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 Åneman, 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, TTM Trial Investigators, Niklas Nielsen, Niklas Nielsen, Tobias Cronberg, David Erlinge, Hans Friberg, Christian Hassager, Janneke Horn, Jan Hovdenes, Jesper Kjaergaard, Michael Kuiper, Yvan Gasche, Thomas Pellis, Pascal Stammet, Michael Wanscher, Jørn Wetterslev, Matt P Wise, Anders Åneman, Per Winkel, Lars V Køber, Djillali Annane, Jan Wernerman, Theis Lange, Gisela Lilja, Ulla-Britt Karlsson, Liz Jergle-Almqvist, Berit Grevstad, Kate Whitfield, Anders Åneman, Sharon Micallef, Parisa Glass, John Myburgh, Manoj Saxena, Antony Stewart, Simon Finfer, Gillian Bishop, Dorrilyn Rajbhandari, Naomi Hammond, Lynsey Willenberg, Manoj Saxena, Jennene Miller, Deborah Inskip, Lewis Macken, Simon Finfer, Noel Eatough, Naomi Hammond, Frances Bass, Elizabeth Yarad, Anne O'Connor, Simon Bird, Timothy Jewell, Gareth Davies, Karl Ng, Sharon Coward, Anders Åneman, Antony Stewart, Sharon Micallef, Sharyn Parker, Dennis Cortado, Sharon Micallef, Ann Gould, Meg Harward, Kelly Thompson, Naomi Hammond, Parisa Glass, John Myburgh, Ondrej Smid, Jan Belholavek, Marketa Kreckova, Ales Kral, Jan Horak, Michal Otahal, Jan Rulisek, Jan Malik, Martin Prettl, Jesper Kjaergaard, Christian Hassager, Michael Wascher, Soeren Boesgaard, Jacob E Moller, John Bro-Jeppesen, Ane Loof Johansen, Vincenzo Campanile, Alberto Peratoner, Francesca Verginella, Daniele Leone, Thomas Pellis, Andrea Roncarati, Eliana Franceschino, Anna Sanzani, Alice Martini, Micol Perlin, Paolo Pelosi, Iole Brunetti, Angelo Insorsi, Stefano Pezzato, Giorgio De Luca, Emanuela Gazzano, Gian Andrea Ottonello, Andrea Furgani, Rosanna Telani, Simona Maiani, Pascal Stammet, Christophe Werer, Jaqueline Kieffer, Janneke Horn, Annelou L vd Veen, Tineke Winters, Nicole P Juffermans, Michael Kuiper, Frank Bosch, Monique A M Raaijmakers, S W L Metz-Hermans, Henrik Endeman, Saskia Rijkenberg, Addy Bianchi, Jan Hovdenes, Jan Frederik Bugge, Hilde Norum, Andreas Espinoza, Viesturs Kerans, Helene Brevik, Morten Svalebjørg, Guro Grindheim, Arne Jan Petersen, Andreas Baratt-Due, Jon Henrik Laake, Ulrik Spreng, Marte Marie Wallander Karlsen, Jørund Langøren, Rune Fanebust, Marianne Sætrang Holm, Stine Iren Flinterud, Carsten Wickman, Jesper Johnsson, Florian Ebner, Nerida Gustavsson, Heléne Petersson, Jörgen Petersson, Faezheh Nasiri, Frida Stafilidou, Kristine Edqvist, Sven Uhlig, Gunilla Sköld, Johan Sanner, Jesper Wallskog, Nicholas Wyon, Martin Golster, Anders Samuelsson, Carl Hildebrand, Taichi Kadowaki, Jessica Larsson-Viksten, Lina De Geer, Patrik Hansson, Henrik Appelberg, Anders Hellsten, Susanne Lind, Malin Rundgren, Thomas Kander, Johan Persson, Martin Annborn, Anne Adolfsson, Ingrid Corrigan, Tobias Cronberg, Hans Friberg, Irina Dragancea, Johan Undén, Marina Larsson, Michelle Chew, Mårten Unnerbäck, Per Petersen, Anna Svedung-Rudebou, Robert Svensson, Hilde Elvenes, Carl Bäckman, Christian Rylander, Patrik Martner, Louise Martinell, Björn Biber, Marita Ahlqvist, Caisa Jacobson, Marie-Louise Forsberg, Roman Desta Lindgren, Fatma Bergquist, Anders Thorén, Martin Fredholm, Johan Sellgren, Lisa Hård af Segerstad, Mikael Löfgren, Ingvor Gustavsson, Christina Henström, Marita Ahlqvist, Bertil Andersson, Karin Thiringer, Nadja Rydholm, Stefan Persson, Jawad Jawad, Ingela Östman, Ida Berglind, Eric Bergström, Annika Andersson, Cathrine Törnqvist, Yvan Gasche, Nubia Lafayete Marques de Mello, Valérie Gardaz, Gian-Reto Kleger, Claudia Schrag, Edith Fässler, Hervé Zender, Matthew Wise, Nicki Palmer, Jen Fouweather, Jade M Cole, Eve Cocks, Paul J Frost, Anton G Saayman, Tom Holmes, Christopher D Hingston, Gareth M Scholey, Helen Watkins, Stephen Fernandez, Andrew Walden, Jane Atkinson, Nicola Jacques, Abby Brown, Julius Cranshaw, Peter Berridge, Robert McCormick, Martin Schuster-Bruce, Michelle Scott, Nigel White, Emma Vickers, Guy Glover, Marlies Ostermann, Paul Holmes, Michael Koutroumanidis, Katie Lei, Barnaby Sanderson, John Smith, Nawaf Al-Subaie, Matthew Moore, Paul Randall, Johannes Mellinghoff, Azul Forti Buratti, Chris Ryan, Jonathan Ball, Gaynor Francis, 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 Åneman, 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, TTM Trial Investigators, Niklas Nielsen, Niklas Nielsen, Tobias Cronberg, David Erlinge, Hans Friberg, Christian Hassager, Janneke Horn, Jan Hovdenes, Jesper Kjaergaard, Michael Kuiper, Yvan Gasche, Thomas Pellis, Pascal Stammet, Michael Wanscher, Jørn Wetterslev, Matt P Wise, Anders Åneman, Per Winkel, Lars V Køber, Djillali Annane, Jan Wernerman, Theis Lange, Gisela Lilja, Ulla-Britt Karlsson, Liz Jergle-Almqvist, Berit Grevstad, Kate Whitfield, Anders Åneman, Sharon Micallef, Parisa Glass, John Myburgh, Manoj Saxena, Antony Stewart, Simon Finfer, Gillian Bishop, Dorrilyn Rajbhandari, Naomi Hammond, Lynsey Willenberg, Manoj Saxena, Jennene Miller, Deborah Inskip, Lewis Macken, Simon Finfer, Noel Eatough, Naomi Hammond, Frances Bass, Elizabeth Yarad, Anne O'Connor, Simon Bird, Timothy Jewell, Gareth Davies, Karl Ng, Sharon Coward, Anders Åneman, Antony Stewart, Sharon Micallef, Sharyn Parker, Dennis Cortado, Sharon Micallef, Ann Gould, Meg Harward, Kelly Thompson, Naomi Hammond, Parisa Glass, John Myburgh, Ondrej Smid, Jan Belholavek, Marketa Kreckova, Ales Kral, Jan Horak, Michal Otahal, Jan Rulisek, Jan Malik, Martin Prettl, Jesper Kjaergaard, Christian Hassager, Michael Wascher, Soeren Boesgaard, Jacob E Moller, John Bro-Jeppesen, Ane Loof Johansen, Vincenzo Campanile, Alberto Peratoner, Francesca Verginella, Daniele Leone, Thomas Pellis, Andrea Roncarati, Eliana Franceschino, Anna Sanzani, Alice Martini, Micol Perlin, Paolo Pelosi, Iole Brunetti, Angelo Insorsi, Stefano Pezzato, Giorgio De Luca, Emanuela Gazzano, Gian Andrea Ottonello, Andrea Furgani, Rosanna Telani, Simona Maiani, Pascal Stammet, Christophe Werer, Jaqueline Kieffer, Janneke Horn, Annelou L vd Veen, Tineke Winters, Nicole P Juffermans, Michael Kuiper, Frank Bosch, Monique A M Raaijmakers, S W L Metz-Hermans, Henrik Endeman, Saskia Rijkenberg, Addy Bianchi, Jan Hovdenes, Jan Frederik Bugge, Hilde Norum, Andreas Espinoza, Viesturs Kerans, Helene Brevik, Morten Svalebjørg, Guro Grindheim, Arne Jan Petersen, Andreas Baratt-Due, Jon Henrik Laake, Ulrik Spreng, Marte Marie Wallander Karlsen, Jørund Langøren, Rune Fanebust, Marianne Sætrang Holm, Stine Iren Flinterud, Carsten Wickman, Jesper Johnsson, Florian Ebner, Nerida Gustavsson, Heléne Petersson, Jörgen Petersson, Faezheh Nasiri, Frida Stafilidou, Kristine Edqvist, Sven Uhlig, Gunilla Sköld, Johan Sanner, Jesper Wallskog, Nicholas Wyon, Martin Golster, Anders Samuelsson, Carl Hildebrand, Taichi Kadowaki, Jessica Larsson-Viksten, Lina De Geer, Patrik Hansson, Henrik Appelberg, Anders Hellsten, Susanne Lind, Malin Rundgren, Thomas Kander, Johan Persson, Martin Annborn, Anne Adolfsson, Ingrid Corrigan, Tobias Cronberg, Hans Friberg, Irina Dragancea, Johan Undén, Marina Larsson, Michelle Chew, Mårten Unnerbäck, Per Petersen, Anna Svedung-Rudebou, Robert Svensson, Hilde Elvenes, Carl Bäckman, Christian Rylander, Patrik Martner, Louise Martinell, Björn Biber, Marita Ahlqvist, Caisa Jacobson, Marie-Louise Forsberg, Roman Desta Lindgren, Fatma Bergquist, Anders Thorén, Martin Fredholm, Johan Sellgren, Lisa Hård af Segerstad, Mikael Löfgren, Ingvor Gustavsson, Christina Henström, Marita Ahlqvist, Bertil Andersson, Karin Thiringer, Nadja Rydholm, Stefan Persson, Jawad Jawad, Ingela Östman, Ida Berglind, Eric Bergström, Annika Andersson, Cathrine Törnqvist, Yvan Gasche, Nubia Lafayete Marques de Mello, Valérie Gardaz, Gian-Reto Kleger, Claudia Schrag, Edith Fässler, Hervé Zender, Matthew Wise, Nicki Palmer, Jen Fouweather, Jade M Cole, Eve Cocks, Paul J Frost, Anton G Saayman, Tom Holmes, Christopher D Hingston, Gareth M Scholey, Helen Watkins, Stephen Fernandez, Andrew Walden, Jane Atkinson, Nicola Jacques, Abby Brown, Julius Cranshaw, Peter Berridge, Robert McCormick, Martin Schuster-Bruce, Michelle Scott, Nigel White, Emma Vickers, Guy Glover, Marlies Ostermann, Paul Holmes, Michael Koutroumanidis, Katie Lei, Barnaby Sanderson, John Smith, Nawaf Al-Subaie, Matthew Moore, Paul Randall, Johannes Mellinghoff, Azul Forti Buratti, Chris Ryan, Jonathan Ball, Gaynor Francis
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-of-hospital 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. (Funded by the Swedish Heart-Lung Foundation and others; TTM ClinicalTrials.gov number, NCT01020916.).
Source: PubMed