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The use of clot-busting drugs after stroke has greatly improved outcomes for many patients. Paradoxically, however, these pharmaceuticals sometimes can lead to additional complications. The restoration of blood flow through thrombolytics can limit tissue damage if delivered within three hours of symptom onset, but that very restoration can cause more tissue damage known as reperfusion injury.
In an attempt to limit reperfusion injury while allowing patients to reap the benefits of thrombolytics, a research team at The Cleveland Clinic Foundation’s Neurological Intensive Care Pro-gram conducted a pilot study that combined strategies to restore blood flow with hypothermia. Their new method, which they have dubbed COOL AID (COOLing for Acute Ischemic Brain Damage), was described in an article in the August 2001 issue of Stroke, published by the American Heart Association.
"The irony [of using clot-busting drugs] is that while restoration of blood flow is a prerequisite for recovery, sometimes this restoration, if it occurs into already damaged tissue, can paradoxically make things worse and thereby antagonize the benefit that the patient may have otherwise enjoyed," notes Michael E. De Georgia, MD, co-principal investigator and head of the Neurological Intensive Care Pro-gram at the Cleveland Clinic Foundation.
Patients were selected for the study based on six criteria:
To induce moderate hypothermia, the patients were placed on a cooling blanket. Ice water and whole body alcohol rubs were performed concurrently. After the core temperature reached 34 degrees centigrade, they were sandwiched between two cooling blankets, and blanket water temperature was maintained at 32 degrees. Hypothermia was maintained for a range of 11 hours to 42 hours (which is a mean of almost 23 hours).
There were 10 patients in the study group, three of whom died. However, explains De Georgia, "these are patients who are really sick, with lots of medical problems." One patient had an aortic dissection, which De Georgia notes had nothing to do with the hypothermia. "Another had a bad disease, the mortality of which was 90%." A third died after discharge.
Reiterating that the patients selected had suffered severe strokes, De Georgia adds that "most of these patients don’t get significantly better, even with thrombolysis. The best you end up with is an 8 (on the NIHSS scale), a moderate to severe outcome. We wanted to treat those patients for whom we had already gone all out, done the most that we could do, and based on the literature would still have a bad outcome, thus warranting an aggressive approach."
In light of the nature of those cases, the researchers concluded, "The results of the present study suggest that moderate hypothermia induced by surface cooling is technically feasible and safe for patients with acute ischemic strokes who are undergoing thrombolytic therapy. Limitations of this study, including small sample size, open design, and nonrandomized concurrent controls, preclude any conclusions about efficacy. However, all outcome trends favor hypothermia."1
De Georgia notes that standard hypothermia protocol has its limitations. To prevent shivering, for example, all patients were endotracheally intubated, sedated, and pharmacologically paralyzed. "Intubation increases the risk of pneumonia and secretions," he explains. However, he adds, "We are now into our next phase of research using different technology — a new endovascular approach." This method, developed by Redwood City, CA-based Radiant Medical Inc., involves the use of a silk catheter that goes into the femoral vein and is in turn fed into the inferior vena cava. In essence, the patient is cooled "from the inside out."
"It’s a closed system, using cold saline, at 4 degrees Celsius, that cools the blood that passes around it," De Georgia explains. "The really cool’ thing is that all our temperature sensors are on outside; the way you know you are cold is by skin sensors, mainly on the chest. We can put a warming blanket on the outside, and medicine into the vein to lower the shivering threshold," he adds. "We can do this down to the same core temperature, but the patient will be alert, awake, and comfortable — and the procedure is far less invasive. It’s kind of like tricking the hypothalamus into thinking you are warm."
It’s also a lot quicker. With the cases described in the Stroke paper, it took 3.5 hours to get to the target temperature; with this new method, it takes an average of 38 minutes. "Hypothermia is probably the gold standard of neural protection, but its usage had been limited by surface cooling," notes De Georgia. "This should make a huge difference in patients with stroke." The second phase, which will be used to determine the safety of the catheter, will involve 40 patients. "Then we’ll do a larger efficacy study, of around 250 to 300 patients, with multiple centers around the world," he says.
Participating institutions include Massachusetts General and Brigham & Women’s Hospital, both in Boston; The Mayo Clinic in Rochester, MN; the University of Pittsburgh; The University of Giessen in Germany; and Royal Melbourne Hospital In Australia, he explains. "Ultimately, we’ll expand to 35 centers around the world," De Georgia predicts.
1. Krieger DW, De Georgia MA, Abou-Chebl A, et al. Cooling for acute ischemic brain damage (COOL AID) — An open pilot study of induced hypothermia in acute ischemic stroke. Stroke 2001; 32:1,847-1,854.
For more information, contact:
• Michael E. De Georgia, MD, Neurological Intensive Care Program, The Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195. Telephone: (216) 445-1626. E-mail: firstname.lastname@example.org.
• Derk W. Krieger, MD, Section of Stroke and Neurological Care, Department of Neurology, Desk S-91, The Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195. E-mail: email@example.com.
• Stroke is available at www.strokeaha.org.