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Epinephrine in cardiac arrest: The PARAMEDIC2 trial

Published online by Cambridge University Press:  14 June 2019

Jarrett Moore
Affiliation:
Cumming School of Medicine, University of Calgary, Calgary, AB
Mark Sanderson
Affiliation:
University of British Columbia Emergency Medicine Residency Program, Kelowna General Hospital, Kelowna, BC
Riyad B. Abu-Laban*
Affiliation:
Vancouver General Hospital, Department of Emergency Medicine, University of British Columbia, Vancouver, BC
*
Correspondence to: Dr. Riyad B. Abu-Laban, Emergency Department, Vancouver General Hospital, 855 West 12th Avenue, Vancouver, BC V6Z 1M9; Email: [email protected]

Abstract

Abstract Link:http://www.nejm.org/doi/10.1056/NEJMoa1806842

Full citation: Perkins GD, Ji C, Deakin CD, et al. A randomized trial of epinephrine in out-of-hospital cardiac arrest. N Engl J Med 2018; epub, NEJMoa1806842.

Article type: Therapy

Ratings: Methods – 4/5 Usefulness – 3.5/5

Type
Commentary
Copyright
Copyright © Canadian Association of Emergency Physicians 2019 

INTRODUCTION

Background

There is clinical uncertainty regarding the safety and efficacy of epinephrine administration in out-of-hospital cardiac arrest (OHCA).Reference Loomba, Nijhawan, Aggarwal and Arora1

Objective

The aim of this study was to assess, in a more definitive manner than prior research, the effect of epinephrine in OHCA and its safety and efficacy.

METHODS

Design

Randomized, double-blind trial

Setting

Five UK National Health Service ambulance services

Subjects

Adults (≥ 16 years of age) with OHCA in whom initial cardiopulmonary resuscitation (CPR) and defibrillation were unsuccessful. Exclusion criteria included suspected pregnancy, cardiac arrest from anaphylaxis or asthma, and epinephrine before the arrival of trial-trained paramedics. Traumatic arrests were excluded at one site.

Intervention

IV or intraosseous epinephrine, 1 mg, or 0.9% normal saline placebo every 3–5 minutes.

Outcomes

Primary outcomes included rate of survival at 30 days. Secondary outcomes included rates of survival until hospital admission, at-hospital discharge and 3-months, lengths of hospital and intensive care unit (ICU) stay, and neurologic outcome at hospital discharge.

RESULTS

Results of the study are shown in Table 1.

Table 1. Primary and secondary outcomes (from Table 2 in Perkins et al., 2017, “A randomized trial of epinephrine in out-of-hospital cardiac arrest”)

APPRAISAL

Strengths

  • Large, multicentre, double-blind randomized controlled trial (RCT), expanding upon previously observational research

  • Outcomes clearly defined and clinically relevant

  • Primary outcome in accordance with International Liaison Committee on Resuscitation (ILCOR) guidelines

  • Well-defined population

  • Similar baseline characteristics between groups

  • CPR data included when available

Limitations

  • Emergency department and hospital care not defined by the study protocol, which could distort the accuracy or generalizability of the results

  • Overall rate of survival following cardiac arrest significantly lower than anticipated

  • Median time to administration of study agent > 21 minutes, which could distort the accuracy or generalizability of the results

  • No discussion on shockable versus non-shockable rhythms included (However, a subgroup analysis reported in the supplementary material found no significant differences.)

  • CPR quality during resuscitation efforts known to contribute heavily to outcomes and not assessed

  • Not necessarily generalizable to other epinephrine dosing strategies

CONTEXT

Multiple cohort studies with conflicting results on the efficacy and safety of epinephrine in OHCA have been published. In 2011, Jacobs et al. published the only other RCT on this topic; however, it was terminated early with incomplete enrolment.Reference Jacobs, Finn and Jelinek2 Current Advanced Cardiac Life Support guidelines recommend the routine administration of 1-mg (standard dose) epinephrine every 3–5 minutes in OHCA, despite a lack of strong evidence to support this practice.Reference Nolan, Hazinski and Aickin3 Trials focused on different epinephrine doses and frequencies, infusions, or other vasopressor agents would be helpful.

BOTTOM LINE

The results of this study provide persuasive evidence to reconsider current epinephrine guidelines in OHCA. Although epinephrine was associated with increased 30-day survival, it did not increase the probability of survival with good neurologic outcome owing to an increased rate of severe neurologic disability in the treatment group. The number needed to treat in this trial to obtain one additional survivor was 112. The slight increased survival coupled with worsened neurologic outcome in the treatment group does not support the routine use of epinephrine in OHCA; however, the possibility of benefit in subgroups remains, and further research is required. Clinicians should continue to use epinephrine in OHCA until such time that society and national guidelines are revised.

Competing interests

None declared.

References

REFERENCES

1.Loomba, RS, Nijhawan, K, Aggarwal, S, Arora, RR. Increased return of spontaneous circulation at the expense of neurologic outcomes: Is prehospital epinephrine for out-of-hospital cardiac arrest really worth it? J Crit Care 2015;30:1376–81.Google Scholar
2.Jacobs, IG, Finn, JC, Jelinek, GA, et al. Effect of adrenaline on survival in out-of-hospital cardiac arrest: a randomised double-blind placebo-controlled trial. Resuscitation 2011;82(9):1138–43.Google Scholar
3.Nolan, J, Hazinski, MF, Aickin, R, et al. Part 1: executive summary 2015 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations. Resuscitation 2015;95:e131.Google Scholar
Figure 0

Table 1. Primary and secondary outcomes (from Table 2 in Perkins et al., 2017, “A randomized trial of epinephrine in out-of-hospital cardiac arrest”)