Feb. 21, 2001 -- It looked good in early studies -- but a large clinical trial now shows that chilling patients with closed head injuries doesn't limit their brain damage.
The reasoning remains sound: a blow to the head releases a flood of brain chemicals that literally causes brain cells to self-destruct. Animal studies show that this process can be halted by lowering the body temperature soon after the initial injury, putting the patient into a condition known as hypothermia. Emergency-room physicians had hoped it would work in humans -- but now it's back to the drawing board.
For brain-trauma patients older than 45 years, the study definitely shows that hypothermia can be dangerous. On the other hand, for patients whose body temperatures already are low -- because they have been lying outside in cold weather, for example -- the results indicate that rewarming may be not be a good idea.
"Hypothermia is as yet unproven. It may have a role in brain injury, but using our protocol didn't work," study leader Guy L. Clifton, MD, tells WebMD. "Cooling patients to achieve hypothermia of 33 degrees Celsius [about 91°F] within eight hours of injury was not beneficial."
One intriguing finding is that among patients 45 years of age and younger, over three quarters of patients who already had a low body temperature at admission had a poor outcome if their body temperature was brought back to normal. For those in whom hypothermia was maintained, only half had a poor outcome.
Clifton, distinguished professor of neurosurgery and chairman of the neurosurgery department at the University of Texas-Houston Health Science Center, says that in continued studies he will explore the implications of this finding.
"This is not the end as far as I am concerned," he says. He intends to see if inducing hypothermia more quickly, especially in patients who may already have a low temperature when they come to the hospital, would provide any benefit. He also feels that studying the rewarming of such patients in more detail would offer further treatment options to doctors.
Raj K. Narayan, MD, chair of the neurosurgery department at the Temple University School of Medicine in Philadelphia, Pa., and chair of the American Brain Injury Consortium, says that hypothermia was a very good idea that didn't work out --- at least so far.
"I wouldn't say this is the end of hypothermia," Narayan tells WebMD. "But this study clearly shows that the thing is more complicated than one would have hoped. We have similarly not had much luck with [drug] approaches to limiting brain injury. Maybe the way hypothermia was done could be modified in a way that is more effective. It would seem to me that the problem is what helps the brain does not necessarily help the body. So if they can find a way to cool the brain without cooling the entire body, that would be nice -- but that is more easily said than done."
A recent, small-scale trial reported by Cleveland Clinic researcher Derk Krieger, MD, PhD, showed that a very similar hypothermia technique successfully reduces brain damage in stroke patients. Like Clifton, Krieger suggests that the window of opportunity to apply hypothermia to human brain-injury patients may be smaller than previously appreciated.
"The Clifton study may have begun too late in the game," Krieger tells WebMD. He says that there is a difference between brain and body temperature and it is possible the researchers never cooled the brain down sufficiently, which could account for the different results of his team.
Both Krieger and Narayan suggest that smaller brain injuries may be more responsive to hypothermia.
Narayan says that one major positive result of the Clifton et al. study is that it validates the use of a controversial "waived consent" policy. Waived consent allows researchers -- under specifically defined conditions -- to enroll patients in a study without informed consent if the patient is unconscious, not accompanied by family, and might be helped by an experimental intervention that must be given right away if it is to do any good. Hospitals participating in such studies must inform their communities that such a trial is underway -- and must make a bona fide attempt to contact patients' families.
"In the Clifton et al. study, 38% of patients were enrolled with waived consent," Narayan says. "That is a very critical point to bring up, because otherwise research in this area will essentially be strangled. Let's say you have a heart attack and we now have a drug we think will be protective for the brain and will be useful to protect the brain while you are being resuscitated. At that point you aren't going to be trying desperately to find the family -- you want to treat as soon as possible. Of course, these drugs would already have gone through preclinical and [preliminary] safety testing before you come to that. [Death and disability] from severe head injury is so great that we need to try to facilitate research rather than hamper it."