Epinephrine in Resuscitation: Curse or Cure?

Robert R Attaran; Gordon A Ewy

Disclosures

Future Cardiol. 2010;6(4):473-482. 

In This Article

Epinephrine versus other Vasopressors: Animal & Human Studies

Is epinephrine the ideal drug? There is a sizeable body of research on alternative or adjunctive drug therapies for cardiac arrest. As noted previously, it has been shown in our laboratory and elsewhere that it is the α-adrenergic and not β-adrenergic effects of epinephrine that are beneficial during resuscitation.[53] In other experimental studies of VF arrest from our laboratory, we found no difference in either the 24-h survival or the neurological outcome between epinephrine and phenylephrine.[54] Huang et al. compared epinephrine, phenylephrine and the combination of epinephrine and esmolol in rats, before attempting defibrillation.[55] The epinephrine-treated rats required more countershocks for ROSC to occur than the other two groups. Furthermore, the epinephrine-treated group demonstrated greater postresuscitation ventricular dysfunction and worse survival. The addition of esmolol to epinephrine appeared to attenuate left ventricular dysfunction and the lower survival associated with epinephrine administration.[55] In another study, pretreatment of rats with the β- and α1-blocker carvedilol before VF, followed by CPR combined with epinephrine, has resulted in improved survival and reduced myocardial dysfunction postresuscitation.[56]

In our laboratory, Hilwig et al. used a swine VF model to compare several groups according to drug therapy during advanced cardiac life support (ACLS): epinephrine (0.02 mg/kg), epinephrine with propranolol (0.04 mg/kg), high-dose epinephrine (0.2 mg/kg) with propranolol and phenylephrine (0.4 mg/kg) with propranolol.[57] The 24-h epinephrine survival was significantly less in the high-dose group even when given with the β-blocker propranolol. There was no difference in ROSC or 24-h survival among the groups. The combination of epinephrine and vasopressin in a swine VF arrest model resulted in improved coronary and cerebral perfusion pressure compared with epinephrine alone.[58]

In VF arrest, comparisons of epinephrine to vasopressin have yielded discordant results. Compared with epinephrine, vasopressin has resulted in improved coronary perfusion pressure,[59] higher coronary venous pH[60] and higher coronary and cerebral flow.[61] In the swine VF model, higher coronary perfusion pressures were observed with vasopressin, but there was no statistically significant difference in ROSC or 24-h neurologically normal survival.[62]

In a large multicenter prospective randomized human trial, patients with OHCA were randomized to receive either epinephrine 1 mg and 40 IU of vasopressin (n = 1442) versus epinephrine alone (n = 1452).[63] There was no significant difference in survival to hospital admission, ROSC, survival to hospital discharge, neurologic recovery or 1-year survival. Notably, the mean down-time in each arm was 16.3 min. As with other human studies of vasopressors, this may be related to the late administration of these vasoactive drugs. Down-times exceeding 10 min are known to confer low ROSC rates.[64]

In a small single-center, double-blind trial of in-hospital cardiac arrest,[65] patients receiving intravenous epinephrine, vasopressin and methylprednisolone during CPR showed improved ROSC (p = 0.003) and survival to discharge rates (p = 0.02) over those receiving epinephrine alone (n = 48).

Endothelin-1 is a potent vasoconstrictor without β-adrenergic effects.[66] It is believed to also possess positive inotropic and chronotropic properties.[67,68] In our laboratory, following prolonged VF, endothelin-1 administration was associated with dramatically higher coronary perfusion pressures during CPR, as well as higher mean arterial pressures postresuscitation.[69] However, in this study, the resulting vasoconstriction was so marked that end-tidal CO2 (a measure of forward blood flow) dropped dramatically and was associated with much lower survival rates compared with epinephrine. More recently, elevated endogenous endothelin-1 levels have been found to predict resuscitation failure in VF.[70]

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