TY - JOUR
T1 - Effects of Hypothermia vs Normothermia on Societal Participation and Cognitive Function at 6 Months in Survivors After Out-of-Hospital Cardiac Arrest
T2 - A Predefined Analysis of the TTM2 Randomized Clinical Trial
AU - Lilja, Gisela
AU - Ullén, Susann
AU - Dankiewicz, Josef
AU - Friberg, Hans
AU - Levin, Helena
AU - Nordström, Erik Blennow
AU - Heimburg, Katarina
AU - Jakobsen, Janus Christian
AU - Ahlqvist, Marita
AU - Bass, Frances
AU - Belohlavek, Jan
AU - Olsen, Roy Bjørkholt
AU - Cariou, Alain
AU - Eastwood, Glenn
AU - Fanebust, Hans Rune
AU - Grejs, Anders M
AU - Grimmer, Lisa
AU - Hammond, Naomi E
AU - Hovdenes, Jan
AU - Hrecko, Juraj
AU - Iten, Manuela
AU - Johansen, Henriette
AU - Keeble, Thomas R
AU - Kirkegaard, Hans
AU - Lascarrou, Jean-Baptiste
AU - Leithner, Christoph
AU - Lesona, Mildred Eden
AU - Levis, Anja
AU - Mion, Marco
AU - Moseby-Knappe, Marion
AU - Navarra, Leanlove
AU - Nordberg, Per
AU - Pelosi, Paolo
AU - Quayle, Rachael
AU - Rylander, Christian
AU - Sandberg, Helena
AU - Saxena, Manoj
AU - Schrag, Claudia
AU - Siranec, Michal
AU - Tiziano, Cassina
AU - Vignon, Philippe
AU - Wendel-Garcia, Pedro David
AU - Wise, Matt P
AU - Wright, Kim
AU - Nielsen, Niklas
AU - Cronberg, Tobias
PY - 2023/10/1
Y1 - 2023/10/1
N2 - IMPORTANCE: The Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial reported no difference in mortality or poor functional outcome at 6 months after out-of-hospital cardiac arrest (OHCA). This predefined exploratory analysis provides more detailed estimation of brain dysfunction for the comparison of the 2 intervention regimens.OBJECTIVES: To investigate the effects of targeted hypothermia vs targeted normothermia on functional outcome with focus on societal participation and cognitive function in survivors 6 months after OHCA.DESIGN, SETTING, AND PARTICIPANTS: This study is a predefined analysis of an international multicenter, randomized clinical trial that took place from November 2017 to January 2020 and included participants at 61 hospitals in 14 countries. A structured follow-up for survivors performed at 6 months was by masked outcome assessors. The last follow-up took place in October 2020. Participants included 1861 adult (older than 18 years) patients with OHCA who were comatose at hospital admission. At 6 months, 939 of 1861 were alive and invited to a follow-up, of which 103 of 939 declined or were missing.INTERVENTIONS: Randomization 1:1 to temperature control with targeted hypothermia at 33 °C or targeted normothermia and early treatment of fever (37.8 °C or higher).MAIN OUTCOMES AND MEASURES: Functional outcome focusing on societal participation assessed by the Glasgow Outcome Scale Extended ([GOSE] 1 to 8) and cognitive function assessed by the Montreal Cognitive Assessment ([MoCA] 0 to 30) and the Symbol Digit Modalities Test ([SDMT] z scores). Higher scores represent better outcomes.RESULTS: At 6 months, 836 of 939 survivors with a mean age of 60 (SD, 13) (range, 18 to 88) years (700 of 836 male [84%]) participated in the follow-up. There were no differences between the 2 intervention groups in functional outcome focusing on societal participation (GOSE score, odds ratio, 0.91; 95% CI, 0.71-1.17; P = .46) or in cognitive function by MoCA (mean difference, 0.36; 95% CI,-0.33 to 1.05; P = .37) and SDMT (mean difference, 0.06; 95% CI,-0.16 to 0.27; P = .62). Limitations in societal participation (GOSE score less than 7) were common regardless of intervention (hypothermia, 178 of 415 [43%]; normothermia, 168 of 419 [40%]). Cognitive impairment was identified in 353 of 599 survivors (59%).CONCLUSIONS: In this predefined analysis of comatose patients after OHCA, hypothermia did not lead to better functional outcome assessed with a focus on societal participation and cognitive function than management with normothermia. At 6 months, many survivors had not regained their pre-arrest activities and roles, and mild cognitive dysfunction was common.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02908308.
AB - IMPORTANCE: The Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial reported no difference in mortality or poor functional outcome at 6 months after out-of-hospital cardiac arrest (OHCA). This predefined exploratory analysis provides more detailed estimation of brain dysfunction for the comparison of the 2 intervention regimens.OBJECTIVES: To investigate the effects of targeted hypothermia vs targeted normothermia on functional outcome with focus on societal participation and cognitive function in survivors 6 months after OHCA.DESIGN, SETTING, AND PARTICIPANTS: This study is a predefined analysis of an international multicenter, randomized clinical trial that took place from November 2017 to January 2020 and included participants at 61 hospitals in 14 countries. A structured follow-up for survivors performed at 6 months was by masked outcome assessors. The last follow-up took place in October 2020. Participants included 1861 adult (older than 18 years) patients with OHCA who were comatose at hospital admission. At 6 months, 939 of 1861 were alive and invited to a follow-up, of which 103 of 939 declined or were missing.INTERVENTIONS: Randomization 1:1 to temperature control with targeted hypothermia at 33 °C or targeted normothermia and early treatment of fever (37.8 °C or higher).MAIN OUTCOMES AND MEASURES: Functional outcome focusing on societal participation assessed by the Glasgow Outcome Scale Extended ([GOSE] 1 to 8) and cognitive function assessed by the Montreal Cognitive Assessment ([MoCA] 0 to 30) and the Symbol Digit Modalities Test ([SDMT] z scores). Higher scores represent better outcomes.RESULTS: At 6 months, 836 of 939 survivors with a mean age of 60 (SD, 13) (range, 18 to 88) years (700 of 836 male [84%]) participated in the follow-up. There were no differences between the 2 intervention groups in functional outcome focusing on societal participation (GOSE score, odds ratio, 0.91; 95% CI, 0.71-1.17; P = .46) or in cognitive function by MoCA (mean difference, 0.36; 95% CI,-0.33 to 1.05; P = .37) and SDMT (mean difference, 0.06; 95% CI,-0.16 to 0.27; P = .62). Limitations in societal participation (GOSE score less than 7) were common regardless of intervention (hypothermia, 178 of 415 [43%]; normothermia, 168 of 419 [40%]). Cognitive impairment was identified in 353 of 599 survivors (59%).CONCLUSIONS: In this predefined analysis of comatose patients after OHCA, hypothermia did not lead to better functional outcome assessed with a focus on societal participation and cognitive function than management with normothermia. At 6 months, many survivors had not regained their pre-arrest activities and roles, and mild cognitive dysfunction was common.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02908308.
UR - http://www.scopus.com/inward/record.url?scp=85174607883&partnerID=8YFLogxK
U2 - 10.1001/jamaneurol.2023.2536
DO - 10.1001/jamaneurol.2023.2536
M3 - Journal article
C2 - 37548968
SN - 2168-6149
VL - 80
SP - 1070
EP - 1079
JO - JAMA Neurology
JF - JAMA Neurology
IS - 10
ER -