Prevention of Adhesions by Surfactants and Cellulose Derivatives in Mice Kristina Falk, 1 Bjo Èrn Lindman, 2 Stig Bengmark, 3 Ka Êre Larsson 3 and Lena Holmdahl 1 From the 1 Department of Surgery, Sahlgrenska University Hospital, Go Èteborg University, Go Èteborg, 2 Department of Physical Chemistry, University of Lund and 3 Ideon Research Center, Lund, Sweden Eur J Surg 2001; 167: 136–141 ABSTRACT Objective: To evaluate the efcacy of hydrophobicall y modied ethyl (hydroxyethyl ) cellulose (cellulose), sodium hyaluronate (hyaluronate ) and phosphatidylglycerol, in the reduction of adhesion formation. Design: Controlled study. Setting: Experimental academic unit, Sweden. Material: NMRI mice. Solutions: (1) cellulose, (2) hyaluronate, (3) phosphatidylglycerol , (4) phosphatidylglycero l and cellu- lose, and (5) phosphatidylglycerol , cellulose and hyaluronate. Interventions: A standard lesion was created in the parietal peritoneum in mice. One of the viscous solutions to be tested, or saline, was given intraperitoneally. Main outcome measures: Amount of adhesions found one week postoperatively. Results: Cellulose; phosphatidylglycero l and cellulose; and phosphatidylglycerol , cellulose and hyaluronate all signicantly reduced the amount of adhesions (p = 0.0002, p = 0.002, p < 0.0001), as did the hyaluronate alone (p < 0.05). Phos- phatidylglycerol alone did not reduce the amount of adhesions. Combining cellulose with phosphatidylglycerol, or with hyaluronate, did not improve efcacy. Conclusion: Cellulose and hyaluronate were effective in reducing the formation of adhesions. Combining cellulose with hyaluronate or phosphatidylglycerol or both did not improve efcacy. Key words: adhesions, cellulose, phospholipids , bioadhesion, peritoneum, hyaluronic acid, prevention. INTRODUCTION Postoperative adhesions are common and often cause bowel obstruction (12). They are a costly complication of operations, result in considerable morbidity and mortality (11) and cause technical difculties and extra time at re-laparotomy. To prevent adhesions from forming, various types of barriers have been investigated, with the aim of separating injured peritoneal surfaces during the critical period when remesothelialisation occurs. After operation an inammatory exudate develops, which contains large amounts of brinogen. Through the action of thrombin and other proteins, the brinogen is turned into a brin gel matrix that readily forms brinous adhesions that connect adjacent structures if they come into close apposition. Surfaces need to be separated for at least 36 hours to prevent adhesions from forming (8). Bioadhesive polymers have received considerable attention in the eld of controlled drug delivery. Their special properties make them adhere to biological surfaces for a long time. We recently reported that such polymers were efcacious in reducing postoperative adhesion formation (4). Phosphatidylglycerol is a phospholipid with surfac- tant properties. Phospholipids signicantly reduce adhesion formation (2, 22) possibly by lubrication and replacement of the endogenous phospholipid layer that normally covers the mesothelium. This layer is thought to be destroyed during operations. Hydro- phobically modied ethyl (hydroxyethyl) cellulose (cellulose ) is a bioadhesive polymer that has been hydrophobically modied and that also reduces post- operative adhesion formation, as we showed in a previous study (4). Hyaluronic acid (hyaluronate) is a polysaccharide that occurs naturally in various human tissues. It inuences wound healing (24) and reduces, but not inhibits, adhesion formation when given preoperatively (23) possibly by coating the peritoneum and protecting it from trauma. Studies on the rheolo- gical properties of hydrophobically modied polymers have shown that their viscosity increases on addition of small amounts of surfactant (14). It is likely that a combination of several agents or methods is necessary to achieve satisfactory control of adhesions. By using a combination of agents to there is a possibility of synergistic effects. In this study, we investigated the effect of two polymers and a surfactant, given separately or in Ó 2001 Taylor & Francis. ISSN 1102–4151 Eur J Surg 167 ORIGINAL ARTICLE