Department of Anesthesiology and Perioperative Medicine and the Center for Diabetes and Obesity Research, University of Louisville, Louisville, KY.
Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH; Department of Outcomes Research, Cleveland Clinic, Cleveland, OH.
Mayo Clin Proc. 2014 Jan;89(1):69-80. doi: 10.1016/j.mayocp.2013.10.008.
To test the primary hypothesis that ondansetron or dolasetron extends the rate-corrected QT electrocardiographic interval (QTc) greater than 60 milliseconds or increases the fraction of patients with QTc greater than 500 milliseconds in patients having noncardiac surgery, and the secondary hypothesis that QTc prolongation is worse in diabetic patients.
We extracted data from the Cleveland Clinic's Perioperative Health Documentation System between March 25, 2006, and September 30, 2010, and additional perioperative medications from Cleveland Clinic pharmacy's Epic Cost of Goods Sold (COGS) system. We searched for patients who had a preoperative electrocardiogram within 1 month of surgery and postoperatively within 2 hours. We excluded patients given an antiemetic drug other than ondansetron or dolasetron perioperatively, and those given amiodarone.
A total of 1429 patients given serotonin-3 receptor (5HT3R) antagonists and 1022 controls met the enrollment criteria. Seventeen percent of patients given 5HT3R antagonists (n=242) and 22% of controls (n=220) had postoperative QTc exceeding 500 milliseconds. Mean ± SD presurgical and postsurgical QTc, respectively, were 438±37 milliseconds and 464±41 milliseconds for 5HT3R antagonist patients and 443±40 milliseconds and 469±47 milliseconds for control patients. Univariable mean ± SD perioperative increases in QTc were 26±39 and 26±48 milliseconds in the 2 groups. After adjusting for confounding variables, there were no differences in the mean increase in QTc in patients who were and were not given 5HT3R antagonists: -0.1 milliseconds (97.5% CI, -5.2 to 5.0 milliseconds; multivariable P=.97). The QTc was prolonged, but not significantly, in diabetic patients given 5HT3R antagonists (P=.16).
The average QTc prolongation from baseline was only 6%. Perioperative use of ondansetron or dolasetron was not associated with extended QT prolongation, and these results did not vary by diabetic status. Perioperative use of 5HT3R antagonists does not produce potentially dangerous perioperative electrocardiographic changes and does not seem to warrant a drug safety warning from the Food and Drug Administration.
检验主要假设,即昂丹司琼或多拉司琼使校正心率的 QT 心电图间期(QTc)延长超过 60 毫秒,或使 QTc 大于 500 毫秒的患者比例增加,在接受非心脏手术的患者中,以及次要假设,即糖尿病患者的 QTc 延长更严重。
我们从 2006 年 3 月 25 日至 2010 年 9 月 30 日期间从克利夫兰诊所的围手术期健康文档系统中提取数据,并从克利夫兰诊所药房的 Epic 商品销售成本 (COGS) 系统中提取围手术期的其他药物信息。我们搜索了术前 1 个月内和术后 2 小时内进行心电图检查的患者。我们排除了围手术期给予昂丹司琼或多拉司琼以外的止吐药的患者,以及给予胺碘酮的患者。
共有 1429 名接受 5-羟色胺 3 受体(5HT3R)拮抗剂的患者和 1022 名对照者符合入选标准。接受 5HT3R 拮抗剂的患者中有 17%(n=242)和对照组有 22%(n=220)的患者术后 QTc 超过 500 毫秒。5HT3R 拮抗剂患者的术前和术后平均(SD)QTc 分别为 438±37 毫秒和 464±41 毫秒,对照组分别为 443±40 毫秒和 469±47 毫秒。两组围手术期 QTc 的平均(SD)增加分别为 26±39 和 26±48 毫秒。在校正混杂变量后,接受和未接受 5HT3R 拮抗剂的患者的 QTc 平均增加无差异:-0.1 毫秒(97.5%CI,-5.2 至 5.0 毫秒;多变量 P=.97)。接受 5HT3R 拮抗剂的糖尿病患者的 QTc 延长,但无统计学意义(P=.16)。
从基线开始的平均 QTc 延长仅为 6%。围手术期使用昂丹司琼或多拉司琼与 QT 延长无关,且这些结果不受糖尿病状态的影响。围手术期使用 5HT3R 拮抗剂不会产生潜在危险的围手术期心电图变化,似乎不需要美国食品和药物管理局发出药物安全性警告。