Author: Bob Kronemyer
A single 10-mg dose of IV amisulpride (BARHEMSYS, Acacia) was statistically more effective than placebo as rescue treatment for postoperative nausea and vomiting (PONV) in high-risk patients who failed prophylactic agents, according to a multicenter phase 3 study. Amisulpride has been approved as an oral antipsychotic for over 30 years in Europe and elsewhere, with a favorable safety profile.
In addition, a post hoc analysis showed that the number of antiemetics given as prophylaxis or the number of baseline PONV risk factors did not influence efficacy.
“PONV is a common complication of surgery and anesthesia,” said principal investigator Sabry Ayad, MD, MBA, FASA, a professor of anesthesiology at Cleveland Clinic Lerner College of Medicine. “Yet, despite receiving prophylaxis, roughly 30% of patients undergoing surgery still experience PONV, and PONV occurs in up to 80% of high-risk patients after surgery.”
PONV is unpleasant and associated with patient discomfort and dissatisfaction during perioperative care. “It can also delay discharge from the recovery room and lead to an extended hospital stay, resulting in potentially avoidable health care costs,” Dr. Ayad said.
The primary end point of the study, which was presented at the 2019 Annual Congress of the American Society for Enhanced Recovery (poster 1), was complete response, which was defined as no emetic episodes (vomiting or retching) or antiemetic rescue medication during the first 24 hours after amisulpride dosing.
Overall, results showed that 41% of the amisulpride group (96/230 patients) achieved a complete response, compared with only 28.5% in the placebo group (67/235 patients), which was statistically significant.
A prespecified secondary end point showed that patients treated with amisulpride also had a longer median time to treatment failure than those who received placebo in every treatment group, regardless of the number of risk factors.
Three major factors increase the likelihood of PONV: patient profile, anesthesia and surgical variables.
“Female gender, prior history of PONV and/or motion sickness are factors that increase the risk of PONV,” Dr. Ayad said. Four other patient factors include preoperative nausea and vomiting, being under the age of 50 years, being a nonsmoker and delayed gastric emptying. Receiving general anesthesia, perioperative opioids and volatile anesthetic agents also place patients at an increased risk for PONV.
“Longer surgery, pain, ambulation, a cholecystectomy, and gynecologic or laparoscopic surgery are risk factors, as well,” Dr. Ayad said.
To reduce PONV, Dr. Ayad recommends avoiding or minimizing the use of nitrous oxide, volatile anesthetics and postoperative opioids.
“Instead, rely on prophylactic agents to prevent PONV in high-risk patients, and place more emphasis on PONV combination therapy,” he said.
Meanwhile, low-dose IV amisulpride “has shown to be an effective antiemetic, reducing the incidence of PONV in moderate- and high-risk patients undergoing surgery under general anesthesia in clinical trials, thus making it a potentially valuable addition to our armamentarium in managing PONV,” Dr. Ayad said.
Besides its efficacy, amisulpride may have a suitable pharmacologic and safety profile for use in combination with other antiemetics, due to its limited metabolism, the fact that it neither induces nor inhibits liver enzymes, and that it causes limited plasma protein binding.
“Integrating PONV prophylaxis and management as an integral part of the enhanced recovery after surgery (ERAS) guidelines would also be beneficial,” Dr. Ayad said.
Interesting, but …
Roy Soto, MD, a professor of anesthesiology at Oakland University William Beaumont School of Medicine, in Royal Oak, Mich., said the value of the study is limited because amisulpride was compared with placebo rather than existing dopamine antagonists. “Therefore, it is very difficult to judge whether this new drug is a better choice for rescue treatment than the older dopamine antagonists,” he said.
Although amisulpride has been studied extensively for prophylaxis, “in this particular study, the drug was used to treat patients after they became nauseated,” Dr. Soto said.
Despite Dr. Soto’s reservations about the study, he noted that PONV continues to be a problem in anesthesia and surgery. “PONV can lengthen hospital stay and make recovery unpleasant,” he said. “Thus, there is a need for medications that reduce the incidence of PONV.”
The cost of amisulpride has yet to be determined, according to Dr. Soto. “But if it costs 50 times more than the old drugs, that is something people are going to have to consider,” he said. “On the other hand, if it has fewer side effects and/or lasts longer, that would be great, but we do not have the answers.”