ILCOR position regarding the new Paramedic2 Trial

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Read the PARAMEDIC2 TRIAL on the New England Journal of Emergency Medical

In 2015 the International Liaison Committee on Resuscitation (ILCOR) published an updated treatment recommendation for the use of epinephrine (adrenaline) during cardiac arrest in adults. The recommendation suggested standard dose epinephrine (1.0 mg) be administered to adult patients in cardiac arrest (weak recommendation, very-low-quality evidence).1,2 This recommendation took into consideration observed benefit in short-term outcomes [return of spontaneous circulation (ROSC) and admission to hospital] and the uncertainty about the benefit or harm on survival to discharge and neurologic outcome. In a subsequent ILCOR publication, the absence of placebo-controlled prospective trials with adequate power to assess the effect of epinephrine on long-term outcome after cardiac arrest was identified as a key knowledge gap as well as the optimal dose and timing of epinephrine during cardiac arrest.3,4

The recently published PARAMEDIC2 study is a prospective double-blind randomised controlled trial of epinephrine compared to placebo in 8016 patients in the United Kingdom treated for out-of-hospital cardiac arrest.5 The study was powered for a primary outcome of survival to 30 days, which was 3.2% in the epinephrine group versus 2.4% in the placebo group (unadjusted odds ratio 1.390; 95% CI 1.062 to 1.819; P=0.017). The important secondary outcome of survival to 3 months with good neurologic function (Modified Rankin Score 0-3) was 2.1% in the epinephrine group and 1.6% in the placebo group 1.306; 95% CI 0.937 to 1.818, P>0.05).

This is the first placebo-controlled clinical trial to detect a long-term survival benefit of epinephrine during cardiac arrest and is therefore an important contribution to the field. However, the study did not demonstrate improved long-term survival with good neurologic function. Limitations of the study include the use of a single fixed epinephrine dosing regimen (1.0 mg every 3-5 minutes) for all patients and an average time from 911 to call to first drug dose of 21 minutes (IQR 16-27 minutes). As noted above, both the optimal dose and timing of epinephrine during cardiac arrest remain important knowledge gaps.

Moving forward, the ILCOR ALS Task Force will evaluate the results of this important study and determine if the current ILCOR treatment recommendations for epinephrine during CPR should be modified. We anticipate that our newly developed continuous evidence evaluation processes will enable ILCOR to respond in a timely manner and rapidly disseminate any revised treatment recommendations.

Robert W. Neumar, MD, PhD

ILCOR Co-Chair

July 18, 2018

Notes:

The International Liaison Committee on Resuscitation (ILCOR) was formed in 1992 and provides a forum for liaison between principal resuscitation organisations
worldwide. ILCORs mission “to save more lives globally through resuscitation” is delivered through our commitment to evidence evaluation, ensuring the best treatments are made available to victims of cardiac arrest around the world.

The membership of ILCOR includes: American Heart Association (AHA), European Resuscitation Council (ERC), Heart and Stroke Foundation of Canada (HSFC), Australian and New Zealand Committee on Resuscitation (ANZCOR), Resuscitation Councils of Southern Africa (RCSA), Inter American Heart Foundation (IAHF), Resuscitation Council of Asia (RCA)

References

1. Callaway CW, Soar J, Aibiki M, et al. Part 4: Advanced Life Support: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Circulation 2015;132:S84-S145.

2. Soar J, Callaway CW, Aibiki M, et al. Part 4: Advanced life support: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Resuscitation 2015;95:e71-e120.

3. Kleinman ME, Perkins GD, Bhanji F, et al. ILCOR Scientific Knowledge Gaps and Clinical Research Priorities for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care: A Consensus Statement. Resuscitation 2018;127:132-46.

4. Kleinman ME, Perkins GD, Bhanji F, et al. ILCOR Scientific Knowledge Gaps and Clinical Research Priorities for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care: A Consensus Statement. Circulation 2018;137:e802-e19.

5. Perkins GD, Ji C, Deakin CD, Quinn T, Nolan JP, Scomparin C, Regan S, Long J, Slowther A, Pocock H, Black JJM, Moore F, Fothergill RT, Rees N, O’Shea L, Docherty M, Gunson I, Han K, Charlton K, Finn J, Petrou S, Stallard N, Gates S, and Lall R, for the PARAMEDIC2 Collaborators* A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest. NEJM 2018 E-publication www.nejm.org/doi/full/10.1056/NEJMoa1806842

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