Abnormal serum chloride is associated with increased mortality among unselected cardiac intensive care unit patients

PLOS ONE RESEARCH ARTICLE Abnormal serum chloride is associated with increased mortality among unselected cardiac intensive care unit patients Thomas J. Breen1, Benjamin Brueske2, Mandeep S. Sidhu2, Kianoush B. Kashani3,4, Nandan S. Anavekar5, Gregory W. Barsness5, Jacob C. Jentzer ID4,5* a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 1 Department of Internal Medicine, Mayo Clinic, Rochester MN, United States of America, 2 Division of Cardiology, Department of Medicine, Albany Medical Center and Albany Medical College, Albany, NY, United States of America, 3 Division of Nephrology & Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, United States of America, 4 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, MN, United States of America, 5 Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, United States of America * Abstract Purpose OPEN ACCESS Citation: Breen TJ, Brueske B, Sidhu MS, Kashani KB, Anavekar NS, Barsness GW, et al. (2021) Abnormal serum chloride is associated with increased mortality among unselected cardiac intensive care unit patients. PLoS ONE 16(4): e0250292. https://doi.org/10.1371/journal. pone.0250292 Editor: Corstiaan den Uil, Erasmus Medical Centre: Erasmus MC, NETHERLANDS We sought to describe the association between serum chloride levels and mortality among unselected cardiac intensive care unit (CICU) patients. Materials and methods We retrospectively reviewed adult patients admitted to our CICU from 2007 to 2015. The association of dyschloremia and hospital mortality was assessed in a multiple variable model including additional confounders, and the association of dyschloremia and post-discharge mortality were assessed using Cox proportional-hazards analysis. Received: December 11, 2020 Results Accepted: April 1, 2021 9,426 patients with a mean age of 67±15 years (37% females) were included. Admission hypochloremia was present in 1,384 (15%) patients, and hyperchloremia was present in 1,606 (17%) patients. There was a U-shaped relationship between admission chloride and unadjusted hospital mortality, with increased hospital mortality among patients with hypochloremia (unadjusted OR 3.0, 95% CI 2.5–3.6, p<0.001) or hyperchloremia (unadjusted OR 1.9, 95% CI 1.6–2.3, p<0.001). After multivariate adjustment, hypochloremia remained associated with higher hospital mortality (adjusted OR 2.1, 95% CI 1.6–2.9, p <0.001). Postdischarge mortality among hospital survivors was higher among patients with admission hypochloremia (adjusted HR 1.3, 95% CI 1.1–1.6; p<0.001). Published: April 26, 2021 Copyright: © 2021 Breen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: The authors received no specific funding for this work. Competing interests: The authors have declared that no competing interests exist. Conclusion Abnormal serum chloride on admission to the CICU is associated with increased short- and long-term mortality, with hypochloremia being a strong independent predictor. PLOS ONE | https://doi.org/10.1371/journal.pone.0250292 April 26, 2021 1 / 17 PLOS ONE Serum chloride and mortality in cardiac intensive care unit Introduction Serum chloride abnormalities are common among hospitalized patients, and both hypochloremia and hyperchloremia have been associated with increased in-hospital mortality among general intensive care unit (ICU) patients [1–4]. Hypochloremia is an independent marker of short- and long-term mortality among patients with heart failure (HF) and predicts a decreased response to diuretics [5–8]. The finding that serum chloride derangements are potentially associated with adverse outcomes among ICU and cardiovascular disease populations reflects the importance of serum chloride in normal physiology. Serum chloride is influenced by numerous pathophysiologic processes and plays a key role in the maintenance of osmotic pressure, acid-base disturbances, and regulation of renal function [9]. Serum chloride and sodium levels correlate closely to maintain plasma electroneutrality, and changes in volume status and plasma tonicity typically produce parallel changes in serum sodium and chloride levels. Unlike serum sodium, chloride levels are also intimately associated with acid-base status, with hyperchloremia typically associated with non-anion gap metabolic acidosis and hypochloremia typically associated with metabolic alkalosis [10–12]. Anion-gap acidosis may be associated with relative hypochloremia and has been linked to adverse outcomes among CICU patients [13]. Prior studies assessing the associations between serum chloride and patient outcomes are limited by the lack of information regarding sodium, anion gap, and acid-base status. The modern cardiac intensive care unit (CICU) cares for a heterogeneous population of critically ill patients with concomitant cardiovascular disease, yet there are no published studies examining the significance of abnormal serum chloride levels among CICU patients. The aim of our study was to clarify whether an abnormal admission chloride level was associated with higher hospital and post-discharge mortality among CICU patients and to provide insights about the effects of associated electrolyte and acid-base disturbances. Methods Participants The Mayo Clinic Institutional Review Board approved this historical cohort study as a minimal risk study that was exempt from informed consent. We analyzed a database of adult Mayo Clinic CICU (Rochester, MN) patients �18 years old whose admission fell entirely between January 1, 2007, and December 31, 2015 and consented to have their medical records used for research under Minnesota state law statute 144.295 [14–17]. The Mayo Clinic CICU cares for medically critically ill patients with cardiovascular disease, not including post-cardiotomy patients or patients receiving extracorporeal membrane oxygenator support. Patients were identified from archived electronic health records, and only the data from the first CICU admission was included to avoid survival bias associated with readmissions [18]. We excluded patients without available data on admission chloride or creatinine values. Collected data Demographics, vital signs, laboratory results, diagnoses, procedures, therapies and length of stay (LOS) were extracted from the electronic medical record (EMR) through the Multidisciplinary Epidemiology and Translational Research in Intensive Care Data Mart [18, 19]. Admission diagnoses were defined as all International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes recorded within one day before or after CICU admission [ (...truncated)