Association of aprotinin with reduced glucose levels during CABG surgery

An anesthesiology research team at Columbia University Medical Center have completed the first human study to show that aprotinin, a protease inhibitor, was associated with lower blood glucose levels during coronary artery bypass graft (CABG) surgery.

The research presented today at the American Society of Anesthesiologists 2005 Annual Meeting in Atlanta, Ga., showed that CABG patients receiving aprotinin had 24 percent lower blood glucose levels and a decrease in perioperative insulin resistance compared to patients not receiving aprotinin.

The association of aprotinin with reduced glucose levels during CABG surgery is an important finding for diabetic patients. Over a half million patients undergo cardiac surgery in the United States every year. Among these patients, one third of them have diabetes and many others are likely to be obese or suffer from impaired glucose tolerance, which are often precursors to diabetes. For diabetic patients undergoing CABG surgery, abnormally high levels of blood glucose can lead to serious complications including cardiac disease, renal dysfunction, and retina damage as well as an increased risk of infections of up to 86 percent.

For all patients undergoing CABG surgery - both with and without diabetes - elevated glucose levels during the surgery have also been associated with longer hospital stays and increased hospitalization costs.

"We are very enthusiastic about these results as our ultimate research goal is to study if aprotinin leads to better outcomes in diabetic patients undergoing CABG surgery," said Robert J. Frumento, Ph.D., lead investigator of the study and researcher at the department of anesthesiology at Columbia University Medical Center. "The next step will be to conduct a larger, randomized trial on non-diabetic patients before expanding studies to the more vulnerable diabetic patient population. We believe that aprotinin may hold the potential to be a standard of care for patients with diabetes undergoing this surgery."

Dr. Frumento and his team observed 96 non-diabetic CABG patients, divided into three groups: 28 received a full dose of aprotinin, 33 received a half dose, and 35 received no aprotinin. Blood was taken and analyzed at three intervals - after the patients received anesthesia, 30 minutes into CABG surgery, and after the surgery. Previous in vivo trials conducted by other researchers have repeatedly demonstrated the drug's effectiveness in reducing hyperglycemia in animals but this was the first study of its kind in humans.

The study led by Dr. Robert J. Frumento, "Effect of Aprotinin on Glucose Levels and Insulin Resistance in Patients Undergoing Cardiac Surgery", was funded by the department of anesthesiology of Columbia University College of Physicians and Surgeons. Dr. Frumento's research team includes Columbia University Medical Center investigators Sanford M. Littwin, M.D., assistant clinical professor of anesthesiology, and Jack S. Shanewise, M.D., professor of clinical anesthesiology and director of cardiothoracic anesthesia division. Elliott Bennett-Guerrero, M.D., former director of cardiac anesthesiology at Columbia University and who has since joined the Duke Clinical Research Institute, also contributed to the research.