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Continuous epidural infusion of racemic methadone results in effective postoperative analgesia and low plasma concentrations

[La perfusion péridurale continue de méthadone racémique produit une analgésie postopératoire efficace et de faibles concentrations plasmatiques]

Pilar Prieto-Alvarez, MD PhD^*, Isabel Tello-Galindo, MD^*, Jesus Cuenca-Peña, MD^*, Maria Rull-Bartomeu, MD PhD and Carmen Gomar-Sancho, MD PhD

^* From the Departments of Anesthesiology Hospital Universitari de Sant Joan de Reus
Hospital Universitari Joan Xxiii, Tarragona
The Hospital Clínic i Provincial Of Barcelona, University of Barcelona, Barcelona, Spain.

Address correspondence to: Dr. Pilar Prieto-Alvarez, Department of Anesthesiology, Hospital Universitari de Sant Joan de Reus, Passatge dels Grallers, 24, 43205 Reus, Tarragona, Spain. Phone: 97 775 0755; E-mail: p-prieto{at}terra.es

Purpose: 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.

Conclusion: 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.

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