Increase in chloride from baseline is independently associated with mortality in critically ill children
To determine if there is an association between mortality and admission chloride levels and/or increases in the chloride level in critically ill children.
We performed a retrospective cohort study of all patients admitted to the paediatric intensive care unit (PICU) from January 2014 to December 2015. Patients were excluded for the following reasons: (1) age < 90 days or > 18 years, (2) admission to the cardiac intensive care unit, (3) no laboratory values upon admission to the PICU, (4) history of end-stage renal disease, (5) a disorder of chloride transport, and (6) admission for diabetic ketoacidosis. The patients were stratified on the basis of admission chloride levels (hypochloraemia, < 96 mEq/L; normochloraemia, 96–109 mEq/L; and hyperchloraemia, ≥ 110 mEq/L) and dichotomised on the basis of an increase in chloride in the first day (< 5 mEq/L, ≥ 5 mEq/L). Our primary outcome was in-hospital mortality.
A total of 1935 patients [55% female, median age 6.3 years IQR (1.9–13.4)] were included. The overall mortality was 4% (n = 71) and day 2 AKI occurred in 17% (n = 333. Hypochloraemia, hyperchloraemia, and an increase in serum chloride ≥ 5 mEq/L occurred in 2%, 21%, and 12%, respectively. After adjusting for confounders, increase in chloride ≥ 5 mEq/L was associated with a 2.3 (95% CI 1.03–5.21) greater odds of mortality.
An increase in serum chloride level in the first day of admission is common and an independent risk factor for mortality in critically ill children. Further studies are warranted to identify how chloride disturbances contribute to mortality risk in critically ill children.
KeywordsHyperchloraemia Hypochloraemia Fluid overload Acute kidney injury Mortality Paediatric
Compliance with ethical standards
Conflicts of interest
The authors have no financial or ethical conflicts of interest to disclose.
- 2.Barhight MF, Lusk J, Brinton J, Stidham T, Soranno DE, Faubel S, Goebel J, Mourani PM, Gist KM (2018) Hyperchloremia is independently associated with mortality in critically ill children who ultimately require continuous renal replacement therapy. Pediatr Nephrol 33(6):1079–1085CrossRefPubMedGoogle Scholar
- 3.Stenson EK, Cvijanovich NZ, Anas N, Allen GL, Thomas NJ, Bigham MT, Weiss SL, Fitzgerald JC, Checchia PA, Meyer K, Quasney M, Hall M, Gedeit R, Freishtat RJ, Nowak J, Raj SS, Gertz S, Grunwell JR, Wong HR (2018) Hyperchloremia is associated with complicated course and mortality in pediatric patients with septic shock. Pediatr Crit Care Med 19:155–160CrossRefPubMedGoogle Scholar
- 10.Sakata F, Ito Y, Mizuno M, Sawai A, Suzuki Y, Tomita T, Tawada M, Tanaka A, Hirayama A, Sagara A, Wada T, Maruyama S, Soga T, Matsuo S, Imai E, Takei Y (2017) Sodium chloride promotes tissue inflammation via osmotic stimuli in subtotal-nephrectomized mice. Lab Investig 97:432–446CrossRefPubMedGoogle Scholar
- 12.Chowdhury AH, Cox EF, Francis ST, Lobo DN (2012) 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 256:18–24CrossRefPubMedGoogle Scholar
- 13.Oh HJ, Kim SJ, Kim YC, Kim EJ, Jung IY, Oh DH, Jeong SJ, Ku NS, Han SH, Choi JY, Song YG, Ryu DR, Kim JM (2017) An increased chloride level in hypochloremia is associated with decreased mortality in patients with severe sepsis or septic shock. Sci Rep 7:15883CrossRefPubMedPubMedCentralGoogle Scholar
- 20.Sutherland SM, Zappitelli M, Alexander SR, Chua AN, Brophy PD, Bunchman TE, Hackbarth R, Somers MJ, Baum M, Symons JM, Flores FX, Benfield M, Askenazi D, Chand D, Fortenberry JD, Mahan JD, McBryde K, Blowey D, Goldstein SL (2010) Fluid overload and mortality in children receiving continuous renal replacement therapy: the prospective pediatric continuous renal replacement therapy registry. Am J Kidney Dis 55:316–325CrossRefPubMedGoogle Scholar
- 22.Semler MW, Self WH, Wanderer JP, Ehrenfeld JM, Wang L, Byrne DW, Stollings JL, Kumar AB, Hughes CG, Hernandez A, Guillamondegui OD, May AK, Weavind L, Casey JD, Siew ED, Shaw AD, Bernard GR, Rice TW, SMART Investigators, Pragmatic Critical Care Research Group (2018) Balanced crystalloids versus saline in critically ill adults. N Engl J Med 378:829–839CrossRefPubMedPubMedCentralGoogle Scholar
- 23.Young P, Bailey M, Beasley R, Henderson S, Mackle D, McArthur C, McGuinness S, Mehrtens J, Myburgh J, Psirides A, Reddy S, Bellomo R, SPLIT Investigators, ANZICS CTG (2015) Effect of a buffered crystalloid solution vs saline on acute kidney injury among patients in the intensive care unit: the SPLIT randomized clinical trial. JAMA 314:1701–1710CrossRefPubMedGoogle Scholar