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Ann Thorac Surg 1997;64:979-981
© 1997 The Society of Thoracic Surgeons

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Original Article: General Thoracic

Effect of Fibrin Glue in the Reduction of Postthoracotomy Alveolar Air Leak

Department of Thoracic Surgery, Royal Brompton Hospital, London, England

Accepted for publication April 15, 1997.

	Abstract

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Background. 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.

Method. 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.

Results. 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.

Conclusion. Fibrin glue does not add to conventional techniques in reducing moderate to severe alveolar air leak after thoracic operations.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Prolonged alveolar air leak (AAL) after thoracotomy may have a devastating effect on patients. It results in longer periods of intercostal drainage and immobility with an increased risk of complications (empyema formation, deep vein thrombosis, and respiratory infection) [1]. This culminates in increased in-hospital stay and costs, which have important implications to a health service that is always under financial constraints. In addition, patients may be quite distressed and depressed by the long periods of intercostal drainage.

The volume and duration of AAL after pulmonary resection is dependant on several factors, including the presence of an incomplete fissure, parenchymal disease (fibrosis or emphysema), residual lung volume, and adhesions, particularly in decortication. Fibrin glue has been demonstrated to reduce AAL both experimentally [2, 3] and in the clinical setting [4–9]. These clinical studies have, however, been less than convincing as the majority have not been randomized and focused on routine use of fibrin glue after lung resection irrespective of whether intraoperative AAL was present and was mild or moderate.

The aim of this randomized trial was to evaluate the efficacy of fibrin glue in reducing the duration of AAL only in patients judged intraoperatively to have moderate to severe air leak after all conventional techniques to control AAL have been used.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Fibrin Glue and its Application
The fibrin glue Tisseel (Immuno Co, Vienna, Austria) was used in this study. The mechanism of fibrin glue has been well described [10]. Briefly, this glue consists of two components: (1) a protein concentrate (fibrinogen, plasma fibronectin, factor XIII, plasminogen) reconstituted in aprotinin solution, and (2) thrombin reconstituted in calcium chloride solution. Both components are mixed and delivered simultaneously as an aerosol using a syringe system. As the sealer protein concentrate and thrombin mix, fibrinogen is converted to fibrin by thrombin and the mixture solidifies. A fixed quantity (5 mL) was sprayed over the "raw" lung surface of patients randomized to its use.

Patient Selection
This study was performed at the Royal Brompton Hospital, London, during a 24-month period (March 1994 through February 1996). Before beginning the study, ethical approval was obtained from the hospital human research committee and patient consent was obtained before the operation. All operations were performed by the senior author (P.G.). So that a homogenous group of patients were studied, only patients undergoing lobectomies, segmentectomies, or decortications were eligible to be included in the study. After their respective procedures, areas of AAL were closed by suturing with a monofilament material where possible and electrocautery. The thoracic cavity was then filled with warm liquid and the lung was ventilated to an airway pressure of 25 mm Hg to assess the degree of AAL.

Patients judged to have moderate to severe AAL were randomized by a "closed envelope" system to serve as controls, in whom nothing further was performed, or to the Tisseel group, in whom the glue was sprayed onto the "raw" lung surface while ventilation was briefly suspended (not more than 2 minutes in all cases).

Management of Intercostal Drains
All patients had two apically placed (anterior and posterior) intercostal drains with basal holes inserted before chest closure. Drains were postoperatively placed under a negative pressure suction of 20 mm Hg during the period of AAL. After cessation of AAL drains were taken off suction and removed after 24 hours provided the lung was fully expanded radiologically and drainage of fluid was less than 100 mL/24 hours.

Analysis of Data
The duration of air leak, intercostal drainage, in-hospital stay, and incidence of complications were used as end points to compare the efficacy of Tisseel. Results were analyzed with the statistical package Instat version 2.0 (GraphPad Software, San Diego, CA). Fisher's exact test with Yates correction or two-tailed Student's t test were used for comparisons between the groups. Differences were considered significant if p was less than 0.05.

	Results

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Patients and Operations
During the 24-month period, only 66 patients satisfied the necessary criteria to be included in the study. Thirty-three patients were randomized to each limb of the trial. The clinical features of both sets of patients were equally matched, particularly the case mix, in which the predominant procedure performed was that of lobectomy with or without segmentectomy (Table 1). Pulmonary resection for malignancy was the most common operation in both groups (76% in control and 84.8% in Tisseel).

One patient in the Tisseel group, who had a right upper lobectomy and chest wall resection for malignancy, had a respiratory arrest secondary to aspiration on the first postoperative day. He was ventilated for 6 days and eventually discharged on the 36th postoperative day. The length of in-hospital stay in this patient and the first patient described were not included in the analysis as their complications were unrelated to AAL.

	Comment

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
The reduction of postthoracotomy AAL lies in its prevention by careful dissection of anatomic planes during lung resection. Suturing or the use of staples when dividing across incomplete fissures may reduce the area of "raw lung" whereas electrocautery may be effective in closing any remaining areas of AAL. When the residual lung is unable to expand to fill the thoracic cavity we have found cryoablation of the phrenic nerve useful, as well as other traditional techniques, including trimming thoracoplasties and pleural tents.

There will, however, be a small proportion of patients in whom AAL may still be extensive despite the use of these conventional techniques. The use of a topical glue to reduce AAL would be invaluable in such a setting and is reflected by the numerous studies and reports in the literature attempting to prove the efficacy of this glue [5–9, 11]. The majority of these studies have been favorable toward the use of fibrin glue but have either been unrandomized or involved a heterogeneous group of patients. There have also been many anecdotal cases demonstrating the use of fibrin glue in reinforcing bronchial stumps, tracheal suture lines, and closing postpneumonectomy bronchopleural fistulae [4, 5, 7, 8, 12]. It would be impossible to draw any convincing conclusions from these reports.

Surprisingly, there has only been a handful of scientifically based experimental work and clinical studies addressing the potential use of fibrin glue in reducing AAL [2, 3, 6, 11]. Turk and associates [3] first described an increase of 29% higher pressure tolerance of suture lines in rat lungs when fibrin glue was added. Furthermore, McCarthy and colleagues [2] demonstrated a 60% decrease in the rate of experimentally induced air leak by the use of fibrin glue after 90 minutes. The data from two randomized trials have been less convincing [6, 11]. Both showed no difference in the use of the glue in the mean duration of air leak, intercostal drainage, and in-hospital stay [6, 13], although Mouritzen and coworkers [6] showed an improvement in intraoperative air leak. One major criticism of both these trials and others in the past has been the fact that they have all focused on the routine use of fibrin glue after lung resection in which AAL may be minimal. Indeed, in the study by Mouritzen and associates [6], a third of the control patients did not have any air leak after resection. Similarly, Fleisher and colleagues [11] applied glue to stapled fissures and any cut surface of lung regardless of the presence or absence of air leak.

The aim of only including patients with a moderate to severe AAL after lung resection and decortication was twofold. First, we were able to study patients with a similar degree of AAL. Furthermore, if fibrin glue was effective in reducing AAL, this would be the group of patients in whom it may be beneficial. Our findings are consistent with those of Fleisher and coworkers [11] and Mouritzen and associates [6] and have demonstrated no advantage in the use of fibrin glue. All variables, including duration of AAL, intercostal drainage, and in-hospital stay, were very similar. There were a few patients who had cessation of air leak within the first 24 hours as seen by Mouritzen and colleagues [6], but these occurrences were too seldom (data not reported) to make any valid conclusions.

We used a fixed amount of glue, and it may be argued that when there is excessive AAL, as in our study, a larger quantity of glue is necessary. However, in a number of cases, we have found thick layers of glue lifting off the surface of the lung soon after its application and we believe that, in these cases, air leak would persist despite repeat applications with more glue. The effectiveness of the glue may well be related to the severity of the leak, and this would explain the subgroup of patients in whom gluing was effective in the study by Mouritzen and colleagues [6].

Our findings support our belief that careful surgical technique is still fundamental in minimizing air leak. Differential inflation is a useful technique in dissecting incomplete fissures as are the use of staplers in the division of fissures [13], although we prefer suturing with monofilament material. Postoperative management of patients with severe air leak is important, also. In our experience, if patients persist with an air leak despite negative pressure suction for more than 14 days, we proceed to a "trial" without suction. If the lung remains expanded for 24 hours this suggests that sufficient adhesions have formed to allow removal of their intercostal drains.

In conclusion, we have shown no advantage in the intraoperative use of fibrin glue in decreasing AAL. The use of a topical adhesive glue is an attractive treatment modality but, its use should not be encouraged without any objective evidence demonstrating its efficacy, particularly in view of its cost (£130.00 for 5 mL, which does not include the cost of the pneumatic system and disposable plastic delivery system required for its administration). Furthermore, fibrin glue is at present prepared from pooled human plasma and may raise some concern of blood-borne infection, although manufacturers assure us of very stringent measures in its sterilization.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Address reprint requests to Mr Goldstraw, Department of Thoracic Surgery, Royal Brompton Hospital, Sydney Street, Chelsea, London SW3 6NP England (e-mail: p.goldstraw{at}RBH.nt.nhs.uk).

	References

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 

1. Keagy B, Lores M, Starek P, Murray GF, Lucas CL, Wilcox BR. Elective pulmonary lobectomy: factors associated with morbidity and operative mortality. Ann Thorac Surg 1985;40:349–51.[Abstract]
2. McCarthy P, Trastek V, Bell D, et al. The effectiveness of fibrin glue sealant for reducing experimental pulmonary air leak. Ann Thorac Surg 1988;45:203–5.[Abstract]
3. Turk R, Weidringer W, Hartel W, Blumel G. Closure of lung leaks by fibrin gluing. Experimental investigation and clinical experience. Thorac Cardiovasc Surg 1983;31:185–6.[Medline]
4. Grunewald D. Intraoperative use of fibrin sealant in pulmonary surgery. A prospective study on a series of 124 procedures. Ann Chir 1989;43:147–50.[Medline]
5. Kjaergard H. Autologous fibrin glue—preparation and clinical use in thoracic surgery. Eur J Cardiothorac Surg 1992;6:52–4.[Abstract]
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7. Orlowski T, Kolodziej J, Domagala J, Schlag G, Redl, eds. Fibrin sealant in operative medicine. New York: Springer-Verlag, 1992: 66–73.
8. Thetter O. Fibrin adhesive and its application in thoracic surgery. Thorac Cardiovasc Surg 1981;29:290–2.[Medline]
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