title: Prolonged mild therapeutic hypothermia versus fever control with tight hemodynamic monitoring and slow rewarming in patients with severe traumatic brain injury: a randomized controlled trial.
abstract: Although mild therapeutic hypothermia is an effective neuroprotective strategy for cardiac arrest/resuscitated patients, and asphyxic newborns, recent randomized controlled trials (RCTs) have equally shown good neurological outcome between targeted temperature management at 33 °C versus 36 °C, and have not shown consistent benefits in patients with traumatic brain injury (TBI). We aimed to determine the effect of therapeutic hypothermia, while avoiding some limitations of earlier studies, which included patient selection based on Glasgow coma scale (GCS), delayed initiation of cooling, short duration of cooling, inter-center variation in patient care, and relatively rapid rewarming. We conducted a multicenter RCT in patients with severe TBI (GCS 4-8). Patients were randomly assigned (2:1 allocation ratio) to either therapeutic hypothermia (32-34 °C, n = 98) or fever control (35.5-37 °C, n = 50). Patients with therapeutic hypothermia were cooled as soon as possible for ≥ 72 h and rewarmed at a rate of <1 °C/day. All patients received tight hemodynamic monitoring under intensive neurological care. The Glasgow Outcome Scale was assessed at 6 months by physicians who were blinded to the treatment allocation. The overall rates of poor neurological outcomes were 53% and 48% in the therapeutic hypothermia and fever control groups, respectively. There were no significant differences in the likelihood of poor neurological outcome (relative risk [RR] 1.24, 95% confidence interval [CI] 0.62-2.48, p = 0.597) or mortality (RR 1.82, 95% CI 0.82-4.03, p = 0.180) between the two groups. We concluded that tight hemodynamic management and slow rewarming, together with prolonged therapeutic hypothermia (32-34 °C) for severe TBI, did not improve the neurological outcomes or risk of mortality compared with strict temperature control (35.5-37 °C).
authors.affiliation: 1 Department of Stress and Bio-response Medicine, Yamaguchi University Graduate School of Medicine , Yamaguchi, Japan .
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Maekawa
authors.forename: Susumu
authors.initials: S
authors.lastname: Yamashita
authors.forename: Seigo
authors.initials: S
authors.lastname: Nagao
authors.forename: Nariyuki
authors.initials: N
authors.lastname: Hayashi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohashi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001831:Body Temperature / Q000502:physiology; D001930:Brain Injuries / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D005334:Fever / Q000503:physiopathology / Q000628:therapy*; D015600:Glasgow Coma Scale; D023261:Glasgow Outcome Scale; D006439:Hemodynamics / Q000502:physiology*; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods*; D008297:Male; D008875:Middle Aged; D017694:Rewarming / Q000379:methods*; D013997:Time Factors; D055815:Young Adult
keywords: cardiac output; cerebral perfusion; intracranial pressure; therapeutic hypothermia.
references.citation: N Engl J Med. 2005 Oct 13;353(15):1574-84
references.pmid: 16221780
references.citation: Lancet. 1975 Mar 1;1(7905):480-4
references.pmid: 46957
references.citation: Stroke. 2006 Jul;37(7):1792-7
references.pmid: 16763179
references.citation: Lancet. 2005 Feb 19-25;365(9460):663-70
references.pmid: 15721471
references.citation: Surg Clin North Am. 2000 Jun;80(3):845-54
references.pmid: 10897264
references.citation: N Engl J Med. 2008 Jun 5;358(23):2447-56
references.pmid: 18525042
references.citation: J Neurosurg. 2001 Nov;95(5):751-5
references.pmid: 11702863
references.citation: J Crit Care. 2007 Sep;22(3):229-35
references.pmid: 17869973
references.citation: J Neurosurg. 2001 Jan;94(1):50-4
references.pmid: 11147897
references.citation: N Engl J Med. 1997 Feb 20;336(8):540-6
references.pmid: 9023090
references.citation: JAMA. 2003 Jun 11;289(22):2992-9
references.pmid: 12799408
references.citation: Circ J. 2010 Jan;74(1):77-85
references.pmid: 19942784
references.citation: N Engl J Med. 2009 Oct 1;361(14):1349-58
references.pmid: 19797281
references.citation: N Engl J Med. 2002 Feb 21;346(8):557-63
references.pmid: 11856794
references.citation: J Trauma. 1988 Jan;28(1):87-90
references.pmid: 3339667
references.citation: J Cereb Blood Flow Metab. 2006 Jun;26(6):771-6
references.pmid: 16306933
references.citation: N Engl J Med. 2013 Dec 5;369(23):2197-206
references.pmid: 24237006
references.citation: Pediatr Neurol. 2005 Jan;32(1):11-7
references.pmid: 15607598
references.citation: J Neurosurg. 2000 Oct;93(4):546-9
references.pmid: 11014530
references.citation: J Neurotrauma. 2002 Mar;19(3):293-301
references.pmid: 11939497
references.citation: Lancet Neurol. 2011 Feb;10(2):131-9
references.pmid: 21169065
references.citation: Crit Care Med. 2000 Dec;28(12):3902-6
references.pmid: 11153633
references.citation: J Neurotrauma. 2008 Jan;25(1):62-71
references.pmid: 18355159
references.citation: N Engl J Med. 2001 Feb 22;344(8):556-63
references.pmid: 11207351
references.citation: N Engl J Med. 2002 Feb 21;346(8):549-56
references.pmid: 11856793
references.citation: Crit Care Med. 2002 Apr;30(4):739-45
references.pmid: 11940738
references.citation: J Neurotrauma. 1993 Fall;10(3):263-71; discussion 273
references.pmid: 8258839