Lipid infusion accelerates removal of bupivacaine and recovery from bupivacaine toxicity in the isolated rat heart

Background and Objectives: Infusion of a lipid emulsion has been advocated for treatment of severe bupivacaine cardiac toxicity. The mechanism of lipid rescue is unknown. These studies address the possibility that lipid infusion reduces cardiac bupivacame content in the context of cardiac toxicity. Methods: We compared the effects of a 1% lipid emulsion with standard Krebs buffer after inducing asystole in isolated rat heart with 500 mu mol/L bupivacaine. We compared times to first heart beat and recovery of 90% of baseline rate pressure product (RPP = heart rate X [left ventricular systolic pressure - left ventricular diastolic pressure]) between controls and hearts receiving 1% lipid immediately after bupivacame. We also used minibiopsies to compare control bupivacame tissue content with hearts getting lipid immediately after an infusion of radiolabeled bupivacame. We then compared bupivacaine efflux from hearts with and without lipid infusion started 75 seconds after radiolabeled bupivacame was administered. Results: Infusion of lipid resulted in more rapid return of spontaneous contractions and full recovery of cardiac function. Average (+/- SEM) times to first beat and to 90% recovery of rate pressure product were 44.6 +/- 3.5 versus 63.8 +/- 4.3 seconds (P <.01) and 124.7 +/- 12.4 versus 219.8 +/- 25.6 seconds (P <.01) for lipid and controls, respectively. Lipid treatment resulted in more rapid loss of bupivacaine from heart tissue (P <.0016). Late lipid infusion, 75 seconds after bupivacame infusion ended, increased the release of bupivacaine measured in effluent for the first 15-second interval compared with controls (183 vs. 121 nmol, n = 5 for both groups, P <.008). Conclusions: Lipid emulsion speeds loss of bupivacaine from cardiac tissue while accelerating recovery from bupivacaine-induced asystole. These findings are consistent with the hypothesis that bupivacaine partitions into the emulsion and supports the concept of a "lipid sink." However, the data do not exclude other possible mechanisms of action.