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A Sprayable Hyaluronate/Carboxymethylcellulose Based Adhesion Barrier Reduces Remote Intraabdominal Adhesion Formation and Does Not Impair Intestinal Healing
Holly K. Sheldon*1, Melanie L. Gainsbury1, Michael R. Cassidy1, M. Jude Colt2, Rubina L. Corazzini2, Olga L. Syrkina2, Keith E. Greenawalt2, Thomas H. Jozefiak2, Arthur F. Stucchi1, James M. Becker1
1General Surgery, Boston Medical Center, Boston, MA; 2Genzyme Corporation, Cambridge, MA

Background: Intraabdominal adhesions are a significant source of postoperative morbidity. While bioresorbable solid physical barriers such as modified hyaluronate/carboxymethylcellulose (HA/CMC) film (Seprafilm - SF) are effective in preventing adhesions, their efficacy is limited to the site of application. The aim of this study was to compare the effectiveness of modified HA/CMC sprayable powder (Sepraspray - SS) and SF in preventing adhesions not only to sites of direct application, but also to remote peritoneal defects to which a barrier was not directly applied. Methods: Adhesion reduction was assessed in a rat ischemic button model and also in a rabbit cecal-sidewall injury model. Intraabdominal adhesions were induced in 30 rats by creating 3 peritoneal sidewall ischemic buttons on each side of a midline incision. SS (5 mg/button) or SF (1 cm2/button) was applied intraoperatively over the 3 ischemic buttons on one side of the midline only. Adhesions were induced in 50 rabbits by cecal abrasion with the concurrent creation of a 3 cm x 5 cm sidewall defect delineated with silk sutures and knots. Operated control animals received no SS or SF. On day 7 adhesions were scored in rats as the percent of buttons with attached adhesions and in rabbits as the % of the sidewall defect covered by adhesions. To assess the effect of either SS or SF on intestinal healing, an additional 27 rats underwent a colonic transection distal to the cecum, which was repaired with an end-to-end anastomosis. SS or SF was applied circumferentially to the anastomosis site. The anastomosed colonic sections were removed 7 days later and their integrity assessed by burst pressure and tensile strength measurements. Results: The direct application of both SS and SF significantly (p<0.04) reduced adhesion formation compared with controls in both efficacy models (Table). While SF had no remote effects on adhesion formation in either model, SS significantly (p<0.01) reduced adhesion formation to ischemic buttons to which the powder was not directly applied. In rabbits, SS reduced remote adhesion formation to the sidewall defect by 70% (p<0.1). In the anastomosis healing model, neither SF nor SS affected intestinal anastomotic burst pressure (Control: 240 ± 8.2 vs. SS 215 ± 19.0 vs. SF: 216 ± 27.2 mm Hg) or tensile strength (Control: 2.4 ± 0.2 vs. SS: 2.3 ± 0.2 vs. SF: 2.2 ± 0.2 Newton). Conclusions: While both SS and SF have comparable adhesion reduction efficacy where applied, SS was additionally effective in reducing adhesion formation at remote sites of peritoneal injury to which SS was not applied directly. These data suggest that SS may have widespread efficacy throughout the peritoneum in reducing adhesion formation without compromising intestinal wound healing.
Application Rat
% Adhesion to buttons
Rabbit
% sidewall defect covered by adhesions
Control (n = 20) 80 +/- 4 27.5 +/- 9.0
SF Direct
(n = 10)
47 +/- 7* 0.4 +/- 0.3*
SF Remote
(n = 10)
83 +/- 7 23.1 +/- 6.7
SS Direct
(n = 10)
30 +/- 10* 4.4 +/- 2.9*
SS Remote
(n = 10)
43 +/- 12* 8.1 +/- 4.4
SS: Sepraspray; SF: Seprafilm. Data are mean +/- SEM. *P< 0.05 compared with control


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