title: Methadone for the induction of anesthesia: plasma histamine concentration, arterial blood pressure, and heart rate.
abstract: Despite the widespread use of methadone for the treatment of acute and chronic pain, the hemodynamic effects of methadone administered by IV bolus have not been studied. We compared the hemodynamic effects of an IV bolus of methadone 20 mg with those of fentanyl 10 microg/kg for the induction of anesthesia in combination with etomidate 0.3 mg/kg. Forty-three patients undergoing major surgery were randomized to one of the two treatments in a double-blinded fashion. Plasma concentrations of histamine were measured before and 2 min after opioid administration. Heart rate and arterial blood pressure were measured via an arterial line just before opioid administration, etomidate administration, and tracheal intubation; during intubation; and 1 min after intubation. There were no significant differences in mean heart rate between the methadone and fentanyl groups at any time point. Systolic and diastolic blood pressures were significantly lower (P < 0.05) in the fentanyl group just before intubation, during intubation, and 1 min after intubation. Mean plasma concentrations of histamine before and after the administration of methadone or fentanyl were 1.54 ng/mL (SD, 0.65 ng/mL) and 1.57 ng/mL (SD, 1.37 ng/mL) or 1.00 ng/mL (SD, 0.58 ng/mL) and 1.04 ng/mL (SD, 0.47 ng/mL), respectively. Despite the lack of a significant change in mean plasma concentrations of histamine, substantial increases in plasma histamine occurred in 2 of 23 patients who received methadone. There were no obvious hemodynamic effects associated with histamine concentrations up to 6.2 ng/mL. Methadone appears to have the potential for producing histamine release. Although methadone administration did not produce hemodynamic instability in this study, the possible hemodynamic side effects of histamine release should be considered when IV boluses of methadone are given.
  
  
  CONCLUSIONS
  The same dose of IV methadone (20 mg) that is effective for postoperative pain is also suitable for the induction of anesthesia in combination with etomidate. The plasma histamine concentration was notably increased in two patients, without obvious hemodynamic sequelae. Therefore, methadone appears to have the potential for producing histamine release.
authors.affiliation: Departments of *Anesthesiology, †Pharmaceutics, and ‡Pharmacy, University of Washington, Seattle, Washington.
authors.forename: T Andrew
authors.initials: TA
authors.lastname: Bowdle
authors.forename: Aaron
authors.initials: A
authors.lastname: Even
authors.forename: Danny D
authors.initials: DD
authors.lastname: Shen
authors.forename: Meghan
authors.initials: M
authors.lastname: Swardstrom
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000758:Anesthesia / Q000379:methods*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D004311:Double-Blind Method; D005260:Female; D005283:Fentanyl / Q000494:pharmacology / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006632:Histamine / Q000097:blood*; D006801:Humans; D008297:Male; D008691:Methadone / Q000494:pharmacology* / Q000627:therapeutic use; D008875:Middle Aged
chemical_list: D006632:Histamine; D008691:Methadone; D005283:Fentanyl