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University of Pittsburgh Medical Center, Heart, Lung, and Esophageal Surgery Institute, Presbyterian University Hospital, 200 Lothrop St, Suite C-700, Pittsburgh, PA 15213
(Email: zehrkj{at}upmc.edu).
| Dr Zehr discloses that he has a financial relationship with Cryolife, Inc.
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I thank Luthra and colleagues [1] for their comments on my article [2]. I agree with them that the surgical use of bovine albumin or glutaraldehyde, or both, entails a serious potential for foreign body reaction, and that there are concerns for their use in infected areas and problems with the glue's constriction of growth in pediatric anastomoses.
Although mindful of these arguments, I wrote the article mainly to emphasize the misconceptions regarding the use of bovine albumin-glutaraldehyde (BAG) glue. I also wished to offer proper techniques of its application in cardiovascular surgery, particularly in situations in which it can be lifesaving. A significant majority of cautionary literature relates to the inappropriate application of BAG glue and its consequences; I suggested ways to avoid these based on my personal experience. For example, LeMaire and colleagues [3] report a series of strokes caused by embolization of the glue from the false lumen of a type A dissection. In my communication, I explained that this can be prevented by quilting the separated aorta, using the glue sparingly, and placing a sponge to distend the true lumen distal to the subclavian artery. Similarly, Ngaage and colleagues [4] report an extensive foreign body reaction related to a large mass of glue left in a false lumen of a type A dissection, which was ultimately associated with a pseudoaneurysm. My recommendation, again, was to quilt the aortic layers prior to application of less glue. I also discussed one of my own cases in which a mechanical valve was stuck at the hinge mechanism, possibly by local seepage of excessive glue. In this case, I recommended turning off the vents and applying the glue to the composite root after letting it partially thicken to prevent the glue from being sucked through the needle holes.
The extent of the inflammatory response reported in the literature has been variable, ranging from "a relative paucity of prominent inflammatory response" [5] to "severe active inflammation surrounding the glue remnant with multiple granulocytes and histiocytes, and a massive foreign-body reaction with numerous multinucleated giant cells" [6]. I suspect a proportional relationship exists between the volume of glue used and the severity of the inflammatory response. Indeed, dose-dependant toxicity of glutaraldehyde from BAG glue has been shown in lung and liver tissue, whereas aortic tissue reaction was restricted to low-grade or medium-grade inflammation [7].
"Near misses" sometimes prove more valuable than the "misses" themselves. My intention was to emphasize how the use of BAG glue can save patients in many a near-miss situation, provided that the correct technique is used. In my experience, BAG glue layered with Surgicel (Ethicon Inc, Sommerville, NJ) was successfully used to repair an iatrogenic left ventricular laceration inflicted during open heart massage, or a cough-induced anterior right ventricular laceration in an open chest patient. I also recall resorting to BAG glue as sealant to reinforce fragile suture lines, as a cross-linking agent between multiple pledgeted sutures while repairing friable aortotomies, and as added safety when attaching the left ventricular assist device cannula into a fragile left ventricular apex, only to be rewarded with a good night's sleep each time.
Interestingly, another glue (ie, gelatin-resorcinol-formaldehyde [GRF]; Cardial, Technipole, Sainte-Etienne, France) with comparable tensile strength has never reached the United States' market, largely because of a few reports of necrosis-related suture line pseudoaneurysms. Ironically, all mishaps reportedly arose after excessive use of the formaldehyde component [8], and could have been avoided with proper technique [9], which involves the use of a mixing tip designed to dispense accurate and properly mixed amounts of the glue's two components.
I read with great interest the facts Luthra and colleagues [1] presented about the historical evolution of bovine serum albumin, its homology with the human form, and the risk of zoonotic diseases attending its casual use. I appreciated the valuable information on the laboratory use and potential side effects of glutaraldehyde. As I continue to use the glue in the operating room, I will certainly make a point of educating my residents with these useful facts. However, I will continue to be mindful of my responsibility to pass on my experience, lest the myths and misconceptions arising from poor technical usage of many such modalities in inexperienced hands overshadow their potential lifesaving capacity. I will also emphasize that it is the individual practitioner's responsibility, before he or she administers a novel modality, to carefully read the "User Manual" and to thoroughly understand the "Package Insert" of potential complications.
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