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Bupivacaine associated chondrolysis after arthroscopic surgery of the shoulder: A review of the current literature

Michael S. Kelleher, MS,1 Carl W. Nissen, MD,2 and Emily A. O’Hara, MS, MA2

1University of Connecticut School of Medicine Farmington, Connecticut 06030

2Elite Sports Medicine Connecticut Children’s Medical Center Farmington, Connecticut 06032  


Address for Correspondence

Carl W. Nissen, MD

Elite Sports Medicine

399 Farmington Avenue

Farmington, CT 06032


Phone: 860-284-0220

Fax: 860-284-0221




Background: Multiple reports in the literature have linked bupivacaine infusion after arthroscopic shoulder procedures with subsequent chondrolysis. We conducted a systematic review of the current literature to evaluate these reports of bupivacaine associated chondrotoxicity in order to identify commonalities among patients who developed chondrolysis. This review expands the bupivacaine literature via increased knowledge regarding associative complications with the hope of avoiding these complications in the future.

Methods: A PubMed search was conducted which identified 5 articles reporting 56 cases of bupivacaine associated chondrolysis.

Results: The average reported patient age was 30.0 years (range of 15-47) at the time of surgery with a male to female ratio of 2.7 to 1. Of the 56 cases identified, 34 of these patients had Bankart procedures and 10 had SLAP repairs. The average onset of chondrolysis after bupivacaine exposure was 7.9 months (range of 2-27.5 months). 93% of cases were associated with constant infusion of bupivacaine. Further, chondrolysis was much more prevalent at high flow rates (greater than 4ml/hr).

Conclusion: Cases of chondrolysis were most likely to be seen with catheter placement in the glenohumeral joint and at high flow rates. The actual dose of bupivacaine had less of an impact on chondrolysis. Based on case reports and in vitro data, the use of constant infusions of bupivacaine cannot be supported. Further, the safety of a one time intraarticular injection of bupivacaine is put into question based on the results of the present study.


J.Orthopaedics 2012;9(4)e7


Chondrolysis; shoulder; glenohumeral; pain pump; arthroscopy

Word count: 2336


Chondrolysis is defined as the loss of articular cartilage due to the dissolution of chondrocytes and the cartilaginous matrix.[1] This pathological change can be diagnosed using a combination of history, physical exam findings, and radiographic evidence. Patients with chondrolysis often will have increasing post-operative pain, joint stiffness and crepitus detected on physical exam, and radiographic indications of joint space narrowing, subchondral sclerosis and cyst

formation.[2-4] Multiple studies have demonstrated the efficacy of constant infusions of bupivacaine at reducing post-operative pain and reducing the need for narcotics.[5,6] Despite its efficacy, the safety of bupivacaine is uncertain given a number of recent reports associating its use in constant infusion pumps with subsequent chondrotoxicity.[2-4,7] Further, multiple in vitro studies and animal models support the association between bupivacaine and chondrotoxicity.[8-14]

To further understand the relationship between bupivacaine and chondrolysis, a systematic review was conducted in order to identify reports of chondrolysis seen in patients post-operatively. The purpose of this study is to identify commonalities among the reported cases of chondrolysis in humans with the hope of improving patient care through avoiding future cases of chondrolysis.


Materials and methods:

A PubMed search was conducted using the following term “((bupivacaine) AND (chondrotoxicity OR chondrolysis)).” The initial search identified 17 articles and 12 articles were excluded (2 editorials, 2 reviews, and 8 studies conducted using animals or in vitro). As a result, 5 articles were included for review.

The following parameters were recorded for each of the 5 articles: number of cases of chondrolysis, patient sex, age, onset of chondrolysis, use of bupivacaine infusion, use of bupivacaine injection, use of epinephrine, and catheter placement. Further, the incidence of chondrolysis was identified.


Results :

In terms of patient demographics, 56 cases of chondrolysis were reported in total with an average patient age of 30.0 years (Table 1). On average, patients presented with chondrolysis 7.9 months post-operatively, and the two most common surgeries performed were the Bankart procedure (n=34) and SLAP repair (n=10).

Table 1 Cumulative Study Characteristics (N = 56)







Age (years)






Onset of chondrolysis (months)






Surgical Procedures


   SLAP Repairs

   Capsular Shifts

   Capsular Plication

   Posterior Labral Repairs

   Idiopathic Frozen Should Repair

   MDI with chondral blisters

   Glenohumeral catheter placement

   Subacromial catheter placement










Percent of bupivacaine infusion

   0.25% at 2.08 ml/h

   0.25% at 4.16 ml/h

   0.50% at 2.00 ml/h

   0.50% at 2.08 ml/h

   0.50% at 4.16 ml/h

   0.50% at 5.00 ml/h

   0.25% or 0.50% (no ml/h specified)

Cases associated with:

   Pain pump

   Presence of epinephrine infusion

   Absence of epinephrine infusion   














Fifty-two (52) out of 56 cases were associated with constant infusion of bupivacaine with 96% of these patients receiving bupivacaine at a high flow rate (greater than 4ml/hour). In terms of bupivacaine concentration, no cases of chondrolysis were seen with 0.25% bupivacaine at low flow rates (2ml/hour) compared to 2 cases with 0.5% bupivacaine at a low flow rate. However, 29 cases of chondrolysis were associated with 0.25% bupivacaine at a high flow rate.

Of the chondrolysis cases occurring with constant infusions pain pumps, 72% included epinephrine with the bupivacaine making it difficult to determine if the bupivacaine alone was the cause of the chondrolysis or if the epinephrine either potentiated or affected the result in any way. The pain pump catheter was placed in the glenohumeral joint in 98% of the cases with one catheter placed in the subacromial space. Comparing the five study results is somewhat difficult as each determined the presence or absence of chondrolysis based on different criteria, including a combination of history, physical exam, and imaging findings as outlined in Table 2. Each study was careful to rule out infection, as a potential cause for chondrolysis in their patients. Additionally, in terms of intra-articular injection of bupivacaine, 36 patients received an injection of 0.25 or 0.5% bupivacaine with or without epinephrine depending on the study (Table 2). Four out of 56 cases of chondrolysis did not receive a constant infusion of bupivacaine, but did have an injection of 0.25% bupivacaine with epinephrine post-operatively.


Table 2. Individual Study Characteristics 



Male/ Female

Mean Age (range)

Mean Onset (range)

Bupivacaine Infusion


Catheter Placement

Anakwenze et al.[1]



22.5 (19-26)

Not reported

Yes (no details provided)


Not reported

Anderson et al.[4]



23.8 (16-39)

9.5 (2-27.5)

0.5% with epinephrine

16 at 5ml/hr

2 at 2ml/hr

0.25% or 0.5% bupivacaine with epinephrine


Bailie et al.[2]



(4 patients not reported)

30.5 (15-47)

9.1 (8-12)

17 had 0.25% without epinephrine at 4.16ml/hr

4 had 0.25% bupivacaine with epinephrine

16 Glenohumeral 

1 Subacromial

Hansen et al.[3]


Not reported

28.9 (16-47)

4.3 (3-13)

0.25% with epinephrine at 4.16ml/h

0.25% bupivacaine with epinephrine and 5mg morphine


Rapley et al.[7]


Not reported

Not reported

7.75 (3.5-12)

0.5% without epinephrine at 4.16ml/hr




The individual study patient’s were similar, as the majority of patients in each were in their 20s and 30s (Table 2), underwent similar procedures (mainly Bankart and SLAP) (Table 3), and all infusions were given for 48 hours.


Table 3. Surgical Procedures Performed in Individual Studies



  Anakwenze et al.[1]

1 Capsular Plication

1 Posterior Labral Repair

Anderson et al.[4]

18 Bankart Procedures

1 SLAP Repair (1 patient had Bankart and SLAP)

Bailie et al.[2]

8 SLAP Repairs

5 Bankart Procedures

1 Repair for MDI with chondral blisters

1 Frozen Shoulder Release

1 Posterior Labral Repair

1 Post-operative rotator cuff repair

Hansen et al.[3]

9 Bankart Procedures

5 Capsular Shifts

1 SLAP Repair

Rapley et al.[7]

2 Bankart Procedures

2 Capsular Plications (1 patient had Bankart and Capsular Plication)



The results of this study demonstrated an association between the constant infusion of bupivacaine at high flow rates and subsequent chondrotoxicity; however, the exact incidence of chondrotoxicity warrants further investigation. Anderson et al. conducted a self-study of all their surgeries performed from which the patients with chondrolysis were identified.[4] The authors identified 32 patients who had similar surgeries and received a constant infusion of 0.5% bupivacaine with epinephrine at a high flow rate, and 12 patients who received the same dose but at a low flow rate. According to their study, the incidence of chondrolysis was 50% (16 out of 32) in the high bupivacaine flow group and 16.7% (2 out of 12) in the low bupivacaine flow group. This finding is inconsistent with Rapley et al. who reported 3 cases of chondrolysis at high flow rates at the glenohumeral joint.[7] In their study, the incidence of chondrolysis was 0% at either flow rate at the subacromial space and at low flow rates at the glenohumeral space and 18.8% (3 out of 16 cases) at high flow rates at the glenohumeral joint. Hansen et al. identified 30 patients that underwent arthroscopic surgery of the glenohumeral joint and received a constant infusion of 0.25% bupivacaine with epinephrine at a high flow rate.[3] As a result, the incidence of chondrolysis in their study is 40% (12 out of 30 cases). The other two studies by Bailie et al. and Anakwenze did not report an incidence of chondrolysis in their studies.[1,2] In aggregate, in the three studies which reported an incidence, average incidence of bupivacaine associated chondrolysis in the glenohumeral joint at low flow rates was 8% (2 out of 25 cases) and 40% (31 out of 78 cases) at high flow rates.

While there are limitations in the literature dedicated to human prevalence of bupivacaine associated chondrotoxicity, recent human ex plant studies as well as animal studies have been conducted investigating the connection between bupivacaine and chondrocyte viability. Dragoo et al. conducted a study where they exposed human articular cartilage in vitro to a constant infusion of 0.25% bupivacaine at 1ml/hr with and without epinephrine for 24 hours.[8] Consistent with the findings of this review, the authors reported no decrease in chondrocyte viability after this amount of time. Bogatch et al. exposed bovine chondrocytes to 0.25 and 0.5% bupivacaine with and without epinephrine and found a small but significant decrease in chondrocyte viability after exposure to anesthetic alone.[9] The investigators then bathed chondrocytes in synovial fluid and exposed the chondrocytes to bupivacaine for one hour, which resulted in a large and significant decrease in cell viability. Bogatch et al. concluded that the chondrotoxic effect of bupivacaine might in part be related to the interaction of bupivacaine with components of synovial fluid.[9] Gomoll et al.

infused rabbit shoulders with 0.25% bupivacaine also with and without epinephrine for 48 hours at 4.16ml/hr.[12] The investigators then analyzed each joint 3 months later and found no difference in cell viability, yet noted a significant increase in phosphatidylglycerol content and elevated sulfa uptake in chondrocytes exposed to bupivacaine, indicating that there was initially chondrocyte damage with subsequent repair. The authors explain that the rabbit glenohumeral joint has a chondrocyte density 8-10 times that of a human, which may have allowed for repair. Despite the lack of chondrocyte death reported in this study, it supports the findings in the present review that high flow bupivacaine is deleterious to chondrocytes. Dragoo et al. analyzed the effect of a constant infusion of 0.25% and 0.5% bupivacaine with and without epinephrine on human chondrocytes in vivo at various time points.[13] The authors report significant chondrocyte death at all time points for both doses of bupivacaine with epinephrine and significant death in chondrocytes exposed to 0.5% bupivacaine for 72 hours. This study supports the link between chondrotoxicity and bupivacaine in both a dose and time dependent fashion. Further, it indicates that the presence of epinephrine amplifies the chondrotoxic effect of bupivacaine. This is particularly relevant to the present review as some of the studies included epinephrine in their constant infusions but the true effect of adding epinephrine to intra-articular injections or as a part of pain pump infusions in humans is still unknown.

As this study demonstrates there does appear to be a link between chondrolysis and constant infusions of bupivacaine. In addition to this association, recent studies have indicated that single injections of bupivacaine may be chondrotoxic as well. Chu et al. exposed bovine and human chondrocytes to concentrations of 0.125%, 0.25% and 0.5% bupivacaine for varying amounts of time.[14] The authors found that >95% of human chondrocytes were dead after 30 minutes of exposure to 0.5% bupivacaine. Further, there was a 41% reduction in cell viability after 1 week in chondrocytes exposed to 0.25% bupivacaine for 15 minutes and the authors concluded a clear dose and time dependent chondrotoxic effect of a single exposure of bupivacaine to chondrocytes in vitro. Interestingly, there was no decrease in chondrocyte viability with exposure to 0.125% bupivacaine. Anz et al. did a similar study where they exposed chondrocytes to a single injection of 0.5% bupivacaine.[11] Two days after exposure, there was nearly a 100% decrease in chondrocyte viability. Recently Chu and colleagues conducted a study in rats where they gave a single injection of 0.5% bupivacaine at the knee and measured chondrocyte viability at 6 months.[10] This study showed a reduced density of chondrocytes at this time point. These studies support the 4 cases of bupivacaine associated chondrolysis that were identified in this review. In each of these cases, patients received an injection of 20-30ml of 0.25% bupivacaine post-operatively in the glenohumeral joint. Given that a single injections of bupivacaine post-operatively is often done, more research needs to be done looking into the association between single injections of bupivacaine and subsequent chondrolysis.

The current review does have some limitations. One of the major problems is that the exact number of patients with bupivacaine associated chondrotoxicity is unknown, as the definition of chondrolysis varies between studies and each of the references studies were retrospective in nature introducing the possibility of recall and selection biases. Since the association between bupivacaine and chondrolysis in the shoulder does appear to exist, the likelihood of determining the exact nature of the association is unlikely to be fully determined.


Based on the results of the present review, the use of constant infusions of bupivacaine at high flow rates is concerning. Further, given the four reports of chondrolysis associated with single injections of 0.25% bupivacaine identified in this study, coupled with the in vitro data, the safety of intra-articular bupivacaine use in the shoulder in general is a concern. More studies are needed on the effects of bupivacaine on chondrocyte viability.


  1. Anakwenze OA, Hosalkar H, Huffman GR. Case reports: two cases of glenohumeral chondrolysis after intraarticular pain pumps. Clin Orthop Relat Res. 2010: 468:2545-9.

    2. Bailie DS, Ellenbecker TS. Severe chondrolysis after shoulder arthroscopy: a case series. J Shoulder Elbow Surg. 2009;18:742-7.

    3. Hansen BP, Beck CL, Beck EP, Townsley RW. Postarthroscopic glenohumeral chondrolysis. Am. J. Sports Med. 2007;35:1628-34.

    4. Anderson SL, Buchko JZ, Taillon MR, Ernst MA. Chondrolysis of the glenohumeral joint after infusion of bupivacaine through an intra-articular pain pump catheter. Arthoscopy, 2010;26:451-61.

    5. Savoie FH, Field LD, Jenkins RN, Mallon WJ, Phelps RA II. The pain control infusion pump for postoperative pain control in shoulder surgery. Arthroscopy. 2000;16:339-42.

    6. Hoenecke HR Jr, Pulido PA, Morris BA, Fronek J. The efficacy of continuous bupivacaine infiltration following anterior cruciate ligament reconstruction. Arthroscopy. 2002;18:854-8.

    7. Rapley JH, Beavis RC, Barber FA. Glenohumeral chondrolysis after shoulder arthroscopy associated with continuous bupivacaine infusion. Arthroscopy.  2009;25:1367-73.

    8. Dragoo JL, Korotkova T, Kim HJ, Jagadish A. Chondrotoxicity of low pH, epinephrine, and preservatives found in local anesthetics containing epinephrine.  Am J Sports Med. 2010;38:1154-9.

    9. Bogatch MT, Ferachi DG, Kyle B, Popinchalk S, Howell MH, Ge D, You Z, Savoie FH. Is chemical incompatibility responsible for chondrocyte death induced by local anesthetics? Am J Sports Med. 2010;38:520-6.

    10. Chu CR, Coyle CH, Chu CT, Szczodry M, Seshadri V, Karpie JC, Cieslak KM, Pringle EK.  J Bone Joint Surg Am. 2010;92: 599-608.

    11. Anz A, Smith MJ, Stoker A, Linville C, Markway H, Branson K, Cook JL. The effect of bupivacaine and morphine in a coculture model of diarthrodial joints. Arthroscopy. 2009;25(3):225-31.

    12. Gomoll AH, Yanke AB, Kang RW, Chubinskaya S, Williams JM, Bach BR, Cole BJ. Long-term effects of bupivacaine on cartilage in a rabbit shoulder model. Am J Sports Med. 2009;37:72-7.

    13. Dragoo JL, Korotkova T, Kanwar R, Wood B. The effect of local anesthetics administered via pain pump on chondrocyte viability. Am J Sports Med. 2008;36:1484-8.

    14. Chu CR, Izzo NJ, Coyle CH, Papas NE, Logar A. The in vitro effects of bupivacaine on articular chondrocytes. J Bone Joint Surg Br. 2008;90:814–20.

This is a peer reviewed paper 

Please cite as :Shu-Fen Sun,The Effects of Three Weekly Intra-articular Injections of a Bacterial-- Sourced Hyaluronate on Pain and Function in Patients with Knee Osteoarthritis.

J.Orthopaedics 2012;9(4)e7




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