Time to Epinephrine Administration and Survival From Nonshockable Out-of-Hospital Cardiac Arrest Among Children and Adults

Q: What are the key findings of this study?

Each minute delay from EMS arrival to epinephrine administration reduced the odds of survival to hospital discharge by 4% (OR 0.96, 95% CI 0.95-0.98) in nonshockable out-of-hospital cardiac arrest.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Out-of-hospital cardiac arrest with nonshockable initial rhythms (n=32101). Intervention: Time from first EMS agency arrival to first dose of epinephrine (per minute delay; also dichotomized as late ≥10 minutes vs early <10 minutes) vs. Earlier epinephrine administration (<10 minutes from EMS arrival). Primary outcome: Survival to hospital discharge (OR 0.96 per minute delay, 95% CI 0.95-0.98).

Q: What does this research mean for the field?

Each minute of delay from EMS arrival to epinephrine administration reduces the odds of survival to hospital discharge by 4% in patients with nonshockable out-of-hospital cardiac arrest. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Matthew Hansen; Robert H. Schmicker; Craig D. Newgard; Brian Grunau; Frank Scheuermeyer; Sheldon Cheskes; Veer Vithalani; Fuad Alnaji; Thomas D. Rea; Ahamed H. Idris; Heather Herren; Jamie Hutchison; Mike Austin; Debra Egan; Mohamud Daya

doi:10.1161/circulationaha.117.033067

March 6, 2018CirculationOpen Access

Time to Epinephrine Administration and Survival From Nonshockable Out-of-Hospital Cardiac Arrest Among Children and Adults

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Key result

Delayed epinephrine linked to ~4% lower odds of discharge survival per minute in nonshockable OHCA.

OR 0.96 per minute delay
95% CI 0.95-0.98
n=32,101

Why the study?

Does earlier time from EMS arrival to epinephrine administration improve survival to hospital discharge in adults and children with out-of-hospital cardiac arrest and nonshockable initial rhythms?

Key Points

To evaluate the association between the timing of first epinephrine administration by emergency medical services and survival to hospital discharge in patients with nonshockable out-of-hospital cardiac arrest.
Secondary analysis of 32,101 prospectively identified patients of all ages with EMS-treated out-of-hospital cardiac arrest and an initial nonshockable rhythm from the Resuscitation Outcomes Consortium (2011–2015).
Excluded patients with return of spontaneous circulation in <10 minutes; analyzed time to first epinephrine dose continuously by minute and dichotomized as early (<10 minutes, n=12,238) versus late (≥10 minutes, n=14,517).
Each additional minute from EMS arrival to epinephrine administration was associated with a 4% decrease in odds of survival to hospital discharge in adults (adjusted OR 0.96; 95% CI, 0.95–0.98), with unadjusted survival of 2.6% in the early group versus 1.7% in the late group (adjusted OR 0.82; 95% CI, 0.68–0.98).
In a subgroup analysis evaluating favorable neurological status (n=13,290), each minute of delay was associated with a 6% decrease in odds of survival with a Modified Rankin Scale score <3 (adjusted OR 0.94; 95% CI, 0.89–0.98).
Among 595 pediatric patients, each minute delay in epinephrine was associated with a 9% reduction in odds of survival, though the finding did not reach statistical significance (adjusted OR 0.91; 95% CI, 0.81–1.01).

Study Design

Type

Cohort (n=32,101)

Multicenter

Yes

Structured PICO

Does earlier time from EMS arrival to epinephrine administration improve survival to hospital discharge in adults and children with out-of-hospital cardiac arrest and nonshockable initial rhythms?

P

Population

32,101 adults and children in the United States and Canada with EMS-treated out-of-hospital cardiac arrest and initial nonshockable rhythms (26,755 treated with epinephrine), excluding those with ROSC <10 minutes, followed to hospital discharge.

E

Exposure

Time (in minutes) from arrival of the first EMS agency on scene to the first dose of epinephrine (administered via IV or IO route); also evaluated dichotomously as late (≥10 minutes, n=14,517 in abstract / 14,417 in text) versus early (<10 minutes, n=12,238) epinephrine administration.

C

Comparator

Earlier administration of epinephrine (<10 minutes from first EMS arrival on scene); sensitivity analyses also included 5,346 patients not treated with epinephrine as part of the late group.

O

Outcome

Survival to hospital dischargehard clinical

Main Result

Odds Ratio: 0.96 (95% CI 0.95–0.98)

Limitations

Secondary observational analysis of a cardiac arrest registry, allowing only assessment of association rather than causation
Potential for residual confounding beyond traditional Utstein variables
Earlier epinephrine administration may be a marker for higher quality ALS care overall and analyses may not fully account for ALS care variability within individual EMS agencies
ROC sites represent mature, high-functioning North American EMS systems that may not be generalizable to other settings
Unable to assess specific aspects of post-resuscitation hospital care such as targeted temperature management and early coronary angiography
Secondary analysis of a registry able to determine association rather than causation
Potential for residual confounding not captured by Utstein covariates
Potential confounding by unmeasured variability in overall ALS care quality within individual EMS agencies
Limited generalizability outside of mature, high-functioning North American EMS systems
Inability to account for post-resuscitation hospital care practices (e.g., targeted temperature management, early coronary angiography)

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Implication

In patients with nonshockable out-of-hospital cardiac arrest, each minute of delay from EMS arrival to epinephrine administration is associated with a 4% reduction in the odds of survival to hospital discharge and worse neurological outcomes, supporting EMS strategies to expedite epinephrine delivery.

Abstract

BACKGROUND: Previous studies have demonstrated that earlier epinephrine administration is associated with improved survival from out-of-hospital cardiac arrest (OHCA) with shockable initial rhythms. However, the effect of epinephrine timing on patients with nonshockable initial rhythms is unclear. The objective of this study was to measure the association between time to epinephrine administration and survival in adults and children with emergency medical services (EMS)-treated OHCA with nonshockable initial rhythms. METHODS: We performed a secondary analysis of OHCAs prospectively identified by the Resuscitation Outcomes Consortium network from June 4, 2011, to June 30, 2015. We included patients of all ages with an EMS-treated OHCA and an initial nonshockable rhythm. We excluded those with return of spontaneous circulation in <10 minutes. We conducted a subgroup analysis involving patients <18 years of age. The primary exposure was time (minutes) from arrival of the first EMS agency to the first dose of epinephrine. Secondary exposure was time to epinephrine dichotomized as early (<10 minutes) or late (≥10 minutes). The primary outcome was survival to hospital discharge. We adjusted for Utstein covariates and Resuscitation Outcomes Consortium study site. RESULTS: From 55 568 EMS-treated OHCAs, 32 101 patients with initial nonshockable rhythms were included. There were 12 238 in the early group, 14 517 in the late group, and 5346 not treated with epinephrine. After adjusting for potential confounders, each minute from EMS arrival to epinephrine administration was associated with a 4% decrease in odds of survival for adults, odds ratio=0.96 (95% confidence interval, 0.95-0.98). A subgroup analysis (n=13 290) examining neurological outcomes showed a similar association (adjusted odds ratio, 0.94 per minute; 95% confidence interval, 0.89-0.98). When epinephrine was given late in comparison with early, odds of survival were 18% lower (odds ratio, 0.82; 95% confidence interval, 0.68-0.98). In a pediatric analysis (n=595), odds of survival were 9% lower (odds ratio, 0.91; 95% confidence interval, 0.81-1.01) for each minute delay in epinephrine. CONCLUSIONS: Among OHCAs with nonshockable initial rhythms, the majority of patients were administered epinephrine >10 minutes after EMS arrival. Each minute delay in epinephrine administration was associated with decreased survival and unfavorable neurological outcomes. EMS agencies should consider strategies to reduce epinephrine administration times in patients with initial nonshockable rhythms.

Discussion

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Cite This Study

Hansen et al. (2018) conducted a cohort in Out-of-hospital cardiac arrest with nonshockable initial rhythms (n=32,101). Time from first EMS agency arrival to first dose of epinephrine (per minute delay; also dichotomized as late ≥10 minutes vs early <10 minutes) vs. Earlier epinephrine administration (<10 minutes from EMS arrival) was evaluated on Survival to hospital discharge (OR 0.96 per minute delay, 95% CI 0.95-0.98). Each minute delay from EMS arrival to epinephrine administration reduced the odds of survival to hospital discharge by 4% (OR 0.96, 95% CI 0.95-0.98) in nonshockable out-of-hospital cardiac arrest.

synapsesocial.com/papers/6a715a2bf3af83f2265d66b9 https://doi.org/10.1161/circulationaha.117.033067

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Time to Epinephrine Administration and Survival From Nonshockable Out-of-Hospital Cardiac Arrest Among Children and Adults

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Time to Epinephrine Administration and Survival From Nonshockable Out-of-Hospital Cardiac Arrest Among Children and Adults

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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