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Correspondence  |   February 2006
Drug-induced Prolongation of the QT Interval: What’s the Point?
Author Affiliations & Notes
  • Paul F. White, Ph.D., M.D., F.A.N.Z.C.A.
    *
  • *University of Texas Southwestern Medical Center, Dallas, Texas.
Article Information
Correspondence
Correspondence   |   February 2006
Drug-induced Prolongation of the QT Interval: What’s the Point?
Anesthesiology 2 2006, Vol.104, 386-387. doi:
Anesthesiology 2 2006, Vol.104, 386-387. doi:
To the Editor:—
In his recent editorial,1 Scuderi appropriately suggested that the action of the US Food and Drug Administration (FDA) in placing a “black box” on the use of low-dose droperidol for the treatment and prevention of postoperative nausea and vomiting “is clearly specious and does a tremendous disservice to the American public.”
Although the editorial is excellent, it incorrectly stated that White et al.  2 “demonstrated a prolongation of QTc when droperidol (either 0.625 or 1.25 mg) is administered intravenously” for antiemetic prophylaxis. In fact, the effect of low-dose droperidol was not found to be different from saline (placebo). Given the rigid position taken by the FDA decision makers in this matter, these findings clearly do not simply “restate the obvious” in their mind. In performing our recently published study,2 we encountered a patient with sinus bradycardia and a corrected “baseline” QT interval of 419 ms on her 12-lead preoperative screening electrocardiographic tracing. According to Liu and Juurlink,3 the corrected QT interval is considered to be prolonged if it is greater than 450 ms in men or greater than 460 ms in women. Although she was not entered into the study and did not receive any antiemetic or antibiotic drugs known to prolong the QT interval during surgery, we performed serial 12-lead electrocardiographic tracings after surgery. On arrival in the recovery room after the patient underwent a superficial operation for removal of a small mass in her neck with use of a propofol–remifentanil intravenous anesthetic technique, the QTc was found to be prolonged to 685 ms. Subsequent 12-lead electrocardiographic tracings at hourly intervals before discharge revealed QTc values of 720, 615, 742, and 641 ms at 1, 2, 3, and 4 h after surgery, respectively. The patient’s postoperative recovery was completely uneventful, and she was discharged home despite the persistently prolonged QTc interval. If this patient had received droperidol (or one of the 5-hydroxytryptamine type 3 antagonists4) for antiemetic prophylaxis, this otherwise “unexplained” prolongation of the QTc interval in the postoperative period would almost certainly have been incorrectly ascribed to the antiemetic drug.
In a recent perspective on drugs and the QT interval, Liu and Juurlink3 stated that “most of what is known about drug-induced QT-interval prolongation derives from spontaneous reporting mechanisms.” Unfortunately, these anecdotal reports are not subject to peer-review, and other potential causative factors for a resultant dysrhythmia are often overlooked. Analogous to the widely used antibiotic erythromycin, droperidol has been successfully used by anesthesiologists for the treatment and prevention of postoperative nausea and vomiting in millions of patients during the past 30+ years.5,6 As a result of the FDA-imposed “black box” warning mandating additional electrocardiographic monitoring when this cost-effective antiemetic is administered, droperidol has been effectively eliminated from the anesthesiologist’s armamentarium at many medical centers in this country and abroad. As pointed out by Roden7 in his recent review article on drug-induced prolongation of the QT interval, “since rare side effects occur with many otherwise highly-effective drugs, their withdrawal from the market probably harms more patients than it helps.”
In the opinion of many clinicians around the world, the FDA’s recent obsession with drug-induced QT prolongation is an example of “making a mountain out of a molehill.”8 Could someone please explain the basis for the FDA’s preoccupation with an apparent nonproblem  of QT prolongation in the population at large?
*University of Texas Southwestern Medical Center, Dallas, Texas.
References
Scuderi PE: You (still) can’t disprove the existence of dragons. Anesthesiology 2005; 102:1081–2Scuderi, PE
White PF, Song D, Abrao J, Klein KW, Navarette B: Effect of low-dose droperidol on the QT interval during and after general anesthesia: A placebo-controlled study. Anesthesiology 2005; 102:1101–5White, PF Song, D Abrao, J Klein, KW Navarette, B
Liu B, Juurlink DN: Drugs and the QT interval: Caveat doctor. N Engl J Med 2004; 351:1053–96Liu, B Juurlink, DN
Charbit B, Albaladejo P, Funck-Brentano C, Legrand M, Samain E, Marty J: Prolongation of QTc interval after postoperative nausea and vomiting treatment by droperidol or ondansetron. Anesthesiology 2005; 102:1094–100Charbit, B Albaladejo, P Funck-Brentano, C Legrand, M Samain, E Marty, J
White PF: Droperidol: A cost-effective antiemetic for over thirty years. Anesth Analg 2002; 95:789–90White, PF
Apfel CC, Korttila K, Abdalla M, Kerger H, Turan A, Vedder I, Zernak C, Danner K, Jokela R, Pocock SJ, Trenkler S, Kredel M, Biedler A, Sessler DI, Roewer N, IMPACT Investigators: A factorial trial of six interventions for prevention of postoperative nausea and vomiting. N Engl J Med 2004; 350:2441–51Apfel, CC Korttila, K Abdalla, M Kerger, H Turan, A Vedder, I Zernak, C Danner, K Jokela, R Pocock, SJ Trenkler, S Kredel, M Biedler, A Sessler, DI Roewer, N IMPACT Investigators,
Roden DM: Drug-induced prolongation of the QT interval. N Engl J Med 2004; 350:1013–22Roden, DM
Bailey P, White PF: Droperidol editorial: Making a mountain out of a molehill! (letter). Anesthesiology 2003; 99:760–1Bailey, P White, PF