Carvedilol mitigates adverse effects of epinephrine during cardiopulmonary resuscitation

Introduction: Earlier studies have implicated the adverse effects of beta- and alpha(1)-adrenergic receptors during cardiopulmonary resuscitation (CPR). Because carvedilol is both a nonselective beta- and alpha(1)-selective adrenergic receptor-blocking agent, we hypothesized that pretreatment with carvedilol would convert the actions of epinephrine to that of a selective alpha(2)-agonist. Methods: Ventricular fibrillation (VF) was induced in Sprague-Dawley rats weighing approximately 500 g. Animals were randomized to 4 groups of 5 animals each: (1) placebo pretreatment and epinephrine treatment, (2) carvedilol pretreatment and placebo treatment, (3) carvedilol pretreatment and epinephrine treatment, and (4) placebo pretreatment and placebo treatment. Carvedilol (50 mu g/kg) was injected as a bolus into the right atrium 15 minutes before VF was induced. VF was untreated for 8 minutes, after which CPR (chest compression and mechanical ventilation) was begun. Epinephrine (30 mu g/kg) was injected into the right atrium 2 minutes after the start of CPR. Electrical defibrillation was attempted after 14 minutes of VF. Results: All but 2 animals were successfully resuscitated. Approximately equivalent increases in coronary perfusion pressure from 23 +/- 1 mm Hg to 30 +/- 3 mm Hg were observed after the injection of epinephrine independently of carvedilol pretreatment. Carvedilol pretreatment followed by epinephrine treatment reduced early postresuscitation ventricular ectopy (116 +/- 147 vs 834 +/- 380, P <.01) and minimized increases in arterial blood lactate at 5 minutes after resuscitation (10.9 +/- 2.1 mmol/L vs 17.4 +/- 3.5 mmol/L, P <.01). The postresuscitation cardiac index measured 4 hours later was increased (307 +/- 43 mL center dot min(-1) center dot kg(-1) vs 210 +/- 6 mL center dot min(-1) center dot kg(-1), P <.05). Left ventricular diastolic pressures were decreased (6 +/- 1 vs 14 +/- 1 mm Hg, P <.05). Animals pretreated with carvedilol survived longer (71 +/- 1 vs 45 +/- 22 hours, P <.05) and with less postresuscitation neurologic deficit. Conclusion: After beta- and alpha-adrenergic blockade with carvedilol before inducing cardiac arrest, epinephrine administered during CPR yielded better postresuscitation myocardial and neurologic functions and significantly increased postresuscitation survival.