Samantha L. Piper

Comparison of ropivacaine and bupivacaine toxicity in human articular chondrocytes.

BACKGROUND It has been shown that bupivacaine, the most commonly used local anesthetic for postoperative intra-articular use, is cytotoxic to bovine articular chondrocytes in vitro. Ropivacaine is as effective as bupivacaine for intra-articular analgesia and has less systemic toxicity. We compared the in vitro viability of human articular chondrocytes after exposure to bupivacaine, ropivacaine, and saline solution control. METHODS Macroscopically normal human articular cartilage was harvested from the femoral head or tibial plateau of five patients. Full-thickness cartilage explants and cultured chondrocytes isolated from these patients were treated with 0.9% normal saline solution, 0.5% ropivacaine, or 0.5% bupivacaine for thirty minutes. Twenty-four hours after treatment, chondrocyte viability was measured with use of the LIVE/DEAD Viability/Cytotoxicity Kit for cartilage explants and with use of the CellTiter-Glo Luminescent Cell Viability Assay for cultured chondrocytes. RESULTS Chondrocyte viability in cartilage explants was significantly greater after treatment with ropivacaine as compared with bupivacaine (94.4% +/- 9.0% compared with 78% +/- 12.6%; p = 0.0004). There was no difference in viability after treatment with ropivacaine as compared with saline solution (94.4% +/- 9.0% compared with 95.8% +/- 5.7%; p = 0.6). The viability of cultured chondrocytes was significantly greater after treatment with ropivacaine as compared with bupivacaine (63.9% +/- 19% as compared with 37.4% +/- 12% of the value in the saline solution group; p < 0.0001). CONCLUSIONS In vitro, 0.5% ropivacaine is significantly less toxic than 0.5% bupivacaine in both intact human articular cartilage and chondrocyte culture.

Effects of Local Anesthetics on Articular Cartilage

Background: Recent basic science studies have demonstrated local anesthetic chondrotoxicity in vivo and in vitro in both human and animal cartilage. Clinically, chondrolysis associated with the use of intra-articular local anesthetic pain pumps has been described by several groups. This has raised concern regarding the clinical use of intra-articular local anesthetics. Methods: The authors undertook a review of the current orthopaedic literature on local anesthetic chondrotoxicity and its potential relationship to clinical chondrolysis. Results: Local anesthetics such as bupivacaine, lidocaine, and ropivacaine are chondotroxic to human articular cartilage in vitro, although ropivacaine is less so. The evidence suggests that there is a greater risk for chondrolysis with a longer exposure to a higher concentration of local anesthetic, such as with a pain pump, than with a single injection. However, late cellular and metabolic changes are seen after even a single injection of bupivacaine in animal models, and the loss of an intact cartilage matrix also leads to more extensive chondrocyte death. Some studies suggest that additives and the pH of the local anesthetic solution may also play a role in chondrotoxicity. Conclusion: Intra-articular local anesthetics should be used with caution, especially continuous infusions of bupivacaine and lidocaine at high concentrations in joints with compromised cartilage. The consequences of a single intra-articular injection of local anesthetic remains unclear and requires further investigation. Clinical Relevance: Intra-articular use of local anesthetics may have lasting detrimental effects on human articular cartilage and chondrocytes, although the clinical relationship between local anesthetic exposure and chondrolysis requires further study.

A comparison of lidocaine, ropivacaine and dexamethasone toxicity on bovine tenocytes in culture

Peri-tendinous injection of local anaesthetic, both alone and in combination with corticosteroids, is commonly performed in the treatment of tendinopathies. Previous studies have shown that local anaesthetics and corticosteroids are chondrotoxic, but their effect on tenocytes remains unknown. We compared the effects of lidocaine and ropivacaine, alone or combined with dexamethasone, on the viability of cultured bovine tenocytes. Tenocytes were exposed to ten different conditions: 1) normal saline; 2) 1% lidocaine; 3) 2% lidocaine; 4) 0.2% ropivacaine; 5) 0.5% ropivacaine; 6) dexamethasone (dex); 7) 1% lidocaine+dex; 8) 2% lidocaine+dex; 9) 0.2% ropivacaine+dex; and 10) 0.5% ropivacaine+dex, for 30 minutes. After a 24-hour recovery period, the viability of the tenocytes was quantified using the CellTiter-Glo viability assay and fluorescence-activated cell sorting (FACS) for live/dead cell counts. A 30-minute exposure to lidocaine alone was significantly toxic to the tenocytes in a dose-dependent manner, but a 30-minute exposure to ropivacaine or dexamethasone alone was not significantly toxic. Dexamethasone potentiated ropivacaine tenocyte toxicity at higher doses of ropivacaine, but did not potentiate lidocaine tenocyte toxicity. As seen in other cell types, lidocaine has a dose-dependent toxicity to tenocytes but ropivacaine is not significantly toxic. Although dexamethasone alone is not toxic, its combination with 0.5% ropivacaine significantly increased its toxicity to tenocytes. These findings might be relevant to clinical practice and warrant further investigation.

Inducible immortality in hTERT-human mesenchymal stem cells

Human mesenchymal stem cells (hMSCs) are attractive candidates for tissue engineering and cell‐based therapy because of their multipotentiality and availability in adult donors. However, in vitro expansion and differentiation of these cells is limited by replicative senescence. The proliferative capacity of hMSCs can be enhanced by ectopic expression of telomerase, allowing for long‐term culture. However, hMSCs with constitutive telomerase expression demonstrate unregulated growth and even tumor formation. To address this problem, we used an inducible Tet‐On gene expression system to create hMSCs in which ectopic telomerase expression can be induced selectively by the addition of doxycycline (i‐hTERT hMSCs). i‐hTERT hMSCs have inducible hTERT expression and telomerase activity, and are able to proliferate significantly longer than wild type hMSCs when hTERT expression is induced. They stop proliferating when hTERT expression is turned off and can be rescued when expression is re‐induced. They retain multipotentiality in vitro even at an advanced age. We also used a selective inhibitor of telomere elongation to show that the mechanism driving immortalization of hMSCs by hTERT is dependent upon maintenance of telomere length. Thanks to their extended lifespan, preserved multipotentiality and controlled growth, i‐hTERT hMSCs may prove to be a useful tool for the development and testing of novel stem cell therapies.

The utility of ultrasound for the detection of fetal limb abnormalities – a 20‐year single‐center experience

The standard obstetric ultrasound examination includes documentation of arms and legs. The purpose of this study is to review the efficacy of ultrasound for the detection of limb anomalies, the type and incidence of associated malformations and pregnancy outcomes.

Thermal Stress Potentiates Bupivacaine Chondrotoxicity

PURPOSE The primary objective of this study was to determine whether thermal stress potentiates the chondrotoxic effect of bupivacaine, resulting in decreased articular chondrocyte viability compared with exposure to bupivacaine alone. METHODS Bovine articular cartilage explants and cultured chondrocytes were treated with a range of thermal exposures (10 to 20 minutes at 37°C to 65°C) to create time/temperature viability curves and to determine threshold conditions for cell death. A second set of experiments was performed to determine whether subthreshold thermal stress potentiates bupivacaine toxicity. Explants were exposed to 37°C or 55°C for 10 or 20 minutes, and cultured chondrocytes were exposed to 37°C or 45°C for 10 or 20 minutes. Thirty minutes later, the explants and chondrocytes were treated with either 0.9% normal saline solution or 0.5% bupivacaine for 30 minutes. Chondrocyte viability was quantified 24 hours after treatment. RESULTS There was a temperature- and time-dependent decrease in chondrocyte viability above the thermo-toxicity threshold in both intact cartilage explants and cultured chondrocytes (55°C and 45°C, respectively; P < .05). Chondrocyte viability in cartilage explants was significantly lower after treatment with thermal stress for 10 or 20 minutes followed by bupivacaine for 30 minutes compared with treatment with bupivacaine at 37°C (bupivacaine and 55°C for 10 minutes, 0.09% ± 0%; bupivacaine and 55°C for 20 minutes, 0.08% ± 0%; bupivacaine and 37°C for 10 minutes, 37.4% ± 1.2% [P < .001]; and bupivacaine and 37°C for 20 minutes, 47.1% ± 0.8% [P < .001]). A similar trend was seen in cultured chondrocytes, although it was not statistically significant (P > .05). CONCLUSIONS Thermal stress potentiates the chondrotoxic effects of bupivacaine in intact cartilage, leading to decreased chondrocyte viability compared with exposure to bupivacaine alone. CLINICAL RELEVANCE Intra-articular injection of bupivacaine after arthroscopic procedures during which cartilage is exposed to elevated temperatures, such as with prolonged use of radiofrequency probes, may increase the risk of chondrocyte toxicity.

Defining Features of the Upper Extremity in Holt-Oram Syndrome

PURPOSE To investigate the distinguishing morphological characteristics of children with radial longitudinal deficiency (RLD) in Holt-Oram syndrome (HOS). METHODS One hundred fourteen involved extremities in 62 patients with a diagnosis of HOS were identified at 3 institutions. Medical records and radiographs were evaluated. Radial longitudinal deficiency and thumb hypoplasia were classified according to the modified Bayne and Klug classification and Blauth classifications, respectively, when possible. Other unusual or distinguishing characteristics were catalogued. RESULTS There was bilateral involvement in 84% of patients. The forearm was involved in 81% of the extremities and a shortened distal radius (Bayne and Klug type I RLD) was the most commonly identified forearm anomaly (40%). Radioulnar synostosis was present in 15% of the extremities, all in the proximal forearms with reduced radial heads. Thumb aplasia (Blauth type V hypoplastic thumb) was the most common type of classifiable thumb abnormality and occurred in 35% of involved thumbs. Twenty-seven percent of abnormal thumbs affected were not classifiable according to the Blauth classification, and 19% of involved thumbs (hypoplastic or absent) had first-web syndactyly. CONCLUSIONS The upper extremity in HOS differs from the typical presentation of RLD. The forearm is more often involved and may demonstrate radioulnar synostosis. The thumb is frequently unclassifiable by the Blauth classification and has first-web syndactyly. The presence of radioulnar synostosis and syndactyly of the radial 2 digits in RLD should prompt the hand surgeon to obtain a cardiac evaluation and consider genetic testing for HOS. TYPE OF STUDY/LEVEL OF EVIDENCE Diagnostic III.

Open Surgical Release of Posttraumatic Elbow Contracture in Children and Adolescents

BACKGROUND Posttraumatic elbow contractures in children and adolescents are challenging to manage, and studies investigating surgical treatment are limited by the rarity of this condition. Small case series have shown variable gains in immediate and long-term elbow arc of motion after open surgical release. We reviewed our experience with open surgical release of posttraumatic elbow contracture in patients <21 years old at 2 institutions. METHODS A retrospective chart review identified patients who underwent posttraumatic open elbow contracture release by 2 surgeons at 2 institutions between 2006 and 2013. Nontraumatic contractures and arthroscopic releases were excluded. Twenty-six patients were included in this study. Mean age at the time of injury was 12 years (5 to 19 y) and at the time of surgery was 14 years (7 to 20 y). Capsulotomy, osteoplasty, removal of hardware, ulnar nerve release or transposition, and ligament reconstruction were performed through medial and lateral approaches as indicated by the pathology. Ten patients had ligament repair or stabilization, and 16 patients used a continuous passive motion (CPM) postoperatively. Outcomes included active range of motion and complications. RESULTS Mean time from injury to surgical release was 29 months. Mean postoperative follow-up was 42 months. Elbow active flexion-extension and forearm rotation arcs both increased significantly by a mean of 49 and 70 degrees, respectively, at final follow-up. A mean 85% of intraoperative flexion-extension arc was maintained at final follow-up. Ligament repair or reconstruction and the use of a postoperative CPM did not significantly change these outcomes. Outcomes were not significantly different if our contracture release was performed within a year from injury. Patients who had surgery before our contracture release had decreased restoration of forearm rotation after release. Complications included 2 recurrent contractures (1 used a CPM and 1 did not), and 2 postoperative ulnar neuropathies (1 used a CPM and 1 did not). CONCLUSIONS Open contracture release for posttraumatic elbow contracture in an adolescent population can significantly improve active range of motion. LEVEL OF EVIDENCE Level 3-therapeutic.Background: Posttraumatic elbow contractures in children and adolescents are challenging to manage, and studies investigating surgical treatment are limited by the rarity of this condition. Small case series have shown variable gains in immediate and long-term elbow arc of motion after open surgical release. We reviewed our experience with open surgical release of posttraumatic elbow contracture in patients <21 years old at 2 institutions. Methods: A retrospective chart review identified patients who underwent posttraumatic open elbow contracture release by 2 surgeons at 2 institutions between 2006 and 2013. Nontraumatic contractures and arthroscopic releases were excluded. Twenty-six patients were included in this study. Mean age at the time of injury was 12 years (5 to 19 y) and at the time of surgery was 14 years (7 to 20 y). Capsulotomy, osteoplasty, removal of hardware, ulnar nerve release or transposition, and ligament reconstruction were performed through medial and lateral approaches as indicated by the pathology. Ten patients had ligament repair or stabilization, and 16 patients used a continuous passive motion (CPM) postoperatively. Outcomes included active range of motion and complications. Results: Mean time from injury to surgical release was 29 months. Mean postoperative follow-up was 42 months. Elbow active flexion-extension and forearm rotation arcs both increased significantly by a mean of 49 and 70 degrees, respectively, at final follow-up. A mean 85% of intraoperative flexion-extension arc was maintained at final follow-up. Ligament repair or reconstruction and the use of a postoperative CPM did not significantly change these outcomes. Outcomes were not significantly different if our contracture release was performed within a year from injury. Patients who had surgery before our contracture release had decreased restoration of forearm rotation after release. Complications included 2 recurrent contractures (1 used a CPM and 1 did not), and 2 postoperative ulnar neuropathies (1 used a CPM and 1 did not). Conclusions: Open contracture release for posttraumatic elbow contracture in an adolescent population can significantly improve active range of motion. Level of Evidence: Level 3—therapeutic.

Distal Forearm Fracture Open Reduction–Internal Fixation: Sonographic Detection of Hardware Malalignment and Associated Tendon Injuries Missed by Radiography

Tendon injury is a known complication of distal radius fracture plate and screw fixation. Targeted musculoskeletal sonography is uniquely capable of assessing both tendon integrity and hardware abnormalities not recognized on radiographs. Each of the 3 patients described presented with pain after an open reduction–internal fixation following a distal forearm fracture. In each patient, radiographic findings, specifically the hardware position, were interpreted as normal. Important radiographically occult observations were subsequently made with sonography, including 3 proud screws and tendon injuries, all of which required surgical treatment. This case series demonstrates the clinical utility of musculoskeletal sonography in symptomatic patients after distal radius open reduction–internal fixation with negative radiographic findings. In our practice, sonography has been the most useful modality for precluding missing or delaying the diagnosis and treatment of these hardware complications. We advocate its use as an adjunct in any department performing musculoskeletal imaging.

Outcomes After Primary Repair and Staged Reconstruction of Zone I and Ii Flexor Tendon Injuries in Children

Background: Delayed diagnosis of flexor tendon injury in children is common, and consequent flexor sheath scarring may necessitate a 2-stage reconstruction. Previous studies show variable outcomes after 2-stage flexor reconstruction in children, especially those below 6 years old. We evaluated functional and subjective outcomes of primary repair and staged reconstruction of zone I and II tendon injuries in children under 6 years of age. Methods: A retrospective chart review identified 12 digits in 10 patients who had undergone surgical treatment of a zone I or II flexor tendon injury. Seven digits had a primary repair and 5 had a 2-stage reconstruction. Time delay from injury to surgery for primary repairs averaged 18 weeks and for 2-stage reconstruction averaged 24 weeks. Outcomes included total active motion, tip pinch and grip strength, sensation, and the Pediatric Outcomes Data Collection Instrument (PODCI). Results: Average follow-up was 8 years. At final follow-up, mean total active and passive motion of the involved digit was similar between the primary reconstruction and staged groups, and 58% had a “good” or “excellent” American Society for Surgery of the Hand; total active motion (ASSH TAM) result (71% in the primary repair group, 40% in the 2-stage reconstruction group). All regained grip and pinch strength equal to the contralateral hand. The average PODCI Upper Extremity score was 99 (99 in the primary repair group, 98 in the 2-stage reconstruction group) and PODCI Global Function score was 94 (97 in the primary repair group, 91 in the 2-stage reconstruction group). No complications occurred. Conclusions: Our small study demonstrates that both primary repair and 2-stage flexor tendon reconstruction have acceptable long-term functional and subjective outcomes in children below 6 years old, although staged reconstruction had a lower overall ASSH TAM score and subcategorical PODCI scores. Although staged reconstruction has acceptable outcomes in this population, prompt primary repair of flexor tendon injuries in children should always be attempted. Level of Evidence: Level 4—therapeutic.