Abstract
Background The benefit of prehospital epinephrine in out-of-hospital cardiac arrest (OHCA) was shown in a recent large placebo-controlled trial. However, placebo-controlled studies cannot identify the nonpharmacologic influences on concurrent or downstream events that might modify the main effect positively or negatively. We sought to identify the real-world effect of epinephrine from a clinical registry using Bayesian network with time-sequence constraints. Methods We analyzed a prospective regional registry of OHCA where a prehospital advanced life support (ALS) protocol named “Smart ALS (SALS)” was gradually implemented from July 2015 to December 2016. Using Bayesian network, a causal structure was estimated. The effect of epinephrine and SALS program was modelled based on the structure using extended Cox-regression and logistic regression, respectively. Results Among 4324 patients, SALS was applied to 2351 (54.4%) and epinephrine was administered in 1644 (38.0%). Epinephrine was associated with faster ROSC rate in nonshockable rhythm (HR: 2.02, 6.94, and 7.43; 95% CI: 1.08–3.78, 4.15–11.61, and 2.92–18.91, respectively, for 1–10, 11–20, and >20 minutes) while it was associated with slower rate up to 20 minutes in shockable rhythm (HR: 0.40, 0.50, and 2.20; 95% CI: 0.21–0.76, 0.32–0.77, and 0.76–6.33). SALS was associated with increased prehospital ROSC and neurologic recovery in noncardiac etiology (HR: 5.36 and 2.05; 95% CI: 3.48–8.24 and 1.40–3.01, respectively, for nonshockable and shockable rhythm). Conclusions Epinephrine was associated with faster ROSC rate in nonshockable rhythm but slower rate in shockable rhythm up to 20 minutes. SALS was associated with improved prehospital ROSC and neurologic recovery in noncardiac etiology.
Highlights
Current guidelines recommend epinephrine for advanced life support (ALS) in out-of-hospital cardiac arrest (OHCA) [1, 2]
If we see the aspect of epinephrine use as an ALS procedure, rather than just focusing on the pharmacologic effect, it is still not clear how its use will manifest in realworld situation because the procedural aspect, such as securing an intravenous access which was controlled in the study by using saline placebo, can have significant impact on other concurrent or downstream events and procedures that might significantly modify the main effect of epinephrine in a positive or a negative way
Prehospital ROSC was dependent on initial rhythm, Smart ALS (SALS), epinephrine, and presumed etiology
Summary
Current guidelines recommend epinephrine for advanced life support (ALS) in out-of-hospital cardiac arrest (OHCA) [1, 2]. E study objectively assessed the averaged pharmacologic effect of the drug in OHCA. If we see the aspect of epinephrine use as an ALS procedure, rather than just focusing on the pharmacologic effect, it is still not clear how its use will manifest in realworld situation because the procedural aspect, such as securing an intravenous access which was controlled in the study by using saline placebo, can have significant impact on other concurrent or downstream events and procedures that might significantly modify the main effect of epinephrine in a positive or a negative way. One alternative approach that can access the real-world effect of epinephrine as an ALS procedure will be conducting an observational study using clinical registries. The treatment allocation in real-world situation is never random and conditioning the appropriate variables is very important. One need to control a set of confounders that will close every open pathway between exposure and outcome variables while being cautious not to open a closed pathway by conditioning colliders [5, 6]
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