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Anesth Analg. 1998 Aug;87(2):462-7.

The efficacy of RS-25259, a long-acting selective 5-HT3 receptor antagonist, for preventing postoperative nausea and vomiting after hysterectomy procedures.

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  • 1Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center at Dallas, 75235-9068, USA.


We evaluated the safety and efficacy of RS-25259, a potent and long-acting selective 5-HT3 receptor antagonist, for the prevention of postoperative nausea and vomiting (PONV) in women undergoing hysterectomy procedures. In this randomized, double-blind, placebo controlled, dose-ranging study, 218 healthy, consenting women were assigned to one of the six treatment groups: placebo or RS-25259 0.1, 0.3, 1.0, 3.0, or 30 microg/kg. All patients underwent a standardized general anesthetic technique. The study medication was administered i.v. 20-30 min before the end of surgery. During the initial 24-h period after surgery, the incidence of vomiting, the need for rescue antiemetics, the time to the first episode of emesis, and administration of rescue antiemetic medication, as well as a nausea visual analog scale and verbal categorical scale scores were recorded. In addition, recovery times from the end of anesthesia and the incidences of perioperative side effects were noted. Only 30 microg/kg RS-25259 significantly decreased the incidence of vomiting and the requirement for rescue antiemetics. The largest dose of RS-25259 also delayed the time to the first emetic episode and reduced the number of treatment failures. However, no differences were found in the severity of postoperative nausea (versus saline), and postoperative headaches were more common after the administration of RS-25259 0.3-30 microg/kg i.v. In conclusion, RS-25259 30 microg/kg i.v. was effective in reducing the incidence of PONV after major gynecologic surgery, but the occurrence of headaches with the larger doses of RS-25259 is a concern. Implications: RS-25259, a long-acting 5-HT3 antagonist, was effective in reducing postoperative vomiting only at the largest dose studied (30 microg/kg). However, RS-25259 had no antinausea activity, and the larger doses were associated with an increased incidence of headaches in the postoperative period.

[PubMed - indexed for MEDLINE]
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