Most pharmacists involved in resuscitation medicine are eagerly awaiting the outcome of the PARAMEDIC2 trial.
Most pharmacists involved in resuscitation medicine are eagerly awaiting the outcome of the PARAMEDIC2 trial.1
This ongoing study in the United Kingdom has been randomizing patients experiencing cardiac arrest to epinephrine or placebo. Its results have the potential to turn the current approach to cardiac arrest on its head.
Epinephrine has been a controversial intervention for cardiac arrest for some time now.2-8 Previous literature supporting the drug’s use relied on return of spontaneous circulation as a surrogate for patient survival, and no Level 1 evidence exists to support its safety or efficacy in this population.9
Now, a new study published in BMJ provides a sneak preview of what’s to come.10
This retrospective (registry) study compared 2 different times when epinephrine was administered to patients with in-hospital cardiac arrest with initial shockable rhythms (pulseless ventricular tachycardia or ventricular fibrillation). One group received epinephrine within 2 minutes of the first shock, and the other received it after the second shock based on the American Heart Association’s Advanced Cardiovascular Life Support (ACLS) guidelines. The primary outcome was survival to hospital discharge.
Data from the Get With The Guidelines-Resuscitation registry was used to collect the outcome measure from the patient population in this study. Those included were patients with an index in-hospital cardiac arrest and a documented initial shockable rhythm who underwent first defibrillation within 2 minutes. Patients were excluded if they had received epinephrine prior to the first defibrillation, had return of spontaneous circulation, or resuscitation was terminated within the same minute as the first defibrillation.
Because this was a retrospective study design, inherent differences between patients who received epinephrine within 2 minutes of the first shock and those who received it after the second shock may have existed. In an attempt to control for those confounders, the investigators conducted a propensity matched score analysis cohort and sensitivity analysis.
A total of 2974 patients were included in this analysis, of whom 1510 received epinephrine early and 1464 received it according to the ACLS guidelines. Early epinephrine administration was associated with a decreased chance of survival (31% vs 48%), with an odds ratio of 0.48 and a 95% confidence interval [CI] of 0.41 to 0.56, p<0.0001.
This negative effect for early epinephrine administration remained after analysis of the propensity matched cohort and sensitivity analysis. With respect to the propensity matched cohort, early epinephrine was associated with a survival odds ratio of 0.70, 95% CI 0.59 to 0.82, p<0.001. After sensitivity analysis, early epinephrine was associated with a survival odds ratio of 0.73, 95% CI 0.62 to 0.87, p<0.001.
Not surprisingly, the authors concluded that early administration of epinephrine is associated with poor outcomes, but their results must be considered in the context of the retrospective design of their study.
Practice isn’t likely to change based on the results of a registry analysis. If anything, the results confirm that practicing outside of guideline recommendations may be harmful.
However, the findings should provide discussion among resuscitation committees or practice groups involved with in-hospital cardiac arrest to focus on interventions associated with improved outcomes such as early chest compressions and early defibrillation, rather than pharmacologic interventions. But, of course, that’s already in the guidelines.
1. Warwick Medical School. Paramedic2. http://www2.warwick.ac.uk/fac/med/research/hscience/ctu/trials/critical/paramedic2/. Accessed April 9, 2016.
2. Perkins GD, et al. Is adrenaline safe and effective as a treatment for out of hospital cardiac arrest? BMJ. 2014;348:g2435.
3. Lin S, et al. Adrenaline for out-of-hospital cardiac arrest resuscitation: a systematic review and meta-analysis of randomized controlled trials. Resuscitation. 2014;85:732-740.
4. Perkins GD, et al. Early adrenaline for cardiac arrest. BMJ. 2014;348:g3245.
5. Callaway CW. Questioning the use of epinephrine to treat cardiac arrest. JAMA. 2012;307:1198-1200.
6. McCartney M. Adrenaline in cardiac arrest: itâ€™s unethical for patients not to know. BMJ. 2014;349:g5258.
7. Atiksawedparit P, et al. Effects of prehospital adrenaline administration on out-of-hospital cardiac arrest outcomes: a systematic review and meta-analysis. Crit Care. 2014;18:463.
8. Krishnamoorthy V, et al. Epinephrine for cardiac arrest: are we doing more harm than good? Anesthesiology. 2014;120:792-794.
9. American Heart Association. 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2015;132(18): Supplement 2.
10. Andersen Lars W, Kurth Tobias, Chase Maureen, Berg Katherine M, Cocchi Michael N, Callaway Clifton et al. Early administration of epinephrine (adrenaline) in patients with cardiac arrest with initial shockable rhythm in hospital: propensity score matched analysis. BMJ. 2016;353:i1577.