title: Effect-site concentration of propofol for recovery of consciousness is virtually independent of fentanyl effect-site concentration.
abstract: Fentanyl reduces the amount of propofol necessary to prevent responses to surgical stimuli. However, opioids have relatively little effect on consciousness. We, therefore, tested the hypothesis that fentanyl minimally alters the effect-site concentration of propofol associated with awakening. Fifty women having gynecologic laparotomy with propofol anesthesia were randomly allocated into the following target effect-site fentanyl concentrations: 0.8, 1.0, 1.4, 2.0, and 3.0 ng/mL. Fentanyl was continued at the designated rate through the initial postoperative phase. The propofol effect-site concentration associated with eye opening in response to verbal command was regarded as the awakening concentration. The estimated propofol effect-site concentrations at awakening did not differ significantly among the groups and were 1.9 +/- 0.5 micro g/mL with a fentanyl effect-site concentration of 0.8 ng/mL; 1.6 +/- 0.4 micro g/mL with 1.0 ng/mL of fentanyl; 1.6 +/- 0.2 micro g/mL with 1.4 ng/mL of fentanyl; 1.7 +/- 0.4 micro g/mL with 2.0 ng/mL of fentanyl; and 1.6 +/- 0.34 micro g/mL with 3.0 ng/mL of fentanyl (mean +/- SD). Seventy percent of the subjects in the 0.8 ng/mL fentanyl group spontaneously complained of pain, whereas none of the patients in the 2 or 3 ng/mL groups did. Five (56%) of 9 women in the 3 ng/mL group had a postoperative respiratory rate <6 breaths/min. Heart rate in one of these women decreased to <40 bpm. These data suggest that the optimal fentanyl effect-site concentration in patients recovering from gynecologic laparoscopy is between 1.4 and 2.0 ng/mL.
  
  
  CONCLUSIONS
  The effect-site concentration for propofol at awakening was virtually independent of the fentanyl effect-site concentration over the range of 0.8 to 3.0 ng/mL; however, 0.8 ng/mL of fentanyl was associated with inadequate postoperative analgesia, and 3.0 ng/mL of fentanyl was associated with respiratory toxicity. The optimal postoperative fentanyl effect-site concentration during recovery from propofol general anesthesia for laparotomy thus appears to be near 2 ng/mL.
authors.affiliation: *Department of Anesthesiology, Tokyo Women's Medical University, Tokyo, Japan; †Department of Anesthesiology, Yamanashi Medical University, Yamanashi, Japan; ‡OUTCOMES RESEARCH™ Institute, Department of Anesthesiology and Pharmacology, University of Louisville, Louisville, Kentucky; and ‡Ludwig Boltzmann Institute, University of Vienna, Vienna, Austria.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Iwakiri
authors.forename: Osamu
authors.initials: O
authors.lastname: Nagata
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsukawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Ozaki
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Sessler
mesh_terms: D000328:Adult; D000762:Anesthesia Recovery Period; D018686:Anesthetics, Intravenous / Q000009:adverse effects / Q000493:pharmacokinetics*; D001285:Atropine; D001919:Bradycardia / Q000139:chemically induced / Q000453:epidemiology; D005260:Female; D005283:Fentanyl / Q000009:adverse effects / Q000493:pharmacokinetics*; D013509:Gynecologic Surgical Procedures; D006801:Humans; D007040:Hypoventilation / Q000139:chemically induced / Q000453:epidemiology; D007813:Laparotomy; D008875:Middle Aged; D018727:Muscarinic Antagonists; D009388:Neostigmine; D019148:Neuromuscular Blockade; D010147:Pain Measurement; D010149:Postoperative Pain / Q000453:epidemiology; D010277:Parasympathomimetics; D015742:Propofol / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D018686:Anesthetics, Intravenous; D018727:Muscarinic Antagonists; D010277:Parasympathomimetics; D009388:Neostigmine; D001285:Atropine; D005283:Fentanyl; D015742:Propofol