Carvedilol mitigates adverse effects of epinephrine during cardiopulmonary resuscitation.
BACKGROUND
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 alpha1-selective adrenergic receptor-blocking agent, we hypothesized that pretreatment with carvedilol would convert the actions of epinephrine to that of a selective alpha2-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 microg/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 microg/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 x min(-1) x kg(-1) vs 210 +/- 6 mL x min(-1) x 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.


CONCLUSIONS
After beta- and alpha1-adrenergic blockade with carvedilol before inducing cardiac arrest, epinephrine administered during CPR yielded better postresuscitation myocardial and neurologic functions and significantly increased postresuscitation survival.
Huang
Lei
L
The Institute of Critical Care Medicine, Palm Springs, CA, USA.
Weil
Max Harry
MH
Sun
Shijie
S
Tang
Wanchun
W
Fang
Xiangshao
X
D000322:Adrenergic Agonists / Q000009:adverse effects / Q000494:pharmacology*; D018674:Adrenergic Antagonists / Q000494:pharmacology*; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D016887:Cardiopulmonary Resuscitation; D000077261:Carvedilol; D004837:Epinephrine / Q000009:adverse effects / Q000494:pharmacology*; D006323:Heart Arrest / Q000139:chemically induced / Q000628:therapy; D008297:Male; D011412:Propanolamines / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014693:Ventricular Fibrillation / Q000139:chemically induced / Q000628:therapy
D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D004837:Epinephrine