Stroke Risk Increased In Patients With High Oxygen Use In Brain

The findings, reported in the Sept. 23/30, 1998 issue of the Journal of the American Medical Association, could have implications for reviving a discarded surgical procedure that increases blood flow to the brain.

Robert L. Grubb Jr., M.D., William J. Powers, M.D., and colleagues report that patients with complete blockage of the carotid artery and a condition called hemodynamic failure, face a stroke risk six to seven times greater than those with just a blocked carotid artery. Hemodynamic failure occurs when the brain is not receiving the normal amount of oxygenated blood.

Using a specialized imaging test called positron emission tomography (PET), the investigators measured both blood flow and oxygen metabolism in the brains of the study subjects. They studied 81 patients over four years. All had complete blockage of one of their carotid arteries and had suffered either a stroke or a transient ischemic attack, which has similar symptoms to stroke but resolves itself in a few hours. The PET scans allowed the researchers to determine whether patients were in hemodynamic failure by revealing the amount of blood that reached the brain and the percentage of oxygen that the brain used.

"Under normal circumstances, the amount of blood that gets to the brain and the amount of oxygen the brain extracts from the blood are pretty well matched," said Powers, a professor of neurology and associate professor of radiology at the School of Medicine. "But using PET, we confirmed that in some patients with blocked carotid arteries, there was an imbalance between blood supply and the amount of oxygen used by the part of the brain supplied by the blocked vessel."

Normally, the brain uses about 30 percent of the oxygen that's carried to it in the blood, but in patients with hemodynamic failure, the rate of oxygen extraction may be 60 or even 70 percent. Of the 81 patients studied, 39 had PET scans that showed increased oxygen extraction, and 42 had normal

scans. In the group with increased oxygen extraction, 12 patients (31 percent) suffered strokes. Only three of the patients (7 percent) with normal oxygen extraction rates had strokes. And 11 of the 12 strokes suffered by patients with increased oxygen extraction occurred on the same side of the brain as the clot, near the area of the brain that was using a higher-than-normal percentage of oxygen.

"We were very surprised by the number of strokes in the group with hemodynamic failure," explained Grubb, the Herbert Lourie Professor of Neurological Surgery and a professor of radiology. "We did not anticipate the discrepancy, but we think this study clearly indicates that oxygen metabolism in the brain is important to stroke risk and that available medical treatments do little to alter risk."

But the investigators think surgical therapy may be helpful. They want to revisit a surgical technique called extracranial-intracranial (EC-IC) bypass surgery. In the operation, a neurosurgeon takes an artery outside of the brain and connects it to a vessel inside the brain.

"The idea is very similar to what cardiac surgeons do in heart bypass surgery. Theoretically, if you can improve blood flow to the brain, you can reduce the risk of stroke," Grubb said.

In 1985, a large, multi-center study showed that the EC-IC bypass was no better than medical therapy in reducing risk of stroke, but that was before the risk of hemodynamic failure had been clarified. Now, Powers and Grubb plan to test the surgery only in patients with known hemodynamic failure.

"Our PET finding shows higher-than-normal oxygen extraction predicts stroke. We know from past studies that PET scans return to normal after bypass surgery. Now, we want to test whether the surgery actually prevents stroke in these patients," Powers said.

Grubb and Powers do not know exactly how the increased rates of oxygen extraction increase stroke risk, but they believe it may be that those using a higher percentage of oxygen have a lower margin for error when a problem occurs.

"Normally, a patient has kind of a safety buffer. If you're only using 30 percent of the oxygen in the blood, and suddenly blood flow drops, the brain can extract a bit more oxygen. But if the brain is already using 60 or 70 percent of the oxygen, and the blood flow drops, there is less of a buffer, and the patient might be at higher risk for stroke," Powers explained.

The current estimate is that 10 to 15 percent of all strokes are related to complete blockage of the carotid arteries. In patients with partial blockage of the carotid artery, surgery to remove the obstruction can eliminate the risk, but in those with total blockage, surgery to remove it will not restore blood flow.

Even with blockage many patients do fine, making it difficult to determine how aggressively to treat these patients. But Powers and Grubb believe the levels of risk in patients with hemodynamic failure warrant a reconsideration of the EC-IC bypass technique.

"Because of the negative findings in the past, we expect we will have to do a fairly large, randomized trial and follow the patients for a few years, but we believe that if the complication rate is not too high, this surgery may become a viable treatment option," Grubb said.