Lipid Emulsion Combined with Epinephrine and Vasopressin Does Not Improve Survival in a Swine Model of Bupivacaine-induced Cardiac Arrest

Background:This study sought to evaluate the efficacy of lipid emulsion in reversing bupivacaine-induced cardiovascular collapse when added to a resuscitation protocol that included the use of epinephrine and vasopressin. Methods:After induction of general anesthesia and instrumentation, 19 mixed-breed domestic swine had cardiovascular collapse induced by an intravenous bolus of 10 mg/kg bupivacaine. After 5 min of resuscitation including chest compressions, epinephrine (100 !g/kg) and vasopressin (1.5 U/kg), animals were randomized to receive either a bolus of 20% lipid emulsion (4 ml/kg) followed by a continuous infusion (0.5 ml · kg "1 · min "1 ) or an equal volume of saline. Investigators were blinded to the treatment assignment. The primary endpoint was return of spontaneous circulation (mean arterial pressure of at least 60 mmHg for at least 1 min). Results:Treatment groups were similar with respect to baseline measurements of weight, sex, and hemodynamic and metabolic variables. The rates of return of spontaneous circulation were similar between groups: (3 of 10) in the lipid group and 4 of 9 in the saline group (P#0.65). Total serum bupivacaine concentrations were higher in the lipid group at the 10-min timepoint (mean$SEM: 23.13$5.37 ng/mlvs.15.33$4.04 ng/ml,P#0.004). More norepinephrine was required in the lipid group compared to the saline group to maintain a mean arterial pressure above 60 mmHg during the 60-min survival period (mean$SEM: 738.6$94.4vs.. 487.3$171.0 !g). Conclusions:In this swine model, lipid emulsion did not improve rates of return of spontaneous circulation after bupivacaine-induced cardiovascular collapse. SYSTEMIC toxicity from local anesthetic overdose can occur from accidental intravascular injection, drug overdose, or rapid absorption from the administration site. The risk of toxicity is low when appropriate dosing and injection are used; the incidence is estimated at 7.5 to 20 events per 100,000 in adults. 1 Toxicity manifests in the central nervous system as confusion, seizure, and coma and in the cardiovascular system as dysrhythmia and eventually cardiac arrest. Treatment of cardiovascular collapse caused by local anesthetic overdose in humans is notoriously difficult to treat. 2‐4 There are conflicting reports in the literature regarding the efficacy of lipid emulsion in the treatment of cardiac arrest caused by local anesthetic toxicity. Rodent and canine models in which cardiac arrest was induced with a rapid bolus of intravenous bupivacaine report 100% survival with the administration of lipid emulsion and 100% mortality without lipid emulsion; no vasopressors were used in either group. 5‐8 These results contrast with the findings in a swine model used by Mayret al. 9,10 in which 100% of swine were resuscitated from a cardiac arrest induced by an intravenous bolus of 5 mg/kg bupivacaine after treatment with chest compressions and vasopressors. When these authors 9 examined the use of lipid emulsion without the use of vasopressors in their model, they found that none of the animals could be resuscitated.