THE EFFECT OF AMRINONE ON RECOVERY FROM SEVERE BUPIVACAINE INTOXICATION IN PIGS

Cardiovascular collapse following intravascular bupivacaine may be resistant to treatment. The effect of amrinone on recovery from bupivacaine-induced severe cardiovascular depression was evaluated in 20 pigs (13-26 kg) in a placebo-controlled randomized double-blind study. Under 0.7% isoflurane anesthesia at FI(O2) 0.21, 0.5% bupivacaine 2 mg . kg-1 . min-1 was infused until mean arterial pressure was 40% of the baseline. Cardiac output and heart rate decreased 75% and 50% from the baseline, respectively. The total dose of bupivacaine was 17 +/- 6 (SD) mg . kg-1 in the control and 19 +/- 5 mg . kg-1 in the amrinone group, resulting in mean plasma concentrations of 42 +/- 6 and 53 +/- 19-mu-g . ml-1, respectively. A bolus of amrinone 4 mg . kg-1 (n = 10) was given immediately after cardiovascular depression, followed by an infusion of 0.6 mg . kg-1 . min-1. The control animals received corresponding volumes of physiologic saline (n = 10). After cardiovascular depression, the lungs were ventilated with FI(O2) 1.0 without anesthetics or sympathomimetic support. Electric activity of the heart ceased in all control animals in 3.9 +/- 2 min after cardiovascular depression despite atropine and external cardiac compression. All animals in the control group and 5 of 10 animals in the amrinone group were given atropine (P < 0.01). The animals receiving amrinone survived without cardiac compression (P < 0.0001). During bupivacaine infusion, all animals developed burst suppression in the electroencephalogram. At the time of cardiovascular depression, in 8 of 10 control and in 6 of 10 amrinone animals, the electroencephalogram was isoelectric. Mean arterial pressure, heart rate, cardiac output, and electroencephalogram recovered during the amrinone therapy. In conclusion, profound cardiovascular depression by bupivacaine in pigs was effectively reversed by amrinone, possibly through intracellular Ca2+-release mechanisms.