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

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DOI

  • Hans Kirkegaard
  • Eldar Søreide, Department of Anesthesiology and Intensive Care, Stavanger University Hospital, Stavanger, Norway3Department of Clinical Medicine, University of Bergen, Bergen, Norway.
  • ,
  • Inge de Haas, Department of Anesthesiology and Intensive Care Medicine, Aalborg University Hospital, and Clinical Institute, Aalborg University, Aalborg, Denmark.
  • ,
  • Ville Pettilä, 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.
  • ,
  • Fabio Silvio Taccone, Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium.
  • ,
  • Urmet Arus, Department of Intensive Cardiac Care, North Estonia Medical Centre, Tallinn, Estonia.
  • ,
  • Christian Storm, Department of Internal Medicine, Nephrology and Intensive Care, Charité-Universitätsmedizin Berlin, Berlin, Germany.
  • ,
  • Christian Hassager, From the Heart Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Odense, Denmark; Department of Cardiology, Odense University Hospital, Odense, Denmark.
  • ,
  • Jørgen Feldbæk Nielsen
  • Christina Ankjær Sørensen, Department of Anesthesiology and Intensive Care Medicine, Aalborg University Hospital, Aalborg, Denmark.
  • ,
  • Susanne Ilkjær
  • ,
  • Anni Nørgaard Jeppesen
  • Anders Morten Grejs
  • Christophe Henri Valdemar Duez
  • Jakob Hjort
  • Alf Inge Larsen, Department of Cardiology, Stavanger University Hospital, Norway16Department of Clinical Science, University of Bergen, Norway.
  • ,
  • Valdo Toome, Department of Anesthesiology, Intensive Care and Emergency Medicine, North Estonia Medical Centre, Tallinn, Estonia.
  • ,
  • Marjaana Tiainen, Department of Neurology, University of Helsinki and Helsinki University Hospital, Finland.
  • ,
  • Johanna Hästbacka, Division of Pain Medicine, Department of Anesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
  • ,
  • Timo Laitio, Department of Anesthesiology and Intensive Care, Turku University Hospital and University of Turku, Finland.
  • ,
  • Markus B Skrifvars, 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.

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.

OriginalsprogEngelsk
TidsskriftJAMA: The Journal of the American Medical Association
Vol/bind318
Nummer4
Sider (fra-til)341-350
Antal sider10
ISSN0098-7484
DOI
StatusUdgivet - 25 jul. 2017

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