The potential utility of fibrin sealant dressing in repair of vascular injury in swine

BACKGROUND: A previous study in which fibrin sealant dressing (FSD) secured hemostasis in major arterial hemorrhage for 96 hours suggested the applicability of this dressing in damage control operations after severe trauma. The objective of this study was to determine the effective duration of FSD hemostatic function in vivo and to examine its potential utility for definitive repair of a major arterial injury in swine. METHODS: High pressure bleeding in an infrarenal aortotomy was controlled by placing FSD on the wound with 4-minute compression (n = 15). If hemostasis was achieved, the abdominal cavity was closed. Surviving animals were killed at 2, 4, 6, and 8 weeks and aortotomy sites collected for histology. RESULTS: FSD stopped arterial hemorrhage after 4-minute compression in 14 of 15 (93%) pigs. Dressings failed in two pigs at 36 and 53 minutes after treatment. Twelve (80%) animals recovered and resumed normal activities. Of the remaining 12, two developed rebleeding at the aortotomy site on days 8 and 11 and were killed; another was killed because of idiopathic low hematocrit on day 10. Nine pigs survived until scheduled to be killed, maintaining hemostasis with stable hematological values. In the surviving animals, serial computed tomography scans showed formation of a pseudoaneurysm at the aortotomy site, which resolved after 2 to 3 weeks. The initial vascular defect and pseudoaneurysm were filled with fibroblast-myoblast collagen rich tissues covered by endothelium. CONCLUSION: FSD can seal an arterial injury, stop high pressure bleeding, and prevent rebleeding for at least 7 days. The dressing may be most beneficial in damage control operations. If combined with an elective interventional radiologic procedure (e.g. embolization or stenting), it may also offer an alternative to suture repair of vascular injuries in cases where profuse bleeding obstructs visualization.     

Development of an animal model for assessment of the hemostatic efficacy of fibrin sealant in vascular surgery

PURPOSE: Sustained hemostatic function of fibrin sealant (FS) is crucial when it is used in cardiovascular surgery. The purpose of this study was to develop a model that can determine the long-term hemostatic efficacy of tissue sealants in a vascular surgery. METHODS: To determine the ability of the model to detect differences in FS performance, various concentrations of FS were prepared and tested. Tensile strength of FS clots was determined in vitro using a tensiometer. Laparotomy was performed on 49 anesthetized rabbits, and a segment of the aorta was occluded, transected, and then sutured in an end-to-end fashion with four or eight interrupted 9-O sutures. The four-suture repair was covered with FS or placebo, and blood flow restored. Spilled blood was absorbed with gauze and weighed to estimate blood loss. Four weeks after surgery the animals were euthanized and the vessels recovered for histology. RESULTS: Average tensile strength of FS clots at 120, 90, and 60 mg/ml topical fibrinogen complex (TFC) concentration was 0.42 +/- 0.07 N, with no significant difference among them. The lowest TFC concentration, 30 mg/ml, produced weaker clots than either 120 or 90 mg/ml (P < 0.05). All rabbits with four-suture anastomoses that were treated with placebo bled to death after the vessel was unclamped (n = 6). Treatment of suture line with standard FS concentration (120 mg/ml TFC, n = 8) sealed the anastomosis and prevented blood loss. Hemostasis was sustained for 4 weeks, allowing vascular healing. All rabbits with the eight-suture anastomosis survived the operation but lost 42 +/- 9.2 ml blood (n = 5). Hemostatic efficacy of FS was unchanged when TFC was diluted to 90 mg/ml (n = 6) but further dilution to 60 mg/ml with water (n = 8) produced significantly less effective clots, with an average blood loss of 5.5 +/- 7.6 ml (P < 0.05) and two fatal clot failures postoperatively. When FS was diluted to 60 mg/ml TFC with a buffer, it maintained its hemostatic strength (n = 6). Further TFC dilution to 30 mg/ml led to consistent bleeding with an average blood loss of 35.3 +/- 10.3 ml (P < 0.001, n = 6). CONCLUSIONS: The four-suture anastomosis of rabbit aorta offers a consistent and reliable method for evaluating the short- and long-term hemostatic efficacy of FS products. This model is not only able to determine the functional differences in various concentrations of FS, but it is also sensitive to detect the subtle changes in FS preparation (e.g., medium composition) that is not detected by in vitro testing.     

Applications of fibrin sealant in surgery

Fibrin sealant has been used with increasing frequency in a variety of surgical field for its unique hemostatic and adhesive abilities. Fibrin sealant mimics the last step of the coagulation cascade and takes place independently of the patient's coagulation status. With rapid advances in minimally invasive surgery, the potential uses for this type of biologic and synthetic material are expanding exponentially. This article reviews the data associated with the application of fibrin sealant in various surgical procedures. From reinforcing gastrointestinal anastomosis to repair perforated duodenal ulcers to mesh fixation in laparoscopic inguinal hernia repair, fibrin sealant is gaining increasing acceptance among surgeons. The applications of fibrin sealant are expanding, and new preparations of fibrin sealant are currently being evaluated.     

Thrombogenic effects of a nonthrombin-based fibrin sealant compared with thrombin-based fibrin sealant on microvenous anastomoses in a rat model

The efficacy and safety of tissue adhesives needs to be clearly defined. A thrombin-based preparation of fibrin sealant has recently been shown to have deleterious effects on microvascular anastomoses in an animal model. The authors found that fibrin sealant constructed with a high concentration of bovine thrombin (1,000 IU per milliliter) was detrimental to microvascular patency when applied to the anastomosis in a rat free flap model. The microvenous anastomosis had the highest rate of thrombosis and failure in this model. A nonthrombin-based fibrin sealant has recently become available for experimental investigation. This study examined the thrombogenic effect of this nonthrombin-based fibrin sealant on microvenous anastomoses in a rat free flap model compared with the effect of traditionally prepared fibrin sealant with varying concentrations of thrombin. The conclusions reveal that flap survival with application of the nonthrombin-based fibrin sealant to the anastomosis was comparable with flap survival of the control animals. Flap survival with application of the traditionally prepared thrombin-based fibrin sealant was also comparable with flap survival of the control animals when a concentration of 500 IU per milliliter of thrombin was used. However, flap survival decreased significantly (p <0.005) when a concentration of 1,000 IU per milliliter of thrombin was used in the construct of the fibrin adhesive. These results support the previous findings of the harmful effects of thrombin when used in high concentrations and applied to the microvenous anastomosis of this free flap model. Moreover, this initial investigation with a nonthrombin-based fibrin sealant did not show any deleterious effects on the microvenous anastomosis compared with control animals.     

Current applications of fibrin sealant in urologic surgery

Biosurgical preparations designed to promote surgical hemostasis and tissue adhesion are being increasingly employed across all surgical disciplines. Fibrin sealant is the most widely studied and utilized biosurgical adjunct in urology. Complex reconstructive, oncologic, and laparoscopic genitourinary procedures are those most appropriate for sealant use. This article details the diverse urologic applications of fibrin sealant in the management of genitourinary injuries, surgery, and complications.     

The use of fibrin sealant in pediatric surgery

After giving a brief historic survey of sealing procedures with biological sealants the authors report on the application of Tisseel/Tissucol in pediatric surgery on the basis of literature and own experiences. Socalled absolute and relative indications are listed in a table. The use of fibrin sealant in neonatal surgery for esophageal atresia as well as splenic and hepatic birth injuries is presented on the basis of casuistics. The completely decapsulated spleen of a newborn baby could be preserved by enveloping the entire organ with fibrin sealant. Postoperative bleeding did not occur. 4 months post surgery normal arterial and venous blood flow was established. In the same infant the hemorrhage from the decapsulated facies diaphragmatica on the left side of the liver could also be managed by the application of fibrin sealant.     

Fibrin sealant in vascular surgery: a review

Fibrin sealant (FS) is a mixture of concentrated fibrinogen and thrombin that creates a fibrin matrix that is slowly degraded by the body's fibrinolytic system. FS is currently being used in the clinical arena for many applications. Perhaps the most relevant indication for vascular surgeons concentrates on FS's hemostatic properties. Current research in many centers is investigating FS's capability to incorporate drugs and cytokines into the fibrin matrix for slow release as a drug delivery system for future clinical use. This review will focus on three main uses of FS: as an anastomotic sealant, as an antibiotic coating, and as an agent for endothelialization of grafts.     

The value of fibrin sealant in thyroid surgery without drainage

Fibrin sealant is widely used to achieve complete hemostasis in many fields of surgery. A retrospective review of the surgical management of 81 patients with thyroid diseases between 1992 and 1998 was undertaken to determine if drainage after thyroid surgery could be safely avoided and substituted by fibrin sealing before closure of the wound. Complications were few and resulted in one patient with hoarseness, four minor oedemas and one case of unexplained fever during 48 h. The subjective discomfort from the collar incision was unusual and aesthetic healing was obtained in most of the cases (93.8%). These results suggest that the application of fibrin sealant can be advocated in thyroid surgery as an adjunct to a good surgical procedure and perhaps that prophylactic drainage is unnecessary.     

Optimized thrombin dilution protocol for a slowly setting fibrin sealant in surgery

Summary BACKGROUND: Fibrin sealants find applications in many surgical fields (e.g., plastic and reconstructive surgery) where a slower setting time of about 30 to 60 s is beneficial. This can be achieved by diluting the thrombin component of the fibrin sealant to a concentration of about 5 IU/ml. This work was carried out to define an optimal dilution medium for thrombin which maintains all relevant functional parameters of the fibrin sealant and which is easy to prepare with components available in most operating theaters. METHODS: Different performance criteria of a fibrin sealant were tested in vitro by the following methods: adhesive strength in a rat skin adhesion model, turbidimetry and scanning electron microscopy to determine the fibrin clots structure, tensile strength of the fibrin clots by measuring the force at break. The cross-linking of the fibrin sealant by factor XIII (FXIII) as a function of the calcium concentration was assessed by quantitative electrophoresis. RESULTS: A dilution medium containing only calcium chloride in a concentration of about 20 mM performed best in most of the applied test systems. Dilution media with high ionic strength resulted in clots with low adhesive and tensile strength, thin fibrin fibers, and low clot elasticity. Dilution media without calcium prevented proper cross-linking of the resulting fibrin clots and led to clots with low tensile and adhesive strength. CONCLUSIONS: We present an optimized simple dilution protocol for the dilution of the thrombin component for a slowly setting fibrin sealant.     

腹腔镜手术中应用医用生物蛋白胶辅助治疗的体会

目的:探讨医用生物蛋白胶(b iom ed ical fibrin sealant,BFS)在腹腔镜手术中的应用优势及前景。方法:在1 215例腹腔镜手术中应用医用生物蛋白胶。结果:所有病例均手术顺利,术后恢复良好。无胆囊床创面渗出、肠吻合口漏、阑尾残端漏等并发症出现。结论:医用生物蛋白胶在各种腹腔镜手术中可以有效的减少创面的渗血,预防小胆管的微小漏和肠吻合口的“针孔漏”;促进组织愈合,为腹腔镜手术提供有效的安全保障,同时减少腹腔粘连,促进恢复,缩短住院时间。     

Systematic review of the use of fibrin sealant in abdominal-wall repair surgery

Purpose  

Our objective was to analyze the advantages and inconveniences associated with the use of fibrin sealant compared with mechanical means for mesh fixation following abdominal-wall surgery.     

Use of a fibrin preparation in the engineering of a vascular graft model.

OBJECTIVE: Morphological and functional characterization of cocultured endothelial cells (EC) and myofibroblasts (MFB) seeded on a matrix composed of a fibrin preparation mimicking the microenvironment of a vascular wall. METHODS: MFB and EC were isolated from human saphenous veins and expanded separately in vitro. MFB were seeded on a composite matrix consisting of a fibrin preparation (with or without transforming growth factor-beta2) and a polyglactin-mesh to form a 3-dimensional structure, which was consecutively reseeded with EC. Seeded matrices were incubated in a bioreactor. Characterization was done including fluorescence staining, live-/dead-assay and immunohistochemistry. RESULTS: High density cocultures in hierarchical structure mimicking the formation of a vascular wall were obtained with nearly complete coverage of the surface with EC. Distribution of preseeded MFB in a 519+/-27 microm thick layer (day 14) was achieved. Cell viability was shown in fluorescence staining for at least 19 days. In deeper layers, no viable cells could be detected within the fibrin preparation. EC covered the surface, had uniform morphology, and their preserved viability was shown for at least 5 days. No EC-ingrowth was found into the fibrin preparation. Neoformation of the matrix proteins laminin and collagen IV was observed. CONCLUSION: A structured coculture of MFB and EC was obtained mimicking the formation of a vascular wall with preserved viability utilizing a fibrin preparation. Nutrition problems seem to limit the maximal extent of MFB in the matrix.     

Four years' experience with fibrin sealant in thoracic and cardiovascular surgery

A single-donor fibrin sealant system was used in 689 thoracic and cardiovascular surgical procedures over the 4-year period between April 1, 1985, and March 31, 1989. An excellent overall success rate (646/689, 94% effective) was achieved with specific applications, including reduction of leakage of air (29/33, 88% effective), blood (595/634, 94% effective), and fluid (14/14, 100% effective), as well as positioning of anatomical structures such as coronary bypass grafts (8/8, 100% effective). Application methods included use of spray bottles (477/497, 96% effective), syringes (165/186, 89% effective), and a Silastic cannula through the flexible fiber-optic bronchoscope (4/6, 67% effective). The system was used in a wide variety of cardiac, pulmonary, esophageal, and vascular procedures to seal staple lines, suture lines, anastomoses, conduits, fistulas, and raw surfaces. No complications with this single-donor system secondary to blood-borne disease have been documented. Overall infection occurred at a nominal rate (16/689, 2%). Thus, fibrin sealant has been a useful tool to control the leakage of air, blood, and fluid during a wide variety of thoracic and cardiovascular procedures and may be of benefit to other surgeons.     

The effect of fibrin sealant on the healing of laser-resurfaced skin

Background: Fibrin sealant is an effective hemostatic agent and a useful tissue sealant. Studies have also suggested that fibrin sealant may accelerate the normal wound-healing process. Objective: This study was designed to ascertain whether fibrin sealant would enhance wound healing after CO₂ laser resurfacing in a guinea pig model. Methods: The CO₂ laser was used to create equal areas of skin resurfacing on both sides of 14 Dunkin Hartley guinea pigs. Fibrin sealant was applied to the treatment side, whereas bacitracin was applied to the control side. Biopsies of these areas were performed on days 1, 3, 7, and 10. A histologic evaluation was performed with the use of a grading scale that compared acute and chronic inflammation, granulation tissue, collagen deposition, and epidermal regeneration. Results: The wounds treated with fibrin sealant demonstrated a statistically significant reduction in the degree of acute and chronic inflammation as well as collagen deposition. At day 7, fibrin sealant was noted to enhance neovascularization and result in a slight delay in reepithelialization. All wounds were completely reepithelialized at day 10. No wound infections or other complications were noted as a result of the application of fibrin sealant. Conclusions: Although wound healing was not accelerated, the application of fibrin sealant after CO₂ laser resurfacing diminished the acute and chronic inflammatory response, enhanced neovascularization, and reduced collagen accumulation. Further research is needed to assess whether the effects of fibrin sealant noted in this study result in improved cosmetic healing after CO₂ laser resurfacing. (Aesthetic Surg J 2001;21:509-517.)     

Evaluation of fibrin sealant for biologic mesh fixation at the hiatus in a porcine model

Background

The ideal method to secure biologic mesh during laparoscopic hiatal hernia repair remains uncertain. Suture or tack fixation can be technically difficult, and serious cardiovascular complications have been reported. Fibrin sealant (FS) offers a potential solution to this problem. We hypothesized that FS provides comparable mesh fixation to suture repair during laparoscopic mesh hiatoplasty.

Study design

Using a porcine model, laparoscopic hiatal hernia repair was performed with suture reapproximation of the crura and reinforcement with an acellular porcine dermal matrix. Prior to repair, animals were randomized to mesh fixation with sutures (S) or FS. After 30-day survival, an esophagram was performed, the diaphragm harvested, and mesh position, fixation, and incorporation were evaluated histologically and biomechanically using a T-peel test.

Results

Twenty (10 S and 10 FS) laparoscopic hiatal hernia repairs were performed. Total operative time was significantly less in the FS group (74.7 versus 127.0?min, p?<?0.01). There were no instances of mesh migration in any animal. Mean peel force did not differ significantly between the S and FS groups (0.21 vs. 0.18?N/mm, respectively; p?=?0.49). There was no significant difference in cellular repopularization or inflammatory changes around the mesh.

Conclusions

Fibrin sealant offers a reasonable alternative to suturing biologic mesh during laparoscopic hiatal hernia repair with equivalent mesh fixation. At 30 days it provides adhesive strength similar to suture fixation, while significantly reducing operative time.     

Intraoperative use of fibrin sealant in pulmonary surgery. A prospective study on a series of 124 procedures

Following lung resection, there is often important air leakage. Application of fibrin sealant on the parenchymal sutures or sites stripped of visceral pleura improves airtightness. The author reports a prospective series of 124 operations complicated by important air leakage, which was treated by application of fibrin sealant. This group is compared to another similar group of patients in which fibrin sealant was not used. All operations were done by the same surgeon. The time of post-operative thoracic drainage is markedly reduced (mean two days), and the post-operative hospital stay time is also reduced. It seems that intra-operative use of fibrin sealant helps to improve the post-operative course in the surgical unit.     

The co-application of sprayed cultured autologous keratinocytes and autologous fibrin sealant in a porcine wound model.

We have explored the potential for cultured autologous keratinocytes to form an epidermis when delivered as a spray intermixed with autologous fibrin sealant. Twelve full-thickness wounds in Large White pigs (six wounds in each of two pigs) were isolated from the surrounding skin by 4 cm diameter polytetrafluoroethylene chambers, and grafted with Integra artificial skin (Ethicon). Autologous fibrin sealant was produced 10 days later, using an automated processor unit (Vivostat System, ConvaTec, Bristol Myers Squibb), from 120 ml of autologous citrated blood taken 30 min before keratinocyte application. Nine wounds were sprayed, using a Vivostat System automated applicator unit, with a mixture of the sealant preparation and freshly trypsinised cultured autologous keratinocytes in growth medium, at a density of 1-3 x 10(5) cm(-2). Three control wounds were sprayed with the same mixture without cells. The sealant-cell mixture polymerised and adhered to the wound surface immediately. Histological analysis of biopsies taken following sealant-cell application showed that isolated spherical keratinocytes were distributed throughout the sealant at between 3.1 x 10(4) cm(-2) and 7.6 x 10(4) cm(-2). After 4 days discreet colonies of keratinocytes were observed on the wound bed. At 14 days a multi-layered undulating epidermis was formed, punctuated by sporadic epidermal cysts; the mean area of epithelium was 50.1% (s.d. = 19.7%, n = 9). There was no epithelium in the controls (s.d. = 0, n = 3). The difference was statistically significant (P=0.016). This study suggests that co-sprayed cultured keratinocytes and autologous fibrin sealant may be an effective means of delivering epithelial cells to assist wound healing.