Researchers at Brigham and Women's Hospital (Boston, MA, USA) analyzed data regarding 51,789 critically ill patients at Massachusetts General and Brigham and Women's Hospital (Boston, MA, USA) from 1998 to 2009 to examine the hypothesis that abnormal chloride after admission to an ICU would be associated with increased mortality. Patients were grouped into deciles of serum chloride values ranging from under 98 mEq/L (hypochloremia) to higher than 112 mEq/L (hyperchloremia). The primary endpoint was 30-day mortality, and all comparisons were versus the reference value of 107-108 mEq/L.

The results showed that patients with hypochloremic serum values had more than twofold higher 30-day mortality, compared with the reference value. The researchers also developed two models--one with and the other without sodium--that adjusted for age, gender, race, medical versus surgical patient, sepsis, creatinine, hematocrit, and other factors. They found that in the model that omitted sodium, serum chloride values remained predictors of increased mortality. After inclusion of sodium, hyperchloremia no longer predicted 30-day mortality risk, but remained an independent predictor of increased mortality up to 104 mEq/L. The study was presented as a poster session at the Society of Critical Care Medicine meeting, held during February 2012 in Houston (TX, USA).

“The present study illustrates a graded, independent relationship between chloride at critical-care initiation and 30-day all-cause mortality,” said study presenter Kenneth Christopher, MD. “Interestingly, hypochloremia is caused by excessive water, and that would include patients with syndrome of inappropriate antiduretic hormone, chronic heart failure, excess chloride loss, and patients on diuretics.”

Abnormal serum chloride values, either elevated or reduced, are common among ICU patients, but the mechanisms controlling this association have remained poorly understood. Studies of this known relationship have produced conflicting results, as some studies have shown an association, whereas others have identified hyperchloremia as a true mortality risk in critically ill patients; in general, however, hypochloremia is not a currently accepted as a risk factor.

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