Distribution and elimination kinetics of midazolam and metabolites after post-resuscitation care: a prospective observational study.

Jaehan Kim, Jang Hee Hong, Jung Sunwoo, Changshin Kang, Hong Joon Ahn, Yeonho You, Jung Soo Park, Jin Hong Min, Wonjoon Jeong, Yong Nam In, So Young Jeon, Ji Hye Song, Hyein Kang, My Tuyen Thi Nguyen

Journal: Scientific reports 2024;14(1):4574

PMID: 38403792

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Abstract

Administration of sedatives for post-resuscitation care can complicate the determination of the optimal timing to avoid inappropriate, pessimistic prognostications. This prospective study aimed to investigate the distribution and elimination kinetics of midazolam (MDZ) and its metabolites, and their association with awakening time. The concentrations of MDZ and its seven metabolites were measured immediately and at 4, 8, 12, and 24 h after the discontinuation of MDZ infusion, using liquid chromatography-tandem mass spectrometry. The area under the time-plasma concentration curve from 0 to 24 h after MDZ discontinuation (AUC) was calculated based on the trapezoidal rule. Of the 15 enrolled patients, seven awakened after the discontinuation of MDZ infusion. MDZ and three of its metabolites were major compounds and their elimination kinetics followed a first-order elimination profile. In the multivariable analysis, only MDZ was associated with awakening time (AUC: R = 0.59, p = 0.03; AUC: R = 0.96, p < 0.001). Specifically, a 0.001% increase in MDZ AUC was associated with a 1% increase in awakening time. In the individual regression analysis between MDZ concentration and awakening time, the mean MDZ concentration at awakening time was 16.8 ng/mL. The AUC of MDZ is the only significant factor associated with the awakening time.

Address: Department of Emergency Medicine, Chungnam National University Hospital, Daejeon, 35015, Republic of Korea.; Department of Emergency Medicine, College of Medicine, Chungnam National University, Daejeon, 35015, Republic of Korea.; Clinical Trials Center, Chungnam National University Hospital, Daejeon, 35015, Republic of Korea.; Department of Emergency Medicine, College of Medicine, Chungnam National University, Daejeon, 35015, Republic of Korea.; Department of Emergency Medicine, Sejong Chungnam National University Hospital, Sejong, 30099, Republic of Korea.; Clinical Trials Center, Chungnam National University Hospital, Daejeon, 35015, Republic of Korea.; Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon, 35015, Republic of Korea.; Clinical Trials Center, Chungnam National University Hospital, Daejeon, 35015, Republic of Korea.; Department of Medical Science, College of Medicine, Chungnam National University, Daejeon, 35015, Republic of Korea.; Department of Food and Nutrition, Chungnam National University, Daejeon, 34134, Republic of Korea.; Department of Food and Nutrition, Chungnam National University, Daejeon, 34134, Republic of Korea.; Department of Food Technology, Can Tho University, Can Tho City, 90000, Vietnam.; Department of Emergency Medicine, Chungnam National University Hospital, Daejeon, 35015, Republic of Korea. [email protected].; Department of Emergency Medicine, College of Medicine, Chungnam National University, Daejeon, 35015, Republic of Korea. [email protected].

DOI: 10.1038/s41598-024-54968-z

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MeSH Terms: Humans, Midazolam, Prospective Studies, Hypnotics and Sedatives, Chromatography, Liquid