Substance P (Neurokinin-1) antagonist prevents postoperative vomiting after abdominal hysterectomy procedures.

BACKGROUND: The safety and antiemetic efficacy of CP-122,721, a novel neurokinin-1 antagonist, was evaluated when administered alone or in combination with ondansetron. METHODS: Using a randomized, double-blind, placebo-controlled study design, CP-122,721 was initially compared with placebo and subsequently to ondansetron alone and in combination for prophylaxis against postoperative nausea and vomiting in 243 women undergoing abdominal hysterectomy. In the dose-ranging studies (n = 86), patients received either CP-122,721 100 mg (vs. placebo) or 200 mg (vs. placebo) orally 60-90 min before induction of anesthesia. In the interaction study (n = 157), patients received CP-122,721 200 mg or placebo 60-90 min before induction of anesthesia, and ondansetron 4 mg or saline 2 ml intravenously 15-30 min before the end of surgery. Patients assessed their level of nausea and pain on arrival in the postanesthesia care unit and at 0.5-, 1-, 1.5-, 2-, 4-, 8-, 12-, and 24-h intervals postoperatively. Emetic episodes, need for rescue antiemetic-antinausea medication, postoperative complications, and patient satisfaction were recorded. RESULTS: In the initial dose-ranging study, only 10% of the patients experienced emesis within the first 8 h after surgery with CP-122,721 200 mg compared with 50% in the placebo group. CP-122,721 200 mg also decreased the need for rescue medication (25% vs. 48%). CP-122,721 100 mg was less effective than 200 mg in decreasing the incidence of repeated episodes of emesis. In the interaction study, 6% of the patients receiving CP-122,721 200 mg orally experienced emesis less than 2 h after surgery compared with 17% with ondansetron alone. With combined therapy, only 2% experienced emesis. In addition, the median times for 75% of patients to remain free from postoperative nausea and vomiting were 82, 75, and 362 min in the ondansetron, CP-122,721, and combination groups, respectively. CONCLUSIONS: Oral CP-122,721 200 mg decreased emetic episodes compared with ondansetron (4 mg intravenously) during the first 24 h after gynecologic surgery; however, there was no difference in patient satisfaction.

The use of a remifentanil infusion for hemodynamic control during intracranial surgery.

UNLABELLED: Remifentanil is an extremely rapid and short-acting opioid analgesic which is effective in controlling acute stress responses during surgery. During neurosurgical anesthesia, laryngoscopy and intubation, application of the head holder, scalp incision, and the craniectomy can produce significant increases in mean arterial pressure (MAP). In this dose-response study, we evaluated the efficacy of a remifentanil infusion in maintaining hemodynamic stability during intracranial surgery under desflurane anesthesia. Forty-five patients were assigned randomly to one of the three remifentanil infusion groups. All patients received a standardized anesthetic induction consisting of midazolam, 2 mg IV, lidocaine 0.75 mg/kg IV, propofol 1.0 mg/kg IV, and remifentanil 0.5 microg/kg IV. Immediately after induction of anesthesia, a remifentanil infusion was started at 0.0625 microg x kg(-1) x min(-1) (Group 1), 0.125 microg x kg(-1) x min(-1) (Group 2), or 0.250 microg x kg (-1) x min(-1)(Group 3) according to a double-blinded study protocol. Maintenance of anesthesia consisted of desflurane 3% (end-tidal) in air/oxygen. If the MAP exceeded 80 mm Hg, a supplemental bolus of remifentanil, 0.5 microg/kg IV was administered, and when the MAP decreased below 65 mm Hg, the remifentanil infusion was discontinued temporarily. "Rescue" cardiovascular medications consisted of nitroprusside (100 microg IV) or phenylephrine (100 microg IV). Heart rate, systolic, diastolic, and MAP values, were recorded every minute for 20 min after each specific stimulus. The overall quality of the intraoperative hemodynamic control was evaluated by the attending anesthesiologist on a scale from 1 = poor to 5 = excellent. The overall quality of the hemodynamic control was superior in Group 2 compared with Group 1 (P < 0.05). Although the total dose of remifentanil administered during the study period did not differ among the three groups, Group 1 required significantly more supplemental boluses of remifentanil (66%-80%) than Groups 2 (13%-33%) and 3 (70% 13%), and the remifentanil infusion was discontinued more often in Group 3 (80%-93%) than in Groups 1 (0%-13%) and 2 (21%-40%). In conclusion, the recommended remifentanil infusion rate for controlling acute autonomic responses during neurosurgical anesthesia is 0.125 microg x kg(-1) x min(-1) when administered during a desflurane-based anesthetic. IMPLICATIONS: Compared with remifentanil 0.0625 microg x kg(-1) x min(-1) and 0.250 microg x kg(-1) x min(-1), a remifentanil infusion rate of 0.125 microg x kg(-1) x min(-1) provided more stable hemodynamic conditions during intracranial surgery under desflurane anesthesia.