Abstract
Background
To evaluate predictors for effect of an intra-articular (IA) bupivacaine and corticosteroid injection in patients with femoroacetabular impingement syndrome (FAIS).
Methods
All patients between 18 and 50 years old with FAIS who received an intra-articular (IA) bupivacaine and corticosteroid injection between 2016 and 2019 were eligible for this retrospective study. Two groups were made, the non-arthroscopy group (patients for whom conservative treatment with physiotherapy and an IA bupivacaine and corticosteroid injection was sufficient) and the arthroscopy group (patients who needed an arthroscopy because conservative treatment and an IA bupivacaine and corticosteroid injection failed). Multiple regression analysis was performed to analyse the effect of the IA corticosteroid injection and to predict arthroscopic intervention based on sex, age, body mass index, duration of complaints, alpha angle and abnormal bone morphology.
Results
In total 103 patients were included; 46 in the arthroscopy group and 57 in the non-arthroscopy group. The groups had similar baseline characteristics. A total of 37 (36%) patients had an effect of 3 months or longer from the IA corticosteroid injection; 31 (54%) were patients in the non-arthroscopy group versus 6 (13%) patients in the arthroscopy group (P < 0.001). Male sex seems to have an negative influence on the duration of the effect of the injection. None of the variables could significantly predict if a patient would undergo arthroscopic intervention (F(7,103) = 8.54, p = 0.3, R2 = 0.11). The effect of the IA injection could not be predicted (p = 0.1; R2 = 0.13).
Conclusion
There are no patient characteristics that predict who would and who would not benefit from the IA bupivacaine and corticosteroid injection in patients with FAIS and who would need an arthroscopic intervention within 1 year after the injection. Only male sex seems to have an negative influence on the duration of the effect of the injection.
Keywords: Hip, Femoroacetabular impingement, Intra-articular injection, Corticosteroids, Conservative treatment, Arthroscopy
1. Introduction
Femoroacetabular impingement syndrome (FAIS) is one of the most common causes of hip pain in (young) adults.1 FAIS knows three different types: 1) the cam type, in which there is a bump at the junction from femur head to femur neck, 2) the pincer type, in which the anterolateral acetabular rim is overhanging, 3) the mixed type, which is a combination of the 2 types mentioned above. Because of this mismatch between the shape of the femur head/neck and the acetabulum, flexion and endorotation of the hip joint may cause intrusion and generates increased contact pressure. This can lead to labral and chondral pathology and patients experience pain in the hip/groin.2,3
An intra-articular (IA) injection with bupivacaine and corticosteroid can be part of the diagnostic process of FAIS. An IA bupivacaine injection is a local anaesthetic and is expected to improve the pain when IA pathology is present. So the injection helps to identify whether the cause of the pain has an intra-articular or extra-articular origin; it has been shown to have a 90% accuracy to diagnose intra-articular pathology.4 A corticosteroid can be used as a treatment as it reduces inflammation and can therefore cause long-term pain relief.5, 6, 7 There are studies about the therapeutic effect of corticosteroid that show different outcomes varying from a very short pain relief till a significant pain relief still present after 12 months.5,8 Also, IA corticosteroid injection might be more effective in patients who also have chondropathy.4,1
The purpose of this study was to determine which patient characteristics of patients with FAIS are a predictor for long-term effect (>1 year) of an IA bupivacaine and corticosteroid injection and the need for an arthroscopy. This is important because, if a corticosteroid has a long-term beneficial effect, surgery of the hip could be avoided and if a patient does not benefit from the injection, standard use of corticosteroid can be avoided. We hypothesise that ageing could be beneficial for a long-term effect of the corticosteroid injection, as with ageing the risk of developing degenerative pathology is increased.
2. Patients and methods
This is a retrospective single centre database study. All patients between January 1st, 2016 and December 31st, 2019 with hip complaints due to FAIS were identified. All patients who underwent an intra-articular hip injection with bupivacaine and corticosteroid with an age between 18 and 50 years were included. Bupivacaine was expected to give a short term (1–2 days) pain relief for all patients, due to the local analgesic effect. The anti-inflammatory effect of the corticosteroid can have a long-term effect (at least 1 year) which was the main focus in this study. Patients with an age above 50 were excluded because of the risk of more developed osteoarthritis and a known risk of poor results of hip arthroscopy. Also patients with prior hip surgery and patients who were loss to follow-up were excluded. In the electronic patients files the variables age, sex, body mass index (BMI), sports, trauma and duration of complaints before the first consult (in months) were retrospectively identified and recorded in an electronic database using RedCap, Vanderbilt, Nashville, USA.9
Patients with symptoms consistent with the clinical presentation of FAIS followed a standard diagnostic protocol via the outpatient clinic. Starting with a supine pelvis anterior-posterior (AP) radiograph and an axiolateral (cross-table lateral) radiograph assessment of the affected side. If suspected for FAIS a magnetic resonance imaging (MRI) arthrogram was made and physiotherapy was initiated, including training of core stability, delordosing exercises and strengthening of hip musculature for 6 weeks. If a labral tear was present on the MRI arthrogram and physiotherapy was insufficient, the decision was made by the orthopaedic surgeon to order a radiographically guided intra-articular injection, performed by an experienced radiologist. An injection with bupivacaine and triamcinolone (synthetic corticosteroid) 6:1 ml or 8:1 ml was used. Patients returned to the outpatient clinic 6 weeks to 3 months after the injection was performed. The effect of injection was assessed based on patients' experience; pain during daily living or pain during sports. If there was not enough improvement after the IA injection, the possibility of a hip arthroscopy was discussed with the patient.
2.1. Diagnostic imaging
Radiographic imaging was used to measure the alpha angle and lateral centre edge angle (LCEA). The alpha angle was measured on an oblique axial MRI. If there was no (oblique axial) MRI imaging available the alpha angle was reported as missing. The presence of cam morphology was defined by an alpha angle greater than 60°. The LCEA was measured on an AP radiograph. Pincer morphology was defined as a LCEA ≥40° or a cross-over sign, a LCEA <20° was defined as acetabular dysplasia.10, 11, 12 When a pincer and a cam were presented, it was categorised as mixed morphology. The radiograph was also used to measure osteoarthritis using the Kellgren and Lawrence score.
2.2. Statistics
IBM SPSS Statistics for Windows, Version 26.0. “Armonk, NY: IBM Corp” was used for all statistical procedures. Patients were divided into a non-arthroscopy group and arthroscopy group. For the patients in the arthroscopy group the conservative treatment with (physiotherapy and) an IA bupivacaine and corticosteroid injection was insufficient. The patients in the arthroscopy group had persistent pain after conservative treatment and therefore proceeded to arthroscopic intervention. The baseline characteristics age, BMI, alpha angle and LCEA were compared using a 2-sided independent Samples T-test taking into account the Levene's Test for equality of variances. For the categorical variables a Pearson Chi-Squared test or a Fisher exact probability test was used. Multiple regression analysis was performed to predict arthroscopic intervention (binary) and the effect of the intra-articular injection (ordinal) based on sex, age, BMI, alpha angle, duration of complaints and abnormal morphology (yes/no). Statistical significance was defined as a p-value <0.05.
2.3. Ethics, funding, data sharing and potential conflict of interest
The study was conducted in accordance with the Helsinki Declaration and was approved by the Institutional Review Board. Individual consent was not required. No grants were received for this study. The data that supports the findings of this study is available from the corresponding author on reasonable request. The authors declare no competing interests.
3. Results
3.1. Patient characteristics
In total 103 patients were included in the study (69 females and 34 males). There were 46 (45%) patients who underwent arthroscopic surgery of the hip (Table 1), this was on average 4.4 months after the IA injection. All baseline characteristics were similar between the arthroscopy group and the non-arthroscopy group (Table 1). In both groups, approximately 70% of the patients participate in sports (at least once per week, excluding walking).
Table 1.
Patient characteristics and diagnostic imaging information (N = 103).
| Arthroscopy (n = 46) | Non-arthroscopy (n = 57) | P-value | ||
|---|---|---|---|---|
| Mean age in years (SD) | 33.7 (7.2) | 34.5 (8.6) | 0.59 | |
| Body Mass Index (SD) | 23.6 (3.2) | 24.9 (4.9) | 0.13 | |
| Sex | Female | 29 (63%) | 40 (70%) | 0.44 |
| Male | 17 (37%) | 17 (30%) | ||
| Trauma | Yes | 6 (13%) | 4 (7%) | 0.34 |
| No | 40 (87%) | 53 (93%) | ||
| Sport | Yes | 33 (72%) | 39 (68%) | 0.30 |
| No | 3 (7%) | 9 (16%) | ||
| Unknown | 10 (22%) | 9 (16%) | ||
| Duration of complaints |
0–6 months | 25 (54%) | 30 (53%) | 0.89 |
| 7–12 months | 8 (17%) | 12 (21%) | ||
| >12 months |
13(28%) |
15 (26%) |
||
| Diagnostic imaging | ||||
| Mean alpha angle in degrees (SD) | 52 (10.1) | 51 (9.2) | 0.68 | |
| Mean LCEA in degrees (SD) | 35 (6.8) | 36 (7.9) | 0.71 | |
| FAI morphology | Pincer | 23 (50%) | 25 (44%) | 0.44 |
| Cam | 6 (13%) | 4 (7%) | ||
| Mixed (pincer + cam) | 5 (11%) | 5 (9%) | ||
| Not present | 12 (26%) | 23 (40%) | ||
| Kellgren and Lawrence | Grade 0 | 43 (94%) | 50 (88%) | 0.51 |
| Grade 1 | 3 (7%) | 7 (12%) | ||
SD: standard deviation; LCEA: lateral centre edge angle; FAI: Femoroacetabular impingement.
3.2. Diagnostic imaging
Diagnostic imaging showed that in total 68 (66%) patients had a cam, pincer or mixed morphology. This is 74% of the patients in the arthroscopy group and 60% in the non-arthroscopy group (p = 0.44). The alpha angle was missing in 4 patients in the non-arthroscopy group due to no, or no good oblique axial MRI image. Alpha angle, LCEA, dysplasia and the Kellgren and Lawrence score were similar between groups. In each group 1 patient had dysplasia. In the arthroscopy group 7% of the patients had a grade 1 Kellgren and Lawrence classification which is doubtful joint space narrowing and possible osteophytic lipping. In the non-arthroscopy group 12% of the patients had a grade 1 Kellgren and Lawrence classification (p = 0.51).
3.3. Effect injection
The effect of the IA injection was categorised in four groups (Table 2). There were 4 patients who did not experience any benefit from the injection, all from the arthroscopy group. These results are categorised as false negatives. Based on the complaints of the patients, the clinical symptoms and the bone morphology on the diagnostic imaging the decision was made to proceed to hip arthroscopy. A total of 47 patients experienced pain relief from the injection for 1 week up to 3 months, 27 (59%) patients in the arthroscopy group and 20 (35%) patients in the non-arthroscopy group. Six (13%) patients in the arthroscopy group experienced an effect for 3 months or longer compared to 31 (54%) in the non-arthroscopy group. Fisher exact test showed a statistically significant difference in effect between groups (P < 0.001).
Table 2.
Classification of the duration of the effect of the intra-articular injection (N = 103).
| Arthroscopy (n = 46) | Non arthroscopy (n = 57) | |
|---|---|---|
| No effect | 4 (9%) | 0 (0%) |
| <1 week | 9 (20%) | 6 (11%) |
| 1 week to 3 months | 27 (59%) | 20 (35%) |
| ≥3 months | 6 (13%) | 31 (54%) |
3.4. Multiple regression analysis
In the multiple regression analysis, sex, age, BMI, duration of complaints, alpha angle and abnormal morphology (yes/no) were included. The analyses showed that none of these variables could significantly predict if a patient would undergo arthroscopic intervention (F(7,103) = 8.5, p = 0.3, R2 = 0.11) (Table 3). Ordinal regression showed that the effect of the intra-articular injection could not significantly be predicted (p = 0.1; R2 = 0.13). Abnormal bone morphology had no significant effect on the effect of the IA injection or the need for an arthroscopy. Only male sex seems to influence the effect of the injection, which results in a shorter effect of the injection.
Table 3.
Results of the multiple regression analyses for predicting arthroscopic intervention and the length of a long-term effect of the intra-articular injection.
| Arthroscopic intervention |
Effect of the intra-articular injection |
||||
|---|---|---|---|---|---|
| P-value | Exp(B) (95%CI) | P-value | Exp(B) (95%CI) | ||
| Sex | 0.28 | 0.56 (0.19–1.62) | 0.02 | 0.31 (0.11–0.82) | |
| Age | 0.97 | 1.00 (0.95–1.06) | 0.33 | 0.97 (0.93–1.03) | |
| Body mass index | 0.06 | 0.89 (0.78–1.01) | 0.13 | 1.09 (0.97–1.22) | |
| Duration of complaints | 0–6 months | 0.51 | – | 0.18 | 0.53 (0.21–1.34) |
| 7–12 months | 0.30 | 0.54 (0.17–1.74) | 0.90 | 1.08 (0.32–3.67) | |
| >12 months | 0.79 | 1.15 (0.42–3.13) | – | – | |
| Alpha angle | 0.76 | 1.01 (0.95–1.07) | 0.70 | 0.99 (0.94–1.04) | |
| Abnormal morphology | 0.08 | 2.32 (0.92–5.89) | 0.89 | 0.94 (0.41–2.18) | |
4. Discussion
Our results show no increase in the duration of the effect of the IA corticosteroid injection with ageing. However, literature shows that patients with mild chondral pathology might have greater pain relief after an IA corticosteroid injection.4,15 In both studies, there was no data about the long-term effect of the IA corticosteroid injection in patients with chondral pathology. This also applies to the long-term effect of an IA corticosteroid injection for patients with FAIS.
In this retrospective cohort study 37 (36%) patients had an effect of 3 months or longer from the IA corticosteroid injection. For 31 (30%) patients the effect of the IA corticosteroid injection was sufficient and a hip arthroscopy was not needed within the follow-up period (mean 1.7 years, range 1–4 years). In two studies with smaller populations a higher percentage of the population had a long-term effect of the IA corticosteroid injection. The prospective study of Pennock et al. focused on the nonoperative management of patients with FAIS. Patients were offered treatment with an IA corticosteroid injection when physiotherapy and activity modification was insufficient. Of the patients who received an IA injection 50% (11/22) did benefit from the injection and did not need a hip arthroscopy.13 In this study 6 patients did not receive an IA corticosteroid injection and continued to a surgical intervention directly. This means that for 6 patients it is unknown what the effect of the injection would be, and the percentage of a successful effect of the injection could be represented too high. The retrospective chart review of Tangtiphaibootana et al. looked at adolescents with hip pain, in which 95% of the patients had a labral tear. To all patients who were still symptomatic after 6 weeks of physiotherapy and no sport activities, an IA corticosteroid injection was given as a treatment. This injection was successful in 48% (9/19) of the patients and no surgical intervention was needed.14 Main difference with these two studies is a younger patient population, mean age 15.3 and 15.1 years. This would suggest that a younger population would have a better long term effect of the corticosteroid injection. However both studies have small populations.
In our study there were no variables that predicted the outcome; a long-term effect of the injection or only a short-term relief and a subsequent need for a hip arthroscopy. Only male sex seems to have an negative influence on the duration of the effect of the injection. Cam morphology is known to be more present in males, which might be an explanation for this phenomena. Different studies show that patients with cam morphology are more likely to undergo surgery. The prospective study of Pennock et al. showed that cam impingement and combined impingement groups were 4.4 times more likely than the pincer group to continue to arthroscopy (P = 0.05).13 The systematic review of Lynch et al. studied the outcomes after a diagnostic hip injection and found least relief in patients with cam impingement.15 Griffin et al., a multicentre randomised controlled trial (RCT), comparing hip arthroscopy with conservative care, showed in a subgroup analysis that patients with cam morphology have an increased treatment effect of the hip arthroscopy (compared to other FAIS morphology).16 These results may suggest that non-operative treatment is more prone to fail in patients with cam morphology.
In our study we also see that BMI and FAIS bone morphology might be important variables in the regression analyses for predicting an arthroscopic intervention (p = 0.06 resp p = 0.08). This is in accordance with literature showing that patients with osseous deformities were more likely to need surgical intervention (RR:10).14 An explanation of this outcome could be that most complaints of patients with FAIS bone morphology are caused by a mechanical problem.
Standard administration of a corticosteroid can have negative side effects on the hip joint, as higher doses of IA corticosteroid are associated with greater risk of cartilage damage.17,18 Also, patients with no or mild osteoarthritis at presentation might develop rapid progressive joint space loss after an IA corticosteroid injection.19 Local anaesthetics, such as bupivacaine, have also shown to have a deleterious effect on knee cartilage chondrocytes in vitro. A systematic review with in vivo and in vitro studies on knee cartilages showed an increase in cytotoxicity when corticosteroids were co-administered.20,21
4.1. Limitations
Our study is a retrospective cohort study, and as a result there were missing data because of incomplete medical records. Duration of pain relief was most of the time noted in the file, but patient reported outcomes, such as a NRS pain score were not recorded. Without a pain score or scale it was not possible to objectify the pain relief. Selection bias and recall bias were minimised. All patients were referred to a physiotherapist specialised in impingement complaints, although the level of intensity and compliance cannot be verified and can differ per patient. Patients who did still benefit from the IA injection after 6–8 weeks were asked to come for a follow-up consult if the complaints returned or increased. Therefore follow-up might not be complete. Patients were sometimes advised to take a step back in sports or stopped doing sports on their own initiative. This can have influenced the amount of pain relief reported in the patient file.
5. Conclusion
Our study showed that there are no patient characteristics that predict who would and who would not benefit from the IA bupivacaine and corticosteroid injection in patients with FAIS and who would need an arthroscopic intervention within 1 year after the injection. Only male sex seems to have an negative influence on the duration of the effect of the injection.
Ethical review committee statement
Approval was obtained from the local ethics committee (Z20.043/pn/mk).
Author contribution
CH and NW had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors were involved with the concept and design, acquisition, analysis, or interpretation of data. Statistical analysis and drafting of the manuscript: CH and NW. Critical revision of the manuscript: All authors.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.
Declaration of competing interest
All authors declare that they have no conflicts of interest.
Acknowledgments
None.
Footnotes
FAIS, femoroacetabular impingement syndrome; IA, intra-articular; LCEA, lateral centre edge angle.
Contributor Information
Catharina W. van den Hoek, Email: willemiekevdhoek@gmail.com.
Laurens Kaas, Email: l.kaas@antoniusziekenhuis.nl.
References
- 1.Wu C.-T., Mahameed M., Lin P.-C., Lu Y.-D., Kuo F.-C., Lee M.S. Treatment of cam-type femoroacetabular impingement using anterolateral mini-open and arthroscopic osteochondroplasty. J Orthop Surg Res. 2019;14(1):1–11. doi: 10.1186/s13018-019-1257-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Rego P., Beaulé P.E., Ayeni O.R., et al. Femoroacetabular impingement: what the surgeon wants to know. Hip and Advanced Musculoskeletal Imaging. 2019;23(3):257–275. doi: 10.1055/s-0039-1683967. [DOI] [PubMed] [Google Scholar]
- 3.Byrd J.W.T., Gaskill R.T., Philippon M.J. third ed. 2013. Operative Hip Arthroscopy, My Approach to Femoroacetabular Impingement; pp. 215–248. (chapter 17)-18. [Google Scholar]
- 4.Kivlan B.R., Martin R.L., Sekiya J.K. Response to diagnostic injection in patients with femoroacetabular impingement, labral tears, chondral lesions and extra-articular pathology. Arthroscopy. 2011;27(5):619–627. doi: 10.1016/j.arthro.2010.12.009. [DOI] [PubMed] [Google Scholar]
- 5.Krych A.J., Griffith B.T., Hudgens L.J., Kuzma S.A., Sierra R.J., Levy B.A. Limited therapeutic benefits of intra-articular cortisone injection for patients with femoro-acetabular impingement and labral tear. Knee Surg Sports Traumatol Arthrosc. 2014;22(4):750–755. doi: 10.1007/s00167-014-2862-3. [DOI] [PubMed] [Google Scholar]
- 6.Atchia I., Kane D., Reed M.R., Isaacs J.D., Birrell F. Efficacy of a single ultrasound-guided injection for the treatment of hip osteoarthritis. Ann Rheum Dis. 2011;70(1):110–116. doi: 10.1136/ard.2009.127183. [DOI] [PubMed] [Google Scholar]
- 7.Kullenberg B., Runesson R., Tuvhag R., Olsson C., Resh S. Intraarticular corticosteroid injection: pain relief in osteoarthritis of the hip? J Rheumatol. 2004;31(11):2265–2268. [PubMed] [Google Scholar]
- 8.Hunt D., Prather H., Hayes M.H., Clohisy J.C. Clinical outcomes analysis of conservative and surgical treatment of patients with clinical indications of pre arthritic, intra-articular hip disorders. PM and R. 2012;4(7):479–487. doi: 10.1016/j.pmrj.2012.03.012. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Harris P.A., Taylor R., Thielke R., Payne J., Gonzalez N., Conde J.G. Research Electronic Data Capture (REDCap) - a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inf X. 2009;42(2):377–381. doi: 10.1016/j.jbi.2008.08.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Mascarenhas V.V., Castro M.O., Rego P.A., et al. The lisbon agreement on femoroacetabular impingement imaging—part 1: overview. Eur Radiol. 2020;30(10):5281–5297. doi: 10.1007/s00330-020-06822-9. [DOI] [PubMed] [Google Scholar]
- 11.Reiman P.M., Agricola R., Kemp J.L., et al. Consensus recommendations on the classification, definition and diagnostic criteria of hip-related pain in young and middle-aged active adults from the International Hip-related Pain Research Network, Zurich 2018. Br J Sports Med. 2020;54(11):631–641. doi: 10.1136/bjsports-2019-101453. [DOI] [PubMed] [Google Scholar]
- 12.Klij P., Reiman P.M., Waarsing J.H., et al. Classifying cam morphology by the alpha angle: a systematic review on threshold values. Orthop Sports Med. 2020;8(8):1–10. doi: 10.1177/2325967120938312. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Pennock T.A., Bomary D.J., Johnson K.P., Randich K., Upasani V.V. Nonoperative management of femoroacetabular impingement: a prospective study. Am J Sports Med. 2018;46(14):3415–3422. doi: 10.1177/0363546518804805. [DOI] [PubMed] [Google Scholar]
- 14.Tangtiphaiboontana J., Zhang A.L., Pandya N.K. Outcomes of intra-articular corticosteroid injections for adolescents with hip pain. J Hip Preserv Surg. 2018;5(1):54–59. doi: 10.1093/jhps/hnx027. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Lynch T.S., Steinhaus M.E., Popkin C.A., Ahmad C.S., Rosneck J. Outcomes after diagnostic hip injection. Arthroscopy. 2016;32(8):1702–1711. doi: 10.1016/j.arthro.2016.02.027. [DOI] [PubMed] [Google Scholar]
- 16.Griffin D.R., Dickenson E.J., Wall P.D.H., et al. Hip arthroscopy versus best conservative care for the treatment of femoroacetabular impingement syndrome (UK FASHIoN): a multicentre randomised controlled trial. Lancet. 2018;391(10136):2225–2235. doi: 10.1016/S0140-6736(18)31202-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Wernecke C., Braun H.J., Dragoo J.L. The effect of intra-articular corticosteroids on articular cartilage A systematic review. Orthop J Sports Med. 2015;3(5):1–7. doi: 10.1177/2325967115581163. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Stone S., Malanga G.A., Capella T. Corticosteroids: review of the history, the effectiveness, and adverse effects in the treatment of joint pain. Pain Physician. 2021;24(S1):233–246. [PubMed] [Google Scholar]
- 19.Kompel J., Roemer F.W., Murakami A.M., Diaz L.E., Crema M.D., Guermazi A. Intra-articular corticosteroid injections in the hip and knee: perhaps not as safe as we thought? Radiology. 2019;293(3):656–663. doi: 10.1148/radiol.2019190341. [DOI] [PubMed] [Google Scholar]
- 20.Jayaram P., Kennedy D.J., Yeh P., Dragoo J. Chondrotoxic effects of local anesthetics on human knee articular cartilage: a systematic review. PMR. 2019;11(4):379–400. doi: 10.1002/pmrj.12007. [DOI] [PubMed] [Google Scholar]
- 21.Jacob B., Zippelius T., Kloss N., et al. Local anesthetics' toxicity toward human cultured chondrocytes: a comparative study between lidocaine, bupivacaine, and ropivacaine. Cartilage. 2019;10(3):364–369. doi: 10.1177/1947603518758436. [DOI] [PMC free article] [PubMed] [Google Scholar]