Fluid resuscitation in children

Robert Henning

Robert Henning FRCA FANZCA Staff Specialist Department of Intensive Care Royal Children's Hospital, Melbourne

Address for correspondence: Dr R Henning Staff Specialist Department of Intensive Care Royal Chuldren's Hospital Flemington Road Parkville Vic 3051

Abstract Children most often need fluid resusci­

tation because of fluid loss (especially from diarrhoea), while bleeding and sepsis account for a minority of cases. The child's immature body systems (especially cardio­vascular and renal), age-dependent fluid compartment sizes and lack of degenera­tive vascular diseases of adulthood affect the child's clinical signs and the response to hypovolaemia and to resuscitation.

The issues of what fluid, how much, how fast and by what route are interde­pendent. In general, aggressive early fluid resuscitation reduces mortality and mor­bidity in children with bums and sepsis, while slow rehydration over 48 hours is safer in dehydrated children with diar­rhoea or diabetic ketoacidosis. There are few specifically paediatric data comparing hyper- or isotonic crystalloid with colloid, or the various colloids with each other, so that legends abound in paediatric resusci­tation. The empirical basis of these legends wQl be discussed in this paper

Safe resuscitation requires close observation of the cardiovascular system, conscious state, urine output and blood chemistry. When close biochemical moni­toring is not possible, a fluid regime should be chosen which is least Ukely to cause biochemical changes.

Second Australian Symposium on Fluid Replacement • 1995 57

Fluid resuscihition m childmi

Introduction The most common reasons why children

require fluid resuscitation are fluid loss, blood loss and sepsis. Dehyd radon due to diarrhoea is the commonest cause of hypovolemia world­wide and causes the deaths of 3.2 million children under the age of five each year, hi the US, there are an average of one to five episodes of diarrhoea per child per year, and diarrhoeal dehydration causes 500 child deaths per year and 10% of preventable post-neonatal infant deaths'. In Australia, diarrhoeal dehydrahon is uncommon as a cause of death but causes severe illness especially in children in isolated commu-nihes.

Children may suffer severe fluid loss from the kidneys (eg in diabetic ketoacidosis and due to diurehc drugs) or from the skin (in hot weather). Distributive losses of fluid into the bowel lumen, serosal cavities and the extravascular compartment are frequently seen in children due to sepsis, anaphylaxis, global hypoxic-ischaemic injuries such as cardiac arrest, near-drowning or near-miss sudden infant death syndrome, as well as after cardiopulmonary bypass. Bleeding due to surgical or accidental trauma occurs commonly. Relative hypovolaemia due to vasodilation is most often due to sepsis or anaphylaxis.

Physiological in:imaturity The physiological response of the child to

hypovolaemia and low cardiac output is influ­enced by the immaturity of several organ systems, especially the heart and kidneys. This immaturity also influences the child's clinical signs of hypovolaemia. Different aspects of the child's physiology mature at different rates, being most immature in preterm infants and in the first few months of life.

Cardiovascular System The infant myocardium has fewer acto-

myosin elements and fewer mitochondria per unit cross-sectional area and smaller noradrenaline stores than the adult, so the irtfant is more dependent on increasing heart rate than on increasing contractility in response to hypovolaemia. Storage and release of calcium from the sarcoplasmic reticulum in the infant myocardium is less efficient than in adults, so that contractility in the infant is more dependent on the concentration of calcium in extracellular fluid". The infant's ventricle is less compliant, resulting in higher atrial pressures for the same degree of ventricular filling. The infant has fewer myocardial beta receptors than the adult

and the response of the infant to stress is bradycardia rather than tachycardia as in the older child and adultl

Absence of the degenerative vascular diseases of the heart and brain gives the infant a higher oxygen supply/demand ratio than the adult, so that the infant tolerates more tachycardia and hypotension, especially as the capacity of the infant heart and brain for anaerobic metabolism is also greater than that of the adult*.

Renal The renal blood flow and glomerular filtra­

tion rate are lower per unit body surface area in the first two years of life than in the adult. The infant kidney is less able to concentrate urine and to handle a sodium load than that of the adult and so is less able to compensate for fluid loss, and there is a smaller safety margin in the administration of resuscitafion fluids.

Body fluid compartments Figure 1 (drawn from data in ref 5) shows that

in the first six months of life, the total body water declines rapidly due to reduction in the extracellular fluid volume. Later in childhood, the extracellular fluid (ECF) volume continues to decline at a slower rate, while intracellular fluid (ICF) volume increases due to ceU multipli­cation. Total body water remains constant.

How much fluid? In hypovolaemic children, resuscitation fluid

consists of: deficit + ongoing losses + maintenance

requirements The maintenance requirement of a term

neonate is 150ml/kg/day. Beyond the newborn period, maintenance fluid needs are calculated the following way:

First 10 kg: lOOml/kg/day plus: Second 10 kg: 50ml/kg/day plus: Thereafter: 20ml/kg/day Thus, a 35kg child requires:

1000 (10kg x lOOml/kg) + 500 (10kg x 50ml/kg) + 300 (15kg x 20ml/kg) ml/day ie 1800 ml/day

The maintenance requirements of sodium are 2-3mmol/kg/day, and of potassium l-2mmol/kg/day.

The assessment of blood volume deficit depends on a combination of clinical signs: 1. Signs of inadequate end-organ perfusion:

reduced conscious state, reduced urine output, metabolic acidosis and Kussmaul breathing.

2. Signs of the deployment of compensatory mechanisms: tachycardia and skin vasoconstriction, cool, mottled extremities.

58 Second Australian Symposium on Fluid Replacement • 1995

Robert Ht'nnin^

Figure 1. Body fluid compartments

lOfl-r

c o

BODY FLUID COMPARTMENTS

TBW

-1 1 1 1 1 1 -

AGE

Table. Clinical s igns of dehydration in children. (Adapted from ref 6.)

Degree of dehydration Nil

Deficit volume <30 ml/kg

Heart rate Normal

Systolic BP Normal

Conscious state Alert

Skin turgor Elastic

Eyes Normal

Mild-moderate (3-10%BWt)

Severe (> 10%BWt)

30-100ml/kg >100ml/kg

Moderate tachycardia Marked tachychardia

Slightly reduced Marked hypotension

Restless and irritable Lethargy, stupor

Pinch retracts slowly Pinch retracts very slowly

Sunken Very sunken

3. Small heart and liver, indicating that cardiac failure is not the cause of these other signs.

It is now recognised that the degree of dehy­dration in children can be no more accurately classified by clinical signs alone than as; severe (>10% body weight), mild (3-10% body weight) and absent (Table).

Skin turgor is the single most reliable sign of dehydration, while heart rate, conscious state and urine output are the best indicators of severity. In children who are hypovolaemic due to blood loss or other causes, the blood pressure is maintained in the normal range by effective compensation mechanisms until 30ml/kg of

Second Australian Symposium on Fluid Replacement • 1995 59

Flmii reauscitatiofi in children

blood (almost half the blood volume) are lost. The fall in blood pressure, when it occurs, may be catastrophic.

Unless an estimate can be made of the fluid deficit (eg in dehydration), monitoring the clinical response to a fluid challenge is the most suitable method of assessing volume require­ments in the child. The response of the heart rate, conscious state, urine output and skin perfusion to a bolus of lOml/kg colloid or 20rTLl/kg crystalloid are particularly effective guides to the need for further fluid resuscitation. The commonest error in the resuscitation of children with blood loss is under-replacement. In children who need or who are likely to need replacement of 30ml/kg of blood loss or more over a short period, fresh frozen plasma 10-20ml/kg and platelets lOml/kg should be given early, to limit the continuing bleeding due to dilutional coagulopathy. If the bleeding is less rapid, the blood clotting studies and platelet count should be monitored regularly to indicate the need for clotting factor replacement.

How rapidly? The resuscitation of a child with significant

blood loss, septic shock or bums should be rapid. In a bleeding child, boluses of blood or colloid (10ml/kg) or crystalloid (20ml/kg) are given at 5-10 minute intervals and the effect on heart rate, blood pressure, skin perfusion and urine output is monitored until normal values are achieved. In children with septic shock, rapid resuscitation (>40ml/kg crystalloid in one hour and >100ml/kg in the first six hours) has been shown to be associated with better survival than slower resuscitation (<40ml/kg in one hour and <100ml/kg in the first six hours)'.

In burned children resuscitated using the Parkland formula (4nil crystalloid/kg/% body surface area (BSA) burned), giving half of this volume in the first four hours and the remainder over the next 20 hours restores the urine output and vital signs faster, with a lower frequency of respiratory failure than when half of the 4ml/ kg/% BSA is given over the first eight hours and the remainder over the next 16 hours".

A child or teenager with hypovolaemic shock due to diabefic ketoacidosis (DKA) should probably be rehydrated over 48 hours rather than over 24 hours to minimise the risk of developing fatal cerebral oedema due to a rapid change in the osmolar gradient across the cell membrane of brain neurons and glial cells although retrospective studies of cerebral oedema in DKA have had insufficient pa dents to elucidate the role of the rehydrafion rate in

the pathogenesis of cerebral oedema. Similarly, children with diarrhoeal dehydration may be rehydrated most safely over 24 hours (48 hours if they are hypernatraemic), generally by the oral route. In both cases, if severe circulatory failure is present, an initial intravenous bolus of 20-40 ml/kg normal saline or 10-20ml/kg of colloid may be needed to restore the blood volume before the slower rehydration is started.

Which fluid? A child who has continuing rapid bleeding of

more than 10ml/kg should be given blood, especially if the haemoglobin is less than lOOgm/L. If the bleeding is slower, the losses may be replaced with crystalloid or colloid and the child and the haemoglobin concentration monitored closely. A term newborn has a mean Hb of llOgm/L (95%CI 95-130) at two months of age, returning to childhood values by six months. A preterm baby (birthweight 1000-ISOOgm) has a mean Hb of 90 (70-115) at two months of age. The child's tolerance of a low haemoglobin concentiation is thought to be the same as that of the adult, although there are no direct comparative data. It is known that the brain and heart of the infant animal tolerate a severely reduced oxygen delivery better than those of the adult animal (see above). There have been reports of planned and successful haemodilution to a Hb 40gm/L during cardiopulmonary bypass in children of Jehovah's Witness families, and of crystalloid resuscitation to a Hb of 45gm/L in child trauma victims, with intact recovery.

Cross-matched fresh whole blood is ideal if blood is to be given, but cross-matched packed red cells are more likely to be available. In the newborn, packed red cells and fresh frozen plasma in a ratio of 2:1 may be used for massive transfusions (>30ml/kg). In emergencies, group O negative blood, or group-specific (the same group as the patient) uncrossmatched blood is usually given. Transfusion incompatibility reactions are seen in fewer than 1% of trans­fused units of O negative blood and fewer than 0.4% of transfused group-specific uncrossmatched units".

The role of blood products in paediatric resuscitation Fresh Frozen Plasma (FFP)

In the last 10 years, it has been recognised that FFP should not be used routinely as a plasma expander because of the risk of trans­mission of infection, incompatibility reactions, expense and because it is a scarce community

60 Second Australian Symposium on Fluid Replacement • 1995

Robert Henning

resource which should not be wasted'". Never­theless, recent letters in the British Medical Journal attest to the fact that some centres use FFP routinely for volume expansion after cardiac surgery in infants, because of alleged advantages of large molecular size in the pres­ence of capillary leak and because synthetic colloids "have not been proven to be safe in childhood"". In the newborn, trials have shown that infusion of FFP in sick, shocked preterm babies reduces the incidence of intraventricular haemorrhage by some means other than its effect on clotting: possibly by "improvement of cerebral vascular stability"'^. There has been no comparison with other colloids.

A retrospective study in children with meningococcal septicaemia showed that those resuscitated with blood or FFP were signifi­cantly more likely to die than those given synthetic colloid. This study suffered from being retrospective and non-randomised, and from the presence of several confounding variables including the choice of antibiotic used and the fact that synthetic colloids were only given in one of the two hospitals studied'l Human albumen 5%

TTiis remains a commonly used plasma expander in paediatrics, due to inertia, tradition and the lack of clinical trials of albumen with synthetic colloids and of widely publicised data on the safety and effectiveness of synthetic colloids in children. Albumen has the significant advantage of a longer plasma half-life than the gelatins or dextrans, while comparison with hydroxyethyl starch is difficult because of the heterogeneity in half-life of the latter. The main constraints to the use of albumen are cost, availability and its shorter shelf-life than the synthetic colloids. The issue of cost is less important in paediatrics because the volumes needed per patient are less than in adult medi­cine. There is still a risk of transmission of infection with albumen should the pasteurisa­tion process fail. Synthetic colloids

There are few specific paediatric data. European reports of the use of the modified gelatins and polysaccharides in large numbers of patients included some children, but were not able to comment specifically the efficacy or side-effects of these agents in children. Controlled trials of hetastarch 6% versus normal saline or 5% albumen in children during surgery found that hetastarch was an adequate substitute for albumen or crystalloid as a plasma expander and caused no excess bleeding despite minor

alterations in some clotting tests such as thrombin time and factor Vlll cofactor assay'l

The modified gelatins are more widely used than polysaccharides as colloid plasma expand­ers in Australian paediatrics and are recom­mended in the literature because of their lower published rate of complications such as coagula­tion defects and anaphylactoid reactions and interference with blood cross-matching". Our practice (in a large general paediatric ICU) is to use polygeline as the first line plasma expander whenever a colloid is indicated (including children and infants after open heart surgery) unless the child is hypoalbumenaemic, in which case 5% albumen is used. Our subjective impres­sion is that this is at least as satisfactory as a previous albumen-based regime for the great majority of children, although children with large deficits (>30ml/kg) may have larger ongoing colloid requirements and become more oedematous if polygeline is used rather than 5% albumen, possibly because of the shorter plasma half-life of polygeline. A randomised controlled trial of the use of albumen and synthetic colloid in critically ill children is in preparation.

Crystalloid versus colloid in childhood

As with synthetic coUoids, there are no specific paediatric trials on this subject. Most workers agree that crystalloid is the appropriate intravenous fluid with which to resuscitate dehydrated children: this applies to dehydration due to diarrhoea and diabetic ketoacidosis. In the first instance, in a profoundly shocked child with dehydration, some centres (notably those in the UK and Australia) use 10-20ml/kg of colloid to restore the blood volume, then rehydrate with crystalloid, while others would use crystalloid alone. Albumen or red cells may be added if hypoalbumenaemia or anaemia are found.

Advocates of crystalloid resuscitation use crystalloids with great success for trauma and for children with capillary leak (eg sepsis, post-asphyxia and in children after cardiac surgery and on ECMO), whilst advocates of colloids use colloids with great success. Paediatric trials are needed, as the lack of these trials is the avowed reason why many paediatricians apparently prefer to use colloid.

Which crystalloid? Fluids with a high content of free water such

as 5% dextrose or 4% dextrose in N / 5 saline are distributed between ECFand ICF in the same

Second Australian Symposium on Fluid Replacement • 1995 61

Fluid reiUicitation in children

ratio as ECF:1CF volumes and as plasma vvfater is approximately 8.5% of the total body water in infants, the blood volume of an infant will only be expanded by about 120ml (allowing for red cell swelling) for each litre of 5% dextrose infused. Normal saline and Hartmann's soluhon which contain little or no free water are the crystalloid solutions most commonly used for resuscitation in children. Large volume infu­sions of normal saline may cause a metabolic acidosis, especially in infants whose ability to excrete a sodium load and to acidify urine is limited.

An unexpectedly high death rate was found in severely dehydrated children in Rwanda who were resuscitated with Hartmann's solution. In the absence of biochemical testing, this was ascribed to hypokalaemia, as the deaths ceased when KCl 20mmol/L and 5% dextrose were added to the Hartmann's solution"'. Hypertonic crystalloid solutions are even less likely to be safe in infants whose ICF volume is small compared to that of the ECF, and whose ability to excrete a sodium load and to concentrate urine is limited.

Safe resuscitation requires constant clinical monitoring of cardiovascular variables such as heart rate, blood pressure, respiratory rate and liver and heart size, especially in children who require large amounts of resuscitation fluid. In addition, the conscious state and urine output require monitoring, as well as the blood chemis­try in which important changes occur rapidly. When biochemical monitoring is not practicable (eg in isolated areas or during emergency transport), the safest course in a dehydrated child (after administration of I0-20ml/kg of colloid or 20-40ml/kg of crystalloid if necessary to restore the circulating blood volume) is to give the form of fluid resuscitahon which is least likely to result in major biochemical disturbance. This means using World Health Organisation (WHO) oral rehydration solution whenever possible, or using intravenous crystalloids containing glucose and enough potassium to allow for hypokalaemia during rehydration.

Summary Diarrhoeal dehydration, bleeding and sepsis

are the most common reasons a child may need fluid resuscitation. The child's immature cardio­vascular and renal system affect the responses to loss of fluid volume and to resuscitation, and the signs of fluid and blood loss. The child has relatively small ICF and a large ECF volume compared to the adult.

Rapid resuscitation is appropriate in the presence of bleeding and sepsis, and slower rehydration (after a small rapid colloid or crystaUoid infusion to restore the blood volume) is appropriate in dehydration or diabetic ketoacidosis.

There are few data on the most appropriate resuscitation fluid in children. Crystalloid is widely used, but synthetic colloids appear to be safe in children although there are few trials of their use.

References I. stern SA, Dronen SC Shock and fluid resuscitation. In:

Reisdorff EJ, Roberts MR, Wiegenstein JG, eds. Pediatric Emergency Medicine. Ptiiladelptiia;WB Saunders, 1993.

2 Maylie JG. Excitation-contraction coupling in neonatal and adult myocardium of cat Am J Ptiysiol 1982;242:H834-843.

3. Heitmiller ES, Zahka KG, Rogers MC, Developmental ptiysiology of tfie cardiovascular system. In: Rogers MC, ed. Textbook of Pediatric Intensive Care, 2nd ed. Balti­more: Williams & Wilkins, 1992,

4 Thurston JH, McDougal DB. Effect of ischemia on metabolism of the brain of the newborn mouse. Am J Physiol 1969;216:348-352.

5. Friis-Hansen B. Body Water Compartments in children: changes during growth and related changes in body composition. Pediatrics 1961:28:169-181.

6 Richards L, Claeson M, Pierce NF Management of acute diarrhea in children: lessons learned. Pediatr Inf Dis J 1993;12:5-9

7. Carcillo JA, Davis AL, Zaritsky A. Role of early fluid resuscitation in pediatric septic shock. JAMA 1991;266:1242-1245

8. Puffinbarger NK, Tuggle DW, Smith El. Rapid isotonic fluid resuscitation in pediatric thermal injury. J Pediatr Surg 1994:29:339-342.

9. Gervin AS, Fischer RP Resuscitation of trauma patients with type-specific uncrossmatched blood. J Trauma 1984:24:327-329.

10 National Institutes of Health. Fresh frozen plasma. Indications and risks. JAMA 1985;253:551-553.

I I . Stuart G, Wardrop C Fresh frozen plasma useful as a volume expander in children. Letter. Br Med J 1993:307:935,

12 McClure G. The use of plasma in the neonatal period. Arch DIS Child 1991;66:373-375.

13, Busund R, Straume B, Revhaug A, Fatal course in severe meningococcemia; clinical predictors and effect of transfusion therapy. Grit Care Med 1993:21:-1699-1705

14, Maclntyre E. Mackie IJ, Ho D, Tinker J, Bullen C, Machin , SJ, The haemostatic effects of hydroxyethyl starch (HES) used as a volume expander, Intens Care Ivied 1985:11:300-303,

15, Huskisson L, Intravenous volume replacement: which fluid and why ' Arch Dis Child 1992;67:649-655-

16, Heyman SN, Nehama H, Horovitz J, Sofer S, Orbach J, Amir Y, Adar A, Sudden death during fluid resuscitation: lesson from Rwanda Lancet 1994:344:1509-1510

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