Harm or futility from hypothermia for traumatic brain injury

For patients with intracranial hypertension following traumatic brain injury (TBI), therapeutic hypothermia added to standard care does not improve functional outcomes relative to standard care alone and may be harmful, according to a new study.

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.

 

All enrolled patients had TBI and intracranial pressure above 20 mmHg for at least 5 minutes despite "stage 1" treatments including mechanical ventilation and sedation management. They were randomly allocated to standard care (control group, 192 patients) or induced hypothermia to a core body temperature between 32 to 35°C plus standard care (195 patients).

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%).

However, a favorable outcome (GOS-E score, 5 to 8, indicating moderate disability or good recovery) was more common in the control group than the hypothermia group (69 of 189 patients, 36.5% vs 49 of 191 patients, 25.7%; P = .03).

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.

"The benefits and harms of other interventions that successfully reduce intracranial pressure have not been assessed. More adequately powered clinical trials of hypertonic therapy, barbiturates, and hyperventilation are required," they add.

http://www.medscape.com/viewarticle/852383?nlid=88983_3404&src=wnl_edit_medn_neur&uac=60196BR&spon=26&impID=853788&faf=1