Severe Hypoxia Enhances Central Nervous System and Cardiovascular Toxicity of Bupivacaine in Lightly Anesthetized Pigs

Toxic systemic reactions to bupivacaine usually involve a number of factors, including hypoxia and acidosis. The objective of this study was to test the hypothesis that cardiovascular and central nervous system responses to bupivacaine overdose are proportional to the severity of hypoxia. The central nervous system and cardiovascular toxicity of bupivacaine was examined in three groups of pigs breathing 30%, 15%, or 10% O2, 70% N2O, and He (FIO2 = 0.15 and 0.1 groups). The 18 2-week-old pigs (6 animals per treatment) were paralyzed with pancuronium and their lungs ventilated mechanically. During the intravenous infusion of bupivacaine 2 mg.kg-1.min-1, four readily identified toxic endpoints (seizures, arrhythmias, isoelectric electroencephalogram, asystole) were observed in all animals, with the exception that 1 pig in the FIO2 = 0.3 group and 1 in the FIO2 = 0.15 group had no arrhythmias. Bupivacaine doses producing seizures, isoelectric EEG, and asystole were significantly less in the FIO2 = 0.1 groups as compared to the other groups. Arrhythmias occurred before seizures in all animals in the FIO2 = 0.1 group but in only 1 of 5 and 2 of 5 animals in the FIO2 = 0.15 and 0.3 groups, respectively. There was no significant difference between the arrhythmic dose of bupivacaine in the FIO2 = 0.3 versus 0.1 animals (8.4 +/- 2.4 vs. 4.0 +/- 1.4 mg.kg-1), but the dose was significantly less in the FIO2 = 0.1 animals than in the FIO2 = 0.15 animals (12.5 +/- 5.6 mg.kg-1). Arterial pH was stable in all three groups during bupivacaine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)