Three Part Question
In [adults with out-of-hospital cardiac arrest] does [pre-hospital epinephrine] affect [long-term morbidity or mortality]?
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.
Ovid MEDLINE® 1946 to January week 2 2016: (exp Epinephrine/)AND (exp out-of-hospital cardiac arrest/). No limits applied.
Fifty-five papers were identified. Three were relevant to the clinical question including two large-scale clinical trials and one recent meta-analysis
|Author, date and country
||Study type (level of evidence)
|Dumas et al.|
|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.|
|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|
|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) |
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.
- 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.
- 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.
- 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.