Still no cardiac arrest survival benefit from epinephrine?
September 1, 2011 by Cliff
Filed under Acute Med, All Updates, EMS, Guidelines, ICU, Resus
A double blind randomised controlled trial showed significantly better rates of return of spontaneous circulation and hospital admission with the use of adrenaline (epinephrine) compared with placebo. This effect was observed with both shockable and non-shockable initial cardiac arrest rhythms. There was no statistically significant difference in the primary outcome of survival to hospital discharge.
Interesting but unfortunate political factors appear to have prevented recruitment to the required numbers of patients for this study so it is underpowered for its primary outcome of survival to hospital discharge, which in the adrenaline group was double that in the placebo group, although this did not reach statistical significance. What was supposed to be a multi-centre study became a single centre one and it was not possible to continue as the study drugs reached their expiry date and no additional funding was available.
So do ROSC and survival to admission matter? The authors make the following point:
While not the primary outcome of our study, ROSC is an increasingly important clinical endpoint as the influence of post resuscitation care interventions (i.e.: therapeutic hypothermia, managing underlying cause, organ perfusion and oxygenation) on survival to hospital discharge are recognised.
Optimum dose and timing of adrenaline remain unknown, along with whether it impacts on long-term outcomes.
BACKGROUND: There is little evidence from clinical trials that the use of adrenaline (epinephrine) in treating cardiac arrest improves survival, despite adrenaline being considered standard of care for many decades. The aim of our study was to determine the effect of adrenaline on patient survival to hospital discharge in out of hospital cardiac arrest.
METHODS: We conducted a double blind randomised placebo-controlled trial of adrenaline in out-of-hospital cardiac arrest. Identical study vials containing either adrenaline 1:1000 or placebo (sodium chloride 0.9%) were prepared. Patients were randomly allocated to receive 1ml aliquots of the trial drug according to current advanced life support guidelines. Outcomes assessed included survival to hospital discharge (primary outcome), pre-hospital return of spontaneous circulation (ROSC) and neurological outcome (Cerebral Performance Category Score – CPC).
RESULTS: A total of 4103 cardiac arrests were screened during the study period of which 601 underwent randomisation. Documentation was available for a total of 534 patients: 262 in the placebo group and 272 in the adrenaline group. Groups were well matched for baseline characteristics including age, gender and receiving bystander CPR. ROSC occurred in 22 (8.4%) of patients receiving placebo and 64 (23.5%) who received adrenaline (OR=3.4; 95% CI 2.0-5.6). Survival to hospital discharge occurred in 5 (1.9%) and 11 (4.0%) patients receiving placebo or adrenaline respectively (OR=2.2; 95% CI 0.7-6.3). All but two patients (both in the adrenaline group) had a CPC score of 1-2.
CONCLUSION: Patients receiving adrenaline during cardiac arrest had no statistically significant improvement in the primary outcome of survival to hospital discharge although there was a significantly improved likelihood of achieving ROSC.
Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial
Resuscitation. 2011 Sep;82(9):1138-43
I’ve wondered what, if anything, would happen if say the dose of epi given on all cardiac arrests was halved. Provided continuous chest compressions, early and appropriate defibrillation, and therapeutic hypothermia I don’t know that we’d necessarily see a difference. A milligram of epinephrine is a lot, even for a dead guy!
However, when I read this article, I was most troubled by the resistance to their study. Considering the existing Level of Evidence for epinephrine in cardiac arrest is largely tradition based, it appears to me to be more harmful to NOT study it’s affects in a RCT.
We’ve got the same problems in EMS, our “traditional” therapies are held in such high regard (high flow O2, long spine boards, two large bore IV’s, etc) that we seem to forget nobody has really studied if it even makes a difference!
I hope the authors do not get demotivated and find a way to continue their study (or other researchers pick up where they left off).
Some of us old farts have knows this for years. We used to joke that with enough epi and calcium, we could give a rock a pulse. but we never saw anyone discharged from the hospital.