A Review of Topical Hemostatic Agents for Use in Cardiac Surgery
2009; Elsevier BV; Volume: 88; Issue: 4 Linguagem: Inglês
10.1016/j.athoracsur.2009.02.092
ISSN1552-6259
AutoresJames Barnard, Russell Millner,
Tópico(s)Blood transfusion and management
ResumoPostoperative hemorrhage, redo sternotomy for bleeding, and transfusion of blood products are all associated with poorer outcomes in cardiac surgery. Topical hemostatic agents are important adjuncts to reduce blood loss after cardiac surgery and can have a role in reducing both "surgical" and "nonsurgical bleeding." There are many topical hemostatic agents to choose from, and with several new products in this field being approved for use in the last few years, the aim of this review is to appraise these agents and to look at the evidence for their efficacy. Postoperative hemorrhage, redo sternotomy for bleeding, and transfusion of blood products are all associated with poorer outcomes in cardiac surgery. Topical hemostatic agents are important adjuncts to reduce blood loss after cardiac surgery and can have a role in reducing both "surgical" and "nonsurgical bleeding." There are many topical hemostatic agents to choose from, and with several new products in this field being approved for use in the last few years, the aim of this review is to appraise these agents and to look at the evidence for their efficacy. Mr Millner discloses that he has a financial relationship with MedTrade Products Limited. Mr Millner discloses that he has a financial relationship with MedTrade Products Limited. Hemostatic agents are a useful tool in reducing perioperative and postoperative bleeding. Patients coming forward for urgent cardiac surgery may have been exposed to aspirin, clopidogrel, or glycoprotein IIb–IIIa inhibitors, in addition to heparin or warfarin resulting in a higher degree of postoperative bleeding [1LeNarz L.A. Coronary artery bypass graft in abciximab-treated patients.Ann Thorac Surg. 2000; 70: S38-S42Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar]. Prolonged time on cardiopulmonary bypass, cooling, and heparinization all contribute to the derangement of blood clotting mechanisms and predispose the patient to postoperative bleeding. Excessive bleeding may necessitate transfusion of blood products with potential associated adverse effects, including anaphylactic transfusion reactions, transfusion-related lung injury, and transmission of infectious agents. Postoperative hemorrhage, transfusion of blood products, and re-exploration for bleeding [2Moulton M.J. Creswell L.L. Mackey M.E. Cox J.L. Rosenbloom M. Reexploration for bleeding is a risk factor for adverse outcomes after cardiac operations.J Thorac Cardiovasc Surg. 1996; 111: 1037-1046Abstract Full Text Full Text PDF PubMed Scopus (305) Google Scholar] are all associated with poorer outcome in cardiac surgery. Surgical causes of postoperative bleeding are found in 66% of cases on re-exploration with the remainder being attributed to coagulopathy [3Hall T.S. Sines J.C. Spotnitz A.J. Hemorrhage related reexploration following open heart surgery: the impact of pre-operative and post-operative coagulation testing.Cardiovasc Surg. 2002; 10: 146-153Crossref PubMed Scopus (23) Google Scholar]. Surgical bleeding is considered to be bleeding at the site of a surgical suture line or anastomosis, whereas nonsurgical bleeding is hemorrhaging of small vessels from a tissue surface and is generally accepted as being as a result of a coagulopathy. A variety of topical hemostatic agents are used with varying efficacy and varying degrees of evidence in favor of their benefits (Table 1). Several new agents have been approved for use in the last few years, including chitosan-based agents, which have shown great promise in controlling major hemorrhaging in the pre-hospital setting and in animal models of major hemorrhaging [4Kozen B.G. Kircher S.J. Henao J. Godinez F.S. Johnson A.S. An alternative hemostatic dressing: comparison of CELOX, HemCon, and QuikClot.Acad Emerg Med. 2008; 15: 74-81Crossref PubMed Scopus (212) Google Scholar]. The aim of this review is to discuss agents that are presently used and agents that are also presently used in other fields and may have an important role to play in cardiac surgery.Table 1Summary of Randomized Controlled Trials of Hemostatic Agents in Cardiovascular SurgeryAgentControlNumberOutcomeColgel [7Sirlak M. Eryilmaz S. Yazicioglu L. et al.Comparative study of microfibrillar collagen hemostat (Colgel) and oxidized cellulose (Surgicel) in high transfusion-risk cardiac surgery.J Thorac Cardiovasc Surg. 2003; 126: 666-670Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar]Surgicel71aCardiovascular procedures including re-do cardiac operations and ascending aortic aneurysm repair.Chest tube drainage in first 24 hr was Colgel 373 ± 143 mL vs Surgicel 571 ± 144 mL, (p = 0.01) and in the first 3 hr it was 132 ± 41 vs 228 ± 57 mL, respectively (p < 0.001).CoStasis [9CoStasis Multi-center Collaborative Writing CommitteeA novel collagen-based composite offers effective hemostasis for multiple surgical indications: Results of a randomized controlled trial.Surgery. 2001; 129: 445-450Abstract Full Text Full Text PDF PubMed Scopus (75) ]*Studies sponsored by industry.Collagen sponges72aCardiovascular procedures including re-do cardiac operations and ascending aortic aneurysm repair.Bleeding controlled within 10 minutes with CoStasis 28/37 vs control 17/37; p = 0.02.Cyanoacrylate Sealant [12Lumsden A.B. Heyman E.R. Prospective randomized study evaluating an absorbable cyanoacrylate for use in vascular reconstructions.J Vasc Surg. 2006; 44: 1002-1009Abstract Full Text Full Text PDF PubMed Scopus (55) ]*Studies sponsored by industry.Oxidized Cellulose151bPeripheral vascular and arteriovenous procedures.Hemostasis mean time 119.3 vs 403.8 seconds (p < 0.001) and immediate hemostasis in 54.5% vs 10% in Cyanoacrylate Sealant and control, respectively.Tisseel [44Rousou J. Levitsky S. Gonzalez-Lavin L. et al.Randomized clinical trial of fibrin sealant in patients undergoing resternotomy or reoperation after cardiac operations A multicenter study.J Thorac Cardiovasc Surg. 1989; 97: 194-203PubMed ]*Studies sponsored by industry.Avitene/Surgicel164aCardiovascular procedures including re-do cardiac operations and ascending aortic aneurysm repair.92.6% bleeding control with Tisseel vs 12.4% with control agents at 5 minutes (p < 0.001).Beriplast [22Codispoti M. Mankad P.S. Significant merits of a fibrin sealant in the presence of coagulopathy following paediatric cardiac surgery: randomised controlled trial.Eur J Cardiothorac Surg. 2002; 22: 200-205Crossref PubMed Scopus (44) ]*Studies sponsored by industry.Surgery alone52cProcedures for congenital heart disease.Fewer transfusions of FFP in the BP group compared with controls (p ≤ 0.05). BP group shorter time to achieve hemostasis (p ≤ 0.05), less bleeding intraoperatively (p ≤ 0.01).CoSeal [24Hagberg R.C. Safi H.J. Sabik J. Conte J. Block J.E. Improved intraoperative management of anastomotic bleeding during aortic reconstruction: results of a randomized controlled trial.Am Surg. 2004; 70: 307-311PubMed ]*Studies sponsored by industry.Gelfoam thrombin54dImplantation of Dacron grafts (DuPont, Wilmington, DE) for the repair of nonruptured aneurysms.Immediate hemostasis in CoSeal 48 of 59 vs control 10 of 27 (p = 0.002).BioGlue [27Coselli J.S. Bavaria J.E. Fehrenbacher J. Stowe C.L. Macheers S.K. Gundry S.R. Prospective randomized study of a protein-based tissue adhesive used as a hemostatic and structural adjunct in cardiac and vascular anastomotic repair procedures.J Am Coll Surg. 2003; 197: 243-253Abstract Full Text Full Text PDF PubMed Scopus (93) ]*Studies sponsored by industry.Surgery alone151eCardiac and vascular repair procedures.BioGlue bleeding (18.8% of anastomoses) vs control (42.9% of anastomoses; p < 0.001).FloSeal [35Oz M.C. Cosgrove 3rd, D.M. Badduke B.R. et al.Controlled clinical trial of a novel hemostatic agent in cardiac surgery The Fusion Matrix Study Group.Ann Thorac Surg. 2000; 69: 1376-1382Abstract Full Text Full Text PDF PubMed Scopus (197) ]*Studies sponsored by industry.Gelfoam thrombin93aCardiovascular procedures including re-do cardiac operations and ascending aortic aneurysm repair.FloSeal stopped bleeding in 94% of the patients (first bleeding site only) within 10 minutes compared with 60% in the control group (p = 0.001).rThrombin [42Weaver F.A. Lew W. Granke K. Yonehiro L. Delange B. Alexander W.A. A comparison of recombinant thrombin to bovine thrombin as a hemostatic ancillary in patients undergoing peripheral arterial bypass and arteriovenous graft procedures.J Vasc Surg. 2008; 47: 1266-1273Abstract Full Text Full Text PDF PubMed Scopus (30) ]*Studies sponsored by industry.bThrombin164bPeripheral vascular and arteriovenous procedures.Hemostasis at 10 minutes 94% bThrombin, 91% rThrombin; p = NS.BP = Beriplast fibrin sealant; bThrombin = bovine plasma-derived thrombin; FFP = fresh frozen plasma; NS = not statistically significant; rThrombin = recombinant thrombin.a Cardiovascular procedures including re-do cardiac operations and ascending aortic aneurysm repair.b Peripheral vascular and arteriovenous procedures.c Procedures for congenital heart disease.d Implantation of Dacron grafts (DuPont, Wilmington, DE) for the repair of nonruptured aneurysms.e Cardiac and vascular repair procedures.* Studies sponsored by industry. Open table in a new tab BP = Beriplast fibrin sealant; bThrombin = bovine plasma-derived thrombin; FFP = fresh frozen plasma; NS = not statistically significant; rThrombin = recombinant thrombin. A systematic English language literature search was conducted using MEDLINE and PubMed between January 1974 and August 2008. Keywords used for the search included bleeding, hemostatic agent, sealant, and cardiac surgery. Additional reports were identified by references cited in the publications found using the search terms and also in published review articles. Emphasis was placed on randomized controlled studies where possible. Compression hemostatic agents absorb blood and provide a scaffold for clot formation in addition to exerting compression on a bleeding site. Surgicel (Johnson & Johnson Medical Inc, Arlington, TX) is a local hemostatic bioabsorbable gauze consisting of oxidized regenerated cellulose. It is a poly anion, the functional unit of which is polyanhydroglucuronic acid. Surgicel provides a scaffold on which platelets can commence the adhesion and aggregation process leading to coagulation, but it is not reported to alter the physiological clotting mechanism. There is evidence of absorption within the first day, and complete absorption can be observed between 4 to 8 weeks, the rate being dependent on the volume of surgicel, local vascularity, and the nature of the tissue bed. Surgicel is also reported to be bacteriostatic [5Scher K.S. Coil Jr, J.A. Effects of oxidized cellulose and microfibrillar collagen on infection.Surgery. 1982; 91: 301-304PubMed Google Scholar] with reported antimicrobial activity, even against antibiotic-resistant micro-organisms including MRSA [6Spangler D. Rothenburger S. Nguyen K. Jampani H. Weiss S. Bhende S. In vitro antimicrobial activity of oxidized regenerated cellulose against antibiotic-resistant microorganisms.Surg Infect (Larchmt). 2003; 4: 255-262Crossref PubMed Scopus (137) Google Scholar]. Microfibrillar collagen was initially described in 1969. It is a water-insoluble acid salt of bovine collagen, which when used topically adheres to the bleeding site and provides some hemostatic effect and initiates platelet activation and aggregation, as well as reinforcing the fibrin clot that is formed. For high transfusion risk cardiac surgery patients, including repeat cardiac operations (such as aorta coronary bypass operations or valvular operations), ascending aortic aneurysm repair necessitating deep hypothermic circulatory arrest and ascending aortic grafting without deep hypothermic circulatory arrest Surgicel has been compared with microfibrillar collagen hemostat (Colgel [Laboratorie Interphar, Aubervilliers, France]) in terms of the ability to reduce postoperative bleeding and was found to be superior in terms of reducing postoperative drainage (Table 1) [7Sirlak M. Eryilmaz S. Yazicioglu L. et al.Comparative study of microfibrillar collagen hemostat (Colgel) and oxidized cellulose (Surgicel) in high transfusion-risk cardiac surgery.J Thorac Cardiovasc Surg. 2003; 126: 666-670Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar]. Microfibrillar collagen is not as good at reducing infection risk as Surgicel [5Scher K.S. Coil Jr, J.A. Effects of oxidized cellulose and microfibrillar collagen on infection.Surgery. 1982; 91: 301-304PubMed Google Scholar] and is reported to cause end-organ damage if shed blood containing it is returned to the circulation by either pump suction or cell salvage devices, as it may readily pass through the filters of these devices [8Robicsek F. Microfibrillar collagen hemostat in cardiac surgery.J Thorac Cardiovasc Surg. 2004; 127: 1228Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar]. CoStasis (Cohesion Technologies, Palo Alto, CA) is a composite of bovine microfibrillar collagen and bovine thrombin in a calcium chloride buffer mixed intraoperatively with an equal volume of autologous plasma obtained at the time of operation. The patient's plasma provides fibrinogen that is cleaved by the thrombin to form a collagen-fibrin gel matrix. The composite is delivered as a spray onto the bleeding site. CoStasis (Cohesion Technologies) has been compared with the use of gauze and collagen sponges and has been shown to achieve hemostasis within 3 minutes in cardiac surgery patients undergoing cardiopulmonary bypass for coronary artery bypass grafting in 76% of cases compared with 46% achieved in the control group [9CoStasis Multi-center Collaborative Writing CommitteeA novel collagen-based composite offers effective hemostasis for multiple surgical indications: Results of a randomized controlled trial.Surgery. 2001; 129: 445-450Abstract Full Text Full Text PDF PubMed Scopus (75) ]. The study does not give exact details regarding the site or timing of application, and the use of CoStasis did not have any impact on reducing transfusion of blood products. It is estimated that thrombin has been used as an adjunctive hemostat in more than half a million surgical procedures per year in the United States [10Schoenecker J.G. Hauck R.K. Mercer M.C. Parker W. Lawson J.H. Exposure to topical bovine thrombin during surgery elicits a response against the xenogeneic carbohydrate galactose alpha1-3galactose.J Clin Immunol. 2000; 20: 434-444Crossref PubMed Scopus (40) Google Scholar]. Thrombin is a serum protease that transforms fibrinogen into fibrin, and activates factor XIII and promotes stabilization of the clot formed by fibrin and other proteins. The majority of thrombin used is derived from bovine plasma, although in January 2008, recombinant human thrombin (Recothrom [ZymoGenetics, Seattle, WA]) gained United States Food and Drug Administration (FDA) approval and has potential advantages in comparison with the bovine or human types, including reduction in the formation of patient thrombin antibodies and exclusion of the risk of transmission of infection while maintaining comparable efficacy [11Chapman W.C. Singla N. Genyk Y. et al.A phase 3, randomized, double-blind comparative study of the efficacy and safety of topical recombinant human thrombin and bovine thrombin in surgical hemostasis.J Am Coll Surg. 2007; 205: 256-265Abstract Full Text Full Text PDF PubMed Scopus (139) Google Scholar]. Omnex (Ethicon Surgical Sealant; Ethicon Inc, Somerville, NJ) is a synthetic tissue adhesive consisting of a blend of two monomers (ie, 2-octyl cyanoacrylate and butyl lactoyl cyanoacrylate). The liquid preparation is contained inside a crushable capsule that delivers the preparation through a porous disc, which contains an initiator agent to activate the delivered sealant. The sealant polymerizes to form a flexible sealing film, which is adherent to both synthetic material and human tissue in a process that is independent of the patient's clotting processes. The seal degrades with time, breaking down into smaller absorbable fragments. A prospective, randomized controlled trial has assessed the efficacy of cyano-acrylate sealants in establishing hemostasis of expanded polytetrafluoroethylene to arterial vascular anastomoses in arteriovenous grafts and femoral bypass grafts in 151 patients [12Lumsden A.B. Heyman E.R. Prospective randomized study evaluating an absorbable cyanoacrylate for use in vascular reconstructions.J Vasc Surg. 2006; 44: 1002-1009Abstract Full Text Full Text PDF PubMed Scopus (55) ]. The mean time from clamp release to hemostasis was 119.3 seconds with cyanoacrylate surgical sealant versus 403.8 seconds, with the control (oxidized cellulose) (p < 0.001). Immediate hemostasis was achieved in 54.5% of patients receiving cyanoacrylate surgical sealant and in 10% of those receiving the control. A subsequent study in patients undergoing arteriovenous access or vascular reconstruction below the diaphragm with the use of cyanacrylate sealant found that immediate hemostasis was achieved in 71.3% (112 of 157) of sites and in 93.6%, 96.8%, and 100% within 1, 5, and 10 minutes, respectively [13Brunkwall J. Ruemenapf G. Florek H.J. Lang W. Schmitz-Rixen T. A single arm, prospective study of an absorbable cyanoacrylate surgical sealant for use in vascular reconstructions as an adjunct to conventional techniques to achieve haemostasis.J Cardiovasc Surg (Torino). 2007; 48: 471-476PubMed Google Scholar]. Fibrin sealant was developed in 1972 by Matras and colleagues [14Matras H. Dinges H.P. Lassmann H. Mamoli B. [Suture-free interfascicular nerve transplantation in animal experiments].Wien Med Wochenschr. 1972; 122: 517-523PubMed Google Scholar] by successfully using a fibrinogen cryoprecipitate in peripheral nerve anastomoses on animal models. Fibrin sealants are made of two components contained in separate vials: (1) a freeze dried concentrate of clotting proteins, mainly fibrinogen, factor XIII, and fibronectin (ie, the sealant) and (2) freeze dried thrombin (ie, the catalyst). Fibrinogen is a precursor of fibrin, which represents the basic element of the clot. The transformation of fibrinogen into stable fibrin occurs by means of thrombin and factor XIII, which in turn are activated by thrombin. Fibrin sealants emulate the final stages of the clotting cascade, but as they are autonomous of the body's clotting mechanism, they are also effective in patients with coagulopathies or those who are receiving heparin or anticoagulants [15Tredree R.B.W. Debrix I. Eisert A. et al.Evaluating the difference between fibrin sealants: recommendations from an international advisory panel of hospital pharmacists.EJHP Science. 2006; 12: 3-9Google Scholar, 16Kheirabadi B.S. Field-Ridley A. Pearson R. MacPhee M. Drohan W. Tuthill D. Comparative study of the efficacy of the common topical hemostatic agents with fibrin sealant in a rabbit aortic anastomosis model.J Surg Res. 2002; 106: 99-107Abstract Full Text PDF PubMed Scopus (50) Google Scholar]. Historically there have been concerns about the use of fibrin sealants with so-called homemade preparations used until the 1990s, predating the United States FDA approval, containing cryoprecipitate not subjected to viral inactivation and containing variable levels of impurities [17Busuttil R.W. A comparison of antifibrinolytic agents used in hemostatic fibrin sealants.J Am Coll Surg. 2003; 197: 1021-1028Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar]. Tisseel (Baxter Healthcare, Fremont, CA) and Beriplast (CSL Behring, King of Prussia, PA) contain bovine aprotinin, whereas Crosseal (Ethicon Inc), marketed in the United Kingdom as Quixil, contains tranexamic acid. These agents are added as antifibrinolytic agents to slow fibrinolysis of the clot, which is produced at the site of application. After a recent report of increased mortality with the use of aprotinin in cardiac surgery patients [18Fergusson D.A. Hebert P.C. Mazer C.D. et al.A comparison of aprotinin and lysine analogues in high-risk cardiac surgery.N Engl J Med. 2008; 358: 2319-2331Crossref PubMed Scopus (851) Google Scholar], Bayer Pharmaceuticals have notified the FDA of their intent to remove their systemically administered aprotinin agent Trasylol from hospital pharmacies. Tisseel (Baxter Healthcare) and Beriplast (CSL Behring) are not affected by this withdrawal, although there are reports of the adverse effects of bovine aprotinin in sealants relating to the highly immunogenic nature of bovine aprotinin in humans. Over 125 anaphylactic reactions having being reported in the literature, with an estimated anaphylaxis incidence of between 0.5 and 5 per 100,000 topical applications [15Tredree R.B.W. Debrix I. Eisert A. et al.Evaluating the difference between fibrin sealants: recommendations from an international advisory panel of hospital pharmacists.EJHP Science. 2006; 12: 3-9Google Scholar]. The Vivostat system (Vivostat A/S, Birkerod, Denmark) is a medical device to produce an autologous fibrin sealant CE marked for use in Europe in 2000. The FDA approval for use of Vivostat (Vivostat A/S) in the United States has been applied for but was not yet granted at the time this article was written. The device can generate 4.5 mL of sealant from 120 mL of the patient's blood in 23 minutes [19Kjaergard H.K. Trumbull H.R. Vivostat system autologous fibrin sealant: preliminary study in elective coronary bypass grafting.Ann Thorac Surg. 1998; 66: 482-486Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar]. The sealant is applied using a spray system. There is no randomized controlled trial using this system in cardiac surgery in which it is compared with a comparable sealing agent, although its tensile strength has been compared with other fibrin sealants and has been found to be comparable [20Velada J.L. Hollingsbee D.A. Physical characteristics of Vivostat patient-derived sealant Implications for clinical use.Eur Surg Res. 2001; 33: 399-404Crossref PubMed Scopus (18) Google Scholar]. Kjaergard and Fairbrother [21Kjaergard H. Fairbrother J. Controlled clinical studies of fibrin sealant in cardiothoracic surgery—a review.Eur J Cardiothorac Surg. 1996; 10: 727-733Crossref PubMed Scopus (69) Google Scholar] have reported 24 trials of the use of fibrin glues in cardiothoracic surgery, with 20 trials reporting a positive benefit in terms of reducing bleeding, 4 studies reporting no difference from controls, and no studies reporting a negative influence on bleeding. More recently a randomized controlled trial in pediatric cardiac surgery cases with a proven coagulopathy has shown a significant reduction in the use of blood products and operating room time to achieve hemostatsis when fibrin sealant has been used [22Codispoti M. Mankad P.S. Significant merits of a fibrin sealant in the presence of coagulopathy following paediatric cardiac surgery: randomised controlled trial.Eur J Cardiothorac Surg. 2002; 22: 200-205Crossref PubMed Scopus (44) ]. A note of caution should also be raised in the use of fibrin sealants in coronary artery bypass grafting as Lamm and colleagues [23Lamm P. Adelhard K. Juchem G. et al.Fibrin glue in coronary artery bypass grafting operations: casting out the Devil with Beelzebub?.Eur J Cardiothorac Surg. 2007; 32: 567-572Crossref PubMed Scopus (27) Google Scholar] have reported an increased risk of myocardial injury or even death in cornary artery bypass grafting patients when Tissucol fibrin sealant was used intraoperatively. They reported that in several cases they had an acute occlusion of bypass grafts after Tissucol was applied in proximity to the anastomoses with immediate embolectomy showing fresh fibrin clot in the lumen of the grafts in each case. This study resulted in the product description being changed to specifically emphasize that special care was necessary when using Tissucol in aortocoronary bypass operations. Polyethylene glycol polymers are synthetic hydrogels intended specifically as tissue sealants (ie, derivatives of polyethylene glycol); they can propagate rapid cross linking with inherent proteins, such as collagen, to form a cohesive matrix that adheres strongly to the applied tissue. The sealing capability of the hydrogel is almost immediate and does not require any human blood products or bovine components to inhibit bleeding. In a randomized controlled trial, the effectiveness of CoSeal (Cohesion Technologies, Palo Alto, CA) was compared with Gelfoam (Upjohn, Kalamazoo, MI) and thrombin for managing anastomotic bleeding after implantation of Dacron grafts (DuPont, Wilmington, DE) during aortic reconstruction for nonruptured aneurysms. A significantly greater proportion of bleeding suture line sites treated with CoSeal (Cohesion Technologies) achieved immediate sealing after re-establishment of bloodflow [24Hagberg R.C. Safi H.J. Sabik J. Conte J. Block J.E. Improved intraoperative management of anastomotic bleeding during aortic reconstruction: results of a randomized controlled trial.Am Surg. 2004; 70: 307-311PubMed ]. Another randomized controlled trial of CoSeal versus Gelfoam (Upjohn) and thrombin during surgical placement of prosthetic vascular grafts showed that overall 10-minute sealing success was equivalent. However, subjects treated with CoSeal achieved immediate anastomotic sealing at more than twice the rate of subjects treated with Gelfoam and thrombin [25Glickman M. Gheissari A. Money S. Martin J. Ballard J.L. A polymeric sealant inhibits anastomotic suture hole bleeding more rapidly than gelfoam/thrombin: results of a randomized controlled trial.Arch Surg. 2002; 137: 326-332Crossref PubMed Scopus (97) Google Scholar]. Duroseal is rarely used in cardiac surgery, although an experimental trial was performed to examine whether it had any benefits in reducing adhesion formation post-cardiac surgery and no benefit was proven [26Patila T. Jokinen J.J. Salminen J. Kankuri E. Harjula A. Polyglycolic acid glue does not prevent intrapericardial adhesions in a short-term follow-up.J Surg Res. 2008; 148: 181-184Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar]. BioGlue (CryoLife Inc, Atlanta, GA) is a bovine serum albumin and glutaraldehyde tissue adhesive. Two separate solutions are dispensed by a controlled delivery system, composed of a double-chambered syringe. Once dispensed, the adhesive solutions are mixed within the applicator tip where cross-linking begins. The glutaraldehyde molecules covalently bond the bovine serum albumin molecules to each other and, upon application, to the tissue proteins at the repair site, creating a flexible mechanical seal independent of the body's clotting mechanism. BioGlue (CryoLife Inc) begins to polymerize within 20 to 30 seconds and reaches its bonding strength within 2 minutes. BioGlue also adheres to synthetic graft materials through mechanical interlocks within the interstices of the graft matrix. A randomized controlled trial has compared the use of BioGlue with a standard control repair of anastomotic bleeding in patients undergoing cardiac and vascular repair. In this study, 49 patients underwent cardiac procedures, 105 aortic procedures, and 48 peripheral vascular procedures. Anastomotic bleeding was significantly reduced in the BioGlue group (18.8% of anastomoses) compared with the control group (42.9% of anastomoses; p < 0.001). Pledget use was reduced in the BioGlue group (26.2%) compared with the control group (35.9%; p = 0.047) [27Coselli J.S. Bavaria J.E. Fehrenbacher J. Stowe C.L. Macheers S.K. Gundry S.R. Prospective randomized study of a protein-based tissue adhesive used as a hemostatic and structural adjunct in cardiac and vascular anastomotic repair procedures.J Am Coll Surg. 2003; 197: 243-253Abstract Full Text Full Text PDF PubMed Scopus (93) ]. Adverse effects have been reported with the use of BioGlue including nerve tissue injury [28Lemaire S.A. Ochoa L.N. Conklin L.D. et al.Nerve and conduction tissue injury caused by contact with BioGlue.J Surg Res. 2007; 143: 286-293Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar], leaking of the BioGlue through needle holes [29LeMaire S.A. Carter S.A. Won T. Wang X. Conklin L.D. Coselli J.S. The threat of adhesive embolization: BioGlue leaks through needle holes in aortic tissue and prosthetic grafts.Ann Thorac Surg. 2005; 80: 106-111Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar], and impaired aortic growth causing anastomotic strictures [30LeMaire S.A. Schmittling Z.C. Coselli J.S. et al.BioGlue surgical adhesive impairs aortic growth and causes anastomotic strictures.Ann Thorac Surg. 2002; 73: 1500-1506Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar]. BioGlue is not recommended in pediatric surgery due to its inability to allow growth of the tissue it is used on. Caution must be exercised in the application of BioGlue as it may spread away from the site of application and has even spread onto valve prostheses causing intraoperative dysfunction [31Devbhandari M.P. Chaudhery Q. Duncan A.J. Acute intraoperative malfunction of aortic valve due to surgical glue.Ann Thorac Surg. 2006; 81: 1499-1500Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar, 32Karimi M. Kerber R.E. Everett J.E. Mechanical aortic valve malfunction: an intraoperative BioGlue complication.J Thorac Cardiovasc Surg. 2005; 129: 1442-1443Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar]. There have been concerns raised regarding the potentially harmful effects of BioGlue to local tissues. Anecdotal reports detail the persistence of BioGlue years after application surrounded by unusually soft and friable native tissues suggesting that BioGlue may impair normal healing [30LeMaire
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