Lovell Amanda G, Protus Bridget McCrate, Saphire Maureen L, Kale Sachin S, Lehman Amy, Hartman Amber
1 Optum Hospice Pharmacy Services, Westerville, OH, USA.
2 The Arthur G. James Cancer Hospital, Richard Solove Research Institute, The Ohio State University, Columbus, OH, USA.
Am J Hosp Palliat Care. 2019 Mar;36(3):177-184. doi: 10.1177/1049909118811904. Epub 2018 Nov 14.
: The effect of methadone on corrected QT interval (QTc) in patients with cancer pain is not well-known.
: To describe and characterize the effect of low-, moderate-, and high-dose enteral methadone on QTc interval in patients with cancer.
: Retrospective cohort study including patients prescribed enteral methadone during the 27-month study period. Participants were divided into 3 methadone daily dose groups: <30 (low dose), 30 to 59 (moderate dose), ≥60 (high dose) mg. The primary outcome was the incidence of QTc prolongation (>450 ms for females and >430 ms for males). Secondary outcomes included the magnitude of change in QTc after starting methadone, the incidence of clinically significant QTc prolongation (>500 ms) and the prevalence of torsades de pointes and syncope.
: Two hundred three patients met study inclusion criteria: 91 (45%) low dose, 52 (26%) moderate dose, and 60 (29%) high dose. Incidence of QTc prolongation for low-, moderate-, and high-dose groups was 50 (55%), 37 (71%), and 43 (72%), respectively ( P = .039, low vs high dose). Incidence of clinically significant QTc prolongation was 10 (11%), 4 (8%), and 7 (12%) for low-, moderate-, and high-dose groups. For patients without QTc prolongation prior to initiating methadone, 62% of moderate-dose patients and 67% of high-dose patients had QTc prolongation, while taking methadone.
: This study found a notably high incidence of QTc prolongation in patients with cancer using enteral methadone. Future studies should aim to determine the risk of adverse cardiac effects in the cancer population and determine appropriate monitoring of methadone for pain management.
美沙酮对癌症疼痛患者校正QT间期(QTc)的影响尚不明确。
描述并阐明低、中、高剂量肠内美沙酮对癌症患者QTc间期的影响。
回顾性队列研究,纳入在27个月研究期间接受肠内美沙酮治疗的患者。参与者被分为3个美沙酮每日剂量组:<30(低剂量)、30至59(中等剂量)、≥60(高剂量)mg。主要结局是QTc延长的发生率(女性>450 ms,男性>430 ms)。次要结局包括开始使用美沙酮后QTc的变化幅度、临床显著QTc延长(>500 ms)的发生率以及尖端扭转型室速和晕厥的患病率。
203例患者符合研究纳入标准:91例(45%)低剂量组,52例(26%)中等剂量组,60例(29%)高剂量组。低、中、高剂量组QTc延长的发生率分别为50例(55%)、37例(71%)和43例(72%)(P = 0.039,低剂量与高剂量组相比)。低、中、高剂量组临床显著QTc延长的发生率分别为10例(11%)、4例(8%)和7例(12%)。对于在开始使用美沙酮之前没有QTc延长的患者,62%的中等剂量患者和67%的高剂量患者在服用美沙酮时出现了QTc延长。
本研究发现癌症患者使用肠内美沙酮时QTc延长的发生率显著较高。未来的研究应旨在确定癌症人群中心脏不良事件的风险,并确定在疼痛管理中对美沙酮进行适当监测的方法。