Elsevier

Journal of Critical Care

Volume 45, June 2018, Pages 45-51
Journal of Critical Care

Renal
Hyperchloraemia is associated with acute kidney injury and mortality in the critically ill: A retrospective observational study in a multidisciplinary intensive care unit

https://doi.org/10.1016/j.jcrc.2018.01.019Get rights and content

Highlights

  • Hyperchloraemia is associated with AKI and death in the critically ill.

  • There is equipoise as to whether this represents an association, an epiphenomenon or causation

  • Unnecessary chloride loads should be avoided in critically ill patients only where circumstances permit.

Abstract

Purpose

The aim of this study was to determine whether serum chloride and changes in serum chloride over time were associated with acute kidney injury (AKI) or intensive care unit (ICU) mortality in a heterogenous critically ill population.

Materials and methods

The study was a retrospective observational study of 250 adult patients admitted to a multidisciplinary academic ICU. Serum chloride within 48 h of admission, changes in chloride, and other biochemical and clinical parameters were evaluated as predictors of AKI and mortality.

Results

Hyperchloraemia occurred in 143 (57.2%) patients within 48 h of ICU admission. Hyperchloraemia at 48 h was significantly associated with AKI, OR = 6.44 (95% CI 2.95–14.10) and mortality, OR = 2.46 (95% CI 1.22–4.94) on univariate analysis, with this association persisting on multivariable analysis. An increase in serum chloride was also associated with a significantly increased risk of AKI and mortality on univariate analysis. Hyperchloraemia on admission was, however, not associated with AKI or death. Of the 150 patients with AKI, 147 (98.0%) had developed AKI by 48 h.

Conclusions

Hyperchloraemia and increasing serum chloride are associated with adverse outcomes in critically ill patients. There is equipoise as to whether this represents an association, an epiphenomenon or causation.

Introduction

Disorders of chloride are relatively under-researched in comparison to disorders of sodium [1]. Traditionally chloride was viewed as the passive anionic companion of sodium. While the association between hyperchloraemia and metabolic acidosis is well established, the clinical consequences of hyperchloraemia are unclear [[2], [3], [4]].

Wilcox demonstrated that hyperchloraemia results in renal vasoconstriction in an animal model, with Chowdhury recently reporting similar findings with the use of 0.9% saline versus balanced salt solutions in human subjects [[5], [6], [7]].

Studies examining AKI and hyperchloraemia have shown conflicting results. While some have shown an association in postoperative, septic and intensive care unit (ICU) patients [[8], [9], [10], [11], [12]], others have shown no such association [13]. Of these studies only one explored the association between chloride kinetics (the change in chloride over time) and AKI and found an increased incidence of AKI in patients who had shown an increase in chloride [12].

A relationship between increased mortality and hyperchloraemia has also been reported [8,[14], [15], [16], [17]]. Other studies have not shown this association [10,12], and there was no significant association between the use of a chloride-liberal or a chloride-restrictive fluid strategy and mortality [[18], [19], [20], [21]].

Despite these previous studies, there are numerous limitations in the current knowledge base. Of the studies discussed above, only 10 specifically evaluated the association between serum chloride and the outcomes of interest, of these, 6 reported AKI as an outcome and 7 reported mortality as an outcome. Only one study each evaluated the association between chloride kinetics and AKI and mortality [12,16]. Six studies evaluated exclusively ICU patients, with only 3 including a proportion (27.8%–64.0%) of non-surgical patients [9,10,15]. Only 3 studies were in low- or middle-income countries, with no studies in Africa. Based on these limitations we aimed to examine the association between hyperchloraemia in the first 48 h of ICU and AKI and mortality in a heterogenous critically ill population in South Africa. We also sought to explore the association between chloride kinetics and the abovementioned outcomes and the association between sodium and acid-base parameters and AKI and mortality.

Section snippets

Materials and methods

This was a retrospective observational study of patients admitted to King Edward VIII Hospital Intensive Care Unit from to 26 September 2015 to 09 May 2016. The study ICU is a multidisciplinary, closed, intensivist-run ICU in a tertiary academic hospital that serves the province of KwaZulu-Natal in South Africa.

AKI was defined according to Kidney Disease Improving Global Outcomes (KDIGO) criteria, using the serum creatinine and renal replacement therapy criteria [22]. Urine output criteria were

Results

The derivation of the study population is shown in Fig. 1 and baseline demographic and outcome data is presented in Table 1.

Of the 150 patients that developed AKI, 31.3% had stage 1 AKI, 31.3% stage 2 AKI and 37.3% stage 3 AKI. Ninety-eight percent had developed AKI by 48 h of ICU admission.

Admission serum chloride was available for all 250 patients, with 48-h chloride available for 163 patients. Hyperchloraemia was noted in 42.0% of patients on ICU admission, and 36.8% at 48 h. Overall 57.2%

Discussion

This study presents data for a cohort of patients that has not previously been represented in the international literature. The cohort was remarkably young, with a median age of 35 years, compared to the 6th and 7th decades for previous studies [9,10,14,15]. The high incidence of sepsis (45.2%) reflects the burden of infectious disease in the study country. The high incidence of shock on admission (53.6%), AKI (60.0%), and ICU mortality rate (39.2%) reflect the increased severity of illness of

Limitations

The retrospective observational nature of the study is a limitation; however, the study did not rely simply on a retrospective analysis of an electronic database but used the patient's original medical record to source individual patient data, optimising the quality of the data collected. Patient weights were not known and thus urine output criteria were not used to diagnose AKI. It is anticipated that the inclusion of urine output criteria would have increased the incidence of AKI, but it is

Conclusions

Hyperchloraemia and increases in serum chloride are associated with increased incidences of both AKI and ICU mortality in a heterogenous ICU population, with hyperchloraemia at 48 h after ICU admission being an independent predictor of both AKI within the first 7 days of ICU admission and ICU mortality. While the findings warrant concern, this study suggests there is still equipoise as to whether the findings represent association, causation or are an epiphenomenon (possibly related to altered

Ethics approval

Approval for the study was obtained from the University of KwaZulu-Natal Biomedical Research Ethics Committee (BE 492/15), King Edward VIII hospital, and the Health Research Committee of the KwaZulu-Natal Department of Health.

Consent for publication

Not applicable.

Availability of data and material

The datasets used during the current study are available from the corresponding author on reasonable request and subject to approval of the above ethics committees.

Competing interests

The authors declare that they have no competing interests.

Funding

This research did not receive any

References (27)

  • N. Patel et al.

    Serum hyperchloremia as a risk factor for acute kidney injury in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention

    Proc (Baylor Univ Med Cent)

    (2016)
  • M.M. Boniatti et al.

    Is hyperchloremia associated with mortality in critically ill patients? A prospective cohort study

    J Crit Care

    (2011)
  • K. de Vasconcellos

    Hyperchloraemia: ready for the big time?

    S Afr J Anaesth Analg

    (2015)
  • S. Scheingraber et al.

    Rapid saline infusion produces hyperchloremic acidosis in patients undergoing gynecologic surgery

    Anesthesiology

    (1999)
  • J.H. Waters et al.

    Cause of metabolic acidosis in prolonged surgery

    Crit Care Med

    (1999)
  • E. O'Dell et al.

    Hyperchloremia is the dominant cause of metabolic acidosis in the postresuscitation phase of pediatric meningococcal sepsis

    Crit Care Med

    (2007)
  • C.S. Wilcox

    Regulation of renal blood flow by plasma chloride

    J Clin Invest

    (1983)
  • A.H. Chowdhury 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)
  • A.H. Chowdhury et al.

    A randomized, controlled, double-blind crossover study on the effects of 1-L infusions of 6% hydroxyethyl starch suspended in 0.9% saline (voluven) and a balanced solution (plasma volume redibag) on blood volume, renal blood flow velocity, and renal cortical tissue perfusion in healthy volunteers

    Ann Surg

    (2014)
  • S.A. McCluskey et al.

    Hyperchloremia after noncardiac surgery is independently associated with increased morbidity and mortality: a propensity-matched cohort study

    Anesth Analg

    (2013)
  • Z. Zhang et al.

    Higher serum chloride concentrations are associated with acute kidney injury in unselected critically ill patients

    BMC Nephrol

    (2013)
  • M. Marttinen et al.

    Association of plasma chloride values with acute kidney injury in the critically ill - a prospective observational study

    Acta Anaesthesiol Scand

    (2016)
  • A. Nadeem et al.

    Chloride-liberal fluids are associated with acute kidney injury after liver transplantation

    Crit Care

    (2014)
  • Cited by (35)

    • Increase in chloride from baseline is independently associated with mortality in intracerebral hemorrhage patients admitted to intensive care unit: A retrospective study

      2022, Journal of Intensive Medicine
      Citation Excerpt :

      Boniatti et al. [22] noted that hyperchloremia was associated with mortality in a prospective cohort of 175 patients. Other reports have found an association between hyperchloremia or chloride perturbations with increased in-hospital mortality [8,9,23,24]. Several investigators have shown the association between chloride abnormalities and increased mortality in neurocritical care patients.

    • Effect of initial serum chloride level on the association between intravenous chloride load and mortality in critically ill patients: A retrospective cohort study

      2022, Journal of Critical Care
      Citation Excerpt :

      When deviating from the physiological range of concentration, serum chloride, similar to sodium, potassium, and other electrolytes, was also associated with adverse outcomes [19]. The impact of both hypochloremia and hyperchloremia have been broadly reported in existing studies, although the exact mechanism remains unclear [4-7,9,25,31,32]. Anyway, the serum chloride level deserves more attention in clinical practice, especially during the management of critically ill patients.

    • Determinants of serum magnesium abnormalities and outcome among admissions to the intensive care unit

      2020, Anaesthesia Critical Care and Pain Medicine
      Citation Excerpt :

      Electrolyte abnormalities are common among patients admitted to intensive care units (ICU) [1]. While the occurrence and outcomes associated with disturbances in serum sodium, potassium, chloride, and calcium are well defined, this is less so the case for other electrolytes including magnesium [1–5]. Magnesium has a range of important physiologic roles not limited to electrolyte homeostasis, energy production, cell membrane stability, and blood pressure regulation [6].

    • Serum Procalcitonin Level Predicts Acute Kidney Injury After Traumatic Brain Injury

      2020, World Neurosurgery
      Citation Excerpt :

      Many studies have explored the effects of hyperchloremia on AKI in various clinical settings. However, the predictive value of hyperchloremia on AKI is controversial in different subgroups of patients.35-40 Some studies indicate that hyperchloremic metabolic acidosis rather than hyperchloremia is valuable in predicting AKI.

    • Physician and nurse research in multidisciplinary intensive care units

      2020, American Journal of Critical Care
      Citation Excerpt :

      A P value of less than.05 was considered to indicate statistical significance. A total of 1849 medical and 425 nursing articles were initially identified using the search strategies, of which 73 and 65, respectively, were screened to obtain the final sample of 50 medical articles8-57 and 50 nursing articles58-107 for inclusion. Of the 23 medical journal articles that were excluded, 1 was a case report, 3 involved pediatric research, 4 were review articles, and 15 were not focused on ICU-related topics.

    View all citing articles on Scopus
    View full text