title: Perioperative doses of ondansetron or dolasetron do not lengthen the QT interval.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anesthesiology and Perioperative Medicine and the Center for Diabetes and Obesity Research, University of Louisville, Louisville, KY. Electronic address: d.obal@louisville.edu.
authors.forename: Detlef
authors.initials: D
authors.lastname: Obal
authors.affiliation: Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH; Department of Outcomes Research, Cleveland Clinic, Cleveland, OH.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Outcomes Research, Cleveland Clinic, Cleveland, OH.
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Sessler
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D008133:Long QT Syndrome / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D017294:Ondansetron / Q000008:administration & dosage*; D011183:Postoperative Complications / Q000517:prevention & control*; D011184:Postoperative Period; D011300:Preoperative Care; D011807:Quinolizines / Q000008:administration & dosage*; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D007211:Indoles; D011807:Quinolizines; D058831:Serotonin 5-HT3 Receptor Antagonists; D017294:Ondansetron; C060344:dolasetron
keywords: 5HT3R; ASA; American Society for Anesthesiologists; BMI; ECG; FDA; Food and Drug Administration; MAC; PACU; QTc; body mass index; electrocardiogram; minimum alveolar concentration; postanesthesia care unit; rate-corrected QT electrocardiographic interval; serotonin-3 receptor