title: Continuous epidural infusion of racemic methadone results in effective postoperative analgesia and low plasma concentrations.
abstract: OBJECTIVE
  To compare two protocols of epidural administration of racemic methadone for postoperative analgesia (continuous infusion and intermittent bolus), focussing on plasma concentration, analgesic efficacy and side effects.
  
  
  METHODS
  Ninety patients undergoing abdominal or lower-limb surgery were randomly assigned to two groups in a prospective double-blind design. The continuous infusion patients (n=60) received initial doses of 3 to 6 mg followed by 6 to 12 mg by continuous infusion over 24 hr. The bolus administration patients (n=30) received repeated boluses of 3 to 6 mg of racemic methadone every eight hours. Pain intensity was assessed on a visual analog scale. Amount of supplementary analgesia was recorded, as was the incidence of side effects. Plasma methadone concentrations were determined by high performance liquid chromatography. Treatment was continued for 72 hr.
  
  
  RESULTS
  Pain relief was good and comparable in both groups throughout the three days of treatment. No accumulation of plasma racemic methadone was observed in either group, although the concentrations were significantly higher in the bolus group. Miosis was significantly more frequent in the bolus group.
  
  
  CONCLUSIONS
  Plasma methadone concentrations were significantly lower with continuous infusion. Plasma methadone accumulation, which is considered the main disadvantage for its purported influence on the incidence of side effects, did not occur at the doses used over the three days of treatment that we report.
authors.affiliation: Department of Anesthesiology, Hospital Universitari de Sant Joan de Reus, Tarragona, Spain. p-prieto@terra.es
authors.forename: Pilar
authors.initials: P
authors.lastname: Prieto-Alvarez
authors.forename: Isabel
authors.initials: I
authors.lastname: Tello-Galindo
authors.forename: Jesus
authors.initials: J
authors.lastname: Cuenca-Peña
authors.forename: Maria
authors.initials: M
authors.lastname: Rull-Bartomeu
authors.forename: Carmen
authors.initials: C
authors.lastname: Gomar-Sancho
mesh_terms: D000328:Adult; D000368:Aged; D015360:Analgesia, Epidural; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001784:Blood Gas Analysis; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008691:Methadone / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D008875:Middle Aged; D010147:Pain Measurement / Q000187:drug effects; D010149:Postoperative Pain / Q000188:drug therapy*; D013237:Stereoisomerism
chemical_list: D000701:Analgesics, Opioid; D008691:Methadone