Both hypothermia and standard care alone reduced intracranial pressure, but patients undergoing cooling had higher mortality and poorer functional outcomes.
"This is another well-conducted study that shows harm from hypothermia after TBI. It should not be used for 1) neuroprotection or 2) first-line therapy to treat raised intracranial pressure above 20 mmHg," first author Peter J.D. Andrews, MD, from the Centre for Clinical Brain Sciences, University of Edinburgh, United Kingdom, told Medscape Medical News...
The Eurotherm3235 study enrolled 387 adults with TBI at 47 centers in 18 countries from November 2009 through October 2014. At this point, recruitment was stopped after the steering committee concluded that there were "signs of harm" with hypothermia and that a result of "futility, at best," would be expected if the trial continued, the study team reports.
The study protocol called for hypothermia to be induced by a bolus of intravenous, refrigerated 0.9% sodium chloride (20 to 30 mL per kg of body weight), thereafter maintained with the usual cooling technique of each site. Guidelines were provided for induction and maintenance of hypothermia, rewarming, and detection and treatment of shivering in the intervention group, the authors note.
In the control group, "stage 2" treatments were added (ie, osmotherapy) as needed to control intracranial pressure. In the hypothermia group, stage 2 treatments were added only if hypothermia failed to control intracranial pressure. Both groups progressed to "stage 3" treatments (barbiturates and decompressive craniectomy) if 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 worse functional outcome) 6 months after injury. At this point, the distribution of GOS-E scores was shifted in an "unfavorable direction" in the hypothermia group (adjusted common odds ratio, 1.53; 95% confidence interval [CI], 1.02 - 2.30; P = .04), the researchers report.
Both therapeutic hypothermia and standard care–only approaches lowered intracranial pressure. Stage 3 treatments were needed to control intracranial pressure in more standard care–only patients than patients treated with hypothermia (54% vs 44%).
In addition, serious adverse events were more frequent in the hypothermia group than in the control group (33 events vs 10 events) and the risk for death favored the control group (hazard ratio, 1.45; 95% CI, 1.01 - 2.10; P = .047). The results were similar in prespecified subgroup analyses.
"The findings suggesting possible harm of hypothermia could be due to a biologic effect of hypothermia or due to the harms or benefits of the other therapies used differentially in the two groups," the researchers say.
http://www.medscape.com/viewarticle/852383?nlid=88983_3404&src=wnl_edit_medn_neur&uac=60196BR&spon=26&impID=853788&faf=1
Andrews PJ, Sinclair HL, Rodriguez A, Harris BA, Battison CG, Rhodes JK,
ReplyDeleteMurray GD; Eurotherm3235 Trial Collaborators. Hypothermia for Intracranial
Hypertension after Traumatic Brain Injury. N Engl J Med. 2015 Oct 7. [Epub ahead
of print]
Abstract
Background In patients with traumatic brain injury, hypothermia can reduce intracranial hypertension. The benefit of hypothermia on functional outcome is unclear. Methods 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). Results 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). Conclusions 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 .).