The effects of levosimendan and dobutamine in experimental bupivacaine-induced cardiotoxicity

BACKGROUND: Accidental intravenous exposure to bupivacaine is highly cardiotoxic and may lead to death. Positive inotropic agents are usually utilized in resuscitative efforts. We have compared the efficacy of levosimendan, a novel inotropic agent, with dobutamine and their combination in a rat model of bupivacaine intoxication. METHODS: Twenty-eight male Wistar albino rats weighing between 250-300 g were divided into these four groups: control (C), levosimendan (L), dobutamine (D) and dobutamine+levosimendan (D+L). Bupivacaine was administered at a dose of 3 mg/kg/min until cardiac arrest occurred or for 120 min. ECG, heart rate, blood pressure, arterial blood gases, and end tidal CO(2) levels were monitored. Levosimendan was administered as a bolus of 12 μg/kg for 10 min and continued as an infusion at 0.3 μg/kg/min. Dobutamine was infused at a dose of 3 μg/kg/min. The time required for a 50% and 75% decrease in heart rate and blood pressure with a total time to cardiac arrest and bupivacaine dose for obtaining cardiac arrest were analyzed. RESULTS: Time periods for heart rate reductions of 50% and 75% were significantly longer in groups L (903, 1198 s), D (984, 1542 s) and L+D (1705, 3152 s) compared with the control group (345, 538 s p < 0.001). Median times to mean blood pressure reductions of 50% and 75% were 399 - 504 s in the control group, 1005 -1204 s in group L, 685 - 1009 s in group D and 1544- 2982 s in group L+D, and the difference was significant compared with the control group. Median time duration to asystole was 703 s in the control group compared with 1385 s in group L, 1789 s in group D and 3557 s in group L+D. Time to cardiac arrest was significantly higher in all 3 study groups. It was also significantly higher in the L+D group compared with both groups L and D separately. CONCLUSION: A combination of dobutamine with levosimendan significantly increased survival times in this bupivacaine-induced toxicity rat model compared with the control, levosimendan, and dobutamine groups.