Epinephrine vs. Advanced Airway First in Pediatric Out‐of‐Hospital Cardiac Arrest

Which comes first, the epinephrine or the endotracheal tube? Several observational studies have found an association between earlier epinephrine administration and survival in pediatric out-of-hospital cardiac arrest. The potential benefits of early placement of advanced airway management compared to bag valve mask ventilation are, however, unclear. On-scene resources may be limited during an out-of-hospital cardiac arrest, so prioritizing an advanced airway or epinephrine could impact other aspects of the resuscitation. In this retrospective observational study from the 2011–2015 Resuscitation Outcomes Consortium (ROC Epistry), Amagasa et al. used sophisticated trial emulation techniques to estimate the impact of the sequence of advanced airway placement vs. epinephrine administration on survival to discharge, neurologically intact survival, and return of spontaneous circulation (ROSC) [1]. They found in the adjusted analysis that (1) the airway sequence was not associated with survival to discharge, (2) epinephrine first was associated with increased odds of ROSC, but not survival to discharge, and (3) advanced airway placement first was associated with increased odds of neurologically intact survival. We commend the authors for their efforts to conduct extensive subgroup and sensitivity analyses to examine effect modifications and the robustness of their findings; however, associations between epinephrine or advanced airway management first with survival to discharge and ROSC were often inconsistent across subgroups, without plausible clinical explanations. Without an RCT comparing the order of epinephrine vs. airway management in pediatric OHCA, this may be the best available evidence on the timing of the advanced airway compared with epinephrine. This study used sophisticated propensity score methods to account for potential confounding variables and resuscitation time bias, and multiple imputation to address missing data. However, the results conflict with recent AHA guideline updates, which emphasize early epinephrine and de-emphasize early advanced airway management based on accumulating observational data [2]. The question is: should EMS medical directors and clinicians change practice to prioritize advanced airway management first, based on the results of this study? Several important limitations should temper enthusiasm to change existing clinical practice based on this analysis. Neurological outcomes were only available on a small subset of the patients. The analysis finding an association between advanced airway placement before epinephrine and improved neurological outcomes only included 13 cardiac arrest survivors. A basic fragility index calculation based on the crude analysis shows that only 2 patients would need to have different outcomes for the results to no longer be statistically significant. Though this does not apply to the adjusted analysis, it indicates that the association between advanced airway management first and improved neurological outcomes is tenuous. Also, inconsistent findings across subgroups undermine the applicability of the main results. The smaller sample size limits subgroup analyses, so it is generally more important to evaluate the consistency in the direction and magnitude of the associations rather than the statistical significance of effect modification. Further, only approximately half of the patients in the study were treated with advanced airways, and the authors could not control for site or the agency, which likely influence the decision to place an advanced airway. From a physiologic standpoint, the goal of all airway management is to provide effective oxygenation and ventilation. Bag-valve-mask ventilation is generally an effective short-term method for providing oxygenation and ventilation in pediatric patients. The benefits of advanced airways may only be realized when bag-valve-mask ventilation is ineffective due to the patient's anatomic characteristics or unsafe due to gastric regurgitation and potential aspiration. There may also be practical considerations in placing an advanced airway before transporting a cardiac arrest patient, since maintaining a good mask seal can be challenging when transporting a patient to a hospital. Based on this reasoning and the currently available evidence, we believe that starting with BVM and escalating to AAM as needed using clinical judgment is a reasonable approach for pediatric OHCA [3]. In addition, newer generation supraglottic airways provide another advanced airway option that has substantially increased in use since the ROC-Epistry era. Future clinical trial data, including the Pediatric Prehospital Airway Resuscitation Trial (Pedi-PART), will provide additional insights. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.