Abstract
A 74-year-old woman underwent replacement of the ascending aorta for acute type A aortic dissection. The patient suffered from bacteremia postoperatively and repeated computed tomography showed an increasing diameter of pseudoaneurysms at the site of the proximal anastomosis due to graft infection. Re-mechanical Bentall operation and arch replacement were therefore performed using a composite graft of a rifampicin-bonded gelatin-sealed 24-mm woven Dacron graft and a mechanical valve. The postoperative course was uneventful. We report the successful in situ reconstruction using the above-mentioned Dacron graft and describe the preparation of the rifampicin solution using a surfactant.
Keywords: prosthetic graft infection, rifampicin-bonded gelatin-sealed woven Dacron graft, rifampicin solution
Introduction
Prosthetic graft infection is one of the most life-threatening complications of vascular surgery. In situ replacement with a rifampicin-bonded graft has been performed after an initial report had been published in 1991.1) In particular, rifampicin is not completely water-soluble, which maintains its anti-infectivity; however, the preparation of the rifampicin solution is not yet standardized. We performed in-situ reconstruction with a rifampicin-bonded gelatin-sealed 24-mm woven Dacron graft for prosthetic graft infection and achieved promising results. We herein report the case and describe the preparation of the rifampicin solution.
Case Report
A 74-year-old woman underwent replacement of the ascending aorta using a 28-mm woven Dacron graft (J Graft Shield Neo; Junken Medical Co., Ltd., Chiba, Japan) for acute type A dissection because of continuous pain in spite of strict antihypertensive treatment and bed rest (Fig. 1). On postoperative day 10, the patient suffered from bacteremia caused by methicillin-sensitive Staphylococcus aureus (MSSA). Thus, we initiated cefazolin sodium infusion at 6 g/day and vacuum assisted closure therapy. Repeated computed tomography (CT) showed an increasing diameter of pseudoaneurysms at the site of the proximal anastomosis due to graft infection (Fig. 2A and 2B). During the deterioration of her physical condition, her body temperature, heart rate, and blood pressure were 38.6°C, 94 bpm, and 158/82 mmHg, respectively. Blood examination revealed maximum leukocyte and C-reactive protein values of 33700/mm3 and 32.8 mg/dL, respectively.
Re-sternotomy was performed and cardiopulmonary bypass was established through the femoral artery and two-staged venous cannula from the right atrium. Under circulatory arrest with selective cerebral perfusion at a rectal temperature of 25.0°C, the aortic root and arch were replaced. The composite graft of a rifampicin-bonded gelatin-sealed 24-mm woven Dacron graft (J Graft Shield Neo; Junken Medical Co., Ltd., Japan) and a 21-mm SJM Regent valve (St. Jude Medical, Inc., St. Paul, Minnesota, USA) were used. Postoperative CT angiography showed no pseudoaneurysm in the aortic root and complete resection of the lesion (Fig. 3).
For the in-situ reconstruction, we prepared the rifampicin solution as follows. Water for injection was obtained from a clear sterilization pot with a stirrer bar and warmed up. Fifty grams of the surfactant Polysorbate 80 (Tween 80; NOF Corp., Tokyo, Japan) was added and dissolved, followed by autoclaving steam sterilization at 115°C for 30 min. A 1-gram drug substance of rifampicin was added to the solution with a stirrer, confirming that the color of the solution was changed to clear red. Bacterial filtration was performed with a 0.22-µm Millipore filter (Vented Millex-GS 0.22 µm; Merck Millipore, Darmstadt, Germany). Finally, 500 mL of the prepared rifampicin solution was sterilized, capped tightly, and preserved in a cool dark place (4°C) (Table 1).
Cefazolin sodium was administered intravenously at 6 g/day for 8 weeks postoperatively and then cephalexin was given orally (capsule form) at 1000 mg/day for chronic suppression. The patient was discharged with no major complication.
Discussion
Prosthetic graft infection is one of the most life-threatening complications of vascular surgery, the incidence of which ranges from less than 1% to 6% in published series.2–7) The infection is difficult to treat and is associated with high mortality and morbidity rates.
Several approaches to treat infected aortic prosthetic grafts have been reported using cryopreserved homografts,8) autologous veins for the abdomen,9) or omentum wrapping.10)
We performed in-situ re-Bentall operation in our case using a rifampicin-bonded gelatin-sealed 24-mm woven Dacron graft, which has been reported to be effective, and we anticipate that more institutions will be able to prepare the rifampicin solution in conjunction with the use of this graft in the near future.11,12) Rifampicin, which was originally developed for use in the oral form, has recently been used in the solution form for the therapy of various diseases. As rifampicin is only slightly soluble in water, rifampicin in this study was dissolved in water using a surfactant to increase its solubility and produce a sufficiently stable rifampicin solution.
It is difficult to prepare a cryopreserved homograft in an emergency situation. After the initial experimental report of the use of a rifampicin-bonded gelatin-sealed Dacron graft by Goëau-Brissonnière, et al.13) and the first clinical report of the use of a rifampicin-bonded graft by Strachen, et al.14) rifampicin has been used and shown to be an effective antibiotic for graft infection. Moreover, rifampicin can maintain its anti-infectivity for at least 3 days by binding with gelatin.15) It is highly essential to maintain anti-infectivity for several days when performing reoperation for an infected prosthetic graft. Furthermore, rifampicin is relatively water-insoluble and therefore it does not readily dissolve in the blood. Accordingly, we treated the graft infection caused by MSSA successfully by dissolving rifampicin completely using a surfactant and soaking the composite graft in the rifampicin solution for 30 min.
Recently, Uchida, et al.16) reported excellent results with the use of a rifampicin-bonded graft and omental pedicle grafting. They prepared rifampicin solution in a similar manner as ours. The differences in their procedure were that they used the rifampicin-bonded graft for mycotic aneurysms, not for postoperative graft infection, and that they performed omental pedicle grafting together with the in-situ replacement of rifampicin-bonded grafting.
In summary, in addition to the complete preparation of the rifampicin solution, determining the affinity between rifampicin and gelatin-sealed woven Dacron may contribute to the maintenance of the local drug concentration and play a critical role in the successful reoperation for an infected prosthetic graft. As we successfully treated only one patient this time using this method, a meticulous follow-up is mandatory and the accumulation of therapeutic experiences will be needed.
Acknowledgement
We are indebted to Associate Professor Edward F. Barroga (PhD) of the Department of International Medical Communications of Tokyo Medical University for his editorial review of the English manuscript.
Disclosure Statement
Yasunori Iida and other co-authors have no conflict of interest.
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