Remifentanil and fentanyl during anaesthesia for major abdominal and gynaecological surgery. An open, comparative study of safety and efficacy.

BACKGROUND: and objective This open, multicentre study compared the efficacy and safety of remifentanil with fentanyl during balanced anaesthesia with 0.8% isoflurane (end-tidal concentration) for major abdominal and gynaecological surgery, and the efficacy and safety of remifentanil for pain management in the immediate postoperative period. METHODS: Two-hundred and eighty-six patients were randomized to receive remifentanil 1 microg kg(-1) followed by 0.2 microg kg(-1) min-1 (n=98), remifentanil 2 microg kg(-1) followed by 0.4 microg kg(-1) min(-1) (n=91) or fentanyl 3 microg kg(-1) (n=97) at induction. Thereafter, the study opioids and isoflurane were titrated to effect during the operation. RESULTS: Compared with fentanyl, remifentanil 2 microg kg(-1) followed by 0.4 microg kg(-1) min(-1) reduced the incidence of response to tracheal intubation (30% vs. 13%, P < 0.01), skin incision (33% vs. 4%, P < 0.001) and skin closure (11% vs. 3%, P < 0.05), respectively. Patients receiving remifentanil 1 microg kg(-1) followed by 0.2 microg kg(-1) min(-1) had fewer responses to skin incision than the fentanyl group (12% vs. 33%, P < 0.001), but the incidences of response to tracheal intubation and skin closure were similar. Significantly fewer patients in both remifentanil groups had > or = 1 responses to surgical stress intraoperatively compared with fentanyl (68% and 48% vs. 87%, P < 0.003). The mean isoflurane concentrations required were less in both remifentanil groups compared with the fentanyl group (0.1%, P=0.05). In remifentanil-treated patients, continuation of the infusion at 0.1 microg kg(-1) min(-1) with titration increments of +/- 0.025 microg kg(-1) min(-1) was effective for the management of immediate postoperative pain prior to transfer to morphine analgesia. However, a high proportion of patients experienced at least moderate pain whilst the titration took place. CONCLUSIONS: Anaesthesia combining isoflurane with a continuous infusion of remifentanil was significantly more effective than fentanyl at blunting responses to surgical stimuli. Significantly fewer patients responded to tracheal intubation with remifentanil at 0.4 microg kg(-1) min(-1), supporting the use of a higher initial infusion rate before intubation. Both remifentanil and fentanyl were well-tolerated, with reported adverse events typical of mu-opioid agonists.

A randomized, blind comparison of remifentanil and alfentanil during anesthesia for outpatient surgery.

UNLABELLED: We compared remifentanil, an esterase-metabolized opioid, with alfentanil as part of balanced anesthesia with at least 0.8% isoflurane during outpatient surgery in a randomized, double-blind trial. One hundred two patients received remifentanil, and 99 patients received alfentanil. Patients who received remifentanil experienced significantly fewer stress responses to surgical stimuli (52.9% and 65.7%, P < 0.05); significantly fewer remifentanil patients responded to skin closure (11% and 22%, P < 0.05) than patients who received alfentanil. Significantly more patients in the alfentanil group required extra analgesia compared with the remifentanil group (P < 0.05). Time to respond to verbal command was shorter for alfentanil than remifentanil (median 7 min vs 9 min), and times to spontaneous respiration (median 5 min vs 8 min), adequate respiratory rate (median 6 min vs 9 min), and tracheal extubation (median 6 min vs 9 min) were significantly shorter for alfentanil in comparison with remifentanil (P < 0.05). Remifentanil patients, however, showed significantly better recovery of psychomotor and psychometric function between 30 and 90 min after surgery (P < 0.05). The incidences of hypotension intraoperatively and shivering postoperatively were significantly higher with remifentanil. No unexpected or serious adverse events were recorded with remifentanil; however, one patient who received alfentanil experienced severe recurrent respiratory depression after surgery. The metabolic profile of remifentanil allowed better intraoperative analgesia without compromising recovery. IMPLICATIONS: The pharmacological profile of remifentanil, a new opioid for use in anesthesia, suggests that rapid recovery will occur after its use. This study of 200 outpatients shows that the differences suggested from kinetic studies are not always borne out in clinical practice, although later recovery variables did, in fact, favor remifentanil.

Role of ondansetron plus dexamethasone in fractionated chemotherapy.

This randomised, double-blind, parallel-group study was carried out to compare the efficacy and safety profile of ondansetron plus dexamethasone and metoclopramide plus dexamethasone in patients receiving fractionated cisplatin (20-25 mg/m2/day) chemotherapy for the treatment of testicular cancer. An interim analysis of 95 patients showed that the ondansetron regimen was significantly superior compared to the metoclopramide regimen (p < 0.001). According to the study protocol the study was terminated at this stage. At the time the decision to stop the study was taken, a total of 113 patients had been enrolled and were evaluable on an 'intention to treat' basis. Fifty-six of these had received ondansetron (32 mg i.v. single dose/day) plus dexamethasone (20 mg i.v. single dose/day) and 57 were given metoclopramide (2 mg/kg or 1 mg/kg i.v. twice a day) plus dexamethasone (20 mg i.v. single dose/day). The ondansetron regimen was significantly superior in the control of emesis and nausea. Seventy-one percent of patients experienced 2 or fewer emetic episodes over the entire 5-day study period compared with 26% of patients given metoclopramide (p < 0.001). Seventy-nine percent of patients in the ondansetron group experienced 'none' or only 'mild' nausea compared with 39% of patients in the metoclopramide group (p < 0.001). The dose of metoclopramide had to be reduced during the study from 2 mg/kg i.v. twice daily to 1 mg/kg i.v. twice daily because 4 of the first 8 patients randomised to this treatment experienced extrapyramidal reactions. Ondansetron was well tolerated and it did not induce any extrapyramidal reactions. The results of this study show that ondansetron plus dexamethasone represents a very effective treatment option for patients receiving fractionated cisplatin chemotherapy for testicular cancer.

A prospective randomized double-blind trial comparing ondansetron versus prochlorperazine for the prevention of nausea and vomiting in patients undergoing fractionated radiotherapy.

In a multicentre, international double-blind trial, patients undergoing courses of five or more daily radiotherapy treatments to the upper abdomen were randomized to receive either oral ondansetron 8 mg t.d.s. or oral prochlorperazine 10 mg t.d.s. throughout their radiation course in order to try to prevent nausea and vomiting. A total of 192 patients were recruited, 135 of whom were included in the efficacy analysis; of these, 70 received ondansetron and 65 prochlorperazine. Forty-three (61%) of the patients prescribed ondansetron and 23 (35%) of those given prochlorperazine had a complete response, with no emetic episodes throughout their treatment course (P = 0.002). There was, however, no significant difference between the two groups with respect to the incidence and severity of nausea. Seventeen (24%) of the patients on ondansetron and 19 (29%) of those given prochlorperazine were treatment failures, experiencing more than five emetic episodes on their worst day during the study. Both drugs were well tolerated, although constipation was seen more commonly with ondansetron.

Efficacy of twice daily versus three times daily oral ondansetron in the prevention of chemotherapy induced emesis: a randomized, single-blind, multicentre study. The Ondansetron International Emesis Study Group.

Following a single intravenous dose given pre-chemotherapy, the efficacy and tolerability of oral ondansetron treatment given twice daily was compared with the established three times daily oral supplementary regimen in the prophylaxis of nausea and vomiting induced by cyclophosphamide (greater than or equal to 500 mg/m2) in combination with doxorubicin (greater than or equal to 40 mg/m2) or epirubicin (greater than or equal to 40 mg/m2). Oral ondansetron given twice daily or three times daily was equally effective in controlling nausea and emesis. The twice daily oral treatment prevented emesis in 73% of patients in the first 24 hours and in 65% of patients over 3 days. Both dose schedules were safe and were tolerated well. Twice daily oral ondansetron showed good efficacy for controlling emesis and nausea in oncology outpatients.

Does dexamethasone enhance control of acute cisplatin induced emesis by ondansetron?

OBJECTIVE: To determine the contribution of dexamethasone to the efficacy of the 5-hydroxytryptamine antagonist ondansetron in control of cisplatin induced nausea and vomiting. DESIGN: Randomised double blind crossover study. SETTING: Two cancer centres in teaching hospitals, one in the United Kingdom and the other in Germany. SUBJECTS: 100 patients (53 men and 47 women) new to cisplatin chemotherapy, 84 of whom completed two consecutive courses of chemotherapy. INTERVENTIONS: Patients were given intravenous dexamethasone (20 mg) or physiological saline with intravenous ondansetron 8 mg before cisplatin, then ondansetron 1 mg/h for 24 hours. Oral ondansetron 8 mg was taken three times daily on days 2-6. MAIN OUTCOME MEASURES: Incidence of complete or major control of emesis (0-2 episodes in the 24 hours after chemotherapy). RESULTS: Complete or major control was obtained in 49 out of 71 (69%) of patients after receiving ondansetron plus dexamethasone compared with 40 out of 71 (56%) when they were given ondansetron alone (p = 0.012). This effect was most pronounced in the first 12 hours after chemotherapy. Patients receiving the combination also had significantly less nausea. Of the 53 patients who expressed a preference, 38 (72%) preferred the combination treatment (p = 0.002) to ondansetron alone. The effect of ondansetron on delayed emesis was less pronounced. CONCLUSIONS: Dexamethasone makes a significant contribution to the efficacy of ondansetron in the control of acute platinum induced emesis.

Results of a randomized, double-blind comparative study of ondansetron and metoclopramide in the prevention of nausea and vomiting following high-dose upper abdominal irradiation.

Ondansetron is a 5-hydroxytryptamine 3-receptor antagonist which has shown activity in the prevention of cytotoxic-induced emesis. Preliminary non-randomized studies also indicated efficacy in preventing sickness following radiotherapy. The present study was therefore undertaken to compare the efficacy and safety of ondansetron (8 mg tds orally) and metoclopramide (10 mg tds orally) in preventing sickness after single-exposure radiotherapy treatments of 8-10 Gy to the upper abdomen. Of 82 evaluable patients 38 received ondansetron and 44 metoclopramide. On the first day after irradiation vomiting or retching was prevented in all but one of the patients on ondansetron whereas metoclopramide achieved complete control of these symptoms in only 46% of subjects (P less than 0.001). Similarly nausea was significantly better controlled by ondansetron in the first 24 hours after treatment (P = 0.001). Complete or major control of vomiting or retching was maintained for 92%-100% of patients on ondansetron during the five days of the study period. In the metoclopramide group the proportion of patients with equivalent control improved from 70% on day 1 to 95 on day 5. Both drugs were well-tolerated.