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The effect of Lidocaine on the viability of cultivated mature human cartilage cells: an in vitro study

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

Abstract

Purpose

More and more orthopedic procedures are performed in an outpatient setting. A commonly used strategy in pain management is the intra-articular injection of local anesthetics. Recent attention has been drawn to their possible toxic effect on chondrocytes. Local anesthetics, and in particular Lidocaine, are also used for diagnostic joint infiltrations. A controlled laboratory study was performed to investigate the possible toxic effect of Lidocaine on human articular chondrocytes.

Methods

Mature human articular chondrocytes were harvested from the knees of human tissue donors or patients undergoing total knee replacement. The cells were exposed to Lidocaine 1 and 2% with and without epinephrine and to a saline 0.9% control group, with variable exposure times in different experiments. The activity and viability of the cells were assessed by lactate dehydrogenase activity, interleukin-6 production and a live/dead cell count.

Results

After a 1-h exposure, devastating results were seen for Lidocaine 1, 2 and 2% with epinephrine showing cell death rates of 91, 99 and 97%, respectively, compared with 26% in the saline control group (P-values of 0.004, 0.010, 0.006, respectively).

Exposing the chondrocytes to a 50/50 mixture of culture medium and local anesthetics substantially decreased cytotoxicity but still showed high toxicity when compared with the saline group (90% dead cells for Lidocaine 2%, P = 0.047). Lidocaine also showed a time-dependent cytotoxicity with gradually more dead cells after exposure for 15, 30 or 60 min.

Conclusion

In vitro, local anesthetics containing Lidocaine are significantly more toxic to mature human articular chondrocytes than a saline 0.9% control group. The effect of Lidocaine on the viability of human chondrocytes in vivo needs further investigation. However, based on our in vitro results, cautious use of intra-articular Lidocaine in clinical practice is recommended.

Level of evidence

Prospective, comparative therapeutic study, Level II.

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References

  1. Alagol A, Calpur OU, Usar PS, Turan N, Pamukcu Z (2005) Intraarticular analgesia after arthroscopic knee surgery: comparison of neostigmine, clonidine, tenoxicam, morphine and bupivacaine. Knee Surg Sports Traumatol Arthrosc 13(8):658–663

    Article  PubMed  CAS  Google Scholar 

  2. Axelsson K, Gupta A, Johanzon E, Berg E, Ekback G, Rawal N, Enstrom P, Nordensson U (2008) Intraarticular administration of ketorolac, morphine, and ropivacaine combined with intraarticular patient-controlled regional analgesia for pain relief after shoulder surgery: a randomized, double-blind study. Anesth Analg 106(1):328–333

    Article  PubMed  CAS  Google Scholar 

  3. Bailie DS, Ellenbecker TS (2009) Severe chondrolysis after shoulder arthroscopy: a case series. J Shoulder Elbow Surg 18(5):742–747

    Article  PubMed  Google Scholar 

  4. Ballieul RJ, Jacobs TF, Herregods S, Van Sint Jan P, Wyler B, Vereecke H, Almqvist F, Herregods L (2009) The peri-operative use of intra-articular local anesthetics: a review. Acta Anaesthesiol Belg 60(2):101–108

    PubMed  CAS  Google Scholar 

  5. Banerjee SS, Pulido P, Adelson WS, Fronek J, Hoenecke HR (2008) The efficacy of continuous bupivacaine infiltration following arthroscopic rotator cuff repair. Arthroscopy 24(4):397–402

    Article  PubMed  Google Scholar 

  6. Barber FA, Herbert MA (2002) The effectiveness of an anesthetic continuous-infusion device on postoperative pain control. Arthroscopy 18(1):76–81

    Article  PubMed  Google Scholar 

  7. Benya PD, Brown PD, Padilla SR (1988) Microfilament modification by dihydrocytochalasin B causes retinoic acid-modulated chondrocytes to reexpress the differentiated collagen phenotype without a change in shape. J Cell Biol 106(1):161–170

    Article  PubMed  CAS  Google Scholar 

  8. Berger RA, Kusuma SK, Sanders SA, Thill ES, Sporer SM (2009) The feasibility and perioperative complications of outpatient knee arthroplasty. Clin Orthop Relat Res 467(6):1443–1449

    Article  PubMed  Google Scholar 

  9. Chu CR, Coyle CH, Chu CT, Szczodry M, Seshadri V, Karpie JC, Cieslak KM, Pringle EK (2010) In vivo effects of single intra-articular injection of 0.5% bupivacaine on articular cartilage. J Bone Joint Surg Am 92(3):599–608

    Article  PubMed  Google Scholar 

  10. 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(6):814–820

    Article  PubMed  CAS  Google Scholar 

  11. Chu CR, Izzo NJ, Papas NE, Fu FH (2006) In vitro exposure to 0.5% bupivacaine is cytotoxic to bovine articular chondrocytes. Arthroscopy 22(7):693–699

    Article  PubMed  Google Scholar 

  12. Decker T, Lohmann-Matthes ML (1988) A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity. J Immunol Methods 115(1):61–69

    Article  PubMed  CAS  Google Scholar 

  13. 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(8):1484–1488

    Article  PubMed  Google Scholar 

  14. 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(6):1154–1159

    Article  PubMed  Google Scholar 

  15. Gomoll AH, Kang RW, Williams JM, Bach BR, Cole BJ (2006) Chondrolysis after continuous intra-articular bupivacaine infusion: an experimental model investigating chondrotoxicity in the rabbit shoulder. Arthroscopy 22(8):813–819

    Article  PubMed  Google Scholar 

  16. Green WT Jr (1971) Behavior of articular chondrocytes in cell culture. Clin Orthop Relat Res 75:248–260

    Article  PubMed  Google Scholar 

  17. Grishko V, Xu M, Wilson G, AWt Pearsall (2010) Apoptosis and mitochondrial dysfunction in human chondrocytes following exposure to lidocaine, bupivacaine, and ropivacaine. J Bone Joint Surg Am 92(3):609–618

    Article  PubMed  Google Scholar 

  18. Guerne PA, Carson DA, Lotz M (1990) IL-6 production by human articular chondrocytes. Modulation of its synthesis by cytokines, growth factors, and hormones in vitro. J Immunol 144(2):499–505

    PubMed  CAS  Google Scholar 

  19. Guo JF, Jourdian GW, MacCallum DK (1989) Culture and growth characteristics of chondrocytes encapsulated in alginate beads. Connect Tissue Res 19(2–4):277–297

    Article  PubMed  CAS  Google Scholar 

  20. Hansen BP, Beck CL, Beck EP, Townsley RW (2007) Postarthroscopic glenohumeral chondrolysis. Am J Sports Med 35(10):1628–1634

    Article  PubMed  Google Scholar 

  21. Henrotin YE, De Groote DD, Labasse AH, Gaspar SE, Zheng SX, Geenen VG, Reginster JY (1996) Effects of exogenous IL-1 beta, TNF alpha, IL-6, IL-8 and LIF on cytokine production by human articular chondrocytes. Osteoarthritis Cartilage 4(3):163–173

    Article  PubMed  CAS  Google Scholar 

  22. Karpie JC, Chu CR (2007) Lidocaine exhibits dose- and time-dependent cytotoxic effects on bovine articular chondrocytes in vitro. Am J Sports Med 35(10):1621–1627

    Article  PubMed  Google Scholar 

  23. Legrand C, Bour JM, Jacob C, Capiaumont J, Martial A, Marc A, Wudtke M, Kretzmer G, Demangel C, Duval D et al (1992) Lactate dehydrogenase (LDH) activity of the cultured eukaryotic cells as marker of the number of dead cells in the medium [corrected]. J Biotechnol 25(3):231–243

    Article  PubMed  CAS  Google Scholar 

  24. Levy JC, Frankle M (2008) Bilateral shoulder chondrolysis following arthroscopy. A report of two cases. J Bone Joint Surg Am 90(11):2546–2547 author reply 2547–2548

    PubMed  Google Scholar 

  25. Levy JC, Virani NA, Frankle MA, Cuff D, Pupello DR, Hamelin JA (2008) Young patients with shoulder chondrolysis following arthroscopic shoulder surgery treated with total shoulder arthroplasty. J Shoulder Elbow Surg 17(3):380–388

    Article  PubMed  Google Scholar 

  26. Lo IK, Sciore P, Chung M, Liang S, Boorman RB, Thornton GM, Rattner JB, Muldrew K (2009) Local anesthetics induce chondrocyte death in bovine articular cartilage disks in a dose- and duration-dependent manner. Arthroscopy 25(7):707–715

    Article  PubMed  Google Scholar 

  27. Masuda K, Sah RL, Hejna MJ, Thonar EJ (2003) A novel two-step method for the formation of tissue-engineered cartilage by mature bovine chondrocytes: the alginate-recovered-chondrocyte (ARC) method. J Orthop Res 21(1):139–148

    Article  PubMed  CAS  Google Scholar 

  28. Pelissier P, Svartz L, Rakotondriamihary S, Nouette-Gaulin K, Dousset V (2008) Postoperative analgesia with continuous intra-articular infusion of ropivacaine following trapeziectomy. Chir Main 27(5):222–226

    Article  PubMed  CAS  Google Scholar 

  29. Piper SL, Kim HT (2008) Comparison of ropivacaine and bupivacaine toxicity in human articular chondrocytes. J Bone Joint Surg Am 90(5):986–991

    Article  PubMed  Google Scholar 

  30. Saltzman M, Mercer D, Bertelsen A, Warme W, Matsen F (2009) Postsurgical chondrolysis of the shoulder. Orthopedics 32(3):215

    Article  PubMed  Google Scholar 

  31. Seshadri V, Coyle CH, Chu CR (2009) Lidocaine potentiates the chondrotoxicity of methylprednisolone. Arthroscopy 25(4):337–347

    Article  PubMed  Google Scholar 

  32. Verbruggen G, Veys EM, Wieme N, Malfait AM, Gijselbrecht L, Nimmegeers J, Almquist KF, Broddelez C (1990) The synthesis and immobilisation of cartilage-specific proteoglycan by human chondrocytes in different concentrations of agarose. Clin Exp Rheumatol 8(4):371–378

    PubMed  CAS  Google Scholar 

  33. Verbruggen G, Wang J, Wang L, Elewaut D, Veys EM (2004) Analysis of chondrocyte functional markers and pericellular matrix components by flow cytometry. Methods Mol Med 100:183–208

    PubMed  CAS  Google Scholar 

  34. Wang J, Verdonk P, Elewaut D, Veys EM, Verbruggen G (2003) Homeostasis of the extracellular matrix of normal and osteoarthritic human articular cartilage chondrocytes in vitro. Osteoarthritis Cartilage 11(11):801–809

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

Study was completed with the support from the Research Grant Program of the Society for Anesthesia and Resuscitation of Belgium. Special thanks to the department of Rheumatology for lending us the necessary equipment and infrastructure.

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Correspondence to Tom F. Jacobs.

Additional information

Dr. T. F. Jacobs and Dr. P. S. Vansintjan have contributed equally to this article.

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Jacobs, T.F., Vansintjan, P.S., Roels, N. et al. The effect of Lidocaine on the viability of cultivated mature human cartilage cells: an in vitro study. Knee Surg Sports Traumatol Arthrosc 19, 1206–1213 (2011). https://doi.org/10.1007/s00167-011-1420-5

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  • DOI: https://doi.org/10.1007/s00167-011-1420-5

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