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Ann Thorac Surg 2002;74:432-437
© 2002 The Society of Thoracic Surgeons

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Original article: cardiovascular

BioGlue surgical adhesive—an appraisal of its indications in cardiac surgery

^a Department of Cardiac Surgery and Research, The Prince Charles Hospital, Brisbane, Australia

Accepted for publication April 9, 2002.

* Address reprint requests to Dr O’Brien, Department of Cardiac Surgery, The Prince Charles Hospital, Rode Road, Chermside QLD 4032, Australia
e-mail: mark_obrien{at}health.qld.gov.au

	Abstract

Top Footnotes Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
Background. The recent emergence of BioGlue Surgical Adhesive has widened the field of surgical adhesives for the cardiac surgeon. We believe the present series, in a wider spectrum of cardiac conditions, is the first larger scale evaluation of the use of this new adhesive.

Methods. BioGlue was used in 115 consecutive patients (90 male and 25 female, age range 5 days to 87 years) from September 9, 1998 to March 12, 2001. Preoperative, intraoperative, and postoperative data were examined to establish its use, indications, and outcomes in patients undergoing cardiac surgical procedures.

Results. The most common underlying pathologic conditions were aortic dissections (30 patients) and aortic aneurysms (39 patients). The procedures carried out were aortic root replacement (36 patients), aortic wall replacement (39), ascending aorta repair (2), coronary artery bypass grafting (28), valve procedures (11), ventricular aneurysm repair (6), repair of postinfarct ventricular septal defect (2), and correction of congenital conditions (13 patients). The indications for BioGlue use were hemostasis in 79 patients, tissue adherence in 21, and tissue strengthening in 30. The hospital mortality was 10.1% (11 patients). Only 1 patient required a late reoperation for dehiscence of a suture line with formation of a false aneurysm. The mean postoperative blood loss at 12 hours was 702 mL. Ten patients developed a cerebrovascular accident postoperatively, which was considered to be unrelated to the use of BioGlue.

Conclusions. All surgeons in this study believed that BioGlue facilitated the operation. Future follow-up of patients is required to validate our early promising results and to assess the long-term outcome of patients treated with BioGlue.

	Introduction

Top Footnotes Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
Several surgical glues are presently used in cardiac surgical procedures. The indications are threefold: support of suture lines to achieve hemostasis, reinforcement or strengthening of fragile tissues, and adherence of tissues (eg, in the obliteration of the false lumen in aortic dissections). Most publications review the use of tissue glues in the surgical treatment of type A aortic dissections. Gelatin-resorcinol-formaldehyde (GRF) glue has been commonly used and reported to improve outcome and reduce mortality from acute type A aortic dissections [1–3]. However, a recent review of the use of GRF glue at our institution [4], as well as reports from other centers [5, 6], have raised concerns about the high reoperation rate, particularly in patients who have undergone local repair of the aorta without graft replacement. There are some reservations about the toxicity and the mutagenicity of the formaldehyde component of GRF glue [7]. Because of our previous experience with GRF glue and because of the subsequent withdrawal and unavailability within Australia, we were required to use an alternative glue. BioGlue (CryoLife International Inc, Kennesaw, GA) was one of the newer available products and subsequently became the most commonly used surgical adhesive at our institution.

The aim of this study was to establish the indications, the best method of use, and the advantage of BioGlue in a cohort of patients with a wide spectrum of pathologic conditions. By including all patients in whom BioGlue was used, we aimed to open up the appraisal and opportunity to explore the glue in more depth. This evaluation is retrospective making comparison with other glues not feasible. The technical application of the glue is somewhat subjective or user-dictated and, therefore, quantitative analysis of the advantages is not possible.

BioGlue consists of a 10% glutaraldehyde and a 45% bovine serum albumin solution. The exposure of bovine serum albumin, extracellular matrix, and cell surfaces to the glutaraldehyde component causes their lysine molecules to bind to each other, creating a strong scaffold. BioGlue is delivered from a reusable, sterile, double-barreled gun loaded with a prefilled, dual cartridge attached to a single nozzle where mixing occurs immediately in situ. Additional nozzles are available for repeated applications. Within 20 seconds, 65% of its final binding power is achieved and its maximum power is obtained within 2 minutes regardless of the surrounding temperature. This occurs under water as well as with air exposure. Once BioGlue solutions are mixed polymerization begins to occur immediately. The biochemical action and delivery system is published in more detail by Raanani [8]. Cartridges of 5 and 10 mL are available. In our experience, for most operations, a 5-mL cartridge was sufficient, the cost of which is approximately $250 (in US dollars).

So far there are only experimental studies [9, 10] reviewing BioGlue or small series of patients in whom the use of BioGlue has been reported for specific conditions such as type A aortic dissections or degenerative aortic aneurysms [8, 11]. The present study is the first larger scale study to review expanded indications for the use of BioGlue in a wider spectrum of cardiac surgical procedures. In Australia, the Therapeutic Goods Administration (TGA, Canberra) has approved the use of BioGlue in cardiac surgery and in all other surgical specialties in February 2001. Before this date, permission from the TGA for individual patient use (IPU) was required and obtained (TGA, file no. 1999/036375).

	Patients and methods

Top Footnotes Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
This retrospective series reviews our experience with BioGlue in cardiac surgical procedures since it was introduced in 1998. Patients were identified from operation records. The variables studied included the following: sex, age, preoperative comorbidities, coagulation status, indication for surgery, procedure performed, site and indication of glue application, postoperative course, and complications. Long-term follow-up was not carried out for this initial short term outcome analysis.

The surgical techniques and method of application of tissue glues, including BioGlue, have been described in previous publications [1, 8, 12]. Our techniques are similar. Attempts are made not to apply BioGlue excessively.

BioGlue was used in 115 patients undergoing cardiac procedures from September 9, 1998, to March 12, 2001 (90 male and 25 female, age range 5 days to 87 years). BioGlue was used during a short trial period in selected neonates and young children. It has not been our policy to use BioGlue in this age group on a routine basis.

Most patients had at least one comorbid condition: hypertension (72 patients), renal impairment (serum creatinine >0.2 mmol/L) [5], pulmonary disease (14 patients), diabetes mellitus (5 patients), ischemic heart disease (33 patients), and Marfan’s syndrome (8 patients). A total of 32 patients presented as emergency cases, and the remainder underwent elective procedures. Preoperative coagulopathy (APTT >50 seconds, platelets <100 x 10⁹/L, International Normalized Ratio >1.5) was detected in 20 patients and 17 patients were taking aspirin at the time of operation. In all, 38 patients (33%) had undergone at least one previous cardiac operation. The underlying pathologic conditions leading to operation included aortic dissection in 30 patients and aortic aneurysm in 39 patients (Table 1). Surgical access was through a median sternotomy in 103 patients and through a left lateral thoracotomy in 13 patients (1 patient having a combined approach). The surgical procedures are outlined in Table 2.

	Results

Top Footnotes Abstract Introduction Patients and methods Results Comment Acknowledgments References

In most patients with aortic dissection, BioGlue was used to obliterate the false lumen of the dissected aorta by gluing the dissected intima layer to the media layer, thereby strengthening the aortic tissue at the site of anastomoses. In many of the aortic root replacements, BioGlue was applied to the outside of the anastomoses of the coronary arteries into the Dacron (C.R. Bard, Haverhill, PA) graft and to the anastomoses between the Dacron graft and the native aorta, to reinforce the suture line and achieve hemostasis. In 12 patients, BioGlue was used to facilitate the patch augmentation of part of the aorta (augmentation of hypoplastic aorta in 10 patients, augmentation of a small aortic root for aortic valve replacement in 2). In 3 patients, BioGlue was used to seal pulmonary air leaks that were inadvertently caused during the operation. In a number of patients (particularly in elderly ones), the strengthening and hemostatic properties of BioGlue proved to be useful in dealing with bleeding from very fragile tissues, such as the aortic and venous canulation sites or the suture line of an aortotomy. Another example was the tissue strengthening of a friable coronarybutton during redo aortic root replacement. The external application of a thin layer of glue on the outside of the button prevents tearing of the tissues during suture anastomosis. Needles customarily used for these operations readily pass through the glue. BioGlue was also used in assisting hemostasis in one instance of bleeding from myocardial veins after grafting an intramyocardial coronary artery, and for strengthening the mitral annulus after extensive decalcification before mitral valve replacemtnt. This last patient represented the only case in which glue was intraluminal. No neurologic sequelae occurred in this patient. There was no coronary occlusion or dehiscence in patients in whom BioGlue was applied to coronary artery suture lines. The median length of postoperative hospital stay was 9 days (range 0 to 176 days).

Mortality
The overall in-hospital mortality was 11/115 (10%). Two patients died in the operating room, 6 patients died in the early postoperative period (within 1 week), and 3 patients died 1 to 3 months after the operation while still in hospital. One additional patient was reported to have died 3 months after a Norwood procedure after having been discharged 11 days postoperatively. Of the 12 patients who died, 9 presented as emergency cases, whereas 3 underwent elective procedures.

Of the 12 deaths, four occurred after an aortic dissection (13% of total dissections), two after a Norwood stage 1 procedure, two after a postinfarct ventricular septal defect repair, one after a coronary artery bypass grafting procedure complicated by gut ischemia, and three after repair of an ascending aortic aneurysm with aortic regurgitation. The causes and times of death are listed in Table 3.

Reoperations
A total of 14 patients (12%) were required to return to the operating room in the early postoperative phase (within 24 hours) for bleeding or tamponade. Table 4 outlines the pathologic condition, type of operation, indication and site for glue use, and bleeding site where identified. For 2 patients, more than one reoperation was required. Nine patients presented as emergencies and 7 had preoperative coagulopathy. In 7 patients, deep hypothermic arrest was instituted during operation. In patients 1 to 7 (Table 4) with aortic dissections, BioGlue was used to obliterate the false lumen by gluing the intima to the media layer of the aorta; in none of those cases was BioGlue applied externally to the anastomosis to achieve additional hemostasis. Only in 1 patient among the whole cohort of 115 patients was bleeding identified from a site where BioGlue had been applied for hemostatic reasons. Two of the take-backs for bleeding occurred in patients in whom BioGlue was used at the initial operation to seal parenchymal air leaks from the left lung surfaces after dissection of adhesions of lung from the descending aorta.

One patient returned to the operating room for insertion of a substernal GoreTex membrane (W.L. Gore & Associates, Flagstaff, AZ) after a Norwood stage 1 procedure. This was believed to be unrelated to the use of BioGlue.

One patient required mitral valve replacement on postoperative day 4 (after initial aortic valve replacement) when echocardiography revealed worsened mitral regurgitation compared with preoperative study. Another patient required an exploratory thoracotomy after iatrogenic injury to the right lung and liver after insertion of an intercostal catheter for drainage of a pleural effusion.

One patient with Marfan’s syndrome underwent aortic root replacement for an ascending aortic aneurysm and subsequently developed dehiscence of the annular suture line with formation of a false aneurysm. He required reoperation at 7 months.

Other morbidity
Ten patients (9%) had transient neurologic deficits postoperatively. Ten patients were diagnosed with a cerebrovascular accident and had persistent symptoms on hospital discharge (Table 5). All but 1 of these patients were hypertensive. Five patients had an episode of total circulatory arrest during their procedure. In none of these patients was BioGlue used on intraluminal surfaces. All patients who survived the acute stage were transferred to our hospital’s rehabilitation unit until they were able to be discharged.

Four patients (3.5%) had a deep sternal wound infection. Three of these patients had previously been taken back to the operating theater in the early postoperative course because of bleeding; in 2 of these 3 patients, more than one take-back was required. In no patient was the infection near or considered to be related to the BioGlue site. Two of these patients required revision and debridement of their wounds; 1 of them went on to have a successful bilateral pectoralis major muscle advancement flap repair, whereas the remaining three responded to long-term antibiotic therapy. Unexplained persistent fevers (38°C) after the third postoperative day did not occur in this series, suggesting that BioGlue did not, in itself, produce postoperative fever.

	Comment

Top Footnotes Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
Gundry and coworkers [10] showed very good adhesive properties of BioGlue in their experimental study of sutureless coronary anastomoses in vitro and in vivo. Hewitt and colleagues [9] showed its usefulness in reducing postoperative blood loss in a sheep model, and also commented on the minimal inflammatory response evoked by BioGlue on histologic examination at 3 months. Bavaria [11] showed that the use of BioGlue in type A dissections significantly reduced periods of circulatory arrest, cardiopulmonary bypass time, and total operation time. Kucukaksu and colleagues [13] reported earlier the beneficial effect of BioGlue in a case involving a patient with repair of an iatrogenic aortic dissection.

In a recent clinical publication, Raanani and colleagues [8] presented their experience with BioGlue in a small series of patients with acute type A aortic dissection (8 patients) and degenerative aortic aneurysms (10 patients). They reported an overall mortality of 17% (two of eight dissections and one of 10 aortic aneurysms); and, in the short-term follow-up (5 to 12 months), none of their patients required reoperation.

After a recent study [4] of the use of GRF glue at our institution, and after the demonstration of vascular stenoses after neonatal surgery, we discontinued use of this glue. Although there have been no late problems in relation to the use of BioGlue in neonates and small children, we do not routinely use or recommend it in this age group. The excellent cohesive strength of BioGlue may have the potential to compromise growth of structures where this glue is applied in full circumferential fashion, especially as its absorption or biodegradability may take up to 2 years. Other biological glues such as Tisseel (Immuno AG, Vienna, Australia) which has a much lesser cohesive strength and is absorbed within a shorter time than BioGlue may be more useful in these circumstances.

BioGlue binds solidly within seconds, does not crumble or fracture, and therefore cannot embolize. However, in general it has never been our practice to apply BioGlue on intraluminal surfaces. For these reasons, we do not consider BioGlue a direct or indirect cause of postoperative cerebrovascular accidents.

In our series BioGlue, failed to achieve its desired effect in only 1 case, in which bleeding occurred from a site where it had been applied for hemostasis. None of the 30 dissections required reoperation to date; only 1 of 36 aortic root replacement patients underwent a second operation after dehiscence of the proximal suture line where BioGlue had been applied externally for hemostasis.

In our opinion, none of the deaths (9 patients being emergency cases) could be attributed to the use of BioGlue. In this series we considered blood loss, use of blood products, length of operative times, and length of postoperative hospital stay to be satisfactory for these pathologic lesions and types of surgery.

In conclusion, our experience has shown BioGlue to be a versatile and reliable alternative to GRF glue, and data from other studies [4, 7] support the hypothesis that BioGlue exhibits less toxic properties and is more biocompatible than the previously favored GRF glue. The diversity of conditions that were treated using BioGlue in this study makes direct comparison of mortality and morbidity with other studies difficult. The surgeons in our institution consider BioGlue, when applied appropriately and without excess, to be effective in its function as a hemostat, tissue strengthener and adherent. The results so far are encouraging; however, further follow-up of patients is necessary to establish the long-term results of surgically treated conditions involving the application of BioGlue.

	Acknowledgments

Top Footnotes Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
Acknowledgment is given to the following: the other cardiac surgeons from our institution who used glue for some of these 115 patients: Drs E. G. Stafford, M. A. H. Gardner, P. G. Pohlner, P. Tesar, T. Fayers, and B. Garlick; to Dr Andrew Simpson who undertook quality assurance check of the data; and to Lauren McCairney for secretarial services. This study was supported by a grant from CryoLife International Inc, Kennesaw, GA.

	Footnotes

Top Footnotes Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
¹ Doctor O’Brien discloses that he has a financial relationship with CryoLife, Inc.

	References

Top Footnotes Abstract Introduction Patients and methods Results Comment Acknowledgments References

 

1. Guilmet D., Bachet J., Goudot B., et al. Use of biological glue in acute aortic dissections. J Thorac Cardiovasc Surg 1979;77:516-521.[Abstract]
2. Bachet J., Goudot B., Dreyfus G., et al. The proper use of glue: a 20 year experience with the GRF glue in acute aortic dissection. J Card Surg 1997;12(Suppl):243-255.[Medline]
3. Fabiani J.-N., Jebara V., Deloche A., Stephan Y., Carpentier A. Use of surgical glue without replacement in treatment of type A aortic dissection. Circulation 1989;80(Suppl):264-268.
4. Bingley J.A., Gardner M.A.H., Stafford E.G., et al. Late compli-cations of tissue glues in aortic surgery. Ann Thorac Surg 2000;69:1764-1768.[Abstract/Free Full Text]
5. Niederhauser U., Kaplan Z., Kunzli A., et al. Disadvantages of local repair in acute type A aortic dissection. Ann Thorac Surg 1998;66:1592-1599.[Abstract/Free Full Text]
6. Fukanaga S., Karck M., Harringer W., Cremer J., Rhein C., Haverich A. The use of gelatin-resorcinol-formalin glue in acute aortic dissection type A. Eur J Cardiothroac Surg 1999;15:564-570.
7. Ennker J., Ennker I.C., Schoon D., et al. The impact of gelatin-resorcinol glue on aortic tissue: a histomorphological evaluation. J Vasc Surg 1994;20:34-43.[Medline]
8. Raanani E., Latter D.A., Errett L.E., et al. Use of "BioGlue" in aortic surgical repair. Ann Thorac Surg 2001;72:638-640.[Abstract/Free Full Text]
9. Hewitt C.W., Marra S.W., Kann B.R., et al. BioGlue surgical adhesive for thoracic aortic repair during coagulopathy. Efficacy and histopathology. Ann Thorac Surg 2001;71:1609-1612.[Abstract/Free Full Text]
10. Gundry R., Black K., Izutani H. Sutureless coronary artery bypass with biologic glued anastomosis: preliminary in vivo and in vitro results. J Thorac Cardiovasc Surg 2000;120:473-477.[Abstract/Free Full Text]
11. Bavaria J. Prospective randomized study of BioGlue tissue adhesive during repair of acute type A aortic dissection. San Diego, CA: AATS meeting, 2001.
12. Borst H.G., Laas J., Buhner B. Efficient tissue gluing in aortic dissection. Eur J Cardio-thorac Surg 1994;8:160-161.[Abstract]
13. Kucukaksu D.S., Akgul A., Cagli K., Tasdemir O. Beneficial effect of BioGlue surgical adhesive in repair of iatrogenic aortic dissection. Tex Heart Inst J 2000;27:307-308.[Medline]

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Homayoun Jalali Robert K.W. Tam Mark F. O’Brien Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Passage, J. Articles by O’Brien, M. F. Search for Related Content PubMed PubMed Citation Articles by Passage, J. Articles by O’Brien, M. F. Related Collections Cardiac - other