TY - JOUR
T1 - Analysis of Epinephrine Dose, Targeted Temperature Management, and Neurologic and Survival Outcomes Among Adults With Out-of-Hospital Cardiac Arrest
AU - Yang, Betty Y.
AU - Bulger, Natalie
AU - Chocron, Richard
AU - Counts, Catherine R.
AU - Drucker, Chris
AU - Yin, Lihua
AU - Parayil, Megin
AU - Johnson, Nicholas J.
AU - Sotoodehenia, Nona
AU - Kudenchuk, Peter J.
AU - Sayre, Michael R.
AU - Rea, Thomas D.
N1 - Funding Information:
Acquisition, analysis, or interpretation of data: Yang, Bulger, Chocron, Counts, Drucker, Yin, Parayil, Johnson, Sotoodehenia, Rea. Drafting of the manuscript: Yang, Chocron. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Yang, Chocron, Parayil. Obtained funding: Sotoodehenia. Administrative, technical, or material support: Bulger, Counts, Drucker, Yin, Parayil, Kudenchuk, Sayre, Rea. Supervision: Drucker, Johnson, Sayre, Rea. Conflict of Interest Disclosures: Dr Yang reported receiving grants from he American Heart Association Strategically Focused Research Network during the conduct of the study. Dr Johnson reported receiving grants as a National Institutes of Health site investigator for the Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients trial, US National Institutes of Health, US Centers for Disease Control and Prevention, US Department of Defense, and University of Washington Royalty Research Fund for unrelated work during the conduct of the study. Dr Sotoodehenia reported receiving grants from the American Heart Association not related to the current study topic. Dr Sayre reported receiving personal fees from Stryker Emergency Response and grants from Flashback Technologies outside the submitted work. Dr Rea reported receiving grants from the American Heart Association not related to the current study topic, grants from Philips Medical Inc not related to the current study topic, grants from Medtronic Foundation not related to the current study topic, and grants from the National Institutes of Health not related to the current study topic outside the submitted work. No other disclosures were reported.
Publisher Copyright:
© 2022 American Medical Association. All rights reserved.
PY - 2022/8/11
Y1 - 2022/8/11
N2 - Importance: Epinephrine 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. Objective: To examine whether targeted temperature management (TTM) modifies the adverse association between increasing prehospital epinephrine dose and neurologically favorable survival. Design, Setting, and Participants: This retrospective cohort study assessed 14612 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. Exposures: Epinephrine dose and TTM during prehospital resuscitation. Main Outcomes and Measures: Favorable neurologic survival (Cerebral Performance Category [CPC] 1 or 2) and survival to hospital discharge. Results: Of the 14612 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 Relevance: This 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.
AB - Importance: Epinephrine 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. Objective: To examine whether targeted temperature management (TTM) modifies the adverse association between increasing prehospital epinephrine dose and neurologically favorable survival. Design, Setting, and Participants: This retrospective cohort study assessed 14612 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. Exposures: Epinephrine dose and TTM during prehospital resuscitation. Main Outcomes and Measures: Favorable neurologic survival (Cerebral Performance Category [CPC] 1 or 2) and survival to hospital discharge. Results: Of the 14612 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 Relevance: This 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.
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U2 - 10.1001/jamanetworkopen.2022.26191
DO - 10.1001/jamanetworkopen.2022.26191
M3 - Article
C2 - 35951327
AN - SCOPUS:85136339744
SN - 2574-3805
VL - 5
SP - E2226191
JO - JAMA network open
JF - JAMA network open
IS - 8
ER -