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Three Part Question

In [adults with out-of-hospital cardiac arrest] does [pre-hospital epinephrine] affect [long-term morbidity or mortality]?

Clinical Scenario

A 74-year-old male presents to the emergency department with out-of-hospital cardiac arrest. Paramedics administered epinephrine prior to arrival to the hospital. The patient is unresponsive but has a faint pulse. You wonder about the long-term benefits of epinephrine which is still recommended by the American Heart Association.

Search Strategy

Ovid MEDLINE® 1946 to January week 2 2016: (exp Epinephrine/)AND (exp out-of-hospital cardiac arrest/). No limits applied.

Search Outcome

Fifty-five papers were identified. Three were relevant to the clinical question including two large-scale clinical trials and one recent meta-analysis

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Dumas et al. 2014 France	1556 patients with non-traumatic out-of-hospital cardiac arrest that achieved successful ROSC between January 2000 and August 2012 1134 (73%) received epinephrine and 442 (27%) did not receive epinephrine Epinephrine vs no epinephrine	Prospective Observational Cohort	Good neurological outcome as measured a cerebral performance category of 1 or 2	17% (194/1134) 63% (255/422) p<0.001	This was an observational study and therefore the results could have been affected by unidentified or unreported confounders Additionally, all of the date from the study was gathered from a single data centre
			Adjusted ORs of intact survival for patients by total dose of epinephrine received	aOR for 1 mg epinephrine, 0.48 (95% CI 0.27 to 0.84) For 2–5 mg epinephrine, 0.30 (95% CI 0.20 to 0.47) For >5 mg, 0.23 (95% CI 0.14 to 0.37)
Lin et al. 2014 Canada	14 RCTs evaluating standard dose adrenaline to placebo, high-dose adrenaline, or vasopressin alone or in combination	Systematic Review and Meta-analysis	ROSC (standard dose adrenaline vs placebo)	RR 2.80 (95% CI 1.78 to 4.41) p<0.00001	Only one trial was placebo controlled and relevant to the question
			Survival to admission (standard dose adrenaline vs placebo)	RR 1.95 (95% CI 1.34 to 2.84) p=0.0004
			Survival to discharge	RR 2.12 (95% CI 0.75 to 6.02) p=0.16
			Neurological outcome	RR 1.73 (95% CI 0.59 to 5.11 p=0.32
Atiksawedparit et al 2014 Thailand	15 eligible papers (14 observational studies and 1 RCT) 13 papers were observational on adults and for each outcome between 4 and 8 were pooled	Systematic review and meta-analysis	Prehospital ROSC	RR 2.89 (95% CI 2.36 to 3.54)	Based on many observational studies
			Overall ROSC Survival to discharge	RR 0.93 (95% CI 0.5 to 1.74) RR 0.69 (95% CI 0.48 to 1)

Comment(s)

Epinephrine is a fundamental part of advanced cardiac life support. It is said to increase coronary and cerebral perfusion. This alpha-adrenergic-mediated process is thought to contribute to ROSC in arrested patients. However, despite epinephrine's integral part in standard resuscitation protocols, there remains little evidence that epinephrine directly impacts patient survival or favourable neurological outcome. There is growing concern that epinephrine may actually be harmful to long-term outcomes by increasing myocardial dysfunction and altering cerebral microcirculation.

Clinical Bottom Line

Epinephrine used as an adjunctive treatment during OHCA improves ROSC and survival to hospital but not survival to discharge or neurological outcome.

References

1. Dumas F , Bougouin W , Geri G , et al Is epinephrine during cardiac arrest associated with worse outcomes in resuscitated patients? J Am Coll Cardiol 2014;64:2360–7.
2. Lin S , Callaway CW , Shah PS , et al . Adrenaline for out-of-hospital cardiac arrest resuscitation: a systematic review and meta-analysis of randomized controlled trials. Resuscitation 2014;85:732–40.
3. Atiksawedparit P , Rattanasiri S , McEvoy M , et al . Effects of prehospital adrenaline administration on out-of-hospital cardiac arrest outcomes: a systematic review and meta-analysis. Crit Care 2014;18:463.