The site of injection is midway between the tip of the coracoid and the bicipital groove.

Next, the safety and efficacy of injectable collagenase Clostridium histolyticum was evaluated for the treatment of adhesive capsulitis. A small, randomized, double-blind, placebo-controlled, single-injection, dose-response, pilot study was conducted and followed by an open-label extension study. Sixty patients, 47 women and 13 men, were evaluated. Mean age was 52 ± 8 years, and mean duration of adhesive capsulitis was 17 months. Patients were randomized to receive a single injection of 0.5 ml placebo (physiologic saline and 2 mM CaCl₂) or 0.145, 0.29, or 0.58 mg collagenase diluted in placebo solution to the same volume. Extra-articular injection was directed at the anterior shoulder capsule in the supine position. Shoulders were serially evaluated for 30 days for range of motion in all planes. Outcome measures (function score, pain score, strength, and stability) were obtained using an American Society of Shoulder and Elbow Surgeons evaluation form. At 30 days postinjection, patients could receive up to 4 open-label 0.58 mg collagenase injections if active elevation was not improved to 160°. Long-term follow-up was up to 60 months. Results from the double-blind phase (one injection) demonstrated significant improvements from baseline in 4 measures of shoulder motion (active elevation, active external rotation, passive external rotation, and function) with collagenase (0.29–0.58 mg) compared with placebo (ANOVA, P < 0.05). In most patients, one injection was not sufficient to restore normal motion and function. Within 30 days after the last open-label phase injection (injection #2, #3, #4) of 0.58 mg collagenase, shoulder motion, function, and pain were comparable to normal values. It appeared that shoulders with more severe limitation of active elevation at baseline required a greater number of collagenase injections. These data suggest that treatment with one or more injections of collagenase may improve shoulder motion, function, and pain in patients with adhesive capsulitis (Badalamente and Wang, 2006). The treatment was well tolerated, and at 60-month follow-up, there were no recurrences.

The next study sought to refine the anterior shoulder capsule injection method using ultrasound guidance.

Ten normal, healthy volunteers were enrolled. There were 8 females and 2 males, mean age 44.7 + 7.2 years. For anterior injection, subjects were supine, and the arm was passively externally rotated with the elbow at the side to 20°. The anterior shoulder area was washed with chlorhexidine prep solution. Landmarks were identified by palpating the bicipital groove and the coracoid process. These sites were marked with a sterile surgical marker pen. The injection site was midway in the coronal plane between these two landmarks.

Next, a local anesthetic of 1 % lidocaine solution in 10 ml was injected subcutaneously and therefore extra-articularly with a 20-gauge, 1 ½ inch needle at the midway point between the defined landmarks. This needle was placed perpendicular to the skin. Five minutes was timed to allow for sufficient lidocaine local anesthesia. The ultrasound probe was placed near the injection site. Next, 10 ml sterile saline was injected using the same needle track as was used for lidocaine anesthesia but using 22-gauge needle (Sprotte needle). All subjects chose to have the non-dominant side injected. Therefore, there were 8 injections to the left shoulder and 2 to the right shoulder.

Ultrasound images were recorded in a serial fashion. First, a posterior image was taken prior to anterior Sprotte needle insertion. When the saline was introduced via the Sprotte needle, the timer was activated. The timer was stopped only when no saline could be seen on the anterior ultrasound images. Finally, a posterior ultrasound image was taken with the subject’s on their side to assure that no saline was visible. The ultrasound imaging of the saline injection itself was performed (Fig. 48.2). The saline fluid remained anterior to the shoulder capsule (also confirmed by the posterior imaging) and extra-articular in all ten subjects. Specifically, nine of ten subjects showed a bolus (pocket) of saline fluid deep to the subscapularis tendon. In the remaining one subject the saline was seen on the anterior surface of the subscapularis. No saline fluid was visible in the glenohumeral joint space by anterior or posterior imaging. This study showed that 10 of 10 subjects who received saline injection to the anterior shoulder using only topographic landmarks as a guide resulted in extra-articular placement of the saline fluid. Palpation of the bicipital groove and the coracoid process were the landmarks used for injection. This injection technique is simple and reliable.

50 patients (10 male, 40 female) at 11 sites throughout the USA with a mean age of 54 years (range, 41–74) were enrolled. Patients were aged ≥18 years, with stage 2 (frozen) unilateral idiopathic AC for 3–12 months before the screening visit. Inclusion criteria were restricted total active ROM (AROM) deficit of ≥60⁰ in all planes and a deficit of ≥ 30⁰ as compared with the contralateral shoulder in one or more of the following planes: forward flexion, abduction, or external/internal rotation. Four cohorts of 10 patients each received up to 3 ultrasound-guided extra-articular injections, directed onto the anterior capsule, of 0.29 mg or 0.58 mg of CCH (in varying volumes: 0.5, 1, or 2 mL), separated by 21 days. After 1 % lidocaine injection onto the anterior capsule for local anesthesia, the CCH dose was injected through the same needle track using a spinal needle. Cohort 5 (n = 10) performed home shoulder exercises only. All patients (cohorts 1–5) were instructed to perform the same home shoulder exercises, three times per day. The primary endpoint was change, in degrees, from baseline to day 92 in AROM forward flexion in the affected shoulder compared to the exercise-only cohort. Secondary endpoints were change from baseline to day 92 in 3 additional planes (abduction, external/internal rotation). Function and pain were assessed using the American Shoulder and Elbow Surgeons scale. Adverse events (AEs) were assessed at every visit. Baseline and end of study day 92 shoulder MRIs were obtained for all patients.

The 0.58 mg/1 mL and 0.58 mg/2 mL dosing arms showed significant improvement from baseline in AROM forward flexion vs. the exercise-only group (P = 0.0131 and P = 0.0385, respectively). Trends with improvement in AROM were also seen in the other CCH-treated cohorts. Twenty-nine patients (72.5 %) received 3 CCH injections, 5 patients received 2 injections, and 6 received 1 injection. Both the 0.58 mg/1 mL and 0.58 mg/2 mL cohorts had significant improvement in pain and function from baseline vs. the exercise-only group (P < 0.05). Treatment-related AEs with CCH were most commonly transient and confined to local injection site. AEs of injection site pain and injection site swelling resolved in ≤7 days without intervention. There were no serious AEs. Baseline and day 92 MRI evaluations indicated that there were no clinically significant rotator cuff injuries or other safety findings.