Experimental amitriptyline poisoning: treatment of severe cardiovascular toxicity with cardiopulmonary bypass

To compare cardiopulmonary bypass (CPB) with more conventional therapy in the treatment of severe amitriptyline poisoning.

Prospective, randomized, controlled, laboratory investigation.

Profound cardiovascular toxicity was induced in 20 anesthetized Yorkshire swine (72 +/- 8.3 kg) by amitriptyline infusion at 0.5 mg/kg/min. Ventilation was adjusted to keep arterial pH at 7.50 +/- 0.05 and the PCO2 at 35 mm Hg. The swine were randomized in a 1:1 ratio to one of two groups, CPB or control. Both groups received amitriptyline infusion until they experienced near-lethal toxicity, defined as a systolic blood pressure below 30 mm Hg for one minute. The control group was then given supportive treatment, including IV fluids, sodium bicarbonate, vasopressors, and standard pharmacologic (advanced cardiac life support) interventions. Control animals failing to respond to supportive measures after five minutes were given open-chest cardiac massage for 30 minutes or until the return of spontaneous circulation. The CPB group received only mechanical support by CPB for 90 to 120 minutes. No sodium bicarbonate, antiarrhythmics, or cardiotonic agents were provided to the CPB group during this resuscitation.

All 20 animals experienced cardiac conduction delays, dysrhythmias, and progressive hypotension within 30 minutes of receiving IV amitriptyline at 0.5 mg/kg/min. The ten swine receiving CPB as treatment for cardiovascular toxicity were able to completely correct the dysrhythmias, cardiac conduction abnormalities, and hypotension produced by the amitriptyline; however, only one of ten control animals could be resuscitated (P = .0001). Nine of ten swine treated with CPB were easily weaned off bypass without any pharmacologic intervention; however, one required norepinephrine to be weaned. All 11 resuscitated swine were able to be salvaged.

CPB improved survival in our swine model of severe amitriptyline poisoning.