Should Holliday Segar formula be challenged

Holliday Segar formula is time tested formula for calculating fluid requirement in children. Understand what makes us revisit it again?

1. Should Holliday Segar Formula be Challenged ? Lokesh Tiwari All India Institute of Medical Sciences, Patna

2. Objectives Basis of HS Formula What is concern now? pitfalls in the formula, if any What does evidence say Take home message

3. Pediatrics 1957; 19 :823–32.

4. Basis Observations that insensible water loss and urinary water loss roughly parallel energy metabolism and not body mass Loss of water is function of energy expenditure Arbitrary equations to calculate energy expenditure in children roughly midway between the basal energy requirement and energy requirement of normal active infants and adults Darrow and Pratt: JAMA 1950 Pickering and Winters PCNA 1954 Talbot F B 1949

5. Holliday & Segar’s traditional guidelines 1mL of water needed for fixed consumption of 1 kcal. Insensible water loss = 50 mL/kg/day. Endogenous water production (oxidative metabolism) = 16 mL/kg/day Net insensible water loss of 34 mL/kg/day . Obligatory urinary losses 66 mL/kg/day (water required to excrete the solute load of cow’s milk) 34 + 66 = 100 mL/100kcal/day of EFW for maintenance therapy.

6. Maintenance formula 0.18 % Saline with 4% Dextrose Energy: 100 k cal / kg/ day for 10 kg child Water: 1 ml / k cal Electrolytes (Na): Healthy milk fed infant’s average intake (3 mEq /100 kcal/ day)

7. Formula has been religiously followed by the pediatricians around the world for more than 50 years!!

8. Why this debate now? Episodes of hyponatremia in hospitalized children leading to adverse events including > 50 deaths Incidence as high as 50% Cerebral edema secondary to hyponatraemia following administration of intravenous 0.18% saline. Choong K, Kho M, Menon K, Bohn D. Arch Dis Child. 2006. Halberthal M, Halperin ML, Bohn D. BMJ. 2001 Hoorn EJ, Geary D, Robb M, Halperin ML, Bohn D. Pediatrics. 2004 Hanna S, Tibby SM, Durward A, Murdoch IA. Acta Paediatr . 2003 Shann F, Germer S. Arch Dis Child. 1985

9. What can cause hyponatremia? Free water accumulation Too much of volume intake Too less of sodium intake Sodium loss from body Energy estimates are high as compared to real expenditure Volume estimates are high Sodium estimates are low

10. Holliday Segar Formula Revisited

11. Energy estimates Based on needs of healthy children with some arbitrary discount for him being in hospital Resting Energy Expenditure + Energy expenditure on activities and growth (almost 50%)

12. Energy estimates REE is closely related to fat free mass Muscles Four major organs (heart, liver, kidneys, and brain) Eighty per cent of REE is accounted for by these four organs (only 7% of total body mass) Weight based calculations overestimate caloric requirements Energy expenditure on activities and growth is an unrealistic goal in acute disease Physical immobility Sedation Facultative metabolism Use of muscle relaxants Mechanical ventilation Illner K, Brinkmann G, Heller M, et al. Am J Physiol Endocrinol Metab 2000;278:E308–15.

13. Actual Energy requirement Actual energy expenditure in hospitalized children is closer to the basal metabolic rate averaging 50–60 kcal/kg/day. Briassoulis G, et al. Crit Care Med 2000 Verhoeven JJ, Hazelot JA, van der Voort E, et al. Crit Care Med 1998 Coss -Bu JA, Klish WJ, Walding D, et al. Am J Clin Nutr 2001 open squares = Holliday and Segar’s weight based method open circles = Crawford’s surface area method referenced against basal metabolic rate.

14. Inference H S Formula commonly results in an overestimation of actual energy expenditure

15. Insensible water loss H S Method (calculations and assumption) Insensible water loss = 50 mL/kg/day. Endogenous water production (oxidative metabolism) = 16 mL/kg/day Net insensible water loss of 34 mL/kg/day Experimental studies Skin 7 ml/kg/day Respiratory tract 5 ml/kg/day Other risk factors may further reduce insensible water loss Humidifiers Thermo neutral environment 10 ml/kg/day in catabolic acute renal failure patients Lamke LO, Nilson Ge, Reithner L. Scan J Clin Lab 1977 Bluemle LW, Potter HP, Elkington JR. J Clin Invest 1956 An over estimate

16. Urinary water loss Holliday and Segar Based on observation of urine output 15/28 infants and 20/25 children (unspecified diagnoses) on i v dextrose produced urine with an ‘‘acceptable’’ urine osmolarity between 150 and 600 mosm /l H2O Obligatory urine output as 50–60 ml/kg/day Assumed 66ml / 100 k cal / day Other studies Hospitalized or acutely ill children produce concentrated urine Approximately 25 ml/kg/ day Judd BA, Haycock GB, Dalton N, et al. Acta Paediatr Scand 1987 Harned HS, Cooke RE. Surg Gynecol Obstet 1957;104:543–50. Pickering DE, Winters RW. Pediatr Clin North Am 1954

17. Inability to excrete EFW: ADH Non-osmotic stimuli Acute illness, pneumonia, bronchiolitis Pain and stress Drugs and anesthetic agents Nausea and vomiting Duke T, Molyneux EM. Lancet. 2003 Gerigk M, Gnehm H, Rascher W. Acta Paediatr . 1996 Neville K, Verge C, O'Meara M, Walker J. Pediatrics. 2005 ADH limits renal water excretion even in the presence of a low plasma osmolality

18. Total fluid loss (sensible plus insensible) during acutely illness or following surgery Skin: 7 Respiratory: 5 Urine: 25 Total: 50–60 ml/kg/day Approx half Arieff AI, Ayus JC, Fraser CL. BMJ 1992 Arieff AI. Paediatr Anaesthes 1998 Endogenous water production also increases in acute disease Daily water loss

19. Inference H S Formula overestimates Water requirement in children H S Formula commonly results in an overestimation of actual energy expenditure

20. Electrolyte requirements (Na) Holliday Segar In healthy breast fed infants 1 mEq /100 calories/ day. Cow milk fed infants 3 mEq / 100 calories / day. 30 mEq /L (0.18% Hypotonic) Based on intake of sodium in healthy, milk fed infants. More Na for Hospitalized children Desalination Natriuretic hormones Urodilatin Gut-related natriuretic peptide ADH: Retention of EFW Steele A, Gowrishankar M, et al. Ann Intern Med 1997 Aronson D, Dragu RE, Nakhoul F, et al. Am J Kidney Dis 2002

21. Desalination Expansion of the ECF volume with isotonic fluids resulted in hyponatremia due to a generation of EFW during excretion of hypertonic urine Multifactorial Volumes of saline infused Increased glomerular filtration Natriuretic peptide Suppression of aldosterone . Risk and severity of hyponatremia are further exacerbated if a hypotonic solution is administered Steele A, Gowrishankar M, Abrahamson S, Mazer CD, Feldman RD, Halperin ML. Ann Intern Med. 1997

22. Inference H S Formula overestimates Water requirement in children H S Formula commonly results in an overestimation of actual energy expenditure H S Formula under estimates sodium requirement in children In an acutely ill child, any exogenous sources of free water, such as hypotonic IV maintenance fluids, will exacerbate water retention and hyponatremia

23. Check the hypothesis Hypotonic vs isotonic fluid therapy Outcome measures Incidence of hyponatremia Hyponatremia related complications Hypernatremia Full volume maintenance vs restricted volume maintenance therapy Outcome measures Outcomes related to Volume overload in sick children Cerebral edema/ pulmonary edema / PICU stay / ventilator free days

24. Evidence Duke et al.: Hypotonic vs isotonic saline solutions for intravenous fluid management of acute infections. Cochrane Database of Systematic Reviews 2003, Issue 3. Administration of large volumes of hypotonic fluids has led to severe hyponatraemia and adverse neurological outcomes There were no randomised controlled trials Moritz et al.: Prevention of hospital-acquired hyponatraemia : A case for using isotonic saline. Pediatrics 2003;111;227-230 Common childhood conditions requiring parenteral fluids are associated with a non-osmotic stimulus for ADH production , which can lead to free water retention and hyponatraemia Administration of isotonic saline in maintenance parenteral fluids is the most important prophylactic measure that can be taken to prevent the development of hyponatraemia Alvarez et al: 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 Hypotonic fluids increases the risk of hyponatraemia when compared with isotonic fluids at 24 hrs Isotonic fluids did not increase the incidence of adverse events compared with hypotonic fluids.

25. Yung et al: Randomized controlled trial of intravenous maintenance fluids. J Paediatr Child Health 2009; 50 patients Fluid type ( P = 0.0063) but not rate ( P = 0.12) was significantly associated with fall in plasma sodium. Kannan et al.: Intravenous fluid regimen and hyponatraemia among children: a randomized controlled trial. Pediatr Nephrol . 2010 0.9% saline in 5% glucose as IV maintenance fluid helps to reduce the incidence of hospital-acquired hyponatraemia among children Saba et al: A randomized controlled trial of isotonic versus hypotonic maintenance intravenous fluids in hospitalized children. BMC Pediatr . 2011 0.9% saline vs 0.45 % saline. [ Na] increased significantly in the 0.9% group and increased, but not significantly, in the 0.45% group 0.45 % saline did not result in a drop in serum sodium during the first 12 hours Confirmation of this result in a larger study is strongly recommended.

26. The Cochrane Library 2014, Issue 12

27. The Cochrane Library 2014, Issue 12

28. Fluid overload is associated with impaired oxygenation and morbidity in critically ill children* Arikan , Ayse A. MD; Zappitelli , Michael MD, MSc; Goldstein, Stuart L. MD; Naipaul, Amrita NP; Jefferson, Larry S. MD; Loftis, Laura L. MD Pediatric Critical Care Medicine: 2012 Total fluid overload percent in the first 5 days of pediatric intensive care unit (PICU) admission stratified by oxygenation index (OI ). Open boxes represent patients with OI less than the median OI of the cohort (OI 11.5.

29. The use of isotonic fluid (D5W.0.9% NaCl ) is recommended in most circumstances. Hypotonic IV fluids containing less than 0.45% NaCl should not be used to provide routine IV fluid maintenance requirements.

30. Conclusion H S model of energy expenditure was based on healthy children An inaccurate assumption of energy expenditure and hence insensible losses during diseased states No consideration of ADH related restricted ability to excrete EFW and desalination

31. Conclusion Currently available limited evidence favors isotonic fluid contrary to hypotonic fluid as suggested in H S Formula. However there is no sufficient evidence on optimum maintenance fluid rate in children There is need of large, adequately powered RCTs in children to reach on best possible maintenance fluid type and rate in children IV Fluid should be treated like any other drug that needs individual dose and rate calculations. There is no ‘one formula fitting all’

32. Thanks