Review Article Hypothermia for spinal cord injury Brian K. Kwon, MD, PhD, FRCSC a,b, * , Cody Mann, BSc a , Hong Moon Sohn, MD, PhD c , Alan S. Hilibrand, MD g , Frank M. Phillips, MD d , Jeffrey C. Wang, MD e , Michael G. Fehlings, MD, PhD, FRCSC, FACS f , the NASS Section on Biologics a ICORD (International Collaboration on Repair Discoveries), University of British Columbia, Room 2469 Biosciences Building, 6270 University Boulevard, Vancouver, BC V6T 1Z4, Canada b CNOSP (Combined Neurosurgical and Orthopaedic Spine Program), Department of Orthopaedics, University of British Columbia, Vancouver General Hospital, D6 Heather Pavilion, 2733 Heather Street, Vancouver, BC V5Z3J5, Canada c Department of Orthopaedics, Chosun University Hospital, Gwangju, Korea d Rush University Medical Center, Chicago, IL, USA e UCLA Comprehensive Spine Center, UCLA School of Medicine, Los Angeles, CA, USA f Division of Neurosurgery, University of Toronto and Spinal Program, Krembil Neuroscience Center, Toronto Western Hospital, Toronto, Ontario, Canada g Jefferson Medical College and Rothmann Institute, Philadelphia, PA, USA Received 5 November 2007; accepted 17 December 2007 Abstract BACKGROUND CONTEXT: Interest in systemic and local hypothermia extends back over many decades, and both have been investigated as potential neuroprotective interventions in a number of clinical settings, including traumatic brain injury, stroke, cardiac arrest, and both intracranial and thoracoabdominal aortic aneurysm surgery. The recent use of systemic hypothermia in an injured National Football League football player has focused a great deal of attention on the potential use of hypothermia in acute spinal cord injury. PURPOSE: To provide spinal clinicians with an overview of the biological rationale for using hy- pothermia, the past studies and current clinical applications of hypothermia, and the basic science studies and clinical reports of the use of hypothermia in acute traumatic spinal cord injury. STUDY DESIGN/SETTING: A review of the English literature on hypothermia was performed, starting with the original clinical description of the use of systemic hypothermia in 1940. Pertinent basic science and clinical articles were identified using PubMed and the bibliographies of the articles. METHODS: Each article was reviewed to provide a concise description of hypothermia’s biolog- ical rationale, current clinical applications, complications, and experience as a neuroprotective intervention in spinal cord injury. RESULTS: Hypothermia has a multitude of physiologic effects. From a neuroprotective stand- point, hypothermia slows basic enzymatic activity, reduces the cell’s energy requirements, and thus maintains Adenosine Triphosphate (ATP) concentrations. As such, systemic hypothermia has been shown to be neuroprotective in patients after cardiac arrest, although its benefit in other clinical set- tings such as traumatic brain injury, stroke, and intracranial aneurysm surgery has not been dem- onstrated. Animal studies of local and systemic hypothermia in traumatic spinal cord injury models have produced mixed results. Local hypothermia was actively studied in the 1970s in human acute traumatic spinal cord injury, but no case series of this intervention has been published since 1984. No peer-reviewed clinical literature could be found, which describes the application of sys- temic hypothermia in acute traumatic spinal cord injury. FDA device/drug status: investigational/not approved (Hypothermia). Research funding: None. The authors do not have a financial relationship that creates, or may be perceived as creating, a conflict related to this article. * Corresponding author. CNOSP (Combined Neurosurgical and Ortho- paedic Spine Program), Department of Orthopaedics, University of British Columbia, Vancouver General Hospital, D6 Heather Pavilion, 2733 Heather Street, Vancouver, BC V5Z3J5, Canada. Tel.: (604) 875-5857; fax: (604) 875-5858. E-mail address: brian.kwon@vch.ca (B.K. Kwon) 1529-9430/08/$ – see front matter Ó 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.spinee.2007.12.006 The Spine Journal 8 (2008) 859–874