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Interact CardioVasc Thorac Surg 2006;5:243-246. doi:10.1510/icvts.2005.121129 © 2006 European Association of Cardio-Thoracic Surgery
Fleece bound sealing prevents pleural adhesions
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Abstract |
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 Top Abstract 1. Introduction2. Material and methods3. Results4. DiscussionAppendix. Conference discussionReferences |
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Key Words: Animal model; Experimental surgery; Haemostatic fleece; Pleural adhesions
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1. Introduction |
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TopAbstract1. Introduction2. Material and methods3. Results4. DiscussionAppendix. Conference discussionReferences |
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Prevention of pleural adhesions has been addressed only in a few studies. Intrapleural application of heparin or urokinase has been shown to decrease pleural adhesions in tetracycline-induced pleural injury in rabbits [7]. Hyaluronate-based bioresorbable membrane has been demonstrated to inhibit postoperative adhesions in the thoracotomy area in a rat model [8]. According to clinical observations published by Osada and colleagues, haemostatic fleece is an effective method of preventing adhesion formation at the application site in gynaecological/obstetric practice [9].
Use of fleece-bound sealants remains a requirement for advanced general thoracic procedures with the aims of treatment of parenchymal air leaks of the lung, achieving adequate haemostasis in diffuse chest wall bleeding and diminishing lymphatic fluid production.1 However, properties of haemostatic fleece have never been evaluated systematically concerning prevention of postoperative pleural adhesions.
The aim of this experiment was to assess the value of haemostatic fleece in the prevention of pleural adhesions in an experimental animal model.
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2. Material and methods |
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TopAbstract1. Introduction2. Material and methods3. Results4. DiscussionAppendix. Conference discussionReferences |
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2.1. Experimental setting and surgical technique
Forty male rats with a median weight of 365 g (range 350–450 g) were planned for bilateral subsequent thoracotomy and randomly assigned to four groups (1, 2, 3, 4) of ten animals each.All procedures were carried out under general anaesthesia. Induction was performed with Ketamin 0.1 ml/100 g (Ketavet ad us vet®) and Xylazinum 0.05 ml (Rompun ad us vet®), inhalation anaesthesia with 0.5% to 2.0% isoflurane in 100% oxygen at a flow rate of 0.5 l/min. Rats were in supine position. After skin preparation with an aqueous iodine solution, subsequent bilateral thoracotomies were performed through the fourth or fifth intercostal space. Further treatment depended on the referring experimental group.
In Group 1 standardized defects of 5 mm were generated in the visceral pleura at the right side (middle lobe) and the parietal pleura at the left side without further coverage.
In Group 2 one prepared 5 mm piece of haemostatic fleece (TachoSil®, Nycomed Denmark) was shortly moistened in saline solution and applied onto the intact visceral and another piece onto the parietal pleura of the contralateral side. TachoSil® consists of an equine derived collagen matrix coated with human fibrinogen and thrombin. Upon contact with blood or other fluids, the coagulation factors form a robust fibrin clot and firmly glue the material to the tissue surface.
In Group 3 standardized pleural defects were completely covered by haemostatic fleece.
The same kind of defect was only partially covered by haemostatic fleece in Group 4 animals.
After completion of this stage the chest was closed in a standard way without placing a chest tube. Intercostal thoracic incision was tightly closed using interrupted 3–0 silk sutures. During closure of thoracotomies animals were maintained with continuous positive airway pressure (CPAP) ventilation 3 cm H2O. Wound closure was carried out with silk and vicryl.
Two ml Dipidolor in 3 ml Glucose 5% was administered subcutaneously at 0.2 ml/100 g every 8 h for 1 day after the procedure.
2.2. Autopsy and histological examination
Five animals of each group were sacrificed 6 weeks, and five animals 12 weeks, after surgery by using pentobarbital over-dose (120 mg/kg body weight) i.p. During autopsy the area of the defect was excised with adjacent structures. The specimens were immersion-fixed in 5% neutral formalin and then processed for histological sectioning. The paraffin sections were cut at 7–10 µm thickness and stained with haematoxylin-eosin, and studied in a Leica light microscope. The areas of interest were first identified at 10x magnification. Then detailed analyses were performed at either 20, 40 or 100x magnification. The pathologist was blinded to which groups the slides belonged to. |
3. Results |
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TopAbstract1. Introduction2. Material and methods3. Results4. DiscussionAppendix. Conference discussionReferences |
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Autopsy at 6 weeks revealed the fleece dislocated and freely lying in the pleural cavity in 66% of applications among Group 2 animals, in 34% the fleece still was in the application area. In Group 3 animals the fleece was found widely unchanged and covered by a smooth serous membrane. In this layer newly built capillaries were detected, which derived from the original pleura and crossed over the implanted collagen fleece.
After 12 weeks the fleece had been completely resorbed in all animals. All other observations were similar to those after 6 weeks.
3.3.1. Six weeks after surgery
3.3.2. Twelve weeks after surgery
Histological studies confirmed complete obliteration of pleural cavity in the defect areas in Group 1 animals. In Groups 2 and 3 treatment areas were covered by regular mesothelium. Remnants of haemostatic fleece were not detected in any of the animals. Concerning Group 4, part of the defect without fleece coverage was completely obliterated, the free surface area covered by regular mesothelium. All discrete focal mononuclear reactions had completely resolved by that time.
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4. Discussion |
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TopAbstract1. Introduction2. Material and methods3. Results4. DiscussionAppendix. Conference discussionReferences |
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In this study, we wanted to assess the value of haemostatic fleece in prevention of pleural adhesions in an experimental animal model. Hence, we did not aim at creating lung defects with air leakage, but looked for a technique to reliably destroy the pleura. In our model this was achieved by electrocautery of visceral and parietal pleura in a defined area of 5 mm in diameter. We feel that the resulting pleural defects nicely mimic the clinical situation we experience in thoracic surgical practice.
The body seems to absorb the collagen material inoculated into the peritoneal cavity within 12 weeks according to clinical observations by a Japanese group [9]. Furthermore, no de novo adhesions were detected at the application site of the fleece. At present, the material is used widely in thoracic and abdominal surgery to cover exposed surfaces following excision, and has been reported to be highly effective in controlling leakage from such areas. This may explain why haemostatic fleece was found dislocated in two thirds of applications on intact pleura in our study. The normal pleural surface obviously did not allow permanent adhesion of the fleece compared to areas with lacking mesothelium. In the one third of applications on normal pleura without dislocation of the fleece we suspect other erratic damage of the pleura with focal exposure of collagen fibres.
In our study histological evaluation six weeks after surgery revealed discrete lymphocyte infiltrations in the areas subjacent to the fleece application. Despite the fact that fibrin mediates acute inflammatory responses to biomaterials [13], biocompatibility studies of haemostatic fleece have shown good histocompatibility, moderate biodegradability, and lack of toxicity of collagen carriers in combination with fibrin glues [14]. The material induces mitogenic and chemotactic processes and thereby improves wound healing. The mononuclear infiltrates observed in our rat model may be interpreted as discrete and transient foreign body reactions, which completely resolved within 12 weeks from surgery. Moreover, none of the animals showed macroscopic signs of a focal reaction or inflammatory process at autopsy.
The main observation of this experimental work is the fact that haemostatic fleece completely prevented the development of pleural adhesions in areas of pleural defects. Without further coverage the creation of pleural defects led to focal pleural obliterations. This was observed in all Group 1 animals and in Group 4 animals with only partially covered defects. In all Group 3 animals with complete coverage of the defects, no adhesions were detected and the inoculated collagen material was perfectly covered by regular neo-pleura within 6 weeks. Later observations at 12 weeks demonstrated complete biodegradation of the fleece without any remnant material.
As clinical findings perfectly reflect the results of our present study and confirm previous reports on the use of TachoSil in abdominal surgery, we assume that applying TachoSil onto the closed pericardium or directly onto the right ventricle would prevent adhesions between the anterior wall of the right ventricle and the inner surface of the sternum in the same way.
In conclusion, haemostatic fleece may be recommended to cover pleural defects in order to prevent pleural obliterations in addition to the already established indications of sealing tissues against oozing fluids and air. This property may have clinical impact in patients with some probability of re-thoracotomy or re-sternotomy for malignant diseases, after cardiac surgery or in potential transplant candidates.
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Appendix. Conference discussion |
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TopAbstract1. Introduction2. Material and methods3. Results4. DiscussionAppendix. Conference discussionReferences |
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Dr Getman: Potential transplant candidates. I mean, first of all, patients who underwent lung volume reduction surgery, for example.
Dr Treasure: So anybody with lung volume reduction surgery?
Dr Getman: Yes, as a bridge to lung transplantation.
Dr Treasure: The question was the total list. What other indications?
Dr Getman: Indications for nonmalignant diseases.
Dr Treasure: I'll tell you my second question, because this is what I'm getting at. Of the patients you treat, only some will come to a subsequent thoracotomy and only some of those would have had troublesome adhesions. So in order to look at a treatment such as this, you need a statistic which would be something like the number needed to treat in order to get one benefit. So what would be your estimate of how many patients would have to have fleece to get to one in whom you would get a real surgical benefit? Do you follow me?
Dr Getman: Yes. I would say that in patients who were treated surgically, as mentioned above transplant candidates, we used hemostatic fleece routinely, and we are strongly in favour of using hemostatic fleece in similar situations.
Dr Treasure: I think one of your colleagues is going to help. It's a slightly difficult question and you may not have followed it.
Dr M. Mueller (Vienna, Austria): I feel that this could be a very good opportunity for patients after metastasectomy. We very frequently see patients for a second or a third intervention for metastases. Especially in osteosarcoma patients there is a very high probability that they would need a further thoracotomy in the future. So in these cases this could be a good option.
Dr Treasure: I think that when you write it up, you should say of patients with metastases, 5% or 95%, or whatever percentages come back, and how often you encounter a problem. How often is the dissection difficult at a second thoracotomy for metastases?
Dr Mueller: You mean the area where we resect?
Dr Treasure: How often does it represent a surgical challenge? Sometimes it's just no problem. You just open the chest and you carry on.
Dr Mueller: Actually it's never a surgical challenge, except the cases where you do 10 resections in the lung.
Dr Treasure: I just recommend that you run that model through your head of the number needed to treat in this way to get a surgical benefit. The reason I'm asking is because I think you might use it 20 times and in 19 of them it wouldn't have mattered anyway because you either don't operate or it's easy. I mean it's quite important when you take on an intervention to not just come up with a theory of when it might help but in how many cases would it help.
Dr L. Von Segesser (Lausanne, Switzerland): What's the size of the patch of fleece that you put there?
Dr Getman: 5 mm in this experiment.
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References |
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TopAbstract1. Introduction2. Material and methods3. Results4. DiscussionAppendix. Conference discussionReferences |
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