Analysis of Epinephrine Dose, Targeted Temperature Management, and Neurologic and Survival Outcomes Among Adults With Out-of-Hospital Cardiac Arrest

Abstract

ImportanceEpinephrine improves return of spontaneous circulation after out-of-hospital cardiac arrest (OHCA). These beneficial cardiac effects do not directly translate to better neurologic outcomes, possibly because of epinephrine-induced microvascular effects that produce critical brain ischemia.ObjectiveTo examine whether targeted temperature management (TTM) modifies the adverse association between increasing prehospital epinephrine dose and neurologically favorable survival.Design, Setting, and ParticipantsThis retrospective cohort study assessed 14 612 adults from Seattle and King County, Washington, with nontraumatic OHCA between January 1, 2008, and December 31, 2018, and included those who achieved return of spontaneous circulation and were unconscious at hospital admission. Data analysis was performed from April 2021 to May 2022.ExposuresEpinephrine dose and TTM during prehospital resuscitation.Main Outcomes and MeasuresFavorable neurologic survival (Cerebral Performance Category [CPC] 1 or 2) and survival to hospital discharge.ResultsOf the 14 612 assessed adults, 5253 (median age, 63 years; IQR, 51-74 years; 3460 [65.8%] male) were eligible for the study. The median epinephrine dose was 2.0 mg (IQR, 1.0-3.0 mg); 3052 patients (58.1%) received TTM. In all, 1889 patients (36.0%) survived with CPC 1 to 2, and 2177 (41.4%) survived to discharge. Increasing doses of epinephrine were associated with a decreasing likelihood of CPC 1 to 2 (odds ratio [OR], 0.46; 95% CI 0.42-0.50 for each additional milligram of epinephrine) and survival (OR, 0.47; 95% CI, 0.43-0.51). The dose-dependent epinephrine association was modified by TTM. After adjusting for Utstein covariates, TTM was associated with a relative stepwise improvement in odds of CPC 1 to 2 (interaction OR, 1.36; 95% CI, 1.22-1.51) and survival (interaction OR, 1.37; 95% CI, 1.24-1.51). A significant interaction was also observed when the analysis was stratified according to initial rhythm among shockable OHCA and nonshockable OHCA (shockable interaction OR, 1.20; 95% CI, 1.04-1.39; and nonshockable interaction OR, 1.24, 95% CI, 1.07-1.45).Conclusions and RelevanceThis cohort study found an interaction between TTM and epinephrine dose such that the beneficial association of TTM increased with increasing epinephrine dose, suggesting that TTM may attenuate the adverse effects of higher-dose epinephrine.

One-Year Review in Cardiac Arrest: The 2022 Randomized Controlled Trials

“…Thus, large and powered RCTs are likely needed to make a solid recommendation for this specific population of patients after IHCA. Nevertheless, it is probably time to investigate hypothermic TTM not alone but in conjunction with more comprehensive interventions potentially impacting outcomes, such as sedation level, duration, and hemodynamics (i.e., with more sharp pressure targets compared to those discussed in the following paragraphs) and in specific populations in which cooling might still have a beneficial role, as suggested by recent reports, i.e., patients resuscitated after long CPR with high epinephrine administration or with severe post-cardiac arrest illness [ 40 , 41 ].…”

Epinephrine Dosing and Post–Cardiac Arrest Targeted Temperature Management—Injury Severity After Resuscitation

“…This selection process could limit moribund patients from receiving TTM, shifting toward a higher effect size of benefit from TTM use among the patients receiving more than 3 to 4 mg and more than 4 mg of epinephrine. In addition, few data were presented by Yang et al 7 regarding post-cardiac arrest care factors, such as timing of care withdrawal or time to administration of TTM therapy, both shown to have important associations with outcomes in patients who have had cardiac arrest. Patients with OHCA in the study cohort were treated at 14 receiving hospitals; it is possible that care practices varied regarding these and other important variables that have been shown to be associated with neurologic outcomes.…”

“…In their cohort study, Yang et al report on a retrospective analysis of OHCA outcomes in Seattle and King County, Washington, to investigate whether post–cardiac arrest TTM was associated with survival benefit in patients who received varying doses of epinephrine during resuscitation efforts. They evaluated an adult nontraumatic cardiac arrest cohort (n = 5253) receiving resuscitation care from 2008 to 2018.…”

“…These findings add to the increasing body of work about the potential survival benefit conferred by TTM use in subgroups of OHCA patients, in particular among those with a greater post–cardiac arrest injury severity. The work of Yang et al provides important insight into epinephrine dosage as a quantitative measure, available early during post–cardiac arrest care, that may guide subsequent decision-making regarding TTM use.…”

“…It is a well-understood concept throughout medicine, and specifically in critical care, that treatment selection depends on disease severity. Just as not all patients with sepsis benefit from vasopressor therapy but some patients require it, the important work of Yang et al adds to the increasing recognition that patients with OHCA cannot be easily bundled under the rubric of a single therapeutic approach. The work ahead will require definition of clinically practical methods to define post–cardiac arrest injury severity to guide decisions for therapies such as TTM, regarding both target temperature and duration of therapy.…”