Rebellion in EM 2019: Pro/Con Debate – Epinephrine in Out of Hospital Cardiac Arrest (OHCA)

Background: Epinephrine (adrenaline) has been used in advanced life support in cardiac arrest since the early 1960s. Despite the routine recommendation for its use, evidence to support administration is less than ideal.  Although it is clear from multiple observational studies that epinephrine improves return of spontaneous circulation (ROSC) and short-term survival, most evidence suggests an absence of improvements in survival with good neurologic outcomes.  In cardiac arrest we want to take advantage of the alpha effects of epinephrine, including peripheral vasoconstriction, and therefore increasing aortic diastolic pressure, which in turn helps augment coronary and cerebral blood flow.  On the other hand, we want to avoid the potentially detrimental beta effects including dysrhythmias, decreased microcirculation, and increased myocardial oxygen demand all of which increase the chances of recurrent cardiac arrest and decreased neurologic recovery.  The only two interventions in cardiac arrest that have shown improve survival with good neurologic outcomes continue to be high-quality CPR and early defibrillation. The debate over the utility of epinephrine in OHCA has been ongoing for several years now and many providers are left with the ultimate question of what to do with epinephrine in OHCA.

Rebellion in EM 2019: Epinephrine in Out of Hospital Cardiac Arrest (OHCA) via Haney Mallemat, MD vs George Willis, MD

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George Willis (@DocWillisMD) – Epinephrine Con

• Epinephrine in out of hospital cardiac arrest doesn’t show a lot in terms of patient-oriented benefits. Data has shown improved return of spontaneous circulation (ROSC) but no improvement in survival with good neurologic outcomes.
• In 2014 Resuscitation published a meta-analysis by Lin S et al [1] which looked at randomized control trials (Fourteen RCTs n = 12,246)that compared:
  • epinephrine vs placebo
  • high dose epinephrine vs standard dose epinephrine
  • vasopressin alone vs combination of epinephrine/vasopressin
• In the meta-analysis by Lin S et al, there was increased survival to admission & increased ROSC, BUT in terms of survival with good neurologic outcomes and survival to discharge no real significant differences between groups
• Based on this data there doesn’t seem to be much need for Epinephrine in OHCA

Haney Mallemat (@CriticalCareNow) – Epinephrine Pro

• Epinephrine in cardiac arrest is good but maybe in moderation, not the current 1mg q3 – 5min which may be too much epinephrine
• In order for the patients to survive cardiac arrest, they need to make it to the hospital first. Epinephrine 1mg q3 – 5minutes gives them the chance of getting to the hospital by improving the rate of ROSC.
• More data is coming out with multiple modalities after the OHCA leading to better outcomes:
  • VA-ECMO
  • Neuroprotective effects like targeted temperature management
  • Targeting higher MAP goals (> 65mmHg)
  • Avoiding Hyperoxia
• It’s not just about epinephrine in cardiac arrest, but everything that happens after the OHCA as well

George Willis – Rebuttal

• An observational cohort study conducted in 2015 [2]looked at OHCA and pre hospital systems comparing ALS vs BLS (≈31k ALS Units vs ≈1.6k BLS Units)
• The study looked at survival to hospital discharge, 30d, and 90d as well as neurological outcomes
• Patients receiving ALS had decreased survival, increased mortality and poorer neurologic outcomes

• • Survival to Hospital Discharge: BLS > ACLS (13.1 vs 9.2%)
  • Survival to 30 days: BLS > ACLS (9.6 vs 6.2%)
  • Survival to 90 days: BLS > ACLS (8.0 vs 5.4%)
  • Poor Neurologic Functioning: BLS < ACLS (6.1 vs 9.7%)
  • Better Neurologic Functioning of Patients Hospitalized: BLS > ACLS (78.2 vs 55.2%)
• Seems that all we really need to improve mortality and survival is good old compressions

Haney Mallemat – Rebuttal

• With ALS we do have data showing that placing advanced airways has led to worse outcomes in patients
• However early defibrillation has a NNT of 5 and chest compressions has NNT of 15, so instead of blaming epinephrine for these poor outcomes perhaps ALS is staying on scene longer doing advanced techniques instead of scooping and running

George Willis – Rebuttal

• In the PARAMEDIC II trial [3] they looked to see if epinephrine was better for patients in OHCA
• Great RCT that enrolled 8000 patients comparing epinephrine versus saline placebo
• The study showed improvement in the group that got epinephrine in terms of survival & ROSC but had poorer neurologic outcomes
  • 30d Survival (Primary Outcome)
    • Epinephrine: 3.2%
    • Placebo 2.4%
    • OR 1.39 (95% CI 1.06 – 1.82)
    • NNT = 112
  • Severe Neurologic Impairment (mRs 4 – 5)
    • Epinephrine: 31.0%
    • Placebo 17.8%

Haney Mallemat – Rebuttal

• With epinephrine we can at least give the patient a fighting chance of making it to the hospital. Once they’ve made it, we can have the difficult discussion with family about goals of care.
• Those patients that make it to the hospital but have poor neurologic outcome also have the possibility of becoming organ donors and saving hundreds to thousands of lives.

References:

1. Lin S et al. Adrenaline for Out-of-Hospital Cardiac Arrest Resuscitation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Resuscitation 2014. PMID: 24642404
2. Saghavi P et al. Outcomes After Out-of-Hospital Cardiac Arrest Treated by Basic vs Advanced Life Support. JAMA Intern Med 2015; 175 (2): 196 – 204.PMID: 25419698
3. Perkins GD et al. A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest. NEJM 2018. PMID: 30021076

Shownotes Written By: Miguel Reyes, MD (Twitter: @miguel_reyesMD)

Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter: @srrezaie)