PARAMEDIC 2 impact case study

Key features

• December 2014 - October 2017

• Over 8,000 patients across five NHS Ambulance Trusts

• Funder: NIHR Health Technology Assessment Programme

• NIHR Clinical Research Network support: patient recruitment, patient and public involvement, guidance on HRA approvals

• Chief Investigator: Professor Gavin Perkins, Professor of Critical Care Medicine at the University of Warwick and NIHR Senior Investigator

Each year 30,000 people sustain a cardiac arrest 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 some studies suggest it also reduces blood flow in very small blood vessels in the brain, which may worsen brain damage. There were no previous definitive 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 (UK) to call for a placebo-controlled trial to determine whether adrenaline is beneficial or harmful.

PARAMEDIC 2 aimed to determine if adrenaline is beneficial or harmful as a treatment for out of hospital cardiac arrest. The trial was led by the University of Warwick, conducted in five NHS Ambulance Trusts and included over 8,000 patients who were in cardiac arrest. Patients were allocated randomly to be given either adrenaline or a placebo. All those involved in the trial including the ambulance crews and paramedics were unaware which of these two treatments the patient received.

The trial was funded by the NIHR Health Technology Assessment Programme and supported by the NIHR Clinical Research Network (CRN) Critical Care National Specialty Group and Local Clinical Research Networks (LCRNs). The lead LCRN in the West Midlands supported with pre-award work around patient and public involvement and guidance in obtaining HRA approvals. Within the West Midlands and nationally, the NIHR CRN supported research paramedics in each of the recruiting ambulance services and supported the study team to set up more than 100 hospitals to track patient outcomes and facilitate follow-up.

Outcomes and findings

The results found that the use of adrenaline in cardiac arrests results in less than 1% more people leaving hospital alive - but almost doubles the risk of severe brain damage for survivors of cardiac arrest. 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.

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 126 patients who had been given adrenaline and who survived to hospital discharge, 39 (31%) had severe brain damage, compared with 16 (17.8%) among the 90 survivors who had been given a placebo.

Value to the NHS

PARAMEDIC 2 has been described as a landmark study, and its results have challenged conventional methods used to prioritise restarting the heart during a cardiac arrest.

Within only a few months of the results being published, the study mobilised widespread international discussion about early interventions and prompted a focus on interventions which do work, such as CPR and defibrillation.

Jonathan Wyllie, President of Resuscitation Council UK and a Professor of Neonatology and Paediatrics at Durham University, said: “I would absolutely want this evidence to be taken into account for future guidelines.”

Gavin Perkins, Chief Investigator and Professor of Critical Care Medicine at the University of Warwick:

“We have found that the benefits of adrenaline are small – one extra survivor for every 125 patients treated – but no improvement in neurological outcomes.

“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.”