Association of esketamine exposure with secondary sclerosing cholangitis in critically ill patients: a retrospective cohort analysis of 20,000 ICU cases.

Abstract

<h4>Background</h4>Secondary sclerosing cholangitis in critically ill patients (SSC-CIP) is a severe cholangiopathy with high mortality observed in ICU survivors. While prolonged mechanical ventilation and COVID-19-associated acute respiratory distress syndrome (ARDS) are established risk factors, the impact of ketamine, a commonly used sedative, remains controversial.<h4>Methods</h4>This retrospective study included 20,973 ICU patients admitted between January 2014 and February 2022 at a tertiary university hospital. Patients with severe cholestasis were preselected (n = 532) and reviewed for SSC-CIP diagnosis or likelihood of SSC-CIP. Multivariate logistic regression was used to evaluate Esketamine exposure and dose dependency while controlling for other risk factors.<h4>Results</h4>SSC-CIP was confirmed in 0.11% of patients; 0.20% had clinical profiles compatible with undiagnosed SSC-CIP. Among COVID-19 ICU patients, the incidence was 3.24%. Esketamine administration was significantly associated with SSC-CIP (70% of SSC cases vs. 7% controls). In a multivariate analysis, cumulative Esketamine dose (OR 1.021 per gram), ICU duration (OR 1.031/day), and COVID-19 status (OR 20.6) were independent predictors.<h4>Conclusion</h4>Esketamine exposure was associated with SSC-CIP in a dose-dependent manner, highlighting the need for judicious sedative use in critically ill patients. Our cholestasis-first screening strategy also demonstrates a novel approach for detecting previously unrecognized SSC-CIP cases. Future prospective trials should evaluate the benefits of ketamine-free sedation strategies in high-risk populations.

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