European Journal of Clinical Pharmacology

, Volume 34, Issue 4, pp 343–352 | Cite as

Influence of naloxone on the postoperative analgesic and respiratory effects of buprenorphine

  • K. A. Lehmann
  • U. Reichling
  • R. Wirtz
Originals

Summary

Eighty patients recovering from major operations were investigated to evaluate the influence of naloxone on the analgesic and respiratory depressant properties of buprenorphine. They were randomly assigned to two groups to self-administer either buprenorphine (Group B) or a mixture of buprenorphine and naloxone (fraction 60%; Group BN) in the early postoperative period by means of the On-Demand Analgesia Computer (ODAC). The duration of patient-controlled analgesia (PCA) was 21.0 h (B) or 23.5 h (BN), during which 12.2 (B) and 18.2 (BN) demands per patient were recorded, representing significantly different consumption of buprenorphine 0.80 (B) and 1.07 (BN) µg·kg−1·h−1. Retrospective pain scores were significantly better in Group B, and respiratory rate was significantly higher in Group BN. The analgesia was judged superior by 81% (B) and 88% (BN) of the patients compared to conventional postoperative pain treatment. The minimum effective buprenorphine concentration (MEC) varied greatly in both groups with no significant differences between them (median 0.4 ng·ml−1, range 0.1–8.6 ng·ml−1); intra-individual variability was lower (67.9% B, and 58.2% BN) than inter-individual variability (107.3% B and 84.0% BN). Accumulation in plasma and acute tolerance did not occur. Thus, admixture of 60% naloxone decreased both the analgesic and respiratory depressant effects of buprenorphine which were generally independent of plasma concentrations. The analgesia achieved with the buprenorphine/naloxone mixture under patient-controlled conditions was comparable to that of other narcotic analgesics. Accordingly, this drug combination may be expected to give clinically adequate analgesia without notable impairement of spontaneous respiration, whilst withdrawal symptoms would probably arise in drug addicts abusing other opiates.

Key words

naxolone buprenorphine drug interaction patient-controlled analgesia adverse effects pain treatment postoperative pain 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Adriaensen H, Mattelaer B, Vanmeenen H (1985) A longterm open, clinical and pharmacokinetic assessment of sublingual buprenorphine in patients suffering from chronic pain. Acta Anaesthesiol Belg 36: 33–40Google Scholar
  2. 2.
    Bartlett AJ, Lloyd-Jones JG, Rance MJ, Flockhart IR, Dockray GJ, Bennett MRD, Moore RA (1980) The radioimmunoassay of buprenorphine. Eur J Clin Pharmacol 18: 339–345Google Scholar
  3. 3.
    Bullingham RES, McQuay HJ, Moore RA, Bennett MRD (1980) Buprenorphine kinetics. Clin Pharmacol Ther 28: 667–672Google Scholar
  4. 4.
    Bullingham RES, McQuay HJ, Dwyer D, Allen MC, Moore RA (1981) Sublingual buprenorphine used postoperatively: Clinical observations and preliminary pharmacokinetic analysis. Br J Clin Pharmacol 12: 117–122Google Scholar
  5. 5.
    Chakravarty K, Tucker W, Rosen M, Vickers MD (1979) Comparison of buprenorphine and pethidine given intravenously on demand to relieve postoperative pain. Br Med J 2: 895–897Google Scholar
  6. 6.
    Gibbs JM, Johnson HD, Davis FM (1982) Patient administration of i.v. buprenorphine for postoperative pain relief using the “Cardiff” demand analgesia apparatus. Br J Anaesth 54: 279–284Google Scholar
  7. 7.
    Gourlay GK, Wilson PR, Glynn CJ (1982) Pharmacodynamics and pharmacokinetics of methadone during the perioperative period. Anesthesiology 57: 458–467Google Scholar
  8. 8.
    Gourlay GK, Willis RJ, Wilson PR (1984) Postoperative pain control with methadone: Influence of supplementary methadone doses and blood concentration-response relationships. Anesthesiology 61: 19–26Google Scholar
  9. 9.
    Gourlay GK, Willis RJ, Lamberty J (1986) A double-blind comparison of the efficacy of methadone and morphine in postoperative pain control. Anesthesiology 64: 322–327Google Scholar
  10. 10.
    Harmer M, Slattery PJ, Rosen M, Vickers MD (1983) Comparison between buprenorphine and pentazocine given i.v. on demand in the control of postoperative pain. Br J Anaesth 55: 21–25Google Scholar
  11. 11.
    Lehmann KA, Gensior J, Daub D (1982) “Analgetische” Fentanyl-Blutkonzentrationen unter Neuroleptanalgesie. Anaesthesist 31: 655–659Google Scholar
  12. 12.
    Lehmann KA (1984) On-Demand Analgesie: Neue Möglichkeiten zur Behandlung akuter Schmerzen. Arzneimittelforsch 34: 1108–1114Google Scholar
  13. 13.
    Lehmann KA, Gördes B, Hoeckle W (1985) Postoperative On-Demand Analgesie mit Morphin. Anaesthesist 34: 494–501Google Scholar
  14. 14.
    Lehmann KA, Tenbuhs B, Hoeckle W (1985) Postoperative On-Demand Analgesie mit Pentazocin (Fortral). Langenbecks Arch Chir 367: 27–40Google Scholar
  15. 15.
    Lehmann KA, Jung C, Hoeckle W (1985) Tramadol und Pethidin zur postoperativen Schmerztherapie: Eine randomisierte Doppelblindstudie unter den Bedingungen der intravenösen On-Demand Analgesie. Schmerz/Pain/Douleur 6: 88–100Google Scholar
  16. 16.
    Lehmann KA, Tenbuhs B, Hoeckle W (1986) Patient-controlled analgesia with piritramid for the treatment of postoperative pain. Acta Anaesthesiol Belg 37: 247–257Google Scholar
  17. 17.
    Lehmann KA, Tenbuhs B (1986) Patient-controlled analgesia with nalbuphine, a new narcotic agonist-antagonist, for the treatment of postoperative pain. Eur J Clin Pharmacol 31: 267–276Google Scholar
  18. 18.
    Lehmann KA, Gördes B (1988) Postoperative On-Demand Analgesie mit Buprenorphin. Anaesthesist 37: 65–70Google Scholar
  19. 19.
    Müller H, Gerlach H, Gips H, Richter M, Börner U, Hempelmann G (1986) Intra- und postoperative Interaktionen zwischen den beiden Opioiden Fentanyl und Buprenorphin. Anaesthesist 35: 219–225Google Scholar
  20. 20.
    Pedersen JE, Chraemmer-Jorgensen B, Schmidt JF, Risbo A (1985) Naloxone — a strong analgesic in combination with high-dose buprenorphine? Br J Anaesth 57: 1045–1046Google Scholar
  21. 21.
    Peeters M, Brugmans J (1980) Postoperative pain relief by demand analgesia. Acta Anaesthesiol Belg 31 [Suppl]: 233–237Google Scholar
  22. 22.
    Rance MJ, Lord JAH, Robinson T (1979) Biphasic dose response to buprenorphine in the rat tail flick assay: Effect of naloxone pretreatment. In: Way EL (ed) Endogenous and exogenous opiate agonists and antagonists. Pergamon-Press, New York, pp 387–390Google Scholar
  23. 23.
    Risbo A (1986) Sublingual buprenorphine/naloxone compared with buprenorphine for postoperative pain relief. Beitr Anaesthesiol Intensivmed 17: 281 AbstractsGoogle Scholar
  24. 24.
    Schmidt JF, Chraemmer-Jorgensen B, Pedersen JE (1985) Postoperative pain relief with naloxone. Severe respiratory depression and pain after high dose buprenorphine. Anaesthesia 40: 583–586Google Scholar
  25. 25.
    Shah MV, Jones DI, Rosen M (1986) “Patient demand” post-operative analgesia with buprenorphine. Comparison between sublingual and i.m. administration. Br J Anaesth 58: 508–511Google Scholar
  26. 26.
    Stoyanov M, Müller H, Waßmuth M (1985) Hämodynamische und respiratorische Wirkungen von Buprenorphin unter N2O-O2-Beatmung und in der frühen postoperativen Phase. Anaesthesist 34 [Suppl]: 298Google Scholar
  27. 27.
    Tamsen A, Hartvig P, Fagerlund C, Dahlström B (1982) Patient-controlled analgesic therapy, part II: Individual analgesic demand and analgesic plasma concentration of pethidine in postoperative pain. Clin Pharmacokinet 7: 164–175Google Scholar
  28. 28.
    Tolksdorf W, Hartung M, Mering T, Glocke M, Müller W (1985) Buprenorphin/Buprenorphin-Naloxon zur intravenösen postoperativen Schmerztherapie — eine Doppelblindstudie. Anaesthesist 34 [Suppl]: 201Google Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • K. A. Lehmann
    • 1
  • U. Reichling
    • 1
  • R. Wirtz
    • 1
  1. 1.Institut für Anaesthesiologie der Universität zu KölnKölnFRG

Personalised recommendations