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Brain cooling after injury not worth the risks

Brain cooling after injury may cause harm: study - Featured Image

Cooling the brain and body soon after a severe traumatic brain injury does not improve patient outcomes as previously thought, and exposes patients to unnecessary harm, a landmark Australian trial has found.

The technique – using a combination of cold intravenous fluids and surface cooling wraps, followed by slow re-warming – has been shown to be neuroprotective in animal studies, and is used in selected patients with severe traumatic brain injury (TBI) in most Australian intensive care units.

The theory is that hypothermia limits secondary brain injury by attenuating inflammation and biochemical cascades set off by trauma.

However limited clinical trial evidence to date has failed to demonstrate that the potential benefits of hypothermia outweigh the known increased risks of bleeding, infection, decreased heart rate and blood pressure and pneumonia.

Now a major study led by researchers from Monash University in Melbourne has been credited with providing definitive evidence that the technique has no impact on patients’ long-term outcomes.

The brain cooling study

Led by Professor Jamie Cooper, director of the Australian and New Zealand Intensive Care Research Centre, the POLAR study randomized 500 traumatic brain injury patients recruited from emergency departments and ambulance services in six countries to either prophylactic hypothermia or normothermia. All other care was at the discretion of the treating physician.

Whereas a previous study (Eurotherm) only used hypothermia in patients with evidence of brain swelling, patients in the POLAR trial were randomised to hypothermia regardless of intracranial pressure. This was in order to ensure hypothermia commenced as soon as possible after injury, to maximise the likelihood of benefit.

The targeted temperature in the hypothermia group was 33-35⁰C for at least 72 hours and up to 7 days. For patients in the normothermia group, the targeted temperature was 37⁰C, with surface-cooling wraps used when required.

At six months follow-up, the study found no benefit to patients receiving hypothermia, as measured by their capacity to live independently. In both groups, 49% of patients had a favourable Glasgow Outcome Scale Extended Score.

Furthermore, hypothermia did not improve secondary outcomes including mortality.

The intervention was, however, associated with increased rates of pneumonia (55% vs 51.3%) and intracranial bleeding (18.1% vs 15.4%), the authors reported in JAMA.

Professor Cooper told doctorportal: “My view is that we should now cease using hypothermia for TBI patients in Australia”.

“From now on, patients should not have to endure the risks of hypothermia because we know there are no benefits.”

Why no effect?

The latest study showed it takes much longer to reach the target temperature in clinical practice than it does in lab rats – even when hypothermia management commences as early as possible. It took 2.5 hours on average to reach the initial target temperature of 35⁰C, and 10 hours to reach the final target temperature of 33⁰C.

The authors said the delay was largely due to the time required to exclude risk factors for bleeding, such as ruptured spleen or persistent hypotension, that would contraindicate hypothermia.

An accompanying editorial by doctors from the University of Edinburgh suggested this time lag might explain why hypothermia “failed in translation from the bench to the bedside”.

The editorialists agreed that the weight of evidence was now firmly against hypothermia initiation during the acute phases of TBI management.

Is there ever a place for hypothermia in TBI?

Professor Cooper said it’s time for an explicit warning that hypothermia has no place in the management of TBI, even when there is significant intracranial pressure.

Current guidelines by the Brain Trauma Foundation only recommend against short-term prophylactic hypothermia for diffuse TBI, and are silent on other indications.

Professor Cooper said there was now clear evidence that if intensive management of intracranial pressure was required, barbiturates were the standard of care – not hypothermia or decompressive craniectomy. In a 2011 study in the New England Journal of Medicine, Professor Cooper’s team found decompressive craniectomy was linked with poorer outcomes compared with standard care.

Professor Stephen Bernard, medical director of Ambulance Victoria told doctorportal: “I think the POLAR trial did in fact provide a definitive answer that there is no benefit in the provision of early, prophylactic therapeutic hypothermia in patients with isolated severe traumatic brain injury.”

He continued: “I understand that there is still some enthusiasm for hypothermia as a last resort for the management of intracranial hypertension after thiopentone infusion, but these patients have a dreadful outcome so it is uncertain whether this will ever be tested in a clinical trial.”

Professor Cooper said the study’s findings were far from expected.

“Few of the authors anticipated that such extensive hypothermia would have such little evidence of any measurable effect at all, other than the known complications,” he said.

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