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Prolongation of the QT Interval by Volatile Anesthetics in Chronically Instrumented Dogs

Received from the Departments of Pharmacology, Medicine, and Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin, and the Veterans Administration Medical Center, Milwaukee, Wisconsin.

Abstract

The influence of volatile anesthetics on ventricular repolarization in vivo (QT interval) has not been studied in a systematic fashion. The purpose of this investigation was to characterize the electrocardiographic and hemodynamic actions of the volatile anesthetics halothane, isoflurane, and enflurane in chronically instrumented dogs. Because autonomic nervous system tone may influence ECG findings, experiments were completed with and without concomitant pharmacologic autonomic nervous system blockade. In six groups comprising 50 experiments with 21 instrumented dogs, anesthesia was mask-induced with nitrous oxide, oxygen, and one of the volatile anesthetics and maintained with the volatile anesthetic in 100% oxygen for 2 hours. Changes in the ECG and in hemodynamics were compared to the conscious state. In the absence of autonomic nervous system blockade, halothane and isoflurane significantly prolonged the QT interval (0.24 ± 0.01 to 0.30 ± 0.01 second and 0.22 ± 0.01 to 0.28 ± 0.01 second, respectively), whereas enflurane produced no change in ventricular repolarization (0.24 ± 0.01 to 0.26 ± 0.01 second). All of the volatile anesthetics increased the QT interval corrected for changes in basal heart rate (QT_c,), and all agents decreased intravascular pressure and dP/dt. Following autonomic nervous system blockade, halothane, isoflurane, and enflurane significantly increased the QT interval and QT_c. The results demonstrate that ventricular repolarization is directly altered by the volatile anesthetics independent of changes in autonomic nervous tone. Whether or not such effects are additive with other congenital or acquired forms of QT_c, prolongation has yet to be examined. The present results indicate that caution should be used during the administration of volatile anesthetics to patients with abnormalities of the QT interval.

Key Words: ANESTHETICS, VOLATILE—enflurane, halothane, isoflurane • HEART, ELECTROCARDIOLOGY—QT interval

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