Investigators from the UPMCs Brain Trauma Research Center found that inducing moderate hypothermia -- lowering the body temperature from the normal range of 37-38o C (98-99o F) to 32-33o C (87-88o F) -- for 24 hours after patients suffer severe traumatic brain injury led to improved patient outcomes (less disability and better recovery) for these patients when compared with those who did not receive the treatment. The standard measure of mental responsiveness is the Glasgow Coma Scale, developed to assess coma by determining motor, verbal and eye-response to stimulus.
Among all participants, good outcomes were achieved by 56 percent of hypothermia patients compared with 33 percent of the patients treated conventionally; mortality rates were 20 percent among those who had received hypothermia treatment and 24 percent in the other patients.
In a subset of patients who showed some brain activity despite unconsciousness at the time of admission (Glasgow Coma Scale 5, 6 or 7, amounting to 61 percent of those in the study), the results were even more dramatic. At six months after their injuries, 73 percent of patients receiving hypothermia treatment had a good outcome (moderate to no disability) compared with 35 percent of patients in the control group. Mortality was also markedly improved in this group of patients: 9 percent in the hypothermia group, 23 percent in the non-hypothermia group. UPMC researchers believe that hypothermia produces improved outcomes in two ways: by reducing swelling due to inflammation and by inhibiting the cascade of neurochemicals (especially glutamate) that kill brain cells.
Principal investigator Donald W. Marion, M.D., associate professor of neurosurgery and chief, neurotrauma service, department of neurological surgery at the UPMC, commented, This study is significant because it verifies the effectiveness of this treatment after more than 15 studies of other therapies proved ineffective. Now, more people who suffer non-penetrating head trauma may be able to resume a normal life. Hypothermia treatment delivered within six hours of trauma is relatively simple and inexpensive to implement and free of unwanted side effects.
Severe brain trauma is a common cause of death and mental impairment, particularly among young people. Annually, 50,000 people suffer such injuries and require long-term care at a cost of more than $20 billion, according to the National Institute of Neurological Disorders and Stroke (NINDS). Motor vehicle accidents are the most common cause of such injuries. Gunshot and other penetrating wounds were an exclusionary factor for this study.
The study, which ran from February 1991 through September 1994, screened 155 patients brought to the UPMC Trauma Department whose injuries left them unresponsive to verbal commands. The 82 patients who met the pre-determined entry criteria were randomly assigned to hypothermia or non-hypothermia groups within six hours of injury.
Patients who received hypothermia were placed in a special bed with cooling blankets connected to pumps that provided continuous circulation of icy water. In addition, patients were cooled by a catheter through the nose to the stomach (nasogastric iced salt water lavage).
Acute care of patients followed the principles described in "Guidelines for the Management of Severe Head Injuries," including surgical reduction of pressure on the brain by swelling in the cranium by removal of large blood clots, halting hemorrhaging and removal of tissue that has died.
After 24-hours of therapy, the patients' body temperatures were gradually increased, one degree per hour.
This research was supported by a grant from the NINDS.
The UPMC also is participating in further studies of this treatment through a national multi-center trial. Future research plans of the UPMC Brain Trauma Research Center include studies of new pharmacological agents combined with hypothermia.
Results from pilot studies, including a September 1993 report by Dr. Marion published in the Journal of Neurosurgery, were so promising that last year Health and Human Services Secretary Donna Shalala waived the usual requirement for obtaining consent from a relative of each (unresponsive) patient before being able to enroll them in the study.
Other authors of the NEJM article include Louis E. Penrod, M.D., Sheryl F. Kelsey, Ph.D., Walter D. Obrist, Ph.D., Patrick M. Kochanek, M.D., Alan M. Palmer, Ph.D., Stephen R. Wisniewski, Ph.D., and Steven T. DeKosky, M.D.
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