June 13, 2002 DURHAM, N.C. -- When given prior to or during coronary artery bypass surgery, a class of heart drugs known as beta-blockers provides significant protection to the brain and its functions, according to a new study by Duke University Medical Center researchers.
"Data is rapidly accumulating that every patient undergoing bypass surgery -- with a few exceptions -- should be given beta-blockers for bypass surgery," said Mark Newman, M.D., Duke chairman of anesthesiology and lead investigator of Duke's Perioperative Organ Protection Consortium. "Since only about 60 percent of bypass patients nationwide are given beta-blockers for surgery, there is certainly much room for improvement in this area."
The results of the Duke analysis were published today (June 13, 2002) in the Journal of Cardiothoracic and Vascular Anesthesia. The research was supported by the National Institutes of Health and the American Heart Association.
In their study, the researchers analyzed the medical records of 2,575 patients who underwent bypass surgery at Duke over a three-year period. They found that only 3.9 percent of the patients receiving beta-blockers suffered adverse neurological events, compared to 8.2 percent of those not on the drugs. The adverse neurological effects of surgery measured were stroke, coma, transient ischemic attacks (TIA), also known as "mini-strokes," and encephalopathy.
For the most severe of the events, stroke and coma, the beneficial effect of beta-blockers was even more striking -- a 1.9 percent rate of adverse effects for those taking the drugs and 4.3 percent for those who did not.
These results follow an earlier study by a different Duke team (May 2002, Journal of the American Medical Association) that showed that beta-blockers given prior to or during bypass surgery reduced the 30-day mortality rate of the procedure from 3.4 percent to 2.8 percent. More than 570,000 of the heart procedures are performed in the U.S. each year.
By blocking the stimulatory effects of the hormones epinephrine and norepinephrine -- the so-called "fight-or-flight" hormones -- beta-blockers act by reducing heart rate and blood pressure. Beta-blockers have been used for more than 30 years for the treatment of such heart ailments as high blood pressure, chest pain, and heartbeat irregularities.
Previous randomized clinical trials have proven the effectiveness of beta-blockers in improving outcomes for heart patients in general, and for patients undergoing cardiac and non-cardiac surgery. The current study is the first to examine the effects of beta-blockers on the brain when given before or during surgery.
"When we started the analysis, we expected to see some modest benefit, but not to this magnitude," Newman said. "There are so many risk factors, such as severity of disease, age and diabetes, that could possibly come into play. But when we controlled for these factors in our analysis, we still found this clinically significant effect."
While the current study was not designed to uncover the mechanism of the neurologic protection, the researchers have several theories about the origins of the benefits. The first is that beta-blockers control atrial fibrillation. It is well known that the drugs can control the occurrence of atrial fibrillation, rapid randomized contractions of one of the heart's pumping chambers. Atrial fibrillation has been implicated as a major risk factor for stroke and sudden heart attack.
"Atrial fibrillation reduces both acute and chronic cardiac output, which makes patients more prone to creating tiny clots, or emboli, which can travel to the brain causing stroke or TIAs," Newman said. "There was a reduction in atrial fibrillation in our group of patients, and while we're pretty confident that this is a factor contributing to the protective effect, it doesn't offer a full explanation."
The second theory is that beta-blockers reduce stress in the patients. The act of surgery itself stresses the body, causing the release massive amounts of epinephrine and norepinephrine, which the beta-blockers "soak up" or neutralize. This neutralization helps preserve a more normalized blood flow to the brain. Additionally, Newman said, some evidence is emerging that beta-blockers may help stabilize blood platelet function after surgery, but this remains speculative.
"The bottom line is that bypass surgery is a very safe procedure, and now we are refining our processes and procedures to improve a patient's quality of life in order to maximize the health benefits," Newman said.
Newman believes that all bypass patients, except for those whose heart pumps at 20 percent of its ability or less, should receive beta-blockers. Less than 20 years ago, surgeons routinely took heart patients off beta-blockers prior to surgery. It was believed that since beta-blockers lowered heart rate and blood pressure, patients would be at greater risk during surgery.
"Now, obviously, we are learning that the opposite is indeed true," Newman said.
While many heart patients might already be taking beta-blockers in pill form prior to surgery, Newman advocates giving all appropriate bypass patients the drug intravenously during surgery, so that the optimal levels of the drug can be maintained during the procedure to achieve the maximum protective effect.
Other members of the Duke team included David Amory, M.D., Alina Grigore, M.D., John Amory, M.D., Mark Gerhardt, M.D., William White, Peter Smith, M.D., Debra Schwinn, M.D., and J.G. Reves, M.D.
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