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

Abstract 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.
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Mayor MeshTerms
Keywords
Journal Title jama
Publication Year Start




PMID- 28742911
OWN - NLM
STAT- In-Process
DA  - 20170725
LR  - 20170725
IS  - 1538-3598 (Electronic)
IS  - 0098-7484 (Linking)
VI  - 318
IP  - 4
DP  - 2017 Jul 25
TI  - Targeted Temperature Management for 48 vs 24 Hours and Neurologic Outcome After
      Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial.
PG  - 341-350
LID - 10.1001/jama.2017.8978 [doi]
AB  - Importance: International resuscitation guidelines recommend targeted temperature
      management (TTM) at 33 degrees C to 36 degrees 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 degrees 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 degrees C) for 48 hours (n = 176) or 24 hours (n = 179), followed by
      gradual rewarming of 0.5 degrees C per hour until reaching 37 degrees 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 degrees C for
      48 hours did not significantly improve 6-month neurologic outcome compared with
      targeted temperature management at 33 degrees 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.
FAU - Kirkegaard, Hans
AU  - Kirkegaard H
AD  - Research Center for Emergency Medicine and Department of Anesthesiology and
      Intensive Care Medicine, Aarhus University Hospital and Aarhus University,
      Aarhus, Denmark.
FAU - Soreide, Eldar
AU  - Soreide E
AD  - Department of Anesthesiology and Intensive Care, Stavanger University Hospital,
      Stavanger, Norway3Department of Clinical Medicine, University of Bergen, Bergen, 
      Norway.
FAU - de Haas, Inge
AU  - de Haas I
AD  - Department of Anesthesiology and Intensive Care Medicine, Aalborg University
      Hospital, and Clinical Institute, Aalborg University, Aalborg, Denmark.
FAU - Pettila, Ville
AU  - Pettila V
AD  - Division of Intensive Care, Department of Anesthesiology, Intensive Care and Pain
      Medicine, University of Helsinki and Helsinki University Hospital,
      Finland6Inselspital, Bern University Hospital, University of Bern, Bern,
      Switzerland.
FAU - Taccone, Fabio Silvio
AU  - Taccone FS
AD  - Department of Intensive Care, Erasme Hospital, Universite Libre de Bruxelles
      (ULB), Brussels, Belgium.
FAU - Arus, Urmet
AU  - Arus U
AD  - Department of Intensive Cardiac Care, North Estonia Medical Centre, Tallinn,
      Estonia.
FAU - Storm, Christian
AU  - Storm C
AD  - Department of Internal Medicine, Nephrology and Intensive Care,
      Charite-Universitatsmedizin Berlin, Berlin, Germany.
FAU - Hassager, Christian
AU  - Hassager C
AD  - Department of Cardiology, The Heart Center, Copenhagen University Hospital,
      Rigshospitalet, Copenhagen, Denmark.
FAU - Nielsen, Jorgen Feldbaek
AU  - Nielsen JF
AD  - Hammel Neurorehabilitation Centre and University Research Clinic, Aarhus
      University, Denmark.
FAU - Sorensen, Christina Ankjaer
AU  - Sorensen CA
AD  - Department of Anesthesiology and Intensive Care Medicine, Aalborg University
      Hospital, Aalborg, Denmark.
FAU - Ilkjaer, Susanne
AU  - Ilkjaer S
AD  - Department of Anesthesiology and Intensive Care Medicine, Aarhus University
      Hospital, Denmark.
FAU - Jeppesen, Anni Norgaard
AU  - Jeppesen AN
AD  - Research Center for Emergency Medicine and Department of Anesthesiology and
      Intensive Care Medicine, Aarhus University Hospital and Aarhus University,
      Aarhus, Denmark.
FAU - Grejs, Anders Morten
AU  - Grejs AM
AD  - Research Center for Emergency Medicine and Department of Anesthesiology and
      Intensive Care Medicine, Aarhus University Hospital and Aarhus University,
      Aarhus, Denmark.
FAU - Duez, Christophe Henri Valdemar
AU  - Duez CHV
AD  - Research Center for Emergency Medicine and Department of Anesthesiology and
      Intensive Care Medicine, Aarhus University Hospital and Aarhus University,
      Aarhus, Denmark.
FAU - Hjort, Jakob
AU  - Hjort J
AD  - Department of Clinical Medicine, Aarhus University, Denmark.
FAU - Larsen, Alf Inge
AU  - Larsen AI
AD  - Department of Cardiology, Stavanger University Hospital, Norway16Department of
      Clinical Science, University of Bergen, Norway.
FAU - Toome, Valdo
AU  - Toome V
AD  - Department of Anesthesiology, Intensive Care and Emergency Medicine, North
      Estonia Medical Centre, Tallinn, Estonia.
FAU - Tiainen, Marjaana
AU  - Tiainen M
AD  - Department of Neurology, University of Helsinki and Helsinki University Hospital,
      Finland.
FAU - Hastbacka, Johanna
AU  - Hastbacka J
AD  - Division of Intensive Care, Department of Anesthesiology, Intensive Care and Pain
      Medicine, University of Helsinki and Helsinki University Hospital, Finland.
FAU - Laitio, Timo
AU  - Laitio T
AD  - Department of Anesthesiology and Intensive Care, Turku University Hospital and
      University of Turku, Finland.
FAU - Skrifvars, Markus B
AU  - Skrifvars MB
AD  - Division of Intensive Care, Department of Anesthesiology, Intensive Care and Pain
      Medicine, University of Helsinki and Helsinki University Hospital,
      Finland20Australian and New Zealand Intensive Care Research Centre, School of
      Public Health and Preventive Medicine, Monash University Melbourne, Australia.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - JAMA
JT  - JAMA
JID - 7501160
EDAT- 2017/07/26 06:00
MHDA- 2017/07/26 06:00
CRDT- 2017/07/26 06:00
AID - 2645105 [pii]
AID - 10.1001/jama.2017.8978 [doi]
PST - ppublish
SO  - JAMA. 2017 Jul 25;318(4):341-350. doi: 10.1001/jama.2017.8978.