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Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

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  • Josef Dankiewicz
  • Tobias Cronberg
  • Gisela Lilja
  • Janus C Jakobsen
  • Helena Levin
  • Susann Ullén
  • Christian Rylander
  • Matt P Wise
  • Mauro Oddo
  • Alain Cariou
  • Jan Bělohlávek
  • Jan Hovdenes
  • Manoj Saxena
  • Hans Kirkegaard
  • Paul J Young
  • Paolo Pelosi
  • Christian Storm
  • Fabio S Taccone
  • Michael Joannidis
  • Clifton Callaway
  • Glenn M Eastwood
  • Matt P G Morgan
  • Per Nordberg
  • David Erlinge
  • Alistair D Nichol
  • Michelle S Chew
  • Jacob Hollenberg
  • Matthew Thomas
  • Jeremy Bewley
  • Katie Sweet
  • Anders M Grejs
  • Steffen Christensen
  • Matthias Haenggi
  • Anja Levis
  • Andreas Lundin
  • Joachim Düring
  • Simon Schmidbauer
  • Thomas R Keeble
  • Grigoris V Karamasis
  • Claudia Schrag
  • Edith Faessler
  • Ondrej Smid
  • Michal Otáhal
  • Marco Maggiorini
  • Pedro D Wendel Garcia
  • Paul Jaubert
  • Jade M Cole
  • Miroslav Solar
  • Ola Borgquist
  • Niklas Nielsen
  • TTM2 Trial Investigators
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BACKGROUND: Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty.

METHODS: In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33°C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, ≥37.8°C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device.

RESULTS: A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P = 0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score ≥4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups.

CONCLUSIONS: In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 number, NCT02908308.).

Original languageEnglish
JournalThe New England journal of medicine
Issue number24
Pages (from-to)2283-2294
Number of pages12
Publication statusPublished - 17 Jun 2021

    Research areas

  • Aged, Body Temperature, Cardiopulmonary Resuscitation/methods, Coma/etiology, Female, Fever/etiology, Humans, Hypothermia, Induced/adverse effects, Kaplan-Meier Estimate, Male, Middle Aged, Out-of-Hospital Cardiac Arrest/complications, Single-Blind Method, Treatment Outcome

ID: 67053236