Targeted Temperature Management for 48 vs 24 Hours and Neurologic Outcome After Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Standard

Targeted Temperature Management for 48 vs 24 Hours and Neurologic Outcome After Out-of-Hospital Cardiac Arrest : A Randomized Clinical Trial. / Kirkegaard, Hans; Søreide, Eldar; de Haas, Inge; Pettilä, Ville; Taccone, Fabio Silvio; Arus, Urmet; Storm, Christian; Hassager, Christian; Nielsen, Jørgen Feldbæk; Sørensen, Christina Ankjær; Ilkjær, Susanne; Jeppesen, Anni Nørgaard; Grejs, Anders Morten; Duez, Christophe Henri Valdemar; Hjort, Jakob; Larsen, Alf Inge; Toome, Valdo; Tiainen, Marjaana; Hästbacka, Johanna; Laitio, Timo; Skrifvars, Markus B.

I: JAMA: The Journal of the American Medical Association, Bind 318, Nr. 4, 25.07.2017, s. 341-350.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Kirkegaard, H, Søreide, E, de Haas, I, Pettilä, V, Taccone, FS, Arus, U, Storm, C, Hassager, C, Nielsen, JF, Sørensen, CA, Ilkjær, S, Jeppesen, AN, Grejs, AM, Duez, CHV, Hjort, J, Larsen, AI, Toome, V, Tiainen, M, Hästbacka, J, Laitio, T & Skrifvars, MB 2017, 'Targeted Temperature Management for 48 vs 24 Hours and Neurologic Outcome After Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial', JAMA: The Journal of the American Medical Association, bind 318, nr. 4, s. 341-350. https://doi.org/10.1001/jama.2017.8978

APA

Kirkegaard, H., Søreide, E., de Haas, I., Pettilä, V., Taccone, F. S., Arus, U., ... Skrifvars, M. B. (2017). Targeted Temperature Management for 48 vs 24 Hours and Neurologic Outcome After Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA: The Journal of the American Medical Association, 318(4), 341-350. https://doi.org/10.1001/jama.2017.8978

CBE

Kirkegaard H, Søreide E, de Haas I, Pettilä V, Taccone FS, Arus U, Storm C, Hassager C, Nielsen JF, Sørensen CA, Ilkjær S, Jeppesen AN, Grejs AM, Duez CHV, Hjort J, Larsen AI, Toome V, Tiainen M, Hästbacka J, Laitio T, Skrifvars MB. 2017. Targeted Temperature Management for 48 vs 24 Hours and Neurologic Outcome After Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA: The Journal of the American Medical Association. 318(4):341-350. https://doi.org/10.1001/jama.2017.8978

MLA

Vancouver

Kirkegaard H, Søreide E, de Haas I, Pettilä V, Taccone FS, Arus U o.a. Targeted Temperature Management for 48 vs 24 Hours and Neurologic Outcome After Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA: The Journal of the American Medical Association. 2017 jul 25;318(4):341-350. https://doi.org/10.1001/jama.2017.8978

Author

Kirkegaard, Hans ; Søreide, Eldar ; de Haas, Inge ; Pettilä, Ville ; Taccone, Fabio Silvio ; Arus, Urmet ; Storm, Christian ; Hassager, Christian ; Nielsen, Jørgen Feldbæk ; Sørensen, Christina Ankjær ; Ilkjær, Susanne ; Jeppesen, Anni Nørgaard ; Grejs, Anders Morten ; Duez, Christophe Henri Valdemar ; Hjort, Jakob ; Larsen, Alf Inge ; Toome, Valdo ; Tiainen, Marjaana ; Hästbacka, Johanna ; Laitio, Timo ; Skrifvars, Markus B. / Targeted Temperature Management for 48 vs 24 Hours and Neurologic Outcome After Out-of-Hospital Cardiac Arrest : A Randomized Clinical Trial. I: JAMA: The Journal of the American Medical Association. 2017 ; Bind 318, Nr. 4. s. 341-350.

Bibtex

@article{67cd3401088641cdbc241f9c6311e862,
title = "Targeted Temperature Management for 48 vs 24 Hours and Neurologic Outcome After Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial",
abstract = "Importance: International resuscitation guidelines recommend targeted temperature management (TTM) at 33°C to 36°C in unconscious patients with out-of-hospital cardiac arrest for at least 24 hours, but the optimal duration of TTM is uncertain.Objective: To determine whether TTM at 33°C for 48 hours results in better neurologic outcomes compared with currently recommended, standard, 24-hour TTM.Design, Setting, and Participants: This was an international, investigator-initiated, blinded-outcome-assessor, parallel, pragmatic, multicenter, randomized clinical superiority trial in 10 intensive care units (ICUs) at 10 university hospitals in 6 European countries. Three hundred fifty-five adult, unconscious patients with out-of-hospital cardiac arrest were enrolled from February 16, 2013, to June 1, 2016, with final follow-up on December 27, 2016.Interventions: Patients were randomized to TTM (33 ± 1°C) for 48 hours (n = 176) or 24 hours (n = 179), followed by gradual rewarming of 0.5°C per hour until reaching 37°C.Main Outcomes and Measures: The primary outcome was 6-month neurologic outcome, with a Cerebral Performance Categories (CPC) score of 1 or 2 used to define favorable outcome. Secondary outcomes included 6-month mortality, including time to death, the occurrence of adverse events, and intensive care unit resource use.Results: In 355 patients who were randomized (mean age, 60 years; 295 [83{\%}] men), 351 (99{\%}) completed the trial. Of these patients, 69{\%} (120/175) in the 48-hour group had a favorable outcome at 6 months compared with 64{\%} (112/176) in the 24-hour group (difference, 4.9{\%}; 95{\%} CI, -5{\%} to 14.8{\%}; relative risk [RR], 1.08; 95{\%} CI, 0.93-1.25; P = .33). Six-month mortality was 27{\%} (48/175) in the 48-hour group and 34{\%} (60/177) in the 24-hour group (difference, -6.5{\%}; 95{\%} CI, -16.1{\%} to 3.1{\%}; RR, 0.81; 95{\%} CI, 0.59-1.11; P = .19). There was no significant difference in the time to mortality between the 48-hour group and the 24-hour group (hazard ratio, 0.79; 95{\%} CI, 0.54-1.15; P = .22). Adverse events were more common in the 48-hour group (97{\%}) than in the 24-hour group (91{\%}) (difference, 5.6{\%}; 95{\%} CI, 0.6{\%}-10.6{\%}; RR, 1.06; 95{\%} CI, 1.01-1.12; P = .04). The median length of intensive care unit stay (151 vs 117 hours; P < .001), but not hospital stay (11 vs 12 days; P = .50), was longer in the 48-hour group than in the 24-hour group.Conclusions and Relevance: In unconscious survivors from out-of-hospital cardiac arrest admitted to the ICU, targeted temperature management at 33°C for 48 hours did not significantly improve 6-month neurologic outcome compared with targeted temperature management at 33°C for 24 hours. However, the study may have had limited power to detect clinically important differences, and further research may be warranted.Trial Registration: clinicaltrials.gov Identifier: NCT01689077.",
keywords = "Aged, Body Temperature, Brain Diseases, Cardiopulmonary Resuscitation, Female, Humans, Hypothermia, Induced, Male, Middle Aged, Out-of-Hospital Cardiac Arrest, Time Factors, Unconsciousness, Comparative Study, Journal Article, Multicenter Study, Pragmatic Clinical Trial, Randomized Controlled Trial",
author = "Hans Kirkegaard and Eldar S{\o}reide and {de Haas}, Inge and Ville Pettil{\"a} and Taccone, {Fabio Silvio} and Urmet Arus and Christian Storm and Christian Hassager and Nielsen, {J{\o}rgen Feldb{\ae}k} and S{\o}rensen, {Christina Ankj{\ae}r} and Susanne Ilkj{\ae}r and Jeppesen, {Anni N{\o}rgaard} and Grejs, {Anders Morten} and Duez, {Christophe Henri Valdemar} and Jakob Hjort and Larsen, {Alf Inge} and Valdo Toome and Marjaana Tiainen and Johanna H{\"a}stbacka and Timo Laitio and Skrifvars, {Markus B}",
year = "2017",
month = "7",
day = "25",
doi = "10.1001/jama.2017.8978",
language = "English",
volume = "318",
pages = "341--350",
journal = "JAMA: The Journal of the American Medical Association",
issn = "0098-7484",
publisher = "American Medical Association",
number = "4",

}

RIS

TY - JOUR

T1 - Targeted Temperature Management for 48 vs 24 Hours and Neurologic Outcome After Out-of-Hospital Cardiac Arrest

T2 - A Randomized Clinical Trial

AU - Kirkegaard, Hans

AU - Søreide, Eldar

AU - de Haas, Inge

AU - Pettilä, Ville

AU - Taccone, Fabio Silvio

AU - Arus, Urmet

AU - Storm, Christian

AU - Hassager, Christian

AU - Nielsen, Jørgen Feldbæk

AU - Sørensen, Christina Ankjær

AU - Ilkjær, Susanne

AU - Jeppesen, Anni Nørgaard

AU - Grejs, Anders Morten

AU - Duez, Christophe Henri Valdemar

AU - Hjort, Jakob

AU - Larsen, Alf Inge

AU - Toome, Valdo

AU - Tiainen, Marjaana

AU - Hästbacka, Johanna

AU - Laitio, Timo

AU - Skrifvars, Markus B

PY - 2017/7/25

Y1 - 2017/7/25

N2 - Importance: International resuscitation guidelines recommend targeted temperature management (TTM) at 33°C to 36°C in unconscious patients with out-of-hospital cardiac arrest for at least 24 hours, but the optimal duration of TTM is uncertain.Objective: To determine whether TTM at 33°C for 48 hours results in better neurologic outcomes compared with currently recommended, standard, 24-hour TTM.Design, Setting, and Participants: This was an international, investigator-initiated, blinded-outcome-assessor, parallel, pragmatic, multicenter, randomized clinical superiority trial in 10 intensive care units (ICUs) at 10 university hospitals in 6 European countries. Three hundred fifty-five adult, unconscious patients with out-of-hospital cardiac arrest were enrolled from February 16, 2013, to June 1, 2016, with final follow-up on December 27, 2016.Interventions: Patients were randomized to TTM (33 ± 1°C) for 48 hours (n = 176) or 24 hours (n = 179), followed by gradual rewarming of 0.5°C per hour until reaching 37°C.Main Outcomes and Measures: The primary outcome was 6-month neurologic outcome, with a Cerebral Performance Categories (CPC) score of 1 or 2 used to define favorable outcome. Secondary outcomes included 6-month mortality, including time to death, the occurrence of adverse events, and intensive care unit resource use.Results: In 355 patients who were randomized (mean age, 60 years; 295 [83%] men), 351 (99%) completed the trial. Of these patients, 69% (120/175) in the 48-hour group had a favorable outcome at 6 months compared with 64% (112/176) in the 24-hour group (difference, 4.9%; 95% CI, -5% to 14.8%; relative risk [RR], 1.08; 95% CI, 0.93-1.25; P = .33). Six-month mortality was 27% (48/175) in the 48-hour group and 34% (60/177) in the 24-hour group (difference, -6.5%; 95% CI, -16.1% to 3.1%; RR, 0.81; 95% CI, 0.59-1.11; P = .19). There was no significant difference in the time to mortality between the 48-hour group and the 24-hour group (hazard ratio, 0.79; 95% CI, 0.54-1.15; P = .22). Adverse events were more common in the 48-hour group (97%) than in the 24-hour group (91%) (difference, 5.6%; 95% CI, 0.6%-10.6%; RR, 1.06; 95% CI, 1.01-1.12; P = .04). The median length of intensive care unit stay (151 vs 117 hours; P < .001), but not hospital stay (11 vs 12 days; P = .50), was longer in the 48-hour group than in the 24-hour group.Conclusions and Relevance: In unconscious survivors from out-of-hospital cardiac arrest admitted to the ICU, targeted temperature management at 33°C for 48 hours did not significantly improve 6-month neurologic outcome compared with targeted temperature management at 33°C for 24 hours. However, the study may have had limited power to detect clinically important differences, and further research may be warranted.Trial Registration: clinicaltrials.gov Identifier: NCT01689077.

AB - Importance: International resuscitation guidelines recommend targeted temperature management (TTM) at 33°C to 36°C in unconscious patients with out-of-hospital cardiac arrest for at least 24 hours, but the optimal duration of TTM is uncertain.Objective: To determine whether TTM at 33°C for 48 hours results in better neurologic outcomes compared with currently recommended, standard, 24-hour TTM.Design, Setting, and Participants: This was an international, investigator-initiated, blinded-outcome-assessor, parallel, pragmatic, multicenter, randomized clinical superiority trial in 10 intensive care units (ICUs) at 10 university hospitals in 6 European countries. Three hundred fifty-five adult, unconscious patients with out-of-hospital cardiac arrest were enrolled from February 16, 2013, to June 1, 2016, with final follow-up on December 27, 2016.Interventions: Patients were randomized to TTM (33 ± 1°C) for 48 hours (n = 176) or 24 hours (n = 179), followed by gradual rewarming of 0.5°C per hour until reaching 37°C.Main Outcomes and Measures: The primary outcome was 6-month neurologic outcome, with a Cerebral Performance Categories (CPC) score of 1 or 2 used to define favorable outcome. Secondary outcomes included 6-month mortality, including time to death, the occurrence of adverse events, and intensive care unit resource use.Results: In 355 patients who were randomized (mean age, 60 years; 295 [83%] men), 351 (99%) completed the trial. Of these patients, 69% (120/175) in the 48-hour group had a favorable outcome at 6 months compared with 64% (112/176) in the 24-hour group (difference, 4.9%; 95% CI, -5% to 14.8%; relative risk [RR], 1.08; 95% CI, 0.93-1.25; P = .33). Six-month mortality was 27% (48/175) in the 48-hour group and 34% (60/177) in the 24-hour group (difference, -6.5%; 95% CI, -16.1% to 3.1%; RR, 0.81; 95% CI, 0.59-1.11; P = .19). There was no significant difference in the time to mortality between the 48-hour group and the 24-hour group (hazard ratio, 0.79; 95% CI, 0.54-1.15; P = .22). Adverse events were more common in the 48-hour group (97%) than in the 24-hour group (91%) (difference, 5.6%; 95% CI, 0.6%-10.6%; RR, 1.06; 95% CI, 1.01-1.12; P = .04). The median length of intensive care unit stay (151 vs 117 hours; P < .001), but not hospital stay (11 vs 12 days; P = .50), was longer in the 48-hour group than in the 24-hour group.Conclusions and Relevance: In unconscious survivors from out-of-hospital cardiac arrest admitted to the ICU, targeted temperature management at 33°C for 48 hours did not significantly improve 6-month neurologic outcome compared with targeted temperature management at 33°C for 24 hours. However, the study may have had limited power to detect clinically important differences, and further research may be warranted.Trial Registration: clinicaltrials.gov Identifier: NCT01689077.

KW - Aged

KW - Body Temperature

KW - Brain Diseases

KW - Cardiopulmonary Resuscitation

KW - Female

KW - Humans

KW - Hypothermia, Induced

KW - Male

KW - Middle Aged

KW - Out-of-Hospital Cardiac Arrest

KW - Time Factors

KW - Unconsciousness

KW - Comparative Study

KW - Journal Article

KW - Multicenter Study

KW - Pragmatic Clinical Trial

KW - Randomized Controlled Trial

U2 - 10.1001/jama.2017.8978

DO - 10.1001/jama.2017.8978

M3 - Journal article

C2 - 28742911

VL - 318

SP - 341

EP - 350

JO - JAMA: The Journal of the American Medical Association

JF - JAMA: The Journal of the American Medical Association

SN - 0098-7484

IS - 4

ER -