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.
Sci Rep. 2024 Feb 25;14(1):4574. doi: 10.1038/s41598-024-54968-z.
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.
镇静剂在复苏后治疗中的应用可能会影响对最佳时机的确定，避免不恰当的、悲观的预后预测。本前瞻性研究旨在调查咪达唑仑（MDZ）及其代谢物的分布和消除动力学，及其与苏醒时间的关系。采用液相色谱-串联质谱法，在 MDZ 输注停止后即刻和 4、8、12 和 24 小时测量 MDZ 及其七种代谢物的浓度。根据梯形法则计算 MDZ 停止输注后 0 至 24 小时的时间-血浆浓度曲线下面积（AUC）。在 15 名入组患者中，有 7 名在 MDZ 输注停止后苏醒。MDZ 和其三种代谢物是主要化合物，其消除动力学呈一级消除特征。在多变量分析中，只有 MDZ 与苏醒时间相关（AUC：R=0.59，p=0.03；AUC：R=0.96，p<0.001）。具体来说，MDZ AUC 增加 0.001%，苏醒时间增加 1%。在 MDZ 浓度与苏醒时间的个体回归分析中，苏醒时的平均 MDZ 浓度为 16.8ng/mL。MDZ 的 AUC 是与苏醒时间唯一显著相关的因素。
