Clinical PaperRapid epinephrine administration improves early outcomes in out-of-hospital cardiac arrest☆
Introduction
Despite an extensive body of research on out of hospital cardiac arrest (OHCA), survival and neurologic outcomes remain relatively poor. In clinical cardiac arrest models, the only interventions that have shown to improve patient survival are early defibrillation and uninterrupted chest compressions.1, 2, 3, 4 The usefulness of both of these interventions is well-known to be time-dependent, with early initiation resulting in increased survival. The value of pharmacologic interventions, in particular epinephrine (Epi), has not been clearly delineated, despite animal models demonstrating favorable survival outcomes. We postulate that this disparity may be due to the timing of Epi administration.
For OHCA, clinical data supports increased rates of return of spontaneous circulation (ROSC) but no advantage to survival or neurologic outcome with Epi administration during resuscitation.5, 6 More recently, Olasveengen et al. performed a randomized controlled trial comparing outcomes in OHCA patients receiving intravenous vs. no intravenous medications. This study demonstrated only short term survival benefit to advanced life support medications. The individual effects of Epi were not assessed separately from other cardioactive medications in this study.7 Subsequently in a large, randomized controlled trial of Epi vs. placebo, Jacobs et al. demonstrated again increased ROSC, but no survival benefit, with Epi.8 Although both studies were multi-year randomized controlled trials, they were not adequately powered to detect a difference in survival. Work by Hayeshi et al. showed paradoxical results, reporting decreased survival in patients who receive any Epi, but improved survival for those patients who received Epi < 10 min.9 Cantrell et al. also evaluated time to vasopressors on outcome of cardiac arrest and demonstrated an improved rate of ROSC with either Epi or vasopressin. However their mean response time was 8.8 min and mean time to first drug was 9.5 min, which make it unlikely that drug administration would have a survival benefit.10 Overall clinical data regarding Epi administration is controversial, with some data supporting improved short term outcomes with Epi administration, and a number of studies that suggest Epi has no benefit for promoting ROSC.11
Assessing the impact of administration of medications in field cardiac arrest studies is complicated by the time to administration. In a literature review by Rittenberger et al. in 2006, the time from EMS dispatch to a patient receiving the first dose of medication was on average 18–19.4 min.12 This is compared to a mean time of 9.5 min in a meta-analysis of animal models.13 For these reasons, our objective is to assess whether the timing of Epi administration was associated with improved rates of ROSC and survival outcomes in OHCA.
Section snippets
Methods
We performed a retrospective analysis of an existing cardiac arrest database from three suburban EMS systems in southeastern Michigan, with a total daytime population of 266,000. EMS agencies were either fire-based or private services; each responding unit was staffed by at least two paramedics; and all agencies operate under identical treatment protocols. Agencies collected cardiac arrest treatment details and Utstein style cardiac arrest variables on an ongoing basis, including outcome data
Results
Data were obtained from 809 out-of-hospital non-traumatic cardiac arrests. Of these patients, 123 were excluded, leaving a study sample of 686 patients (Fig. 1). Their mean age was 68.8 ± 17 years and the majority were male (62.0%). The average response time from 911 call to EMS arrival was 4.7 ± 2.3 min. The mean time from 911-first Epi administration was 14.3 ± 5.5 min. A small proportion of patients, 155 (22.6%), received Epi within 10 min of 911 call. Epi was most often given IV (81.8%) but was also
Discussion
In this study, our data identifies that early Epi administration during resuscitation for OHCA increased the rate of ROSC, but not survival to discharge. We observed that in patients with bystander witnessed cardiac arrest, there was an unadjusted doubling in the rate of ROSC and survival to discharge. In a multivariable analysis of the rate of ROSC, time to EPI remained significant, but it was not statistically significant for survival to hospital discharge. We also identified that amongst
Limitations
In our study, interpretation of the survival benefit of early Epi administration is limited by possible confounding variables that are known predictors of cardiac arrest survival. In our population of witnessed arrests, groups with early Epi were more likely to be public arrests and to have received bystander CPR, which may have improved outcomes. Although we were able to control for these variables in multivariable analysis, the fit of these models was only fair, and it is likely that a larger
Conclusion
Within the limitations of our study, these data identify improved rates of ROSC with early Epi administration during OHCA resuscitation. This finding was also observed in patients with PEA arrests. In bystander witnessed arrests, the univariate analyses demonstrated an improved rate of ROSC and survival to discharge. However, in a multi-variable analysis, these patients had a twofold increase of ROSC with early Epi, but no significant improvement in survival to discharge. Clearly more work is
Conflict of interest statement
No conflicts of interest to declare.
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A Spanish translated version of the summary of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2013.03.023.