Optimal Treatment Sequence Identified for Out-of-Hospital Cardiac Arrest

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Additional research may be necessary to look at the sequence of epinephrine administration and advanced airway management in settings in which alternative epinephrine administration strategies are utilized.

The optimal sequence of treatment for individuals with out-of-hospital cardiac arrest (OHCA) may be intravenous epinephrine prior to the placement of an advanced airway, according to new findings.1

These findings were the results of a recent study conducted to evaluate which sequence of intervention measures for out-of-hospital cardiac arrest are the most ideal. Commonly-implemented interventions include epinephrine and advanced airway management (AAM) with clinicians using supraglottic airway insertion as well as endotracheal intubation.

This research was led by Masashi Okubo, MD, from the department of emergency medicine at the University of Pittsburgh School of Medicine in Pennsylvania. Okubo and colleagues acknowledged that the consensus by the International Liaison Committee on Resuscitation related to emergency cardiovascular care had pointed 1 notable knowledge gap on the ideal point in time during cardiopulmonary resuscitation (CPR) to shift to alternate airway management techniques.2

“Consequently, our objective was to evaluate the association of the sequence of intra-arrest epinephrine administration and AAM with patient outcomes after OHCA, comparing the epinephrine-first strategy with the AAM-first strategy,”

Background and Methods

The investigators carried out their retrospective study through the use of data drawn from the All-Japan Utstein Registry, a population-based registry used all around Japan to document out-of-hospital cardiac arrest occurrences which had been evaluated by emergency medical services (EMS) personnel.

Personnel for EMS personnel include 1 emergency life-saving technician and must follow Japanese resuscitation rules. These technicians are given permission to carry out various types of interventions while given online medical instructions. Some of these actions include providing intravenous (IV) epinephrine administration as well as placement of supraglottic airways (SGA).

From October 2022 - May 2023, the study was conducted. The investigators placed subjects into 2 distinct subcohorts which were determined due to subjects’ initial rhythm on arrival at EMS, the first being the ‘shockable’ subcohort and the second being the ‘nonshockable’ rhythm subcohort.

The team, to address any discrepancies in demographics, characteristics of patients’ cardiac arrests, or bystander and prehospital interventions, made use of propensity scoring and inverse probability of treatment weighting (IPTW) in both the shockable and nonshockable initial rhythm subgroups.

As far as primary outcomes assessed by the investigators, the investigators looked mainly as survival rates at 1-month. The secondary outcomes assessed by the research team included single-month survival with a prehospital return of spontaneous circulation and favorable functional status.

The team looked at several variables throughout the study, including EMS interventions, demographic data, circumstances surrounding the cardiac event, and outcome measures such as patients’ prehospital returns of spontaneous circulation (ROSC), their functional status, and their 1-month survival.


Overall, there ended up being a pool of 259,237 eligible subjects, all of whom had a median age of 79 years and 58.7% of whom were reported to be male. Among this group of participants, 8.3% were found by the investigators to have exhibited an initial shockable rhythm.

The remaining 91.7% of the subjects were shown to have an initial nonshockable rhythm by the team. After using inverse probability of treatment weighting, the investigators found that the distribution of each of the covariates between the epinephrine-first and AAM-first groups was balanced.

The investigators added that standardized mean differences had been consistently below 0.100. They reported that after post-inverse probability of treatment weighting adjustment, the cohort who were epinephrine-first showed a greater likelihood of single-month survival rates among both the shockable (odds ratio [OR], 1.19; 95% CI, 1.09-1.30) and nonshockable (OR, 1.28; 95% CI, 1.19-1.37) rhythms as opposed to those in the AAM-first cohort.

Furthermore, in their assessment of secondary outcomes, the investigators found that those in the epinephrine-first arm of the study, when juxtaposed with the AAM-first cohort, showed greater likelihood of receiving favorable functional status and of prehospital return of spontaneous circulation in both the nonshockable and shockable rhythms.

“The findings of this cohort study suggest that administration of IV epinephrine first for adult OHCA is associated with an increased likelihood of 1-month survival, 1-month survival with favorable functional status, and prehospital ROSC among Japanese patients with shockable and nonshockable rhythms compared with an AAM-first strategy,” they wrote.


  1. Okubo M, Komukai S, Izawa J, et al. Sequence of Epinephrine and Advanced Airway Placement After Out-of-Hospital Cardiac Arrest. JAMA Netw Open. 2024;7(2):e2356863. doi:10.1001/jamanetworkopen.2023.56863.
  2. Soar J, Maconochie I, Wyckoff MH, et al. 2019 International consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations: summary from the Basic Life Support; Advanced Life Support; Pediatric Life Support; Neonatal Life Support; Education, Implementation, and Teams; and First Aid Task Forces. Circulation. 2019;140(24):e826-e880. doi:10.1161/CIR.0000000000000734.