Duration of Device-Based Fever Prevention after Cardiac Arrest

Christian Hassager; Henrik Schmidt; Jacob E Møller; Johannes Grand; Simon Mølstrøm; Rasmus P Beske; Søren Boesgaard; Britt Borregaard; Ditte Bekker-Jensen; Jordi S Dahl; Martin S Frydland; Dan E Høfsten; Yusuf A Isse; Jakob Josiassen; Vibeke R Lind Jørgensen; Daniel Kondziella; Matias G Lindholm; Emil Moser; Benjamin C Nyholm; Laust E R Obling; Laura Sarkisian; Frederik T Søndergaard; Jakob H Thomsen; Jens J Thune; Søren Venø; Sebastian C Wiberg; Matilde Winther-Jensen; Martin A S Meyer; Jesper Kjaergaard

doi:10.1056/NEJMoa2212528

Duration of Device-Based Fever Prevention after Cardiac Arrest

Christian Hassager^*, Henrik Schmidt, Jacob E Møller, Johannes Grand, Simon Mølstrøm, Rasmus P Beske, Søren Boesgaard, Britt Borregaard, Ditte Bekker-Jensen, Jordi S Dahl, Martin S Frydland, Dan E Høfsten, Yusuf A Isse, Jakob Josiassen, Vibeke R Lind Jørgensen, Daniel Kondziella, Matias G Lindholm, Emil Moser, Benjamin C Nyholm, Laust E R OblingLaura Sarkisian, Frederik T Søndergaard, Jakob H Thomsen, Jens J Thune, Søren Venø, Sebastian C Wiberg, Matilde Winther-Jensen, Martin A S Meyer, Jesper Kjaergaard

^*Corresponding author for this work

Abstract

BACKGROUND: Guidelines recommend active fever prevention for 72 hours after cardiac arrest. Data from randomized clinical trials of this intervention have been lacking.

METHODS: We randomly assigned comatose patients who had been resuscitated after an out-of-hospital cardiac arrest of presumed cardiac cause to device-based temperature control targeting 36°C for 24 hours followed by targeting of 37°C for either 12 or 48 hours (for total intervention times of 36 and 72 hours, respectively) or until the patient regained consciousness. The primary outcome was a composite of death from any cause or hospital discharge with a Cerebral Performance Category of 3 or 4 (range, 1 to 5, with higher scores indicating more severe disability; a category of 3 or 4 indicates severe cerebral disability or coma) within 90 days after randomization. Secondary outcomes included death from any cause and the Montreal Cognitive Assessment score (range, 0 to 30, with higher scores indicating better cognitive ability) at 3 months.

RESULTS: A total of 393 patients were randomly assigned to temperature control for 36 hours, and 396 patients were assigned to temperature control for 72 hours. At 90 days after randomization, a primary end-point event had occurred in 127 of 393 patients (32.3%) in the 36-hour group and in 133 of 396 patients (33.6%) in the 72-hour group (hazard ratio, 0.99; 95% confidence interval, 0.77 to 1.26; P = 0.70) and mortality was 29.5% in the 36-hour group and 30.3% in the 72-hour group. At 3 months, the median Montreal Cognitive Assessment score was 26 (interquartile range, 24 to 29) and 27 (interquartile range, 24 to 28), respectively. There was no significant between-group difference in the incidence of adverse events.

CONCLUSIONS: Active device-based fever prevention for 36 or 72 hours after cardiac arrest did not result in significantly different percentages of patients dying or having severe disability or coma. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials.gov number, NCT03141099.).

Original language	English
Journal	The New England journal of medicine
Volume	388
Issue number	10
Pages (from-to)	888-897
Number of pages	10
ISSN	0028-4793
DOIs	https://doi.org/10.1056/NEJMoa2212528
Publication status	Published - 9 Mar 2023

Keywords

Body Temperature
Cardiopulmonary Resuscitation
Coma/etiology
Consciousness
Fever/etiology
Humans
Hypothermia, Induced/adverse effects
Out-of-Hospital Cardiac Arrest/complications
Treatment Outcome

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10.1056/NEJMoa2212528

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Hassager, C., Schmidt, H., Møller, J. E., Grand, J., Mølstrøm, S., Beske, R. P., Boesgaard, S., Borregaard, B., Bekker-Jensen, D., Dahl, J. S., Frydland, M. S., Høfsten, D. E., Isse, Y. A., Josiassen, J., Lind Jørgensen, V. R., Kondziella, D., Lindholm, M. G., Moser, E., Nyholm, B. C., ... Kjaergaard, J. (2023). Duration of Device-Based Fever Prevention after Cardiac Arrest. The New England journal of medicine, 388(10), 888-897. https://doi.org/10.1056/NEJMoa2212528

Hassager, C, Schmidt, H, Møller, JE, Grand, J, Mølstrøm, S, Beske, RP , Boesgaard, S, Borregaard, B, Bekker-Jensen, D, Dahl, JS, Frydland, MS , Høfsten, DE , Isse, YA , Josiassen, J , Lind Jørgensen, VR , Kondziella, D , Lindholm, MG, Moser, E, Nyholm, BC , Obling, LER, Sarkisian, L, Søndergaard, FT , Thomsen, JH , Thune, JJ, Venø, S, Wiberg, SC , Winther-Jensen, M, Meyer, MAS & Kjaergaard, J 2023, 'Duration of Device-Based Fever Prevention after Cardiac Arrest', The New England journal of medicine, vol. 388, no. 10, pp. 888-897. https://doi.org/10.1056/NEJMoa2212528

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title = "Duration of Device-Based Fever Prevention after Cardiac Arrest",

abstract = "BACKGROUND: Guidelines recommend active fever prevention for 72 hours after cardiac arrest. Data from randomized clinical trials of this intervention have been lacking.METHODS: We randomly assigned comatose patients who had been resuscitated after an out-of-hospital cardiac arrest of presumed cardiac cause to device-based temperature control targeting 36°C for 24 hours followed by targeting of 37°C for either 12 or 48 hours (for total intervention times of 36 and 72 hours, respectively) or until the patient regained consciousness. The primary outcome was a composite of death from any cause or hospital discharge with a Cerebral Performance Category of 3 or 4 (range, 1 to 5, with higher scores indicating more severe disability; a category of 3 or 4 indicates severe cerebral disability or coma) within 90 days after randomization. Secondary outcomes included death from any cause and the Montreal Cognitive Assessment score (range, 0 to 30, with higher scores indicating better cognitive ability) at 3 months.RESULTS: A total of 393 patients were randomly assigned to temperature control for 36 hours, and 396 patients were assigned to temperature control for 72 hours. At 90 days after randomization, a primary end-point event had occurred in 127 of 393 patients (32.3%) in the 36-hour group and in 133 of 396 patients (33.6%) in the 72-hour group (hazard ratio, 0.99; 95% confidence interval, 0.77 to 1.26; P = 0.70) and mortality was 29.5% in the 36-hour group and 30.3% in the 72-hour group. At 3 months, the median Montreal Cognitive Assessment score was 26 (interquartile range, 24 to 29) and 27 (interquartile range, 24 to 28), respectively. There was no significant between-group difference in the incidence of adverse events.CONCLUSIONS: Active device-based fever prevention for 36 or 72 hours after cardiac arrest did not result in significantly different percentages of patients dying or having severe disability or coma. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials.gov number, NCT03141099.).",

keywords = "Body Temperature, Cardiopulmonary Resuscitation, Coma/etiology, Consciousness, Fever/etiology, Humans, Hypothermia, Induced/adverse effects, Out-of-Hospital Cardiac Arrest/complications, Treatment Outcome",

author = "Christian Hassager and Henrik Schmidt and M{\o}ller, {Jacob E} and Johannes Grand and Simon M{\o}lstr{\o}m and Beske, {Rasmus P} and S{\o}ren Boesgaard and Britt Borregaard and Ditte Bekker-Jensen and Dahl, {Jordi S} and Frydland, {Martin S} and H{\o}fsten, {Dan E} and Isse, {Yusuf A} and Jakob Josiassen and {Lind J{\o}rgensen}, {Vibeke R} and Daniel Kondziella and Lindholm, {Matias G} and Emil Moser and Nyholm, {Benjamin C} and Obling, {Laust E R} and Laura Sarkisian and S{\o}ndergaard, {Frederik T} and Thomsen, {Jakob H} and Thune, {Jens J} and S{\o}ren Ven{\o} and Wiberg, {Sebastian C} and Matilde Winther-Jensen and Meyer, {Martin A S} and Jesper Kjaergaard",

note = "Copyright {\textcopyright} 2022 Massachusetts Medical Society.",

year = "2023",

month = mar,

day = "9",

doi = "10.1056/NEJMoa2212528",

language = "English",

volume = "388",

pages = "888--897",

journal = "The New England journal of medicine",

issn = "0028-4793",

publisher = "Massachusetts Medical Society",

number = "10",

}

TY - JOUR

T1 - Duration of Device-Based Fever Prevention after Cardiac Arrest

AU - Hassager, Christian

AU - Schmidt, Henrik

AU - Møller, Jacob E

AU - Grand, Johannes

AU - Mølstrøm, Simon

AU - Beske, Rasmus P

AU - Boesgaard, Søren

AU - Borregaard, Britt

AU - Bekker-Jensen, Ditte

AU - Dahl, Jordi S

AU - Frydland, Martin S

AU - Høfsten, Dan E

AU - Isse, Yusuf A

AU - Josiassen, Jakob

AU - Lind Jørgensen, Vibeke R

AU - Kondziella, Daniel

AU - Lindholm, Matias G

AU - Moser, Emil

AU - Nyholm, Benjamin C

AU - Obling, Laust E R

AU - Sarkisian, Laura

AU - Søndergaard, Frederik T

AU - Thomsen, Jakob H

AU - Thune, Jens J

AU - Venø, Søren

AU - Wiberg, Sebastian C

AU - Winther-Jensen, Matilde

AU - Meyer, Martin A S

AU - Kjaergaard, Jesper

PY - 2023/3/9

Y1 - 2023/3/9

N2 - BACKGROUND: Guidelines recommend active fever prevention for 72 hours after cardiac arrest. Data from randomized clinical trials of this intervention have been lacking.METHODS: We randomly assigned comatose patients who had been resuscitated after an out-of-hospital cardiac arrest of presumed cardiac cause to device-based temperature control targeting 36°C for 24 hours followed by targeting of 37°C for either 12 or 48 hours (for total intervention times of 36 and 72 hours, respectively) or until the patient regained consciousness. The primary outcome was a composite of death from any cause or hospital discharge with a Cerebral Performance Category of 3 or 4 (range, 1 to 5, with higher scores indicating more severe disability; a category of 3 or 4 indicates severe cerebral disability or coma) within 90 days after randomization. Secondary outcomes included death from any cause and the Montreal Cognitive Assessment score (range, 0 to 30, with higher scores indicating better cognitive ability) at 3 months.RESULTS: A total of 393 patients were randomly assigned to temperature control for 36 hours, and 396 patients were assigned to temperature control for 72 hours. At 90 days after randomization, a primary end-point event had occurred in 127 of 393 patients (32.3%) in the 36-hour group and in 133 of 396 patients (33.6%) in the 72-hour group (hazard ratio, 0.99; 95% confidence interval, 0.77 to 1.26; P = 0.70) and mortality was 29.5% in the 36-hour group and 30.3% in the 72-hour group. At 3 months, the median Montreal Cognitive Assessment score was 26 (interquartile range, 24 to 29) and 27 (interquartile range, 24 to 28), respectively. There was no significant between-group difference in the incidence of adverse events.CONCLUSIONS: Active device-based fever prevention for 36 or 72 hours after cardiac arrest did not result in significantly different percentages of patients dying or having severe disability or coma. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials.gov number, NCT03141099.).

AB - BACKGROUND: Guidelines recommend active fever prevention for 72 hours after cardiac arrest. Data from randomized clinical trials of this intervention have been lacking.METHODS: We randomly assigned comatose patients who had been resuscitated after an out-of-hospital cardiac arrest of presumed cardiac cause to device-based temperature control targeting 36°C for 24 hours followed by targeting of 37°C for either 12 or 48 hours (for total intervention times of 36 and 72 hours, respectively) or until the patient regained consciousness. The primary outcome was a composite of death from any cause or hospital discharge with a Cerebral Performance Category of 3 or 4 (range, 1 to 5, with higher scores indicating more severe disability; a category of 3 or 4 indicates severe cerebral disability or coma) within 90 days after randomization. Secondary outcomes included death from any cause and the Montreal Cognitive Assessment score (range, 0 to 30, with higher scores indicating better cognitive ability) at 3 months.RESULTS: A total of 393 patients were randomly assigned to temperature control for 36 hours, and 396 patients were assigned to temperature control for 72 hours. At 90 days after randomization, a primary end-point event had occurred in 127 of 393 patients (32.3%) in the 36-hour group and in 133 of 396 patients (33.6%) in the 72-hour group (hazard ratio, 0.99; 95% confidence interval, 0.77 to 1.26; P = 0.70) and mortality was 29.5% in the 36-hour group and 30.3% in the 72-hour group. At 3 months, the median Montreal Cognitive Assessment score was 26 (interquartile range, 24 to 29) and 27 (interquartile range, 24 to 28), respectively. There was no significant between-group difference in the incidence of adverse events.CONCLUSIONS: Active device-based fever prevention for 36 or 72 hours after cardiac arrest did not result in significantly different percentages of patients dying or having severe disability or coma. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials.gov number, NCT03141099.).

KW - Body Temperature

KW - Cardiopulmonary Resuscitation

KW - Coma/etiology

KW - Consciousness

KW - Fever/etiology

KW - Humans

KW - Hypothermia, Induced/adverse effects

KW - Out-of-Hospital Cardiac Arrest/complications

KW - Treatment Outcome

UR - http://www.scopus.com/inward/record.url?scp=85150000006&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa2212528

DO - 10.1056/NEJMoa2212528

M3 - Journal article

C2 - 36342119

SN - 0028-4793

VL - 388

SP - 888

EP - 897

JO - The New England journal of medicine

JF - The New England journal of medicine

IS - 10

ER -

Duration of Device-Based Fever Prevention after Cardiac Arrest

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Keywords

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