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

^* 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{at}iupui.edu

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.

Key Words: action potentials • arrhythmia • dogs • electrophysiology • haloperidol • QT intervals • torsades de pointes