Update: Hypothermia for Intracranial Hypertension after Traumatic Brain Injury

In patients with traumatic brain injury, hypothermia can reduce intracranial hypertension. The benefit of hypothermia on functional outcome is unclear.


We randomly assigned adults with an intracranial pressure of more than 20 mm Hg despite stage 1 treatments (including mechanical ventilation and sedation management) to standard care (control group) or hypothermia (32 to 35°C) plus standard care. In the control group, stage 2 treatments (e.g., osmotherapy) were added as needed to control intracranial pressure. In the hypothermia group, stage 2 treatments were added only if hypothermia failed to control intracranial pressure. In both groups, stage 3 treatments (barbiturates and decompressive craniectomy) were used if all stage 2 treatments failed to control intracranial pressure. The primary outcome was the score on the Extended Glasgow Outcome Scale (GOS-E; range, 1 to 8, with lower scores indicating a worse functional outcome) at 6 months. The treatment effect was estimated with ordinal logistic regression adjusted for prespecified prognostic factors and expressed as a common odds ratio (with an odds ratio <1.0 favoring hypothermia).


We enrolled 387 patients at 47 centers in 18 countries from November 2009 through October 2014, at which time recruitment was suspended owing to safety concerns. Stage 3 treatments were required to control intracranial pressure in 54% of the patients in the control group and in 44% of the patients in the hypothermia group. The adjusted common odds ratio for the GOS-E score was 1.53 (95% confidence interval, 1.02 to 2.30; P=0.04), indicating a worse outcome in the hypothermia group than in the control group. A favorable outcome (GOS-E score of 5 to 8, indicating moderate disability or good recovery) occurred in 26% of the patients in the hypothermia group and in 37% of the patients in the control group (P=0.03).


In patients with an intracranial pressure of more than 20 mm Hg after traumatic brain injury, therapeutic hypothermia plus standard care to reduce intracranial pressure did not result in outcomes better than those with standard care alone. (Funded by the National Institute for Health Research Health Technology Assessment program; Current Controlled Trials number, ISRCTN34555414.).
Andrews PJ, Sinclair HL, Rodriguez A, Harris BA, Battison CG, Rhodes JK, Murray GD; Eurotherm3235 Trial Collaborators. Hypothermia for Intracranial Hypertension after Traumatic Brain Injury. N Engl J Med. 2015 Dec 17;373(25):2403-12. doi: 10.1056/NEJMoa1507581. Epub 2015 Oct 7. PubMed PMID:

We still lack scientific support as a first-tier therapy for the use of therapeutic hypothermia

A literature search for relevant articles in English published from year 2000 up to December 2013 found 19 studies. No signs of improvement in outcome from hypothermia were seen in the five pediatric studies. Varied results were reported in 14 studies on adult patients, 2 of which reported a tendency of higher mortality and worse neurological outcome, 4 reported lower mortality, and 9 reported favorable neurological outcome with hypothermia. The quality of several trials was low. The best-performed randomized studies showed no improvement in outcome by hypothermia-some even indicated worse outcome. TBI patients may suffer from hypothermia-induced pulmonary and coagulation side effects, from side effects of vasopressors when re-establishing the hypothermia-induced lowered blood pressure, and from a rebound increase in intracranial pressure (ICP) during and after rewarming. The difference between body temperature and temperature set by the biological thermostat may cause stress-induced worsening of the circulation and oxygenation in injured areas of the brain. These mechanisms may counteract neuroprotective effects of therapeutic hypothermia.
We still lack scientific support as a first-tier therapy for the use of therapeutic hypothermia in TBI patients for both adults and children, but it may still be an option as a second-tier therapy for refractory intracranial hypertension (( Sandestig A, Romner B, Grände PO. Therapeutic Hypothermia in Children and Adults with Severe Traumatic Brain Injury. Ther Hypothermia Temp Manag. 2014 Mar 1;4(1):10-20. Review. PubMed PMID: 24660099.))

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