OBJECTIVE We previously demonstrated in rats that intravenous infusion of a lipid emulsion increases survival in resuscitation from severe bupivacaine cardiac toxicity. The present studies were undertaken to determine if this method is similarly effective in a non-rodent model using a larger animal. METHODS Bupivacaine, 10 mg/kg, was administered intravenously over 10 seconds to fasted dogs under isoflurane general anesthesia. Resuscitation included 10 minutes of internal cardiac massage followed with either saline or 20% lipid infusion, administered as a 4-mL/kg bolus followed by continuous infusion at 0.5 mL/kg/min for 10 minutes. Electrocardiogram (EKG), arterial blood pressure (BP), and myocardial pH (pHm) and pO2 (pmO2) were continuously measured. RESULTS Survival after 10 minutes of unsuccessful cardiac massage was successful for all lipid-treated dogs (n = 6), but with no survivors in the saline controls (n = 6) (P <.01). Hemodynamics, PmO2, and pHm were improved during resuscitation with lipid compared with saline treatment in which dogs did not recover. CONCLUSIONS We found that infusing a lipid emulsion during resuscitation from bupivacaine-induced cardiac toxicity substantially improved hemodynamics, pmO2, and pHm and increased survival in dogs.