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Hypothermia for traumatic head injury

  1. Emma Sydenham1,*,
  2. Ian Roberts1,
  3. Phil Alderson2

Editorial Group: Cochrane Injuries Group

Published Online: 15 APR 2009

Assessed as up-to-date: 6 APR 2009

DOI: 10.1002/14651858.CD001048.pub4


How to Cite

Sydenham E, Roberts I, Alderson P. Hypothermia for traumatic head injury. Cochrane Database of Systematic Reviews 2009, Issue 2. Art. No.: CD001048. DOI: 10.1002/14651858.CD001048.pub4.

Author Information

  1. 1

    London School of Hygiene & Tropical Medicine, Cochrane Injuries Group, London, UK

  2. 2

    National Institute for Health and Clinical Excellence, Manchester, UK

*Emma Sydenham, Cochrane Injuries Group, London School of Hygiene & Tropical Medicine, Room 280, Keppel Street, London, WC1E 7HT, UK. emma.sydenham@Lshtm.ac.uk.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 15 APR 2009

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Characteristics of included studies [ordered by study ID]
Adelson 2005 HYPO1

MethodsMulticentre, randomised, controlled trial.


ParticipantsPatients less than 13 years of age, with a Glasgow coma scale (GCS) score of ≤8.


InterventionsHypothermia patients: Cooling to 32-33C within 6 hours of injury for 48 hours. Passively rewarmed by 1C every 3-4 hours.
Normothermia patients: no intervention/not reported.


OutcomesICP
CPP
Mortality
Infection
Arrhythmia
Coagulopathy
Pneumonia


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?Yes'The investigators were blinded to the allocation. The statistician and data systems manager controlled the randomisation protocol and were blinded to the site.' Adelson 2008b

Adelson 2005 HYPO2

MethodsSingle centre, randomised, controlled trial.


ParticipantsPatients less than 17 years of age, with a GCS score of ≤8.


InterventionsHypothermia patients: Cooling to 32-33C for 48 hours. Passively rewarmed by 1C every 3-4 hours.
Normothermia patients: no intervention/not reported.


OutcomesICP
CPP
Mortality
Infection
Arrhythmia
Coagulopathy
Pneumonia


NotesThe time between injury and randomisation was more than 6 hours. In some cases there was an unknown time of injury (e.g. child abuse).


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?Yes'The investigators were blinded to the allocation. The statistician and data systems manager controlled the randomisation protocol and were blinded to the site.' Adelson 2008b

Aibiki 2000

MethodsRandomised controlled trial.
Four patients were excluded from the normothermic group after randomisation because of abdominal or chest injuries.


ParticipantsPatients aged 4 to 76, within 8 hours of traumatic brain injury. GCS score of ≤8 on admission to emergency room.


InterventionsHypothermia patients: Cooling to 32-33C within 4 hours of injury for 3-4 days. Rewarming at 1C per day.
Normothermia patients: maintained at 36-37C.


OutcomesDeath and Glasgow Outcome Scale (GOS) score at 6 months.
Thromboxane A2 and prostaglandin I2 levels during study. Complications during treatment.


NotesGOS assessed by "independent neurosurgeon who were not aware of the study". p.3904


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?Unclear'Patients were assigned randomly to each group.' p.3903 No mention of allocation concealment.

Biswas 2002

MethodsRandomised controlled trial.


ParticipantsChildren up to 18 years old, with closed traumatic brain injury and a GCS score of ≤8.


InterventionsHypothermia patients (n=10): cooled to 32 to 34 degrees Celsius for 48 hours, by cooling blanket placed underneath the body. Rewarming over a period of 12 hours.
Control patients (n=11): rectal temperature was maintained between 36.5 and 37.5 degrees Celsius.


OutcomesDeath.
GOS score at three, six and 12 months.
ICP and CPP.


NotesGOS score assessed blind to allocation.
Analysis on an intention-to-treat basis.

Two patients in the hypo group were lost to follow-up at the end of the study period. (2/10 lost to follow-up.)

Five patients in the control group were lost to follow-up at the end of the study period. (5/11 lost to follow-up.)


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearNot described.

Clifton 1992

MethodsRandomised controlled trial.


ParticipantsPatients with GCS score of 4-8 with closed head injury but no major systemic injuries, in whom cooling could begin within 6 hours of injury.


InterventionsHypothermia patients: cooling to 30-32C for 24 hours using cooling blankets and iced saline stomach lavage. Rewarming over a period of 24 hours.
Control patients: No active temperature management.


OutcomesDeath and GOS score at 3 months.
Complications during treatment phase.


NotesGOS score was not assessed blind to treatment allocation.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesBy 'sealed envelopes'.

Clifton 1993

MethodsRandomised controlled trial.


ParticipantsPatients age 16 to 60, GCS score of 4-7 with closed head injury but no major systemic injuries, in whom cooling could begin within 6 hours of injury.


InterventionsHypothermia patients: cooling to 32-33C for 48 hours using cooling blankets. Rewarming over a period of 48 hours.
Control patients: Cooling blankets were used to maintain body temperature at 37C for 80 hours.


OutcomesDeath and GOS score at 3 months.
Complications during treatment period.
ICP during treatment period.


NotesGOS score assessed blind to treatment allocation.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesBy 'sealed envelopes'.

Clifton 2001

MethodsRandomised controlled trial.


ParticipantsPatients aged 16 to 65 with a non-penetrating head injury and a GCS score of 3 to 8 after resuscitation.


InterventionsHypothermia patients: cooling to 32.5-34C for 48 hours using ice, cold gastric lavage, unwarmed ventilator gases, and then temperature control pads. Rewarming at rate of up to 0.5C in 2 hours.
Control: Body temperature maintained at 37C.


OutcomesDeath and GOS score at 6 months.
ICP monitored during treatment.
Nine neurobehavioural and neuropsychological scales at 6 months.


NotesGOS score was assessed blind to treatment allocation.
Outcome data missing for 7 patients, and not presented for 17 patients whose entry details were incomplete.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesAllocation concealment unclear, but report states that "only the study biostatistician was aware of each patient's treatment group assignment". p557

Harris 2009

MethodsRandomised controlled trial.


ParticipantsPatients over 18 years of age with a Glasgow coma scale score of ≤8, who required an ICP monitor and Foley catheter as part of routine treatment.


InterventionsHypothermia patients (n= 12): the 'Discrete Cerebral Hypothermia System cooling cap' was used to reduce cerebral temperature to a target 33 degrees Celsius for 24 hours. 'Using heating blankets, patients' core body temperatures were kept above 36 degrees Celsius to avoid systemic hypothermia' p.3.
Control patients (n= 13): Patients did not receive a cooling cap, and remained at normal body temperature.


OutcomesDeath, ICP, FIM, and GOS score at days 1, 2, 3, 4, 14, 21, 28 and 1 month (or at hospital discharge, if sooner than one month).


NotesCooling was begun within 48 hours of hospital admission.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?Yes'After informed consent was obtained, all study patients were blindly randomized in a 1:1 ratio to the treatment or control group; patients in the treatment group received the cooling cap and the controls did not. The randomization was determined by the Department of Biostatistics using computer-generated random numbers. These numbers were assigned to each patient based on their order in the study and GCS score on initial assessment (severe [5-8] vs critical [3-4]), to allow for block randomization and to provide an initial balance in severity between the 2 groups.' p.3

Hashiguchi 2003

MethodsRandomised controlled trial. Allocation method not stated.


ParticipantsParticipants age 10 years or older, with a GCS score of ≤8, 'who required continuous infusion of barbiturates to control intracranial hypertension.' p.1055


InterventionsHypothermia patients (n=9): intracranial temperature in the lateral ventricle was maintained at 33.5 to 34.5 degrees Celsius for 48 hours, by water circulating blankets above and below the body. Rewarming over a period of 3 days, by 1 degree Celsius each day.
Control patients (n=8): intracranial temperature was maintained between 36.5 and 37.5 degrees Celsius for 5 days, by water circulating blankets above and below the body.

Barbiturates were given to both groups at 6 to 8 mg/kg/h for the first 48 hours, then at 2 mg/kg/h for 3 days.


Outcomes


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearNot described.

Hirayama 1994

MethodsRandomised controlled trial. Allocation method not stated.


ParticipantsPatients age 18 to 81, GCS 3-7 with closed head injury. Hypothermia started within 6 hours of injury.


InterventionsHypothermia patients: cooling to 32-33C for 48 hours using cooling blankets. Rewarming over a period of 48 hours.
Control patients: Not stated.


OutcomesDeath and GOS score at 3 months.
ICP during treatment period.


NotesBlinding of outcome assessment not stated.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearNot described.

Hutchison 2008

MethodsRandomised controlled trial.


ParticipantsPatients age 1-17 years, with a recent traumatic brain injury (within 8 hours) and a GCS score of ≤8.


InterventionsHypothermia patients: cooling to 32-33C for 24 hours with surface cooling. Rewarming at a rate of 0.5C every 2 hours.
Control patients: temperature was maintained at 36.5 to 37.5C.


OutcomesUnfavourable outcome at 6 months post-injury.
Pediatric Cerebral Performance Category scale at pre-injury, and at 1, 3 and 12 months post-injury.


Notes'Overall, 20 out of the 225 patients (9%) were lost to follow-up at 6 months -- 6 out of 108 patients (6%) in the hypothermia group and 14 of 117 (12%) in the normothermia group.' p.2451


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?Yes'...a study physician randomly assigned the patient to a treatment group with the use of a central telephone-based system that was available 24 hours a day. The randomization, prepared by an independent statistician, was blocked in groups of four (participating centers were unaware of the block size) and included two stratification variables: center and age (less than 7 years of age and 7 years of age or more).' p.2448

Ishikura 1998

MethodsRandomised controlled trial. Allocation by 'random sampling'.


ParticipantsPatients with GCS score of 3-8 with closed head injury.


Interventions'Moderate hypothermia' without any details.


OutcomesThrombopoetin levels during treatment.
Deaths in hypothermia arm only.


NotesAbstract only.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?Unclear'11 patients with severe closed head injuries were divided into two groups by random sampling.' No information provided on allocation concealment.

Jiang 2000

MethodsRandomised controlled trial. Allocation method not clear.


ParticipantsPatients with mean age of 41 years, and GCS score of 3-8.


InterventionsHypothermia patients: 'Mild hypothermia' induced using cooling blankets until ICP within 'normal range' for 24 hours.
Control patients: Temperature maintained between 37-38C for 14 days.


OutcomesDeath and GOS score at 12 months.
Complications.


NotesAssessment by MD blinded to treatment allocation.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearNot described.

Marion 1997

MethodsRandomised controlled trial. Allocation by 'sealed envelopes'.


ParticipantsPatients age 16 to 75, GCS score of 3-7 with closed head injury, in whom cooling could begin within 6 hours of injury.


InterventionsHypothermia patients: Cooling to 32-33C for 24 hours using cooling blankets and nasogastric lavage. Rewarming over a period of 12 hours.
Control patients: Active management of temperature to 37-38.5C during five day treatment period.


OutcomesDeath and GOS score at 3, 6 and 12 months.
ICP and CPP values during treatment phase.
Complications for subset.


NotesGOS score assessment by psychiatrist blinded to treatment allocation.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?Yes'Using a block-randomization scheme, we assigned patients with a Glasgow coma score of 3 or 4 to a treatment group separately from those with a score of 5 to 7 by choosing among equal numbers of sealed envelopes containing the group assignments.' p.540

Meissner 2003a

MethodsRandomised controlled trial.


ParticipantsPatients with severe blunt head injury. Intervention was started within 8 hours of injury.


InterventionsHypothermia patients: Cooling to 32-33C for 48 hours.
Control patients: Temperature maintained at 36-37C.


OutcomesHeart rate.
Mean blood pressure.
Plasma cortisol.


NotesPrimary outcome of study was moderate hypothermia on the cardiovascular and cortisol response in severe head injury.
No mortality data reported.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearNot described.

Meissner 2003b

MethodsRandomised controlled trial.


ParticipantsPatients aged 18 or older, with severe closed head injury with a GCS score of ≤9. The intervention was started within 8 hours of injury.


InterventionsHypothermia patients: Cooling to 32-33C for 24-48 hours. Cooling was by water blankets and forced air.
Control patients: Temperature maintained at 36-37C.


OutcomesTSH
TT4
FT4
TT3
FT3
RT3


NotesThis study examined thyroid hormone response in relation to therapeutic hypothermia.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearNot described.

Qiu 2007

MethodsRandomised, controlled, double-blind trial.


ParticipantsPatients 18-65 years old with traumatic brain injury with a Glasgow Coma Scale score of ≤8.


InterventionsHypothermia patients: Cooling to 33-35C for 4 days after craniotomy, using a cooling blanket and cooling head cap with circulating water at 4C. 'Natural' rewarming.
Normothermia patients: cooling not used.


OutcomesMortality.
ICP.
Serum superoxide dismutase level.
Glasgow Outcome Scale score at 1 year post-intervention.


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?Yes'Allocation and randomization was concealed so that the study investigators were not aware to which group the patient would be assigned, and the allocation sequence was protected until assignment.' p.230

Shiozaki 1993

MethodsRandomised controlled trial.


ParticipantsPatients age 10 or over, with a GCS score of ≤8 with head injury, who 'required continuous infusion of barbiturates to control intracranial hypertension'. p.363


InterventionsHypothermia patients: cooling to 33.5-34.5C using water-circulating cooling blankets for a minimum of 48 hours and until ICP was below 20 mmHg for 24 hours. Rewarming over a period of 24 hours.
Control patients: No active temperature management.


OutcomesDeath and GOS score at 6 months.
Pneumonia.
Complications during treatment.
ICP and CPP values during treatment period for hypothermic arm only.


NotesGOS score assessed blind to treatment allocation.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearNot described.

Shiozaki 1999

MethodsRandomised controlled trial. Allocation concealment not clear.
No loss to follow up.


ParticipantsPatients age 10 and above with traumatic brain injury, a Glasgow coma scale score of ≤8, and 'who required continuous infusion of barbiturate medication to control intracranial hypertension.' p.185


InterventionsHypothermia patients: cooling to 33.5-34.5C for 48 hours, using water circulating blankets. Rewarming at 1C per day.
Normothermia patients: maintained at 36.5-37.5C.


OutcomesDeath and GOS score at 6 months.
Complications.


NotesBlinding of outcome assessment not stated.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearNot described.

Shiozaki 2001

MethodsRandomised controlled trial.
Allocation concealment not clear.
No loss to follow up.


ParticipantsPatients with traumatic brain injury, a Glasgow coma scale score of ≤8, and 'in whom ICP was maintained below 25mmHg by conventional therapies'. p.50


InterventionsHypothermia patients: Cooling to 33.5-34.5C for 48 hours, using cooling blankets and gastric lavage. Rewarming at 1C per day.
Normothermia patients: maintained at 36.5-37.5C.


OutcomesDeath and GOS score at 3 months.
Complications.


NotesBlinding of outcome assessment not stated.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearNot described.

Smrcka 2005

MethodsRandomised controlled trial - randomisation method not described.
No loss to follow up described.


ParticipantsPatients with traumatic brain injury with a Glasgow Coma Scale score of ≤8, who were up to age 61 years of age.


InterventionsHypothermia (n=37): surface cooling to 34C for 72 hours. Temperature measured in urinary bladder. Passive rewarming.

Normothermia (n=35): cooling not used.


OutcomesICP
CPP
SvjO2 (jugular bulb oxygen saturation)
GOS


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearNot described.

Yan 2001

MethodsRandomised controlled trial.
Allocation concealment not described.
No loss to follow up described.


ParticipantsPatients with traumatic brain injury within 10 hours of injury and a Glasgow Coma Scale score of 3 to 8 on initial assessment.


InterventionsHypothermia patients: Cooling to 32-34C for 3-5 days, using a cooling bed and, in some, ice blocks. 'Natural' rewarming.
Normothermia patients: cooling not used.


OutcomesDeath, follow up period unclear.
Neuroelectrophysiological measurements.


NotesBlinding of outcome assessment not stated.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearNot described.

Zhang 2000

MethodsRandomised controlled trial.
Allocation concealment not described. No loss to follow up mentioned.


ParticipantsPatients aged under 65 with traumatic brain injury and a Glasgow Coma Scale score of 3-8 on admission to hospital.


InterventionsHypothermia patients: Cooling to 32-33C for 3-8 days.
Normothermia patients: temperature not stated.


OutcomesDeath, follow up period unclear.


NotesBlinding of outcome assessment not stated.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearNot described.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Bayir 2009Report on antioxidant status of paediatric patients treated with hypothermia. These patients have already been included in this review as part of the Adelson 2005 HYPO1 and Adelson 2005 HYPO2 trial.

Chen 2001Unclear method of randomisation. Unable to confirm method of randomisation with trial report authors.

Chouhan 2006Patients were not cooled for a minimum of 12 consecutive hours.

Fukuoka 2004Quasi-randomised study design.

Gal 2002Not a randomised study.

Gentilello 1997Randomised trial of rewarming therapy after accidental hypothermia in trauma.

Guo 2004Not a randomised trial.

Hayashi 2002Not a randomised study.

Hayashi 2005Not a randomised study.

Legros 1985Not a randomised study.

Li 2008Unclear if randomised trial. Unable to confirm method of randomisation with trial report authors.

Liu 2005Patients who died within 72 hours of participating in the study were not included in the analysis.

Liu 2006Patients were not cooled for a minimum of 12 consecutive hours.

Meissner 1998No mention of method of randomisation.

Mrlian 2006Not a randomised study.

Nara 1997Unable to find sufficient information on study design.

Nordby 1984Not a randomised comparison, and hypothermia confounded with barbiturate therapy.

Qiu 2005Unclear if randomised trial. Unable to confirm method of randomisation with trial report authors.

Qiu 2006Not a randomised study.

Schulman 2005Patients in this study were excluded if they had evidence of acute brain injury and if they had previous traumatic brain injury.

Shen 2000Not a randomised trial.

Wang 2005Unclear if randomised trial. Unable to confirm method of randomisation with trial report authors.

Wang 2007Unclear if randomised trial. Unable to confirm method of randomisation with trial report authors.

Wusi 2006Not a randomised trial.

Xia 2005Not a randomised trial.

Yamagami 1997Not a randomised trial; hypothermia group GCS 4-6, normothermia group GCS 8-10.

Yan 2007Unclear if randomised trial. Unable to confirm method of randomisation with trial report authors.

Zhi 2003Unclear if randomised trial. Unable to confirm method of randomisation with trial report authors.

 
Characteristics of ongoing studies [ordered by study ID]
Adelson 2007

Trial name or titlePediatric traumatic brain injury consortium: hypothermia.

MethodsTreatment, Randomized, Single Blind (outcome assessor), single group assignment, efficacy study.

ParticipantsTBI patients under 16 years of age, with a GCS </= 8.

InterventionsPatients in the treatment arm will be cooled to 32-33C for 48 hours and then slowly rewarmed.

Outcomes
  • To determine the effect of induced moderate hypothermia (32-33C) after severe TBI in children on mortality.
  • To determine the effect of hypothermia after severe TBI in children on global function and neurocognitive outcomes in the areas of intellectual ability/development, memory and learning, and behaviour.
  • To determine the effect of hypothermia after severe TBI in children of different age ranges (<6y and 6 to <16y) on mortality and 6- and 12-month functional and neurocognitive outcomes.
  • To determine the effect of hypothermia after severe TBI in children on reducing intracranial hypertension and maintaining adequate cerebral perfusion pressure (CPP).

Starting dateNovember 2007

Contact informationDavid Adelson +1(412)692-6347 david.adelson@chp.edu

Danielle Brown +1(412)692-8794 brownds2@upmc.edu

NotesPhase III Clinical Trial.

The sites participating in this trial are: Duke University, Durham, North Carolina; Johns Hopkins University, Baltimore, Maryland; Schneider Children’s Hospital, New Hyde Park, New York; Penn State University College of Medicine, Hershey, Pennsylvania; University of California, Davis, Sacramento, California; Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; University of Miami, Coral Gables, Florida; University of North Carolina, Chapel Hill, North Carolina; University of Pittsburgh, Pittsburgh, Pennsylvania; University of Tennessee, Memphis, Tennessee; University of Texas Southwestern, Dallas, Texas; University of Washington, Seattle, Washington.

Beca 2006

Trial name or titlePilot Study of Early and Prolonged Hypothermia in Severe Traumatic Brain Injury in Children.

MethodsInternational, multi-centre, randomised controlled trial, safety/efficacy study.

ParticipantsChildren of both genders age 1 to 16. The patients must have a severe traumatic brain injury as defined by a GCS ≤8 and an abnormal CT scan (intracranial haemorrhage, cerebral oedema or diffuse axonal injury) or a motor score ≤3 and a normal CT scan. The patients must be mechanically ventilated.

InterventionsPatients will be randomised within 6 hours of injury. Patients will be stratified by 1) centre and 2) Glasgow Coma Score. Half the patients will be cooled to 32-33 degrees Celsius for 72 hours and then slowly rewarmed. The other patients will have their body temperature maintained at 36-37 degrees Celsius.

OutcomesPaediatric Cerebral Performance Category (PCPC) at 6 and 12 months after injury; neuropsychological outcomes at 6 and 12 months after injury, intracranial pressure/cerebral perfusion pressure; duration of mechanical ventilation; intensive care and hospital length of stay; adverse effects.

Starting dateNovember 2006

Contact informationJohn Beca +61 649 307 4903 johnbeca@adhb.govt.nz

Laura Whelan +61 649 307 4903 LCWhelan@adhb.govt.nz

NotesThe sites participating in this trial are: in Australia -- Royal Alexandra Hospital for Children, New South Wales; Sydney Children's Hospital, New South Wales; Queensland Paediatric Intensive Care Services, Queensland; Women's and Children's Hospital, South Australia; Royal Children's Hospital, Victoria; Princess Margaret Hospital, Western Australia; and in New Zealand -- Starship Children's Hospital, Auckland.

Clifton 2002

Trial name or titleNational Acute Brain Injury Study: Hypothermia II (NABISH II).

MethodsRandomized, prospective, multi-center trial. Hypothermia for 48 hours, begun within 6 hours of severe brain injury.

ParticipantsPatients aged 16 to 45 years inclusive who have a closed head injury, present to the Emergency Department with a Glasgow Coma Scale score between 3-8, have a body temperature (bladder or rectal) of 35 degrees Celsius or less at admission, and an Abbreviated Injury Score (AIS) of 4 or less for the rest of the body.

InterventionsThe patients will be randomly allocated to either the hypothermia group or the normothermia group. A cooling suit will be used to cool the hypothermia patients down to a body temperature of 33 degrees Celsius. This temperature of 33 degrees will be maintained in the hypothermia patients for 48 hours. After 48 hours, the study nurses will gradually re-warm the hypothermia patients no faster than one degree every four hours. This takes at least 16 hours sometimes longer depending upon the stability of the patient's vital signs. The control group - normothermia will be allowed to re-warm gradually upon arrival to the hospital with no medical intervention to raise or lower the body temperature.

OutcomesMortality and GOS. ICP and complications.
Outcomes will be measured 6 months post injury by Harvey Levin, MD at Baylor College of Medicine. The personnel conducting outcome measurements will be blinded to the patient's assigned treatment protocol (whether hypothermia or normothermia).

Starting date4/1/02 - 6/30/08

Contact informationGuy L. Clifton, MD
Chairman Neurosurgery Dept., University of Texas Medical School
6431 Fannin St., Suite 7.148
Houston, TX 77030
713-500-6135
guy.l.clifton@uth.tmc.edu

Emmy R. Miller, RN, PhD, Co-investigator NABISH II
Associate Professor of Neurosurgery
University of Texas Medical School, Houston, TX
6431 Fannin St., Suite 7.148
Houston, TX 77030
713-500-6145
Emmy.R.Miller@uth.tmc.edu

NotesThere are other study sites participating in NABISH II.

They are:
University of Pittsburgh, Duke University, University of California at Los Angeles, University of California at Sacramento, University of California at San Francisco, University of Virginia at Fairfax, University of Cincinnati, University of Mississippi at Jackson.

Preliminary publication and description of treatment protocol: Clifton 2009.

Maekawa 2002

Trial name or titleTherapeutic Strategy for Severe Head Trauma Patients With Mild Hypothermia and Estimation of Medical Expenses in Japan.

MethodsRandomized controlled trial with parallel assignment, safety/efficacy study. Hypothermia to 32-34 degrees Celsius for 72 hours, initiated within 6 hours of injury.

ParticipantsPatients age 15 to 69 years, of both genders, with a closed head injury and a Glasgow Coma Scale score of 4-8.

InterventionsPatients will be randomized into two groups. The mild hypothermia group will be kept at 32-34 degrees Celsius for 72 hours, initiated within six hours of injury. Patients in the control group will have their body temperature maintained at 35.5 to 37 degrees Celsius for 72 hours. The Glasgow Outcome Scale score at six months after injury, and the total medical expenses of the two groups will be evaluated.

OutcomesNeurological outcomes including GOS score and neuropsychological performance at 6 months after injury, total medical expenses, physiological data, and laboratory data.

Starting dateDecember 2002

Contact informationYamaguchi University Hospital

University Hospital Medical Information Network (UMIN, Japan)
Japan Clinical Research Support Unit (J-CRSU)

Tsuyoshi Maekawa, MD, PhD +81-836-22-2343 tmaekawa@yamaguchi-u.ac.jp

Susumu Yamashita, MD +81-836-22-2656 sum-ygc@umin.ac.jp

NotesContact: Susumu Yamashita, MD

 
Comparison 1. Immediate hypothermia versus normothermia

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Death at final follow-up211587Odds Ratio (M-H, Fixed, 95% CI)0.85 [0.68, 1.06]

 2 Death at final follow-up stratified by trial quality211587Odds Ratio (M-H, Fixed, 95% CI)0.85 [0.68, 1.06]

    2.1 Concealed allocation
9891Odds Ratio (M-H, Fixed, 95% CI)1.11 [0.82, 1.51]

    2.2 Non-concealed allocation
12696Odds Ratio (M-H, Fixed, 95% CI)0.62 [0.44, 0.86]

 3 Unfavourable outcome at final follow-up211587Odds Ratio (M-H, Fixed, 95% CI)0.77 [0.62, 0.94]

 4 Unfavourable outcome stratified by trial quality21Odds Ratio (M-H, Fixed, 95% CI)Subtotals only

    4.1 Concealed allocation
9891Odds Ratio (M-H, Fixed, 95% CI)0.93 [0.70, 1.23]

    4.2 Non-concealed allocation
12696Odds Ratio (M-H, Fixed, 95% CI)0.60 [0.44, 0.82]

 5 Unfavourable outcome stratified by treatment duration14Odds Ratio (M-H, Fixed, 95% CI)Subtotals only

    5.1 24 hours
4321Odds Ratio (M-H, Fixed, 95% CI)1.03 [0.65, 1.65]

    5.2 48 hours
10683Odds Ratio (M-H, Fixed, 95% CI)0.96 [0.70, 1.31]

 6 Unfavourable outcome at various times during follow-up15Odds Ratio (M-H, Fixed, 95% CI)Subtotals only

    6.1 3 months
6271Odds Ratio (M-H, Fixed, 95% CI)0.85 [0.52, 1.39]

    6.2 6 months
9839Odds Ratio (M-H, Fixed, 95% CI)0.76 [0.57, 1.01]

    6.3 12 months
4262Odds Ratio (M-H, Fixed, 95% CI)0.52 [0.31, 0.87]

 7 Pneumonia during the treatment period11559Odds Ratio (M-H, Fixed, 95% CI)1.35 [0.95, 1.91]

    7.1 Concealed allocation
4306Odds Ratio (M-H, Fixed, 95% CI)0.84 [0.52, 1.35]

    7.2 Non-concealed allocation
7253Odds Ratio (M-H, Fixed, 95% CI)2.47 [1.44, 4.23]