Acute cholestasis as a side effect of intravenous levomepromazine in ICU-patients

Abstract

Levomepromazine has been used as an adjunct to standard sedative therapies in mechanically ventilated ICU patients, despite a relative lack of safety data. This addition could increase the risk of cholestasis, a side effect common among phenothiazines. The aim of our study was to assess whether the addition of an infusion of levomepromazine to midazolam increases the risk of cholestasis. The index group was retrospectively defined by patients with an infusion of levomepromazine in addition to infusion of midazolam. The control group was retrospectively defined by patients with infusion of midazolam alone. Liver function tests were retrieved from patient data records. Exclusion criteria were serum AP, GGT, ALAT levels more than a 2-fold increase of the upper limit of normal value (ULN), on the first day of therapy. Drug-induced cholestatic liver injury was defined as more than a 2-fold increase from baseline of the ULN of alkaline phosphatase. No statistically significant differences were found for age, sex, duration of therapy and liver function tests between index and reference groups at the start of therapy. In the index group, midazolam infusion started 5.39/7.2 days before levomepromazine was added. Fourteen of 64 (21.9%) patients in the index group versus 32 of 270 (11.9%) in the reference group developed drug-induced cholestasis (p0/0.029). No statistically significant co-variables were identified. We found that the addition of levomepromazine to midazolam was associated with a 10% increased incidence for developing acute cholestasis. Future research should include extensive risk-factor analysis.