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Release: Sept. 9, 1999

UI receives $8.1 million NIH grant

IOWA CITY, Iowa -- The University of Iowa has received an $8.1 million grant from the National Institutes of Health to oversee a multi-site trial testing the use of hypothermia as a way to improve neurologic outcomes in patients needing a certain common brain operation.

"This trial is an exciting prospect," said Michael Todd, M.D., UI professor of anesthesia and the project's principal investigator. "If successful, it will almost certainly benefit other areas of medicine in which brain protection is needed."

The trial, which will involve 25 to 30 sites around the United States and the world, will focus on improving the treatment of a sometimes-fatal condition called a subarachoid hemorrhage. The problem, usually caused by a ruptured intracranial aneurysm, involves blood vessels near the base of the brain that leak and fill the surrounding cavity with blood. The condition affects roughly 30,000 people annually in the United States and Canada alone, said Todd, who put the worldwide figures at several hundreds of thousands.

A third of those with such hemorrhages die instantly or never recover from complications. For the remaining patients, treatment has typically involved the neurosurgical placement of a clothespin-like clip around the aneurysm to prevent another, even more devastating episode of bleeding. However, since surgery is often urgent and because the brain may already be damaged from the original hemorrhage, about 25 percent of the patients wake up from surgery with stroke or some other additional neurological condition. Although other treatments for such aneurysms are being explored and used, such surgery is still quite common.

"Most people accept the risk of stroke or other neurological injury as a reasonable trade-off," Todd said. "But they may not have to if the trial shows that hypothermia works."

During the next five years, researchers hope to enroll 1,000 patients in the trial. After determining whether someone is eligible, researchers will randomly assign the patient to one of two groups. For the control group, researchers will keep the patients' body temperatures at the normal level of 37 degrees Celsius (98.6 degrees Fahrenheit). For the other group, researchers will drop the body temperature to 33 degree Celsius (91.4 degrees Fahrenheit). The patients will remain at the lower temperature until just after the surgeon clips the aneurysm. For three months following surgery, the researchers will monitor patients in each group for any neurological impairment and for their ability to perform routine activities of daily living.

Previous research and Todd's pilot study suggest that there is a strong possibility that hypothermia might prevent neurological problems. However, the reason why is unclear. The traditional view that many hypothermia advocates have argued is that cooling the body simply slows down the brain's metabolism and enables it to better tolerate the jarring and other hits it takes during surgery.

"The reason why hypothermia might prevent neurological problems is probably much more complicated than that," Todd said.

Cooling an individual in the operating room does have risks. In other operations, there have been increased rates of heart attacks, surgical wound infections and problems with the blood not clotting normally, Todd said.

"We think that those risks are very low for what we are proposing," he said. "In fact, in a pilot study, we didn't see any of those problems occur."

Todd and his colleagues have been working on the project, which included a pilot study, since 1991.

About 20 UI researchers will work on the five-year trial. The UI is the coordinating center and will manage the 25 to 30 centers involved -- including sites in Australia, Canada, England, Austria and, likely, Germany.

Coordinating the multi-site trial involves faculty in several departments within the College of Medicine and the new College of Public Health. Other College of Medicine faculty involved, in addition to Todd, include: Bradley Hindman, M.D., associate professor of anesthesia; Patricia Davis, M.D., professor of neurology; Daniel Tranel, Ph.D., professor of neurology; Steven Anderson, Ph.D., assistant professor of neurology; and Matthew Howard III, M.D., associate professor of neurosurgery. Harold Adams, M.D., professor of neurology, will serve as patient safety monitor.

The College of Public Health group will be directed by Robert Woolson, Ph.D., UI professor and head of biostatistics, and includes William Clarke, Ph.D., UI professor and head of the UI Clinical Trials Statistical and Data Management Center, who will oversee the trial's data collection; and Jim Torner, Ph.D., professor and head of epidemiology. At least 10 other UI staff members will also be involved.

"It really is an enormous collaborative effort," Todd said. "Winning this grant wouldn't have happened without all these people pulling it together. It is a unique trial because it requires the collaboration of at least four different medical specialties: anesthesiology, neurosurgery, neurology and public health. Most trials just involve one particular department.