MAGNESIUM POTENTIATES KETAMINE-INDUCED CHANGES IN THE THRESHOLD FOR ISOFLURANE ANESTHESIA IN THE RAT

Abstract

S354 INTRODUCTION: Magnesium sulfate (MgSO4), used in obstetrics to inhibit premature labor and in the therapy of pre-eclampsia and eclampsia, has been demonstrated to alter the minimum alveolar concentration (MAC) of halothane at clinically relevant concentrations [1]. The interactions of ketamine and volatile anesthetics have been reported previously [2]. This study was undertaken to examine the potential anesthetic interactions of MgSO4 and ketamine during isoflurane anesthesia. METHODS: After institutional animal care committee approval had been obtained, we examined the reduction of the MAC of isoflurane in response to increasing doses of ketamine and in the presence and absence of elevated serum magnesium concentrations. Briefly, forty-six male Sprague-Dawley rats were anesthetized with isoflurane in oxygen. Control MAC was established according to the methods reported previously [3]. Following the administration of either ketamine (10, 25, 50, 75, or 100 mg/kg via i.v. injection), or MgSO4 (at a rate of 5.0 mg/kg/min for at least 30 min), or both MgSO4 and ketamine (10, 25, or 50 mg/kg), isoflurane MAC was again determined. Alveolar gas concentrations, hemodynamic monitoring, and arterial blood gas measurements were obtained as described previously [3]. RESULTS: Ketamine dose-dependently reduced the MAC for isoflurane (39.6 +/- 5.7% at the 100 mg/kg dose), while exhibiting no ceiling effect. MgSO4 produced an approximately 14% reduction in the MAC for isoflurane at plasma concentrations of 6 to 8 mg/dL. The combination of MgSO4 and ketamine resulted in a significant enhancement in the isoflurane MAC reduction, which was especially pronounced at the lower ketamine concentrations. (Figure 1)Figure 1DISCUSSION: We confirmed the MAC reducing effect of MgSO4, as was previously shown for halothane anesthesia. Ketamine dosedependently reduced the MAC for isoflurane, however, 2 of 4 animals died at the highest dose (100 mg/kg). This is consistent with the LD50 of ketamine in rats. The significant enhancement in the isoflurane MAC reduction by the combination of MgSO4 and ketamine, which was especially pronounced at the lower ketamine concentrations, was devoid of any significant side effects and was hemodynamically well tolerated. The mechanism of this enhanced MAC reduction is under further investigation. Supported by a FAER/Zeneca Anesthesiology Young Investigator Award