Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest

Niklas Nielsen; Jørn Wetterslev; Tobias Cronberg; David Erlinge; Yvan Gasche; Christian Hassager; Janneke Horn; Jan Hovdenes; Jesper Kjaergaard; Michael Kuiper; Tommaso Pellis; Pascal Stammet; Michael Wanscher; Matt P Wise; Anders Aneman; Nawaf Al-Subaie; Søren Boesgaard; John Bro-Jeppesen; Iole Brunetti; Jan Frederik Bugge; Christopher D Hingston; Nicole P Juffermans; Matty Koopmans; Lars Køber; Jørund Langørgen; Gisela Lilja; Jacob Eifer Møller; Malin Rundgren; Christian Rylander; Ondrej Smid; Christophe Werer; Per Winkel; Hans Friberg; the TTM Trial Investigators

doi:10.1056/NEJMoa1310519

Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest

Niklas Nielsen, Jørn Wetterslev, Tobias Cronberg, David Erlinge, Yvan Gasche, Christian Hassager, Janneke Horn, Jan Hovdenes, Jesper Kjaergaard, Michael Kuiper, Tommaso Pellis, Pascal Stammet, Michael Wanscher, Matt P Wise, Anders Aneman, Nawaf Al-Subaie, Søren Boesgaard, John Bro-Jeppesen, Iole Brunetti, Jan Frederik BuggeChristopher D Hingston, Nicole P Juffermans, Matty Koopmans, Lars Køber, Jørund Langørgen, Gisela Lilja, Jacob Eifer Møller, Malin Rundgren, Christian Rylander, Ondrej Smid, Christophe Werer, Per Winkel, Hans Friberg, the TTM Trial Investigators

Department of Clinical Medicine

1608 Citations (Scopus)

Abstract

BACKGROUND: Unconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temperatures, both intended to prevent fever. METHODS: In an international trial, we randomly assigned 950 unconscious adults after out-ofhospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33°C or 36°C. The primary outcome was all-cause mortality through the end of the trial. Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale. RESULTS: In total, 939 patients were included in the primary analysis. At the end of the trial, 50% of the patients in the 33°C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36°C group (225 of 466 patients) (hazard ratio with a temperature of 33°C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P=0.51). At the 180-day follow-up, 54% of the patients in the 33°C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36°C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78). In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87). The results of analyses adjusted for known prognostic factors were similar. Conclusions In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33°C did not confer a benefit as compared with a targeted temperature of 36°C.

Original language	English
Journal	New England Journal of Medicine
Volume	369
Pages (from-to)	2197-2206
Number of pages	10
ISSN	0028-4793
DOIs	https://doi.org/10.1056/NEJMoa1310519
Publication status	Published - 5 Dec 2013

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10.1056/NEJMoa1310519

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Nielsen, N., Wetterslev, J., Cronberg, T., Erlinge, D., Gasche, Y., Hassager, C., Horn, J., Hovdenes, J., Kjaergaard, J., Kuiper, M., Pellis, T., Stammet, P., Wanscher, M., Wise, M. P., Aneman, A., Al-Subaie, N., Boesgaard, S., Bro-Jeppesen, J., Brunetti, I., ... Investigators, T. TTM. T. (2013). Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest. New England Journal of Medicine, 369, 2197-2206. https://doi.org/10.1056/NEJMoa1310519

Nielsen, N, Wetterslev, J, Cronberg, T, Erlinge, D, Gasche, Y, Hassager, C, Horn, J, Hovdenes, J, Kjaergaard, J, Kuiper, M, Pellis, T, Stammet, P, Wanscher, M, Wise, MP, Aneman, A, Al-Subaie, N, Boesgaard, S, Bro-Jeppesen, J, Brunetti, I, Bugge, JF, Hingston, CD, Juffermans, NP, Koopmans, M, Køber, L, Langørgen, J, Lilja, G, Møller, JE, Rundgren, M, Rylander, C, Smid, O, Werer, C, Winkel, P, Friberg, H & Investigators, TTTMT 2013, 'Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest', New England Journal of Medicine, vol. 369, pp. 2197-2206. https://doi.org/10.1056/NEJMoa1310519

@article{d5f5fb46025b4b329a77097eb52d8d4c,

title = "Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest",

abstract = "BACKGROUND: Unconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temperatures, both intended to prevent fever. METHODS: In an international trial, we randomly assigned 950 unconscious adults after out-ofhospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33°C or 36°C. The primary outcome was all-cause mortality through the end of the trial. Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale. RESULTS: In total, 939 patients were included in the primary analysis. At the end of the trial, 50% of the patients in the 33°C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36°C group (225 of 466 patients) (hazard ratio with a temperature of 33°C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P=0.51). At the 180-day follow-up, 54% of the patients in the 33°C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36°C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78). In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87). The results of analyses adjusted for known prognostic factors were similar. Conclusions In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33°C did not confer a benefit as compared with a targeted temperature of 36°C.",

author = "Niklas Nielsen and J{\o}rn Wetterslev and Tobias Cronberg and David Erlinge and Yvan Gasche and Christian Hassager and Janneke Horn and Jan Hovdenes and Jesper Kjaergaard and Michael Kuiper and Tommaso Pellis and Pascal Stammet and Michael Wanscher and Wise, {Matt P} and Anders Aneman and Nawaf Al-Subaie and S{\o}ren Boesgaard and John Bro-Jeppesen and Iole Brunetti and Bugge, {Jan Frederik} and Hingston, {Christopher D} and Juffermans, {Nicole P} and Matty Koopmans and Lars K{\o}ber and J{\o}rund Lang{\o}rgen and Gisela Lilja and M{\o}ller, {Jacob Eifer} and Malin Rundgren and Christian Rylander and Ondrej Smid and Christophe Werer and Per Winkel and Hans Friberg and Investigators, {the TTM Trial}",

year = "2013",

month = dec,

day = "5",

doi = "10.1056/NEJMoa1310519",

language = "English",

volume = "369",

pages = "2197--2206",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachusetts Medical Society",

}

TY - JOUR

T1 - Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest

AU - Nielsen, Niklas

AU - Wetterslev, Jørn

AU - Cronberg, Tobias

AU - Erlinge, David

AU - Gasche, Yvan

AU - Hassager, Christian

AU - Horn, Janneke

AU - Hovdenes, Jan

AU - Kjaergaard, Jesper

AU - Kuiper, Michael

AU - Pellis, Tommaso

AU - Stammet, Pascal

AU - Wanscher, Michael

AU - Wise, Matt P

AU - Aneman, Anders

AU - Al-Subaie, Nawaf

AU - Boesgaard, Søren

AU - Bro-Jeppesen, John

AU - Brunetti, Iole

AU - Bugge, Jan Frederik

AU - Hingston, Christopher D

AU - Juffermans, Nicole P

AU - Koopmans, Matty

AU - Køber, Lars

AU - Langørgen, Jørund

AU - Lilja, Gisela

AU - Møller, Jacob Eifer

AU - Rundgren, Malin

AU - Rylander, Christian

AU - Smid, Ondrej

AU - Werer, Christophe

AU - Winkel, Per

AU - Friberg, Hans

AU - Investigators, the TTM Trial

PY - 2013/12/5

Y1 - 2013/12/5

N2 - BACKGROUND: Unconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temperatures, both intended to prevent fever. METHODS: In an international trial, we randomly assigned 950 unconscious adults after out-ofhospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33°C or 36°C. The primary outcome was all-cause mortality through the end of the trial. Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale. RESULTS: In total, 939 patients were included in the primary analysis. At the end of the trial, 50% of the patients in the 33°C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36°C group (225 of 466 patients) (hazard ratio with a temperature of 33°C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P=0.51). At the 180-day follow-up, 54% of the patients in the 33°C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36°C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78). In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87). The results of analyses adjusted for known prognostic factors were similar. Conclusions In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33°C did not confer a benefit as compared with a targeted temperature of 36°C.

AB - BACKGROUND: Unconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temperatures, both intended to prevent fever. METHODS: In an international trial, we randomly assigned 950 unconscious adults after out-ofhospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33°C or 36°C. The primary outcome was all-cause mortality through the end of the trial. Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale. RESULTS: In total, 939 patients were included in the primary analysis. At the end of the trial, 50% of the patients in the 33°C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36°C group (225 of 466 patients) (hazard ratio with a temperature of 33°C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P=0.51). At the 180-day follow-up, 54% of the patients in the 33°C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36°C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78). In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87). The results of analyses adjusted for known prognostic factors were similar. Conclusions In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33°C did not confer a benefit as compared with a targeted temperature of 36°C.

U2 - 10.1056/NEJMoa1310519

DO - 10.1056/NEJMoa1310519

M3 - Journal article

SN - 0028-4793

VL - 369

SP - 2197

EP - 2206

JO - New England Journal of Medicine

JF - New England Journal of Medicine

ER -

Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest

Abstract

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