Mater Misericordiae University Hospital, Dublin, Ireland.
Addiction. 2012 Jun;107(6):1132-9. doi: 10.1111/j.1360-0443.2011.03767.x. Epub 2012 Feb 28.
The aim of this study was to investigate the frequency of corrected QT interval (QTc) prolongation in a methadone maintenance therapy (MMT) population, and to examine potential associations between this QTc interval and methadone dose as well as concurrent use of opiates, cocaine and benzodiazepines.
Cross-sectional study of patients attending a specialist drug treatment clinic from July 2008 to January 2009.
Single-centre inner-city specialist drug treatment clinic, Ireland.
A total of 180 patients on stable MMT attending for daily methadone doses, over a 6-month period, where a total of 376 patients were attending during the study period.
All patients agreeing to participate in the study underwent 12-lead electrocardiograms and QTc analysis, as well as analysis of urine toxicology screen results for opiates, benzodiazepines and cocaine. ECGs were carried out prior to methadone dose being received, regardless of time of day (trough ECG).
The average age was 32.6 ± 7.1 years, with mean [standard deviation (SD)] methadone dose 80.4 ± 27.5 mg. The mean (SD) QTc was 420.9 ± 21.1 ms, range 368-495 ms. Patients who had a positive toxicology screen for opiates were receiving significantly lower doses of methadone (77.8 ± 23.5 mg versus 85.0 ± 21.4 mg, P = 0.04). No significant association was noted between QTc interval prolongation and presence of cocaine metabolites in the urine (P = 0.13) or methadone dose (P = 0.33). 8.8% of patients had evidence of prolonged QTc interval (8.3% male QTc ≥ 450 ms and 0.5% female QTc ≥ 470 ms), with 11.1% (n = 20) having QTc intervals > 450 ms.
Drug-induced corrected QT interval prolongation is evident (ranging from 8.8-11.1%, depending on definition applied) in patients receiving relatively low daily doses of methadone therapy, with no evidence of a dose-response relationship. The presence of cocaine metabolites in urine does not appear to be associated with increased corrected QT interval. Increased awareness of cardiac safety guidelines, including relevant clinical and family history, baseline and trough dose ECG monitoring, should be incorporated into methadone maintenance therapy protocols.
本研究旨在调查美沙酮维持治疗（MMT）人群中校正 QT 间期（QTc）延长的频率，并探讨该 QTc 间期与美沙酮剂量以及阿片类药物、可卡因和苯二氮䓬类药物同时使用之间的潜在关联。
2008 年 7 月至 2009 年 1 月期间，对参加专门药物治疗诊所的患者进行横断面研究。
爱尔兰市中心专门药物治疗诊所。
在研究期间，共有 180 名接受稳定美沙酮治疗的患者接受了每日美沙酮剂量，共有 376 名患者在研究期间接受了治疗。
所有同意参加研究的患者均接受了 12 导联心电图和 QTc 分析，以及阿片类药物、苯二氮䓬类药物和可卡因尿液毒理学检测结果分析。在接受美沙酮剂量之前进行心电图检查，无论一天中的时间如何（谷底心电图）。
患者平均年龄为 32.6 ± 7.1 岁，平均（标准差）美沙酮剂量为 80.4 ± 27.5mg。平均（标准差）QTc 为 420.9 ± 21.1ms，范围 368-495ms。阿片类药物毒理学检测呈阳性的患者接受的美沙酮剂量明显较低（77.8 ± 23.5mg 与 85.0 ± 21.4mg，P=0.04）。尿液中可卡因代谢物的存在与 QTc 间期延长之间没有显著关联（P=0.13）或美沙酮剂量（P=0.33）。8.8%的患者存在 QTc 间期延长的证据（8.3%的男性 QTc≥450ms，0.5%的女性 QTc≥470ms），11.1%（n=20）的患者 QTc 间期>450ms。
在接受相对较低的每日美沙酮治疗剂量的患者中，药物引起的校正 QT 间期延长是明显的（范围为 8.8-11.1%，具体取决于应用的定义），且没有剂量-反应关系的证据。尿液中可卡因代谢物的存在似乎与校正 QTc 间期延长无关。应将对心脏安全性指南的认识，包括相关的临床和家族史、基线和谷底剂量心电图监测纳入美沙酮维持治疗方案中。
