Research Article: Chloride alterations in hospitalized patients: Prevalence and outcome significance

Date Published: March 22, 2017

Publisher: Public Library of Science

Author(s): Charat Thongprayoon, Wisit Cheungpasitporn, Zhen Cheng, Qi Qian, Yu Ru Kou.


Serum Cl (sCl) alterations in hospitalized patients have not been comprehensively studied in recent years. The aim of this study is to investigate the prevalence and outcome significance of (1) sCl alterations on hospital admission, and (2) sCl evolution within the first 48 hr of hospital admission. We conducted a retrospective study of all hospital admissions in the years 2011–2013 at Mayo Clinic Rochester, a 2000-bed tertiary medical center. Outcome measures included hospital mortality, length of hospital stay and discharge disposition. 76,719 unique admissions (≥18 years old) were studied. Based on hospital mortality, sCl in the range of 105–108 mmol/L was found to be optimal. sCl <100 (n = 13,611) and >108 (n = 11,395) mmol/L independently predicted a higher risk of hospital mortality, longer hospital stay and being discharged to a care facility. 13,089 patients (17.1%) had serum anion gap >12 mmol/L; their hospital mortality, when compared to 63,630 patients (82.9%) with anion gap ≤12 mmol/L, was worse. Notably, patients with elevated anion gap displayed a progressively worsening mortality with rising sCl. sCl elevation within 48 hr of admission was associated with a higher proportion of 0.9% saline administration and was an independent predictor for hospital mortality. Moreover, the magnitude of sCl rise was inversely correlated to the days of patient survival. In conclusion, serum Cl alterations on admission predict poor clinical outcomes. Post-admission sCl increase, due to Cl-rich fluid infusion, independently predicts hospital mortality. These results raise a critical question of whether iatrogenic cause of hyperchloremia should be avoided, a question to be addressed by future prospective studies.

Partial Text

Chloride (Cl) is the most abundant anion in extracellular fluid, playing a fundamental role in the maintenance of osmotic pressure, water distribution and acid–base balance [1]. Cl channels are expressed in almost all cells in the body. Dysfunctions in the Cl channel result in a broad spectrum of diseases [2].

The Institutional Review Board approved the study and waver of consent. All participants had provided Mayo Clinic with research authorization. Participant records were de-identified and analyzed anonymously. Adults (age >18 years) admitted to Mayo Clinic Rochester between January 1, 2011 and December 31, 2013 were enrolled (Fig 1). Patients without admission sCl (≤24hr of admission) were excluded. For patients with multiple admissions, data from the first admission were analyzed. Charlson comorbidity index [20] was computed for each patient at the index admission. Clinical data, including principal diagnosis based on the ICD-9 (International Classification of Diseases, 9th Revision) codes, were extracted from our institutional electronic database. sCl values were grouped, based on hospital mortality data (Fig 2) into: <95, 95–100, 100–105, 105–108 (optimal), 108–113, 113–118 and >118 mmol/L. Acid-base status was determined (Box 1). DiffNa-Cl and Cl:Na ratio were used as surrogates for SID [4, 5], and AG (Na-Cl-HCO3) used to estimate UMAs.

In this large, single center study of all hospital admission, sCl alterations are not only common, but also independently associated with elevated risks for hospital mortality, LOS and discharge to a care facility. Furthermore, in adjusted analysis, post-admission sCl increase, associated with a higher percentage saline infusion, independently predicted fewer days of patient survival, when compared to patients without sCl increase.

sCl alterations outside of 100–108 mmol/L range are common at hospital admission and can independently predict poor clinical outcomes, including hospital mortality. Post-admission sCl increase, associated with Cl-rich 0.9% saline infusion, is not only associated with higher hospital mortality, but is also inversely correlated with days of patient survival. Given that sCl values are routinely obtained and available for vast majority of patients, attention should be paid to the sCl value. Although our study results do not establish causality, they do raise an important question of whether Cl-rich fluids compromise patient outcomes. This question should be addressed with future prospective randomized trials.




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