Recent Advances in Pediatric Anesthesia Kirti N Saxena
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Perioperative Fluid TherapyChapter 1

Kirti N Saxena,
Akhil Singhal
It has long been known that the physiology of children is very different from that of an adult. Due to the higher metabolic rate, and the various other changes at birth and during neonatal life, the fluid requirements of neonates, infants and smaller children is different from adults. Perioperative infusion therapy should be adapted to the physiologic differences between newborns and adults, and fluid and electrolyte regulation during growth. Fluid requirements and maturation of the kidney set limits on the type and quantity of intraoperative fluids administered.
Renal System and Fluid Balance1
The extracellular fluid volume (ECF) is equivalent to about 40% of the body weight in neonates as opposed to 20% in adults. This difference has disappeared by the age of two years. In contrast, intracellular water increases with fetal maturation and reaches 33% of body weight at birth. Postnatalposed to 20% in adults. This difference has disappeared intracellular water increases rapidly and reaches the adult values of 44% by three months of age. Postnatal reduction of extracellular volume is a high physiological priority and is accompanied by natriuresis and diuresis. The neonatal kidney is characterized by a decrease in glomerular filtration rate, sodium excretion, concentrating ability and excreting excess extracellular fluid.1 These values slowly approach those of the adult by 12 months of age. Consequently, the infant cannot handle a large water load and may be unable to excrete electrolytes.
It is recommended that in neonates, for the initial two days, maintenance intravenous fluids should consist of 10% dextrose only. After that sodium (2–4 mEq/kg) and potassium (2–3 mEq/kg) should also be added to dextrose. These requirements are generally well met by 0.18% saline in 4% dextrose or five percent dextrose in quarter normal saline solution (5% dextrose + N/4 saline).
Various calculations using body weight, surface area or caloric expenditure have been used to determine fluid therapy for infants.2
Body Surface Area Method
In this method fluid and energy requirement is based on the concept that caloric expenditure is directly proportional to the body surface area. Based on this the water requirement are 1500 ml/m2, sodium requirements are 30 to 50 ml/m2 and potassium requirements are 20 to 40 mEq/m2 but however such estimates are not accurate and are not followed now.
Calorie Consumption and Body Weight
Holliday and Segar3 estimated the fluid requirement on caloric basis for infants who were spontaneously breathing and were nursed in a neutral thermal environment. For every 100 calories consumed 67 ml of water is required for solute excretion and 50 ml/100 calories was associated with insensible loss, but 17 ml/100 calories was produced by oxidation.
For weights ranging from 0 to 10 kg, the caloric expenditure is 100 cal/kg/day; from 10 to 20 kg the caloric expenditure is 1000 cal plus 50 cal/kg for each kilogram of body weight more than 10; over 20 kg the caloric expenditure is 1500 cal plus 20 cal/kg for each kilogram more than 20.
Maintenance fluid requirements are calculated on an hourly basis depending on the body weight. A suitable way of working this out is as follows:
Table 1.1   Fluid requirements (Holliday and Segar)
Body weight
Fluid requirements
4 ml/kg/hr
10–20 kg
40 ml/hr and 2 ml/kg/hr for every kg above 10
20–30 kg
60 ml/hr and 1 ml/kg/hr for every kg above 20
Table 1.2   Fluid requirements of neonates (ml/kg body weight/day)4
Day of life
Birth weight >1.5 kg(ml/kg)
Birth weight 1 to 1.5 kg(ml/kg)
7 onwards
Maintenance fluid requirements must take into account the following losses:
Insensible losses
Increased urine output allowance by 12% per °C>37.8
Insensible Water Loss
In the calculation of fluid requirements by the 4-2-1 formula insensible water losses account for 50 ml/100 calories consumed. Insensible water loss is the invisible, continuous loss of water from the lungs (respiratory water loss) and the skin (transepithelial water loss). In contrast, sweating (sensible water loss) is visible and rarely represents significant water loss in infants and neonates.
  1. Respiratory water loss: It comprises of one third of the total insensible loss in a full term and premature infant greater than 32 weeks.
  2. Transepithelial water losses: In infants of all gestational ages transepithelial water loss is the major component of insensible water loss. This is because of the poorly developed stratum corneum, which allows minimal resistance to the passage of water.
  3. Exposure to the ionising radiations: Exposing the infant to ionizing radiations by infant warmers and phototherapy increases the insensible water loss.
In neonates for the initial two days, maintenance intravenous fluids should consist of 10% dextrose only. 10% dextrose in continued till the glucose levels is stable or it is given to neonates born to diabetic mother.4 After the first two days of life applying the Holliday and Segar formula for a 3 kg child the amount and the type of fluid can be determined.
The hourly fluid needs can be estimated as 4 ml/kg/hr and for every 100 ml of water, an infant needs 3 mEq of sodium, 2 mEq of potassium, 3 mEq of chloride and 5 g glucose.
Total fluid required by a 3 kg infant will be 300 ml/day.
Sodium requirement comes out be 9 mEq/day.
In NS 1 mEq is provided by 6.5 ml of fluid so to meet the requirement of 9 mEq a total of 58.5 ml of NS will be required for the day.
Total fluids = 300 ml; 5% dextrose/NS = 58.5 ml and 5% dextrose/water = 241.5 ml.
The 5% dextrose/NS is approximately 20% of the total; hence 5 % glucose in 0.25 NS may be generally used for maintenance solutions. For the purpose of convenience 4 parts of dextrose 5% are mixed with 0.9%NS (4% dextrose solution in 0.18% NS).1 These proposal over time have accepted as (four-two-one and fourth and a fifth).5
Intraoperative fluid therapy may involve the initiation of fluid management or continuation of the ongoing therapy. It can be as simple as providing the the deficits from preoperative NPO status and providing maintenance fluid to as complex as correcting preoperative abnormal deficits, blood loss 4and electrolyte derangements. It is better to discuss each of these factors separately before discussing the general guidelines.
The fasting period before induction of anesthesia should be adjusted by timing the feeding and surgery such as to minimize the chances of aspiration while simultaneously taking into account significant hypoglycemia and dehydration that might occur due to prolonged fasting. The usually followed guidelines for minimum fasting period are tabulated below6:
Table 1.3   Guidelines for minimum fasting period
Fasting for clear fluids (hr)
Fasting for Fasting forbreast milk (hr)
Fasting for formula or cow milk (hr)
Fasting for solids (hr)
Infant less than 3 months
Infants more than 3 months
However, delays in surgical schedule can predispose the infant to dehydration and hypoglycemia and in such situation it is prudent to start intravenous fluid prior to surgery. The amount of deficit fluid can calculated by multiplying the hourly requirements of the infant with the number of hours the child has been fasting. This deficit may be replaced by giving half the volume in the first hour of surgery and the other half over the next two hours in addition to the maintenance fluids.
Intraoperative Third Space Loss
Surgical trauma and host of other condition are associated with isotonic transfer of fluid from the extracellular fluid compartment to the nonfunctional interstitial compartment. This isotonic transfer of fluid is termed as third space loss. If these are not replaced adequately the plasma volume will decline. The magnitude of such loss varies with the type of surgery and is maximum with an infant undergoing abdominal surgery. In infants third space loss during abdominal surgery is about 6 to 10 ml/kg/hr, for intrathoracic surgery it is 4 to 7 ml/kg/hr and for superficial surgeries it is 1 to 2 ml/kg/hr. Other losses such as ryles tube aspirate, chest tubes, etc. must be taken into account. Generally, lactated Ringer solution, normal saline solution or plasma lyte is used to replace such losses.
Since the publication of the paper by Holliday and Segar a debate has been going on for the last five decades regarding the type of fluid to be used in 5infants and small children. Two types of fluid may be indicated for a pediatric surgical patient: one type of fluid replaces the deficit or the maintenance and the second type the third space loss. Classically for long procedure with extensive third space loss, 5% dextrose/0.25 NS solution is used for maintenance and deficit replacement while a balanced salt solution was used for the third space losses. As per this regime, in patients, who have short surgical procedures with minimal third space loss), one type of fluid suffices (5% dextrose in lactated Ringers solution or 5% dextrose/0.9% saline).7 Various studies then revealed conflicting results about the intraoperative use of glucose. Usually infants who were fasted for greater than 6 hours showed intraoperative hypoglycemia8 while other studies failed to demonstrate hypoglycemia in infants fasted for 6 to 8 hours.9 Because of the high metabolic rate and oxygen consumption of infants and small, 5% dextrose was advocated for infants prone to hypoglycemia as a result of preoperative fasting.
Older infants and children who were given 5% dextrose in lactated Ringers solution for maintenance showed intraoperative hyperglycemia (glucose >200 mg). Elevated blood sugar levels may cause osmotic diuresis and exacerbate neurological injury. This diuresis may cause intracellular dehydration in the brain followed by intracranial hemorrhage more so in a stressed infant. Therefore, blood glucose control is a reasonable goal and critical in a few. One way to avoid hyperglycemia was to decrease the amount of 5% dextrose but this could cause hypotension in a fluid depleted child. A less concentrated solution of glucose (2.5% dextrose in lactated Ringer solution) when given at normal maintenance rates would provide adequate volume replacement with out the risk of hypoglycemia and hyperglycemia. In infants undergoing prolonged routine surgery however, these concerns about the infant undergoing hypoglycemia may be exaggerated as fasting times have been liberalized in recent years, and even healthy infants have been shown to maintain blood glucose concentrations within normal limits during surgery, with or without added dextrose. Use of dextrose 0.9 or 1% is sufficient to avoid hypoglycemia and prevent ketosis in infants but fluids containing dextrose 4 or 5% are associated with hyperglycemia, which may have deleterious effects. There is no justification to use either dextrose 4%/saline 0.18% or dextrose 2–5%/saline 0.45% as maintenance during surgery as this fluid will be associated with dilutional hyponatremia and hyperglycemia. Intraoperative fluid should be an isotonic solution with or without low-dose dextrose (0.9–1%).10
Dextrose 4%/saline 0.18% and dextrose 2.5%/saline 0.45% are isotonic when administered but effectively hypotonic once the glucose has been metabolized; these are referred to as hypotonic solutions hereafter. There have been many case reports of neurological injury as a result of hospital-acquired hyponatremia in children, many cases after routine surgery for the common conditions of childhood. Concerns have focused on the use of 6hypotonic fluids for maintenance therapy, in particular, the use of dextrose 4%/saline 0.18%.
Children are particularly vulnerable to the effects of acute hyponatremia and become symptomatic at higher plasma sodium concentrations than adults. More than 50% of children with serum sodium <125 mmol litre−1 develop hyponatremic encephalopathy.11
Dilutional hyponatremia occurs when there is a source of electrolyte-free water and an inability to excrete free water in the kidney. The excretion of water in the kidney is controlled by vasopressin (antidiuretic hormone, ADH). Vasopressin release is controlled by osmotic stimuli so that healthy individuals are able to excrete large volumes of dilute urine in response to a water load by suppression of vasopressin release. Plasma osmolality is thus regulated within narrow limits despite wide variations in fluid intake. Vasopressin release is also controlled by a variety of non-osmotic stimuli. These include factors commonly encountered in the preoperative period—decreased extracellular fluid volume, hypovolemia, pain, nausea, stress and drugs such as morphine, also CNS and pulmonary disturbances. These non-osmotic stimuli override the osmotic control so that the perioperative period is characterized by high concentrations of vasopressin and an inability to excrete a free water load. Administration of hypotonic fluids in this situation will lead to hyponatremia.12
During the intraoperative period, the stress response to surgery causes maximal vasopressin release and urinary losses will be low. Insensible losses (sweating/respiratory water losses) will also be low—the requirement for maintenance water is low. However, there is a need to maintain arterial pressure to counter the effect of anesthetic agents, and to replace fluid deficits because of fasting and ongoing losses associated with surgery. These deficits/losses are from the extra cellular compartment and should logically be replaced by a solution approximating to the composition of extracellular fluid. Hypotonic solutions would be expected to result in a decrease in plasma sodium. During acute illness, a number of physiological stimuli such as fever, pain, nausea, and stress are associated with the non-osmotic release of antidiuretic hormone, thereby limiting the renal excretion of water free of electrolytes. The source of electrolyte free water in these circumstances is often not recognized because standard maintenance fluids (4% dextrose with 0.18% saline) are calculated to provide the correct water and salt requirements for healthy children, rather than the correct tonicity for sick children. Under these conditions, treatment with even “normal quantities” of hypotonic fluid will result in the net accumulation of electrolyte free water when antidiuretic hormone acts, and hence hyponatremia will occur.13
When a simple calculation based on a tonicity balance is used, a “standard” fluid maintenance regimen of 100ml/kg/day of 4% dextrose and 0.18% saline would result in the accumulation of about 50ml/kg/day 7of electrolyte free water (here we are assuming that half the water intake is excreted renally or as insensible losses in an acutely ill-child when antidiuretic hormone acts). This represents a gain of about 8% in electrolyte free water relative to the total body water (600ml/kg total body water+50 ml/kg electrolyte free water), which would proportionally drop the serum sodium concentration from 140mmol/l to 129mmol/l (8% of 140) after 24hours.
With evidence mounting towards dilutional hyponatremia with hypotonic fluid certain modification were proposed to the type of fluid being administered. A balanced salt solution was used for all deficit and third space losses and 5% dextrose in 0.45% normal saline to be administered by “piggyback” infusion at maintenance rates.1415
One such guideline prescribes using maintenance fluid of 10% D and 0.75 NS with 20 mEq/l of NaHCO3 for neonates as neonates have a propensity to develop metabolic acidosis 5% D and NS is used for other children. Addition of KCl 20 mEq/l has been recommended if K+ falls below 3.5 mEq/l. Replacement of blood loss in excess of 20 ml/kg is done with packed red cells.
Table 1.4   Guidelines for fluid in the perioperative period16
Age of the child
Type of solution to be used
Maintenance fluid; 4 ml/kg/hr 5% to 10% dextrose in 0.75% saline
<3 years
Maintenance fluid; 4 ml/kg/hr 5% dextrose in normal saline
Taylor and Durward17 have previously assembled the arguments as to why the Holliday and Segar approach of relating water requirements to energy expenditure (and, via a simplification, to weight) produces a variable overestimate of the volume of water needed for maintenance. Most energy expenditure (80%) occurs in the major metabolic organs (heart, liver, kidney and brain), which account for only 7% of total body mass, so relating increased weight to increased energy expenditure will always produce an overestimate; insensible water losses are probably less than supposed; and relatively inactive and ill children in hospital require less water than their active healthy counterparts from whom figures were first derived.
The argument for lower-volume but continued hypotonic replacement has been proposed. The fluid requirements overall have been overestimated; fluid losses are made up of two components—an electrolyte-free insensible water loss and an electrolyte-containing urinary loss. Losses from both components have been overestimated but it is the renal loss that is affected by the action of ADH; thus, overall less replacement fluid is required but there is a need for some of this replacement to be ‘free water’—hence we should continue to use hypotonic replacement fluids but at volumes of about 60% of current values.18198
Let us see what would happen if children were to be given isotonic maintenance fluid? It is argued that if maintenance fluids were to be given as saline 0.9% at the current recommended volumes then this should remove the danger of hyponatremia from most patients. It would mean that children would receive a large (5-fold) increase in sodium intake and potentially many more children would develop some degree of hyperchloremic acidosis. Using Hartmann's solution rather than saline might ameliorate this.20 Either saline 0.9% or Hartmann's solution could be presented with dextrose solutions in circumstances where hypoglycemia was perceived to be a potential threat. Giving smaller volumes of isotonic maintenance fluid than currently recommended could decrease the electrolyte load. The potential problems with such an approach are that it would expand the extracellular compartment in all cases. Applied across the board, this might be very disadvantageous to certain ill children. Also, it gives no free water.
However, the whole notion that giving isotonic fluids would provide a guarantee against postoperative hyponatremia has been questioned. It has been demonstrated that women undergoing gynecological surgery and receiving only near isotonic perioperative fluids show a decrease in their serum sodium concentration in the first 24–36 hours after surgery. During this time these patients pass relatively large volumes of urine that is hypertonic to their serum that is their kidneys generate free water. This is explained by the fact that in the postoperative period ADH is increased. Leading to the expansion of the extracellular compartment by the near isotonic fluid that they receive. This induces natriuresis at a time when the raised ADH concentration associated with the perioperative period prevents the kidneys from excreting dilute urine—a process that has been labeled desalination.21
Holliday argued against the use of isotonic saline for routine maintenance but highlighted the importance of correcting volume deficits with isotonic fluid boluses. He suggested that isotonic maintenance fluids would be associated with hypernatremia or fluid overload and possible desalination as a consequence.22 However, in the presence of elevated ADH concentrations, Holliday and others recommend fluid restriction to 50% of maintenance requirements.
Now we come to the most challenging question. In the postoperative period, maintenance fluids are required to replace insensible losses, urinary losses and provide a source of dextrose when oral intake is precluded or inadequate. In addition, isotonic replacement fluids may be required for ongoing or abnormal losses (such as gastrointestinal losses the requirement for water was related to the caloric expenditure in healthy children, with estimations for average insensible losses and average urinary losses. 9However, it may be pointed out that caloric expenditure is reduced in hospitalized children and urinary losses may vary according to the clinical situations and the effects of ADH; thus maintenance fluid requirements should be restricted postoperatively.19 It was suggested that the ideal maintenance fluid in children was hypotonic dextrose saline but that volume deficits should be replaced with a 20–40 ml kg−1 bolus of isotonic saline. Experts have emphasized the dangers of administration of hypotonic saline solution in the presence of elevated ADH concentrations in a child who is acutely unwell, either advocating only isotonic solutions (with dextrose) in the postoperative patient,11 or avoiding hypotonic solutions if the plasma sodium decreases below 138 mmol litre. Recently, there have been both retrospective23 as well as prospective studies24 to suggest that infusion of hypotonic fluids leads to hyponatremia and that isotonic fluids should be used in the postoperative period.
Taking into account the above discussion the following guidelines have been proposed by American Pediatric Academy25
  1. Oral fluid management prior to surgery
    • Clear fluids can be allowed safely two hours prior to surgery without increasing the risk of aspiration and also reducing the fasting duration
    • Older children to be fasted of solids and milk for 6 hours prior to surgery
    • Fasting of four hours for breast milk and six hours for formula milk prior to surgery.
  2. Correction of fluid deficit
    • Child for minor elective surgery has usually minimal fluid deficit, which is not necessary to correct
    • Child for major elective surgery should have deficit similar to that of minor surgery as clear fluid are allowed two hours prior to surgery and any such deficit is corrected by 10 ml/kg bolus during the first hour of surgery
    • All such deficit should be corrected by isotonic fluid such as 0.9% normal saline or lactated Ringer solution.
  3. Maintenance fluid requirements in children
    • Maintenance fluid requirement can be calculated according to formula described by Holliday and Segar for infants greater than four weeks of age
    • For a term neonate greater than 36 weeks of gestation 10% dextrose should be given at rates of 2 to 4 ml/kg/hr for the first two days of life
    • Neonatal input recommends that from the third day of life onwards 0.18% normal saline in 10% dextrose should be given at 4 ml/kg/hr.
  4. Fluid and dextrose management during surgery
    • Maintenance fluid used during surgery should be isotonic; 0.9% normal saline or lactated Ringer solution
    • During surgery majority of the children can be managed by fluids containing no dextrose; If no dextrose is given the blood sugar levels are to monitored
    • Neonates during the first two days of life should be given 10% dextrose
    • All term and preterm neonates who are on dextrose containing fluid should continue to receive them during surgery
    • All infant and children receiving parentral nutrition preoperatively should continue to receive it intraoperatively or should be shifted to dextrose containing fluids and blood sugar levels monitored during the surgery
    • Children with low body weight (<3 rd centile) or having major surgery or having extensive regional anesthesia should be given fluids containing (1 to 2.5% dextrose) intraoperatively or blood sugar should be monitored.
  5. Management of other losses during surgery
    • All other losses including third space losses should be replaced with isotonic fluid like normal saline and lactated Ringers solution
    • In infants greater than three months of age hematocrit may be allowed to fall till 25% whereas in smaller infants no guidelines have been proposed and children with cyanotic heart disease will require higher haematocrit values for maintaining oxygenation.
  6. Postoperative fluid management
    • Surgery, pain, nausea and vomiting are all potent stimuli for non osmotic ADH release. All maintenance fluid in postoperative period should be isotonic, but consensus cannot be achieved on the rate and the type of fluid to be administered which remains an area of research and should be tailored according to the needs of patients: All ongoing losses from drains and nasogastric tubes should be replaced with isotonic fluid.
Inspite of the plethora of recent literature on pediatric fluids, a recent survey26 in England found that practitioners continue to use hypotonic solutions preoperatively putting children at risk of hyponatremia. No such survey has been conducted in India and it is not known whether the old formula3 is being followed for fluid administration or the above mentioned newer guidelines are being followed.
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  1. Bikhazi GB, Cook DR. Perioperative fluid therapy and blood replacement in Smith's anesthesia for infants and children. Published by: CV Mosby Company;  5th Ed: 1990: 331–44.
  1. Thomas DKM. Hypoglycemia in children before operation, its incidence and prevention. Br J Anaesth 1974; 46: 66–8.
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  1. Hoorn EJ, Geary DG, Robb M, Halperin ML, Bohn D. Acute hyponatremia related to intravenous fluid administration in hospitalized children: an observational study. Pediatrics 2004; 113: 1279–84.
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  1. Demetrius Ellis. Regulation of fluids and electrolytes in infants and children. Smiths anesthesia for infants and children. Published by Elseiver;  7th Ed: 2006: 109–52.
  1. Taylor D, Durward A. Pouring salt on troubled waters. Arch Dis Child 2004; 89: 411–14.
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  1. Scheingraber S, Rehm M, Sehmiisch C, Finsterer U. Rapid saline infusion produces hyperchloremic acidosis in patients undergoing gynaecologic surgery. Anesthesiology 1999; 90: 1265–70.
  1. Steele A, Gowrishankar M, Abrahamson S, Mazer CD, Feldman RD, Halperin ML. Postoperative hyponatremia despite isotonic saline infusion: a phenomenon of desalination. Ann Intern Med 1997; 126: 20–5.
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