Association Between Timing of Epinephrine Administration and Intact Neurologic Survival Following Out‐of‐hospital Cardiac Arrest in Japan: A Population‐based Prospective Observational Study

Abstract

ACADEMIC EMERGENCY MEDICINE 2012; 19:782–792 © 2012 by the Society for Academic Emergency Medicine Abstract Objectives: This study aimed to investigate whether early epinephrine administration in out‐of‐hospital cardiopulmonary arrest (OHCA) patients was associated with improved outcomes and to address the selection bias inherent in observational studies (more severe cases are more likely to receive epinephrine). Methods: This was a retrospective analysis of prospectively collected population‐based data of adult bystander‐witnessed OHCA patients from a nationwide Japanese registry between January 2007 and December 2008. To address selection bias, those who attained early return of spontaneous circulation (ROSC) without epinephrine administration were excluded, leaving 49,165 patients in the analysis. The outcomes were intact neurologic survival, defined as survival with cerebral performance category score 1or 2, and any survival at 1 month or at discharge (whichever was earlier). The primary predictor was the time from the start of cardiopulmonary resuscitation (CPR) by emergency medical services (EMS) to first epinephrine administration, with early epinephrine defined as within 10 minutes. Results: Multivariate logistic regression analysis showed that cardiac origin OHCA patients who received early epinephrine (≤10 minutes) had significantly higher rates of intact neurologic survival (odds ratio [OR] = 1.39, 95% confidence interval [CI] = 1.08 to 1.78) and any survival (OR = 1.73, 95% CI = 1.46 to 2.04) than those who did not receive early epinephrine, after adjusting for potential confounders. Results for noncardiac OHCA patients were similar. Conclusions: Early epinephrine administration may be associated with higher rates of intact neurologic survival and any survival in adult bystander‐witnessed OHCA patients. This article provides a potential method to address the selection bias inherent in observational studies that examine the effects of drug administration in OHCA patients.

Part 7: Adult Advanced Cardiovascular Life Support

“…A study of 209 577 OHCA patients 133 showed improved 1-month survival when outcomes from administration of epinephrine at less than 9 minutes of EMS-initiated CPR were compared with those in which epinephrine was administered at greater than 10 minutes. Another study enrolling 212 228 OHCA patients 134 showed improved survival to discharge with early epinephrine (less than 10 minutes after EMS-initiated CPR) compared with no epinephrine. A smaller study of 686 OHCA patients 135 showed improved rates of ROSC with early epinephrine (less than 10 minutes after 9-1-1 call) when the presenting rhythm was pulseless electrical activity.…”

Part 4: Advanced Life Support

“…16 and OR, 1.78; 95% CI, 1.5-2.1). Another study 133 showed an association with improved survival with early epinephrine (less than 10 minutes from EMS CPR): for arrests of cardiac origin: OR, 1.73 (95% CI, 1.46-2.04); for noncardiac origin: OR, 1.89 (95% CI, 1.37-2.61). A third study 134 did not show any overall survival benefit for early epinephrine compared with late (epinephrine at more or less than 10 minutes): OR, 0.91 (95% CI, 0.35-2.37).…”

“…For the critical outcome of neurologically favorable survival at hospital discharge (assessed with CPC 1 or 2), there was very-low-quality evidence (downgraded for risk of bias, inconsistency, indirectness, and imprecision) from 4 observational studies [130][131][132][133] involving more than 262 556 OHCAs, showing variable benefit from early administration of epinephrine. One study of 1556 OHCAs who had achieved ROSC 130 demonstrated an association between the administration of epinephrine and worse CPC, but shorter times of administration were associated with less negative effects: adjusted OR of 0.54 (95% CI, 0.32-0.91) for good CPC with epinephrine at less than 9 minutes versus no prehospital epinephrine, and adjusted OR of 0.17 (95% CI, 0.09-0.34) for epinephrine at more than 22 minutes.…”

“…Another study enrolling 3161 subjects 132 showed an association with improved 1-month neurologic outcome in VF/pVT OHCA with early epinephrine (at 10 minutes or less from EMS call to administration) compared with no S104 Circulation For the critical outcome of survival to hospital discharge after OHCA, there was very-low-quality evidence (downgraded for risk of bias, inconsistency, indirectness, and imprecision), from 4 observational studies 127,131,133,134 enrolling more than 420 000 OHCAs that showed variable effect from early administration of adrenaline. Goto 131 showed no significant difference in 1-month survival for shockable rhythms, but improved 1-month survival for shockable rhythms with epinephrine at less than 9 minutes (OR, 0.95; 95% CI, 0.77-1.…”

The fast emergency vehicle pre-emption system improved the outcomes of out-of-hospital cardiac arrest

“…Because tracheal intubation and epinephrine administration have been shown to affect OHCA outcomes [16,[18][19][20][21][22] and because the incidences of these procedures widely differed between the two groups (Table 2), we analyzed the impact of FAST TM on the outcomes of OHCAs managed prior to hospital arrival without tracheal intubation or epinephrine administration.…”