Pentamidine Decreases Adhesion Formation After Flexor Tendon Repair

• Format: Other/Unknown Material
• Language: English
• Published: Morressier 2017
• Subjects: Pennington; SCAR
• Online Access: https://openresearchlibrary.org/viewer/4436ca2e-fab5-4bf6-b3e9-a551096bf61f; https://openresearchlibrary.org/ext/api/media/4436ca2e-fab5-4bf6-b3e9-a551096bf61f/assets/external_content.pdf; https://doi.org/10.26226/morressier.5c0a5c96f0ad58000b08a24f

INTRODUCTION: Adhesion formation is a frequent complication after repair of flexor tendon injuries. Fibrotic tissue scarring occurs as a normal process of healing that results in adhesion formation between tendon and surrounding tissues leading to impaired tendon gliding and adversely impacts digit functions. A combination of factors is thought to contribute to adhesion formation, including tissue damage, inflammation, suture, and immobilization.1,2 While improvements in repair and care techniques have led to reduced adhesions, many pharmacological agents have also been described. In particular, anti-inflammatory drugs such as indomethacin and ibuprofen have been demonstrated to decrease flexor tendon adhesions.3 Pentamidine is a FDA-approved drug for antimicrobial purposes. It has also been demonstrated to have anti-inflammatory properties and data from our lab has shown that it can inhibit fibrosis in rabbit models of hypertrophic scar. Herein, using a previously described turkey model for flexor tendon repair,4 we investigated the effect of local pentamidine application during surgery in reducing preitendinous adhesion formation.METHODS: The study was approved by the Institutional Animal Care and Use Committee (IACUC). Twelve adult Bourbon Red turkeys were randomly assigned into either control (surgery only) or pentamidine (surgery with drug treatment) groups. The other non-operated third digit served as baseline. The third (middle) digit on either the right or left foot of each turkey was randomly chosen to be surgically repaired. A Z-shaped incision was made at the level of the proximal interphalangeal (PIP) joint on the volar side of the third digit. The flexor digitorum profundus tendon was exposed and a laceration was made 1cm distal to the proximal vinculum. Tendon was repaired with the modified Pennington technique and a circumferential running suture. Fifty mg of pentamidine was then applied to the repair site and skin was closed. The digits were wrapped in cotton and immobilized in a flexion position with a hard cast. Turkeys were allowed to roam free in a large cage fed ad libitum until euthanasia at 6th week postoperatively. Tendon adhesion was evaluated and scored using a previously described system5 by 3 individuals blinded to the treatment groups. Work of flexion (WOF) at the PIP joint was assessed with a combined tensile transducer and a motion analysis system (Figure 1). Tendon breaking strength was tested with a servo-hydraulic machine. RESULTS: All turkeys survived except for 1 turkey in the control group that deceased. Gap (> 2 mm) between the repaired tendons was found in the 4 (1 control, 3 drug-treated) out of the first batch of 6 turkeys during dissection after they were tested for work of flexion. A change of WOF setup was done and 1mm gaps were found in 2 (drug treated) out of the later 6 turkeys. Under a constant 5N force applied to the FDP tendon, PIP joint flexion could be produced for an average of 27.09 degrees (range, 16.60-37.36) on the non-operated third digit, an average of 2.27 degrees (range, 1.22-3.33) for the non-treated digits, an average of 10.94 degrees (range, 9.98-12.31) (p = 0.0001). Average adhesion score in the non-treated group was 5.8 (range, 3-8) and 2 (range, 1-3) (p = 0.0013) in the treated group (Figure 2). Average breaking strength in the time zero immediate repair digits was 32.46 N (24.67-37.54), non-treated was 46.81 (31.46-55.62), and treated was 25.24 N (11.59-43.69) (p = 0.09).DISCUSSION: Pentamidine treatment resulted in reduced adhesion formation evidenced by higher degrees of flexion produced under a constant force and a lower average adhesion score. However, although not statistically significant, the strength of the repaired tendon decreased possibility due to delayed healing caused by the anti-inflammatory property of the drug. Our pilot data showed some promising results of using pentamidine in preventing adhesion formation after flexor tendon repair. Further studies with longer time points and more specimens are needed to better understand the effect of pentamidine on flexor tendon healing.