西沙必利对慢性血液透析患者QT间期及QT离散度影响的回顾性分析。

Mathis A S, Costeas C, Barone J A

Department of Pharmacy Practice and Administration, College of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, USA.

Am J Kidney Dis. 2001 Dec;38(6):1284-91. doi: 10.1053/ajkd.2001.29226.

Cisapride is contraindicated in patients with end-stage renal disease (ESRD) and gastrointestinal motility disorders. Ventricular arrhythmias have been associated with both cisapride and hemodialysis (HD). However, reports conflict regarding the safety of cisapride in HD patients. We undertook this study to characterize the effects of cisapride on QT intervals and QT dispersion (QTD) in HD patients. Baseline and steady-state electrocardiograms (ECGs) were retrospectively selected for calendar year 1999 for each patient administered cisapride if ECGs showed sinus rhythm, potassium level was 3.5 mEq/dL or greater, and there was no pharmacokinetic drug interaction. QT intervals were measured by two investigators, and QTDs were calculated (maximum [QT(max)] - minimum QT interval [QT(min)]). Averages between investigator measures (+/- SD), presented for each value, were evaluated using Wilcoxon's signed-rank test. Thirty-one HD patients were administered cisapride. Seventeen patients failed to meet entry criteria, and no patient had a pharmacokinetic drug interaction. In included patients (6 men, 8 women), heart rates were 86.71 +/- 20.87 beats/min at baseline and 86.57 +/- 14.23 beats/min during treatment (P = not significant). Serum potassium levels were 4.97 +/- 1.2 mEq/dL at baseline and 4.94 +/- 0.76 mEq/dL during treatment (P = not significant). Average baseline QT(max) and QT(min) were 391.07 +/- 42.43 and 330.71 +/- 40.94 milliseconds, respectively. Treatment QT(max) and QT(min) were 391.43 +/- 38.2 and 343.93 +/- 35.69 milliseconds, respectively (P = not significant for both). QTD was 60.36 +/- 17.59 milliseconds at baseline and 47.5 +/- 19.59 milliseconds during treatment (P = 0.074). Mean corrected QT (QTc) intervals increased from 426.57 +/- 26.62 to 431.71 +/- 29.98 milliseconds (P = 0.55) from baseline to treatment. No ventricular arrhythmia was observed during at least 160 days (range, 2 to 830 days) of cisapride exposure. Two patients died during this study, both of other causes 4 days after discontinuing cisapride therapy. Cisapride did not significantly increase mean QTc interval, QT(max), or QTD in patients with ESRD managed by HD when potassium levels were stable and pharmacokinetic drug interactions were avoided.

西沙必利禁用于终末期肾病（ESRD）和胃肠动力障碍患者。室性心律失常与西沙必利和血液透析（HD）均有关联。然而，关于HD患者使用西沙必利的安全性，报告存在矛盾。我们开展这项研究以明确西沙必利对HD患者QT间期和QT离散度（QTD）的影响。回顾性选取1999年每位接受西沙必利治疗患者的基线和稳态心电图（ECG），条件为ECG显示窦性心律、血钾水平为3.5 mEq/dL或更高且无药代动力学药物相互作用。QT间期由两名研究者测量，并计算QTD（最大[QT(max)] - 最小QT间期[QT(min)]）。对每个值给出的研究者测量值之间的平均值（±标准差），使用Wilcoxon符号秩检验进行评估。31例HD患者接受了西沙必利治疗。17例患者未达到入选标准，且无患者存在药代动力学药物相互作用。在纳入的患者（6例男性，8例女性）中，基线时心率为86.71±20.87次/分钟，治疗期间为86.57±14.23次/分钟（P = 无显著性差异）。基线时血清钾水平为4.97±1.2 mEq/dL，治疗期间为4.94±0.76 mEq/dL（P = 无显著性差异）。平均基线QT(max)和QT(min)分别为391.07±42.43和330.71±40.94毫秒。治疗期间QT(max)和QT(min)分别为391.43±38.2和343.93±35.69毫秒（两者P均无显著性差异）。基线时QTD为60.36±17.59毫秒，治疗期间为47.5±19.59毫秒（P = 0.074）。从基线到治疗，平均校正QT（QTc）间期从426.57±26.62增加到431.71±29.98毫秒（P = 0.55）。在至少160天（范围为2至830天）的西沙必利暴露期间未观察到室性心律失常。两名患者在本研究期间死亡，均在停用西沙必利治疗4天后因其他原因死亡。当血钾水平稳定且避免药代动力学药物相互作用时，西沙必利在接受HD治疗的ESRD患者中未显著增加平均QTc间期、QT(max)或QTD。