Retrospective analysis of the effects of cisapride on the QT interval and QT dispersion in chronic hemodialysis patients.
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.
Mathis
A S
AS
Department of Pharmacy Practice and Administration, College of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, USA. smathis@sbhcs.com
Costeas
C
C
Barone
J A
JA
D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000175:diagnosis; D020117:Cisapride; D000075202:Contraindications; D004347:Drug Interactions; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D005765:Gastrointestinal Agents; D005767:Gastrointestinal Diseases / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000097:blood; D006435:Renal Dialysis; D012189:Retrospective Studies
D005765:Gastrointestinal Agents; D011188:Potassium; D020117:Cisapride