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

  • Pilar Prieto-AlvarezEmail author
  • Isabel Tello-Galindo
  • Jesus Cuenca-Peña
  • Maria Rull-Bartomeu
  • Carmen Gomar-Sancho
Regional Anesthesia and Pain

Abstract

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.

Keywords

Fentanyl Continuous Infusion Epidural Analgesia Sufentanil Analgesic Efficacy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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

Résumé

Objectif

Comparer deux protocoles d’administration épidurale de méthadone racémique (perfusion continue et bolus intermittent), pour analgésie postopératoire: concentration plasmatique, efficacité analgésique et effets secondaires.

Méthode

Quatre-vingt-dix patients qui furent soumis a une intervention chirurgicale abdominale ou des membres inférieurs ont participé à cette étude prospective. Ils ont été divisés en deux groupes de manière randomisée et en double-aveugle. Le groupe de patients avec perfusion continue (n=60) a reçu une dose initiale de 3 à 6 mg suivie de 6 à 12 mg en perfusion continue toutes les 24 h. Le groupe des patients avec bolus a reçu des bolus répétés toutes les huit heures de 3 à 6 mg de méthadone racémique.

L’intensité de la douleur a été mesurée avec une échelle visuelle analogique. On a enregistré les besoins supplémentaires d’analgésie, ainsi que l’incidence des effets secondaires. La concentration de méthadone plasmatique a été déterminée par chromatographie liquide d’haute résolution. Le traitement a été poursuivi pendant 72 h.

Résultats

Le soulagement de la douleur a été bon et comparable entre les deux groupes pendant les trois jours du traitement. On n’a pas observé d’accumulation plasmatique de méthadone racémique dans aucun groupe; néanmoins les concentrations ont été significativement plus élevées dans le groupe bolus. La présence de myosis a été significativement plus fréquente dans le groupe bolus.

Conclusion

La perfusion continue est une technique sûre; elle est indiquée parce que la concentration plasmatique de méthadone a été significativement plus basse qu’avec les bolus. L’accumulation plasmatique de méthadone, qui est considerée comme le principal inconvément de son influence sur l’incidence des effets secondaires n’est pas observée avec les doses utilisées pendant les trois jours de ce traitement dans aucun des deux groupes.

References

  1. 1.
    Benedetti C, Bonica JJ. Recent advances in intraspinal pain therapy. Acta Anesthesiol Scand 1987; 31: S85.Google Scholar
  2. 2.
    Hodgson PS, Neal JM, Pollock JE, Liu SS. The neurotoxicity of drugs given intrathecally (spinal). Anesth Analg 1999; 88: 797–809.PubMedCrossRefGoogle Scholar
  3. 3.
    Cousins MJ, Mather LE. Intrathecal and epidural administration of opioids. Anesthesiology 1984; 61: 276–310.PubMedCrossRefGoogle Scholar
  4. 4.
    Glass PSA, Estok P, Ginsberg B, Goldberg JS, Sladen RN. Use of patient-controlled analgesia to compare the efficacy of epidural to intravenous fentanyl administration. Anesth Analg 1992; 74: 345–51.PubMedCrossRefGoogle Scholar
  5. 5.
    Camu F, Debucquoy F. Alfentanil infusion for postoperative pain: a comparison of epidural and intravenous routes. Anesthesiology 1991; 75: 171–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Geller E, Chrubasick J, Graf R, Chrubasick S, Schulte-Mönting J. A randomized double-blind comparison of epidural sufentanil versus intravenous sufentanil or epidural fentanyl analgesia after major abdominal surgery. Anesth Analg 1993; 76: 1243–50.PubMedCrossRefGoogle Scholar
  7. 7.
    Flórez J, Reig E. Analgésicos opiáceos: características y propiedades.In: Flórez J, Reig E (Eds.). Terapéutica Farmacológica Del Dolor. Barañáin-Pamplona, Universidad de Navarra SA, 1993: 40–80.Google Scholar
  8. 8.
    Prieto-Álvarez MP, Fuentes-Bellido JG, Lopez-Cebollada J, Lorenzo-Foz JP. Estudio comparativo de la analgesia postoperatoria con metadona y fentanilo en perfusión peridural continua. Rev Esp Anestesiol Reanim 1997; 44: 305–9.PubMedGoogle Scholar
  9. 9.
    Gomar C, Villalonga A. Metadona epidural en el dolor postoperatorio. Dolor 1991; Suppl 3: 59–60.Google Scholar
  10. 10.
    Villalonga A, Gomar C, Nalda MA. Influencia de la concentración de metadona peridural en la analgesia postoperatoria. Rev Esp Anestesiol Reanim 1989; 36: 260–3.PubMedGoogle Scholar
  11. 11.
    Magora F, Chrubasik J, Damm D, Schulte-Mönting J, Shir Y. Application of a new method for measurement of plasma methadone levels to the use of epidural methadone for relief of postoperative pain. Anesth Analg 1987; 66: 1308–11.PubMedCrossRefGoogle Scholar
  12. 12.
    Nilsson MI, Meresaar U, Änggard E. Clinical pharmacokinetics of methadone. Acta Anaesthesiol Scand 1982; Suppl 74: 66–9.Google Scholar
  13. 13.
    Prieto Alvarez MP. Eficacia y seguridad de la analgesia postoperatoria con metadona en perfusion epidural continua [tesis doctoral]. Universidad Rovira y Virgili de Tarragona. Facultad de Medicina, 1994.Google Scholar
  14. 14.
    Shir Y, Eimerl D, Magora F, Damm D, Schulte-Monting J, Chrubasik J. Plasma concentrations of methadone during postoperative patient-controlled extradural analgesia. Br J Anesth 1990; 65: 204–9.CrossRefGoogle Scholar
  15. 15.
    Wolff K, Sanderson M, Hay AWM, Raistrick D. Methadone concentrations in plasma and their relationship to drug dosage. Clin Chem 1991; 37: 205–9.PubMedGoogle Scholar
  16. 16.
    Ramsay MAE, Savege TM, Simpson BRJ, Goodwin R. Controlled sedation with alphaxalone-alphadolone. Br Med J 1974; 2: 656–9.PubMedGoogle Scholar
  17. 17.
    Wang JM, Knarr DC, Raj PP, Denson D. Continuous epidural methadone for the management of postoperative pain after lower abdominal surgery. Reg Anesth 1992; 17: 26–8.PubMedGoogle Scholar
  18. 18.
    Dottrens M, Rifat K, Morel DR. Comparison of extradural administration of sufentanil, morphine and sufentanil-morphine combination after caesarean section. Br J Anaesth 1992; 69: 9–12.PubMedCrossRefGoogle Scholar
  19. 19.
    Salomäki TE, Laitinen JO, Nuutinen LS. A randomized double-blind comparison of epidural versus intravenous fentanyl infusion for analgesia after thoracotomy. Anesthesiology 1991; 75: 790–5.PubMedCrossRefGoogle Scholar
  20. 20.
    Hosoda R, Hattori M, Shimada Y. Favorable effects of epidural analgesia on hemodynamics, oxygenation and metabolics variables in the inmediate post-anesthetic period. Acta Anaesthesiol Scand 1993; 37: 469–74.PubMedGoogle Scholar
  21. 21.
    Jayr C, Thomas H, Rey A, Farhat F, Lasser P, Bourgain J-L. Postoperative pulmonary complications. Epidural analgesia using bupivacaine and opioids versus parenteral opioids. Anesthesiology 1993; 78: 666–76.PubMedCrossRefGoogle Scholar
  22. 22.
    Haynes SR, Davidson I, Allsop JR, Dutton DA Comparison of epidural methadone with epidural diamorphine for analgesia following caesarean section. Acta Anaesthesiol Scand 1993; 37: 375–80.PubMedCrossRefGoogle Scholar
  23. 23.
    Etches RC, Sandler AN, Daley MD. Respiratory depression and spinal opioids. Can J Anaesth 1989; 36: 165–85.PubMedGoogle Scholar

Copyright information

© Canadian Anesthesiologists 2002

Authors and Affiliations

  • Pilar Prieto-Alvarez
    • 1
    Email author
  • Isabel Tello-Galindo
    • 1
  • Jesus Cuenca-Peña
    • 1
  • Maria Rull-Bartomeu
    • 2
  • Carmen Gomar-Sancho
    • 3
  1. 1.Department of AnesthesiologyHospital Universitari de Sant Joan de ReusReusSpain
  2. 2.Department of AnesthesiologyHospital Universitari Joan XXIIITarragona
  3. 3.Hospital Clínic i Provincial of BarcelonaUniversity of BarcelonaBarcelonaSpain

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