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Even when all goes well, surgery patients may carry an increased risk of cardiovascular disease and possibly cancer for weeks or even years, say physician-scientists studying the unintended effects of surgery.

"The first insight we take away from this is that when bad things happen down the road, months, maybe even years later, that we cannot, as we have in the past, just attribute it to the natural course of illness," says Dr. Steffen E. Meiler, anesthesiologist and vice chair for research in the Medical College of Georgia Department of Anesthesiology and Perioperative Medicine. "We have to start taking responsibility for some of it, certainly not all of it."

That requires more basic science and human studies to understand the mechanisms underlying ill effects and a concerted effort by all members of the health care team to avoid them, says Dr. Meiler. He talked on this topic at the 53rd Annual Meeting of the Japanese Society of Anesthesiologists June 1-3 and is guest editor of the June issue of Anesthesiology Clinics of North America devoted to the matter.

A few studies have been done across the broad spectrum of the topic, including whether short-term surgical complications, such as infections or pulmonary problems, predict an increase in long-term complications and whether mutations in genes involved in inflammation result in higher stroke rates after cardiopulmonary bypass surgery.

These studies are providing mounting evidence that there are short- and long-term increased risks, particularly for surgery patients with serious underlying disease, says Dr. Meiler.

Changes in the immune response that can result from surgery are a major player.

"The inflammatory response to surgery, for the most part, is a very good thing. We need it to protect ourselves against infection," he explains. "We need it to heal the surgical wound properly. But if you are in a high-risk group, if you are not generally healthy except for your specific surgical indication, then that protective inflammatory process may also stir up trouble."

Inflammation is a player in most major diseases, from cardiovascular disease to cancer. A heart patient, for example, already has chronic inflammation and the coronary bypass surgery he needs, ironically, may accelerate it. "It's like stepping on the gas pedal," says Dr. Meiler.

Studies have shown that taking drugs such as statins, used to treat high cholesterol, or beta blockers and clonidine, used for hypertension, can protect against some of this risk. "Giving beta blockers, statins, making sure your blood sugar doesn't rise during surgery, minimizing blood transfusions, these are all things that we have not paid enough attention to," says Dr. Meiler.

Even body temperature is a factor. "We now have solid evidence that if patients drop their core temperatures during surgery below 36 degrees Celsius (96.8 degrees Fahrenheit), the complication rate from postoperative infections for certain surgical procedures may be as high as threefold."

Infections and even cancer are concerns postsurgically as lower body temperature, blood transfusions and apparently volatile anesthetics actually suppress the immune response.

"Patients come for their cancer operation and now they receive volatile anesthetics, they receive blood transfusions, they become cold and they become immunosuppressed," Dr. Meiler says. "There is concern that these events may create an immunological milieu in which it's easier for tumor cells that have become dislodged and are now in the bloodstream to escape surveillance, engraft at a different site and, maybe months later, blossom as a new tumor growth."

Still, this is one of many issues related to surgical effects that need more exploration. "I can't tell you that volatile anesthetics definitely have a contributory effect, only that animal models would suggest they do," he says.

His research is showing the impact of even a small infection in the face of chronic inflammation. Using an animal model of sickle cell disease, a disease marked by systemic inflammation, he's studying the host's defense to microbial products such as lipopolysaccharide.

He's found a resulting transformation of macrophages, which typically work like garbage collectors for the immune system, into large, pro-inflammatory cytokine-spewing cells. "Macrophages residing in areas of sickle cell-induced tissue injury become large, express different receptors on their surface and, when exposed to a superimposed infectious stimulus like lipopolysaccharide, respond with an overwhelming release of pro-inflammatory cytokines that are harmful to the host."

The mice die rapidly and these re-programmed macrophages may help explain why children with sickle cell disease are more prone to overwhelming and potentially deadly infections following surgery.

"We need more investigations, more data on humans," says Dr. Meiler, noting that while short-term outcomes of inflammation in response to surgery are pretty well established, proof of longer-term outcomes will take more work.

In the meantime, patients can benefit from early, ongoing collaboration by all members of the health care team to ensure risk reduction through steps such as minimizing surgical incisions, avoiding transfusions whenever possible and, when indicated, pharmacological treatment before surgery to help reduce cardiovascular complications.

"The challenge will be to incorporate these measures consistently across the health care process so that all eligible patients benefit from these insights," Dr. Meiler says.

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