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Eur J Cardiothorac Surg 2001;19:4-9
© 2001 Elsevier Science NL
a Department of Thoracic Surgery, University of Freiburg, Hugstetterstrasse 55, 79106 Freiburg i. Br., Germany
b Institute of Pathology, Ludwig-Aschoff-Haus, Albertstrasse 19, 79104 Freiburg i. Br., Germany
Received 22 May 2000; received in revised form 18 September 2000; accepted 30 October 2000.
Corresponding author. Tel.: +49-761-2702457; fax: +49-761-2702499
e-mail: hasse{at}ch11.ukl.uni-freiburg.de
| Abstract |
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Key Words: Bronchial anastomosis Lung parenchyma Experimental gluing
| 1. Introduction |
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Replacement or support of sutures by gluing procedures has been investigated for many years. The fibrin glue, used most frequently today, did not warrant reliable sealing [5,6]. Cyanoacrylate and gelatin-resorcin-formaldehyde adhesives have not been accepted generally in clinical practice because of problematic histocompatibility [6,7]. However, a non-toxic, durable, and easy to use adhesive has not been available for lung surgery.
A surgical adhesive of bovine serum albumin cross-linked by glutaraldehyde as an adjunct in vascular repairs involving procedures such as vascular anastomosis, carotid endarterectomy, and repair of aortic dissection has been used. So far there has been no published experience with this glue in general thoracic surgery.
The present study was performed to evaluate the adjunctive use of this tissue adhesive as a sealant for bronchial anastomosis and parenchyma lesions. The effect of the glue on the bronchial mucosa and the parenchyma of the lung was investigated.
| 2. Material and methods |
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All animals received human care in compliance with the European Convention on Animal Care, and study was approved by the institutional ethics committee. BioGlue® is licensed in the EU as an adjunct in human vascular and pulmonary repair surgery.
2.1. Operative procedure
A central venous access was placed in the jugular vein and a venous cannula was placed in the ear vein. The animals were intubated under induction dose with 6 mg/kg intravenous propofol. They were maintained under anesthesia using 1.62.0% isoflurane in O2/NO2 (FiO2>0,4) and 0.01 mg/kg fentanyl intravenous as needed. At operation the animals had controlled ventilation with intermittent positive pressure.
After lateral thoracotomy through the fifth intercostal space, the left main bronchus was transected in 22 animals (four controls and 18 experimental). In the two remaining control animals, after severing of the right upper lobe, the bronchus was reanastomosed. The bronchobronchial anastomosis was performed in a conventional manner with the use of an air-tight twice interrupted, running, absorbable 4-0 Maxon suture (Braun-Dexon GmbH, Spangenberg, Germany). The experimental group had broncho-bronchial anastomosis performed with only four or five, not air-tight, interrupted 4-0 Maxon sutures for approximation of the tissue margins. The anastomotic line was then circumferentially covered with BioGlue® (both components are mixed in a double helix syringe outlet and appear as a liquid at the tip). Surrounding soft tissue was allowed to bind with the glue. No additional flaps were employed.
The application of glue was done under apnoeic conditions of 2 min to allow for complete set-up prior to exposure and potential removal from escaping air. Underwater, proof of tightness was achieved with pressure controlled inflation (ventilation pressure between 30 and 35 mmHg).
In addition, the experimental animals had a repair of a surgically created parenchymal defect. A large Satinsky exclusion clamp (Aesculap, Tuttlingen, Germany) was applied to the upper lung lobe. Once clamped, an incision was made with a scalpel blade at 23 cm in depth and 3 cm in length. Closure of the clamp was tight as to prevent bleeding from the severed parenchyma. Wound surfaces were then covered with an even layer of an estimated 0.5 mm thickness of the adhesive. The clamp was released after approximately 2 min to allow for complete set-up of the adhesive.
This procedure was not included in the controls, since a non-sutured/reduced sutured repair would have lead to air fistula and required chest drainage.
2.2. Peri-operative management
Bupivacain (intraperitoneal) was given as an analgesic at dose of 1.54 mg/kg before closing the thorax. The chest was closed in layers after insertion of a single chest tube through a stab incision and connected to a Heimlich ventil (Vygon, Ecouen, France). This was removed under hyperinflation of the lung. Anaesthesia was ended and animals were extubated when sufficiant spontaneous breathing was achieved. 50 mg/kg of Metamizol every 6 h for the first 2 days was administered through the ear vein cannula. Cannula was removed after 48 h, when most of the animals were sent out to graze (others were sent out after up to 96 h for logistical reasons).
2.3. Post-operative examination of the glued bronchial anastomosis and lung parenchyma
At the termination of the study, all animals were reoperated under full anesthesia and the same approach was used to expose the bronchial anastomosis and the site of parenchymal repair. The thoracic cavity was examined for abnormalities. The surgical sites, bronchial anastomosis and parenchymal repair, were removed, photographed and placed into formalin 4%.
Macroscopic evaluation included tissue fragility, presence or absence of sutures or adhesive, macroscopic lumen loss or constriction. Microscopic evaluation was done using traditional paraffin-embedded sections, stained with Hematoxylin and Eosin (H&E) and Elastica-vanGieson (EvG). The sections were examined for the presence of sutures or tissue adhesive, epithelial hyperplasia, fibrin deposition, thrombus formation, peri-bronchial granulocytosis, chronic inflammation (fibroblasts/fibrosis, neovascularisation, granulomatous inflammation, giant cells), lymphoid nodules, tissue necrosis, and hemorrhage.
| 3. Results |
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Histologic examination of the control animals (hand sutured group) revealed a fibroangioblastic granulation tissue overlying the bronchial anastomosis after 4 weeks. No foreign body giant cells and granulomatous tissue were found (Table 1). Neither earlier nor later controls were investigated.
On post-operative week 12 macroscopic examination revealed adhesive perifocal to the bronchial anastomosis and the parenchymal defect. In general, fibroangioblastic granulation tissue and fibrous tissue scar was seen (Figs.3 and 4). In rare cases single multinucleated giant cells were detected (Table 1).
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| 4. Discussion |
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Extended lymph node dissection for lung cancer increases the risk of bronchial wall ischemia and anastomotic dehiscence [11], which may result from disruption of the vascular supply [12]. Extended resection also may result in excessive tension on the bronchial suture line, leading to anastomotic dehiscence or stricture [13].
Early dehiscence with associated parabronchial infection may provoke critical situations, in particular when broncho-vascular fistulas occur. In a series reported by Kawahara et al. [14] among 112 patients, six patients developed a broncho-pleural fistula and two patients died from massive bleeding from a broncho-vascular fistula. In another series of 100 cases, two patients died from post-operative broncho-atrial fistula and pneumonia, stricture occurred in six patients, and reanastomosis and completion pneumonectomy (one each) were required [3].
Bronchopleural fistulas occur in 23% of patients after pulmonary resection [15]. After lung volume reduction surgery, air leaks are the most common complications with an occurrence of 50% [16]. In patients with poor tissue or in those who are immunocompromised, application of sutures and staples may be compromised by the undesirable result of multiple pinpoint air leaks [17]. Consequences of pleural defects include the formation of pleural adhesions [18].
Many methods have been advocated to encourage healing and prevent fistulization, including pleural flap, dermal grafts, intercostal muscle bundle, omentum, pericardial flap, and staple devices [1923]. Replacement or support of sutures would provide an additional adjunct to this array of surgical procedures [24].
Fibrin glue and other synthetic sealants, including gelatine-resorcinol-formaldehyde, gelatine-resorcinol-dialdehyde, and cyanoacriylate have been studied primarily. Fibrin glue adhesive strenght is relatively low, formaldehyde containing glue is reported to be toxic, and biocompatibility of the cyanoacrylate glue is poor [5].
This investigation was designed to quantitate the effectiveness of a new tissue adhesive, BioGlue®, for sealing bronchial anastomoses and lung parenchyma. BioGlue® is composed of bovin serum albumin cross-linked by glutaraldehyde and has already been approved for use in general vascular repair. Polymerization of this surgical adhesive begins immediately upon application, reaching full binding strength within 2 min.
In our study 24 sheep were investigated. The primary intention of the surgery was to perform a formal upper lobe sleeve resection on the right side with a consecutive anastomosis between the main and intermediate bronchus. However, in the first two sheep it was noted that the interlobar fissure was poorly developed and incomplete. The anatomical feature, which was subsequently confirmed in all remaining sheep, required a modification of the procedure to sever the left main bronchus with subsequent reanastomosis. Because of the great caliber and length of the trachea, a single lumen tube (Mallinckrodt Medical, Athlone, Ireland) was employed. Therefore, the left bronchial origin had to be clamped before the division and the anastomotic suture. Application of the adhesive took place in an apnoeic state, after approximating sutures were done.
Sheep were investigated 2, 4 and 12 weeks after primary surgery. On macroscopic examination the glued bronchial anastomosis in all cases proved tightly closed, which suggest a sufficient tensile strength under physiologic conditions. Residual glue was found in all postoperative specimens.
Endoluminally, no reactive formation of granulation tissue occurred, even in one case, where a deposit of glue was found to have blocked a segmental bronchus. This is in contrast to former investigations, where the use of gelatine-resorcinol-dialdehyde adhesive for gluing the stump of a main bronchus after pneumonectomy in rats caused marked erosive and ulcerative lesions of the mucosa [25]. However, different experimental animal and various anatomic sites may influence the tissue reaction to the adhesive.
The study demonstrated that bronchial anastomosis can be sealed with minor suturing using BioGlue® as an adjunct. This is beneficial in complex repairs because a safe anastomosis could be achieved. Over-tightening of the anastomotic suture, which can lead to compromised vascularity, necrosis and finally dehiscence, can be reduced by adjunctional gluing.
Although in healthy human lungs, parenchymal lesions could be sewn without difficulties this is not the case for the repair of an emphysematous lung. In particular, when steroids were used preoperatively, significantly longer air leakage could be found [26,27].
It does appear that the most striking benefit would apply to the emphysematous lung, where prolonged air leakage, despite the use of buttressed staplers, could be found.
In regard to the parenchymal repair, the application of adhesive lead to an air and blood tight repair in all post-operative cases. Pleural adhesions in the long term follow-up could not be detected. However, the amount of adhesive applied influences the healing of the glued tissue. Long-term investigations have to prove the persistence and biomechanical property. From our experiments it can be concluded that other indications would warrant an application, such as segmental resection in the anatomical plane with depleuralized areas.
If the absence or reduction of adhesions between the area of BioGlue® and parietal pleura can be confirmed in humans, this would offer another advantage in patients undergoing excision of pulmonary metastasis who are often at a risk of repeated operations. And, conservation of lung may be of considerable value for patients undergoing large or multiple resections and for patients with marginal pulmonary reserve [24].
| 5. Conclusion |
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| Acknowledgments |
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| Footnotes |
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| References |
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