Lower-dose epinephrine administration and out-of-hospital cardiac arrest outcomes

Abstract

Background: International guidelines recommend administration of 1 mg of intravenous epinephrine every 3-5 min during cardiac arrest. The optimal dose of epinephrine is not known. We evaluated the association of reduced frequency and dose of epinephrine with survival after out-of-hospital cardiac arrest (OHCA).

Methods: Included were patients with non-traumatic OHCA treated by advanced life support (ALS) providers from January 1, 2008 to June 30, 2016. During the before period, providers were instructed to give epinephrine 1 mg intravenously at 4 min followed by additional 1 mg doses every eight minutes to patients with OHCA with a shockable rhythm and 1 mg doses every two minutes to patients with a non-shockable rhythm (higher dose). On October 1, 2012, providers were instructed to reduce the dose of epinephrine treatment during out-of-hospital cardiac arrest (OHCA): 0.5 mg at 4 and 8 min followed by additional doses of 0.5 mg every 8 min for shockable rhythms and 0.5 mg every 2 min for non-shockable rhythms (lower dose). Patients with shockable initial rhythms were analyzed separately from those with non-shockable initial rhythms. The primary outcome was survival to hospital discharge with a secondary outcome of favorable neurological status (Cerebral Performance Category [CPC] 1 or 2) at hospital discharge. Multiple logistic regression modeling was used to adjust for age, sex, presence of a witness, bystander CPR, and response interval.

Results: 2255 patients with OHCA were eligible for analysis. Of these, 24.6% had an initially shockable rhythm. Total epinephrine dose per patient decreased from a mean ± standard deviation of 3.4 ± 2.3 mg-2.6 ± 1.9 mg (p < 0.001) in the shockable group and 3.5 ± 1.9 mg-2.8 ± 1.7 mg (p < 0.001) in the non-shockable group. Among those with a shockable rhythm, survival to hospital discharge was 35.0% in the higher dose group vs. 34.2% in the lower dose group. Among those with a non-shockable rhythm, survival was 4.2% in the higher dose group vs. 5.1% in the lower dose group. Lower dose vs. higher dose was not significantly associated with survival: adjusted odds ratio, aOR 0.91 (95% CI 0.62-1.32, p = 0.61) if shockable and aOR 1.26 (95% CI 0.79-2.01, p = 0.33) if non-shockable. Lower dose vs. higher dose was not significantly associated with favorable neurological status at discharge: aOR 0.84 (95% CI 0.57-1.24, p = 0.377) if shockable and aOR 1.17 (95% CI 0.68-2.02, p = 0.577) if non-shockable.

Conclusion: Reducing the dose of epinephrine administered during out-of-hospital cardiac arrest was not associated with a change in survival to hospital discharge or favorable neurological outcomes after OHCA.

Keywords: Cardiac arrest; Emergency medical services; Epinephrine.