Is adrenaline safe and effective as a treatment for out of hospital cardiac arrest?BMJ 2014; 348 doi: https://doi.org/10.1136/bmj.g2435 (Published 07 April 2014) Cite this as: BMJ 2014;348:g2435
- Gavin D Perkins, professor of critical care medicine1,
- Peter Cottrell, medical student2,
- Simon Gates, professor of clinical trials2
- 1Warwick Medical School and Heart of England NHS Foundation Trust, Warwick Clinical Trials Unit, Coventry CV4 7AL, UK
- 2Warwick Medical School, Coventry, UK
- Correspondence to: G D Perkins
- Accepted 18 February 2014
Adrenaline (epinephrine) has been an integral component of advanced resuscitation algorithms since the early 1960s. Initial guidelines for the treatment of cardiac arrest recommended the use of intracardiac adrenaline (0.5 mg) or high dose intravenous adrenaline (10 mg), repeating with larger doses if required.1 The mechanism of action for adrenaline in cardiac arrest is attributed to stimulation of α2 receptors in vascular smooth muscle, causing vasoconstriction. This increases aortic diastolic pressure, which in turn leads to increased coronary perfusion pressures, which improves short term survival. Experimental studies, however, suggest that adrenaline impairs cerebral macrovascular2 and microvascular blood flow,3 4 increases ventricular arrhythmias, and increases myocardial dysfunction after return of spontaneous circulation.5 This creates the paradox of better short term survival but at the potential cost of worse long term outcomes.
What is the evidence of uncertainty?
We searched Medline, Embase, the Cochrane Library, and trial registries for systematic reviews, randomised controlled trials, and observational studies relating to the use of adrenaline in the treatment of cardiac arrest.
A systematic review linked to the International Liaison Committee for Resuscitation 2010 evidence appraisal of vasoactive drugs in the treatment of cardiac arrest6 identified 53 articles, of which five compared adrenaline with placebo (three randomised trials6 7 8 and two observational studies9 10). The review concluded that adrenaline is associated with improved short term survival compared with placebo, but no long term survival benefit was seen. A more recent systematic review,11 which focused solely on adrenaline in cardiac arrest, identified 10 studies (two randomised trials6 8 and eight observational studies9 10 12 13 14 15 16 17). Meta-analysis found no significant effect on long term survival in randomised trials (odds …