PARAMEDIC2
A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest
On this page
Overview
In OHCA, epinephrine improved 30-day survival versus placebo but did not improve favorable neurologic outcome, with more severe impairment among survivors.
Clinical takeaway
PARAMEDIC2 supports epinephrine for 30-day survival after out-of-hospital cardiac arrest, with the caveat that favorable neurologic outcome did not improve.
Key result
Thirty-day survival was 3.2% with epinephrine vs 2.4% with placebo (unadjusted OR 1.39; p=0.02).
Practice impact
Use epinephrine in OHCA as usual, but do not treat a survival gain as a neurologic win.
Evidence
Study design
Randomized, double-blind trial of parenteral epinephrine versus saline placebo, given with standard care, in out-of-hospital cardiac arrest.
Enrollment
8,014
Follow-up
Primary outcome at 30 days; neurologic outcome assessed at hospital discharge.
Geography
United Kingdom
Clinical question
Does parenteral epinephrine improve 30-day survival compared with saline placebo in out-of-hospital cardiac arrest?
Population
- Adults with out-of-hospital cardiac arrest treated by paramedics from five National Health Service ambulance services.
Intervention
Parenteral epinephrine plus standard care.
Comparator
Saline placebo plus standard care.
Primary outcome
Survival at 30 days.
Epinephrine increased 30-day survival versus placebo without a significant difference in favorable neurologic outcome.
Odds ratio / 1.39 / 95% CI 1.06-1.82 / p=0.02
Key results
- Thirty-day survival: 130 of 4015 (3.2%) with epinephrine vs 94 of 3999 (2.4%) with placebo; unadjusted OR 1.39 (95% CI 1.06-1.82; p=0.02).
- Survival to discharge with favorable neurologic outcome (modified Rankin scale score of 3 or less) did not differ: 2.2% vs 1.9%; unadjusted OR 1.18 (95% CI 0.86-1.61).
- Among survivors at discharge, severe neurologic impairment (modified Rankin scale score of 4 or 5) was more common with epinephrine (31.0% vs 17.8%).
Harms
- More survivors in the epinephrine group had severe neurologic impairment at hospital discharge (31.0% vs 17.8%).
Clinical Use
Practice impact
- Use epinephrine in out-of-hospital cardiac arrest as usual, but counsel that better 30-day survival does not mean better neurologic recovery.
Applicability
- Most applicable to adults with out-of-hospital cardiac arrest treated in a prehospital ambulance system similar to the United Kingdom trial setting.
Limitations
- Favorable neurologic outcome was a secondary end point and was not significantly different.
- The abstract does not report the epinephrine dose or rhythm-specific effects.
- The neurologic tradeoff is described among survivors at discharge, not as a primary safety end point.
Common misinterpretations
- A 30-day survival benefit is not the same as a neurologic benefit; favorable neurologic outcome did not differ.
- The trial does not show that epinephrine is useless; 30-day survival was higher with epinephrine than with placebo.
Related evidence
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;379(8):711-721. doi:10.1056/NEJMoa1806842
In adults with out-of-hospital cardiac arrest, the use of epinephrine resulted in a significantly higher rate of 30-day survival than the use of placebo, but there was no significant between-group difference in the rate of a favorable neurologic outcome because more survivors had severe neurologic impairment in the epinephrine group.
- PMID
- 30021076