Welsh heart patients to be given salt water placebo during cardiac arrest
Welsh heart failure patients will be among 4,000 people given a placebo instead of adrenaline when undergoing resuscitation attempts as part of a trial that will break 50 years of medical practice.
Patients and their families will not know whether they are part of the study before taking part.
The double-blind trial has been approved by the Oxford Research Ethics Committee and comes after concerns were raised over the long-term effects of adrenaline – which has been used since the early 1960s to help re-start the heart after cardiac arrest.
The International Liaison Committee for Resuscitation (ILCOR) has previously called for urgent studies to find out the effects of adrenaline treatment for cardiac arrest.
The natural hormone remains an integral part of the Advanced Life Support Algorithm – the process of keeping patients alive after an arrest – and is backed by the Resuscitation Council, who draw up the UK’s resuscitation guidelines.
The council however, are supporting the upcoming trial, titled Paramedic 2: the adrenaline trial, which aims to study the effects of adrenaline versus placebo on 8,000 patients, who will not be able to give their consent.
The trial is being spearheaded by academics at the University of Warwick, in conjunction with five NHS ambulance trusts. Paramedics will administer the placebo or adrenaline to eligible patients suffering out-of-hospital cardiac arrest.
It will seek to answer whether the use of adrenaline in such cases is clinically and cost effective and is being funded by the National Institute of Health Research (NIHR) at a cost of more than £2.75m.
Professor Gavin Perkins, who is one of those leading the trial, said: “The need to do this research is underpinned by a serious concern that although using adrenaline might help restart the heart in the short term, it causes severe brain damage leading to death a few hours or days later.
“We want the best possible outcomes for all people who have a cardiac arrest, both now and in the future.
“All patients will receive the treatment that is proven to improve survival from cardiac arrest, CPR and de-fibrillation. Adrenaline is an unproven treatment for cardiac arrest and may be harmful, which is why there is a need for this study.”
Initial resuscitation is effective in roughly just one in four heart failure patients but half of those who survive die in intensive care due to brain damage, which experts believe could be worsened by adrenaline.
But relatives of patients who may die having taken part in the trial will not automatically be made aware of their involvement in the study.
Dr David Hunter, Professor of Medical Ethics at Flinders University in Adelaide, worked at the Centre for Professional Ethics at Keele University until 2011 and believes the study is “probably ethically justifiable – although ethically challenging because of the potential for harms to those who can’t consent to them”.
However Dr Hunter has raised concerns.
He said: “I’m not that keen on using passive means to inform relatives that their now deceased loved ones were part of a trial.
“While there are costs and indeed risks as they note in doing this directly the risks are incurred by doing it indirectly and I think its a matter of respect that you inform people.
“Also it isn’t clear if you can opt out – it says ‘patients can opt out’ in a similar fashion to opting out of resuscitation – I assume this only applies to present patients, so a small subset of the possible trial population.”
The passive measures to be used to inform relatives are outlined in the trial’s protocol and involve placing information about the trial in publicly accessible places, rather than directly informing relatives of patients involved in the study.
Other academics who support the trial have raised queries about consent and concerns that families of the dead will have to seek information about the study themselves.
Professor Paul Kinnersley is a GP and Personal Chair of Cardiff University’s Institute of Primary Care and Public Health, who also represents Wales as part of the Institute for Medical Ethics . He supports the study despite outlining some ethical risks.
He said: “Obviously you can’t get consent for everyone who is going to to have a cardiac arrest but there’s an ethical duty to do the trial.”
Professor Kinnersely said families should be informed carefully, but not passively, to avoid adding to grief and believes NHS staff and the research academics should not be defensive when doing so.
He said: “There is a risk of compensation claims but ambulance trusts need to cope with that and explain the trial and be positive about why they’re doing it.”
A spokesman for the NIHR said the ethics application that has been approved could not be made public due to commercial interests, but Professor Perkins defended the ethics of the trial.
He said: “It is not possible to obtain consent in the immediate emergency situation. A member of the research team will seek consent to continue in the study as soon as possible once the initial emergency has passed.
“People who do not want to be part of the trial may opt out in advance by contacting their local ambulance service.
“Information about the study will be available from local ambulance services once the trial starts and families will be able to contact the ambulance service or the study team to discuss any concerns and seek further information and support.”
Dr Jasmeet Soar, Consultant in Intensive Care Medicine & Anaesthetics and former Chair of the Resuscitation Council (UK), defended including the cost-effectiveness of adrenaline as part of the study.
She said: “The findings of this study will provide greater understanding of the role of adrenaline for the treatment of cardiac arrest, and help inform future advanced life support guidelines.
“Cost-effectiveness of an intervention is an important part of any study, although adrenaline itself is relatively inexpensive, its use may decrease, or increase costs due to unnecessary complications that could be avoided by not using it.
“We simply do not know, and a study of this size will help answer what costs are associated with the use of adrenaline. Indeed economic analyses help direct funds to those interventions that offer the best chance of survival.”
The Welsh Ambulance Service NHS Trust, the London Ambulance Service, the West Midlands Ambulance Service NHS Trust, the North East Ambulance Service NHS Foundation Trust and the South Central Ambulance Service NHS Foundation Trust will be taking part in the trial.
Paramedics and clinicians will be blind to whether they are administering adrenaline or placebo.
Nigel Rees, Senior Research Lead at the Welsh Ambulance Service, said: “Given the uncertainty of the evidence and the life-threatening nature of the condition being treated, it is important that we obtain the best evidence we can to provide the best treatment possible.
“When doctors, nurses and paramedics do not know whether a treatment is effective it is common to undertake a research study.
“We will always endeavour to act in the best interests of our patients, their safety of which is paramount.”
The trial was due to begin in March this year, running until 2016, but a spokesperson for the University of Warwick said it is now due to begin in the autumn.
Background use on adrenaline
More than 50,000 people die each year in the UK following an out-of-hospital cardiac arrest. Initial resuscitation efforts restart the heart in about 25% to 30% of cases, but most patients die in hospital in a few days from severe brain damage. Overall survival is less than 10%.
The guidelines for the use of adrenaline to treat out-of-hospital cardiac arrest patients were originally written in 1961. Professor Peter Safar recommended the use of very large doses of adrenaline – 10mg intravenously or 0.5mg intracardiac.
Studies on animals have shown that injection of adrenaline during cardiac arrest increases aortic tone and helps blood flow, but there is limited data as to the effects of adrenaline in the long-term.
In 2010 the International Liaison Committee for Resuscitation said there needed to be trials to assess its long-term effectiveness.
There have been two previous studies carried out into its long-term effects, but their relatively small numbers have led to their results being uncertain.
One was carried out in 2011 in Western Australia. The study aimed to enroll 5,000 patients but at the time it closed, only 601 patients had been randomised. The rate of short-term survival was higher in those receiving adrenaline, but there was no clear evidence of a benefit to survival in the long-term.
Similar results were also found in a 2009 study in Oslo, Norway, which looked at 851 patients.
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