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ORIGINAL ARTICLE |
Department of General Thoracic Surgery Iizuka Hospital Fukuoka, Japan
Kozo Nakanishi, PhD Tel: +81 48 462 1101 Fax: +81 48 464 1138 Email: konakanishi-ths{at}umin.ac.jp, Department of General Thoracic Surgery, National Saitama Hospital, 2-1 Suwa, Wako, Saitama, 351-0102, Japan.
ABSTRACT
Fibrin glues are widely used for various pulmonary operations, but commercially produced glues are made of heterogeneous fibrinogen that has infection risks. We used autologous cryoprecipitate and evaluated its clinical value as a fibrin sealant instead of the commercially available glue. One hundred patients who underwent thoracoscopic bullectomy for primary spontaneous pneumothorax were studied. The apical visceral pleura was covered with an absorbable mesh and a fibrin glue. Autologous cryoprecipitate glue was used in 30 patients (group A), and commercially produced fibrinogen was used in 70 (group B). The mean duration of postoperative chest drainage was 1.9 days in group A and 1.5 days in group B. The cumulative 2-year postoperative recurrence rate was 3.4% in group A and 6.5% in group B. There were no differences in clinical results after surgery for primary spontaneous pneumothorax, using either autologous cryoprecipitate or commercially produced fibrinogen. The production autologous cryoprecipitate was easy and low-cost. We propose that autologous cryoprecipitates be used in operations for primary spontaneous pneumothorax.
Key Words: cryoprecipitate coagulum [Substance Name] • Fibrin Tissue Adhesive • Pneumothorax • Thoracic Surgery • Video-Assisted
INTRODUCTION
For surgical treatment of spontaneous pneumothorax, procedures to patch an absorbable mesh onto the visceral pleura with fibrin glue are becoming widely used to reduce postoperative recurrence.1,2 Fibrin glues are used to prevent air leakage through stapled surgical margins in the short term, and an absorbable mesh fixed to the pleura with fibrin glue prevents postoperative pneumothorax recurrence in the long term. However, these glues are commercial products derived from donated or sold blood.3,4 Therefore, there is always some risk of viral or unknown pathogen infection for the patient. Cryoprecipitate is an alternative material including dense fibrinogen, which can be produced from the patient’s own blood.5 Theoretically, using an autologous cryoprecipitate instead of commercially produced fibrinogen should reduce the infection risk.5,6 We used our patients’ own cryoprecipitates instead of commercial fibrin glues, and evaluated the clinical outcomes.
PATIENTS AND METHODS
This was a retrospective study conducted in 100 patients who underwent first-time thoracoscopic stapled bullectomy (Table 1
). They also received a covering procedure of the apical visceral pleura, using an absorbable mesh and fibrin glue for primary spontaneous pneumothorax, in Iizuka Hospital, Fukuoka, Japan, between October 1, 1998 and March 31, 2007. The study included all patients who underwent surgery for primary spontaneous pneumothorax, regardless of air leakage or frequency of pneumothorax. Each patient decided preoperatively whether the covering procedure with absorbable mesh and fibrin glue should be added to the bullectomy. From October 2002, when we began to produce autologous cryoprecipitate glue at our institution, patients who wanted the mesh covering procedure decided which glue should be used: autologous cryoprecipitate or commercial fibrin glue. Patients who underwent computed tomography for secondary spontaneous pneumothorax were ruled out. Patients with hemopneumothorax and those who had procedures for bullectomy alone, ligation, or cautery of bullae were excluded from this study. Bullectomy combined with other pleural symphysial therapies, such as chemical pleurodesis, parietal pleurectomy, or pleural abrasion, were also excluded. The 30 patients who chose autologous cryoprecipitate glue were categorized in group A, and 70 who chose commercially produced fibrin glue (3 mL of Beriplast P; CSL Behring, Marburg, Germany) were assigned to group B. Beriplast P contained 80 mg·mL–1 of fibrinogen. The mean duration of postoperative chest drainage in each group was determined to evaluate the short-term effectiveness of the glue, and the recurrence rate was used to assess the long-term effectiveness. Body temperature was monitored to check for disorders arising from these procedures. All patients gave written informed consent, and the study was approved by our institutional ethics committee.
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All surgical treatments were performed thoracoscopically. Based on the position of the bullae, 3 access ports were constructed in the chest wall. All detectable bullae were resected with endoscopic staplers under videothoracoscopy. A sealing test was not performed after bullectomy. A 15 x 15-cm piece of woven biodegradable mesh (Vicryl; Ethicon, USA) was inserted into the pleural cavity through an access port, and placed on the apical parietal pleura. Cryoprecipitate and thrombin solutions were sprayed onto the apical visceral pleura around the stapled surgical margin in all cases in group A. In group B, commercially produced fibrin glue containing fibrinogen and thrombin was sprayed in the same manner as for group A. The spray device designed for thoracoscopic surgery, provided in the Beriplast kit, was used to distribute the glue in both groups. A sheet of mesh was immediately applied to the apical visceral pleura with endoscopic forceps after inflating both lungs. A chest drain was placed in the chest cavity for at least one night. The same antibiotic was used routinely for 2 days in all patients, to prevent wound infection. A 28F drain tube was placed near the 3rd rib in the posterior chest cavity through the 5th intercostal space of the anterior axillary line. The drain was suctioned at –10 cm H2O after surgery. The drain was removed immediately after confirming that there was no air leakage, the suctioned pleural effusion was <150 mL per day, and there was no sign of infection. Chest radiography was performed every day during chest drainage and on the day after removal of the drain tube. Recurrence of pneumothorax was confirmed by chest radiography. Chest computed tomography was carried out to detect recurrent lesions, if the patient gave consent. Reoperation was undertaken if the patient so desired.
StatView version 5.5 computer software (SAS Institute, Inc., NC, USA) was used for statistical analysis. Proportions were compared by the chi-squared test. Body temperature changes were compared using one-way analysis of variance. Recurrence rates were calculated by the Kaplan-Meier method, and comparisons were made by the log-rank test. A p value <0.05 was used to indicate statistical significance.
RESULTS
There was no operative mortality (within 30 days), and no patient needed to be converted to thoracotomy. Postoperative chest drainage is shown in Table 2 and Figure 1. Although the sample size was small, there were no significant differences in the mean durations of postoperative drainage or hospital stay between the 2 groups. The highest body temperature after the operation was 38.2 ± 0.7°C in group A and 37.9 ± 0.8°C in group B on postoperative day 1, after which temperatures decreased in both groups (Figure 2). There was no significant difference in postoperative body temperature between the 2 groups (one-way analysis of variance: p =0.11). Although the postoperative body temperature of most patients in both group rose and persisted >37.5°C, it returned spontaneously to the preoperative level within 5 days without administration of additional antibiotics. There was no case of postoperative pyothorax in either group. One patient in group A and 4 in group B suffered a recurrence of pneumothorax; one in each group underwent reoperation. After the first operation, both of these patients showed moderate adhesions around the apex on which the absorbable mesh was placed. The recurrence in group A was caused by a new bulla in the visceral pleura of the upper lobe, without adhesion to the parietal pleura. One recurrence in group B was caused by a new bulla in the pleura of the lower lobe. In the other 3 cases, the cause of recurrence was not confirmed, although chest radiography in all 3 patients showed that the apex of the upper lobe was attached to the chest wall and the lower lobe had collapsed; they improved without treatment. There were late recurrences in 5 (5.0%) patients during the first 3 years postoperatively: 1 (3.3%) in group A and 4 (5.7%) in group B. The cumulative 2-year recurrence rate was 3.4% in group A and 6.5% in group B (Figure 3). There was no significant difference in cumulative recurrence rates between groups A and B (log-rank test: p =0.648).
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In Japan, bullectomy alone is the primary surgical treatment for spontaneous pneumothorax, because chemical agents for pleurodesis are not approved for treatment of pneumothorax.7 In contrast, bullectomy combined with pleural symphysis is the treatment of choice for spontaneous pneumothorax in other countries. The postoperative recurrence rates in Japanese institutions are relatively high in comparison to those in other countries.2,8,9 Surgeons in Japan have been trying to establish an alternative to chemical pleural symphysis. Mesh covering is one means of preventing pneumothorax recurrence. In this procedure, the apex and surgical margins of the lung after bullectomy are covered with an absorbable mesh and fibrin glue.
The technique reduces pneumothorax recurrence after bullectomy, and is accepted widely in our country. Fibrin glue has been widely used in various lung operations after it was shown to be effective in reducing air leakage after lung resection.10,11 Because commercial fibrin glues are biologic in origin, we must be mindful of infection risks when using a commercially produced sealant.3 Thus it is extremely important to develop an alternative method to avoid this infection risk.
The primary purpose in using these products in lung surgery is not hemostasis but prevention of air leakage.12 For this purpose, commercial fibrin glues are widely used for lung operations in Japan, even in young patients with associated spontaneous pneumothorax. In addition, biologic glues are becoming more widely used since it was reported that covering the apical visceral pleura around stapled surgical margins with an absorbable mesh and fibrin glue reduced postoperative pneumothorax recurrences.8,13 Such covering techniques tend to be well accepted by Japanese surgeons, as a substitute for pleural symphysial procedures to prevent pneumothorax recurrence.2
Commercially produced fibrin glues consist of 4 heterogeneous proteins in 2 solutions: one contains fibrinogen and factor XIII, and the other is a thrombin solution.12 In addition, an anti-plasmin aprotinin to prevent dissolution of fibrin complexes is found in both solutions. Although all components of fibrin glues, except aprotinin, can be produced from autologous whole blood in a technically advanced institution, the procedures are not so easy for a blood transfusion department in a general hospital. At our institute, we can produce a cryoprecipitate that contains highly concentrated factor VIII, factor I, factor XIII, and von Willebrand factor. Cryoprecipitate was used as a fibrin glue before a commercial product of concentrated fibrinogen became available.3,14 Therefore, in this study, we made autologous fibrin glues using cryoprecipitates instead of producing fibrinogen solutions. The concentration of fibrinogen in the cryoprecipitates produced from 400 mL of whole blood is actually lower than that of commercial products. However, our impression was that the viscosity of the cryoprecipitate glue was no less than that of commercially produced glue. The viscosity has been reported to be equal to that of commercial glue in vitro.15 If needed, the amount of fibrinogen could be increased by simply increasing the amount of donated whole blood. Although the auto-logous cryoprecipitates had variable fibrinogen concentrations, the clinical performance was no less than that of the commercial product in this study.
To prevent postoperative pneumothorax recurrence in the long term, fibrin glue fixes the mesh to the pleura because fibrosis begins around the mesh.16 The viscosity of autologous glue was sufficient to allow quick fixation of the absorbable mesh to the visceral pleura during the operations in all cases, and there was no difference in the cumulative 2-year postoperative recurrence rates between the 2 groups. We estimate that the autologous cryoprecipitate glue succeeded as well as the commercially produced glue in the covering procedures.
Producing the autologous cryoprecipitate had the advantage of being simple. Freezing, thawing, and centrifugation of autologous blood were carried out only twice each.5 The cost of the production process was extremely low. We incurred only the cost of a blood collection bag (280 Japanese Yen; Terumo Co., Tokyo, Japan) and 2 inexpensive solutions (glucuronic calcium, 87 Yen per 10 mL, and thrombin, 760 Yen per 5,000 U). In contrast, commercial glue is very expensive, priced at 10,768 Yen per mL. Red blood cells and cryoprecipitate-reduced plasma, which were also produced from donated auto-logous whole blood, were available for transfusion during the operation if necessary. A limitation is that autologous cryoprecipitate glue would not be available for use in an emergency operation. The process to produce autologous cryoprecipitate takes at least 2 days for cryopreservation and low-temperature fusion. For emergency operations, we have to use commercial fibrin glue, with the patient’s consent. No emergency cases were included in this study. The volume of autologous cryoprecipitate was sufficient in all patients. If more glue had been needed after using all of the autologous cryoprecipitate, we would have used commercially produced fibrinogen solution. The absolute volume of cryoprecipitate depends on the volume of whole blood collected from the patient, and the volume of the cryoprecipitate solution depends on the volume of cryosupernatant plasma that is removed after the final centrifugation. There is a risk of bacterial contamination during autologous blood transfusion. However, the main threat of bacterial contamination arises from storing platelet concentrates at room temperature and red cell concentrates at low temperature. The cryoprecipitate is extracted from frozen plasma at 4°C and stored at –40°C. We think that the possibility of proliferation of bacteria is low.
We recognize that the issue of the infection risk from the use of bovine thrombin has not been resolved. It was too complex a process to produce a thrombin solution from donated whole blood at our institute.7 However, an instrument that produces thrombin from autologous whole blood has been developed.9 Unfortunately, in our county, such devices for extracting thrombin are not allowed at present; therefore, Japanese surgeons have no choice but to buy commercial thrombin. Aprotinin was not used because aprotinin is unnecessary for fibrin formation in practice. It is difficult to determine whether autologous cryoprecipitate can decrease the infection risk. Currently available commercial fibrin glues are extremely safe, and no serious infections have been reported from the use of these products, except for parvovirus infection.4 However, in Japan, hepatitis C viral infection caused by tainted fibrinogen recently became a major social concern.17 Some of our patients refused commercially produced fibrin glue in their operations. Thus it is important to develop an alternative method to avoid the infection risk originating from biological products, even if 1 in 4 of the proteins in the fibrin glue have been changed.
We concluded that cryoprecipitate is a suitable substitute for commercially produced fibrinogen solution in surgery for primary spontaneous pneumothorax. In this study, autologous cryoprecipitate reduced air leakage from stapled surgical margins and postoperative pneumothorax recurrence just as well as commercially produced fibrinogen. Using cryoprecipitate sealant instead of commercial fibrin glue, we can avoid the infection risk originating from biologic fibrinogen products, at least theoretically.
REFERENCES
Asian Cardiovasc Thorac Ann 2010;
18:27-32
© 2010 by SAGE Publications
DOI: 10.1177/0218492309355329
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