Treating cardiac arrests with adrenaline during resuscitation by paramedics slightly increases survival compared with placebo. Though adrenaline initially helped restore circulation in a third of cases, 3.2% of people survived to 30 days compared to 2.4% of people in the placebo group. Severe brain damage was nearly twice as likely in those who survived after adrenaline injections.
Cardiac arrest occurs when the heart no longer pumps blood around the body, usually due to an irregular heart rhythm which can have a variety of causes including coronary heart disease.
This NIHR-funded trial of 8,014 people who had a cardiac arrest outside hospital provides high-quality UK-based evidence on the benefits and harms of adrenaline use during advanced cardiopulmonary resuscitation (CPR).
Due to the low overall survival rate, the jury is still out on whether adrenaline should be reserved for use in certain heart rhythms or within a particular time period and not for others. Early bystander recognition and CPR, plus early defibrillation probably have a greater impact on survival.
Why was this study needed?
Adrenaline injections have been commonly used during CPR for cardiac arrest for more than 60 years, without clear evidence if it is helpful or harmful. Adrenaline can increase the likelihood that the heart will regain a normal rhythm as it directs blood flow to the heart. However, it also causes constriction of small blood vessels which can reduce blood flow to other organs, including the brain, and may lead to neurological damage.
Use of adrenaline has been linked to better short-term survival in observational studies, so it has remained in the cardiac arrest guidelines. Randomised controlled trials have been needed to determine if the benefits outweigh the potential harms. This study assessed routine adrenaline use in cardiac arrests occurring outside hospital.
What did this study do?
The PARAMEDIC2 randomised controlled trial allocated 8,014 people with cardiac arrest to receive either 1mg adrenaline or placebo saline injections as part of advanced CPR treatment by paramedics at the scene. On average people in the adrenaline, group received a total dose of 4.9mg.
The average age was 70. Bystander CPR was also performed in 59% of each group. The ambulances took just over six minutes to arrive and gave the injections on average 21 minutes after emergency services were first called. Major outcomes were adjusted for variations in these factors.
Over a third of cases had unwitnessed cardiac arrest, over half had no heart electrical activity (asystole), and only 19% had a shockable rhythm. This may have contributed to the low survival rates.
Overall this large, well-designed trial provides much-needed UK-based, high-quality evidence to inform practice.
What did it find?
- People who received adrenaline had a slightly higher rate of survival at 30 days, 130/4,105 (3.2%) compare to 94/3,999 (2.4%) who received the saline placebo (adjusted odds ratio [OR] 1.47, 95% confidence interval [CI] 1.09 to 1.97).
- Return of spontaneous circulation was much more likely with adrenaline, occurring in 1,457 (36.3%) people in the adrenaline group versus 468 (11.7%) people in the placebo group. A substantially higher number of people given adrenaline survived until hospital admission, 947 (23.8%) compared with 319 (8%) of the placebo group.
- Although the overall rate of survival at 30 days was slightly better with adrenaline, 39/126 (31%) people had severe neurological disability in the adrenaline group, compared with 16/90 (17.8%) in the placebo group. Severe neurological disability was defined as a score of 4 or 5 on the modified Rankin scale.
- Only 27 people in total had no neurological symptoms at discharge. There were a similar number of people in each group when combining those with no symptoms, mild or moderate neurological disability, modified Rankin scale 0 to 3 (OR 1.19, 95% CI 0.85 to 1.68).
What does current guidance say on this issue?
The 2015 Resuscitation Council UK guideline recommends giving adrenaline every three to five minutes during CPR if a normal heart rhythm is absent. Guidance on the early management of people who have had a cardiac arrest by the Faculty of Pre-Hospital Care at the Royal College of Surgeons of Edinburgh (2017) emphasises the importance of recognising that the person is having a cardiac arrest and beginning CPR as soon as possible.
What are the implications?
Adrenaline improved the return of spontaneous circulation and likelihood of survival to reach hospital but only slightly increased survival rates at 30 days. More of those survivors had severe neurological problems.
It remains unclear if out of hospital protocols should change as a result of this trial. The findings are also not able to inform hospital cardiac arrest protocols, as use of adrenaline typically occurs within three minutes of cardiac arrest.
Other studies of out of hospital cardiac arrest have shown better outcomes from prompt recognition, bystander CPR and defibrillation. Strategies to increase public training in CPR and make more defibrillators available may increase the number of people surviving out of hospital cardiac arrest.
Citation and Funding
Perkins GD, Ji C, Deakin CD, et al. PARAMEDIC2 Collaborators. A randomized trial of adrenaline in out-of-hospital cardiac arrest. N Engl J Med. 2018; 379(8):711-21.
This project was funded by the National Institute for Health Research HTA Programme (project number 12/127/126).
Deakin C, Brown S, Jewkes F, et al. Prehospital resuscitation. London: Resuscitation Council (UK); 2015.
Monsieurs KG, Nolan JP, Bossaert LL, et al. European Resuscitation Council Guidelines for Resuscitation 2015 Section 1. Executive summary. Resuscitation. 2015;95:1-80.
Resuscitation Council (UK). Resuscitation to recovery. London: Resuscitation Council (UK); 2017.
Soar J, Deakin C, Lockey A, et al. Adult advanced life support. London: Resuscitation Council (UK); 2015.
Produced by the University of Southampton and Bazian on behalf of NIHR through the NIHR Dissemination Centre