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Opioids as an alternative to amide-type local anaesthetics for intra-articular application

  • Experimental Study
  • Published:
Knee Surgery, Sports Traumatology, Arthroscopy Aims and scope

Abstract

Purpose

Recently, the safety profile of local anaesthetics in intra-articular use became into focus of investigation. Opioid drugs have a different mode of action and may be a safe and potent alternative for intra-articular application. The purpose of this in vitro study is to provide evidence for significant chondrotoxicity of amide-type local anaesthetics even after short-term application on human chondrocytes and to demonstrate the absence of such negative effects for opioids [morphine, morphine-6-glucuronide (M6G)].

Method

Visually intact cartilage explants of human, mainly osteoarthritic joints (n = 9), were harvested and cultivated in monolayer for expansion and transferred into alginate bead. The beads were incubated for increasing incubation times (15 min, 1 and 4 h) in decreasing concentrations (full, ½, ¼ for 15 min) of bupivacaine, ropivacaine, morphine, M6G or saline control. Adenosine triphosphate content of 798 beads was measured 3 days post-incubation to assess cell viability.

Results

A clear ranking of cytotoxic potency: bupivacaine > ropivacaine > morphine = M6G = saline was observed. Results reveal a dose- and time-dependent manner of cytotoxic effects on human chondrocytes for bupivacaine and ropivacaine but not for opioids. Cell viability after exposure to morphine and M6G was comparable to exposure to saline.

Conclusion

The results confirm dose- and time-dependent cytotoxic effects on human chondrocytes for amide-type local anaesthetics. This study confirms the safety of morphine and M6G in terms of an absence of cytotoxic effects after intra-articular application, making them safe potential alternatives in clinical practice.

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References

  1. Anderson SL, Buchko JZ, Taillon MR, Ernst MA (2010) Chondrolysis of the glenohumeral joint after infusion of bupivacaine through an intra-articular pain pump catheter: a report of 18 cases. Arthroscopy 26:451–461

    Article  PubMed  Google Scholar 

  2. Anz A, Smith MJ, Stoker A et al (2009) The effect of bupivacaine and morphine in a coculture model of diarthrodial joints. Arthroscopy 25:225–231

    Article  PubMed  Google Scholar 

  3. Bailie DS, Ellenbecker TS (2009) Severe chondrolysis after shoulder arthroscopy: a case series. J Shoulder Elb Surg 18:742–747

    Article  Google Scholar 

  4. Boden BP, Fassler S, Cooper S, Marchetto PA, Moyer RA (1994) Analgesic effect of intraarticular morphine, bupivacaine, and morphine/bupivacaine after arthroscopic knee surgery. Arthroscopy 10:104–107

    Article  CAS  PubMed  Google Scholar 

  5. Bogatch MT, Ferachi DG, Kyle B et al (2010) Is chemical incompatibility responsible for chondrocyte death induced by local anesthetics? Am J Sports Med 38:520–526

    Article  PubMed  Google Scholar 

  6. Brandsson S, Karlsson J, Morberg P, Rydgren B, Eriksson BI, Hedner T (2000) Intraarticular morphine after arthroscopic ACL reconstruction: a double-blind placebo-controlled study of 40 patients. Acta Orthop Scand 71:280–285

    Article  CAS  PubMed  Google Scholar 

  7. Campo MM, Kerkhoffs GM, Sierevelt IN, Weeseman RR, Van der Vis HM, Albers GH (2012) A randomised controlled trial for the effectiveness of intra-articular ropivacaine and bupivacaine on pain after knee arthroscopy: the DUPRA (Dutch pain relief after arthroscopy)-trial. Knee Surg Sports Traumatol Arthrosc 20:239–244

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Chaumeron A, Audy D, Drolet P, Lavigne M, Vendittoli PA (2013) Periarticular injection in knee arthroplasty improves quadriceps function. Clin Orthop Relat Res 471:2284–2295

    Article  PubMed Central  PubMed  Google Scholar 

  9. Chen S, Chen Z, Jin Y et al (2013) Pharmacokinetics and efficacy of ropivacaine in Chinese patients following intra-articular administration. Int J Clin Pharmacol Ther 51:393–400

    Article  CAS  PubMed  Google Scholar 

  10. Chen Y, Mestek A, Liu J, Hurley JA, Yu L (1993) Molecular cloning and functional expression of a mu-opioid receptor from rat brain. Mol Pharmacol 44:8–12

    CAS  PubMed  Google Scholar 

  11. Christrup LL (1997) Morphine metabolites. Acta Anaesthesiol Scand 41:116–122

    Article  CAS  PubMed  Google Scholar 

  12. Chu CR, Coyle CH, Chu CT et al (2010) In vivo effects of single intra-articular injection of 0.5% bupivacaine on articular cartilage. J Bone Joint Surg Am 92:599–608

    Article  PubMed  Google Scholar 

  13. Chu CR, Izzo NJ, Coyle CH, Papas NE, Logar A (2008) The in vitro effects of bupivacaine on articular chondrocytes. J Bone Joint Surg Br 90:814–820

    Article  CAS  PubMed  Google Scholar 

  14. Chu CR, Izzo NJ, Papas NE, Fu FH (2006) In vitro exposure to 0.5% bupivacaine is cytotoxic to bovine articular chondrocytes. Arthroscopy 22:693–699

    Article  PubMed  Google Scholar 

  15. Dragoo JL, Korotkova T, Kanwar R, Wood B (2008) The effect of local anesthetics administered via pain pump on chondrocyte viability. Am J Sports Med 36:1484–1488

    Article  PubMed  Google Scholar 

  16. Dragoo JL, Korotkova T, Kim HJ, Jagadish A (2010) Chondrotoxicity of low pH, epinephrine, and preservatives found in local anesthetics containing epinephrine. Am J Sports Med 38:1154–1159

    Article  PubMed  Google Scholar 

  17. Gomoll AH, Yanke AB, Kang RW et al (2009) Long-term effects of bupivacaine on cartilage in a rabbit shoulder model. Am J Sports Med 37:72–77

    Article  PubMed  Google Scholar 

  18. Grishko V, Xu M, Wilson G, Pearsall A (2010) Apoptosis and mitochondrial dysfunction in human chondrocytes following exposure to lidocaine, bupivacaine, and ropivacaine. J Bone Joint Surg Am 92:609–618

    Article  PubMed  Google Scholar 

  19. Gungor I, Yilmaz A, Ozturk AM, Ergun MA, Menevse S, Kaya K (2014) Bupivacaine and levobupivacaine induce apoptosis in rat chondrocyte cell cultures at ultra-low doses. Eur J Orthop Surg Traumatol 24:291–295

    Article  PubMed  Google Scholar 

  20. Gupta A, Bodin L, Holmstrom B, Berggren L (2001) A systematic review of the peripheral analgesic effects of intraarticular morphine. Anesth Analg 93:761–770

    Article  CAS  PubMed  Google Scholar 

  21. Hansen BP, Beck CL, Beck EP, Townsley RW (2007) Postarthroscopic glenohumeral chondrolysis. Am J Sports Med 35:1628–1634

    Article  PubMed  Google Scholar 

  22. Herten M, Rothamel D, Schwarz F, Friesen K, Koegler G, Becker J (2009) Surface- and nonsurface-dependent in vitro effects of bone substitutes on cell viability. Clin Oral Investig 13:149–155

    Article  CAS  PubMed  Google Scholar 

  23. Jaureguito JW, Wilcox JF, Cohn SJ, Thisted RA, Reider B (1995) A comparison of intraarticular morphine and bupivacaine for pain control after outpatient knee arthroscopy. A prospective, randomized, double-blinded study. Am J Sports Med 23:350–353

    Article  CAS  PubMed  Google Scholar 

  24. Kalso E, Smith L, McQuay HJ, Andrew Moore R (2002) No pain, no gain: clinical excellence and scientific rigour-lessons learned from IA morphine. Pain 98:269–275

    Article  CAS  PubMed  Google Scholar 

  25. Karpie JC, Chu CR (2007) Lidocaine exhibits dose- and time-dependent cytotoxic effects on bovine articular chondrocytes in vitro. Am J Sports Med 35:1621–1627

    Article  PubMed  Google Scholar 

  26. Liguori GA, Chimento GF, Borow L, Figgie M (2002) Possible bupivacaine toxicity after intraarticular injection for postarthroscopic analgesia of the knee: implications of the surgical procedure. Anesth Analg 94:1010–1013

    Article  PubMed  Google Scholar 

  27. Lo IK, Sciore P, Chung M et al (2009) Local anesthetics induce chondrocyte death in bovine articular cartilage disks in a dose- and duration-dependent manner. Arthroscopy 25:707–715

    Article  PubMed  Google Scholar 

  28. Malik S, Ullah S, Afzal M, Lal K, Haque S (2013) Clinical and descriptive genetic study of polydactyly: a Pakistani experience of 313 cases. Clin Genet. doi:10.1111/cge.12217

    Google Scholar 

  29. Piper SL, Kim HT (2008) Comparison of ropivacaine and bupivacaine toxicity in human articular chondrocytes. J Bone Joint Surg Am 90:986–991

    Article  PubMed  Google Scholar 

  30. Seok HH, Park JU, Kwon ST (2013) New classification of polydactyly of the foot on the basis of syndactylism, axis deviation, and metatarsal extent of extra digit. Arch Plast Surg 40:232–237

    Article  PubMed Central  PubMed  Google Scholar 

  31. Serrato JA Jr, Fleckenstein CM, Hasan SS (2011) Glenohumeral chondrolysis associated with use of an intra-articular pain pump delivering local anesthetics following manipulation under anesthesia: a report of four cases. J Bone Joint Surg Am 93:91–98

    Google Scholar 

  32. Seshadri V, Coyle CH, Chu CR (2009) Lidocaine potentiates the chondrotoxicity of methylprednisolone. Arthroscopy 25:337–347

    Article  PubMed  Google Scholar 

  33. Stein C, Comisel K, Haimerl E et al (1991) Analgesic effect of intraarticular morphine after arthroscopic knee surgery. N Engl J Med 325:1123–1126

    Article  CAS  PubMed  Google Scholar 

  34. Tanaka H, Matsumura M, Veliky IA (1984) Diffusion characteristics of substrates in Ca-alginate gel beads. Biotechnol Bioeng 26:53–58

    Article  CAS  PubMed  Google Scholar 

  35. van Dorp EL, Kest B, Kowalczyk WJ et al (2009) Morphine-6beta-glucuronide rapidly increases pain sensitivity independently of opioid receptor activity in mice and humans. Anesthesiology 110:1356–1363

    Article  PubMed  Google Scholar 

  36. van Dorp EL, Morariu A, Dahan A (2008) Morphine-6-glucuronide: potency and safety compared with morphine. Expert Opin Pharmacother 9:1955–1961

    Article  PubMed  Google Scholar 

  37. van Dorp EL, Romberg R, Sarton E, Bovill JG, Dahan A (2006) Morphine-6-glucuronide: morphine’s successor for postoperative pain relief? Anesthes Analg 102:1789–1797

    Article  Google Scholar 

  38. Wang JB, Imai Y, Eppler CM, Gregor P, Spivak CE, Uhl GR (1993) mu opiate receptor: cDNA cloning and expression. Proc Nat Acad Sci USA 90:10230–10234

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Wang X, Jia D, Chen X, Xu Y (2013) Comparison of intra-articular low-dose sufentanil, ropivacaine, and combined sufentanil and ropivacaine on post-operative analgesia of isolated anterior cruciate ligament reconstruction. Knee Surg Sports Traumatol Arthrosc 21:1140–1145

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The present study was financed by a research grant to the Orthopedic Department of the University from the Research Commission of the Medical Faculty University Düsseldorf, Germany.

Conflict of interest

None of the authors have any financial and personal relationships with other people or organizations that could potentially and inappropriately influence (bias) the present manuscript and conclusions.

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Correspondence to Monika Herten.

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Ickert, I., Herten, M., Vogl, M. et al. Opioids as an alternative to amide-type local anaesthetics for intra-articular application. Knee Surg Sports Traumatol Arthrosc 23, 2674–2681 (2015). https://doi.org/10.1007/s00167-014-2989-2

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  • DOI: https://doi.org/10.1007/s00167-014-2989-2

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