Hypothermia for Intracranial Hypertension after Traumatic Brain Injury
Peter J D Andrews, H Louise Sinclair, Aryelly Rodriguez, Bridget A Harris, Claire G Battison, Jonathan K J Rhodes, Gordon D Murray, Eurotherm3235 Trial Collaborators, David Noble, Sally Galt, Jane Taylor, Jenni Addison, Charles Wallis, Ross Paterson, Gill Harris, Brian Mullan, Vanessa Quinn, Leona Bannon, Anthony Gordon, Maie Templeton, Robert Wilson, Elfyn Thomas, Helen McMillan, Kate Tantam, Andrew Gratrix, Neil Smith, Victoria Martinson, Casiano Barrera-Groba, Ian Littlejohn, Gavin Spurling, Philip Hopkins, Sarah Casboult, Dan Hadfield, Justin McKinlay, Zoe Beardow, Stuart Elliot, Rajesh Jain, Antonio Bellini, Theresa McCluskey, Dan Harvey, Marc Chikhani, Anna Bolland, Carl Waldmann, Nicola Jacques, Heather Prowse, David Turnbull, George Eapen, Kathryn Birchall, Vishi Verma, Thais Creary, Edyta Niebrzegowska, Thomas Owen, Jackie Baldwin, Alex Williams, Christopher Thompson, Ruth Salt, David Cartlidge, Angus Vincent, Verity Calder, Carmen Scott, Paul Ferris, Justin Roberts, Tracey Evans, Neil Burgess, Valentina Della Torre, Johannes Mellinghoff, Martin Stotz, Verena Hauer, Adaeze Ochelli-Okpue, Catherine McMahon, Ian Tweedie, Lorna Murray, Christopher Bassford, Geraldine Ward, Marie McCauley, Matt Wise, Nicki Palmer, Jade Cole, François Damas, Noël Xavier, Guy-Loup Dulière, Gaetan Simoens, Patrick Biston, Ann Joosten, Marc Simon, Aurélie Antoine, Bénédict Zieppen, Pierre Bulpa, Alain Dive, Sandrina Bouhon, Fabio Taccone, Jean-Louis Vincent, Dominique Durand, Herbert Spapen, Joris Troubleyn, Claire Van Malderen, Valdo Toome, Piret Sillaots, Inga Koger, Ralph Stuttmann, Jens Jakubetz, Sebastian Langer, Martha Michalia, Phyllis-Maria Clouva-Molyvdas, Ioannis Vassiliadis, Serafim Nanas, Lina Douka, Stavros Dimopolous, Ioannis Pneumatikos, Christos Dragoumanis, Georgios Kouliatsis, George Nakos, Eleonora Kostanti, Epaminondas Zakynthinos, Demosthenes Makris, Eleni Palli, George Koukoulitsios, Kyriaki Tsikritsaki, Alexander Kalogeromitros, Eva Nagy, Claire Lampiri, Maria Valtoy, Pal Barzo, David Kis, Bela Fulop, Deepak Gupta, Ashish Bindra, Dorothy Breen, Joan Barry, Emer Neau, Maria Spoto, Nadia Fusilli, Silvia Malossini, Massimo Antonelli, Anselmo Caricato, Alessandra Tersali, Filipa Seabra, Irene Aragão, Rui Antunes, Sergey Petrikov, Julia Titova, Alexander Solodov, Ahmed Al-Jabbary, Ahmad Deeb, Hania Richi, Maite Misis del Campo, Jose Maria Toboso Casado, Eva Benveniste Pérez, Arturo Zabalegui Pérez, Marta Arroyo Diez, Sergio Ossa Echeverri, Antonio Blesa, Francisco Romero, Miguel Sanchez, Mathieu van der Jagt, Iain Haitsma, Ditty van Duijn, Paul Dennesen, Marjan Koole, Kalpana Krishnareddy, Mohammed Hegazi, B S Sharma, Peter J D Andrews, H Louise Sinclair, Aryelly Rodriguez, Bridget A Harris, Claire G Battison, Jonathan K J Rhodes, Gordon D Murray, Eurotherm3235 Trial Collaborators, David Noble, Sally Galt, Jane Taylor, Jenni Addison, Charles Wallis, Ross Paterson, Gill Harris, Brian Mullan, Vanessa Quinn, Leona Bannon, Anthony Gordon, Maie Templeton, Robert Wilson, Elfyn Thomas, Helen McMillan, Kate Tantam, Andrew Gratrix, Neil Smith, Victoria Martinson, Casiano Barrera-Groba, Ian Littlejohn, Gavin Spurling, Philip Hopkins, Sarah Casboult, Dan Hadfield, Justin McKinlay, Zoe Beardow, Stuart Elliot, Rajesh Jain, Antonio Bellini, Theresa McCluskey, Dan Harvey, Marc Chikhani, Anna Bolland, Carl Waldmann, Nicola Jacques, Heather Prowse, David Turnbull, George Eapen, Kathryn Birchall, Vishi Verma, Thais Creary, Edyta Niebrzegowska, Thomas Owen, Jackie Baldwin, Alex Williams, Christopher Thompson, Ruth Salt, David Cartlidge, Angus Vincent, Verity Calder, Carmen Scott, Paul Ferris, Justin Roberts, Tracey Evans, Neil Burgess, Valentina Della Torre, Johannes Mellinghoff, Martin Stotz, Verena Hauer, Adaeze Ochelli-Okpue, Catherine McMahon, Ian Tweedie, Lorna Murray, Christopher Bassford, Geraldine Ward, Marie McCauley, Matt Wise, Nicki Palmer, Jade Cole, François Damas, Noël Xavier, Guy-Loup Dulière, Gaetan Simoens, Patrick Biston, Ann Joosten, Marc Simon, Aurélie Antoine, Bénédict Zieppen, Pierre Bulpa, Alain Dive, Sandrina Bouhon, Fabio Taccone, Jean-Louis Vincent, Dominique Durand, Herbert Spapen, Joris Troubleyn, Claire Van Malderen, Valdo Toome, Piret Sillaots, Inga Koger, Ralph Stuttmann, Jens Jakubetz, Sebastian Langer, Martha Michalia, Phyllis-Maria Clouva-Molyvdas, Ioannis Vassiliadis, Serafim Nanas, Lina Douka, Stavros Dimopolous, Ioannis Pneumatikos, Christos Dragoumanis, Georgios Kouliatsis, George Nakos, Eleonora Kostanti, Epaminondas Zakynthinos, Demosthenes Makris, Eleni Palli, George Koukoulitsios, Kyriaki Tsikritsaki, Alexander Kalogeromitros, Eva Nagy, Claire Lampiri, Maria Valtoy, Pal Barzo, David Kis, Bela Fulop, Deepak Gupta, Ashish Bindra, Dorothy Breen, Joan Barry, Emer Neau, Maria Spoto, Nadia Fusilli, Silvia Malossini, Massimo Antonelli, Anselmo Caricato, Alessandra Tersali, Filipa Seabra, Irene Aragão, Rui Antunes, Sergey Petrikov, Julia Titova, Alexander Solodov, Ahmed Al-Jabbary, Ahmad Deeb, Hania Richi, Maite Misis del Campo, Jose Maria Toboso Casado, Eva Benveniste Pérez, Arturo Zabalegui Pérez, Marta Arroyo Diez, Sergio Ossa Echeverri, Antonio Blesa, Francisco Romero, Miguel Sanchez, Mathieu van der Jagt, Iain Haitsma, Ditty van Duijn, Paul Dennesen, Marjan Koole, Kalpana Krishnareddy, Mohammed Hegazi, B S Sharma
Abstract
Background: In patients with traumatic brain injury, hypothermia can reduce intracranial hypertension. The benefit of hypothermia on functional outcome is unclear.
Methods: We randomly assigned adults with an intracranial pressure of more than 20 mm Hg despite stage 1 treatments (including mechanical ventilation and sedation management) to standard care (control group) or hypothermia (32 to 35°C) plus standard care. In the control group, stage 2 treatments (e.g., osmotherapy) were added as needed to control intracranial pressure. In the hypothermia group, stage 2 treatments were added only if hypothermia failed to control intracranial pressure. In both groups, stage 3 treatments (barbiturates and decompressive craniectomy) were used if all stage 2 treatments failed to control intracranial pressure. The primary outcome was the score on the Extended Glasgow Outcome Scale (GOS-E; range, 1 to 8, with lower scores indicating a worse functional outcome) at 6 months. The treatment effect was estimated with ordinal logistic regression adjusted for prespecified prognostic factors and expressed as a common odds ratio (with an odds ratio <1.0 favoring hypothermia).
Results: We enrolled 387 patients at 47 centers in 18 countries from November 2009 through October 2014, at which time recruitment was suspended owing to safety concerns. Stage 3 treatments were required to control intracranial pressure in 54% of the patients in the control group and in 44% of the patients in the hypothermia group. The adjusted common odds ratio for the GOS-E score was 1.53 (95% confidence interval, 1.02 to 2.30; P=0.04), indicating a worse outcome in the hypothermia group than in the control group. A favorable outcome (GOS-E score of 5 to 8, indicating moderate disability or good recovery) occurred in 26% of the patients in the hypothermia group and in 37% of the patients in the control group (P=0.03).
Conclusions: In patients with an intracranial pressure of more than 20 mm Hg after traumatic brain injury, therapeutic hypothermia plus standard care to reduce intracranial pressure did not result in outcomes better than those with standard care alone. (Funded by the National Institute for Health Research Health Technology Assessment program; Current Controlled Trials number, ISRCTN34555414.).
Source: PubMed