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Perineural morphine in patients with chronic ischemic lower extremity pain: efficacy and long-term results

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Abstract

Purpose

To compare the efficacy, safety, and impact on daily activity of peripherally administered morphine plus a local anesthetic with that of a local anesthetic alone in patients with chronic ischemic lower extremity pain.

Methods

Fifty patients with lower extremity ischemic pain due to peripheral vascular disease who had undergone surgical sympathectomy and who were not responding to systemic analgesics were included. Study treatments were bupivacaine plus morphine or bupivacaine alone administered via popliteal catheter. Each patient received both study treatments consecutively, with a washout period, in a double-blind fashion. The effects of treatments on pain severity (numerical rating scale), duration of analgesia, and daily activity were evaluated. Then, patients were asked to state which one of the treatments they preferred for the long term, during which catheter outcomes were evaluated.

Results

Both treatments provided significant pain control compared to baseline at all time points, both at rest and during activity. However, the combination treatment provided superior pain control at 8 and 12 h, and longer analgesia duration (12 ± 2 h vs 9 ± 1 h; P < 0.001). During the long term, treatments were similar in terms of analgesia. The combination treatment had a higher incidence of side effects (30% vs 0%; P < 0.001).

Conclusion

A peripherally administered bupivacaine plus morphine combination provided better and longer analgesia for ischemic pain compared to bupivacaine alone for the short term, but not for the long term. On the other hand, our results show that continuous popliteal treatment is an effective, safe, and comfortable modality for long-term use in the home setting for patients with intractable chronic pain.

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References

  1. Fields HL, Emson PC, Leigh BK, Gilbert RF, Iversen LL. Multiple opiate receptor sites on primary afferent fibres. Nature. 1980;284:351–353.

    Article  PubMed  CAS  Google Scholar 

  2. Stein C. Peripheral mechanisms of opioid analgesia. Anesth Analg. 1993;76:182–191.

    Article  PubMed  CAS  Google Scholar 

  3. Machelka H. Targeting of opioid-producing leukocytes for pain control. Neuropeptides. 2007;41:355–363.

    Article  Google Scholar 

  4. Boogaerts J, Lafont N. Mechanism of action and clinical use of opioids administered by the peripheral perineural route. Cah Anesthesiol. 1991;39:91–95.

    PubMed  CAS  Google Scholar 

  5. Stein C, Millan MJ, Shippenberg TS, Peter K, Herz A. Peripheral opioid receptors mediating antinociception in inflammation. Evidence for involvement of mu, delta and kappa receptors. J Pharmacol Exp Ther. 1989;248:1269–1275.

    PubMed  CAS  Google Scholar 

  6. Bazin JE, Massoni C, Bruelle P, Fenies V, Groslier D, Schoeffler P. The addition of opioids to local anaesthetics in brachial plexus block: the comparative effects of morphine, buprenorphine and sufentanil. Anaesthesia. 1997;52:858–862.

    Article  PubMed  CAS  Google Scholar 

  7. Likar R, Schäfer M, Paulak F, Sittl R, Pipam W, Schalk H, Geissler D, Bernatzky G. Intraarticular morphine analgesia in chronic pain patients with osteoarthritis. Anesth Analg. 1997;84:1313–1317.

    Article  PubMed  CAS  Google Scholar 

  8. Candido KD, Franco CD, Khan MA, Winnie AP, Raja DS. Buprenorphine added to the local anesthetic for brachial plexus block to provide postoperative analgesia in outpatients. Reg Anesth Pain Med. 2001;26:352–356.

    PubMed  CAS  Google Scholar 

  9. Kaczmarzyk T, Stypulkowska J. Assessment of the effectiveness of peripheral administration of morphine with local articaine anaesthesia for surgery in infl amed oral and maxillofacial tissues. Pain. 2005;115:348–354.

    PubMed  CAS  Google Scholar 

  10. Zhou L, Zhang Q, Stein C, Schäfer M. Contribution of opioid receptors on primary afferent versus sympathetic neurons to peripheral opioid analgesia. J Pharmacol Exp Ther. 1998;286:1000–1006.

    PubMed  CAS  Google Scholar 

  11. Likar R, Koppert W, Blatnig H, Chiari F, Sittl R, Stein C, Schäfer M. Efficacy of peripheral morphine analgesia in inflamed, noninflamed and perineural tissue of dental surgery patients. J Pain Symptom Manage. 2001;21:330–337.

    Article  PubMed  CAS  Google Scholar 

  12. Stein C. Opioid receptors on peripheral sensory neurons. Adv Exp Med Biol. 2003;521:69–76.

    PubMed  CAS  Google Scholar 

  13. Mousa SA, Straub RH, Schäfer M, Stein C. Beta-endorphin, Met-enkephalin and corresponding opioid receptors within synovium of patients with joint trauma, osteoarthritis and rheumatoid arthritis. Ann Rheum Dis. 2007;66:871–879.

    Article  PubMed  CAS  Google Scholar 

  14. Kabli N, Cahill CM. Anti-allodynic effects of peripheral opioid receptors in neuropathic pain. Pain. 2007;127:84–93.

    Article  PubMed  CAS  Google Scholar 

  15. Sayeed MM. Signaling mechanisms of altered cellular responses in trauma, burn, and sepsis: role of Ca2+. Arch Surg. 2000;135:1432–1442.

    Article  PubMed  CAS  Google Scholar 

  16. Singelyn FJ, Gouverneur JM, Gribomont BF. Popliteal sciatic nerve block aided by a nerve stimulator: a reliable technique for foot and ankle surgery. Reg Anesth Pain Med. 1991;16:278–281.

    CAS  Google Scholar 

  17. Ilfeld BM, Morey TE, Wang RD, Enneking FK. Continuous popliteal sciatic nerve block for postoperative pain control at home: a randomized, doubleblinded, placebo-controlled study. Anesthesiology. 2002;97:959–965.

    Article  PubMed  CAS  Google Scholar 

  18. White PF, Issioui T, Skrivanek GD, Early JS, Wakefield C. The use of a continuous popliteal sciatic nerve block after surgery involving the foot and ankle: does it improve the quality of recovery? Anesth Analg. 2003;97:1303–1309. Erratum in: Anesth Analg. 2003;97:557.

    Article  PubMed  Google Scholar 

  19. Navas AM. Stimulating catheters in continuous popliteal block. Anesth Analg. 2006;102:1594; author reply 1594–5.

    Article  PubMed  Google Scholar 

  20. Calder JD, Elliot R, Seifert C. Technical tip: lateral popliteal sciatic nerve block with continuous infusion for foot and ankle surgery. Foot Ankle Int. 2007;28:1106–1107.

    Article  PubMed  Google Scholar 

  21. Horlocker TT, Wedel DJ, Benzon H, Brown DL, Enneking FK, Heit JA, Mulroy MF, Rosenquist RW, Rowlingson J, Tryba M, Yuan CS. Regional anesthesia in the anticoagulated patient: defining the risks (the second ASRA Consensus Conference on Neuraxial Anesthesia and Anticoagulation). Reg Anesth Pain Med. 2003;28:172–197.

    PubMed  Google Scholar 

  22. Lorenz IH, Egger K, Schubert H, Schnürer C, Tiefenthaler W, Hohlrieder M, Schocke MF, Kremser C, Esterhammer R, Ischebeck A, Moser PL, Kolbitsch C. Lornoxicam characteristically modulates cerebral pain-processing in human volunteers: a functional magnetic resonance imaging study. Br J Anaesth. 2008;100:827–833.

    Article  PubMed  CAS  Google Scholar 

  23. Fitzcharles MA, Costa DD, Pöyhiä R. A study of standard care in fi bromyalgia syndrome: a favorable outcome. J Rheumatol. 2003;30:154–159.

    PubMed  Google Scholar 

  24. Impellizzeri FM, Maffiuletti NA. Convergent evidence for construct validity of a seven-point likert scale of lower limb muscle soreness. Clin J Sport Med. 2007;17:494–496.

    PubMed  Google Scholar 

  25. Antonijevic I, Mousa SA, Schäfer M, Stein C. Perineurial defect and peripheral opioid analgesia in inflammation. J Neurosci. 1995;15:165–172.

    PubMed  CAS  Google Scholar 

  26. Janson W, Stein C. Peripheral opioid analgesia. Curr Pharm Biotechnol. 2003;4:270–274.

    Article  PubMed  CAS  Google Scholar 

  27. Møiniche S, Dahl JB, Kehlet H. Peripheral antinociceptive effects of morphine after burn injury. Acta Anaesthesiol Scand. 1993;37:710–712.

    Article  PubMed  Google Scholar 

  28. Dionne RA, Lepinski AM, Gordon SM, Jaber L, Brahim JS, Hargreaves KM. Analgesic effects of peripherally administered opioids in clinical models of acute and chronic infl ammation. Clin Pharmacol Ther. 2001;70:66–73.

    Article  PubMed  CAS  Google Scholar 

  29. Stein A, Yassouridis A, Szopko C, Helmke K, Stein C. Intraarticular morphine versus dexamethasone in chronic arthritis. Pain. 1999;83:525–532.

    Article  PubMed  CAS  Google Scholar 

  30. Duckett JW, Cangiano T, Cubina M, Howe C, Cohen D. Intravesical morphine analgesia after bladder surgery. J Urol. 1997;157:1407–1409.

    Article  PubMed  CAS  Google Scholar 

  31. Guay J. Peripheral nerve blocks for postoperative pain relief after total knee replacement: more questions than answers. Anesth Analg. 2005;100:1547; author reply 1547-8.

    Article  PubMed  Google Scholar 

  32. Boezaart AP. Perineural infusion of local anesthetics. Anesthesiology. 2006;104:872–880.

    Article  PubMed  Google Scholar 

  33. Richman JM, Liu SS, Courpas G, Wong R, Rowlingson AJ, McGready J, Cohen SR, Wu CL. Does continuous peripheral nerve block provide superior pain ontrol to opioids? A metaanalysis. Anesth Analg. 2006;102:248–257.

    Article  PubMed  Google Scholar 

  34. Ilfeld BM, Mariano ER, Williams BA, Woodard JN, Macario A. Hospitalization costs of total knee arthroplasty with a continuous femoral nerve block provided only in the hospital versus on an ambulatory basis: a retrospective, case-control, cost-minimization analysis. Reg Anesth Pain Med. 2007;32:46–54.

    PubMed  Google Scholar 

  35. Ilfeld BM, Morey TE, Wang RD, Enneking FK. Continuous popliteal sciatic nerve block for postoperative pain control at home: a randomized, doubleblinded, placebo-controlled study. Anesthesiology. 2002;97:959–965.

    Article  PubMed  CAS  Google Scholar 

  36. Fanelli G, Casati A, Garancini P, Torri G. Nerve stimulator and multiple injection technique for upper and lower limb blockade: failure rate, patient acceptance, and neurologic complications. Study Group on Regional Anesthesia. Anesth Analg. 1999;88:847–852.

    Article  PubMed  CAS  Google Scholar 

  37. Zaric D, Boysen K, Christiansen J, Haastrup U, Kofoed H, Rawal N. Continuous popliteal sciatic nerve block for outpatient foot surgery—a randomized, controlled trial. Acta Anaesthesiol Scand. 2004;48:337–341.

    Article  PubMed  CAS  Google Scholar 

  38. Ilfeld BM, Thannikary LJ, Morey TE, Vander Griend RA, Enneking FK. Popliteal sciatic perineural local anesthetic infusion: a comparison of three dosing regimens for postoperative analgesia. Anesthesiology. 2004;101:970–977.

    Article  PubMed  CAS  Google Scholar 

  39. Klein SM. Continuous peripheral nerve blocks: fewer excuses. Anesthesiology. 2005;103:921–923.

    Article  PubMed  Google Scholar 

  40. Evans H, Steele SM, Nielsen KC, Tucker MS, Klein SM. Peripheral nerve blocks and continuous catheter techniques. Anesthesiol Clin North America. 2005;23:141–162.

    Article  PubMed  Google Scholar 

  41. Ilfeld BM, Morey TE, Enneking FK. New portable infusion pumps: real advantages or just more of the same in a different package? Reg Anesth Pain Med. 2004;29:371–376.

    PubMed  Google Scholar 

  42. Ilfeld BM, Enneking FK. Continuous peripheral nerve blocks at home: a review. Anesth Analg. 2005;100:1822–1833.

    Article  PubMed  Google Scholar 

  43. Nitescu P, Dahm P, Appelgren L, Curelaru I. Continuous infusion of opioid and bupivacaine by externalized intrathecal catheters in long-term treatment of “refractory” nonmalignant pain. Clin J Pain. 1998;14:17–28.

    Article  PubMed  CAS  Google Scholar 

  44. Cuvillon P, Ripart J, Lalourcey L, Veyrat E, L’Hermite J, Boisson C, Thouabtia E, Eledjam JJ. The continuous femoral nerve block catheter for postoperative analgesia: Bacterial colonization, infectious rate and adverse effects. Anesth Analg. 2001;93:1045–1049.

    Article  PubMed  CAS  Google Scholar 

  45. Capdevila X, Dadure C, Bringuier S, Bernard N, Biboulet P, Gaertner E, Macaire P. Effect of patient-controlled perineural analgesia on rehabilitation and pain after ambulatory orthopedic surgery: a multicenter randomized trial. Anesthesiology. 2006;105:566–573.

    Article  PubMed  CAS  Google Scholar 

  46. Collins TC, Beyth RJ, Nelson DB, Petersen NJ, Suarez-Almazor ME, Bush RL, Hirsch AT, Ashton CM. Process of care and outcomes in patients with peripheral arterial disease. J Gen Intern Med. 2007;22:942–948.

    Article  PubMed  Google Scholar 

  47. Schug SA, Gandman N. Opioids: clinical use. In: McMahon SB, Koltzenberg M, editors. Wall and Melzack’s textbook of pain. 5th ed. China; Elsevier/Churchill Livingstone: 2006. p. 443–457.

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Keskinbora, K., Aydinli, I. Perineural morphine in patients with chronic ischemic lower extremity pain: efficacy and long-term results. J Anesth 23, 11–18 (2009). https://doi.org/10.1007/s00540-008-0700-9

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  • DOI: https://doi.org/10.1007/s00540-008-0700-9

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