Duceppe Marc-Alexandre, Perreault Marc M, Frenette Anne Julie, Burry Lisa D, Rico Philippe, Lavoie Annie, Gélinas Céline, Mehta Sangeeta, Dagenais Maryse, Williamson David R
Pharmacy Department, McGill University Health Centre, Montreal, Quebec, Canada.
Faculté de Pharmacie, Université de Montréal, Montreal, Quebec, Canada.
J Clin Pharm Ther. 2019 Apr;44(2):148-156. doi: 10.1111/jcpt.12787. Epub 2018 Dec 19.
Many critically ill patients are exposed to opioids and benzodiazepines at high doses for prolonged periods, and upon discontinuation of these drugs, they may be at risk for iatrogenic withdrawal. Although this syndrome was associated with worse outcomes in the critically ill, limited guidance exists regarding its evaluation, prevention and treatment. This systematic review examined the frequency, risk factors and symptomatology of iatrogenic withdrawal from opioids and/or benzodiazepines in critically ill neonates, children and adults.
The literature search was conducted in PubMed, Medline, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane register of systematic reviews, DARE, CINAHL, Trip database, CMA infobase and NICE evidence from inception to February 2018. Grey literature was examined. We included studies reporting frequency, risk factors or symptomatology of iatrogenic withdrawal of opioids, benzodiazepines (or both) in critically ill patients. We considered all study designs except case reports and case series. We excluded studies on neonatal abstinence syndrome, alcohol withdrawal, studies on chronic opioid and/or benzodiazepine users and studies on prevention or treatment of withdrawal in critical care patients. Two independent reviewers applied the inclusion and exclusion criteria. Pairs of reviewers independently abstracted data and evaluated methodological quality using the Cochrane Collaboration Tool, Newcastle-Ottawa or QUADAS-2. Details regarding study design, outcomes, definition, evaluation and type of withdrawal (opioid, benzodiazepine or mixed) were collected. Cumulative doses and duration of opioids and benzodiazepines were collected.
We identified 21 866 unique citations and 153 full texts were assessed for eligibility. Thirty-four studies were included; the majority were observational and few included adults. In prospective studies, mixed withdrawal was observed in 7.5%-100% of patients in paediatric studies and ranged from 16.7% to 55% in adults. Symptomatology of withdrawal was not well described. Risk factors included higher cumulative dose and prolonged administration of opioids and benzodiazepines.
Iatrogenic withdrawal appears to be a frequent syndrome in critical care patients who received regular doses of opioids and/or benzodiazepines for ≥72 hours. Larger studies are required, especially in critically ill adults, to better define the syndrome and its symptomatology.
许多重症患者长时间大剂量使用阿片类药物和苯二氮䓬类药物，在停用这些药物后，可能面临医源性戒断风险。尽管这一综合征与重症患者的不良预后相关，但在其评估、预防和治疗方面的指导有限。本系统评价研究了重症新生儿、儿童和成人中阿片类药物和/或苯二氮䓬类药物医源性戒断的发生率、危险因素和症状。
在PubMed、Medline、EMBASE、Cochrane对照试验中心注册库、Cochrane系统评价注册库、DARE、CINAHL、Trip数据库、CMA信息库和NICE证据平台中进行文献检索，检索时间从建库至2018年2月。同时查阅灰色文献。纳入报告重症患者中阿片类药物、苯二氮䓬类药物（或两者）医源性戒断发生率、危险因素或症状的研究。除病例报告和病例系列外，考虑所有研究设计。排除关于新生儿戒断综合征、酒精戒断、慢性阿片类药物和/或苯二氮䓬类药物使用者的研究，以及关于重症监护患者戒断预防或治疗的研究。两名独立的评审员应用纳入和排除标准。评审员对独立提取的数据使用Cochrane协作工具、纽卡斯尔-渥太华量表或QUADAS-2评估方法学质量。收集有关研究设计、结果、定义、评估和戒断类型（阿片类、苯二氮䓬类或混合性）的详细信息。收集阿片类药物和苯二氮䓬类药物的累积剂量和使用持续时间。
我们识别出21866条独特的文献引用，对153篇全文进行了资格评估。纳入34项研究；大多数为观察性研究，很少有涉及成人的研究。在前瞻性研究中，儿科研究中7.5%-100%的患者出现混合性戒断，成人中这一比例为16.7%-55%。戒断症状描述不佳。危险因素包括阿片类药物和苯二氮䓬类药物的累积剂量较高以及使用时间延长。
医源性戒断似乎是接受常规剂量阿片类药物和/或苯二氮䓬类药物≥72小时的重症监护患者中常见的综合征。需要开展更大规模的研究，尤其是针对重症成人患者，以更好地定义该综合征及其症状。
