Adhesion formation to hemostatic agents and its reduction with a sodium hyaluronate/carboxymethylcellulose adhesion barrier

Abstract

The impact of hemostatic agents on postoperative adhesion formation has not been well studied. We hypothesized that hemostatic agents would be a significant nidus for adhesion formation and that a resorbable barrier would effectively reduce adhesions to hemostatic agents. Four commercial hemostatic agents, each composed of a different biomaterial matrix, were implanted in female Sprague-Dawley rats, and adhesion formation was examined 7 days after surgery. In separate studies, the effects of serosal trauma (via cecal abrasion), added blood, and the presence of chemically modified sodium hyaluronate/carboxymethylcellulose (HA/CMC) barrier on adhesion formation to hemostatic agents were studied. Significant adhesions formed to hemostatic agents even in the absence of traumatized tissue. When applied after cecal abrasion, the incidence of adhesions to the hemostatic agents increased. Addition of blood to this model increased adhesion formation even further, causing adhesions in every animal in the study. An HA/CMC adhesion barrier reduced adhesions to hemostatic agents in the presence of serosal trauma and maintained effectiveness even in the presence of blood. In conclusion, hemostatic agents potentiated adhesion formation at the site of application in a model without trauma. In more challenging models, their adhesiogenic contribution was overwhelmed by trauma and blood. HA/CMC adhesion barrier applied over hemostatic agents at the time of surgery provided significant protection against postoperative adhesions in these preclinical models.

Prevention of postsurgical adhesions using an ultrapure alginate-based gel

“…Alginate gel is a foreign body and may elicit an inflammatory response, leading to increased adhesion formation. However, this has not been demonstrated for HA/CMC powder and also seems unlikely for alginate gel, given the moderate foreign body response shown histologically and the almost absent inflammatory response found in previous studies 15,30 .…”

“…During this interval fibrous adhesions form and mesothelial healing is completed, which makes formation of new adhesions unlikely. HA/CMC‐based adhesion barrier, which is absorbed fully from the abdominal cavity within 30 days, showed efficacy within 5–7 days.…”

Antiadhesive effect and safety of sodium hyaluronate-carboxymethyl cellulose membrane in thyroid surgery

“…Adhesion barrier devices that are used to separate tissue surfaces and prevent adhesions are an increasingly accepted adjunct to abdominopelvic surgery. Many studies have shown the antiadhesive effect of HA-CMC in animal models, human abdominal surgery, human facial surgery, human esophageal surgery, human breast surgery and human craniotomy [ 15 - 22 ]. Among them, there were interesting studies on a novel antiadhesive film based on cross-linked carboxymethylcellulose and atorvastatin, with that of sodium hyaluronate-carboxymethylcellulose [ 23 , 24 ].…”

<p>A review of the application of cellulose hemostatic agent on trauma injuries</p>

“…20 Greenawalt et al (2012) showed a sodium hyaluronate/carboxymethylcellulose barrier used for hemostatic agents at the time of surgery presented effects on after surgery adhesions in these preclinical models. 21 They hypothesized that a resorbable barrier would effectively reduce the adhesions to hemostatic agents and that hemostatic agents would be a significant nidus for adhesion formation.…”