Skip to main content
Erschienen in: Knee Surgery, Sports Traumatology, Arthroscopy 7/2011

01.07.2011 | Experimental Study

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

verfasst von: Tom F. Jacobs, Pieter S. Vansintjan, Nathalie Roels, Sofie S. Herregods, Gust Verbruggen, Luc L. Herregods, Karl F. Almqvist

Erschienen in: Knee Surgery, Sports Traumatology, Arthroscopy | Ausgabe 7/2011

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat 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):658–663PubMedCrossRef 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):658–663PubMedCrossRef
2.
Zurück zum Zitat 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):328–333PubMedCrossRef 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):328–333PubMedCrossRef
3.
Zurück zum Zitat Bailie DS, Ellenbecker TS (2009) Severe chondrolysis after shoulder arthroscopy: a case series. J Shoulder Elbow Surg 18(5):742–747PubMedCrossRef Bailie DS, Ellenbecker TS (2009) Severe chondrolysis after shoulder arthroscopy: a case series. J Shoulder Elbow Surg 18(5):742–747PubMedCrossRef
4.
Zurück zum Zitat 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):101–108PubMed 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):101–108PubMed
5.
Zurück zum Zitat 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):397–402PubMedCrossRef 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):397–402PubMedCrossRef
6.
Zurück zum Zitat Barber FA, Herbert MA (2002) The effectiveness of an anesthetic continuous-infusion device on postoperative pain control. Arthroscopy 18(1):76–81PubMedCrossRef Barber FA, Herbert MA (2002) The effectiveness of an anesthetic continuous-infusion device on postoperative pain control. Arthroscopy 18(1):76–81PubMedCrossRef
7.
Zurück zum Zitat 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):161–170PubMedCrossRef 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):161–170PubMedCrossRef
8.
Zurück zum Zitat 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):1443–1449PubMedCrossRef 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):1443–1449PubMedCrossRef
9.
Zurück zum Zitat 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):599–608PubMedCrossRef 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):599–608PubMedCrossRef
10.
Zurück zum Zitat 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):814–820PubMedCrossRef 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):814–820PubMedCrossRef
11.
Zurück zum Zitat 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):693–699PubMedCrossRef 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):693–699PubMedCrossRef
12.
Zurück zum Zitat 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):61–69PubMedCrossRef 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):61–69PubMedCrossRef
13.
Zurück zum Zitat 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):1484–1488PubMedCrossRef 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):1484–1488PubMedCrossRef
14.
Zurück zum Zitat 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):1154–1159PubMedCrossRef 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):1154–1159PubMedCrossRef
15.
Zurück zum Zitat 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):813–819PubMedCrossRef 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):813–819PubMedCrossRef
16.
Zurück zum Zitat Green WT Jr (1971) Behavior of articular chondrocytes in cell culture. Clin Orthop Relat Res 75:248–260PubMedCrossRef Green WT Jr (1971) Behavior of articular chondrocytes in cell culture. Clin Orthop Relat Res 75:248–260PubMedCrossRef
17.
Zurück zum Zitat 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):609–618PubMedCrossRef 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):609–618PubMedCrossRef
18.
Zurück zum Zitat 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):499–505PubMed 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):499–505PubMed
19.
Zurück zum Zitat Guo JF, Jourdian GW, MacCallum DK (1989) Culture and growth characteristics of chondrocytes encapsulated in alginate beads. Connect Tissue Res 19(2–4):277–297PubMedCrossRef Guo JF, Jourdian GW, MacCallum DK (1989) Culture and growth characteristics of chondrocytes encapsulated in alginate beads. Connect Tissue Res 19(2–4):277–297PubMedCrossRef
20.
Zurück zum Zitat Hansen BP, Beck CL, Beck EP, Townsley RW (2007) Postarthroscopic glenohumeral chondrolysis. Am J Sports Med 35(10):1628–1634PubMedCrossRef Hansen BP, Beck CL, Beck EP, Townsley RW (2007) Postarthroscopic glenohumeral chondrolysis. Am J Sports Med 35(10):1628–1634PubMedCrossRef
21.
Zurück zum Zitat 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):163–173PubMedCrossRef 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):163–173PubMedCrossRef
22.
Zurück zum Zitat 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):1621–1627PubMedCrossRef 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):1621–1627PubMedCrossRef
23.
Zurück zum Zitat 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):231–243PubMedCrossRef 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):231–243PubMedCrossRef
24.
Zurück zum Zitat 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 2547–2548PubMed 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 2547–2548PubMed
25.
Zurück zum Zitat 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):380–388PubMedCrossRef 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):380–388PubMedCrossRef
26.
Zurück zum Zitat 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):707–715PubMedCrossRef 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):707–715PubMedCrossRef
27.
Zurück zum Zitat 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):139–148PubMedCrossRef 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):139–148PubMedCrossRef
28.
Zurück zum Zitat 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):222–226PubMedCrossRef 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):222–226PubMedCrossRef
29.
Zurück zum Zitat Piper SL, Kim HT (2008) Comparison of ropivacaine and bupivacaine toxicity in human articular chondrocytes. J Bone Joint Surg Am 90(5):986–991PubMedCrossRef Piper SL, Kim HT (2008) Comparison of ropivacaine and bupivacaine toxicity in human articular chondrocytes. J Bone Joint Surg Am 90(5):986–991PubMedCrossRef
30.
Zurück zum Zitat Saltzman M, Mercer D, Bertelsen A, Warme W, Matsen F (2009) Postsurgical chondrolysis of the shoulder. Orthopedics 32(3):215PubMedCrossRef Saltzman M, Mercer D, Bertelsen A, Warme W, Matsen F (2009) Postsurgical chondrolysis of the shoulder. Orthopedics 32(3):215PubMedCrossRef
31.
Zurück zum Zitat Seshadri V, Coyle CH, Chu CR (2009) Lidocaine potentiates the chondrotoxicity of methylprednisolone. Arthroscopy 25(4):337–347PubMedCrossRef Seshadri V, Coyle CH, Chu CR (2009) Lidocaine potentiates the chondrotoxicity of methylprednisolone. Arthroscopy 25(4):337–347PubMedCrossRef
32.
Zurück zum Zitat 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):371–378PubMed 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):371–378PubMed
33.
Zurück zum Zitat 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 100:183–208PubMed 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 100:183–208PubMed
34.
Zurück zum Zitat 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):801–809PubMedCrossRef 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):801–809PubMedCrossRef
Metadaten
Titel
The effect of Lidocaine on the viability of cultivated mature human cartilage cells: an in vitro study
verfasst von
Tom F. Jacobs
Pieter S. Vansintjan
Nathalie Roels
Sofie S. Herregods
Gust Verbruggen
Luc L. Herregods
Karl F. Almqvist
Publikationsdatum
01.07.2011
Verlag
Springer-Verlag
Erschienen in
Knee Surgery, Sports Traumatology, Arthroscopy / Ausgabe 7/2011
Print ISSN: 0942-2056
Elektronische ISSN: 1433-7347
DOI
https://doi.org/10.1007/s00167-011-1420-5

Weitere Artikel der Ausgabe 7/2011

Knee Surgery, Sports Traumatology, Arthroscopy 7/2011 Zur Ausgabe

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Mehr Frauen im OP – weniger postoperative Komplikationen

21.05.2024 Allgemeine Chirurgie Nachrichten

Ein Frauenanteil von mindestens einem Drittel im ärztlichen Op.-Team war in einer großen retrospektiven Studie aus Kanada mit einer signifikanten Reduktion der postoperativen Morbidität assoziiert.

TEP mit Roboterhilfe führt nicht zu größerer Zufriedenheit

15.05.2024 Knie-TEP Nachrichten

Der Einsatz von Operationsrobotern für den Einbau von Totalendoprothesen des Kniegelenks hat die Präzision der Eingriffe erhöht. Für die postoperative Zufriedenheit der Patienten scheint das aber unerheblich zu sein, wie eine Studie zeigt.

Lever-Sign-Test hilft beim Verdacht auf Kreuzbandriss

15.05.2024 Vordere Kreuzbandruptur Nachrichten

Mit dem Hebelzeichen-Test lässt sich offenbar recht zuverlässig feststellen, ob ein vorderes Kreuzband gerissen ist. In einer Metaanalyse war die Vorhersagekraft vor allem bei positivem Testergebnis hoch.

Ein Drittel der jungen Ärztinnen und Ärzte erwägt abzuwandern

07.05.2024 Klinik aktuell Nachrichten

Extreme Arbeitsverdichtung und kaum Supervision: Dr. Andrea Martini, Sprecherin des Bündnisses Junge Ärztinnen und Ärzte (BJÄ) über den Frust des ärztlichen Nachwuchses und die Vorteile des Rucksack-Modells.

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.