Trial of a novel synthetic sealant in preventing air leaks after lung resection. [Use of a biological glue in partial pulmonary excision surgery. Results of a controlled trial in 50 patients]. A prospective randomized trial comparing completion technique of fissures for lobectomy: stapler versus precision dissection and sealant. The effect of fibrin glueing to seal bronchial and alveolar leakages after pulmonary resections and decortications. Efficacy and safety of topical application of human fibrinogen/thrombin-coated collagen patch (TachoComb) for treatment of air leakage after standard lobectomy. Effect of fibrin glue in the reduction of postthoracotomy alveolar air leak. Randomized controlled trial of a synthetic sealant for preventing alveolar air leaks after lobectomy. The effect of autologous fibrin sealant (Vivostat) on morbidity after pulmonary lobectomy: a prospective randomised, blinded study. Experimental and clinical evaluation of a new synthetic, absorbable sealant to reduce air leaks in thoracic operations. Effect of routine fibrin glue use on the duration of air leaks after lobectomy. A prospective, randomized, controlled trial of the effectiveness of BioGlue in treating alveolar air leaks. Fibrin glue in pulmonary resection: a prospective, randomized, blinded study. Efficiency of fleece-bound sealing (TachoSil) of air leaks in lung surgery: a prospective randomised trial. Prospective randomized study evaluating a biodegradable polymeric sealant for sealing intraoperative air leaks that occur during pulmonary resection.
Postoperative air leaks are a major cause of morbidity after lung resections. This study was designed to evaluate the efficacy and safety of a new synthetic, bioresorbable surgical sealant in preventing air leaks after pulmonary resection.
                In a multicenter trial, 172 patients undergoing thoracotomy were randomized intraoperatively in a 2:1 ratio to receive surgical sealant applied to sites at risk for air leak after standard methods of lung closure (treatment group) or to have standard lung closure only (control group). The primary outcome variable was the percentage of patients free of air leakage throughout hospitalization. Secondary outcome variables were the control of air leaks intraoperatively and the time to postoperative air leak cessation. Time to chest tube removal, time to hospital discharge, and safety outcomes were also evaluated.
                Air leaks were identified before randomization in 89 of 117 patients in the treatment group and in 39 of 55 patients in the control group. Application of the sealant resulted in control of air leaks in 92% of treated patients (p < or = 0.001). A significantly higher percentage of treated patients than control patients remained free of air leaks during hospitalization (39% versus 11%, p < or =0.001). The mean times to last observable air leak were 30.9 hours in the treatment group and 52.3 hours in the control group (p = 0.006). In the treatment group, trends were observed for reduced time to chest tube removal and earlier discharge. No significant difference was identified in postoperative morbidity and mortality between the two groups.
                Air leaks after lung resection occur in most patients. The application of this novel surgical sealant appears to be effective and safe in preventing postoperative air leaks. A controlled study concerning the surgical use of a fibrin glue was conducted in 50 patients undergoing partial pulmonary excision. In 25 of these patients, chosen at random, hemostasis and aerostasis of the fissural, and/or intersegmentary dissection planes were achieved by electrocoagulation, in the other 25 by the application of fibrin glue. The statistical study did not show any significant difference between the two groups in terms of the surgical indication, the type of excision and the associated surgical procedures (pleurectomy and parietectomy). No significant statistical difference was observed concerning the quality of aerostasis, the post-operative drainage, the persistance of residual collection or faulty reexpansion after removal of the latter, and the necessity for repeated drainage. The same applied to the length of post-operative hospital stay. This study seems to demonstrate that the surgical application of fibrin glue on the fissural and/or intersegmentary dissection planes is feasible but, as compared to electrocoagulation, does not significantly improve the quality of the surgical results for partial pulmonary excision; however its use could reduce the duration of post-operative drainage. Alveolar air leaks are common after pulmonary resection, often prolonging hospitalization and increasing surgical morbidity and costs. Air leakages result from lung tissue traumatized by the dissection of fissures. This randomized and controlled trial evaluates 2 different surgical techniques for the completion of interlobar fissures during pulmonary lobectomy to establish which is superior in preventing air leakage.
                There were 20 patients in each of the 2 groups: Electrocautery was used for precision dissection and collagen patches were coated with human fibrinogen and thrombin (TachoSil, Nycomed, Vienna, Austria) for aerostasis in the electrocautery and sealant group (ES), and the approved routine surgical procedure with staplers was used in the stapler group (ST).
                Statistically significant reductions of air leakage were found in the ES group in the overall incidence of air leaks (50% vs 95%, P = .0001), duration of air leaks (1.7 days vs 4.5 days, P = .003), and procedure costs (425 euros vs 630.5 euros, P = .0001). There were no complications related to the use of the patches, and a significantly lower incidence of dead pleural space was observed in the ES group (5% vs 40%, P = .020).
                The use of electrocautery dissection and collagen patches coated with human fibrinogen and thrombin (TachoSil, Nycomed, Vienna, Austria) for aerostasis to complete interlobar fissures seems to be safe and effective in reducing alveolar air leaks and procedure costs. Although this pilot study showed advantages in terms of hospitalization and cost benefits, further multicentric studies are required to clarify that these differences are statistically significant. In order to investigate the effect of fibrin glueing on the treatment or prevention of air leakages, 114 patients undergoing pulmonary resections and pneumonectomies were studied in two treatment groups: surgery alone (59 patients) or analogous surgical treatment followed by the application of fibrin glue (55 patients). The patients were randomly assigned to treatment groups within two strata: pulmonary resections (63 patients) and pneumonectomies (51 patients). Intraoperatively, 81% of the patients undergoing pulmonary resection who suffered from air leakages after conventional suturing showed improved results of the airway-tolerance-pressure test after the application of fibrin glue (one-sided P value < 0.01; 95% confidence interval: 58-95%). Treatment with fibrin glue reduced the incidence of postoperative leakages significantly from 66% in the control group to 39% in the treatment group (one-sided P-value < 0.02; estimated risk reduction 41%; 95% confidence interval 2-65%). An additional reduction of the duration of post-operative air leakages by the treatment with fibrin glue could not be shown. In terms of minor response criteria, slight trends for an advantage of treatment with fibrin glue could be observed for the duration of stay in hospital and the number of patients with complications. There were no obvious trends concerning fever, intraoperative and postoperative intubation times, the amount of secretion from thoracic tubes and the general condition of the patients. No adverse drug event related to fibrin glueing was observed. Persisting air leakage after pulmonary resection remains a significant problem. The aim of the study was to evaluate the incidence of air leakage after standard lobectomy and test the efficacy and safety of TachoComb (TC).
                A total of 189 patients undergoing lobectomy were enrolled in a multi-centre, open, randomised, and prospective study to test the efficacy and safety of TachoComb (TC) for air leakage treatment. Air leakage was assessed by water submersion test, and scored as grades 0 if no, 1 if countable, 2 if a stream of and 3 if coalescent bubbles have been observed. Any sites with grade 3 air leakage received further stapling or limited suturing until grade 0, 1 or 2 was obtained. Treatment of air leakage was done with TC or suturing according to randomisation. Air leakage was assessed by further submersion tests. Postoperative air leakage was assessed using the Pleur-Evac system.
                Overall incidence of air leakage 48+/-6 h after surgery was 34% for TC and 37% for standard treatment (P=0.76). The reduction of intra-operative air leak intensity in the subgroup with grades 1-2 was significantly higher for the TC group (P=0.015). Postoperative air leakage intensity in the subgroup with air leakage grades 1-2 was lower for TC than standard treatment (P=0.047). The mean duration of postoperative air leakage in the subgroup with grades 1-2 was shorter for the TC group than for standard treatment, i.e. 1.9+/-1.4 vs. 2.7+/-2.2 days (P=0.015).
                TC could be proven as well-tolerated and safe. In the subgroup of patients with established air leakage, TC showed superior potential in reduction of intra-operative air leakage as well as in reduction of intensity and duration of postoperative air leakage. Intraoperative use of fibrin glue has been advocated in reducing postthoracotomy alveolar air leak, although most studies have not been randomized and have focused on its routine use after lung resection.
                This study specifically addresses the effectiveness of fibrin glue in reducing alveolar air leak only in patients considered intraoperatively to have continued moderate to severe alveolar air leak after all conventional measures to reduce it have been used.
                During a 24-month period, 66 patients undergoing lobectomies, segmentectomies, or decortication were randomized either to serve as controls (n = 33) or to have fibrin glue sprayed on the "raw" lung surface (n = 33). The median duration of intercostal drainage and in-hospital stay was 6 and 9 days, respectively, in the control group and 6 and 8 days, respectively, when fibrin glue was used. Statistical analysis revealed no differences between the groups.
                Fibrin glue does not add to conventional techniques in reducing moderate to severe alveolar air leak after thoracic operations. The intraoperative application of synthetic surgical lung sealant (SLS) to surfaces leaking air or at risk of air leaks has been advocated to reduce alveolar air leaks (AAL) after lobectomy.
                This study was designed to investigate the effectiveness of SLS in reducing AAL in patients considered intraoperatively to have moderate to severe AAL, after all conventional measures to reduce such leaks had been used. Over 17 months, 124 patients undergoing standard lobectomy were randomized to standard closure of parenchymal surgical sites, with or without SLS.
                In treated patients, the mean numbers of intraoperative AAL after application of SLS were significantly smaller than in untreated patients (38.5 mL versus 59.9 mL, p = 0.0401). Postoperatively, the mean time to last observable AAL was shorter in the treated group (33.7 hours versus 63.2 hours, p = 0.0134) and the mean percentage of patients free of AAL at days 3 and 4 was smaller (87% versus 58.5%, p = 0.002). However, the occurrence of incomplete lung expansion after drain removal, and the length of the postoperative hospital stay due to prolonged AAL, were not different. In the treatment group, 4 patients developed localized empyema and incomplete lung expansion without bronchopleural fistula 7, 12, 15, and 20 days, respectively, after operation. In these 4 patients, inserted chest tubes drained infected sealant.
                Surgical lung sealant may be a useful adjunct to conventional techniques for reducing moderate and severe AAL after lobectomy, but its use seems to increase the risk of postoperative empyema. 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. Air leaks after pulmonary resections may contribute to increased patient morbidity, delayed removal of chest drainage tubes, and prolonged hospitalization.
                The purpose of this study was to investigate the effects of a new synthetic, absorbable sealant on the healing of healthy bronchial and lung tissues (experimental study) and its safety and efficacy to stop air leaks after lung resection (clinical study).
                Fifteen large white pigs underwent a left upper lobectomy. All parenchymal surgical sites were sealed; the bronchial stump was either stapled, sealed, or both (n = 5 each). In the clinical study, 26 consecutive patients were prospectively randomized, intraoperatively, to standard closure of parenchymal surgical sites with (n = 15) or without (n = 11) the sealant.
                In the experimental study, no postoperative air leaks occurred, with intact bronchial closures and normal tissues at death. In the clinical study, 100% of intraoperative leaks were sealed versus 18% of control patients (P =.001). Although 77% (n = 10) of treated patients remained leak-free from the end of the operation to chest tube removal versus 9% (n = 1) of control patients (P =.001), there was no statistical difference in the duration of postoperative chest tube time, hospital stay, or cost. There were no acute or late undesirable side-effects related to the sealant application.
                The surgical adhesive investigated here demonstrated a compelling safety profile and significant clinical efficacy to stop air leaks after lung resections. The effectiveness of fibrin glue as a sealant to reduce postoperative air leaks after pulmonary lobectomy was evaluated in 28 consecutive patients between November 1988 and May 1989. A fibrin glue spray was used in 14 patients, and 14 patients served as controls. Assignment of either group was made before thoracotomy. Nine male and 5 female patients with a mean age of 63.8 years were in the fibrin glue experimental group, and 8 male and 6 female patients with a mean age of 59 years, in the control group. An equal number of complete and incomplete fissures were in each group. All fissures were handled in the same way (stapled). Two milliliters of fibrin glue was applied through a double-syringe delivery system and sprayed on the staple line and any cut surface of the inflated lung just before thoracotomy closure. The fibrin glue-treated group had a mean air leak duration of 2.3 +/- 3.7 days, chest tube drains for 6 +/- 4.1 days, and a postoperative hospitalization of 9.8 +/- 3.1 days. The control group had a mean air leak duration of 3.3 +/- 3.3 days (p = 0.94), chest tube drains for 5.9 +/- 3.9 days (p = 0.95), and a postoperative hospitalization of 11.5 +/- 3.9 days (p = 0.21). We conclude that the routine use of a fixed quantity of fibrin glue is not effective in reducing the duration of air leaks, chest tube drainage, or hospitalization after uncomplicated pulmonary lobectomy. The use of tissue glues has been advocated to reduce post-thoracotomy alveolar air leaks, but outcomes have been inconclusive. The aim of this study was to determine the effectiveness of BioGlue (CryoLife Europa Ltd, Hampshire, United Kingdom) in eliminating post-thoracotomy alveolar air leaks.
                A prospective, randomized, single-blind, controlled trial was conducted in which patients were stratified according to the severity of post-thoracotomy air leak that could not be controlled by conventional surgical techniques. They were allocated to a control arm (surgical treatment only) or an interventional arm (surgical treatment and BioGlue). Duration of air leak, intercostal drainage, and hospital stay comprised primary study end points.
                From December 2002 to January 2005, 52 patients were randomized, 29 (56%) of whom were men. The mean age was 59 +/- 15 years, and other characteristics were comparable in both groups. Indications for surgery were malignancy in 46 patients (88%), carcinoid tumor in 2 patients (4%), and infective disease in 4 patients (8%). Patients in the BioGlue arm had shorter median duration of air leaks, 1 (0-2) versus 4 (2-6) days (P < .001); intercostal chest drainage, 4 (3-4) versus 5 (4-6) days (P = .012); and hospital stay, 6 (5-7) versus 7 (7-10) days (P = .004), compared with controls. No major complications were encountered using BioGlue.
                This study demonstrates clear benefit from BioGlue in the treatment of alveolar air leaks through reduction of air leak duration, chest drainage time, and hospital stay. Systematic use of BioGlue may be warranted in adult thoracic surgical procedures (except pneumonectomy and decortication) when an air leak remains after all other steps to control it have failed. In contrast to the rare large-airway bronchopleural fistulas after lung resection, peripheral or alveolar air leaks (AAL) are very common, often prolong hospital stay, increase utilization of resources, and on occasion result in significant morbidity. Various adjuncts have been used in attempts to reduce AAL. One of these, the topical application of fibrin glue, has to date failed to demonstrate efficacy in small clinical trials. This study reexamines the role of fibrin glue in routine lobar and wedge pulmonary resections.
                Of 113 patients enrolled, 13 became ineligible because of intraoperative findings. The remaining 100 patients were randomly assigned to one of two groups at the conclusion of lung resection, regardless of the presence or absence of identifiable air leak. The control group received no additional intervention. The experimental group underwent application of 5 mL of fibrin glue delivered by a pressurized, aerosolized spraying mechanism. Postoperatively a blinded clinical observer recorded outcomes including the incidence and duration of AAL, prolonged AAL (PAAL), the volume of pleural drainage, the time to tube removal, and the postoperative length of stay (LOS), as well as any complications related to treatment.
                Both groups were comparable with regard to demographics, diagnoses, and procedures. Statistically significant reductions were found in the experimental group in the overall incidence of AAL (34% versus 68%, p = 0.001), mean duration of AAL (1.1 versus 3.1 days, p = 0.005), mean time to chest tube removal (3.5 versus 5.0 days, p = 0.02), and the incidence of PAAL (2% versus 16%, p = 0.015). There was no significant difference in the volume of chest tube drainage or LOS (4.6 days glue and 4.9 days control, p = 0.318). There were no complications related to the use of fibrin glue.
                Aerosolized fibrin glue appears to be safe and effective in reducing AAL. The overall incidence of AAL was reduced by 50% and PAAL occurred in only 1 treated patient (2% versus the usually reported 15%). Further studies with this and other methods are required to delineate routine versus selective use, to compare methods, and clarify cost benefit. Persistent air leakage following pulmonary resection is a major limiting factor for discharge from hospital. The aim of this study was to evaluate the sealing capacity of TachoSil for the closure of alveolar air leaks following parenchymal resections and to determine its effect on time to chest drain removal and duration of hospitalisation.
                A total of 173 patients undergoing lobectomy or segmentectomy were enrolled in a single-centre, randomised study to compare the efficacy of TachoSil with standard treatment. Alveolar air leaks were evaluated intraoperatively by submersion of the resection site in saline and were graded according to the Macchiarini scale as 0 (no bubbles), 1 (single bubbles), 2 (stream of bubbles), 3 (coalescent bubbles). Patients with grade 1 or 2 air leaks were randomised to TachoSil or standard treatment. Grade 3 patients received standard treatment until the air leak was downgraded to grade 1 or 2 at which point they were randomised. Patients with grade 0 leakage were excluded. The primary efficacy endpoints of the study were postoperative quantification of air leakage on postoperative days 1 and 2. Other efficacy measurements included mean time to chest drain removal and mean time to hospital discharge.
                The mean intraoperative post-treatment air leakage was significantly lower in the TachoSil group (153.32ml/min, range: 10-450ml/min) compared with the standard treatment group (251.04ml/min, range: 15-970ml/min; P=0.009). The significant difference in air leakage volume observed intraoperatively post-treatment was maintained postoperatively. TachoSil showed a trend towards reduced incidence of postoperative leakage when measured >48h or >7 days after surgery (30.7% vs 38.96% and 24% vs 32.46%, respectively). The mean times to chest drain removal and to hospital discharge were significantly reduced following the use of TachoSil (5.1 days vs 6.3 days, P=0.022 and 6.2 days vs 7.7 days, P=0.01, respectively).
                The use of TachoSil following pulmonary resection resulted in a reduction in air leakage compared with standard techniques. This reduction in air leakage resulted in a significant reduction in both the time to chest drain removal and the period of hospitalisation. To evaluate the safety and effectiveness of a new biodegradable polymeric sealant to close intraoperative air leaks after pulmonary resection.
                In a multicenter prospective randomized trial, 161 patients with a median age of 67 years old (range 18-85 years old), were randomized in a 2:1 ratio to receive sealant or control for at least one significant air leak (> or = 2.0 mm in size) after pulmonary resection. In the sealant group, all significant air leaks underwent attempted repair by standard methods (sutures, staples, or cautery) prior to the application of sealant. The control group underwent only standard methods. Blood was analyzed for immunologic response. Patients were followed up 1 month after surgery.
                Intraoperative air leaks were sealed in 77% of the sealant group compared with 16% in the control group (p < 0.001). The sealant group had significantly fewer patients with postoperative air leaks compared with the control group (65% vs 86%, p = 0.005). Median length of hospitalization was 6 days (range, 3-23 days) for the sealant group compared with 7 days (range 4-38 days) for controls (p = 0.028). There was no difference in mortality, morbidity, duration of chest tubes, or immune responses between the two groups.
                This study demonstrates the effectiveness of a biodegradable polymer when used as an adjunct to standard closure methods for sealing significant intraoperative air leaks that develop from pulmonary surgery. Use of the sealant led to a reduction in postoperative air leaks, which may have decreased the length of hospitalization.