title: Cooling for cerebral protection during brain surgery.
abstract: BACKGROUND
  Patients undergoing neurosurgery are at risk of cerebral ischaemia with resultant cerebral hypoxia and neuronal cell death. This can increase both the risk of mortality and long term neurological disability. Induced hypothermia has been shown to reduce the risk of cerebral ischaemic damage in both animal studies and in humans who have been resuscitated following cardiac arrest. This had lead to an increasing interest in its neuroprotective potential in neurosurgical patients. This review was originally published in 2011 and did not find any evidence of either effectiveness or harm in these patients. This updated review was designed to capture current evidence to readdress these issues.
  
  
  OBJECTIVE
  To evaluate the effectiveness and safety profile of induced hypothermia versus normothermia for neuroprotection in patients undergoing brain surgery. Effectiveness was to be measured in terms of short and long term mortality and functional neurological outcomes. Safety was to be assessed in terms of the rate of the adverse events infection, myocardial infarction, ischaemic stroke, congestive cardiac failure and any other adverse events reported by the authors of the included studies.
  
  
  METHODS
  For the original review, the authors searched the databases Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OvidSP), EMBASE (OvidSP) and LILACS to November 2010. For the updated review all these databases were re-searched from November 2010 to May 2014.For both the original and updated versions, grey literature was sought by searching reference lists of identified studies and relevant review articles, and conference proceedings. No language restrictions were applied.
  
  
  METHODS
  As in the original review, we included randomized controlled trials (RCTs) of induced hypothermia versus normothermia for neuroprotection in patients of any age and gender undergoing brain surgery, which addressed mortality, neurological morbidity or adverse event outcomes.
  
  
  METHODS
  Three review authors independently extracted data and two independently assessed the risk of bias of the included studies. Any discrepancies were resolved by discussion between authors.
  
  
  RESULTS
  In this updated review, one new ongoing study was found but no new eligible completed studies were identified. This update was therefore conducted using the same four studies included in the original review. These studies included a total of 1219 participants, mean age 40 to 54 years. All included studies were reported as RCTs. Two were multicentred, together including a total of 1114 patients who underwent cerebral aneurysm clipping, and were judged to have an overall low risk of bias. The other two studies were single centred. One included 80 patients who had a craniotomy following severe traumatic brain injury and was judged to have an unclear or low risk of bias. The other study included 25 patients who underwent hemicranicectomy to relieve oedema following cerebral infarction and was judged to have an unclear or high risk of bias. All studies assessed hypothermia versus normothermia. Overall 608 participants received hypothermia with target temperatures ranging from 32.5 °C to 35 °C, and 611 were assigned to normothermia with the actual temperatures recorded in this group ranging form 36.5 °C to 38 °C. For those who were cooled, 556 had cooling commenced immediately after induction of anaesthesia that was continued until the surgical objective of aneurysm clipping was achieved, and 52 had cooling commenced immediately after surgery and continued for 48 to 96 hours.Pooled estimates of effect were calculated for the outcomes mortality during treatment or follow-up (ranging from in-hospital to one year); neurological outcome measured in terms of the Glasgow Outcome Score (GOS) of 3 or less; and adverse events of infections, myocardial infarction, ischaemic stroke and congestive cardiac failure. With regards to mortality, the risk of dying if allocated to hypothermia compared to normothermia was not statistically significantly different (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.59 to 1.27, P = 0.47). There was no indication that the time at which cooling was started affected the risk of dying (RR with intraoperative cooling 0.95, 95% CI 0.60 to 1.51, P = 0.83; RR for cooling postoperatively 0.67, 95% CI 0.34 to 1.35, P = 0.26). For the neurological outcome, the risk of having a poor outcome with a GOS of 3 or less was not statistically different in those who received hypothermia versus normothermia (RR 0.80, 95% CI 0.61 to 1.04, P = 0.09). Again there was no indication that the time at which cooling was started affected this result. Regarding adverse events, there was no statistically significant difference in the incidence in those allocated to hypothermia versus normothermia for risk of surgical infection (RR 1.20, 95% CI 0.73 to 1.97, P = 0.48), myocardial infarction (RR 1.86, 95% CI 0.69 to 4.98, P = 0.22), ischaemic stroke (RR 0.93, 95% CI 0.82 to 1.05, P = 0.24) or congestive heart failure (RR 0.85, 95% CI 0.60 to 1.21, P = 0.38). In contrast to other outcomes, where time of application of cooling did not change the statistical significance of the effect estimates, there was a weak statistically significant increased risk of infection in those who were cooled postoperatively versus those who were not cooled (RR 1.77, 95% CI 1.05 to 2.98, P = 0.03). Overall, as in the original review, no evidence was found that the use of induced hypothermia was either beneficial or harmful in patients undergoing neurosurgery.
  
  
  CONCLUSIONS
  We found no evidence that the use of induced hypothermia was associated with a significant reduction in mortality or severe neurological disability, or an increase in harm in patients undergoing neurosurgery.
authors: Queen's University, Kingston, ON, Canada.
authors: Imelda M
authors: IM
authors: Galvin
authors: Ron
authors: R
authors: Levy
authors: J Gordon
authors: JG
authors: Boyd
authors: Andrew G
authors: AG
authors: Day
authors: Micheal C
authors: MC
authors: Wallace
mesh_terms: D001921:Brain / Q000601:surgery*; D002545:Brain Ischemia / Q000517:prevention & control*; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods* / Q000401:mortality; D007431:Intraoperative Complications / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic
references: Clin Neurol Neurosurg. 2002 Sep;104(4):318-21
references: 12140097
references: Annu Rev Neurosci. 1990;13:171-82
references: 1970230
references: J Neurosurg. 1994 Jan;80(1):112-9
references: 8270997
references: J Neurosurg. 1955 May;12(3):240-55
references: 14381931
references: Anesthesiology. 1968 Nov-Dec;29(6):1107-12
references: 5726746
references: J Trauma. 2003 Dec;55(6):1054-60
references: 14676650
references: Bratisl Lek Listy. 2006;107(4):113-7
references: 16796137
references: J Neurosurg. 2003 Jul;99(1):47-51
references: 12854743
references: Cochrane Database Syst Rev. 2012 Feb 15;(2):CD008445
references: 22336843
references: Anesth Analg. 2002 May;94(5):1298-303, table of contents
references: 11973207
references: Eur J Anaesthesiol Suppl. 1995 Sep;11:95-106
references: 8557016
references: JAMA. 1994 Apr 13;271(14):1114-20
references: 8151856
references: J Neurosurg Anesthesiol. 1997 Jul;9(3):205-10
references: 9239580
references: J Neurosurg Anesthesiol. 2003 Jul;15(3):240-8
references: 12826972
references: Control Clin Trials. 1986 Sep;7(3):177-88
references: 3802833
references: J Cereb Blood Flow Metab. 2006 Jun;26(6):771-6
references: 16306933
references: Anesthesiology. 1994 Aug;81(2):361-7
references: 8053586
references: Arch Surg. 1959 Sep;79:362-4
references: 14401007
references: Int J Stroke. 2013 Jul;8(5):383-7
references: 23782729
references: J Cereb Blood Flow Metab. 2002 Jan;22(1):21-8
references: 11807390
references: Anaesth Intensive Care. 2002 Apr;30(2):167-70
references: 12002923
references: J Neurotrauma. 1992 May;9 Suppl 2:S487-95
references: 1613808
references: Best Pract Res Clin Anaesthesiol. 2003 Dec;17(4):485-98
references: 14661653
references: Lancet. 1974 Jul 13;2(7872):81-4
references: 4136544
references: Neurosurgery. 2000 Sep;47(3):594-9; discussion 599-601
references: 10981746
references: Cerebrovasc Dis. 2006;21(1-2):79-85
references: 16330868
references: Middle East J Anaesthesiol. 2005 Jun;18(2):313-32
references: 16438006
references: Clin Perinatol. 2014 Mar;41(1):161-75
references: 24524453
references: Lancet. 1975 Mar 1;1(7905):480-4
references: 46957
references: Biochim Biophys Acta. 1999 Sep 20;1455(1):23-34
references: 10524226
references: Cochrane Database Syst Rev. 2011 Oct 05;(10):CD006638
references: 21975755
references: Int J Dev Neurosci. 2003 Oct;21(6):353-6
references: 12927584
references: Neurosurgery. 1999 Jan;44(1):23-32; discussion 32-3
references: 9894960
references: Clin Neurol Neurosurg. 2012 Sep;114(7):827-32
references: 22652238
references: Minerva Anestesiol. 1994 Oct;60(10):537-40
references: 7830915
references: Trends Neurosci. 1995 Feb;18(2):57-8
references: 7537407
references: Neurosurgery. 1993 Jun;32(6):980-4; discussion 984-5
references: 8327102
references: J Neurosurg. 2012 Oct;117(4):714-20
references: 22839656
references: Anesthesiology. 2006 Jan;104(1):33-8
references: 16394687
references: Neuroreport. 1997 Oct 20;8(15):3359-62
references: 9351672
references: Anesthesiology. 2010 Aug;113(2):327-42
references: 20571361
references: Br J Anaesth. 2004 Sep;93(3):343-7
references: 15220173
references: Pediatr Res. 1995 Dec;38(6):919-25
references: 8618794
references: J Neurotrauma. 2009 Nov;26(11):1905-9
references: 19469686
references: Bratisl Lek Listy. 2008;109(2):66-70
references: 18457312
references: Stroke. 1998 Dec;29(12):2461-6
references: 9836751
references: Crit Care. 1999;3(6):167-172
references: 11056742
references: N Engl J Med. 2002 Feb 21;346(8):549-56
references: 11856793
references: N Engl J Med. 2005 Jan 13;352(2):135-45
references: 15647576
references: No To Shinkei. 1972 Apr;24(4):403-10
references: 5067432
references: J Neurol Neurosurg Psychiatry. 1988 Nov;51(11):1457
references: 3236024
references: J Neurosurg. 2009 Jun;110(6):1256-64
references: 19249933
references: J Int Med Res. 2006 Jan-Feb;34(1):58-64
references: 16604824
references: Anaesthesist. 2004 Dec;53(12):1168-76
references: 15597156
references: Acta Neurochir Suppl. 1998;71:131-4
references: 9779165
references: Anesthesiology. 1980 Mar;52(3):224-30
references: 7369510
references: J Crit Care. 2007 Sep;22(3):229-35
references: 17869973
references: Eur Heart J. 2000 Sep;21(18):1502-13
references: 10973764
references: Acta Neurochir (Wien). 2000;142(9):1013-9; discussion 1019-20
references: 11086810
references: J Cereb Blood Flow Metab. 1991 Jan;11(1):114-21
references: 1983995
references: Curr Opin Anaesthesiol. 2012 Oct;25(5):548-55
references: 22895122
references: J Neurosurg. 2001 Jan;94(1):50-4
references: 11147897
references: Anesthesiology. 2010 Jan;112(1):86-101
references: 19952722
references: BMJ. 2003 Sep 6;327(7414):557-60
references: 12958120