NK-1 receptor antagonists very effective at reducing vomiting after surgery

Oct 24 2005

The results of a new Phase III clinical trial have demonstrated that a new class of drugs, called "NK-1 receptor antagonists," is more effective at reducing vomiting after surgery than the most commonly used drug, according to the Duke University Medical Center researchers who led the trial.

The finding is important, the researchers said, because despite decades of advances in surgical technique and improved anesthetic agents, one out of three patients will still experience nausea and vomiting after surgery. These events not only influence patient satisfaction with their procedure, but can also prolong recovery, lengthen hospital stays and negatively impact the surgery itself, the researchers said.

"There are more than thirty-five million surgical procedures performed each year in the U.S., so postoperative nausea and vomiting is an extremely important health care issue," said Tong Joo (TJ) Gan, M.D., Duke anesthesiologist who led the trial. He presented the results of the trial Oct. 24, 2005, at the annual scientific sessions of the American Society of Anesthesiologists in Atlanta.

"Vomiting is also an issue that most physicians do not take seriously enough -- they see it as a short-term nuisance that will soon pass," Gan said. "However, studies have shown that nausea and vomiting after surgery is the major factor influencing whether or not patients are satisfied with their surgery. When I talk to patients before their surgeries, most are more afraid of the vomiting afterwards than they are of the pain."

"Most of the anti-emetic drugs we have today just aren't that effective in controlling this side effect," Gan continued. "So, an effective drug to treat postoperative vomiting could be a great advance for our patients."

Compared to existing drugs, the NK-1 receptor antagonist blocks at a different site the cascade of biological signals leading to nausea and vomiting. Specifically, 95 percent of patients taking the NK-1 receptor antagonist before surgery did not experience vomiting 24 hours after surgery, compared to 74 percent for the most commonly used drug, ondansetron. The results were similar 48 hours after surgery, 93 percent vs. 67 percent.

"This new drug offers significant advantages in reducing the incidence of vomiting in patients after surgery," said Gan. "This is the first time that an anti-sickness drug provides a sustained protection against postoperative vomiting in more than 90 percent of patients."

While the trial found a significant improvement in the incidence of vomiting, there was little difference between the two drugs in reducing nausea. Also, Gan said, the NK-1 receptor antagonist was well-tolerated by the patients enrolled in the trial.

For the trial, researchers from 30 centers enrolled 805 patients who were receiving general anesthesia for abdominal surgery requiring overnight hospitalization. Patients were randomized to receive either a high or a low dose of the NK-1 receptor antagonist. The NK-1 receptor antagonist was given orally one hour prior to surgery, while ondansetron was administered at the beginning of surgery..

While both groups who received the NK-1 receptor antagonist had significantly higher reductions in vomiting when compared to ondansetron, patients on the higher dose experienced the highest reductions.

The currently used drugs, like ondansetron, block signals in the gut and chemoreceptor trigger zone (CTZ), which is located in the brainstem. Typically, a nausea impulse begins in the CTZ, travels to the vomiting center within the brain, and then on to the stomach, Gan explained.

"However, not only are there NK-1 receptors in the CTZ, they are also present in abundance in the brain's vomiting center," Gan continued. "So while the NK-1 receptor antagonist has an effect on the CTZ, it can also effectively block the impulses farther downstream."

Gan said that future studies will explore combining the NK-1 receptor antagonist with other anti-nausea medications to see if the overall rate of postoperative nausea and vomiting (PONV) can be reduced even more.

According to Gan, patients undergoing certain procedures tend to have higher rates of PONV. For example, more than 70 percent of patients undergoing brain surgery suffer from PONV. Since the act of vomiting can raise the pressure within brain, controlling this side effect is quite important for the medical recovery of these patients, Gan said. The same holds true for patients undergoing surgery of the upper gastrointestinal tract, he added, since the act of vomiting could cause sutures to come apart.