Originally created 11/06/02

Drugs tested to halt mental decline after heart bypass surgery



WASHINGTON -- Call it brain fog, that loss of memory and thinking ability that strikes tens of thousands of patients after open-heart surgery, and sometimes other big operations, every year.

Now doctors are studying if giving patients certain drugs just before a heart bypass could prevent this mental decline by essentially protecting the patients' brain cells from the rigors of surgery.

The clinical trials mark a turning point: For decades, doctors didn't know what to make of patient complaints that in getting their hearts fixed, something hurt their brains.

Today, few doubt it's a real problem that affects not just heart patients but those undergoing other major surgeries, too, such as hip or knee replacements. Often, patients recover. But one study found 42 percent of heart-bypass patients suffer significant drops in mental sharpness that can last not just months but years. Other research suggests 10 percent of hip-replacement patients suffer similar mental decline.

In some ways this "postoperative cognitive dysfunction" is a byproduct of the modern operating room. As surgery - particularly the half-million heart bypasses performed every year - has become increasingly successful, aftershocks such as a muddled brain draw more concern.

"It's a big quality of life issue," says Dr. James Cottrell, president of the American Society of Anesthesiologists.

No one knows yet what's to blame. It may be that only certain people are at high risk, such as those whose brain blood vessels are starting to clog and something about surgery speeds up the disease.

For now, suspects range from the heart-lung machine that circulates bypass patients' blood - it can dislodge tiny bits of fat, blood clots or air bubbles that flow to the brain - to the inflammation and post-surgery fever that are a risk after any major operation.

Surgery's stresses spark inflammation and other reactions that "in some ways is the body's way of healing itself," explains Dr. Mark Newman, anesthesiology chairman at Duke University and a leading expert on post-surgery mental decline. "But the question is if it goes beyond a certain level, do you end up with problems?"

That's where much of the prevention research centers: If surgery even temporarily blocks oxygen in part of the brain or sparks severe inflammation, the body reacts with a chemical cascade that injures or kills brain cells.

Newman and other scientists are studying if injecting patients with one of three different medications before a bypass could block that chain reaction and spare brain cells:

-Two small studies suggest lidocaine, normally used for irregular heartbeat, can prevent bypass patients' brain fog. Duke now is testing 250 bypass patients, half given lidocaine and half not, to see who has better brain function a year after surgery. Newman says lidocaine might work by blocking a pathway that lets toxic doses of calcium flood into oxygen-deprived brain cells.

-Certain levels of magnesium seem to block that toxicity, too, as well as lessen cell damage from inflammation. So, using federal money, Duke is enrolling 400 bypass patients into a study to see if magnesium might block brain fog.

-Initial testing of an experimental drug called pexelizumab, thought to block an inflammation-causing immune system protein, showed bypass patients who received the drug had slightly less mental decline. Duke and several other hospitals are participating in a 3,000-patient study of pexelizumab, sponsored by the drug makers Alexion Pharmaceuticals and Procter & Gamble.

Some companies also are testing if filters put onto heart-lung machines can help by keeping debris from flowing to the brain.

Until those studies are done, Newman advises patients worried about coming surgery to ask their anesthesiologists about one step believed to lower brain risk - rewarming their cooled-down bodies more slowly than usual after the operation is done.

The key is intense temperature monitoring that tells when the brain, which warms faster than other organs, reaches 98.6 degrees, Newman explains. At that point, doctors should stop warming and let other organs gradually reach normal temperature on their own.