Failure of Cyanoacrylate Tissue Glue (Flucrylate, MBR4197) to Stop Bleeding from Experimental Canine Gastric Ulcers

Failure of Cyanoacrylate Tissue Glue (Flucrylate, MBR4197) to Stop Bleeding from Experimental Canine Gastric Ulcers R.L. PROTELL, MD, F.E. SILVERSTEIN, MD, C. GULACSIK, BS, T.R. MARTIN, MD, M.B. DENNIS, DVM, D.C. AUTH, PhD, and C.E. RUBIN, MD A plastic tissue adhesive, trifluoroisopropyl 2-cyanoacrylate (Flucrylate TM, MBR4197), was tested for hemostatic efficacy in acute laparotomy experiments using a canine model of acute bleeding gastric ulcer. An improved delivery system suitable for endoscopic use was developed. Hemostatic efficacy o f the adhesive was tested in both briskly bleeding ulcers and in oozing ulcers after partial treatment with a heater probe. In pilot studies at laparotomy, primary and adjunctive cyanoacrylate therapy of 81 bleeding ulcers were evaluated in seven unheparinized foxhounds. Hemostasis was produced in 11% of ulcers treated with cyanoacrylate alone and in 31% of ulcers treated with cyanoacrylate as an adjunctive after partial heater-probe treatment; no sham-treated control ulcers stopped bleeding under the conditions of the experiment. To evaluate Flucrylate TM using our standard heparinized ulcer model, a randomized study was performed in six heparinized foxhounds at laparotomy. Ulcers were randomized to treatment with cyanoacrylate alone, adjunctive cyanoacrylate, heater probe alone or untreated control. Sham-treated control ulcers or ulcers treated with cyanoacrylate alone did not stop bleeding; 42% of ulcers treated with cyanoacrylate as an adjunctive stopped bleeding; all ulcers treated with a heater probe stopped bleeding. In this experimental model o f acute bleeding gastric ulcer, trifluoroisopropyl 2-cyanoacrylate (Flucrylate r~t, MBR4197) did not stop severe bleeding and was unpredictable as an adjunctive treatment. The ideal endoscopic treatment for acute bleeding upper gastrointestinal lesions would be: (1) convenient and easy to use; (2) 100% effective in stopping bleeding; and (3) nontoxic and minimally injurious to the underlying tissue. Electrocoagulative techniques (1, 2), lasers (3-6), heater probes (7), hemostatic clips (8), and injection techniques (9) have all been considered for treatment of upper-gastrointestinal hemorrhage. Although some are better than From the Departments of Medicine and Electrical Engineering, Universityof Washington,and the Departmentof Medicine, University of Minnesota. This study was supported by United States Public Health Service ContractNO1-AM-5-2211 and Grant5 F22 AM00608-03. Address for reprint requests: Dr. Robert L. Protell, Department of Medicine, RG-20, University of Washington, Seattle, Washington 98195. others, none of these techniques fulfills all three requirements for the ideal agent. Cyanoacrylate tissue glues adhere strongly to tissue and to virtually all other substances except Teflon or polyethylene. They can be applied from a distance as an aerosol spray. Although cyanoacrylates are relatively nontoxic, the shorter-chain analogs cause local tissue necrosis (10-12), and some analogs occasionally cause fibrosarcomas and other tumors when embedded in rodent tissue (11, 13, 14). Application of cyanoacrylates to the surface of bleeding gastrointestinal lesions is technically possible and may prove to be permissable clinically if they can be shown to safely stop brisk bleeding. Layers of cyanoacrylate sprayed on bleeding lesions may fall off in time, but toxicity of degradation products DigestiveDiseases,rot. 23, No. t0 ~Oc,ob~r1978~ 0002-921 ff78/1000-0903505.00/1 9 1978 Digestive Disease Systems, Inc. 903