Epinephrine in cardiac arrest reanalysed

A post hoc reanalysis was performed on a 2009 JAMA paper comparing patients randomised to receive or not receive prehospital drugs and iv access for cardiac arrest.
This was done to evaulate the effect of adrenaline/epinephrine. The reason for the reanalysis was that in the original intention-to-treat analysis, some of the following issues may have influenced the results:

  • Some patients randomised to adrenaline never received it as they had ROSC before the drug could be given, thus yielding a selection bias with the most easily resuscitated patients in the post hoc no-adrenaline group
  • At least 1 of 5 patients randomised to receive IV access and drugs did not receive adrenaline as it was regarded futile or it was impossible to gain intravenous access
  • 1 of 10 patients randomised to not receive drugs received adrenaline after they had regained spontaneous circulation for > 5 min.

The purpose of this post hoc analysis on the RCT data was to compare outcomes for patients actually receiving adrenaline to those not receiving adrenaline.
The actual use of adrenaline was associated with increased short-term survival, but with 48% less survival to hospital discharge. The improved survival to hospital admission is consistent with the results of a recent Australia study, and the negative association with longer term survival is similar to a multivariate analysis of observational Swedish registry data where patients receiving adrenaline were 57% less likely to be alive after one month.
Yet more evidence that we haven’t found any drugs proven to improve survival in cardiac arrest. At least not until the human studies on sodium nitroprusside come out?
I bet some of you are still going to be giving the epi exactly every four minutes though.
**Update: see Prehospital Epinephrine Use and Survival Among Patients With Out-of-Hospital Cardiac Arrest – more prospective data from Japan, this time showing epinephrine improves prehospital ROSC, but decreases chance of survival and good functional outcomes 1 month after the event.**

PURPOSE OF THE STUDY: IV line insertion and drugs did not affect long-term survival in an out-of-hospital cardiac arrest (OHCA) randomized clinical trial (RCT). In a previous large registry study adrenaline was negatively associated with survival from OHCA. The present post hoc analysis on the RCT data compares outcomes for patients actually receiving adrenaline to those not receiving adrenaline.

MATERIALS AND METHODS: : Patients from a RCT performed May 2003 to April 2008 were included. Three patients from the original intention-to-treat analysis were excluded due to insufficient documentation of adrenaline administration. Quality of cardiopulmonary resuscitation (CPR) and clinical outcomes were compared.

RESULTS: Clinical characteristics were similar and CPR quality comparable and within guideline recommendations for 367 patients receiving adrenaline and 481 patients not receiving adrenaline. Odds ratio (OR) for being admitted to hospital, being discharged from hospital and surviving with favourable neurological outcome for the adrenaline vs. no-adrenaline group was 2.5 (CI 1.9, 3.4), 0.5 (CI 0.3, 0.8) and 0.4 (CI 0.2, 0.7), respectively. Ventricular fibrillation, response interval, witnessed arrest, gender, age and endotracheal intubation were confounders in multivariate logistic regression analysis. OR for survival for adrenaline vs. no-adrenaline adjusted for confounders was 0.52 (95% CI: 0.29, 0.92).

CONCLUSION: Receiving adrenaline was associated with improved short-term survival, but decreased survival to hospital discharge and survival with favourable neurological outcome after OHCA. This post hoc survival analysis is in contrast to the previous intention-to-treat analysis of the same data, but agrees with previous non-randomized registry data. This shows limitations of non-randomized or non-intention-to-treat analyses.

Outcome when adrenaline (epinephrine) was actually given vs. not given – post hoc analysis of a randomized clinical trial
Resuscitation. 2012 Mar;83(3):327-32