咪达唑仑与肝毒性

以下文章来源于小麻哥的日常 ，作者两只小绵羊

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前言  

咪达唑仑是一种静脉注射的苯二氮卓类药物，用作小手术清醒镇静的麻醉剂和全身麻醉的辅助药物。咪达唑仑与治疗期间血清转氨酶升高无关，也与临床上明显的肝损伤病例无关。

背景  

咪达唑仑是一种苯二氮卓类药物，具有特别有效的镇静活性。 苯 二氮卓类药物的镇静活性是由它们通过与GABA A受体结合来增强γ-氨基丁酸（GABA）介导的抑制突触传递的能力介导的。 咪达唑仑的使用主要作为静脉麻醉剂。 咪达唑仑用于短期门诊手术的清醒镇静，如上下内窥镜检查、支气管镜检查、肝活检和心导管插入术。 它还用于诱导全身麻醉和术前镇静。 咪 达唑仑与顺行性遗忘有关，通常便于进行不舒服的微创手术。 咪达唑仑一般（以前以Versed品牌名称）以注射剂型[1 mg/mL，1-、2-、5-和10 mL每瓶]、处置注射器以及作为围手术期儿科使用的口服溶液提供。 成人清醒镇静的典型剂量为 1-4 mg，静脉使用，持续 2-5 分钟。 静脉注射咪达唑仑的常见副作用包括恶心、低血压、意识模糊、急性躁动和呼吸抑制。 咪达唑仑急性过量可导致呼吸停止和死亡。 咪达唑仑在其产品标签中有一个关于使用后严重呼吸抑制风险的框框警告，一个关于与阿片类药物联合使用的警告，并且需要个性化剂量，监测呼吸和心脏状态，并提供复苏药物和设备。

肝毒性

与其他苯二氮卓类药物一样，咪达唑仑很少与血清ALT 或碱性磷酸酶升高相关。 尚未报告咪达唑仑引起的临床上明显的肝损伤，如果发生的话，一定是极其罕见的。 已有其他苯二氮卓类药物（包括阿普唑仑、利氮卓、氯硝西泮、地西泮、氟西泮、劳拉西泮和三唑仑）联合出现临床上明显肝损伤的孤立单一病例的报道。 苯二氮卓类药物急性肝损伤的临床模式通常是胆汁淤积，但氯拉西酯和氯硫西泮的肝细胞损伤模式已有报道。 损伤的严重程度通常为轻至中度，发病时间为 1-6 个月，停用苯二氮卓类药物后可迅速恢复。 发热和皮疹不常见，自身抗体形成也不常见。 可能性评分：E（不太可能的临床上明显肝损伤的原因）。

损伤机制

咪达唑仑被肝脏广泛代谢为无活性代谢物，这些代谢物在尿液中排泄。苯二氮卓类药物引起的肝损伤可能是由于很少产生的中间代谢物造成的。 没有肝损伤可能是由于治疗持续时间短和使用的剂量低。

结果和管理

在孤立的病例中，苯二氮卓类药物引起的肝损伤报告在停药后恢复迅速和完全，没有残留或慢性损伤的证据。尚无因咪达唑仑引起的急性肝炎、肝衰竭或慢性肝损伤的报道。没有关于与其他苯二氮卓类药物交叉反应的信息，但可能发生一定程度的交叉敏感性 。

原文

Midazolam

Last Update:June 22, 2023.

OVERVIEW

Introduction

Midazolam is an intravenously administered benzodiazepine used as an anesthetic for conscious sedation for minor procedures and as an adjunct for general anesthesia. Midazolam has not been associated with serum aminotransferase elevations during therapy and has not been linked to cases of clinically apparent liver injury.

Background

Midazolam (mi daz' oh lam) is a benzodiazepine with particularly potent sedative activity. The sedative activity of the benzodiazepines is mediated by their ability to enhance gamma-aminobutyric acid (GABA) mediated inhibition of synaptic transmission through binding to the GABA A receptor. The use of midazolam has been largely as an intravenous anesthetic agent. Midazolam is used for conscious sedation for short-term, outpatient procedures such as upper and lower endoscopy, bronchoscopy, liver biopsy and cardiac catheterization. It is also used for induction of general anesthesia and for preoperative sedation. Midazolam is associated with anterograde amnesia which is often convenient for uncomfortable, minimally invasive procedures. Midazolam is available generically (and formerly under the brand name Versed) in parenteral forms for injection [1 mg/mL in 1-, 2-, 5-, and 10-mL vials], in disposal syringes and as an oral solution for pediatric use perioperatively. The typical dose for conscious sedation in adults is 1 to 4 mg intravenously over 2 to 5 minutes. Common side effects of the use of intravenous midazolam include nausea, hypotension, confusion, acute agitation, and respiratory depression. Acute overdose of midazolam can cause respiratory arrest and death. Midazolam has a boxed warning in its product label about the risks of severe respiratory depression with its use, a warning against combined use with opiates, and need to individualize the dose, to monitor respiratory and cardiac status, and have resuscitative drugs and equipment available.

Hepatotoxicity

Midazolam, like other benzodiazepines, is rarely associated with serumALT or alkaline phosphatase elevations. Clinically apparent liver injury from midazolam has not been reported and must be extremely rare, if it occurs at all. Isolated single cases of clinically apparent liver injury have been reported with other benzodiazepines including alprazolam, chlordiazepoxide, clonazepam, diazepam, flurazepam, lorazepam, and triazolam. The clinical pattern of acute liver injury from benzodiazepines is typically cholestatic, but hepatocellular patterns of injury have been reported with clorazepate and clotiazepam. The injury is usually mild to moderate in severity with a time to onset of 1 to 6 months and rapid recovery once the benzodiazepine is stopped. Fever and rash are uncommon as is autoantibody formation.

Likelihood score: E (unlikely cause of clinically apparent liver injury).

Mechanism of Injury

Midazolam is extensively metabolized by the liver to inactive metabolites which are excreted in the urine. The liver injury from benzodiazepines is probably due to a rarely produced intermediate metabolite. The absence of liver injury is perhaps due to the short duration of therapy and low doses used.

Outcome and Management

In the isolated case reports of hepatic injury due to benzodiazepines recovery was rapid and complete after stopping the medication, without evidence of residual or chronic injury. No cases of acute hepatitis, liver failure, or chronic liver injury due to midazolam have been described. There is no information about cross reactivity with other benzodiazepines, but some degree of cross sensitivity may occur.

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本公众平台所刊载原创或转载内容不代表米勒之声的观点或立场。文中所涉及药物使用、疾病诊疗等内容仅供医学专业人士参考。

END

编辑：Michel.米萱

校对：MiLu.米鹭

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