title: A pilot study evaluating the efficacy of a fully acetylated poly-N-acetyl glucosamine membrane formulation as a topical hemostatic agent.
abstract: BACKGROUND
  Topical hemostatic agents are frequently needed for control of intraoperative bleeding. Currently available topical products each have potential drawbacks, making a more effective topical hemostatic agent desirable. This study was performed to evaluate the effectiveness of a particular formulation of a newly available polysaccharide polymer, poly-N-acetyl glucosamine (p-GlcNAc), as a topical hemostatic agent for use in the operating room. Swine splenic incision and splenic capsular stripping hemorrhage models were initially used, with a subsequent pilot human study then performed.
  
  
  METHODS
  For the swine splenic incision model, anesthetized immature female Yorkshire white swine had a 3 x 8 mm incision created on the spleen. One of 3 agents (p-GlcNAc membrane, oxidized cellulose, or absorbable collagen) was sequentially applied to individual wounds and digitally compressed for 20 seconds. The wound was observed without pressure for 2 minutes. Up to 8 wounds per animal were created in 7 animals. For the swine splenic capsular stripping model a 2 x 2 cm area of capsular stripping on the surface of the spleen to a depth of 3 mm was created. Either p-GlcNAc membrane or oxidized cellulose was applied and digitally compressed for 60 seconds, followed by observation without pressure for 2 minutes. Six wounds per animal were created in 2 animals. If bleeding persisted in either model, a new cycle of compression was applied. These steps were repeated until hemostasis was achieved. No change in hemodynamics or coagulation factors was observed in either model. Subsequently, 10 consecutive patients undergoing elective small-bowel surgery were enrolled on pilot study. A 5 x 3 x 3 mm cruciate incision was created midway between the mesenteric and antimesenteric borders of the small bowel. Either p-GlcNAc membrane formulation or oxidized cellulose was applied (the sequence alternated per patient) with a 400-mg weight used for even, direct pressure. A second cruciate incision was then created on the contralateral side of the bowel to evaluate the second material. The number of applications required for hemostasis was assessed. Hemodynamics, small-bowel pathologic condition, and hematologic parameters were evaluated.
  
  
  RESULTS
  The p-GlcNAc membrane required fewer cycles of compression in the swine splenic incision model to achieve hemostasis than either absorbable collagen or oxidized cellulose (1.25 vs 2.58 and 3.41, respectively; P < .01) and caused more effective immediate cessation of bleeding (79% for p-GlcNAc vs 17% for both absorbable collagen and oxidized cellulose). With the more traumatic splenic capsular stripping model, p-GlcNAc required fewer cycles of compression to achieve hemostasis than oxidized cellulose (average, 2.5 versus 6.8 respectively; P < .01) and was able to achieve hemostasis with greater efficacy (50%) in 2 applications than did oxidized cellulose (0%; P < .01). When used in the human pilot study, p-GlcNAc membranes required fewer cycles of compression than oxidized cellulose (2.5 vs 5.4, respectively; P < .002), was able to stop bleeding with greater efficacy in 1 cycle of compression (50% vs 0%, respectively; P < .01), and ultimately accomplished hemostasis in 80% of the cases as opposed to 20%.
  
  
  CONCLUSIONS
  On the basis of its greater hemostatic efficacy as compared with collagen or oxidized cellulose-based products, p-GlcNAc holds promise as an effective topical hemostatic agent and deserves further evaluation.
authors.affiliation: Department of Surgery, Medical University of South Carolina, Charleston 29425, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Cole
authors.forename: R J
authors.initials: RJ
authors.lastname: Connolly
authors.forename: M W
authors.initials: MW
authors.lastname: Chan
authors.forename: S D
authors.initials: SD
authors.lastname: Schwaitzberg
authors.forename: T K
authors.initials: TK
authors.lastname: Byrne
authors.forename: D B
authors.initials: DB
authors.lastname: Adams
authors.forename: P L
authors.initials: PL
authors.lastname: Baron
authors.forename: P H
authors.initials: PH
authors.lastname: O'Brien
authors.forename: J S
authors.initials: JS
authors.lastname: Metcalf
authors.forename: M
authors.initials: M
authors.lastname: Demcheva
authors.forename: J
authors.initials: J
authors.lastname: Vournakis
mesh_terms: D000107:Acetylation; D000117:Acetylglucosamine / Q000008:administration & dosage* / Q000737:chemistry; D000287:Administration, Topical; D000328:Adult; D000818:Animals; D013505:Digestive System Surgical Procedures / Q000009:adverse effects; D004195:Disease Models, Animal; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000517:prevention & control; D006489:Hemostatic Techniques; D006490:Hemostatics / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D007421:Intestine, Small / Q000473:pathology / Q000601:surgery; D008297:Male; D010865:Pilot Projects; D011134:Polysaccharides / Q000008:administration & dosage* / Q000737:chemistry; D019106:Postoperative Hemorrhage / Q000517:prevention & control; D013154:Spleen / Q000601:surgery; D013552:Swine
chemical_list: D006490:Hemostatics; D011134:Polysaccharides; C113831:poly-N-acetyl glucosamine; D000117:Acetylglucosamine