Evaluation of different intraarticular injection volumes to assess optimum efficient amount; an experimental study in rat knee joints

Aytekin, Kürşad; Uysal, Murat; Şahiner, Göksel Gültekin; Danışman, Murat; Baş, Orhan; Takır, Selçuk; Coskun, Zafer Unsal; Akdeniz, Esra; Esenyel, Cem Zeki

doi:10.1016/j.vascn.2019.106658

Cited by 8 publications

(7 citation statements)

References 16 publications

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“…Typical intra-articular injection volumes for the human knee do not exceed 2 mL and one study examined 61 patients who underwent endoprosthetic joint replacement and found their knee joint volumes range from 40 to 290 mL with an average of 131 mL. 43,44 Although joint volume may not scale linearly with body weight, our estimates, in vivo experience, and cadaveric MRI imaging studies all suggest that 50 µl is an excessive volume for the rat knee.…”

Section: Discussionmentioning

confidence: 79%

“…One prior study investigated intra‐articular injection volumes in rat knees, where intra‐articular injections exceeding 30 µl commonly resulted in subdermal leakage outside of the joint capsule 42 . It is important that injection volumes in preclinical animal models are physiological or approximately equivalent to injection volumes delivered to human patients, especially when pain and functional outcomes are being measured.…”

Section: Discussionmentioning

confidence: 99%

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Assessment of osteoarthritis functional outcomes and intra‐articular injection volume in the rat anterior cruciate ligament transection model

Wang

Wagner

et al. 2022

Journal Orthopaedic Research

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The rat surgical anterior cruciate ligament transection (ACLT) model is commonly used to investigate intra‐articular osteoarthritis (OA) therapies, and histological assessment is often the primary outcome measure. However, histological changes do not always correlate well with clinical outcomes. Therefore, this study evaluated functional outcomes in the rat surgical ACLT model and compared intra‐articular injection volumes ranging from 20 to 50 μl. Unilateral ACLT was surgically induced and static weight‐bearing, mechanical allodynia, motor function, and gait were assessed in four groups of male, Sprague‐Dawley rats (n = 6 per group). Intra‐articular injections of 20 µl Dulbecco's phosphate‐buffered saline (DPBS), 50 µl DPBS, or 50 µl of synthetic biomimetic boundary lubricant were administered once weekly for 3 weeks postoperatively. Structural changes were evaluated histologically at 20 weeks. Rat cadaver knees were injected with 20, 30, 40, or 50 µl of gadolinium solutions and were imaged using magnetic resonance imaging (MRI). Static weight‐bearing, mechanical allodynia, and gait parameters in ACLT groups revealed differences from baseline and naïve controls for 4 weeks post‐ACLT; however, these differences did not persist beyond 6 weeks. Different intra‐articular DPBS injection volumes did not result in functional or histological changes; however, peri‐articular leakage was documented via MRI following 50, 40, and 30 µl but not 20 µl gadolinium injections. Statement of clinical significance: Differences in functional parameters were predominantly restricted to early, postoperative changes in the rat surgical ACLT model despite evidence of moderate histologic OA at 20 weeks. Injection volumes of 20–30 µl are more appropriate for investigating intra‐articular therapies in the rat knee.

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Assessment of osteoarthritis functional outcomes and intra‐articular injection volume in the rat anterior cruciate ligament transection model

Wang

Wagner

et al. 2022

Journal Orthopaedic Research

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“…However, the most commonly tested injection volumes in rats were 100–250 μl (0.1–0.25 ml) 34–37,39,40,42,43 . Of note, IA injections greater than 30 μl are not recommended for rats and IA injection volumes of 100 μl have been associated with rat knee joint capsular tears and fluid overflow into the subdermal space 44 …”

Section: Resultsmentioning

confidence: 99%

“…In addition, it is possible that the non‐specific inflammation found in animal safety models was related to high joint injection volumes. Injection volumes of 100–250 μl were routinely used in the rat IA NSAID safety models, but injection volumes of greater than 100 μl to the rat knee joint have been associated with capsular tear 44 . Side effects in human studies were also rare, generally mild and in some cases may not have been related to the IA NSAID injection.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics, safety and efficacy of intra‐articular non‐steroidal anti‐inflammatory drug injections for the treatment of osteoarthritis: A narrative review

Selig

Kress

Horton

et al. 2022

Clinical Pharmacy Therapeu

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What is known and Objective Osteoarthritis (OA) is a common cause of joint disease and activity limitation in adults. Common therapies to treat OA‐related pain are oral and topical non‐steroidal anti‐inflammatory drugs (NSAIDs) and intra‐articular (IA) corticosteroids. However, prolonged courses of oral NSAIDs are associated with systemic adverse effects and repeat IA corticosteroid injections may cause cartilage degeneration. IA NSAIDs may be an alternative therapy possibly minimizing systemic side effects while maintaining efficacy. Therefore, we sought to summarize the pharmacokinetics, safety and efficacy of IA NSAIDs to help providers make a more informed decision on the use of IA NSAIDs. Methods We searched the National Library of Medicine Database with terms “intraarticular and nsaid”, yielding 1032 results. Only traditional formulations of NSAIDs were considered for inclusion. Animal studies were included if animals were healthy or if the method of arthritis induction was a reasonable model of osteoarthritis. Human studies were included if humans were healthy or if the primary disease studied was osteoarthritis of a large joint. Of 1032 results, 31 research articles met the inclusion criteria and were summarized in this review. Results and Discussion We found that single doses of IA NSAIDs provided far less total systemic and synovial exposure compared to a one week course of oral NSAIDs, but maximum concentrations to the synovium with IA administration were much higher. IA NSAIDs had an excellent safety profile in small animals, large animals and humans, although these injections were associated with non‐specific cartilage inflammation in healthy animals. In animal models, IA NSAIDs had similar efficacy to PO NSAIDs in treating OA‐related pain. In humans, IA NSAIDs had similar efficacy to PO NSAIDS and IA corticosteroids in treating OA‐related pain; however, many trials did not have a placebo control and outcome measures were heterogeneous. What is new and Conclusion Overall, single doses of IA NSAIDs appear safe and efficacious across animals and humans. The optimal use of IA NSAIDs is still to be determined and further research is needed. However IA NSAIDs may be an additional beneficial therapy to treat OA‐related pain. Potential uses may be to augment IA corticosteroids injections, to interrupt multiple IA corticosteroid injections or as an alternative in patients that are high risk for corticosteroid‐related adverse events.

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“…Therefore, by adjusting the injection volume, the hydrogels can function in vivo without adhesion ability. It is reported that 30 μL of the solution can fill up the cavity of the rat knee's joint without overflowing [ 60 ]. Thus, an injection volume of 30 μL was chosen in this study.…”

Section: Methodsmentioning

confidence: 99%

Shear-responsive boundary-lubricated hydrogels attenuate osteoarthritis

Lei

Wang

Liao

et al. 2022

Bioactive Materials

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Evaluation of different intraarticular injection volumes to assess optimum efficient amount; an experimental study in rat knee joints

Cited by 8 publications

References 16 publications

Assessment of osteoarthritis functional outcomes and intra‐articular injection volume in the rat anterior cruciate ligament transection model

Assessment of osteoarthritis functional outcomes and intra‐articular injection volume in the rat anterior cruciate ligament transection model

Pharmacokinetics, safety and efficacy of intra‐articular non‐steroidal anti‐inflammatory drug injections for the treatment of osteoarthritis: A narrative review

Shear-responsive boundary-lubricated hydrogels attenuate osteoarthritis

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