Analysis of factors related to prolonged midazolam action: A multicenter, case-control study

Abstract

Background Benzodiazepine midazolam is characterized by a rapid onset of action and a short half-life and is used for deep sedation in critically ill patients; however, hepatic and renal dysfunction, obesity, and prolonged use of midazolam are reported to prolong midazolam action. A few studies have investigated the association between midazolam use and hypoalbuminemia in critically ill patients. Therefore, this study aimed to investigate the effects of patient background on the prolonged action of midazolam by focusing on previously reported factors and albumin levels. Methods A total of 196 patients aged ≥ 18 years who were admitted to the University Hospital and Matsuyama Shimin Hospital intensive care unit between January 2015 and May 2022 and were administered midazolam continuously for ≥ 24 h were enrolled. Patient data, such as background, laboratory test values, and status of sedative drug use, including midazolam, were obtained from medical records. The primary outcome was the time required for improvement of the Richmond Agitation–Sedation Scale score after midazolam administration. Factors related to the prolongation of midazolam action were analyzed using the Mann–Whitney U test and logistic regression analysis. Statistical analyses were performed using EZR (version 1.61). Statistical significance was set at P < 0.05. Result In total, 68 patients were included in this study. The time required for Richmond Agitation–Sedation Scale score improvement after discontinuation of midazolam was < 48 h in 52 patients (76.4%) and > 48 h in 16 patients (23.5%).The factors related to prolonged midazolam action were age (P < 0.05), renal function (P < 0.01), risk factors reported in previous studies, and albumin levels (P < 0.01). The multivariate logistic regression analysis revealed that only albumin influenced the prolongation of midazolam activity (odds ratio, 0.61; 95% confidence interval, 0.44–0.85; P < 0.05). Conclusions Renal function, body mass index, age, and duration of midazolam administration are established factors that enhance and prolong the action of midazolam. In this study, the serum albumin level was identified as a new factor of relevance. Therefore, sedation in patients with low albumin levels should be carefully performed to avoid the prolongation and potentiation of midazolam action.