Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats

Background: The authors sought to confirm a chance observation that intravenous lipid treatment increases the dose of bupivacaine required to produce asystole in rats. The authors also measured the partitioning of bupivacaine between the lipid and aqueous phases of a plasma-lipid emulsion mixture. Methods: Anesthetized Sprague-Dawley rats were used in pretreatment (protocol 1) and resuscitation (protocol 2) experiments. In protocol 1, animals were pretreated with saline or 10%, 20%, or 30% Intralipid (n = 6 for all groups), then received 0.75% bupivacaine hydrochloride at a rate of 10 ml.kg.min(-1) to asystole. In protocol 2, mortality was compared over a range of bolus doses of bupivacaine after resuscitation with either saline or 30% Intralipid (n = 6 for all groups). The lipid:aqueous partitioning of bupivacaine in a mixture of plasma and Intralipid was measured using radiolabeled bupivacaine. Results: Median doses of bupivacaine (in milligrams per kilogram) producing asystole in protocol 1 were for 17.7 for saline, 27.6 for 10% Intralipid, 49.7 for 20% Intralipid, and 82.0 for 30% Intralipid (P < 0.001 for differences between all groups). Differences in mean +/- SE concentrations of bupivacaine in plasma (in micrograms per milliliter) were significant (P < 0.05) for the difference between saline (93.3 +/- 7.6) and 30% Intralipid (212 +/- 45). In protocol 2, lipid infusion increased the dose of bupivacaine required to cause death in 50% of animals by 48%, from 12.5 to 18.5 mg/kg. The mean lipid:aqueous ratio of concentrations of bupivacaine in a plasma-Intralipid mixture was 11.9 +/- 1.77 (n = 3). Conclusions: Lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats. Partitioning of bupivacaine into the newly created lipid phase may partially explain this effect. These results suggest a potential application for lipid infusion in treating cardiotoxicity resulting from bupivacaine.