Clinical paperEffect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial☆
Introduction
Cardiac arrest occurring out of hospital is a significant public health issue with an estimated incidence in the United States of 95.7 per 100,000 person years.1, 2 The overall case fatality varies across different emergency medical services, but is mostly in excess of 90% and has improved little over the last three decades.2 The routine use of adrenaline (epinephrine) in treating cardiac arrest has been recommended for over half a century, being first described in 1906.3 The International Liaison Committee on Resuscitation (ILCOR) include adrenaline in their advanced life support (ALS) resuscitation guidelines, despite there being no randomised placebo-controlled trials in humans evaluating its efficacy in cardiac arrest.4 In 2010 ILCOR identified the need for randomised clinical trials of vasopressor drugs in the treatment of cardiac arrest.4
Animal studies have shown that adrenaline improves coronary and cerebral perfusion.5 The survival outcomes in human studies (non randomised and observational) have been equivocal.6, 7, 8, 9 A meta-analysis of high dose versus standard dose adrenaline did not include a comparison with no adrenaline and showed some benefit of high dose adrenaline on return of spontaneous circulation (ROSC) but not survival to hospital discharge.10 In contrast, there has been some concern regarding the potential harmful effects of adrenaline on post cardiac arrest myocardial function and cerebral microcirculation.11, 12
Despite adrenaline being universally considered “standard of care” in the treatment of cardiac arrest there has never been a randomised placebo-controlled trial to establish its efficacy. This study, the first randomised placebo-controlled clinical trial of adrenaline in cardiac arrest, was undertaken to address this knowledge deficit.
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Study patients and setting
The study was undertaken in Western Australia (WA), an area covering 2.5 million km2 with a population of 1.96 million. Approximately 12% of the population are aged over 64 years and 73% of the population reside in the capital city of Perth.13 WA is served by a single emergency ambulance service provided under government contract by St John Ambulance Western Australia (SJA-WA). All calls for ambulances throughout WA are received centrally and ambulances dispatched by the ambulance service
Results
A total of 4103 out of hospital cardiac arrests were attended by the Ambulance Service in Perth during the study period. Only 2 cases recruited outside Perth and subsequently excluded as randomisation number lost. Of these 3502 were excluded from the study, including 2513 because resuscitation efforts were not commenced by paramedics as death had clearly been established. Of the 601 patients randomised, 67 were unable to be analysed due to randomisation number not being recorded, resulting in
Discussion
This is the first randomised placebo-controlled trial of adrenaline in cardiac arrest. Our study demonstrated that adrenaline resulted in a statistically significant increase in ROSC (OR 3.4; 95% CI 2.0–5.6) but not in the primary outcome of survival to hospital discharge (OR 2.2; 95% CI 0.7–6.3). However, the only two survivors with a poor neurological outcome were in the adrenaline group. For both shockable and non-shockable initial cardiac arrest rhythms we observed significantly better
Conclusion
The use of adrenaline in cardiac arrest significantly improves the proportion of patients achieving ROSC prehospital, but failed to demonstrate a better survival to hospital discharge, possibly due to inadequate sample size. Further studies on the role of adrenaline in cardiac arrest are required to determine optimal dose and timing for drug administration.
Conflicts of interest
No conflicts of interest to declare.
Acknowledgements
The investigators would like to acknowledge the support of St John Ambulance Western Australia and the paramedics who were willing to participate in the study. Appreciation is extended to: Pharma Laboratories who prepared the adrenaline and placebo vials; to and Laraine Salo and Tena Rowe who undertook data entry; and to Dr Tiew-Hwa Teng who derived the CPC scores. This study was funded by the National Health and Medical Research Council (Grant No. 254537). The funding body had no involvement
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A Spanish translated version of the abstract of this article appears as Appendix in the final online version at doi:10.1016/j.resuscitation.2011.06.029.