FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 344:556-563 February 22, 2001 Number 8 Next

	Full Text PDF Editorial by Narayan, R. K. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Induction of hypothermia in patients with brain injury was shown to improve outcomes in small clinical studies, but the results were not definitive. To study this issue, we conducted a multicenter trial comparing the effects of hypothermia with those of normothermia in patients with acute brain injury.

Methods The study subjects were 392 patients 16 to 65 years of age with coma after sustaining closed head injuries who were randomly assigned to be treated with hypothermia (body temperature, 33°C), which was initiated within 6 hours after injury and maintained for 48 hours by means of surface cooling, or normothermia. All patients otherwise received standard treatment. The primary outcome measure was functional status six months after the injury.

Results The mean age of the patients and the type and severity of injury in the two treatment groups were similar. The mean (±SD) time from injury to randomization was 4.3±1.1 hours in the hypothermia group and 4.1±1.2 hours in the normothermia group, and the mean time from injury to the achievement of the target temperature of 33°C in the hypothermia group was 8.4±3.0 hours. The outcome was poor (defined as severe disability, a vegetative state, or death) in 57 percent of the patients in both groups. Mortality was 28 percent in the hypothermia group and 27 percent in the normothermia group (P=0.79). The patients in the hypothermia group had more hospital days with complications than the patients in the normothermia group. Fewer patients in the hypothermia group had high intracranial pressure than in the normothermia group.

Conclusions Treatment with hypothermia, with the body temperature reaching 33°C within eight hours after injury, is not effective in improving outcomes in patients with severe brain injury.

Source Information

From the Vivian L. Smith Center for Neurologic Research, Department of Neurosurgery, University of Texas–Houston Medical School, Houston (G.L.C., E.R.M.); the Departments of Biostatistics and Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, Richmond (S.C.C.); the Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston (H.S.L., S.M.); the Department of Neurosurgery, St. Louis University, St. Louis (K.R.S.); the Department of Neurological Surgery, University of California at Davis, Sacramento (J.P.M., F.C.W.); the Brain Trauma Research Center, Department of Neurosurgery, University of Pittsburgh, Pittsburgh (D.W.M.); the Division of Neurosurgery, Indiana University, Indianapolis (T.G.L.); the Department of Neurosurgery, Oregon Health Sciences University, Portland (R.M.C.); and the Department of Neurosurgery, Sunnybrook Medical Centre, University of Toronto, Toronto (M.S.).

Address reprint requests to Dr. Clifton at the Department of Neurosurgery, Vivian L. Smith Center for Neurologic Research, University of Texas–Houston Health Science Center, 6431 Fannin, Suite 7.148, Houston, TX 77030, or at guy.l.clifton{at}uth.tmc.edu.

Full Text of this Article

This article has been cited by other articles:

• Lasarzik, I., Winkelheide, U., Thal, S. C., Benz, N., Lorscher, M., Jahn-Eimermacher, A., Werner, C., Engelhard, K. (2009). Mild Hypothermia Has No Long-Term Impact on Postischemic Neurogenesis in Rats. Anesth. Analg. 109: 1632-1639 [Abstract] [Full Text]  
• Sessler, D. I. (2009). Defeating Normal Thermoregulatory Defenses: Induction of Therapeutic Hypothermia. Stroke 40: e614-e621 [Abstract] [Full Text]  
• Hemphill, J. C. III, Farrant, M., Neill, T. A. Jr (2009). Prospective validation of the ICH Score for 12-month functional outcome. Neurology 73: 1088-1094 [Abstract] [Full Text]  
• Mittal, R, Vermani, E, Tweedie, I, Nee, P A (2009). Critical care in the emergency department: traumatic brain injury. Emerg. Med. J. 26: 513-517 [Abstract] [Full Text]  
• Trivedi, M., Coles, J. P. (2009). Blood Pressure Management in Acute Head Injury. J Intensive Care Med 24: 96-107 [Abstract]  
• Frost, E. A. M. (2009). Essentials of Neuroanesthesia and Neurointensive Care. Anesth. Analg. 108: 678-679 [Full Text]  
• Yenari, M., Kitagawa, K., Lyden, P., Perez-Pinzon, M. (2008). Metabolic Downregulation: A Key to Successful Neuroprotection?. Stroke 39: 2910-2917 [Abstract] [Full Text]  
• Polderman, K. H., Mayer, S. A., Menon, D., Kochanek, P. M., Bell, M. J., Adelson, P. D., Kornecki, A., Morrison, G., Karakitsos, D., Karabinis, A., Hutchison, J. S., Lacroix, J., Hebert, P. C. (2008). Hypothermia Therapy after Traumatic Brain Injury in Children. NEJM 359: 1178-1180 [Full Text]  
• Hutchison, J. S., Ward, R. E., Lacroix, J., Hebert, P. C., Barnes, M. A., Bohn, D. J., Dirks, P. B., Doucette, S., Fergusson, D., Gottesman, R., Joffe, A. R., Kirpalani, H. M., Meyer, P. G., Morris, K. P., Moher, D., Singh, R. N., Skippen, P. W., the Hypothermia Pediatric Head Injury Trial Invest, (2008). Hypothermia Therapy after Traumatic Brain Injury in Children. NEJM 358: 2447-2456 [Abstract] [Full Text]  
• Bouch, D. C., Thompson, J. P., Damian, M. S. (2008). Post-cardiac arrest management: more than global cooling?. Br J Anaesth 100: 591-594 [Full Text]  
• Fukuda, S., Warner, D. S. (2007). Cerebral protection. Br J Anaesth 99: 10-17 [Abstract] [Full Text]  
• Coles, J. P. (2007). Imaging after brain injury. Br J Anaesth 99: 49-60 [Abstract] [Full Text]  
• Helmy, A., Vizcaychipi, M., Gupta, A. K. (2007). Traumatic brain injury: intensive care management. Br J Anaesth 99: 32-42 [Abstract] [Full Text]  
• Nortje, J., Gupta, A. K. (2006). The role of tissue oxygen monitoring in patients with acute brain injury. Br J Anaesth 97: 95-106 [Abstract] [Full Text]  
• McDonagh, D. L., Allen, I. N., Keifer, J. C., Warner, D. S. (2006). Induction of hypothermia after intraoperative hypoxic brain insult.. Anesth. Analg. 103: 180-181 [Abstract] [Full Text]  
• Mishra, L., Rajkumar, N, Hancock, S. (2006). Current controversies in neuroanaesthesia, head injury management and neuro critical care. Contin Educ Anaesth Crit Care Pain 6: 79-82 [Full Text]  
• Vincent, J.-L., Fink, M. P., Marini, J. J., Pinsky, M. R., Sibbald, W. J., Singer, M., Suter, P. M., Cook, D., Pepe, P. E., Evans, T. (2006). Intensive care and emergency medicine: progress over the past 25 years.. Chest 129: 1061-1067 [Abstract] [Full Text]  
• Luscombe, M., Andrzejowski, J. C (2006). Clinical applications of induced hypothermia. Contin Educ Anaesth Crit Care Pain 6: 23-27 [Full Text]  
• Fairchild, K. D., Singh, I. S., Carter, H. C., Hester, L., Hasday, J. D. (2005). Hypothermia enhances phosphorylation of I{kappa}B kinase and prolongs nuclear localization of NF-{kappa}B in lipopolysaccharide-activated macrophages. Am. J. Physiol. Cell Physiol. 289: C1114-C1121 [Abstract] [Full Text]  
• NINDS ICH Workshop Participants, (2005). Priorities for Clinical Research in Intracerebral Hemorrhage: Report From a National Institute of Neurological Disorders and Stroke Workshop. Stroke 36: e23-e41 [Abstract] [Full Text]  
• Todd, M. M., Hindman, B. J., Clarke, W. R., Torner, J. C., the Intraoperative Hypothermia for Aneurysm Surger, (2005). Mild Intraoperative Hypothermia during Surgery for Intracranial Aneurysm. NEJM 352: 135-145 [Abstract] [Full Text]  
• Powner, D. J., Miller, E. R., Levine, R. L. (2005). CVP and PAoP Measurements Are Discordant During Fluid Therapy After Traumatic Brain Injury. J Intensive Care Med 20: 28-33 [Abstract]  
• Guha, A (2004). Management of traumatic brain injury: some current evidence and applications. Postgrad. Med. J. 80: 650-653 [Abstract] [Full Text]  
• Warner, D. S., Borel, C. O. (2004). Treatment of Traumatic Brain Injury: One Size Does Not Fit All. Anesth. Analg. 99: 1208-1210 [Full Text]  
• Kimme, P., Fridrikssen, S., Engdahl, O., Hillman, J., Vegfors, M., Sjoberg, F. (2004). Moderate hypothermia for 359 operations to clip cerebral aneurysms. Br J Anaesth 93: 343-347 [Abstract] [Full Text]  
• De Georgia, M. A., Krieger, D. W., Abou-Chebl, A., Devlin, T. G., Jauss, M., Davis, S. M., Koroshetz, W. J., Rordorf, G., Warach, S. (2004). Cooling for Acute Ischemic Brain Damage (COOL AID): A feasibility trial of endovascular cooling. Neurology 63: 312-317 [Abstract] [Full Text]  
• Zygun, D. (2004). Hypertonic Saline for Prehospital Treatment of Traumatic Brain Injury. JAMA 291: 2943-2944 [Full Text]  
• Cooper, D. J., Myles, P. S., For the HTS Study Investigators, (2004). Hypertonic Saline for Prehospital Treatment of Traumatic Brain Injury--Reply. JAMA 291: 2944-2945 [Full Text]  
• Danton, G. H., Dietrich, W. D. (2004). The Search for Neuroprotective Strategies in Stroke. Am. J. Neuroradiol. 25: 181-194 [Full Text]  
• Smith, M. (2003). Diffuse axonal injury in adults. Trauma 5: 227-234 [Abstract]  
• Tobin, M. J. (2003). The Role of a Journal in a Scientific Controversy. Am. J. Respir. Crit. Care Med. 168: 511-511 [Full Text]  
• Okuyama, K., Matsukawa, T., Ozaki, M., Sessler, D. I., Nishiyama, T., Imamura, M., Kumazawa, T. (2003). Doxapram Produces a Dose-Dependent Reduction in the Shivering Threshold in Rabbits. Anesth. Analg. 97: 759-762 [Abstract] [Full Text]  
• Mack, W. J., Huang, J., Winfree, C., Kim, G., Oppermann, M., Dobak, J., Inderbitzen, B., Yon, S., Popilskis, S., Lasheras, J., Sciacca, R. R., Pinsky, D. J., Connolly, E. S. Jr (2003). Ultrarapid, Convection-Enhanced Intravascular Hypothermia: A Feasibility Study in Nonhuman Primate Stroke. Stroke 34: 1994-1999 [Abstract] [Full Text]  
• McIntyre, L. A., Fergusson, D. A., Hebert, P. C., Moher, D., Hutchison, J. S. (2003). Prolonged Therapeutic Hypothermia After Traumatic Brain Injury in Adults: A Systematic Review. JAMA 289: 2992-2999 [Abstract] [Full Text]  
• Kochanek, P. M., Safar, P. J. (2003). Therapeutic Hypothermia for Severe Traumatic Brain Injury. JAMA 289: 3007-3009 [Full Text]  
• Doufas, A. G., Lin, C.-M., Suleman, M.-I., Liem, E. B., Lenhardt, R., Morioka, N., Akca, O., Shah, Y. M., Bjorksten, A. R., Sessler, D. I. (2003). Dexmedetomidine and Meperidine Additively Reduce the Shivering Threshold in Humans. Stroke 34: 1218-1223 [Abstract] [Full Text]  
• Shimokawa, M., Kitaguchi, K., Kawaguchi, M., Sakamoto, T., Kakimoto, M., Furuya, H. (2003). The Influence of Induced Hypothermia for Hemostatic Function on Temperature-Adjusted Measurements in Rabbits. Anesth. Analg. 96: 1209-1213 [Abstract] [Full Text]  
• Dietrich, W. D., Kuluz, J. W. (2003). New Research in the Field of Stroke: Therapeutic Hypothermia after Cardiac Arrest. Stroke 34: 1051-1053 [Full Text]  
• Ichiba, S, Killer, H M, Firmin, R K, Kotecha, S, Edwards, A D, Field, D (2003). Pilot investigation of hypothermia in neonates receiving extracorporeal membrane oxygenation. Arch. Dis. Child. Fetal Neonatal Ed. 88: F128-F133 [Abstract] [Full Text]  
• Bonicalzi, V., Canavero, S., Baxter, P., Stack, C., Short, J., Gaber, T. A, Mobayed, M. (2002). Treating head injuries. BMJ 325: 1420-1420 [Full Text]  
• Doufas, A. G., Akca, O., Barry, A., Petrusca, D. A., Suleman, M.-I., Morioka, N., Guarnaschelli, J. J., Sessler, D. I. (2002). Initial Experience with a Novel Heat-Exchanging Catheter in Neurosurgical Patients. Anesth. Analg. 95: 1752-1756 [Abstract] [Full Text]  
• Tator, C H (2002). Strategies for recovery and regeneration after brain and spinal cord injury. Inj. Prev. 8: iv33-36 [Abstract] [Full Text]  
• Dunn, L. T (2002). RAISED INTRACRANIAL PRESSURE. J. Neurol. Neurosurg. Psychiatry 73: i23-27 [Full Text]  
• Shibano, T., Morimoto, Y., Kemmotsu, O., Shikama, H., Hisano, K., Hua, Y. (2002). Effects of mild and moderate hypothermia on apoptosis in neuronal PC12 cells. Br J Anaesth 89: 301-305 [Abstract] [Full Text]  
• Marik, P. E., Varon, J., Trask, T. (2002). Management of Head Trauma*. Chest 122: 699-711 [Abstract] [Full Text]  
• Harris, O. A., Colford, J. M. Jr, Good, M. C., Matz, P. G. (2002). The Role of Hypothermia in the Management of Severe Brain Injury: A Meta-analysis. Arch Neurol 59: 1077-1083 [Abstract] [Full Text]  
• Fernandes, H., Gregson, B. A., Siddique, M. S., Mendelow, A. D., Hemphill, J. C. III, Bonovich, D. C., Johnston, S. C., Manley, G. T. (2002). Testing the ICH Score * Response:. Stroke 33: 1455-1456 [Full Text]  
• Wainwright, M. S., Sheng, H., Sato, Y., Burkhard Mackensen, G., Steffen, R. P., Pearlstein, R. D., Warner, D. S. (2002). Pharmacological correction of hypothermic P50 shift does not alter outcome from focal cerebral ischemia in rats. Am. J. Physiol. Heart Circ. Physiol. 282: H1863-H1870 [Abstract] [Full Text]  
• Mayer, S. A., Chong, J. Y. (2002). Critical Care Management of Increased Intracranial Pressure. J Intensive Care Med 17: 55-67 [Abstract]  
• Leker, R. R., Ovadia, H., Schwab, S., Georgiadis, D., Schellinger, P. D., Berrouschot, J., Graffagnino, C., Mayer, S. A. (2002). Re: Feasibility and Safety of Moderate Hypothermia After Massive Hemispheric Infarction. Stroke 33: 877-878 [Full Text]  
• The Hypothermia after Cardiac Arrest Study Group, (2002). Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest. NEJM 346: 549-556 [Abstract] [Full Text]  
• Bernard, S. A., Gray, T. W., Buist, M. D., Jones, B. M., Silvester, W., Gutteridge, G., Smith, K. (2002). Treatment of Comatose Survivors of Out-of-Hospital Cardiac Arrest with Induced Hypothermia. NEJM 346: 557-563 [Abstract] [Full Text]  
• Gupta, A. K., Al-Rawi, P. G., Hutchinson, P. J., Kirkpatrick, P. J. (2002). Effect of hypothermia on brain tissue oxygenation in patients with severe head injury. Br J Anaesth 88: 188-192 [Abstract] [Full Text]  
• Kasner, S. E., Wein, T., Piriyawat, P., Villar-Cordova, C. E., Chalela, J. A., Krieger, D. W., Morgenstern, L. B., Kimmel, S. E., Grotta, J. C., Koennecke, H.-C. (2002). Acetaminophen for Altering Body Temperature in Acute Stroke: A Randomized Clinical Trial * Editorial Comment: A Randomized Clinical Trial. Stroke 33: 130-135 [Abstract] [Full Text]  
• Mustafa, S., Thulesius, O. (2002). Cooling-Induced Carotid Artery Dilatation: An Experimental Study in Isolated Vessels. Stroke 33: 256-260 [Abstract] [Full Text]  
• Georgiadis, D., Schwarz, S., Kollmar, R., Schwab, S. (2001). Endovascular Cooling for Moderate Hypothermia in Patients With Acute Stroke: First Results of a Novel Approach. Stroke 32: 2550-2553 [Abstract] [Full Text]  
• Mokhtarani, M., Mahgoub, A. N., Morioka, N., Doufas, A. G., Dae, M., Shaughnessy, T. E., Bjorksten, A. R., Sessler, D. I. (2001). Buspirone and Meperidine Synergistically Reduce the Shivering Threshold. Anesth. Analg. 93: 1233-1239 [Abstract] [Full Text]  
• Felberg, R. A., Krieger, D. W., Chuang, R., Persse, D. E., Burgin, W. S., Hickenbottom, S. L., Morgenstern, L. B., Rosales, O., Grotta, J. C. (2001). Hypothermia After Cardiac Arrest: Feasibility and Safety of an External Cooling Protocol. Circulation 104: 1799-1804 [Abstract] [Full Text]  
• Rossi, S, Zanier, E R., Mauri, I, Columbo, A, Stocchetti, N (2001). Brain temperature, body core temperature, and intracranial pressure in acute cerebral damage. J. Neurol. Neurosurg. Psychiatry 71: 448-454 [Abstract] [Full Text]  
• Safar, P., Fine, R. H., von Baeyer, H., Eisenberg, M. S., Mengert, T. J. (2001). Cardiac Resuscitation. NEJM 345: 546-547 [Full Text]  
• Krieger, D. W., De Georgia, M. A., Abou-Chebl, A., Andrefsky, J. C., Sila, C. A., Katzan, I. L., Mayberg, M. R., Furlan, A. J. (2001). Cooling for Acute Ischemic Brain Damage (COOL AID): An Open Pilot Study of Induced Hypothermia in Acute Ischemic Stroke. Stroke 32: 1847-1854 [Abstract] [Full Text]  
• Sakas, D. E., Dimopoulou, I., Safar, P., Kochanek, P. M., Clifton, G. L. (2001). Lack of Effect of Induction of Hypothermia after Acute Brain Injury. NEJM 345: 66-66 [Full Text]  
• Dippel, D. W.J., van Breda, E. J., van Gemert, H. M.A., van der Worp, H. B., Meijer, R. J., Kappelle, L. J., Koudstaal, P. J. (2001). Effect of Paracetamol (Acetaminophen) on Body Temperature in Acute Ischemic Stroke : A Double-Blind, Randomized Phase II Clinical Trial. Stroke 32: 1607-1612 [Abstract] [Full Text]  
• (2001). Induced Hypothermia Not Beneficial for Patients with Acute Brain Injury. JWatch Emergency Med. 2001: 10-10 [Full Text]  
• Narayan, R. K. (2001). Hypothermia for Traumatic Brain Injury -- A Good Idea Proved Ineffective. NEJM 344: 602-603 [Full Text]