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J Thorac Cardiovasc Surg 2008;136:843-849
© 2008 The American Association for Thoracic Surgery
General Thoracic Surgery |
a Division of Thoracic Surgery, University Hospital Zürich, Zurich, Switzerland
b Department of Biostatistics, University Hospital Zürich, Zurich, Switzerland
c Division of Pneumology, University Hospital Zürich, Zurich, Switzerland
Received for publication August 3, 2007; revisions received December 19, 2007; accepted for publication February 12, 2008. * Address for reprints: D. Lardinois, MD, Division of Thoracic Surgery, University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerland. (Email: dlardinois{at}uhbs.ch).
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Abstract |
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 Top Abstract IntroductionPatients and MethodsDesignResultsDiscussionReferences |
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Methods: Twenty-five patients underwent bilateral thoracoscopic lung volume reduction surgery. In each patient, an autologous fibrin sealant was applied along the staple lines on one side, whereas no additional measure was taken on the other side. Randomization of treatment was performed at the end of the resection on the first side. Air leak was assessed semiquantitatively by use of a severity score (0 = no leak; 4 = continuous severe leak) by two investigators blinded to the treatment.
Result: Mean value of the total severity scores for the first 48 hours postoperative was significantly lower in the treated group (4.7 ± 7.7) than in the control group (16.0 ± 10.1) (P < .001), independently of the length of the resection. Prolonged air leak and mean duration of drainage were also significantly reduced after application of the sealant (4.5% and 2.8 ± 1.9 days versus 31.8% and 5.9 ± 2.9 days) (P = .03 and P < .001).
Conclusions: Autologous fibrin sealant for reinforcement of the staple lines after lung volume reduction surgery significantly reduces prolonged air leak and duration of chest tube drainage.
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Introduction |
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TopAbstractIntroductionPatients and MethodsDesignResultsDiscussionReferences |
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Various techniques of minimizing this complication have been tried with mixed results, but the overall incidence of air leaks remains higher than 60% in the early postoperative period.5 However, with the exception of very large air leaks or association with a significant residual postresection space, most air leaks are benign and resolve within a few days with appropriate drain management. Prolonged air leaks occur in more than 15% of patients.6
Several prospective studies have demonstrated that lung volume reduction surgery (LVRS) reduces dyspnea and improves lung function and quality of life in selected patients with severe pulmonary emphysema.7-12 It has been shown that severe emphysema is one of the most important risk factors for prolonged air leak.6 This increases the risk for infections in patients undergoing LVRS. Inasmuch as prolonged air leak may affect nearly half of the patients after LVRS in some series,6,13 such patients are an ideal subgroup in which to evaluate new techniques to avoid or to reduce the occurrence of this type of complication.
A variety of biologic and synthetic materials including fibrin sealants, collagen fleece, and synthetic glues are commercially available to reinforce parenchymal staple lines in an effort to decrease occurrence of postoperative air leak after pulmonary resection.1-5,14-18 The use of fibrin sealant in cardiothoracic surgery was pioneered in the mid-1970s. Today, fibrin sealant is used primarily as a hemostatic and adhesive agent and as a sealant of pulmonary air leaks.
The aim of this prospective randomized monocenter study was to evaluate the effect of reinforcing the stapler lines with an autologous fibrin sealant in a series of patients undergoing LVRS, regarding incidence of prolonged air leak and duration of chest tube drainage.
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Patients and Methods |
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TopAbstractIntroductionPatients and MethodsDesignResultsDiscussionReferences |
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All patients included in the study had severe airflow obstruction with a mean forced expiratory volume in 1 second (FEV1) of 0.74 ± 0.08 L (27% ± 6.14% predicted), a mean total lung capacity of 7.66 ± 1.14 L (137% ± 18.31% predicted), a mean residual volume of 5.14 ± 1.06 L (244% ± 56.63% predicted), and a severe hyperinflation with a mean residual volume/total lung capacity ratio of 0.68 ± 0.1. Emphysema was scored on preoperative chest computed tomography as homogeneous, intermediately heterogeneous, or markedly heterogeneous according to a previously validated classification.9 The study was approved by the Human Investigation Committee of our institution. Patients were invited to participate after explanation of the purpose and potential risks and benefits and were required to sign informed consent. Inasmuch as only patients who agreed to participate were included, it was not a consecutive series of patients.
LVRS was performed bilaterally by video-assisted thoracoscopy as previously described, using 60-mm and 45-mm stapler devices.9 The most damaged zones of lung parenchyma were identified on computed tomography and perfusion scintigraphy and were resected with endoscopic staplers. In patients with homogeneous emphysema, the resection was performed mostly in the upper lobes. A cumulative lung volume of approximately 30% on each side was resected. All procedures were performed by the same surgeon who has a large experience with LVRS. All patients had intraoperative and postoperative thoracic epidural analgesia. After removal of the catheter, a combination of paracetamol (Dafalgan) und metamizol (Novalgin) was generally considered for basic analgesia.
The Vivostat (Vivostat A/S, Alleroed, Denmark) system is a commercially available medical device for the preparation of an autologous fibrin sealant from 120 mL of the patient's blood in the operating room.19 The system is fully automated and microprocessor controlled and is made up of three components: an automated processor unit, an automated applicator unit, and a disposable, single-patient-use unit, which includes a preparation set and a Spraypen applicator for thoracoscopic use. Time required to prepare autologous fibrin sealant with this system is 20 minutes and the fibrin solution may be kept at room temperature for up to 8 hours before application without a loss of sealant effectiveness. The device provides a fine aerosolized mist spray of fibrin sealant under pressure. The sealant polymerizes on contact and sets over several minutes.19-21 We did not receive any financial support from Vivostat A/S.
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Design |
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TopAbstractIntroductionPatients and MethodsDesignResultsDiscussionReferences |
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Statistical analysis was carried out using the software Statistical Package for the Social Sciences (SPSS, Inc, Chicago, Ill). The sample size was calculated to get 80% power for the primary end point (drainage duration) and increased by a few units to account for the patients who are inevitably lost to follow-up. The Vivostat group and the control group were compared by a Wilcoxon signed rank test for the continuous end points (length of resection, total of severity scores, duration of drainage) and a McNemar test for the binary end point (air leak). For drainage duration and air leak, only the 22 patients who could be observed until the end of the study (who were still alive and who did not require reintubation) have been included. For total severity scores, only the patient who died after 24 hours was not included.
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Results |
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TopAbstractIntroductionPatients and MethodsDesignResultsDiscussionReferences |
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The volume of fibrin sealant obtained from the patients' blood was very reproducible, with a mean value of 4.8 mL (ranging from 4.6 to 5 mL). Vivostat was used on the first operated side in 10 patients and on the second side in 12 patients. Length of resection was very comparable and not significantly different in the two groups, with 21.6 ± 7.3 cm in the treated group versus 21.7 ± 6.3 cm in the control group (P = .93). LVRS was performed in the upper lobe, in the lower lobe, or in combination of several lobes in 9, 2, and 11 treated sides and in 7, 4, and 11 control sides, which was comparable. There was no difference in the mean time spent during the procedure on the first and on the second sides (32 ± 9 minutes vs 34 ± 11 minutes) and there was no difference in the operation time between treated and control sides.
At the first observation time 2 hours postoperatively, severity score 0, 1, 2, 3, or 4 was found 25, 10, 0, 5, and 4 times in the Vivostat group and 6, 13, 6, 7, and 12 times in the control group (P < .02). Total severity score was significantly lower in the Vivostat group (4.7 ± 7.7) than in the control group (16.0 ± 10.1) (P < .001). No correlation with the localization of the resection and with the length of the staple lines was observed. The two observers were in very good agreement, the weighted kappa calculated on the basis of all ratings made by each observer 48 hours postoperative being 0.89.
Prolonged air leak (>7 days) was observed in 8 (18.2%) of 44 operated sides. However, prolonged air leak was found in only 1 (4.5%) of 22 treated sides as compared with 7 (31.8%) of 22 control sides (P = .031). Among the 7 patients with prolonged air leak on a control side, reoperation was necessary in 2 patients after 11 and 12 days.
Mean duration of chest tube drainage was also significantly reduced after application of the sealant (2.83 ± 1.96 days vs 5.88 ± 2.96 days; P < .001). Again, the localization of the resection as well as the length of resection had no influence on the duration of drainage. It was also impossible to find a difference in the duration of air leak between the first and the second operated sides, ruling out an influence of the pressure applied on the first operated side during operation on the second side. Mean duration of air leak for the first operated sides was 4.9 ± 3.1 days in comparison with 4.1 ± 2.7 days for the second side. This observation was also noted if the comparison was only performed in the subgroup Vivostat sides (Vivostat on the first side vs Vivostat on the second side) and in the subgroup nontreated sides (no treatment on the first side vs no treatment on the second side). After removal of the drains and before discharge from the hospital, chest radiography was routinely performed. The lungs were completely expanded in each patient. Clinical and radiologic studies at 3, 6, 9, 12, 15, 18, and 24 months were performed postoperatively at our center. After a mean follow-up time of 17.3 months, no recurrent pneumothorax was documented.
With the design of this study, it was not possible to compare postoperative analgesics requirement and duration of hospitalization, since a treated side and a control side were randomly assigned in each patient. The mean duration of hospitalization was 10.5 ± 3.2 days.
No adverse effects owing to the sealant were recorded during the study.
In-hospital mortality rate was 12% (3/25). Two patients died of pulmonary embolism 1 day after surgery and of pneumonia at 10 days, 3 days after reintubation. The third patient died 13 days after LVRS of intracerebral bleeding.
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Discussion |
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TopAbstractIntroductionPatients and MethodsDesignResultsDiscussionReferences |
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Several methods have already been described to reduce the incidence of air leak after pulmonary resection. Previous studies of the effects of fibrin sealants in pulmonary surgery have given inconsistent results with regard to air leakage and the duration of chest tube drainage. Wong and Goldstraw,15 in a randomized trial of 66 patients with alveolar air leaks after pulmonary surgery, identified a nonsignificant but shorter duration of chest tube drainage and hospitalization. Fleischer and associates14 were also unable to identify a significant effect of fibrin sealant in reducing the duration of chest tube drainage and hospitalization and in the duration of air leakage. Gagarine and colleagues,4 in a retrospective study of 360 patients, did identify a significant reduction of drainage in patients who received fibrin sealant, but the incidence of prolonged air leak was comparable. A possible explanation for these heterogeneous results is that most of air leaks after anatomic pulmonary resection resolve spontaneously in a few days. The study by Fabian, Federico, and Ponn5 was the first randomized trial showing a decrease in the duration of chest tube drainage (3.5 days vs 5 days) after lung resection for malignant and benign diseases. However, the fibrin sealant used was not autologous. Conventional fibrin sealants use components prepared from pooled human plasma and sometimes animal-derived components. The Vivostat system overcomes the potential infective and antigenic risks associated with the use of other available fibrin sealants containing products derived from pooled human fibrinogen or using exogenous thrombin, especially of bovine origin.21 A recent prospective randomized trial by Anegg and coworkers22 showed that the use of fleece-bound sealing after 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 length of hospitalization. The major disadvantage of this method is the great difficulty in using fleece-bound sealing thoracoscopically.
In patients with severe emphysema undergoing LVRS, buttressing of staple lines with bovine pericardial strips or polytetrafluoroethylene sleeves achieved popularity in dealing with the rarefied emphysematous lung tissue of patients with severe emphysema and has also been applied to routine lobectomy. However, its effectiveness remains unclear. Hazelrigg and associates23 found a 2- to 3-day reduction in length of hospital stay when buttressing. In a randomized, three-center trial, Stammberger and coworkers24 reported a statistically significant reduction in air leak duration after bilateral, buttressed, thoracoscopic LVRS, but no reduction in length of stay. A disadvantage of this technique consists in the extensive inflammatory reaction with formation of dense adhesions associated with the use of bovine pericardium, which makes lung transplantation after LVRS particularly challenging when indicated.
In the National Emphysema Treatment Trial, more than 95% of the surgical patients underwent staple-line buttressing, the majority with pericardium and polytetrafluorethylene. Within 30 days of LVRS, 90% of patients had an air leak.8 The authors concluded that the surgical approach, buttressing, and intraoperative adjunctive procedures were not associated with fewer or less prolonged air leaks. However, fibrin sealant was only used in 32 patients (5.8%) in this multicentric study, which does not allow the drawing of any strong conclusion on its application. Interestingly, the occurrence of air leak in the National Emphysema Treatment Trial was more common and its duration prolonged in patients with lower diffusing capacity, upper lobe disease, and important pleural adhesions. Duration was also protracted in patients using inhaled steroids and those with a lower FEV1.8 Cerfolio and coworkers25 also observed that persistent air leak mostly developed in patients with an FEV1 of less than 79% predicted. The authors concluded that the occurrence and the duration of air leaks were associated with patients' characteristics and disease severity and not with a specific surgical technique. In our study, patients' characteristics could not explain the difference between the two groups, since in each patient a treated side and a control side were assigned. Furthermore, all the operations were performed by the same surgeon, using the same technique of resection. We found that the localization of resection and length of the staple lines were correlated neither with the incidence and the intensity of air leak nor with the duration of chest tube drainage. The only difference between the two sides was the application or not of autologous fibrin sealant.
The autologous fibrin sealant Vivostat was first used in cardiac surgery and has already been applied at the anastomoses, the mammary artery pedicle, the mediastinum, and the sternal marrow for hemostasis.19,20 It has also been used in lung surgery and has been shown to reduce postoperative air leakage and drainage volumes after lobectomy.18 However, no difference was observed in the duration of drainage and in the length of hospital stay. Again, this might underline that most air leaks after anatomic pulmonary resection are generally innocuous and can be managed conservatively by chest tube drainage.
Advantages of the Vivostat system are multiple. It is a fully automated device and autologous fibrin sealant can be prepared with a stable concentration and volume by a nurse or perfusionist. Thoracoscopic application is easy and safe. The Spraypen system allows the surgeon to spray the solution evenly over the target tissue in a controlled fashion. Application is controlled by a foot pedal and can be stopped and restarted without the problem of the fibrin congealing. The sealant polymerizes immediately on application and crosslinks over several minutes. Fibrin sealant Vivostat sealant is flexible and compliant to accommodate the volume changes of the lung, resulting in a uniform surface load and minimizing the potential for secondary tearing of tissue at the application site.21
The incidence of prolonged air leak, defined as an air leak that lasts at least 7 days after the procedure, was 31.8% in the control group. This compares favorably with the 40% to 60% observed in the literature.6,13 In the treated group, this incidence was 4.5%, which was comparable with the data of the most important reports using fibrin sealants but was better than with other techniques (24% after fleece-bound sealing).22 Additionally, this incidence could have been expected to be higher, inasmuch as prolonged air leak is observed more frequently in patients with severe emphysema.13 Our data demonstrate that autologous fibrin sealant considerably reduces the incidence of air leak, but does not eliminate it. This can be easily explained in patients with severe emphysema, in whom a minimal trauma of the fragile lung parenchyma, particularly during reinflation, suffices to produce a pleural fistula. In a study of hospital stay after thoracic operations, prolonged air leak was identified as the most common cause of the delay in discharge.4,26 In a previous report estimating hospital costs attributable to prolonged air leak in pulmonary lobectomy, Varela and colleagues26 found that prolonged air leak calculated costs were over 13,000 euros per year in his institution. However, the techniques used to reduce air leaks are also often expensive, for example, up to 350 euros. The cost of the fibrin sealant prepared with the Vivostat system is about 200 euros, which compares favorably with the other sealing techniques. Moreover, the application system with the Spraypen allows delivery of the fibrin to larger areas than with many other techniques. In our opinion, reinforcement of the staple lines after lung resection is not routinely required. The main reason is that most of the leaks will resolve spontaneously if the lung can re-expand.
Mean duration of chest tube drainage in the Vivostat group was 2.8 days, which is shorter than in most prospective randomized trials evaluating the effect of fibrin sealants (5 to 6 days).14,15 Only the study by Fabian and associates5 revealed a value of 3.5 days, but after anatomic pulmonary resection.
The mortality rate of 12% found in this study is high and does not reflect the mortality rate of our published series of 194 patients who underwent LVRS at our institution, which is 2.6%.27 As already mentioned, the inclusion criteria for LVRS were the same as in previously published reports from our center. This high rate is probably coincidental, owing to the small number of patients included in the study.
Our study has some drawbacks. First, the number of patients included was relatively small. This is partially due to the fact that although our institution is one of the leading reference centers for LVRS, this procedure is only performed in highly selected patients. On the other hand, this study presents the possible advantages of a monocenter study, inasmuch as the surgeon and the technique used for resection, as well as perioperative management, were identical in all patients. Additionally, the design assigning a treated and a control side in each patient allowed increasing the number of observations. Second, the intensity of air leak was not exactly quantified. However, precise quantification of air leak is still not the standard of care in most centers and has not been demonstrated to change and to influence clinical decision-making regarding removal of the chest tubes. Third, randomization was not performed for each side but only for the first side after LVRS had been performed, the second side being automatically assigned to the other group. This design has been chosen for the following reason: the preparation of autologous fibrin sealant needs about 20 minutes. A randomization for each side might have provoked delay in the operating theater if both sides had been assigned to the treatment group. Our study design allowed having more observations (2 in each patient), ruling out the influence of patients' characteristics and of localization of emphysema.
In conclusion, this study demonstrated that the use of autologous fibrin sealant Vivostat significantly reduces the incidence of prolonged air leak and duration of chest tube drainage in patients undergoing LVRS for severe emphysema. Reinforcement of the staple lines with this technique is surely a safe and efficient way, in addition to a careful surgical technique by an experienced surgeon and adequate postoperative care, to prevent and minimize potential complications in these patients, which is key to successful LVRS. As a consequence, the autologous fibrin sealant Vivostat might be systematically used in this highly selected subgroup of patients.
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Acknowledgments |
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References |
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TopAbstractIntroductionPatients and MethodsDesignResultsDiscussionReferences |
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1-antitrypsin deficiency. J Thorac Cardiovasc Surg 2004;128:408-413.This article has been cited by other articles:
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  G. Cardillo, F. Carleo, L. Carbone, A. R. De Massimi, A. Lococo, P. F. Santini, A. Janni, and A. Gonfiotti Adverse effects of fibrin sealants in thoracic surgery: the safety of a new fibrin sealant: multicentre, randomized, controlled, clinical trial Eur J Cardiothorac Surg, December 16, 2011; (2011) ezr083v1. [Abstract] [Full Text] [PDF]
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 A. Hashimoto, M. Kuwabara, Y. Hirasaki, H. Tsujimoto, T. Torii, T. Nakamura, and A. Hagiwara Reduction of air leaks in a canine model of pulmonary resection with a new staple-line buttress J. Thorac. Cardiovasc. Surg., August 1, 2011; 142(2): 366 - 371. [Abstract] [Full Text] [PDF]
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 G. Malapert, H. A. Hanna, P. B. Pages, and A. Bernard Surgical Sealant for the Prevention of Prolonged Air Leak After Lung Resection: Meta-Analysis Ann. Thorac. Surg., December 1, 2010; 90(6): 1779 - 1785. [Abstract] [Full Text] [PDF]
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S. Singhal and J. B. Shrager Should buttresses and sealants be used to manage pulmonary parenchymal air leaks? J. Thorac. Cardiovasc. Surg., December 1, 2010; 140(6): 1220 - 1225. [Full Text] [PDF]
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 W. D. Spotnitz and S. Burks State-of-the-Art Review: Hemostats, Sealants, and Adhesives II: Update As Well As How and When to Use the Components of the Surgical Toolbox Clinical and Applied Thrombosis/Hemostasis, October 1, 2010; 16(5): 497 - 514. [Abstract] [PDF]
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 B. S. Bleier, N. M. Cohen, J. D. Bloom, J. N. Palmer, and N. A. Cohen Laser Tissue Welding in Lung and Tracheobronchial Repair: An Animal Model Chest, August 1, 2010; 138(2): 345 - 349. [Abstract] [Full Text] [PDF]
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