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体外治疗钙通道阻滞剂中毒:EXTRIP 工作组的系统评价和建议。

Extracorporeal treatment for calcium channel blocker poisoning: systematic review and recommendations from the EXTRIP workgroup.

机构信息

Austin Toxicology Unit and Emergency Department, Victorian Poisons Information Centre, Austin Health, Heidelberg, Victoria, Australia.

Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.

出版信息

Clin Toxicol (Phila). 2021 May;59(5):361-375. doi: 10.1080/15563650.2020.1870123. Epub 2021 Feb 8.

Abstract

BACKGROUND

Calcium channel blockers (CCBs) are commonly used to treat conditions such as arterial hypertension and supraventricular dysrhythmias. Poisoning from these drugs can lead to severe morbidity and mortality. We aimed to determine the utility of extracorporeal treatments (ECTRs) in the management of CCB poisoning.

METHODS

We conducted systematic reviews of the literature, screened studies, extracted data, summarized findings, and formulated recommendations following published EXTRIP methods.

RESULTS

A total of 83 publications (6 and 1 animal experiments, 55 case reports or case series, 19 pharmacokinetic studies, 1 cohort study and 1 systematic review) met inclusion criteria regarding the effect of ECTR. Toxicokinetic or pharmacokinetic data were available on 210 patients (including 32 for amlodipine, 20 for diltiazem, and 52 for verapamil). Regardless of the ECTR used, amlodipine, bepridil, diltiazem, felodipine, isradipine, mibefradil, nifedipine, nisoldipine, and verapamil were considered not dialyzable, with variable levels of evidence, while no dialyzability grading was possible for nicardipine and nitrendipine. Data were available for clinical analysis on 78 CCB poisoned patients (including 32 patients for amlodipine, 16 for diltiazem, and 23 for verapamil). Standard care (including high dose insulin euglycemic therapy) was not systematically administered. Clinical data did not suggest an improvement in outcomes with ECTR. Consequently, the EXTRIP workgroup recommends against using ECTR in addition to standard care for patients severely poisoned with either amlodipine, diltiazem or verapamil (strong recommendations, very low quality of the evidence (1D)). There were insufficient clinical data to draft recommendation for other CCBs, although the workgroup acknowledged the low dialyzability from, and lack of biological plausibility for, ECTR.

CONCLUSIONS

Both dialyzability and clinical data do not support a clinical benefit from ECTRs for CCB poisoning. The EXTRIP workgroup recommends against using extracorporeal methods to enhance the elimination of amlodipine, diltiazem, and verapamil in patients with severe poisoning.

摘要

背景

钙通道阻滞剂(CCBs)常用于治疗动脉高血压和室上性心律失常等疾病。这些药物中毒可导致严重的发病率和死亡率。我们旨在确定体外治疗(ECTR)在 CCB 中毒管理中的作用。

方法

我们对文献进行了系统评价,筛选研究,提取数据,总结发现,并按照已发表的 EXTRIP 方法制定建议。

结果

共有 83 篇出版物(6 篇和 1 篇动物实验,55 篇病例报告或病例系列,19 项药代动力学研究,1 项队列研究和 1 项系统评价)符合 ECTR 效果的纳入标准。关于 210 名患者(包括氨氯地平 32 名,地尔硫卓 20 名,维拉帕米 52 名)的毒代动力学或药代动力学数据可用。无论使用何种 ECTR,氨氯地平、贝普地尔、地尔硫卓、非洛地平、伊拉地平、米贝地尔、硝苯地平、尼索地平、和维拉帕米被认为不可透析,证据水平各不相同,而对于尼卡地平、尼群地平则无法进行透析能力分级。对 78 名 CCB 中毒患者(包括氨氯地平 32 名患者,地尔硫卓 16 名患者,维拉帕米 23 名患者)进行了临床分析。未系统给予标准护理(包括高剂量胰岛素血糖控制治疗)。临床数据并未表明 ECTR 可改善预后。因此,EXTRIP 工作组建议在标准护理的基础上,对严重中毒的氨氯地平、地尔硫卓或维拉帕米患者不使用 ECTR(强烈建议,证据质量非常低(1D))。由于缺乏临床数据,工作组虽然承认 ECTR 的透析能力低,生物学上不合理,但无法为其他 CCB 制定建议。

结论

可透析性和临床数据均不支持 ECTR 对 CCB 中毒的临床益处。EXTRIP 工作组建议对严重中毒的患者不使用体外方法来增强对氨氯地平、地尔硫卓和维拉帕米的清除。

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