Adrenaline to improve survival in out-of-hospital cardiac arrest: the PARAMEDIC2 RCT.
ADRENALINE
CARDIAC ARREST
PLACEBO
Journal
Health technology assessment (Winchester, England)
ISSN: 2046-4924
Titre abrégé: Health Technol Assess
Pays: England
ID NLM: 9706284
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
entrez:
16
4
2021
pubmed:
17
4
2021
medline:
26
10
2021
Statut:
ppublish
Résumé
Adrenaline has been used as a treatment for cardiac arrest for many years, despite uncertainty about its effects on long-term outcomes and concerns that it may cause worse neurological outcomes. The objectives were to evaluate the effects of adrenaline on survival and neurological outcomes, and to assess the cost-effectiveness of adrenaline use. This was a pragmatic, randomised, allocation-concealed, placebo-controlled, parallel-group superiority trial and economic evaluation. Costs are expressed in Great British pounds and reported in 2016/17 prices. This trial was set in five NHS ambulance services in England and Wales. Adults treated for an out-of-hospital cardiac arrest were included. Patients were ineligible if they were pregnant, if they were aged < 16 years, if the cardiac arrest had been caused by anaphylaxis or life-threatening asthma, or if adrenaline had already been given. Participants were randomised to either adrenaline (1 mg) or placebo in a 1 : 1 allocation ratio by the opening of allocation-concealed treatment packs. The primary outcome was survival to 30 days. The secondary outcomes were survival to hospital admission, survival to hospital discharge, survival at 3, 6 and 12 months, neurological outcomes and health-related quality of life through to 6 months. The economic evaluation assessed the incremental cost per quality-adjusted life-year gained from the perspective of the NHS and Personal Social Services. Participants, clinical teams and those assessing patient outcomes were masked to the treatment allocation. From December 2014 to October 2017, 8014 participants were assigned to the adrenaline ( The estimate for survival with a favourable neurological outcome is imprecise because of the small numbers of patients surviving with a good outcome. Adrenaline improved long-term survival, but there was no evidence that it significantly improved neurological outcomes. The incremental cost-effectiveness ratio per quality-adjusted life-year exceeds the threshold of £20,000-30,000 per quality-adjusted life-year usually supported by the NHS. Further research is required to better understand patients' preferences in relation to survival and neurological outcomes after out-of-hospital cardiac arrest and to aid interpretation of the trial findings from a patient and public perspective. Current Controlled Trials ISRCTN73485024 and EudraCT 2014-000792-11. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Cardiac arrest is a medical emergency that happens when the heart suddenly stops pumping effectively. When cardiac arrest happens, awareness is lost within seconds. If emergency treatment is not started quickly, the person will die. The first treatments of cardiac arrest involve pressing on the chest, giving rescue breaths and defibrillation (electric shocks applied to the heart). If these treatments do not work, ambulance paramedics use a drug called adrenaline to try to restart the heart. Although this treatment has been used for many years, some recent research suggests that it may cause more harm than good. In this research study, we compared the effects of giving adrenaline with the effects of not giving adrenaline to people who had a cardiac arrest in the community. The research showed that adrenaline was effective at restarting the heart, so more people survived long enough to be admitted to hospital. Thirty days later, 130 out of 4012 patients (3.2%) who received adrenaline and 94 out of 3995 (2.4%) who did not receive adrenaline were alive. However, adrenaline did not improve the number of patients who went home from hospital having made a good recovery and were able to care for themselves. The evidence suggests that adrenaline represents a poor use of NHS funds on cost-effectiveness grounds. In a community survey, 95% of people who responded thought that long-term survival with good brain function was more important than just being alive. Further research exploring the opinions of patients and the public will help to understand the results of this research for the NHS.
Sections du résumé
BACKGROUND
Adrenaline has been used as a treatment for cardiac arrest for many years, despite uncertainty about its effects on long-term outcomes and concerns that it may cause worse neurological outcomes.
OBJECTIVES
The objectives were to evaluate the effects of adrenaline on survival and neurological outcomes, and to assess the cost-effectiveness of adrenaline use.
DESIGN
This was a pragmatic, randomised, allocation-concealed, placebo-controlled, parallel-group superiority trial and economic evaluation. Costs are expressed in Great British pounds and reported in 2016/17 prices.
SETTING
This trial was set in five NHS ambulance services in England and Wales.
PARTICIPANTS
Adults treated for an out-of-hospital cardiac arrest were included. Patients were ineligible if they were pregnant, if they were aged < 16 years, if the cardiac arrest had been caused by anaphylaxis or life-threatening asthma, or if adrenaline had already been given.
INTERVENTIONS
Participants were randomised to either adrenaline (1 mg) or placebo in a 1 : 1 allocation ratio by the opening of allocation-concealed treatment packs.
MAIN OUTCOME MEASURES
The primary outcome was survival to 30 days. The secondary outcomes were survival to hospital admission, survival to hospital discharge, survival at 3, 6 and 12 months, neurological outcomes and health-related quality of life through to 6 months. The economic evaluation assessed the incremental cost per quality-adjusted life-year gained from the perspective of the NHS and Personal Social Services. Participants, clinical teams and those assessing patient outcomes were masked to the treatment allocation.
RESULTS
From December 2014 to October 2017, 8014 participants were assigned to the adrenaline (
LIMITATIONS
The estimate for survival with a favourable neurological outcome is imprecise because of the small numbers of patients surviving with a good outcome.
CONCLUSIONS
Adrenaline improved long-term survival, but there was no evidence that it significantly improved neurological outcomes. The incremental cost-effectiveness ratio per quality-adjusted life-year exceeds the threshold of £20,000-30,000 per quality-adjusted life-year usually supported by the NHS.
FUTURE WORK
Further research is required to better understand patients' preferences in relation to survival and neurological outcomes after out-of-hospital cardiac arrest and to aid interpretation of the trial findings from a patient and public perspective.
TRIAL REGISTRATION
Current Controlled Trials ISRCTN73485024 and EudraCT 2014-000792-11.
FUNDING
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in
Cardiac arrest is a medical emergency that happens when the heart suddenly stops pumping effectively. When cardiac arrest happens, awareness is lost within seconds. If emergency treatment is not started quickly, the person will die. The first treatments of cardiac arrest involve pressing on the chest, giving rescue breaths and defibrillation (electric shocks applied to the heart). If these treatments do not work, ambulance paramedics use a drug called adrenaline to try to restart the heart. Although this treatment has been used for many years, some recent research suggests that it may cause more harm than good. In this research study, we compared the effects of giving adrenaline with the effects of not giving adrenaline to people who had a cardiac arrest in the community. The research showed that adrenaline was effective at restarting the heart, so more people survived long enough to be admitted to hospital. Thirty days later, 130 out of 4012 patients (3.2%) who received adrenaline and 94 out of 3995 (2.4%) who did not receive adrenaline were alive. However, adrenaline did not improve the number of patients who went home from hospital having made a good recovery and were able to care for themselves. The evidence suggests that adrenaline represents a poor use of NHS funds on cost-effectiveness grounds. In a community survey, 95% of people who responded thought that long-term survival with good brain function was more important than just being alive. Further research exploring the opinions of patients and the public will help to understand the results of this research for the NHS.
Autres résumés
Type: plain-language-summary
(eng)
Cardiac arrest is a medical emergency that happens when the heart suddenly stops pumping effectively. When cardiac arrest happens, awareness is lost within seconds. If emergency treatment is not started quickly, the person will die. The first treatments of cardiac arrest involve pressing on the chest, giving rescue breaths and defibrillation (electric shocks applied to the heart). If these treatments do not work, ambulance paramedics use a drug called adrenaline to try to restart the heart. Although this treatment has been used for many years, some recent research suggests that it may cause more harm than good. In this research study, we compared the effects of giving adrenaline with the effects of not giving adrenaline to people who had a cardiac arrest in the community. The research showed that adrenaline was effective at restarting the heart, so more people survived long enough to be admitted to hospital. Thirty days later, 130 out of 4012 patients (3.2%) who received adrenaline and 94 out of 3995 (2.4%) who did not receive adrenaline were alive. However, adrenaline did not improve the number of patients who went home from hospital having made a good recovery and were able to care for themselves. The evidence suggests that adrenaline represents a poor use of NHS funds on cost-effectiveness grounds. In a community survey, 95% of people who responded thought that long-term survival with good brain function was more important than just being alive. Further research exploring the opinions of patients and the public will help to understand the results of this research for the NHS.
Identifiants
pubmed: 33861194
doi: 10.3310/hta25250
pmc: PMC8072520
doi:
Substances chimiques
Epinephrine
YKH834O4BH
Banques de données
ISRCTN
['ISRCTN73485024']
EudraCT
['2014-000792-11']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-166Subventions
Organisme : Department of Health
ID : 12/127/126
Pays : United Kingdom
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