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Laboratory and Animal Investigations |

Influence of IV Haloperidol on Ventricular Repolarization and Monophasic Action Potential Duration in Anesthetized Dogs*

Saeed Rasty, PharmD; Neeta B. Amin, PharmD; Hani N. Sabbah, PhD, FCCP; Takayuki Mishima, MD; Steven Borzak, MD; James E. Tisdale, PharmD
Author and Funding Information

*From the Department of Pharmacy Services (Drs. Rasty, Amin, and Tisdale), Division of Cardiovascular Research (Drs. Mishima and Sabbah), and the Henry Ford Heart & Vascular Institute (Dr. Borzak), Henry Ford Hospital and the Eugene Applebaum College of Pharmacy & Health Sciences, Wayne State University (Dr. Tisdale), Detroit, MI.

Correspondence to: James Tisdale, PharmD, Department of Pharmacy Practice, School of Pharmacy and Pharmacal Sciences, Purdue University, W7555, Myers Building, 1001 West Tenth St, Indianapolis, IN 46202; e-mail: jtisdale@iupui.edu



Chest. 2004;125(5):1821-1829. doi:10.1378/chest.125.5.1821
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Introduction: IV haloperidol is used commonly for sedation in critically ill patients. However, IV haloperidol has been shown to cause the life-threatening ventricular tachyarrhythmia torsades de pointes. Mechanisms by which haloperidol causes torsades de pointes have not been widely investigated in controlled studies.

Study objectives: To determine the effects of IV haloperidol on electrophysiologic parameters known to promote torsades de pointes.

Interventions: Monophasic action potential catheters were guided under fluoroscopy into the right and left ventricles of 14 chloralose-anesthetized dogs (haloperidol, nine dogs; placebo, five dogs). Effective refractory period (ERP), action potential duration at 90% repolarization (APD90), and QTc interval measurements were performed at baseline and after each of four doses of haloperidol (0.15, 0.5, 2.0, and 3.0 mg/kg) or placebo at three different pacing cycle lengths (450, 300, and 250 ms).

Measurements and results: IV haloperidol significantly prolonged left and right ventricular ERP by a magnitude of 12 to 20% at all pacing cycle lengths. ERP values in the placebo group did not change significantly from pretreatment values in either ventricle. Haloperidol significantly prolonged left ventricular APD90 at a pacing cycle length of 300 ms. The effects of haloperidol on right ventricular APD90 approached significance at a cycle length of 450 ms. Overall, haloperidol prolonged APD90 by 7 to 11%, with less consistent and more variable effects than those for the ERP. APD90 was not significantly altered in the placebo groups. Haloperidol produced significant prolongation in QTc intervals. The electrophysiologic effects of haloperidol were related to dose, with a plateau reached at the 0.5 mg/kg dose for ERP measurements and at the 2 mg/kg dose for the APD90 and QTc interval measurements.

Conclusions: IV haloperidol prolongs ventricular ERP and APD90 in intact canine hearts. These electrophysiologic effects are likely associated with the clinical torsades de pointes-inducing actions of IV haloperidol in critically ill patients.

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