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A retrospective analysis of critically-ill patients with hypoxic hepatitis (HH) to characterize the biochemical profile and to identify predictors of mortality using the Medical Information Mart for Intensive Care III database.HH was defined as a rapid increase in AST/ALT ≥ 800 IU/L after exclusion of other causes. We investigated the correlation between various clinical and laboratory parameters and mortality rates using regression models.Among 38,645 ICU-patients, 565 (1.46%) were diagnosed with HH; 57.9% were males; median age was 63 years. The unique biochemical profile of HH was confirmed; lactate dehydrogenase (LDH) was higher than both ALT and AST; AST > ALT for the first 2 days then the ratio is reversed until recovery. All-cause hospital mortality was 44.1%. All-cause hospital mortality was 44.1%. On multivariate analysis, older age, higher SAPS-II, higher INR, higher bilirubin, higher LDH, acute kidney injury (AKI), and the need for vasopressors were independently associated with mortality.Older age, higher SAPS-II, LDH, INR and bilirubin levels, concomitant AKI and the need for vasopressors were all factors associated with increased mortality. The diagnosis of HH was an important harbinger of mortality in this population, which appears to be driven mainly by the severity of the underlying conditions.Hypoxic hepatitis is relatively uncommon however is associated with high mortality.Recognition of the unique biochemical injury pattern is essential for the diagnosis of HH.LDH was found as a novel risk factor for mortality in HH.