediate antibiotic administration, wound debridement, soft-tissue coverage, and fracture stabilization are necessary.
The results of cultures of post-debridement specimens and sensitivity testing may help in the selection of the best agents for subsequent procedures. The antibiotic therapy should target both the gram-positive and the gram-negative pathogens contaminating the wound. A commonly used regimen consists of a first-generation cephalosporin (e.g. cefazolin), which is active against gram-positive organisms, combined with an aminoglycoside (e.g. gentamicin or amikacin), which is active against gram-negative organisms. Substitutes for aminoglycosides include quinolones, third-generation cephalosporins, or other antibiotics with gram-negative coverage.
Clostridial myonecrosis (gas gangrene) is of particular concern when an injury is contaminated with anaerobic organisms (e.g. farm injuries) or when there is vascular injury that may create conditions of ischemia and low oxygen tension. Therefore, in such cases, ampicillin or penicillin should be added to the antibiotic regimen to provide coverage against anaerobes.
Antibiotic administration should be started promptly, as a delay of more than three hours has been shown to increase the risk of infection. The recommended duration of therapy is three days. An additional three days of administration of antibiotics—selected on the basis of the results of initial cultures—is recommended for subsequent surgical procedures, such as wound coverage and bone-grafting.
Local antibiotic delivery must be considered when extensive contamination is present. This is commonly done with an “antibiotic bead-pouch” construct formed with antibiotic powder and polymethylmethacrylate (PMMA) cement.
 
SURGICAL DEBRIDEMENT AND IRRIGATION
The timing of initial surgical intervention has wide variance within the literature. Historically, the 6-hour rule has been employed as the time limit within which an open fracture should be taken to the operating room for initial debridement. Open fractures should be taken to the operating room in an urgent manner using appropriate surgical judgment. There are certain scenarios when emergency debridement may be needed. These may include Type III injuries with vascular injury and/or gross fecal or soil contamination. Wound is dressed and splinted, the covering should not be lifted until the patient is delivered to the operating room as this practice can increase the infection rate.
Perhaps the most important aspect in the treatment of open fractures is the initial surgical intervention with irrigation and meticulous debridement of the injury zone. This initial debridement should include a sequential evaluation of skin, fat, fascia, muscle, and bone. One of the most important assessments in the debridement process is vascularity to the affected tissues.
Irrigation, along with debridement, is absolutely crucial in the management of open fractures, the removal of contaminating debris and the decrease of 547potentially infective bacterial loads. A popular protocol for lavage is usage of 3 L for a Type I open fracture, 6 L for a Type II open fracture, and 9 L for a Type III open fracture. Surgeons should favor using a low-to-medium pressure lavage device as higher-pressure devices have been associated with added tissue or bone damage.
 
WOUND CLOSURE
Options for wound closure in the treatment of open fractures include primary closure of the skin, split-thickness skin-grafting, and the use of either free or local muscle flaps. Historically, surgeons have opted to delay closure because of the perceived risks of clostridial infections and gas gangrene. This concern is certainly present in the grossly contaminated open fracture. Current treatment strategies correctly emphasize the importance of debridement and irrigation, and adhering to these principles has allowed surgeons to consider earlier closure and immediate primary closure in some cases when certain criteria are met. Recommendation is toward primary closure of Type I, Type II, and a few selected Type IIIA fractures. The most important factors in our decision-making process is the adequacy of the initial debridement and the degree of wound contamination.
 
SKELETAL FIXATION (Figs 77.1 to 77.5)
Early stabilization of open fractures provides many benefits to the injured patient. It protects the soft tissues around the zone of injury by preventing further damage from mobile fracture fragments. It also restores length, alignment, and rotation—all vital principles of fracture fixation. This restoration of length also helps decrease soft tissue dead spaces and has been shown in studies to decrease the rates of infection in open fractures. The surgeon has many choices when deciding on fixation constructs—skeletal traction, external fixation, and intramedullary nails and plates. The choice of fixation involves the bone fractured and the fracture location (intra-articular, metaphyseal, diaphyseal), the extent of the soft-tissue injury and the degree of contamination, and the physiologic status of the patient.
Fig. 77.1: Open tibial shaft fracture
548
Fig. 77.2: External fixation done for open tibial fracture
Fig. 77.3: Mangled lower extremity
549
Fig. 77.4: Extensive degloving injury
Fig. 77.5: Postdebridement and external fixation
External fixation is a valuable tool in the surgeon's arsenal for acute open fracture management. Indications for external fixation are grossly contaminated 550open fractures with extensive soft-tissue compromise, the Type IIIA-C injuries, and when immediate fixation is needed for physiologically unstable patients. This later indication involves the damage control concept of orthopedic trauma.
Plate fixation is generally indicated for open upper extremity fractures and periarticular fractures where reconstruction of the articular surface is paramount. Current plating technology and less-invasive techniques are lowering these rates and providing patients with good to excellent results.
Intramedullary nail fixation remains the mainstay of treatment for most open tibial shaft fractures and for selected femoral fractures. Prophylactic bone grafting can also be used in the early treatment of open fractures. The literature has several examples of studies pertaining to immediate or early prophylactic bone grafting, and this practice has reported to shorten the time to fracture union and reduce the rate of delayed union.
 
BIBLIOGRAPHY
  1. Brumback RJ, Jones AL. Interobserver agreement in the classification of open fractures of the tibia: The results of a survey of two hundred and forty-five orthopaedic surgeons. J Bone Joint Surg Am. 1994;76:1162-6.
  2. Buchholz RW, Court-Brown CM, Heckman JD, Tornet P. Rockwood and green textbook of orthopaedics, 7th edition. Philadelphia: Lippincott, Williams & Wilkins; 2010.
  3. Canale ST, Beaty JH. Campbell textbook of orthopaedics, 12th edition. Philadelphia: Mosby; 2013.
  4. Court-Brown CM, McQueen MM, Quaba AA. Management of open fractures. St Louis; London: Mosby; M Dunitz; 1996.
  5. Court-Brown CM, Rimmer S, Prakash U, McQueen MM. The epidemiology of open long bone fractures. Injury. 1998;29:529-34.
  6. Gustilo RB, Anderson JT. Prevention of infection in the treatment of one thousand and twenty-five open fractures of long bones: Retrospective and prospective analyses. J Bone Joint Surg Am. 1976;58:453-8.
  7. Gustilo RB, Gruninger RP, Davis T. Classification of type III (severe) open fractures relative to treatment and results. Orthopedics. 1987;10:1781-8.
  8. Gustilo RB, Mendoza RM, Williams DN. Problems in the management of type III (severe) open fractures: A new classification of type III open fractures. J Trauma. 1984;24:742-6.
  9. Information about Orthopaedic Patients and Conditions - AAOS. 2008. (4/8/2008)
  10. Johansen K, Daines M, Howey T, Helfet D, Hansen ST. Jr Objective criteria accurately predict amputation following lower extremity trauma. J Trauma. 1990;30:568–72.
  11. Praemer A, Furner S, Rice DP. Musculoskeletal conditions in the United States. Park Ridge, Ill: American Academy of Orthopaedic Surgeons; 1992.
  12. Rajasekaran S. Early versus delayed closure of open fractures. Injury. 2007;38:890-5.
  13. Sharma S, Devgan A, Marya KM, Rathee N. Critical evaluation of mangled extremity severity scoring system in Indian patients. Injury. 2003;34:493-6.
  14. Tscherne H, Oestern HJ. A new classification of soft-tissue damage in open and closed fractures. Unfallheilkunde. 1982;85:111-5.

PELVIC FRACTURESCHAPTER 78

K Gunalan  
INTRODUCTION
Fractures of the pelvic ring comprise about 2% of all fractures (Fig. 78.1), but the incidence is increasing due to increasing numbers of high-speed vehicular crashes and suicide attempts. Parameters predicting mortality are age, injury severity score (ISS) and the existence of severe hemorrhage. Exsanguinating hemorrhage is the major cause of death in the first 24 hours after trauma. Immediate recognition of hemorrhagic shock and effective control of bleeding must be pivotal in every resuscitation effort. Appropriate recognition and management of serious pelvic fractures is also integral to resuscitative strategy.
Fig. 78.1: Pelvic ring disruption
552Management of these potentially lethal injuries requires expedited stabilization by a multidisciplinary team of trained personnel with a defined treatment protocol. Multidisciplinary clinical-pathway and coordinated joint decision-making improves patient survival. The understanding of these potentially fatal injuries are progressing and early management of pelvic ring injuries are evolving.
 
ADVANCED TRAUMA LIFE SUPPORT
Upon arrival in the emergency department, patients should be resuscitated according to the guidelines of the Advanced Trauma Life Support. The primary survey emphasizes immediate assessment of the airway and breathing while maintaining cervical spine precautions. Attention is then focused on the cardiovascular system. Quickly identifying the site of hemorrhage in a hemodynamically unstable patient is both critical and time-dependent. Volume resuscitation is generally begun after intravenous (IV) access has been established and it is only an adjunct to aggressive hemorrhage control.
If the patient shows signs of hypovolemia, a thorough and systematic search must be initiated to identify the source of bleeding. Plain radiographs of the chest (CXR) and pelvis are obtained at this stage. Optimally, this is followed by an evaluation for intra-abdominal bleeding, through either diagnostic peritoneal lavage (DPL) or, increasingly by focused assessment with sonography for trauma (FAST) exam.
 
HEMODYNAMIC STATUS
Hypovolemia should be carefully evaluated and hemorrhagic shock should be diagnosed and graded promptly. Specific attention should be paid for assessing the pulse, respiratory rate and tissue perfusion. Tachycardia and cool peripheries are early indicators, and a narrowed pulse pressure may suggest significant blood loss. In the early resuscitative phase, clinical signs and symptoms, along with measurement of hourly urine output, continue to be the most practical indicators of systemic perfusion.
 
FRACTURE STABILITY
If pelvic radiographs reveal obvious radiological instability of the ring, aggressive physical examination with compression and distraction will not provide additional information on injury severity, but rather could potentially cause further injury or aggravate bleeding. In hemodynamically unstable patients with no obvious site of hemorrhage, careful clinical examination of the pelvis is mandatory even when radiographs look normal. Physical examination of the pelvis should include thorough inspection of the flanks, lower abdomen, groin, perineum and buttocks to detect any wounds or bruises. The genitals and rectum should be inspected carefully to detect any blood at the urethral meatus. In the presence of signs suggestive of a genitourinary injury, insertion of a urinary catheter should be avoided, and a retrograde urethrogram is performed.
553Orthopedic assessment should also note any clinical deformity of the pelvis, limb-length discrepancy or malrotation. In patients who are both hemodynamically and mechanically unstable, and in whom the major bleeding is thought to be related to the pelvic fracture, external stabilization of the pelvis becomes the first priority. Because the main sources of bleeding are most frequently the presacral venous plexus and fractured bony surfaces, external stabilization decreases the hemorrhage by reducing the volume of the pelvic basin and approximating the fracture ends.
 
PNEUMATIC ANTISHOCK GARMENT
The pneumatic antishock garment (PASG) can be helpful for immediate mechanical stabilization at an accident scene. The PASG may provide an initial redistribution of blood from the limb to the trunk and restrict the expansion of a pelvic hematoma. It impedes access to limbs and abdomen, making assessment of the patient in the emergency room more difficult. Currently, the role of PASG and MAST is limited.
 
PELVIC BINDERS
Circumferential pelvic binders or sheets are gradually replacing anterior external fixation (AEF) as the method of choice of immediate external stabilization, and currently they are part of the ATLS protocol. These binders are noninvasive, simple to apply, inexpensive and can be applied at a prehospital stage. To perform this method of stabilization, either an ordinary broad sheet can be tied at the level of the greater trochanter, or a commercial pelvic binder can be used. It must be positioned appropriately or be moveable when required, to provide access to the entire abdomen and groin. Safe, noninvasive method seems to be a logical first resuscitative step with a serious pelvic fracture, to provide early hemorrhage control before considering invasive methods.
 
ANTERIOR EXTERNAL FIXATOR (Figs 78.2 and 78.3)
Immediate anterior external fixator (AEF) of an unstable pelvic injury has been the mainstay of acute stabilization for the past few decades. Skeletal stabilization of pelvic injury should be viewed as part of resuscitation rather than reconstruction. The anterior fixator is thought to contribute to hemostasis by maintaining a reduced pelvic volume, allowing tamponade, and by decreasing bony motion at the fracture site, allowing clots to stabilize. The pelvic fractures most amenable to this form of treatment are the open book fracture, and the unstable shear type when combined with longitudinal traction. Lateral compression injuries incur fewer benefits from this method. Its judicious use before laparotomy can both reduce further bleeding and prevent hypotension from decompression of the tamponade effect upon opening the abdominal wall.
The application of AEF requires training and can be difficult to accomplish in the trauma room. It is hard to maintain a sterile environment, and contamination of the pin tracts can jeopardize definitive care of pelvic fractures.554
Fig. 78.2: Anterior external fixation
Figs 78.3A and B: Anterior external fixator and symphyseal plating
 
ACUTE FRACTURE FIXATION
The patient undergoes a laparotomy to deal with visceral injuries, symphyseal disruption and medial ramus fractures should be plated at the same time. Because neither blood loss nor operative time are greatly increased, combining these repairs decreases the risk of complications in a patient who is already compromised.
Percutaneous pelvic fixation techniques allow for acute and definitive treatment of anterior and posterior pelvic ring injuries, without extensive dissection. Accurate early pelvic stabilization diminishes pain and hemorrhage, provides better patient nursing and comfort, and allows early mobilization.
 
ANGIOGRAPHY
Interventional angiographic procedures are increasingly being used as adjuncts to hemorrhage control in cases of solid-organ trauma. Although the 555source of bleeding is non-arterial in most cases, arterial injury can account for hemodynamic instability in 10–20% of patients.
Patients who remain hemodynamically labile after external stabilization and other resuscitative measures but have no major intraperitoneal bleeding are potential candidates for pelvic angiography. Other indications for pelvic angiography include the incidental discovery of an arterial “blush” in a contrast CT scan in an apparently stable patient, and as a last-ditch effort in thermally stable patients who remain in shock after exploratory laparotomy and surgical control of all other sources of bleeding.
In practice, angiography has some drawbacks. It is time-consuming and currently requires transfer of a severely injured, unstable patient to the angiography suite, which may hamper resuscitative efforts.
 
PELVIC PACKING
The rationale behind pelvic packing derives from the fact that the major source of hemorrhage from pelvic ring injury is venous. This technique seems particularly applicable to patients with multiple hemorrhagic sources, both intra- and retroperitoneal, whose visceral injuries mandated a laparotomy as the first operative resuscitative measure.
 
OPEN PELVIC FRACTURES (FIG. 78.4)
Open fractures of the pelvis by definition communicate with the rectum, the vagina, or the outside environment by disruption of the skin. An open pelvic fracture prompts recommendations for colostomy to prevent soft-tissue sepsis in an expanded perineum. In addition to hemorrhage control and stabilization of the pelvic ring, meticulous debridement of the wound and administration of broad-spectrum antibiotics are required. In open pelvic fractures with continuing hemorrhage, packing can be life-saving.
Fig. 78.4: Internal fixation after primary stabilization
556
 
BIBLIOGRAPHY
  1. American College of Surgeons, committee on trauma. Advanced trauma life support for doctors: student course manual, 7th Edition. Chicago: American College of Surgeons; 2004.
  2. Bode PJ, Niezen RA, van Vugt AB, Schipper J. Abdominal ultrasound as a reliable indicator for conclusive laparotomy in blunt abdominal trauma. J Trauma. 1993;34: 27-31.
  3. Bottlang M, Krieg JC. Introducing the pelvic sling: pelvic fracture stabilization made simple. JEMS. 2003;28:84-93.
  4. Buchholz RW, Court-Brown CM, Heckman JD, Tornet P. Rockwood and green textbook of orthopaedics, 7th edition. Philadelphia: Lippincott, Williams and Wilkins; 2010.
  5. Canale ST, Beaty JH. Campbell textbook of orthopaedics, 12th edition. Philadelphia: Mosby; 2013.
  6. Demetriades D, Karaiskakis M, Toutouzas K, et al. Pelvic fractures: epidemiology and predictors of associated abdominal injuries and outcomes. J Am Coll Surg. 2002;195: 1-10.
  7. Giannoudis PV, Pape HC. Damage control orthopaedics in unstable pelvic ring injuries. Injury. 2004;35:671-7.
  8. Hamill J, Holden A, Paice R, Civil I. Pelvic fracture pattern predicts pelvic arterial haemorrhage. Aust NZJ Surg. 2000;70:338-43.
  9. Hildebrand F, Giannoudis PV, van Griensven M, Chawda M, Pape HC. Pathophysiologic changes and effects of hypothermia on outcome in elective surgery and trauma patients. Am J Surg. 2004;187:363-71.
  10. Mattox KL. Introduction, background, and future projections of damage control surgery. Surg Clin North Am. 1997;77:753-9.
  11. Niwa T, Takebayashi S, Igari H, et al. The value of plain radiographs in the prediction of outcome in pelvic fractures treated with embolisation therapy. Br J Radiol. 2000; 73:945-50.
  12. Ramzy AI, Murphy D, Long W. The pelvic sheet wrap: initial management of unstable fractures. JEMS. 2003;28:68-78.
  13. Schurink GW, Bode PJ, van Luijt PA, van Vugt AB. The value of physical examination in the diagnosis of patients with blunt abdominal trauma: a retrospective study. Injury. 1997;28:261-5.
  14. Shapiro MB, Jenkins DH, Schwab CW, Rotondo MF. Damage control: collective review. J Trauma. 2000;49:969-78.
  15. Tile M. Acute pelvic fractures. I: causation and classification. J Am Acad Orthop Surg. 1996;4:143-51.
  16. Tile M. Acute pelvic fractures. II: principles of management. J Am Acad Orthop Surg. 1996;4:152-61.

FAT EMBOLISM SYNDROMECHAPTER 79

Sushma Vijay Pingale
Fat embolism syndrome (FES) is the term used to describe the intravascular appearance of fat globules along with a specific cluster of respiratory, dermatologic, and neurologic symptoms and signs. It is less common but a potentially fatal event carrying a mortality rate of 10–15%.
 
ETIOLOGY
  • Long bone fractures—especially femur and tibia
  • Acute pancreatitis
  • Parenteral infusion of lipids
  • Cardiopulmonary bypass
  • Liposuction.
 
PATHOGENESIS
It has been proposed that fracture of long bones causes disruption of fat cells and release of shower of fat globules and bone marrow debris. These fat globules enter the circulation through tears in the medullary vessels of the fractured bones. The fat globules are then said to exert toxic effects on the capillary walls and the alveolar membrane and cause the release of vasoactive amines and prostaglandins and lead to a generalized proinflammatory response, eventually leading to microvascular occlusions by platelets and fibrin in various beds and interstitial leakage of protein and neutrophil rich fluids. This may result in acute respiratory distress syndrome (ARDS). They also damage the capillaries of cerebral circulation causing cerebral edema.
 
CLINICAL FEATURES
Fat embolism syndrome typically presents 24–72 hours after fracture of long bones or after bone manipulation. It presents in the form of triad of hypoxemia, confusion and petechiae. The patient has tachycardia and may develop fever and refractory hypoxemia. A peculiar petechial rash is seen on the upper torso or head and neck and conjunctiva is almost pathognomonic of FES. Fat globules may be found in the retina, urine or sputum. The patient may be acutely agitated, confused, stuporous or comatose and a focal neurological deficit may also be present. 558
 
DIAGNOSIS
Although there is no definitive test to diagnose fat embolism the laboratory tests provide a data supportive towards diagnosis. Thrombocytopenia and prolonged clotting time is commonly observed. Cryostat test can detect fat globules in clotted blood that has been rapidly frozen. The serum lipase is elevated in 50% of patients with fat embolism syndrome but returns to normal within 24 hours of injury and thus does not have any relation with the severity of the disease. X-ray chest may show diffuse pulmonary infiltrates. The ECG will show ischemic ST segment changes and right-sided heart strain pattern. The Arterial blood gas analysis will show that the ratio of partial arterial oxygen pressure and fraction of inspired oxygen (PaO2/FiO2) is less than 40. CT and MRI scans shows nonspecific findings. Biopsy of skin lesions may help by revealing fat globules on staining.
Based on the Gurd criteria (Table 79.1) which can be used for diagnosis, the presence of any one major criteria plus four minor criteria and evidence of fat macroglobulinemia is required for the diagnosis of FES. Fat embolism syndrome can be diagnosed by Schonfeld index (Table 79.2). Score >5 is required for diagnosis of fat embolism syndrome. According to recent studies, the presence of fat globules does not correlate with the severity of FES.
Table 79.1   Gurd criteria for diagnosis of fat embolism syndrome
Major features (at least one)
  • Respiratory insufficiency
  • Cerebral involvement
  • Petechial rash
Minor features (at least four)
  • Pyrexia
  • Tachycardia
  • Retinal changes
  • Jaundice
  • Renal changes
Laboratory features
  • Fat microglobulinemia (required)
  • Anemia
  • Thrombocytopenia
Table 79.2   Schonfeld fat embolism syndrome index
Sign
Score
Petechial rash
5
Diffuse alveolar infiltrates
4
Hypoxemia PaO2<70 mm Hg, FiO2 100%
3
Confusion
1
Fever >38°C (>100.4°F)
1
Heart rate >120 beats/minute
1
Respiratory rate >30
1
Abbreviations: PaO2, arterial oxygenation; FiO2, inspired oxygen concentration
559
 
MANAGEMENT
The management can be described as prophylactic and supportive. Early stabilization of fractures has shown to bring down the incidence of ARDS and FES. Prophylactic methylprednisolone (6 mg per kg IV in 6 doses) after trauma has been shown to reduce the incidence of fat embolism to as low as 2.5% but recent studies has questioned its role. Finally if FES does develop, then supplementation of oxygen via mask or continuous positive airway pressure or mechanical ventilation as appropriate is necessary.
 
BIBLIOGRAPHY
  1. Babalis GA, Yiannakopoulos CK, Karliaftis K, et al. Prevention of post-traumatic hypoxemia in isolated lower limb long bone fractures with a minimal prophylactic dose of corticosteroids. Inj Int J Care Injured. 2004;35:309-17.
  2. Behrman SW, Fabian TC, Kudsk KA, et al. Improved outcome with femur fractures: early vs delayed fixation. J Trauma. 1990;30:792-8.
  3. Bulger EM, Smith DG, Maier RV, et al. Fat embolism syndrome: a 10 year review. Arch Surg. 1997;132:435-9.
  4. Edward Morgan G, Jr, Maged S Mikhail, Michael J Murray. Clinical Anesthesiology, 5th edn. McGraw-Hill Publications; 2007.
  5. Gurd AR, Wilson RI. The fat embolism syndrome. J Bone Joint Surg Br. 1974;56:408-16.
  6. Irwin, Richard S Rippe, James M. Irwin and Rippe's Intensive Care Medicine, 6th Edn. Lippincott Williams & Wilkins; 2008.
  7. Robinson CM. Current concepts of respiratory insufficiency syndromes after fracture. J Bone Joint Surg Br. 2001;83B:781-9.
  8. Ronald D Miller. Miller's Anesthesia, 7th edn. 2009. Elsevier Publications, 2009.
  9. Schonfeld SA, Ploysongsang Y, DiLisio R, et al. Fat embolism prophylaxis with corticosteroids: a prospective study in high risk patients. Ann Int Med. 1983;99:438-43.

ABDOMINAL TRAUMACHAPTER 80

Marun Raj  
INTRODUCTION
The nature of wound is the same whether made by accidents, war and of course by surgeon's knife, but they differ only in degree. The way in which a wound is sustained will frequently determine the amount of damage to the tissues, some of which, concealed from superficial view, can be inferred from the injury. Factors contributing to blunt trauma in motor vehicle accidents are steering wheel which leads onto organ injuries like liver, stomach, diaphragm, and seat belt injury leads on to mesenteric tear or avulsion, rupture of small bowel or colon and iliac artery or abdominal aortic thrombosis. Shoulder harness usually leads onto rupture of upper abdominal viscera, and air bag is notorious to produce cardiac rupture and blunt injury to visceral organs.
 
MECHANISM OF INJURY
  • Direct compression from blunt injury leads onto crush, or sheer injury to abdominal viscera and in fact, any organ can be injured, though most commonly injured are solid visceral organs and bowel.
  • Shock waves that radiate from the point of impact leads on to injury to hollow organs like small and large bowel and diaphragm.
  • High speed deceleration injuries may produce differential movements of fixed (DJ flexure and ileocecal junction) and nonfixed structures, ends up in unpredictable injuries disproportionate to intensity of injuries.
Commonly affected organs are solid organs followed by bowel, and the least involved ones are arteries and veins. Spleen is the most commonly involved solid organ in blunt abdominal trauma which accounts for 40–45% and grading of splenic injury is given in Table 80.1, and the next commonly affected solid organ is liver, which accounts for 35–40%. The hollow visceral organs, especially small bowel accounts for around 10% of injuries due to their nonattachment and blood vessels account for less than 5% of injuries.
 
DIAGNOSTIC PRINCIPLES IN GENERAL
The most important part of the abdominal trauma is history taking regarding the mode of injury, which most of the time clinches the diagnosis, and predicts the organ involved in the injury. It is not uncommon for a driver or front-seat 561passenger to sustain a chain of injuries one or the other side ending up in scalp laceration or hematoma, fractured lower or upper limb, lacerated chest wall. It is not even difficult to imagine that the abdomen had been similarly struck and a careful examination will reveal signs of injury that otherwise might have been missed. Side-swipe injury also should arouse the suspicion of intra-abdominal damage, even if they are no external signs visible. Apart from the above facts, the features that suggest intra-abdominal injury are those of peritoneal irritation, abdominal distension and hypovolemia out of proportion to external blood loss.
Table 80.1   Grading of splenic injury
Grade
Injury description
1
Hematoma—subscapular <10% surface area
Laceration—capsular tear <1 cm parenchymal depth
2
Hematoma—subcapsular 10–50% surface area, intraparenchymal < 5 cm diameter
Laceration—parenchymal depth of 1–3 cm without involvement of vessel
3
Hematoma—subcapsular >50% surface area or with expansion
Ruptured subcapsular or parenchymal hematoma. Intraparenchymal hematoma >5 cm
Laceration—parenchymal depth of >3 cm or involvement of vessels
4
Laceration of segmental or hilar vessels producing >25% of splenic vascular compromise
5
Completely shattered spleen—Hilar vascular injury with complete splenic vascular compromise
Vomiting is usually a late occurrence, but the patients who had been vomiting frequently and inexplicably should raise the suspicion of abdominal injury (intraperitoneal or retroperitoneal visceral rupture). Bowel sounds are infrequently of value as silent abdomen raises the suspicion of visceral injury, but can occur in the setting of hypotension also. There are some special signs which may help in diagnosing the intra-abdominal injuries.
 
Grey-Turner Sign
It is the bluish discoloration of lower flanks, lower back, associated with retroperitoneal bleeding of pancreas, kidney, or pelvic fracture.
 
Cullen Sign
Bluish discoloration around umbilicus, which indicates peritoneal bleeding, often pancreatic hemorrhage.
 
Kehr Sign
Left shoulder pain while supine, caused by diaphragmatic irritation (splenic injury, free air, intra-abdominal bleeding).562
 
Balance Sign
Dull percussion in left upper quadrant area indicates splenic injury.
 
LAB INVESTIGATIONS
 
X-rays
Plain X-ray films taken in erect posture is more useful than supine film, though lateral decubitus may be preferred for those who are unconscious, or could not stand due to multiple associated injuries. Gas under the diaphragm though confirms visceral perforation, it may not happen for all cases, and tiny visceral punctures may go unnoticed. More help is likely to come from observing signs of injury to the bony structures on the sides of abdomen like chest, pelvis and lumbar spines. These injuries may confirm the energy of impact and direct the attention to nearby structures. Loss of psoas shadow may be helpful in diagnosing retroperitoneal collection.
 
Ultrasonogram
Focused assessment with sonography for trauma (FAST) is gaining momentum in case of intra-abdominal injuries. The four quadrants methods include perihepatic, perisplenic, pelvis and pericardium, which are screened rapidly to rule out injuries and they are very useful in mass casualties to triage the patients, which not only saves the patients but also the resources and manpower.
 
Computerized Tomography Scan
Contrast-enhanced CT scan has now replaced almost all the investigatory methods in diagnosing intra-abdominal injuries and if available, it can be swiftly done with a high degree of accuracy without interpretation error. Even in advanced centers CT has replaced angiography and scintigraphy in the assessment of both solid and visceral injuries.
 
DIAGNOSTIC PERITONEAL LAVAGE
 
Indications
  • Equivocal signs on physical examination
  • Unconscious patient with suspicion of intra-abdominal pathology.
 
Procedure for Diagnostic Peritoneal Lavage
  • Bladder should be empty and if needed insert a nasogastric tube
  • Midline incision is done 3 cm below umbilicus and of 3 cm length
  • Peritoneum grasped with forceps and purse string sutures applied
  • Peritoneum is opened with careful observation
  • Peritoneal dialysis catheter or 8–10 fr catheter inserted into pelvis as the purse string is tightened
  • 563One liter of NS infusion done in few minutes
  • Patient is log rolled and the empty bottle is brought down
  • Fluid is taken for analysis.
 
Interpretation of Diagnostic Peritoneal Lavage
  • Laparotomy is indicated under the following criteria:
    • >10 mL of blood/bile/vegetable fiber/feculent fluid
    • RBC >100000/mm3
    • WBC >500/mm3
    • Amylase >175 IU/dL
  • Doubtful injury: RBC—50000–100000/mm3, WBC—100–500/mm3
  • Nonoperative conservative management is done if RBC <50000/mm3, WBC <100/mm3.
 
Limitations of Diagnostic Peritoneal Lavage
  • Time consuming and dependent on skill of surgeon and the lab technician
  • Relatively contraindicated in patients with previous exploratory laparotomy, pregnancy, obesity
  • Retroperitoneal hemorrhage can be missed.
 
ANGIOGRAPHY
Conventional angiogram is indicated mainly in case of retroperitoneal injuries, though CT angiogram has almost replaced the indication. Angiogram can be done if planned for any adjunct procedure in same sitting, otherwise its role is limited nowadays.
 
PREOPERATIVE MANAGEMENT
Its mandatory to get an adequate large bore vascular access for volume replacement to stabilize the circulation. Adequate volume of blood and blood products should be available in case, if there is suspicion of abdominal hemorrhage. Aim is to push the patient into the operating table as early as possible without any delay with packed red cells on table. Even with new techniques of anesthesia, the presence of solid food or fluid in stomach is still at risk during induction of anesthesia. If the stomach contains much fluid, there exists the risk of regurgitation into the pharynx, trachea and lungs, which occurs between the moment of loss of cough reflux, which follows induction of anesthesia, and the insertion of an endotracheal tube. It is reasonable, if the condition of the patient needs it to insert a nasogastric tube to aspirate fluid from the stomach but it is of little use to aspirate solid food and nasogastric tube cannot prevent aspiration even after the gastric contents are aspirated. It is best removed before induction as it is capable of keeping the cardiac and esophageal sphincters open and may cause aspiration during induction of anesthesia. Rapid sequence induction (RSI) along with cricoid pressure is done by the anesthesiologist to prevent aspiration during induction. Nasogastric tube is reinserted after endotracheal intubation to empty the stomach before the end of surgery. All patients should have 564bladder catheterized to empty the bladder and for monitoring of urine output during intraoperative and postoperative period. Prophylactic antibiotics are administered according to the protocol of the institution before induction and should be continued in the postoperative period.
 
DAMAGE CONTROL SURGERY
  • Triad of coagulopathy, acidosis and hypothermia leads to poor outcome
  • Goal is to minimize operative time
  • Control bleeding rapidly
  • Expedite primary repair or resection with stapling device OR ligate bowel with umbilical tape or equivalent.
  • Close only skin or alternatively implant plastic prosthesis to cover the wound.
  • Re-explore after 48–72 hours (after stabilizing physiology of the patient).
 
ABDOMINAL COMPARTMENT SYNDROME
Abdominal compartment syndrome (ACS) has been defined as the “cardiovascular, pulmonary, renal, splanchnic, abdominal wall and intracranial disturbances resulting from elevated intra-abdominal pressures”. Normal intra-abdominal pressure ranges from 0 to 5 mm Hg and intra-abdominal hypertension is defined as intra-abdominal pressure (IAP) at or above 12 mm Hg. IAP above 20 mm Hg leads onto organ dysfunction/failure. IAP >25 mm Hg requires immediate decompression. Actually abdominal perfusion pressure (APP) is nothing but the intra-abdominal pressure subtracted from mean arterial pressure (APP = MAP – IAP) and it reflects actual gut perfusion better than IAP alone, and optimizing APP to >50–60 mm Hg should probably be primary endpoint, which is more sensitive and specific.
 
Clinical Features
Clinical features are given in Table 80.2.
Table 80.2   Clinical manifestations of various systems
Cardiovascular system
Hypotension
Reduced venous return
Reduced cardiac output
Central nervous system
Increased intracranial pressure
Respiratory system
Dyspnea, tachypnea due to increased intrathoracic pressure
↓ PaO2
↓ or ↑ PaCO2
Gastrointestinal system
↓ Splanchnic perfusion
Bacterial translocation
Anastomotic leak
Renal system
↓ Renal blood flow
↓ GFR
↓ Urine output
Abdominal wall
Delayed wound healing
565
Fig. 80.1: Measurement of intra-abdominal pressure
 
Measurement of Intra-abdominal Pressure (Fig. 80.1)
It can be measured intragastrically, intracolonically, intravesically. Among these, intravesical method is the most common method.
 
Procedure
50 mL of sterile saline is instilled into the bladder through the aspiration port of the Foleys catheter with the drainage tube clamped. A 18-gauge needle attached to a pressure transducer is then inserted in the aspiration port and the pressure is measured, the transducer should be zeroed at the level of pubic symphysis. Another simple method of measuring bladder pressure is via the fluid column in a Foley catheter. This requires disconnection of the Foley to instill saline and careful bending of the Foley to ensure correct measurement.
 
Treatment
Abdominal compartment syndrome with IAP >25 mm Hg is a surgical emergency which requires immediate decompression. Principles of decompression fasciotomy are:
  • Avoid primary closure of the abdomen
  • Fascia should not be closed
  • Skin edges are not sutured
  • Laparostomy
  • Closure is done with silo (plastic) bag
  • Vacuum-assisted closure.566
 
BIBLIOGRAPHY
  1. American College of Surgeons Committee on Trauma. Abdominal Trauma. In: ATLS Student Course Manual, 8th edn. American College of Surgeons; 2008.
  2. Christiano JG, Tummers M, Kennedy A. Clinical significance of isolated intraperitoneal fluid on computed tomography in pediatric blunt abdominal trauma. J Pediatr Surg. 2009;44(6):1242-8.
  3. DeMars JJ, Bubrick MP, Hitchcock CR. Duodenal perforation in blunt abdominal trauma. Surgery. 1979;86(4):632-8.
  4. Gifford RR, Sr, Hymes AC. Duodenal rupture after blunt abdominal trauma. Minn Med. 1980;63(2):83-7.
  5. Holmes JF, Offerman SR, Chang CH, Randel BE, Hahn DD, Frankovsky MJ, et al. Performance of helical computed tomography without oral contrast for the detection of gastrointestinal injuries. Ann Emerg Med. 2004;43(1):120-8.
  6. Mokka RE, Kairaluoma MI, Huttunen R, Larmi TK. Retroperitoneal injuries of the duodenum caused by blunt abdominal trauma. Ann Chir Gynaecol. 1976;65(1):33-7.
  7. Palomar J, Polanco E, Frentz G. Rupture of the bladder following blunt trauma: a plea for routine peritoneotomy in patients with extraperitoneal rupture. J Trauma. 1980; 20(3):239-41.
  8. Roman E, Silva YJ, Lucas C. Management of blunt duodenal injury. Surg Gynecol Obstet. 1971;132(1):7-14.
  9. Shanmuganathan K. Multidetector row CT imaging of blunt abdominal trauma. Semin Ultrasound CT MR. 2004;25(2):180-204.
  10. Talbot WA, Shuck JM. Retroperitoneal duodenal injury due to blunt abdominal trauma. Am J Surg. 1975;130(6):659-66.

VASCULAR TRAUMA OF EXTREMITIESCHAPTER 81

Marun Raj  
INTRODUCTION
In today's competitive world, extremity vascular trauma presents a huge problem due to the morbidity and mortality, it carries inspite of huge advancement made in the field of medicine. Since most of the time (Golden Hour) period is wasted while shifting patient to tertiary care centers.
 
HISTORICAL PERSPECTIVE
The standard of care of all extremity vascular injuries during the World War I and II were only ligation of affected arteries with subsequent amputations as the surest way of avoiding death. Although, the vascular repair techniques had been to some extent established by this period, the unsanitary conditions which prevailed, lack of timely transportation, absence of effective anesthesia methods, antibiotics and effective blood banking made the surgeons life who were taking care of those patients a nightmare to manage these cases on a large scale.
The report by the Debakey and Simone of 2470 vascular injuries during the World War II which involved ligation of popliteal arteries resulted in a huge amputation of nearly 72% of cases, the highest of any extremity vessels in the literature. Even in those limbs salvaged, arterial ligation led to significant problems with functional and neurological disability. Injured arteries were first repaired on a large scale in Korean war and the limb amputation rate was only 29% and similar results were also reported in Vietnam war which was 27%. D ‘Sa et al. reported 66 cases of vascular injuries from Ireland with a mere amputation rate of 12% for arterial injuries and 8% for venous injuries. S'Fier et al. reported amputation rate of 14% overall from the hostilities in Lebanon in the year 1980. These reports clearly demonstrated the effectiveness of vascular repair in saving the limbs and also the life of so many young patients with good quality of life.
 
EPIDEMIOLOGY
The exact incidence of injury to the extremity vessels are difficult to quantify as the site of injury, mechanisms of injury (whether penetrating trauma and blunt injury) and ethnic differences vary. To give an example 12% of arterial injuries among survivors in World War I were due to popliteal artery injuries and 20% of 568those in Korean war were due to femoropopliteal segment. Over the post-years, the civilian sector has provided the bulk of experience with these injuries, in which setting blunt mechanisms amount for 19% of all extremity arterial injuries and have an incidence of 5.6 per 1000 cases of penetrating trauma and 1.6 per 1000 cases of blunt trauma. The exact incidence of trauma cases in Indian continent widely varies from one area to others and no exact data available as of now.
Table 81.1   Clinical features of vascular injuries
Hard signs
  • Active hemorrhage
  • Absent or diminished distal pulses
  • Presence of bruit or thrill
  • Hemorrhage, expanding or pulsatile hematoma
  • Distal ischemia—classical 6Ps (Pain, Paresthesia, Pallor, Poikilothermia, Pulselessness and Paralysis)
Soft signs
  • Proximity of injury to major vessel
  • Presence of neurological deficits
  • Transient hypotension
  • Stable hematoma
 
CLINICAL PRESENTATION (TABLE 81.1)
Most cases of extremity vascular injuries present with obvious clinical manifestations, generally called as Hard sings of vascular injury. It is widely agreed that, in the settings of uncomplicated penetrating trauma to the lower extremity, the presence of any one or more hard signs mandate immediate intervention, either surgical or endovascular.
The clinical picture in this circumstance answers only two questions necessary to make a surgical decision, namely whether a significant vascular injury exists, which it does, with a probability approaching 100%, and where it does, the wounds demonstrate. Any further imaging or diagnostic test is therefore, unnecessary, superfluous, costly and potentially dangerous considering the adverse impact of delay on outcome. Most limb-threatening complications of delayed diagnosis of extremity vascular injury are the result of overlooking hard signs, rather than an absence of signs, on initial evaluation.
 
NONINVASIVE IMAGING
Noninvasive studies have recently seen an increase in the armamentarium of vascular injuries diagnosis. Central to the debate surrounding the role of non-invasive studies in penetrating extremity injuries is whether the immediate cost reduction of little or no diagnostic testing beyond physical examination and observation is outweighed by the long-term expense and medicolegal exposure associated with vascular injuries that have been missed. Noninvasive vascular studies include Duplex ultrasonography and angiography.569
 
Duplex Ultrasonography
Duplex ultrasound has the advantage of being rapidly available, less costly, non-invasive and documenting arterial injury by measuring the arterial pressure index, which is the ratio of systolic pressure distal to an injured extremity, to that in an uninjured extremity. Accuracy of this study mainly depends on operator and may vary from 80% to 95%. Its major limitations are operator dependability and failure to recognize intimal flaps and small pseudoaneurysms.
 
Angiography
Computerized tomography and magnetic resonance angiography have picked up the momentum during the last decade. Even though these modalities are not available widely, it has the advantages, compared with other modalities of being noninvasive, and imaging multiple organs in a single test and more objective and less operator dependent. The major drawbacks are that nonavailability, intravascular contrast in case of CT angiogram and presence of orthopedic instrumentation or pacemakers in case of MR studies.
 
INVASIVE STUDIES
Contrast arteriography by puncturing the vessels directly may be indicated to confirm or exclude extremity vascular injuries sometimes, even in the presence of hard signs, when the physical examination is not sufficiently reliable to allow for a therapeutic decision. Blunt trauma and complex trauma to the lower extremity, which cause extensive bone and soft tissue injury, may manifest hard signs that do not arise from vascular injury at all but from soft tissue and bone bleeding, direct nerve damage, and so on.
Arteriography is recommended here to exclude arterial injury and thus, prevent a high rate of unnecessary surgical exploration in these already compromised limbs. Imaging is also of value in shotgun wounds because of multiple possible sites of injury that may be missed on surgical exploration. Arteriography should be used liberally in elderly patients with chronic vascular insufficiency following extremity trauma because pulse deficit and ischemia may not be related to an acute vascular injury. In these circumstances, arteriography should be performed by direct hand-injection of contrast percutaneous into the femoral artery at the groin in the trauma center or opening room by the surgeon to save time, and with acceptable accuracy.
Imaging for vascular injury is generally unnecessary in the absence of hard signs following extremity trauma. Extremity wounds that place vessels at risk and yet do not manifest hard signs have long posed a diagnostic dilemma; many studies have shown that vascular injuries do still occur in this setting in 10–25% of these cases. These injuries include penetrating trauma in proximity to the major extremity vessels and any high-risk blunt trauma such as, lower extremity crush, distal femur, proximal tibia and supracondylar fracture humerus. In the past, routine surgical exploration or arteriography was recommended in patients with these asymptomatic extremity injuries to avoid any missed extremity trauma, with its known limb-threatening consequences. More recently, several studies have provided compelling evidence that most of the asymptomatic 570vascular injuries that occur in this setting are nonocclusive, have a benign and self-limited natural history with a high rate of spontaneous resolution, do not require surgical repair, and therefore do not require the considerable expenses and resources necessary for detection. The minimal reported missed injury rate when clinical management of injured extremities are decided entirely from the physical examination alone is comparable to that of arteriography and surgical exploration but is far less expensive and invasive.
 
MANAGEMENT OF EXTREMITY TRAUMA
The management of any trauma can be classified as prehospital, emergency room and operative room care.
 
Prehospital Care
Time is the most precious commodity for patients with open major vascular injuries. The concepts of “scoop and run” should be applied whenever possible. No time should be made to resuscitate or place intravenous lines in the field which unnecessarily delays the treatment. The only prehospital care should be control of any external bleeding by direct pressure and administration of oxygen by mask or nasal cannula.
 
Emergency Room Care
The initial assessment and management should follow the standard advanced trauma life support protocol irrespective of site of injury. Intravenous lines should be inserted always in the upper limb and in case of upper limb injuries, lower limb should be considered. The patient should be placed in Trendelenburg position to prevent air embolism in case of major upper limb and supraclavicular venous injuries. External bleeding should be controlled by direct pressure over the wound whenever possible; however, sometime bleeding behind the bony prominence, may cause troublesome bleeding which may not be controlled by external pressure alone. A Foley's catheter in such situation passed through open wound if any may control bleeding. Initial evaluation of patients should be done by advance trauma life support team once the patient reaches hospital.
 
Operative Room Management
 
Subclavian and Axillary Vessels (Figs 81.1 and 81.2)
The anatomical knowledge is very critical for surgical exposure of any vessel in the body. Surgical exposures, especially in the presence of active bleeding, can be very difficult and may challenge the skills of any experienced vascular surgeon also. The patient is placed in supine position with the arm abducted at 30° and the head turned to the opposite side. The incision starts at sternoclavicular junction, extends over the medial half of the clavicle; for proximal subclavian injuries trap door incision involves median clavicular incision, an upper median sternotomy and an anterior left thoracotomy through the third or fourth intercostal space.571
Figs 81.1A and B: Stab injury in the supraclavicular area leading to subclavian artery injury which was repaired using great saphenous vein conduit
Figs 81.2A and B: Accidental shotgun injury to axillary artery and X-ray showing two pellets in axilla
For distal axillary vascular injuries, the incision is started below the middle of the clavicle and extends into the deltopectoral groove. There are different choices of vessel reconstruction ranging from direct end-to-end anastomosis to interposition grafts, either in the form of autologous vein graft or synthetic graft which depends on many factors. Venous injuries should be repaired only if it can be performed by simple suturing without producing severe stenosis and without the use of any complex reconstructive techniques, which not only delays the procedure time but also severely affect the overall outcome. Ligation of the vein is very well tolerated by almost all patients, and there is no evidence that complex reconstruction reduces the probability of development of compartment syndrome. Following ligation, the patient often develops transient edema that subsides within a few days of limb elevation and compression bandage. In patients with arterial injury and prolonged limb ischemia, especially in the presence of associated venous trauma, perioperative administration of mannitol may prevent the development of compartment syndrome and avoid the need for fasciotomy, though mannitol should be used in caution in case of hypotension.572
 
Brachial and Upper Radial and Ulnar Vessel Injuries (Figs 81.3 and 81.4)
The brachial and upper forearm arterial injuries are quite common in children, who usually fall on outstretched hand. The brachial and upper forearm vessel injuries are almost always associated with bony injuries, which needs to be managed comprehensively by a team of orthopedic and vascular surgeons. One needs high index of suspicion and expertise to diagnose and make surgical intervention decision since the size of vessels are small and sometimes surgical exposure would produce more catastrophic vessel spasm. The usual incision made is lazy S, where the upper end of the incision starts approximately 4–5 cm above and lateral to elbow crease and ends below and medial to the crease. Upper limb fasciotomy as a routine does not warranted considering the muscle mass and ample collaterals and close monitoring and fasciotomy on demand avoids unnecessary fasciotomy.
 
Lower Radial and Ulnar Vessel Injuries
Radial and ulnar vessels injuries are most common in crush and cut injuries. These injuries are usually associated with involvement of median and/or ulnar nerves also. Most injuries need interposition vein graft considering the nature of injury and size of injured vessel. Primary nerve repair should always be done as most of these injuries may not be life-threatening even if the repair takes some more time.
 
Femoral Vessel Injury (Figs 81.5A and B)
In patients with proximal injuries to the femoral vessels, it is often wise to initially expose the distal common iliac vessels through separate incision above the inguinal ligament and to obtain proximal vascular control before entering the femoral region.
Fig. 81.3: Severe upper limb injury who presented in 3 hours of injury underwent successful repair of brachial artery with skeletal stabilization
573
Fig. 81.4: Radial and ulnar artery injury
Figs 81.5A and B: Penetrating trauma involving both common femoral artery which was lacerated with thrombus in situ
Once proximal control is obtained, one can safely explore the femoral arteries through vertical groin incision, extending along the medial border of sartorius muscle and exposing the injury in a detailed manner. Bleeding from the femoral region may sometimes be challenging especially with combined arterial and venous injuries. Venous bleeding can be more difficult to manage, more often can be controlled by direct pressure from the source of bleeding. Blind clamping is strongly discouraged because damage to femoral nerve and numerous collateral may adversely affect the outcome of vascular repair.
 
Popliteal Vessel Injury (Fig. 81.6)
Distal superficial femoral and proximal popliteal vessel injuries is managed by the longitudinal incision made over the medial border of sartorius muscle from mid-thigh to above knee level in supine position. Proximal popliteal vessels need incision of adductor hiatus tendon. Placing the patient in prone position is generally discouraged as the isolated mid-popliteal vessel injuries are rare. Distal popliteal and tibioperoneal trunk injuries can be managed by placing the patient 574in supine position and making incision in the below knee medial aspect, just above the anterior border of medial gastrocnemius.
Fig. 81.6: Penetrating trauma causing popliteal injury
 
Tibial Vessel Injury
Involvement of both tibial arteries, even in both bone fractures of lower limb are very rare. Most of the time nonsurgical management of tibial injuries are recommended for isolated single tibial artery with good collateralization by other tibial artery. Anterior tibial vessel control is done by putting longitudinal incision made in the anterior compartment and posterior tibial vessel control just below the medial border of tibial bone.
 
COMPARTMENT SYNDROME
Compartment pressure is usually elevated in combined arterial and venous injuries, prolonged ischemia of more than six hours, complex and multiple extremity fractures, combined vascular and bone or soft tissue injury and thrombosed arterial and venous repair which leads to compartment syndrome. This is characterized by a compromise in capillary perfusion, and ultimately necrosis of muscle and nerves. Ischemic tissue damage gives rise to the classic manifestations of pain out of proportion to injury, and worsened by passive stretch, sensorimotor deficits and tenseness of the extremities. Prompt treatment is necessary when these findings are present, but tissue loss is usually established at this point. Palpable pulses do not rule out this condition, and absent pulses always should be attributed to vascular injury and not compartment syndrome.
Fasciotomy is the definitive treatment, involving complete incision and decompression of skin and investing fascia of each of the compartment of extremities (Figs 81.7A and B). It is generally agreed that prophylactic fasciotomy, which is done before the development of symptoms and tissue loss in asymptomatic patients with high-risk injuries and findings mentioned earlier, is 575far preferable to therapeutic fasciotomy done after the development of symptoms and signs of tissue loss. Careful serial examination of injured extremities at high risk for compartment syndrome is a valid option, but such observation must include serial measurements of compartment pressure due to the insensitivity and unreliability of physical findings. Any pressure measurement of more than 25 mm Hg mandates immediate fasciotomy.
Figs 81.7A and B: Patient presented with tibial condyle fracture with compartment syndrome blebs and successfully underwent four compartment fasciotomy
 
BIBLIOGRAPHY
  1. Agarwal N, Shah PM, Clauss RH, et al. Experience with 115 civilian venous injuries. J Trauma. 1982;22;827-32.
  2. Anderson RJ, Hobson RW II, Lee BC, et al. Reduced dependency in angiography for penetrating extremity trauma. J Trauma. 1990;30:1059-65.
  3. Attebery LR, Dennis JW, Russo-Alesi F, et al. Changing patterns of arterial injuries associated with fractures and dislocations. J Am Coll Surg. 1986;183:377-83.
  4. Bermudez KM, Knudson MM, Nelken NA, et al. Long-term results of lower extremity venous injuries. Arch Surg. 1997;132:963-8.
  5. Biffl WL, Moore EE, Burch JM. Femoral arterial graft failure caused by secondary abdominal compartment syndrome. J Trauma. 2001;50:740-2.
  6. Bigger IA. Treatment of traumatic aneurysms and arteriovenous fistula. Arch Surg. 1944;49:170-82.
  7. Bynoe RP, Miles WS, Bell RM, et al. Noninvasive diagnosis of vascular trauma by duplex ultrasonography. J Vas Surg. 1991;14:346-52.
  8. Degiannis E Levy RD, Potokar T, et al. Penetrating injuries of axillary artery. Aust NZ J Surg. 1995;65:327-30.
  9. Demetrios, et al. Subclavian and axillary vascular injuries. Surg Clinics of North America. 2001;81:1357-65.
  10. Eddy, et al. Femoral vessel injuries and its management. Surg. Clinics of North America. 2002;82:49-65.
  11. Marin ML, Veith FJ, Panetta TF, et al. Transluminally placed endovascular graft repair for arterial trauma. Vasc Surg. 1994;20:466-73.
  12. Menzoian JO. A comprehensive approach to extremity vascular trauma. Arch Surg. 1985;120:801-7.
  13. Moniz MP, Ombrellaro MP, Stevens SL, et al. Concomitant orthopaedic and vascular injuries as predictor for limb loss in blunt lower extremity trauma. Am Surg. 1997;63(1): 24-8.
  14. Old W, Oswaks R. Clavicular excision in management of vascular trauma. Am Surg. 1984;50:286-9.

TRAUMATIC HEAD INJURYCHAPTER 82

Sushma Vijay Pingale, V Thanga Thirupathi Rajan  
INTRODUCTION
Head injury is one of the leading cause of morbidity and mortality across all ages and amongst all types of injuries. The trauma to the central nervous system consists of both the primary injury, in which tissue is disrupted by mechanical force, and a secondary injury which is a cascade of processes that occurs hours or days after the primary injury and further damages the brain parenchyma.
 
PRIMARY INJURY
The primary injury which occurs at the moment of impact can be in the form of a hematoma, contusion or diffuse axonal injury. The primary injury can only be modified by the trauma prevention programs.
The hematoma can be subdural, extradural or intracranial. Subdural hematoma is the most common focal intracranial lesion seen in 24% of severe traumatic brain injury (TBI) patients with a 50% mortality rate. It is defined as the presence of blood between the duramater and the arachnoid mater. The accumulation of blood could arise from rupture of the bridging veins or the cortical arteries. It spreads over the cerebral convexity but the extension into contralateral hemisphere is prevented by the dural reflections of the falx cerebri. Subdural hematoma (SDH) can be classified as acute, subacute or chronic. The acute hematomas appear bright white on the CT whereas the subacute lesions are isodense with brain tissue and the chronic hematomas are hypodense (Fig. 82.1). All acute subdural hematomas with a thickness greater than 10 mm or a midline shift greater than 5 mm should be surgically evacuated promptly. Factors which predict the outcome in patients with SDH are age of the patient, time from injury to treatment, presence of pupillary abnormalities, GCS/motor score on admission, immediate coma or lucid interval, CT findings (thickness of hematoma, extent of midline shift, and the presence of underlying brain swelling) postoperative intracranial pressure and the type of surgery.
The extradural hematoma (EDH) is defined as the collection of blood between the inner table of skull and the dura. It occurs as a result of tear in the middle meningeal artery or one of its branches (Fig. 82.2). Extradural hematomas are more common in the temporal or parietal regions and carry a mortality rate of 15–20%. They appear as hyperdense mass lesions on CT having a classic biconvex or lenticular shape and a smooth inner border because they strip the dura from 577the inner table of the skull as they enlarge. But unlike subdural hematomas, their spread is limited by the suture lines of the skull where the dura is very adherent. The indication for surgical evacuation is EDH greater than 30 cm3. The factors predicting outcome in patients with EDH are same as those mentioned above for SDH.
Fig. 82.1: Subdural hematoma with midline shift
Fig. 82.2: Extradural hematoma showing the biconvex shape
Intracranial hematoma is the hemorrhage within the brain tissue and is seen after a very severe TBI. Duret's hemorrhage is one of the type of intraparenchymal 578hemorrhage in which the bleeding is seen within the base of pons or midbrain and almost results in death or vegetative state.
Figs 82.3A to C: Subarachnoid hemorrhage
Fig. 82.4: Left-sided contusion
Studies have shown that traumatic subarachnoid hemorrhage (SAH) is seen in up to 60% of admissions for TBI. It is associated with vasospasm in 20% of patients which can aggravate the secondary injury (Figs 82.3A to C). Prolongation of QTc interval is also commonly found in patients with traumatic SAH. Use of nimodipine has level 1 evidence from randomized control trials in management of predominantly traumatic SAH. Nimodipine, when administered prophylactically from diagnosis for 21 days, offers modest improvement in outcome and incidence of ischemic deficit.
Contusions are common after TBI and are seen most commonly in the inferior frontal cortex and the anterior temporal lobes where the surface of the inner table of the skull is very irregular. They may not be visible in the initial CT scan. They evolve over time and may appear as small areas of punctate hyperdensities (hemorrhages) with surrounding hypodensity (edema) given in Figure 82.4. Generally small contusions are asymptomatic or may present with headache. Larger contusions especially if present in frontal lobes may cause an increase in the intracranial pressure and patient may land up in coma. Focal neurological symptoms may be evident if the contusion is located in an eloquent 579area of the brain, such as the motor or speech areas. The contusions located in temporal area if enlarged can result in uncal herniation. Because of this risk of enlargement (20–30%) during the first 24–48 hours, continuous monitoring of their size by serial CT scans is recommended. If an enlargement is noticed, unilateral frontal or temporal contusion evacuation can be done to provide space for the expanding brain without the risk of any significant neuro deficit.
Table 82.1   Grading of diffuse axonal injury (DAI)
Clinical grading of DAI
  • Mild DAI—duration of coma is between 6 and 24 hours
  • Moderate DAI—duration of coma is for >24 hours but without presence of decerebrate posturing as the best motor response on nociceptive stimulation.
  • Severe DAI—duration of coma is for >24 hours and with presence of decerebrate posturing as a motor response on nociceptive stimulation.
MRI grading of DAI
  • Grade 1—small scattered lesions on the white matter of cerebral hemisphere
  • Grade 2—grade 1 plus focal lesions on the corpus callosum
  • Grade 3—grade 1 and 2 plus additional focal lesions on the brainstem.
Diffuse axonal injury (DAI) refers to laceration or punctate contusions at the interface between the gray and the white matter. Grading of DAI is given in Table 82.1. Traumatic coma of greater than 6 hours is usually attributed to DAI and less than 6 hours is considered as concussion. It is a common cause of persistent vegetative state or prolonged coma.
 
SECONDARY INJURY
The primary insult to the brain tissue initiates a series of secondary injury processes which further aggravate the injury to the brain. These processes manifest in the form of raised intracranial pressure and alteration in the cerebral blood flow.
Studies have described a typical phasic cerebral blood flow pattern which consists of early cerebral hypoperfusion followed by hyperemia followed in the later phase by occurrence of post-traumatic vasospasm. The occurrence and degree of hyperperfusion within 12 hours after traumatic head injury has shown to closely correlate with mortality. The vasospasm sets in 4–5 days of injury. These alterations in cerebral blood flow have been correlated with a decrease of saturation of hemoglobin in the bulb of IJV (Jugular venous O2 saturation) and studies have shown that jugular bulb venous oxygen saturation (SjVO2) below 50% was associated with a poor neurologic outcome.
The normal resting intracranial pressure (ICP) is less than 10 mm Hg. It is determined by the volume of CSF, blood and the brain tissue in the cranial vault as indicated by Monro Kelly doctrine. The brain has its own mechanisms to maintain the normal intracranial pressure like altering the blood volume, increasing the CSF absorption and the compressible texture of the brain tissue. When these compensatory buffering mechanisms have been exhausted, the intracranial pressure starts rising leading to intracranial hypertension which if left uncorrected may approximate the mean arterial pressure leading to impediment 580of the blood supply to the brain. Intracranial hypertension develops in 50% of comatose patients following severe TBI. It is defined as sustained intracranial pressure greater than 20 mm Hg. Studies have found that mortality and morbidity increased significantly when the intracranial pressure persistently remains above this threshold. The early immediate increase in brain water seen after trauma is probably vasogenic in origin also called as vasogenic edema whereas that in the later postinjury period is cellular in origin called as cellular edema.
 
Management of Traumatic Brain Injury
As discussed above, the primary brain injury cannot be prevented after the trauma but by preventing hypoxemia, hypotension, hypercarbia and intracranial hypertension one can largely limit the secondary injury and improve the outcome. Thus, the aim of management of TBI should be to prevent the secondary injury by effective management of the above parameters.
The traumatic brain injury is classified clinically by the Glasgow coma scale as given below (Table 82.2). Best score —15 points and worst score—3 points. CT scan categories for head injury is given in Table 82.3.
The recent ATLS guidelines recommend that any trauma evaluation should first include a “primary survey” that includes simultaneous efforts to identify and treat life- and limb-threatening injuries, beginning with the most immediate. The focus should be on urgent problems which should be captured in the “golden hour”. Once these urgent needs are taken care of, a meticulous “secondary survey” and further diagnostic studies designed to reduce the incidence of missed injuries should follow. ATLS emphasizes the ABCDE mnemonic—airway, breathing, circulation, disability, and exposure.
Table 82.2   Glasgow coma scale
Eye-opening response
4 = Spontaneous
3 = To speech
2 = To pain
1 = None
Verbal response
5 = Oriented to name
4 = Confused
3 = Inappropriate speech
2 = Incomprehensible sounds
1 = None
Motor response
6 = Follows commands
5 = Localizes to painful stimuli
4 = Withdraws from painful stimuli
3 = Abnormal flexion (decorticate posturing)
2 = Abnormal extension (decerebrate posturing)
1 = None
Severity of GCS
Score
Need of CT - brain
Management
Mild
14, 15
Yes
Observation
Moderate
9–13
Yes
Observation in ICU
Severe
3–8
Yes
Mechanical ventilation with ICP monitoring
581
Table 82.3   Marshall scale: CT scan categories for head injury
Category
Definition
Diffuse injury I
No visible intracranial pathologic process
Diffuse injury II
Cisterns with midline shift of 0–5 mm are present ± lesion densities present; no high or mixed density lesions at ≥25 mL
Diffuse injury III
Cisterns compressed or absent, with midline shift of 0–5 mm; no high or mixed density lesions of ≥25 mL
Diffuse injury IV
Midline shift of >5 mm; no high or mixed density lesion of ≥25 mL
Evacuated mass lesion (V)
Any lesion surgically evacuated
Nonevacuated mass lesion (VI)
High or mixed density lesion of ≥25 mL; not surgically evacuated
 
Airway
The airway is best managed by endotracheal intubation in comatose patients. Rapid sequence induction with thiopentone (3–5 mg/kg) or fentanyl (3–5 µg/kg) followed by a short acting neuromuscular blocking agent like succinylcholine (1–2 mg/kg) should be done. Succinylcholine can increase the intracranial pressure transiently but its use will lead to faster intubation, its benefits may outweigh its risks. Hence, one must weigh the use of succinylcholine in each individual situation based on the acuity of CNS injury, the anticipated speed with which intubation can be accomplished, and the likelihood that hypoxia will develop. Alternatives to succinylcholine are rocuronium (0.9–1.2 mg/kg) and vecuronium (0.1–0.2 mg/kg). But both these agents have longer duration of action as compared to succinylcholine. The use of thiopentone may result in hypotension in volume depleted patients hence etomidate would be a better choice in these patients. The patient should be adequately preoxygenated by giving 100% oxygen for 5 minutes or 4 vital capacity breaths if possible. The patient should be intubated in neutral head position with a manual-in line cervical spine immobilization which is discussed in the chapter under airway management. The placement of the endotracheal tube should be confirmed by auscultation in prehospital setup and by a capnometer and X-ray in hospital setup. The endotracheal tube not only helps in establishing good oxygenation and ventilation but also protects against aspiration. When oral intubation is difficult, as seen in severe maxillofacial trauma or difficult airway, then urgent surgical airway should be established by a cricothyrotomy or tracheostomy.
 
Breathing
Breathing if found shallow and inadequate mandates mechanical ventilation and the rate should be kept at 10–12 breaths per minute in adults so as to maintain an end tidal concentration of carbon dioxide of around 35 mm Hg. Prophylactic hyperventilation (PaCO2 < 25 mm Hg), especially during the first 24 hours of injury is not recommended now because hyperventilation reduces the ICP by causing cerebral vasoconstriction which further reduces the blood flow to an 582already ischemic injured brain. Without ICP monitoring, hyperventilation is indicated only if rapid deterioration of neurologic status is seen.
 
Circulation
The guidelines for management of severe traumatic brain injury recommend that a systolic blood pressure <90 mm Hg and PaO2 <60 mm Hg should be avoided or rapidly corrected. The traumatic coma data bank (TCDB) studies have shown that a single prehospital observation of hypotension (SBP <90 mm Hg) was among the five most powerful predictors of outcome after TBI. A single episode of hypotension was found to increase the morbidity and double the mortality when compared with groups that did not have hypotension. Hypoxia coupled with hypotension increased the mortality from severe TBI by three fold.
The guidelines for management of severe traumatic brain injury recommend that the cerebral perfusion pressure (CPP) should be targeted in the range of 50–70 mm Hg. The CPP is calculated as
CPP = MAP – ICP
(MAP is mean arterial pressure, ICP is intracranial pressure)
The patients in whom autoregulation is intact do well with higher CPP whereas those with impaired autoregulation are better managed with a CPP in the range of 50–60 mm Hg with more emphasis on the acute management of ICP.
Isotonic crystalloids (normal saline, lactated Ringer's solution, Plasma-Lyte A) are the recommended resuscitative fluids which should be infused through large bore IV cannulas to achieve normotension (early goal of systolic BP 90–100 mm Hg). Hypertonic saline is more preferred as an osmotic agent for reducing ICP rather than resuscitation because studies have not found any benefit over crystalloids for resuscitating trauma victims.
 
Intracranial Hypertension
Once airway, breathing and circulation are taken care of, the next step is to assess the patient's neurological status and disability by noting the GCS and doing CT scan of head from C2 vertebra to the vertex. The medical conditions that increase the intracranial pressure, e.g. fever, seizures, agitation and jugular venous outflow obstruction should be treated.
Measures taken to decrease the intracranial pressure include:
  • Head end elevation by 30–40 degrees avoiding excessive neck flexion.
  • Anticonvulsant prophylaxis with phenytoin is recommended for post-traumatic seizures only for first seven days in patients with TBI. Beyond that, its use is not recommended and any late post-traumatic seizures (after 7 days) should be managed in accordance with the treatment regimen for new onset seizure disorder.
  • Sedation with a narcotic and paralysis with a neuromuscular blocker like vecuronium should be done after securing the airway in a patient who is agitated or posturing. Morphine or fentanyl can be used in small doses. Before giving narcotic, the patient should be made normovolemic so as to avoid narcotic-induced hypotension. Oxygen saturation should be monitored by using a pulse oximeter.
  • 583Intermittent CSF drainage (1–2 mL) can be tried by placing a ventricular catheter to decrease the ICP when it is higher than the therapeutic goal of 20 mm Hg if above methods fail. This asserts the role of ventriculostomy and intracranial pressure monitoring.
    Clinical symptoms such as headache, nausea, and vomiting which are said to be clinical markers of raised ICP are impossible to elicit in comatose patients. CT scan findings of midline shift and compressed basal cisterns are predictive of raised ICP, but intracranial hypertension can occur without these findings. Hence, it is difficult to reliably determine intracranial hypertension using these parameters. These limitations make direct monitoring of ICP necessary.
    Indications for ICP monitoring
    • Patients with GCS of 8 or less after resuscitation and an abnormal CT scan.
    • Patients with GCS of 8 or less and a normal CT but adverse features such as age over 40 years, systolic blood pressure of 90 mm Hg or less, or unilateral or bilateral motor posturing.
    The only contraindication for ICP monitoring in these cases is severe coagulopathy. Placement of the ventriculostomy catheter is the gold standard for measurement of ICP in TBI patients. The ventricular catheter is positioned with its tip in the frontal horn of the lateral ventricle and is coupled by fluid-filled tubing to an external strain gauge transducer and is found to give most accurate readings and is very cost-effective. It can be reset to zero and can be recalibrated in situ. The ventriculostomy ICP monitor also helps in the treatment of an increased ICP by intermittent drainage of the cerebrospinal fluid.
    The other transducers used for ICP monitoring are the microsensor transducer and the fiberoptic transducer which can also be placed in ventricular catheter and provide similar benefits but at a higher cost. The other ICP monitors are the parenchymal ICP monitors which cannot be recalibrated and the epidural, subdural and the subarachnoid fluid coupled or pneumatic monitors which are less accurate.
    Observation of the trends in the ICP recordings have a prognostic significance (e.g. Lundberg “A” or the “plateau” ICP wave which indicate critical cerebral compliance and impending herniation). The brain trauma foundation guidelines for management of severe traumatic brain injury recommend an upper threshold of 20–25 mm Hg for the intracranial pressure.
    The complications of ICP monitoring are infection (6%), hemorrhage, malfunction, obstruction or malposition. Studies have shown that keeping the ventricular catheter in situ for more than 5 days increases the risk of ventriculitis and hence is not recommended.
  • The hyperosmolar therapy with mannitol or hypertonic saline (3% or 7.5%) can be tried if the above measures are not enough to decrease the ICP.
    Mannitol is an osmotic diuretic which acts promptly on infusion by expanding the plasma, reducing the hematocrit and increasing the deformability of erythrocytes thereby decreasing the blood viscosity and causing an increase in the cerebral blood flow and cerebral oxygen delivery. Its effect on decreasing the ICP starts within minutes and is most marked in patients with low CPP. The osmotic effect is delayed for 15–30 minutes 584and persists for a variable period of 90 minutes to ≥6 hours depending on the clinical condition. It is given as IV rapid infusion of 0.25–1 gm/kg and it will maximally decrease the ICP within 10 minutes of administration. Intermittent bolus infusion is preferred over continuous because the later may result in extravasation of the drug into the brain tissue causing a reverse osmotic gradient and an increase in the edema and ICP. Serum osmolality and the sodium levels should be monitored frequently during mannitol administration to minimize the risk of acute tubular necrosis and renal failure. It is contraindicated when the serum osmolality is >320 mosm/L and the serum sodium is >160 mEq/L and hypovolemia.
    Hypertonic saline acts by osmotically mobilizing the water across the intact blood brain barrier and thereby decreasing the cerebral water content. It also dehydrates endothelial cells and erythrocytes, leading to an increase in the diameter of the vessels and deformability of erythrocytes leading to plasma volume expansion with improved blood flow. Dose is 0.1–1 mL/kg/hour administered on a sliding scale. The major complication is central pontine myelinolysis if it is given to patients with preexisting chronic hyponatremia. It may induce or aggravate pulmonary edema in patients with underlying cardiac or pulmonary problems. Hence, it is usually tried in patients whose ICP is refractory to mannitol therapy.
  • Hyperventilation as a means to decrease the ICP is indicated only when there is rapid deterioration of patient's neurological status. As mentioned earlier it should be avoided or used cautiously in the first 24–48 hours since it causes cerebral vasoconstriction in the areas which are CO2 responsive and further decreases the blood supply to the brain whose blood supply is already compromised due to injury. If hyperventilation is used, the brain PO2 and jugular venous oxygen saturation should be monitored to detect any cerebral ischemia that may ensue due to the therapy. If the brain tissue PO2 is <10 mm Hg, the risk of ischemia increases.
  • The definitive treatment for a surgical mass lesion causing significant midline shift is urgent craniotomy and evacuation of the mass. Indications for surgery in traumatic brain injury is given in Table 82.4.
    Mass effect on CT scan is defined as distortion, dislocation, or obliteration of the fourth ventricle; compression or loss of visualization of the basal cisterns, or the presence of obstructive hydrocephalus.
  • Barbiturate therapy: Barbiturates decrease the cerebral metabolic demand and the blood flow. High-dose barbiturate therapy may help in decreasing the ICP when all the medical and surgical treatment modalities have failed. Pentothal sodium is the preferred drug. It is given in a loading IV dose of 10–15 mg/kg over 1–2 hours followed by a maintenance infusion of 1 mg/kg/hour. The dose can be increased till ICP decreases or MAP begins to fall. Studies have shown that one in four patients treated with barbiturate will develop hypotension hence the risk benefit ratio has to be considered. Normovolemia should be ensured before starting barbiturate therapy. It is not recommended as a prophylactic measure for ICP management.
  • Hypothermia: This therapy consists of decreasing the body temperature to 32–33°C as soon as possible after injury and maintenance of that temperature at least for the next 24–48 hours. This is achieved by using surface cooling 585techniques. Studies have shown that hypothermia maintained for more than 48 hours decreases the mortality and improves the Glasgow coma score. It has been thought to significantly decrease the ICP.
Table 82.4   Indications for surgery in traumatic brain injury
  • An acute SDH with a thickness >10 mm or a midline shift >5 mm on CT regardless of the patient's GCS score
  • SDH <10 mm thick and midline shift <5 mm with GCS score <9
  • An extradural hematoma (EDH) >30 cm3 regardless of the patient's GCS
  • Patients with GCS scores of 6 to 8 with frontal or temporal contusions >20 cm3 in volume with midline shift of at least 5 mm and/or cisternal compression on CT scan, and patients with any lesion >50 cm3 in volume
  • If the GCS score decreases between the time of injury and hospital admission by 2 or more points and/or the patient presents with asymmetric or fixed and dilated pupils and/or the ICP exceeds 20 mm Hg
  • Patients with parenchymal mass lesions and signs of progressive neurologic deterioration referable to the lesion, medically refractory intracranial hypertension, or signs of mass effect on CT scan
  • Patients with posterior fossa mass lesions having mass effect on CT scan or with neurologic dysfunction or deterioration referable to the lesion
  • Patients with open (compound) cranial fractures depressed greater than the thickness of the cranium should undergo operative intervention to prevent infection
Mild (GCS 14,15) and moderate (GCS 9–13) brain injuries usually manifest in the form of loss of consciousness at the time of injury to the head and some amount of retrograde amnesia. They are generally referred to as concussions and do not have any significant intracranial pathology. Mild injury patients can be kept under standard observation and if they are found to be completely normal neurologically after 1–2 hours, they can be discharged with a companion and with instructions to revert back to hospital if they develop any symptoms. Moderate injury patients need ICU admission and serial evaluation.
 
General Care of TBI Patients
While managing patients with TBI one has to keep in mind that the recovery may take a long time and hence the other issues of the patient's body also should be attended. This includes starting enteral nutrition as soon as possible or parenteral nutrition if enteral is not possible. The resting metabolic expenditure increase by 140% in a nonparalysed patient and is 100% in paralysed patient with severe TBI. Hence, while calculating the caloric requirement, this has to be taken note of and at least 15% of the caloric requirements should consist of protein especially branched chain amino acids.
Deep venous thrombosis prophylaxis should be started with sequential compression devices. Low dose heparin is effective but carries a risk of intracranial bleed in TBI patients.
Short course of antibiotics can be given during intubation to prevent pneumonia but the long-term prophylactic use of antibiotics is not recommended. Generally, antibiotics should be given only when infection develops. 586
 
Physiotherapy and Rehabilitation
Physiotherapy plays a major role in getting the TBI patient back to lead their normal or near normal life. It should be started within the first few days after injury, by a trained physiotherapist. Initially passive range of exercises should be started. Gradually the patient should be made to sit. Studies have shown that early sitting in comatose patient helps in the early recovery of consciousness.
 
BIBLIOGRAPHY
  1. ATLS for Doctors. Student Manual, 7th edition. Chicago, American College of Surgeons; 2004.
  2. Barzo P, Marmarou A, Fatouros P, et al. Biphasic pathophysiological response of vasogenic and cellular edema in traumatic brain swelling. Acta Neurochir Suppl (Wien). 1997;70:119-22.
  3. Barzo P, Marmarou A, Fatouros P, et al. Contribution of vasogenic and cellular edema to traumatic brain swelling measured by diffusion-weighted imaging. J Neurosurg. 1997;87:900-7.
  4. Brain Trauma Foundation: Guidelines for the management of severe head injury. US Brain Trauma Foundation, 2007.
  5. Bullock RM, Chesnut R, Ghajar J, et al. Guidelines for the surgical management of traumatic brain injury. Neurosurgery. 2006;58(3 Suppl):S1-S62.
  6. Chesnut RM, Marshall LF, Klauber MR, et al. The role of secondary brain injury in determining outcome from severe head injury. J Trauma. 1993;34:216-22.
  7. Collier BR, Miller SL, Kramer GS, et al. Traumatic subarachnoid hemorrhage and QTc prolongation. J Neurosurg Anesthesiol. 2004;16:196-200.
  8. Dorhout Mees SM, Rinkel G, Feigin V, et al. Calcium antagonists for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev. 2007;(3):CD000277.
  9. Doyle JA, Davis DP, Hoyt DB. The use of hypertonic saline in the treatment of traumatic brain injury. J Trauma. 2001;50:367-83.
  10. Eisenberg HM, Frankowski RF, Contant CF, et al. High-dose barbiturate control of elevated intracranial pressure in patients with severe head injury. J Neurosurg. 1988; 69:15-23.
  11. Foulkes M, Eisenberg HM, Jane JA, et al. The Traumatic Coma Data Bank: design, methods, and baseline characteristics. J Neurosurg. 1991;75(Suppl):S8-S13.
  12. Gennarelli TA, Spielman GM, Langfitt TW, et al. Influence of the type of intracranial lesion on outcome from severe head injury: a multicenter study using a new classification system. J Neurosurg. 1982;56:26-32.
  13. Hlatky R, Contant CF, Diaz-Marchan P, et al. Significance of a reduced cerebral blood flow during the first 12 hours after traumatic brain injury. Neurocrit Care. 2004;1: 69-83.
  14. Irwin Rippe RS, James M. Intensive Care Medicine, 6th edition. Lippincott Williams and Wilkins; 2008.
  15. Jones NR, Molloy CJ, Kloeden CN, et al. Extradural haematoma: Trends in outcome over 35 years. Br J Neurosurg. 1993;7:465-71.
  16. Lundberg N, Troupp H, Lorin H. Continuous recording of the ventricular fluid pressure in patients with severe acute traumatic brain damage. A preliminary report. J Neurosurg. 1965;22:581-90.
  17. Marshall LF, Marshall SB, Klauber MR, et al. A new classification of head injury based on computerized tomography. J Neurosurg. 1991;75:S14-S20.
  18. Martin NA, Patwardhan RV, Alexander MJ, et al. Characterization of cerebral hemodynamic phases following severe head trauma: hypoperfusion, hyperemia, and vasospasm. J Neurosurg. 1997;87:9-19.
  19. 587Massaro F, Lanotte M, Faccani G, et al. One hundred and twenty-seven cases of acute subdural haematoma operated on. Correlation between CT scan findings and outcome. Acta Neurochir (Wien). 1996;138:185-91.
  20. Mattioli C, Beretta L, Gerevini S, et al. Traumatic subarachnoid hemorrhage on the computerized tomography scan obtained at admission: A multicenter assessment of the accuracy of diagnosis and the potential impact on patient outcome. J Neurosurg. 2003;98:37-42.
  21. Miller RD. Miller's Anesthesia, 7th edition. Elsevier Publications; 2009.
  22. Muizelaar JP, Marmarou A, Ward JD, et al. Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial. J Neurosurg. 1991;75:731-9.
  23. Narayan RK, Kishore PRS, Becker DP, et al. Intracranial pressure: to monitor or not to monitor? A review of our experience with severe head injury. J Neurosurg. 1982;56: 650-9.
  24. Servadei F. Prognostic factors in severely head injured adult patients with acute subdural haematomas. Acta Neurochir (Wien). 1997;139:279-85.
  25. Tempkin NR, Dikmen SS, Wilensky AJ, et al. A randomized, double-blind study of phenytoin for the prevention of post-traumatic seizures. NEJM. 1990;323:497-502.
  26. Zumkeller M, Behrmann R, Heissler HE, et al. Computed tomographic criteria and survival rate for patients with acute subdural hematoma. Neurosurgery. 1996;39: 708-12.

THORACIC TRAUMACHAPTER 83

Sushma Vijay Pingale, Marun Raj
Thoracic trauma is one of the leading cause of trauma-related deaths. The major potentially life-threatening injuries in thoracic trauma are given in the Table 83.1.
 
INJURY TO CHEST WALL
Rib fractures by themselves are not very harmful but they are accompanied by more severe injuries like pulmonary contusion which are more of a concern. The age of the patient and the location of the rib fracture are other major determinants of the morbidity and mortality associated with rib fracture. Studies have shown that elderly patients with rib fractures have twice the mortality of younger patients with similar injuries. The left-sided fractured ribs are generally associated with splenic injuries and the right-sided rib fractures are associated with injury to the liver. The first rib may be associated with injury to the subclavian artery.
The number of fractured ribs also has significant bearing on the outcome as shown by the study of Flagel et al. The overall mortality rate for patients with rib fractures is around 10% and is said to increase with each additional rib fracture independent of age.
 
Flail Chest
It is a condition defined as the fracture of at least four consecutive ribs in two or more places in a parallel vertical orientation. It results in an incompetent segment of chest wall which causes paradoxical movement of the rib cage. As the patient inspires, the negative pressure that is generated is dissipated by the movement of the flail segment inwards while the remainder of the thoracic cage moves outward during inspiration. The associated lung injury may further contribute to hypoxia by causing a mismatch in the ventilation and perfusion. The mainstay of treatment in this type of injury is to support the ventilation and give excellent pain relief in the form of epidural analgesia. Positive pressure ventilation is the gold standard as it forces the flail segment to rise and fall normally with inspiration. Epidural anesthesia abolishes the pain associated with the multiple rib fractures and thereby avoids the splinting and hypoventilation associated with it and hence become one of the major treatment for such injuries. Intercostal nerve block can also be tried whenever epidural analgesia is not feasible.
Table 83.1   Life-threatening injuries in thoracic trauma
  • Injury to chest wall—Rib fractures and flail chest
  • Injury to pleura—Pneumothorax and hemothorax
  • Injury to lung parenchyma—Contusion and tracheobronchial injury
  • Injury to heart—Cardiac contusion, rupture and valvular injury
  • Injury to aorta
  • Injury to esophagus
589
 
INJURY TO PLEURA
The pleural space is the potential space between the parietal and visceral pleura. An injury to any of these pleurae can result in air or blood accumulating in this space which can compress the lung parenchyma and cause collapse of the lung.
 
Pneumothorax
Pneumothorax is a condition in which there is presence of free air in the pleural space resulting in partial or total lung collapse. It can occur due to disruption of parietal pleura or visceral pleura. It can be spontaneous (due to rupture of some bulla) or traumatic. A traumatic pneumothorax can arise as a result of a blunt or penetrating trauma.
 
Clinical Features
Pneumothorax is identified by chest pain and dyspnea, sinus tachycardia, decreased breath sounds and expansion of chest wall on the affected side. If the patient is hemodynamically stable, a chest radiograph can be obtained in the upright position which is diagnostic in most of the cases. X-ray in the supine position may show anterolateral air which typically increases the radiolucency at the costophrenic sulcus creating the “deep sulcus sign”. Small pneumothoraces which are not visible on plain radiographs can be picked up by the CT scan of thorax (Figs 83.1A and B).
Figs 83.1A and B: (A) X-ray—bilateral pneumothorax and (B) CT scan— left-sided massive pneumothorax
590
Figs 83.2A and B: Right-sided tension pneumothorax shifting the mediastinum to the left side
Tension pneumothorax is a life-threatening condition in which there is progressive accumulation of trapped air in the pleural space which increases the intrapleural pressure causing total collapse of the lung on the affected side and shift of the mediastinum to the opposite side thus jeopardising the cardiac output (Figs 83.2A and B). It is a clinical diagnosis and if not decompressed immediately, it can cause complete hemodynamic collapse. Emergency decompression with a 14- or 16-gauge catheter in the midclavicular line of the second intercostal space may be lifesaving while preparations for chest tube insertion are being made.
Hemothorax is defined as the accumulation of blood in the pleural space. The source of the blood may be bleeding anywhere in the chest cavity including the chest wall, lung parenchyma, heart, major thoracic vessels or diaphragm. Patients with hemothorax present with tachycardia, tachypnea, decreased breath sounds and chest wall movement and dullness to percussion on the affected side. In case of massive hemothorax they may also present with shock.
Massive hemothorax is one in which there is accumulation of more than 1500 mL of blood in the pleural space. It is more common on the left side and is usually due to aortic rupture in a blunt trauma or pulmonary hilar or major vessel injury due to a penetrating trauma.
Small hemothoraces (<15% of the volume of hemithorax) may not be visible on X-ray because the blunting of the costophrenic angle in a radiograph requires accumulation of 200–250 mL of blood. CT scan is useful in such occult hemothorax.
 
Treatment of Pneumothorax and Hemothorax
Tube thoracostomy is the definitive treatment for most pneumothoraces as well as hemothorax. The fifth intercostal space in the mid-axillary line on the affected side is the preferred site for the tube placement and the optimal position is posterior to facilitate dependent drainage of blood and the tube is directed to the apex of the pleural cavity. Tube size preferred in adults is generally 36 Fr. A chest radiograph should always be taken after doing a tube thoracostomy.
In case of an open pneumothorax (caused when a penetrating chest injury opens the pleural space to the atmosphere) a sterile occlusive dressing covering three sides of the wound is done so as to allow it to function as a one way valve allowing air to escape during expiration and occlude during negative pressure inspiration. A chest tube is inserted under aseptic precautions at a site away from the site of injury to treat any possible tension pneumothorax that may 591arise. Oxygen should be supplemented and the airway and breathing should be controlled if required.
Table 83.2   Indications for exploration in thoracic injury
  • Caked hemothorax (high volume output initially followed by an abrupt decrease in the volume)
  • Drainage of more than 1500 mL of blood on insertion of chest tube
  • Continuous hemorrhage of more than 200 mL/hour for three consecutive hours
  • Large air leak with inadequate ventilation or persistent collapse of lung
  • Esophageal perforation
  • Pericardial tamponade
A moderate-sized hemothorax (500–1500 mL) which stops bleeding immediately after the insertion of chest tube can be managed conservatively with a closed drainage system. The removal of tube should be done only after the pneumothorax and air/blood leak has resolved completely. Indications for exploration in thoracic injury is given in Table 83.2.
 
INJURY TO LUNG
Pulmonary contusion is a common problem in a majority of patients sustaining major chest trauma. It may result due to direct blunt trauma, shearing at gas liquid interface or the transmission of a shock wave. The pathophysiological changes are hemorrhage and interstitial edema. A flail chest is associated with pulmonary contusion in approximately three fourths of thoracic trauma cases and this doubles the morbidity and mortality. The patient will be tachypnoeic with increased work of breathing, will have hypoxia and hypercarbia commonly. A chest radiograph may not show any signs up to 6 hours of injury and hence CT scan is useful during the early phase of injury. Treatment is supportive and includes supplementation of oxygen, pulmonary toileting (through nasotracheal suction, chest physiotherapy or postural drainage or bronchoscopy) and adequate pain relief. The intravenous fluids are given judiciously since hypervolemia may exacerbate the fluid extravasation into the alveolar space and thus worsen the parenchyma consolidation. The degree of pulmonary dysfunction usually peaks at 72 hours and generally resolves within 7 days in the absence of associated infection.
Tracheobronchial injury though uncommon should be suspected in the presence of cervical subcutaneous emphysema, pneumomediastinum or pneumothorax with a persistent air leak. A bronchoscopy is diagnostic. More than 80% of tracheobronchial injury due to blunt trauma is located within 2.5 cm of the carina. Oral intubation may be required in patients who have respiratory difficulty. Injury to the trachea can be primarily repaired or converted to a tracheostomy if necessary for airway control. When a major bronchus is injured, lobectomy is advocated with closure of the bronchial stump debrided back to healthy tissue.
 
INJURY TO HEART
Blunt cardiac injuries can result from motor vehicle crashes or due to any trauma to the chest. The injury may result in cardiac contusion, rupture or valvular injury. 592Generally the cardiac contusion is not considered serious if the ECG and the serum troponin levels are normal at the time of presentation and 8 hours later. But if the ECG and the troponin levels are abnormal then the patient needs good cardiac monitoring as it may lead to cardiogenic shock resistant to ionotropic support. Then alternatives like the intra-aortic balloon counterpulsation may be required.
Cardiac rupture can present as cardiac tamponade. Hypotension is seen in the absence of overt blood loss. Ultrasonography may show hemopericardium. Creation of a pericardial window in the operating room can be both diagnostic and therapeutic. Traumatic valve insufficiency, depending on the severity and the valve involved may necessitate early surgical treatment.
 
INJURY TO AORTA
Though not uncommon for the civilian population to have thoracic vascular injuries, most of the injuries are treatable if the patient present within the golden hours. Medical fraternity needs further training in these aspect since most of the time these injuries are easily missed due to inadequacy of the expertise available and the need for tertiary care setup to deal all these injuries.
 
Evaluation of the Chest Injuries
Patients admitted to emergency department with life-threatening chest traumatic injuries need several things to be performed in a swift manner without wasting time.
  • Evaluation of the patient clinically to rule out the possibility of pericardial tamponade, pneumothorax or cardiorespiratory compromise and any dangerous extrathoracic injuries.
  • Respiratory failure and airway obstruction are managed by immediate endotracheal intubation, assisted ventilation if necessary and tracheobronchial suction.
  • A central venous catheter is inserted into jugular vein to accurately assess the volume requirement and at the same time to replace the volume in swift manner without producing compromise although a wide bore peripheral cannula is better than central venous cannula for rapid infusion of fluids and blood products.
  • Chest X-ray taken in erect posture if possible reveals many factors including rib fractures, pleural effusion, diaphragmatic position and mid line shift if any.
Once the above said stages of clinical evaluation are over and the patient is stabilized, then triage can be completed. In triage, it is essential to distinguish those patients with airway obstruction, pericardial tamponade and tension pneumothorax, since the delay in treatment in order to take investigations or imaging is hazardous. Next step is grouping the patients with injuries such as traumatic rupture of aorta or massive hemothorax, where intervention by exploratory thoracolaparotomy is urgent but is preceded by rapid investigation. The last group compromises the majority of trauma victims who at most 593need minor intervention and in hospital observation. The classification of chest injuries by triage is further classified based on the anatomy of the lesion involved:
  • Chest wall and diaphragm
  • Intrathoracic viscera.
 
Traumatic Rupture of Aorta
Following a deceleration injury, the aorta may rupture at the isthmus just distal to the origin of the left subclavian artery. The intima and media rupture circumferentially but the adventitia remains intact and the patient will survive until the adventitia ruptures, which may occur at any time. There are usually no specific clinical sings that point directly at the lesion, but its presence is always looked for whenever there is a history of a severe fall or motor-vehicle accident. On chest X-ray, the superior mediastinum is broadened and sometimes in anteroposterior view, mediastinum may look widened. Hence in that case, clinical presentation helps in diagnosing the condition. Venous hemorrhage is a source of mediastinal hematoma and will radiographically mimic a rupture. Other radiographic signs of great importance are loss of aortic knuckle, rightward displacement of the trachea and the esophagus and a left hemothorax. Injury to the thoracic skeleton is a marker for the severity of the deceleration and therefore the likelihood of rupture. The diagnosis must be confirmed by CT of the thorax or angiography of the thoracic aorta. The aortic rupture is then repaired through a fifth interspace thoracotomy with cross-clamp control gained proximally across the arch between left common carotid and subclavian arteries and distally opposite the pulmonary veins. Distal perfusion during cross-clamping is maintained with a heparinized shunt running from aortic arch to distal descending thoracic aorta or femoro-femoral bypass. The rupture is repaired with an interposition Dacron of PTFE synthetic graft.
 
Dissection of Aorta
Aneurysm results from a transverse split through the aortic intima into the media. From the entry point the aneurysm tunnels through the media and creates a double lumen aorta. The true lumen bounded by normal aortic wall and the dissection flap of intima and media and a false lumen bounded by the dissection flap centrally and the residual media and adventitia externally. When a dissection occurs, the patient experiences sudden-onset central chest pain radiating to the back. There may not be any abnormality on physical examination, but evidence of branch artery damage such as neurological signs, aortic incompetence and diminished peripheral pulses with leg symptoms. CT angiogram has almost replaced the conventional angiogram nowadays. Type A dissection is treated with prosthetic replacement of the ascending aorta with or without aortic valve resuspension and coronary artery bypass grafting. Acute type B dissection are mostly managed medically and chronic type 2 with complications need surgical replacement of aorta.594
 
INJURY TO ESOPHAGUS
Esophageal perforation is more common iatrogenically during endoscopy. Patient complains of pain. There may be presence of fever, crepitus and subcutaneous or mediastinal air. A plain radiograph of chest may show subcutaneous emphysema. Contrast studies are confirmatory and also point to the exact site of perforation. When the perforation is small, conservative approach consisting of broad spectrum intravenous antibiotics and keeping the patient nil by mouth is helpful. Nasogastric tube is avoided and surgery is indicated when there is a free communication of the leak with either the peritoneal or thoracic cavities or in case of presence of mediastinal abscess.
 
BIBLIOGRAPHY
  1. Avery EE, Morch ET, Benson DW. Critically crushed chest: a new method of treatment with continuous mechanical hyperventilation to produce alkalotic apnea and internal pneumatic stabilization. J Thorac Cardiovasc Surg. 1956;32:291-311.
  2. Bulger EM, Arneson MA, Mock CN, et al. Rib fractures in the elderly. J Trauma. 2000; 48:1040-7.
  3. Clark GC, Schecter WP, Trunkey DD. Variables affecting outcome in blunt chest trauma: flail chest vs pulmonary contusion. J Trauma. 1988;28:298-304.
  4. Flagel BT, Luchette FA, Reed RL, et al. Half-a-dozen ribs: the breakpoint for mortality. Surgery. 2005;138:717-25.
  5. Gupta A, Jamshidi M, Rubin JR. Traumatic first rib fracture: is angiography necessary? A review of 730 cases. Cardiovasc Surg. 1997;5:48-53.
  6. Irwin RS, Rippe JM. Irwin and Rippe's Intensive Care Medicine, 6th edition Lippincott Williams and Wilkins; 2008.
  7. Lynn RB, Iyengar K. Traumatic rupture of the bronchus. Chest. 1972;61:81-3.
  8. Miller RD. Miller's Anesthesia. 7th edition. Elsevier Publications; 2009.
  9. Sherwood SF, Hartsock RL. Thoracic injuries. In: McQuillian KA, Von Rueden KT, Hartstock RL, et al. (Eds): Trauma Nursing from Resuscitation through Rehabilitation. 3rd edition. Philadelphia, Saunders; 2002. pp. 543-90.
  10. Shweik E, Klen J, Wood GC, et al. Assessing the true risk of abdominal solid organ injury in hospitalized rib fracture patients. J Trauma. 2001;50:684-8.
  11. Velmahos GC, Karaiskakis M, Salim A, et al. Normal electrocardiography and serum troponin I levels preclude the presence of clinically significant blunt cardiac injury. J Trauma. 2003;54(1):45-51.
  12. Yamamoto L, Schroeder C, Morley D, et al. Thoracic trauma: the deadly dozen. Crit Care Nurs Q. 2005;28(1):22-40.
595Ultrasonography
Chapter 84 Role of Ultrasound in Critical Care Prem Kumar596

ROLE OF ULTRASOUND IN CRITICAL CARECHAPTER 84

Prem Kumar  
INTRODUCTION
Ultrasound is a recently introduced technology in the field of anesthesiology, critical care and emergency room. The growing concern for procedures to be performed in real time, reducing complications, aiding diagnosis and interventions has made ultrasound to be one of the best modality in critical care. Ultrasound has become the gold standard for bedside diagnosis, hemodynamic assessment and for guidance in performing interventions in real time in critically ill patients (Fig. 84.1).
Fig. 84.1: Portable ultrasound machine
598
 
PHYSICS OF ULTRASOUND
Ultrasound is high frequency sound waves with frequency >20 KHz (human ears can hear sound frequencies between 20 Hz and 20 KHz). Medical ultrasound has a frequency of 2.5 MHz–15 MHz. It allows noninvasive imaging of tissues in real time based on reflection and scattering. This is based on a phenomenon called piezoelectric effect where there is mechanical deformation in response to an electric field applied to lead zirconate titanate. The term piezoelectric means pressure electric effect. By incorporating piezoelectric elements into transducer, it converts electric energy into mechanical oscillations thereby acting both as transmitter and receiver.
Terminologies to be understood in ultrasound physics:
  • Acoustic velocity
  • Acoustic impedance
  • Axial and lateral resolution
  • Attenuation coefficient.
Acoustic velocity is the speed at which sound wave travels through a medium which is equal to frequency times the wavelength. Acoustic impedance is the degree of impedance a sound wave undergoes while it travels through a medium. There are two types of spatial resolution—axial and lateral. The minimal distance of the superior and inferior planes along the axis of the beam is axial resolution. The ultrasound wave undergoes various characteristics as it travels through the tissues—reflection, scattering and absorption.
There are 2 properties in ultrasound which determines the selection of probe—wavelength and frequency. Wavelength is the distance between two areas of maximal rarefaction and penetration of the ultrasound wave is proportional to wavelength. Frequency is the number of wavelengths that pass per unit time. It is measured as cycles per second and the unit is hertz (Hz). Higher the frequency, better the resolution but the lower the penetration and vice versa in case of lower frequency.
 
Imaging Modes
 
A-mode
The transducer emits ultrasound wave into medium and a single dimensional image is generated as a series of vertical peaks which corresponds to the depth of the tissues. This mode does not provide information about the spatial relationship of the structures, hence it is a basic mode for imaging the structures.
 
B-mode
This mode produces a 2 dimensional image due to a linear array of many piezoelectric crystals in the transducer. This mode produces dots of different brightness based on the amplitude of a series of A scans. Intensity of gray scale indicates the strength of echogenicity and the side to side and upward downward distance in the display reflects the real distances in the tissue. Since this mode 599provides cross-sectional image, this mode is commonly used in regional anesthesia and critical care.
 
M-mode
This mode produces a single beam with a motion signal where structural movement like heart valve can be visualized in a waveform manner. This mode is used for cardiac valve imaging and fetal cardiac imaging.
 
Doppler
This is superimposed on a B mode image in which the color depends on whether blood flow direction is towards the transducer or away from it. Red and blue color indicates the direction and velocity of blood flow where red color indicates the flow away from the probe and blue color indicates the flow towards the probe.
 
Selection of Ultrasound Transducer
Frequency is the main element of transducers and they are also described by their array (e.g. linear) configuration. Based on frequency, transducers are classified into high, mid and low frequency transducers (Table 84.1 and Fig. 84.2).
Table 84.1   Transducers and its indications
High frequency (>10 MHz)
Suited to visualize structures within 3 cm from the skin surface. Good to visualize superficial structures (e.g. internal jugular vein, nerve blocks)
Mid frequency (5–10 MHz)
Suited for structures within 3–6 cm from skin surface. Used for nerve blocks, deeper vascular structures
Low frequency (<5 MHz)
Used for visualizing deeper structures (e.g. IVC collapsibility)
Fig. 84.2: Transducers—linear array and curvilinear
600
 
ULTRASOUND IMAGE CHARACTERISTICS
Any image obtained on the screen can be controlled by depth and gain. The intensity of the returned ultrasound waves is depicted by the brightness on the screen (echogenicity). Strong reflection of a structure back to the transducer is portrayed as white color on screen (hyperechoic or echogenic). Less reflection of the structure which shows dark image on the screen is depicted as hypoechoic. Bone, pleura are seen as hyperechoic and nerves, fluids, muscle tissues are seen as hypoechoic (Table 84.2).
 
Transducer Movements (Figs 84.3 to 84.7)
  • Sliding
  • Tilting
  • Rotating
  • Angling
  • Compression.
Before starting to scan, the orientation of the transducer is confirmed in relation to the image on the screen. The U symbol in the top left screen corner represents the palpable prominence on one side of the transducer. Transducer position on the screen is confirmed by placing the finger on one side of the transducer to note a change in the image of the screen. It is better to always orient ourselves that the left and right side of the screen image corresponds to the left and right side of the structure of interest in the patient.
Table 84.2   Ultrasound appearance of various structures
Structure
Appearance
Artery
Hypoechoic, pulsatile, noncompressible. Doppler shows pulsatile flow
Vein
Hypoechoic, nonpulsatile, compressible. Valsalva effect, Doppler shows continuous flow
Bone
Hyperechoic
Tendon
Hyperechoic with anisotropy—bright lines longitudinally or bright dots at right angles fibrillary pattern
Nerves
Variable hypo- or hyperechoic with anisotropy fascicular pattern
Muscle
Hypoechoic with multiple hyperechoic lines
Figs 84.3A and B: Sliding
601
Figs 84.4A to C: Angling
Fig. 84.5: Compression
Figs 84.6A and B: Rotation
 
Short-axis view: Imaging is a cross-sectional view of the structure with the transducer kept at right angle to the direction of the structure of interest.602
Figs 84.7A and B: Tilting
Figs 84.8A and B: Ultrasound image of internal jugular vein—short axis view and long axis view
Long-axis view: Probe and target structure are aligned in a way or kept parallel so that the image of the structure is in longitudinal axis.
 
NEEDLE ORIENTATION
When needles are introduced into the field, they are depicted as being in plane or out of plane based on whether the needle is in or out of the plane of the ultrasound beam (Figs 84.9 and 84.10).
In plane imagingneedle is introduced to the target structure in the same plane of the ultrasound beam, hence the needle can be seen in its entire length. So the needle tip can be seen and positioned precisely in the area of interest.
Out of plane imaging—needle is introduced to the target structure perpendicular to the ultrasound beam, hence the needle can be seen as a bright spot on the screen. Disadvantage is this method does not indicate the needle tip position.603
Fig. 84.9: Needle orientation—in plane
Fig. 84.10: Needle orientation—out of plane
 
Clinical Uses of Ultrasound in ICU (Table 84.3)
  • Diagnosis and assessment—thoracic, cerebral, abdominal, vascular, ocular structures. RUSH protocol is done for diagnosing the cause of shock (Tables 84.4 and 84.5, Fig. 84.11). e-FAST (Focused Assessment with Sonography for Trauma) protocol is done for patients coming to emergency room with trauma (Figs 84.12A to F). Aortic view can be seen in Figures 84.13A to D.
  • Echocardiography—diagnosis and assessment of volumes
  • Procedural—central venous catheterization, regional nerve blocks, etc.
 
PULMONARY EMBOLISM
The echocardiographic findings suggestive of pulmonary embolism are RV dilation, impairment of the RV free wall contraction, paradoxical septal wall motion, or dilation of the right pulmonary artery, in a patient with hemodynamic instability/collapse.604
Table 84.3   Uses of ultrasound in critical care
Site
Findings
Diagnosis
Abdomen
Free fluid
Abdominal aorta >3 cm
Intraperitoneal fluid/blood
Abdominal aortic aneurysm
Thorax
Lung sliding sign (absence) (Figs 84.18, 84.20 to 84.22)
Comet tail artifacts (absence)
Echo-free space between visceral and parietal pleura
A, B lines (Fig. 84.19)
Pneumothorax
Pleural effusion
Pulmonary edema
Vascular (lower limb)
Compressibility of common femoral vein and popliteal vein (Figs 84.14 and 84.15).
Deep venous thrombosis
Echocardiography (TTE)
Assessment of left ventricular (LV) and right ventricular (RV) function/Regional wall motion abnormalities
Assessment of the pericardial space
Dilated right ventricle, right atrium
Underfilled ventricles, IVC diameter and collapsibility on respiration (Figs 84.16A and B)
Ventricular activity
Myocardial ischemia/infarction
Pericardial effusion
Pulmonary embolism
Hypovolemia
Cardiac arrest
Transcranial Doppler
Flow velocity, pulsatile index
Cerebral vasospasm, cerebral artery obstruction
Ocular
Optic sheath diameter >5 mm
Increased intracranial pressure
Table 84.4   RUSH protocol
RUSH exam
Hypovolemic shock
Cardiogenic shock
Obstructive shock
Distributive shock
Pump
Underfilled ventricles
Dilated ventricles
Pericardial effusion dilated RV Hypercontractile heart
Hypercontractile heart (early sepsis) hypocontractile heart (late sepsis)
Tank
Flat IVC
Peritoneal fluid pleural fluid
Distended IVC
RWMA
Distended IVC Absent lung
Sliding
Comet tail artifacts
Normal/small IVC normal/small IJV
Pleural fluid (empyema)
Peritoneal fluid (peritonitis)
Pipes
Aortic dissection
Normal
DVT
Normal
605
Table 84.5   Stepwise approach in RUSH protocol
Step no. 1
Step no. 2
Step no. 3
Pump
Pericardial effusion:
  • Effusion?
  • Signs of tamponade?
  • Diastolic collapse of RV
Left ventricular contractility:
Normal or reduced?
Right ventricular strain:
  • Increased size of RV?
  • Septal displacement from right to left
Tank
Inferior vena cava:
Size, collapsibility based on inspiration.
E-FAST exam:
  • Free fluid abd/pelvis?
  • Free fluid thoracic cavity?
  • Pulm edema: Lung rockets?
Tension pneumothorax:
Absent lung sliding?
Absent comet tails?
Pipes
Abdominal aorta aneurysm:
Abdominal aorta >3 cm
Femoral or popliteal vein DVT?
Compressible?
Figs 84.11A to C: RUSH protocol: (A) Parasternal view; (B) Subxiphoid view; (C) Apical view
Figs 84.12A to F: e-FAST (Focused Assessment with Sonography for Trauma) protocol: (A) Subxiphoid view; (B) Perihepatic and hepatorenal view; (C) Perisplenic view; (D) Pelvic view; (E) Pleural view
606
Figs 84.13A to D: Probe positions for aortic view. (A) Suprasternal; (B) Parasternal; (C) Epigastric; (D) Supraumbilical
Fig. 84.14: Common femoral vein for DVT
 
Bedside Lung Ultrasound in Emergency Protocol for Acute Respiratory Failure
Bedside lung ultrasound in emergency (BLUE) protocol is a fast protocol which requires less than minutes for an expert and little longer for a novice. The purpose of BLUE protocol is that it allows diagnosis of acute respiratory failure based on the venous analysis (Flow chart 84.1). Pulmonary edema, pulmonary embolism, 607pneumonia, chronic obstructive pulmonary disease, asthma, and pneumothorax yield specific profiles in this protocol.
Fig. 84.15: Popliteal vein for DVT
Figs 84.16A and B: Ultrasound-guided IVC imaging showing collapsibility in the second image
BLUE-points: Two hands are placed on the chest with the upper hand touching the clavicle, thumbs excluded which correspond to the location of the lung. This allows three standardized points to be defined. The upper-BLUE-point is at the middle of the upper hand. The lower-BLUE-point is at the middle of the lower palm. The PLAPS (posterolateral alveolar or pleural syndromes) point is defined by the intersection of a horizontal line at the level of the lower BLUE-point; a vertical line at the posterior axillary line (Figs 84.17A and B).
 
Cardiac Arrest Ultrasound Exam Protocol for Cardiac Arrest
Cardiac arrest ultrasound exam (CAUSE). This protocol helps in identifying the cause of pulseless electrical activity or asystole and guides the management (Flow chart 84.2).608
Flow chart 84.1: Algorithm showing the bedside lung ultrasound in emergency protocol for lung ultrasound
Figs 84.17A and B: BLUE and PLAPS points
 
Fluid Administration Limited by Lung Sonography Protocol
Fluid administration limited by lung sonography (FALLS). This protocol is mainly used for hemodynamic assessment of circulatory failure using lung ultrasound. This protocol identifies causes based on lung ultrasound for circulatory failure.
 
Secure European System for Applications in a Multi-vendor Environment (SESAME) Protocol
This is done for identifying the causes of cardiac arrest.
 
PROCEDURAL USES OF ULTRASOUND
  • Central vein catheterization: It is used for both central and peripheral vein catheterization. NICE guidelines recommend the use of ultrasound for catheterization of central veins.609
    Flow chart 84.2: Algorithm showing the cardiac arrest ultrasound exam protocol for cardiac arrest
    Abbreviations: RV, right ventricle; LV, left ventricle; RA, right atrium; PE, pulmonary embolus
    Fig. 84.18: B-mode showing the bat sign and lung sliding sign
    610
    Fig. 84.19: Normal lung image by M-mode showing A-lines which are reverberation artifacts
    Fig. 84.20: Sea shore sign in M–mode (normal lung sliding with respiration)
    611
    Fig. 84.21: Bar code sign indicating pneumothorax
    Fig. 84.22: Lung point indicating the transition between normal lung and pneumothorax
  • Percutaneous tracheostomy: To determine the site of puncture and to identify aberrant vessels (Fig. 84.23).
  • Thoracentesis: Done with ultrasound guidance for all pleural procedures (e.g. Needle thoracotomy or intercostal drainage for pneumothorax, draining pleural effusion).612
    Fig. 84.23: Ultrasound image showing trachea for percutaneous tracheostomy
    Fig. 84.24: Ultrasound image for intercostal nerve block for analgesia in chest injury
  • Regional nerve blocks: It is the gold standard for performing peripheral nerve blocks for patients with trauma for pain relief and to reduce the inflammatory process (Fig. 84.24).613
 
BIBLIOGRAPHY
  1. Hendrickson RG, Dean AJ, Costantino TG. A novel use of ultrasound in pulseless electrical activity: the diagnosis of an acute abdominal aortic aneurysm rupture. J Emerg Med. 2001;21:141-4.
  2. Hernandez C, et al. CAUSE: Cardiac arrest ultra-sound exam—A better approach to managing patients in primary non-arrhythmogenic cardiac arrest. Resuscitation. 2008;76:198-206.
  3. Joyner CR, Herman RJ, Reid JM. Reflected ultrasound in the detection and localisation of pleural effusion. JAMA. 1967;200:399-402.
  4. Kirkpatrick AW, Sirois M, Laupland KB, Liu D, Rowan K, Ball CG, et al. Hand-held thoracic sonography for detecting post-traumatic pneumothoraces: the Extended Focused Assessment with Sonography for Trauma (EFAST). J Trauma. 2004;57(2): 288-95.
  5. Legome E, Pancu D. Future applications for emergency ultrasound. Emerg Med Clin North Am. 2004;22:817-27.
  6. Lichtenstein D, Menu Y. A bedside ultrasound sign ruling out pneumothorax in the critically ill: lung sliding. Chest. 1995;108:1345-8.
  7. Lichtenstein D, Mezière G, Biderman P, Gepner A, Barré O. The comet-tail artifact: an ultrasound sign of alveolar-interstitial syndrome. Am J Respir Crit Care Med. 1997; 156:1640-6.
  8. Lichtenstein D, Mezière G, Biderman P, Gepner A. The comet-tail artefact an ultrasound sign ruling out pneumothorax. Intensive Care Med. 1999;25:383-8.
  9. Lichtenstein D, Mezière G, Lagoueyte JF, Biderman P, Goldstein I, Gepner A. A-lines and B-lines: lung ultrasound as a bedside tool for predicting pulmonary artery occlusion pressure in the critically ill. Chest. 2009;136:1014-20.
  10. Lichtenstein D, Mezière G. The BLUE-points: three standardized points used in the BLUE-protocol for ultrasound assessment of the lung in acute respiratory failure. Crit Ultrasound J. 2011;3:109-10.
  11. Lichtenstein D. FALLS-protocol. In Whole Body Ultrasonography in the Critically Ill. Edited by. Heidelberg, Berlin, New York: Springer-Verlag; 2010.pp.223-41.
  12. Lichtenstein DA. Lung ultrasound in the critically ill. Lichtenstein Annals of Intensive Care. 2014;4:1.
  13. Lyon M, Blaivas M, Brannam L. Sonographic measurement of the inferior vena cava as a marker of blood loss. Am J Emerg Med. 2005;23:45-50.
  14. Mayo PH, Goltz HR, Tafreshi M, Doelken P. Safety of ultrasound-guided thoracentesis in patients receiving mechanical ventilation. Chest. 2004;125(3):1059-62.
  15. Miller RD. Miller's Anesthesia. 7th edition. Elsevier Publications; 2009.
  16. Miniati M, Monti S, Pratali L, et al. Value of transthoracic echocardiography in the diagnosis of pulmonary embolism: results of a prospective study in unselected patients. Am J Med. 2001;110(7):528-35.
  17. Salen P, Melniker L, Chooljian C, et al. Does the presence or absence of sonographically identified cardiac activity predict resuscitation outcomes of cardiac arrest patients? Am J Emerg Med. 2005;23:459-62.
  18. Slasky BS, Auerbach D, Skolnick ML. Value of portable real-time ultrasound in the intensive care unit. Crit Care Med. 1983;11:160-4.
  19. Vignon P, Chastagner C, Berkane V, Chardac E, Francois B, Normand S, Bonnivard M, Clavel M, Pichon N, Preux PM, Maubon A, Gastinne H. Quantitative assessment of pleural effusion in critically ill patients by means of ultrasonography. Crit Care Med. 2005;33:1757-63.
  20. Volpicelli G, El Barbary M, Blaivas M, Lichtenstein D, Mathis G, Kirkpatrick AW, Melniker L, Gargani L, Noble VE, Via G, Dean A, Tsung JW, Soldati G, Copetti R, Bouhemad B, Reissig A, Agricola E, Rouby JJ, Arbelot C, Liteplo A, Sargsyan A, Silva F, Hoppmann R, Breitkreutz R, Seibel A, Neri L, Storti E, Petrovic T. International evidence-based recommendations for point-of-care lung ultrasound. Intensive Care Med. 2012;38:577-91.
614Acid-base disorders
Chapter 85 Basics of Acid-Base Balance Sushma Vijay Pingale
Chapter 86 Metabolic and Respiratory Acid-Base Disorders Sushma Vijay Pingale
Chapter 87 Interpretation of Acid-Base Disorder Sushma Vijay Pingale615

BASICS OF ACID-BASE BALANCECHAPTER 85

Sushma Vijay Pingale
Acid-base disturbances are one of the most common disorders seen in the critically-ill patients. The normal blood pH is 7.35–7.45. Any value less than 7.35 is acidosis and more than 7.45 is alkalosis. Maintenance of blood pH at 7.40 is necessary to stabilize intracellular pH at 7.20, which is very important chemical condition for optimal cell physiology.
 
BASIC CONCEPTS AND TERMINOLOGIES
pH is defined in terms of [H+]. The hydrogen ion concentration [H+] in the extra-cellular fluid is calculated as
  [H+] nEq/L  = 24 × (PCO2/HCO3)
Normal arterial  PCO2  = 40
Therefore  [H+]  = 24 × 40/24
    = 40 nEq/L.
Since the [H+] ion concentration is measured in nEq which is very minute (nEq is one millionth of a mEq), the [H+] ion concentration is routinely expressed in terms of pH which is defined as the negative logarithm to the base 10 of the [H+] ion concentration in nEq/L. Thus, a normal [H+] of 40 nEq/L will correspond to a pH of 7.40.
  Normal arterial pH  = – log (40 × 109)
    = 7.40
An increase in [H+] concentration will decrease the pH and vice versa because the pH is negative logarithm of the [H+]. [H+] ion concentration between 16 and 160 nEq/L (i.e. pH of 6.8–7.8) is compatible with life.
An acid as defined by Arrhenius is a compound that contains hydrogen and reacts with water to form hydrogen ions. A strong acid is a substance that readily and almost irreversibly gives up an H+ and increases [H+] concentration.
Where Ka is a dissociation constant.
Strong acids have high dissociation constant.
A weak acid is a substance which reversibly donates H+ and tends to have less of an effect on [H+]. Biological compounds are either weak acids or weak bases.618
The negative logarithm of this equation is called as the Henderson-Hasselbalch equation.
  pH  = pka + log([A]/[HA])
Where pka is the negative logarithm of the dissociation constant pKa. Thus Henderson-Hasselbalch equation enables the calculation of pH.
Base is defined as a compound that produces hydroxide ions in water. A strong base avidly binds H+ and decreases [H+]. A weak base reversibly binds H+.
 
Actual Bicarbonate
Actual bicarbonate is the bicarbonate concentration in the plasma measured in mEq or mmoles/L. It is estimated from the carbon dioxide content of blood by the Van Slyke apparatus or from a nomogram by the Astrup technique. It cannot be estimated directly.
 
Standard Bicarbonate
Standard bicarbonate is the bicarbonate content in the plasma of blood which has been equilibrated at a PCO2 of 40 mm Hg as also with oxygen so as to saturate it with oxygen. It is the mobile, most active and rapidly reacting fraction of the total buffer potential. It is a measure of nonrespiratory bicarbonate and its rate of excretion and retention is governed by the kidneys. Normal standard bicarbonate denotes metabolic equilibrium. A decrease in standard bicarbonate indicates metabolic acidosis whereas an increase in its concentration indicates metabolic alkalosis.
 
Base Excess
Base excess is defined as the amount of strong acid or base that must be added for blood pH to return to 7.40 and PaCO2 to return to 40 mm Hg at full oxygen saturation and 37°C.
It defines the presence in blood of excess or deficit of base, and represents the metabolic component of an acid-base disturbance. It adjusts for non-carbonic buffering in the blood and requires measurement of hemoglobin concentration for its estimation. A positive base excess denotes metabolic alkalosis and a negative value indicates metabolic acidosis.
 
Indications for Arterial Blood Gas Analysis
The arterial blood gas analysis is one of the best tools to assess the disturbances in ventilatory and metabolic homeostasis. PaCO2 is the best index for assessment of alveolar ventilation and PaO2 is the best index for assessment of the oxygenation. The bicarbonate levels help in assessing the nature of the disturbance. Thus, the arterial blood gas analysis helps in assessing the alveolar ventilation, the 619oxygenation, the oxygen carrying capacity of the blood and the degree of compensation. Conditions such as shock, exacerbation of chronic obstructed pulmonary disease, diabetic ketoacidosis mandate arterial blood gas analysis, and hence the critical care guidelines mandate availability of 24 hours arterial blood gas analysis.
Arterial blood gas analysis also helps in assessing a patient's response to therapeutic intervention like ventilator management, weaning, etc. Some circulatory interventions can also be based on the arterial blood gas analysis. Lastly, the arterial blood gas analysis also enjoys a role preoperatively in assessing a patient for surgical evaluation, e.g. in the pulmonary resection.
Some arterial blood gas analyzers also provide information about the hemoglobin and serum electrolytes and this can be of great value in deciding the treatment in the critically ill patients especially when the laboratory data will take time.
 
Regulation of the Acid-Base Balance
The metabolic homeostasis is maintained by excreting all the acids produced by the body. These acids can be classified as respiratory (volatile) and metabolic (fixed) acids. Carbon dioxide is called as respiratory volatile acid because it can be excreted via the lungs. It is produced as an end product of complete oxidation of carbohydrate and fatty acids. Daily basal carbon dioxide production is estimated to be between 12000 and 13000 mmoles/day. It can be calculated as follows:
In a resting adult, oxygen consumption is 250 mL/minute and carbon dioxide production is 200 mL/minute (respiratory quotient: 0.8)
Daily CO2 production = 0.2 × 60 × 24 liter/day.
If we divide it by 22.4 liters/mole, we get 12857 mmoles/day.
An increase in the metabolic activity will increase the carbon dioxide production.
The fixed acids, also called as metabolic acids are produced due to incomplete metabolism of carbohydrate, fats (ketones) and protein (sulphate, phosphate) and are usually referred to by their anion (lactate, phosphate, sulphate, acetoacetate or beta-hydroxy butyrate). They are called fixed because they are not excreted by the lungs and they are referred to as anions inspite of being acids because the dissociation of the acid must have produced one hydrogen ion for every anion so the amount of anions present accurately reflects the number of hydrogen ions that must have been produced in the original dissociation. Daily production of hydrogen ions in an adult is approximately 70 to 100 mmoles/day, and it is excreted by the kidney. This excludes lactate since majority of lactate produced is metabolized and not excreted so there is no net lactate requiring excretion from the body. Buffering mechanisms is given in Table 85.1.
Table 85.1   Buffering mechanisms
The body defends itself against the acid-base perturbations by three compensatory mechanisms:
1. Chemical buffering (Immediate)
2. Respiratory compensation (whenever possible)
3. Renal compensation (Slower but effective)
620
 
Chemical Buffering
A buffer is a solution of two or more chemicals that minimizes changes in pH in response to the addition of an acid or base. Ideally, a buffer has a pka that is equal to the pH and an ideal body buffer should have a pka between 6.8 and 7.2.
Physiologically important buffers in human body are bicarbonate (H2CO3/HCO3), hemoglobin (HbH/Hb) other intracellular proteins, phosphates (H2PO4/HPO42) and ammonia (NH3+/NH4+). By far bicarbonate is the most important of all in the extracellular fluid compartment. Buffering by plasma bicarbonate is almost immediate whereas that due to interstitial bicarbonate requires 15–20 minutes. It is the most important extracellular fluid buffer for metabolic acids but not for respiratory acid-base disturbances and changes in bicarbonate concentration do not reflect the severity of respiratory acidosis.
  H2O + CO2  → H2CO3 → HCO3 + H+
When we look at this reaction from the angle of the role of bicarbonate as a buffer one can say that when H+ enters tissue fluids:
  H+ + HCO3  → H2CO3 → CO2 + H2O
The CO2 is rapidly washed out by lungs and thus a rapid control of H+ ion at the cost of depletion of [HCO3] is produced. The Henderson–Hasselbalch equation for the bicarbonate carbonic acid reaction illustrates the role played by this reaction in regulating acid-base balance.
  pH  = pk + log HCO3/H2CO3
    = 6.1 + log HCO3/H2CO3. pk for HCO3 is 6.1
    = 6.1 + log HCO3/0.03 × PCO2
0.03 is the solubility of CO2 in plasma and PCO2 the partial pressure of CO2 in plasma. If instead of pH one considers the H+ ion concentration, then a more simplified and practical derivation of the Henderson-Hasselbalch equation for the bicarbonate buffer is as follows:
  [H+]  = 24 × PCO2/ [HCO3]
Thus, substituting the normal values
  [H+]  = 24 × 40/24
    = 40 nmol/liter
Below 7.40, [H+] increases 1.25 nEq/L for each 0.01 decrease in pH, above 7.40, [H+] decreases 0.8 nEq/L for each 0.01 increase in pH.
 
Hemoglobin
Hemoglobin is the most important noncarbonic buffer in extracellular fluid. It is rich in histidine which is an effective buffer from pH 5.7 to 7.7 (pka 6.8). It is capable of buffering both carbonic (CO2) and noncarbonic (volatile) acids. This is in contrast to the bicarbonate buffer which is capable of buffering only the metabolic acids.
Deoxygenated hemoglobin is a strong base. The CO2, which easily crosses the erythrocyte membrane, combines with H2O in the erythrocyte under the 621influence of carbonic anhydrase to form H2CO3. This H2CO3 ionizes to H+ and HCO3. The hydrogen ions bind to the histidine residues on deoxyhemoglobin (Haldane effect) and HCO3– is actively pumped from cells. To maintain the electroneutrality, the chloride moves inward (Chloride shift). Thus, there would be huge increase in the pH of venous blood, if hemoglobin did not bind H+ ions produced by metabolism. Hemoglobin can also directly buffer CO2 by forming carbaminohemoglobin.
 
Respiratory Compensation
The respiratory compensation means the alterations that occur in the pH secondary to the changes in ventilation. These changes in alveolar ventilation are mediated by chemoreceptors within the brainstem which sense the changes in the pH of the cerebrospinal fluid. Every 1 mm Hg increase in PaCO2 increases the minute ventilation by 1–4 L/minute. A decrease in plasma bicarbonate concentration by 1 mEq/L triggers an increase in the alveolar ventilation and decrease in PaCO2 by 1–1.5 mm Hg below 40 mm Hg. On the contrary, an increase in arterial blood pH depresses the respiratory center. The resulting decrease in alveolar ventilation tends to elevate PaCO2 and restore arterial pH towards normal. But the response is less predictable in this case and if hypoxemia ensues due to the progressive hypoventilation then eventually the oxygen sensitive chemoreceptors are activated which stimulate ventilation and thus limit the pulmonary compensatory response.
For every 1 mEq/L increase in bicarbonate concentration the PaCO2 is found to be increased by 0.25–1 mm Hg.
 
Renal Compensation
Renal compensation begins to appear slowly in 6–12 hours and is fully developed over 2–3 days. The kidneys regulate plasma bicarbonate concentration through three main processes:
  1. Reabsorption of HCO3 when there is accumulation of H+ ions in the Blood: 80–90% of HCO3 is reabsorbed in the proximal tubule. The remainder is reabsorbed by the distal nephron which secretes H+ to defend systemic pH. This reabsorption of bicarbonate greatly depends on the PaCO2.
    In respiratory acidosis, the carbon dioxide (CO2) present in the renal tubular cells combines with water (H2O) in the presence of carbonic anhydrase to form carbonic acid (H2CO3). This H2CO3 dissociates rapidly into H+ and HCO3. The HCO3 ion enters the peritubular capillary and thus into the circulation. The H+ ion is secreted into the renal tubule where it reacts with the filtered HCO3 to form H2CO3. This H2CO3 again dissociates into H2O and CO2 in the presence of luminal carbonic anhydrase. The CO2 thus formed reenters the renal tubular cell to replace the CO2 which was consumed originally.
    ↑ PaCO2→↑ HCO3 reabsorption →↑ HCO3 levels.
    ↓ PaCO2 →↓ HCO3 reabsorption →↓ plasma HCO3 levels.
      In metabolic acidosis, chloride is preferentially excreted by the kidney and it reabsorbs HCO3 when there is accumulation of H+ ions in the blood along 622with excretion of titratable acid and NH4 to counter for the increase of H+ ions in the blood.
  2. Excretion of titratable acid and increased formation of ammonia:
    Once the filtered bicarbonate is reabsorbed completely, the H+ ion coming into the tubular lumen is buffered by HPO4 ion which combines with it and forms H2PO4 which is excreted in the urine. Once the phosphate buffer is also consumed, the ammonia produced during acidosis acts as the next important buffer. The ammonia which is formed in the mitochondria of proximal tubular cells by deamination of glutamine passively crosses the luminal membrane of the cell and enters the tubular fluid. Here it buffers the H+ by combining with it and forming NH4+ which is then excreted in the urine.
  3. Increased bicarbonate excretion in the urine when there is primary increase in plasma bicarbonate
 
BIBLIOGRAPHY
  1. Androgue HJ, Madias N. Management of life-threatening acid-base disorders. Part 2. N Engl J Med. 1998;338:107-11.
  2. Bear RA, Gribik M. Assessing acid-base imbalances through laboratory parameters. Hosp Practice; 1974. pp. 157.
  3. Figge J, Jabor A, Kazda A, Fencl V. Anion gap and hypoalbuminemia. Crit Care Med. 1998;26:1807-10.
  4. Ganang WF. Review of Medical Physiology, 21st edn. McGraw-Hill publications; 2003.
  5. Irwin RS, Rippe JM. Irwin and Rippe's Intensive Care Medicine, 6th edn. Lippincott Williams & Wilkins; 2008.
  6. Kraut JA, Madias NE. Approach to patients with acid-base disorders. Respir Care. 2001;46:392. [PMID: 11262558].
  7. Marino, Paul L. The ICU Book, 3rd edn. Lippincott Williams & Wilkins; 2007.
  8. Miller RD. Miller's Anesthesia, 7th edn. Elsevier Publications; 2009.
  9. Morgan GE Jr, Maged SM, Murray MJ. Clinical Anesthesiology, 5th edn. McGraw-Hill publications; 2007.
  10. Narins RG, Emmett M. Simple and mixed acid-base disorders: a practical approach. Medicine. 1980;59:161-87.
  11. Udwadia FE. Principles of Critical Care, 2nd edn. Oxford Publications.

METABOLIC AND RESPIRATORY ACID-BASE DISORDERSCHAPTER 86

Sushma Vijay Pingale  
METABOLIC ACIDOSIS (TABLE 86.1)
When the acidosis is due to a decrease in bicarbonate, it is called as metabolic acidosis. Metabolic acidosis is divided into two groups:
  1. Normal anion gap metabolic acidosis
  2. High anion gap metabolic acidosis.
 
Normal Anion Gap Acidosis
The anion gap is nothing but the difference between the measured cations (Na+) and the measured anions (Cl and HCO3)
Table 86.1   Causes of metabolic acidosis
High anion gap
Overproduction of acid
Exogenous acid
Reduced excretion
Diabetic ketoacidosis
Lactic acidosis type A (Hypoxia, Shock) or Type B (Biguanides)
Starvation
Salicylates
Methanol
Ethylene glycol
Renal failure
Normal anion gap
Bicarbonate loss
Addition of acid
(with chloride)
Extrarenal
Diarrhea
Biliary/Pancreatic fistula
Ileostomy
Ureterosigmoidostomy
Renal
Renal tubular acidosis
Carbonic anhydrase inhibitors
HCL, NH4CL,
Arginine or lysine hydrochloride
624
Anion gap = Na+ – (Cl + HCO3)
Therefore Na+ + unmeasured cations = (Cl + HCO3) + unmeasured anions
Therefore, Na+ – (Cl + HCO3) = unmeasured anions – unmeasured cations
The basis of the anion gap is that the concentration of positively charged cations should equal the concentration of negatively charged anions in order to maintain the electrochemical balance.
The unmeasured anions are proteins, organic acids, phosphates and sulphates. The unmeasured cations are potassium (K+), calcium (Ca2+) and magnesium (Mg++). Thus, the anion gap is an estimate of the relative increase in the number of unmeasured anions and helps in determining whether the metabolic acidosis is due to accumulation of nonvolatile acids (e.g. lactic acid) or a net loss of bicarbonate (e.g. diarrhea).
The normal value of the anion gap is 7 ± 4 mEq/L (range is 3 to 11 mEq/L) in accordance with the newer automated systems which measure the serum electrolytes more accurately.
Metabolic acidosis with a normal anion gap is also called as hyperchloremic acidosis. The loss of bicarbonate in the metabolic acidosis which can be either via stools or intestinal fistulas results in replacement of chloride for the lost bicarbonate to preserve electroneutrality. This replacement of bicarbonate by chloride causes a hyperchloremic acidosis.
The interpretation of the anion gap is altered in presence of hypoalbuminemia. Serum albumin constitutes about half of the unmeasured anion pool. Hence, a decrease in albumin by 50% in absence of any derangement in serum electrolytes and bicarbonate will decrease the anion gap by 5-6 mEq/L. Thus, the anion gap has to be adjusted in hypoalbuminemic patients. This can be calculated as:
Adjusted anion gap = Observed anion gap + 2.5 × [4.5 – measured albumin (g/dL)]
4.5 is the normal albumin concentration in g/dL.
 
High Anion Gap Acidosis
High anion gap is caused due to the addition of a fixed acid into the extracellular space. The acid dissociates to produce H+ ions and anions. The hydrogen ions are neutralized by combining with HCO3 ions to form carbonic acid. The ensuing increase in the unmeasured anions increases the anion gap. Thus, as the bicarbonate decreases the anion gap increases as can be seen from the equation:
Anion gap  =  Na – (Cl + HCO3)
The causes of high anion gap acidosis are given in Table 86.1. Some conditions like diabetic ketoacidosis are associated with a high anion gap as well as normal anion gap metabolic acidosis. The identification of the normal anion gap acidosis can be made by comparing the change in anion gap to the change in the plasma bicarbonate concentration. This is called as the delta gap.
Delta gap = Change in anion gap – change in bicarbonate
If the delta gap is significantly positive (> +6), a metabolic alkalosis is usually present because the rise in anion gap is more than the fall in bicarbonate concentration. On the contrary, a significantly negative delta gap value (<–6) 625suggests hyperchloremic acidosis because the rise in anion gap is less than the fall in bicarbonate.
This ratio is also called as the gap-gap. In the presence of a high anion gap metabolic acidosis, a gap ratio of <1 indicates that a normal anion gap metabolic acidosis coexists. Whereas a gap ratio of >1 indicates that a metabolic alkalosis coexists.
 
Compensation for Metabolic Acidosis
The primary change in metabolic acidosis is a decrease in bicarbonate and increase in H+. Therefore, the pH decreases which stimulates the respiratory center in the brainstem causing a fall in PaCO2 which is given by the formula:
  Expected PaCO2  =  [1.5 × HCO3] + 8
Range of ± 2
 
Clinical Features of Metabolic Acidosis
Acidosis is associated with alterations in transcellular ion pumps and increased ionized calcium. These changes are particularly detrimental to the cardiovascular system and result in vasodilation and diminished muscular performance (particularly myocardial), and arrhythmias as the pH decreases to <7.2. The oxyhemoglobin dissociation curve shifts rightward to increase the oxygen delivery to the tissues. Rapid-onset metabolic acidosis may be associated with profound hypotension, cardiac arrhythmias, and death.
The breathing is a typical Kussmaul's breathing in which there is an increase in tidal volume instead of respiratory rate. The manifestation of acidosis in various organs is given Table 86.2.
Table 86.2   Manifestations of metabolic acidosis on various systems
Central nervous system
  • Obtundation
  • Coma
Respiratory system
  • Respiratory muscle fatigue
  • Hyperventilation
  • Breathlessness
Cardiovascular system
  • ↓ CO, blood pressure, response to catecholamines
  • ↑ potential for ventricular fibrillation
  • Cardiac arrhythmias
  • Impaired myocardial contractility
Metabolism
  • Hyperkalemia
  • Insulin resistance
626
 
Management of Metabolic Acidosis
The management of metabolic acidosis mainly consists of treatment of the cause and supporting the circulation and breathing, if it is severely compromised. Whenever a respiratory acidosis coexists, then it is important to first correct the respiratory acidosis.
  • In diabetic ketoacidosis, the management of the acidosis is focused on correction of the hyperglycemia and volume depletion by giving insulin and IV fluids. Infection, if any present should be treated by starting antibiotics. The detailed management of DKA is discussed in detail under chapter 57.
  • Lactic acidosis: The normal lactate levels are ≤2 mEq/L. While treating lactic acidosis one needs to keep in mind the causes of increased lactic acid e.g. shock, hypoxia especially when associated with a low cardiac output, severe uncorrected anemia (Hb <5 g/dL) which is not compensated for by a hyperdynamic circulation, marked liver cell dysfunction, thiamine deficiency, D lactic acid acidosis (which is seen following small bowel resection or jejunoileostomy) and usage of drugs like epinephrine or sodium nitroprusside. The major crux of the treatment should be to improve tissue perfusion first and then treat the cause.
    The use of sodium bicarbonate is restricted nowadays to correct a pH of 7.25 or less and when bicarbonate is <10 mmol/L. The formula for calculation of sodium bicarbonate dose for severe lactic acidosis is:
    NaHCO3 = 0.3 × body weight × base deficit
    One half of the calculated amount is given as an intravenous bolus and the remaining deficit is corrected over next 4–6 hours.
    The problem with sodium bicarbonate treatment is the production of undesirable effects which include hyperosmolarity, fluid overload, hypokalemia, hypocalcemia and increased serum lactate levels. Hence, it should be avoided in lactic acidosis. The standard sodium bicarbonate solutions contain a PCO2 of 200 mm Hg which can produce increased CO2 load in patients with respiratory acidosis. Carbicarb is an alternative buffer solution which contains sodium bicarbonate and disodium carbonate in equal proportion. It has a PCO2 of 3 mm Hg which is much lower than the standard bicarbonate solution.
  • Alcoholic ketoacidosis: The treatment consists of infusion of dextrose containing solutions. The glucose helps retard hepatic ketone production, while the infused volume promotes the renal clearance of ketones.
  • Ethylene glycol poisoning: Inhibition of alcoholic dehydrogenase by using fomepizole is recommended. The dose of Fomepizole is 15 mg/kg IV as an initial dose, then 10 mg/kg every 12 hours for 48 hours, then 15 mg/kg every 12 hours until the plasma ethylene glycol level is 25 mEq/L or lower.
 
Metabolic Alkalosis
Metabolic alkalosis is defined as a primary increase in plasma [HCO3]. It is classified as chloride sensitive and chloride resistant metabolic alkalosis. Causes of metabolic alkalosis are given in Table 86.3.627
Table 86.3   Causes of metabolic alkalosis
Chloride-responsive (urine chloride <20 mmol/L)
Loss of acid
Gastrocolic fistula
Chloride depletion
Excessive alkali
Chloride-resistant (urine chloride >20 mmol/L)
  • Primary or secondary hyperaldosteronism
  • Cushing's syndrome
  • Severe hypokalemia
  • Carbenoxolone
 
Chloride Sensitive Metabolic Alkalosis
The basic cause for this type of alkalosis is depletion of extracellular volume and chloride. The common causes are vomiting, nasogastric suction and diuretic use. In vomiting or nasogastric suction about 50–100 mEq/L of H+ ions present in the gastric juice are lost along with water, Cl, Na+ and K+. Loop diuretics inhibit Na+K+2Cl symport whereas thiazides inhibit Na+Cl symport. Thus, Cl and K+ are lost via the urine along with Na+ and water. The Cl that is not reabsorbed is replaced by bicarbonate. This enhanced bicarbonate reabsorption leads to or maintains the alkalosis. The increased loss of K+ in the urine leads to an increase in H+ ion secretion into the distal tubules in an attempt to reabsorb K+ at the cost of H+. Mg2+ is also lost in the urine during diuresis and this further enhances K+ loss. The ensuing volume depletion stimulates aldosterone release which in turn stimulates H+ and K+ secretion in order to retain Na+ and further exaggerates the alkalosis. The urinary Cl concentration in a chloride sensitive metabolic alkalosis is low (<15 mEq/L).
 
Chloride-resistant Metabolic Alkalosis
The genesis of chloride-resistant metabolic alkalosis is due to an increased mineralocorticoid activity or severe potassium depletion. The Na+ H+ K+ transport system in the distal tubules is responsive to aldosterone, which promotes the reabsorption of Na+ and the secretion of H+ and K+. This type of metabolic alkalosis is usually associated with volume expansion rather than volume depletion. Urinary chloride concentration is >25 mEq/L.
 
Compensation for Metabolic Alkalosis
The compensatory response for metabolic alkalosis is an increase in the PaCO2. But this is limited by the hypoxemia which ensues due to hypoventilation (in order to raise the PaCO2). The expected increase in PaCO2 is given by the formula:628
Table 86.4   Manifestations of metabolic alkalosis on various systems
Central nervous system
Respiratory system
  • Arterial hypoxemia
  • Hypoventilation
  • ↑PaCO2
Cardiovascular system
  • ↓Coronary perfusion
  • Arterial vasoconstriction
  • Potential for cardiac arrhythmias
Metabolism
↓K+, Ca+, PO4, Mg2+
PaCO2  =  (0.7 × HCO3) + 20
Range ± 2.
 
Clinical Features of Metabolic Alkalosis
Metabolic alkalosis is silent most of the times. Severe alkalosis (pH >7.6) can result in seizures, mental obtundation, cardiac dysfunction, arrhythmias and hypoventilation. The oxygen dissociation curve is shifted to the left causing a decrease in oxygen delivery to the tissues. The manifestations of metabolic alkalosis in various organs are given in Table 86.4.
 
Treatment of Metabolic Alkalosis
Most common type of metabolic alkalosis in the critically ill patients in the ICU is the chloride sensitive one and hence infusion of normal saline to correct the volume and chloride deficit is the mainstay of treatment.
The volume of isotonic saline (0.9%) needed can be determined by estimating the chloride (Cl) deficit, as shown here:
Chloride deficit (mEq) = 0.2 × weight (kg) × (normal Cl – Actual Cl)
The factor 0.2 represents the extracellular volume as a fraction of body weight.
Volume of saline to be infused = Chloride deficit/154
154 is the mEq of chloride present in 1L of normal saline. The hypokalemia should be corrected by infusion of potassium chloride (20–40 mEq in dextrose). Hypokalemia, if left uncorrected can perpetuate the alkalosis. Magnesium deficiency, if present should also be corrected.
The aim of treatment in the chloride resistant metabolic alkalosis is to treat the underlying cause of mineralocorticoid excess and correct the K+ deficit. It responds to drugs such as acetazolamide which blocks HCO3 reabsorption in the kidneys by inhibiting the carbonic anhydrase enzyme. The dose is 5–10 mg/kg IV. 629
 
Use of Hydrochloric Acid in Metabolic Alkalosis
This is reserved for patients with severe alkalemia (pH >7.5) when other treatment fails.
H+ deficit (mEq) = 0.5 × weight (kg) × (actual HCO3 – desired HCO3)
Volume (L) of 0.1NHCl = H+ deficit/100
Volume (L) of 0.25 NHCl = H+ deficit/250
Infusion rate = 0.2 mEq/kg/hour.
0.1 NH4Cl which contains 100 mEq of H+ per liter is the best option and is given through a central line. Ammonium chloride and arginine chloride can also be given but are less safe. Extravasation can cause tissue necrosis.
 
Respiratory Acidosis
Respiratory acidosis is defined as an acidosis associated with and caused by an elevation of the PaCO2 (Table 86.5). The causes, types and clinical features and treatment of respiratory acidosis are discussed in detail in the chapter on respiratory failure.
The compensatory response to acute (6–12 hour) elevations in PaCO2 is limited and is primarily provided by hemoglobin and the exchange of extracellular H+ for Na+ and K+ from bone and the intracellular fluid compartment. As such the bicarbonate response is very limited in the acute respiratory acidosis being just an increase of 1 mEq/L for 10 mm Hg increase in PaCO2 above 40 mm Hg. If a respiratory alteration persists, however, renal mechanisms increase or decrease serum HCO3 in a direction that pushes the H+ back toward normal.
After the renal compensation sets in, the compensatory increase in bicarbonate for the chronic respiratory acidosis is 4 mEq/L mm Hg per 10 mm Hg increase in PaCO2 above 40 mm Hg.
Thus, after renal compensation occurs, the ΔH+/ΔPCO2 ratio is also altered. The ΔH+/ΔPCO2 is calculated as the change in H+ from baseline (i.e. 40 nanoequivalents/liter) divided by the change in PaCO2 from baseline (i.e. 40 mm Hg). This alteration represents the chronic state. A ratio of 0.8 implies an acute respiratory acidosis. A ratio of 0.3 implies a chronic (and compensated) respiratory acidosis. The ΔH+/ΔPCO2 ratio between 0.3 and 0.8 corresponds to an acute-on-chronic respiratory acidosis (as often occurs with an exacerbation of chronic obstructive pulmonary disease).
Table 86.5   Causes of respiratory acidosis
  • Drug-induced respiratory depression
  • Status asthmaticus
  • Upper airway obstruction
  • Restriction of ventilation (rib fractures/flail chest)
  • Disorders of neuromuscular function—GBS, myasthenia gravis
  • Permissive hypercapnia
  • Malignant hyperthermia
630
Table 86.6   Causes of respiratory alkalosis
  • Iatrogenic (mechanical hyperventilation)
  • Arterial hypoxemia causing hyperventilation
  • Central nervous system injury
  • Liver disease
  • Pregnancy
  • Aspirin overdose
 
Management
Respiratory acidosis is treated by correcting the condition responsible for hypoventilation and mechanical ventilation may be needed when there is marked increase in PaCO2. Rapid reduction of chronically increased PaCO2 levels by mechanical ventilation reduces the CO2 stores more than the decrease in HCO3 concentration thus producing metabolic alkalosis. Hence, it is better to reduce PaCO2 slowly to permit sufficient time for renal tubular elimination of bicarbonate.
 
Respiratory Alkalosis
Respiratory alkalosis is defined as an alkalosis caused by a primary decrease in PaCO2 (Table 86.6). The main cause for respiratory alkalosis is hyperventilation which results in the washout of carbon dioxide. The causes are described in the chapter on respiratory failure.
The compensation for acute decrease in PaCO2 is a decrease in Plasma [HCO3] by 2 mEq/L for each 10 mm Hg acute decrease in PaCO2 below 40 mm Hg. The distinction between acute and chronic respiratory alkalosis is not always made, because the compensatory response to chronic respiratory alkalosis is quite variable: plasma [HCO3] generally decreases by 4 mEq/L for each 10 mm Hg decrease in PaCO2 below 40 mm Hg.
 
BIBLIOGRAPHY
  1. Androgue HJ, Madias N. Management of life-threatening acid-base disorders. Part 2. N Engl J Med. 1998;338:107-11.
  2. Bear RA, Gribik M. Assessing acid-base imbalances through laboratory parameters. Hosp Practice; 1974. p. 157.
  3. Figge J, Jabor A, Kazda A, Fencl V. Anion gap and hypoalbuminemia. Crit Care Med. 1998;26:1807-10.
  4. Ganong WF. Review of Medical Physiology, 21st edn. 2003. McGraw-Hill publications.
  5. Butterworth IV JF, Mackey DC, Wasnick JD. Morgan & Mikhail's Clinical Anesthesiology, 5th edn. McGraw-Hill publications; 2007.
  6. Irwin RS, Rippe JM Irwin and Rippe's. Intensive Care Medicine, 6th edn. Lippincott Williams & Wilkins; 2008.
  7. Kraut JA, Madias NE. Approach to patients with acid–base disorders. Respir Care. 2001;46:392. [PMID: 11262558].
  8. Narins RG, Emmett M. Simple and mixed acid-base disorders: a practical approach. Medicine (Baltimore). 1980;59(3):161-87.
  9. Paul ML. The ICU Book, 3rd edn. Lippincott Williams & Wilkins; 2007.
  10. Ronald D Miller. Miller's Anesthesia, 7th ed. Elsevier Publications; 2009.
  11. Udwadia FE. Principles of critical care, 2nd ed. Oxford Publications.

INTERPRETATION OF ACID-BASE DISORDERCHAPTER 87

Sushma Vijay Pingale
The acid-base disorders can be classified as acidosis and alkalosis. Acidosis is an abnormal state leading to an increase in the acid in the body. Acidemia is a condition where the pH of the arterial blood falls below 7.35. The alkalosis is an abnormal state leading to a fall in acid or an increase in the alkali in the body. Alkalemia is a condition where the pH of the arterial blood is above 7.45.
Both acidosis and alkalosis can further be divided into respiratory and metabolic depending on the etiology. As we have already seen:
[H+] (nEq/L) = 24 × PCO2/HCO3
Thus, to keep the pH within the normal limits, the PCO2/HCO3 ratio has to be kept constant. Therefore, if there is an increase in PCO2 as in respiratory acidosis, then it should be accompanied by a compensatory increase in HCO3 so that the pH remains constant. Similarly if there is a change in HCO3 as in the metabolic disorders, then the PCO2 also should change in the same direction as the bicarbonate. The initial change in the PCO2 or HCO3 is termed as the primary acid-base disorder and the change that follows the primary disorder in an effort to neutralize the pH is called as the compensatory change.
One needs to keep in mind that the compensatory changes do not correct the acid-base disturbances (Table 87.1). They only limit the change in the pH caused by the primary disorder. If the compensatory change is more or less than expected, then by definition a mixed acid-base disorder exists.
 
STEPWISE APPROACH FOR INTERPRETATION OF ABG
 
ARTERIAL BLOOD GAS EXERCISES
  1. A 40-year-old moderately dehydrated man was admitted with 3 days history of acute severe diarrhea.
    Electrolyte results (in mmol/L): Na+ 136, K+ 3.0, Cl 110, HCO3 15, Anion gap 11.
    pH 7.31
    pCO2 32 mm Hg
    pO2 90 mm Hg
    HCO3 15 mmol/L
633
 
Interpretation
  • Step 1: pH is 7.31, so it is acidemia.
  • Step 2: The PaCO2 is 32, i.e. it has decreased (normal-40 mm Hg). This is not consistent with the change in pH because if the pH is acidotic, then the PCO2 should increase to call it as a respiratory acidosis.
  • Step 3: The HCO3 is 15, i.e. it has decreased (normal-24 mm Hg). This is consistent with the change in pH as it suggests a metabolic component to the acidosis.
  • Step 4: Thus, the primary diagnosis is metabolic acidosis.
  • Step 5: As per the Table 87.1 in case of metabolic acidosis, the PaCO2 should also decrease as a compensatory response to the decrease in HCO3 and it is given by the formula:
    Expected PaCO2  =  (1.5 × HCO3) + 8
    =  (1.5 × 15) + 8
    =  30.5
    The actual value of PaCO2 given is 32 which is close to (±2). Hence, the compensation is adequate.
  • Step 6: Since this is metabolic acidosis, we need to calculate the anion gap to find out whether it is high or normal anion gap acidosis.
    Anion gap  =  Na+ – (Cl + HCO3)
    =  136 – (110 + 15)
    =  11.
 
ABG Diagnosis = Normal Anion Gap Metabolic Acidosis
2.  A 50-year-old male patient with chronic renal failure was on treatment with tablet furosemide for the past 3 years. Now the patient presents to the emergency room with profound weakness and areflexia. His oral intake had been poor for a few days.
Her Sr electrolytes Na+ 145, K+ 3.5, Cl 86, bicarbonate 45
pH = 7.58
pCO2 = 49 mm Hg
pO2 = 85 mm Hg
HCO3 44 mmol/L
Urinary chloride = 10 mEq/L
 
Interpretation
  • Step 1: pH is 7.58 so it is alkalemia.
  • Step 2: PaCO2 is 49, i.e. it has increased. This is not consistent with the change in pH because the PaCO2 should be decreased to call it alkalosis due to a respiratory cause.
  • Step 3: The HCO3 is 44, i.e. it has increased. This is consistent with the change in pH and suggests a metabolic cause for the alkalemia.
  • Step 4: Thus, the primary diagnosis is metabolic alkalosis.
  • Step 5: In metabolic alkalosis, the compensatory change should be an increase in HCO3 and this is given by the formula:
    Expected PaCO2 = (0.7 × HCO3) + 20
    634=  (0.7 × 44) + 20
    =  50.8
    The actual value of PaCO2 is 49 which is close to the expected PaCO2 and hence the compensation is adequate.
  • Step 6: Urinary chloride is 10 mEq/L, so this is chloride sensitive metabolic alkalosis.
 
ABG Diagnosis = Chloride Sensitive Metabolic Alkalosis
3.  A healthy 30-year-old woman undergoes elective lap appendicectomy under general anesthesia. She has no significant past medical history. Preoperative urea and electrolytes were all within the reference range.
pH = 7.20
pCO2 = 70 mm Hg
pO2 = 75 mm Hg
HCO3 = 27 mmol/L.
 
Interpretation
  • Step 1: pH is 7.20 so it is acidemia.
  • Step 2: The PaCO2 is 70, i.e. it has increased. This is consistent with the change in pH because if the pH is acidotic, then the PCO2 should increase to call it as a respiratory acidosis.
  • Step 3: The HCO3 is 27, i.e. it has increased.
  • Step 4: Thus, the primary diagnosis is acute respiratory acidosis.
  • Step 5: As per Table 87.1 in case of acute respiratory acidosis, the HCO3 should also increase as a compensatory response to the increase in PaCO2 and it is given by the formula:
    Expected HCO3 = 1 mEq/L for every 10 mm Hg increase in PaCO2 above 40 mm Hg.
    The expected HCO3 for 70 mm Hg of PaCO2 will be 24 + 3 = 27 mm Hg. Hence, it is adequate (actual HCO3 = 27 mEq/L).
 
ABG Diagnosis = Acute Respiratory Acidosis with Fully Compensated Metabolic Alkalosis
4. A 10-year-old malnourished boy presents with a one-day history of productive cough, fever and increasing dyspnea. In the ER, the chest X-ray shows hilar opacities. His oxygen saturation is 85% on room air.
An arterial blood gas is obtained and it reveals a
  • pH–7.55
  • PCO2–30
  • PO2–60
  • HCO3–22
635
 
Interpretation
  • Step 1: pH is 7.55 so it is alkalemia.
  • Step 2: The PaCO2 is 30, i.e. it has decreased. This is consistent with the change in pH because if the pH is alkalotic, then the PaCO2 should decrease to call it as a respiratory alkalosis.
  • Step 3: The HCO3 is 22, i.e. it has decreased.
  • Step 4: Thus the primary diagnosis is acute respiratory alkalosis.
  • Step 5: As per the Table 87.2 in case of acute respiratory alkalosis the HCO3 should also decrease as a compensatory response to the decrease in PaCO2 and it is given by the formula:
    Expected HCO3 = 2 mEq/L for every 10 mm Hg decrease in PaCO2 below 40 mm Hg.
    The expected HCO3 for 30 mm Hg of PaCO2 will be 24 – 2 = 22 mm Hg. Hence, it is adequate (actual HCO3 – 22 mEq/L).
 
ABG Diagnosis = Acute Respiratory Alkalosis with Fully Compensated Metabolic Acidosis
5.  A 50-year-old man with COPD presented with dyspnea, fever. He was on a thiazide diuretic for 10 months following a previous admission with congestive cardiac failure.
Arterial blood results:
pH   7.4
pCO2   50 mm Hg
pO2   75 mm Hg
HCO3   32 mmol/L
K+   2.5 mmol/L
 
Interpretation
  • Step 1: The pH is 7.4 so it is normal but looking at the clinical scenario, one should keep a suspicion of an acid-base disturbance in this patient.
  • Step 2: The PaCO2 is 50, i.e. it has increased suggesting respiratory acidosis. This is expected since the patient is having COPD.
  • Step 3: The HCO3 is 32, i.e. it has increased suggesting metabolic alkalosis.
  • Step 4: Thus in any acid-base disturbance, the pH can approach the normal value but not the median value of 7.4, it that occurs, it indicates the presence of a 2 primary acid-base disorders. Hence, the diagnosis is respiratory acidosis with acute exacerbation along with metabolic alkalosis.
  • Step 5: Respiratory acidosis with a pCO2 of 50 mm Hg would predict a [HCO3] of about 28 mmol/L at maximal compensation. The actual value is much higher than this so a metabolic alkalosis must also be present indicating a mixed acid-base disorder.
 
ABG Diagnosis = Mixed Respiratory Acidosis and Metabolic Alkalosis
636
 
BIBLIOGRAPHY
  1. Androgue HJ, Madias N. Management of life-threatening acid-base disorders. Part 2. N Engl J Med. 1998;338:107-11.
  2. Bear, RA, Gribik, M. Assessing acid-base imbalances through laboratory parameters. Hospital Practice. 1974;9:157
  3. Figge J, Jabor A, Kazda A, Fencl V. Anion gap and hypoalbuminemia. Crit Care Med. 1998;26:1807-10.
  4. Ganong WF. Review of Medical Physiology. 21st edn. McGraw-Hill publications; 2003.
  5. Irwin RS, Rippe JM. Irwin and Rippe's Intensive Care Medicine, 6th Edn Lippincott Williams & Wilkins, 2008.
  6. Kraut JA, Madias NE. Approach to patients with acid–base disorders. Respir Care. 2001;46:392. [PMID: 11262558].
  7. Miller RD. Miller's Anesthesia, 7th edn. Elsevier Publications; 2009.
  8. Morgan GE, Jr, MS Mikhail, Murray MJ. Clinical Anesthesiology, 5th edn. McGraw-Hill publications; 2007.
  9. Narins RG, Emmett M. Simple and mixed acid-base disorders: a practical approach. Medicine. 1980;59:161-87.
  10. Paul ML. The ICU Book, 3rd edn. Lippincott Williams & Wilkins; 2007.
  11. Udwadia FE. Principles of Critical Care, 2nd edn. Oxford Publications.
637Nutritional support
Chapter 88 Nutrition and Metabolism in Critically Ill Patients Sushma Vijay Pingale
Chapter 89 Enteral and Parenteral Nutrition Sushma Vijay Pingale638

NUTRITION AND METABOLISM IN CRITICALLY ILL PATIENTSCHAPTER 88

Sushma Vijay Pingale
Good nutrition is an important prerequisite for a healthy body and more so for a body that is fighting a critical illness. The principles of management of nutrition in the critically ill patients have undergone a sea change over a period of time as mankind has explored the various biochemical and pathophysiological changes that take place in the human body in an illness. In order to manage the nutrition of patients in the intensive care unit, one needs to first understand these biochemical and pathophysiological changes that occur during a disease.
 
PATHOPHYSIOLOGY OF NUTRITION IN ILLNESS
Human body, when normal, has a perfect balance of anabolism and catabolism depending on the food intake. Stress in any form, i.e. surgery, trauma or infection disrupts this balance and results in an increase in the catabolic response also called as “autocannibalism”. The extent and duration of this catabolic response is largely determined by the magnitude of the injury. This stress response basically comprises the release of several catecholamines and catabolic hormones like glucagon, growth hormone and cortisol. These hormones act synergistically and promote increased glucose production via the gluconeogenesis. The main substrates for gluconeogenesis are glycerol (from lipolysis), alanine (from proteolysis) and lactate (from wound). These changes are associated with a decrease in insulin sensitivity, which in turn, is the result of decreased phosphorylation of the insulin receptor and second messenger. This post-receptor defect hinders cellular glucose uptake. The unremitting gluconeogenesis causes hyperglycemia which despite an increase in insulin level, does not help in providing the glucose to the cells. The cytokines interleukin -1(IL-1), interleukin -6, (IL-6) and tumor necrosis factor (TNF) may directly or indirectly enhance these hyperglycemic responses.
The insulin levels in the serum are normal or elevated but cannot prevent the ensuing hyperglycemia because the ability to decrease blood glucose concentration per insulin concentration is markedly diminished. This large amount of glucose is then presented to noninsulin-mediated glucose uptake pathway because of which the overall uptake of glucose is maintained. This 640hyperglycemia also ensures a steady supply of glucose to cells like the immune cells and the wound inflammatory cells which are predominantly glucose dependent.
Thus, the limited uptake of glucose in cells due to insulin resistance causes a decrease in glucose oxidation pathway and an increase in lipid oxidation pathway and breakdown of proteins mainly the skeletal proteins. There is increased synthesis of acute phase proteins in stress occurring simultaneously with decrease in the synthesis of binding proteins like albumin, transthyretin, retinol-binding protein and transferrin. The decrease in concentration of these binding proteins increases the plasma concentration of free hormones like the cortisol and thus the vicious cycle of autocannibalism continues.
 
NUTRITIONAL ASSESSMENT
The aim of nutritional assessment is to identify the type and degree of malnutrition and direct the treatment towards correcting it. The nutritional assessment in the critically ill patients in the intensive care unit can be done based on the following:
  • Patient's history
  • Clinical examination
  • Anthropometric measurements
  • Laboratory data.
 
History
The history taking should include asking about the patient's nutritional intake before becoming ill because studies have found that a history of weight loss of 10% over the previous 12 months is an indicator of protein-calorie malnutrition resulting mainly due to inadequate caloric intake. Weight loss of 20–30% suggests moderate protein calorie malnutrition and weight loss of more than 30% suggests severe calorie malnutrition. A history relating to the medical and surgical illnesses with specific reference to conditions which could impair ingestion, digestion or absorption of nutrients should be sought.
 
Clinical Examination
Physical examination should include observation of the general appearance of the patient with emphasis on evidence of temporal, upper body and upper extremity wasting of skeletal muscle mass.
 
Anthropometric Measurements
The anthropometric parameters which should be measured include the height and the body weight. However, the weight may be a misleading factor in the critically ill patients because it is often related to alterations in the hydration status of the patient. The other indices are measurements of triceps skin-fold thickness and mid-arm muscle circumference which are found to be reasonably accurate even in the presence of edema since the excess of body water accumulates to a lesser extent in the upper extremity.641
 
Laboratory Examination
The laboratory data needed to assess nutrition includes complete blood count to know the hematopoietic function, the renal function tests, the liver function tests and serum electrolytes. Apart from these, the investigations which need to be done are the total serum proteins, serum albumin levels, serum transferrin, thyroxine-binding prealbumin, retinol-binding protein, fibronectin and the 24 hours urinary urea nitrogen excretion and determination of nitrogen balance.
The half-life of serum albumin is 20 days. The serum albumin levels, following nutritional repletion may not rise significantly before 4–5 weeks. Moreover, the serum albumin levels may fall after rapid intravenous fluid infusion, after decreased synthesis due to liver dysfunction or due to increased loss through big wounds, burns or renal dysfunction. Hence, it is not an ideal marker to reflect acute responses to nutritional therapy. It can be used as a good prognostic marker of a patient's chronic nutritional state.
The 24 hours urinary urea nitrogen excretion evaluates the somatic protein breakdown. Two thirds of the N2 derived from this protein breakdown is excreted in the urine. Protein is 16% nitrogen hence each gram of urinary nitrogen represents 6.25 grams of degraded protein.
Thus, the total body nitrogen balance can be calculated as follows:
The factor 4 represents the daily nitrogen loss (in grams) in feces and other losses. The goal of nitrogen balance is to maintain a positive balance of 4–6 grams. The above equation holds true as long as the major source of nitrogen loss is urine. In patients on enteral feeds having diarrhea or extensive weeping wounds or in renal insufficiency, this equation may not give a correct estimate. Improvement in nitrogen balance suggests that nutritional support is adequate or the catabolism has decreased.
 
Nutritional Requirements
The aims of calculating the nutritional requirement and support are:
  • To provide enough energy to promote anabolic functions and at the same time avoid any caloric overload.
  • To prevent oxidative cellular injury.
  • To favorably modulate the immune response.
The basic principle in treating any underlying protein malnutrition also is to give caloric food first and treatment of stresses that lead to the severe autocannibalism. In general, most patients do well with a caloric support of 25 kcal/kg ideal body weight per day. The patients with renal failure, liver failure, congestive cardiac failure, burns, etc. need specific requirements and are discussed later in the chapter. The ASPEN (American Society of Parenteral and Enteral Nutrition) guidelines suggest that if the patient is obese, then the adjusted body weight should be used in the calculation.
642The human body derives its energy from combustion of the three carbon-based organic fuels namely carbohydrate, proteins and lipids. The energy yield per gram of lipid is 9 kcal/g, per gram of protein is 4 kcal/g and per gram of glucose is 3.7 kcal/g. The body's energy expenditure, the total body oxygen consumption (VO2) and the carbon dioxide production (VCO2) are the summation of the combustion of these three substrates.
The respiratory quotient (RQ) is the ratio of VCO2 to VO2.
RQ = VCO2/VO2
The daily energy expenditure can be calculated by two ways:
  1. Harris–Benedict equation
  2. Indirect calorimetry.
 
Harris–Benedict Equation
The daily or the basal energy expenditure (BEE) is the heat production of basal metabolism in the resting and fasted state. The resting energy expenditure (REE) is the heat production of basal metabolism in the resting state. It is equivalent to BEE plus the thermal effect of food.
The Harris–Benedict (HB) equation determines the BEE based on sex, body weight (kg) and height (cm) (Table 88.1).
These are the calculations for healthy adults. Stress and illness increase the catabolism and hence the caloric requirement increases. The Calvin long's stress factors are hence applied to these equations to take into account the increased caloric requirement due to the catabolism.
Studies which have compared the predicted and actual energy expenditure in critically ill patients have shown that the predictive equations with the multiplication factor for the degree of stress overestimate daily energy needs by 20–60% (Table 88.2).
Table 88.1   Harris–Benedict equation
Men
BEE (kcal/24 hr) = 66.5 + (13.7 × weight) + (5 × height) – (6.8 × age)
Women
BEE (kcal/24 hr) = 66.5 + (9.6 × weight) + (1.7 × height) – (4.7 × age)
Table 88.2   Calculation of calorie requirement
Thus, the caloric requirement is calculated as:
  • 1.3 × HB for sepsis or uncomplicated major surgery
  • 1.5 × HB for complicated sepsis (with organ failure) and burns less than 20%
  • 2 × HB for burns more than 20%.
643
Table 88.3   Calculation of resting energy expenditure (REE)
REE (kcal/min) = 3.94 (VO2) + 1.1(VCO2)
REE (kcal/day) = REE × 1440
 
Indirect Calorimetry
Indirect calorimetry is the technique by which one measures the metabolic energy expenditure of the body indirectly by measuring the whole body VO2 and VCO2 (Table 88.3). It is based on the principle that the use of energy involves the consumption of oxygen (VO2) and the production of carbon dioxide (VCO2), nitrogen wastes and water and when matter is converted to heat by the body, measurement of VO2 and VCO2 indirectly reflects the metabolic energy expenditure.
Specialized apparatus called metabolic carts are used to measure the exchange of oxygen and carbon dioxide across the lungs, i.e. they measure the oxygen concentration of inhaled oxygen and the carbon dioxide concentration of exhaled gas. It can be used at the bedside and can easily be connected to the ventilator tubings to measure the VO2 and VCO2.
The VO2 and VCO2 are measured for 30 minutes and this data is then used to calculate REE for a 24 hours period. The REE calculates the metabolic requirement at rest. Critically ill patients, whose body is constantly in a state of catabolism, requires much more daily expenditure than REE calculated by indirect calorimetry, hence the requirements have to be increased by 10 to 15%.
The limitations of indirect calorimetry are that it is expensive, time consuming and unreliable at high fraction of inspired oxygen (>60%). Thus, it is reserved for selected patients who need careful rotation of daily energy intake.
Thus, although there are various ways to calculate the caloric requirements, the current guidelines for nutrition in critical care recommend an average intake of 25–35 kcal/kg ideal body weight per day. Out of this, 40–60% calories should be provided by carbohydrate, 20–30% by fat and 15–25% by proteins. Carbohydrates and proteins provide 4 kcal/g and fats provide 9 kcal/g.
 
Carbohydrate Requirements
Carbohydrates are the main energy-giving fuel for our body. Glucose forms the main substrate for many pathways generating energy in human body. The tissues which are completely dependent on glucose are the red blood cells, the immune cells, the transparent tissues of the eyes, renal medulla and the muscle during anaerobic contraction. Tissues like brain are strongly but not totally dependent on glucose. Brain can also utilize ketones and lactate when the availability of glucose is low. All the other remaining tissues in the body are not directly dependent on glucose. The rate of normal endogenous glucose production of the human body is 2–3 g/kg/day. In order to maintain the normoglycemia, the exogenous intake should at least correspond to the endogenous rate of glucose production. Approximately, 60% of non-protein energy should be supplied as glucose with an intake of 3–3.5 g/kg/day. Patients who are at increased risk of hyperglycemia for example, patients with diabetes mellitus, sepsis, steroid therapy, should initially 644be given carbohydrate at the rate of 1–2 g/kg/day and then treated depending on the blood sugar levels.
The main concern while giving carbohydrate as a part of nutrition in the critically ill patients is the blood glucose levels. Hyperglycemia increases the morbidity and mortality in the critically ill patients whereas acute hypoglycemia can result in sudden death especially in patients who are on sedation in the ICU. The multicenter Normoglycemia in Intensive Care Evaluation and Surviving Using Glucose Algorithm Regulation (NICE-SUGAR) trial found that patients in the ICU, who were treated with insulin to achieve a target blood glucose of 81–108 mg/dL, had greater mortality and more hypoglycemia (6.8% versus 0.5%) than the patients who were treated to a target level of less than 180 mg/dL. Thus, achieving a target blood glucose level of less than 180 mg/dL is preferable over tight control.
A study done by McCowen et al. demonstrated that giving hypocaloric total parenteral nutrition was not effective in preventing hyperglycemia and infectious complications and provision of total parenteral nutrition to a goal of 25 kcal/kg was not associated with more hyperglycemia or infections than the hypocaloric diet. They found that a regimen of 1.5 g/kg of protein in conjunction with 25 kcal/kg provided significant nutritional benefits in terms of nitrogen balance.
 
Lipids
Lipids provide the maximum energy as compared to the other organic fuels. Linoleic acid is the only dietary fatty acid which is considered essential. Linoleic acid should form 4% of the total caloric intake and at least 0.5% of the dietary fatty acids. A deficient intake of linoleic acid produces a clinical disorder characterized by a scaly dermopathy, cardiac dysfunction, neutropenia, thrombocytopenia and increased susceptibility to infection. It can be prevented by oral intake of 10–15 mL/day of safflower oil or by the use of IV lipid emulsions.
 
Proteins
Critically ill patients in the ICU can lose 16% of total body proteins in the first 21 days with most (67%) of this coming from the skeletal muscle. In a study described by Martindale et al., the thigh muscle biopsy samples of 63 critically ill patients who were in ICU for more than 7 days and ventilated for more than 48 hours, showed that 29% of the tissue had been lost in 10 days in these hyperdynamic patients. Thus, supplementing amino acids is important to increase protein synthesis and maintain muscle mass.
On an average a protein intake of 0.75–1 g/kg/day is sufficient for most patients in ICU. Protein requirements are higher in patients with severe burns, trauma or fulminant tetanus and may be up to 2.5 g/kg/day. The nitrogen balance studies can help adjust the protein intake. A rising blood urea nitrogen exceeding 100 mg/dL or an increase in serum ammonia level are indications to decrease the protein administration. Adding resistance exercise to the protein supplement regimen can have additional benefits including increasing nutrient uptake in muscles and other tissues, decreasing inflammation and lowering the insulin resistance.645
 
Micronutrients
 
Vitamins
Amongst the micronutrients, there are 12 essential vitamins which need to be supplemented. These are vitamin A, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K, vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B6 (pyridoxine), pantothenic acid, biotin and folate. The requirements of vitamins are very high in the hypermetabolic seriously ill patients.
Thiamine deficiency is frequently observed in the ICU and deserves a special mention. Thiamine deficiency can manifest as cardiac dysfunction (Beri Beri disease), peripheral neuropathy, metabolic encephalopathy (Wernicke's encephalopathy) or lactic acidosis. All these disorders are quite common in the ICU patients and hence a high index of suspicion towards thiamine deficiency should be kept in mind while treating such patients.
 
Trace Elements
The trace elements which should be supplemented are iron, zinc, manganese, molybdenum, copper, chromium, selenium, iodine and cobalt. In general, the enteral feeds of 1000–1500 mL will have these vitamins and minerals in adequate amount according to the required daily allowance. They need to be supplemented in enteral feeds less than 1000 mL and in total parenteral nutrition. As regards the fluid intake, in general, patients should receive 25 mL of fluid per kg actual dry body weight to avoid dehydration.
 
BIBLIOGRAPHY
  1. Apostolakos MJ, Papadakos PJ. The Intensive Care Manual. McGraw-Hill publications; 2001.
  2. Bankhead R, et al. Enteral nutrition practice recommendations. Journal of Parenteral, and Enteral Nutrition. 2009;33(2):122-67.
  3. Bolder U, Ebener C. Working group for developing the guidelines for parenteral nutrition of the German Association for Nutritional Medicine. Ger Med Sci. 2009,7: Doc 23.
  4. Brunicardi FC. Schwartz's Principles of Surgery, 8th edn. McGraw-Hill publications; 2004.
  5. Carrol Rees Parrish. The Hitchhiker's Guide to Parenteral Nutrition Management for Adult Patients. Practical Gastroenterology. July 2006.
  6. Dhaliwal, et al. The Canadian critical care nutrition guidelines in 2013: an update on current recommendations and implementation strategies. Nutrient Clin Pract. 2014; 29(1):29-43.
  7. Driscoll DF, Blackburn GL. Total parenteral nutrition 1990: a review of its current status in hospitalized patients. The need for patient-specific feeding. Drugs. 1990; 40:346-63.
  8. Fink MP, Abraham E, Vincent JL, Kochanek PM. Textbook of Critical care, 5th edn. Elsevier Saunders publications.
  9. Giner M, Laviano A, Meguid MM, et al. In 1995 a correlation between malnutrition and poor outcome in critically ill still exists. Nutrition. 1996;12:23-9.
  10. Irwin JM, Rippe RS. Irwin and Rippe's Intensive Care Medicine. 6th edn. Lippincott Williams & Wilkins publications; 2008.
  11. 646KC, Friel C, Sternberg J, Chan S, Forse RA, Burke PA, Bistrian BR. Hypocaloric total parenteral nutrition: effectiveness in prevention of hyperglycemia and infectious complications—a randomized clinical trial. Crit Care Med. 2000;28(11):3606-11.
  12. Marino PL. The ICU Book, 3rd edn. Lippincott Williams & Wilkins; 2007.
  13. Miller RD. Miller's Anesthesia, 7th edn. Elsevier Publications 2009.
  14. Monk DN, et al. Ann Surg. 1996;223(4):395-405.
  15. Singer P, et al. ESPEN Guidelines on Parenteral Nutrition: Intensive Care. Clinical Nutrition, 2009(28);387-400.
  16. Udwadia FE. Principles of critical care, 2nd edn Oxford Publications.

ENTERAL AND PARENTERAL NUTRITIONCHAPTER 89

Sushma Vijay Pingale  
TIMING OF NUTRITIONAL SUPPORT
A study done by Giner et al. has shown that nutritional therapy considerably reduces morbidity and mortality in the critically ill patients. The European Society of Parenteral and Enteral Nutrition (ESPEN) guidelines on EN5 state that “The insufficient provision of nutrients is likely to result in undernutrition within 8–12 days following surgery and/or ICU admission. In order to prevent undernutrition and related adverse effects, all ICU patients who are not expected to be on a full oral diet within three days should receive EN”.
The European (ESPEN) and Canadian Society for Clinical Nutrition (CSCN) clinical guidelines recommend the initiation of EN within 24 hours or 24–48 hours, respectively, after admission to ICU. The guidelines also recommend that if the enteral route is contraindicated then the parenteral mode should be used and the parenteral nutrition should also ideally be initiated within 24–48 hours. But before starting nutritional therapy, one needs to keep in mind that in an acute, hypercatabolic critical illness, stabilization of hemodynamics, and correction of the fluid and electrolytes and acid-base disturbances should take precedence over the nutritional therapy. Nutritional requirement in specific conditions are discussed in this chapter.
 
ROUTES FOR GIVING NUTRITIONAL SUPPORT
There are two routes through which the nutritional support can be given—enteral and parenteral. Enteral route means through the gastrointestinal tract and parenteral means through intravenous route. So far the enteral route is considered the most physiological route and hence is the preferred one.
 
Enteral Nutrition
Nutrition provided through the gastrointestinal tract via a tube, catheter, or stoma that delivers nutrients distal to the oral cavity is called as enteral nutrition.
Enteral route for giving nutritional support is indicated when swallowing is inadequate or impossible but gastrointestinal function is otherwise intact. For example, patients who have an oropharyngeal lesion, esophageal lesion, burns or a neurological disorder, where swallowing and the upper GI tract are affected 648and patients on ventilatory support are the candidates in whom the enteral route is preferred.
Reasons for using enteral route as the preferred route for giving nutrients are:
  • The enteral route maintains the structural and functional integrity of the gut.
  • Complete bowel rest will lead to progressive atrophy and disruption of the intestinal mucosa. This is because the bowel mucosa gets its nutrients from those present in the bowel lumen. The amino acid glutamine is thought to play an important role in this process as it is considered as the principal metabolic fuel for intraepithelial cells.
  • The mucosal disruption that may ensue due to lack of nutrition may lead to translocation of enteric pathogens across the bowel mucosa and into the systemic circulation. This potential to prevent sepsis of bowel origin is considered as one of the foremost reasons for preferring enteral route over the parenteral one.
Studies have suggested that giving enteral feeds in shock increased oxygen demand in a segment of the bowel that was poorly perfused, hence stabilizing the patient hemodynamically is a prerequisite to starting enteral nutrition. Enteral nutrition can be given via an infusion into the stomach, duodenum or the jejunum via the nasogastric tubes, nasoduodenal tubes or the nasojejunal tubes. The tubes can be passed beyond the pylorus under fluoroscopic guidance.
The feeding tubes that are currently favored are narrower (8 to 10 French) and more flexible than standard nasogastric tubes are longer in length and come with a stylet for insertion. Care has to be taken during their insertion since they may enter the larynx and the respiratory tract if the cough response of the patient is not strong. The tip of the tube is radiopaque. The gold standard for the confirmation of the tube placement is a properly obtained and interpreted radiograph which visualizes the entire course of the tube. The auscultatory method can neither distinguish between gastric and small bowel placement nor can it detect the placement of the tip of the tube in the esophagus. Hence, a radiograph is mandatory before starting the feeds. Another method to assess the tube placement is measuring the pH of the specimen aspirated from the tube. If the pH of the aspirate is less than 5.0, then the tube is most likely placed in the stomach. However, if the gastric pH is more than 6.0, then the pH method is of no benefit in predicting tube location in the gastrointestinal tract.
The other problem with the tubes is that they can get misplaced during the course of the feeds (Table 89.1). To confirm their correct positioning, daily bedside methods like determining whether the external length of the tubing has changed since the time of the confirmatory radiograph, observing for negative pressure while attempting to withdraw fluid from the feeding tube, observing for changes in residual volumes and measuring pH of the aspirate obtained from the tip of the tube have to be followed. An acute increase in the gastric residual volume may indicate the displacement of the tube from the small bowel into the stomach. An increase in the negative pressure is more likely to be felt while aspirating the fluid from the small bowel than from a gastric tube. If the external length of the tube has increased significantly then displacement should be suspected and a radiograph should be obtained to ascertain the tube position.
Table 89.1   Contraindications for nutritional support through enteral route
  • Bowel ileus or obstruction
  • Enterocutaneous fistulas with an output of more than 500 mL/day
  • Acute fulminant necrotizing pancreatitis
  • Severe shock
649Apart from the nasally inserted tubes, procedures like the percutaneous endoscopic gastrostomy and jejunostomy can also be done to give the enteral feeds. In patients who are at risk of aspiration due to reflux and the patients who require feeding for a longer time (>4 weeks) direct placement of percutaneous gastric or jejunal tube is recommended.
 
Starting the Enteral Feeds
The American Society for Parenteral and Enteral Nutrition (ASPEN) guidelines recommend that the enteral feeds should be started postoperatively in surgical patients without waiting for flatus or bowel movement. These feedings can be initiated within 24–48 hours. Percutaneous endoscopic gastrostomy tube may be utilized for feedings within 2 hours in adults and 6 hours in infants and children.
The test infusion comprising volume of normal saline equivalent to the desired hourly feeding volume should be infused into the stomach for one hour to check for the safety. The tube should then be clamped for half an hour and then the aspirate is measured. If the gastric residual volume is <50%, then the feeding can be started safely.
The initiation and advancement of the enteral nutrition regimens should be based on the patient's demographics, enteral route (gastric versus small bowel), nutrition requirements and the GI status. For the initial feeding regimen, full strength isotonic formulas are preferred. The ‘starter regimens’ which begin with dilute formulas and slow infusion rates and then gradual increase in the concentration and the infusion rate over a few days, are preferred for small bowel (duodenum and jejunum) who have a limited reservoir function. Starter regimens are not necessary for gastric feedings because the stomach has a good reservoir capacity and the gastric secretions can dilute the full feedings and reduce the osmotic load associated with them.
The enteral feeds can be given as intermittent bolus feedings or continuous infusions. Bolus feedings are defined as formula delivered by gravity via a syringe over approximately 15 minutes. These are usually tolerated when infused into the stomach. The ASPEN guidelines recommend that the feedings may be initiated with full strength formula 3–8 times per day with increases of 60–120 mL every 8–12 hours as tolerated up to the goal volume. The feeds can be given by continuous infusions over a period of 16 hours. The chances of aspiration and diarrhea are found to be less by this technique and also result in good weight gain and positive nitrogen balance. The feeding tubes should be flushed with 30 mL of water every 4 hours during continuous feeding or before and after intermittent feedings.650
Table 89.2   Classification of enteral feeds
The enteral feeds are classified on the basis of nature of nutrients or the ease of absorption into the following types:
  • Liquidized or blenderized food: These are the liquidized versions of the food we eat. For example, rice, boiled vegetables, curd, milk, fruit juice, etc.
  • Lactose-free formulas: These formulas are indicated in patients with a normal gastrointestinal tract but who are intolerant to lactose. For example, Sustacal HC 1.5 kcal/mL, Isocal 1 kcal/mL, HCN 2 kcal/mL.
  • Chemically derived formulas: These formulas contain protein in the hydrolysated form. These are indicated in patients whose ability to absorb nutrients is impaired. For example, vital HN.
  • Elemental formulas: These contain amino acids. These are often used in patients with limited absorptive capacity. They are well-absorbed from jejunum hence often used for jejunal feeds. For example, Vivonex 1 kcal/mL.
 
Nursing a Patient on Enteral Feeds
The backrest of the patient's bed should be elevated to a minimum 30° and preferably to 45° for all patients receiving the enteral feeds if there is no contraindication. The gastric residual volume should be checked every 4 hours during the first 48 hours in gastric route-fed patients. If the gastric residual volume is more than 250 mL after a second gastric residual check then a prokinetic agent should be considered. If gastric stony occurs then the gastric feeds need to be withheld. If the gastric residual volumes are consistently more than 500 mL then the placement of the feeding tube below the ligament of Treitz should be considered. The fluid and electrolytes and other metabolic parameters based on the patient's clinical situation should be monitored regularly.
Most of the enteral formulas provide 14–20% of calories as protein and contain medium or long chain triglycerides (Table 89.2).
 
Complications of Enteral Feeding
Gastric retention, aspiration pneumonia, diarrhea and tube blockage are the main complications that can be encountered during enteral feeding. Head elevation by 30°–45° degrees, small bowel feeds, use of prokinetic agents, less use of narcotics and using feeding protocols in which the residual gastric volume is monitored, are some of the ways by which gastric retention and aspiration can be prevented. To tackle diarrhea reduction of feeds by half, avoidance of bolus feeding and lactose in the feeding and avoidance of sorbitol-containing liquid medicines can be tried. Supplementation of amino acids containing formula feeds is recommended. To prevent tube blockage flushing the tube before and after the feeds, filling with water and plugging them when not in use should be done.
 
Parenteral Nutrition
The nutrition given through the intravenous route is called as parenteral nutrition. Parenteral nutrition is associated with an increased risk of infectious complications, especially line infection, and increased cost unlike enteral nutrition.651
 
Indications
  • Enteral nutrition is not feasible (short bowel syndrome, enterocutaneous fistulas with a large leak >500 mL, severe diarrhea, complete bowel obstruction, active GI bleeding, pseudo-obstruction with intolerance to food)
  • Target caloric requirement cannot be achieved via enteral feeding alone (in this case, parenteral nutrition is given as a supplement to enteral nutrition)
  • Relative indications include nonhealing moderate-output enteric-cutaneous fistulas, acute radiation enteritis, marked abdominal distention and ileus due to intra-abdominal sepsis, chylothorax unresponsive to a medium-chain triglyceride diet.
 
Access for the Parenteral Nutrition
The parenteral nutrition is usually given through a central vein (long term) or a peripheral vein (short term). The major limitation in using the peripheral vein for parenteral nutrition is the development of thrombophlebitis due to the high osmolality of the nutrient solutions (osmolality >900 mOsm/L). Centrally administered parenteral nutrition can cover all nutritional needs as vessel tolerance to hyperosmolar solutions is usually not a limitation. The central veins preferred are the internal jugular and the subclavian vein. They can be cannulated using single or triple lumen catheters and these catheters can be kept for 10–12 days provided strict asepsis is maintained while handling them. Most peripheral vein catheters last about 48–72 hours from the time of insertion. Peripherally inserted central venous catheters (PICC) last longer and can be used to provide hypertonic parenteral nutrition mixtures.
 
Parenteral Nutrition Solutions
Carbohydrates
Carbohydrates are usually provided in amounts of up to 60% of total kcal/day. Dextrose solutions in the concentration of 10, 20 and 50 percentage constitute the carbohydrate content of parenteral nutrition.
Proteins
These are mainly supplied in the form of amino acid solutions. The standard amino acid solutions contain approximately 50% essential amino acids and 50% nonessential amino acids. The protein content of these amino acids can be arrived at by multiplying the nitrogen content in grams by 6.2. The metabolism of essential amino acids causes less increase in the blood urea nitrogen concentration than the metabolism of nonessential amino acids. This is because the nitrogen present in essential amino acids is partially recycled for the production of nonessential amino acids. It is for this reason that the essential amino acids are preferred in renal failure. The amino acids preferred in patients with hepatic failure are those containing a high concentration of branched chain aminoacids (leucine, isoleucine, valine). Glutamine should be supplemented in parenteral nutrition in the form of glutamic acid because it is the main metabolic fuel for intestinal 652epithelial cells and is instrumental in maintaining the functional integrity of the bowel mucosa.
Lipids
Intravenous fat emulsions provide 20–30% of daily kcals. The main source of fatty acids in the lipid emulsions are the vegetable oils (safflower or soybean oil). They contain 50–65% of linoleic acid and 4–9% of linolenic acid. They are available in strength of 10% and 20%. The 10% emulsions provide 1 kcal/mL approximately and the 20% emulsions provide 2 kcal/mL. They are made isotonic by addition of glycerol.
Vitamins and Electrolytes
Vitamins A, B, C and D, and electrolytes—sodium, chloride, potassium and magnesium and few trace elements are also added to the parenteral nutrition formulas to combat their deficiency.
 
Formulations and Administration
The parenteral nutrition formulations are available as three-in-one (dextrose, amino acid, lipids) or two-in-one packs (dextrose and amino acids). The lipid emulsions are to be infused separately when the two-in-one packs are used.
The example of three-in-one formula is Vitrimix which provides 1000 kcals in 1000 mL of solution. It contains 75 grams of dextrose,7 grams of nitrogen and 20% of lipids in 250 mL. Its osmolality is 960 mosm/L.
The example of two-in-one formula is Aminomix which provides 1000 kcals and contains 200 grams of dextrose and 8.2 grams of nitrogen (Table 89.3).
 
Monitoring
Estimation of complete hemogram, serum electrolytes, blood glucose, urea, creatinine, blood NPN, liver function tests, serum proteins, calcium, phosphorus and arterial blood gas should be done before starting the TPN and followed up at least once or twice a week. The blood glucose and serum electrolytes need frequent monitoring. The blood glucose should be maintained between 120 and 180 mg/dL.
 
Complications of Total Parenteral Nutrition
  • Hyperglycemia (due to the use of high concentration of dextrose-containing solutions)
  • Hypoglycemia (due to sudden stoppage of dextrose infusion)
  • Hypophosphatemia
  • Hypomagnesemia
  • Hepatic steatosis
  • Thrombophlebitis
  • Catheter-related sepsis.653
Table 89.3   Nutrition in specific conditions
Diagnosis
Caloric requirement
Proteins
Special points
Acute renal failure (not on dialysis)
25 kcal/kg/day
0.5 g/kg/day
Restrict fluid to <1/day, if urine output is low
Acute renal failure (on dialysis)
25 kcal/kg/day
1.5 g/kg/day
Loss of 6–12 g of amino acids and 25–30 g of glucose during a six-hour session of hemodialysis should be replenished
Hepatic failure (no encephalopathy)
25 cal/kg/day
1 g/kg/day
Branch chain amino acids preferred
Hepatic failure (encephalopathy)
25 kcal/kg/day
0.3 g/kg/day
Branched chain amino acids improve encephalopathy and should be given
Respiratory failure (COPD)
25 kcal/kg/day
1.2 g/kg/day
  • Restrict carbohydrates (to ↓CO2 production)
  • Give carbohydrate and fat in ratio of 40:60
Respiratory failure (ARDS)
25 kcal/kg/day
1.2 g/kg/day
Reduce fats and give carbohydrate and fat in ratio of 65:35 (since lipid emulsion interferes with gas exchange)
Cardiac failure
25 kcal/kg/day (start with half caloric requirement initially)
1 g/kg/day
Restrict salt and water
Severe burns
30–35 kcal/kg/day
1.5–2.5 g/kg/day
Protein intake should be increased to combat hypoalbuminemia
Multiple trauma
25 kcal/kg/day
1.2–1.5 g/kg/day
Immune enhancing formulas (glutamine, arginine, omega 3 fatty acids and antioxidant vitamins) should be tried
 
REFEEDING SYNDROME
The body of a nutritionally depleted patient, i.e. one who has lost ≥10% of body weight over ≤6 months gets adapted to the minimal nutrient intake. Refeeding such patients must be done gradually with caution as their metabolic system may not be able to tolerate the overload. To start with a balanced diet comprising carbohydrates, fats and proteins at intakes less than the REE should be given and then gradually increased over 10 days. The patients will be in negative N2 balance initially and hence protein intake has to be increased gradually to help in rebuilding of the muscle tissue. This should be accompanied by exercise. Phosphate which is an important component of tissue membranes, enzymes and nucleosides is utilized as new tissues are being formed and hence can result in hypophosphatemia. Hypophosphatemia leads to weakness of major muscle and glucose intolerance also known as refeeding syndrome. Muscle weakness 654may also be exacerbated if there is coexistent hypokalemia, hypocalcemia and hypomagnesemia. Thus serum phosphate, calcium, magnesium, potassium levels apart from serum electrolytes should be monitored daily and their replacement should be done promptly. Fluid overload should be avoided.
 
BIBLIOGRAPHY
  1. Apostolakos MJ, Papadakos PJ. The Intensive Care Manual. McGraw-Hill publications; 2001.
  2. Bankhead R, et al. Enteral nutrition practice recommendations. Journal of Parenteral, and Enteral Nutrition. 2009;33(2):122-67.
  3. Bolder U, Ebener C. Working group for developing the guidelines for parenteral nutrition of the German Association for Nutritional Medicine. Ger Med Sci. 2009,7: Doc 23.
  4. Brunicardi FC. Schwartz's Principles of Surgery, 8th edn. McGraw-Hill publications; 2004.
  5. Carrol Rees Parrish. The Hitchhiker's Guide to Parenteral Nutrition Management for Adult Patients. Practical Gastroenterology. July 2006.
  6. Dhaliwal, et al. The Canadian critical care nutrition guidelines in 2013: an update on current recommendations and implementation strategies. Nutrient Clin Pract. 2014; 29(1):29-43.
  7. Driscoll DF, Blackburn GL. Total parenteral nutrition 1990: a review of its current status in hospitalized patients. The need for patient-specific feeding. Drugs. 1990; 40:346-63.
  8. Fink MP, Abraham E, Vincent JL, Kochanek PM. Textbook of Critical care, 5th edn. Elsevier Saunders publications.
  9. Giner M, Laviano A, Meguid MM, et al. In 1995 a correlation between malnutrition and poor outcome in critically ill still exists. Nutrition. 1996;12:23-9.
  10. Irwin JM, Rippe RS. Irwin and Rippe's Intensive Care Medicine. 6th Edition. Lippincott Williams & Wilkins Publications; 2008.
  11. KC, Friel C, Sternberg J, Chan S, Forse RA, Burke PA, Bistrian BR. Hypocaloric total parenteral nutrition: effectiveness in prevention of hyperglycemia and infectious complications—a randomized clinical trial. Crit Care Med. 2000;28(11):3606-11.
  12. Marino PL. The ICU Book, 3rd edn. Lippincott Williams & Wilkins; 2007.
  13. Miller RD. Miller's Anesthesia, 7th edn. Elsevier publications. 2009.
  14. Monk DN, et al. Ann Surg. 1996;223(4):395-405.
  15. Singer P, et al. ESPEN Guidelines on Parenteral Nutrition: Intensive Care. Clinical Nutrition, 2009(28);387-400.
  16. Udwadia FE. Principles of critical care, 2nd edn. Oxford publications.
655Sedation and Analgesia in ICU
Chapter 90 Sedation and Analgesia for Critical Care Patients Prem Kumar
Chapter 91 Patient-controlled Analgesia Prem Kumar656

SEDATION AND ANALGESIA FOR CRITICAL CARE PATIENTSCHAPTER 90

Prem Kumar
Pain and agitation is one of the major problems in ICU patients and can be a major cause of morbidity. Patients with acute postoperative pain are inadequately treated because of the fear of complication, arbitrary management of among intensivists, lack of availability of proper assessment and management protocols. Pain is subjective, hence questionnaire related to pain assessment is asked and is supplemented with objective scales. Inadequate pain relief is the most common cause of agitation in ICU patients. Recent studies demonstrate that inadequate treatment of acute pain can evolve into chronic pain. Proper staff education is vital to the success of pain management. Appropriate sedation reduces the duration of mechanical ventilation and ICU stay.
There are three dimensions for pain:
  1. Sensory—discriminative
  2. Affective—motivational
  3. Cognitive—evaluative.
 
ISSUES TO BE ADDRESSED FOR MANAGEMENT OF PAIN AND SEDATION IN ICU
  • Define the cause of agitation and pain
  • Associated comorbid conditions?
  • Hepatic and renal function for metabolism?
  • Options of using regional/intravenous analgesia according to the status of the patient
  • Choosing a relevant pain scale for the patient.
 
PAIN AND SEDATION CONSIDERATIONS
  • Inadequately treated severe pain can lead to a change in the response of the neural tissue to painful stimuli—this phenomenon is called neuroplasticity. This can lead to chronic pain in the future which can debilitate the patient.
  • Stress response to pain can cause release of catecholamines, pro-inflammatory cytokines, acute phase reactants, cortisol. Activation of renin-angiotensin system (RAS), coagulation disturbances and altered immune response is one of the major causes for morbidity and mortality.
  • 658Because of anxiety and the other psychological disturbances, patient may end up with post-traumatic stress disorder.
  • Making out the cause of pain is vital to its management. Pharmacological management is based on patient assessment, response to treatment, maintenance of adequate drug level. Frequent evaluation and modification of pain approaches and drug dosages are done.
  • One more important point to stress is the importance of using regional analgesia with local anesthetics and opioids for pain control since it reduces the stress response of pain.
  • Analgesia and sedation required in keeping the patient calm and comfortable but arousable is what is recommended in recent literature since this reduces the duration of mechanical ventilation and ICU stay.
  • Daily sedation interruption (sedation holiday) leads to better outcome in ICU patients. Interrupted doses are preferred than continuous infusions. Spontaneous breath trials are done during the time of sedation holiday.
 
ASSESSMENT OF PAIN (Tables 90.1 and 90.2)
  • It is mainly subjective assessment by way of different pain questionnaire
  • Objective pain scales are used to supplement subjective assessment.
  • Objective signs like tachycardia, tachypnea, hypotension and grimacing can be used for assessing pain. But these are not reliable since they can be caused by other factors too.
  • Patients who are at risk for undertreated pain are infants, patients with difficulty in communication like language alteration, developmental retardation, and psychiatric disease.
  • Assessment of pain can be done with unidimensional and multidimensional pain questionnaires.
  • Unidimensional: Visual analog scale, numeric rating scale, verbal descriptor scale, Wong-Baker FACES pain scale.
  • Multidimensional–McGill pain questionnaire, memorial pain assessment card (MPAC), brief pain inventory–short form (BPI-SF).
Table 90.1   Clinical evaluation of pain
  • Location of pain
  • Severity of pain: Visual, verbal, or numeric analog scales
  • Feel of the pain: Somatic or visceral or neuropathic or breakthrough pain
    • Neuropathic pain occurs due to injury of the peripheral nervous system and is due to dysfunction of the sodium channels and NMDA receptor
    • Breakthrough pain: It is an episodic increase in pain with a background of adequately controlled pain. It can occur due to some precipitating factor or just before the administration of regular analgesic dose.
    • Incident pain: It is a form of breakthrough pain which occurs due to movement or during change of dressing.
  • History of analgesic intake and other drugs which may influence its effect
  • Frequency of pain
  • Timing of pain
  • Precipitating factors
659
Table 90.2   Differences between somatic and visceral pain
Somatic pain
Visceral pain
  • Can be superficial or deep
  • Superficial pain is due to nociceptive input arising from skin, subcutaneous tissues, and mucous membranes
  • Deep pain arises from muscles, tendons, joints, or bones
  • Superficial pain is sharp, pricking, well localized
  • Deep pain is dull aching, less well localized
  • It is due to some disease process or abnormality in the function of internal organ or its superficial structure (parietal pleura, pericardium, and peritoneum)
  • It is associated with nausea, vomiting, sweating, and changes in hemodynamics
 
PAIN SCALES
  • Visual analog scale (VAS)
  • Numeric rating scale (NRS)
  • Wong-Baker FACES pain scale
  • Verbal descriptor scale
  • McGill pain questionnaire.
 
Visual Analog Scale
The VAS is a continuous scale comprised of usually 10 cm in length, anchored by 2 verbal descriptors, one for each symptom extreme. The scale reads 0—no pain and 10—worst possible pain. This is the most common scale used by intensivist's for pain assessment.
 
Numeric Rating Scale
Numeric rating scale (NRS) is an 11 point scale and can be used verbally and the NRS scale increases as the intensity of pain increases. A NRS or VS ≤3 is an indication that the patient has adequate analgesia.660
 
Wong-Baker FACES Pain Scale
Faces
Pain scale comment
Happy, no hurt
Hurts a little bit
Hurts little more
Hurts even more
Hurts whole lot
Hurts worst
 
Verbal Descriptor Scale
 
Short-form McGill Pain Questionnaire (Tables 90.3 and 90.4)
It includes 5 measures:
  1. Pain location (sensory dimension).
  2. Pain intensity (sensory dimension).661
    Table 90.3   Short-form McGill pain questionnaire (SF-MPQ)
    Quality of pain
    None
    Mild
    Moderate
    Severe
    Throbbing
    Shooting
    Stabbing
    Sharp
    Cramping
    Gnawing
    Hot burning
    Aching
    Heavy
    Tender
    Splitting
    Tiring—exhausting
    Sickening
    Fearful
    Punishing-cruel
    No pain ……………… worst possible pain
    Table 90.4   Present pain intensity (PPI)
    0
    No pain
    1
    Mild
    2
    Discomforting
    3
    Distressing
    4
    Horrible
    5
    Excruciating
  3. Pain quality (sensory, affective, and cognitive dimensions).
  4. Pain pattern (sensory dimension).
  5. Alleviating and aggravating factors (behavioral dimension).
The original McGill pain questionnaire had descriptors divided into four major groups: sensory (S), 1–10; affective (A), 11–15; evaluative (E), 16; and miscellaneous (M), 17–20. The sum of the values is the pain rating index (PRI). In the short-form McGill pain questionnaire, Descriptors l–11 represent the sensory dimension of pain experience and 12–15 represent the affective dimension. Each descriptor is ranked on an intensity scale of 0 = none, 1 = mild, 2 = moderate, 3 = severe.662
 
Scales Used for Sedation Assessment in ICU
  • Richmond agitation sedation scale
  • Ramsay sedation score.
 
Scale Used for Assessing Delirium in ICU
Confusion assessment method for the intensive care unit (CAM-ICU).
 
Management of Pain and Sedation (Flow charts 90.1 and 90.2)
Opioids and benzodiazepines remains the mainstay of sedation and analgesia management in ICU. Recently dexmedetomidine has gained popularity due its pharmacokinetic and pharmacodynamic profile and there are studies where it has been used in ventilated patients for 7 days but still FDA approval for its use is limited to 24 hours. The advantage of dexmedetomidine is the lack of respiratory depression. Wherever possible, regional analgesia should be supplemented with sedative agents.
Flow chart 90.1: Managing pain and sedation in ICU
Abbreviations: TENS, Transcutaneous electrical nerve stimulation; NSAIDs, Nonsteroidal anti-inflammatory drugs
663
Flow chart 90.2: Algorithm for pain/sedation/delirium management in ICU
664
 
Options of Regional Analgesia
  • In case of nonventilated awake postoperative patients—Intravenous patient controlled analgesia (PCA) or patient controlled epidural analgesia (PCEA) is used (Table 90.5).
  • Epidural analgesia
  • Continuous peripheral nerve catheter based analgesia.
Table 90.5   Drugs used for pain and sedation in ICU
Drug
Dose
Metabolism
Comments
NSAIDs and acetaminophen
Paracetamol— liver
NSAIDs—Liver and kidney
Opioids
Morphine
Fentanyl
Tramadol
1.1–0.2 mg/kg IV 6th hourly or
2–5 mg/hr in case of infusion.
1–2 µg/kg IV every 30– 60 minutes or
1–5 µg/kg/hr
50–100 mg 12th hourly
Liver and kidney
  • Respiratory depression
  • Histamine release
  • Reduce morphine dose by 50% in case of renal failure
  • Tramadol may precipitate serotonin syndrome in patients taking SSRI
Ketamine
1 mg/kg IV or 5 µg/kg/min for sedation and analgesia. Duration of action = 15–20 minutes
Liver
  • Should be combined with glycopyrrolate and benzodiazepines.
  • Causes hypertension, tachycardia, increased ICT, IOP
Propofol
Loading dose of 0.5–1 mg/kg followed by 50– 200 µg/kg/min IV
Liver and lung
  • Dose >4 mg/kg/hr for >48 hours can cause propofol infusion syndrome (metabolic acidosis, hemoglobinuria)
  • Hypotension, bradycardia
665
Benzodiazepines
Midazolam 50–100 µg/kg IV every 15–90 min or 1–3 mg or 0.05–0.1 mg/kg/hr
Lorazepam 0.02–0.06 mg/kg every 2–5 hours or 0.01–0.1 mg/kg/hr
Liver.
Midazolam requires minor reduction of dose in renal disease but lorazepam does not
  • Can cause hypotension in patients with hypovolemia
  • Can cause respiratory depression
  • Midazolam is most common BZD used for sedation for short term
  • Lorazepam is used if prolonged sedation is required
Haloperidol
2–10 mg IV every 20–30 minutes
  • Prolonged QT interval, torsades de pointes, neuroleptic malignant
  • Due to its delayed onset, it has to be combined with benzodiazepine
Dexmedetomidine
FDA approved sedation is limited to 24 hours. Loading dose = 1 µg/kg over 10 minutes followed by Infusion dose = 0.4–0.7 µg/kg/hr
Liver
  • Highly selective α2 agonist
  • Advantage of having anxiolysis, sedation, analgesia, sympatholysis with an arousable patient
  • Hypotension, biphasic heart rate response
  • Hypertension can occur with rapid administration
Anesthetic conserving device
(AnaConDa)
Isoflurane or sevoflurane
Liver
  • Certain studies have compared its efficacy with intravenous sedatives but this device is yet to get FDA approval
666
Table 90.6   Ramsay sedation scale
Score
Description
1
Anxious and agitated or restless, or both
2
Cooperative, orientated, and tranquil
3
Drowsy, but responds to commands
4
Asleep, brisk response to light glabellar tap or loud auditory stimulus
5
Asleep, sluggish response to light glabellar tap or loud auditory stimulus
6
Asleep and unarousable
Ramsay sedation scale (RSS) and Richmond agitation sedation scale (RASS) is primarily used for measuring sedation in ICU patients on mechanical ventilation and is primarily used to measure the level of sedation rather than agitation (Tables 90.6 and 90.7). Agitation is measured by confusion assessment method for the intensive care unit (CAM–ICU) method (Table 90.8).
Table 90.7   Richmond agitation sedation scale
Score
Label
Description
+4
Combative
Combative, violent, immediate danger to staff
+3
Very agitated
Pulls to remove tubes or catheters; aggressive
+2
Agitated
Frequent non-purposeful movement, fights ventilator
+1
Restless
Anxious, apprehensive, movements not aggressive
0
Alert and calm
Spontaneously pays attention to caregiver
-1
Drowsy
Not fully alert, but has sustained awakening to voice
(eye opening and contact >10 sec)
-2
Light sedation
Briefly awakens to voice (eyes open and contact <10 sec)
-3
Moderate sedation
Movement or eye opening to voice (no eye contact)
-4
Deep sedation
No response to voice, but movement or eye opening
to physical stimulation
-5
Unarousable
No response to voice or physical stimulation
Table 90.8   Confusion assessment method for the intensive care unit
Features and descriptions
Absent
Present
I.  Acute onset or fluctuating course
  A. Is there evidence of an acute change in mental status from the baseline?
  B. Or, did the (abnormal) behavior fluctual during the past 24 hours, that is, tend to come and go or increase and decrease in severity as evidenced by fluctuations on the Richmond agitation sedation scale (RASS) or the Glasgow coma scale?
II.  Inattention
  Did the patient have difficulty focusing attention as evidenced by a score of <8 correct answers on either the visual or auditory components of the attention screening examination (ASE)?
667III.  Disorganized thinking
  Is there evidence of disorganized or incoherent thinking as evidenced by incorrect answers to 3 or more of the 4 questions and inability to follow the commands?
Questions
  1. Will a stone float on water?
  2. Are there fish in the sea?
  3. Does 1 pound weigh more than 2 pounds?
  4. Can you use a hammer to pound a nail?
Commands
  1. Are you having unclear thinking?
  2. Hold up this many fingers. (Examiner holds 2 fingers in front of the patient.)
  3. Now do the same thing with the other hand (without holding the 2 fingers in front of the patient)
(If the patient is already extubated from the ventilator, determine whether the patient's thinking is disorganized or incoherent, such as rambling or irrelevant conversation, unclear or illogical flow of ideas, or unpredictable switching from subject to subject.)
IV.  Altered level of consciousness
  Is the patient's level of consciousness anything other than alert, such as being vigilant or lethargic or in a stupor, or coma?
Alert: Spontaneously fully aware of environment and interacts appropriately
Vigilant: Hyperalert
Lethargic: Drowsy but easily aroused, unaware of some elements in the environment or not spontaneously interacting with the interviewer; becomes fully aware and appropriately interactive when prodded minimally
Stupor: Difficult to arouse, unaware of some or all elements in the environment or not spontaneously interacting with the interviewer;becomes incompletely aware when prodded strongly; can be aroused only by vigorous and repeated stimuli and as soon as the stimulus ceases, stuporous subject lapses back into unresponsive state
Coma: Unarousable, unaware of all elements in the environment with no spontaneous interaction or awareness of the interviewer so that the interview is impossible even with maximal prodding
Overall CAM-ICU Assessment (Features 1 and 2 and either Feature 3 or 4):yes…No…
 
Regional Analgesia Techniques
  • Epidural analgesia
  • Continuous peripheral nerve catheter analgesia.
 
Epidural Analgesia (Table 90.9)
The advantages of analgesia is reduced incidence of systemic adverse effects like respiratory depression, improvement of pulmonary function in patients who have been done upper abdominal and thoracic surgery, preservation of gastrointestinal function and reduced release of stress hormones due to surgery and trauma thus reducing the inflammatory response and morbidity and mortality.668
Table 90.9   Dose for epidural analgesia
Timing of injection
Dose
Initial dose
10–15 mL of a 0.25%–0.125% solution of 0.5% bupivacaine
or
10–15 mL of a 0.1%–0.2% solution of ropivacaine
Continuous infusion
0.0625 or 0.125% bupivacaine at 5–15 mL/hr
or
0.2% ropivacaine at 5–15 mL/hr
Indications
  • Thoracic and upper abdominal surgery
  • Orthopedic procedures
  • Penetrating or blunt thoracic trauma ± rib fracture.
American society of regional anesthesia (ASRA) guidelines should be followed for patients who are on anticoagulants. In case of sepsis, epidural analgesia is better avoided due to the risk of infection and hypotension. Either intermittent or continuous analgesia can be given for epidural analgesia.
 
Continuous Peripheral Nerve Catheter Analgesia
  • Peripheral nerve block can be done both for upper and lower extremities with ultrasound or peripheral nerve stimulation.
  • It can be used for pain relief in both trauma and post surgery.
 
BIBLIOGRAPHY
  1. Anand KJ, Hickey PR. Halothane-morphine combined with high dose sufentanil for anesthesia and postoperative analgesia in neonatal cardiac surgery. N Engl J Med. 1992;326:1.
  2. Banning A, Sjögren P, Henriken H. Pain causes in 200 patients referred to a multidisciplinary cancer pain clinic. Pain. 1991;45:45.
  3. Burckhardt CS, Jones KD. Adult measures of pain: The McGill Pain Questionnaire (MPQ), Rheumatoid Arthritis Pain Scale (RAPS), Short-Form McGill Pain Questionnaire (SF-MPQ), Verbal Descriptive Scale (VDS), Visual Analog Scale (VAS), and West Haven-Yale Multidisciplinary Pain Inventory (WHYMPI). Arthritis Rheum. 2003;49:S96-104.
  4. Burton JH, Miner J. Emergency sedation and pain management, 1st edn. 2008. Canmbridge university publications.
  5. Cohen S, Christo P, Moroz L. Pain management in trauma patients. Am J Phys Med Rehabil. 2004;83(2):142.
  6. Dickenson AH. Spinal pharmacology of pain. Br J Anaesth. 1995;75:193.
  7. Elliott K, Minami N, Kolesnikov Y, et al. The NMDA receptor antagonists, LY274614 and MK-801, and the nitric oxide synthase inhibitor, NG-nitro-L-arginine, attenuate analgesic tolerance to the mu opioid morphine but not to the kappa opioids. Pain. 1994;56:69.
  8. Hedderich R, Ness TJ. Analgesia for trauma and burns. Crit Care Clin. 1999;15:167.
  9. Huskisson EC. Measurement of pain. Lancet. 1974;2:1127-31.
  10. Jacob E, Puntillo K. Variability of analgesic practices for hospitalized children on different pediatric specialty units. J Pain Symptom Manage. 2000;20:59.
  11. 669Jensen MP, Karoly P, Braver S. The measurement of clinical pain intensity: a comparison of six methods. Pain. 1986;27:117-26.
  12. Melzack R. The McGill Pain Questionnaire: Major properties and scoring methods. Pain. 1975;1:277-99.
  13. Monitoring sedation status over time in ICU patients: Reliability and validity of the Richmond agitation-sedation scale (RASS). JAMA. 2003;289(22):2983-91.
  14. Schreiber S, Galai-Gat T. Uncontrolled pain following physical injury as the core-trauma in post-traumatic stress disorder. Pain. 1993;54:107.
  15. Whipple JK, Lewis KS, Quebberman EJ, et al. Analysis of pain management in critically ill patients. Pharmacotherapy. 1995;15:592.
  16. Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science. 2000; 288:1765.
  17. Yeager MP, Glass DD, Neff RK, et al. Epidural anesthesia and analgesia in high-risk surgical patients. Anesthesiology. 1987;66:729.

PATIENT-CONTROLLED ANALGESIACHAPTER 91

Prem Kumar
Patient-controlled analgesia (PCA) is an effective way of administering pain relief for acute pain. It can be given either through intravenous route (PCA) or epidural route (PCEA) or peripheral nerve blockade. The advantage of PCA is its efficacy because the administration is controlled by the patient and thus resulting in more patient satisfaction, better analgesia, reduced complications compared with other modes of analgesia. In this chapter, we will discuss the various methods of PCA, drugs used, and its merits and demerits.
 
PRE-REQUISITES
  • Awake, nonventilated patients.
  • Should be educated enough before surgery to understand the method of administration and its adverse effects in patients used for postoperative pain relief. Both the patient and the relatives must be taught about the device.
  • Strict adherence to operation by the patient and not by proxy.
 
MECHANICS ABOUT THE DEVICE
Patient-controlled analgesia works on the principle of electronic infusion pump with a button which should be pressed by the patient when the patient senses pain. To reduce the incidence of adverse effects due to overdose, the device is enabled with a feature called lockout interval where the infusion pump is disabled for a time irrespective of operation of the pain button. This lockout interval differs for different agents and it is determined by the peak effect of the drug. (e.g. lockout interval of morphine is 10–20 min).
 
HOW TO WRITE AN ORDER FOR PCA?
  • Loading (bolus) dose (if required)
  • Demand dose
  • Lockout interval
  • Background infusion (if any)
  • 1 and 4 hour limit
671
 
Information to be Gathered While Using PCA Pump
  • Drug name
  • Dose
  • Concentration
  • Amount of drug administered
  • Number of successful and unsuccessful doses
  • Breakthrough analgesics administered.
 
Advantages of PCA
  • Superior analgesia compared with other methods
  • More patient satisfaction
  • Reduced complications
  • Minimal effect of pharmacokinetic and pharmacodynamic variability
  • Less requirement of nursing care
  • Improved respiratory function.
 
Disadvantages
  • Cost
  • Possibility of operation error
  • Device malfunction (rare)
  • No difference found in the hospital or ICU stay compared with other methods
  • Higher incidence of pruritus.
 
Key Points About PCA
  • Optimal demand dose should be chosen since it differs for every patient. Inadequate dose can cause inadequate analgesia and excessive demand dose results in respiratory depression. Dosages of drugs used for PCA and patient-controlled epidural analgesia (PCEA) is given in Tables 91.1 and 91.2.
  • With the exclusion of background infusion, the incidence of respiratory depression is less since respiratory depression is common only with the use of background infusion. Patients who have opioid tolerance like patients on chronic malignant or non-malignant pain with persistence of pain even after usual or incremental PCA dose is one of the indication for background infusion.
  • Standard institution guidelines, documentation and monitoring are required to avoid adverse effects.
  • Factors associated with respiratory depression are old age, associated pulmonary disease, background infusion, concomitant administration of sedatives.
  • Management of side effects of opioid administration like nausea and vomiting is done by prescribing serotonin or dopamine antagonists. Pruritus is treated by diphenhydramine and in case of excessive sedation, opioid is changed.
  • Multimodal analgesic approach can reduce the complications associated with most of the drugs.672
Table 91.1   Patient-controlled analgesia dose for intravenous opioids in adults
Drug concentration
Continuous infusion
Demand dose (PCA bolus)
Lockout interval
4 hour limit
Morphine
(1 mg/mL)
1–2 mg/hr
1–2 mg
5–10 minutes
30 mg or equivalent/hr
Fentanyl
(10 µg/mL)
0–50 µg/hr
20–50 µg
5–10 minutes
Buprenorphine
(30 µg/mL)
30–100 µg
10–20 minutes
Tramadol
0–20 mg/hr
10–20 mg
5–10 minutes
Table 91.2   Patient-controlled epidural analgesia dose in adults
Drug concentration
Continuous infusion
Demand dose (PCA bolus)
Lockout interval
Maximum limit
Thoracic surgery
0.0625%–0.125% bupivacaine + 5 µg/mL fentanyl
0.1%–0.2% ropivacaine + 5 µg/mL fentanyl
3–4 mL/hr
3–4 mL/hr
2–3 mL
2–3 mL
10–15 minutes
10–20 minutes
Abdominal and lower extremity surgery
0.0625%–0.125% bupivacaine + 2 µg/mL fentanyl
0.1%–0.2% ropivacaine + 2 µg/mL fentanyl
4–6 mL/hr
3–5 mL/hr
3–4 mL
2–5 mL
10–15 minutes
10–20 minutes
Labor analgesia
0.0625%–0.125% bupivacaine + 2 µg/mL fentanyl
0.1%–0.2% ropivacaine + 2 µg/mL fentanyl
4–6 mL/hr
4–6 mL/hr
3–4 mL
3–4 mL
10–15 minutes
10–15 minutes
25 mL/hr
30 mL/hr
Much of the complications associated with epidural and intravenous route like hypotension, bradycardia and the adverse effects of opioids can be reduced by the use of continuous peripheral nerve blockade infusions.
 
Advantages of Peripheral Nerve Block Infusions (Table 91.3)
 
BIBLIOGRAPHY
  1. Camu F, Van Aken H, Bovill JG. Postoperative analgesic effects of three demand-dose sizes of fentanyl administered by patient-controlled analgesia. Anesth Analg. 1998; 87:890.
  2. Dawson PJ, Libreri FC, Jones DJ, et al. The efficacy of adding a continuous intravenous morphine infusion to patient-controlled analgesia (PCA) in abdominal surgery. Anaesth Intensive Care. 1995;23:453.
  3. Etches RC. Respiratory depression associated with patient-controlled analgesia: A review of eight cases. Can J Anaesth. 1994;41:125.
  4. Hudcova J, McNicol E, Quah C, et al. Patient controlled opioid analgesia versus conventional opioid analgesia for postoperative pain. Cochrane Database Syst Rev. 2006;4:CD003348.
  5. Looi-Lyons LC, Chung FF, Chan VW, et al. Respiratory depression: An adverse outcome during patient-controlled analgesia therapy. J Clin Anesth. 1996;8:151.
  6. Macintyre PE. Safety and efficacy of patient-controlled analgesia. Br J Anaesth. 2001; 87:36.
  7. Paech MJ. Patient controlled epidural analgesia in obstetrics. Int J Obstet Anesth. 1996;5:115-25.
674Airway Management in ICU
Chapter 92 Rapid Sequence Induction Prem Kumar
Chapter 93 Endotracheal Intubation in Critical Care Prem Kumar, Dianitta Devapriya Veronica
Chapter 94 Tracheostomy A Meenakshi Sundaram675

RAPID SEQUENCE INDUCTIONCHAPTER 92

Prem Kumar
Rapid sequence induction (RSI) is an airway management technique to secure the airway with tracheal intubation as fast as possible to reduce the risk of pulmonary aspiration and hypoxemia. The risk of pulmonary aspiration is high in patients who had recent food intake and comes to the emergency department or intensive care unit (ICU) due to various causes (e.g. head injury) for airway management. Hence, RSI is done to reduce the incidence of pulmonary aspiration during endotracheal intubation.
 
ESSENTIAL COMPONENTS OF RAPID SEQUENCE INDUCTION (TABLE 92.1)
In case of hemodynamically unstable patients, ketamine (1–2 mg/kg) or etomidate (0.2–0.3 mg/kg) can be given. Before the cricoid pressure is released, the cuff of endotracheal tube is inflated, bilateral air entry checked over both sides and end tidal carbon dioxide (EtCO2) confirmation is also done. In patients with cardiac arrest, the technique is modified such that intravenous anesthetic agent or muscle relaxant is not administered. 10 N (Newtons) approximately equals 1 kg or equal to the pressure which causes pain on application of pressure to nasal bridge.
 
INDICATIONS OF RAPID SEQUENCE INDUCTION
  • Full stomach patients
  • Emergency surgery
  • Traumatic head injury with Glasgow coma scale ≤ 8
  • Emergency intubations.
 
CRICOID PRESSURE
The principle behind application of cricoid pressure is that it causes compression of tracheal and esophageal lumen and thus preventing passive regurgitation of stomach contents. Positioning is head up position since it has been shown to reduce rise of intragastric pressure thus reducing the risk of passive regurgitation. Cricoid pressure can reduce the lower esophageal sphincter tone, cause difficulty in laryngoscope insertion, reduce the view of larynx, causes difficulty in introducing the endotracheal tube and produces impediment to application of external laryngeal manipulation by the assistant to improve laryngeal view during intubation. If there is vomiting during application of cricoid pressure, there is chance of esophageal rupture. In that case, low cricoid pressure can be given to prevent esophageal rupture. Though the application of cricoid pressure is controversial on the basis of its impediment to intubation and laryngoscopy, still because of ethical issues, studies could not be done to validate its value. According to current literature, its use in emergency department and ICU is still practiced. There is a practice of inserting nasogastric tube before induction to empty the stomach contents although pulmonary aspiration can still occur even after emptying the stomach with nasogastric tube. To prevent aspiration pneumonitis, drugs like H2 receptor antagonists, proton pump inhibitors can be given increase the pH. This can be prescribed if there is some time before intubation like obstetric patients, patients with risk of gastroesophaseal reflux disease (GERD). In patients with trauma and suspected cervical spine injury, RSI with manual inline stabilization is done for endotracheal intubation.
In case of desaturation, cricoid pressure is released on the basis of risk benefit ratio, bag and mask ventilation is done. Failed intubation plan should be borne in mind with all the necessary equipment kept ready prior to induction in patients who are performed RSI. Laryngeal mask airway, combitube are all alternative 679devices useful in failed intubation during RSI. Succinylcholine dose can be lowered (0.25–1 mg/kg) in critically ill patients since the recovery of spontaneous ventilation from lower doses is also faster. In patients with anticipated difficult intubation, obese patients, hemodynamically unstable patients, the usual dose of 1–2 mg/kg is recommended.
 
ALTERNATIVE TO SUCCINYLCHOLINE–ROCURONIUM?
In patients where there are contraindications to the use of succinylcholine such as burns, muscular dystrophies, hyperkalemia, open globe injury, massive soft tissue injuries, rocuronium is the best alternative since it has short onset of action. Rocuronium, 0.9–1.2 mg/kg is the only nondepolarizing muscle relaxant with short onset of action (60–90 seconds). Disadvantage is its long duration of action and the possibility of failed intubation which may end up in airway catastrophe.
 
BIBLIOGRAPHY
  1. Henderson JJ, Popat MT, Latto IP, et al. Difficult Airway Society guidelines for management of the unanticipated difficult intubation. Anaesthesia. 2004;59:675-94.
  2. Hocking G, Roberts FL, Thew ME. Airway obstruction with cricoid pressure and lateral tilt. Anaesthesia. 2001;56:825-8.
  3. Maltby JR, Beriault MT. Science, pseudoscience and Sellick. Can J Anaesth. 2002; 49:443-7.
  4. Mellin-Olsen J, Fasting S, Gisvold SE. Routine preoperative gastric emptying is seldom indicated. A study of 85,594 anaesthetics with special focus on aspiration pneumonia. Acta Anaesthesiol Scand. 1996;40:1184-8.
  5. Neelakanta G, Chikyarappa A. A review of patients with pulmonary aspiration of gastric contents during anesthesia reported to the Departmental Quality Assurance Committee. J Clin Anesth. 2006;18:102-7.
  6. Smith KJ, Dobranowski J, Yip G, et al. Cricoid pressure displaces the esophagus: An observational study using magnetic resonance imaging. Anesthesiology. 2003;99: 60-4.

ENDOTRACHEAL INTUBATION IN CRITICAL CARECHAPTER 93

Prem Kumar, Dianitta Devapriya Veronica
Endotracheal (ET) intubation is one of the common procedures done in intensive care unit (ICU). The purpose of intubation is to ensure optimal oxygenation and ventilation in critically ill patients. Usually endotracheal intubation is done in patients where noninvasive methods of securing airway has failed and in patients who require immediate airway management due to life-threatening risk factors (e.g. upper airway obstruction). This chapter discusses the basic anatomy, indications, preintubation fast-track airway assessment, techniques of airway management, difficult airway management and complications.
 
BASIC ANATOMY
The nasopharynx is important with respect to airway. The base of the skull forms the roof of the nasopharynx, and the soft palate forms the floor. Hence, the enlargement of adenoids can cause obstruction of upper airway and can get injured during nasal intubation. In the same way, tonsillar enlargement can cause impediment in viewing the larynx during laryngoscopy. Larynx is related superiorly by the hypopharynx and inferiorly continues with the trachea (Fig. 93.1).
The larynx consists of articulating cartilages—thyroid, cricoid, arytenoids, epiglottic, corniculate and cuneiform cartilages. The cricoid cartilage completely encircles the airway and is attached to the first tracheal ring by the cricotracheal ligament. In case of securing the airway by performing a needle cricothyrotomy, the cricoid cartilage is palpated and the cricotracheal ligament is pierced. The true vocal cords and space between them is called glottis. All muscles of larynx are supplied by the recurrent laryngeal nerve except the cricothyroid which is supplied by the external branch of the superior laryngeal nerve. Glottis is the narrowest region of the upper airway in an adult whereas cricoid region is the narrowest in children. The carina is located at T4 level and the angulation of right main bronchus is less acute than the right making the right side more prone for endobronchial intubation (Table 93.1).
 
FAST-TRACK EVALUATION AND AIRWAY ASSESSMENT BEFORE INTUBATION
In case of emergency, where the need for intubation is immediate, a fast-track evaluation of the patient and the airway is done to avoid catastrophe. In the 681period of evaluation, the technique of intubation with the least possible trauma is planned.
Fig. 93.1: Laryngeal view on direct laryngoscopy
Table 93.1   Indications of endotracheal intubation
  • Acute airway obstruction
    • Traumatic airway injury
    • Infection—epiglottitis, laryngotracheobronchitis, retropharyngeal abscess
    • Burns causing smoke inhalation
    • Laryngeal edema
    • Laryngospasm
  • Head injury with GCS ≤8
  • Drug poisoning
  • Respiratory failure—causes of types 1 and 2
    • Acute respiratory distress syndrome
    • Pulmonary edema
    • Obesity hypoventilation syndrome
    • Neuromuscular disorders—Guillain Barré syndrome
    • Atelectasis
  • Cerebrovascular accident
  • Cardiac arrest
  • Patients who require pulmonary toileting
The following are examined before induction:
  • Head
  • Upper airway
  • Cervical spine
  • Temporomandibular joint
  • Dentition.
A faster way of assessing airway before induction is done. An evaluation to do that is LEMON assessment of airway (Table 93.2).682
Table 93.2   LEMON airway assessment
L—Look
E—Evaluate
M—Mallampatti class
O—Obstruction
N—Neck mobility
L—Look for external anatomic features suggestive of difficult airway
E—Evaluate interincisor distance, hyomental distance, distance between thyroid cartilage and floor of mouth
Interincisor distance—should accommodate 3 fingers
Hyomental distance—should accommodate 3 fingers
Thyroid cartilage to floor of mouth distance—should accommodate 2 fingers
M—Mallampati class
Mallampatti class is done to assess the oropharyngeal view. It should be done with the patient sitting in upright position with protrusion of tongue and without phonation. It has 4 grades. Grade 3 and 4 indicate difficult airway.
Grade 1—faucial pillars, uvula, soft palate, hard palate visible
Grade 2—uvula, soft palate, hard palate visible
Grade 3—base of uvula or none, soft palate, hard palate visible
Grade 4—only hard palate visible
O—Obstruction
Conditions causing obstruction in the airway (e.g. epiglottitis) should be assessed.
N—Neck mobility
Look for adequate neck flexion and extension. Patients with cervical spine collar will have difficulty in intubation. Normal flexion is 15–25 degree and extension is 75–85 degrees.
 
ADJUNCTS FOR AIRWAY MANAGEMENT
  • Face mask (Fig. 93.2)
  • Triple maneuver—head tilt, chin lift, jaw thrust
  • Airway—oropharyngeal, nasopharyngeal (Fig. 93.3)
  • Bag and mask ventilation
  • Laryngeal mask airway (Fig. 93.4)
  • Endotracheal tubes.
In this chapter, we will discuss the techniques with respect to endotracheal intubation (Fig. 93.5).
 
Equipment Required for Endotracheal Intubation (Fig. 93.6)
  • Mask with bag and valve device (Fig. 93.7)
  • Oral and nasal airways
  • Laryngoscope with different blades—straight and curved (Fig. 93.8)
  • ET tubes of various sizes (Table 93.3)
  • Stylet, bougies (Fig. 93.9)
  • Tape to fix ET tube (Fig. 93.10)683
    Fig. 93.2: Anatomical transparent silicone face mask
    Fig. 93.3: Oropharyngeal airway
  • Suction
  • Magill forceps (Fig. 93.11)
  • Syringe for cuff inflation
  • Poppits pillow
  • Difficult airway cart684
Fig. 93.4: Laryngeal mask airway (LMA)
Fig. 93.5: Position of intubation
685
Fig. 93.6: Airway equipment required in ICU for airway management
Fig. 93.7: Mask with bag and valve device (adult and pediatric)
686
Fig. 93.8: Laryngoscope with various size blades
Table 93.3   ET tube size for different ages
Age
Internal diameter in millimeter (mm)
Preterm neonate
2.5
Full term
3.0
≤6 years
Age/3 + 3.5
7 years and more
Age/4 + 4.5
Adult females
7.0–8.0 mm
Adult males
8.0–9.0 mm
Fig. 93.9: Gum elastic bougie for aiding intubation
687
Fig. 93.10: Endotracheal tubes of various sizes
Fig. 93.11: Magill's forceps
 
INTUBATION TECHNIQUES
  • General anesthesia with rapid sequence induction
  • Local anesthesia
  • Awake intubation with flexible fiberoptic bronchoscopy
Most of the patients who require intubation in ED or ICU are patients who have depressed consciousness with poor GCS. In patients who are prone for aspiration, rapid sequence induction is done. In awake and alert patients, sedation with anesthetic agents may be required. In patients who require awake 688intubation, lignocaine is given topically to anesthetize the upper airway (Table 93.4). In cases of emergency, orotracheal intubation is done and is preferred by most intensivists. But nasotracheal intubation can be done if the intubation is not an emergency and there are no contraindications for it. Nasotracheal intubation has the advantage of having better patient tolerability and lesser incidence of tube kink due to biting by the patient. The intensivist/anesthesiologist who does the intubation should have the standard monitoring—electrocardiogram (ECG), noninvasive blood pressure, pulse oximetry, and capnography.
Table 93.4   Drugs used for endotracheal intubation
Drug
Dose
Adverse effects
Comments
Propofol
1–2 mg/kg
Hypotension, propofol infusion syndrome
Can be used in all patients who are hemodynamically stable
Thiopentone
3–5 mg/kg
Hypotension, precipitates porphyria
Reduces intracranial tension by reducing cerebral blood flow. Hence preferred in traumatic brain injury
Ketamine
0.5–2 mg/kg
Hypertension, increased ICT
Used in hemodynamically unstable patients
Etomidate
0.2–0.3 mg/kg
Adrenocortical suppression
Can be used in hypotension
Midazolam
0.02–0.5 mg/kg
Hypotension
Muscle relaxants
Succinylcholine
Rocuronium
1–2 mg/kg
0.9–1.2 mg/kg
Hyperkalemia, increased ICT, phase 2 block
Duration can be prolonged in liver disease. Used for rapid sequence induction.
Can be used as an alternative for succinylcholine in patients with contraindications for succinylcholine
In emergency, intubation is done with rapid sequence induction (RSI). RSI is discussed in detail in the next chapter.
 
MANAGEMENT OF DIFFICULT AIRWAY
American Society of Anesthesiologists (ASA) definition for difficult airway is the clinical situation where conventionally trained anesthesiologist experiences difficulty with mask ventilation, tracheal intubation or both (Flow chart 93.1).
It can be either anticipated (e.g. orofacial trauma) or unanticipated. In patients with anticipated difficult airway, awake intubation through various techniques can be used like direct laryngoscopy after topical anesthesia, intubating LMA, blind nasal intubation, retrograde intubation, rigid bronchoscopy, lighted stylet, flexible fiberoptic bronchoscope or surgical airway. Among these, flexible fiberoptic bronchoscopy is the commonly used technique among awake intubations.689
Flow chart 93.1: Difficult airway algorithm for unanticipated difficult airway
 
Suspected Cervical Spine Injury
A trauma patient is always considered to have full stomach and is at risk for aspiration during induction. The causes of pulmonary aspiration are recent intake of food or liquid, delayed gastric emptying due to trauma-induced stress response, swallowed blood from oral or nasal injuries. It is imperative to administer nonparticulate antacids to a trauma patient before induction if there is possibility of delay for intubation and the patient is alert with good airway reflexes. The usual practice is that all blunt trauma victims are considered to have cervical spine involvement unless proved otherwise. The airway management in these patients requires attention since the usual laryngoscopy would cause 690movement of cervical joint and thus cause worsening of cervical injury. Thus, the management in these patients requires manual in-line axial stabilization to prevent worsening of cervical injury. This technique requires 4 personnel trained in the procedure. One person to perform mask ventilation, one person to provide in-line cervical stabilization, one person to give cricoid pressure, one person to administer drugs (Fig. 93.12). If cervical collar is present, it should be removed since it will interfere with laryngoscopy. Video laryngoscopes like bullard or glidescope can be useful in these scenarios. Flexible fiberoptic bronchoscope can be used for cooperative patients who are devoid of oropharyngeal bleeding, airway bleeding and secretions and rapid hypoxemia.
Fig. 93.12: Manual in-line axial stabilization (MIAS) for suspected cervical spine injury
 
CARE OF ENDOTRACHEAL TUBE IN ICU
Securing the ET tube is of prime importance and it is secured with an adhesive tape fixed to the cheeks. In case of burns patient, a strap is tied to the back of neck. Adequate suctioning of the ET tube with a separate suction catheter is done according to need in patients with ET tube to prevent blockade. Suctioning is done along with ventilation through the suction port to avoid hypoxemia (closed ventilation suctioning). In case of nonavailability of closed ventilation system, high FiO2 is kept for few minutes before suctioning. Complications like hypertension, hypoxemia, cardiac arrhythmias, mucosal damage, and increased ICT can occur during suctioning. Suction catheters are usually 45–50 cm in length and to avoid obstruction of the ET tube, the outer diameter of the suction catheter should be less than half the size of the internal diameter of the endotracheal tube. The practice of instilling normal saline into the airway before suctioning to aid secretion removal is not recommended. Cuff pressures are monitored with manometers and maintained between 15 and 25 mm Hg. Complications of endotracheal intubation is given in Table 93.5.691
Table 93.5   Complications of endotracheal intubation
Cardiac complications
  • Tachycardia
  • Hypertension
  • Bradycardia due to vagal stimulation
  • Cardiac arrhythmias
During intubation
  • Dental injury
  • Injury to oral cavity, trachea, larynx
  • Arytenoid cartilage dislocation
  • Bleeding
  • Aspiration
  • Spinal cord injury
  • Hypoxemia
Sore throat
Vocal cord injury—edema
Hypoglossal nerve injury
Laryngitis
Complications due to ET tube
  • Blocking of ET tube due to secretions
  • Kinking
  • Endobronchial intubation
  • Tracheal stenosis
Since the ET tube bypasses the natural orifices, humidification is required in patients where invasive mechanical ventilation is done. There are two devices which can be used for humidification in ventilated patients:
  1. Heated water bath humidifier—external active source of heat and water is given.
  2. Heat and moisture exchanger filter (HMEF): It passively retains the heat and humidity, leaving the trachea during expiration and recycles it during the next inspiration. HMEFs are also known as hygroscopic condenser humidifiers. HMEFs are nowadays combined with bacterial filters to prevent infection. Disadvantage is increased resistance which can cause increased work of breathing.
 
BIBLIOGRAPHY
  1. ATLS for Doctors. Student Manual, 7th edn. Chicago, American College of Surgeons, 2004.
  2. Cooper RM, Pacey JA, Bishop MJ, et al. Early clinical experience with a new video laryngoscope (GlideScope) in 728 patients. Can J Anaesth. 2005;52:191-8.
  3. Ehrhart IC, Hofman WF, Loveland SR. Effects of endotracheal suction versus apnea during interruption of intermittent or continuous positive pressure ventilation. Crit Care Med. 1981;9:464.
  4. Harold Ellis, Stanley Feldman, William harrop Griffith. Anatomy for anaesthetists, 8th edn. Denmark: Blackwell Publications; 2004.
  5. 692Hurni J-M, Feihl F, Lazor R, et al. Safety of combined heat and moisture exchanger filters in long-term mechanical ventilation. Chest. 1997;111:686.
  6. Landa JF, Kwoka MA, Chapman GA, et al. Effects of suctioning on mucociliary transport. Chest. 1980;77:202.
  7. Majernick TG, Bieniek R, Houston JB, et al. Cervical spine movement during orotracheal intubation. Ann Emerg Med. 1986;15:417-20.
  8. Murphy MF, Walls RM. Manual of Emergency Airway Management. Chicago; Lippincott Williams and Wilkins; 2000.
  9. Rau JL. Airway management. In: Wilkins RL, Stoller JK, Scanlan CL (Eds). Egan's Fundamentals of Respiratory Care, 8th edn, St. Louis: Mosby; 2003.p.627.
  10. Sackner MA, Landa JF, Greeneltch N, et al. Pathogenesis and prevention of tracheobronchial damage with suction procedures. Chest. 1973;64:284.
  11. Shim C, Fine N, Fernandez R, et al. Cardiac arrhythmias resulting from tracheal suctioning. Ann Intern Med. 1969;71:1149.
  12. Snell RS, Katz J. Clinical Anatomy for Anesthesiologists. Norwalk, CT, Appleton and Lange, 1988.
  13. Turkstra TP, Craen RA, Pelz DM, et al. Cervical spine motion: A fluoroscopic comparison during intubation with lighted stylet, Glide Scope, and Macintosh laryngoscope. Anesth Analg. 2005;101:910-5.
  14. Wahlen BM, Gercek E. Three-dimensional cervical spine movement during intubation using the Macintosh and Bullard laryngoscopes, the Bonfils fibrescope and the intubating laryngeal mask airway. Eur J Anaesthesiol. 2004;21:907-13.

TRACHEOSTOMYCHAPTER 94

A Meenakshi Sundaram
Tracheostomy is a common procedure done for many medical conditions. It is one of the most common procedures done in intensive care units.
Tracheotomy: Operative procedure that creates an opening in the trachea.
Tracheostomy: Creation of permanent or semi-permanent opening in the trachea. Based on the need for tracheostomy, it is broadly classified as:
  • Emergency tracheostomy
  • Elective tracheostomy.
 
EMERGENCY TRACHEOSTOMY
Most basic and gold standard procedure in emergency room for upper airway obstruction is tracheostomy. It is employed when airway obstruction is complete or almost complete and there is an urgent need to establish the airway where intubation or laryngotomy are either not possible or feasible in such cases.
 
Indications
Upper airway obstruction due to:
  • Foreign body
  • Trauma: External injury of larynx and trachea, trauma due to endoscopies, especially in infants and children, fractures of mandible or maxillofacial injuries.
  • Infections: Acute laryngotracheobronchitis, acute epiglottitis, diphtheria, Ludwig's angina, peritonsillar, retropharyngeal or parapharyngeal abscess, tongue abscess.
  • Laryngeal edema: Due to steam, irritant fumes or gases, allergy (angioneurotic or drug sensitivity), radiation.
  • Bilateral abductor paralysis
  • Congenital anomalies: Laryngeal web, cysts, tracheoesophageal fistula, bilateral choanal atresia
  • Malignancies: Benign and malignant neoplasms of larynx, pharynx, upper trachea, tongue and thyroid.694
 
Prerequisites for Emergency Tracheostomy
  • Nonmetallic tracheostomy tube with vent for connecting the ventilator
  • Retractors, cricoid hook, tracheal dilator, artery forceps curved and straight
  • 2% lignocaine with adrenaline suction, good lighting.
 
Technique for Emergency Tracheostomy
Whenever possible, endotracheal intubation should be done before tracheostomy. This is specially important in infants and children. Positioning is supine position with a pillow under the shoulders for neck extension. Usually anesthesia is not required for these patients since most of them are either unconscious or it is emergency. In conscious patients, infiltration is done with 2% lignocaine with adrenaline or in some patients, general anesthesia with intubation may be necessary before performing tracheostomy.
 
Steps of Tracheostomy
  • Incision (vertical or horizontal) is made 1 cm below the cricoid cartilage or halfway between cricoid and sternal notch.
  • Retractors are placed, the skin is retracted, and the strap muscles are visualized in the midline. The muscles are divided along the raphe, then retracted laterally.
  • The thyroid isthmus lies in the field of the dissection. Typically, the isthmus is 5–10 mm in its vertical dimension, mobilize it away from the trachea and retract it, then using syringe loaded with 4% lignocaine, the lumen is punctured and the syringe is aspirated to visualize air bubbles to confirm the position and 0.5 cc of lignocaine is injected into trachea to reduce the cough reflex and then place the tracheal incision in the second or third tracheal ring.
  • Tracheostomy tube of appropriate size is introduced after dilating the stoma with tracheal dilator.
  • The position of tube is confirmed by connecting to ambu bag and auscultating the chest.
  • The tube is fixed and secured around the neck.
  • The tube cuff inflated at a cuff pressure of 20–25 mm Hg.
  • Skin incision should not be sutured or packed tightly as it may lead to development of subcutaneous emphysema.
  • Gauze dressing is placed between the skin and flange of the tube around the stoma.
 
ELECTIVE TRACHEOSTOMY
This is a well-planned procedure done in various settings (Table 94.1).
 
Types of Elective Tracheostomy
It is of two types
  1. Therapeutic: To relieve respiratory obstruction, remove tracheobronchial secretions or give assisted ventilation.695
    Table 94.1   Indications of elective tracheostomy
    • Major head and neck surgery (often temporary airway)
    • Bypassing upper airway obstruction
    • Chronic ventilator dependency
    • Relieving OSA
    • Eliminating pulmonary dead space
    • Management of secretions, including aspiration:
      • Inability to cough
        • Coma of any cause, e.g. head injuries, cerebrovascular accidents, narcotic overdose
        • Paralysis of respiratory muscles, e.g. spinal injuries, polio, Guillain-Barré syndrome, myasthenia gravis
        • Spasm of respiratory muscles, tetanus, eclampsia, strychnine poisoning
      • Painful cough
        Chest injuries, multiple rib fractures, pneumonia
      • Aspiration of pharyngeal secretions
        Bulbar polio, polyneuritis, bilateral laryngeal paralysis
    Fig. 94.1: Types of tracheostomy
  2. Prophylactic: To guard against anticipated respiratory obstruction or aspiration of blood or pharyngeal secretions such as in extensive surgery of tongue, floor of mouth, mandibular resection or laryngofissure.
 
TYPES OF TRACHEOSTOMY (FIG. 94.1)
 
High Tracheostomy
It is done above the level of thyroid isthmus. Perichondritis of the cricoid cartilage and subglottic stenosis are complications of high tracheostomy. Only indication is carcinoma of larynx because in such cases, total larynx anyway would ultimately be removed and a fresh tracheostome made in a clean lower area.
 
Mid-tracheostomy
This is the preferred one. It is done through the 2nd or 3rd ring and would entail division of the thyroid isthmus or its retraction upwards or downwards to expose this part of trachea.696
 
Lower Tracheostomy
It is done below the level of isthmus. Trachea is deep at this level and close to several large vessels and also there are difficulties with tracheostomy tube which impinge on suprasternal notch.
 
Tracheostomy Tubes
An ideal tracheostomy tube should be flexible enough to reduce tissue damage, increase patient comfort and rigid enough to maintain airway. A tracheostomy is arc-shaped which is called as Jackson curve.
 
Parts of a Tracheostomy tube
  • Outer cannula: This forms the main body of the tube that passes into the trachea. The inner diameter of outer tube mostly forms the stated size of the tube.
  • Inner cannula: This can be inserted into the outer tube and can be removed for cleaning purpose.
This tube is longer and narrower than outer tube. It secured in place by locking it with outer tube (Figs 94.2 and 94.3) (Tables 94.2 and 94.3).
Table 94.2   Types of tracheostomy tubes
  • Single lumen tubes
  • Double lumen tubes
  • Uncuffed tubes
  • Cuffed tubes
  • Fenestrated tubes
  • Adjustable flange tubes.
Table 94.3   Different features of tracheostomy tubes
Manufacturer
Material
Inner tube
Cuffed tube
Speaking valve
Portex
Polyurethane
No
Both
Yes
Shiley
PVC
Yes
Both
Yes
Tracoe
Polyurethane
Yes
Both
Yes
Bivona
Silicone
No
Cuffed
No
Moore
Silastic
No
Uncuffed
No
Negus
Silver
Yes
Uncuffed
Yes
 
CRICOTHYROIDOTOMY/MINITRACHEOSTOMY
It is a procedure of creating a communication between airway and skin through cricothyroid membrane.697
Fig. 94.2A and B: Metal Fuller's tracheostomy tube
Figs 94.3A and B: Portex cuffed tracheostomy tube
 
Types
  • Needle cricothyroidotomy
  • Open
  • Percutaneous.
Advantages of minitracheostomy
  • Simplicity
  • Relatively bloodless field
  • Minimal training required
  • Avoids hyperextension of neck in patients with cervical injury.698
 
Cricothyroidotomy in Children
The clear cutoff age for doing cricothyroidotomy in children is unclear. It is commonly agreed that it is not usually done in children below 12 years. In young children, membrane is more smaller, larynx is funnel-shaped, rostral and compliant and hence there are more chances of subglottic stenosis.
 
Anatomy
Neck kept in neutral or extended position, the thyroid prominence is palpated. The next big prominence just below it is cricoid cartilage. Just one finger above cricoid cartilage is a depression, which is cricothyroid membrane.
Surgical anatomy: Entry point is the cricothyroid membrane in the midline below the level of the vocal cords. The tube enters through the skin, subcutaneous fat, middle cricothyroid ligament of cricothyroid membrane and subglottic larynx mucosa.
Needle cricothyroidotomy: Needle size of 12 or 14 gauge is used. It is done only when there no other options for securing the airway in emergency situations.
 
Surgical Steps
  • Position the patient with the neck extended and exposed.
  • Identify the landmarks, thyroid cartilage, cricoid cartilage, cricothyroid membrane.
  • Prepare a sterile field
  • Inject 2% lidocaine with 1 in 1,00,000 epinephrine into skin and through the cricothyroid membrane into airway to anesthetize and suppress cough reflex
  • Fix the thyroid cartilage with 1st and 3rd fingers of non-dominant hand and freely palpate with 2nd finger the cricothyoid membrane.
  • With the dominant hand, insert the 14-gauge intravenous cannula attached to syringe with normal saline directing it caudally at 45°.
  • As the needle is advanced, apply negative pressure. Air bubbles will enter the fluid-filled syringe as the needle enters the membrane and enters the trachea.
  • Advance the cannula and remove the needle.
  • Apply jet ventilation at 15 L/minute.
  • Auscultate for breath sounds and monitor with pulse oximetry.
 
Potential Advantages of Tracheostomy Over Tracheal Intubation
  • Lesser sedation needed for tube acceptance
  • More patient comfort with regard to oral hygiene, mobilization and phonation
  • Reduced risk of laryngeal damage due to prolonged intubation
  • Reduced airway resistance and respiratory effort
  • Shorter duration of weaning from mechanical ventilation
  • More effective cough
  • Shorter ICU stay.699
 
Percutaneous Dilational Tracheostomy
Percutaneous dilational tracheostomy (PDT) usually requires general anesthesia. Neuromuscular blockers may be needed.
 
Instruments Required
  • PDT-kit.
  • Laryngoscope, intubation tray, equipment for difficult airway should be kept ready.
  • Optional: Fiberoptic bronchoscope.
  • Optional: Ultrasound.
 
Technique
  • Patient positioning with neck extended, pillow under the shoulders.
  • Direct laryngoscopy done after retracting the ET tube such that the cuff is just beneath the vocal cords and difficult airway assessed.
  • The cricoid and thyroid cartilage are marked. The optimal site of tracheostomy is below the lower border of cricoid cartilage corresponding to second and tracheal cartilage. More proximal placement raises the chance of subglottic stenosis whereas more distal placement raises the chances of erosion of great vessels in mediastinum.
  • After sterile preparation, local infiltration given along with adrenaline.
  • A 8–12 mm horizontal incision made at chosen level. Smaller incision is made to reduce the amount of bleeding, chance of infection and keeping a tight-fitting stoma.
  • Introduction of guidewire: The cuff of tracheal tube is deflated and trachea is punctured in midline and guidewire is introduced. Clinical confirmation of intratracheal placement is done.
  • Stomal dilation with one or more dilators possibly with dilating forceps.
  • Choice of tracheal cannula is done by clinical judgement.
 
Rule of Thumb for Selecting the Cannula
  • Use adjustable flange for patients with deep seated trachea.
  • Use tube wire for patients with chances of tube kinking (short neck, obesity, caudally placed stoma).
 
Tracheostomy Care
  • Humidification: After the procedure, the normal physiology of the respiratory tract is altered. Humidifiers are used for patients on tracheostomy tubes for humidification.
    Types of humidifiers:
    • Hot-water humidifier
    • Cold-water humidifier
    • Heat and moisture exchanger
    • Nebulization
  • 700Suctioning: Every tracheostomy patient needs adequate suctioning at appropriate timing for avoiding block by secretions. Things required for suctioning are suction unit, suction catheter, O2 through t-piece.
 
Suctioning Technique
Explain the procedure if patient is conscious. The appropriate size catheter is introduced with the suction kept off. Once the depth needed is reached, suction unit is switched on and the airway suctioned with oxygen being given through the tube. Suctioning is done at frequent intervals to avoid block by secretions.
 
BIBLIOGRAPHY
  1. Claudia Russell, Basil Matta. Tracheostomy: A Multiprofessional Handbook. 1st Edition, Cambridge University Press.
  2. Fagan J. Cricothyroidotomy and Needle cricothyroidotomy, 1st edn. University of Cape Town.
  3. Gleeson, Scott Brown's otorhinolaryngology, Head and Neck surgery, 7th edn. Butterworth-Heinemann.
  4. Paul W Flint, Bruce H Haughey, Valerie J Lund, John K Niparko, Mark A Richardson, K Thomas Robbins, J Regan Thomas. Cummings otolaryngology Head and neck surgery, 6th edn. Elsevier Publications.
701Transfusion practice in ICU
Chapter 95 Blood Transfusion: Components and Indications Prem Kumar
Chapter 96 Complications of Blood Transfusion Prem Kumar

BLOOD TRANSFUSION: COMPONENTS AND INDICATIONSCHAPTER 95

Prem Kumar
Blood transfusion therapy is one of the important interventions done in critically ill patients to increase hematocrit, correct coagulation abnormalities and optimize oxygen delivery. Since blood components are associated with adverse effects due its use, its use is restricted to specific indications. In critical care, anemia, thrombocytopenia and coagulation abnormalities are all frequent indications for use of blood component therapy. In this chapter, we will discuss the method of blood component separation and indications of blood components.
 
COMPONENT SEPARATION (Flow chart 95.1)
Various blood components separated from whole blood are:
  • Packed red cells
  • Platelets
  • Fresh frozen plasma
  • Cryoprecipitate
Flow chart 95.1: Blood component separation
704
Table 95.1   Preservatives used in packed red cells
Citrate—anticoagulant
Phosphate—buffer
Dextrose—red cell energy source
Adenine—it allows RBCs to resynthesize adenosine triphosphate (ATP), thus extending the storage time from 21 days to 35 days
 
Packed Red Cells
Packed red cells are obtained by removing plasma from whole blood. Usual volume of packed red cells is 350 mL which is stored at 1–6°C. The hematocrit value is 40% in whole blood and 70% in packed red cells. Whole blood was used in the past decade for volume expansion and increasing O2 carrying capacity but according to recent guidelines, packed red cells can be used for most of the indications related to whole blood with respect to blood loss, anemia. Whole blood can be used in severe hemorrhage. Solutions recommended for administering reconstituted packed red cells are 5% dextrose in half normal saline, 5% dextrose in 0.9% saline, 0.9% saline with a pH of 7.4. Citrate phosphate dextrose adenine (CPDA-1) is an anticoagulant preservative added with blood. Other preservatives that can be used are adsol, optisol. Hypothermia slows the rate of glycolysis (Table 95.1).
 
Compatibility
In case of emergency where the patient sustains massive blood loss, it is permissible to transfuse O-ve packed red cells but the sample should be sent for grouping before transfusion. But with modern technology, it is possible to obtain ABO compatibility within 5 minutes and cross matching within 30 minutes.
 
Storage
On storage, intracellular release of potassium occurs, RBC's metabolize glucose to lactate, hydrogen ions accumulate, and plasma pH decreases and many intensivists believe that prolonged storage is less effective in O2 carrying capacity than the fresh one. The storage temperatures of 1–6°C stimulates sodium-potassium pump and hence the RBC loses potassium and gain sodium. Osmotic fragility increases thus resulting in lysis and there is progressive decrease in RBC concentrations of ATP and 2,3-DPG. To avoid such complications, storage of blood in an electrostatic field of 500–3000 V decreases hemolysis and reduces the decrease in pH.
Other guidelines from various societies—American Society of Anesthesiologists task force, the British Committee for Standards in Haematology have recommended that transfusion is generally not indicated when the hemoglobin concentration is above 10 g/dL but is indicated when it is less than 6–7 g/dL. They have not mentioned a specific transfusion trigger. But according to recently published guidelines (Table 95.2), they recommend a restrictive blood transfusion strategy that is when the hemoglobin level is <7 g/dL for adult trauma and critical care patients, with the exception of patients with acute myocardial ischemia.705
Table 95.2   Indications of packed red cells
The AABB (American Association of Blood Banks) recommends a restrictive transfusion strategy.
  • Red cell transfusion should be considered at hemoglobin concentrations of ≤7 g/dL in adult and pediatric intensive care unit patients. Patients should be hemodynamically stable– class 1 recommendation.
  • In postoperative surgical patients, transfusion should be considered at a hemoglobin concentration of ≤8 g/dL or when there are symptoms (orthostatic hypotension or tachycardia unresponsive to fluid resuscitation, chest pain, congestive heart failure)—class 2 recommendation
  • In cardiovascular disease, red cell transfusion is considered when hemoglobin is ≤8 g/dL but the evidence is less for its strong recommendation although it can be considered.
Other indications
  • Symptomatic anemia
  • Prophylaxis in life-threatening anemia
  • Hemorrhage—to restore the O2 carrying capacity
  • Exchange transfusion
  • Sickle cell disease
  • Severe parasitic infection (malaria, babesiosis)
  • Severe methemoglobinemia
  • Severe hyperbilirubinemia of newborn
 
Dosage and Administration
ABO group of RBC products must be compatible with ABO group of recipient, red cells should be serologically compatible with the patient. After therapy, 1 unit of packed red cells raise the hemoglobin by approximately 1 g/dL or hematocrit of 3%. This principle holds good only in a patient weighing 70–80 kg. The rate of transfusion is approximately over 15 minutes and transfusion is completed within 4 hours. As a general guide, transfusing a volume of 4 mL/kg will typically give an Hb increase of 1 g/dL. In patients with minor blood loss but ongoing, Hb should be regularly monitored, after every 2–3 units of red cells. Pediatric red cell transfusions should be prescribed in milliliters. It may take up to 24 hours for equilibration of intravascular volume after transfusion.
 
Processing of RBC's
  • Leukocyte reduction—decrease the risk of febrile nonhemolytic transfusion reactions, infections and HLA alloimmunization
  • Washing is done for removal for residual plasma—decrease the risk of anaphylactic reactions.
  • Irradiation—prevents transfusion associated graft-versus-host disease (TA-GVHD).
 
Platelets
Platelet concentrates are obtained by differential centrifugation from freshly drawn blood or from donors from whom large amount of platelets are obtained by platelet pheresis techniques. Indications of platelet transfusion is given in 706Table 95.3. Platelets play an important role in the initial phase of hemostasis where platelets adhere by von Willebrand factor (vWF) and adhesive proteins to the subendothelium. Platelets are the only blood component that is stored under room temperature and can be stored for 5 days according to current guidelines. It is stored under room temperature since platelets lose shape and release their granular contents when refrigerated. Bacterial contamination is common because of its storage under room temperature and still higher if kept at 20–24°C. Sepsis from a bacterially contaminated platelet transfusion is the most frequent infectious complication from any blood product. Any patient who develops fever within 6 hours of platelet transfusion, sepsis from platelets should be considered. Platelets are responsible for allergic and nonhemolytic febrile reactions.
Table 95.3   Indications of platelet transfusion
Hospitalized adult patients with therapy-induced hypoproliferative thrombocytopenia
  • Prophylactic transfusion in adults with platelet count of ≤10 × 109/L to reduce the risk for spontaneous bleeding
  • Transfusion up to a single apheresis unit or equivalent. Greater doses are not more effective, and lower doses equal to one half of standard apheresis unit are equally effective
Adult patients having minor invasive procedures
  • Prophylactic platelet transfusion for patients having elective central venous catheter placement with a preprocedure platelet count of 20 × 109 cells/L
  • Prophylactic platelet transfusion for patients having elective diagnostic lumbar puncture with a preprocedure platelet count of 50 × 109 cells/L
Adult patients having major elective noneuraxial surgery
  • Prophylactic platelet transfusion for patients having major elective nonneuraxial surgery with a preprocedure platelet count of 50 × 109 cells/L
  • Platelet transfusion is considered for patients on CPB (cardiopulmonary bypass) who exhibit perioperative bleeding with perioperative bleeding with thrombocytopenia and platelet dysfunction
  • Routine prophylactic administration of platelets are not recommended in patients on CPB
Adult patients receiving antiplatelet therapy who have intracranial hemorrhage (traumatic or spontaneous)
  • There is no specific recommendation for or against platelet transfusion for patients receiving antiplatelet therapy who have intracranial hemorrhage
Patients who are not bleeding or having invasive procedures or surgery
  • Prophylactic platelet transfusion is done to patients with a platelet count below 10×109 per liter who are not bleeding or having invasive procedures or surgery, and who do not have any of the following conditions (chronic bone marrow failure, autoimmune thrombocytopenia, heparin-induced thrombocytopenia, thrombotic thrombocytopenic purpura.)
 
Different Types of Platelet Processing
  • Apheresis (collecting more platelets from one donor to avoid pooling of platelets from multiple donors)
  • Leukocyte—depleted platelets
  • Ultraviolet B–irradiated platelets
Whenever possible, ABO compatible platelets should be administered. Up to 8 units of platelets, each from a separate donor can be pooled into a single bag for transfusion and all units should be from the same ABO type. The usual adult dose is 1 unit/15 kg of body weight. In case of prophylactic transfusions, 7074–6 units of pooled random donor platelets are used. 1 unit of platelet transfusion increases platelet count by 7000–10,000/mm3 in a patient with 70 kg weight when checked 1 hour after transfusion. The raise of platelet count may vary according to associated illness like sepsis, splenomegaly.
 
Fresh Frozen Plasma
1 unit of fresh frozen plasma (FFP) is the plasma obtained from 1 unit of whole blood and it contains all plasma proteins. Factors 5 and 8 reduces on storage. It should be frozen within 8 hours of collection and may provided as frozen or thawed. 1 unit contains 250 mL and ABO compatibility is done. The administration of both red cells and FFP is not recommended except in few situations like massive blood transfusion. It has high-risk of infection like hepatitis B, hepatitis C, and HIV. Indications of FFP is given in Table 95.4
 
Dosage
Fresh frozen plasma is given at a volume of 10–15 mL/kg except for reversal of warfarin where 5–8 mL/kg is sufficient. Usually doses are given to achieve a minimum of 30% of coagulation factors concentration. 1 unit of FFP raises coagulation factors by 2–3%.
 
Cryoprecipitate
Cryoprecipitate is prepared from plasma and it contains fibrinogen, von Willebrand factor, factor VIII, factor XIII, and fibronectin. Cryoprecipitate is the only adequate fibrinogen concentrate available for transfusion. It is given ABO compatible.
 
Indications
 
Dosage and Administration
  • 1 bag will increase fibrinogen concentration by 7–8 mg/dL in a 70 kg patient.
  • In case of use in von Willebrand disease or hemophilia, the usual dose is 1 bag per 10 kg of body weight.
  • Cryoprecipitate should be administered rapidly and through a filter and the rate of administration should be at least 200 mL/hour, and infusion should be completed within 6 hours of thawing.
  • Fibrin glue can be prepared from cryoprecipitate for local hemostasis.
 
BIBLIOGRAPHY
  1. British Committee for Standards in Haematology (BCSH) Guideline on the Administration of Blood Components. August 2012.
  2. Carson JL, Terrin ML, Noveck H, Sanders DW, Chaitman BR, Rhoads GG, et al. FOCUS Investigators. Liberal or restrictive transfusion in high-risk patients after hip surgery. N Engl J Med. 2011;365:2453-62.
  3. Dunne WM, Case LK, Isgriggs L. In-house validation of the BACTEC 9240 blood culture system for detection of bacterial contamination in platelet concentrates. Transfusion. 2005;45:1138-42.
  4. He'bert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med. 1999;340:409-17.
  5. Jeffrey L Carson, et al. Red blood cell transfusion: A clinical practice guideline from the AABB. Ann Intern Med. 2012;157:49-58.
  6. Lacroix J, He'bert PC, Hutchison JS, Hume HA, Tucci M, Ducruet T, et al. TRIPICU Investigators. Transfusion strategies for patients in pediatric intensive care units. N Engl J Med. 2007;356:1609-19.
  7. Moore GL, Peck CC, Sohmer PR, et al. Some properties of blood stored in CPDA-1 solution. Transfusion. 1981;21:135.
  8. Napolitano LM, Kurek S, Luchette FA, Anderson GL, Bard MR, Bromberg W, et al. EAST Practice Management Workgroup. Clinical practice guideline: red blood cell transfusion in adult trauma and critical care. J Trauma. 2009;67:1439-42.
  9. Nishiyama T, Hayashi D. Electrostatic field can preserve red blood cells in stored blood preparations. J Anesth. 2007;21:42-6.
  10. Richard M Kaufman, et al. Platelet Transfusion: A clinical practice guideline from the AABB. Ann Intern Med. 2015;162:205-13.
  11. Roback, et al. Evidence-Based Practice Guidelines For Plasma Transfusion. Transfusion. 2010;50:1227-39.
  12. Slichter SJ. Principles of platelet transfusion therapy, In: Hoffman R, Benz EJ, Shattil SJ, et al (Eds): Hematology Basic Principles and Practice. New York, Churchill-Livingstone; 1991.pp.1610-22.
  13. Valeri CR. Measurement of viable ADSOL-preserved human red cells. N Engl J Med. 1985;312:377.
  14. Weigert AL, Schafer AL. Uremic bleeding: pathogenesis and therapy. Am J Med Sci. 1998;316:94-104.

COMPLICATIONS OF BLOOD TRANSFUSIONCHAPTER 96

Prem Kumar
Complications due to transfusion can cause infections, anaphylactic reactions, electrolyte disturbances, coagulation abnormalities and acid-base disturbances. Adverse reactions due to transfusion occur in spite of checks. In this chapter, we will discuss the various complications due to blood component therapy (Table 96.1).
 
ADVERSE REACTIONS TO TRANSFUSION
Adverse reactions can occur with mild symptoms and signs in the background of severe reactions. In the event of an adverse reaction, transfusion should be immediately stopped and reported to the blood bank.
Certain reactions can be reduced or prevented by filtering, irradiating or washing blood components. The incidence of viral infections has come down due to screening although the transfusion reactions and bacterial sepsis continue.
 
Transfusion Reactions (Table 96.2)
 
Febrile Nonhemolytic Transfusion Reaction
It is the most common common transfusion reaction occurring after transfusion of component containing cellular elements. This occurs due to sensitization of antigens on donor leukocytes, HLA antigens and cytokines; and it usually occurs within 1 hour of completion of the transfusion. Leukodepletion will reduce the incidence of these reactions.710
Table 96.1   Complication of blood transfusion
Types of complication
Comments
Infectious
Hepatitis B
Hepatitis C
HIV–1, –2
CMV
Human T-lymphotropic virus (HTLV-II)
Malaria
Babesiosis
West Nile virus
Uncommon infections—syphilis, Chagas’ disease, variant Creutzfeldt-Jakob disease, parvovirus B19, and severe adult respiratory syndrome (SARS)
Transfusion reactions
Febrile nonhemolytic transfusion reaction
Delayed hemolytic reaction
Transfusion-related acute lung injury (TRALI)
Acute hemolytic reaction
Anaphylactic
Other reactions
RBC allosensitization
HLA allosensitization
Graft-versus-host disease (GVHD)
Table 96.2   Types of reactions
Immune mediated  
Nonimmune mediated
Acute hemolytic transfusion reactions
Delayed hemolytic transfusion reactions
Febrile nonhemolytic transfusion reactions
Anaphylactic reactions
Allergic reactions
Graft-versus-host disease (GVHD)
Transfusion-related acute lung injury (TRALI)
Post-transfusion purpura
Alloimmunization
Hypothermia
Iron toxicity
Electrolyte disturbances
Hypotension
Immunomodulation
 
Acute Hemolytic Transfusion Reactions
Immunemediated hemolysis occurs when the recipient has preformed antibodies and among these, ABO isoagglutinins are the reason for most of these reactions. Clinical features include chills, fever, chest and flank pain, flushing, nausea, hemoglobinemia, hemoglobinuria, hypotension, tachypnea, tachycardia. Lab investigations include measurement of serum haptoglobin, lactate dehydrogenase (LDH), and indirect bilirubin levels which are indicative of hemolysis. Coagulation studies are also done. Error of patient identification and mislabelling are all causes of reaction and in the blood bank, direct Coombs test is done. Immune complex resulting from the reaction can cause renal dysfunction and RBC lysis which, in turn, releases tissue factor which may initiate DIC. Management of acute hemolytic transfusion reactions is given in Table 96.3.711
Table 96.3   Management of acute hemolytic transfusion reactions
  • Terminate the transfusion immediately
  • Maintain urine output of 0.5–1 mL/kg/hour by administering IV fluids and diuretics (furosemide 20–40 mg, mannitol 0.5 g/kg over 10–20 minutes)
  • Alkalinization of urine is done by administering bicarbonate of 40–70 mEq. Goal is to raise urine pH to 8
  • Do coagulation studies, serum and urine hemoglobin concentration
  • Send the blood bag to blood bank for investigation where direct antiglobulin test is done. Also to send patient blood and urine.
 
Delayed Hemolytic Reaction
It can occur due to patients who are previously sensitized to RBC alloantigens with low antibody levels resulting in negative alloantibody screen. Usually the alloantibodies are detected in the circulation after 1–2 weeks post-transfusion. No specific treatment is required for patients where these reactions have occurred.
 
Anaphylactic and Allergic Reactions
It can occur even with a few milliliter of blood component. Clinical features are dyspnea, bronchospasm, vomiting, hemodynamic instability, respiratory failure. Management includes immediate termination of the transfusion, epinephrine 0.5–1 mL of 1:1000 subcutaneously. Steroids may be required. Patients who have an event of anaphylactic or allergic reactions to any blood component should be tested for IgA deficiency. Plasma proteins can cause urticarial lesions and it can be treated by diphenhydramine 50 mg orally or intramuscularly. It can be prevented by administering diphenhydramine before transfusion. Washing of cellular components to remove residual plasma can reduce the incidence of this complication.
Transfusion-related acute lung injury
Transfusion-related acute lung injury (TRALI)—Acute respiratory distress, either 1–2 hours after transfusion or within 6 hours of transfusing the patient and presents as noncardiogenic pulmonary edema. Clinical features include fever, dyspnea, fluid in the endotracheal tube, severe hypoxia, bilateral interstitial infiltrates on chest X-ray. There is absence of left atrial hypertension. TRALI usually results from the transfusion of plasma although any blood product can cause it. Pathophysiology is that the anti-HLA antibodies in the donor plasma binds the recipient leukocytes and gets aggregated in the pulmonary vessels and causes increased capillary permeability causing pulmonary edema. Management is mainly supportive and the patient usually recovers within 4–5 days. TRALI is the leading cause of transfusion-related death.
Graft versus host disease
It is a complication of allogeneic stem cell transplantation where the donor T lymphocytes recognize the recipient HLA antigens and initiate immune response. Clinical features include fever, diarrhea, cutaneous eruption, leukopenia, thrombocytopenia and liver function abnormalities. Irradiation of blood component can reduce the incidence of this complication. Sepsis is the cause of death in GVHD.712
 
Nonimmunologic Reactions
 
ODC Curve
Shift of ODC curve to the left can occur when there is decrease in 2,3 DPG and thus causing more affinity of oxygen to hemoglobin thus resulting in reduced O2 delivery.
 
Citrate Intoxication and Hyperkalemia
Citrate toxicity occurs due to binding of calcium by citrate and thus causing hypocalcemia. Clinical features of hypocalcemia include narrow pulse pressure, hypotension but the incidence is rare. It can occur in a few situations such as liver disease, massive blood transfusion, pediatric patients, during liver transplant and hypothermia.
On prolonged storage of blood, RBC lysis can cause intracellular release of potassium and it can be as high as 20 mEq/L in blood stored for more than 2 weeks. It requires more than 120 mL/minute for the occurrence of hyperkalemia which can occur only in massive blood transfusion. Hence, rapid infusion rate is a risk factor for hyperkalemia although still it is very rare. Management is administration of 10% calcium gluconate, beta 2-agonists and insulin with dextrose.
 
Hypothermia
Administration of blood stored at 4°C and frozen plasma without warmers can cause of hypothermia resulting in cardiac arrhythmias. Increased warming of blood can cause RBC lysis. The practice of warming blood in warm water before administration should be avoided.
 
Acid-base Disturbances
The pH of the stored blood is acidic because of the addition of preservative which is acidic hence the pH of blood reduces over prolonged storage. Acidosis is both metabolic and respiratory, respiratory acidosis is due to the plastic bag from which the CO2 doesn't have a way for diffusion although this becomes insignificant after transfusion because of ventilation by the patient. But on massive transfusion, citrate gets converted to bicarbonate thus causing metabolic alkalosis.
 
Coagulation Abnormalities
In case of trauma, coagulation cascade is initiated and may cause consumption coagulopathy. It is due to the volume of blood given and the duration of hypotension which determines the coagulopathy. On massive transfusion, the most common cause of bleeding is due to dilutional thrombocytopenia rather than DIC. Other causes of bleeding include low factor 5 and 8, hemolytic transfusion reaction, DIC-like syndrome. Low fibrinogen level suggests DIC-like syndrome.713
Table 96.4   Lab investigations for diagnosing various transfusion-related infections
Virus
Lab test
Hepatitis B
Hepatitis B surface antigen (HbsAg)
Hepatitis C
Antibodies to HCV and HCV RNA
HIV
Antibodies to HIV–1, HIV–1 p24 antigen, and HIV RNA using NAT
Cytomegalovirus
Antibody to CMV
Human T-lymphotropic virus (HTLV)
Antibody to HTLV-I and -II
Infectious complications
It can be viral or bacterial. Viral infections cause morbidity and mortality. Other than the viruses mentioned above in Table 96.4, lab tests for screening other agents like parasites (malaria, dengue, etc.) are done according to the geographical incidence and local infection epidemiology.
Bacterial contamination
Usually, bacterial contamination occurs due to platelet since they are stored at room temperature. The risk of bacterial overgrowth is more with single unit platelet than apheresis product. Patients infected with bacteria can develop rapid onset (usually within minutes of transfusion) of fever and chills which differentiates bacterial contamination from febrile nonhemolytic transfusion reaction. The end result of bacterial contamination is sepsis. Coagulase-negative staphylococci, Gram-negative organisms are common. Management is immediate termination of the transfusion, reporting to blood bank, broad spectrum antibiotics, supportive treatment and the blood is sent for culture. Though packed RBC and FFP are not commonly contaminated with bacteria because of the storage temperature of 1–6°C, still gram-negative organisms like Pseudomonas, Escherichia, Serratia, Acinetobacter can contaminate the blood component.
 
MASSIVE BLOOD TRANSFUSION
 
Definition
Transfusion of blood more than patient's blood volume in 24 hours or transfusion of >10% blood volume in <10 minutes or >50% of blood volume in 4 hours in an adult. Massive transfusion is given in detail in Chapter 76.
 
Complications
Hypocalcemia due to citrate, hypothermia, hyperkalemia due to release of potassium on cell lysis, metabolic alkalosis due to citrate conversion to lactate and, in turn, to bicarbonate, ARDS, DIC. The most common cause of bleeding following massive blood transfusion is dilutional thrombocytopenia.714
 
BIBLIOGRAPHY
  1. Brohi K, Cohen MJ, Ganter MT, et al. Acute traumatic coagulopathy: Initiated by hypoperfusion. Ann Surg. 2007;245:812-8.
  2. Brubaker DB. Clinical significance of white cell antibodies in febrile nonhemolytic transfusion reactions. Transfusion. 1990;30:733-7.
  3. Cohen ND, Muñoz A, Reitz BA, et al. Transmission of retroviruses by transfusion of screened blood in patients undergoing cardiac surgery. N Engl J Med. 1989;320:1173.
  4. Heddle NM, Kelton JG. Febrile nonhemolytic transfusion reactions. In: Popovsky MA (Ed): Transfusion Reactions, 2nd edn. Bethesda, MD, AABB Press; 2001.pp.55-62.
  5. Kleinman S, Caulfield T, Chan P, et al. Toward an understanding of transfusion-related acute lung injury: statement of a consensus panel. Transfusion. 2004;44:774-89.
  6. Linko K, Tigerstedt I. Hyperpotassemia during massive blood transfusions. Acta Anaesthesiol Scand. 1984;28:220.
  7. Miller RD, Robbins TO, Tong MJ, et al. Coagulation defects associated with massive blood transfusions. Ann Surg. 1971;174:794.
  8. Miller RD. Complications of massive blood transfusions. Anesthesiology. 1973;39:82.
  9. Parshuram CS, Jaffe AR. Prospective study of potassium-associated acute transfusion events in pediatric intensive care. Pediatr Crit Care Med. 2003;4:65-8.
  10. Toy P, Popovsky MA, Abraham E, et al. Transfusion-related acute lung injury: definition and review. Crit Care Med. 2005;33:721-6.
  11. Zhou L, Giacherio D, Cooling L, Davenport RD. Use of B-natriuretic peptide as a diagnostic marker in the differential diagnosis of transfusion-associated circulatory overload. Transfusion. 2005;45:1056-63.
715Fluid Management
Chapter 97 Perioperative Fluid Balance Prem Kumar
Chapter 98 Fluid Resuscitation Prem Kumar716

PERIOPERATIVE FLUID BALANCECHAPTER 97

Prem Kumar
Understanding fluid balance is vital to the fluid management in perioperative and critically ill patients admitted in ICU. This chapter deals with the basic physiology and assessment of fluid balance.
 
BASIC PHYSIOLOGY OF FLUID BALANCE
 
Fluid Compartments (Fig. 97.1 and Table 97.1)
Total body water (TBW) constitutes approximately 60% of body weight.
The ions present in ECF are sodium (Na+), chloride (Cl), bicarbonate (HCO3) and relatively little contribution from potassium (K+), magnesium (Mg2+), and plasma proteins (albumin). The ions present in ICF are potassium (K+), magnesium (Mg2+) and phosphates (PO42+). Potassium maintains electroneutrality.
Fig. 97.1: Fluid compartments
Table 97.1   Composition of various fluid compartments
Ion
Plasma (mOsm/L)
Interstitial space (mOsm/L)
Intracellular (mOsm/L)
Na+
142
139
14
K+
4
4
140
Cl
108
108
4
HCO3
24
28
10
HPO4 H2PO4
2
2
11
Mg+
0.8
0.7
20
Protein
1.2
0.2
4
Total osmolality
301
300
301
718Osmolality is defined as the number of osmoles which determines the osmotic pressure and is expressed in milliosmoles per kg of water (mOsm/kg). Osmosis is the net diffusion of water across a selectively permeable membrane from a region of high water concentration to one that has lower water concentration. The pressure required to drive this migration is called osmotic pressure. The osmolal concentration of a solution is called osmolality when the concentration is expressed as osmoles per kilogram of water and it is called osmolarity when it is expressed as osmoles per liter of solution.
Water distribution across compartments depends mainly on Na+ and K+ content of each compartment, hence the effective osmolality of each compartment is determined mainly by the osmotic effect of Na+ and K+ acting across the cell membrane. Cell membrane is highly permeable to water but less permeable to sodium and chloride. So water moves across the cell membrane rapidly, so that the intracellular fluid remains isotonic with the extracellular fluid.
The primary site of exchange of water between interstitial and intravascular space are the post capillary venules and capillaries. Diffusion is also another mechanism involved in the exchange of ions. Net filtration of water and ions are determined by starling's law which is dependent upon hydrostatic and oncotic pressure.
Net filtration = Kf x (Pc – Pif – pc + pif)
where,
Kf is the capillary filtration coefficient
Pc is the capillary hydrostatic pressure,
Pif is the interstitial fluid hydrostatic pressure,
pc is the capillary plasma colloid osmotic pressure,
pif is the interstitial fluid colloid osmotic pressure.
Therefore, fluid homeostasis is critical in any perioperative patient since there are fluctuations in both water and solute balance. Preservation of blood volume by autoregulation at various systems (especially cellular level and kidneys) thus maintaining normal circulatory volume and adequate cardiac output is the key for tissue perfusion. Both volume regulation and regulation of osmolality plays important role in fluid homeostasis.
 
Normal Exchange of Fluid and Electrolytes
Normally a person consumes about 1.5–2 liters of water per day. But the daily water loss is approximately 1 liter in urine, 500 mL as insensible loss (skin and respiratory system) and 250 mL in stools. In critically ill patients, conditions causing increased basal metabolic rate and metabolism like fever, hyperventilation, sepsis, etc. can increase the insensible water loss. Increased sweating can cause loss of water and electrolytes. Electrolyte homeostasis is maintained by kidneys.719
Table 97.2   Conditions with reduced and normal extracellular volume
Reduced ECF volume
Normal ECF volume
1. Hemorrhage—trauma, blood loss
2. Renal loss of sodium—use of diuretics, diabetes insipidus, hypoaldosteronism
3. Extrarenal loss of sodium—GI loss, third space loss, respiratory loss
1. Cardiac failure
2. Pulmonary embolism
3. Valvular heart disease
 
Regulation of Fluid Balance
Effective circulatory volume is based on the regulation of sodium balance and is dependent on renin angiotensin aldosterone system (RAAS), sympathetic activity, natriuresis by atrial natriuretic peptide and vasopressin. Sympathetic activation causes release of catecholamines and regulates vascular resistance and cardiac output. Reduced renal perfusion causes activation of RAAS, and angiotensin causes vasoconstriction and Na+ retention by secreting aldosterone. Fluid balance in the perioperative period requires knowledge about the negative fluid balance caused by fasting, third space loss, blood loss calculation and allowable blood loss, vasodilatation caused by anesthetic agents. Fluid management in perioperative period requires calculation of the volume, choosing the type of fluid according to the fluid and electrolyte requirement.
 
Disturbances in Fluid Balance
Surgical patients have fluid disturbances in the intraoperative and postoperative period, and deficits in the extracellular volume is most commonly seen (Table 97.2). It can be acute and chronic. Acute volume deficit is associated with tachycardia, hypotension, oliguria, azotemia. Chronic volume deficits cause decrease in skin turgor, weight loss, ileus. Volume deficits cause elevation in blood urea nitrogen levels, hemoconcentration, low urine sodium (< 20 mEq/L), urine osmolality > serum osmolality. Sodium level cannot be taken as a reliable marker to reflect volume status since it can be high, normal or even low during hypovolemia. Common cause of extracellular fluid loss in perioperative surgical patients are loss of gastrointestinal fluids (nasogastric suction, vomiting, diarrhea, or fistula), burns, intra-abdominal infections, peritonitis, soft tissue injuries, burns, prolonged surgery, intestinal obstruction (Table 97.3).
 
Assessment of Fluid Balance
A feasible and a rational approach has to be formulated according to the resources available. Based upon this, the following approach is useful for assessment of fluid balance in perioperative period:
  • History
  • Clinical assessment
  • Monitoring and diagnosing the cause of fluid imbalance.720
Table 97.3   Electrolyte composition of GI fluids and sources of losses in the perioperative period
Source of loss
Na+
K+
HCO3
Cl
Gastric fluid (e.g. vomiting)
50–80
5–15
100–120
Duodenum (e.g. fistula)
130–140
5–10
10–40
70–100
Pancreatic fluid (e.g. fistula)
120–140
5–10
90–100
50–90
Biliary (e.g. fistula)
130–150
5–10
30–50
80–110
Ileal (e.g. fistula)
100–130
5–10
20–40
80–100
Colon (obstruction, colostomy, diarrhea)
50–70
20–40
20–40
30–50
Sweat (e.g. hypermetabolism)
20–50
5–10
40–60
 
History
  1. Comorbid illness
  2. Hydration and volume status of the preoperative period.
Clinical assessment is done in terms of hemodynamics—heart rate, blood pressure. Tissue and organ perfusion in terms of urine output, intact consciousness, mental function and capillary refilling time.
721Monitoring can be done both by routine monitors or in case of critically ill patients, advanced hemodynamic monitoring is done to indirectly know the intravascular volume status with cardiac filling, heart function, and end-organ perfusion (lactate). In patients with hypovolemia, anesthetic drugs and stress response secondary to surgery and pain cause derangements in blood pressure and heart rate. Invasive beat to beat blood pressure monitoring, central venous pressure, cardiac filling pressures with transesophageal echocardiography, mixed venous oxygen tension (SvO2), pulmonary artery catheterization are all done to know the static hemodynamic parameters. Pulse pressure variation, stroke volume variation are all dynamic parameters done for hemodynamic assessment. In the past, fluid boluses were given as challenge to see the hemodynamic response and management is done thereafter according to the response but nowadays fluid challenge is said to be obsolete and dynamic tests with volume challenge without administering fluids are done with PLRT (passive leg raising test). It is clear from studies that incorrect and improper fluid management results in increased morbidity and mortality.
 
BIBLIOGRAPHY
  1. F Charles Brunicardi. Schwartz's Principles of Surgery, 8th edn. McGraw-Hill publications; 2004
  2. Ganong WF. Review of Medical Physiology, 21st edn. McGraw-Hill publications; 2003.
  3. Guyton and Hall. Textbook of Medical Physiology, 11th edn. 2006. Elsevier publications.
  4. Lobo DN, Macafee DA, Allison SP. How perioperative fluid balance influences postoperative outcomes. Best Pract Res Clin Anaesthesiol. 2006;20:439-55.
  5. Miller RD. Miller's Anesthesia, 7th edn. Elsevier publications; 2009.
  6. Starling EH. On the absorption of fluids from the connective tissue spaces. J Physiol. 1896;19:312-26.
  7. Taylor AE. Capillary fluid filtration: Starling forces and lymph flow. Circ Res. 1981; 49:557-75.

FLUID RESUSCITATIONCHAPTER 98

Prem Kumar
Fluid management is vital in both postoperative and critically ill patients in ICU since fluid homeostasis are required to maintain adequate tissue and organ perfusion. The aim of fluid therapy in postoperative and critically ill patients is to maintain an effective circulatory volume to produce adequate cardiac output while avoiding fluid overload. Maintaining an optimal fluid balance is quite challenging since it is difficult to measure the end points of optimal fluid balance. In this chapter, we will discuss the principles of fluid therapy in postoperative and critically ill patients along with details of crystalloids and colloids and fluid management for various specific conditions.
 
FLUID MANAGEMENT IN PERIOPERATIVE PATIENTS
Perioperative patients require maintenance fluids to replace the ongoing losses of water and electrolytes under normal physiological conditions. Apart from this, replacement fluid therapy is given for deficits resulting from bleeding, third space loss, GI loss, sweating and loss associated with open surgical site.
 
Maintenance Fluid Therapy
Maintenance fluid therapy is administered to replace the ongoing losses of water and electrolytes under normal physiologic conditions and is calculated based on the standard ongoing loss in an adult weighing 70 kg which is 30–35 mL/kg/day. Maintenance fluid is calculated according to the 4–2–1 rule till the patient is fasting (Table 98.1).
Table 98.1   4–2–1 rule
For the 1st 10 kg
4 mL/kg/hr
For the next 10 kg (11–20 kg)
Add 2 mL/kg/hr
For weight >20 kg
Add 1 mL/kg/hr
Maintenance fluid is administered with isotonic crystalloids with the calculated volume of fluids. For example, maintenance fluid requirement for a 60 kg patient is calculated here: 40 mL/hr + 20 mL/hr + 40 mL/hr = 100 mL/hr.723
For the 1st 10 kg
4 mL/kg/hr–40 mL/hr
For the next 10 kg (11–20 kg)
Add 2 mL/kg/hr–20 mL/hr
For weight >20 kg
Add 1 mL/kg/hr–40 mL/hr
 
Replacement Fluid Therapy (Table 98.3)
The purpose of administering replacement fluids in the perioperative period is correcting the current existing deficit along with ongoing water and electrolyte loss. It is usually given for deficits resulting from bleeding, third space loss, GI loss, sweating and loss associated with open surgical site. Total fluid deficit due to the former enumerated causes can't be calculated like maintenance fluid, hence the fluid therapy is arbitrarily done by clinical assessment (hemodynamics, pulse volume, capillary refilling), measured fluid loss, and plasma Na+ which is not a reliable estimate for intravascular volume although it can estimate water balance.
The choice of fluid administered for this purpose is based on the clinical condition or scenario causing the loss, volume of fluid lost and electrolyte disturbance. The Table 98.2 depicts the choice of fluid for various clinical scenarios.
Table 98.2   Choice of fluid in certain clinical conditions
Clinical condition causing loss 
Choice of fluid
Blood loss
Replace 1 mL of blood loss with 3 mL of balanced, isotonic crystalloid solution or 1 mL of colloid solution/blood
Third space loss, bile, pancreas, and small bowel losses
Replace with balanced isotonic crystalloid solutions
Gastric and colonic losses
Replace with 5% dextrose and ½ normal saline with 30 mEq KCl/L
Profuse sweating (e.g. fever)
Replace with 5% dextrose and ¼ normal saline with 5 mEq KCl/L
Table 98.3   Key elements in the fluid management of perioperative patients
Preoperative period
Intraoperative period
Postoperative period
  • Preoperative evaluation of volume status and electrolyte abnormality and its correction
  • Third space loss should be corrected preoperatively in patients having burns, intestinal obstruction, and severe soft tissue injuries
  • Administration of maintenance fluids with 4–2–1 rule
  • Fluid management includes calculation of loss with respect to blood loss, anesthetic drugs causing vasodilatation, third space loss, ongoing loss
  • Correction of third space loss secondary to abdominal surgeries where bowel is exposed
  • Correction of volume deficit in the preoperative and intraoperative period
  • Correction of ongoing loss, third space loss along with maintenance therapy
  • All specific GI loss should be replaced with the appropriate fluid
  • Initial fluid of choice is isotonic crystalloids followed by dextrose with half normal saline in the 2nd or the 3rd postoperative day in case there is contraindication for enteral nutrition
  • In case of difficulty in ascertaining the volume deficit, advanced hemodynamic monitors are used to guide fluid therapy
724
Fig. 98.1: Classification of intravenous fluids
Fluid resuscitation is guided by the reversal of signs of volume deficit like return of hemodynamics to normal, maintenance of adequate urine output (0.5–1 mL/kg/hour), and correction of base deficit. In conditions where patients do not respond or fail to get corrected of their volume deficit (e.g. renal failure, cardiac failure), they require advanced hemodynamic monitoring in the intraoperative and postoperative period.
 
Intravenous Fluids
Intravenous fluids are broadly classified into crystalloids and colloids (Fig. 98.1). The choice of fluid administered depends on the electrolyte abnormality and the volume status. Crystalloids are aqueous solutions of inorganic and small organic molecules with or without glucose. Colloids are homogeneous non-crystalline substances containing large molecules especially proteins or large glucose polymers. Depending upon the concentration of solute and osmolality, crystalloids can be divided into isotonic, hypotonic, and hypertonic solutions but colloids with the capacity of containing large molecules remain in the intravascular space for a long time and maintain plasma colloid on cotic pressure than crystalloids and hence act as volume expanders.
 
Crystalloids
Crystalloids can be classified into balanced and unbalanced solutions. Crystalloids are nontoxic, cost-effective and generally safe since there is no incidence of allergic reactions. Balanced solutions contain physiologic electrolyte composition and buffers resembling plasma unlike unbalanced solutions. Isotonic crystalloids are preferred in perioperative period and ICU. Disadvantage of isotonic crystalloids is its reduced ability to stay longer in the intravascular space since sodium is the predominant ion present in most of the isotonic crystalloids and Na+ equilibrates over the whole ECF compartment and only ¼th of the administered crystalloid solution remains intravascular. Hence, in case of replacement of blood loss with isotonic crystalloids, 1: 3–4 times the volume of crystalloids has to be replaced for the intravascular blood loss. The intravascular half-life of crystalloids is 72520–30 minutes. The choice of the fluid is based upon the electrolyte composition especially Na+, K+, and Cl and its buffering capacity. Hypertonic 3% saline is administered in the treatment of severe symptomatic hyponatremia. 3% to 7.5% saline can be given for resuscitation of patients in hypovolemic shock but should be administered slowly through a central vein catheter. Along with colloids, hypertonic saline can be used for severe hemorrhage—this concept is called small volume resuscitation. In cases of severe hyponatremia, plasma Na+ concentration should be corrected slowly at a rate <10 mEq/L/day to avoid central pontine myelinolysis. Rate of correction should not exceed 15 mEq/L/day.
Complications due to administration of crystalloids: Normal saline causes non anion gap hyperchloremic metabolic acidosis on administration of large volumes. Other isotonic crystalloids like ringer lactate contains lactate which gets converted to HCO3 which may result in metabolic alkalosis and since it contains potassium, it should be cautiously used in patients with renal disease or in patients prone for hyperkalemia. Ringer lactate should not be coadministered with blood products or certain drugs like thiopentone since the presence of calcium in ringer lactate will precipitate these agents. In spite of administering 2–3 liters of crystalloids, if there is poor response of hemodynamics, colloids are added. Composition of various crystalloids is given in Table 98.4.
 
Colloids
Colloids are homogeneous noncrystalline substances containing large molecules especially proteins or large glucose polymers. Colloids remain in the intravascular space for a long time than crystalloids because of its large molecular weight. Its intravascular half-life is 3–6 hours. Colloids can be used for patients with hemorrhagic shock in case of delay in arrival of blood and in patients where hypovolemia is present with severe hypoalbuminemia (e.g. burns). Most of the colloids are manufactured in isotonic electrolyte solutions. Almost all the colloids interfere with blood typing and cross matching. Blood-derived colloids are albumin, synthetic colloids are dextran, hydroxyethyl starch, gelatin. Composition of various colloids is given in Table 98.5.
Table 98.4   Composition of various crystalloids
Fluid
Na+
K+
Cl
Glucose (g/L)
Buffers
Ca2+
Mg2+
pH
Osmolality
Normal saline (NS)
154
154
6.0
308
Ringer lactate (RL)
130
4
109
Lactate 28
3
6.5
274
Plasmalyte
140
5
98
Acetate 27 Gluconate 23
3
7.4
294
5% Dextrose
50
4.5
252
10% Dextrose
100
505
50% Dextrose
500
2530
5% Dextrose with ½ NS
77
77
50
5.0
406
5% dextrose with ¼ NS
3% Hypertonic saline
513
513
1026
7.5% Hypertonic saline
1284
1284
6.0
2568
726
Table 98.5   Composition of various colloids
Colloid
Sodium (meq/L)
Molecular Weight
Osmolality
Albumin 5%
130–150
70,000
300
Albumin 25%
130–150
70,000
1500
Hetastarch
154
4,50,000
310
Dextran 40
154
40,000
308
Dextran 70
154
70,000
308
 
Human Albumin
It is the purified form of human plasma and is available as 5% and 25%. Albumin has been used in the past for patients with hypovolemic shock, burns or hypoalbuminemia but according to recent studies, it is shown that albumin administration for such indications have not improved the outcome compared with crystalloids, hence considering the cost of albumin, its use is restricted only to specific indications. It use has been shown to maintain the plasma oncotic pressure for distribution of fluids. The incidence of allergic reactions is less compared with other colloids.
 
Dextran
It is synthesized from sucrose and it comes in 2 formulations—Dextran 40 and 70. Dextran molecules <50 KD are eliminated by the kidneys and the specific indication is improving the microcirculation by reducing blood viscosity and improving rheology. Useful for increasing perfusion of microvascular anastomoses in perioperative period. Maximal daily dose is 1.5 g/kg. Dextran induces dose dependent hyperfibrinolysis and decrease in vWF and associated factor VIII (VIII:c) which can cause bleeding. It has to be cautiously used in renal failure. Dextran 70 is used for volume expansion and Dextran 40 is used for improving microcirculation. It can cause anaphylactic reactions.
 
Gelatin
Gelatin is produced by degradation of bovine collagen. The molecular weight of gelatin is 30 kD with a concentration of 3.5–5.5%. Gelatin is excreted unchanged by the kidneys and by the reticuloendothelial system. It requires higher volume for adequate volume expansion. Hemostasis can be impaired by gelatin which 727causes impairment in fibrin polymerization and dysfunction of coagulation factors. They have increased risk of transmitting prion diseases and gelatin has the highest incidence of anaphylactic reactions among all the colloids.
 
Hydroxyethyl Starch (HES)
Hydroxyethyl starches are modified polysaccharides similar to glycogen and derived from amylopectin and cleaved by amylase. Various preparations of starch are hetastarch, tetrastarch, pentastarch and available as 3% and 6% solution. Small molecules are rapidly excreted by kidneys and large molecules are hydrolyzed by α-amylase before elimination. Plasma half-life increases with increase in molecular weight. HES is nonantigenic and anaphylactic reactions are less.
 
BIBLIOGRAPHY
  1. Alderson P, Bunn F, Lefebvre C, et al. Human albumin solution for resuscitation and volume expansion in critically ill patients. Cochrane Database Syst Rev. 2004;(4): CD001208.
  2. de Jonge E, Levi M. Effects of different plasma substitutes on blood coagulation: A comparative review. Crit Care Med. 2001;29:1261-7.
  3. Dubick MA, Bruttig SP, Wade CE. Issues of concern regarding the use of hypertonic/hyperoncotic fluid resuscitation of hemorrhagic hypotension. Shock. 2006;25:321-8.
  4. F Charles Brunicardi. Schwartz's Principles of Surgery, 8th edn. 2004. McGraw-Hill Publications.
  5. Finfer S, Bellomo R, Boyce N, et al. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. 2004;350:2247-56.
  6. Goldwasser P, Feldman J. Association of serum albumin and mortality risk. J Clin Epidemiol. 1997;50:693-703.
  7. Guyton, Hall. Textbook of Medical Physiology, 11th edn. Elsevier publications; 2006.
  8. Jacob M, Chappell D, Rehm M. Clinical update: Perioperative fluid management. Lancet. 2007;369:1984-6.
  9. Laxenaire MC, Charpentier C, Feldman L. Anaphylactoid reactions to colloid plasma substitutes: incidence, risk factors, mechanisms. A French multicenter prospective study. Ann Fr Anesth Reanim. 1994;13:301-10.
  10. Niemi TT, Suojaranta-Ylinen RT, Kukkonen SI, Kuitunen AH. Gelatin and hydroxyethyl starch, but not albumin, impair hemostasis after cardiac surgery. Anesth Analg. 2006; 102:998-1006.
  11. Roberts JS, Bratton SL. Colloid volume expanders: Problems, pitfalls, and possibilities. Drugs. 1998;55:621.
  12. Ronald D Miller. Miller's Anesthesia, 7th edn. Elsevier publications; 2009.
  13. Waters JH, Gottlieb A, Schoenwald P, et al. Normal saline versus lactated Ringer's solution for intraoperative fluid management in patients undergoing abdominal aortic aneurysm repair: An outcome study. Anesth Analg. 2001;93:817-22.
728Cardiopulmonary Resuscitation
Chapter 99 Basic Life Support Prem Kumar
Chapter 100 Advanced Cardiac Life Support Prem Kumar
Chapter 101 Cardiac Arrest in Special Situations Prem Kumar729

BASIC LIFE SUPPORTCHAPTER 99

Prem Kumar  
INTRODUCTION
Basic life support (BLS) is the cornerstone for resuscitating a patient with sudden cardiac arrest and stroke. It constitutes 4 things—early recognition of cardiac arrest, activation of emergency response system (ERS), early CPR cardiopulmonary resuscitation (CPR), and rapid defibrillation. If resuscitation is done outside the hospital, paramedical personnel use automated external defibrillator (AED) for BLS. AED's are present in most of the public places in order to resuscitate a patient with sudden cardiac arrest. AED correctly assesses heart rhythm, allowing the rescuer who is not trained with cardiac arrhythmias to correctly defibrillate the patient. This chapter deals with the basic life support as recommended by American Heart Association 2010 guidelines.
Sudden cardiac arrest can be:
  • In or out of hospital
  • Witnessed or unwitnessed
  • Cardiac or noncardiac cause.
Recognizing cardiac arrest is difficult for a lay person, hence if a lay person sees a person unresponsive, the lay person should immediately activate the ERS and start CPR. The reason for poor survival in patients with sudden cardiac arrest is the delay to start CPR. Hence, early chest compression is the critical component of CPR and it should not be delayed. Recommendation is to push hard and push fast for chest compressions but insertion of advanced airway and defibrillation should not delay or interrupt compressions. Rapid defibrillation is the best predictor of successful resuscitation following VF/VT-induced sudden cardiac arrest. The reduction in the duration between cardiac arrest and defibrillation has improved survival in patients sustaining cardiac arrest both in and out of hospital. Adult chain of survival is given in Table 99.1
Key changes from 2005 to 2010 AHA recommendations:
 
PHYSIOLOGY OF CARDIOPULMONARY RESUSCITATION
There are two mechanisms of cardiac output associated with chest compressions:
  1. Cardiac pump mechanism
  2. Thoracic pump mechanism.
 
Cardiac Pump Mechanism
Cardiac pump mechanism is based on the mechanism that chest compression causes ejection of blood from the ventricles due to compression between the sternum and vertebral column. On performing echocardiography during CPR, there was reduction in ventricular volumes on the LV and RV, closure of mitral and tricuspid valves and ejection of blood into great vessels indicating the cardiac pump mechanism.
 
Thoracic Pump Mechanism
Chest compression produces increase in intrathoracic pressure which equalizes the intravascular pressure within the thorax. There is venous collapse at the thoracic inlet and the arterial system being resistant to collapse transmits blood into extrathoracic vessels. The arteriovenous difference thus allows forward blood flow into the extrathoracic vessels. During increase in intrathoracic pressure, pulmonary valve is closed, mitral and aortic valves are open during chest compression indicating the thoracic pump mechanism. Vigorous cough causes increased intrathoracic pressure and it sustains consciousness during VF/VT cardiac arrest and increases forward blood flow-cough CPR.733
 
ADULT BASIC LIFE SUPPORT SEQUENCE (Flow chart 99.1)
 
Immediate Recognition and Activation of the Emergency Response System
If an unresponsive patient is seen, the bystander has to tap the patient for his responsiveness and if the patient is unresponsive, ERS is activated and if the patient does not have normal breathing or gasping, the patient is considered to have cardiac arrest and CPR is started immediately. Pulse should not be checked by the lay rescuer before starting CPR. In case of healthcare provider, he should not check the pulse for more than 10 seconds (Fig. 99.1 and Flow chart 99.2),
Flow chart 99.1: Adult basic life support sequence
Fig. 99.1: Rescuer specific cardiopulmonary resuscitation strategies
734
Flow chart 99.2: Adult basic life support for healthcare providers
Early defibrillation is the best predictor for survival in patients sustaining cardiac arrest. When more than 1 rescuer is present, one rescuer should start chest compression and the other one should activate the ERS and get an AED as soon as possible. Once the AED arrives, AED is turned on and the AED prompts are followed.
 
SEQUENCE OF ADULT BASIC LIFE SUPPORT SKILLS
Chest compression should be given with the patient kept on a firm surface. Hence, it is better to keep a back board on the bed before chest compression in order to give high quality CPR though there is limited evidence of its use. Rescuer should keep the heel of one hand on the middle of the patient's chest which corresponds to the lower half of sternum and other heel of the other hand is kept on the top of 735the first and it should be overlapped and parallel. Compressions are given at a rate of 30:2 with at least 100/minute and depth of at least 5 cm and the chest should be allowed to recoil completely after compression (Table 99.2). Incomplete recoil during CPR is associated with increased intrathoracic pressure which causes decreased coronary, myocardial and cerebral perfusion. The compression rate refers to the speed of compressions, not the actual number of compressions delivered per minute. The number of chest compressions delivered per minute is an important determinant of return of spontaneous circulation (ROSC) and intact neurological status. After 1 minute of CPR, fatigue is common and after 2 minutes or 5 cycles of CPR, switching of compressors is done. Interruptions should not exceed for >10 seconds.
Table 99.2   Early cardiopulmonary resuscitation
Chest compressions
Rescue breaths
  • Chest compressions are done by application of compression over the lower-half of sternum
  • Compressions increase cardiac output by direct compression of the heart and increasing intrathoracic pressure
  • Compression rate should be atleast 100/min and the depth should be atleast 5 cm with minimal interruption during compressions
  • Compression-ventilation ratio of 30:2 is recommended for adults
  • Lay rescuer can give only chest compressions in case of hesitation to give mouth to mouth rescue breaths
  • Trained rescuer can deliver rescue breaths by mouth to mouth or bag mask to provide ventilation and oxygenation
  • Deliver each rescue breath over 1 second
  • Sufficient tidal volume to produce visible chest rise is given on delivering rescue breaths
Once the advanced airway is in place, chest compressions are given continuously without interruptions and breaths are given at a rate of 8–10/minute (1 breath every 6–8 seconds).
 
AIRWAY MANAGEMENT (TABLE 99.3)
Head tilt–chin lift maneuver is done to open up the airway, and in case of suspected cervical spine injury, jaw thrust is given instead of head tilt–chin lift. It has been shown from studies that the cardiac output is approximately 25–30% of normal and hence oxygen uptake and carbon dioxide delivery to the lungs are also reduced and hence a low tidal volume of approximately 6–7 mL/kg (500–600 mL) is sufficient for effective oxygenation and ventilation during CPR. Excessive ventilation is deleterious since it increases intrathoracic pressure and impedes the venous return to the heart and causes reduced cardiac output. The routine use of cricoid pressure is not recommended since it was found to impede ventilation and delay the placement of advanced airway.
 
Special Situations
  • Acute coronary syndromes
  • Drowning
  • Stroke736
Table 99.3   Methods of ventilation
Mode of ventilation
Comments
Mouth-to-mouth breathing
Open the victim's airway, pinch the victim's nose, and create an airtight mouth-to-mouth seal
Take a regular breath and give 1 breath over 1 second
Mouth-to-barrier device breathing
Can be used in case of hesitation to do mouth-to-mouth breathing
Mouth-to-nose and mouth-to-stoma ventilation
Mouth-to-nose ventilation is given if ventilation through the patient's mouth is not possible and mouth to stoma rescue breaths is given in case of a patient with tracheal stoma
Bag and mask
Bag and mask device with an oxygen reservoir and oxygen inlet is used to allow delivery of high oxygen concentrations. Disadvantage is gastric insufflation
Bag and mask ventilation is done when there are ≥2 rescuers. The rescuer should use an adult reservoir (1–2 L) bag to deliver approximately 600 mL tidal volume and oxygen is supplemented with FiO2 >40% with minimum flow rate of 10–12 L/minute
Supraglottic airway
Recommended devices are LMA, esophageal-tracheal combitube and the King airway device. Acceptable alternative to bag and mask ventilation.
Endotracheal tube
Usual standard of airway in ICU but it needs more expertize and should be done by professionals for in hospital cardiac arrest.
  • Foreign body obstruction
  • Hypothermia.
 
Acute Coronary Syndromes
Early recognition, diagnosis and treatment of acute coronary syndrome improves the survival in these group of patients. The classic symptoms are chest discomfort, shortness of breath, sweating, nausea, and lightheadedness and the symptoms last more than 15 minutes. Immediate advice to chew aspirin (160–325 mg) is given. If the patient has a STEMI on ECG, it is better to immediately shift the patient for PCI and the survival is improved if the transport is <30 minutes and initial contact to balloon time is <90 minutes. Oxygen supplementation is given and nitroglycerine can be given for patients with chest discomfort and suspected ACS provided the patient is hemodynamically stable and does not have inferior wall or right ventricular infarction. Intravenous morphine is administered for persistent chest pain.
 
Drowning
The most important consequence of submersion is hypoxia, hence in drowning victims the guidelines recommends individualization of the sequence according to the presumed cause. CPR is done in ABC sequence in drowning victims owing to the hypoxic nature of the arrest. Prompt initiation of rescue breathing increases the victim's chance of survival. When the victim is taken from the water, 737the rescuer should open the airway, check for breathing and in case there is no breathing, 2 rescue breaths should be given. Chest compressions are given after rescue breaths. Chest compressions are difficult to perform in water and the maneuvers of relieving foreign body obstruction is not recommended and in fact causes more complications and delay in CPR. The most important determinant of outcome is the duration and severity of hypoxia.
 
Stroke
Early recognition, activation of EMS, immediate shifting to a tertiary center, and early administration of fibrinolytic therapy (within a few hours) to indicated patients improves outcome. Clinical features include sudden numbness or weakness of the face, arm, or leg, especially on one side of the body; trouble speaking or understanding; sudden trouble seeing in one or both eyes; loss of balance or severe headache, dizziness.
 
Foreign-body Airway Obstruction
Most of the cases of obstruction occurs in children while playing or eating and is usually witnessed and immediate intervention has very good outcome. Foreign bodies can cause either mild or severe obstruction. Usually it is either witnessed or the patient clutches the neck showing the classic choking sign. In case of mild obstruction, allow the patient to cough. In case of severe obstruction, attempts are done to relieve the obstruction. Signs of severe obstruction are difficult respiration, silent cough, stridor and an unresponsive victim. In case of responsive adults and children ≥1 year of age, back blows, chest thrusts and abdominal thrusts were all proved to be effective. Abdominal thrusts are recommended for children <1 year since it may cause injury. For obese patients and pregnant patients, chest thrusts should be given since it is difficult to encircle the hands around the abdomen. In case of an unresponsive victim, the rescuer should carefully place the patient on the ground, activate the EMS and start CPR. Chest thrusts can be done and the rescuer should look for an object in the victim's mouth each time when he opens the airway and remove the foreign body if found. Finger sweep can be done but is harmful to the rescuer and not recommended.
 
Hypothermia
Cardiopulmonary resuscitation is immediately started if the patient is found unresponsive and to prevent further heat loss, the victim's wet clothes are removed. The victim is insulated from cold and also ventilated with warm humidified oxygen. The victim is immediately shifted to a hospital as fast as possible. In case of VF/VT, patient is delivered shocks. Passive warming can be used in out of hospital cardiac arrest.
 
Monitoring Cardiopulmonary Resuscitation
Chest compression rate, depth, ventilation rate, chest recoil and end tidal CO2 were used to guide CPR performance but still real-time CPR prompting and 738feedback technology such as visual and auditory prompting devices can improve the quality of CPR. Partial pressure of end-tidal carbon dioxide (Petco2) is useful in the confirmation of placement of ET tubes in the trachea and also for monitoring the quality of CPR. It should be >10 mm Hg for a high quality CPR. In cases of low pulmonary blood flow, Petco2 is not reliable to differentiate between esophageal and tracheal intubation. In that case, esophageal detector device is useful. The rapid increase in Petco2 can be used as an evidence of return of spontaneous circulation.
 
BIBLIOGRAPHY
  1. Berg RA, et al. Adult Basic Life Support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122:S685-S705.
  2. Berg RA, Kern KB, Hilwig RW, Berg MD, Sanders AB, Otto CW, et al. Assisted ventilation does not improve outcome in a porcine model of single-rescuer bystander cardiopulmonary resuscitation. Circulation. 1997;95:1635-41.
  3. Christenson J, Andrusiek D, Everson-Stewart S, Kudenchuk P, Hostler D, Powell J, Callaway CW, Bishop D, Vaillancourt C, et al. Chest compression fraction determines survival in patients with out-of-hospital ventricular fibrillation. Circulation. 2009;120:1241-7.
  4. Deshmukh HG, Weil MH, Gudipati CV, et al. Mechanism of blood flow generated by precordial compression during CPR. I. Studies on closed chest precordial compression. Chest. 1989;95:1092.
  5. Le May MR, So DY, Dionne R, Glover CA, Froeschl MP, Wells GA, Davies RF, Sherrard HL, Maloney J, et al. A citywide protocol for primary PCI in ST-segment elevation myocardial infarction. N Engl J Med. 2008;358:231-40.
  6. Redberg RF, Tucker KJ, Cohen TJ, et al. Physiology of blood flow during cardiopulmonary resuscitation. A transesophageal echocardiographic study. Circulation. 1993; 88:534.
  7. Redding JS. The choking controversy: critique of evidence on the Heimlich maneuver. Crit Care Med. 1979;7:475-9.
  8. Rumball CJ, MacDonald D. The PTL, Combitube, laryngeal mask, and oral airway: a randomized prehospital comparative study of ventilatory device effectiveness and cost-effectiveness in 470 cases of cardiorespiratory arrest. Prehosp Emerg Care. 1997;1:1-10.
  9. Sasson C, Rogers MA, Dahl J, et al. Predictors of survival from out-of-hospital cardiac arrest: a systematic review and metaanalysis. Circ Cardiovasc Qual Outcomes. 2010;3:63-81.
  10. Soroudi A, Shipp HE, Stepanski BM, Ray LU, Murrin PA, Chan TC, et al. Adult foreign body airway obstruction in the prehospital setting. Prehosp Emerg Care. 2007;11:25-9.
  11. Valenzuela TD, Roe DJ, Cretin S, et al. Estimating effectiveness of cardiac arrest interventions: a logistic regression survival model. Circulation. 1997;96:3308-13.
  12. Von Goedecke A, Bowden K, Wenzel V, et al. Effects of decreasing inspiratory times during simulated bag-valve-mask ventilation. Resuscitation. 2005;64:321-5.

ADVANCED CARDIAC LIFE SUPPORTCHAPTER 100

Prem Kumar  
INTRODUCTION
As a follow on from basic life support, almost all patients necessarily require advanced cardiac life support (ACLS) for interventional follow-up care. ACLS requires training and expertise and it is done in hospital by intensivists, anesthesiologists, and physicians. ACLS is a required skill in ICU, ED, and operation theaters. Latest ACLS training is one of the important predictors for proper management of patients with cardiac arrest. Interventions are aimed at preventing cardiac arrest, treating cardiac arrest and improving outcome in patients who achieve return of spontaneous circulation (ROSC) after cardiac arrest (Table 100.1).
Key changes from 2005 to 2010 AHA recommendations:
 
ADJUNCTS FOR AIRWAY MANAGEMENT
The purpose of ventilation in cardiac arrest patients is to maintain adequate oxygenation and to eliminate CO2. Both systemic and pulmonary perfusion are reduced in patients with cardiac arrest, hence less than normal minute ventilation is sufficient for maintaining ventilation perfusion ratio. 100% O2 can be used when available.
The airway adjuncts that can be used for resuscitation of patients with cardiac arrest are:
  • Oropharyngeal airway
  • Nasopharyngeal airway
  • Supraglottic airway devices—Laryngeal mask airway, laryngeal tube, combitube (esophageal-tracheal tube)
  • Endotracheal tube.
Oropharyngeal airways are useful as an aid in delivering ventilation with bag and mask and for avoiding tongue fall in unconscious patients. Nasopharyngeal airways are useful in patients where there is airway obstruction with the patient clenching the jaw. In patients who have known or suspected basal skull fracture or severe coagulopathy, nasopharyngeal airway is avoided. Although the timing of advanced airway is not specific, studies have shown that advanced airway secured within 5 minutes improves survival although it was not associated with improved ROSC. In achieving airway control, a backup strategy for ventilation should be on mind. Once the advanced airway is placed, confirmation of placement is done by bilateral auscultation, visible chest rise and by capnography.
Insertion of supraglottic airway device does not require interruption of chest compressions or laryngoscope for visualization of cords unlike endotracheal intubation. During CPR, supraglottic airway is a reasonable alternative to bag and mask ventilation and endotracheal intubation. Esophageal-tracheal tube has advantage of less risk of aspiration, and more reliable ventilation compared with bag and mask ventilation. Laryngeal tube is more compact and less complicated for insertion than combitube. Laryngeal mask airway gives a reliable means of ventilation than the face mask but the disadvantage of LMA is that LMA does not offer full protection against aspiration.
Endotracheal intubation should be done by only trained personnel since it causes delay and interruptions during chest compressions. Frequent training is required for those who perform endotracheal intubation. Continuous waveform capnography is recommended as the most reliable method of confirming and monitoring correct placement of an endotracheal tube. Other devices used for confirming placement are exhaled CO2 detectors and esophageal detector device (EDD). EDD can be used if capnography is not available. After placement of an advanced airway, the compressor should continue chest compressions without 741pauses for ventilation. Ventilation rate should be given at a rate of 1 breath every 6–8 seconds (8–10 breaths/minute) and both the compressor and the ventilator should switch roles every 2 minutes. During intubation, interruption of chest compression should not exceed more than 10 seconds. Indications for endotracheal intubation are absence of protective airway reflexes and inability to ventilate the patient using bag and mask. Advantages of ET tube is that it provides a route for delivery of high O2 concentration, protects airway form aspiration, facilitates delivery of selected tidal volume, alternative route of drug delivery for some drugs, most reliable airway among all airway devices. ET tube should be secured with a tape and continuously monitored with capnography. Automatic transport ventilators can be used if available. Suction devices can be either installed or portable and is used for clearing respiratory secretions. The installed suction unit should provide airflow of >40 L/minute at the end of the delivery tube and a vacuum of >300 mm Hg when the tube is clamped.
 
MANAGEMENT OF ADULT CARDIAC ARREST
Cardiac arrest can be due to four rhythms (Table 100.2):
  1. Ventricular fibrillation (VF)
  2. Pulseless ventricular tachycardia (VT)
  3. Pulseless electrical activity (PEA)
  4. Asystole.
Survival of patients with cardiac arrest rests with high quality CPR and rapid defibrillation within minutes of cardiac arrest and integrated postcardiac arrest care. Diagnosing and treating the underlying cause of cardiac arrest is the cornerstone of managing cardiac arrest (Flow chart 100.1 and Fig. 100.1). Apart from CPR, defibrillation is the only therapy which increases survival in patients having VF/VT. If the patient achieves ROSC, postcardiac arrest care is started immediately to prevent cardiac arrest and for improved neurological function.
 
Cardiopulmonary Resuscitation Quality
  • Push hard (≥2 inches [5 cm]) and fast (≥100/min) and allow complete chest recoil
  • Minimize interruptions in compressions
Table 100.2   Definition of cardiac arrest rhythms
Rhythm
Definition
VF
Disorganized electrical activity with lack of generation of significant forward blood flow
VT
Organized electrical activity of ventricular myocardium with lack of generation of significant forward blood flow
PEA
Group of organized electrical rhythms with lack of mechanical ventricular activity or mechanical ventricular activity that is insufficient to generate a clinically detectable pulse
Asystole
Absence of detectable ventricular electrical activity with or without atrial electrical activity
742
Flow chart 100.1: Algorithm for management of adult cardiac arrest
  • Avoid excessive ventilation
  • Rotate compressor every 2 minutes
  • If there is no advanced airway, compression–ventilation ratio of 30:2 is given743
Fig. 100.1: Rhythm-based management of cardiac arrest
  • Quantitative waveform capnography
    If Petco2 <10 mm Hg, attempt to improve CPR quality
  • Intra-arterial pressure.
    If relaxation phase (diastolic) pressure <20 mm Hg, attempt to improve CPR quality.
 
Return of Spontaneous Circulation (ROSC)
  • Pulse and blood pressure
  • Abrupt sustained increase in Petco2 (typically ≥40 mm Hg)
  • Spontaneous arterial pressure waves with intra-arterial monitoring.744
 
Shock Energy
  • Biphasic: Manufacture recommendation (e.g. initial dose of 120–200 J); if unknown, use maximum available. Second and subsequent doses should be equivalent, and higher doses may be considered.
  • Monophasic: 360 J.
 
Drug Therapy
  • Epinephrine IV/IO dose: 1 mg every 3–5 minutes
  • Vasopressin IV/IO dose: 40 units can replace first or second dose of epinephrine
  • Amiodarone IV/IO dose: First dose: 300 mg bolus. Second dose: 150 mg.
 
Advanced Airway
  • Supraglottic advanced airway or endotracheal intubation
  • Waveform capnography to confirm and monitor ET tube placement
  • 8–10 breaths per minute continuous chest compressions.
 
Reversible Causes
  • Hypovolemia
  • Hypoxia
  • Hydrogen ion (acidosis)
  • Hypo-/hyperkalemia
  • Hypothermia
  • Tension pneumothorax
  • Tamponade, cardiac
  • Toxins
  • Thrombosis, pulmonary
  • Thrombosis, coronary
 
Defibrillation
If VF/VT terminated by a shock recur later, subsequent shocks are delivered at the previously successful energy level. Doing CPR while a defibrillator is made ready for use is strongly recommended for all patients in cardiac arrest.
 
Drug Therapy (Tables 100.3 and 100.4)
A vasopressor can be given when there is persistent VF/pulseless VT after at least 1 shock and 2-minute CPR period. The goal of administering vasopressor in VF/VT is to increase myocardial blood flow during CPR and achieve ROSC. Though the optimal timing of vasopressor is not well established, usually it is given when a shock fails to generate a perfusing rhythm as to increase the myocardial blood flow before the next shock but vasopressors could theoretically cause deleterious effects if the patient is given vasopressor after achieving ROSC. Amiodarone can be considered when VF/VT is unresponsive to CPR, defibrillation, and vasopressor therapy. Lignocaine is an alternative to amiodarone. Magnesium sulfate is used for torsades de pointes (Polymorphic VT with prolonged QT interval).
The goal of administering vasopressor in PEA/asystole is increasing myocardial and cerebral blood flow. The use of atropine for PEA/asystole is not recommended since it does not have any therapeutic benefit. The reversible causes of cardiac arrest should be identified and corrected. 745
Table 100.3   Role of medications in cardiac arrest
Drug
Comments
Epinephrine
α adrenergic stimulation increase coronary and cerebral perfusion pressure.
β stimulation is controversial since it can increase myocardial work and reduce subendocardial perfusion.
Dose: 1 mg dose of IV/IO epinephrine every 3–5 minutes for adults.
Vasopressin
  • Nonadrenergic peripheral vasoconstrictor
  • It causes coronary and renal vasoconstriction
  • Studies have not shown any advantage over epinephrine
Dose: Vasopressin 40 units IV/IO may replace either the first or second dose of epinephrine.
Atropine
Routine use of atropine for PEA/asystole is not recommended.
Amiodarone
  • Has action on sodium, potassium, and calcium channels
  • It has α and β adrenergic blocking properties
  • Given for VF/VT unresponsive to shock, CPR and vasopressor
Dose: Initial dose of 300 mg IV/IO followed by 1 dose of 150 mg IV/IO.
Lignocaine
Lignocaine can be considered if amiodarone is not available.
Dose: Initial dose is 1–1.5 mg/kg IV. If VF/pulseless VT persist, additional doses of 0.5–0.75 mg/kg IV administered at 5–10 minute intervals to a maximum dose of 3 mg/kg.
Magnesium sulfate
Indicated in torsades de pointes.
Dose: 1–2 g diluted in 10 mL of 5% dextrose.
Calcium
Routine administration of calcium is not recommended.
Soda bicarbonate
Routine administration is not recommended. Bicarbonate can be beneficial to patients with pre-existing severe metabolic acidosis, hyperkalemia, or tricyclic antidepressant overdose.
Dose: 1 mEq/kg
Table 100.4   Doses and details of drugs and cardioversion/defibrillation
Synchronized cardioversion
Initial recommended doses
  • Narrow regular: 50–100 J
  • Narrow irregular: 120–200 J biphasic or 200 J monophasic
  • Wide regular: 100 J
  • Wide irregular: Defibrillation dose (NOT synchronized)
Adenosine IV dose
First dose: 6 mg rapid IV push; follow with normal saline flush
Second dose: 12 mg if required
Antiarrhythmic infusions for stable wide—QRS tachycardia
  • Procainamide IV dose: 20–50 mg/minute until arrhythmia gets suppressed, hypotension ensues, QRS duration increases >50%, or maximum dose 17 mg/kg is given. Maintenance infusion: 1–4 mg/minute Avoid if there is prolonged QT or CHF.
  • Amiodarone IV dose: First dose: 150 mg over 10 minutes. Repeat as needed if VT recurs.
    Follow by maintenance infusion of 1 mg/min for first 6 hours.
  • Sotalol IV dose: 100 mg (1.5 mg/kg) over 5 minutes. Avoid if prolonged QT.
746
 
Return of Spontaneous Circulation after Cardiac Arrest
If ROSC occurs after resuscitation, postcardiac arrest care is started and identification along with treatment of the precipitating causes of cardiac arrest is done to prevent recurrent arrest. Importance is given for the diagnosis and treatment of causes like hypoxemia, hypotension and STEMI. Therapeutic hypothermia is initiated if the patient is comatose.
 
Monitoring Cardiopulmonary Resuscitation
Chest compression rate, depth, ventilation rate, chest recoil and end tidal CO2 were used to guide CPR performance but still real-time CPR prompting and feedback technology such as visual and auditory prompting devices can improve the quality of CPR. Partial pressure of end-tidal CO2 (Petco2) is useful in the confirmation of placement of ET tubes in the trachea and also for monitoring the quality of CPR. It should be >10 mm Hg for high quality CPR. Normal Petco2 = 35–40 mm Hg and if ventilation is constant, Petco2 correlates with cardiac output. Persistent low Petco2 values (<10 mm Hg) during CPR in intubated patients are an indication that the ROSC is unlikely. In cases of low pulmonary blood flow, Petco2 is not reliable to differentiate between esophageal and tracheal intubation. In that case, esophageal detector device is useful. The rapid increase in Petco2 can be used as an evidence of return of spontaneous circulation. Arterial relaxation (diastolic pressure) should be >20 mm Hg since this is close to aortic relaxation pressures during CPR. Changes in central venous oxygen saturation (ScvO2)reflect changes in oxygen delivery by means of changes in cardiac output. ScvO2 monitoring is an indicator of cardiac output and oxygen delivery during CPR. Pulse oximetry and arterial blood gas analysis is not reliable. Echocardiography can be used in the diagnosis of treatable causes like pericardial tamponade and help in the diagnosis and treatment.
 
Access for Delivering Parenteral Medications
  • Peripheral venous drug administration is done along with 20 mL bolus of intravenous fluid to facilitate drug delivery into central circulation.
  • IO access is done in case of difficulty in achieving IV access.
  • Central venous line either internal jugular or subclavian vein can be cannulated during cardiac arrest. Advantage is shorter drug circulation time and can be used for monitoring ScvO2. Disadvantage is that it interrupts CPR.
  • If IV or IO access cannot be established, lignocaine, epinephrine, vasopressin can be administered by endotracheal route during cardiac arrest but the absorption is slow. The usual dose administered via ET tube is 2–2.5 times the recommended IV dose. The drug is diluted with 5–10 mL of sterile water or normal saline and administered.747
Flow chart 100.2: Algorithm for management of bradycardia
 
Other Therapies and its use in Cardiac Arrest
Empirical fibrinolytic therapy can be considered in patients who have or is presumed to have cardiac arrest due to pulmonary embolism. Electrical pacing is not routinely used for patients with cardiac arrest due to any rhythm.
 
Precordial Thump
Precordial thump can be considered for termination of witnessed monitored unstable ventricular tachyarrhythmias when a defibrillator is not immediately ready for use but that should not delay CPR and shock.
748Algorithm for the management of bradycardia (Flow chart 100.2) and tachycardia (Flow chart 100.3) is given below. Etiology of narrow and wide QRS complex tachycardia is given in Table 100.5.
Flow chart 100.3: Algorithm for management of tachycardia
Table 100.5   Causes of narrow and wide QRS complex tachycardia
Narrow–QRS-complex (SVT) tachycardias (QRS < 0.12 second), in order of frequency
Wide–QRS-complex tachycardias (QRS ≥ 0.12 second)
  • Sinus tachycardia
  • Atrial fibrillation
  • Atrial flutter
  • AV nodal reentry
  • Accessory pathway—mediated tachycardia
  • Atrial tachycardia (including automatic and re-entry forms)
  • Multifocal atrial tachycardia (MAT)
  • Junctional tachycardia (rare in adults)
  • Ventricular tachycardia (VT) and ventricular fibrillation (VF)
  • SVT with aberrancy
  • Pre-excited tachycardias [Wolff-Parkinson-White (WPW) syndrome]
  • Ventricular paced rhythms
749
 
BIBLIOGRAPHY
  1. Barthell E, Troiano P, Olson D, et al. Prehospital external cardiac pacing: a prospective, controlled clinical trial. Ann Emerg Med. 1988;17:1221-6.
  2. Bhende MS, Thompson AE. Evaluation of an end-tidal CO2 detector during pediatric cardiopulmonary resuscitation. Pediatrics. 1995;95:395-9.
  3. Dorges V, Wenzel V, Knacke P, et al. Comparison of different airway management strategies to ventilate apneic, nonpreoxygenated patients. Crit Care Med. 2003;31:800-4.
  4. Grmec S, Klemen P. Does the end-tidal carbon dioxide (EtCO2) concentration have prognostic value during out-of-hospital cardiac arrest? Eur J Emerg Med. 2001;8:263-9.
  5. Grmec S, Kupnik D. Does the Mainz Emergency Evaluation Scoring (MEES) in combination with capnometry (MEESc) help in the prognosis of outcome from cardiopulmonary resuscitation in a prehospital setting? Resuscitation. 2003;58:89-96.
  6. Lefrancois DP, Dufour DG. Use of the esophageal tracheal combitube by basic emergency medical technicians. Resuscitation. 2002;52:77-83.
  7. Michael JR, Guerci AD, Koehler RC, Shi AY, Tsitlik J, Chandra N, Niedermeyer E, Rogers MC, Traystman RJ, et al. Mechanisms by which epinephrine augments cerebral and myocardial perfusion during cardiopulmonary resuscitation in dogs. Circulation. 1984;69:822-35.
  8. Neumar RW, et al. Adult advanced cardiovascular life support : 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2010;122:S729-S67.
  9. Schalk R, Byhahn C, Fausel F, Egner A, Oberndorfer D, Walcher F, et al. Out-of-hospital airway management by paramedics and emergency physicians using laryngeal tubes. Resuscitation. 2010;81:323-6.
  10. Stiell IG, Wells GA, Hebert PC, et al. Association of drug therapy with survival in cardiac arrest: limited role of advanced cardiac life support drugs. Acad Emerg Med. 1995;2:264-73.
  11. Stone BJ, Chantler PJ, Baskett PJ. The incidence of regurgitation during cardiopulmonary resuscitation: a comparison between the bag valve mask and laryngeal mask airway. Resuscitation. 1998;38:3-6.
  12. The use of the laryngeal mask airway by nurses during cardiopulmonary resuscitation: results of a multicentre trial. Anaesthesia. 1994;49:3-7.
  13. Warner KJ, Carlbom D, Cooke CR, Bulger EM, Copass MK, Sharar SR. Paramedic training for proficient prehospital endotracheal intubation. Prehosp Emerg Care. 2010;14:103-8.
  14. Wong ML, Carey S, Mader TJ, et al. Time to invasive airway placement and resuscitation outcomes after inhospital cardiopulmonary arrest. Resuscitation. 2010;81:182-6.
  15. Yakaitis RW, Otto CW, Blitt CD. Relative importance of α- and β-adrenergic receptors during resuscitation. Crit Care Med. 1979;7:293-6.

CARDIAC ARREST IN SPECIAL SITUATIONSCHAPTER 101

Prem Kumar  
INTRODUCTION
Cardiac arrest occurring during special situations requires certain changes in the resuscitation. This chapter deals with the following special conditions—anaphylaxis, pregnancy, pulmonary embolism, morbid obesity, trauma, hypothermia, asthma, electrolyte disturbances, drowning, electric shock/lightening strike, percutaneous coronary intervention (PCI), cardiac tamponade, cardiac surgery.
 
ANAPHYLAXIS
Anaphylaxis is a severe, life-threatening, generalized or systemic hypersensitivity reaction involving IgG and IgE. It is characterized by rapidly developing, life-threatening problems involving the airway, breathing and circulation.
 
Basic Life Support Modifications
  • Airway should be secured rapidly and should not be delayed because of anticipated risk of developing oropharyngeal or laryngeal edema.
  • Intramuscular adrenaline should be given on the anterolateral aspect of the middle third of thigh since it gives high peak blood concentration. Absorption and achieving plasma drug concentration of subcutaneous adrenaline is slower than intramuscular route especially in patients with shock.
  • Adrenaline should be administered in all patients with signs of systemic allergic reactions like hypotension, airway swelling, or difficulty breathing and the dose of adrenaline is 0.2–0.5 mg IM of 1:1000 concentration. It is repeated every 5–10 minutes in case of lack of clinical improvement. For basic life support, adrenaline is given though auto injectors. In patients with anaphylactic cardiac arrest, the use of adrenaline autoinjector is recommended if it is available.
 
Advanced Cardiac Life Support Modifications
  • Potential for difficult airway is present in patients who develop airway symptoms, hence a plan for advanced airway management including surgical airway is recommended.
  • 751In patients not responding to vasopressors, aggressive fluid resuscitation with isotonic crystalloids is given to raise the blood pressure.
  • If an intravenous line is in place, intravenous adrenaline is a reasonable alternative to IM route for patients with anaphylactic shock.
  • If patients are not in cardiac arrest but in anaphylactic shock, IV adrenaline is given at a dose of 50–100 µg/kg but hemodynamic monitoring should be done. Infusion of IV adrenaline (5–15 µg/min) can be used as an alternative to bolus dose in patients who are not in cardiac arrest.
  • Alternative vasopressors like vasopressin, norepinephrine, methoxamine, and metaraminol can be considered in patients with cardiac arrest due to anaphylaxis who does not respond to adrenaline.
  • Antihistamines, inhaled β-2 agonists and corticosteroids can be considered in patients in cardiac arrest.
 
PREGNANCY
Although pregnant patients are predominantly young, still their outcome is poor after cardiac arrest. There are 2 potential patients in the resuscitation of pregnant patient—mother and fetus. The best chance for fetal survival is the survival of the mother. The rescuers should be aware of the physiological changes in pregnant patient.
 
Key Interventions to Prevent Arrest
  • Place the patient in full left lateral position to relieve the aortocaval compression produced by the uterus.
  • Give 100% O2 and to establish IV line above the diaphragm.
  • Systolic blood pressure of <100 mm Hg or <80% of baseline is defined as maternal hypotension and should be treated with crystalloids or colloids and vasopressors (ephedrine).
 
Basic Life Support Modifications
  • Manual left uterine displacement in the supine position is done to relieve the aortocaval compression. Manual uterine displacement is done by 2 hand technique from the left side of the patient or 1 hand technique from the right side of the patient.
  • If the former technique is not successful and a wedge is available, a left lateral tilt of 30o is given using a wedge to support the thorax and the pelvis.
  • Airway management is difficult in pregnant patients owing to the left lateral tilt and also the altered upper airway anatomy with reduced pulmonary reserve (↓ FRC and ↑ O2 demand). Therefore, the risk of desaturation and aspiration is higher. Hence, optimal use of bag mask ventilation with suctioning along with preparation for advanced airway placement is critical in the airway management of a pregnant patient with cardiac arrest.
  • Tidal volume can be reduced owing to reduced lung capacity.
  • Chest compression should be done slightly higher on the sternum than the usual position to adjust for the elevation of diaphragm.752
 
Advanced Cardiac Life Support Modifications
  • Because of the altered upper airway anatomy, there is a risk of failed intubation in pregnant patients which can also be a cause of morbidity and mortality during anesthesia, hence a difficult airway cart should be kept ready and difficult airway management should be done in case of difficult airway.
  • Bag and mask ventilation with 100% O2 should be done before intubation.
  • Dosages of various drugs used for cardiac arrest in pregnant patients are the same dose that is used for any adult cardiac arrest patient.
  • Defibrillation should be given at the recommended ACLS defibrillation doses. Cardioversion and defibrillation on the external chest are safe at all stages of pregnancy except for a small risk of causing fetal cardiac arrhythmias. In case there are fetal monitors during defibrillation, it has to be removed before administering shock.
  • Causes of cardiac arrest specific to pregnancy should be aware of—cardiac disease (most common)—especially myocardial infarction and aortic dissection, hypertensive disorders (pre-eclampsia/eclampsia), magnesium sulphate toxicity, amniotic fluid embolism, massive pulmonary embolism, anesthesia.
  • In case of cardiac arrest in a pregnant patient, a team for doing emergency cesarean delivery should be ready. In case of >24 weeks of gestation, the survival rate of the infant is better when the infant is delivered not more than 5 minutes after cardiac arrest of the mother. Hence, regardless of the viability of the fetus, emergency cesarean section can be considered at 4 minutes after onset of cardiac arrest if there is no ROSC.
  • If therapeutic hypothermia is instituted, the fetus is continuously monitored for bradycardia.
 
Pulmonary Embolism
  • Cardiac arrest caused by pulmonary embolism (PE) mostly presents as PEA.
  • In patients with cardiac arrest due to presumed or known PE, it is reasonable to administer fibrinolytics. Surgical embolectomy can also be done. Patients without known PE should not be given fibrinolytic therapy.
 
Morbid Obesity
  • Airway management is quite challenging and changes in the thorax make resuscitation efforts difficult.
  • There are no modifications to standard BLS and ACLS.
 
TRAUMA
Common causes of cardiac arrest in trauma patients are hypoxia, hypovolemia, diminished cardiac output secondary to pneumothorax or pericardial tamponade, and hypothermia.753
 
Basic Life Support Modifications
  • Cervical spine should be stabilized, jaw thrust should be given instead of head tilt and chin lift to open the airway.
  • Any visible hemorrhage is compressed and if the victim is unresponsive, standard BLS is initiated.
 
Advanced Cardiac Life Support Modifications
  • In case of inadequate bag mask ventilation, advanced airway is placed while maintaining cervical spine stabilization. If insertion of advanced airway is not possible, cricothyroidotomy is considered.
  • Identification of reversible causes is the cornerstone of resuscitation in trauma victims along with cardiopulmonary resuscitation (CPR).
  • Unilateral reduction in breath sounds should raise suspicion of pneumothorax, hemothorax and diaphragmatic rupture.
  • Resuscitative thoracotomy can be done in selected patients.
  • Commotio cordis is VF triggered by a blow to the anterior chest during cardiac repolarization. It usually happens in young persons involved in sports where a sudden blow to the anterior chest by a ball causes VF. Rapid defibrillation is critical in these patients.
 
HYPOTHERMIA
  • Severe hypothermia (<30°C) is associated with interference of critical functions of the body especially cardiac system (cardiac arrhythmias).
  • Prevent heat loss by removing wet garments and passive rewarming is done for patients with mild hypothermia (>34°C).
  • External warming is done for victims with moderate hypothermia (30–34°C).
  • Core rewarming is used for victims with severe hypothermia. Even external rewarming is effective in these victims.
  • Core rewarming techniques are warm water lavage of thoracic cavity and with partial cardiopulmonary bypass. Warm IV fluids and warm humidified O2 can be used.
  • Warming techniques should not delay airway management and insertion of intravenous cannula.
 
Basic Life Support Modifications
  • Detection of pulse is difficult in hypothermic patients
  • Rewarming should be done along with BLS.
 
Advanced Cardiac Life Support Modifications
  • In patients with cardiac arrest due to hypothermia, aggressive active core rewarming techniques is the primary therapeutic modality.
  • It is reasonable to administer vasopressors to patients with hypothermia induced cardiac arrest.
  • 754After ROSC, patients should be warmed with a goal of 32–34°C.
  • Patients should not be considered dead before warming has been provided.
 
ASTHMA
  • There are no BLS modifications.
  • ACLS modifications—Autopositive end-expiratory pressure (PEEP) produce adverse effects on the coronary perfusion. Ventilation strategy of low respiratory rate and tidal volume is followed to prevent the effects of auto-PEEP. During resuscitation of asthmatic patients with cardiac arrest, brief disconnection of bag mask ventilation or ventilator is done to prevent air trapping. In case of ventilation difficulty in asthmatic patients with cardiac arrest, tension pneumothorax should be suspected.
 
Electrolyte Disturbances
Electrolyte disturbances are associated with cardiac arrhythmias and interfere with resuscitative efforts and hemodynamic recovery.
 
Potassium
Potassium disturbances are associated with life-threatening events. Severe hyperkalemia is defined as K+ concentration >6.5 mmol/L and can cause cardiac arrhythmias and cardiac arrest. Renal failure and drug-induced toxicity are common causes. The first sign is the presence of peaked T waves in ECG and as serum potassium rises, flattened or absent P waves, prolonged PR interval, widened QRS complex, and sine wave pattern appear on ECG. Untreated or very high potassium levels may cause ventricular arrhythmias and asystolic cardiac arrest.
 
Advanced Cardiac Life Support Modifications
Management of severe hyperkalemia is aimed at antagonizing the effects of potassium on excitable cell membrane. Treatment is given to shift potassium into cells and removing potassium from the intravascular compartment.
The priorities of treatment for hyperkalemia are:
  • Stabilizing the myocardial cell membrane with 10% calcium gluconate 15–30 mL IV over 2–5 minutes or 10% calcium chloride 5–10 mL IV over 2–5 minutes.
  • Shifting K+ into cells by glucose with insulin. 50 mL of 50% dextrose and 10 U of regular insulin IV are given over 15–30 minutes, nebulized albuterol 10–20 mg in 4 mL of normal saline over 15 minutes.
  • In case of severe metabolic acidosis with hyperkalemia, sodium bicarbonate of 50 meq IV is given over 5 minutes.
  • Promoting K+ excretion by IV furosemide 40–80 mg, kayexalate 15–50 g with sorbitol orally or rectally, dialysis.
755In case of hypokalemia, U waves, T-wave flattening, ventricular arrhythmias are common. They may deteriorate faster if hypokalemia becomes severe and may end up in PEA and asystole. Bolus administration of IV potassium for suspected hypokalemia-induced cardiac arrest is not recommended.
 
Magnesium
  • Hypermagnesemia: Administration of 10% calcium gluconate 15–30 mL IV over 2–5 minutes or 10% calcium chloride 5–10 mL IV over 2–5 minutes may be considered during cardiac arrest associated with hypermagnesemia
  • Hypomagnesemia: It is associated with polymorphic ventricular tachycardia (torsades de pointes). IV magnesium 1–2 g of MgSO4 bolus IV is recommended.
 
DROWNING
The most important consequence of submersion is hypoxia, hence in drowning victims, the guidelines recommend individualization of the sequence according to the presumed cause. CPR is done in ABC sequence in drowning victims owing to the hypoxic nature of the arrest. Prompt initiation of rescue breathing increases the victim's chance of survival. When the victim is taken from the water, the rescuer should open the airway, check for breathing and in case there is no breathing, 2 rescue breaths should be given. Chest compressions are given after rescue breaths. Chest compressions are difficult to perform in water and the maneuvers of relieving foreign body obstruction is not recommended and in fact causes more complications and delay in CPR. The most important determinant of outcome is the duration and severity of hypoxia.
 
Electric Shock/Lightening Strike
Electric shock and lightning strike cause direct effects of current on the heart and brain, cell membranes, and vascular smooth muscle thus causing cardiac arrest due to VF or asystole. Alternating current flows through the heart during the relative refractory period and can cause VF. Lightening causes massive direct current shock simultaneously depolarizing the whole myocardium and causes thoracic muscle spasm causing respiratory arrest. Lightening causes catecholamine release, prolongation of QT interval, myocardial necrosis, and intracranial hemorrhages.
 
Basic Life Support Modifications
  • The rescuer should make himself safe on the scene of cardiac arrest before rescuing the victim. Once the rescuer keeps the victim in a safe place, he can start resuscitative efforts.
  • Associated cervical spine injury can occur, hence spinal stabilization is done. Removing the clothes, belt can avoid further thermal damage.
756
 
Advanced Cardiac Life Support Modifications
  • Early intubation is done in view of the extensive burns caused by injury.
  • For patients with ROSC, rapid IV fluid administration is done to counteract distributive shock. Maintaining diuresis is important to prevent acute kidney injury due to extensive tissue injury.
 
PERCUTANEOUS CORONARY INTERVENTION
There is always a risk of cardiac arrest during percutaneous coronary intervention (PCI), and standard CPR techniques are followed in case of cardiac arrest. Mechanical chest compression devices can be used for resuscitation. Emergency cardiopulmonary bypass can be used, cough CPR can be used as a temporary measure to maintain blood pressure and consciousness during initial phase of ventricular arrhythmias. Intracoronary verapamil has been used but its use is not validated.
 
CARDIAC TAMPONADE
Increasing fluid and pressure compromises atrial and ventricular filling thus reducing stroke volume and cardiac output leading to hypotension and cardiac arrest. Rapid pericardiocentesis guided by echocardiography is the most effective method to relieve tamponade in a nonarrest setting. If there is no echocardiography, emergency pericardiocentesis without echocardiography guidance can be done. Thoracotomy can be done for trauma-induced pericardial tamponade to remove blood clots.
 
CARDIAC SURGERY
Common causes of cardiac arrest are ventricular fibrillation, hypovolemia, cardiac tamponade, tension pneumothorax. Resternotomy is done in a well equipped ICU. Though there are reports of damage to heart due to external chest compressions, chest compressions should not be withheld if resternotomy is not done. Cardiopulmonary bypass may be started in patients who fail to respond to usual resuscitative measures.
 
BIBLIOGRAPHY
  1. Brown O, Davidson N, Palmer J. Cardioversion in the third trimester of pregnancy. Aust NZJ Obstet Gynaecol. 2001;41:241-2.
  2. Cardosi RJ, Porter KB. Cesarean delivery of twins during maternal cardiopulmonary arrest. Obstet Gynecol. 1998;92(pt 2):695-7.
  3. Dijkman A, Huisman CM, Smit M, Schutte JM, Zwart JJ, van Roosmalen JJ, et al. Cardiac arrest in pregnancy: increasing use of perimortem caesarean section due to emergency skills training? BJOG. 2010;117:282-7.
  4. Kill C, Wranze E, Wulf H. Successful treatment of severe anaphylactic shock with vasopressin: two case reports. Int Arch Allergy Immunol. 2004;134:260-1.
  5. Kornberger E, Schwarz B, Lindner KH, et al. Forced air surface rewarming in patients with severe accidental hypothermia. Resuscitation. 1999;41:105-11.
  6. 757Kyriacou DN, Arcinue EL, Peek C, et al. Effect of immediate resuscitation on children with submersion injury. Pediatrics. 1994;94(pt 1):137-42.
  7. Maron BJ, Doerer JJ, Haas TS, Estes NA, Hodges JS, Link MS. Commotio cordis and the epidemiology of sudden death in competitive lacrosse. Pediatrics. 2009;124:966-71.
  8. Maron BJ, Estes NA III. Commotio cordis. N Engl J Med. 2010;362:917-27.
  9. Marx GF, Berman JA. Anesthesia-related maternal mortality. Bull NY Acad Med. 1985;61:323-30.
  10. Nanson J, Elcock D, Williams M, et al. Do physiological changes in pregnancy change defibrillation energy requirements? Br J Anaesth. 2001;87:237-9.
  11. Page-Rodriguez A, Gonzalez-Sanchez JA. Perimortem cesarean section of twin pregnancy: case report and review of the literature. Acad Emerg Med. 1999;6:1072-4.
  12. Rees GA, Willis BA. Resuscitation in late pregnancy. Anaesthesia. 1988;43:347-9.
  13. Rees SG, Thurlow JA, Gardner IC, et al. Maternal cardiovascular consequences of positioning after spinal anaesthesia for caesarean section: left 15 degree table tilt vs left lateral. Anaesthesia. 2002;57:15-20.
  14. Sheikh A, Shehata YA, Brown SG, et al. Adrenaline (epinephrine) for the treatment of anaphylaxis with and without shock. Cochrane Database Syst Rev. 2008;No. 4:CD006312.
  15. Sheridan RL, Goldstein MA, Stoddard FJ Jr, et al. Case records of the Massachusetts General Hospital: case 41–2009: a 16-year-old boy with hypothermia and frostbite. N Engl J Med. 2009;361:2654-62.
  16. Simons FE, Gu X, Simons KJ. Epinephrine absorption in adults: intramuscular versus subcutaneous injection. J Allergy Clin Immunol. 2001;108:871-3.
  17. Vanden Hoek TL, et al. Part 12: cardiac arrest in special situations: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2010;122:S829-S61.
  18. Vasdev GM, Harrison BA, Keegan MT, et al. Management of the difficult and failed airway in obstetric anesthesia. J Anesth. 2008;22:38-48.
  19. Yilmaz R, Yuksekbas O, Erkol Z, et al. Postmortem findings after anaphylactic reactions to drugs in Turkey. Am J Forensic Med Pathol. 2009;30:346-9.
  20. Yunginger JW, Sweeney KG, Sturner WQ, Giannandrea LA, Teigland JD, Bray M, Benson PA, York JA, Biedrzycki L, et al. Fatal food-induced anaphylaxis. JAMA. 1988;260:1450-2.
758Brain Death
Chapter 102 Care of a Brain Dead Patient Sumathy, Prem Kumar, Deepalakshmi759

CARE OF A BRAIN DEAD PATIENTCHAPTER 102

Sumathy, Prem Kumar, Deepalakshmi
The concept of brain death was first introduced by Mollaret et al. Determination of brain death requires the confirmation of irreversible cessation of all functions of the brain which includes also the brainstem. The term irreversible cessation of brain function refers that none of the treatment can be expected to reasonably change the condition. Although testing of the brain function can be done, it is determined clinically by loss of consciousness, loss of brainstem responses, apnea. As the concept of brain death grew, the idea of organ harvesting from brain dead patients for organ transplantation came into practice, hence critical care management of potential organ donors is crucial in maximizing the number and the quality of transplanted organs.
Following are the duties of the critical care physician are:
  • Early identification of brain death
  • Brain death certification
  • The responsibility to offer the patient's family the opportunity to donate organs/tissues
  • Obligation to unknown recipients to provide the best possible organs and tissue.
 
DEFINITION
Brain death is defined as the irreversible loss of all the functions of the brain including the brainstem due to total necrosis of the cerebral neurons following loss of blood flow and oxygenation when the proximate cause is known.
 
PHYSIOLOGY OF BRAIN DEATH
 
Central Nervous System
Brain death is the total irreversible loss of all functions of brain excluding the spinal cord. Brain stem reflexes such as pupillary, oculocephalic, oculovestibular, and pharyngeal reflexes are absent and they are tested to confirm brain death. 762
 
Respiratory System
Respiratory center is located in medulla oblongata. In brain death patients, there is loss of spontaneous respiration even when the PaCO2 rises up to 60 mm Hg. Mechanical stimulation of carina to cause cough reflex can be used for detecting residual functioning of the medullary respiratory neurons.
 
Cardiovascular System
Vasomotor center is in pons and medulla. Increased intracranial tension due to intracranial bleed or any cause can cause hypertension and bradycardia. Transtentorial herniation can cause pressure over the pons and cause Cushing's response. This causes ischemia of vasomotor centers of brain and causes central autonomic dysfunction leading to catecholamine surge causing hypertension, tachycardia, and increased myocardial contractility. Over hours after brain death, autonomic surge decreases and catecholamines decrease causing hemodynamic instability due to reduced sympathetic outflow, cardiac output, and systemic vascular resistance. If autonomic reflexes are intact in brain death patients, surgical stimulation can lead to hypertension and tachycardia. This is the reason why general anesthesia should be used for brain death organ donors.
 
Temperature Regulation
Body temperature is regulated in hypothalamus. The neural communication between temperature regulating center and peripheral tissues is lost in brain death patients. Hence, patients with brain death tend to be hypothermic.
 
Hypothalamopituitary Function
Hypothalamic and anterior pituitary functions are preserved for a certain period of time after the onset of brain death. Thyroid-stimulating hormone, prolactin, growth hormone, and luteinizing hormone are all found at a normal level in brain death patients. The levels of vasopressin, T3, T4 are decreased.
 
Immune System
Though the immune system is intact, response to stimulation is suppressed and there is increased level of proinflammatory mediators, such as cytokines (IL-1β, IL-6, TNF-α) which is responsible for the failure rate of organ transplantation.
 
Privileging
Each hospital should establish a process for identifying the privileging physicians to make brain death determination. The legal and expert guidelines for organ transplantation in India are given by Transplantation of Human Organs and Tissues Rules, 2014. The guidelines can be accessed in the website - http://notto.nic.in/.
According to the Transplantation of Human Organs Rules, 1995 (THO Rules) of the Tamil Nadu Government, the following four doctors are authorized to certify brain death.763
Table 102.1   Guidelines for determining brain death
Prerequisites
  • Clinical or neuroimaging evidence of an acute central nervous system condition that is compatible with the clinical diagnosis of brain death
  • There should not be severe electrolyte, acid-base, or endocrine disturbance that would confound the clinical diagnosis of brain death
  • No drug intoxication or poisoning
  • Core temperature ≥32°C (90°F)
  • Doctor No: 1-RMP
    (Registered medical practitioner): In charge of the hospital in which brainstem death has occurred.
      Who is RMP?: RMO, ARMO, Duty RMO or the RMP in charge of the hospital
  • Doctor No: 2-RMP - (Physicians, surgeons, intensivists) nominated from the panel of names approved by the appropriate authority (Director of medical and rural health services)
  • Doctor No: 3-(Neurologist or neurosurgeon) nominated from the panel of names approved by the appropriate authority
  • Doctor No: 4-RMP - Treating the aforesaid person.
 
Notification
Hospitals should make reasonable efforts to notify the next of kin or person closest to the individual that the process of evaluating brain death has begun.
 
Reasonable Accommodation
Hospitals must establish written procedures for the reasonable accommodation of the individual's religious or moral objections to use of the brain death standards to determine death when such an objection has been expressed by the patient prior to the loss of decision making capacity, or by the next of the kin or other person closest to the individual.
 
Responsibilities of the Physician Determining Brain Death
The diagnosis of brain death is primarily clinical. No other tests are required if the full clinical examination, including each of two assessments of brainstem reflexes and the apnea test is conclusively performed. Prerequisites for diagnosing brain death is given in Table 102.1.
 
STEPS FOR DETERMINING BRAIN DEATH
  • Evaluate the irreversibility and potential causes of coma
  • Initiate the hospital policy for notifying the next of kin
  • Conduct and document the first clinical assessment of brainstem reflexes
  • 764Observe the individual during a defined waiting period for any clinical inconsistencies with the diagnosis of brain death
  • Conduct and document the clinical assessment of brainstem reflexes
  • Perform and document the apnea test
  • Perform confirmatory test, if needed
  • If the individuals religious or moral objection to the brain death standard is known, implement hospital policies for reasonable accommodation
  • Certify brain death
  • Withdraw cardiorespiratory support in accordance with hospital policies, including those for organ donation.
 
DIAGNOSTIC CRITERIA FOR THE CLINICAL DIAGNOSIS OF BRAIN DEATH
The three prime findings in brain death are following:
  1. Coma or unresponsiveness
  2. Absence of brainstem reflexes
  3. Apnea.
 
Coma or Unresponsiveness
Absence of cerebral motor response to pain in all extremities is tested by applying supraorbital pressure. The patient should be in coma and have GCS ≤3. Spinal motor responses (i.e. the Lazarus sign) may occur spontaneously during apnea testing.
 
Absence of Brainstem Reflexes
Absence of pupillary response to light, absence of oculocephalic reflex, absence of corneal, pharyngeal and tracheal reflexes are all features consistent in patients with brainstem death. Oculovestibular reflex is tested by irrigation of cold water which shows no deviation of eyes to irrigation in each ear with 50 mL of cold water. Pharyngeal and tracheal reflex is tested by stimulation of the posterior pharynx with tongue blade or by bronchial suctioning. The criteria of the American Academy of Neurology for brain death include light reflex, oculocephalic reflex, caloric (vestibular) test, corneal reflex, jaw reflex, pharyngeal reflex, and cough reflex.
Tests for the function of cranial nerves of the brainstem:
  • Absence of pupillary light response (II, III)
  • Absence of corneal reflexes (V, VII)
  • No facial response to painful stimuli in the face, trunk or limbs (V, VII)
  • Absence of gag reflex (IX)
  • Absence of cough reflex (X)
  • Absence of nystagmus with instillation of 30–50 mL of ice cold water into the EAC (external auditory canal)—oculovestibular testing (VIII) (Flow chart 102.1).765
Flow chart 102.1: Oculovestibular testing
Abbreviations: EAC, external auditory canal; CSF, cerebrospinal fluid.
 
Apnea Test
The apnea test is performed after the clinical examination of brainstem reflexes.
Prerequisites:
  • Core temperature >36.5°C/97.7°F
  • Systolic blood pressure ≥90 mm Hg
  • Euvolemia: Positive fluid balance in the previous 6 hours
  • Normal PaCO2: PaCO2 ≥ 40 mm Hg
  • Normal PaO2: Preoxygenate to obtain arterial PaO2 ≥200 mm Hg
Procedure of the apnea testing:
  • Preoxygenate the patient with 100% O2 for 10 minutes
  • Do a baseline ABG
  • Connect a pulse oximeter
  • Disconnect the ventilator
  • Deliver 100% O2 by administering 6 L/minute into the trachea by placing a cannula at the level of carina
  • Look closely for respiratory movements (abdominal or chest excursions that produce adequate tidal volumes)
  • Measure arterial PaO2, PaCO2, and pH by taking ABG sample after approximately 8 minutes and reconnect the ventilator.766
Table 102.2   Apnea test interpretations
Apnea test positive supports Diagnosis of brain death
Negative test
  • Patient remains apneic, without any respiratory movements
  • PaCO2 ≥60 mm Hg (20 mm Hg ↑ in PaCO2 over the baseline)
  • Presence of respiratory efforts
  • Test should be repeated
Indeterminate test
PaCO2 <60 mm Hg/PaCO2 ↑ is <20 mm Hg over baseline
Abort the test and immediately take a ABG sample if:
  • The systolic BP becomes <90 mm Hg
  • Arterial desaturation
  • Cardiac arrhythmias.
If PaCO2 is ≥60 mm Hg or PaCO2 increase is ≥20 mm Hg over baseline PaCO2, the apnea test result is positive. If PaCO2 is < 60 mm Hg or PaCO2 increase is <20 mm Hg over baseline PaCO2, the result is indeterminate, and an additional confirmatory test can be considered (Table 102.2).
Two clinical examinations followed by apnea testing separated by 6 hours are required for establishing the diagnosis of brain death. Confirmatory tests in the determination of brain death are not always mandatory, but they may be required especially if there is a confusing clinical presentation.
 
Confirmatory Tests for Brain Death
Confirmatory tests to record the loss of bioelectrical activity of the brain or the cerebral circulatory arrest are not always mandatory for adults, but it is commonly done for children < 1 year to confirm brain death.
  • Cerebral angiography
  • Electroencephalography
  • Cerebral scintigraphy
  • Transcranial Doppler ultrasonography.
Electroencephalography (EEG) and evoked potential
EEG is the most commonly used test to confirm brain death. Isoelectric EEG is a reliable finding for brain death. Electrocerebral inactivity (ECI) or electrocerebral silence (ECS) is defined as absence of electroencephalographic activity above 2 µV/mm when recorded from scalp electrode. But EEG can be altered by anesthetic agents and sedatives leading to false positive results. Unlike EEG, somatosensory evoked potentials (SSEP) and brainstem auditory evoked potentials (BAEP) are minimally affected by drugs, hence can be used for diagnosis of brain death.
Cerebral blood flow
Absence of cerebral circulation can indicate irreversible brain damage. This can be done by 4 vessel angiography, CT and MRI angiography, transcranial Doppler ultrasonography.
 
MANAGEMENT OF HEARTBEATING BRAIN DEATH ORGAN DONOR
The standards of medical management of the potential organ donor should be the same as those of any brain-injured patient until the irreversibility of injury is 767confirmed. The patient must be medically suitable for organ donation. The criteria for suitability may change from time to time and according to circumstances.
 
General Medical Criteria
  • Age—up to 75 years
  • Irreversible loss of brain function
  • Has been maintained on ventilator with intact circulation
  • Has no malignancy except primary brain/skin malignancy
  • Has no major untreated sepsis
  • No major significant system specific disease (e.g. cardiac, pulmonary, liver)
  • No significant infectious disease
  • Cause of death not due to massive poisoning with potential for transplant organ dysfunction (cyanide, carbon monoxide, etc.).
 
Exclusion Criteria for Organ Donation
  • HIV
  • Hepatitis B and C positive donors (Refer to transplant co-coordinator for individual assessment)
  • Any malignancy other than primary skin/CNS lesion
  • Treatment with human pituitary growth hormone and other hormones of pituitary origin
  • Untreated bacterial, viral, fungal infection
  • Creutzfeld–Jacobs's disease, family history of dementia.
 
Obtaining Consent for Organ Donation
After explanation of the illness, brain injury and the concept of brain death, the coordinator and intensivist should get consent for organ donation from the family members.
  • Contact local organ-procurement organization (OPO)
  • In conjunction with OPO, obtain verbal consent to perform noninvasive blood testing (blood sampling, ECG, radiology studies) to determine suitability for organ donation
  • Establish diagnosis of brain death
  • After brain death has been declared and in conjunction with OPO, obtain written family consent for donation.
 
Investigations
  • Before 1st apnea test—blood grouping and typing, complete blood count, liver function test, renal function test
  • After getting consent—HIV, Hbs Ag, anti–HCV, CMV, VDRL
  • Kidney donor—HLA typing, ultrasound kidney
  • Liver—USG
  • Heart—12 lead ECG, echocardiography if donor is >50 years, coronary angiogram
  • Lung—chest X-ray, ABG, bronchoscopy.768
Table 102.3   Two clinical phases of brain death
1st phase
2nd phase
Hypertension and tachycardia due to autonomic surge.
This is treated by:
  • SNP—0.5–5 µg/kg/minute
  • Esmolol—100–500 µg/kg bolus followed by 100–300 µg/kg/minute
  • Catecholamine depletion/↓ Sympathetic drive
  • Volume depletion due to diuretics mannitol, furosemide is used in the Rx of cerebral edema
  • Continuous blood loss from injuries
  • Insensible fluid loss
  • Diabetes insipidus
  • Metabolic/endocrine abnormalities
  • Hypothermia
  • Myocardial dysfunction
Abbreviation: SNP, sodium nitroprusside
 
Clinical Management of the Organ Donor
Severe brain injury and brain death create a variety of extracerebral organ manifestations including autonomic storm, neuroendocrine hormone deficiencies, systemic inflammatory response syndrome (SIRS), neurogenic pulmonary edema (NPE), myocardial stunning, electrolyte and immunologic derangements (Table 102.3).
The challenge of ICU physician is maintaining adequate organ perfusion and metabolism. Maximal ICU management strategies should be employed to bring out improved outcomes. The outcomes are the following:
  • Larger number of organs transplanted
  • Longer recipient survival times
  • Improved organ function following transplantation.
 
MANAGEMENT OF 2ND PHASE
 
Management of Cardiovascular System
 
Monitoring
  • Central venous monitoring is recommended for patients with brain death
  • PA catheter is not routinely placed in brain death patients but inserted for the following indications—ejection fraction ≤40% and patient on high vasopressor support.
 
Management of Hypotension
  • Rapid replacement of blood volume by infusing crystalloids/colloids with titration of CVP to 8–10 mm Hg with goal of systolic blood pressure >100 mm Hg, MAP = 60–70 mm Hg and heart rate <100/minute.
  • In case of inotrope/vasopressor support,
    • Dopamine - <10 µg/kg/minute.
    • Dobutamine - <10 µg/kg/minute.
    • 769There has been a recent trend towards use of vasopressin for circulatory support. Dose is 0.5–4 units/hour (0.01-0.04 U/min).
    • Second line agents are noradrenaline, adrenaline, and phenylephrine.
  • In case of monitoring with pulmonary artery is present, targets are PCWP = 12–14 mm Hg, cardiac index - >2.4 L/min/m2, SVR = 800–1200 dynes/sec/cm–5
  • Bradyarrhythmias can occur in brain death patients since heart is denervated and hence it is resistant to atropine. Dopamine or small doses of adrenaline 50–100 µg is given for treating it.
 
MANAGEMENT OF RESPIRATORY SYSTEM
The concerns related to respiratory system in brain death patients:
  • Lung injury (Release of proinflammatory cytokines)
  • Aspiration
  • Pulmonary contusion/pneumonia
  • Volutrauma/barotrauma
  • Pulmonary embolism
  • V/Q mismatch
  • Neurogenic pulmonary edema.
Neurogenic pulmonary edema occurs due to intense vasoconstriction (α-receptor stimulation) thus, leading to shifting of fluid from peripheral to central circulation thus, causing increase in left atrial pressure and pulmonary capillary pressure leading to pulmonary edema.
 
Interventions for Pulmonary Stability
  • Aggressive pulmonary care—Repositioning (every 2 hours); Chest physiotherapy and suctioning; Oral hygiene.
  • Careful fluid management—CVP-guided fluid therapy to avoid pulmonary edema.
  • Ventilation strategies
    FiO2 titrated to keep O2 saturation ≥95%
    PaO2 ≥80 mm Hg 
    pH—7.35–7.45
    PaCO2—35–45 mm Hg
    PEEP—5 cm H2O
    TV—6–8 mL/kg
    PIP—<30 cm H2O.
    }
    Goals of ventilation
  • Intervention of the inflammatory process.
    Methylprednisolone—15 mg/kg plays an important role in diminishing the systemic inflammatory response and it improves oxygenation.
  • It has been recommended that bronchoscopy should be undertaken in every lung organ donor for therapeutic bronchial toileting and for isolation of potential pathogens. Antimicrobial therapy should be tailored to bronchial wash Gram stain or culture results. Empirical antibiotics are not recommended.
770
 
MANAGEMENT OF ENDOCRINE SYSTEM
 
HPA Axis Dysfunction
 
Anterior Hypothalamic: Pituitary Endocrine Function
It was demonstrated from studies that T3 and T4 were reduced in brain death patients, hence the deficiencies are managed by supplementation with intravenous T3 of 4 µg bolus followed by 3 µg/hour infusion. This causes improved myocardial contractility and increased cardiac output. Adrenal insufficiency also occurs in brain death patients and this is the cause for reduced stress response during hypotension and can also cause organ failure. This is managed by administering methylprednisolone—15 mg/kg/day.
 
Posterior Hypothalamic Pituitary Deficiency
Diabetes insipidus (DI)
90% of donors have low or undetectable vasopressin (ADH) levels resulting in diabetes insipidus which can be diagnosed by:
  • Urine output—>500 mL/hour
  • Serum Na—>155 mEq/L
  • Urine specific gravity—>1.005
  • Serum osmolality—>305 mOsm/L.
Treatment
  • Volume replacement (with hypotonic saline or 5% dextrose in water)
  • DI in isolation can be treated with a continuous infusion of vasopressin or intermittent DDAVP.
  • Vasopressin infusion should be the first choice if hemodynamic support with vasopressin is required or combined hormonal therapy is indicated.
Desmopressin (DDAVP)
It's a highly selective V2 receptor activity with long half life and has diuretic action with minimal vasopressor activity. Dose is loading—8 ng/kg, infusion—4 ng/kg/hour.
Arginine vasopressin
In contrast to desmopressin, this has vasopressor activity. Therefore, administration of vasopressin treats diabetes insipidus as well as lowers the vasopressor requirement for the donor. Dose is 1 U bolus followed by infusion of 0.01–0.04 U/minute.
 
QUADRUPLE HORMONAL REPLACEMENT THERAPY (TABLE 102.4)
The Cardiac Work Group of the Crystal City Conference led by United Network for Organ Sharing (UNOS) recommended donor management protocol which includes four-drug hormonal resuscitation (T3, vasopressin, methylprednisolone, and insulin). It is given to patients who are hemodynamically unstable or with LV ejection fraction of <45%. Procurement and transplantation Network (OPTN)/UNOS did studies based on hormonal treatment of brain-dead donors (T3/T4, methylprednisolone, and arginine vasopressin) and they found better survival of organs in recipients and increased organ transplants.771
Table 102.4   Quadruple hormonal replacement therapy for brain death patients
  • T3: 4 µg bolus followed by 3 µg/hour infusion
  • Vasopressin: 1 U bolus followed by infusion of 0.01–0.04 U/minute
  • Methylprednisolone: 15 mg/kg/day
  • Insulin: Glycemic control with insulin infusion titrated to blood glucose target of 6–8 mmol/L
 
Renal System
Maintain systolic blood pressure >80–90 mm Hg to maintain renal perfusion.
 
Hepatic System
Depletion of liver glycogen occurs in 12 hours following brain death. Hence, administration of glucose and insulin may improve glycogen storage as well as improve glycemic control. If there is hypernatremia, it can cause accumulation of idiogenic osmoles within the liver and leads to graft dysfunction. Totsuka et al., has demonstrated that correcting donor sodium levels to <155 mmol/L decreases the incidence of liver allograft loss.
 
Hypothermia
In brain death patients, there is loss of neural connection between the temperature-regulating center and peripheral body tissues, hence there is hypothermia. Hypothermia is deleterious since it can cause cardiac arrhythmias, myocardial depression, shift of oxygen dissociation curve (ODC) curve to left side and coagulopathies. Interventions which can be done to maintain core temperature are warm IV fluids, warm blankets, humidified gases, thyroid hormone replacement and external warming devices.
 
Hematology
A hemoglobin target of 9–10 g/dL is the most appropriate to optimize cardiopulmonary function in the face of hemodynamic instability. The lowest hemoglobin limit allowable for ICU management of stable donors is 7 g/dL. Coagulopathy can be due to release of thromboplastin, hypothermia and dilutional effect.
 
BIBLIOGRAPHY
  1. Act and rules under Transplant of Human Organs Act (THOA) - http://notto.nic.in/.
  2. Amado JA, Lopez-Espadas F, Vazquez-Barquero A, et al. Blood levels of cytokines in brain-dead patients: Relationship with circulating hormones and acute-phase reactants. Metabolism. 1995;44:812.
  3. Harms J, Isemer FE, Kolenda H. Hormonal alteration and pituitary function during course of brainstem death in potential organ donors. Transplant Proc. 1991;23:2614.
  4. Mollaret P, Goulon M. Le coma dépassé (mémoire préliminaire). Rev Neurol (Paris). 1959;101:3.
  5. Novitzky D, Cooper DK, Rosendale JD, et al. Hormonal therapy of the brain-dead organ donor: experimental and clinical studies. Transplantation. 2006;82:1396.
  6. 772Practice parameters for determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 1995; 45:1012.
  7. Ropper AH. Unusual spontaneous movements in brain dead patients. Neurology. 1984;34:1089.
  8. Schrader H, Krogness K, Aakvaag A, et al. Changes of pituitary hormones in brain death. Acta Neurochir (Wien). 1980;52:239.
  9. Sugimoto T, Sakano T, Kinoshita Y, et al. Morphological and functional alterations of the hypothalamic-pituitary system in brain death with long term bodily living. Acta Neurochir (Wien). 1992;115:31.
  10. Walker AE, Diamond EL, Moseley J. The neuropathological findings in irreversible coma: a critique of the “respirator brain”. J Neuropathol Exp Neurol. 1975;34:295.
  11. Wijdicks EF. The diagnosis of brain death. N Engl J Med. 2001;344:1215.
  12. Young PJ, Matta BF. Anaesthesia for organ donation in the brainstem dead—why bother? Anaesthesia. 2000;55:105.
  13. Zaroff JG, Rosengard BR, Armstrong WF, et al. Consensus conference report: maximizing the use of organs recovered from the cadaver donor: Cardiac recommendations. Circulation. 2002;106:836.
773Medical Ethics
Chapter 103 Ethics in Critical Care Prem Kumar774

ETHICS IN CRITICAL CARECHAPTER 103

Prem Kumar
Medical ethics is a code of conduct that deals with moral values and choices resulting in the best course of action for patients suffering from medical conditions. Medical ethics relates the relationship between health care personnel and patients and is not limited to doctors alone. Ethics primarily deals with the human behavior (differentiation between the right and the wrong). Intensivists should make moral and ethical reasoning along with the patient and the kith and kin for end-of-life care with relevance to prognosis. Although it can be philosophical and based on religion and cultural backgrounds, the decision of the patient and relationship between the patient and intensivist–patient relationship is vital in the decision making towards end-of-life care. There can be differences in opinion regarding what is best for the patient between the patient and intensivist. Fair allocation of nursing care and resources with respect to critical care irrespective of the patient's financial condition, medical condition and prognosis should be done.
Intensive care is one of the costlier branches in medical care since it involves many health care providers, equipment and technology. Hence, it is important for the public, government and critical care expert panel to determine the budget which should be allocated for health in terms of critical care thus providing equitable access of medical care for all citizens. Ethical issues arise when there is clash of values. Resolving the ethical issues of intensive care is quite difficult and depends on the discussion of healthcare committee and the recognition of values.
 
END-OF-LIFE CARE
Over time, intensive care has become more costly, and bearing the economic burden is still more painful for patients and relatives in developing countries like India. Hence, it is clear that we need a comprehensive national initiative to bridge the gap between the problem and the patient. Although the practice of intensive care has become more systematic and standardized in India in the past decade, the biggest challenge for intensivists is the balance between financial burden of the patient and the provision of prolonged life support in patients where there is minimal chance of recovery/survival. The intensivist does not have the right to withhold life support against the will of the patient or the relatives.
In certain countries of the western world, there are laws for end-of-life care where the intensivist can withhold life support with the consent of the patient 776which is many times not possible or usually the kith and kin. In India, there is lack of a national end-of-life care (EOLC) policy. Indian association of palliative care (IAPC) has drafted consensus guidelines for end-of-life and palliative care in intensive care.
According to the guidelines, the steps involved in providing good end-of-life care are:
  • Recognize the dying process
  • End-of-life decision making process
  • Initiation of EOLC/EOLC pathway
  • Process of EOLC
  • Scope of palliative care in EOLC
  • After-death care
  • Medical care review meeting
  • Bereavement support.
The six principles of Gold Standards Framework include:
  1. Identification of patients needing EOLC
  2. Assessment of needs
  3. Planning of EOLC
  4. Provision of the EOLC
  5. Ongoing assessment of the process of EOLC
  6. Reflection on and improvisation of the EOLC process.
End-of-life care decision making process (Flow chart 103.1)
Once the decision to withdraw life support is taken, the whole process of decision making to withdraw life support, consent of the patient or relatives, the rationale and the method of withdrawing support is documented. According to studies, people of India preferred to die at their homes rather than in hospitals. In Indian set up, the most relevant option is palliative care at home.
Flow chart 103.1: End-of-life care decision making process
777
 
BIBLIOGRAPHY
  1. Chapman L, Ellershaw J. Care in the last hours and days of life. Medicine (Baltimore). 2011;39:674-7.
  2. End-of-life Care Strategy. Department of Health Publication. London; 2008.
  3. Jayaram R, Ramakrishnan N. Cost of intensive care in India. Indian J Crit Care Med. 2008;12:55-61.
  4. Macaden SC, Salins N, Muckaden M, Kulkarni P, Joad A, Nirabhawane V, et al. IAPC Consensus Position Statement on End-of-life Care Policy for the dying. Indian J Palliat Care. 2014;20:171-81.
  5. Macaden SC. Moving toward a national policy on palliative and end-of-life care. Indian J Palliat Care. 2011;17Suppl:S42-4.
  6. Mani RK, Amin P, Chawla R, Divatia J, Kapadia F, Khilnani P, et al. Guidelines for end-of-life and palliative care in Indian intensive care units’ ISCCM consensus ethical position statement. Indian J Crit Care Med. 2012;16:166-81.
Appendices
Appendix 1 Normal Biochemical Values
Appendix 2 Clinical Scores, Indices and Equations
Appendix 3 Drugs, Dosages and Side Effects
Appendix 4 ICU Rounds780

NORMAL BIOCHEMICAL VALUESAPPENDIX 1

 
REFERENCE VALUES FOR LABORATORY TESTS
Blood analytes
Lipid profile
Conventional unit
SI unit
Total cholesterol
Desirable
<200 mg/dL
<5.17 mmol/L
Borderline high
200–239 mg/dL
5.17–6.18 mmol/L
High
>240 mg/dL
>6.21 mmol/L
LDL cholesterol
Optimal
<100 mg/dL
<2.59 mmol/L
Near optimal
100–129 mg/dL
2.59–3.34 mmol/L
Borderline high
130–159 mg/dL
3.36–4.11 mmol/L
High
160–189 mg/dL
4.14–4.89 mmol/L
Very high
>190 mg/dL
>4.91 mmol/L
HDL cholesterol
Desirable
30–75 mg/dL
0.75–1.95 mmol/L
Low
<40 mg/dL
<1.03 mmol/L
High
>60 mg/dL
>1.55 mmol/L
Triglycerides
Desirable
30–200 mg/dL
0.34–2.26 mmol/L
Glucose
Fasting
Normal–Adult
75–110 mg/dL
4.2–6.1 mmol/L
Neonate
30–60 mg/dL
1.7–3.3 mmol/L
Newborn
40–80 mg/dL
2.2–4.5 mmol/L
Child
60–100 mg/dL
3.3–5.6 mmol/L
Impaired glucose tolerance (adult)
111–125 mg/dL
6.2–6.9 mmol/L
Diabetes mellitus (adult)
>125 mg/dL
>7.0 mmol/L
2 hours post-prandial
Normal (adult)
70–120 mg/dL
3.9–6.7 mmol/L
Glycated hemoglobin (HbA1c)
4–6%
0.04–0.06 Hb fraction
Aceto-acetate
0.2–1.0 mg/dL
20–99 μmol/L
Lactic acid
5–12 mg/dL
0.5–1.2 mmol/L782
Iron hemostasis parameters
Iron
41–141 μg/dL
7–25 μmol/L
Ferritin
Male
29–248 ng/mL
29–248 μg/L
Female
10–150 ng/mL
10–150 μg/L
Transferrin
200–400 mg/dL
2.0–4.0 g/L
Liver function test
Total protein
Newborn
4.6–7.0 g/dL
46–70 g/L
>2 years
6.0–8.0 g/dL
60–80 g/L
Adult
6.7–8.6 g/dL
67–86 g/L
Albumin
Male
4.0–5.0 g/dL
40–50 g/L
Female
4.1–5.3 g/dL
41–53 g/L
Globulin
2.0–3.5 g/dL
20–35 g/L
Bilirubin
Total
Direct
Indirect
0.3–1.3 mg/dL
5.1–22 μmol/L
0.1–0.4 mg/dL
1.7–6.8 μmol/L
0.2–0.9 mg/dL
3.4–15.2 μmol/L
Prothrombin time
12.7–15.4 s
12.7–15.4 s
Ceruloplasmin
25–63 mg/dL
250–630 mg/L
Markers of liver cell injury
Alanine aminotransferase (SGPT)
7–41 U/L
0.12–0.70 μkat/L
Aspartate aminotransferase (SGOT)
12–38 U/L
0.2–0.65 μkat/L
Markers of cholestasis
Alkaline phosphatase (ALP)
33–96 U/L
0.56–1.63 μkat/L
Gamma glutamyl transferse (GGT)
9–58 U/L
0.15–0.99 μkat/L
Ammonia
19–60 μg/dL
11–35 μmol/L
Kidney function test
Creatinine
Newborn
0.3–1.0 mg/dL
27–88 μmol/L
Infant
0.2–0.4 mg/dL
18–35 μmol/L
Child
0.3–0.7 mg/dL
27–62 μmol/L
Adolescent
0.5–1.0 mg/dL
44–88 μmol/L
Male
0.6–1.2 mg/dL
53–106 μmol/L
Female
0.5–0.9 mg/dL
44–80 μmol/L783
Urea
15–40 mg/dL
5.4–14.3 mmol/L
Blood urea nitrogen
7–20 mg/dL
2.5–7.1 mmol/L
Creatinine clearance
91–130 mL/min
1.5–2.2 mL/s
Inulin clearance
Male
124 ± 25.8 mL/min
2.1 ± 0.4 mL/s
Female
119 ± 12.8 mL/min
2.0 ± 0.2 mL/s
Uric acid
Male
3.1–7.0 mg/dL
0.18–0.41 μmol/L
Female
2.5–5.6 mg/dL
0.15–0.33 μmol/L
Thyroid function test
TSH
Adult
0.34–4.25 μIU/mL
0.34–4.25 mIU/L
Pregnancy
0.3–5.2 μIU/mL
0.3–5.2 mIU/L
Cord blood
2.3–13.2 μIU/mL
2.3–13.2 mIU/L
Children
0.7–6.4 μIU/mL
0.7–6.4 mIU/L
Newborn screening (Whole blood heel puncture)
<20 μIU/mL
<20 mIU/L
T4
Cord blood
7.4–13.1 μg/dL
95–168 nmol/L
1–5 years
7.3–15.0 μg/dL
94–194 nmol/L
5–10 years
6.4–13.3 μg/dL
83–172 nmol/L
10–15 years
5.6–11.7 μg/dL
72–151 nmol/L
Male
4.6–10.5 μg/dL
59–135 nmol/L
Female
5.5–11.0 μg/dL
65–138 nmol/L
Free T4
Newborn
2.2–5.3 ng/dL
28.4–68.4 pmol/L
Children
0.8–2.0 ng/dL
10.3–25.8 pmol/L
Adult
0.8–2.7 ng/dL
10.3–34.7 pmol/L
Pregnancy
0.5–1.6 ng/dL
6.4–20.6 pmol/L
T3
Cord blood
5–141 ng/dL
0.08–2.17 nmol/L
Adult
77–135 ng/dL
1.2–2.1 nmol/L
Pregnancy
80–260 ng/dL
1.25–4.00 nmol/L
Free T3
Cord blood
1.5–3.91 pg/mL
0.2–6.0 pmol/L
Pregnancy
2.0–3.8 pg/mL
3.1–5.9 pmol/L
Children and adult
2.4–4.2 pg/mL
3.7–6.5 pmol/L
Arterial blood gas analysis
pH
7.35–7.45
7.35–7.45
Bicarbonate
22–30 mEq/L
22–30 mmol/L
pCO2
32–45 mm/Hg
4.3–6.0 kpa
pO2
72–104 mm/Hg
9.6–13.8 kpa
Anion gap
7–16 mEq/L
7–16 mmol/L
Osmolality
275–295 mOsmol/kg
275–295 mOsmol/kg784
Electrolytes
Sodium
136–146 mEq/L
136–146 mmol/L
Potassium
3.5–5.0 mEq/L
3.5–5.0 mmol/L
Chloride
102–109 mEq/L
102–109 mmol/L
Calcium
Total
8.7–10.2 mg/dL
2.2–2.6 mmol/L
Ionized
4.5–5.3 mg/dL
1.12–1.32 mmol/L
Phosphorus
2.5–4.3 mg/dL
0.81–1.4 mmol/L
Magnesium
1.5–2.3 mg/dL
0.62–0.95 mmol/L
Lead
<10 μg/dL
<0.5 μmol/L
Mercury
0.6–59 μg/L
3.0–294 nmol/L
Arsenic
2–23 μg/L
0.03–031 μmol/L
Cadmium
<5.0 μg/L
<44.5 nmol/L
Zinc
75–120 μg/dL
11.5–18.5 μmol/L
Cardiac markers
Creatine kinase (CK)
Total–Male
51–294 U/L
0.87–5.0 μkat/L
Female
39–238 U/L
0.66–4.0 μkat/L
CPK-MB
0.0–5.5 ng/mL
0.0–5.5 μg/L
Troponins
Troponin I
0.0–0.08 ng/mL
0.0–0.08 μg/L
Troponin T
0.0–0.01 ng/mL
0.0–0.01 μg/L
Lactate dehydrogenase (LDH)
115–221 U/L
2.0–3.8 μkat/L
Myoglobin
Male
19–92 μg/L
19–92 μg/L
Female
12–76 μg/L
12–76 μg/L
Pancreatic function test
Amylase
20–96 U/L
0.34–1.6 μkat/L
Lipase
3–43 U/L
0.51–0.43 μkat/L
Insulin
2–20 μU/mL
14.35–143.5 pmol/L
C-peptide
0.5–2.0 ng/mL
0.17–0.66 nmol/L
Gastric function test
Gastrin
<100 pg/mL
<100 ng/mL
Glucagon
20–100 pg/mL
20–100 ng/L
OPC poisoning
Cholinesterase
5–12 U/mL
5–12 kU/L
Pseudocholinesterase
8–18 IU/mL
785Urine analysis
Specific gravity
1.001–1.035
1.001–1.035
Acidity
20–40 mEq/d
20–40 mmol/d
pH
5.0–9.0
5.0–9.0
Urea
10–20 g/d
0.43–0.71 mol/d
Creatinine
Male
14–26 mg/kg/d
124–230 μmol/kg/d
Female
11–20 mg/kg/d
97–177 μmol/kg/d
Uric acid
250–800 mg/d
1.49–4.76 mmol/d
Glucose
50–300 mg/d
0.3–1.7 mmol/d
Total protein
<150 mg/d
<0.15 g/d
Albumin
Normal
0–30 mg/d
0.0–0.03 g/d
Microalbuminuria
30–300 mg/d
0.03–0.30 g/d
Macroalbuminuria
>300 mg/d
>0.3 g/d
Ammonia
30–50 mEq/d
30–50 mmol/d
Amylase
4–400 U/L
Calcium
<300 mg/d
<7.5 mmol/d
Phosphate
400–1300 mg/d
12.9–42.0 mmol/d
Sodium
100–260 mEq/d
100–260 mmol/d
Chloride
110–250 mEq/d
110–250 mmol/d
5-Hydroxy indole acetic acid (5–HIAA)
2–9 mg/d
10–47 μmol/d
Vannilyl mandelic acid (VMA)
1.4–6.5 mg/d
7–33 μmol/d
CSF analysis
Osmolarity
292–297 mOsmol/L
292–297 mmol/kg H2O
Volume
150 mL
CSF pressure
50–180 mm H2O
pH
7.31–7.34
7.31–7.34
pCO2
45–49 mm Hg
6–7 kpa
Glucose
40–70 mg/dL
2.22–3.89 mmol/L
Protein (lumbar)
15–50 mg/dL
0.15–0.5 g/L
Lactate
10–20 mg/dL
1–2 mmol/L
Ammonia
25–80 μg/dL
15–47 μmol/L
Red blood cells
nil
nil
Leukocytes
0–5 mononuclear cells/mm3
0–5 mononuclear cells/μL786
Electrolytes
Sodium
135–145 mEq/L
135–145 mmol/L
Potassium
2.7–3.9 mEq/L
2.7–3.9 mmol/L
Calcium
2.1–3.0 mEq/L
1.0–1.5 mmol/L
Chloride
116–122 mEq/L
116–122 mmol/L
Magnesium
2.0–2.5 mEq/L
1.0–1.2 mmol/L
Hormones
Adreno-
corticotrophic hormone (ACTH)
Newborn
10–185 pg/mL
2.2 – 41pmol/L
Adult
<120 pg/mL
<26 pmol/L
Aldosterone
Adult–Supine
3–16 ng/dL
0.08–0.44 nmol/L
Upright
7–30 ng/dL
0.19–0.83 nmol/L
Androstenedione
Child
<5 ng/dL
0.2 nmol/L
Adults–Male
75–205 ng/dL
2.6–7.2 nmol/L
Female
82–275 ng/dL
3.0–9.6 nmol/L
Antidiuretic hormone (ADH)
270–280
mOsm/kg
<1.5 ng/L
<1.4 pmol/L
280–285
mOsm/kg
<2.5 ng/L
<2.3 pmol/L
285–290
mOsm/kg
1–5 ng/L
0.9–4.6 pmol/L
290–294
mOsm/kg
2–7 ng/L
1.9–6.5 pmol/L
295–300
mOsm/kg
4–12 ng/L
3.7–11.1 pmol/L
Catecholamines
Epinephrine
Adults–Supine
(30 min)
<50 pg/mL
<273 pmol/L
Sitting (15 min)
<60 pg/mL
<328 pmol/L
Standing (30 min)
<90 pg/mL
<491 pmol/L
Norepinephrine
Adults–Supine
(30 min)
110–410 pg/mL
650–2423 pmol/L
Sitting (15 min)
120–680 pg/mL
709–4019 pmol/L
Standing (30 min)
125–700 pg/mL
739–4137 pmol/L
Dopamine
Adult (all positions)
<87 pg/mL
<475 pmol/L
Chorionic gonadotropin
Male and non-pregnant female
<5.0 mIU/mL
<5.0 IU/L
Pregnancy (depends on weeks)
5–15000 mIU/mL
5–15000 IU/L
Trophoblastic disorders
>100,000 mIU/mL
>100,000 IU/L787
Cortisol–total
Cord blood
5–17 μg/dL
138–469 nmol/L
Infant
2–11 μg/dL
55–304 nmol/L
Child
3–21 μg/dL
83–580 nmol/L
Adult
5–23 μg/dL
138–635 nmol/L
Cortisol–free
0.6–1.6 μg/dL
17–44 nmol/L
Dehydro-epiandrosterone
Male
180–1250 ng/dL
6.25–43.4 nmol/L
Female
130–980 ng/dL
4.51–34.0 nmol/L
11-Deoxy cortisol
Cord blood
295–554 ng/dL
9–16 nmol/L
Adult
20–158 ng/dL
0.6–4.6 nmol/L
Dihydrotestosterone
Child
<3 ng/dL
<0.10 nmol/L
Male
30–85 ng/dL
1.03–2.92 nmol/L
Female
4–22 ng/dL
0.14–0.76 nmol/L
Estradiol
Male
10–50 pg/mL
37–184 pmol/L
Female
20–450 pg/mL
73–1652 pmol/L
Postmenopausal
<21 pg/mL
<74 pmol/L
Estriol–free
Male and nonpregnant female
<2.0 ng/mL
<6.9 nmol/L
Pregnancy
0.30–28.9 ng/mL
1.04–100.3 nmol/L
Estriol–Total
Pregnancy
38–460 ng/mL
132–1596 nmol/L
Male
1.0–11.0 μg/day
3.5–38.2 nmol/day
Female
0–60.0 μg/day
0–38.2 nmol/day
Postmenopausal
0–11.0 μg/day
0–38.2 nmol/day
Estrone
Male
15–65 pg/mL
55–240 pmol/L
Female
15–250 pg/mL
55–925 pmol/L
Postmenopausal
15–55 pg/mL
55–204 pmol/L
Follicular-stimulating hormone
Male
1.4–15.4 mIU/mL
1.4–15.4 IU/L
Female
1.4 – 92 mIU/mL
1.4–92 IU/L
Postmenopausal
19.3–100. 6 mIU/mL
19.3–100.6 IU/L
Growth hormone
Basal
2–5 ng/mL
2–5 μg/L
Insulin tolerance test
>10 ng/mL
>10 μg/L788
17-Hydroxy progesterone
Male
27–199 ng/dL
0.8–6.0 nmol/L
Female
15–290 ng/dL
0.4–8.7 nmol/L
Pregnancy
200–1200 ng/dL
6.0–36.0 nmol/L
Post ACTH
<320 ng/dL
<9.6 nmol/L
Post-menopausal
<70 ng/dL
<2.1 nmol/L
Insulin
2–25 μIU/mL
12–250 pmol/L
Insulin-like growth factor 1
135–449 ng/mL
135–449 μg/L
Insulin-like growth factor 2
288–736 ng/mL
288–736 μg/L
Luteinizing hormone
Male
1.2–7.8 mIU/mL
1.2–7.8 IU/L
Female–Follicular
1.7–15.0 mIU/mL
1.7–15.0 IU/L
Midcycle peak
21.9–56.6 mIU/mL
21.9–56.6 IU/L
Luteal phase
0.6–16.3 mIU/mL
0.6–16.3 IU/L
Post-menopausal
14.2–52.3 mIU/mL
14.2–52.3 IU/L
Parathormone
10–65 pg/mL
10–65 ng/L
Parathormone-related peptide (PTHRP)
<1.4 pmol/L
<1.4 pmol/L
Proinsulin
1.1–6.9 pmol/L
1.1–6.9 pmol/L
Prolactin
Male
3.0–14.7 ng/mL
3.0–14.7 μg/L
Female
3.8–23.0 ng/mL
3.8–23.0 μg/L
Pregnancy
95–473 ng/mL
95–473 μg/L
Testosterone–total
Male
50–210 pg/mL
174–729 pmol/L
Female
1.0–8.5 pg/mL
3.5–29.5 pmol/L
Testosterone–free
Male
260–1000 ng/dL
9–34.72 nmol/L
Female
15–70 ng/dL
0.52–2.43 nmol/L

CLINICAL SCORES, INDICES AND EQUATIONSAPPENDIX 2

 
APACHE II SCORING SYSTEM
APACHE II Score=Acute Physiology Score + Age Points + Chronic Health Points
+4
+3
+2
+1
0
+1
+2
+3
+4
Rectal temperature (0°C)
≥ 41
39– 40.9
38–38.9
36– 38.4
34– 35.9
32–33.9
30–31.9
<29.9
MAP (mm Hg)
>160
130–159
110–129
70–109
50– 69
<49
HR (beats/min)
>180
140–179
110–139
70–109
55– 69
40–54
<39
RR (beats/min)
>50
35–49
25–34
12–24
10 –11
6–9
<5
O2 delivery (mL/min)
>500
350–499
200–349
<200
PaO2 (mm/Hg)
>70
61–70
55–60
<55
pH
>7.7
7.6–7.69
7.5 – 7.59
7.3 – 7.49
7.25– 7.3
7.15 – 7.2
<7.15
Na
>180
160–179
155–159
150–154
130 –149
120–129
111–119
<110
K
>7
6–6.9
5.5 – 1.9
3.5 – 5.4
3–3.4
2.5 –2.9
<2.5
Cr
>3.5
2–3.4
1.5–1.9
0.6 – 1.4
<0.6
Hct
>60
50–59.9
46–49.9
30–45.9
20–29.9
<20
WBC count
>40
20–39.9
15–19.9
3–14.9
1–2.9
<1
790
Age
Points
<44
0
45–54
2
55–64
3
65–74
5
>75
6
History of severe organ insufficiency
Points
Nonoperative patients
5
Emergency postoperative patients
5
Elective postoperative patients
2
 
MODS SCORING SYSTEM
Variable
0
1
2
3
4
PaO2/FiO2
>300
226–300
151–225
76–150
≤5
Platelet count (103/mm3)
>120
80–120
50–80
21–50
≤20
Bilirubin (mg/dL)
≤1.2
1.2–3.5
3.5–7.0
7.0–14
≥14
HR X CVP/MAP
≤10
10.1–15
15.1–20
20.1–30
>30
Glasgow Coma Scale score
15
13–14
10–12
7–9
≤6
Creatinine (mg/dL)
≤1.1
1.1–2.3
2.3–4
4.0–5.7
5.7
Abbreviations: HR, heart rate; CVP, central venous pressure; MAP, mean arterial pressure
 
SOFA SCORING SYSTEM
Variable
1
2
3
4
PaO2 (mm Hg)
<400 ± MV
<300 ± MV
<200 + MV
< 100 + MV
Platelet count (103/mm3)
<150
<100
<50
<20
Cardiovascular system
MAP <70 mm Hg
Dopa/dobutamine ≤5 μg/kg min
Dopa >5 μg/kg/min, adr/NA ≤0.1 μg/min
Dopa >15 μg/kg min, adr/NA >0.1 μg/min
Glasgow Coma Scale
13–15
10–12
6–9
<6
Bilirubin (mg/dL)
1.2–1.9
2–5.9
6–11.9
>12
Cr (mg/dL) or Urine output
1.2–1.9
2–3.4
3.5–4.9 or
<500 mL/day
>5 or
<200 mL/day
Abbreviations: MV, mechanical ventilation; MAP, mean arterial pressure; NA, noradrenaline
791
 
GOLD CRITERIA FOR GRADING SEVERITY OF COPD
GOLD stage–severity
Spirometry
0 – At risk
Normal
I – Mild
FEV1/FVC <0.7 and FEV1 ≥80% predicted
II – Moderate
FEV1/FVC <0.7 and 50% ≤FEV1 <80% predicted
III – Severe
FEV1/FVC <0.7 and 30% ≤FEV1 <50% predicted
IV – Very severe
FEV1/FVC <0.7 and FEV1<30% predicted
or
FEV1 <50% predicted with respiratory failure or signs of right heart failure
 
LEVELS OF RISK ASSOCIATED WITH INCREASING BODY MASS INDEX
Classification
BMI (kg/m2)
Risk of developing health problems
Underweight
<18.5
Increased
Normal weight
18.5–24.9
Least
Overweight
25.0–29.9
Increased
Obese
Class 1
30.0–34.9
High
Class 2
35.0–39.9
Very high
Class 3
40.0–49.9
Extremely high
Superobese
≥50
Exceedingly high
 
WAIST CIRCUMFERENCE AND RISK
Waist Circumference
Body Mass Index (kg/m2)
Normal Weight
Overweight
Obese Class 1
< 102 cm (♂)
Least risk
Increased risk
High risk
< 88 cm (♀)
≥ 102 cm (♂)
Increased risk
High risk
Very high risk
Nitrogen balance (g) = protein intake (g) – (24 hours urinary urea nitrogen excretion + 4) 6.25
The respiratory quotient (RQ) is the ratio of VCO2 to VO2.
  RQ  = VCO2/VO2
Harris Benedict equation:
  • Men: BEE (kcal/24 hr) = 66.5 + (13.7 × weight) + (5 × height) – (6.8 × age)
  • Women: BEE (kcal/24 hr) = 66.5 + (9.6 × weight) + (1.7 × height) – (4.7 × age)
792Calculation of REE:
  • REE (kcal/min) = 3.94 (VO2) + 1.1(VCO2)
  • REE (kcal/day) = REE × 1440
 
SF-MPQ (SHORT FORM–MCGILL PAIN QUESTIONNAIRE)
Quality of pain
None
Mild
Moderate
Severe
Throbbing
Shooting
Stabbing
Sharp
Cramping
Gnawing
Hot burning
Aching
Heavy
Tender
Splitting
Tiring–exhausting
Sickening
Fearful
Punishing-cruel
No pain ...................................................................................worst possible pain
Table 1   Present pain intensity (PPI)
0
No pain
1
Mild
2
Discomforting
3
Distressing
4
Horrible
5
Excruciating
793
 
RAMSAY SEDATION SCALE (RSS)
Score
Description
1
Anxious and agitated or restless, or both
2
Cooperative, orientated, and tranquil
3
Drowsy, but responds to commands
4
Asleep, brisk response to light glabellar tap or loud auditory stimulus
5
Asleep, sluggish response to light glabellar tap or loud auditory stimulus
6
Asleep and unarousable
 
RICHMOND AGITATION SEDATION SCALE (RASS)
Score
Label
Description
+4
Combative
Combative, violent, immediate danger to staff
+3
Very agitated
Pulls to remove tubes or catheters; aggressive
+2
Agitated
Frequent non-purposeful movement, fights ventilator
+1
Restless
Anxious, apprehensive, movements not aggressive
0
Alert and calm
Spontaneously pays attention to caregiver
-1
Drowsy
Not fully alert, but has sustained awakening to voice
(eye opening and contact >10 sec)
-2
Light sedation
Briefly awakens to voice (eyes open and contact <10 sec)
-3
Moderate sedation
Movement or eye opening to voice (no eye contact)
-4
Deep sedation
No response to voice, but movement or eye opening to physical stimulation
-5
Unarousable
No response to voice or physical stimulation
 
Oxygen Saturation at Various Chambers and Vessels
Sampling chamber or vessel
Oxygen saturation (in %)
SVC
70
IVC
80
RA
75
RV
75
Pulmonary artery
75794
 
Parameters Measured by Pulmonary Artery (PA) Catheter
Variable
Normal range (Units)
Central venous pressure (CVP)
0–8 mm Hg
Right ventricular systolic pressure (RVSP)
15–30 mm Hg
Right ventricular end-diastolic pressure (RVEDP)
0–8 mm Hg
Pulmonary artery systolic pressure (PAP)
15–30 mm Hg
Pulmonary artery diastolic pressure (PADP)
4–12 mm Hg
Pulmonary artery occlusion pressure (PAOP)
2–12 mm Hg
Mean pulmonary artery pressure
10–18 mm Hg
 
Derived Parameters Obtained with Data from PA Catheter
Variable
Formula
Normal range
Body surface area (BSA)
Weight(kg)0.425 × height (cm) 0.725 × 0.007184
Arterial oxygen content (CaO2)
SaO2 × Hb × 1.39 + PaO2 (mm Hg) × 0.003
180 mL liter–1
Mixed venous oxygen content (CVO2)
SvO2 × Hb × 1.39 + PvO2 (mm Hg) × 0.003
130 mL liter–1
Oxygen delivery (DO2)
× CaO2
800–1000 mL min –1
Oxygen consumption (VO2)
/(Cao2/CvO2)
180–300 mL min–1
Oxygen delivery index (DO2I)
DO2/BSA
500–650 mL min–1 m–2
Oxygen consumption (VO2 I)
VO2/BSA
100–180 mL min–1 m–2
Cardiac index (CI)
/BSA
2.5–4.0 liter min1 m–2
Stroke volume (SV)
/HR
60–80 mL
Stroke index (SI)
SV/BSA
30–65 mL m–2
Left ventricular stroke work index (LVSWI)
CI × (MAP – PAOP) × 0.0136
40–60 g m–1 m–2
Systemic vascular resistance (SVR)
(MAP – CVP) × 80/
900–1200 dyn s cm5 m–2
Systemic vascular resistance index (SVRI)
(MPA – CPA) × 80/CI
1500–2500 dyn s cm–5 m–2
Mean pulmonary artery pressure (mPAP)
[PASP + (2 × PADP)]/3
10–20 mm Hg
Right ventricular stroke work index (RVSWI)
Cl × (MPAP – CVP) × 0.0136
6–12 g m–1 m–2
Pulmonary Vascular resistance (PVR)
(MPAP – PAOP) × 80/
50–150 dyn s cm–5 m–2
Pulmonary vascular resistance index (PVRI)
(MPAP – PAOP) × 80/CI
250–350 dyn s cm –1 m2
Ō, cardiac output
795
 
Grading of Diffuse Axonal Injury (DAI)
Clinical grading of DAI
1.
Mild DAI—duration of coma is between 6 and 24 hours.
2.
Moderate DAI—duration of coma is for >24 hours but without presence of decerebrate posturing as the best motor response on nociceptive stimulation.
3.
Severe DAI—duration of coma is for >24 hours and with presence of decerebrate posturing as a motor response on nociceptive stimulation.
MRI grading of DAI
1.
Grade 1—small scattered lesions on the white matter of cerebral hemisphere
2.
Grade 2—grade 1 plus focal lesions on the corpus callosum
3.
Grade 3—grade 1 and 2 plus additional focal lesions on the brainstem.
 
Glasgow Coma Scale
Eye-opening response
4 = Spontaneous
3 = To speech
2 = To pain
1 = None
Verbal response
5 = Oriented to name
4 = Confused
3 = Inappropriate speech
2 = Incomprehensible sounds
1 = None
Motor response
6 = Follows commands
5 = Localizes to painful stimuli
4 = Withdraws from painful stimuli
3 = Abnormal flexion (decorticate posturing)
2 = Abnormal extension (decerebrate posturing)
1 = None
Severity of GCS
Score
Need of CT–Brain
Management
Mild
14, 15
Yes
Observation
Moderate
9–13
Yes
Observation in ICU
Severe
3–8
Yes
Mechanical ventilation with ICP monitoring
796
 
Marshall Scale: CT Scan Categories for Head Injury
Category
Definition
Diffuse injury I
No visible intracranial pathologic process
Diffuse injury II
Cisterns with midline shift of 0–5 mm are present ± lesion densities present; no high or mixed density lesions at ≥ 25 mL
Diffuse injury III
Cisterns compressed or absent, with midline shift of 0–5 mm; no high or mixed density lesions of ≥ 25 mL
Diffuse injury IV
Midline shift of >5 mm; no high or mixed density lesion of ≥ 25 mL
Evacuated mass lesion (V)
Any lesion surgically evacuated
Nonevacuated mass lesion (VI)
High or mixed density lesion of ≥ 25 mL; not surgically evacuated
 
Differences Between Pre-renal Azotemia and Acute Kidney Injury
Pre-renal azotemia
Acute kidney injury
BUN/creatinine ratio above 20
FeNa <1%
Urine sodium concentration < 10 mEq per L
Urine specific gravity >1.018
Urine osmolality >500 mOsm/kg
Urine sediment shows hyaline casts
FeNa typically >1%
Urine sediment often contains granular casts, renal tubular epithelial cell casts.
Urine osmolality < 500 mOsm/kg
Table 2   RIFLE criteria for acute renal dysfunction
Category
GFR
Urine output
Risk
Increased creatinine × 1.5 or GFR decrease >25%
UO < 0.5 mL/kg/hr × 6 hr
High sensitivity
Injury
Increased creatinine × 2 or
GFR decrease >50%
UO < 0.5 mL/kg/hr × 12 hr
Failure
Increased creatinine × 3 or
GFR decrease >75%
UO < 0.3 mL/kg/hr × 24 hr or anuria × 12 hrs
High specificity
Loss
Persistent ARF = complete loss of function > 4 weeks
High specificity
ESRD
End stage disease

DRUGS, DOSAGES AND SIDE EFFECTSAPPENDIX 3

 
CARDIOVASCULAR SYSTEM
S.No.
Drugs
Loading dose
Maintenance dose
Adverse effects
Acute myocardial infarction
1
Anti-platelets
Clopidogrel
75 mg PO Daily
Nausea, vomiting, diarrhea, bleeding, thrombotic thrombocytopenic purpura
2
Beta-blockers
Metoprolol
5 mg IV X 3 Dose
50–200 mg PO q 12
Bradycardia, hypotension, fatigue, bronchospasm, heart block depression, sexual dysfunction
Esmolol
500 mg/kg
50–300 mg/kg/minute
3
Direct thrombin inhibitors
Argatroban
350 mg/kg
25 mg/kg/minute
Bleeding and hypersensitivity reactions
Bivalirudin
1 mg/kg
2.5 mg/kg/hr
4
Fibrinolytics
Alteplase
15 mg
0.75 mg/kg (50 mg) x 30 minute
0.5 mg/kg (35 mg) x 60 minute
100 mg over 90 minute
Mild hypotension, bleeding
Reteplase
10 mg IV
10 mg IV after 30 minute of first dose
Tenectaplase
≤60 kg– 30 mg
61–70 kg–35 mg
71–80 kg–40 mg798
81– 90 kg–45 mg
≥90 kg–50 mg
Streptokinase
1.5 million units over 2 hrs
5
Gp IIb/IIIa inhibitors
Abciximab
0.25 mg/kg
0.125 mg/kg/minute
Thrombocytopenia, bleeding
Eptifibitide
180 mg/kg
2 mg/kg/minute
Tirofiban
0.4 mg/kg/min x 30 min
0.1 mg/kg/minute
6
Low molecular weight heparins
Enoxaparin
1 mg/kg SC q12h
Dalteparin
120 U/kg SC q12h
7
Nitrates
Nitroglycerin
10–200 mg/min
Headache, flushing, dizziness, hypotension, tachycardia
Isosorbide dinitrate
5–40 mg PO TID
Isosorbide mono nitrate
30–120 mg PO daily
8
Nsaids
Aspirin
160–325 mg/D– PO
Bleeding, dyspepsia, gastritis. Tinnitus, anaphylaxis
9
Opioids
Morphine
2–4 mg IV q5 minute
Constipation, dyspepsia, nausea, drowsiness, respiratory depression, hypotension, pruritis
10
Unfractioned heparin
60 U/kg/hr
12 U/kg/hr
Bleeding, type 1 and type 2 heparin-induced thrombocytopenia, bleeding, hyperkalemia799
Anti arrhythmics and conduction abnormalities
1
Adenosine
6 mg (repeat 12 mg if first dose is not effective)
Flushing, headache, nervousness, anxiety
2
Amiodarone
300 mg
1 mg/min x 6 hr
0.5 mg/minute for ≥18 hour
Bradycardia, hypotension, nausea, heart block, pulmonary fibrosis, blue gray discoloration, optic neuropathy
3
Atropine
1 mg IV q 3–5 minute
Dry eyes, dry mouth, urinary retention, tachycardia
4
Calcium channel blockers
Diltiazem
0.25 mg/kg
5–15 mg/hr
Bradycardia, hypotension, constipation, headache, flushing edema, heart block and heart failure
Verapamil
5 mg
5–15 mg/hr
5
Epinephrine
1 mg IV q 3–5 minute
Tachycardia, hypertension
6
Lidocaine 
1–1.5 mg/kg
1–4 mg/minute
Confusion, drowsiness, slurred speech, psychosis, muscle twitch, bradycardia, seizure
7
Procainamide
15–18 mg/kg
1–6 mg/kg
Diarrhea, nausea, vomiting, torsade de pointes
8
Vasopressin
40 units IV
Bradycardia, precipitates angina, congestion, rhinitis, epistaxis, fluid retention, hyponatremia
Congestive heart failure
1
Angiotensin-converting enzyme (ACE) inhibitors
Captopril
6.25 – 50 mg PO TID
Cough, hyperkalemia, hypotension, renal insufficiency, anaphylaxis, angioneurotic edema
Lisinopril
2.5–40 mg PO BID
Enalapril
2.5–10 mg PO BID
Ramipril
1.25–5 mg PO BID
2
Aldosterone receptor blockers
Spironolactone
12.5–50 mg PO
Hyperkalemia, gynecomastia, hyponatremia
Eplerenone
25–50 mg PO
800
3
Digoxin
10–15 mg/kg (50 % in initial dose, and 25 % at 6–12 hrs x 2)
0.125–0.5 mg/day
Bradycardia, arrhythmias, heart block, visual disturbances, mental disturbances
4
Loop diuretics
Furosemide
20–80 mg/day IV or PO IN 2 – 3 divided dose
Hypokalemia, hypomagnesemia, hypocalcemia, orthostatic hypotension, azotemia,ototoxicity
Torasemide
10 – 20 mg IV/PO daily
Bumetanide
0.5 – 2 mg/day in 1 –2 doses
5
Nesiritide
2 mg/kg
0.01–0.03 mg/kg/min
Hypotension, increased serum creatinine
Hypertensive emergencies
1
Angiotensin-converting enzyme (ACE) inhibitors
Enalaprilat
1.25 – 5 mg IV q6h
Hypotension, hyperkalemia, renal insufficiency, anaphylaxis, angiodema
2
Beta and alpha adrenergic blocker
Labetalol
20 – 40 mg
0.5–2 mg/minute if needed
Nausea, vomiting, hypotension, bradycardia, heart block, bronchoconstriction
3
Calcium channel blockers
Nicardipine
3 – 15 mg/hr
Hypotension, tachycardia, flushing, peripheral edema
4
Central sympatholytics
Clonidine
0.1 – 0.3 mg PO BID–TID
Drowsiness, dizziness,hypotension, bradycardia, dry mouth
5
Vasodilators
Hydralazine (arteriolar)
10 – 40 mg IV q4–q6 h Or
10 – 75 mg PO TID – QID
Hypotension, tachycardia, flushing, headache, lupus like syndrome, peripheral neuropathy
Nitroprusside (arteriolar and venous)
0.25 – 3 mg/kg/min
(max 10 mg/kg/min)
Nausea, vomiting, hypotension, tachycardia, thiocyanate and cyanide toxicity, muscle spasm
 
RESPIRATORY SYSTEM
S.No.
Drugs
Loading dose
Maintenance dose
Adverse effects801
Acute respiratory distress syndrome (ARDS)/asthma, chronic obstructive pulmonary disease (copd)
1
Anticholinergics
Ipratropium
2–4 puffs BID to QID
Dry mucus membranes, tachycardia
2
Beta agonists
Albuterol
2–4 puffs BID to QID
Tachycardia, insomnia, irritability, nervousness, tremor, hyperglycemia, hypokalemia
Levalbuterol
0.63–0.125 mg TID
3
Corticosteroids
Methyl prednisolone
2 mg/kg in divided doses
Short term
Hyperglycemia, mood changes, insomnia, gastrointestinal (GI) irritation, increased appetite
Long term osteoporosis, acne, thin skin, muscle wasting,cataracts, infection, HPA axis suppression
Pulmonary hypertension
1
Anticoagulants
Warfarin
Target INR
Bleeding, skin necrosis, purple toe syndrome
2
Calcium channel blockers
Diltiazem
Up to 720 mg/day
Peripheral edema, flushing, headache, dizziness, hypotension, gingival hyperplasia, increased cardiovascular events
Nifedipine
Up to 240 mg/day
3
Endothelin antagonist
Bosentan
62.5 mg PO BID x 1 month
125 mg PO BID
Headache, flushing, hypotension, hepatotoxicity anemia
4
PDE – 5 inhibitors
Sildenafil
20 mg PO TID
Headache, flushing, hypotension, dyspepsia, vision changes
Nitric oxide
5–40 PPM
Hypotension, methemoglobinemia, elevated nitrogen dioxide802
5
Prostacyclins
Epoprostenol
2–50 ng/kg/min IV
5000– 20000 ng/mL continuous nebulization
Jaw pain, nausea, headache, flushing, hypotension, infusion site pain
Treprostinil
10–150 ng/kg/min
iloprost
2.5–5 mg inhaled 6–9 times daily
Shock
1
Corticosteroids
Hydrocortisone
200–300 mg/day in 3 to 4 divided doses
Short-term hyperglycemia, mood changes, insomnia, GI irritation, increased appetite, osteoporosis,acne, thin skin, muscle wasting,cataract, infection, HPA axis suppression
2
Drotrecogin alpha
24 mg/kg/hr x 96 hrs
Bleeding
3
Inotropes/vasopresors
Norepinephrine
0.02–3 mg/kg/minute
Hyperglycemia, tissue hypoxia, tachycardia, arrhythmias, myocardial ischemia, tissue necrosis
Epinephrine
0.01–0.1 mg/kg/minute
Hyperglycemia, tachycardia, arrhythmias, myocardial ischemia, splanchnic and renal hypoxia
Phenylephrine
0.5–10 mg/kg/minute
Tachycardia, reduced cardiac output, myocardial ischemia, necrosis
Dopamine
5–20 mg/kg/min
Tachycardia803
Vasopressin
0.01–0.04 U/minute
Reduced cardiac output, myocardial ischemia, hepato-splanchnic hypoperfusion, thrombocytopenia, hyponatremia
Dobutamine
2.5–20 mg/kg/minute
Tachycardia, arrhythmia
4
Mineralocorticoids
Fludrocortisone
50–100 mg PO q24h
Hypertension, edema, hypernatremia, hypokalemia
5
Mixed dilators
Milrinone
50 mg/kg
0.25–0.75 mg/kg/minute
Hypotension, thrombocytopenia, arrhythmia
6
Thrombolytics
Alteplase
100 mg IV over 2 hrs
Bleeding
 
ELECTROLYTE IMBALANCE
S.No.
Drugs
Loading dose
Maintenance dose
Adverse effects
Hyperkalemia
Albuterol
10–20 mg nebulized over 30–60 minute
Tachycardia, insomnia, irritability, nervousness, tremor, hyperglycemia, hypokalemia
Calcium gluconate
1 g IV over 2 minute
Hypercalcemia, constipation, arrhythmias, phlebitis
Regular human insulin
10–20 U IV
(~ 1 U FOR 4–5 g dextrose)
Hypoglycemia, allergy, edema, local reactions
Sodium bicarbonate
1 mEq/kg/IV
Hypoglycemia, hypokalemia, weight gain, local skin reactions
804Hypercalcemia
1
Calcitonin
4 U/kg (up to 8 U/kg)
Facial flushing, nausea, vomiting, allergic reactions
2
Bisphosphonates
Pamidronate
60–90 mg IV
Fever, fatigue, thromboplebitis, bone, joint and muscle pain
Zoledronic acid
4 mg IV
Hypophosphatemia
Phosphate salts
Potassium phosphate
Sodium phosphate
0.08–0.16 mmol/kg IV over 6 hr
Hyperphosphatemia, hypocalcemia, hypomagnesemia, hyperkalemia, hypernatremia, diarrhea
 
ENDOCRINE DISORDERS
S.No.
Drugs
Loading dose
Maintenance dose
Adverse effects
Adrenal insufficiency
1
Corticosteroids
Hydrocortisone
100 mg IV q8h
Short-term
Hyperglycemia, mood changes, insomnia, GI irritation, increased appetite
Long-term
Osteoporosis,acne, thin skin, muscle wasting,cataracts, infection, HPA axis suppression
Dexamethasone
10 mg IV prior to ACTH stimulation test
Fludrocortisone
50–200 mg PO q24h
Hypertension, edema, hypernatremia, hypokalemia
Hyperthyroidism
1
Thio urea drugs
Propylthiouracil
300–600 mg/day in 3 divided doses q8h
50–300 mg/day
Rash, fever, arthralgias, leukopenia, agranulocytosis, aplastic anemia, hepatotoxicity, lupus like syndrome, hypo-prothrombinemia, polymyositis
Methimazole
30–60 mg/day in divided dose q8h
5–30 mg/day
805
2
Beta blockers
10–40 mg PO q6h
Bradycardia, hypotension, fatigue, bronchospasm,heart block depression, sexual dysfunction, dyslipidemia, altered glucose metabolism cold extremities
3
SS potassium iodide
1–2 drops PO q12h
Metallic taste, nausea, stomach upset,salivary gland swelling, hypersensitivity reactions
Hypothyroidism
1
Thyroid hormones Levothyroxine
50–100 μ IV q6–q8 x 24 hr
100 mg IV q24 hr
Symptoms of hyperthyroidism
Temperature control
1
Acetaminophen
325–1,000 mg PO q4–q6 PRN
Hepatotoxicity
2
Bromocriptine
2–205 mg PO TID
Headache, dizziness, nausea, diarrhea, hypotension, nasal congestion
3
Dantrolene
1–2.5 mg/kg IV (may repeat q5–q10 min up to 10 mg/kg
Drowsiness, dizziness, diarrhea, vomiting, hepatotoxicity, muscle weakness
4
Nsaids
Ibuprofen
200–800 mg PO q3–q6 h PRN
Gastric irritation, nausea, gastric ulcer, acute renal failure
Ketorolac
15–30 mg IM or
10 mg PO PRN
 
GASTROINTESTINAL DISORDERS
S. No.
Drugs
Loading dose
Maintenance dose
Adverse effects
806Proton pump inhibitors
1
Pantoprazole
20–40 mg PO q12– q24 h
80 mg IV bolus
8 mg/hr x 72 hrs
Headache, dizziness, somnolence, diarrhea, constipation, nausea
Omeprazole
20–40 mg PO q12–q24 h
Lansoprazole
30–60 mg PO q12–q24 h
Esomeprazole
20–40 mg PO q24 h
2
Octreotide
25–50 mg IV bolus
25–50 mg/hr infusion
Diarrhea, flatulence, nausea, abdominal cramps, bradycardia, arrhythmia, conduction abnormalities, hypothyroidism, cholelithiasis
 
HEPATIC DYSFUNCTION
S. No.
Drugs
Loading dose
Maintenance dose
Adverse effects
1
Lactulose
20–30 g (30–45 mL) PO q2h
Diarrhea, flatulence, nausea
2
Neomycin
500–2000 mg PO q6–q12
Nausea, vomiting, diarrhea, irritation, soreness of mouth or rectal area, nephrotoxicity, neurotoxicity
3
Nonspecific
Beta blockers
Bradycardia, hypotension, fatigue, bronchospasm,heart block depression, sexual dysfunction, dyslipidemia, altered glucose metabolism, cold extremities
Propranolol
20–80 mg PO q12h
Nadolol
20–80 mg PO q12h
4
Rifaximin
400 mg PO TID
Headache
 
HEMATOPOIETIC DISORDERS
S.No.
Drugs
Loading dose
Maintenance dose
Adverse effects
1
Ddavp
0.3 mg/kg
Facial flushing, hyponatremia, hypotension, tachycardia, thrombosis807
2
Direct thrombin inhibitors
Lepirudin
0.1–0.15 mg/kg/hr
Bleeding, allergic reactions
Argatroban
2 mg/kg/min
3
Phytonadione
1–10 mg q24h
Anaphylaxis, hypotension
4
Warfarin
1–5 mg/day
Bleeding, skin necrosis, purple toe syndrome
 
CENTRAL NERVOUS SYSTEM
S.No.
Drugs
Loading dose
Maintenance dose
Adverse effects
808Status epilepticus
1
Benzodiazepines
Lorazepam
0.1 mg/kg at 2 mg/min up to 8 mg
Central nervous system (CNS) depression, paradoxical excitation, hypotension, respiratory depression
Midazolam
0.2 mg/kg
0.75–10 mg/kg/minute
2
Hydantoin
Fos phenytoin
20 mg phenytoin eq/kg/IV/IM
Hypotension, bradycardia, phlebitis, gingival hyperplasia, folic acid deficiency, hirsutism, acne, vitamin D deficiency, osteomalacia
3
Levetriacetam
500–1000 mg IV/PO q12h
Somnolence, nausea, vomitng, behavioral disturbances
4
Barbiturate Phenobarbitol
20 mg/kg IV
Sedation, nystagmus, ataxia, nausea, vomiting, hypotension, bradycardia, respiratory depresssion, rash, bone marrow suppression
5
Phenytoin
20 mg/kg IV
5–7 mg/kg/day
Nystagmus, diplopia, ataxia, sedation, lethargy, behavioral changes, coma, seizures, idiosyncratic reactions like rash, bone marrow suppression, Steven–Johnson syndrome, hepatitis809
6
Propofol
30–250 mg/kg/min
Hypotension, bradycardia, cns depression hypertriglyceridemia, pancreatitis, propofol infusion syndrome
7
Valproate
1000–2500 mg/day IV/PO in 2–4 divided dose
Somnolence, diplopia, nausea, diarrhea, hepatotoxicity, pancreatitis, thrombocytopenia, hyperammonemia, rash
Elevated ict
1
Hypertonic saline
30–50 mL q3–q6h
Hypernatremia, hyperchloremia
2
Mannitol
1–1.5 g/kg/IV
0.25–1 g/kg q3 –q6
Hypotension, acute renal failure, fluid and electrolyte imbalances
Stroke
1
Alteplase (ischemic stroke)
0.9 mg/kg IV (10 % as initial bolus)
Bleeding
2
Factor vii (hemorrhagic stroke)
1.2–4.8 mg IV
Hypertension, thrombosis
Delirium
Butyrophenones
Haloperidol
2–80 mg IV/PO q6h
Cns depression, orthostatic hypotension, qt prolongation, extra-pyramidal side effects, neuroloptic malignant syndrome
Sedation
1
Benzodiazepines
Lorazepam
2–4 mg
0.5–4 mg/hr
Cns depression, paradoxical excitation, hypotension, respiratory depression
Midazolem
1–5 mg
1–10 mg/hr
810
Propofol
25–100 mg/kg/minute
Hypotension, bradycardia, cns depression hyper-triglyceridemia, pancreatitis, propofol infusion syndrome
2
Dexmedetomidine
0.2–0.7 mg/kg/hr
Hypotension, bradycardia
 
INFECTIOUS DISEASES
S. No.
Drugs
Loading dose
Maintenance dose
Adverse effects
Antibacterial drugs
1
Aminoglycosides
Amikacin
8 mg/kg IV 12 h Or
15 mg/kg
Nephrotoxicity, ototoxicity
Gentamicin
3 mg/kg
2 mg/kg IV q8 h or
5–7 mg/kg
Anti-staphylococcal
2
Penicillins
Nafcillin
2 g IV q4–q6
Diarrhea, nausea, vomiting, rash anaphylaxis, neutropenia, thrombocytopenia, acute interstitial nephritis, hepatotoxicity
Oxacillin
2 g IV q4–q6 h
3
Beta lactam/lactamase inhibitors
Amoxicillin/clavulanate
875 mg PO BID
Anaphylaxis, seizure, hemolytic anemia, neutropenia, thrombocytopenia, Clostridium difficile colitis, cholestatic jaundice, drug fever
Ampicillin/sulbactam
1.5–3 g IV q6h
Piperacillin/tozabactam
3.375–4.5 g IV q6h
Ticarcillin/clavulanate
3.1g IV q4–q6 h
4
Carbapenems
Imipenem
500 mg– 1 g IV q6–q8 h
Diarrhea, nausea, vomiting, anaphylaxis, seizures, drug fever, C. difficile colitis
Meropenam
1 g IV q8h
Ertapenam
1 g IV q 24 h
5
Cephalosporins
Cefazolin
1–2 g IV q8 h
Diarrhea, nausea, vomiting, rash anaphylaxis, seizure, hemolytic anemia, neutropenia, thrombocytopenia, drug fever
Cefoxitin
1–2 g IV q4–q8h
Ceftriaxone
1–2 g IV q12–q24 h
Cefepime
500 mg– 2 g IV q8–q12 h
6
Clindamycin
600–900 mg IV q8h
Nausea, vomiting, diarrhea, rash, abdominal pain, C. difficile colitis
7
Tetracyclins
Ciprofloxacin
500–750 mg PO BID or
400 mg IV q8–q12 h
Nausea, vomiting, diarrhea, photosensitivity, rash, anaphylaxis, qt prolongation, joint toxicity in children, tendon rupture
Levofloxacin
500–750 mg IV/PO q24 8h
Cns stimulation, dizziness, somnolance
Moxifloxacin
400 mg IV/PO q24 h
Gemifloxacin
320 mg PO q24 h
8
Glycopeptides
Vancomycin
15 mg/kg IV q12 h
Red man syndrome, ototoxicity, nephrotoxicity, thrombocytopenia
9
Glycylcyclines
Tigecycline
100 mg IV
50 mg IV q12 h
Nausea, vomiting, diarrhea
10
Ketolides
Telithromycin
800 mg po q24 h
Nausea, vomiting, diarrhea, acute hepatic failure, qt prolongation
81111
Lipopeptides
Daptomycin
4–6 mg/kg iv q24 h
Constipation, diarrhea, vomiting, myopathy, anemia
12
Macrolides
Erythromycin
250–500 mg PO QID Or
0.5–1.0 g IV q6h
Nausea, vomiting, diarrhea, abnormal taste, qt prolongation, cholestasis
Azithromycin
250–500 mg IV/PO daily
Clarithromycin
250–500 mg PO BID
13
Metronidazole
500 mg IV/PO q8h
Nausea, vomiting, metallic taste, disulfiram like reaction, seizure, peripheral neuropathy
14
Oxazolidinediones
Linezolid
600 mg IV/PO q12 h
Diarrhea, peripheral and optic neuropathy, myelosuppression, lactic acidosis
15
Penicillins
Ampicillin
2–3 g IV q4–q6 h
Diarrhea, nausea, vomiting, rash anaphylaxis, seizure, hemolytic anemia, neutropenia, thrombocytopenia, drug fever
Aqueous penicillin g
2–4 million U IV q4h
16
Streptogramin
Quinupristin/dalfopristin
7.5 mg/kg IV q8h
Arthralgia, myalgia, inflammation, pain edema at infusion site, hyperbilirubinemia
81217
Tetracyclins
Tetracyclin
250–500 mg PO q6 h
Photosensitivity, diarrhea, tooth discoloration, bone and growth retardation, renal tubular necrosis, dizziness, vertigo, pseudotumor cerebri
Doxycyclin
100 mg IV/PO q12 h
Minocyclin
200 mg PO
100 mg PO q12 h
18
Trimethoprim/sulfamethoxazole
5 mg/kg Iv q8h
Rash, nausea, vomiting, diarrhea, myelosuppression, Stevens–Johnson syndrome, hyperkalemia, aseptic meningitis, hepatic necrosis
Antifungal drugs
1
Amphotericin B
Amphotericin B deoxycholate
0.3–1.5 mg/kg q24 h
Infusion-related reactions, hypokalemia, hypomagnesemia, nephrotoxicity, acute liver failure, myelosuppression
2
Azoles
Fluconazole
100–80 mg PO/IV daily
Nausea, vomiting, diarrhea, rash, visual disturbances, phototoxicity, hepatic failure, cvs toxicity, hypertension, edema
Itraconazole
200 mg IV/PO q24 h
Voriconazole
4 mg/kg IV q12 h
Or
200 mg PO BID
8133
Echinocandins
Caspofungin
70 mg IV
50 mg IV q24 h
Hepatotoxicity, rash, flushing, itching
Micafungin
50–150 mg IV q24 h
4
Flucytosine
25–37.5 mg/kg PO q6 h
Nausea, vomiting, diarrhea, rash, myelosuppression, hepatotoxicity, confusion, hallucination, sedation
Toxicology
1
Activated charcoal
25–100 g
Vomiting, constipation, fecal discoloration, bowel obstructions
2
Benzodiazepine poisoning
Flumazenil
0.2–0.5 mg IV q1 minute (up to 5 mg)
Withdrawal symptoms (sweating, agitation, hypertension, tachycardia, nausea, vomiting, cvs events, seizures)
3
Iron chelating agent
Deferoxamine
1 g IV
500 mg IV q4 h x 2 doses
Urine–orange discoloration, hypotension, tachycardia, erythema, urticaria, anaphylaxis, respiratory distress syndrome
4
Methyl alcohol poisoning
Fomepizole
15 mg/kg IV
10 mg/kg IV q12 h x 4 doses
15 mg/kg IV q12 h until methanol level <20
No specific side effects
5
Morphine poisoning
Naloxone
0.4–2 mg IV q2 min (up to 10 mg)
Withdrawal symptoms (sweating, agitation, hypertension, tachycardia, nausea, vomiting, cvs events, seizures, pulmonary edema)
6
Paracetamol poisoning
N–acetyl cysteine
Oral
140 mg/kg
IV
150 mg/kg
Oral
70 mg/kg q4 h x 17 doses
IV
1.5 mg/kg/hr x 4hr
Then
6.25 mg/kg/hr x 16 hr
Nausea, vomiting, unpleasant odor, anaphylatic reactions814
Pregnancy
1
Hydralazine
10–40 mg IV q4–q6 h
Or
10–75 mg PO TID–QID
Hypotension, flushing, tachycardia, headache, drug-induced lupus like syndrome, peripheral neuropathy
2
Labetalol
100–800 mg PO q 8–q12 (max 2.4 g/day)
Hypotension, bradycardia, nausea, vomiting, heart block, broncho-constriction
3
Magnesium sulfate
4–6 g IV over 15 –20 minute
2 g/hr infusion
Hypermagnesemia, diarrhea
4
Phenytoin
20 mg/kg IV
5–7 mg/kg/day
Nystagmus, diplopia, ataxia, sedation, lethargy, behavioral changes, coma, seizures, idiosyncratic reactions like rash, bone marrow suppression, Steven–Johnson syndrome, hepatitis, gingival hyperplasia, folic acid deficiency, hirsutism, acne, vitamin D deficiency, osteomalacia

ICU ROUNDSAPPENDIX 4

 
ESSENTIAL DATA AND ASSESSMENT FOR MANAGEMENT OF CRITICALLY ILL PATIENTS
 
History
  • Review the ICU chart or progress notes
  • Review the overnight events
  • Review medication.
 
Physical Examination
  • Focussed examination on all systems
  • Mental status
  • Sedation status (Ramsay sedation score)
  • Degree of pain (Visual analogue score).
 
External Device Data
  • Review ventilator settings
  • Assess the patency of catheters and tubes
  • Review all infusions.
 
Laboratory Data
  • Complete blood count
  • Tests of specific interest to the patient
  • ABG.
 
Imaging Data
  • Chest X-ray
  • CT/MRI
  • Angiogram.
Index
Page numbers followed by f refer to figure, fc refer to flow chart, and t refer to table.
A Abciximab Abdomen , Abdominal compartment syndrome , Abdominal infections management of pathophysiology of , Abdominal trauma mechanism of injury Abdominal wall Acalculous cholecystitis , Acetaminophen , , , poisoning , treatment toxicity Acid, overproduction of Acid-base balance basics of regulation of disorder , interpretation of disturbances imbalances Acquired nephrogenic diabetes insipidus Activated charcoal Active myocardial ischemia Acute coronary syndrome, mechanical complications of Acute exacerbation, pathophysiology of Acute kidney injury dialysis in etiology of intrinsic Acute liver failure, etiology of Addison's disease , Adenosine , antagonists Adrenal crisis pathophysiology Adrenal emergencies Adrenal insufficiency etiology of primary causes, etiology of secondary causes, etiology of signs of symptoms of Adrenocorticotropic hormone stimulation test Adult basic life support sequence , skills Adult cardiac arrest, management of , Adult chain of survival Advanced airway Advanced cardiac life support , modifications , , , , Advanced trauma life support , , Afibrinogenemia Air embolism , , Air-conditioning system Airflow obstruction Airway assessment before intubation disorders equipment management , , , adjuncts for , of difficult obstruction acute , causes of in trauma patients, causes of pressure alarm high low pressure release ventilation Albumin , , Albuterol , , Alcohol withdrawal syndrome symptoms of , Alcoholic ketoacidosis Alcoholic mania Aldosterone antagonists receptor blockers Alkalosis management Allergic reactions Alpha adrenergic blocker Alteplase , , Alveolar hemorrhage oxygen , American College of Chest Physicians American Society of Parenteral and Enteral Nutrition Amikacin , Aminoglycoside , Amiodarone , , , Ammonia , Amniotic fluid embolism , , diagnosis of management pathophysiology Amoxicillin Amphotericin B deoxycholate Ampicillin , , Amylase Anal fissure Analgesia adequate patient-controlled pump, patient-controlled techniques, regional Anaphylactic reaction , causes of diagnosing Anaphylaxis , management of Anatomical transparent silicone face mask Anderson's syndrome Androstenedione Anemia , , Anesthetic conserving device Angiodysplasia Angioectasias Angiography , , , Angioplasty Angiotensin converting enzyme inhibitor receptor blocker , Angiotensin-converting enzyme inhibitors , Anion gap acidosis, high Anorectal disease Antepartum hemorrhage Anterior external fixator , Antibiotic , based on organisms cover dosage prescription, principles of principles of resistance, prevent Antibiotic-associated colitis Anticholinergic , Anticholinesterase drugs medications test Anticoagulants , Anticoagulation, benefits of Antidepressants treatment Antidiuretic hormone , , Antidotes, specific Antihistamine Antihypertensive therapy Anti-inflammatory response syndrome, compensatory Antimalarial drugs, dosages of Antimicrobial therapy treatment Anti-musk antibodies Antiplatelet , therapy Anti-staphylococcal Antithrombin III deficiency Antivenom indications of Anuria Aorta dissection of injury to Aortic counter pulsation Aortic dissection , acute Aortic regurgitation , Apnea alarm Apnea test interpretations Aprotinin Aqueous penicillin g Argatroban , Arginine vasopressin antagonists Arrhythmia , , Arrhythmic complications Arrhythmogenic right ventricular cardiomyopathy Arsenic Arterial blood gas analysis , exercises Arterial hypoxemia causing hyperventilation Arterial oxygen content , , Arterial oxygenation , Arterial pH , Arterial pressure mean , , , monitoring, recent advances in waveforms Arterial systolic pressure Arterial waveform dampening of phases of Arteriography Arteriovenous hemodiafiltration, continuous hemofiltration, continuous Artery atherosclerotic disease, large Ascending paralysis Aspiration pneumonitis Aspirin , , overdose Associations of acute hepatic failure Asthma , , acute severe dosages of drugs in exacerbation of exacerbation classification of management of severity of pathophysiology of acute severe Asymptomatic hyponatremia Asynchrony signs of variables contributing to Atracurium Atrial fibrillation , classification clinical features etiology mechanism postoperative Atrial flutter , treatment Atrial pressure, right Atrioventricular nodal reentrant tachycardia , Atrioventricular reentrant tachycardia treatment Atropine , Auditory canal, external Autoimmune disease, caused by Automated control system in ventilator Automated external defibrillator Auxiliary liver transplantation Axillary artery , injury to Axillary vessels Azathioprine , Azithromycin , Azoles B Bacterial contamination Bacterial meningitis acute , causes of acute Balance sign Balloon counterpulsation, intra-aortic pump, intra-aortic tube tamponade Barbiturate phenobarbitol Barbiturate therapy Barometric pressure Basic life support modifications , , , Bat sign Beats per minute Behçet disease Benzodiazepines , , , , Beri-beri disease Beta-agonists Beta-blocker , , , , , dosage Beta-lactamase, extended-spectrum Bezold Jarisch reflex Bicarbonate loss Bicarbonate actual therapy Bilevel positive airway pressure , , Bilirubin Binders-containing aluminum Bioartificial liver support systems Biochemical values, normal Biphasic positive airway pressure Bisphosphonates Bivalirudin Bladder, carcinoma of Bleeding emergency treatment of acute intra-abdominal postoperative , Blenderized food Blood component administration separation investigations , loss , in obstetric hemorrhage, classification of management of severe pressure , control replacement stream infection catheter-related , tests transfusion complication of , urea nitrogen , , Blunt chest trauma Blunt trauma, high-risk Body mass index Boerhaave's syndrome , Bone , formation, accelerated net Bosentan Bowel losses, small Brachial artery , Brachial ulnar injuries Bradycardia, management of Brain dead patient, care of Brain death , clinical phases of confirmatory tests for diagnosis of patients physiology of steps for determining Brainstem reflexes, absence of Breakthrough pain Breath mandatory type Breathing , , type of Bromocriptine Bronchogenic carcinoma Brugada syndrome type Budd-Chiari syndrome, acute Buffering mechanisms Bumetanide Bundle branch block Buprenorphine Burch and Wartofsky diagnostic criteria Burn , assessment causing inhalational injury center referral criteria chemical classification depth of , evaluation of injury classification types of management of pathophysiology of patient perioperative care of priorities in managing severe C Cadmium Calcimimetic drugs Calcineurin inhibitors Calcitonin , Calcium , , , , channel blockers , , , functions of gluconate , metabolism Calcium-channel blockers , Calorie requirement, calculation of Calorimetry, indirect Candida Capillary refill test Capsule endoscopy Captopril , Carbamate poisoning Carbapenems Carbohydrate requirements Carbon dioxide analysis, end tidal production of Carbon monoxide , poisoning management of Carcinoma Cardiac abnormalties Cardiac arrest , , , , , causes of in special situations rhythm based management of role of medications in Cardiac arrhythmia , , , , Cardiac catheterization Cardiac causes Cardiac complications Cardiac damage, serum markers of Cardiac dysfunction Cardiac effects of hypermagnesemia Cardiac enzymes Cardiac failure , Cardiac index , , Cardiac output high measuring reduced Cardiac perforation Cardiac pump mechanism Cardiac surgery , Cardiac tamponade , , , management pathophysiology Cardiac troponins Cardinal symptoms Cardioembolism, risk factors for Cardiogenic pulmonary edema acute Cardiogenic shock , , , , , causes of characteristics etiology of high-risk patients for invasive procedures in management of , pathogenesis of , Cardiomyopathy Cardiopulmonary arrest bypass , manifestations resuscitation , , early physiology of quality Cardiorenal syndrome Cardiothoracic surgery Cardiovascular diseases dysfunction effects system , , , , , , , management of Carotid artery, internal Carotid sinus massage Catecholaminergic polymorphic ventricular tachycardia Caterpillars treatment Catheter management of protocol for tip position, confirming Catheter-associated of urinary tract infection, prevention of Catheterizing right femoral vein, technique of internal jugular vein, technique of , subclavian vein, technique of , Catheter-related bloodstream infections, prevention of Cavernous sinus thrombosis Cefazolin , , Cefotaxime Cefoxitin Ceftazidime Ceftriaxone , Central arteries, waveform of Central diabetes insipidus , , treatment of Central nervous system , , , , , , effects injury Central sleep apnea Central sympatholytics Central vein catheterization Central venous catheterization , , monitoring, waveforms of pressure , , , , , , , , monitoring , Cephalosporins Cerebellar hemorrhage Cerebral blood flow disturbance edema , , , management of embolization infarction Cerebrospinal fluid , , , analysis , Cerebrovascular accident , , diseases Ceruloplasmin Cervical spine injury , Chaotic atrial tachycardia Chemical buffering Chemically derived formulas Chest injury analgesia in evaluation of wall injury to Chlorhexidine Chloride , Cholesterol, total Cholinergic drugs Cholinergic symptoms Chorionic gonadotropin Chvostek's sign Cigarette smoking Cinacalcet Ciprofloxacin , Citrate intoxication Clarithromycin Clavulanate Cleistanthus collinus Clevidipine Clindamycin Clonidine Clopidogrel , Clostridial myonecrosis Clostridium difficile Coagulation abnormalities Coagulopathy patients with Cobra bite treatment Cobra venom Coexisting diseases Colitis Colloids , composition of Colonic losses Coma , , Common antiarrhythmic agents, dosages of Common femoral vein Common organisms causing nosocomial infections , Common-facial nerve Compartment syndrome , management of Congenital adrenal hyperplasia anomalies nephrogenic diabetes insipidus Congestive cardiac failure , , Congestive heart failure acute Connective tissue disease Contusion, left-sided Copper Cor pulmonale, acute Coral snake bite treatment Coronary artery disease , , Coronary atherosclerosis Coronary syndrome, acute , Corrosive poisoning Corticosteroid , , , biosynthetic enzyme defects sparing agents Cough Cranial nerve dysfunction of brainstem, function of palsies Creatine kinase Creatinine , , , Creative phosphokinase Cricoid pressure Cricothyroidotomy , in children Critical care patients analgesia for sedation for Critical illness polyneuropathy pathogenesis of , pathology treatment Critically ill patient physiology of Crotalinae bites Crush injuries Cryoprecipitate Crystalloids , complications of composition of Cullen sign Cushing's response Cushing's syndrome Cyclophosphamide Cyclosporine Cystatin C Cytomegalovirus , Cytotoxic hypothesis D Dalfopristin Dalteparin , , Damage control surgery Dantrolene Daptomycin Decompensated heart failure Deep vein thrombosis prophylaxis treatment Deep venous thrombosis Dehydroepiandrosterone Delirium symptoms of tremens management management of , Dengue , hemorrhagic fever management of Depletional hyponatremia Desmopressin administration Dexamethasone Dexmedetomidine Dextran Dextrose Diabetes insipidus , causes of classification of complications management of partial central types of mellitus , , , , , undiagnosed Diabetic ketoacidosis , , , , basic pathophysiology of complications of pathogenesis of triad of Diagnostic peritoneal lavage interpretation of Dialysis Diarrhea , , , severe Diastolic dysfunction increases end-diastolic volume Diastolic runoff Dicrotic notch Diffuse alveolar infiltrates Diffuse axonal injury, grading of , Digoxin , , , Dihydrotestosterone Diltiazem , , Diphenhydramine Diplopia Dipsogenic diabetes insipidus Direct thrombin inhibitors , , Disseminated intravascular coagulation , causes of pathophysiology Diuretics , Dizziness Dobutamine , , , adverse effects Dofetilide Dopamine , , , , agonists low-dose Doppler echocardiography Dorsalis pedis artery Doxycyclin Dressler's syndrome Drotrecogin alfa Drowning , Drug causing exacerbation Drug overdose Drug poisoning Drug resistance, mechanisms of Drug therapy Drug, dosages of Drug, side effects of Drugs in acute exacerbation, dosages of Duodenal carcinoma Duodenum Duplex ultrasonography Dynamic hyperinflation Dyspnea , , severity of E Echocardiography Eclampsia , management Elapid bite treatment Elective tracheostomy types of Electric injury Electric shock Electroconvulsive therapy Electrolyte , , abormalities correction disturbance , , homeostasis normal exchange of Elevated liver enzyme levels Elevated serum amylase Embolic complications Embolic stroke Embolism, sizes of Emergency response system Emergency room care Emergency tracheostomy prerequisites for technique for Emergency transvenous pacemakers Empirical antibiotic therapy on infection site Empirical antimicrobial therapy , Enalapril Enalaprilat , Encephalitis End-diastolic pressure Endocrine causes disorders , system system, management of End-of-life care decision making process Endoscopy Endothelin antagonist Endotracheal intubation , , , basic anatomy complications of drug for in critical care in trauma patients Endotracheal tube care of Enoxaparin , , Enoximone Enteral feeding, complications of Enteral feeds classification of starting Enteral nutrition Enteric fever , Enteric gram-negative bacilli Enterobacter Enterobacteriaceae Envenomation , Enzyme-linked immunosorbent assay Epidural analgesia dose for Epinephrine , , , , , , , in anaphylaxis, role of Eplerenone Epoprostenol Epsilon-aminocaproic acid Epstein-Barr virus , Eptifibatide Ertapenam Erythromycin Esmolol , Esomeprazole Esophageal detector device Doppler Esophagus, injury to Estradiol Estrogens Ethics in critical care Ethylene glycol methanol poisoning Etomidate European Society of Parenteral and Enteral Nutrition guidelines Euvolemic hyponatremia Ewing's sarcoma Exercise tolerance Exogenous acid Extensive degloving injury External fixation Extracellular fluid Extradural hemorrhage Extradural hematoma , Extrarenal causes Extravascular hemolysis Extremity trauma, management of Eye signs symptoms Eye-opening response F Facial nerve Facial palsy Falciparum malaria Familial periodic paralysis Fast-flush test effects of Fat embolism , , embolism syndrome , diagnosis of etiology management pathogenesis Fatty liver of pregnancy acute , , complications, acute management, acute pathophysiology, acute Febrile nonhemolytic transfusion reaction , Femoral artery , , Femoral block Femoral vein , anatomy of right cannulation technique right Femoral vessel injury Femoro-femoral bypass Fenoldopam Fentanyl , Fever , Fibrinolysis Fibrinolytic , agents dosages Flail chest , Fluconazole Fludrocortisone , Fluid balance assessment of basic physiology of disturbances in regulation of calculation in burns, formulas for compartments , composition of management , , normal exchange of replacement responsiveness, dynamic parameters of resuscitation , therapy, replacement Flutter waves Focal atrial tachycardias Focal neurological symptoms Follicular-stimulating hormone Fondaparinux Foreign-body airway obstruction Fosphenytoin over phenytoin, advantages of Fossa tumors, posterior Fracture classification, open fixation, acute open stability Free water restriction Fresh frozen plasma , Fulminant hepatic failure causes of death in Fungal meningitis Furosemide , , Fusion beats G Gallium nitrate Gas gangrene Gastric carcinoma fluid lavage , losses mucosal irritants, ingestion of Gastroesophageal reflux disease Gastrointestinal bleeding , diseases disorders loss , system , Gastrointestinal-hepatic dysfunction Gelatin Gemifloxacin Gentamicin , , Gestational diabetes insipidus , Glasgow Coma Scale , , Globulin Glomerular filtration rate Glucocorticoids , , replacement Glucose , , , control Glycemic control Glyceryl trinitrate Glycopeptides Glycylcyclines Graft disease , Gram-negative organisms Great saphenous vein Grey-Turner sign Growth hormone Guillain-Barré syndrome , , , , etiology pathogenesis subtypes of symptoms of Gum elastic bougie for aiding intubation Gustilo open fracture classification H Haemophilus influenzae , , , Hagen-Poiseuille formula Hallucinatory insanity of drunkards Hallucinosis Haloperidol Hampton's hump Harris-Benedict equation , HDL cholesterol Head injury Headache Healthcare providers, adult basic life support for Heart catheterization, left chambers, right failure acute , , acute hypertensive classification, acute clinical features, acute dosages of inotropes for dosages of vasodilators for management of acute pathophysiology, acute , signs, acute symptoms of , symptoms, acute therapy for acute treatment of acute injury to rate Heartbeating brain death organ donor, management of HELLP syndrome , , diagnosis of Hematological disorders Hematology , Hematopoietic disorders Hemodialysis , , acute Hemodynamic assessment , Hemodynamic monitoring parameters of Hemodynamic status Hemodynamic support Hemodynamic variations Hemoglobin Hemoglobinuria Hemolysis Hemolytic anemia - complications diagnosis treatment Hemolytic reaction, delayed Hemolytic transfusion reactions acute delayed management of acute , Hemorrhage resuscitation of Hemorrhagic shock pathophysiology of resuscitation of Hemorrhagic stroke , , Hemorrhoids Hemothorax, treatment of Heparin Heparin-induced thrombocytopenia , Hepatic encephalopathy , , scale Hepatic failure acute encephalopathy no encephalopathy Hepatic hemorrhage Hepatic system Hepatitis B , C , virus A B C D E Hepatorenal syndrome Hepatotoxic Herpes simplex , virus Hip fracture Histoplasma capsulatum Hormone replacement Host disease , Human albumin immunodeficiency virus insulin, regular T-lymphotropic virus Humidifiers, types of Hydralazine , , arteriolar Hydration , Hydrochloric acid in metabolic alkalosis Hydrocortisone , Hydroxyethyl starch Hypercalcemia , bisphosphonates, treatment of causes of diuretics, treatment of hydration, treatment of steroids, treatment of treatment of Hypercapnic respiratory failure Hyperkalemia , , , causes of , correction of treatment for , Hyperkalemic periodic paralysis treatment Hypermagnesemia , , causes of treatment Hypermetabolic phase Hypernatremia causes Hyperosmolar hyperglycemic state , pathophysiology Hyperphosphatemia , causes of signs of symptoms of Hypertension , , severe Hypertensive crisis precipitating factors of with encephalopathy Hypertensive disorders in pregnancy, classification of of pregnancy Hypertensive emergency , Hypertensive encephalopathy Hypertensive urgencies , Hyperthermia , , malignant , Hyperthyroidism Hypertonic saline , , , use of Hyperventilation Hypervolemic hyponatremia , Hypnotics treatment Hypocalcemia , , causes of , chronic Hypofibrinogenemia Hypoglycemia , , , Hypokalemia , , causes of , management of treatment for Hypokalemic periodic paralysis , types Hypomagnesemia , causes of treatment mild cases severe cases Hyponatremia , -, , causes diagnosis of etiology of , pathogenesis of steps in correcting symptoms of treatment of Hypophosphatemia mild mild-to-moderate severe , Hypotension , , , , management of mild postural severe Hypothalamic-pituitary adrenal axis dysfunction deficiency, posterior Hypothalamopituitary function Hypothermia , , , , , , , , Hypoventilation syndrome Hypovolemia Hypovolemic hyponatremia Hypovolemic shock , , etiology management pathophysiology Hypoxemia, severe , Hypoxemic respiratory failure Hypoxia I Ibuprofen Ibutilide Imipenem Immune disorders system thrombocytopenia thrombocytopenic purpura acute chronic classification of pathogenesis treatment Immunoglobulins , Immunosuppressants Immunosuppressive drugs Inappropriate antidiuretic hormone, syndrome of , Inappropriate secretion of antidiuretic hormone, syndrome of Indian Society of Critical Care Medicine Infection , , , abdominal catheter-related causes of classification, abdominal focus of primary intra-abdominal management, abdominal of meninges site Infectious complications Infective endocarditis Inflammatory bowel disease , Inflammatory complications Inflammatory demyelinating polyneuropathy acute chronic Inflammatory disease Inhaled bronchodilators Initial ventilator settings , , Injury secondary severity score Inotropes Inspiratory flow pattern Insulin , administration therapy Insulin-like growth factor Intensive care unit , , , Intercostal nerve block Interferon Interleukin , , Intermediate syndrome Intermediate-dose dopamine Intermittent hemodialysis Intermittent pneumatic compression device Intermittent porphyria, acute Internal fixation Internal jugular vein , , , anatomy of right left Interscalene block Interstitium Intestinal absorption, impaired Intestinal fistulas Intestinal losses, increased Intestinal phosphate absorption, impaired Intestine Intra-abdominal infection, complicated pressure, measurement of , Intra-arterial embolization Intracardiac tumors Intracerebral hemorrhage Intracranial hemorrhage hypertension pressure , Intravascular hemolysis Intravenous atropine fluids classification of hydralazine immunoglobulin opioid Inulin clearance Invasive arterial blood pressure monitoring Invasive blood pressure Ipratropium bromide Iron , , Ischemia, manifestations of Ischemic enteritis Ischemic hepatitis Ischemic stroke , , , pathophysiology Isosorbide dinitrate , Isosorbide mononitrate Isotonic crystalloids Istaroxime Itraconazole J Jaundice , , Jugular vein external right internal K Kehr sign Kerosene poisoning Ketamine , Ketolides Ketorolac Kidney , function test injury acute , , , , , , categories, acute complications of acute diagnosis, acute Killip's prognostic classification Klebsiella Knee-jerk reaction L Labetalol , , , Labetdilol Lactate dehydrogenase , , Lactic acid Lactose-free formulas Lambert-Eaton myasthenic syndrome Language disturbances Lansoprazole Lanthanum carbonate Laryngeal mask airway Laryngoscope LDL cholesterol Lead Left ventricle Left ventricular failure Leg fracture raising test, passive Lepidoptera Lepirudin Leukocyte reduction Leukoencephalopathy syndrome, posterior reversible Levalbuterol , Levetriacetam Levine sign Levofloxacin Levosimendan , Levothyroxine Lid twitch sign Lidocaine , Lightening strike Lignocaine Linezolid Lipase Lipids , parenteral infusion of Lipopeptides Lipopolysaccharide Liposuction Liquid ventilation total Liquidized food Lisinopril Listeria monocytogenes Liver disease , failure acute , causes of acute classification, acute investigations of acute prognosis, acute treatment, acute transplantation Long bone fracture , Loop diuretic , intravenous bolus of Lorazepam , Low blood pressure Low dose unfractionated heparin Low minute ventilation alarm Lower gastrointestinal bleeding Lower limb Lower radial injuries Low-expired tidal volume alarm Low-molecular-weight heparin Lung disease chronic obstructive severe dynamics , infection injury to acute , direct indirect parenchymal diseases recruitment maneuver sliding sign sonography protocol Luteinizing hormone Lymphoma M Macrolides Magill's forceps Magnesium , , , adverse effects of sulfate , , , actions dosage regimens pharmacokinetics Maintain perfusion pressure Maintenance fluid therapy Malaria diagnosis, severe in pregnancy, severe management, severe manifestations of severe mixed severe Mallory-Weiss tear Managing hemorrhagic shock Mannitol Mask with bag and valve device Massive blood transfusion complications Massive pneumothorax, left-sided Massive transfusion protocol goals of Maximal inspiratory pressure MDR gram-negative bacteria Mechanical hyperventilation Mechanical ventilation , , , , , basics of initiation of paralyzing patient in weaning from Meckel's diverticulum Medical ethics Meningitis signs of symptoms of Mental status Mercury Meropenem , Metabolic abnormalities Metabolic acidosis , , , , , , , , , causes of compensation for fully compensated management of Metabolic alkalosis , , , , causes of chloride sensitive , chloride-resistant compensation for fully compensated treatment of Metabolic disorder disturbance Metabolism , in critically ill patients Metal fuller's tracheostomy tube Metastatic calcification Metered-dose inhaler Methemoglobinia Methicillin-resistant Staphylococcus aureus Methimazole Methylprednisolone , , Metronidazole , , Microcirculation Micronutrients Midazolam , Mid-tracheostomy Miller-Fisher syndrome Milrinone , , Mineralocorticoid deficiency signs caused by symptoms caused by Mineralocorticoids Minitracheostomy advantages of Minnesota tube Minocyclin Mitochondria Mitochondrial level Mitral regurgitation acute treatment, acute Mitral stenosis , Mivacurium Molecular weight heparin, low , Mollaret meningitis Monitoring cardiopulmonary resuscitation , Monoclonal antibodies Morbid obesity Morphine , , , Mortality to asthma Moths Motor axonal neuropathy, acute Motor response Motor sensory axonal neuropathy, acute Motor symptoms Moxifloxacin Moyamoya disease Mucosal tonometry , Müller maneuvers Multidrug resistant pathogen Multifocal atrial tachycardia , , Multiple organ dysfunction syndrome , etiology pathophysiology of , Multiple organ failure Multiple trauma Muscle biopsy proteolysis, causes relaxants specific kinase weakness Muscle-like cells Myasthenia gravis , , etiology pathogenesis treatment Myasthenic crisis , causes treatment Mycobacterium tuberculosis Mycophenolate mofetil , Myocardial dysfunction Myocardial infarction , , acute , , , , , causes of complications of acute pathophysiology, acute , Myocardial ischemia Myoglobin Myoid cells Myotonia Myxedema coma , , , management modalities of N Nafcillin Nasal O therapy Nasogastric intubation benefits of disadvantages of Nasogastric suctioning Natriuretic peptide testing Nausea Nebulizer solution Neck stiffness Needle cricothyroidotomy Needle orientation Negative pressure pulmonary edema ventilation Neisseria meningitidis Neoplasm , Nephrogenic diabetes insipidus , , treatment of Nephropathy, contrast Nephrotoxic substances, avoid Nerve blocks, regional conduction study Nesiritide , , Neural hormone Neurally adjusted ventilatory assist Neurologic causes Neurological disorders Neurological examination Neuromuscular blockade Neuromuscular disorders , Neuromuscular drugs Neuromuscular electrical stimulation Neuromuscular function, disorders of Neuromuscular irritability signs of symptoms of Nicardipine , Nicotinic symptoms Nifedipine , , Nitrates , , Nitric oxide , Nitrogen balance Nitroglycerin , , Nitroprusside Noncardiac causes Noncardiogenic pulmonary edema Nonendoscopic treatment options for varices Nonfocal neurological symptoms Nonimmune-mediated reactions, causes of Nonimmunologic reactions Noninvasive positive pressure ventilation , Noninvasive ventilation , , , Noninvasive ventilatory modes Non-neurologic causes Nonpancreatic causes Nonpharmacologic therapies Nonsteroidal anti-inflammatory drugs , , Nonventilator therapy Norepinephrine , , , , Normal anion gap acidosis metabolic acidosis Nosocomial diarrhea Nosocomial infection, causes of Nosocomial infections Nosocomial pneumonia , , Novel agents Nuchal rigidity Nuclear scintigraphy Numeric rating scale Nutrition , enteral in illness, pathophysiology of in specific conditions parenteral Nutritional assessment Nutritional requirements Nutritional support , , routes for giving timing of O O exchange, measures of Obesity hypoventilation syndrome , , Obstetric emergencies hemorrhage causes of classification Obstructive hypoventilation syndrome Obstructive shock , , causes mechanism of pathophysiology pathophysiology of Obstructive sleep apnea , , classification for severity of diagnosis Obtunded consciousness Octreotide Ocular myasthenia gravis Ocular symptoms Oculovestibular testing Oduvanthalai poisoning Oliguria , Omeprazole Operative room management Opioids , cause sedation Optic atrophy Oral anticoagulants, new Organ donation obtaining consent for Organ donor Organ failure, sequence of Organochlorine compounds and pyrethroids Organophosphorus , compounds , Oropharyngeal airway carcinoma lesion Orthopedic surgery Orthotopic liver transplantation Oscillatory ventilation, high frequency Osmolar load in diet, increasing Osmotic demyelination syndrome Osmotic diuresis Osteoarthritis Oxacillin Oxazolidinediones Oxygen , cascade , steps of concentration, inspired consumption , , content delivery , , , index , , dissociation curve dynamics, indices of indices, regional inspired concentration of saturation , transport Oxygenation, adequate P Packed cell volume Packed red cells , , Pain abdominal , algorithm for and sedation, management of , , assessment of clinical evaluation of control drugs for feel of incident intensity, present , location of quality of scales severity of somatic visceral Palla's sign Pamidronate Pancreas carcinoma of Pancreatic cancer Pancreatic fluid Pancreatitis acute , causes of acute etiology, acute severity of acute Pancuronium Pantoprazole Paracetamol , poisoning Parathormone Parathormone-related peptide Parathyroid agenesis destruction dysfunction glands hormone levels levels, low production of resistance syndromes Paravertebral block Parenteral benzodiazepines Parenteral nutrition , solutions total , , , Patient ventilator asynchrony , causes of , management of , physiologic effects of Patient-controlled analgesia advantages of disadvantages of Peak expiratory flow , rate , , Peak inspiratory flow pressure Pelvic binders circumferential Pelvic fractures open Pelvic packing Pelvic ring disruption Pelvis Penetrating artery disease Penetrating trauma causing popliteal injury Penicillin , G Pentamidine Peptic ulcer endoscopic therapy for Percutaneous coronary intervention , , Percutaneous dilational tracheostomy Percutaneous pelvic fixation techniques Percutaneous tracheostomy Pericardial pressure Pericardiocentesis Pericarditis early late Periodic paralysis , Perioperative fluid balance Perioperative patients, management of Peripheral arterial catheterization Peripheral arteries, waveform of Peripheral circulation Peripheral nerve block infusions, advantages of catheter analgesia Peripheral venous cannulation, steps of catheter Peripherally inserted central venous catheters , Peritoneal dialysis Peritoneal lavage limitations of diagnostic procedure for diagnostic Peritonitis localized primary secondary Permissive hypercapnia Phenylephrine , Phenytoin , Phosphate salts Phosphodiesterase inhibitors enoximone milrinone Phosphorus Physician determining brain death Physics of ultrasound Physiological disturbances Physiotherapy Phytonadione Piperacillin Pit viper bites Pituitary endocrine function Placenta abruption of previa Placental abruption, complications with Plasma ketones , osmolality increased normal Plasmalyte Plasmapheresis Plasminogen activators deficiency Plateau pressure Platelet , antibodies, tests for count dysfunction level syndrome, low processing, types of transfusion Pleura, injury to Pneumatic antishock garment Pneumonia , , , Pneumothorax , , bar code sign indicating bilateral low-risk of treatment of Poisoning , general principles of Polydipsia, primary , Polyneuropathy, delayed Polyps Popliteal sciatic block Popliteal vein Popliteal vessel injury Porphyria, acute Portable ultrasound machine Portex cuffed tracheostomy tube Portosystemic shunts, surgical Positive airway pressure , , , , Positive end expiratory pressure , , , Positive pressure ventilation effects of Postcoronary artery bypass grafting Postpartum hemorrhage , Postrenal acute kidney injury Potassium , , , , balance in disease health phosphate sensitivity Potassium-aggravated myotonia Prasugrel Precipitate ketoacidosis Precipitating event Precordial thump Prednisolone Pre-eclampsia complications of severe pathogenesis of severe Pregnancy Pregnancy-induced hypertension Prerenal azotemia , , , Pressure control mode with mandatory breaths ventilation , , , Pressure support , ventilation , , , , , Pressure waveform, supported breaths in Pressure-controlled ventilation Pressure-regulated volume control Presurgery antibiotic prophylaxis Procainamide , Proinsulin Prolactin Prophylactic treatment Propofol , , Proportional assist ventilation Propylthiouracil Prostacyclins Prostate, carcinoma of Protein , C recombinant activated total Proteinuria Prothrombin concentrate Prothrombin time Proton pump inhibitors , Proximal injectate lumen Pseudo emergency pathophysiology Pseudohyperkalemia Pseudohyponatremia Pseudomonas aeruginosa , , Ptosis Pulmonary arterial hypertension Pulmonary artery catheter lumens parameters measured by placement of , catheterization , , , , diastolic pressure , occlusion pressure , , pressure mean , , , , monitoring systolic pressure , wedge pressure Pulmonary capillary wedge pressure Pulmonary complications Pulmonary contusion Pulmonary disease, chronic obstructive , , Pulmonary edema , , , acute , Pulmonary embolism -, , , , , Pulmonary function test , Pulmonary hypertension Pulmonary hypoplasia Pulmonary infarct, right Pulmonary infarction score, clinical Pulmonary O transfer, indices of Pulmonary stability, interventions for Pulmonary vascular resistance , , , index Pulmonary veno-occlusive disease Pulse contour analysis index contour continuous cardiac output oximetry pressure variation , , , , Pulsus paradoxus Pupils Push enteroscopy Pyrethroid poisoning Q QRS complex tachycardia causes of narrow wide diagnosis of narrow wide Quadruple hormonal replacement therapy , Quinidine Quinupristin R Radial artery , injury Radiation colitis Radioallergosorbent test Ramipril Ramsay sedation scale , Rapid sequence induction , technique of Rapid shallow breathing index Reactions, types of Reactive oxygen species , Recent cardiac surgery Refeeding syndrome Regional analgesia, options of Rehabilitation , Rehabilitative phase Renal abnormalities Renal causes Renal compensation Renal disease end stage pre-existing Renal disturbances Renal dysfunction acute Renal failure , , , , , acute causes of chronic treatment for established Renal function effects of decreased tests Renal insufficiency, acute Renal loss , Renal parenchymal disease Renal phosphate excretion Renal replacement therapy , , , , , adverse effects of complications of Renal system , , Renal tubular acidosis Renin-angiotensin aldosterone system , system Renovascular disease Reptile bites Respiratory acid-base disorder Respiratory acidosis , , , acute causes of Respiratory alkalosis , acute causes of Respiratory care Respiratory compensation Respiratory depression, drug-induced Respiratory diseases Respiratory distress syndrome, acute , , , , Respiratory failure , , , , , , acute , causes of acute etiology of types of , Respiratory infections Respiratory rate alarm, high Respiratory stimulants Respiratory system , , , , , management of Resting energy expenditure Resuscitation fluid type of Resuscitative phase, early Reteplase , Retinopathy advanced papilledema Reversible causes Reyes syndrome Rhabdomyolysis , Rib fractures Richmond agitation sedation scale , Rifaximin Right ventricle end diastolic pressure , , volume Right ventricular dysfunction, treatment of stroke work index , systolic pressure , Rocuronium , Rodenticide poisoning Rush protocol , S Salbutamol Saline, normal Salt wasting nephropathies Schonfeld fat embolism syndrome index Scorpionidae Scorpions treatment Scrub typhus Sedation, drugs for Sedatives treatment Seizure prophylaxis rum fits whiskey fits Seldinger's technique Selenium Sellick's maneuver , Sengstaken-Blakemore tube Sensory symptoms Sepsis , criteria for diagnosis of intra-abdominal , management of severe screening of severe spectrum of Sepsis-induced hypotension Septic encephalopathy Septic shock management of pathogenesis of , resuscitation in Serum albumin amylase, increased bicarbonate , concentration of magnesium cortisol level creatinine magnesium , level osmolality parathyroid hormone phosphorus potassium urea Sevelamer hydrochloride Severe organ insufficiency Shock , , , classification of , degrees of diagnosis of distributive energy etiology of obstructive inotropes for management types of vasopressors for Short-acting beta- agonist , , Sibson's fascia Sickle cell anemia crisis , management of pathophysiology Sildenafil Sinoatrial exit block Sinus arrest bradycardia pause Skeletal fixation Skin , layers of losses Slow low efficiency dialysis Snake bite first aid measures for history of manifestations of Soda bicarbonate , Sodium , , , bicarbonate channel expected change in fractional excretion of level in infusate nitroprusside , , phosphate Somatic pain Sonography for trauma Sotalol Specific hypertensive crises, management of Speech disturbances Spinal injury, acute Spinal surgery Spironolactone Splenectomy Splenic injury, grading of Spontaneous attacks breath , trial breathing patients circulation return of , Square wave test Standard bicarbonate Staphylococcus aureus , , Static compliance, measurement of Statins Status asthmaticus Status epilepticus complications etiology treatment types STEMI, management of patient with Stenotrophomonas maltophilia Streptococcus agalactiae Streptococcus pneumoniae , , , , Streptogramin Streptokinase Stress ulcer prophylaxis Stroke , acute assessment of acute index types volume , , variation , , , Subarachnoid hemorrhage , , Subclavian artery injury Subclavian vein , anatomy of right cannulation right Subclavian vessels Subdural hematoma , with midline shift Substance abuse Succinylcholine , Suctioning technique Sulbactam Sulfamethoxazole Sulfonamides Superficial burns Supplemental oxygen therapy Supraventricular arrhythmias Supraventricular reentrant tachycardias Surgical-wound infections Surviving sepsis campaign bundles Symphyseal plating Symptomatic hypocalcemia, severe Symptomatic hyponatremia Synchronized cardioversion Synchronized intermittent mandatory ventilation , Syndrome of inappropriate antidiuretic hormone causes of , diagnosis of , diagnostic criteria of Systemic arterial pressure, cyclical variation of Systemic inflammatory response syndrome , , Systemic vascular resistance , , , index , , Systolic blood pressure , decline peak pressure variation , , , upstroke T Tachycardia , , , , management of Tachypnea Technetium-labeled red blood cell Telithromycin Temperature regulation Tendon Tenecteplase , Tension pneumothorax right-sided Terbutaline Terminal delirium etiology sundowning Testosterone free total Tetracyclin , , Thermoregulatory dysfunction Thevetia peruviana Thiazides Thiourea drugs Thiopentone , Thoracic bioimpedance plethysmography , Thoracic injury, exploration in Thoracic pump mechanism Thoracic surgery Thoracic trauma life-threatening injuries in Thorax , Thromboembolism, prevention of Thrombolytic therapy Thrombolytics , in ischemic stroke Thrombopoietin receptor agonists Thromboxane Thrombus in situ Thumb for selecting cannula, rule of Thymoma Thyroid emergencies hormone severe deficiency of therapy ophthalmopathy storm , Tibial artery, posterior Tibial condyle fracture Tibial fracture open shaft, open Tibial vessel injury Ticagrelor Ticarcillin Tigecycline Tirofiban Tissue oxygenation adequacy of impaired Tonic clonic movements Torasemide Torsades de pointes , causes treatment Total parenteral nutrition, complications of Toxic states Tazobactam Trace elements Trachea for percutaneous tracheostomy Tracheostomy care high lower steps of tube , , parts of types of types of , Tracheotomy Tramadol Transcellular shifts Transcutaneous Doppler ultrasonography Transcutaneous electrical nerve stimulation Transducer movements Transferrin Transfusion adverse reactions to of blood reactions , Transfusion-related acute lung injury infections Transient ischemic attack management of Transthoracic echocardiography , Transvenous cardiac pacing intrahepatic portosystemic shunts pacing Trauma , patient Traumatic airway injury Traumatic brain injury management of severe severe surgery in Traumatic cerebrovascular disease Traumatic head injury Traumatic rupture of aorta Traumatic spine injury Treprostinil Triglycerides Trimethoprim Troponins Troubleshooting PEEP alarms ventilator alarms Trousseau sign treatment True hyponatremia Tubercular meningitis Tumor necrosis factor , , , , U Ulnar artery injury Ulnar vessel injuries Ultrasound in critical care, role of Ultrasound transducer, selection of Unanticipated difficult airway Unfractionated heparin , , dose Upper airway obstruction Upper gastrointestinal bleeding causes of Upper limb injury, severe Upper radial injuries Urapidil Urea , Ureter, carcinoma of Uric acid , Urinary catheter use of drainage bag colonization tract infection , , , , Urine abnormalities calcium output , routine analysis sodium level Urosepsis, treatment of Uterine atony, pharmacologic therapy for V Vagal maneuvers Valproate Valproic acid Valsalva maneuvers Valvular heart disease , Vancomycin , Vaptans, role of Variceal bleed Varicella zoster virus Varices, endoscopic therapy for Vasa previa Vascular anomaly Vascular injury Vascular trauma of extremities Vascular-enteric fistula , Vasodilators , classification Vasopressin , , , Vasopressors , Vecuronium Vein compressibility, loss of Vena cava, superior Venous oxygen content, mixed , , tension, mixed saturation, mixed , Venous thromboembolism pathophysiology of Venous ultrasonography Venovenous hemodiafiltration, continuous Venovenous hemofiltration, continuous Ventilation adaptive support , adequate alarm, high minute basic modes of closed loop components of continuous mandatory high frequency initiation of inverse ratio methods of modes of restriction of strategy system types of high frequency Ventilator alarms asynchrony, diagnosis of patient design interaction Ventilator-associated pneumonia Ventricle, right Ventricular aneurysm treatment Ventricular arrhythmias Ventricular fibrillation Ventricular flutter and fibrillation Ventricular free wall rupture treatment Ventricular premature complex , Ventricular pseudoaneurysm Ventricular septal defect rupture treatment Ventricular tachycardia Verapamil , Verbal descriptor scale response Vessel, small Vestibular symptoms Vinca alkaloids Viperidae Vipers Viral encephalitis pharmacologic management of hepatitis , meningitis Visceral pain Visual analog scale disturbance symptoms Vitamin , D deficiency preparations K antagonist Vogt-Koyanagi-Harada syndrome Volume control mode with mandatory breaths Volume-controlled ventilation , Vomiting , , Voriconazole W Waist circumference and risk , Warfarin , , , Water deficit calculate correction of Water vapor pressure Weaning process Wernicke's encephalopathy Westermark's sign Wheeze Wilsons disease Withdrawal states Withdrawal symptoms, management of Wolff-Chaikoff effect Wolff-Parkinson-White syndrome Wolfram syndrome Wong-Baker faces pain scale Wound closure management phase Z Zinc Zoledronic acid