The effect of magnesium sulfate administration on cerebral and cardiac toxicity of bupivacaine in dogs

Abstract

The effect of acutely elevated serum magnesium on the CNS and cardiac toxicity of bupivacaine was studied. Anesthesia was induced in mongrel dogs with thiopental, 25 mg/kg, and ventilation was controlled. Sedation was maintained with fentanyl (25 μg/kg bolus and 5 μg·kg-1 h-1) and pancuronium (0.15 mg/kg bolus and 0.05 mg·kg-1 h-1) provided paralysis. Two hours after thiopental bolus, all animals received an intravenous (iv) infusion of bupivacaine (1 mg·kg-1 min-1). The control group (5 animals) received bupivacaine only. The Mg++ group (5 animals) received MgSO4 140 mg/kg iv and 80 mg·kg-1 h-1 15 min prior to beginning the bupivacaine infusion. Lead II ECG, cardiac hemodynamics, and two-channel EEG were continuously monitored. Serum magnesium concentrations in the Mg++ group rose from 0.67 mM (1.3 mEq/L) to 2.42 mM (4.8 mEq/L). The bupivacaine infusion caused PR and QRS interval prolongation in both groups, but QRS widening was greater in the control group. QT interval corrected for heart rate (QTI(c)) lengthened only in the control group. A depression of left ventricular stroke work index (LVSWI) occurred to an equal extent in both groups. The seizure dose of bupivacaine was not different between the two groups: 12.9 ± 2.3 (SEM) mg/kg in the control group and 13.9 ± 2.5 mg/kg in the Mg++ group. This corresponded to plasma bupivacaine concentrations of 12.2 ± 1.8 μg/ml and 12.8 ± 1.4 μg/ml in the control and Mg++ groups, respectively. Serious cardiac dysrhythmias occurred at an average bupivacaine dose of 9.5 ± 1.7 mg/kg in the control group but did not occur at all in four of five animals in the Mg++ group before cardiovascular collapse. Magnesium has cardiac electrophysiologic effects that may explain its ability to suppress bupivacaine-induced cardiac dysrhythmias.