A pilot study of the effects of Vivostat patient-derived fibrin sealant in reducing blood loss in primary hip arthroplasty. Fibrin sealant reduces suture line bleeding during carotid endarterectomy: a randomised trial. Application of fibrin glue sealant after hepatectomy does not seem justified: results of a randomized study in 300 patients. Prospective randomized multicenter trial of fibrin sealant versus thrombin-soaked gelatin sponge for suture- or needle-hole bleeding from polytetrafluoroethylene femoral artery grafts. Use of fibrin sealant to reduce bloody drainage and hemoglobin loss after total knee arthroplasty: a brief note on a randomized prospective trial. The effect of autologous fibrin sealant (Vivostat) on morbidity after pulmonary lobectomy: a prospective randomised, blinded study. A prospective, randomized trial evaluating the safety and efficacy of fibrin sealant in tubeless percutaneous nephrolithotomy. The effect of fibrin sealant combined with fibrinolysis inhibitor on reducing the amount of lymphatic leakage after axillary evacuation in breast cancer. A prospective randomized clinical trial. Hemostatic efficacy of fibrin sealant (human) on expanded poly-tetrafluoroethylene carotid patch angioplasty: a randomized clinical trial.
A pilot study evaluated the effectiveness of Vivostat patient-derived fibrin sealant in reducing blood loss in patients who underwent primary hip arthroplasty. Eighty adult patients undergoing elective surgery were randomized to receive either Vivostat sealant or control (no additional hemostatic treatment). Patients allocated Vivostat sealant donated 120 mL of blood, which was then processed perioperatively to produce a fibrin sealant that was applied to the bleeding wound surfaces just before closure. Transfusion requirements, blood loss during surgery, drain volumes, and daily hematocrit and hemoglobin levels were measured. Hospitalization times, adverse events, and postoperative wound complications were also monitored. Blood loss during surgery and wound drainage volume was lower in the Vivostat group than in the control group, although the differences were not significantly different. Transfusion requirements (median, 270 mL of packed red blood cells) and hospitalization times (both median 7 days) were the same for both groups. No adverse events related to the use of Vivostat occurred. There were indications of a possible reduction in the incidence of postoperative wound oozing (15% vs 25%) and hematomas (6% vs 11%) with the use of Vivostat compared with the control group, although differences were not statistically significant. In conclusion, in this pilot study, use of Vivostat patient-derived fibrin in hip arthroplasty was not associated with a significant reduction in blood loss. Further studies, with larger numbers of patients, may be warranted to investigate a possible benefit of Vivostat in reducing postoperative wound complications. To determine whether topical fibrin sealant reduced suture line bleeding during carotid endarterectomy with polytetrafluoroethylene (PTFE) patch closure.
                Prospective randomised non-blinded control trial.
                Regional vascular surgery unit.
                Seventeen patients undergoing carotid endarterectomy were randomised either to receive fibrin sealant as a topical haemostatic agent at the arteriotomy suture line or to act as control.
                Time taken to achieve haemostasis at the suture line. Intraoperative blood loss. Total operative time.
                The median time to achieve haemostasis was 5.5 min (range 4-31 min) in the treatment group and 19 min (range 10-47 min) in the control group. This difference was statistically significant p < 0.005 by Mann-Whitney test. There was no statistical difference in total operative time. Operative blood loss was lower in the treatment group (median 420ml, range 300-500ml) than in the control group (median 550ml, range 350-1200ml) but this difference was not statistically significant. One patient in the control group suffered a perioperative thrombo-embolic event.
                Fibrin sealant is an effective topical haemostatic agent for arteriotomy suture lines involving PTFE material. To evaluate the efficacy, amount of hemorrhage, biliary leakage, complications, and postoperative evolution after fibrin glue sealant application in patients undergoing liver resection.
                Fibrin sealants have become popular as a means of improving perioperative hemostasis and reducing biliary leakage after liver surgery. However, trials regarding its use in liver surgery remain limited and of poor methodologic quality.
                A total of 300 patients undergoing hepatic resection were randomly assigned to fibrin glue application or control groups. Characteristics and debit of drainage and postoperative complications were evaluated. The amount of blood loss, measurements of hematologic parameters liver test, and postoperative evolution (particularly involving biliary fistula and morbidity) was also recorded.
                Postoperatively, no differences were observed in the amount of transfusion (0.15 +/- 0.66 vs. 0.17 +/- 0.63 PRCU; P = 0.7234) or in the patients that required transfusion (18% vs. 12%; P = 0.2), respectively, for the fibrin glue or control group. There were no differences in overall drainage volumes (1180 +/- 2528 vs. 960 +/- 1253 mL) or in days of postoperative drainage (7.9 +/- 5 vs. 7.1 +/- 4.7). Incidence of biliary fistula was similar in the fibrin glue and control groups, (10% vs. 11%). There were no differences regarding postoperative morbidity between groups (23% vs. 23%; P = 1).
                Application of fibrin sealant in the raw surface of the liver does not seem justified. Blood loss, transfusion, incidence of biliary fistula, and outcome are comparable to patients without fibrin glue. Therefore, discontinuation of routine use of fibrin sealant would result in significant cost saving. We evaluated the safety and efficacy of the fibrin sealant Beriplast P (FSBP; Aventis-Behring) for hemostasis in anastomosis of polytetrafluoroethylene (PTFE) grafts to the femoral artery.
                In a single-blinded randomized prospective multicenter clinical trial, FSBP was compared with thrombin-soaked gelatin sponge (TSG) for efficacy in stopping bleeding from needle or suture holes in PTFE grafts after anastomosis to the femoral artery. Patients were randomized to FSBP application, which requires a 3-minute period of arterial clamping to enable the fibrin clot to adhere, or to TSG application, which requires pressure from gauze sponges, after completion of the femoral artery anastomosis. The primary end point was hemostasis, defined as absence of any detectable bleeding as judged by the operating surgeon, by 4 minutes after randomization. Secondary end points included actual time from randomization to hemostasis, time to beginning of wound closure, measured blood loss (weighed sponges), incidence of recurrent bleeding, stay in the intensive care unit, and hospital length of stay. Data were analyzed with the intention-to-treat method.
                Two hundred thirty-five subjects were enrolled at 26 medical centers; 34 were subsequently excluded from the study. Of the 201 randomized subjects, 100 received FSBP and 99 received TSG. Hemostasis was achieved by 4 minutes in 64 subjects (63%) in the FSBP group and 40 subjects (40%) in the TSG group (P =.0018). In the FSBP group, compared with the TSG group, time to hemostasis was shorter (median, 4.0 minutes; 95% confidence interval [CI], 3.8-4.18 minutes vs median, 5.6 minutes, 95% CI, 4.5-7.0; P =.008), blood loss was less (mean, 4.0 +/- 29.7 g vs mean, 15.6 +/- 28.4 g; P <.0001), and time to wound closure was shorter (median, 15 minutes; 95% CI, 10.47-18.67 minutes vs median, 22.8 minutes; 95% CI, 18.67-30.67; P =.005). There were no differences in recurrent bleeding or any other adverse events. There was no significant difference in ICU stay, but hospital length of stay was shorter in the FSBP group compared with the TSG group, and the difference approached significance (median, 6.5 days; 95% CI, 5.00-7.00 days vs median, 7.0 days; 95% CI,. 6.00-8.00 days; P =.0565).
                FSBP is more effective than TSG for achieving hemostasis of needle or suture hole bleeding from PTFE femoral artery grafts. A phase-III trial that included fifty-three patients undergoing unilateral primary total knee arthroplasty with cement was conducted to investigate the hemostatic efficacy of fibrin sealant.
                Following cementing of the joint, 10 mL of fibrin sealant was sprayed onto the wound before tourniquet deflation and wound closure. No placebo was used in the control group. All patients received drains.
                Within twelve hours after the surgery, the amount of bloody drainage was 184.5 +/- 28.9 mL (mean and standard error) in the fibrin-sealant group (information available for twenty-three patients) and 408.3 +/- 54.6 mL in the control group (information available for twenty-three patients) (p = 0.002, after adjustment for variance in the time that the drainage was measured). On the first postoperative day, the hemoglobin level had decreased by 20.1 +/- 2.1 g/L in the fibrin-sealant group (information available for twenty-two patients) and by 27.3 +/- 2.1 g/L in the control group (information available for twenty-four patients). After adjustment for baseline values, the decrease in the hemoglobin level was 28.9% less in the fibrin-sealant group than in the control group (p = 0.005, 95% confidence limits = 10.2, 43.7). There were no seroconversions in the fibrin-sealant group.
                These results suggest that fibrin sealant can safely reduce bloody drainage following total knee arthroplasty while maintaining higher hemoglobin levels. Postoperative air leakage is the most frequent complication after pulmonary surgery. The development of modern surgical techniques has been influenced strongly by the need to manage air leakage effectively during pulmonary resection. This study evaluated the effect of using an autologous fibrin sealant (Vivostat) during lobectomy on morbidity following surgery.
                This was a prospective, blinded, randomised clinical study. Patients undergoing lobectomy were enrolled into two groups (Vivostat or non-treatment control, 20 per group). Air leakage was measured over a 1-h period (using a mechanical suction pump) on the day of operation, and both air leakage and bleeding/exudation (drainage volume) were recorded every morning postoperatively until the chest tubes were removed. Personnel recording these parameters were blinded to the intervention received. Results: Compared with the control group, mean bleeding/exudate volumes were significantly reduced in the Vivostat group (day 1,370 vs. 525 ml; total, 424 vs. 782 ml; both P<0.001), and drains were inserted for a shorter time (medians, 1 vs. 2 days, P=0.07). Significantly fewer patients had air leakage at any time in the Vivostat group (40 vs. 80%, P=0.02), and air leakage volumes were significantly lower compared with the control group (median differences: day of surgery: 0.6l/min, P=0.01; total 0.8l/min, P=0.03). Postoperative hospitalisation time was shorter in the Vivostat group than in the control group but the difference was not significant (0.5 days, P=0.12).
                Vivostat fibrin sealant significantly reduces post-surgical air leakage and drainage volumes following lobectomy in pulmonary surgery and is suitable for routine use in this procedure. We performed a prospective, randomized trial to assess the safety and efficacy of fibrin sealant in tubeless percutaneous nephrolithotomy.
                A total of 63 patients undergoing tubeless percutaneous nephrolithotomy were randomized to receive Tisseel vapor heated sealant at the end of the procedure. Fibrin sealant was instilled under direct vision in the nephrostomy tract at the end of the procedure. Patients younger than 14 years and those undergoing staged percutaneous nephrolithotomy or bilateral simultaneous percutaneous nephrolithotomy were excluded from study. Patients needing greater than 2 percutaneous tracts, those with significant bleeding or associated pyonephrosis and those with a residual stone burden were also excluded from study. The perioperative outcome in these patients (experimental group) was compared with the outcome in those undergoing tubeless percutaneous nephrolithotomy without fibrin sealant (control group).
                Fibrin sealant was instilled in 32 patients. There was no difference in the hematocrit decrease and blood transfusion requirement in the 2 groups. Patients in the experimental group experienced less postoperative pain and required less analgesia. They were discharged home 5 hours earlier than patients in the control group. However, this difference was not statistically significant. Complete stone clearance was achieved in 87.5% of patients in the experimental group and in 90.32% of controls.
                The instillation of Tisseel fibrin glue is safe for tubeless percutaneous nephrolithotomy. It is associated with less postoperative pain and a lower analgesic requirement. Additional prospective, randomized studies are required to better define its clinical role in the future. One third of women undergoing mastectomy with axillary evacuation for primary breast cancer suffer from postoperative seromas leading to unnecessary costs and complications such as infections and new operations. Different methods to prevent seroma formation have been tried without permanent success. The aim of this prospective randomised study was to examine the effect of fibrin sealant with fibrinolysis inhibitor firstly on the reduction of the amount of lymphatic leakage after axillary evacuation and secondly on the reduction of days with drains and postoperative seroma punctures.
                40 patients with primary breast cancer were prospectively randomised to the treatment group (n = 19) getting fibrin glue combined with fibrinolysis inhibitor (aprotinin) sprayed into the axillary fossa and to the control group (n = 21).
                There were no differences in the incidence of postoperative seromas between the groups. However, the seromas were easier to treat if fibrin clue was used. Total quantity (mean+/-SD) of lymphorrhea and total number of aspirations (mean+/-SD) were almost twice as high in the patients of the control group compared to those having fibrin sealant. In the treatment group seromas resolved after one or occasionally after two aspirations in 71 % of patients, while in the control group 90 % of patients needed three or more aspirations.
                Potentially, fibrin sealant combined with fibrinolysis inhibitor might be used for the treatment of post- axillary evacuation lymphorrhea and seroma. The efficacy of solvent-detergent-treated fibrin sealant (human [FSH]) for controlling anastomotic bleeding from expanded polytetrafluoroethylene (ePTFE) patch angioplasty during carotid endarterectomy was evaluated, and FSH was compared with thrombin-soaked gelatin sponge (Gelfoam; TSG).
                The study was of a randomized, open-label, single-site, single-treatment, parallel design that took place in a referral center with hospitalized patients. Forty-seven adult patients (33 men, 14 women) underwent elective carotid endarterectomy. Patients were randomized to receive either FSH (N = 24) or TSG (N = 23). FSH was obtained as an investigational new drug. FSH was applied as a liquid by means of a dual-syringe technique. Heparin anticoagulation, patch thickness, and suture type were standardized. Two different needle sizes were used (CV-6, PT-13: N = 21 [FSH: N = 10, TSG: N = 11]; CV-6, PT-9: N = 26 [FSH: N = 14, TSG: N = 13]). The FSH or TSG was applied to the ePTFE patch, and then blood flow was restored through the carotid artery. Degree of anticoagulation was assessed by anti-factor Xa activity. The time from restoration of carotid blood flow until achieving hemostasis was recorded. The blood loss from patch suture hole bleeding was measured. Completion intraoperative duplex ultrasound scanning was performed in all cases. Heparin was reversed with protamine sulfate. The primary end point was successful hemostasis within 15 minutes of restoration of carotid blood flow. The secondary end points were the amount of blood loss caused by suture line bleeding and the time to achieve hemostasis.
                There was no difference in the number of patients with complete hemostasis at 15 minutes (TSG, 13 of 23; FSH, 12 of 24; P =.77). The measured blood loss was 99.0 +/- 119.9 (SD) mL for TSG, and 105.0 +/- 107.9 mL for FSH (P =.86). The time to hemostasis was the same for both groups (TSG, 16.5 +/- 16.5 minutes; FSH, 16.6 +/- 14.2 minutes; P =.97). Within both treatment groups, the use of larger needles (PT-13) was associated with greater blood loss (FSH, 169.7 +/- 124.2 mL; TSG, 172.7 +/- 151.5 mL) than was the use of smaller needles (PT-9; FSH, 58.8 +/- 66.3 mL; TSG, 34.1 +/- 25.6 mL; P =.036, P =.001, respectively). There were no postoperative strokes or bleeding complications in either group. No abnormalities were shown in either group by means of completion carotid duplex ultrasound scanning.
                FSH was equivalent, but not superior to, TSG in achieving hemostasis during carotid endarterectomy performed with ePTFE patch angioplasty. Adhesion properties of FSH to ePTFE are possibly different than those to native tissue and warrant additional investigation.
Overall, the results suggest that fibrin sealants are efficacious in reducing both post-operative blood loss and peri-operative exposure to allogeneic RBC transfusion. Although treatment-effect heterogeneity was observed for these primary efficacy outcomes, heterogeneity was generally in terms of the size of effect rather than the direction of effect. Fibrin sealants appeared to demonstrate their greatest beneficial effects in the context of orthopaedic surgery, where blood loss is often substantial. Trials not involving orthopaedic surgery generally showed a trend toward decreased post-operative blood loss but the observed reductions were not clinically significant. The majority of trials included in this review were small, which raises concerns about the potential effects of publication bias. Funnel plot assessment indicates that there is some evidence of publication bias in the form of a missing population of small negative trials. We believe that large, methodologically rigorous, randomised controlled trials of fibrin sealants are needed.