Background and Objectives Changes in acid base balance within the body, oxygen delivery to tissue, and carbon dioxide elimination, as well as general anesthetics, influence the toxicity of local anesthetics. The objective of this study was to test the hypothesis that light halothane anesthesia, hypercapnia, and hypoxia act together to alter the central nervous system and cardiovascular toxicity of bupivacaine.

Methods Three groups of 2-week-old pigs were lightly anesthetized with N₂O in O₂ and paralyzed with pancuronium. One group (n = 6) was made hypercapnic (group A; PaCO₂ ≥ 60 mg Hg), another group (n = 6) was made hypercapnic and hypoxic (group B; F₁O₂ = 0.1, PaCO₂ = 66.8 ± 9.91 mm Hg, PaO₂ = 29.2 ± 3.53 mm Hg), and another group (group C; n = 5) was made hypercapnic and hypoxic and given 0.5% halothane (PaCO₂ = 68.54 ± 4.18, PaO₂ = 31.06 ± 1.96). Bupivacaine was infused intravenously at 1 mg·kg⁻¹·min⁻¹ until the animals developed cardiac asystole.

Results Arrhythmias, seizures, isoelectric electroencephalogram (isoEEG), and asystole were readily identified in groups 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 that 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). Doses of bupivacaine producing all toxic endpoints except seizures were lower in group B animals than in group A, but only the isoEEG doses were 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 versus 17.7 ± 2.2 mg·kg⁻¹). No differences in seizure pattern or type of arrhythmia were detected. Mean arterial pressure decreased during bupivacaine infusion, the rate of decrease was fastest (P < .05) in the animals receiving halothane and slowest in the hypercapnic animals. Mean arterial pressure in group A increased significantly compared to control (to 135.5 ± 14.4% of control; P < .01) before decreasing. Heart rate decreased and the differences over time among groups differed significantly.

Conclusions Bupivacaine is significantly more lethal, as judged by the doses producing asystole, in young pigs that are hypercapnic, hypoxic, and receiving halothane than in young pigs that are hypercapnic.