Rewarmed Blood Linked to Complications After Cold Bypass

Rewarming of blood after hypothermic cardiopulmonary bypass appears to impair autoregulation of blood flow in the brain, increasing the patient’s risk for stroke in the process, researchers have found.

Investigators at Johns Hopkins University in Baltimore found that patients with impaired autoregulation of cerebral blood during rewarming were four times as likely to experience a stroke or transient ischemic attack as patients without the problem (95% confidence interval, 1.8-9.5; P<0.001).

“Hypoperfusion is an important cause of brain injury during cardiac surgery with cardiopulmonary bypass,” said Charles Hogue, MD, associate professor of anesthesiology and critical care medicine at Johns Hopkins, who led the study. “In looking at previous research, we’ve observed that some patients seem to get really dysregulated during rewarming and have a high incidence of stroke. It suggests that the rewarming period is one of vulnerability to the brain.”

Clinicians empirically manage cardiac bypass patients by choosing a target blood pressure they believe to be appropriate. “But they have no real way of monitoring,” Dr. Hogue said. “So our idea is that if we can monitor cerebral blood flow autoregulation in real time, we might be able to individualize blood pressure to be above a patient’s lower autoregulatory threshold.”

Dr. Hogue’s group presented its findings at the 2010 annual meeting of the Society of Cardiovascular Anesthesiologists, in New Orleans (abstract SCA31).

The observational study involved 127 adults undergoing cardiopulmonary bypass. All had transcranial Doppler monitoring of blood flow velocity in the middle cerebral artery. Eleven patients undergoing so-called “warm” bypass—where arterial inflow temperature exceeded 35 C—served as a control group.

The mean velocity index (Mx) was calculated as a moving, linear correlation coefficient between slow waves of blood velocity in the middle cerebral artery and mean arterial pressure. Patients with intact autoregulation of cerebral blood pressure have Mx values that approach zero, Dr. Hogue said. Those with impaired autoregulation have Mx values approaching 1.

The researchers found that Mx was significantly greater during cooling (left, 0.29±0.18; right, 0.28±0.18) than at baseline (left, 0.17±0.21; right, 0.17±0.20; P<0.0001). It increased during rewarming (left, 0.40±0.19; right, 0.39±0.19), when it was greater than at either baseline (P<0.001) or the cooling (P<0.0001), indicating impaired cerebral blood flow autoregulation. The Mx after bypass was greater than at baseline, but significantly less than during rewarming (P<0.0005).

Overall, 68 patients had Mx values that exceeded 0.4 during rewarming; nine of these patients suffered strokes. By comparison, nine of 11 warm-bypass controls had an average Mx below 0.4 during the entire bypass period.

Several possible explanations exist for the high rate of stroke observed in patients with deregulation, Dr. Hogue told Anesthesiology News.

“I think the brain receives a lot of the blood flow from the heart and lung machine because the returning cannula is right at the base of the cerebral vessels,” he said. “And it may be that when you rewarm, the cerebral metabolic rate increases quickly and you get vasodilatation, which may lead to cerebral edema. It also could be that vasodilatation leads to more embolism, because the higher the blood flow the more emboli, and at a time when the aortic cross clamp is going to be coming off.

Rewarming also may affect endothelial function, Dr. Hogue added. “Rewarming may lead to an oxidative stress or some other abnormality that makes the endothelium nonresponsive to the usual stimuli.”

Hilary P. Grocott, MD, professor of anesthesia and surgery at the University of Manitoba in Winnipeg, Alberta, Canada, and adjunct professor of anesthesiology at Duke University in Durham, N.C., said the potential for adverse cerebral effects from rewarming has fallen with the current trend in cardiac surgery toward warmer bypass temperatures with less need for subsequent rewarming. “However, there will always be a need for rewarming in the increasing number of patients presenting for complex aortic surgery requiring deep hypothermic circulatory arrest,” he said.

Dr. Hogue’s group offers “a plausible biologic mechanism for the dangers of rewarming,” Dr. Grocott added. “Importantly, identifying this mechanism also highlights a relatively simple intervention [not rewarming] that can now be investigated more rigorously.”