Epinephrine in out-of-hospital cardiac arrest:A critical review

doi:10.5847/wjem.j.issn.1920-8642.2013.02.001

Abstract

Abstract:

BACKGROUND: Epinephrine is recommended in advanced cardiac life support guidelines for use in adult cardiac arrest, and has been used in cardiopulmonary resuscitation since 1896. Yet, despite its long time use and incorporation into guidelines, epinephrine suffers from a paucity of evidence regarding its influence on survival. This critical review was conducted to address the knowledge deficit regarding epinephrine in out-of-hospital cardiac arrest and its effect on return of spontaneous circulation, survival to hospital discharge, and neurological performance.
METHODS: The EMBASE and MEDLINE (through the Pubmed interface) databases, and the Cochrane library were searched with the key words "epinephrine", "cardiac arrest" and variations of these terms. Original research studies concerning epinephrine use in adult, out-of-hospital cardiac arrest were selected for further review.
RESULTS: The search yielded nine eligible studies based on inclusion criteria. This includes five prospective cohort studies, one retrospective cohort study, one survival analysis, one case control study, and one RCT. The evidence clearly establishes an association between epinephrine and increased return of spontaneous circulation, the data were conflicting concerning survival to hospital discharge and neurological outcome.
CONCLUSIONS: The results of this review exhibit the paucity of evidence regarding the use of epinephrine in out of hospital cardiac arrest. There is currently insufficient evidence to support or reject its administration during resuscitation. Larger sample, placebo controlled, double blind, randomized control trials need to be performed to definitively establish the effect of epinephrine on both survival to hospital discharge and the neurological outcomes of treated patients.

Key words: Emergency medicine, Epinephrine, Cardiac arrest, Prehospital, Out-of-hospital, Resuscitation

Peter M. Reardon, Kirk Magee. Epinephrine in out-of-hospital cardiac arrest:A critical review[J]. World Journal of Emergency Medicine, 2013, 4(2): 85-91.

Figures/Tables 1

Table 1

Summarizing the characteristics of studies comparing the use of epinephrine versus no epinephrine in out-of-hospital cardiac arrest.

Study	Description	Patients	Outcomes	Findings	Study quality
Hagihara et al 2012	Prospective cohort study	417 188 adult patients with OHCA, mean age 72 years, 63.5% male (epi), 58.8% male (no epi). VF/VT 13.7% (epi), 7.2% (no epi). Bystander CPR 45.1% (epi), 36% (no epi). Excluded cases were greater than 60 min from call to scene arrival or greater than 480 min from call to hospital.	ROSC, survival at 1 month, 1 month cerebral performance with CPC, and survival with no, mild, or moderate neurological disability with OPC	A positive association was detected between prehospital epinephrine use and ROSC before hospital arrival. A negative association was detected with respect to prehospital epinephrine use and both 1 month survival, and cerebral performance.	High: propensity matched controls to minimize confounders and bias; no individuals lost to follow-up; very large sample size.
Jacobs et al 2011	Randomized, double-blind, placebo-controlled study	601 adult patients with OHCA, mean age 65 years, 73% male. VF/VT in 46% of cases, 51% received bystander CPR. Cases excluded if loss of randomization or resuscitation not commenced.	Primary: survival to hospital discharge Secondary: ROSC, cerebral performance at hospital discharge with CPC	Nonsignificant increase in survival to hospital discharge in epinephrine group. Significant increase in ROSC for epinephrine. Nonsignificant worse neurological outcomes in epinephrine group.	High: strong method of design; regression analysis to limit bias and confounders; main flaw in sample size due to ethical issues. Planned sample size was 5000.
Olasveegan et al 2011	Prospective cohort study	841 adult patients with OHCA, mean age 66, 71% male, VF/VT 32% (epi), 35% (no epi). Bystander CPR in 63%. Cases excluded if loss of randomization, or if unable to determine drug administration.	Primary: survival to hospital discharge Secondary: ROSC, survival to hospital admission, and neurological outcome at hospital discharge	Epinephrine associated with increased short term survival, but with decreased survival to hospital discharge, and decreased favourable neurological outcome.	Low: method of design flawed. Confounding effects include selection bias and effects of other drugs.
Yanagawa and Sakamoto 2010	Case control study	713 adult patients with OHCA occurring between November 2005 and April 2007, mean age 69, 60% male, bystander CPR 34%. Patients excluded if untreated due to death or postmortem signs.	Prehospital ROSC and neurological outcome based on CPC	Epinephrine was associated with prehospital ROSC, but was not significantly associated with "good recovery".	Low: populations were divided based on prehospital ROSC and neurological recovery. The populations were dissimilar and despite multiregression analysis, many confounding variables present.
Ong et al 2007	Prospective cohort study	1291 patients in OHCA, mean age 64 years, 69% male, bystander CPR 19%, VF 20%, VT 0.7%. Exclusion criteria were traumatic cause, death, and younger than 8 years old.	Primary: survival to hospital discharge	No significant difference in survival to hospital discharge, ROSC, or survival to hospital admission. Neurological performance similar in both groups.	Moderate: confounders and bias adequately controlled in selection of controls and regression analysis. Limitations include low sample due to inadequate IV access and disparities in protocol (ie no other drugs given and only one dose of epi permitted).
Oshinge et al 2005	Prospective cohort study	434 patients in OHCA, mean age 69, 62% male. No exclusion criteria identified.	Primary: ICU admission rate and 1 month survival	No statistical difference between group resuscitated with epinephrine and reference group with no epinephrine.	Low: confounding variables as intravenous drugs was not the sole difference in care between groups, and the level of training of personnel differed. No regression analysis done to limit bias.
Wang et al 2005	Survival analysis	1496 patients with OHCA, mean age 67, 56.9 percent male, bystander CPR 46.4%, VF/VT 34.1%. Excluded paediatric patients.	Primary: elapsed time to death	Epinephrine was associated with increased risk of death both early (on day 1) and late (after day 1).	Low: potential for confounders as definitive controls not identified and case matched. Susceptible to selection bias inherent in decision to administer epinephrine or not.
Holmberg et al 2002	Prospective cohort study	10966 cases of OHCA, mean age 67, male: 73.5% (epi) 71.3% (no epi), bystander CPR: 34.6% (epi) 30.5% (no epi), VF 51% (epi) 60.9% (no epi).	1 month survival	Survival rate significantly lower in those given epinephrine.	Low: patient groups not comparable. Several differences indicated.
Herlitz et al 1995	Retrospective cohort study	1203 patients with OHCA in VF; median age: 71 years (epi), 70 years (no epi); 80% men, bystander CPR 20%. Exclusions: Any rhythm other than VF, inadequate information.	ROSC, survival to hospital admission, survival to hospital discharge	Overall: patients in the two groups had similar initial rates of survival. Group treated with epinephrine with lower rates of survival to discharge. Certain rhythm defined subgroups with increased ROSC and survival to hospital.	Low: differences between groups. Difficult to account for actions of other drugs, level of training of personnel.

Table 1

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