The highly-awaited PARAMEDIC2 trial results are in:

• Multicenter, double-blinded, randomized controlled trial of prehospital OHCA care
• 1mg IV epinephrine vs saline placebo, every 3-5 minutes
• 8014 OHCA patients over the age of 16 (excluded pregnant patients, anaphylactic and asthmatic cardiac arrests)
• Primary outcome: 30 day survival
• Secondary outcomes: 
  • Survival to hospital admission
  • ICU and hospital LOS
  • Survival to hospital discharge and at 3 months
  • Neurologic outcomes at hospital discharge and at 3 months, "favorable" if mRS≤3
• Results: 
  • Higher 30 day survival in Epi group (3.2 vs 2.4%, unadj OR 1.39; 95% CI 1.06 to 1.82; P=0.02)
  • No difference in ICU or hospital LOS
  • No difference in favorable neurologic outcomes at discharge or 3 month
  • Worse neurologic outcomes in the epinephrine survivors (mRS 4 or 5 in 31% of epi group vs. 17.8% of placebo)

 

Interestingly, the authors also queried the public as to what mattered to them most: 

 

Bottom Line:

• As has been demonstrated in previous studies, use of bolus-dose epinephrine results in increased rates of ROSC. 
• This survival comes with the trade-off of worsened neurologic function, a condition not in a majority of patients' personal wishes.
• Epinephrine "1mg every 3-5 minutes'" should no longer be the dogma of OHCA resuscitation.

Additional Information

A Few Things:

• Why such a low overall survival rate, and fewer shockable rhythms?  Patients responding to initial CPR and defibrillation were not included in the study (as they clearly did not need epinephrine).

• The survival benefit of epi in this study had a fragility index of 6 -- meaning that if six patients in the epi group had not survived, the benefit would have been nonstatistically significant.

• Epinephrine may have had more robust benefit if the average time of administration was earlier, during the circulatory phase of cardiac arrest (approx <15-20 minutes from arrest) before major metabolic and acid-base derangements kick in. Median time from EMS call to administration in the study was 21 minutes.

• As a prehospital study, once patients reached the hospital their resuscitations were managed by the EPs at the hospital, presumably with epinephrine being given to the placebo group. As mentioned above, the time delay prior to this crossover likely negates its importance.

• We still do not know whether and what dosing adjustments (bolus vs continuous, longer than q3-5 minutes, etc) may improve epinephrine's performance.

• While heroic efforts to resuscitate a dead patient with epinephrine may not result in good functional outcomes for patients overall, considerations should be made in a variety of specific scenarios, such as achieving ROSC despite poor neurologic outcomes in known/potential organ donors. 

• As the authors point out, there are more important aspects to resuscitation than epinephrine (NNT =112), like bystander CPR (NNT=15), early recognition of cardiac arrest (NNT=11), and early defibrillation (NNT=5).

References

Perkins GD, Ji C, Deakin CD, et al. A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest. N Engl J Med. 2018. doi: 10.1056/NEJMoa1806842.