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 μg kg^-1 followed by 0.2 μg kg^-1 min^-1 (n = 98), remifentanil 2 μg kg^-1 followed by 0.4 μg kg^-1 min^-1 (n = 91) or fentanyl 3 μg 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 μg kg^-1 followed by 0.4 μg 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 μg kg^-1 followed by 0.2 μg 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 ≥ 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 μg kg^-1 min^-1 with titration increments of ± 0.025 μg 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 μg 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 μ-opioid agonists.