use of epinephrine improves ROSC incidence but not long term benefit

The rationale for the use of epinephrine during cardiac arrest for many decades rested on studies in animal models that increasing vascular tone with this agent during cardiac arrest with chest compressions ongoing resulted in a greater amount of blood shunted to the coronary circulation and therefore a greater likelihood of achieving return of spontaneous circulation (ROSC). Indeed, one of the consistent findings of recent prospective clinical trials has been that epinephrine does increase the incidence of ROSC.

Clinical trials were conducted because of concerns that despite ROSC there might not be more long-term patient-oriented benefits from the use of this agent. In one large prospective observational trial, the use of epinephrine in out-of-hospital arrest was associated with a higher incidence of ROSC but a lower survival and lower incidence of good functional recovery at 1 month. A recent prospective randomized placebo-controlled trial (PARAMEDIC2) enrolled more than 8,000 patients. The incidence of overall 30-day survival in the trial was quite low (3.4% in the epinephrine group; 2.4% in the placebo group; adjusted OR, 1.47; CI, 1.09-1.97 favoring epinephrine use). Although survival at 30 days was significantly higher in the epinephrine group, the incidence of survivors with severe neurological impairment was also higher in the epinephrine group, calling into question any benefit from the greater likelihood of ROSC seen with the drug. There were no differences seen in time in the ICU or length of hospitalization between the two groups. Again, there was a robust increase in the incidence of ROSC achieved with the use of epinephrine (36.3% vs 11.7%).

These results have called into question the benefits of the use of epinephrine in out-of-hospital arrest or at least have called for evaluation of additional therapies to improve outcome. Experts in the field do recommend caution in extrapolating these results to in-hospital arrest circumstances, since the median time before paramedics administered epinephrine in PARAMEDIC2 was 21 min, whereas during in-hospital arrests the median time ranges from 3 to 5 min. This earlier administration of the agent may be associated with enhanced benefit.1234

Footnotes

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  2. Aves T, Chopra A, Patel M, et al. Epinephrine for out-of-hospital cardiac arrest: an updated systematic review and meta-analysis [published online ahead of print November 27, 2019]. Crit Care Med. doi: 10.1097/CCM. PubMed ↩

  3. Hagihara A, Hasegawa M, Abe T, et al. Prehospital epinephrine use and survival among patients with out-of-hospital cardiac arrest. JAMA. 2012;307(11):1161-1168. PubMed ↩

  4. Perkins GD, Ji C, Deakin CD, et al; PARAMEDIC2 Collaborators. A randomized trial of epinephrine in out-of-hospital cardiac arrest. N Engl J Med. 2018;379(8):711-721. PubMed ↩