Painkiller may prevent adhesions after surgery
BOSTON -- A controversial painkiller might hold the key to preventing adhesions, a painful, costly, and sometimes deadly problem that has been the bane of surgeons for as long as there has been surgery.
A new study from Children's Hospital shows that the prescription drug Celebrex -- which recently has come under intense scrutiny because of suspected links to heart disease -- blocked adhesions in mice given the painkiller just before and for several days after surgery.
Adhesions commonly occur during the healing process when tissues such as the intestines stick to other surfaces, such as the abdominal wall, and begin growing together. They must be separated by further surgery, sometimes over and over again. There is no pharmacological fix for the disorder, which kills about 2,000 Americans a year, according to David Wiseman, founder of the International Adhesions Society.
The discovery, reported recently in the Annals of Surgery, came when pediatric surgeons Mark Puder, Arin Greene, and their colleagues at Children's Hospital noticed that mice given doses of Celebrex seemed to avoid adhesions after surgery. The intent of their research was to see if Celebrex influences how the liver regrows after surgical damage. The lack of adhesions was a big surprise.
"It was just one of those lucky things," said Puder, who plans to study whether Celebrex will work as well in people.
Dr. Patricia L. Roberts, chairwoman of the department of colon and rectal surgery at the Lahey Clinic Medical Center in Burlington, said she would be grateful for any medication that limited adhesions. But even if Celebrex works as well in people as it did in mice, it's not clear whether the drug would also reduce the related infertility problems and bowel obstructions that make adhesions so troubling and dangerous.
"Through the ages there have been multiple things people have looked at," said Roberts, who has extensively studied Seprafilm, a product that decreases adhesions, but is costly and has significant side effects. "Unfortunately, we don't have a quick answer."
Puder and Greene discovered that Celebrex, a so-called COX-2 inhibitor, completely eliminated adhesions in more than half of their experimental animals. The remaining mice also had fewer adhesions, while mice given placebos experienced the usual number of adhesions. The tests were repeated over and over in large numbers of mice.
"The results were dramatic," said Puder, whose research was funded by Children's Hospital.
There is, of course, a problem with Celebrex. Although it is still on the market, and is very widely prescribed, recent studies suggested that Celebrex damages the heart when used at high doses for long periods. The maker of another popular COX-2 inhibitor, Vioxx, already pulled it from the market because of similar concerns.
But "if Celebrex works in humans" the way it has in mice, Puder said, "you could give it to patients on the day of the abdominal surgery, and the 10 days after surgery." That would avoid the long-term, high dose uses of the drug, and perhaps reduce any danger to the heart, while protecting against adhesions.
In addition to Celebrex, the researchers also tested drugs such as Vioxx, ordinary aspirin, and a placebo. In the first of many tests, six out of 11 Celebrex-treated mice were completely free of adhesions. After 25 days of further testing, there was only one Celebrex mouse with adhesions, five in the Vioxx group, eight in the aspirin group, and 11 in the mice that got a placebo.
Given such results, Puder hopes to soon set up a clinical trial using Celebrex in adult surgical patients in several medical centers.
At present, surgeons sometimes try to avoid adhesions by implanting some sort of barrier, such as a gel, to keep tissue surfaces apart so they don't bind together and grow. These treatments all have problems of their own, such as immune reactions, infections, and retarding the rate of healing.
