LAUSR

The association of epinephrine with outcomes from out-of-hospital cardiac arrest (OHCA) remains poorly understood, despite epinephrine being routinely used in cardiac arrest resuscitation for more than 50 years. Randomized clinical trial 1 evidence has shown that epinephrine increases initial survival but with an increased rate of neurologic injury, although other work 2 has suggested that the benefit of epinephrine is dependent on the timing of administration, with earlier administration during arrest being associated with increased benefit. Whether post–cardiac arrest care using targeted temperature management (TTM), generally with a target of 33 °C or 36 °C, could lessen neurologic injury after epinephrine use in OHCA remains an important question. Although TTM is a widely used mitigation strategy for post–cardiac arrest cerebral injury, randomized clinical trials have called into question whether TTM is effective when compared with careful avoidance of fever after resuscitation. 3 Recent work 4-6 from multiple teams has suggested that TTM to 33 °C is associated with neurologic survival benefit in subgroups of patients with OHCA with more severe injury. The future development of robust methods to assign individual patients with OHCA to optimal TTM treatment plans is a critical step to improving outcomes. Epinephrine dosage could potentially serve as an early guide for subsequent decisions regarding TTM strategy. In their cohort study, Yang et al 7 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. Data were collected primarily through review of emergency medical services records, with TTM use and hospital outcomes reported by receiving hospitals. The study’s primary outcome was neurologically favorable survival, defined as a Cerebral Performance Category of 1 or 2. Theauthorsfirstdemonstratedanassociationbetweenlargercumulativeepinephrinedoseand worse neurologic outcomes, confirming findings from previous work. Neurologically favorable survival decreased with each additional milligram of epinephrine administrated: 75% at 0 mg, 38% at more than 0 to 1 mg, 24% at more than 1 to 2 mg, 17% at more than 2 to 3 mg, 16% at more than 3 to 4 mg, and 15% at more than 4 mg. The study data suggest that TTM attenuates this adverse association, particularly among patients with shockable initial rhythms. After OHCA with shockable rhythms, 31.1% of patients receiving more than 3 to 4 mg of epinephrine achieved a Cerebral Performance Category of 1 or 2 after undergoing TTM as opposed to 18.9% of a comparator group that did not receive TTM. Overall, the use of TTM was associated with improved neurologic survival. Thesefindingsaddtotheincreasingbodyofworkaboutthepotentialsurvivalbenefitconferred 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 7 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.