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Original Articles: Pediatric Cardiac

A Novel Bioresorbable Film Reduces Postoperative Adhesions After Infant Cardiac Surgery

^a Division of Thoracic and Cardiovascular Surgery, Duke University Medical Center, Durham, North Carolina
^b Divison of Cardiothoracic Surgery, Childrens Hospital Los Angeles, Los Angeles, California
^c Division of Cardiovascular-Thoracic Surgery, Children's Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, Illinois
^d Division of Cardiac Surgery, Children's Mercy Hospital, Kansas City, Missouri
^e Cardiovascular and Thoracic Surgery, Kosair Children's Hospital and the University of Louisville, Louisville, Kentucky
^f Department of Cardiac Surgery, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts
^g Department of Cardiothoracic Surgery, Tulane University, New Orleans, Louisiana
^h Congenital Heart Institute, Arnold Palmer Hospital for Children and Women, Orlando, Florida
ⁱ Boston Biostatistics Research Foundation, Framingham, Massachusetts
^j Department of Cardiothoracic Surgery, Children's Hospital at Montefiore, Bronx, New York

Accepted for publication April 24, 2008.

^_* Address correspondence to Dr Lodge, Division of Cardiovascular and Thoracic Surgery, Duke University Medical Center, Box 3340, Durham, NC 27710 (Email: andrew.lodge{at}duke.edu).

Presented at the Forty-fourth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 28–30, 2008.

Drs Backer, O'Brien, Lavin, and Weinstein disclose that they have a financial relationship with SyntheMed, Inc.

 

	Abstract

Top Abstract Introduction Material and Methods Results Comment Discussion Acknowledgments References

 
Background: Adhesions encountered in reoperative cardiac surgery can prolong operating time and increase risk. This study was designed to evaluate the ability of a novel bioresorbable barrier film to reduce adhesions in infants.

Methods: A comparative, evaluator-masked, randomized, multicenter study design was used. Before chest closure, infants undergoing initial sternotomy for eventual staged palliative cardiac operations were randomized to barrier film placement (n = 54) or control (no treatment, n = 49) at 15 centers. At repeat sternotomy 2 to 13 months later, the extent and severity of adhesions at the investigational surgical site (ISS) were assessed. A four-grade adhesion severity scoring system was standardized as follows: none, mild (filmy, noncohesive, requiring blunt dissection), moderate (filmy, noncohesive, requiring sharp and blunt dissection), and severe (dense, cohesive, requiring extensive sharp dissection).

Results: There were significantly fewer patients with any severe adhesions (29.6% vs 71.4%, p < 0.0001), and a significantly lower percentage of the ISS had severe adhesion involvement (21.1 ± 36.9% vs 49.5 ± 42.7%, p = 0.0005) in the barrier group compared with the control group at the second sternotomy. Delayed chest closure (p = 0.0101), Norwood procedure (p = 0.0449), and cardiopulmonary bypass (p = 0.0001) were univariate risk factors for more severe adhesions. Multivariate analysis revealed only control group to be a significant risk factor for more severe adhesions (p = 0.003). There were no statistically significant differences in adverse events between the groups. No adverse events were definitely attributed to the study device.

Conclusions: Use of a novel bioresorbable film was safe and effective in reducing the extent and severity of postoperative adhesions in infants undergoing repeat median sternotomy.

Many patients that have cardiac surgery must undergo reoperative procedures through a median sternotomy, and some require multiple repeat sternotomies. These operations are complicated by the universal presence of adhesions between the heart and the mediastinal structures including the sternum, which increases the difficulty and potentially the risks of the procedure [1, 2].

A variety of strategies to reduce postoperative adhesions have been investigated, ranging from the instillation of solutions into the pericardial space which never came into clinical use [3] to the use of autologous tissue patches which are invasive and impractical [4]. Many of the techniques studied suffered from poorly designed or clinically irrelevant investigative protocols or cumbersome application. As a result, no accepted therapy exists for reducing adhesion formation after cardiac surgery.

To address this deficiency, a bioresorbable polymeric barrier film was developed to reduce the formation of postoperative adhesions in the chest during the period of scar formation before being absorbed. Preliminary animal experiments suggested efficacy and safety of the study device [5, 6]. This trial was designed to evaluate this barrier film in a clinically relevant pediatric population undergoing planned repeat sternotomies for complex congenital heart disease. Features that increase the risk of redo sternotomy include multiple reoperations and enlarged vessels or cardiac chambers, which are often features of congenital cardiac procedures [7]. The hypothesis of this study is that the use of the experimental barrier film after open cardiac procedures will reduce the extent and severity of adhesions encountered on subsequent operation.

	Material and Methods

Top Abstract Introduction Material and Methods Results Comment Discussion Acknowledgments References

 
Study Design
The trial was a multicenter, randomized, evaluator-masked design to study neonates undergoing planned staged sternotomies. The rationales for this design were the following: a relatively uniform group of patients was desired; a predictable and uniform interval between operations was necessary to facilitate and standardize evaluation of the adhesions; and given the patient population, a number of centers were necessary to achieve an adequate number of subjects. Approval was obtained from the institutional review board at each institution. Informed consent was obtained from the patients' parents prior to enrollment.

Patients were identified as potential subjects by diagnosis and anticipated need for staged surgery through a median sternotomy where the second sternotomy would occur within two to eight months of the initial operation. Randomization to either the experimental treatment (barrier) or control group (see below) occurred just prior to chest closure based on a by-center, computer-generated block randomization code. Exclusion criteria are shown in Table 1. Data were collected by the investigator or study coordinator at each site and entered into a central electronic database administered by the sponsor.

Surgical Procedures
Surgical procedures were performed according to the operating surgeon's usual preference. At the time of chest closure in the experimental group, the study device was applied over the epicardial surface of the heart and sutured in place with interrupted polyglycolic acid sutures. Application was limited to one piece of barrier film applied to the area directly below the sternotomy such that it did not overlap the cut pericardial edge by more than one centimeter (Fig 1). The remainder of the closure was per the routine of the individual surgeon. Control patients were closed routinely without the use of adjuncts such as absorbable hemostats. The majority of chest closures (n = 83) were performed as a delayed primary closure 1 to 4 days after the cardiac procedure.

View larger version (39K): [in this window] [in a new window]   Fig 1. Illustrations of the technique of barrier film implantation are shown. The left panel shows a frontal view demonstrating how the barrier film overlaps the cut pericardial edges slightly and is tacked to the pericardium with four sutures. The right panel is an axial diagram showing the relationship of the sternum, pericardium, barrier film, and heart after implantation.

View larger version (78K): [in this window] [in a new window]   Fig 2. The view of the heart is illustrated during the second sternotomy to show the investigational surgical site (ISS). The ISS, or area assessed for adhesions, is between the cut pericardial edges (outlined in blue and described by white arrows).

Study Endpoints
The primary endpoint of the study was the mean patient-specific percentage of the ISS with severe (grade 3) adhesions at the time of the second sternotomy. Secondary endpoints were the percentage of patients with no greater than moderate (grade 2) adhesions, the mean patient-specific percentage of the surgical site with grade 0, 1, and 2 adhesions, and the time to placement of the sternal retractor (dissection time) at the second sternotomy.

Statistics
The study goal was for 100 patients (50 per group) to undergo a second sternotomy to determine the extent of each adhesion grade. The study had 80% power to detect a 20% reduction in the mean percent of severe adhesions using a two-sided test with 5% type I error. A prospectively approved statistical analysis plan included tests to evaluate time to second sternotomy, mean percent area with severe adhesions (primary endpoint), overall distribution of adhesion area grades, percent of patients with severe adhesions as worst degree, and overall distribution of patients by worst grade. The primary endpoint was evaluated at the time of the second surgery. A 5% two-sided p value was required to establish statistical significance.

Statistical analysis was performed using SAS version 8.2 (SAS Institute, Cary, NC). All p values were calculated using a Fisher exact test for categoric variables, a Wilcoxon rank sum test for ordinal outcomes, a Wilcoxon-Gehan test for time to event outcomes, a two-sided t test for continuous variables, and analysis of covariance was used to test for treatment differences in mean percent area of grade 3 adhesions while controlling for study site and baseline covariates (gender, Norwood or non-Norwood, on/off cardiopulmonary bypass, primary or delayed chest closure, evaluator blinded or unblinded) with p less than 0.10 required to retain baseline covariates in the final model. Results were displayed within these subgroups to confirm effectiveness. Study site was examined both as a fixed and random effect.

	Results

Top Abstract Introduction Material and Methods Results Comment Discussion Acknowledgments References

 
A total of 142 patients (73 in the treatment [barrier] group and 69 in the control group) were randomized and treated at 15 centers between 2003 and 2006. The data were analyzed and reported for three populations. First, the safety population consisted of all patients who were randomized and treated and was primarily studied for adverse events and features related to safety of the study device. Patient demographics are shown for the safety population in Table 3. The intent-to-treat (ITT) population consisted of all randomized patients who underwent adhesion assessment at the time of the planned second sternotomy (barrier, n = 56; control, n = 54). The per-protocol (PP) population (barrier, n = 54; control, n = 49) included patients who had the second sternotomy at least two months after randomization, underwent adhesion evaluation, and had no major protocol violations (Table 4). Both of the latter populations were used to assess effectiveness and surgical site observations. No differences in results were found between the ITT and PP populations. For simplicity the effectiveness results that follow represent the PP population because these patients completed the study as designed and no differences were observed compared with the ITT population.

Effectiveness by Treatment Group
There was no difference in the time to second sternotomy between the barrier (169 ± 70 days) and the control groups (160 ± 56 days, p = 0.4844). At the second sternotomy procedure there was no visible evidence of the barrier film. The extent to which the investigational surgical site was involved with adhesion formation is shown in Table 5 and Fig 3. Adhesions were observed in all patients as demonstrated by the lack of patients with grade 0 adhesions in both groups. The barrier group had significantly less of the ISS involved with severe adhesions and significantly more of the ISS involved with mild adhesions than the control group; the overall adhesion distribution was significantly more favorable for the barrier group (p = 0.0006). In addition, there were significantly fewer patients with severe adhesions (29.6% vs 71.4%, p < 0.0001) in the barrier group compared with the control group at the second sternotomy.

View larger version (15K): [in this window] [in a new window]   Fig 3. Graph showing the distribution of adhesions by severity grade between the experimental barrier (black bars) and control (white bars) groups. The barrier group had significantly more mild adhesions and significantly less severe adhesions than the control group.

Dissection Time
Dissection time was defined as the time from skin incision to the placement of the sternal retractor as this essentially correlated with dissection of the ISS. There was no difference in dissection time between the barrier and control groups (26.6 ± 21.1 minutes vs 25.7 ± 22.7 minutes, respectively; p = 0.8414). However, there was a significant difference in the dissection time between patients that had severe adhesions (30.7 ± 22.4 minutes) compared with those without severe adhesions (21.7 ± 20.4 minutes, p = 0.0368).

Subgroup Confirmation Analysis
Several subgroups of patients were analyzed relative to the primary effectiveness endpoint of the study (Table 6). The p values in the table are provided as descriptive statistics as the study was not designed or powered for subgroup analyses. To summarize the finding in the subgroups, a general trend for reduction in grade 3 adhesions for the barrier group is apparent in all subgroups. There appeared to be more pronounced effects on the reduction of adhesions in the more complex patients (ie, the Norwood procedure patients and patients who had undergone operations requiring cardiopulmonary bypass and delayed chest closure).

Safety
As expected, adverse events were frequent given the complex nature of the study population. There was no difference in the rate of prospectively defined adverse events between the barrier and control groups (163 vs 144, p = 1.000). There was no difference in the rate of events that were deemed possibly, probably, or definitely related to the study device in the barrier group compared with the control group (6 vs 1, p = 0.1167), and no difference in the number of serious adverse events (4 vs 0, p = 0.1203). There were 12 deaths in barrier patients and 9 in control patients (p = 0.6405).

There were no differences in wound healing or infectious complications between the groups in this study. After the first sternotomy, 7 patients (9.6%) in the barrier group and 8 patients (11.6%) in the control group were diagnosed with superficial sternal wound dehiscence or infection (p = 0.788). Two patients (2.7%) in the barrier group and 1 patient (1.4%) in the control group were diagnosed with deep sternal wound infection or mediastinitis (p = 1.000). After the second sternotomy, 2 patients in the barrier group (3.6%) and no patients in the control group developed mediastinitis (p = 0.4956). Healing of the sternotomy incision was also assessed one month after the second sternotomy. Healing appeared normal in 91.1% of the barrier group patients and 92.6% of the control patients (p = 0.7570).

There were 8 cardiac injuries reported at the time of the second sternotomy, 4 in each group. All injuries involved premature entry into the right atrium, were small, and were easily repaired. No patient suffered morbidity related to inadvertent cardiac injury, and none required the emergent institution of cardiopulmonary bypass for control.

	Comment

Top Abstract Introduction Material and Methods Results Comment Discussion Acknowledgments References

 
Several studies have been performed with the goal of reducing postoperative adhesions after cardiac surgery in order to facilitate reoperation and reduce its risks. Most of the experimental animal studies are limited by small numbers, models that are not clinically relevant, and short 2 to 3 week intervals between treatment and adhesion assessment [8–11]. While some showed a reduction in adhesions, it is not clear that the findings are applicable to humans or whether, given the short time frame of the studies, adhesions were prevented or just delayed. Two animal models evaluated adhesions at a longer interval. Seeger and colleagues [3] used blinded observers to grade adhesions at 6 weeks in dogs and found that experimental solutions were effective in preventing adhesions. In similar studies in pigs and dogs, resorbable membranes were found to be effective in reducing pericardial adhesions evaluated at 4 to 8 weeks [12, 13]. Neither of these studies led to the development of a product that is in clinical use. Others have studied synthetic nonabsorbable patches, which may facilitate sternal reentry by creating a safe plane between the sternum and the heart rather than by preventing adhesions [14]. Nonabsorbable products also raise the theoretic concerns for infection and constriction. Sprayable polymers have been investigated in animal models and a small human study, but these products are either not available in this country or do not have demonstrated efficacy in humans [10, 15]. Walther and colleagues [16] have reported that an adhesion barrier reduces adhesions in patients undergoing surgery for complex congenital heart disease, but that study was limited by small numbers, lack of subject randomization, a heterogeneous patient population, and nonblinded evaluators. Our study was a randomized, evaluator blinded trial that has the additional advantages of evaluating a more homogenous patient population within a more uniform time frame.

There is currently no approved product in the United States for the prevention of adhesions after cardiac surgery. The rationale for using an absorbable film is to provide a temporary mechanical barrier to reduce or prevent the formation of fibrinous adhesions between opposing surfaces such as the epicardium and sternum during the early phases of tissue repair. Similar previously studied products have been reported to be difficult to handle in the operating room [16, 17]. The compliance and nonadherence of the film used in this study contribute to its desirable handling properties when utilized during cardiac surgery. These properties facilitate the intraoperative placement of the barrier film.

The results presented here show that the investigational device significantly reduced the degree of severe adhesions in the chest as assessed at the time of redo median sternotomy in infants and met the primary endpoint of the study. The secondary endpoint of reducing the percentage of patients with severe adhesions was also met. There was a statistical difference in patient weight between the study groups, but this was not felt to represent a clinically important finding. Although the study failed to demonstrate differences between the control and barrier groups in dissection time or complications related to sternal reentry, the study lacked sufficient power to test these secondary outcomes. Dissection time was reduced in patients without severe adhesions and the experimental device reduced severe adhesions in treated patients, implying that a relationship exists that might become more evident with larger patient numbers. In addition, the reported dissection time may inherently include some variability as dissection technique may vary substantially from surgeon to surgeon.

Catastrophic cardiac injury related to sternal reentry is a rare event, and therefore it is not unexpected that it was not observed in a study of this size [2]. The small number of cardiac injuries attributed to dissection likely reflects the familiarity of the congenital heart surgeon with reoperative surgery. However, fewer adhesions may facilitate sternal reentry in less experienced hands, such as those of surgical trainees. Interestingly, all reentry associated injuries were to the right atrium, the majority of which was not covered by the barrier film as specified by the study protocol. In clinical practice, covering the right atrium or whatever structures are deemed to be most at risk of injury with the absorbable barrier film may be prudent.

The study device was found to be safe in this study population. No adverse events were associated with the use of the device. Several cases of mediastinitis were encountered, distributed between the groups. Mediastinitis has been reported to occur in 1.4% to 6.7% of pediatric patients [18–20]. It has been defined by the presence of purulent discharge in the mediastinum requiring surgical debridement, positive mediastinal cultures, or sternal instability with positive blood cultures [20]. Three patients in the study developed mediastinitis after the first sternotomy. Two of these, one in each group, developed the infection within the first 2 weeks after surgery, which is the time frame generally acknowledged to be operation related. One patient in the barrier group developed mediastinitis 120 days after the first procedure after diagnostic cardiac catheterization. It is unlikely that this was related to the operation itself. Two patients (3.6%) in the barrier group developed mediastinitis at 4 and 30 days after the second sternotomy. The latter was felt to be related to a gastrostomy tube. Both of these infections occurred well after the study device would have been resorbed and are difficult to connect to implantation of the device.

Two further observations from the subgroup analyses seem worth mentioning. The data suggest that increasing procedural complexity increases the severity of adhesions and therefore the potential benefit conferred by the absorbable barrier. In addition, when the surgeon evaluating the adhesions was not blinded at the second sternotomy due to clinical circumstances, the grading of adhesions was not appreciably different than that of the masked evaluators.

There were some limitations of the study. The use of a multicenter design was necessary to achieve adequate statistical power in this patient population, but it introduces potential variability in dissection time and adhesion severity grading. In addition, given the small number of patients, we were unable to demonstrate a beneficial effect of the study device on dissection time and the reduction of sternal reentry complications. Finally, some of the patients underwent evaluation at the second sternotomy by a nonblinded investigator.

To conclude, the investigational device, REPEL-CV, is a product that is easy to handle and to apply in the operating room. It was found to be safe in both preclinical and clinical use. REPEL-CV is effective in reducing both the severity and extent of postoperative adhesions after cardiac surgery in infants. It was found to be safe and effective when used in patients having delayed sternal closure. Further study is warranted to determine its effects on reducing operative time and preventing cardiac injury in those patients who require repeat median sternotomies.

	Discussion

Top Abstract Introduction Material and Methods Results Comment Discussion Acknowledgments References

 
DR JOSEPH M. FORBESS (Dallas, TX): One question I had about your "dissection time" and your definition thereof. You've got it defined as the time to getting a sternal retractor in, but there might be some of us that would think that the time to getting on bypass is what is really clinically relevant. I was wondering if you had that measured as well, to see if the adhesions elsewhere in the posterior aspects of the mediastinum and whatnot were any different in the control versus the barrier group?

DR LODGE: The study was designed to try to capture the dissection time as it related to placement of the study device at the investigational surgical site and that was felt to be best represented by the time to placement of the sternal retractor. The problem with that variable was that there was a vast amount of variability in the dissection times reported from the different institutions, and even within the individual institutions between surgeons. And that has to do with, I think, individual style and how much dissection is done before placing the retractor.

Time to heparinization was also tracked, which would more closely correlate with what you're talking about. But, there was also a lot of variability in that as you would expect, and so that did not fall out as being a significant difference between the groups.

DR JOSEPH J. AMATO (Chicago, IL): I congratulate all the institutional units that have used this material. I had the opportunity of discussing a similar paper yesterday. About approximately two years ago I had the opportunity to review (I believe this material) originally called "MAST," and the series of injuries reported by them.

In 1996, I was part of a multiinstitutional study that reported "Expanded PTFE membrane to prevent injury during resternotomy for congenital heart disease" [Jacobs JP, Iyer RS, Weston JS, et al. Ann Thorac Surg 1996;62:1778-82]. We conducted a study of 1,085 patients and reported only one injury and no deaths. Both these two bioresorbable products, I believe, report an 88% effectiveness of preventing sternal adhesions and injury to the heart when opening the sternum. I strongly believe that the PTFE [polytetrafluoroethylene] membrane still presents with little injury (1%) and no mortality used properly underneath the sternum. My recommendation has been to place a thin strip of PTFE directly beneath the sternum in combination with a larger sheet of the bioresorbable membrane combination around the rest of the heart. The major concern of any of us who do pediatric cardiac surgery is the sternal opening. I believe all of us can then therefore dissect adhesions; however, it seems to have them more easily dissected with the use of these materials.

My previous suggestion is to use the bioresorbable material as a barrier for the whole heart, however, to place a small strip of PTFE directly beneath the sternum and the right atrium so as to prevent any injury to the heart upon opening the chest.

DR LODGE: I agree with your comments and some of your concerns. I think that I and several of the other investigators involved in the study also felt that if the membrane were used to cover more of the surface area of the heart that it might be more beneficial. In the study, all of the injuries that were observed were to the right atrium and most of that structure was not covered. It was felt that perhaps if the right atrium were more incorporated into the closure with the membrane that it would be more protected. Of course, we don't know that, and the study was designed to try and make the data as uniform as possible.

The advantage of this type of product compared to Gore-Tex is, I think, twofold. One major point is that I think everybody who uses Gore-Tex has complained (and we have used it fairly routinely in our patients), that it creates this sort of peel under it, over the heart, and can obscure the anatomy somewhat. Then the other thing is that I think most people are nervous about using it in a delayed chest closure setting. So those are two potential advantages of an absorbable product.

DR AMATO: I totally agree with the advantages of the bioresorbable membrane and that if you place the PFTE over the entire heart you will get adhesions. I am merely suggesting the use of the PTFE in a small area directly beneath the sternum to prevent injury to perhaps either an existing homograft or the right atrium in that position. I am not suggesting the use of the entire sheet of PTFE, but rather to include this with the bioresorbable film.

DR HENRY L. WALTERS (Detroit, MI): I congratulate you. We don't have many prospective, randomized blinded studies in pediatric cardiac surgery and when we do it's a real treat.

I understand the use of an objective variable and that your results showed that the distribution of the character of adhesions was favorable with the REPEL-CV. My question is very, I guess, basic and practical. Do you notice a real clinical advantage?

DR LODGE: Well, it's hard to say, I think, from patient to patient. I think at our institution there was a positive difference in dissection time. From a practical standpoint, does 10 minutes make that much of a difference? I'm not sure that it does just for that reason. But I think as Dr Amato pointed out, if it's easier, we're all more comfortable doing the dissection. I think as congenital heart surgeons we get used to doing a lot of redo surgery and are pretty familiar with taking down the adhesions, and I think that's one of the reasons why there was a lack of significant cardiac injuries or any catastrophic injuries in the study.

But I think that some settings where it might be beneficial are, for example, if you have a trainee opening the sternum or you have a system where junior people may be opening in redo situations and the senior staff member may not be there. In those situations, it may be more beneficial. And that would be something that would be hard to capture in a study, but that would be a more practical advantage of something like this.

	Acknowledgments

Top Abstract Introduction Material and Methods Results Comment Discussion Acknowledgments References

 
This work was supported by SyntheMed, Inc, Iselin, New Jersey, which provided financial support to the individual centers to cover study costs and maintained the central study database at its own expense. The authors would like to express their appreciation to Eli Pines, PhD, Vice President and Chief Scientific Officer of SyntheMed, Inc for his support and assistance. The sponsor, SyntheMed, Inc, provided the device used in this study at no cost to the study centers. The authors had full control of the design of the study, methods used, outcome parameters, analysis of data and production of the written report.

	References

Top Abstract Introduction Material and Methods Results Comment Discussion Acknowledgments References

 

1. Athanasiou T, De LSR, Kumar P, Cherian A. Video assisted resternotomy in high-risk redo operations - the St Mary's experience Eur J CardioThorac Surg 2002;21:932-934.[Abstract/Free Full Text]
2. Follis FM, Pett Jr. SB, Miller KB, Wong RS, Temes RT, Wernly JA. Catastrophic hemorrhage on sternal reentry: still a dreaded complication? Ann Thorac Surg 1999;68:2215-2219.[Abstract/Free Full Text]
3. Seeger JM, Kaelin LD, Staples EM, et al. Prevention of postoperative pericardial adhesions using tissue-protective solutions J Surg Res 1997;68:63-66.[Medline]
4. Pacholewicz JK, Daloisio C, Shawarby OA, Dharan SM, Gu J, McGrath LB. Efficacy of autologous peritoneum as a biological membrane in cardiac surgery Eur J Cardiothorac Surg 1994;8:563-565.[Abstract]
5. Okuyama N, Rodgers KE, Wang CY, et al. Prevention of retrosternal adhesion formation in a rabbit model using bioresorbable films of polyethylene glycol and polylactic acid J Surg Res 1998;78:118-122.[Medline]
6. Okuyama N, Wang CY, Rose EA, et al. Reduction of retrosternal and pericardial adhesions with rapidly resorbable polymer films Ann Thorac Surg 1999;68:913-918.[Abstract/Free Full Text]
7. Macmanus Q, Okies JE, Phillips SJ, Starr A. Surgical considerations in patients undergoing repeat median sternotomy J Thorac Cardiovasc Surg 1975;69:138-143.[Abstract]
8. Connors RC, Muir JJ, Liu Y, et al. Postoperative pericardial adhesion prevention using Carbylan-SX in a rabbit model J Surg Res 2007;140:237-242.[Medline]
9. Krause TJ, Zazanis G, Malatesta P, Solina A. Prevention of pericardial adhesions with N-O carboxymethylchitosan in the rabbit model J Invest Surg 2001;14:93-97.[Medline]
10. Marc Hendrikx M, Mees U, Hill AC, Egbert B, Coker GT, Estridge TD. Evaluation of a novel synthetic sealant for inhibition of cardiac adhesions and clinical experience in cardiac surgery procedures Heart Surgery Forum 2001;4:204-210.[Medline]
11. Soga Y, Takai S, Koyama T, et al. Attenuation of adhesion formation after cardiac surgery with a chymase inhibitor in a hamster model J Thorac Cardiovasc Surg 2004;127:72-78.[Abstract/Free Full Text]
12. Iliopoulos J, Cornwall GB, Evans RO, et al. Evaluation of a bioabsorable polylactide film in a large animal model for the reduction of retrosternal adhesions J Surg Res 2004;118:144-153.[Medline]
13. Mitchell JD, Lee R, Neya K, Vlahakes GJ. Reduction in experimental pericardial adhesions using a hyaluronic acid bioabsorbable membrane Eur J Cardiothorac Surg 1994;8:149-152.[Abstract]
14. Kajihara N, Eto M, Oishi Y, et al. Three-layered synthetic pericardial substitutes reduce postoperative pericardial adhesions J Thorac Cardiovasc Surg 2005;129:18-24.[Abstract/Free Full Text]
15. Konertz WF, Kostelka M, Mohr FW, et al. Reducing the incidence and severity of pericardial adhesions with a sprayable polymeric matrix Ann Thorac Surg 2003;76:1270-1274.[Abstract/Free Full Text]
16. Walther T, Rastan A, Dahnert I, et al. A novel adhesion barrier facilitates reoperations in complex congenital cardiac surgery J Thorac Cardiovasc Surg 2005;129:359-363.[Abstract/Free Full Text]
17. Cohen Z, Senagore AJ, Dayton MT, et al. Prevention of postoperative abdominal adhesions by a novel, glycerol/sodium hyaluronate/carboxymethylcellulose-based bioresorbable membrane: a prospective, randomized, evaluator-blinded multicenter study Dis Colon Rectum 2005;48:1130-1139.[Medline]
18. Pollack EM, Ford-Jones EL, Rebeyka I, et al. Early nosocomial infections in pediatric cardiovascular surgery patients Crit Care Med 1990;18:378-384.[Medline]
19. Mehta PA, Cunningham CK, Colella CB, Alferis G, Weiner LB. Risk factors for sternal wound and other infections in pediatric cardiac surgery patients Pediatr Infect Dis J 2000;1:1000-1004.
20. Long CB, Shah SS, Lautenbach E, et al. Postoperative mediastinitis in children Pediatr Infect Dis J 2005;24:315-319.[Medline]

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