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Open Access 01-12-2019 | Acute Kidney Injury | Research

Hyperchloremia is not associated with AKI or death in septic shock patients: results of a post hoc analysis of the “HYPER2S” trial

Authors: Morgane Commereuc, Camille Nevoret, Peter Radermacher, Sandrine Katsahian, Pierre Asfar, Frédérique Schortgen, HYPER2S investigators

Published in: Annals of Intensive Care | Issue 1/2019

Abstract

Background

Recent data suggest that hyperchloremia induced by fluid resuscitation is associated with acute kidney injury (AKI) and mortality, particularly in sepsis. Experimental studies showed that hyperchloremia could affect organ functions. In patients with septic shock, we examined the relationship between serum chloride concentration and both renal function and survival.

Methods

Post hoc analysis of the “HYPER2S” trial database (NCT01722422) including 434 patients with septic shock randomly assigned for resuscitation with 0.9% or 3% saline. Metabolic parameters were recorded up to 72 h. Metabolic effects of hyperchloremia (> 110 mmol/L) were studied stratified for hyperlactatemia (> 2 mmol/L). Cox models were constructed to assess the association between chloride parameters, day-28 mortality and AKI.

Results

413 patients were analysed. The presence of hyperlactatemia was significantly more frequent than hyperchloremia (62% versus 71% of patients, respectively, p = 0.006). Metabolic acidosis was significantly more frequent in patients with hyperchloremia, no matter the presence of hyperlactatemia, p < 0.001. Adjusted risk of AKI and mortality were not significantly associated with serum chloride, hyperchloremia, maximal chloremia and delta chloremia (maximal-H0 [Cl]).

Conclusions

Despite more frequent metabolic acidosis, hyperchloremia was not associated with an increased risk for AKI or mortality.

Trial registration ClinicalTrials.gov, identifier: NCT01722422, registered 2 November 2012

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Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017;43:304–77. https://doi.org/10.1007/s00134-017-4683-6.CrossRefPubMed

Hammond NE, Taylor C, Finfer S, et al. Patterns of intravenous fluid resuscitation use in adult intensive care patients between 2007 and 2014: an international cross-sectional study. PLoS ONE. 2017;12:e0176292. https://doi.org/10.1371/journal.pone.0176292.CrossRefPubMedPubMedCentral

Pfortmueller CA, Uehlinger D, von Haehling S, et al. Serum chloride levels in critical illness-the hidden story. Intensive care Med Exp. 2018;6:10. https://doi.org/10.1186/s40635-018-0174-5.CrossRefPubMedPubMedCentral

Semler MW, Self WH, Wanderer JP, et al. Balanced crystalloids versus saline in critically ill adults. N Engl J Med. 2018;378:829–39. https://doi.org/10.1056/NEJMoa1711584.CrossRefPubMedPubMedCentral

Young P, Bailey M, Beasley R, et al. 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. 2015;314:1701–10. https://doi.org/10.1001/jama.2015.12334.CrossRefPubMed

Semler MW, Wanderer JP, Ehrenfeld JM, et al. Balanced crystalloids versus saline in the intensive care unit. The SALT randomized trial. Am J Respir Crit Care Med. 2017;195:1362–72. https://doi.org/10.1164/rccm.201607-1345oc.CrossRefPubMedPubMedCentral

Xue M, Zhang X, Liu F, et al. Effects of chloride content of intravenous crystalloid solutions in critically ill adult patients: a meta-analysis with trial sequential analysis of randomized trials. Ann Intensive Care. 2019;9:30. https://doi.org/10.1186/s13613-019-0506-y.CrossRefPubMedPubMedCentral

Semler MW, Kellum JA. Balanced crystalloid solutions. Am J Respir Crit Care Med. 2018. https://doi.org/10.1164/rccm.201809-1677ci (Epub ahead of print).CrossRefPubMedPubMedCentral

Kellum JA, Song M, Li J. Lactic and hydrochloric acids induce different patterns of inflammatory response in LPS-stimulated RAW 264.7 cells. Am J Physiol Regul Integr Comp Physiol. 2004;286:R686–92. https://doi.org/10.1152/ajpregu.00564.2003.CrossRefPubMed

10.

Asfar P, Schortgen F, Boisrame-Helms J, et al. Hyperoxia and hypertonic saline in patients with septic shock (HYPERS2S): a two-by-two factorial, multicentre, randomised, clinical trial. Lancet Respir Med. 2017;5:180–90. https://doi.org/10.1016/s2213-2600(17)30046-2.CrossRefPubMed

11.

McCluskey SA, Karkouti K, Wijeysundera D, et al. Hyperchloremia after noncardiac surgery is independently associated with increased morbidity and mortality: a propensity-matched cohort study. Anesth Analg. 2013;117:412–21.CrossRef

12.

Neyra JA, Canepa-Escaro F, Li X, et al. Association of hyperchloremia with hospital mortality in critically ill septic patients. Crit Care Med. 2015;43:1938–44.CrossRef

13.

Suetrong B, Pisitsak C, Boyd JH, et al. Hyperchloremia and moderate increase in serum chloride are associated with acute kidney injury in severe sepsis and septic shock patients. Crit Care. 2016;20:315. https://doi.org/10.1186/s13054-016-1499-7.CrossRefPubMedPubMedCentral

14.

Shaw AD, Schermer CR, Lobo DN, et al. Impact of intravenous fluid composition on outcomes in patients with systemic inflammatory response syndrome. Crit Care. 2015;19:015–1045.CrossRef

15.

Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 2016;315:801–10. https://doi.org/10.1001/jama.2016.0287.CrossRefPubMedPubMedCentral

16.

Acute Kidney Injury work group. Improving global outcomes (KDIGO), KDIGO clinical practice guideline for acute kidney injury. Kidney Inter Suppl. 2012;2:89–115.CrossRef

17.

Palevsky PM, Molitoris BA, Okusa MD, et al. Design of clinical trials in acute kidney injury: report from an NIDDK workshop on trial methodology. Clin J Am Soc Nephrol. 2012;7:844–50. https://doi.org/10.2215/cjn.12791211.CrossRefPubMed

18.

Demiselle J, Wepler M, Hartmann C, et al. Hyperoxia toxicity in septic shock patients according to the Sepsis-3 criteria: a post hoc analysis of the HYPER2S trial. Ann Intensive Care. 2018;8:90. https://doi.org/10.1186/s13613-018-0435-1.CrossRefPubMedPubMedCentral

19.

Engels JM, Diehr P. Imputation of missing longitudinal data: a comparison of methods. J Clin Epidemiol. 2003;56:968–76.CrossRef

20.

Marttinen M, Wilkman E, Petaja L, et al. Association of plasma chloride values with acute kidney injury in the critically ill—a prospective observational study. Acta Anaesthesiol Scand. 2016;60:790–9. https://doi.org/10.1111/aas.12694.CrossRefPubMed

21.

Shaw AD, Raghunathan K, Peyerl FW, et al. Association between intravenous chloride load during resuscitation and in-hospital mortality among patients with SIRS. Intensive Care Med. 2014;40:1897–905. https://doi.org/10.1007/s00134-014-3505-3.CrossRefPubMedPubMedCentral

22.

Yessayan L, Neyra JA, Canepa-Escaro F, et al. Effect of hyperchloremia on acute kidney injury in critically ill septic patients: a retrospective cohort study. BMC Nephrol. 2017;18:346. https://doi.org/10.1186/s12882-017-0750-z.CrossRefPubMedPubMedCentral

23.

Jung B, Rimmele T, Le Goff C, et al. Severe metabolic or mixed acidemia on intensive care unit admission: incidence, prognosis and administration of buffer therapy. A prospective, multiple-center study. Crit Care. 2011;15:R238. https://doi.org/10.1186/cc10487.CrossRefPubMedPubMedCentral

24.

Gunnerson KJ, Saul M, He S, et al. Lactate versus non-lactate metabolic acidosis: a retrospective outcome evaluation of critically ill patients. Crit Care. 2006;10:R22.CrossRef

25.

Scheingraber S, Rehm M, Sehmisch C, et al. Rapid saline infusion produces hyperchloremic acidosis in patients undergoing gynecologic surgery. Anesthesiology. 1999;90:1265–70.CrossRef

26.

Raghunathan K, Shaw A, Nathanson B, et al. Association between the choice of IV crystalloid and in-hospital mortality among critically ill adults with sepsis*. Crit Care Med. 2014;42:1585–91. https://doi.org/10.1097/CCM.0000000000000305.CrossRefPubMed

27.

Sen A, Keener CM, Sileanu FE, et al. Chloride content of fluids used for large-volume resuscitation is associated with reduced survival. Crit Care Med. 2017;45:e146–53. https://doi.org/10.1097/CCM.0000000000002063.CrossRefPubMedPubMedCentral

28.

Zampieri FG, Ranzani OT, Azevedo LC, et al. Lactated ringer is associated with reduced mortality and less acute kidney injury in critically ill patients: a retrospective cohort analysis. Crit Care Med. 2016;44:2163–70. https://doi.org/10.1097/CCM.0000000000001948.CrossRefPubMed

29.

Cooper DJ, Myles PS, McDermott FT, et al. Prehospital hypertonic saline resuscitation of patients with hypotension and severe traumatic brain injury: a randomized controlled trial. JAMA. 2004;291:1350–7.CrossRef

30.

Wu MC, Liao TY, Lee EM, et al. Administration of hypertonic solutions for hemorrhagic shock: a systematic review and meta-analysis of clinical trials. Anesth Analg. 2017;125:1549–57. https://doi.org/10.1213/ane.0000000000002451.CrossRefPubMed

31.

Quilley CP, Lin YS. McGiff JC Chloride anion concentration as a determinant of renal vascular responsiveness to vasoconstrictor agents. Br J Pharmacol. 1993;108:106–10.CrossRef

32.

Wilcox CS. Regulation of renal blood flow by plasma chloride. J Clin Invest. 1983;71:726–35.CrossRef

33.

Olivier PY, Beloncle F, Seegers V, et al. Assessment of renal hemodynamic toxicity of fluid challenge with 0.9% NaCl compared to balanced crystalloid (PlasmaLyte((R))) in a rat model with severe sepsis. Ann Intensive Care. 2017;7:66. https://doi.org/10.1186/s13613-017-0286-1.CrossRefPubMedPubMedCentral

34.

Chowdhury AH, Cox EF, Francis ST, et al. A randomized, controlled, double-blind crossover study on the effects of 2-L infusions of 0.9% saline and plasma-lyte(R) 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers. Ann Surg. 2012;256:18–24.CrossRef

35.

Oliveira RAG, Mendes PV, Park M, et al. Factors associated with renal Doppler resistive index in critically ill patients: a prospective cohort study. Ann Intensive Care. 2019;9:23. https://doi.org/10.1186/s13613-019-0500-4.CrossRefPubMedPubMedCentral

Title: Hyperchloremia is not associated with AKI or death in septic shock patients: results of a post hoc analysis of the “HYPER2S” trial
Authors: Morgane Commereuc
Camille Nevoret
Peter Radermacher
Sandrine Katsahian
Pierre Asfar
Frédérique Schortgen
HYPER2S investigators
Publication date: 01-12-2019
Publisher: Springer International Publishing
Keywords: Acute Kidney Injury
Metabolic Acidosis
Septic Shock
Acute Kidney Injury
Published in: Annals of Intensive Care / Issue 1/2019
Electronic ISSN: 2110-5820
DOI: https://doi.org/10.1186/s13613-019-0570-3

At a glance: The STEP trials

Springer Medicine

Hyperchloremia is not associated with AKI or death in septic shock patients: results of a post hoc analysis of the “HYPER2S” trial

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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