Abstract
Background: Impaired liver function and cholestasis are frequent findings in critically ill patients and are associated with poor outcomes. We tested the hypothesis that hypoxic liver injury and hypoxic cholangiocyte injury are detectable very early in patients with ARDS, may depend on the severity of hypoxemia, and may be aggravated by the use of rescue therapies (high PEEP level and prone positioning) but could be attenuated by extracorporeal membrane oxygenation (ECMO). Methods: In 70 patients with ARDS, aspartate-aminotransferase (AST), alanin-aminotransferase (ALT) and gamma glutamyltransferase (GGT) were measured on the day of the diagnosis of ARDS and three more consecutive days (day 3, day 5, day 10), total bile acids were measured on day 0, 3, and 5. Results: AST levels increased on day 0 and remained constant until day 5, then dropped to normal on day 10 (day 0: 66.5 U/l; day 3: 60.5 U/l; day 5: 63.5 U/l, day 10: 32.1 U/l), ALT levels showed the exact opposite kinetic. GGT was already elevated on day 0 (91.5 U/l) and increased further throughout (day 3: 163.5 U/l, day 5: 213 U/l, day 10: 307 U/l), total bile acids levels increased significantly from day 0 to day 3 (p = 0.019) and day 0 to day 5 (p < 0.001), but not between day 3 and day 5 (p = 0.217). Total bile acids levels were significantly correlated to GGT on day 0 (p < 0.001), day 3 (p = 0.02), and in a trend on day 5 (p = 0.055). PEEP levels were significantly correlated with plasma levels of AST (day 3), ALT (day 5) and GGT (day 10). Biomarker levels were not associated with the use of ECMO, prone position, the cause of ARDS, and paO2. Conclusions: We found no evidence of hypoxic liver injury or hypoxic damage to cholangiocytes being caused by the severity of hypoxemia in ARDS patients during the very early phase of the disease. Additionally, mean PEEP level, prone positioning, and ECMO treatment did not have an impact in this regard. Nevertheless, GGT levels were elevated from day zero and rising, this increase was not related to paO2, prone position, ECMO treatment, or mean PEEP, but correlated to total bile acid levels.
Highlights
The patients in our cohort with extracorporeal membrane oxygenation (ECMO) and those treated without ECMO, as well as patients proned and those not treated in ICU 3.9 days mean prior to ARDS diagnosis/enrollment in our trial (median proned with respect to any of the measured biomarkers (Tables S2 and S3); the cause of
In our cohort of 70 patients with ARDS of all severity levels, we found no evidence that hypoxic liver injury or hypoxic damage to cholangiocytes was caused by the severity of hypoxemia in ARDS patients during the very early phase of the disease
The mean positive endexpiratory pressure (PEEP) level, prone positioning, and ECMO treatment did not have an impact in this regard
Summary
Impaired liver function and cholestasis are frequent findings in critically ill patients [1]. Are associated with poor outcomes [1,2,3,4,5,6,7,8]. Hypoxia of hepatocytes has been proposed to be the main cause of impaired liver function in critically ill patients [1,9,10,11,12]. When liver dysfunction is present, mortality rates of up to 50% have been consistently reported [1,3,9,13]. Hypoxic liver injury is caused by one of the following mechanisms:
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