Intra-articular Corticosteroids Are Widely Used for Adhesive Capsulitis, But Alternatives Are Required for Patients With Contraindications. Hyaluronic Acid (HA) and Ketorolac Have Shown Individual Benefits. However, Evidence on Their Combination Remains Limited.

Adhesive capsulitis, or frozen shoulder, is characterized by pain and stiffness due to capsular inflammation and fibrosis. Corticosteroid injections are commonly used but may be contraindicated in some patients. Hyaluronic acid (HA) and ketorolac each have shown benefit, yet evidence on their combined use is limited.

This randomized, double-blind, controlled trial enrolled 56 adults with adhesive capsulitis. Participants were randomized 1:1 to receive either HA plus ketorolac or ketorolac alone as a single intra-articular injection, followed by standardized rehabilitation. Follow-up assessments were conducted at 2, 6, 12, and 24 weeks.

The primary outcome was functional outcome measured by the Thai SPADI. Secondary outcomes included pain (VAS), PROM, analgesic use, and adverse events. Both groups improved significantly in function and pain, without significant between-group differences. However, the HA+ketorolac group showed modest but significant improvements in external rotation and adduction range of motion. Safety outcomes were favorable in both groups, with only one mild adverse event reported.

This study demonstrates that intra-articular HA combined with ketorolac and ketorolac alone are safe and effective alternatives to corticosteroid injection for adhesive capsulitis. The combination may provide additional benefit in range of motion recovery and can be considered in patients for whom corticosteroids are unsuitable.

• Intra-articular Hyaluronic Acid and Ketorolac (Drug), also known as Hyaluronic Acid and Ketorolac injection: Single intra-articular injection containing 2 mL moderate-molecular-weight hyaluronic acid (20 mg/2 mL), 1 mL ketorolac (30 mg/mL), and 2 mL lidocaine (10 mg/mL), total volume 5 mL. Administered under aseptic technique (ultrasound-guided or landmark-based) followed by standardized rehabilitation program.
• Intra-articular Ketorolac (Drug), also known as Ketorolac injection: single intra-articular injection containing 1 mL ketorolac (30 mg/mL), 2 mL lidocaine (10 mg/mL), and 2 mL normal saline, total volume 5 mL. Administered under aseptic technique (ultrasound-guided or landmark-based) followed by standardized rehabilitation program.

Primary outcomes

• Shoulder function (Thai SPADI score) [Baseline, 2, 6, 12, and 24 weeks post-injection]: Shoulder Pain and Disability Index (Thai version), patient-reported outcome measure, score range 0-100 (higher score = worse disability)

Secondary outcomes

• Pain intensity (VAS score) [Baseline, 2, 6, 12, and 24 weeks post-injection]: Visual Analog Scale for shoulder pain, 0-10 (higher score = worse pain)
• Passive range of motion (PROM) [Baseline, 2, 6, 12, and 24 weeks post-injection]: Passive range of motion of the affected shoulder (flexion, extension, abduction, adduction, internal and external rotation) measured with goniometer in degrees
• Adverse events [0-24 weeks post-injection]: Number and type of treatment-related adverse events (mild, moderate, or severe) reported by participants or observed by investigators

Sex: All, ages: 18 Years to 70 Years

Eligible participants were adults diagnosed with adhesive capsulitis defined by limitation of shoulder motion ≥25 degrees in at least two planes compared to the contralateral side

Inclusion Criteria:

* Adults aged 18-70 years
* Symptom duration of 1-12 months
* Provision of informed consent.

Exclusion Criteria:

* History of trauma or prior surgery to the affected shoulder
* Bilateral adhesive capsulitis
* Uncontrolled diabetes (HbA1C > 7%)
* Abnormal thyroid function
* Prior intra-articular injection in the affected shoulder
* Full-thickness rotator cuff tear on imaging
* History of gastrointestinal bleeding
* Known allergy to hyaluronic acid or NSAIDs
* Systemic conditions affecting joint pain (e.g., SLE, rheumatoid arthritis, osteoarthritis)
* Neurological disorders affecting muscle strength or sensation coagulopathy or bleeding disorders withdrawal or refusal of consent at any time

• Results publication: Lee SC, Rha DW, Chang WH. Rapid analgesic onset of intra-articular hyaluronic acid with ketorolac in osteoarthritis of the knee. J Back Musculoskelet Rehabil. 2011;24(1):31-8. doi: 10.3233/BMR-2011-0272. PMID 21248398
• Results publication: Taheri P, Dehghan F, Mousavi S, Solouki R. Comparison of Subacromial Ketorolac Injection versus Corticosteroid Injection in the Treatment of Shoulder Impingement Syndrome. J Res Pharm Pract. 2017 Oct-Dec;6(4):223-227. doi: 10.4103/jrpp.JRPP_17_57. PMID 29417082
• Results publication: Xu J, Qu Y, Li H, Zhu A, Jiang T, Chong Z, Wang B, Shen P, Xie Z. Effect of Intra-articular Ketorolac Versus Corticosteroid Injection for Knee Osteoarthritis: A Retrospective Comparative Study. Orthop J Sports Med. 2020 Apr 10;8(4):2325967120911126. doi: 10.1177/2325967120911126. eCollection 2020 Apr. PMID 32313809
• Results publication: Mao B, Peng R, Zhang Z, Zhang K, Li J, Fu W. The Effect of Intra-articular Injection of Hyaluronic Acid in Frozen Shoulder: a Systematic Review and Meta-analysis of Randomized Controlled Trials. J Orthop Surg Res. 2022 Mar 3;17(1):128. doi: 10.1186/s13018-022-03017-4. PMID 35241100
• Results publication: Uhm KE, Chang MC. Comparison of Effectiveness of Intraarticular Hyaluronate and Corticosteroid injections in Adhesive Capsulitis: A Systematic Review and Meta-analysis. Pain Physician. 2024 Sep;27(7):387-400. PMID 39353107

• Pratantat Charoenchaipong, MD, Principal investigator, Ramathibodi Hospital
• Sorawut Thamyongkit, MD, Study director, Chakri Naruebodindra Medical Institute