Trial evidence may support epinephrine use in resuscitation
MedWire News: Administration of epinephrine (adrenaline) during out-of-hospital resuscitation of patients with cardiac arrest improves some outcomes, shows a randomized trial.
Epinephrine has been included in resuscitation guidelines for decades, despite thin evidence for its efficacy, say Ian Jacobs (University of Western Australia, Crawley) and colleagues.
This situation has led to "clinical equipoise," they say. The team's study was intended to involve five ambulance services, but four declined to take part because of concerns about withholding epinephrine in the control group. Also, participation of individual paramedics was voluntary, so only 40% of eligible patients were included.
Thus the trial was underpowered for its primary endpoint of survival to hospital discharge.
The study included data on 534 patients who underwent resuscitation for cardiac arrest and were randomly assigned to receive epinephrine according to current Australian guidelines, or placebo.
More patients given epinephrine than placebo survived to hospital discharge, at 4.0% versus 1.9%, the researchers report in the journal Resuscitation. However, this 2.2-fold increase in survival was not statistically significant.
One outcome improved with epinephrine: pre-hospital return of spontaneous circulation (ROSC), which occurred in 23.5% of patients given epinephrine versus 8.4% of those given placebo. This equated to a significant 3.4-fold improved chance of ROSC for patients given epinephrine.
The beneficial effect of epinephrine on ROSC was most notable among patients with non-shockable rhythms, in whom it conferred a 6.9-fold increase in the likelihood of ROSC, relative to placebo. In this patient subgroup, 1.3% of patients given epinephrine versus 0.0% of patients in the placebo group survived to hospital discharge, but this difference was not significant.
All but two patients achieved good neurologic outcomes, with a Cerebral Performance Category (CPC) of 1 or 2. The two patients with unfavorable outcomes (CPC 3 or 4) were both given epinephrine.
Editorialists Jasmeet Soar (North Bristol NHS Trust, UK) and Jerry Nolan (Royal United Hospital NHS Trust, Bath, UK) said that the study "has weaknesses that are acknowledged by the authors but it does provide us with the best evidence to date about the role of adrenaline [epinephrine] in the treatment of cardiac arrest."
They added: "The difficulties faced by the investigators and the study findings raise important questions for future research on the role of adrenaline in cardiac arrest, and indeed other resuscitation interventions."
Soar and Nolan described the positive study finding as "valuable," but noted that the effect of epinephrine on long-term outcomes is still unknown, and there is no evidence to suggest an optimal dose or timing for epinephrine.
"Adrenaline has been part of advanced life support guidelines for over 50 years," they concluded. "Unless there is a study of sufficient size that shows at least equivalence or inferiority to a placebo for both short and longer-term outcomes, adrenaline is likely to remain in resuscitation guidelines for the foreseeable future."
By Eleanor McDermid