Asian Cardiovasc Thorac Ann 2008;16:309-312
© 2008 Asia Publishing EXchange Ltd
Novel Anti-Adhesive Pericardial Substitute for Multistage Cardiac Surgery
Goki Matsumura, MD,
Toshiharu Shin’oka, MD,
Yoshito Ikada, PhD1,
Takahiko Sakamoto, MD,
Hiromi Kurosawa, MD
Department of Cardiovascular Surgery, The Heart Institute of Japan, Tokyo Women’s Medical University, Tokyo
1 Department of Medicine, Nara Medical University, Nara, Japan
For reprint information contact: Goki Matsumura, MD Tel: 81 3 3353 8111 Fax: 81 3 3356 0441 Email: smatumur{at}hij.twmu.ac.jp, Cardiovascular Surgery, The Heart Institute of Japan, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
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ABSTRACT
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Dense adhesions in the retrosternal space make reoperations difficult in the field of cardiovascular surgery. Several substitutes for pericardium have been employed to prevent dense adhesions forming, but they have been unsatisfactory because of peel formation, calcification, and infection. To overcome these drawbacks, a novel biodegradable pericardial substitute was developed from gelatin obtained from specific-pathogen-free porcine skin and a bioabsorbable polyester mesh, which persists while the adhesion reaction occurs in the retrosternal space. A clinical pilot study of this gelatin sheet was carried out in patients scheduled to receive multistage cardiac surgery. From February 2003 to July 2004, the material was used in 5 patients aged 0.4 to 3.0 years. There were no complications related to the gelatin sheet. The effectiveness of the material was evaluated when the sternum was reopened 1.4 ± 0.5 years later. It took 24.5 ± 6.0 min for the resternotomy, and all surgeons who participated in the surgery rated the effectiveness of the gelatin sheet as "good". This anti-adhesive sheet prevented dense adhesions, suggesting that this material may be useful as a pericardial substitute for multistage pediatric cardiac surgery.
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INTRODUCTION
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Recently a large number of patients with congenital heart defects have required repeat sternotomy because reoperations and staged surgical procedures are increasing. Repeat sternotomy and dissections carry a risk of further reoperation because mediastinal adhesion formation may result in iatrogenic injury of the heart, arteries, or veins. In addition, mediastinal adhesions make it difficult for surgeons to identify anatomical features, prolong the operating time for dissections, and increase blood transfusion requirements.1 Closure of the pericardium is one of the strategies to prevent these drawbacks. However, pericardial closure is usually impossible because it may cause cardiac tamponade or late constriction after surgery. Moreover, in a 2nd or 3rd repeat sternotomy, there remains no pericardium available for chest closure. So far, various materials, such as silicone rubber, polyurethane, fascia lata, expanded polytetrafluoroethylene (ePTFE), heterologous porcine, equine, or bovine pericardium, Dacron, and dura mater have been employed as pericardial substitutes to secure safer resternotomy.2–11 The widely used ePTFE sheet is reported to be safe and effective in preventing cardiac injury at resternotomy.4,5 However, such nonabsorbable material might cause dense adhesions and severe inflammatory reactions including fibrotic change, calcification, and mediastinitis after implantation.6,7,11 An ideal pericardial substitute to prevent these drawbacks in reoperations is required, especially in the field of pediatric cardiac surgery where multistage operations are often needed. As previous animal experiments revealed a cross-linked gelatin had anti-adhesion effects, we decided to move forward to a clinical pilot study.13–15
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PATIENTS AND METHODS
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In a non-controlled clinical study, 5 patients who were expected to require further repair of congenital defects received the anti-adhesive sheet between February 2003 and July 2004. There were 3 boys and 2 girls, ranging in age from 0.4 to 3.0 years (mean age, 1.5 ± 1.0 years). The main diagnosis and surgical procedures when the sheet was applied and when the sternum was reopened are shown in Table 1
. The Tokyo Women’s Medical University Institutional Review Board approved the protocol. All of the patients’ families were informed and consented to the use of the material. The anti-adhesive effects of the substitute were evaluated by 3 surgeons who participated in the surgery, and scored as follows: 4, excellent (without adhesion); 3, good (slightly adhesive); 2, fair (quite adhesive); and 1, poor (densely adhesive).
An aqueous solution of gelatin derived from porcine skin was cast on a glass plate where a bioabsorbable polyglycolide mesh was laid, and allowed to dry in air, yielding a sheet of 0.2 mm in thickness. After cross-linking, the sheet was cut into 6 x 9 cm2 sections and sterilized with ethylene oxide gas. Prior to use as a pericardial substitute, the sheet was immersed in physiological saline for a few minutes, and fixed in the mediastinum with surgical sutures. The gelatin sheet is shown in Figure 1.
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Figure 1. The anti-adhesion gelatin sheet after immersion in physiological saline. The sheet is translucent, flexible, and durable, and supports a surgical suture.
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RESULTS
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The sternum was reopened 1.4 ± 0.5 years after the sheet had been placed (Table 1
). There was no mortality or morbidity such as prolonged inflammatory response, infectious complication, signs of tamponade, or early repeat thoracotomy due to the gelatin material. The mean white blood cell counts on postoperative day 1, 2 and 3 were 15,718 ± 6,796, 15,482 ± 3,890, and 14,990 ± 5,410 cells per microliter, respectively. The mean C-reactive protein levels on postoperative day 1, 2, and 3 were 4.3 ± 1.0, 5.4 ± 5.0, and 1.3 ± 1.4 mg·L–1, respectively. White blood cell counts normalized within 7 to 16 days in these patients. The resternotomy took 19 to 34 min (mean, 24.5 ± 6.0 min) from the start of the operation to sternal reopening (Table 2). In each case, the resternotomy was easily performed. All surgeons who participated in the operation scored the anti-adhesive effectiveness as "good". The impression of adhesiveness in the site where the gelatin sheet was used and at other sites in the mediastinum, the time from the onset of the operation until the sternum was reopened, and the time from sternal reopening to the institution of cardiopulmonary bypass are listed in Table 2. Photographs of case no. 5 are shown in Figure 2. The anti-adhesion gelatin sheet was laid on the surface of the heart and vessels when this patient had a bidirectional Glenn shunt and repeat pulmonary artery banding (Figure 2A). When the patient had a repeat sternotomy 0.8 years later, there was no gelatin sheet left on the heart, and dense adhesions were not observed where the sheet had been applied (Figure 2B). However, dense adhesions were found between the inferior wall of the right ventricle and the diaphragm which had not been covered by the anti-adhesive sheet. It took approximately 19 min from the skin incision to resternotomy in this case, and it was 179 min before cardiopulmonary bypass was started (Table 2).
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Figure 2. Photographs of the operation in case no. 5. (A) The anti-adhesion gelatin sheet laid on the surface of the heart. (B) The surface of the heart when the sternum was reopened 0.84 years after the sheet had been applied.
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DISCUSSION
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The difficulty due to adhesions in reoperations is well known. The presence of retrosternal adhesions prolongs reentry during cardiac surgery and carries a risk of direct myocardial injury and catastrophic hemorrhage.16 The pathogenesis of these adhesions is related to serosal denudation in association with intrapericardial blood.17 Unfortunately, early correction of congenital heart defects incurs a high probability of repeat surgery.4 Moreover, certain complex defects necessitate multistage repair, with one or more repeated thoracotomies. In reoperations requiring resternotomy, pericardial and mediastinal adhesions can obscure important anatomic structures, causing catastrophic bleeding and considerable morbidity and mortality.12,18,19 Therefore, a pericardial substitute that avoids damage to the heart and great vessels should be employed between the sternum and the heart. However, several commonly used pericardial substitutes have been less than satisfactory. This fact prompted the development of a more favorable substitute for pericardium.
Our new anti-adhesive gelatin sheet fabricated from heterologous protein is designed to exist in the pericardial cavity during the inflammatory and adhesion responses after surgery, followed by degradation and absorption with time. As great effectiveness of a gelatin sheet in preventing adhesions was reported in an animal model, we modified the material utilizing bioabsorbable polyester mesh to reinforce the gelatin and provide suture stability.15 The gelatin degrades by enzymatic digestion and the mesh degrades by non-enzymatic hydrosis, so all foreign material remains in the pericardial cavity for a limited period after surgery. The advantages of a gelatin sheet reinforced with polyglycolic mesh might be expected to include reduced incidence of the drawbacks of the other pericardial substitutes commonly used in cardiac surgery. For safe application, we used gelatin derived from porcine skin to avoid unwanted infection such as bovine spongiform encephalopathy.15
Recently, a number of experimental studies on biodegradable materials as pericardial substitutes have been reported. Gabbay and colleagues20 demonstrated the feasibility of a biodegradable polyglycolic acid mesh that is rapidly absorbed and forms a thin layer of host collagen. They also reported the influence of cardiopulmonary bypass on the formation of adhesions in the retrosternal space. Absorbable materials are useful as they do not remain in vivo for a long time, and have less potential to form adhesions. We found the gelatin sheet to be effective as a pericardial substitute to prevent the formation of dense adhesions in the retrosternal space. However, we were not completely satisfied with the results because the only part covered by the sheet was between the retrosternal space and the right ventricle, and most of the heart and vessels that need to be dissected in further surgery were not covered. Nevertheless, we are convinced that utilizing the gelatin sheet can shorten the time for repeat sternotomy and dissection compared to the ePTFE sheet as a pericardial substitute (data not shown).
In congenital heart surgery, which often requires multistage operations, it is very important to dissect the anatomical structures easily and without any complication to conduct the next operation as safely and as quickly as possible. Therefore, we speculate that greater efficacy of the sheet would be achieved when it can cover the whole area of the heart and vessels that might be dissected in further operations. This improved efficacy would decrease the incidence of several risks in reoperations, lessen the incidence of blood transfusion, and shorten the operating time. These merits would benefit patients who require multistage surgery and also the surgeons who have to carry them out. In this study, postoperative blood tests showed prolonged high white blood cell counts. We could not conclude whether or not these effects were related to the gelatin sheet. Further studies with a larger number of patients is required. We included only 5 patients in this pilot study. To verify the efficacy of the gelatin sheet, a case-matched randomized controlled study should be performed in the future.
It was concluded that this novel anti-adhesive gelatin sheet prevented dense adhesions after sternotomy in humans, suggesting its effectiveness. This gelatin sheet could become a pericardial substitute and also an anti-adhesive material to avoid dense adhesion of the heart and vessels in patients requiring multistage cardiac surgery.
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REFERENCES
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ABSTRACT
INTRODUCTION
