Conference Lectures

ISOLYTE P IN CHILDREN

Dr Jaya Lalwani
Perioperative fluid management in paediatric surgical patients has been the focus for considerable interest and debate. 1 It is a medical prescription for which both the volume and composition should be adapted as per patient status, type of operation and the expected events in the perioperative period. The total body water of a newborn is 75-80% and decreases gradually as fat and muscle content increase with age to the adult level of approximately 60%. The extracellular fluid (ECF) fluid represents 45% of body weight in term neonates and 30% by the age of 1 year, compared with 20% in adults. 2 The term infant can compensate more than the preterm infant, but newborns with a large surface-to-weight ratio, higher total water content, limited renal ability to concentrate, greater insensible water loss from thin skin and high blood flow all can become clinically dehydrated in a very short period of time. 3 A meticulous fluid management is required in paediatric patients because of an extremely limited margin for error.
Crystalloids: The ′4/2/1′ Rule
Holliday and Segar in 1957 first presented a practical method to prescribe IV fluids based on the estimated metabolic requirements for patients at bed rest. 4 The calorie expenditure calculated was 100 kcal/kg for infants weighing 3-10 kg, 1000 kcal +50 kcal/kg for each kilogram over 10 kg but <20 kg for children ranging from 10 to 20 kg, and 1500 kcal +20 kcal/kg for each kilogram over 20 kg for children 20 kg and above. Under normal conditions, 1 ml of water is required to metabolise 1 kcal, taking into account insensible water losses across the skin and respiratory tract, and urinary water loss. Therefore, in the awake child, calorie and water consumption are considered equal and the corresponding weight-based rule for hourly water requirement evolved into what is termed the "4 / 2/1 rule" for maintenance fluid therapy in children. 5 In the same study, Holliday and Segar defined daily maintenance electrolyte requirements considering the electrolyte composition of same volume of human milk and cow′s milk; they recommended 2 mEq/100 kcal/day of both potassium and chloride and 3 mEq/100 kcal/day of sodium. These electrolyte requirements are theoretically met by the hypotonic maintenance fluid commonly used in hospitalised children by 5% dextrose (D5) with 0.45% normal saline (NS). For many decades, the fluid given to children by paediatricians was one-fourth to one-third strength saline based on this concept. 6 Recent studies have shown that use of hypotonic solutions along with stress-induced increased secretion of antidiuretic hormone (ADH) perioperatively can lead to hyponatraemic encephalopathy, permanent neurological damage and even death in children. 7,8,9                   
IV Solutions                            Na(mEq/L)                       %Electrolyte free water
5% dextrose                                       0                                               100
Isolyte P                                            26                                               84%
0.45% NS                                          77                                               50%
0.45% NS in 5% dextrose                 77                                               50%
0.9% NS in 5% dextrose                   154                                              0
Ringer Lactate                                   131                                               16%
0.9% NS                                             154                                              0   
Sodium ions do not cross cell membranes as quickly as water does. We live in tropics, due to the hot climate free water loss is more. So isolyte P can be used to match daily loss of EFW in sweat in a patient with P Na > 138 mM  ; P Na > 145 ; ongoing free water losses ( renal , GI , skin)  and in established third space overload eg. Congestive heart failure, nephritic syndrome, cirrhosis.           
Volume and composition of maintenance fluid
The conventional composition of maintenance fluid is 2 to 3 mEq of sodium and 1
to 2 mEq of potassium per 100 ml of MIF 1. The maintenance fluid requirement can be easily calculated depending on the body weight as given in Table 2.
Maintenance fluid contains 5% dextrose which provides 17cal/100ml i.e. approximately 20% of the daily caloric needs. The minimum amount of glucose required to prevent protein catabolism is 3g/kg/day. The solutions containing
5% dextrose provide adequate carbohydrates that prevents gluconeogenesis, protein catabolism and ketogenesis. Therefore all parenteral maintenance fluids should contain 5% dextrose. Maintenance fluids contain 3mEq/kg/day of sodium and when calculated as per table 2 approximates to 5% dextrose with 1/4th  to ½ normal saline. Higher the body weight higher is the concentration of sodium in maintenance fluid. Potassium in maintenance fluid is 2 mEq/ 100ml.
It is imperative that potassium should be added only after ensuring adequate urine output. Most of the commercially available maintenance fluids are approximately 1/ 6th normal saline* with 5 % dextrose and potassium.(* 154 mEq/1000 ml of Na
+ in normal saline and 25.6 mEq/1000 ml of Na + in 1/6 normal saline)
• For a 15 kg child (see Table 2) maintenance fluid requirement for 24 hrs would be 1250 ml of 5% dextrose with 45 mEq of sodium (i.e. 3 mEq/kg/day) and 25 mEq of potassium (i.e. 2 mEq/100ml).
• For a 50 kg child maintenance fluid requirement for 24 hrs would be 2100 ml of
5% dextrose with 150 mEq of sodium (i.e. ~ ½ Normal Saline) and 42 mEq of potassium (i.e. 2mEq/100ml). (Fig 2).

The recommendations are to replace the deficit with 0.9% saline with 5% dextrose and not to use 0.18% saline with 4% dextrose. In many case control studies it has been shown that the most important factor contributing to hospital acquired hyponatremia was administration of hypotonic fluids

Controversies / Newer concepts
Composition:
Sodium – There is a growing concern regarding development of hyponatremia
in children on the maintenance fluid therapy with 0.2 normal saline (most of the
commercially available maintenance fluids). This stems from the following issues:
1. It is believed that especially in an older child the requirement of sodium is more than 0.2 Normal Saline.
2. Utilization of dextrose in maintenance fluid makes this fluid all the more hypotonic in vivo.
3. Release of vasopressin during stress (not uncommon during illness) leads to retention of free water causing hyponatremia.
Hence maintenance fluid in older child should contain 0.45% normal saline with 5%
dextrose.
Hyponatremia  is termed Acute  when Na+ < 136 mmol/l within 48 hrs and is  severe if Na + is < 130 mmol/L or any level of hyponatremia associated with clinical signs.hyponatremic encephalopathy develops in children with Na+ < 125 mmol/L and has a mortality rate of 8%.children have a poorer outcomethan adults for a given level of hyponatremia

Sodium requirement is 3 mEq / kg /day while potassium requirement is 2 mEq / 100ml of maintainenance intravenous fluids.
Always add potassium after the patient has voided urine.
This ensures that the sodium concentration in the fluid increases with increase in weight but that of potassium remains the same. Administration of the parenteral fluid should be considered as an invasive procedure with deleterious effect which may culminate in long term morbidity and mortality. Patients on parenteral fluids need to be closely monitored. The essence of successful management of fluid and electrolyte abnormalities is frequent clinical and laboratory monitoring of patients. The younger the child, the more frequent this needs to be done.
Points to remember
• The commercially available maintenance fluid may not be able to meet the sodium
requirement for all the age groups. Iatrogenic hyponatremia is known to occur in the patients on maintenance therapy especially in older age group.
• Potassium and dextrose concentration in maintenance fluid is constant irrespective
Avoid using hypotonic solutions like Isolyte-P during the perioperative fluid therapy of children. Isolyte – P has 80% free water and hence becomes hypotonic once the glucose gets metabolized. Infusion of such hypotonic solutions can lead to iatrogenic hyponatremia with its serious consequences of morbidity and mortality, including intractable seizures due to cerebral oedema and encephalopathy.

Recommendations to avoid the use of a solution of 4% dextrose with 0.18% Normal Saline similar to Isolyte P has been made by the Royal College of Paediatrics and Child Health,UK so as to prevent the occurrence of hyponatremia.
Hence, its suggested that
· All fluids should be carefully calculated and aliquots dispensed in small volume ie. 100ml burette sets or by infusion pump to children below 15 kg body weight so as to avoid accidental fluid overload.
· All intraoperative fluid replacement should be with isotonic solutions (Ringer lactate).
· Children with anticipated additional fluid losses should have them replaced with isotonic solutions only (sodium chloride 0.9% or Ringer lactate).
· If hypotonic fluids (5%D or Isolyte-P) are given postoperataively for maintenance, fluid balance and electrolytes (serum Na and K) must be monitored 12 hrly.
· If the baby has been starved for a long time or the baby is undernourished he may require dextrose. Check blood sugar and give dextrose slowly. Monitor electrolytes
· There is, however, agreement that sodium chloride 0.18% solutions at standard maintenance rates are unacceptable and should be abandoned as a replacement or maintenance fluid for children in the peri operative period.

Remember: Isolyte-P is not an ideal maintenance fluid for older children
Reason: In children as weight increases, water requirement reduces rapidly, 100 ml/Kg (1-10 kg)? 50 ml/Kg (11-20 kg) ? 20 ml/Kg (> 20 kg)
But sodium requirement remains static (2.5 mEq/kg). So children with greater weight will need I.V. fluids with greater sodium concentration.
Example: In older children with 30 kg water requirement is 1000 + 500 + 200 = 1700 ml and sodium requirement is 75 mEq. So sodium concentration required is 44 mEq/l, while Isolyte-P contains only 25 mEq/l sodium. Because of low sodium concentration Isolyte-P is not an ideal maintenance I.V. fluid for older children.

Consequences of improper selection of maintenance fluid ...

References
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2. Friis-Hansen BJ, Holiday M, Stapleton T, Wallace WM. Total body water in children. Pediatrics. 1951;7:321–7. [PubMed]
3. Holliday MA, Ray PE, Friedman AL. Fluid therapy for children: Facts, fashions and questions. Arch Dis Child. 2007;92:546–50. [PMC free article] [PubMed]
4. Holliday MA, Segar WE. The maintenance need for water in parenteral fluid therapy. Pediatrics. 1957;19:823–32. [PubMed]
5. Oh TH. Formulas for calculating fluid maintenance requirements. Anesthesiology. 1980;53:351. [PubMed]
6. Murat I, Dubois M. Perioperative fluid therapy in pediatrics. Pediatr Anesth. 2008;18:363–70. [PubMed]
7. Halberthal M, Halperin ML, Bohn D. Lesson of the week: Acute hyponatraemia in children admitted to hospital: Retrospective analysis of factors contributing to its development and resolution. BMJ. 2001;322:780–2. [PMC free article] [PubMed]
8. Dearlove OR, Ram AD, Natsagdoy S, Humphrey G, Cunliffe M, Potter F. Hyponatraemia after postoperative fluid management in children. Br J Anaesth. 2006;97:897–8. author reply 898. [PubMed]
9. Montañana PA, Modesto i Alapont V, Ocón AP, López PO, LópezPrats JL, Toledo Parreño JD. The use of isotonic fluid as maintenance therapy prevents iatrogenic hyponatremia in pediatrics: A randomized, controlled open study. Pediatr Crit Care Med. 2008;9:589–97. [PubMed]