Autologous fibrin gel: bactericidal properties in contaminated hepatic injury

Fibrin glue is an effective hemostatic agent in a variety of clinical situations; its utility is limited by potential transmission of viral infection. We studied the bactericidal properties of fibrin gel (FG) in a murine contaminated hepatic injury model and in vitro by agar plate culture method. Intra-abdominal abscess formation and adhesion rate were assessed following controlled liver injury in association with abdominal contamination with 10(7) Bacteroides fragilis and hepatorrhaphy (H, n = 15) or FG (n = 12). Animals treated by hepatorrhaphy had a significantly greater intra-abdominal abscess rate (15/15 vs. 4/12, p less than 0.05) and adhesion rate (14/15 vs. 6/12, p less than 0.05) than animals treated with FG. Fibrin gel is bactericidal to Bacteroides fragilis, Enterobacter faecium, Escherichia coli, and Staphylococcus aureus but has no effect against Klebsiella pneumoniae or Pseudomonas aeruginosa; the plasma component appears active. Fibrin gel demonstrates significant improvement in adhesion formation and intra-abdominal abscess rate when compared with suture hepatorrhaphy. Fibrin gel appears protective in contaminated hepatic injury.     

Fibrin gel limits intra-abdominal adhesion formation.

Autologous fibrin gel (FG) has recently been reported efficacious in hepatic injury; the effects of fibrin compounds on intra-abdominal adhesion formation is controversial. This study evaluated intra-abdominal adhesion formation in a rabbit devascularization model. Seventeen New Zealand rabbits were anesthetized and laparotomy was done. The uterine horns were abraded to punctate bleeding followed by bilateral uterine devascularization. Treatment consisted of 10 cc saline control (c) or FG applied to the uterine horns. Peritoneal lavage was done at 15 minutes for red blood cell (RBC) analysis. Autopsy was performed at 1 week. Adhesions were graded from grade 0 (no adhesions) to grade III (dense adhesions). Adhesion grading revealed no difference in average adhesion grade between FG and C with small bowel (1.0 +/- 1.3 vs 0.5 +/- 1.0); bladder (2.1 +/- 1.1 vs 2.4 +/- 1.2); or uterus (1.2 +/- vs 2.0 +/- 1.2). Adhesion grade was significantly less in FG compared to C for the colon and the abdominal incision (0.4 +/- 0.5 vs 1.7 +/- 1.1 and 1.2 +/- 1.1 vs 3.0 +/- 1.2; P less than 0.05 by t-test). There were no differences in lavage RBC count between FG and C (13.1 x 106 +/- 4.1 x 10(6) vs 8.7 x 106 +/- 3.2 x 10(6)). Fibrin gel significantly decreased incisional and colonic adhesions and reduced other abdominal adhesion formation by a nonhemostatic dependent mechanism.     

Techniques of splenic preservation using fibrin glue

Fibrin glue (FG) was used to achieve hemostasis of 16 splenic injuries in 14 patients. The etiologies of injury included five gunshot wounds, two stab wounds, four iatrogenic injuries, and five patients with blunt splenic trauma. The intraoperative blood loss averaged 1.8 +/- 2.4 (SD) liters and patients were transfused 3 +/- 2 units of blood perioperatively. The amount of FG required to achieve splenic hemostasis averaged 11 +/- 8 ml and varied directly with the grade of injury. One patient with a splenic hilar vascular injury (Grade V) underwent splenectomy following failure to achieve complete hemostasis despite the use of 25 ml of FG. All other splenic injuries were successfully managed using less than 25 ml of FG. Postoperative computerized tomographic (CT) scanning, performed in ten patients, was negative for rebleeding or abscess formation. The overall splenic salvage rate was 86%. FG was effective in achieving hemostasis of both superficial and deep splenic injuries. Its use as an adjunct in trauma surgery should result in increased splenic salvage rates compared with that obtained using conventional surgical techniques.     

Prevention of intra-abdominal abscesses with fibrinolytic agents

Fibrin deposition during secondary peritonitis predisposes to abscess formation by protecting bacteria from host-defence mechanisms. To test the hypothesis that local fibrinolytic therapy can prevent the formation of intra-abdominal abscess, daily injections of the fibrinolytic enzymes trypsin and tissue plasminogen activator (t-PA) were administered intraperitoneally to Wistar rats inoculated intraperitoneally with infected fibrin clots. After 5 days, trypsin (1 mg/ml) had significantly (p less than 0.001) reduced abscess formation in animals inoculated with monomicrobial Bacteroides fragilis clots (20% versus 87%) or mixed Escherichia coli-B. fragilis clots (11% versus 91%). Bacteroides fragilis abscesses were also completely prevented with t-PA (0.25 mg/ml). The number of B. fragilis organisms present in residual abscesses in the trypsin-treated group was significantly (p less than 0.05) lower than in the control group (8.2 +/- 0.2, n = 7 versus 5.7 +/- 1.4, n = 4, log CFU/g abscess). In-vitro studies demonstrated that trypsin had no bactericidal effect on B. fragilis, suggesting enhanced clearance of bacteria. From these studies it appears that controlled fibrinolysis at operation may be a useful adjunct to surgery and systemic antibiotics in preventing abscess formation postoperatively.     

Inhibition of intra-abdominal adhesions: a comparison of hemaseel APR and cryoprecipitate fibrin glue.

Our previous studies demonstrated fibrin glue (FG) prepared from cryoprecipitate (cryo) inhibits intra-abdominal adhesions in rats. A new FG, Hemaseel APR, is Food and Drug Administration (FDA) approved for hemostasis during cardiac surgery and splenic trauma. This study was undertaken to determine if Hemaseel FG prevents intra-abdominal adhesions, and to compare it to cryo FG. Forty-five rats underwent laparotomy. Bilateral peritoneal-muscular defects were created. Polypropylene mesh was sewn into each defect with a running silk suture. The bowel was abraded with gauze. The rats were then randomized to mesh covered with Hemaseel FG, cryo FG, or control. On postoperative day 7, the severity of adhesions were graded by percentage of mesh covered by adhesion (0-100%) and degree of adhesion (0-3). The mean percentage of mesh covered by adhesion was 9% for Hemaseel FG, 43% for cryo FG (p = .005), and 65% for the controls (p < .0001). The mean density adhesion score was 0.5 for Hemaseel FG, 1.2 for cryo FG (p = .04), and 2.1 for the controls (p < .0001). In the Hemaseel FG group, 77% of patches had no adhesions, compared with 37% in the cryo FG group (p = .004) and 13% in the controls (p < .0001). Thus, Hemaseel FG significantly decreases intra-abdominal adhesions, and is more effective than cryo FG.     

Inhibition of Intra-Abdominal Adhesions: A Comparison of Hemaseel APR and Cryoprecipitate Fibrin Glue

Our previous studies demonstrated fibrin glue (FG) prepared from cryoprecipitate (cryo) inhibits intra-abdominal adhesions in rats. A new FG, Hemaseel APR, is Food and Drug Administration (FDA) approved for hemostasis during cardiac surgery and splenic trauma. This study was undertaken to determine if Hemaseel FG prevents intra-abdominal adhesions, and to compare it to cryo FG. Forty-five rats underwent laparotomy. Bilateral peritoneal-muscular defects were created. Polypropylene mesh was sewn into each defect with a running silk suture. The bowel was abraded with gauze. The rats were then randomized to mesh covered with Hemaseel FG, cryo FG, or control. On postoperative day 7, the severity of adhesions were graded by percentage of mesh covered by adhesion (0-100%) and degree of adhesion (0-3). The mean percentage of mesh covered by adhesion was 9% for Hemaseel FG, 43% for cryo FG (p = .005), and 65% for the controls (p &lt; .0001). The mean density adhesion score was 0.5 for Hemaseel FG, 1.2 for cryo FG (p = .04), and 2.1 for the controls (p &lt; .0001). In the Hemaseel FG group, 77% of patches had no adhesions, compared with 37% in the cryo FG group (p = .004) and 13% in the controls (p &lt; .0001). Thus, Hemaseel FG significantly decreases intra-abdominal adhesions, and is more effective than cryo FG.     

Fibrin glue reduces intra-abdominal adhesions to synthetic mesh in a rat ventral hernia model

Postoperative intra-abdominal adhesions are associated with significant morbidity and mortality. In this study, the effect of topical fibrin glue (FG) on adhesion formation in a rat model was investigated. Forty Sprague-Dawley male rats underwent midline laparotomy. Bilateral peritoneal-muscular abdominal wall defects were created and then replaced with premeasured soft tissue Goretex patches. Rats were randomized to FG sprayed over the patches or to a control group. Two observers blinded to the randomization assessed the severity of adhesions to the patch by scoring the density of adhesions (grades 0-3) and the percentage of the patch area covered by adhesions (0-100%). The mean percentage of the patch covered by adhesions was 32.8 +/- 6.1 per cent for the FG group versus 57.9 +/- 6.7 per cent for the control group (P < 0.01). The mean density of adhesions for the FG group was 0.95 (+/-0.17) versus 2.0 (+/-0.21) for the control group (P = 0.001). Topical FG reduces the severity and density of intra-abdominal adhesions in a rat model.     

生物蛋白胶预防鸡趾鞘管区屈肌腱粘连的实验研究

目的 研究生物蛋白胶预防鸡趾鞘管区屈肌腱粘连的作用。方法 种禽褐鸡60只，随机分为生物蛋白胶组（FG）和生理盐水组（NS），每组各30只动物。将第三、四趾趾深屈肌腱切断，作改良Kessler法缝合，不修复腱鞘，然后在腱鞘内肌腱周围及皮下按分组注入相应药物。术后第2、4、6周取材，分别进行大体观察、组织学检查、生物力学测定。结果 术后2、4、6周，组织学检查示两组动物肌腱吻合处的炎症细胞浸润情况及肌腱的愈合进程无明显差别。缝合处粘连半定量评分、将肌腱拉出鞘管所需最大力量、耗功，FG组与NS组相比，差异均无显性意义（P＞0．05）。结论 局部应用FG不能有效预防术后肌腱粘连，但不影响肌腱的愈合进程，也不引起额外的炎症反应。     

Comparison of the topical haemostatic agents for the prevention of suture hole bleeding. An experimental study.

OBJECTIVE: using a rabbit vascular graft model we investigated the use of fibrin glue (FG), gelatin-resorcinol-formaldehyde (GRF), and collagen (C) as a means of reducing suture hole bleeding. MATERIALS AND METHODS: twenty-eight rabbits were divided into four groups: fibrin glue, gelatin-resorcinol-formaldehyde, collagen and control. A 1 cm incision was made in the abdominal aortic wall of each animal. Incisions were covered with a polytetrafluoroethylene patch sutured with a 7-0 polypropylene. Fibrin Glue, GRF, and C were applied to cover suture holes in the groups 1, 2 and 3, respectively, but nothing in controls (group 4). The fibrin clot was allowed to achieve strength for 3 minutes before the clamps were reopened. After reopening the clamps, blood was collected from the surgical site using a syringe for a total of 2 min. RESULTS: mean blood loss was significantly lower in the FG, GRF, and C compared with control group (p=0.0022, p=0.0022, and p=0.0017, respectively). The volume of blood lost and the time of haemostasis in the group 1 (FG) was less than those in groups 2 and 3 (GRF and C, respectively) (p=0.001). The haemostasis (defined 2 min later) was achieved only in group 1 (FG) (p=0.00067). CONCLUSIONS: FG, GRF and C all reduce blood loss. Fibrin glue containing factor XIII was the most effective.     

Delayed presentation of perisplenic abscess following arterial embolization

INTRODUCTIONSplenic abscess formation is a rare but significant complication that may occur after non-operative management (NOM) of a blunt splenic injury (BSI). we describe an unusual case of perisplenic abscess formation nearly 4 months after splenic artery angioembolization for a grade III splenic laceration.PRESENTATION OF CASEA 52-year-old male was transferred to the Emergency Department (ED) of our institution after falling off his bicycle. He was hemodynamically stable but complained of left upper quadrant pain. Computed tomography (CT) was notable for a Grade III splenic laceration. The patient underwent a successful splenic artery embolization on hospital day 1. He had an uneventful post-embolization course and was discharged 3 days later, afebrile, with a stable hematocrit. Four months after his initial presentation, the patient presented to the ED with fever, malaise, and left upper quadrant abdominal pain. A CT scan revealed a multiloculated perisplenic abscess. He underwent a splenectomy and drainage of peri-splenic abscess, received a course of antibiotics, and had an uneventful recovery.DISCUSSIONNOM including splenic angioembolization (SAE) is the standard of care for blunt splenic trauma in hemodynamically stable patients. Known complications from SAE include bleeding, missed injuries to the diaphragm and pancreas, and splenic abscess. This report documents a delayed perisplenic abscess following NOM of blunt splenic trauma, a rare but potential complication of SAE.CONCLUSIONFormation of a perisplenic abscess may occur several months after NOM of a blunt splenic injury. Prompt surgical management and antibiotic therapy are critical to avoid life-threatening complications.     

Genius,Creativity, and Leadership

Research in reduced suture fibrin glue (FG) and sutureless FG anastomosis has been lagging behind FG utilization in other surgical fields. A review of the literature for vascular, esophageal, tracheal, gastrointestinal, common bile duct, ureteral, vas deferens, and Fallopian tube FG anastomosis indicates that reduced suture FG and sutureless FG procedures may be performed with less training, reduced operating time, leakage, ischemia, inflammation, and necrosis compared to sutured techniques. Reduced suture FG vasular anastomosis augments early anastomotic strength. Suture number for esophageal, tracheal, and tracheobronchial anastomoses can be reduced with FG. Bursting strength in pig small intestine and rat colon was lower at 4 days postoperatively, but returned to sutured strength at 7 days. Mortality was unaffected, and 18-month follow-up in sutureless FG intestinal anastomosis in pigs showed no stenosis. Preliminary ureteral studies have demonstrated successful sutureless FG and reduced suture FG laparoscopic techniques in pigs. Reduced suture FG and sutureless FG vas deferens anastomosis may reduce sperm granuloma rates, with increased patency and pregnancy rates. Patency and pregnancy rates have been similar for tubal FG, reduced suture FG, autologous fibrin glue (AFG), and sutured anastomosis. Any risk of viral transmission or immune response is eliminated by AFG. While there are few studies in many areas of FG hollow vessel anastomosis, the current literature illustrates many of the advantages of FG over other anastomotic techniques and should provide impetus for continued research in this promising field of surgery.     

Sutureless and reduced suture anastomosis of hollow vessels with fibrin glue: a review.

Research in reduced suture fibrin glue (FG) and sutureless FG anastomosis has been lagging behind FG utilization in other surgical fields. A review of the literature for vascular, esophageal, tracheal, gastrointestinal, common bile duct, ureteral, vas deferens, and Fallopian tube FG anastomosis indicates that reduced suture FG and sutureless FG procedures may be performed with less training, reduced operating time, leakage, ischemia, inflammation, and necrosis compared to sutured techniques. Reduced suture FG vascular anastomosis augments early anastomotic strength. Suture number for esophageal, tracheal, and tracheobronchial anastomoses can be reduced with FG. Bursting strength in pig small intestine and rat colon was lower at 4 days postoperatively, but returned to sutured strength at 7 days. Mortality was unaffected, and 18-month follow-up in sutureless FG intestinal anastomosis in pigs showed no stenosis. Preliminary ureteral studies have demonstrated successful sutureless FG and reduced suture FG laparoscopic techniques in pigs. Reduced suture FG and sutureless FG vas deferens anastomosis may reduce sperm granuloma rates, with increased patency and pregnancy rates. Patency and pregnancy rates have been similar for tubal FG, reduced suture FG, autologous fibrin glue (AFG), and sutured anastomosis. Any risk of viral transmission or immune response is eliminated by AFG. While there are few studies in many areas of FG hollow vessel anastomosis, the current literature illustrates many of the advantages of FG over other anastomotic techniques and should provide impetus for continued research in this promising field of surgery.     

Fibrin glue reduces the severity of intra-abdominal adhesions in a rat model

BACKGROUND: The purpose of this study was to determine whether fibrin glue inhibits intra-abdominal adhesions. METHODS: Twenty rats underwent midline laparotomy. To maximize adhesions, bilateral peritoneal muscular defects were created and covered with polypropylene mesh sewn with a braided suture. The bowel was abraded with dry gauze. Rats were randomized to either fibrin glue (FG) sprayed over the mesh or to control (no further treatment) groups. At 1 week, the adhesion density (graded 0 to 3), the percentage of the patch covered by adhesion (0% to 100%), and adhesion type were recorded. RESULTS: The mean adhesion density was 1.45+/-0.33 for FG versus 2.8+/-0.11 for controls (P = 0.001). The mean percentage of adhesions was 36+/-9.9 for the FG group and 94+/-3.7 for controls (P = 0.0002). Bowel or solid organs were adherent to the patch in 6 of 20 (30%) in the FG group versus 12 of 20 (70%) in controls (P = 0.057). CONCLUSIONS: Topical fibrin glue reduces the density and severity of intra-abdominal adhesions in a rat model.     

Fibrin sealant in high-risk colonic anastomoses

The use of fibrin sealant has been advocated to enhance the healing of high-risk intestinal anastomoses. Colonic anastomoses were performed in 162 rats randomly assigned to four groups: control animals with or without fibrin sealant applied to the anastomosis and steroid-treated animals with or without fibrin sealant. At five days postoperatively, the use of steroids alone significantly reduced the anastomotic bursting pressure (ABP) and enhanced abscess and adhesion formation. The addition of fibrin sealant to the anastomosis in steroid-treated animals did not improve ABP and, in fact, further increased abscess formation. In control animals, the use of fibrin sealant also reduced ABP and enhanced abscess and adhesion formation. By ten days, there was no difference in ABP among the groups, and the rate of abscess formation was reduced in all groups. These findings indicated that short-term treatment with steroids delayed colonic anastomotic healing. Fibrin sealant did not enhance the integrity of these high-risk anastomoses. The present data do not support the use of fibrin sealant in high-risk colonic anastomoses.     

Hemostasis and healing of superficial splenic injuries using Nd:YAG laser and nonsuture techniques: Preliminary report

This study was designed to compare Nd:YAG laser to fibrin glue, electrocautery, and avitene in the management of superficial splenic injury. Six dogs were submitted to laparotomy. A #11 blade scalpel was used to sharply excise the splenic capsule inflicting four 1″ × 1″ superficial injuries on each spleen. The lesions were treated. All animals had a second laparotomy (“first relaparotomy”); 2 dogs each were reexplored on postop days 3, 7, and 14. Morphologic and histologic observations were made. A third and final relaparotomy was performed on all dogs at 21 days with repeated morphologic and histologic assessments. Hemostatic times, grades of adhesions, and microscopic changes were not significantly different among the various treatments (P > 0.25). Capsular plaque formations were significantly different at the first relaparotomy (P < 0.01) and at final relaparotomy (P < 0.05). Both adhesions and capsular plaque formation were least at fibrin glue-treated sites, whereas Nd:YAG (1.06 μm) was most effective for average hemostatic time (mean = 109.67 s). Electrocautery produced the greatest necrosis at treatment sites. We conclude that all modalities are effective in controlling hemorrhage. © 1994 Wiley-Liss, Inc.     

Fibrin in peritonitis. V. Fibrin inhibits phagocytic killing of Escherichia coli by human polymorphonuclear leukocytes.

Fibrin deposition initiated by peritonitis is thought to be an important local defense mechanism because it sequesters and walls off bacterial spillage. However, fibrin has been shown to predispose to residual abscess formation in rat peritonitis model. To examine the potential mechanisms of this effect, fibrin was tested in vitro for its inhibitory effect on neutrophil function. At all concentrations tested (50-1000 mg/dl), fibrin significantly impaired the ability of neutrophils to kill Escherichia coli. This inhibition occurred in a dose dependent fashion with almost complete prevention of killing at the highest concentration tested. Further studies showed that pre-exposure to fibrin did not reduce the neutrophil's ability to degranulate, undergo a respiratory burst, or kill E. coli, indicating that fibrin did not cause irreversible damage to the normal microbicidal functions of the neutrophil. However, fibrin, at physiologic concentrations, significantly impaired phagocytosis of radiolabeled E. coli. The data support the concept that phagocytosis of bacteria is impaired by neutrophils enmeshed in fibrin. Thus, contaminated fibrin could act as a nidus for residual abscesses formation following peritonitis even if an adequate number of normal leukocytes were present.     

Use of autologous fibrin glue in the treatment of splenic trauma: an experimental study.

There is little doubt that preserving the spleen will contribute to a much more favourable outcome in patients undergoing splenic surgery, as a result of avoiding the well known risks of splenectomy. Among many operative methods described for splenic salvage, application of autologous fibrin glue (AFG) is particularly promising because of its unique characteristics. The use of AFG has been evaluated and its efficacy and tissue compatibility assessed in the treatment of splenic trauma in 15 partially splenectomized New Zealand White rabbits. The application of the AFG to the resected splenic surface achieved complete haemostasis in all animals. The animals were divided into four groups and were killed at varying intervals ranging from 24 h to 10 weeks. During re-exploration there was no evidence of recurrent bleeding and histopathological examination revealed progressive absorption of the AFG with a minimal inflammatory response. It is concluded that AFG is an effective haemostatic agent with good systemic and local compatibility and can be used in splenic salvage, which thereby avoids the use of non-autologous products with their risks of disease transmission.     

Antibiotics fail to prevent abscess formation secondary to bacteria trapped in fibrin clots

We inoculated 120 rats with 2 X 10(9) Escherichia coli or 2 X 10(9) Bacteroides fragilis suspended in normal saline solution or incorporated into fibrin clots. In the control group, all animals died after inoculation with E coli, but none died after the inoculation with B fragilis; both were suspended in normal saline solution. Escherichia coli entrapped in fibrin did not cause mortality but did result in abscess formation in all animals. Bacteroides fragilis incorporated into fibrin clots resulted in abscess formation in the majority of animals. Treatment with gentamicin sulfate, ampicillin sulfate, and cefoxitin sodium completely abolished the mortality secondary to E coli suspended in normal saline solution but did not influence the rate of abscess formation secondary to E coli incorporated into fibrin clots. Similarly, cefoxitin and clindamycin phosphate did not significantly change abscess formation secondary to B fragilis incorporated into fibrin clots. We conclude that systemic antibiotics are ineffective in the prevention of abscesses secondary to bacteria trapped in fibrin, either because they do not reach bactericidal levels in the fibrin clot, as in the case of gentamicin, ampicillin, and clindamycin, or, as in the case of cefoxitin, because of the inoculum effect caused by the high number of bacteria. Fibrinogen or fibrin itself do not afford any protection of bacteria against the action of antibiotics.     

Orally delivered antibiotics which lower bacterial numbers decrease experimental intra-abdominal adhesions

BACKGROUND: Postsurgical adhesion formation is a common occurrence after most surgical procedures and is still a major cause of postoperative morbidity because no satisfactory treatment or prophylaxis has yet been developed. Further elucidation of the basic mechanisms of postsurgical adhesion formation is needed. Recent studies using germfree rats have found the indigenous bowel flora to be important in the adhesive response. The present study examined whether antibiotic treatment affects intra-abdominal adhesion formation. METHODS: Using the cecal crush model to inflict adhesions, groups of rats ( n=12) were treated with placebo or amoxicillin/clavulanic acid in the drinking water. Treatment started 3 days before operation and continued until evaluation. Adhesion scores were recorded after 7 days. Bacterial counts were made from cultures of fecal samples on operation day and at termination. RESULTS: Amoxicillin/clavulanic acid decreased adhesion score compared to placebo. Adhesion incidence was 50% in the treatment group and 92% in the placebo group. Bacterial numbers were lower in the treatment group. CONCLUSIONS: Antibiotic treatment which lowers bacterial numbers can decrease adhesions.     

Fibrin glue for partial nephrectomy.

Fibrin glue, a mixture of concentrated autologous fibrinogen and bovine-derived thrombin, was used to achieve hemostasis during 7 partial nephrectomies. After transected vessels were suture ligated, topically applied fibrin glue filled all renal defects with an adherent clot that resulted in immediate hemostasis. There was no case of delayed hematoma or abscess formation, and no complications were referrable to the use of fibrin glue. Although fibrin glue is no substitute for early vascular control and careful surgical technique, its ability to stop venous oozing from the cut surface of renal parenchymal tissue dramatically facilitates hemostatic control.