Elsevier

Resuscitation

Volume 84, Issue 7, July 2013, Pages 915-920
Resuscitation

Clinical Paper
Rapid epinephrine administration improves early outcomes in out-of-hospital cardiac arrest

https://doi.org/10.1016/j.resuscitation.2013.03.023Get rights and content

Abstract

Introduction

Early administration of epinephrine (Epi) improves outcomes in animal models of cardiac arrest, but there is limited time-dependent clinical data regarding its benefit.

Objective

Our objective was to assess whether timing of Epi administration was associated with improved outcomes after out of hospital cardiac arrest (OHCA).

Methods

We performed a retrospective analysis of a cardiac arrest database from a suburban EMS system from November 2005 to April 2011. Data was abstracted from EMS run sheets, including drug treatment, route and timing of drug administration, and other Utstein variables. Our primary outcome was return of spontaneous circulation (ROSC). Secondary outcomes measured were survival to hospital admission and discharge. For analysis, data were dichotomized according to timing of Epi administration: early Epi group (defined as 911 call to Epi administration of ≤10 min) and late Epi group (>10 min). Further, exploratory analyses were conducted looking at subgroups sorted by initial rhythm and whether the arrest was witnessed. Wilcoxon rank sum tests, chi-square tests, 95% confidence intervals, and multi-variable regression were used for statistical analysis.

Results

We reviewed 809 patients from study communities: 123 patients were excluded, leaving a sample size of 686 for study analysis. The mean time from 911-Epi was 14.3 ± 5.5 min, with 155 (22.6%) receiving early Epi. Key arrest and treatment characteristics were similar between groups. Patients who received early Epi were more likely to have ROSC (32.9% vs. 23.4%, OR 1.59 (1.07, 2.38)), however, no significant increase in survival to admission or discharge was observed. Patients with an initial rhythm of PEA had an increased rate of ROSC (48.6% vs. 21.5%, OR 3.45 (1.56, 7.62)) but not survival to discharge (5.9% vs. 2.6%), OR 2.35 (0.38, 14.7) with early Epi. In a multivariable analysis of bystander witnessed arrests, early Epi was associated with a higher rate of ROSC (OR 3.20 (1.75, 5.88) but not survival to discharge (OR 1.48 (0.50, 4.36)). No improvement in ROSC or secondary outcomes was noted in patients with other arrest rhythms or un-witnessed arrest with Early Epi.

Conclusions

Within the limitations of our study, this data suggests improved rates of ROSC with early Epi administration during OHCA resuscitation, but this study lacks adequate sample size to demonstrate impact on survival to discharge. Large prospective trials are needed to further delineate the benefit of early Epi administration in OHCA.

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.

References (27)

  • K.B. Kern et al.

    Myocardial perfusion pressure: a predictor of 24 hour survival during prolonged cardiac arrest in dogs

    Resuscitation

    (1988)
  • W.D. Weaver et al.

    Improved neurologic recovery and survival after early defibrillation

    Circulation

    (1984)
  • L.A. Cobb et al.

    Influence of cardiopulmonary resuscitation prior to defibrillation in patients with out-of-hospital ventricular fibrillation

    JAMA

    (1999)
  • Cited by (0)

    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.

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