Copyright 2006 P.G. Publishing Co.
By JOE FAHY
Pittsburgh Post-Gazette (Pennsylvania)
Treatment for stroke has literally become a chilling experience for some patients.
In January, the University of Pittsburgh Medical Center began recruiting for a national study to determine if lowering body temperature by several degrees helps stroke patients.
A separate UPMC study is testing whether the brain, rather than the entire body, can be cooled by having patients wear a hood that circulates cold air around the head.
Inducing abnormally low body temperature has tremendous potential for treatment of stroke, said Dr. Lawrence Wechsler, director of UPMC’s Stroke Institute, noting that the approach already has shown benefits in patients with cardiac arrest.
Studies published in 2002 in the New England Journal of Medicine found that such patients had fewer neurological problems when they were treated with mild hypothermia than patients who did not receive the cooling treatments.
If hypothermia helps those patients, who have interrupted blood flow to the entire brain, it also should benefit stroke patients, who suffer disrupted blood flow to only part of the brain, Dr. Wechsler said.
Experts believe hypothermia may be especially effective in delaying a cascade of harmful changes that can develop in the brain during a stroke.
The interruption of blood flow triggers energy failure in brain cells, which begin losing their ability to maintain proper concentrations of essential chemicals. The most severely affected areas of the brain can die within minutes. Surrounding areas can die as well if blood flow is not restored.
Lowering temperature appears to reduce the metabolic demands on brain cells and slow the degenerative process, Dr. Wechsler said.
Animal studies indicate that when a brain artery is blocked, hypothermia can lessen the amount of brain tissue that becomes damaged. Several early studies in humans suggest a similar benefit, said Dr. Maxim Hammer, an assistant professor of neurology at the Stroke Institute.
Those results led to the national study that is underway at UPMC and other centers. Known as the intravascular cooling in the treatment of stroke, or ICTuS, trial, it is the first large, randomized clinical trial involving hypothermia and stroke patients.
The trial, headed by a team at the University of California at San Diego, is designed to test the combined effectiveness of hypothermia and the clot-busting drug tPA. Patients generally must have had a stroke from three to six hours earlier and not have a history of heart problems or bleeding in the brain, Dr. Hammer said.
Patients in the study are randomly assigned to one of four groups. Some receive both tPA and hypothermia treatment, while others receive tPA without having their body temperature lowered. Still others receive only hypothermia treatment, while another group has neither that treatment nor tPA.
Patients receiving both hypothermia and tPA should have somewhat better outcomes than those in the other groups, Dr. Hammer said. The study will involve about 130 patients over two years.
Patients are cooled through a catheter placed through a femoral vein and into the inferior vena cava, a vein that collects blood returning to the heart. The catheter, which contains freezing cold liquid, can cool the body within an hour to a little over 91 degrees Fahrenheit -- about 7 degrees cooler than the normal 98.6 degree body temperature.
Patients are kept cool for 24 hours, then rewarmed over 12 hours to normal temperature. But the optimum cooling temperature, length of cooling and rewarming times are still unknown, Dr. Hammer said.
Even lowering body temperature by a few degrees can cause shivering, but use of blankets or drugs can alleviate that symptom and make patients feel comfortable, he said.
The other study at UPMC, known as the Frosty trial, will cool only the head, so stroke patients can be included who do not qualify for the ICTuS trial because of cardiac problems or other complications.
Patients don a hood similar to a ski mask and are connected to hoses that lead to what is essentially an air conditioning unit, Dr. Hammer said. Wearing the hood “feels like sticking your head out of the window of your car when you’re driving around in February,” he said.
At first, the study will determine whether the procedure will cool the brain effectively. Later on, it will focus on whether the release of certain brain chemicals after a stroke is lessened in patients treated with hypothermia. Eventually, the trial will measure whether the treatment has a clinical benefit.
“If we can show cooling the brain has the same clinical effect, in terms of protection, as cooling the body, then everyone is going to switch to cooling the head because it’s much less invasive,” Dr. Hammer said.
He noted that other head-cooling units being tested are small enough to allow ambulance crews to begin the therapy before patients are taken to the hospital.