Henriksen Jakob Nørgaard, Rosenquist Sara Buttrup, Illum Dorte Goldbækdal, Andersen Charlotte Uggerhøj
Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark.
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Basic Clin Pharmacol Toxicol. 2025 Apr;136(4):e70018. doi: 10.1111/bcpt.70018.
Chlordiazepoxide is effective in treating alcohol withdrawal syndrome, but it poses a risk of long-term sedation. The prevalence of this side effect and its risk factors remain uncertain. This retrospective cross-sectional study aimed to estimate both using data from Aarhus University Hospital's BI portal. We identified and manually reviewed patient records from 1 September 2019 to 31 August 2021, including the treating physicians' conclusions on ICU admissions to determine whether they were likely due to chlordiazepoxide toxicity. Chlordiazepoxide was administered to 1363 unique patients in the study period. We identified 32 ICU admissions preceded by chlordiazepoxide administration, 5 of which (16%) were likely related to chlordiazepoxide toxicity. Patients with chlordiazepoxide-induced admissions received higher cumulative doses compared to other admissions (425 mg vs. 150 mg, p = 0.01), had longer ICU stays (median 8 vs. 2 days, p = 0.01) and required higher doses of flumazenil (p = 0.04). Their median age was above 60 years, and not all had known liver disease. The overall incidence of long-term chlordiazepoxide toxicity was approximately 0.35%, with risk factors including higher doses and age above 60. Our findings suggest increased caution when treating not only patients with liver disease but also elderly patients with chlordiazepoxide for alcohol withdrawal symptoms.
氯氮卓对治疗酒精戒断综合征有效,但存在长期镇静的风险。这种副作用的发生率及其风险因素尚不确定。这项回顾性横断面研究旨在利用奥胡斯大学医院BI门户网站的数据对两者进行评估。我们识别并人工审查了2019年9月1日至2021年8月31日期间的患者记录,包括主治医生关于重症监护病房(ICU)入院情况的结论,以确定是否可能是由于氯氮卓毒性所致。在研究期间,1363名不同患者接受了氯氮卓治疗。我们识别出32例在使用氯氮卓后入住ICU的病例,其中5例(16%)可能与氯氮卓毒性有关。与其他入院患者相比,因氯氮卓导致入院的患者接受的累积剂量更高(425毫克对150毫克,p = 0.01),在ICU的停留时间更长(中位数8天对2天,p = 0.01),且需要更高剂量的氟马西尼(p = 0.04)。他们的年龄中位数在60岁以上,并非所有人都患有已知的肝脏疾病。氯氮卓长期毒性的总体发生率约为0.35%,风险因素包括更高的剂量和60岁以上的年龄。我们的研究结果表明,在使用氯氮卓治疗酒精戒断症状时,不仅对肝病患者,而且对老年患者都应更加谨慎。