BUPIVACAINE TOXICITY IN LIGHTLY ANESTHETIZED PIGS WITH RESPIRATORY IMBALANCES PLUS OR MINUS HALOTHANE

Background and Objectives. Changes in acid base balance within the bod y, oxygen delivery to tissue, and carbon dioxide elimination, as well as general anesthetics, influence the toxicity of local anesthetics. T he objective of this study was to test the hypothesis that light halot hane anesthesia, hypercapnia, and hypoxia act together to alter the ce ntral nervous system and cardiovascular toxicity of bupivacaine. Metho ds. Three groups of 2-week-old pigs were lightly anesthetized with N2O in O2 and paralyzed with pancuronium. One group (n = 6) was made hype rcapnic (group A; PaCO2 greater-than-or-equal-to 60 mg Hg), another gr oup (n = 6) was made hypercapnic and hypoxic (group B; F1O2 = 0.1, PaC O2 = 66.8 +/- 9.91 mm Hg, PaO2 = 29.2 +/- 3.53 mm Hg), and another gro up (group C; n = 5) was made hypercapnic and hypoxic and given 0.5% ha lothane (PaCO2 = 68.54 +/- 4.18, PaO2 = 31.06 +/- 1.96). Bupivacaine w as infused intravenously at 1 mg.kg-1.min-1 until the animals develope d cardiac asystole. Results. Arrhythmias, seizures, isoelectric electr oencephalogram (isoEEG), and asystole were readily identified in group s A and B. None of the animals given halothane had seizures, but they did exhibit the other three toxic endpoints. The doses of bupivacaine producing asystole were significantly less in group C than in group A (7.9 +/- 1.8 versus 17.7 +/- 2.2 mg.kg-1). The doses of bupivacaine th at produced isoEEG were significantly lower in groups B and C than in group A (8.9 +/- 6.2, 5.0 +/- 1.1, 14.6 +/- 3.2 mg/kg, respectively). Does of bupivacaine producing all toxic endpoints except seizures were lower in group B animals than in group A, but only the isoEEG doses w ere statistically different (arrhythmias 2.3 +/- 1.1 versus 3.7 +/- 1. 1; isoEEG 8.9 +/- 6.2 versus 14.6 +/- 3.2; asystole 12.1 +/- 7.5 versu s 17.7 +/- 2.2 mg.kg-1). No differences in seizure pattern or type of arrhythmia were detected. Mean arterial pressure decreased during bupi vacaine infusion, the rate of decrease was fastest (P < .05) in the an imals receiving halothane and slowest in the hypercapnic animals. Mean arterial pressure in group A increased significantly compared to cont rol (to 135.5 +/- 14.4% of control; P < .01) before decreasing. Heart rate decreased and the differences over time among groups differed sig nificantly. Conclusions. Bupivacaine is significantly more lethal, as judged by the doses producing asystole, in young pigs that are hyperca pnic, hypoxic, and receiving halothane than in young pigs that are hyp ercapnic.