Epinephrine is recommended for the treatment of non-shockable out of hospital cardiac arrest (OHCA) to obtain return of spontaneous circulation (ROSC). Epinephrine efficiency and safety remain under debate.

We propose to describe the association between the cumulative dose of epinephrine and the failure of ROSC during the first 30 min of advanced life support (ALS).

A retrospective observational cohort study using the Paris SAMU 75 registry including all non-traumatic OHCA. All OHCA receiving epinephrine during the first 30 min of ALS were enrolled. Cumulative epinephrine dose given during ALS to ROSC was retrieved from medical reports.

Among 1532 patients with OHCA, 776 (51%) had initial non-shockable rhythm. Fifty-four patients were excluded for missing data.

The mean value of cumulative dose of epinephrine was 10 ± 4 mg in patients who failed to achieve ROSC (ROSC−) and 4 ± 3 mg (p = 0.04) for those who achieved ROSC.

ROC curve analysis indicated a cut-off point of 7 mg total cumulative epinephrine associated with ROSC− (AUC = 0.89 [0.86–0.92]).

Using propensity score analysis including age, sex and no-flow duration, association with ROSC− only remained significant for epinephrine > 7 mg (p ≤10–3, OR [CI95] = 1.53 [1.42–1.65]).

An association between total cumulative epinephrine dose administered during OHCA resuscitation and ROSC− was reported with a threshold of 7 mg, best identifying patients with refractory OHCA. We suggest using this threshold in this context to guide the termination of ALS and early decide on the implementation of extracorporeal life support or organ harvesting in the first 30 min of ALS.