The heart-lung bypass machine that stills the heart while surgeons bypass an adult’s clogged arteries or repair a baby’s malformed heart can also trigger a potentially deadly inflammatory response.
That unfortunate fact has Medical College of Georgia surgeons participating in an international study of a drug that may block the most deadly of these responses in adults who have coronary bypass surgery.
It also has them trying to better understand the process in children whose complex heart defects often mean they spend hours or even days on heart-lung bypass.
“We have to remember that blood is a very complex fluid with many components,” says Dr. Kevin P. Landolfo, chief of the MCG Section of Cardiothoracic Surgery. Like the heart, three to six liters of blood run through the heart-lung bypass machine per minute, which means total blood volume goes through the machine many times in the hours it takes to perform bypass surgery. “It’s a massive physiologic insult like a major trauma, so our body comes alive with an inflammatory response to circulating through this unit,” Dr. Landolfo says.
The response helps prevent infection, but it can cause blood clots that lead to serious complications – including lung or kidney injury, a heart attack or stroke – in 7 percent to 10 percent of patients.
MCG is part of a study to determine whether giving the complement blocker pexelizumab intravenously before, during and after bypass surgery blocks the worst aspect of the inflammatory response. “The immune system is still revved up but we block the most dangerous component of it,” says Dr. Landolfo.
Surgeons have long recognized the ill effects of bypass. They have changed the way they do surgery, even doing cases without bypass when possible, and the machine itself has been improved, says Dr. Landolfo. “We are pretty good at having patients survive, but it’s all the morbidity related to heart surgery. Much of what remains is related to the heart-lung machine.”
The study of 5,000 heart bypass patients in about 40 states and three foreign countries is looking at this drug in at-risk patients, including those who have had a previous stroke or heart attack or have diabetes. Women also at risk for serious complications, possibly because their smaller size causes their blood to pass through the machine even more times, Dr. Landolfo says, noting treatment protocols already take this risk into consideration.
He’s optimistic all bypass patients may one day benefit from some form of short-term suppression of the protective immune response, but for purposes of the study – sponsored by Alexion Pharmaceuticals Inc. and P&G Pharmaceuticals – it’s easier to show results in high-risk patients.
His colleague, Pediatric Cardiothoracic Surgeon James D. St. Louis, is trying to understand this potentially lethal inflammatory response in children. “Their response can be profoundly different and profoundly more intense than adults. Children die from it,” Dr. St. Louis says. “We have at least one or two children a year where the operation goes fine then the children will have this spiraling set of circumstances where there is nothing you can do. It’s an immune response,” he says of systemic inflammatory response syndrome following bypass.
“Remember, the vast majority of children do fine,” says Dr. St. Louis. But he thinks some children, particularly those with low oxygen levels before surgery, have trouble activating a natural mechanism that could correct some cell damage caused by bypass.