Treatment of rupture of the Achilles tendon with fibrin sealant

BACKGROUND: The optimal management strategy for acute Achilles tendon ruptures is controversial. These injuries historically were treated by nonoperative methods (cast immobilization, bandaging); however, operative repair of the ruptured tendon has become popular. METHODS: Thirty-two patients who had rupture of the Achilles tendon were treated operatively with use of fibrin sealant, and clinical and functional performance measures were assessed after a mean followup of at least 6 months between November, 1998, and July, 2003. All of the patients were male. Average age was 38.18 (30 to 45) years. All of the patients were followed for at least 18 months after surgery. Average followup time was 22.4 (18 to 56) months. We evaluated all patients according to the scoring system of Thermann et al. RESULTS: Our results were excellent in 24 patients and good in eight patients. One patient had rerupture 3 weeks after surgery. CONCLUSION: Fibrin sealants are biologically compatible, hemostatic agents derived from human plasma that can be used instead of suture or suture support. We think that the treatment of rupture of the Achilles tendon with fibrin sealant is a useful treatment, and there is less risk of complications, such as deep infection, than in other operative procedures. We had no wound closure problems, the incision size was small, and the operating time was short. However, it must be remembered that the risk of disease transfer by fibrin sealant application is still present.     

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.     

Treatment of bronchopleural fistula with small intestinal mucosa and fibrin glue sealant

Bronchopleural fistula can be a devastating complication of pulmonary resections. Treatment options are often limited and carry significant morbidity or mortality, or both. We present a case of bronchopleural fistula occurring after pulmonary lobectomy for aspergilloma in a patient with recurrent acute lymphoblastic leukemia. The bronchopleural fistula was treated using bronchoscopic obliteration with Tisseel VH Fibrin Sealant (Baxter Healthcare Corp, Westlake Village, CA) and small intestinal submucosa with complete resolution and no morbidity. The relevant literature is reviewed.     

Closure of subarachnoid-pleural fistulae with fibrin sealant

Subarachnoid-pleural fistulae are rare and require closure if conservative therapy has failed. A simple and effective method is described using a pleural graft sealed with fibrin glue. The closure is immediate and long lasting.     

Treatment of fractures of the humeral capitulum using fibrin sealant

Summary Three patients with fresh displaced fractures of the capitulum humeri were treated by the fibrin sealant method, without additional internal fixation. At follow-up, between 1 1/2 and 4 1/2 years after surgery, clinical results were very good. Fibrin sealant has many advantages over traditional osteosynthesis techniques and is therefore recommended as an effective method for treating such serious but uncommon fractures of the elbow joint.     

载药磷酸钙骨水泥治疗慢性骨髓炎研究进展

抗生素缓释系统具有局部抗生素浓度高，全身毒副作用小，缓慢释放，持续时间长等优点，已逐渐成为治疗慢性骨髓炎的一种重要方法。载药磷酸钙骨水泥（CPC）具有药物载体和修复骨缺损的双重作用，且能诱导骨的生长并同步降解，是一种理想的安全可靠的抗生素缓释载体材料。在彻底病灶清除的基础上用载药CPC植入骨缺损处为治疗慢性骨髓炎的一种理想的行之有效的方法，具有操作简便、效果佳、住院时间短等优点。本文拟就载药磷酸钙骨水泥的生物特性、实验研究和临床应用等方面作一综述。     

Injectable tissue-engineered cartilage using a fibrin sealant

OBJECTIVE: To investigate a commercially available fibrin sealant as a vehicle for developing injectable tissue-engineered cartilage. METHODS: Fibrin glue was mixed with autogenous chondrocytes from rabbits (n = 15). This isolate was injected along their nasal dorsa using 1 of 3 different fibrin glue concentrations. The samples were harvested at 8 weeks and compared with elastin and hyaline cartilage controls. RESULTS: Neocartilage was created along a linear injection tract on the dorsa of the nasal bones in 5 of 15 rabbits. Higher thrombin concentrations proved to be directly correlated with successful creation of injectable cartilage. Histologically, the staining patterns of both hematoxylin-eosin and safranin O stains were identical to that of normal auricular control cartilage. The presence of elastin fibers was observed following Verhoeff staining. No foreign body reaction was observed from the host. CONCLUSIONS: This study demonstrated a successful method for percutaneous injection of tissue-engineered cartilage as a mixture of chondrocytes suspended in fibrin glue. The thrombin concentration, along with the concentration of fibrinogen and chondrocytes, must be optimized to succeed consistently in cartilage growth.     

Drain-free simple retropubic prostatectomy with fibrin sealant

PURPOSE: We present our preliminary experience with liquid fibrin sealant during simple retropubic prostatectomy. MATERIALS AND METHODS: We reviewed 18 consecutive simple retropubic prostatectomies performed for symptomatic advanced benign prostatic hyperplasia at our institution between 1997 and 2001. Adenoma enucleation was performed via transverse anterior prostatic capsulotomy. In the first 13 cases (group 1) a Jackson-Pratt suction drain was placed in the pelvis after prostatic capsular closure. In the remaining 5 cases (group 2) 2 ml. liquid fibrin sealant were administered over the closed prostatic capsule instead of a pelvic drain. RESULTS: The 2 groups were matched for age and prostate size. Average time to drain removal in control group was 3.92 days, while the fibrin sealant group had no clinically apparent adverse sequelae despite the lack of pelvic drainage. Average hospitalization in group 1 was 4.38 days, while all group 2 patients were discharged home after 2 days (p = 0.001). In addition, a trend toward earlier resumption of a full diet was noted in the sealant group (2.61 versus 1 day, p = 0.075). CONCLUSIONS: Liquid fibrin sealant appears to expedite recovery and shorten hospitalization when used as an adjunct during simple prostatectomy.     

Evaluation of a fibrin sealant free of bovine-derived components in an experimental vas anastomosis study

OBJECTIVES: The risk of transmission of bovine spongiform encephalopathy cannot be excluded from the use of bovine-derived products. The present study was undertaken to evaluate the performance of a new fibrin glue free of bovine-derived components in vas anastomosis and to compare this product to conventional vas anastomosis with fibrin glue. METHODS: Bilateral delayed vas anastomosis was performed in 40 Sprague-Dawley rats. All animals underwent a fibrin glue-assisted vas anastomosis with three transmural sutures tied prior to fibrin glue application. The composition and preparation of fibrin glue was similar for all vas anastomoses except the fibrinolysis inhibitor component which was aprotinin (3,000 KUI/ml) in group 1 and tranexamic acid (10 mg/ml) in group 2. The animals (20 rats in both groups) were sacrificed 7 weeks postoperatively and evaluated for gross patency, presence of sperm granuloma and tensile strength measurements at the anastomosis site. RESULTS: No difference was found between the 2 groups for all parameters evaluated whether a bovine-derived or a synthetic fibrinolysis inhibitor component was used. CONCLUSION: This study showed that tranexamic acid, a fibrinolysis inhibitor, can be substituted for conventional fibrin glue thereby avoiding the risks of bovine products.     

The effectiveness of fibrin glue sealant for reducing experimental pulmonary ari leak

The effectiveness of fibrin glue as a biological sealant for pulmonary air leaks was determined in 16 dogs. A standardized pleural defect was made in the left lower lobe, and the quantity of air passing through a chest tube was assessed with a Collins respirometer. For the 8 randomly assigned control animals, the air leak decreased over 90 minutes from a mean of 1.4 L/min to a mean of 1.1 L/min (mean decrease, 19.8%). In the 8 randomly assigned fibrin glue-treated animals, the air leak decreased from a mean of 2.1 L/min to a mean of 0.5 L/min (mean decrease, 80.8%) (p less than 0.0001). Postoperative evaluation of survivors disclosed no increased adhesions in the glue-treated animals and complete resorption of the glue at 3 months. We conclude that in this animal model, fibrin glue reduced the size of pulmonary air leaks in the early period after thoracotomy and did not lead to increased intrapleural adhesions.     

Treatment of spontaneous intracranial hypotension with percutaneous placement of a fibrin sealant. Report of four cases

Spontaneous intracranial hypotension due to a cerebrospinal fluid (CSF) leak in the spine is an important cause of new, daily persistent headaches. Most patients respond well to conservative treatments including epidural blood patching. Limited options for effective treatment are available for patients in whom these treatments fail. The authors treated four patients (mean age 38 years; range 26-43 years) with percutaneous placement of a fibrin sealant. All these patients presented with intractable positional headaches. The CSF leak was located in the lower cervical spine in three patients and in the lower thoracic spine in one patient. Four to 20 milliliters of fibrin sealant was injected at the site of the CSF leak. Two of the four patients became asymptomatic within days of the procedure and thus avoided surgery. There were no complications of this procedure. Percutaneous placement of a fibrin sealant is a safe, minimally invasive treatment for spontaneous spinal CSF leaks and should be considered in patients in whom conservative treatment has failed.     

Pretreatment of prosthetic valve sewing-ring with the antibiotic/fibrin sealant compound as a prophylactic tool against prosthetic valve endocarditis

Prosthetic valve endocarditis (PVE) remains a dreaded complication following heart valve replacement despite perioperative antibiotic (AB) prophylaxis. In order to increase the AB concentration in the sewing ring, an experimental study including topical application of the gentamicin derivative EMD 46/217 and fibrin sealant (F) as AB-carrier was initiated. In vitro pretreatment of Dacron with the gentamicin derivative and F was followed by constant AB release for 3 weeks. In a subsequent animal study, four Dacron rings with different pretreatment were implanted in the descending aorta of 10 pigs after direct contamination with 10(8) Staphylococcus aureus solution. One ring was pretreated with the AB/F compound, a second ring with the AB alone. Ring 3 (no pretreatment) and ring 4 (F alone) served as controls. After 1 week, the sewing rings and their corresponding implantation sites were assayed for measurement of AB-content and for culture. The AB content of AB/F-rings was 24.99 +/- 7.16 micrograms/g wet weight, while rings pretreated with the AB alone contained no measurable drug amounts with the exception of one specimen (0.5 microgram/g) (AB/F vs. AB-rings: P less than 0.0005). The corresponding implantation sites to AB/F rings contained 1.07 +/- 0.54 micrograms/g AB, whereas in only 2 of 10 implantation sites of AB rings, low AB levels were found (0.05 and 0.2 micrograms/g) (AB/F vs. AB ring implantation sites: P less than 0.0005). While all control rings and 9 of 10 AB rings were infected, 5 of 10 AB/F rings remained sterile after culture (AB/F vs. AB rings: P = 0.05). This finding correlated with the AB content in the suture rings.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of a new fibrin sealant with standard topical hemostatic agents

BACKGROUND: Bleeding following liver resection continues to be a significant morbidity of the procedure. Fibrin sealants represent an improvement over conventional topical hemostatic agents, because they contain components that actively form clot. However, most available agents contain nonhuman protein, which represents an immunologic risk. HYPOTHESIS: An investigational surgical fibrin sealant (Crosseal; American Red Cross, Washington, DC) composed of human clottable proteins and human thrombin is more effective than standard topical hemostatic agents in reducing the time required to achieve hemostasis after liver resection. DESIGN: Prospective, randomized, controlled trial. SETTING: Fifteen major referral centers in the United States and the United Kingdom. METHODS: After liver resection using standard surgical techniques, 121 patients seen between May 1999 and May 2000 were randomized to treatment with a 2-component fibrin sealant (n=58) or to standard topical hemostatic agents, used singly or in combination (n=63). Up to 10 mL of Crosseal was administered by a spray applicator, as recommended by the manufacturer, whereas agents used in the control group were applied according to their instructions for use. MAIN OUTCOME MEASURES: The primary outcome measured was time to hemostasis. Secondary outcomes measured included blood loss between application of the hemostatic agent and closure of the abdomen, duration of postoperative biliary drainage, and the occurrence of complications, defined a priori as reoperation for any reason, development of abdominal fluid collections, or bilious appearance of drained fluid for at least 1 day postoperatively. RESULTS: The mean time to hemostasis was 282 seconds with Crosseal, compared with 468 seconds with standard agents (2-sided; P =.06), for the 116 efficacy-evaluable patients. Hemostasis was achieved within 10 minutes in 53 patients (91.4%) treated with the study fibrin sealant and in 44 control patients (69.8%) (2-sided; P =.003). Intraoperative blood loss was similar in the 2 groups. In the Crosseal group, the percentage of patients developing postoperative complications was 17.2%, compared with 36.5% in the control group (2-sided; P =.02). CONCLUSIONS: Compared with the use of standard topical hemostatic agents, Crosseal fibrin sealant significantly reduced the time to achieve hemostasis following liver resection. Patients treated with the new fibrin sealant also experienced significantly fewer postoperative complications.     

Treatment of experimental osteomyelitis with antibiotic-impregnated bone graft substitute

The model of Norden was used to induce osteomyelitis in the left tibia of New Zealand White rabbits. Twenty-one days following inoculation, the animals had primary debridement and then were randomized into one of three treatment groups. Group I received no additional treatment; in Group II, plain hydroxyapatite beads were packed into the defect; and in Group III, gentamicin crobefat-loaded hydroxyapatite beads were packed into the defect. The animals were observed for 40 days after the primary debridement and then were killed. The intensity of infection was determined by swab cultures and quantitative bacterial cultures of the debrided material. At primary debridement, all of the animals in each group were equally infected. At the time of secondary debridement, only the animals in Group III had a statistically significant reduction in infection (p < 0.001). In this study, we demonstrated that an antibiotic-loaded osteoinductive ceramic bead can effectively eliminate bacteria from an osteomyelitic cavity.     

Production and clinical application of fibrin sealant with high concentrated fibrin (fibrin patch)

OBJECT: The sealing properties of fibrin sealant with high concentrated fibrin (fibrin patch) were examined. MATERIAL AND METHODS: A commercial fibrin sealant (Bolheal) produced from pooled human plasma was utilized for this study. The fibrin sealant made of fibrinogen and thrombin solutions mixed in a volume ratio 5:1 was applied as the fibrin sealant with high concentrated fibrin (fibrin patch). The burst pressure of the fibrin clots of either 1:1 or 5:1 mixing ratio, which sealed the small holes, was measured by a water-leak preventing model. The tensile strength of the fibrin patch was measured by the breaking pressure of the fibrin clot. The burst pressure of the fibrin patch, which sealed the dural defect with a diameter of 15 mm, was compared with that of expanded polytetrafluoroethylene (ePTFE). RESULTS: The burst pressure was elevated from 287 +/- 23.1 to 445 +/- 30.5 mmHg by changing the mixing ratio from 1:1 to 5:1. The breaking pressure of the fibrin patch showed 131 +/- 25.4 mmHg and that of the patch mixed at the ratio of 1:1 showed 46.6 +/- 9.9 mmHg. The result of dural repair with the fibrin patch revealed higher sealing effectiveness than that of ePTFE. The burst pressure averaged 70.5 +/- 21.4 mmHg in the fibrin patch samples and 51.4 +/- 13 mmHg in the ePTFE samples. CONCLUSION: The fibrin patch revealed higher performance as a sealant and has the potential to be a candidate for acceptance as the new dural repair material.     

In vivo efficacy of a new autologous fibrin sealant

BACKGROUND: Fibrin-based sealants are commonly used to arrest bleeding following surgery. A new method has been developed for preparation of autologous fibrin sealant (FS) from protamine-precipitated fibrinogen concentrate. This FS has the potential to be a low-cost, safe, and convenient alternative to commercial sealants or cryoprecipitates usually prepared from patient or banked plasma. In this study, the efficacy of human FS was evaluated in a rat kidney model. MATERIALS AND METHODS: FS containing various fibrinogen concentrations (ranging from 15 to 60 mg/mL) were applied to controlled renal incisions, and bleeding time and blood loss were measured. Bleeding from the wounds was also predicted using a mathematical model based on tensile strength and adhesion strength of the sealants. RESULTS: The sealants, when applied under controlled conditions, reduced the blood loss and bleeding time more effectively than controls (where no sealant, plasma, or the commercial product Tisseel (Baxter Healthcare Corp., Westlake Village, CA) was applied). The sealant also significantly reduced bleeding time with a concomitant decrease in blood loss in rats that were anticoagulated with heparin. Bleeding times predicted by the mathematical model agreed well with experimental data and demonstrated that the ability of sealant to reduce bleeding time largely depended on its adhesion strength. CONCLUSION: The autologous fibrin sealant can be prepared with any volume (e.g., 5 to 500 mL) of patient's blood, within minutes, and exhibits equal or greater hemostatic efficacy compared with the leading commercial sealant.     

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.     

Treatment of chronic osteomyelitis using calcium hydroxyapatite ceramic implants impregnated with antibiotic

Summary. We treated eighteen patients with chronic osteomyelitis by implanting pieces of antibiotic-impregnated calcium hydroxyapatite ceramic into a cavity produced after thorough surgical excision of necrotic tissue. Within three months the infected sites had all healed. During follow-up ranging from 24 to 75 months there was no recurrence of infection. Two of the patients had infected prosthetic joints which were successfully revised. Infection was controlled and incorporation of the ceramic material into host bone was demonstrated radiographically. We recommend the use of porous pieces of calcium hydroxyapatite impregnated with antibiotic as a new system for drug delivery in the treatment of chronic osteomyelitis.

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Résumé. Les auteurs rapportent le traitement de 18 patients atteints d’ostéomyélite chronique par excision chirurgicale suivie d’implantation de fragments d’hydroxyapatite de calcium imprégnés d’antibiotique. Tous les sites d’infection ont cicatrisé dans un délai de 3 mois. Pendant la période de suivi, allant de 24 à 75 mois, il n’y a pas eu de récidive de l’infection. 2 des patients avaient une infection sur prothèse articulaire qui ont été révisés avec succès. En plus du contr?le de l’infection, il a été constaté radiologiquement une incorporation de l’hydroxyapatite. Les auteurs recommandent donc l’utilisation des ces fragments poreux d’hydroxyapatite de calcium imprégnés d’antibiotique pour le traitement de l’ostéomyélite chronique.

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Accepted: 15 October 1997     

Closure of a post-pneumonectomy bronchopleural fistula with fibrin sealant (Tisseel).

A persistent post-pneumonectomy bronchopleural fistula and empyema were successfully treated by draining and cleansing the empyema cavity and then occluding the fistula with fibrin sealant.