Carvedilol Mitigates Adverse Effects of Epinephrine During Cardiopulmonary Resuscitation

Abstract

Introduction: Earlier studies have implicated the adverse effects of β- and α₁-adrenergic receptors during cardiopulmonary resuscitation (CPR). Because carvedilol is both a nonselective β- and α₁-selective adrenergic receptor-blocking agent, we hypothesized that pre-treatment with carvedilol would convert the actions of epinephrine to that of a selective a2-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 µg/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 µg/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 • min^-1• kg^-1 vs 210 ±6 mL • min^-1• 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 β- and α₁-adrenergic blockade with carvedilol before inducing cardiac arrest, epinephrine administered during CPR yielded better postresuscitation myocardial and neurologic functions and significantly increased postresuscitation survival.