Epinephrine vs. Norepinephrine for Post-Resuscitation Shock

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David Zimmerman
David Zimmerman
Dave is an associate professor at Duquesne University School of Pharmacy and emergency medicine pharmacist at UPMC Mercy Hospital. He completed residency training at The Johns Hopkins Hospital and Maimonides Medical Center in Brooklyn, NY. His practice interests include medication dosing in patients that are obese and pain management in the ED.

The Pre-brief

We have all been in the situation where we are relieved when a team member says they feel a pulse during CPR and we can begin post-ROSC care but then only to hear of an initial low blood pressure reading. So, you decide to start a vasopressor but which one: epinephrine or norepinephrine? 

What did they do?

  • Observational multicenter study of consecutive patients between 2011-2018 for post-resuscitation shock from out of hospital cardiac arrest (OHCA) registry
  • Multi-center from five hospitals in France
  • Post-resuscitation shock was defined as hypotension with a need for vasopressors for more than 6 hours despite adequate fluid loading
  • Exclusion
    • Obvious extra-cardiac cause of cardiac arrest (trauma, drowning, drug overdose, electrocution, or asphyxia)
    • Refractory cardiac arrest without sustainable return of ROSC
    • Refractory shock requiring extracorporeal membrane oxygenation (ECMO)
    • Absence of continuous IV treatment with epinephrine or norepinephrine
    • Continuous IV treatment with both epinephrine and norepinephrine
  • Statistics
    • Primary outcome was all-cause mortality during hospital stay
    • Secondary endpoint included cardiovascular-specific mortality, unfavorable neurological status at hospital discharge using the Cerebral Performance Category (CPC) score of 3-5

Results

  • 1,421 patients were identified in the database, but 766 were included in the final analysis after exclusion criteria were evaluated

  • 481 (63%) were treated with norepinephrine and 285 (37%) with epinephrine

  • Demographics

    • Median age: 64 years 

    • Male: 73%

    • Median time from collapse to CPR was 5 minutes (IQR 1-10)

    • Median time from CPR to ROSC was 22 min (IQR 15-30)

    • Patients receiving epinephrine had a significantly lower blood pressure, higher lactate, and higher heart rate

    • Inotropic equivalent was also significantly higher in the epinephrine group vs. norepinephrine, 68 vs. 49 (p<0.003), respectively

 

  • Primary outcome: All cause hospital mortality was significantly higher in the epinephrine group (OR 2.6; 95% CI 1.4-4.7; p = 0.002)

 

  • Secondary outcomes: 

    • Cardiovascular hospital mortality was also significantly higher in the epinephrine group (aOR 5.5l 95% CI 3-10.3; p <0.001)

    • Unfavorable neurologic outcome was also higher in the epinephrine group (OR 3; 95% CI 1.6-5.7; p = 0.001)

Strengths

  • Large cohort with detailed analysis of variables, outcomes, and potential confounders

Limitations

  • Observational study design leading to potential bias with selection of vasopressor and dose titration
  • Numerous differences between patient groups including initial shockable rhythm, time from CPR to ROSC, myocardial dysfunction)

The Debrief

  • Epinephrine was found to have a higher all-cause hospital mortality compared to norepinephrine for patients with post-resuscitation shock
  • Norepinephrine may be the preferred vasopressor, but additional confirmatory evidence is needed

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