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• Is hyperchloraemic acidosis a problem in children with gastroenteritis rehydrated with normal saline
  Kristen A Neville
  Published on: 22 March 2016
• Adverse effects of rapid isotonic saline infusion.
  Michael Eisenhut
  Published on: 22 March 2016
• Intravenous fluids in hypernatraemic dehydration: the conundrum goes on.
  Munib Haroon
  Published on: 22 March 2016
• Intravenous rehydration of children with gastroenteritis: which solution is better?
  Marciano Sánchez-Bayle
  Published on: 22 March 2016

• Published on: 22 March 2016

  Is hyperchloraemic acidosis a problem in children with gastroenteritis rehydrated with normal saline

  • Kristen A Neville, Endocrinologist
  • Other Contributors:
    • Charles F Verge, Andrew R Rosenberg, Matthew W O'Meara, Jan L Walker

  Dear Editor,

  The letter from Eisenhut (1) questions the benefits of intravenous rehydration of children with gastroenteritis with Normal Saline because of the possibility of hyperchloraemic acidosis and suggests that Ringers Lactate (RL) or an equivalent solution might offer advantages over Normal Saline (NS).

  Our study of 102 children with gastroenteritis judged to need intravenous fluids, compared p...

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  Dear Editor,

  The letter from Eisenhut (1) questions the benefits of intravenous rehydration of children with gastroenteritis with Normal Saline because of the possibility of hyperchloraemic acidosis and suggests that Ringers Lactate (RL) or an equivalent solution might offer advantages over Normal Saline (NS).

  Our study of 102 children with gastroenteritis judged to need intravenous fluids, compared plasma and urinary electrolyte changes after randomisation to receive either 0.9% saline + 2.5% dextrose (NS n=51) or 0.45% saline + 2.5% dextrose (N/2 n=51).(2) The infusion rate was at the discretion of the treating physician according to either a rapid replacement protocol (RRP; 10mL/kg/hour for 4 hours) or standard replacement protocol (SRP; replacement of estimated percent dehydration over 24 hours).

  Data on acidosis and plasma concentrations of chloride were not presented in our original manuscript (2) but are available in all children. At baseline, the children were normochloraemic (mean +SD chloride 100.4 ±3.4 mmol/L) with a raised anion gap (AG). Mean bicarbonate (a surrogate for acidosis) was low (17.8 ±3.0 mmol/L). Ninety of 102 had a bicarbonate <22 mmol/L associated with a mean AG of 21 ±3.5 mmol/L.

  After 4 hours (T4) the chloride concentration increased to 105 ±3.0 mmol/L in the NS group, versus 102 ±2.7 mmol/L in the N/2 group (p<0.001). At the same time both groups experienced a similar improvement in their acid base status, with a rise in bicarbonate (mean ±SD T4 bicarbonate NS vs N/2 19 ±3.2 mmol/L vs 19 ±2.6 mmol/L respectively, p=0.12) and fall in AG (mean T4 AG NS vs N/2 16 ±3.8 mmol/L vs 17 ±2.6 mmol/L respectively, p=0.2). Separate analysis of the approximately three quarters of children that completed 4 hours of the RRP demonstrated almost identical chloride, bicarbonate and anion gap changes (data not shown). In the 16 children (NS n=8, N/2 n=8) who received IV fluids for 24 hours the chloride changes persisted (median [range] T24 chloride NS vs N/2 107 mmol/L [105-115] vs 105 mmol/L [100-110] respectively, p=0.04) but with continued improvement in bicarbonate and AG in both groups (median T24 bicarbonate NS vs N/2 19 mmol/L [15-20] vs 20 mmol/L [12-24] respectively, p=0.4, median T24 AG NS vs N/2 16 mmol/L [10- 17] vs 16 mmol/L [13-20] respectively, p=0.4).

  Infusion of normal saline was associated with hyperchloraemia but not acidosis even after 24 hours of intravenous fluids compared with a lower chloride solution. The near identical changes in bicarbonate and anion gap in these two groups could have one of two explanations. Firstly, the chloride load from normal saline in the volumes given does not cause acidosis. Alternatively, the chloride load may have some impact on acidosis that is offset by the superior ability of normal saline over a hypotonic saline solution to refill the intravascular space and improve tissue perfusion, important in dehydration.

  Infusion of large volumes of normal saline including during resuscitation or surgery can result in hyperchloraemic acidosis.(3-9) This has also been reported in response to RL or its equivalents, albeit to a lesser extent.(3,6,9) Studies comparing the two fluids have usually shown no difference in clinical outcome,(3,5,6,9,10) except in those at high risk such as the elderly.(7) There are no data in children apart from the report of Durward et al,(11) who found that the development of hyperchloraemic acidosis in children post cardiac surgery receiving normal saline as their ‘maintenance’ fluid had no clinical sequelae. As far as we are aware there are also no data comparing normal saline and RL in adults who are salt depleted as is frequently the case with gastroenteritis.(12)

  The improvement in plasma sodium in our study patients who received NS versus N/2, together with the similar improvements in bicarbonate and anion gap in the two groups casts doubt on the clinical significance of the modest hyperchloraemia demonstrated. When infused in large volumes normal saline has been shown to maintain a normal plasma sodium compared to a drop with RL.(5,8) In the setting of pre-existing salt depletion and non-osmotic ADH activity such as we have shown in gastroenteritis (13) this may be important.

  Eisenhut also questions the safety of rapid intravenous replacement of dehydration in children with gastroenteritis. It was not a primary aim of our study to identify clinical and biochemical differences between those who received RRP compared with SRP; however in both this (2) and an earlier observational study of children receiving only N/2,(13) we found that the children receiving more prolonged fluids (either SRP alone or RRP followed by SRP) rather than those receiving RRP alone who experienced potentially clinically significant dilutional hyponatraemia. Further, it has been well documented that rapid replacement of fluid deficit either orally or intravenously in childhood gastroenteritis is safe and well tolerated,(14-16) has significant health economics benefits and is widely recommended.(17-19)

  K Neville, C Verge, A Rosenberg, M O’Meara, J Walker

  References:

  1. Eisenhut M. Adverse effects of rapid isotonic saline infusion. Archives of Disease in Childhood.91(9):797, 2006.

  2. Neville KA, Verge CF, Rosenberg AR, O'Meara MW, Walker JL. Isotonic is better than hypotonic saline for intravenous rehydration of children with gastroenteritis: a prospective randomised study. Archives of Disease in Childhood.91(3):226-32, 2006.

  3. Brill SA, Stewart TR, Brundage SI, Schreiber MA. Base deficit does not predict mortality when secondary to hyperchloremic acidosis. Shock.17(6):459-62, 2002.

  4. Reid F, Lobo DN, Williams RN, Rowlands BJ, Allison SP. (Ab)normal saline and physiological Hartmann's solution: a randomized double-blind crossover study. Clinical Science.104(1):17-24, 2003.

  5. Scheingraber S, Rehm M, Sehmisch C, Finsterer U. Rapid saline infusion produces hyperchloremic acidosis in patients undergoing gynecologic surgery.. Anesthesiology.90(5):1265-70, 1999.

  6. Waters JH, Gottlieb A, Schoenwald P, Popovich MJ, Sprung J, Nelson DR. Normal saline versus lactated Ringer's solution for intraoperative fluid management in patients undergoing abdominal aortic aneurysm repair: an outcome study. Anesthesia & Analgesia.93(4):817- 22, 2001.

  7. Wilkes NJ, Woolf R, Mutch M, Mallett SV, Peachey T, Stephens R et al. The effects of balanced versus saline-based hetastarch and crystalloid solutions on acid-base and electrolyte status and gastric mucosal perfusion in elderly surgical patients.. Anesthesia & Analgesia.93(4):811-6, 2001.

  8. Williams EL, Hildebrand KL, McCormick SA, Bedel MJ. The effect of intravenous lactated Ringer's solution versus 0.9% sodium chloride solution on serum osmolality in human volunteers. Anesthesia & Analgesia.88(5):999-1003, 1999.

  9. Kellum JA. Fluid resuscitation and hyperchloremic acidosis in experimental sepsis: improved short-term survival and acid-base balance with Hextend compared with saline. Critical Care Medicine.30(2):300-5, 2002.

  10. Lowery BD, Cloutier CT, Carey LC. Electrolyte solutions in resuscitation in human hemorrhagic shock. Surgery, Gynecology & Obstetrics.133(2):273-84, 1971.

  11. Durward A, Tibby SM, Skellett S, Austin C, Anderson D, Murdoch IA. The strong ion gap predicts mortality in children following cardiopulmonary bypass surgery. Pediatric Critical Care Medicine.6(3):281- 5, 2005.

  12. Hirschhorn N. The treatment of acute diarrhea in children. An historical and physiological perspective. American Journal of Clinical Nutrition.33(3):637-63, 1980.

  13. Neville KA, Verge CF, O'Meara MW, Walker JL. High antidiuretic hormone levels and hyponatremia in children with gastroenteritis. Pediatrics.116(6):1401-7, 2005.

  14. Nager AL, Wang VJ. Comparison of nasogastric and intravenous methods of rehydration in pediatric patients with acute dehydration. Pediatrics. 2002;109:566-72.

  15. Phin SJ, McCaskill ME, Browne GJ, Lam LT. Clinical pathway using rapid rehydration for children with gastroenteritis. Journal of Paediatrics & Child Health.39(5):343-8, 2003.

  16. Reid SR, Bonadio WA. Outpatient rapid intravenous rehydration to correct dehydration and resolve vomiting in children with acute gastroenteritis. Annals of Emergency Medicine.28(3):318-23, 1996.

  17. Practice parameter: the management of acute gastroenteritis in young children. American Academy of Pediatrics, Provisional Committee on Quality Improvement, Subcommittee on Acute Gastroenteritis. Pediatrics. 1996;97:424-35.

  18. Armon K, Stephenson T, MacFaul R, Eccleston P, Werneke U. An evidence and consensus based guideline for acute diarrhoea management. Archives of Disease in Childhood. 2001;85:132-42.

  19. Sandhu BK. European Society of Pediatric Gastroenterology Hanwood. Practical guidelines for the management of gastroenteritis in children. Journal of Pediatric Gastroenterology & Nutrition. 2001;33:Suppl-9.

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  Conflict of Interest:
  None declared.

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• Published on: 22 March 2016

  Adverse effects of rapid isotonic saline infusion.

  • Michael Eisenhut, Consultant Paediatrician

  Dear Editor,

  Neville et al reported on a randomized controlled trial of hypotonic versus isotonic saline for rehydration of children with gastroenteritis. They found that isotonic saline was superior with regards to correction of hyponatraemia [1]. The majority of patients in the study received a “rapid replacement protocol” which entailed the infusion of 40ml/kg of isotonic saline over 4 hours in the isotonic salin...

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  Dear Editor,

  Neville et al reported on a randomized controlled trial of hypotonic versus isotonic saline for rehydration of children with gastroenteritis. They found that isotonic saline was superior with regards to correction of hyponatraemia [1]. The majority of patients in the study received a “rapid replacement protocol” which entailed the infusion of 40ml/kg of isotonic saline over 4 hours in the isotonic saline arm of the study. The authors did not report on important known adverse effects associated with rapid infusion of isotonic saline which have been reported in previous randomized controlled trials [RCT] of volume support with isotonic saline versus other fluids. Rapid isotonic saline infusion predictably results in hyperchloremic acidosis [2]. The acidosis is due to a reduction in the strong anion gap by an excessive rise in plasma chloride as well as excessive renal bicarbonate elimination [2]. In a randomized controlled trial with a mixed group of patients undergoing major surgery isotonic saline infusion was compared to Hartmann’s solution with 6% hetastarch with a balanced electrolyte and glucose solution. Two thirds of patients in the saline group but none in the balanced fluid group developed postoperative hyperchloraemic metabolic acidosis [3]. The hyperchloraemic acidosis was associated with reduced gastric mucosal perfusion on gastric tonometry. Another double blind randomized controlled trial of isotonic saline versus lactated Ringer’s in patients undergoing aortic reconstructive surgery confirmed this result and the acidosis required interventions like bicarbonate infusion and was associated with the application of more blood products [4]. Hyperchloremia was found to have profound effects on eicosanoid release in renal tissue leading to vasoconstriction and a reduction of the glomerular filtration rate [5].The increased eicosanoid release may also explain the findings of reduced gastric perfusion in hyperchloraemia mentioned above [3]. The main adverse effect of saline induced hyperchloraemic acidosis however may be the action which is taken to correct the abnormality. Acidosis is often seen as a reflection of poor organ perfusion and poor myocardial function and a negative base excess may prompt the application of boluses of more saline containing fluids exacerbating the acidosis, the use of blood products, escalation of inotropic support and initiation of ventilatory support [6]. The safety of hyperchloremic acidosis has not been established in prospective studies and in patients with different types of critical illness. Particularly in critically ill patients with co-morbidities like renal disease more physiological electrolyte solutions (e.g. Ringers lactate solution) may be preferable to isotonic saline and a slow replacement protocol safer than rapid infusions.

  References:

  1. Neville KA, Verge CF, Rosenberg AR, O’Meara MW, Walker JL. Isotonic is better than hypotonic saline for intravenous rehydration of children with gastroenteritis: a prospective randomised study. Arch Dis Child 2006;91:226-32.

  2. Prough DS, Bidani A. Hyperchloremic metabolic acidosis is a predictable consequence of intraoperative infusion of 0.9% saline. Anesthesiology 1999;90:1247-49.

  3. Wilkes NJ, Woolf R, Mutch M, Mallett SV, Peachey T, Stephens R, Mythen MG. The effects of balanced versus saline-based hetastarch and crystalloid solutions on acid-base and electrolyte status and gastric mucosal perfusion in elderly surgical patients. Anesthesia and analgesia 2001;93:811-6.

  4. Waters JH, Gottlieb A, Schoenwald P, Popovich MJ, Sprung J, Nelson DR. Normal saline versus lactated Ringer’s solution for intraoperative fluid management in patients undergoing abdominal aortic aneurysm repair: an outcome study. Anesthesia and analgesia 2001;93:817-22.

  5. Bullivant EMA, Wilcox CS, Welch WJ. Intrarenal vasoconstriction during hyperchloremia: role of thromboxane. Am J Physiol 1989;256:152-7.

  6. Brill SA, Stewart TR, Brundage SI, Schreiber MA. Base deficit does not predict mortality when secondary to hyperchloremic acidosis. Shock 2002;17: 459-462.

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  Conflict of Interest:
  None declared.

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• Published on: 22 March 2016

  Intravenous fluids in hypernatraemic dehydration: the conundrum goes on.

  • Munib Haroon, Specialist Registrar Paediatrics
  • Other Contributors:
    • Sophie N Haroon.

  Dear Editor,

  We read with interest and welcomed the article by Neville et al on the use of different fluids in children with normo and hyponatraemic gastroenteritis[1] and also the Best practice article by Haycock on hypernatraemia.[2] We have recently looked at intravenous fluid use by paediatric trainees for children with hypernatraemic dehydration due to gastroenteritis, where enteral fluids cannot be administer...

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  Dear Editor,

  We read with interest and welcomed the article by Neville et al on the use of different fluids in children with normo and hyponatraemic gastroenteritis[1] and also the Best practice article by Haycock on hypernatraemia.[2] We have recently looked at intravenous fluid use by paediatric trainees for children with hypernatraemic dehydration due to gastroenteritis, where enteral fluids cannot be administered.

  A standardised structured telephone questionnaire was administered, after piloting, to 57 trainees (27 Specialist Registrars, 29 Senior House Officers) in England and Scotland. Questions were based around the scenario of a child with gastroenteritis, who was dehydrated with a serum sodium of 165mmol/L.

  Contrary to most guidelines,[3,4] 11% (n=6) would use 0.18% saline with 4%dextrose (or more hypotonic fluids); 32% (n = 18) would attempt to fully correct the dehydration in less than 24 hours; 27% (n=15) believed that correcting the sodium at, or, more rapidly than 1mmol/L/hr was appropriate while only 5% (n=4) would have discussed such a case with a more senior doctor.

  Part of the reason for such variability in management can be attributed to the different treatment protocols used by hospitals and to different recommendations in paediatric textbooks.(This includes suggestions of 0.18% saline with 5% dextrose, and 0.9% saline.)[5,6] We hypothesise that this may be due to the lack of randomised controlled trials in children, investigating which regimens are better. This is compounded by the fact that hypernatraemic dehydration is an uncommon biochemical finding and trainees are not adept in its management. Addressing this issue requires not only educational/training attention but also better evidence on which to base future protocols.

  No competing interests.

  References:

  1. Neville K A, Verge C F, Rosenberg A R et al. Isotonic is better than hypotonic saline for intravenous rehydration of children with gastroenteritis: a prospective randomised study. Arch Dis Child 2006; 91:226-232.

  2. Haycock G B. Hypernatraemia: Diagnosis and management.Arch Dis Child Educ Pract Ed 2006;91:ep8-ep13

  3. Royal Children’s Hospital. Melbourne. Clinical Practice Guidelines. Hypernatraemia.[online] Available from: http://www.rch.org.au/clinicalguideline [cited 9 April 2006].

  4. Armon K, Stephenson T, Macfaul R. An evidence and consensus based guideline for acute diarrhoea management. Arch Dis Child. 2001;85: 132- 142.

  5. Webb N, Postlethwaite R. eds., 2003 Clinical Paediatric Nephrology. Third edition. New York: Oxford University Press Inc.

  6. Davies G, Elliman D A C et al. 2001. Manual of Childhood Infections. Second Edition. London: W.B Saunders.

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  Conflict of Interest:
  None declared.

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• Published on: 22 March 2016

  Intravenous rehydration of children with gastroenteritis: which solution is better?

  • Marciano Sánchez-Bayle, Pediatrics
  • Other Contributors:
    • Almudena Alonso-Ojembarrena, Julia Cano Fernández

  Dear Editor,

  We would like to take into consideration recent publications that have recently appeared about the possibility of developing hyponatraemia in children with gastroenteritis treated with intravenous hypotonic saline and the risks derived from such complication.[1-3]

  Even though we belive these papers have been well designed and developed, we cannot agree with their results for we are carrying...

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  Dear Editor,

  We would like to take into consideration recent publications that have recently appeared about the possibility of developing hyponatraemia in children with gastroenteritis treated with intravenous hypotonic saline and the risks derived from such complication.[1-3]

  Even though we belive these papers have been well designed and developed, we cannot agree with their results for we are carrying out a similar study in our centre (81 cases up to now) that is leading to the opposite conclusion: our children with gastroenteritis didn’t develop hyponatraemia although they were all treated with hypotonic intravenous solutions (0.3% saline with 5% glucose) while isotonic fluids were only used in the “pre-sock” situations. To begin with, the incidence of hyponatraemia at the time of diagnosis is lower in our study (9%) than in those published before (range from 30% to 50%), dates that can be due to differences in climate or diet. In the analysis, we separated children according to whether they were hyponatraemic, normonatraemic or hypernatraemic at presentation: in the first group the hypotonic intravenous saline increased their mean plasma sodium (132.4 mEq/l, standard derivation, SD: 2.07, to 135.3, SD: 2.21), while decreased lightly in the second group without leading to hyponatraemia (139.2, SD: 2.9, to 137.3, SD: 2.9), and also did in the third group (150.4, SD: 4.12, to 140.6, SD: 3.6). No cases of hyponatraemia post-infussion were detected. Hoorn et al[4] with a sample of 1586 children pointed out that the cases of hyponatraemia in their study were all due to wrong treatments with fluid apports higher than needed. We also want to emphasize the fact that we have found an important number of children (10 cases: 16,3%) in our study that presented glucose levels lower than 70 mg/dl, and in one case it was as low as 40 mg/dl. If these children were treated with isotonic fluids without addecuate apports of glucose, their levels would never increase as needed, with serious consequences. These dates are not deffinitive but we think that should be taken into consideration before taking decissions about which solution should be better to treat these patients and carry out new studies with different designs to increase the existing evidence.

  References:

  1 Neville KA, Verge CF, Rosenberg AR, et al. Isotonic is better than hypotonic saline for intravenous rehydration of children with gastroenteritis: a prospective randomised study. Arch Dis Child. 2006;91:226-32.

  2 Duke T, Molyneux EM. Intravenous fluids for seriously ill children: time to consider. Lancet. 2003;362:1320-3.

  3 Neville KA, Verge CF, O’Meara MW, et al. High antidiuretic hormone levels and hyponatraemia in children with gastroenteritis. Pediatrics. 2005;116:1401-7.

  4 Hoorn EJ, Geary D, Robb M, et al. Acute hyponatremia related to intravenous fluid administration in hospitalized children: an observational study. Pediatrics. 2004;113:1279-84.

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  Conflict of Interest:
  None declared.

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