Epinephrine injection in lipid-based resuscitation from bupivacaine-induced cardiac arrest: transient circulatory return in rabbits

Abstract

Background: IV lipid emulsion has demonstrated to be effective therapy for bupivacaine-induced cardiotoxicity. However, the role of epinephrine when coadministered with lipid emulsion in toxin-induced cardiac arrest is unclear. We postulated superior resuscitation outcome in the absence of epinephrine in a rabbit model of bupivacaine-induced cardiac arrest resuscitated with IV lipid emulsion.

Methods: Twenty sedated, instrumented New Zealand White rabbits received 10 mg/kg IV bupivacaine producing asystole. Mechanical ventilation and external chest compressions were commenced at 30 seconds. At 1 minute, animals received 5 mL/kg 20% lipid emulsion in addition to 1 of 4 additional IV treatments (n = 5 all groups): 0.9% saline, 2.5 microg/kg epinephrine, 10 microg/kg epinephrine, 100 microg/kg epinephrine; all at 1 mL/kg. Lipid emulsion bolus was repeated at 4 minutes. Return of spontaneous circulation and hemodynamic metrics were obtained to 15 minutes. Saline group animals additionally received high-dose epinephrine (100 microg/kg) treatment at 15 minutes, and were monitored to 20 minutes.

Results: High-dose epinephrine administration was associated with increased rate of return of spontaneous circulation compared with saline control (0 of 5 saline-treated animals; 0 of 5 animals in the 2.5 microg/kg epinephrine group; 3 of 5 in the 10 microg/kg group [P = 0.167]; and 4 of 5 in the 100 microg/kg group [P = 0.048]). Spontaneous but decreasing circulation was maintained at 15 minutes in 4 of 5 animals in the 100 microg/kg group alone (P = 0.048); mean arterial blood pressure at 15 minutes was 12.8 (SEM 2.8) mm Hg saline, 12.0 (2.5) mm Hg 2.5 microg/kg epinephrine, 20.6 (2.7) mm Hg 10 microg/kg epinephrine, and 26.4 (3.9) mm Hg 100 microg/kg epinephrine (P = 0.008). Four of five animals in the saline-treated group exhibited return of spontaneous circulation after delayed epinephrine treatment (P = 0.048). High-dose epinephrine administration was associated with a significant increase in coronary perfusion pressure before return of spontaneous circulation.

Conclusions: Epinephrine seemed to be necessary for return of spontaneous circulation, but was subsequently associated with declining hemodynamic variables in this rabbit model of bupivacaine-induced cardiac arrest. Further study is required to define the role of epinephrine in lipid-based resuscitation from local anesthetic-induced cardiac arrest.