A major NIHR-funded clinical trial of the use of adrenaline in cardiac arrests has found that its use results in less than 1% more people leaving hospital alive – but almost doubles the risk of severe brain damage for survivors of cardiac arrest.
Each year 30,000 people sustain a cardiac arrest (different to a heart attack) in the UK and less than one-in-ten survive. The best chance of survival comes if the cardiac arrest is recognised quickly and someone starts cardiopulmonary resuscitation (CPR) and defibrillation is applied without delay.
The application of adrenaline is one of the last things tried in attempts to treat cardiac arrest. It increases blood flow to the heart and increases the chance of restoring a heartbeat. However it also reduces blood flow in very small blood vessels in the brain, which may worsen brain damage.
The Pre-hospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug administration In Cardiac arrest (Paramedic 2) trial was undertaken to determine if adrenaline is beneficial or harmful as a treatment for out of hospital cardiac arrest.
There were no previous randomised controlled trials looking at the safety and effectiveness of adrenaline as a treatment for cardiac arrest, which led to the International Liaison Committee on Resuscitation (ILCOR) and Resuscitation Council to call for a placebo-controlled trial to determine whether adrenaline is beneficial or harmful.
The trial, led by the University of Warwick, ran from December 2014 through October 2017 and was supported by the Critical Care and Injuries and Emergencies clinical specialties within the NIHR Clinical Research Network. It was conducted in five NHS Ambulance Trusts and included 8,000 patients who were in cardiac arrest. Patients were allocated randomly to be given either adrenaline or a salt-water placebo. All those involved in the trial including the ambulance crews and paramedics were unaware which of these two treatments the patient received.
Of 4,012 patients given adrenaline, 130 (3.2%) were alive at 30 days compared with 94 (2.4%) of the 3,995 patients who were given placebo. However, of the 128 patients who had been given adrenaline and who survived to hospital discharge 39 (30.1%) had severe brain damage, compared with 16 (18.7%) among the 91 survivors who had been given a placebo. In this study a poor neurological outcome (severe brain damage) was defined as someone who was in a vegetative state requiring constant nursing care and attention, or unable to walk and look after their own bodily needs without assistance.
The reasons why more patients survived with adrenaline and yet had an increased chance of severe brain damage are not completely understood. One explanation is that although adrenaline increases blood flow in large blood vessels, it paradoxically impairs blood flow in very small blood vessels, and may worsen brain injury after the heart has been restarted. An alternative explanation is that the brain is more sensitive than the heart to periods without blood and oxygen and although the heart can recover from such an insult, the brain is irreversibly damaged.
Study chief investigator Gavin Perkins Professor of Critical Care Medicine at Warwick Medical School, said:
“We have found that the benefits of adrenaline are small – one extra survivor for every 125 patients treated – but the use of adrenaline almost doubles the risk of a severe brain damage amongst survivors.”
“Patients may be less willing to accept burdensome treatments if the chances of recovery are small or the risk of survival with severe brain damage is high. Our own work with patients and the public before starting the trial identified survival without brain damage is more important to patients than survival alone. The findings of this trial will require careful consideration by the wider community and those responsible for clinical practice guidelines for cardiac arrest.”
Jonathan Wyllie, president of Resuscitation Council UK and a professor of neonatology and paediatrics at Durham University, said it was a “groundbreaking” study. “I would absolutely want this evidence to be taken into account for future guidelines,” he said. “If I ever require resuscitation, I hope it is based on evidence such as this rather than merely the opinion of experts.”
The trial’s results have been published in the New England Journal of Medicine (NEJM).
More information on the study is available on the NIHR Journals Library