Spina Sean P, Ensom Mary H H
Division of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Pharmacotherapy. 2007 Mar;27(3):389-98. doi: 10.1592/phco.27.3.389.
Midazolam is a commonly used sedative in critically ill, mechanically ventilated patients in intensive care unit (ICU) settings worldwide. We used a nine-step decision-making algorithm to determine whether therapeutic monitoring of midazolam in the ICU is warranted. Midazolam has a higher clearance and shorter half-life than other benzodiazepines, and prolonged sedation is achieved with continuous infusion. There appears to be very good correlation between plasma concentrations of both midazolam and its active metabolite, alpha1-hydroxymidazolam, and the degree of sedation. However, due to high interpatient variability, it is not possible to predict the level of sedation in any given individual based on plasma concentration of midazolam or its metabolites. Moreover, no simple and practical assay is available to quantitate midazolam plasma concentrations in the acute ICU setting. Many scales are available to assess the sedative effects of midazolam. Because the plasma concentration of midazolam required to achieve a constant level of sedation is highly variable, it is usually more prudent for the clinician to monitor for sedation with a validated clinical scale than by plasma concentrations alone. Various physiologic parameters, including age-related effects, compromised renal function, and liver dysfunction affect the pharmacokinetics of midazolam and alpha1-hydroxymidazolam. Although routine drug monitoring for all critically ill patients receiving midazolam is not recommended, this practice is likely beneficial in patients with neurologic damage in whom sedation cannot be assessed and in patients who have renal failure with a prolonged time to awakening.
咪达唑仑是全球重症监护病房（ICU）中危重症机械通气患者常用的镇静剂。我们使用了一种九步决策算法来确定在ICU中对咪达唑仑进行治疗监测是否必要。与其他苯二氮䓬类药物相比，咪达唑仑具有更高的清除率和更短的半衰期，通过持续输注可实现长时间的镇静。咪达唑仑及其活性代谢物α1-羟基咪达唑仑的血浆浓度与镇静程度之间似乎存在非常好的相关性。然而，由于患者间差异很大，无法根据咪达唑仑或其代谢物的血浆浓度预测任何特定个体的镇静水平。此外，在急性ICU环境中，没有简单实用的检测方法可用于定量咪达唑仑的血浆浓度。有许多量表可用于评估咪达唑仑的镇静效果。由于达到恒定镇静水平所需的咪达唑仑血浆浓度差异很大，临床医生通常更谨慎的做法是使用经过验证的临床量表监测镇静情况，而不是仅依靠血浆浓度。各种生理参数，包括年龄相关影响、肾功能受损和肝功能障碍，都会影响咪达唑仑和α1-羟基咪达唑仑的药代动力学。虽然不建议对所有接受咪达唑仑治疗的危重症患者进行常规药物监测，但这种做法可能对无法评估镇静情况的神经损伤患者以及苏醒时间延长的肾衰竭患者有益。
