title: Remifentanil and fentanyl during anaesthesia for major abdominal and gynaecological surgery. An open, comparative study of safety and efficacy.
abstract: 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.
authors.affiliation: Department of Anaesthesia, Derriford Hospital, Plymouth, PL6 8DH, Devon, UK. rsneyd@pms.ac.uk
authors.forename: J R
authors.initials: JR
authors.lastname: Sneyd
authors.forename: F
authors.initials: F
authors.lastname: Camu
authors.forename: A
authors.initials: A
authors.lastname: Doenicke
authors.forename: C
authors.initials: C
authors.lastname: Mann
authors.forename: O
authors.initials: O
authors.lastname: Holgersen
authors.forename: J H
authors.initials: JH
authors.lastname: Helmers
authors.forename: L
authors.initials: L
authors.lastname: Appelgren
authors.forename: D
authors.initials: D
authors.lastname: Noronha
authors.forename: B K
authors.initials: BK
authors.lastname: Upadhyaya
mesh_terms: D000005:Abdomen / Q000601:surgery*; D000328:Adult; D000762:Anesthesia Recovery Period; D000768:Anesthesia, General; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000009:adverse effects; D013509:Gynecologic Surgical Procedures; D006801:Humans; D007530:Isoflurane; D008297:Male; D010100:Oxygen / Q000097:blood; D010149:Postoperative Pain / Q000453:epidemiology / Q000517:prevention & control; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects; D000077208:Remifentanil; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology
chemical_list: D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D010880:Piperidines; D007530:Isoflurane; D000077208:Remifentanil; D010100:Oxygen; D005283:Fentanyl