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Previous studies comparing the thrombotic complications of cryoprecipitated fibrin sealant containing bovine thrombin on microvascular venous anastomoses in a rat epigastric free flap model revealed deleterious outcomes regarding flap survival with higher concentrations of topical bovine thrombin. This study was designed to compare three internationally available fibrin sealants, one experimental fibrin monomer sealant that does not require thrombin, and human thrombin alone as to their effects on the survival of an established rat epigastric free flap model. Ninety Sprague-Dawley rats (400 to 600 g) were prepared for abdominal surgery, and an epigastric-based skin flap was raised. The single vein draining the flap was clamped, divided, and reconnected using standard microvascular suturing techniques. Before release of the clamps, the chosen additive was applied precisely to the anastomosis. Additional material was then added to the raw surface of the flap. The animals were divided into seven treatment groups, each receiving 1 ml of commercial or investigational fibrin sealant or human thrombin alone: one control group receiving no additive treatment, four fibrin sealant groups receiving treatment with commercial or investigational fibrin sealant preparations, and two groups receiving different concentrations (500 IU/ml and 1000 IU/ml) of human thrombin applied to the anastomoses and the surrounding tissue. Flap survival was assessed at 7 days postoperatively. This study supports the contention that microvascular free flap survival based on microvascular venous anastomotic patency was adversely effected by high concentrations of thrombin. Lower concentrations (500 IU/ml and less) of thrombin did not seem to affect flap survival. One test product was composed of a fibrin monomer sealant, which obviates the need for the thrombin additive. This group's survival rate was not statistically different from that of the control group. Thus, for microvascular anastomoses, lower concentrations of thrombin or a sealant devoid of thrombin seem to be best for microvascular anastomotic patency.

Background: Patients who have axillary dissections during lumpectomy or modified radical mastectomy for breast carcinoma accumulate serosanguinous fluid, potentially resulting in a seroma. Currently accepted practice includes insertion of one or more drains for fluid evacuation. This multicenter, randomized, controlled, phase II study was undertaken to evaluate whether a virally inactivated, investigational fibrin sealant is safe and effective when used as a sealing agent to reduce the duration and volume of serosanguinous fluid drainage and to determine the dose response of this effect., Study Design: Patients undergoing lumpectomy or modified radical mastectomy were randomized to treatment with 4, 8, or 16 mL of fibrin sealant or control (no agent) at the axillary dissections site. Patients undergoing modified radical mastectomy also received an additional 4 or 8 mL of fibrin sealant at the skin flap site. Efficacy was evaluated by the number of days required for wound drainage and the volume of fluid drainage compared with control. Safety was confirmed by clinical course, the absence of viral seroconversion, and no major complications attributable to the sealant., Results: The 4-mL axillary dissection dose of fibrin sealant significantly reduced the duration and quantity of fluid drainage from the axilla following lumpectomy (p < or = 0.05). In the modified radical mastectomy patients, a 16-mL axillary dissection dose combined with an 8-mL skin flap dose was significantly effective in reducing the number of days to drain removal (p < or = 0.05) and fluid drainage (p < or = 0.01). There were no fibrin sealant patient viral seroconversions and no major complications attributable to the sealant. A number of wound infections were noted, although this may represent a center-specific effect., Conclusions: Application of fibrin sealant following axillary dissection at the time of lumpectomy or modified radical mastectomy can significantly decrease the duration and quantity of serosanguinous drainage. The viral safety of the product was also supported.

The utilization of fibrin sealants to augment hemostasis, seal tissues, and facilitate targeted delivery of drugs is increasing. In 1985, a hospital-based program was established to provide autologous and allogeneic cryoprecipitate that serves as a fibrin sealant when combined with bovine thrombin. To date, more than 4,000 patients have been treated with this product at our institution, with an efficacy rate greater than 90%. Collaboration among surgical services and the blood bank fostered multispecialty expertise with this product that led, in 1997, to the establishment of the University of Virginia Tissue Adhesive Center. The Tissue Adhesive Center is a multidisciplinary center whose physician director and nursing and administrative support staff facilitate basic research, laboratory investigation, and preclinical and clinical trials with collaborators throughout the university. The Tissue Adhesive Center also provides educational programs and clinical consultation, and tracks and participates in peer review of sealant use. The licensure of a commercially produced, virally inactivated, pooled-plasma fibrin sealant in May 1998 provided an alternative source of adhesive. Utilization of the commercial product surpassed use of the blood bank product in April 1999. At present, use of the commercial product is approximately 3 times that of the blood bank-produced sealant. This report reviews the clinical uses of fibrin sealant, its regulatory history, the production of fibrin sealants, the evolution of a blood bank fibrin sealant program, the development of the Tissue Adhesive Center, and the utilization of commercial and blood bank-produced sealant at our university hospital.

Persistent intrathoracic airspace and bronchopleural fistula remain a problem following lung resection or in patients with severe bullous disease experiencing a spontaneous pneumothorax. Although fibrin sealant has been used successfully to manage such air-leaks, precise nonoperative intrathoracic application is difficult. This report describes a novel technique using computed tomography fluoroscopy for catheter-directed FS application through a previously placed thoracostomy tube. Continuous computed tomography-fluoroscopy images allowed real-time catheter manipulation for precise placement of fibrin sealant.

Objective: Osseous defects of the head and neck are a common challenge for the otolaryngologist. To develop improved reconstructive options, osteoconductive engineering experiments are being conducted. A nasal critical-size defect (CSD) model has previously been described in which less than 7% bone healing is observed over 6 months. An implant containing fibrin sealant with and without osteoprogenitor cells is evaluated in this model., Study Design: Randomized controlled trial using a rodent model., Methods: A nasal CSD was surgically created in 18 male retired breeder Sprague-Dawley rats. Six animals were not implanted with any material, six received fibrin sealant consisting of fibrin (25 mg/mL) and thrombin (1000 U/mL), and six were implanted with fibrin sealant and rat calvarial osteoprogenitor cells (1.8 x 10(6) cells/mL). Thirty days later, the animals were examined at necropsy by planimetry, histological analysis of new bone growth, and radiodensitometric analysis of bone thickness., Results: A thin layer of bone covered the defect in all of the treated animals. A statistically significant increase in bone density (P < .05) between fibrin sealant plus osteoprogenitor cells and each of the other groups was shown using radiodensitometric analysis. Histological analysis also confirmed this difference., Conclusion: Osteoprogenitor cells contained within fibrin sealant result in a greater augmentation of bone regeneration than controls or fibrin sealant alone.

The spray application of cryo-based fibrin sealant was evaluated for reducing hemorrhage in a complex, anticoagulated canine model of knee joint arthroplasty. Nine heparinized dogs underwent bilateral knee arthroplasty under tourniquet control with each animal having 3 mL of fibrin sealant sprayed onto one joint and the other joint serving as control. The fibrin sealant significantly reduced total and incremental bleeding as compared to the control side (P < .05). In addition, the hemostatic effectiveness of the fibrin sealant increased as bleeding propensity increased (P < .05). This study suggests that fibrin sealant may reduce bleeding from orthopedic joint replacement in human patients undergoing routine operations as well as those receiving forms of anticoagulation to reduce the incidence of deep venous thrombosis and pulmonary embolus.

Purpose: Needle biopsy of the liver is a common diagnostic procedure. Although relatively safe, bleeding remains a potential complication and may occur more frequently in patients with coagulopathy. The purpose of this study was to evaluate the utility of a fibrin sealant in preventing bleeding after a 15-gauge needle biopsy of the liver in a canine model heparinized to simulate coagulopathy., Materials and Methods: Fibrin sealant was delivered to biopsy tract sites in eight dogs anticoagulated with heparin (activated clotting time 387 seconds +/- 94) using the same sheath system that was employed to obtain the biopsy specimen., Results: The results demonstrated complete hemostasis in the sealant-plugged tracts as compared to controls. Continuous bleeding was observed in none of the fibrin sealant-treated sites, compared with all of the control biopsy sites (P = .0078)., Conclusion: These results demonstrate the high degree of efficacy of fibrin sealant delivered through a sheath system in plugging liver biopsy tracts and eliminating bleeding in a severely coagulopathic animal model. This indicates that fibrin sealant use in cutting needle biopsies can reduce major and minor complications associated with the procedure.

FTA is a promising adjunct treatment in many fields of surgery, mainly in patients with acquired and congenital bleeding disorders or in procedures with high risk of postoperative bleeding or leaking of air, blood, fluids. Numerous report exist for variety of indications, however, very few are well controlled and conclusive. There is controversy and contradicting data that stem from variability in FTA formulation the selection and design of the operative indication the methodology of application including the application devices and the skills of the surgeon. Understanding of all these differences and the requirements for the certain indication are important for the successful use of FTA. It is important to remember that FTA is a blood product and even with more than one viral inactivation techniques there should have a clear indication for its use. If no clinically important benefit is proven for a certain indication it means that contraindication exists.

Fibrin sealant, a surgical tissue adhesive, has gained widespread use for its ability to achieve three major clinical goals: reducing hemorrhage, increasing tissue adherence, and allowing drug delivery. The object of this state-of-the-art review is to clarify the most recent developments in this field from a surgical perspective. The areas of greatest interest and progress relating to surgical uses for fibrin sealant--specifically, new methods of sealant production, new experimental or clinical uses, and new potential complications--are explored in this review.

Fibrin sealant (FS) has been used successfully as an effective adhesive and hemostatic agent in a variety of surgical procedures. At the University of Virginia, autologous fibrin sealant is used to reduce the potential accumulation of serous fluid after axillary dissection in patients undergoing modified radical mastectomy (MRM) for carcinoma of the breast. Unilateral MRM, including level I and II axillary lymph node dissection, was performed upon 21 patients prospectively randomized into treatment and control groups. Surgical procedures between both groups differed only by the application of autologous FS prior to axilla closure in the treatment group. Drainage was collected and measured at 24-hour intervals following the operation. Drains were removed following the measurement of 40 ml or less during a 24-hour interval. Cumulative drainage for the first 3 postoperative days in the treatment group averaged 198 +/- 83 ml compared to 467 +/- 138 ml in the control group (P < 0.0003). Day of drain removal averaged 3.9 +/- 1.7 for the treatment group and 6.9 +/- 1.2 for the control group (P < 0.0001). In the treatment group, there was a reduction in cumulative drainage over the first 3 days of 268 ml or 57 per cent, and there was a reduction in the number of days before drains can be removed of 3.0 days, or 43 per cent. We conclude that local application of FS significantly reduced the total drainage measured in patients undergoing MRM and enabled earlier drain removal.

Fibrin sealant use in the United States has been limited because of the lack of a commercially available, government approved product. However, the significant need and usefulness of this material at the time of surgical operations has stimulated alternative sources of production. At the University of Virginia, the Blood Bank produces concentrated single donor or autologous fibrinogen for use with commercially available bovine thrombin in order to make fibrin sealant. The hemostatic and adhesive properties of fibrin sealant have been used since 1985 at this Center in a wide variety of operations with over 90% effectiveness. This chapter will review the development and role of this material in modern clinical surgery at this institution. The advantages, disadvantages, and never applications of this substance in various forms will be assessed. The role of fibrin sealant is increasing in this country and additional developmental work is continuing. The era of a commercially available product in the United States appears to be on the horizon.

Closure of bronchopleural fistulas can be accomplished by applying fibrin glue through a flexible fiberoptic bronchoscope. The advantages of this method include the avoidance of general anesthesia and thoracotomy and the excellent extended access to the bronchial tree provided by the flexible bronchoscope.

Fibrin glue can be a useful adjunct to hemostasis in surgical patients. An effective technique for spray application of fibrin glue during cardiac operations is described.

Seroma is a frequent sequelae of neck dissection involving cervical lymphadenectomy. The incidence is correlated with flap elevation, lymphovascular interruption, and tissue removal. Current methods of resolving seroma, such as vacuum drainage, are not risk free. A novel approach to this problem was the use of intraoperative topical fibrin glue. A model producing seromas was developed by modified radical neck dissection on Sprague-Dawley rats. Forty rats underwent this procedure. Twenty rats were treated with saline solution (control group) and 20 were treated with fibrin glue. At necropsy on day 5, a significant reduction in the frequency of seroma was noted in the fibrin glue group. Seventeen of 20 control rats had seroma whereas only 2 of 20 experimental animals had serous collection. The Fisher exact statistical correlation revealed p less than 0.000002; therefore, the use of fibrin glue in this role merits further evaluation.

There is continued controversy regarding the effectiveness and potential adverse effects of fibrin glue. Thus, we chose to evaluate it in a model of experimental calf aortic valve replacement that has been previously well established. Concentrated fibrinogen and topical thrombin were sprayed to form a thin layer of fibrin glue over the mediastinal tissues of 20 consecutive calves undergoing aortic valve replacement. Chest tube outputs of these animals were compared with those of the preceding 20 consecutive calves undergoing aortic valve replacement without fibrin glue. All procedures were performed by the same surgeon, and no other technical changes were made between the two series. Total postoperative chest tube output (mean +/- standard error) was 553 +/- 50 mL for the calves treated with fibrin glue and 1,155 +/- 103 mL for the control calves (p less than 0.001). On histological examination of mediastinal tissues from 5 treated calves killed 6 weeks after operation, there was no evidence of inflammation, fibrosis, or residual fibrin. To our knowledge, this is the first controlled laboratory study to show that fibrin glue spray is an effective hemostatic agent and that it produces no long-term tissue reaction.

European surgeons have used fibrin glue extensively during thoracic, cardiovascular, and general surgical operations. Until now, however, it has been available only as a commercial preparation made from pooled human plasma, and it has not been approved by the U.S. Food and Drug Administration for use in the United States because of a high associated risk of hepatitis and acquired immune deficiency syndrome. Methods of obtaining fibrinogen, an essential component of fibrin glue, from cryoprecipitate or fresh frozen plasma have been published recently. However, the cryoprecipitate method results in relatively low concentrations of fibrinogen, which can reduce glue effectiveness. The fresh frozen plasma method is more expensive and does not meet the standards of the American Association of Blood Banks for the "closed" system required for safe handling and management of blood component products. Both the cryoprecipitate and the fresh frozen plasma methods result in waste of unstable clotting factors. These factors are necessary to replace human plasma clotting deficiencies but are not necessary for the production of fibrin glue. The authors have developed an efficient, high-concentration blood bank method for producing and maintaining a local supply of a safer and less expensive but equally effective material derived from stored human plasma. This material is produced using approved blood bank techniques for a "closed" system in blood component production, thus reducing the risks of contamination and infection, and its fibrinogen concentration is higher than that of standard cryoprecipitate. The cost of 1 unit of this fibrin glue is comparable to that for 1 unit of cryoprecipitate and less than that for 1 unit of fresh frozen plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Early tangential excision and immediate grafting of the burn-injured patient has been shown to be effective. Along with the use of this technique, however, comes the potential for significant blood loss, prolonged operative time, and partial loss of graft due to underlying hematoma formation. Based on experience using a pooled fibrinogen preparation, European and Japanese surgeons have provided evidence for the positive hemostatic and skin transplant fixation effects of fibrin glue. This commercial preparation, however, has not been approved by the U.S. Food and Drug Administration for use in the United States because of high risk of hepatitis and HIV transmission. Using a method of preparing highly concentrated fibrinogen utilizing standard blood bank techniques developed at the University of Virginia, we have applied single-donor fibrin glue as an adjunct in the early excision and grafting of 26 patients. Since we have been using fibrin glue, we have noted a marked reduction in operative blood loss and time involved in obtaining hemostasis. Additionally, we have found the application of the grafts to be facilitated by the "stickiness" of the recipient bed. In follow-up, grafts applied utilizing the fibrin glue technique have proceeded to uncomplicated wound healing with an overall 98% graft take.

A variety of published techniques for the production of concentrated fibrinogen from units of screened single-donor human plasma have led to increasing clinical use of fibrin glue in the United States. We have adapted a method of applying this material with a disposable plastic sprayer. In 20 consecutively treated patients, fibrin glue was sprayed on the anterior mediastinum before closure of the median sternotomy incision. A control group of 20 patients undergoing the identical cardiac operations (13 coronary artery bypass grafting procedures [CABG], 4 valve replacements [including 1 reoperative procedure], and 3 combined valve replacements and CABG) by the same surgeon within a one-year period was chosen for comparison of chest tube outputs. Specifically, chest tube outputs were as follows for treated and untreated patients, respectively: at 12 hours, 461 +/- 40 ml (mean +/- 1 standard error of the mean versus 731 +/- 80 ml; at 24 hours, 714 +/- 73 ml versus 1,016 +/- 109 ml; and at 48 hours, 863 +/- 93 ml versus 1,187 +/- 137 ml. The differences between control and spray chest tube output are statistically significant by unpaired t test (p less than 0.05) at both 12 and 24 hours. Thus, this method can reduce perioperative hemorrhage from the anterior mediastinum after cardiac operations.

We have investigated the feasibility of applying fibrin glue to liver injuries using laparoscopic guidance and have examined the gross and microscopic changes that occurred in hepatic lacerations treated with fibrin glue. These studies indicate that fibrin glue may be effectively applied to liver injuries using laparoscopic control, hepatic bleeding may be rapidly controlled when fibrin glue is applied into the base of the wound, there is no gross or microscopic evidence of hepatic toxicity related to the use of fibrin glue, and healing of liver lacerations treated by fibrin glue occurs by ingrowth of granulation tissue coupled with fibrinolysis of the fibrin glue.