- Approach to a Poisoned PatientOmender Singh, Prashant Nasa, Deven Juneja
- Laboratory Testing in PoisoningAruna Dewan, Ashwin Patel
- Acid-base Disorders in PoisoningPradeep Rangappa, Shivakumar Mutnal, Ipe Jacob
- AntidotesOmender Singh, Anish Gupta
- Lipid Emulsion TherapyOmender Singh, Deven Juneja
- Forensic Toxicology for the Critical Care SpecialistSudhir K Gupta, Neha Sharma
INTRODUCTION
The patients with suspected poisoning are commonly encountered by acute medicine and critical care physicians. The poisoning in these cases may be accidental or intentional (suicidal or homicidal). Any chemical available can be potentially toxic to humans, provided the quantity is large. The high index of suspicion is warranted to identify these patients early especially when direct history of intoxication is not available. The knowledge and recognition of a specific toxidrome is critical, but one has to be aware of pitfalls like symptoms either may be nonspecific or masked (e.g. intracranial hemorrhage in cocaine poisoning).
The physical examination should be focused in case of critical condition and comprehensives once the patient is stabilized. The vital signs and level of consciousness is paramount in assessing the degree of toxicity. Initial vitals assessment by emergency staff or other paramedic must include respiratory rate, heart rate, blood pressure, and temperature; are of utmost importance as clinical signs may change by treatment. The patient neurological state (level of consciousness), pupils size, reaction to light, and presence of seizures may provide clues regarding the identity of the ingested poison.
The management approach in these patients is based on rapid and early diagnosis, decontamination and prevent further exposure, appropriate specific treatment while providing multiorgan supportive care. We have divided this chapter into following sections:
- Initial resuscitation and assessment
- Toxidromes
- Laboratory testing in poisoning
- Advanced cardiac life support concerns in poisoning
- Antidotes.
INITIAL RESUSCITATION AND ASSESSMENT
Most of the patients with poisoning respond well with early general intensive supportive measures with close watch on red flag signs. The supportive measures can be similar to any critically ill patient with “ABCD” approach (airway, breathing, circulation) however D in poisoning is different and means disability and decontamination. In case patient has an altered level of consciousness, the priority is airway management and cervical spine must be immobilized till it is clear of any injury. The initial resuscitation of patient is similar to any critical patient with systematic approach to evaluate and identify a life-threatening problem, and treat the problem before proceeding to next. The ABCD approach usually employed in critical care or emergency is useful.
Airway
Airway patency should be assessed in all cases unless a conscious-oriented patient without signs of upper airway obstruction. In case of altered sensorium or patient with stridor, hoarseness and other signs of upper airway4 obstruction, airway should be secured with maneuver like headtilt-chinlift or may need airway adjuncts. Endotracheal intubation may be required in these patients for airway protection and patency. The other indications are acute respiratory failure, high supplemental oxygen in case of carbon monoxide poisoning.1 The urine or blood toxicology screening should be obtained before any sedatives or hypnotics are administered. Some toxins (acid or alkali ingestion) require special care during airway management and involve an expert help in such cases. Whenever endotracheal intubation is required in patients with unknown poisoning, rapid sequence induction (RSI) using short-acting sedatives and paralytics is generally preferred as time from last meal is either unknown or erroneous. The succinylcholine is the neuromuscular paralytic agent of choice; however, it should be avoided in suspected organophosphorus poisoning as duration may be prolonged in view of decreased acetylcholinesterase levels. The intubation is necessary for most patients with above indications, but if possible intubation in aspirin (difficult to attain hyperventilation) and gamma-hydroxybutyrate (rapid recovery) poisoning can be avoided or delayed unless the patients present with clinical or blood gas evidence of respiratory failure.1
Breathing
If breathing or respiratory effort is inadequate beside the endotracheal intubation, respiratory support is also required. Endotracheal intubation besides altered level of consciousness to protect airway is indicated in acute respiratory failure. The supplemental oxygen in case of poisoning like carbon monoxide poisoning is additional indication.
The patient's oxygen saturation (SpO2) with standard bedside pulse oximetry can be misleading in poisoning with dyshemoglobinemias (e.g. carbon monoxide poisoning), where co-oximeter should be used to identify abnormal hemoglobins and true SpO2. The target SpO2 is 94–99% for most of the poisoning except in some poisoning where high SpO2 is associated with oxygen-mediated toxicity, e.g. chlorine gas, paraquat and diquat.2 In these patients lowest possible PaO2 (~50–60 mm Hg) and SpO2 (~90–93%) should be targeted essential to prevent tissue hypoxia and in order to avoid oxygen-mediated toxicity.3
If standard lung-protective invasive ventilation strategy is acceptable for most of the poisoning except in salicylates where any acidosis due to hypoventilation during intubation and/or lung protective ventilation may cause clinical deterioration.4,5
The patients where intubation may be required for correction of hypoxemia or other presentation of respiratory failure should be identified and managed early (Table 1).
Circulation
The patients with poisoning may present with hypotension or hypertension, brady- or tachyarrhythmias (Tables 2 and 3). The continuous monitoring of electrocardiogram along with blood preesure and heart is thus vital for all these patients.
Bradycardia and/or Hypotension: Bradycardia is mainly seen with β-blockers and calcium-channel blockers but sometimes significant enough to require temporary pacing especially if associated with hemodynamic instability (Table 3).
- Hypotension/Bradycardia—calcium-channel blockers, β-blockers, digoxin, aluminum phosphide (celphos) insecticide
- Hypertension/Tachycardia—Sympathomimetics, cocaine.
The cause of hypotension in a patient with poisoning can be multifactorial which includes hypovolemia, poison causing direct myocardial depression, arrhythmias, and/or profound systemic vasodilation. The patients with intoxication of sympathomimetic drugs, anticholinergics, ergot derivatives, cocaine and withdrawal of nicotine, alcohol, and sedatives instead present with hypertension. The initial resuscitation must include peripheral venous access using two large bore cannula (16- or 18-gauge) with targeted fluid resuscitation and/or vasopressors or inotropes if required for correction of hypotension. The treatment of hypertension is goal-oriented and may depend on factors like inciting agent, severity and associated complications.6
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DISABILITY AND DECONTAMINATION
The target-oriented neurological assessment in poisoned patients presenting with altered mental status is must (Box 1). In patients presenting with focal neurological deficit an imaging may be required to rule out any structural brain injury. There are simple bedside scores like Glasgow Coma Score or Alert/Verbal/Painful/Unresponsive (AVPU) score which can be used to assess consciousness and need to protect the airways. However neither has been validated and found to predict prognosis of the poisoned patient.3
Seizure is common neurological finding along with pupillary abnormalities. The assessment of pupil may help to suspect some poison along with other systemic findings (Table 4).
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The “coma cocktail” traditionally included dextrose (1 ampule of D50% IV), oxygen (5–10 L/min), flumazenil (0.2 mg IV), naloxone (2 mg IV), and thiamine (100 mg IV) and was advocated in unknown poisoning with unconsciousness and coma. This is helpful in prehospital to avoid intubation and to treat common causes of altered level of consciousness. The later studies have found use of flumazenil in this cocktail was counterproductive.
The flumazenil was used for diagnosis of intentional benzodiazepine overdose. However empirical flumazenil can increase the risk of seizures and agitation by benzodiazepine withdrawal in chronic abuse.7 It can also stimulate seizure, ventricular tachycardia in mixed overdose, e.g. amitriptyline, chloral hydrate.7–10
In a very large meta-analysis with more than 900 patients treated with flumazenil in emergency room, the number of patients needs to be treated for a very severe adverse events (e.g. arrhythmia and seizure) and for any adverse event (e.g. vomiting, agitation, and dysphoria) were 50 and 6.2 respectively.11 The patients given flumazenil has higher risk of seizures especially those on chronic treatment or abusing benzodiazepines, pre-existing seizure disorder or traumatic head injury, and patients who have been co-overdosed with tricyclic antidepressants.12 In light of available evidence on flumazenil epileptogenic effect, chances of precipitating an acute withdrawal, and some studies showed supportive management for benzodiazepine overdose is as effective; the use of empirical flumazenil is reduced in recent years and is currently recommended for highly selective subgroup of patients.13,14
The empirical naloxone can also precipitate opioid withdrawal or vomiting in nonopioid cause of coma. Fortunately with short half-life of naloxone, in case withdrawal is seen, symptoms wear off in 1–2 hours. However, the higher mortality of the opioids overdose over the benzodiazepines in view of respiratory depression still continue to recommend its use but dose titration should be to respiration rather to wakefulness.14 The administration of empirical thiamine is considered with history or suspicion of chronic alcohol abuse and in patients with severe malnutrition. There is a small risk of severe anaphylaxis with intravenous thiamine. Oxygen should be target to SpO2 95–99%. The “coma cocktail” can thus be revisited into more evidence based (Table 5).14
Decontamination
The evidence-based literature regarding proper decontamination methods are limited. There is paucity about the approved agents and there therapeutic indications and most of the principles have been taken from warfare fields and radiation accident protocols. Healthcare workers should use appropriate personal protective equipments (PPEs) like splash resistant goggles, gloves and gowns, while decontaminated patients with unknown poisoning to prevent any dermal or eye exposure. The decontamination is avoided in prehospital setting if adequate PPEs and other decontamination equipment are not available. The decontamination is effective only if done early and should not be delayed pending identification of the definitive offending agent.
Dermal and Eye Decontamination
In poisoning with possible dermal route, the patients’ clothings should be removed and a mild soap, and copious amount of lukewarm water should be used for decontamination. The body temperature should be monitored to avoid hypothermia, strong detergents, or hot water however should be avoided. In case of eye contamination, decontamination should be done with copious irrigation of normal saline solution and periodic monitoring of pH under supervision of ophthalmologists.3
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Gastrointestinal Decontamination
Gastrointestinal (GI) decontamination can be simply defined as measures to prevent or reduce the absorption of an ingested substance. The process of GI decontamination has evolved significantly over the last three decades and focus is now on minimally or less invasive techniques. This has happened partially because of recent research showed lack of benefit with many techniques of GI decontamination and in some cases serious complications with these procedures. There have been updation of many position statements by the American Academy of Clinical Toxicology (AACT) and the European Association of Poison Centers and Clinical Toxicologists (EAPCCT) on various techniques of GI decontamination.15
Cathartics: It can decrease the absorption of substances by its prokinetic effect and their rapid expulsion of poisons from the GI tract. There are broadly two types of osmotic cathartics: saccharide based (sorbitol) or saline based (magnesium citrate, magnesium sulfate and sodium sulfate). The mechanism of action is mainly useful for slowly absorbed poisons. Based on recent evidence, the current policy statement of AACT and EAPCCT on cathartics, there is no definite indication for them in poisoning. Besides there are contraindications such as corrosives, ileus or intestinal obstruction, recent abdominal trauma or surgery, and intestinal perforation. Magnesium cathartics is contraindications with renal failure, renal insufficiency, or heart block. Cathartics is to be avoided in elderly or the very young (<1 year of age) and hypotensive patients or electrolyte imbalances.16
Gastric lavage: It is used for removal of unabsorbed poison and to small extent decrease absorption of ingested substances for over 200 years. The technique has been described using a wide bore, orogastric tube (16–18 gauge) with patient position trendelenburg position (head down) and left lateral decubitus position. The lavage is then performed with approximately 250 mL (or around 10 mL/kg in pediatric patients) of water or saline followed by aspiration. The procedure is repeated until the aspirated solution is clear of any particulate matter.3,6 The gastric lavage is associated with complications sunch as aspiration, esophageal perforation, epistaxis, hypothermia. It is not indicated in patients with nontoxic overdoses or combative and uncooperative patients and contraindicated in suspected corrosive substance or a volatile hydrocarbon poisoning (kerosene) as may cause aspiration associated lung injury.3,6
In recent policy statement of AACT and EAPCCT the evidence supporting for gastric lavage routinely in poisoned patients is weak. If physicians on their clinical judgment decide to use gastric lavage it should be done under supervision with preference for activated charcoal or only observation over gastric lavage.17
Ipecac syrup: Ipecac-induced emesis is less traumatic than gastric lavage, and is therefore being still used in prehospital settings or in pediatric patients. Ipecac is most useful if administered immediately after ingestion with effectiveness decreases rapidly to only 30–40% removal rate even 1 hour after ingestion. The Ipecac is contraindicated in unconscious patients; seizures, poisoning with corrosives, and petroleum products are absolute contraindications due to risk of aspiration and lung injury.3,6 The Ipecac use is benign with complications relatively uncommon and easily treatable like diarrhea and/or vomiting. Serious complications are reported, e.g. Mallory–Weiss tears, pneumomediastinum, and aspiration pneumonia but are very rare.3 In case of Ipecac use, the activated charcoal should only be given after 1–2 hours. The current policy statement of AACT and EAPCCT on Ipecac-induced emesis is insufficient evidence supporting its use after poison ingestion.18 The Ipecac if considered should be administered early (within 60 minutes) in a patient who has consumed significant toxic dose and no altered consciousness.
Activated charcoal: This is an inert, nontoxic, powerful, and nonspecific substance which produces irreversible bonds to many intraluminal drugs and thus may interfere with their absorption. The process of activation includes steam heating and chemical treatment, where the surface area of charcoal is increased and available for adsorption. The activated charcoal can create a diffusion gradient between blood and gut, and can secondarily decreased serum drug levels of absorbed drug a process referred to as “GI dialysis” (Table 6). Charcoal can either be sole GI decontaminating agent or can be administered after both gastric lavage and Ipecac-induced emesis. The activated charcoal is generally well-tolerated with complications which are infrequent. The usual contraindications of all GI decontaminants like altered state of consciousness and/or unprotected airway, protracted vomiting, and intestinal obstruction or perforation too applies to activated charcoal.8
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Few uncommon side effects like aspiration pneumonia bronchiolitis obliterans, ARDS, and death has been reported in literature.3,7,19 The ideal dose should give a charcoal-to-drug ratio of 10:1. The dose required in children is 0.5–1 g/kg body weight, while in adults a fixed single dose of 50–100 g is indicated.19,20 The charcoal can be administered with cathartics (magnesium sulfate, magnesium citrate) to avoid its constipation effect. There are few drugs where charcoal is not found effective (Box 2).
Single-dose charcoal: The routine administration of single-dose activated charcoal is not indicated in poisoned patient. It should be considered only in a patient with significant toxic dose and when presented within the first hour of the event.
Mutidose-activated charcoal: The multiple dose is initial dose of 50–100 g (pediatric 10–25 g) followed by repeated frequency of hourly, 2 hourly, or 4 hourly at equivalent dose of 12.5 g/h. This repeated dose is the main principle behind GI dialysis. The evidence for multiple doses of activated charcoal in decreased morbidity or mortality is lacking and therefore routine administration is not recommended in the poisoned patient.20–22 Indications for administration of multi-dose activated charcoal (any of the following criteria):
- Intake of the poison exceeds the capacity to be adsorbed by a single dose.
- Drugs with significant enterohepatic circulation: To prevent the reabsorption by enterohepatic circulation of the active substance, metabolite, or drug conjugate.
- Intoxication by drugs with sustained release.
- Poisoning by drugs that decrease GI transit (anticholinergics, tricyclic antidepressants, opioids, and phenothiazine).
Whole bowel irrigation (WBI): The WBI works on the principle of preventing absorption of ingested matter by inducing a liquid stool through use of an osmotically balanced solvent [e.g. polyethylene glycol electrolyte solution (PEG-ES)].19 In current policy statement by AACT and EAPCTT, in view of lack of sufficient evidence, WBI was not recommended as a routine GI decontamination method and can be considered only in certain situations.23
Indications where WBI can be considered:19
- Sustained release products, medicines (like potassium chloride)
- Body Stuffers/Packers
- Drugs where activated charcoal does not work (heavy metals—iron, lithium or lead foreign body)
- Ingestion whole transdermal patches like fentanyl, clonidine, etc.
Contraindications for WBI:
- Bowel perforations
- Bowel obstruction, ileus
- Significant GI bleeding
- Unprotected airway
- Hypotensive patient
- Protracted vomiting
- Signs of leakage of illicit drug packets.
Renal elimination: Forced diuresis and urine alkalanization are the most used methods of renal elimination.3,19
Forced diuresis: The factors which decide renal excretion of a substance are glomerular filtration rate (GFR), tubular secretion if any and passive tubular reabsorption. The GFR depends on molecular weight, protein-binding and volume of distribution of a substance inside the body. The substance with larger volume of distribution, high degree of protein binding and/or higher molecular weight will have only a small fraction available for filtration and, therefore, forced diuresis will not be helpful. The efficacy of this technique has not been found in limited number of toxins (Table 7).9
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Urine alkalinization: It works on the principle of increased elimination of substance in urine by altering urine pH to cause increased ionized form of active substance and which decreases its tubular reabsorption. The drug should have mainly renal elimination, high volume of distribution, and high protein-binding. The alkalnization is done using 20–35 mEq/L of bicarbonate diluted in 5% dextrose with half-normal saline with target of urine output at 3–6 mL/kg/h and urine pH 7.5–8.5. Hypokalemia is the most common complication and tetany because of alkalosis and intracellular calcium shift is reported very rarely. The most definitive indication is for salicylate poisoning is that it can be used for other poisioning (Table 7), the evidence supporting its use in them is insufficient.24
Urine acidification: Urine acidification in weak bases toxicity was tried for their enhanced renal excretion. The ammonium chloride or ascorbic acid can be used for acidification and is tried for poisoning like amantadine, amphetamine, quinidine, or phencyclidine poisoning. The procedure is now obsolete because of only moderate elimination and significant complications (metabolic acidosis).24
Extracorporeal elimination of toxins: Extracorporeal treatments encompass heterogeneous modalities of treatments for either endogenous or exogenous poisons. The various techniques have been used for extracorporeal elimination of toxins (Box 3).
Principles for Selection of Extracorporeal Therapy
Screening of patients: After the initial stabilization of a poisoned patient, a detailed assessment is required to determine the need and modality of extracorporeal therapy (ECTR). There is lack of randomized controlled trials comparing ECTR to conservative conventional management because of various issues like ethical, cost, unbiased randomization and infrastructure. Even the observation studies are uncommon and very heterogeneous. In absence of evidence-based medicine, the need of ECTR is to be decided by crude measures like dose of poison, availability of any antidote, condition of the finally whether availability and expertise of ECTR is present in the hospital. Time bound decisions is critical too as most studies show effectiveness of ECTR when initiated early. In cases where risk of mortality (aluminum phosphide, paraquat, salicylates) or irreversible injury (blindness with methanol poisoning) is high, the decision tilts in favor of ECTR based on cost-effectiveness ratio (Tables 8 and 9). In other scenarios where either effective antidotes are available or morbidity is not much severe (e.g. methanol poisoning without acidosis), decision of ECTR should be taken case-by-case basis.25
Toxicokinetic considerations: There are four critical determinants which can be used to identify the success of ECTR in enhance poison removal: (1) molecular weight, (2) degree of protein binding, (3) any endogenous clearance, and (4) poison extracellular volume of distribution.
TOXIDROMES
The detailed and targeted history from patients or accompanying attendants is essential to understand the timeline of symptoms and/or withdrawal state.10
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The history should not be limited to but also include the amount of substance consumed, time since the last exposure (acute versus chronic), amount taken, and route of administration (i.e. ingestion, intravenous, and inhalation). The history must include prescription and nonprescription drugs, nonallopathic like herbal, ayurvedic products and empty bottles/containers if any found. The vial “pill count” to ascertain the number of consumed pills can be helpful to assess the amount. The history from the patient and/or attendant may not always be reliable. The medical record of any previous medical exposure before admission, and data from emergency medical staff is vital and should be registered. Initial vital signs, presenting state, neurological assessment (autonomic excitability, peripheral reflexes, and cognition affection) should be noted, along with previous medication history. The subsequent change in vital signs during the hospital course should be included in decision making about diagnosis of either a new toxin or effect of treatment process and/or withdrawal from chronic used substances.
The different clinical and laboratory features can be used for a clinical diagnosis of suspected group of poisoning or a particular toxidrome. The toxidrome is a constellation of symptoms and signs, laboratory results and/or ECG changes which can guide to a specific class of poisons and thus subsequent management.3,19,26
The common toxidromes encountered based on clinical settings and their associated class of poisons are discussed in Table 10. The specific toxicologic syndromes, or toxidromes, are helpful in narrowing the wide-list of differential diagnosis to a specific class of poisons and guide subsequent management. They may not be useful for a diagnosis of individual drug but can guide immediate class specific management.
While toxidromes are useful in emergency after initial resuscitation to identify possible class of drug, it is important to understand their limitations.19,26 Firstly, the toxidromes can have several overlapping feature, i.e. the sympathomimetic agents can have findings similar to anticholinergic baring few exception like sympathomimetic agents produce diaphoresis, on the other hand warm, dry, and flushed skin is seen with anticholinergics.11
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Secondly, the findings seen in individual toxidromes may not be all present and can be altered by inter-individual variability, comorbid conditions, and coingestants or polypharmacy. Thirdly, the individual agents in a class may not have one or more toxidrome findings, i.e. pethidine produces mydriasis instead of miosis seen with other opiates.
Laboratory Toxidromes
Osmolol gap
The serum osmole gap (OG) can be used as an important bedside laboratory test in evaluating poisoned patients. Serum osmolality (mOsm/kg) or osmolarity (mOsm/L) can be measured (Osmmae) using osmometer, which works on principle of freezing point depression and calculated (Osmcal) using sodium, blood urea nitrogen (serum urea) and glucose.
Osmcal: 2(sodium) + (urea nitrogen)/2.8 or blood urea/6 + (glucose)/18
Osmotically active substances that are reported in milligrams per deciliter (e.g. urea nitrogen and glucose), are converted using a conversion factor. The conversion factor for urea nitrogen is 2.8 and for glucose 18. In case of unusual osmotically active substances like ethanol and toxical alcohol, the equation will be:
Osmcal: 2(sodium) + (urea nitrogen)/2.8 + (glucose)/18 + (ethanol)/4.6+ (methanol)/3.2 +(ethylene glycol)/6.2 + (isopropanol)/6.0.12
The serum OG can then be calculated using Osmmae and Osmcal. The Osmmae is in units of osmolality (milliosmoles per kilogram) and the calculated form is in units of osmolarity (milliosmoles per liter), however for clinical purpose this is considered insignificant and OG can be written in any unit.
OG = Osmmae – Osmcal
An increase in the OG is a marker of presence of an osmotically active substance in the blood. There are however limitations dependent on the baseline OG and time when test was done in relation to substance ingestion. An OG of 10 has been conventionally defined as normal. Many studies have debated that this so-called normal value has revealed a wide range from −9 to +20 mOsmol/kg. The OG helps in identification of poisoning with abnormal osmotic active substance, however there is wide variation in acceptable normal (Table 11). The patient with OG of 9 mOsm/kg—near-normal value (10 mOsm/kg), but if this patient had ingested a toxic alcohol and had baseline (preingestion) OG of −5 mOsm/kg, the patient's OG has to be raised by 14 mOsm/kg to reach 9 mOsm/kg, which in certain poisoning like ethylene glycol is equivalent to a toxic level of 86.8 mg/dL. In other patients where there is delay in testing of OG, the poison is already metabolized where metabolites will not influence the OG because being anions they will displace bicarbonate and will double the serum sodium. Finally, the contribution of OG is dependent on molecular weight of active compound. Compounds with larger molecular weights contribute less to the osmolal gap and hence less significant OG (e.g. ethylene glycol).26–29
The OG interpretation should be done with above limitations and is used as an adjunct to clinical decision making. The positive value has significance and leads to further investigation; however, a “normal” osmole gap should be interpreted with caution, appropriate therapy should be initiated on suspicion pending confirmation of serum levels of suspected poison.
Anion Gap
The basic electrolytes (sodium, potassium, chloride and bicarbonate) should be done in all patients with poisoning. Whenever metabolic acidosis or low serum bicarbonate is seen an anion gap must be calculated using the equation:
Anion gap (AG) = Na+ – (Cl− + HCO3−)
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Essentially the AG is a difference of major cations and major known anions in body. In case of poisoning multiple substance acting as anions (e.g. sulfate, phosphate, or organic anions) cannot be measured and may contribute to AG. The anion gap thus helps in measuring or suspecting these “unmeasured” ions. The normal range for the anion gap is 8–16 mEq/L.19,26 The unmeasured anions may be endogenous (e.g. lactate) or exogenous (e.g. salicylate) and a common cause have been enumerated (Table 12).
The increased anion gap metabolic acidosis should identify the individual cause as hypoperfusion and resultant lactic acidosis may cause elevation of AG. This AG, however, may improve after adequate initial resuscitation and supportive care including hydration and oxygenation. If, AG metabolic acidosis worsen or does not improve despite adequate initial supportive care, the other causes of high AG metabolic acidosis should be checked especially toxic alcohols (Table 12).
Electrocardiogram Toxidromes
There are wide varieties of electrocardiogram (ECG) changes that can be seen in a poisoned patient. However, many of them are either nonsignificant or multiple unrelated drugs overdose may have common ECG effects. The ECG changes can be broadly divided into two toxidromes (depending on predominant mechanism of channel blockade): QT prolongation (cardiac potassium channel blockade) and QRS prolongation (sodium channel blockade).
QT prolongation: This is a relative common finding in drug overdoses (around 3% of all noncardiac prescriptions may cause QT prolongation). The primary mechanism is efflux potassium channel blockade causing prolongation of repolarization manifesting on ECG as QT prolongation and T or U wave abnormalities.13
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The abnormal prolonged repolarization actually produces inward depolarization current (early after depolarization) which may promote an auto-trigging causing re-entry phenomenon and hence malignant polymorphic ventricular tachycardia (torsades de pointes variant) (Table 13). QT prolongation is independently associated with higher mortality.27
QT interval is calculated from the Q wave of the QRS complex, till to the end of the T wave. QT interval is influenced by many factors including patient's age, sex, and heart rate. The calculation of the QT interval should include patient's heart rate which is known as corrected QT interval (QTc) using the Bazett formula (QTc = QT/RR1/2). Significant QT prolongation is considered when the QTc interval is greater than 440 milliseconds (msec) in men and 460 msec in women with torsades seen mostly with values greater than 500 msec. There is not only inter-drug but also inter-individual variation for arrhythmia for a given QT interval. The drugs commonly associated with QT prolongation are mentioned in (Table 13).
QRS prolongation: Cardiac sodium channels are usually present in the cell membrane and involved in cellular depolarization. The drugs which may block sodium channel basically bind to the transmembrane side and decrease the availability of number of channels for depolarization. This effect is considered traditionally as membrane stabilizing effect, but in toxic concentrations, it may cause slowing of upslope of depolarization and manifesting as wide QRS complex on ECG.
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Due to progressive QRS prolongation, the difference of ventricular and supraventricular rhythms becomes difficult; and finally, produces a sine wave pattern or, even asystole. The sodium channel blockers can also produce various conduction blocks, or a re-entry causing ventricular tachycardia or ventricular fibrillation. Bradyarrhythmias are also rarely seen in clinical practice because of associated anticholinergic or sympathomimetic properties of some drugs. The drugs causing QRS prolongation may cause blockade of other channels like calcium influx or potassium efflux channels (Table 14). The prominent R’ wave in lead aVR as well as the deep S wave in lead I is pathognomonic of tricyclic antidepressants cardiotoxicity.19,26
These drugs are however one common management, the administration of hypertonic saline or sodium bicarbonate in case of QRS prolongation of more than 120 msec. The patients with prolonged QRS interval and hemodynamic stability can be treated empirically with 1–2 mEq/kg of sodium bicarbonate.
LABORATORY TESTING OF POISONING
A basic laboratory panel of investigations should be obtained in all poisoned patients:
- Complete blood count
- Serum electrolytes
- Blood urea nitrogen and creatinine
- Blood glucose and bicarbonate level
- Liver functions test
- Arterial blood gases
- ECG
- A pregnancy test in a female of child-bearing age, unless proven otherwise
- The anion gap, serum osmolality, and osmolality gap
- Chest and plain abdominal X-ray
- The gastric content testing is controversial and has no effect on clinical decision making; is required only for regulatory requirements and/or medicolegal considerations.
Specific Investigations
Sample for urine toxicology screening for common drugs must be taken before giving any sort of sedation to these patients. Common urine test available in hospital.
- Cocaine
- Opiates
- Barbiturates
- Amphetamines
- Propoxyphene
- Phencyclidine (PCP)
- Tricyclic antidepressants.
In general, urine toxicology screens are mere screening tests and have low clinical utility than do serum assays. The urine toxicology has poor correlation to clinical signs and symptoms, also has low sensitivity and specificity for clinical diagnosis. There are many point-of-care urine assays (with the exception of that for the cocaine metabolite) available which have poor specificity with high false positive rate and require clinical interpretation. There are also assays which have principle of antibody binding to drug metabolites. The assays are however influenced by time of ingestion, fat solubility of poison, and associated drugs consumed. There are some drugs in which urine assays may be positive many days after use and can be unrelated to current clinical picture. The review of current drug usage is important. The routine urine drug testing has been proved of little impact of on patient management and should be discouraged.30–33
On the other hand, few drugs of abuse are not detected on routine urine drug screen, e.g. gamma-hydroxybutyrate (GHB), fentanyl, and ketamine. There are many false positive and false negatives seen in some urine assays [EMIT (DuPont Medical Products, Wilmington, DE, USA) and TDx (Abbott Laboratories, North Chicago, IL, USA) urine immunoassays], e.g. false positive benzodiazepine in patients who have ingested nonsteroidal anti-inflammatory drug like oxaprozin.26,34
The urine assays results are thus to be used with clinical judgment and other suggestive laboratory, and other investigations like ECG but not in isolation. The serum toxicology assays are more specific to drug intoxication and to be sent in case of high index of suspicion/history of drug overdose or abuse (Table 15).15
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- The cholinesterase level for organophosphorus poisoning: Specific levels of cholinesterase can guide treatment
- Oxygen saturation gap (SaO2 – SpO2 ): An oxygen saturation gap is diagnosed when more than a 5% difference between arterial blood gas (SaO2) saturation and saturation measured by CO-oximetry (SpO2). An elevated oxygen saturation gap is commonly found in carbon monoxide, methemoglobinemia, cyanide, and hydrogen sulfide poisoning.
ADMISSION TO INTENSIVE CARE UNIT
- Respiratory depression (PaCO2 > 45 mm Hg)
- Emergency intubation
- Seizures
- Cardiac arrhythmia (QT prolongation, preferably corrected QTc)
- QRS duration more than 0.12 ms
- Second- or third-degree atrioventricular block
- Systolic BP less than 80 mm Hg
- Unresponsiveness to verbal stimuli
- Glasgow Coma Scale score less than 12
- Need for emergency dialysis, hemoperfusion, or extracorporeal membrane oxygenation
- Increasing metabolic acidosis
- Pulmonary edema induced by toxins (including inhalation) or drugs
- Tricyclic or phenothiazine overdose manifesting anticholinergic signs, neurologic abnormalities, QRS duration more than 0.12 s, or QT more than 0.5 s
- Administration of pralidoxime in organophosphate toxicity
- Antivenom administration in envenomation
- Need for continuous infusion of naloxone.
ANTIDOTES
Most poisoned patients require intensive supportive care and have an uneventful recovery but in some cases an antidote can change the outcome. Antidotes are substances which either may antagonize the toxic effect or minimize the effect by competitive or noncompetitive action to primary drug. They can have their own toxicity and are indicated only in specific clinical circumstances. With the exception of naloxone, the role of other antidotes in unknown poisoning is very limited. The clinician should be familiar with the types of antidotes, their indications, and the availability with adequate stocking case of emergency (Table 16). Although antidotes can be “life-saving” but their use is very limited in bedside toxicology and in a minority of poisonings.35,36
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- Acetylcysteine
- Activated charcoal
- Atropine
- Pralidoxime
- Calcium gluconate/calcium chloride
- Hydroxocobalamin
- Diazepam
- Flumazenil
- Glucagon
- Glyceryl trinitrate
- Methylene blue
- Naloxone
- Sodium bicarbonate
- Sodium nitrite
- Sodium thiosulfate.
ADVANCED LIFE SUPPORT CONSIDERATIONS
Advanced life support is an important terminal event in a critically ill-poisoned patient. The patient may develop cardiac arrest on initial presentation, or may have out of hospital cardiac arrest and admitted after or with ongoing resuscitation.
The focused assessment along with standard resuscitation as per American Heart Association guidelines is important. The resuscitation must include consideration of poisoning and events preceding to cardiac arrest which may help in identifying the precipitating cause and specific management. There are antidotes or toxin-specific interventions that are recommended besides standard resuscitation during resuscitation from cardiac arrest.19,26,36,37
A simple mnemonic for special consideration to poisoning can be:
R—Resuscitation and risk assessment
I—Investigations
D—Decontamination
E—Enhanced elimination
A—Antidotes if indicated.
Resuscitation
- The airway obstruction or drugs/poisons with inhalation toxicity should be considered and when hypoxia is the precipitating cause—early intubation and ventilation with 100% oxygen should be considered
- 100% oxygen is recommended for certain poisoning like cyanide, carbon monoxide
- Hyperventilation is to be avoided in resuscitation, however, may be considered in cases with salicylate and cyanide poisoning.
- 100% oxygen and hydroxocobalamin, with or without sodium thiosulfate, is recommended for cyanide poisoning
- Cardiac toxicity by certain drugs will need specific management, e.g. high-dose insulin therapy, IV glucagon, calcium for refractory shock with β-blocker and/or calcium-channel blocker toxicity. Digoxin-specific antibodies for digoxin toxicity causing bradyarrhythmia and cardiac arrest
- Sodium bicarbonate can be considered in case of cardiac arrest due to tricyclic antidepressant overdose
- No role of naloxone and standard life support should be followed in case of in opioid overdose causing cardiac arrest
- Atropine consideration and (at higher doses) for organophosphorous poisoning
- Role of prolonged cardiopulmonary resuscitation (CPR) and extracorporeal membrane oxygenation (ECMO) for poisoning patient with cardiac arrest also need to mention and have been evidenced as salvage measure in few case reports.
Intravenous fat emulsion (IFE) has been suggested as a probably beneficial therapy in the management of local anesthetic overdose. It has also been tried in several other poisoning with varied results. The exact mechanism of action of IFE in poisoning is unknown, it is postulated to mediate antidote activity or act by compartmentalization of the offending xenobiotic into lipid phase, and hence moving it away from its target receptors (Table 17). As per one strategy, 20% emulsion is given in bolus at 1.5 mL/kg, and can be repeated 1–2 more times in case of persistent cardiac arrest. This can be followed by an infusion at 0.25 mL/kg/min for 30–60 minutes.19,38,39
CONCLUSION
An approach to unknown poisoning is based on standard principles of management in Intensive care like securing airway, breathing and circulation. The approach may be general but a index of suspicion and knowledge of toxidromes may be helpful in diagnosis. The lack of availability of antidotes for all poisoning, and lack of clear recommendations on reduction of absorption and enhanced eliminations make the management difficult. There is increasing trends of poisoning with multiple substances and chronic drug abuse which should be considered while using general and specific therapies.17
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KEY POINTS
- Keep a high index of suspicion for intoxication
- Initiate initial resuscitation based on ABCDE approach
- Gastric lavage and aspiration if required should be done within 1 hour
- Obtaining a detailed history is vital in diagnosing poisoning
- General supportive measures and measures to reduce absorption and enhance elimination should be instituted immediately
- Apart from routine investigations, an ABG and specific investigations like drug levels should be sent, as per the suspected poisoning
- Specific therapy or antidotes, if available, should be started early
- Most of these patients would require ICU care and monitoring.
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