A novel approach to prevention of postoperative nausea and vomiting (PONV) failed to reduce its incidence after exposure to general anesthesia. Results of a study, which entailed a gradual preconditioning of several receptor groups involved in the nausea reflex arc, showed a trend toward improved outcomes, but a statistically significant difference was not observed.
“We cannot ascertain from this limited study whether other preconditioning combinations might offer significant efficacy in reducing PONV,” said C. Andrew Fleming, MD, an anesthesiologist at St. Vincent Indianapolis Hospital. “This approach has never been tried before. We chose one strategy somewhat empirically, but other combinations may have success.”
As Dr. Fleming reported at the International Anesthesia Research Society 2017 annual meeting (abstract 1446), nausea and vomiting are protective reflexes that can be triggered by exposure to toxic or foreign substances. This reflex may be exacerbated, he said, in drug-naive patients receiving general anesthesia.
“In the course of a few hours, patients are exposed to large doses of some of the most powerful drugs that are available,” he explained. “It’s not surprising then that nausea and vomiting may ensue.”
In nonsurgical patients, however, the emetogenic response can be modulated by gradual escalation of doses, rather than starting at higher doses. This has been observed in dopaminergic medications and with selective serotonin reuptake inhibitors (SSRIs), of which serotonin is a known intermediary in the nausea and vomiting reflex arc. The gradual escalation of SSRIs, Dr. Fleming noted, can ameliorate the problem of nausea with the onset of therapy.
“In addition, chronic smokers, who have broad desensitization to the many chemical components of cigarette smoke, have a lower incidence of PONV than nonsmokers,” Dr. Fleming said. “This led us to hypothesize that preconditioning in drug-naive patients could reduce the effects of subsequent exposure to general anesthesia.”
Reviewing their institution’s surgery schedules, Dr. Fleming and his colleagues identified a population at high risk for PONV: patients who were ASA physical status I to III, aged 18 to 65 years, women and scheduled to undergo abdominal procedures under general anesthesia. Patients were excluded if they were taking SSRIs, opioids, dopaminergics or any antiemetics.
With the exception of hydrocodone, patients were blinded to the medications and assigned to a blinded staff anesthesiologist. Primary outcomes included the incidence of PONV in the PACU, as recorded by a blinded PACU nurse, and in the first 24 hours postoperatively, based on interviews with patients by the study authors. Secondary outcomes included the use of rescue antiemetic medications in the PACU or postoperative period.
As Dr. Fleming reported, of the 129 patients enrolled, 110 finished the protocol, with 59 randomly assigned to the control group and 51 to the treatment group (Table). Analysis of both patient-reported nausea or vomiting (P=0.44) and PACU-observed nausea or vomiting (P=0.22) showed no difference between the treatment and placebo groups. Several patients failed to complete the protocol for a variety of reasons, with five dropping out due to reported side effects of the medication regimen (three in the treatment group and two in the placebo group).
| Table. Postoperative Nausea or Vomiting in Treatment and Control Groups | ||||
| PACU-Observed N or V, Per Nurse | Patient-Reported PACU-Observed N or V | Patient-Reported N or V 24 hours Postoperatively | Patient-Reported N or V Anytime Postoperatively | |
|---|---|---|---|---|
| Nontreatment group (n=59) | 25.4% | 11.8% | 49% | 61% |
| Treatment group (n=51) | 15.7% | 11.8% | 35% | 47% |
| N, nausea; V, vomiting | ||||
Idea Requires More Research
Although disappointed by the outcomes with the chosen regimen, negative results should not invalidate the preconditioning approach entirely, Dr. Fleming said.
“The ideal way would be to try each receptor group individually with a study, but that’s beyond our capacity to do at our institution. We’d like to see if we can find other, more research-oriented institutions to pursue this question with us and test some of those other approaches,” Dr. Fleming concluded.
Moderator of the session, Shahzad Shaefi, MBBS, an anesthesiologist/intensivist at Beth Israel Deaconess Medical Center, in Boston, asked how the regimen was chosen.
“It was somewhat empiric,” Dr. Fleming acknowledged. “There are many different receptor-stimulating regimens that could be used in a preconditioning model, but this is the one we thought might have a chance at impact. We chose 5-HTP, a precursor for serotonin, as a way of increasing serotonin levels gradually. We also gave them some levodopa, commonly used to treat Parkinson’s, to stimulate the dopamine receptors. And because opioids are always an important part of nausea and vomiting, we gave patients a small, increasing dose of those, as well.”
“Would this strategy be cost-feasible to implement?” Dr. Shaefi asked.
“These drugs are all generic medications, so they’re very cheap,” Dr. Fleming said. “We provided each patient with an instruction booklet, but if you were to implement this on a larger scale, a blister pack customized for patient compliance would probably work best.”