Premedication with oral dexmedetomidine alters hemodynamic actions of intravenous anesthetic agents in chronically instrumented dogs

Abstract

Dexmedetomidine (the D-stereoisomer of medetomidine), a highly selective α2-adrenoceptor agonist, has been demonstrated to produce analgesia and sedation and attenuate hemodynamic responses to emergence from inhalational anesthetics, which suggests a potential use for this drug as a premedicant for general anesthesia. The authors examined hemodynamic interactions between dexmedetomidine and three commonly used intravenous anesthetic agents with markedly different hemodynamic effects. Conscious, chronically instrumented dogs received intravenous induction doses of ketamine, propofol, or etomidate, followed by continuous infusions of each drug at four different doses for 15-min intervals on different days. Studies in six separate groups (range, 9-12 dogs/group) with and without pretreatment with oral dexmedetomidine (20 μg/kg) were completed. Heart rate, arterial pressure, left ventricular pressure, rate of increase of left ventricular pressure at 50 mmHg (dP/dt50), and cardiac output were continuously recorded. Dexmedetomidine administration caused a significant (P < 0.05) decrease in heart rate, rate-pressure product, left ventricular dP/dt50, and cardiac output. Dexmedetomidine abolished or attenuated the increase in heart rate, rate-pressure product, cardiac output, and arterial pressure produced during induction of anesthesia with ketamine. After the dexmedetomidine pretreatment, continuous infusion of ketamine caused no increase in heart rate or rate-pressure product. However, ketamine significantly reduced left ventricular dP/dt50 compared to control in dogs premedicated with dexmedetomidine. Except for a significant reduction in systemic vascular resistance, dexmedetomidine did not significantly affect the hemodynamic response to induction of anesthesia with propofol. Similarly, dexmedetomidine did little to alter the hemodynamic response to induction of anesthesia with etomidate. However, in the presence of dexmedetomidine, infusion of etomidate increased systemic vascular resistance and arterial pressure compared to unpremedicated dogs. The results demonstrate that oral dexmedetomidine administered 1 h before intravenous induction with ketamine may alter the hemodynamic response observed with these anesthetics. This may provide beneficial actions in certain patients, but caution should be used in patients in whom an increase or maintenance of sympathetic tone during induction of anesthesia with ketamine is desirable. In addition, in certain patients, large increases in peripheral vascular resistance during combined administration of dexmedetomidine and etomidate may be detrimental.