In 2010 the International Liaison Committee on Resuscitation (ILCOR)noted that despite the widespread use of adrenaline (epinephrine) and other vasopressors during resuscitation in some countries, there was an absence of high quality evidence to inform treatment recommendations about their use. Some observational studies suggested either no effect or potentially harmful effects on long-term survival and neurological outcome., ILCOR called for placebo-controlled trials to determine the safety and effectiveness of these drugs in humans.
The European Resuscitation Council (ERC) therefore welcomes the publication of the PARAMEDIC 2 study, a randomised controlled trial of adrenaline compared to placebo in 8016 patients with out of hospital cardiac arrest in the UK. The trial provides high quality evidence about the effects of adrenaline on short and long-term outcomes. The primary outcome of the study, survival to 30 days, was 3.2% in the adrenaline group versus 2.4% in the placebo group (unadjusted odds ratio 1.390; 95% CI 1.062 to 1.819; P=0.017). At the time of hospital discharge, however, severe neurologic impairment had occurred in more of the survivors in the adrenaline group than in the placebo group (39 of 126 patients [31.0%] vs. 16 of 90 patients [17.8%]).
The interpretation of these results will require careful consideration by the ERC Advanced Life Support Science and Education Committee (ALS SEC). The results of the PARAMEDIC 2 trial will also be considered by ILCOR in its continuous evidence evaluation process. Any changes in ILCOR treatment recommendations will be considered carefully by the ERC ALS SEC in case an update to ERC Guidelines is required.
Professor Koen Monsieurs, ERC Vice chair and Professor of Emergency Medicine at the University of Antwerp said:
“This is a landmark trial in resuscitation that may prove very important to many patients. The trial compared adrenaline with placebo in more than 8000 out of hospital cardiac arrest patients. The results show that the use of adrenaline during resuscitation resulted in more survivors at 30 days with adrenaline, but their neurologic function was worse than survivors who received placebo. So it appears that with adrenaline we save more hearts but not more brain. It would be very valuable to know how potential victims of cardiac arrest (which is all of us) feel about this. The results of this trial will now be analysed and discussed by ILCOR in view of all previous evidence. The resulting ILCOR recommendation will be considered by the ERC, so look out for an updated ERC guideline on adrenaline soon!”
The European Resuscitation Council was formed in 1989 and “…aims to preserve human life by making high-quality resuscitation available to all”. A network of 33 National Resuscitation Councils (NRCs) represents the ERC at national level. Each NRC oversees delivery of guidelines, resuscitation training and quality control in its respective country.
Deakin CD, Morrison LJ, Morley PT, et al. Part 8: Advanced life support: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Resuscitation 2010;81 Suppl 1:e93-e174.
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:e71-120.
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.
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
Soar J, Nolan JP, Bottiger BW, et al. European Resuscitation Council Guidelines for Resuscitation 2015: Section 3. Adult advanced life support. Resuscitation 2015;95:100-47.