J Pediatr Intensive Care 2023; 12(01): 018-023
DOI: 10.1055/s-0041-1728788
Original Article

Hyperchloremia on Admission to Pediatric Intensive Care in Mechanically Ventilated Children is Associated with Impaired Renal Function

1   Paediatric Intensive Care Unit, Imperial College Healthcare NHS Trust, London, United Kingdom
,
1   Paediatric Intensive Care Unit, Imperial College Healthcare NHS Trust, London, United Kingdom
2   Children's Acute Transport Service, Great Ormond Street Hospital NHS Foundation Trust, London, United Kingdom
,
3   Paediatric Intensive Care Unit, Addenbrookes' Hospital, Cambridge University Hospitals NHS Trust, Cambridge, United Kingdom
› Author Affiliations

Abstract

Objective There is recent interest in the association between hyperchloremic metabolic acidosis and adverse outcomes. In vitro, hyperchloremia causes renal vasoconstriction and fall in glomerular filtration rate (GFR). The objective of this retrospective, observational study is to examine associations between chloride level at admission to pediatric intensive care (PICU) and worst GFR and requirement for renal replacement therapy.

Materials and Methods All admissions to PICU between 2009 and 2019 who received invasive mechanical ventilation and had blood gas analysis performed were included. Data analyzed included patient characteristics (age, gender, diagnosis, pediatric index of mortality [PIM]-2 score); results of initial blood gas; and maximum serum creatinine (then used to calculate minimum GFR). Primary outcome measure was worst GFR during PICU stay. Secondary outcome measures were requirement for renal replacement therapy and PICU mortality. Multivariable regression analysis was used to assess if admission chloride level was independently predictive of minimum GFR during PICU stay and to examine associations between hyperchloremia (>110 mEq/L) at admission and requirement for renal replacement therapy after adjustment for confounders.

Results Data were available for 2,217 patients. Median age was 16.4 months and 39% of patients were hyperchloremic at admission to PICU. Admission chloride level was independently predictive of worst GFR during PICU stay after adjustment for known confounders. Patients with hyperchloremia were not more likely to require renal replacement therapy or die than patients with normochloremia.

Conclusion Prospective studies are necessary to determine if high chloride, specifically chloride containing resuscitation fluids, have a causal relationship with poor outcomes.

Note

The study was registered as an audit/service evaluation with Imperial College Healthcare NHS Trust Information Governance department reference number 377. The need for informed individual patient consent was waived.


Supplementary Material



Publication History

Received: 26 December 2020

Accepted: 13 March 2021

Article published online:
19 May 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Carcillo JA, Davis AL, Zaritsky A. Role of early fluid resuscitation in pediatric septic shock. JAMA 1991; 266 (09) 1242-1245
  • 2 Evans IVR, Phillips GS, Alpern ER. et al. Association between the New York sepsis care mandate and in-hospital mortality for pediatric sepsis. JAMA 2018; 320 (04) 358-367
  • 3 Paul R, Neuman MI, Monuteaux MC, Melendez E. Adherence to PALS sepsis guidelines and hospital length of stay. Pediatrics 2012; 130 (02) e273-e280
  • 4 Lane RD, Funai T, Reeder R, Larsen GY. High reliability pediatric septic shock quality improvement initiative and decreasing mortality. Pediatrics 2016; 138 (04) e20154153
  • 5 Han YY, Carcillo JA, Dragotta MA. et al. Early reversal of pediatric-neonatal septic shock by community physicians is associated with improved outcome. Pediatrics 2003; 112 (04) 793-799
  • 6 Carcillo JA, Kuch BA, Han YY. et al. Mortality and functional morbidity after use of PALS/APLS by community physicians. Pediatrics 2009; 124 (02) 500-508
  • 7 van Paridon BM, Sheppard C, ,G GG, Joffe AR. Alberta Sepsis Network. Timing of antibiotics, volume, and vasoactive infusions in children with sepsis admitted to intensive care. Crit Care 2015; 19 (01) 293
  • 8 Davis AL, Carcillo JA, Aneja RK. et al. The American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock: executive summary. Pediatr Crit Care Med 2017; 18 (09) 884-890
  • 9 Maitland K, Kiguli S, Opoka RO. et al; FEAST Trial Group. Mortality after fluid bolus in African children with severe infection. N Engl J Med 2011; 364 (26) 2483-2495
  • 10 Weiss SL, Peters MJ, Alhazzani W. et al. Surviving Sepsis Campaign International Guidelines for the management of septic shock and sepsis-associated organ dysfunction in children. Pediatr Crit Care Med 2020; 21 (02) e52-e106
  • 11 Levin M, Cunnington AJ, Wilson C. et al. Effects of saline or albumin fluid bolus in resuscitation: evidence from re-analysis of the FEAST trial. Lancet Respir Med 2019; 7 (07) 581-593
  • 12 Weiss SL, Keele L, Balamuth F. et al. Crystalloid fluid choice and clinical outcomes in pediatric sepsis: A matched retrospective cohort study. J Pediatr 2017; 182: 304-310.e10
  • 13 Wilcox CS. Regulation of renal blood flow by plasma chloride. J Clin Invest 1983; 71 (03) 726-735
  • 14 Chowdhury AH, Cox EF, Francis ST, Lobo DN. A randomized, controlled, double-blind crossover study on the effects of 2-L infusions of 0.9% saline and plasma-lyte® 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers. Ann Surg 2012; 256 (01) 18-24
  • 15 Wagner CA, Imenez Silva PH, Bourgeois S. Molecular pathophysiology of acid-base disorders. Semin Nephrol 2019; 39 (04) 340-352
  • 16 Kellum JA, Song M, Almasri E. Hyperchloremic acidosis increases circulating inflammatory molecules in experimental sepsis. Chest 2006; 130 (04) 962-967
  • 17 Emrath ET, Fortenberry JD, Travers C, McCracken CE, Hebbar KB. Resuscitation with balanced fluids is associated with improved survival in pediatric severe sepsis. Crit Care Med 2017; 45 (07) 1177-1183
  • 18 Barhight MF, Brinton J, Stidham T. et al. Increase in chloride from baseline is independently associated with mortality in critically ill children. Intensive Care Med 2018; 44 (12) 2183-2191
  • 19 Stenson EK, Cvijanovich NZ, Allen GL. et al. Hyperchloremia is associated with acute kidney injury in pediatric patients with septic shock. Intensive Care Med 2018; 44 (11) 2004-2005
  • 20 Kimura S, Iwasaki T, Shimuzu K. et al. Hyperchloremia is not an independent risk factor for postoperative acute kidney injury in paediatric cardiac patients. J Cardiothorac Vasc Anesth 2019; 33 (07) 1930-1945
  • 21 Barhight MF, Lusk J, Brinton J. et al. Hyperchloremia is independently associated with mortality in critically ill children who ultimately require continuous renal replacement therapy. Pediatr Nephrol 2018; 33 (06) 1079-1085
  • 22 Slater A, Shann F, Pearson G. Pediatric Index of Mortality (PIM) Study Group. PIM2: a revised version of the Pediatric Index of Mortality. Intensive Care Med 2003; 29 (02) 278-285
  • 23 Schwartz GJ, Muñoz A, Schneider MF. et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol 2009; 20 (03) 629-637
  • 24 World Health Organisation Child Growth Standards Length/height for age tables. Accessed December 5, 2019 at: www.who.int/childgrowth/standards/
  • 25 Hatherill M, Salie S, Waggie Z. et al. Hyperchloremic metabolic acidosis following open cardiac surgery. Arch Dis Child 2005; 90 (12) 1288-1292