I was hopeful this would help since most hospitals would easily be able to do this in the ER.
Body Cooling May Not Help Patients with Severe Brain Injury
Results run contrary to lab outcomes, which may reflect real-world limitations
Cooling
the brain as early as possible after severe traumatic brain injury
(TBI) did not improve neurologic outcomes at 6 months, the POLAR
randomized clinical trial found.
In a study of over 500 adults with TBI, the proportion of patients with favorable neurologic outcomes at 6 months was 48.8% after hypothermia, compared with 49.1% after normothermia, reported D. James Cooper, MD, of Monash University in Melbourne, Australia, and colleagues in JAMA.
"POLAR is the largest randomized trial done on this topic and the findings are very clear: cooling the brain as early as possible after head injury does not improve long-term patient outcomes and has important complications," Cooper said.
"The best temperature for doctors to target after a severe head injury in the future is the normal one, not the cool one," he told MedPage Today.
POLAR sought to answer a decades-old controversy about whether cooling the brain early and long after severe TBI improves long-term patient outcomes, as it does in many lab studies.
"A systematic review of these laboratory studies supported prophylactic hypothermia for neuroprotection," noted Peter Andrews, MD, of Western General Hospital in Edinburgh, Scotland, and co-authors in an accompanying editorial. "Even more compelling was the report that when these studies were stratified according to risk of bias, data from the higher-quality studies showed that hypothermia was effective when delivered immediately or soon after injury."
But the benefits of hypothermia failed in translation to clinical trials, with four large multicenter trials showing either no effect or harm, the editorial noted. And none of these trials delivered early hypothermia -- and therefore didn't test the preclinical intervention.
In POLAR (Prophylactic Hypothermia Trial to Lessen Traumatic Brain Injury), a multicenter trial in six countries, researchers randomized 511 patients with TBI to either hypothermic (n=266) or normothermic (n=245) treatment from 2010 to 2017. The average patient age was 34.5, and about 80% were men. The median Glasgow Coma Scale score of the group was 6. Most patients (70.6%) had diffuse brain injury, and the median time to randomization was 1.9 hours.
The researchers managed temperature in both groups for 7 days; all other care was at the discretion of the treating physician. The intervention protocol was to induce and maintain hypothermia for at least 72 hours at 33°C/91.4°F (or 35°C/95°F, if there were bleeding concerns) with a combination of cold intravenous fluids and surface cooling wraps. The intervention was started as early as possible regardless of intracranial pressure, either before arriving at the hospital or in the emergency department, and continued for up to 7 days, followed by a gradual rewarming.
Achieving the protocol target was more difficult than expected: 33% of patients received less than 48 hours of hypothermia, and 27% never reached the final target temperature of 33°C because of complications or physician decisions.
In the normothermic group, the researchers targeted 37°C (98.6°F), using surface-cooling wraps when required.
Favorable functional outcomes -- defined as a score of 5 to 8 on the Glasgow Outcome Scale–Extended at 6 months -- occurred in 48.8% of the hypothermia group and 49.1% of the normothermia group (absolute risk difference, -0.4 percentage points, 95% CI −9.4 to 8.7; RR 0.99, 95% CI 0.82-1.19). While some patients in the hypothermia group were rewarmed prematurely either because the clinicians believed that the injury was not as severe as first thought or the patients developed serious bleeding problems, favorable outcomes were no different between the protocol or as-treated groups.
There were no significant differences in secondary outcomes, including mortality at hospital discharge and at 6 months. The proportions of patients with adverse events for new or increased intracranial bleeding were 18.1% in the hypothermia group and 15.4% in the normothermia group. For pneumonia, they were 55.0% in the hypothermia group and 51.3% in the normothermia group.
The median time to reach 33°C in this study was greater than 10 hours. Real-world protocols require time to exclude undiagnosed injuries, Cooper and his group noted: this may be why hypothermia lab studies don't translate to trauma patients.
Poor protocol adherence -- with both the target temperature range and the duration of cooling -- was a limitation of the trial, Andrews and co-authors observed. The researchers increased the study's external validity by enrolling patients regardless of intracranial pressure, but one in three patients in the hypothermia group had the intervention for less than 48 hours and one in four patients didn't reach the target temperature.
"Yet, this may reflect the realities of utilizing prophylactic hypothermia for patients with severe TBI in clinical practice, and there was still no benefit noted in the per-protocol or as-treated analyses," the editorial pointed out. It also was not possible to blind clinicians or patients' families in this trial.
Despite these limitations, "whether hypothermia has any place in intensive care in selected patients with severe traumatic brain injury and dangerously high brain pressures will now be questioned even more intently than in the past," Cooper said.
In a study of over 500 adults with TBI, the proportion of patients with favorable neurologic outcomes at 6 months was 48.8% after hypothermia, compared with 49.1% after normothermia, reported D. James Cooper, MD, of Monash University in Melbourne, Australia, and colleagues in JAMA.
"POLAR is the largest randomized trial done on this topic and the findings are very clear: cooling the brain as early as possible after head injury does not improve long-term patient outcomes and has important complications," Cooper said.
"The best temperature for doctors to target after a severe head injury in the future is the normal one, not the cool one," he told MedPage Today.
POLAR sought to answer a decades-old controversy about whether cooling the brain early and long after severe TBI improves long-term patient outcomes, as it does in many lab studies.
"A systematic review of these laboratory studies supported prophylactic hypothermia for neuroprotection," noted Peter Andrews, MD, of Western General Hospital in Edinburgh, Scotland, and co-authors in an accompanying editorial. "Even more compelling was the report that when these studies were stratified according to risk of bias, data from the higher-quality studies showed that hypothermia was effective when delivered immediately or soon after injury."
But the benefits of hypothermia failed in translation to clinical trials, with four large multicenter trials showing either no effect or harm, the editorial noted. And none of these trials delivered early hypothermia -- and therefore didn't test the preclinical intervention.
In POLAR (Prophylactic Hypothermia Trial to Lessen Traumatic Brain Injury), a multicenter trial in six countries, researchers randomized 511 patients with TBI to either hypothermic (n=266) or normothermic (n=245) treatment from 2010 to 2017. The average patient age was 34.5, and about 80% were men. The median Glasgow Coma Scale score of the group was 6. Most patients (70.6%) had diffuse brain injury, and the median time to randomization was 1.9 hours.
The researchers managed temperature in both groups for 7 days; all other care was at the discretion of the treating physician. The intervention protocol was to induce and maintain hypothermia for at least 72 hours at 33°C/91.4°F (or 35°C/95°F, if there were bleeding concerns) with a combination of cold intravenous fluids and surface cooling wraps. The intervention was started as early as possible regardless of intracranial pressure, either before arriving at the hospital or in the emergency department, and continued for up to 7 days, followed by a gradual rewarming.
Achieving the protocol target was more difficult than expected: 33% of patients received less than 48 hours of hypothermia, and 27% never reached the final target temperature of 33°C because of complications or physician decisions.
In the normothermic group, the researchers targeted 37°C (98.6°F), using surface-cooling wraps when required.
Favorable functional outcomes -- defined as a score of 5 to 8 on the Glasgow Outcome Scale–Extended at 6 months -- occurred in 48.8% of the hypothermia group and 49.1% of the normothermia group (absolute risk difference, -0.4 percentage points, 95% CI −9.4 to 8.7; RR 0.99, 95% CI 0.82-1.19). While some patients in the hypothermia group were rewarmed prematurely either because the clinicians believed that the injury was not as severe as first thought or the patients developed serious bleeding problems, favorable outcomes were no different between the protocol or as-treated groups.
There were no significant differences in secondary outcomes, including mortality at hospital discharge and at 6 months. The proportions of patients with adverse events for new or increased intracranial bleeding were 18.1% in the hypothermia group and 15.4% in the normothermia group. For pneumonia, they were 55.0% in the hypothermia group and 51.3% in the normothermia group.
The median time to reach 33°C in this study was greater than 10 hours. Real-world protocols require time to exclude undiagnosed injuries, Cooper and his group noted: this may be why hypothermia lab studies don't translate to trauma patients.
Poor protocol adherence -- with both the target temperature range and the duration of cooling -- was a limitation of the trial, Andrews and co-authors observed. The researchers increased the study's external validity by enrolling patients regardless of intracranial pressure, but one in three patients in the hypothermia group had the intervention for less than 48 hours and one in four patients didn't reach the target temperature.
"Yet, this may reflect the realities of utilizing prophylactic hypothermia for patients with severe TBI in clinical practice, and there was still no benefit noted in the per-protocol or as-treated analyses," the editorial pointed out. It also was not possible to blind clinicians or patients' families in this trial.
Despite these limitations, "whether hypothermia has any place in intensive care in selected patients with severe traumatic brain injury and dangerously high brain pressures will now be questioned even more intently than in the past," Cooper said.
The trial was
supported by grants from the National Health and Medical Research
Council of Australia; the Victorian Neurotrauma Initiative; the Teaching
Hospital of Besançon, France; and the Health Research Board of Ireland
Clinical Trial Network Program.
Cooper reported receiving consulting fees from Pressura Neuro to Monash University for an unrelated traumatic brain injury drug trial.
Andrews reported receiving speaker fees from BARD, manufacturer of a cooling device.
Cooper reported receiving consulting fees from Pressura Neuro to Monash University for an unrelated traumatic brain injury drug trial.
Andrews reported receiving speaker fees from BARD, manufacturer of a cooling device.
last updated
Primary Source
JAMA
Source Reference: Cooper DJ, et al "Effect of early sustained prophylactic hypothermia on neurologic outcomes among patients with severe traumatic brain injury: the POLAR randomized clinical trial" JAMA 2018; doi:10.1001/jama.2018.17075.Secondary Source
JAMA
Source Reference: Docherty A, et al "Hypothermia after traumatic brain injury" JAMA 2018; doi:10.1001/jama.2018.17121.
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