The use of therapeutic hypothermia to reduce intracranial pressure in patients with traumatic brain injury leads to worse outcomes than if the procedure were avoided altogether, a new study suggests.
Their findings, published in The New England Journal of Medicine 2015 Oct. were so striking that the team from Scotland stopped the study before it was completed, when an interim analysis indicated that it would have been unethical to continue.
“It was a big surprise,” said Peter Andrews, MD, the study’s chief investigator and an honorary professor in the Department of Anesthesia at the University of Edinburgh. “The laboratory data, and the small clinical trials of prophylactic hypothermia for brain protection, all signaled toward benefits.”
The resesearchers initially enrolled 2,498 patients from centers around the world, all adults with an intracranial pressure of more than 20 mm Hg despite having received first-line treatments, such as mechanical ventilation and sedation management. Between November 2009, when the trial began, and October 2014, when it was halted for safety reasons, 387 patients were randomly assigned to either the control or the hypothermia group.
The control group received standard of care and any second-line treatment needed to control intracranial pressure, whereas the hypothermia group received hypothermia in addition to standard of care, plus any second-line treatment needed if hypothermia failed to relieve intracranial pressure. Patients in both groups received third-line treatments, including barbiturates and decompressive craniectomy, in the event that second-line treatments failed.
The six-month score on the Extended Glasgow Outcome Scale (GOS-E; range 1-8, with lower scores indicating a worse functional outcome) was the primary outcome measured. The investigators expressed the treatment effect, adjusted for prespecified prognostic factors, as a common odds ratio, with a value of less than 1.0 indicating that hypothermia was effective.
Contrary to their expectations, Dr. Andrews and his colleagues found that the adjusted common odds ratio for the GOS-E score was 1.53 (95% CI, 1.02 to 2.30;P=0.04), strongly indicating that the hypothermia group experienced worse outcomes than the control group. Moreover, they observed that a favorable outcome, defined as a GOS-E score of 5 to 8, signaling moderate disability or good recovery, occurred in 26% of the patients in the hypothermia group, compared with 37% of the patients in the control group (P=0.03).
The paper also noted that third-line treatments were required to control intracranial pressure in 54% of the patients in the control group, as opposed to only 44% of the patients in the hypothermia group.
Dr. Andrews was unequivocal in his assessment of using hypothermia in this context: “I don’t think hypothermia should be used after traumatic brain injury,” he said.
Others in the field expressed agreement and strong praise for the study, which was presented at the 2015 annual meeting of the Neurocritical Care Society, in Arizona, prior to publication.
“This is a major paradigm shift in how we treat patients,” said Peter Papadakos, MD, a specialist in anesthesiology and critical care medicine at the University of Rochester Medical Center, in New York, and a member of the Anesthesiology News advisory board. “We were commonly using hypothermia for severe traumatic brain injury to reduce intracranial pressure. And I believe, based on this paper, practice is going to change. And it’s going to lead to more research on other modalities to decrease intracranial pressure.
“It’s going to shift the way we think about hypothermia,” he continued. “I believe this study is going to open up a lot more evidence-based research on outcomes using hypothermia with other neurological conditions, such as anoxic brain injury, intracranial bleeds from aneurysms—we’re currently actively using hypothermia after cardiac arrest.
As for the next steps in this line of research, Dr. Andrews said it would be useful to answer the question of whether controlling patients’ temperatures leads to better outcomes, compared with not attempting temperature management in the first place.
Meanwhile, Dr. Andrews emphasized: “The message to not use hypothermia after traumatic brain injury is the important one to get out there.”