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Ann Thorac Surg 1996;62:640-645
© 1996 The Society of Thoracic Surgeons
Clinic for Cardiovascular Surgery, University Hospital, Zurich, Switzerland
| Abstract |
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Methods. Between January 1991 and July 1995, homografts were used in 19 patients (mean age, 61 ± 13 years; range, 4085 years) with mycotic aneurysms (9/19; 47%) or infected grafts (10/19; 53%) in the thoracic (7/19; 37%) or abdominal (12/19; 63%) aorta. Sepsis was present preoperatively in 14 of 19 (74%) patients, and 18 of 19 (95%) had received antibiotic treatment for 6.4 ± 6 months (range, 136 months). Up to ten previous vascular procedures had been done in 11 of 19 patients (58%).
Results. There was one (5.2%) early and two (11%) late deaths, with one (5.5%) of the late deaths being homograft related. The mean hospital stay was 27 ± 26 days (range, 784 days). Antibiotics were given postoperatively for 30 ± 12 days (range, 484 days). During the follow-up period of 18.6 ± 13 months (range, 760 months), there were no instances of reinfection, suture line rupture, homograft stenosis, or anastomotic aneurysms.
Conclusions. Cryopreserved arterial homografts allow safe in situ reconstruction, decrease early and midterm mortality, and reduce antibiotic requirements. Early and midterm reoperations are unnecessary.
| Introduction |
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The treatment of mycotic aneurysms and infected arterial graft poses special challenge to the vascular surgeon. As late as 1967, Benett and Cherry [1] considered infected aneurysms of the abdominal aorta to be invariably fatal. A large variety of treatments have been developed for the management of this problem, and overall results have now improved. Currently the surgical treatment involves either complete removal of all infected prosthetic material and reconstruction with an extraanatomic bypass graft or prosthetic in situ replacement of mycotic aneurysms and infected grafts. Despite these new approaches to treatment, mortality rates of up to 50% and amputation rates of up to 60% are reported [2]. Above all, the surgical treatment for mycotic aortic aneurysms and aortic graft infections remains the most demanding technical challenge.
The favorable experience with homograft valves in the treatment of infective aortic valve endocarditis and the excellent long-term survival of implanted cryopreserved human cardiac valves [3] prompted us to attempt the use of cryopreserved homografts for the treatment of major vascular infections. We summarize here our current clinical experience with the use of cryopreserved arterial homografts for the single-stage, in situ repair of thoracic and abdominal aortic mycotic aneurysms and infected aortic grafts.
| Material and Methods |
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The thoracic aorta was affected in 7 patients (37%): 4 had a mycotic aneurysm (one in the ascending aorta after a chronic type A dissection, one in the descending aorta after spondylodiscitis, one in the descending aorta with an aortobronchial fistula, and one in the descending aorta with an aortobronchial fistula after previous repair for coarctation of the aorta) and 3 had a prosthetic aortic graft infection (one in a supracoronary graft after an acute type A dissection, one in a composite graft after repair for annuloaortic ectasia, and one in a descending aortic graft and in the aortic arch after repair for an acute type B dissection). Two patients presented with acute massive hemoptysis resulting from an aortobronchial fistula. In 1 patient, infectious spondylodiscitis of the sixth thoracic vertebral body was diagnosed 2 months before operation. The patient with a chronic type A dissection had a history of acute cholecystitis, and a mycotic aneurysm of the ascending aorta developed in this patient. One patient presented with an infected vascular prosthesis and bacterial aortitis of the transverse aortic arch after graft replacement of the proximal descending thoracic aorta for an acute type B dissection.
The abdominal aorta was affected in 12 patients (63%):
Five patients had a mycotic aneurysm of the infrarenal aorta and 7 had prosthetic aortobiiliac or aortobifemoral graft infection. Five patients presented with persistent bleeding of the sinus tracts, 1 of whom had a ureterocutaneous fistula, and in all patients the bleeding drained into the groin along the aortobifemoral prosthesis. One patient with a 14-day history of abdominal pain had a symptomatic infrarenal aortic aneurysm combined with perforated diverticulitis of the sigmoid colon. Another patient presented with an inflammatory juxtarenal aortic aneurysm, which became infected. A 55-year-old patient had received an aorto-bifemoral Dacron prosthesis 7 years before. He had undergone ten reoperations for the treatment of prosthetic graft infection and finally presented with acute bleeding through the left groin. He had six different prosthetic grafts reaching from the infrarenal aorta to the distal part of the superficial femoral artery on both the right and left sides. Two patients were on dialysis because of diabetic end-stage nephropathy. One was hospitalized continuously during the 6 months before homograft insertion, and this was necessitated by renal transplantation, removal of a necrotic renal graft, aortoiliac reconstruction, and placement of an extraanatomic bypass graft with secondary infection. The other was repeatedly hospitalized during the 2 years before the implantation of the homograft. He had a mycotic aneurysm of the infrarenal aorta, an infected aortoiliac Dacron prosthesis, and a huge, infected pseudoaneurysm that extended into the left retroperitoneal space; it contained Pseudomonas aeruginosa.
Preoperative antibiotic treatment had already been instituted in 18 patients (95%) and was either empirical or determined on the basis of preoperative microbiologic results. Seven patients (37%) had received prolonged antibiotic treatment for up to 3 years before homograft implantation, and this had consisted of multiple combinations of different antibiotics.
Homograft Selection and Preparation
Large arteries are procured under sterile conditions from brain-dead multiorgan donors or nonheart-beating cadavers, aged 18 to 40 years. All donors who fulfill heart valve selection criteria according to the European standards for cryopreserved heart valve homografts [4] are considered potential donors of the ascending aorta, with or without the transverse aortic arch; of the descending aorta, aortic bifurcation, and iliac and femoral vessels, including the superficial femoral artery; and of the proximal part of the deep femoral artery. The arteries are packed in ice-cold sterile transport solution and sent to the European Homograft Bank in Brussels, where they are further prepared inside a first-grade laminar flow room. Their internal diameters are measured with calibrated Hegar's dilators. Possible intraluminal alterations are assessed by angioscopy, and specimens for histologic examination are taken. The arteries are decontaminated by being immersed in a low-concentration antibiotic cocktail at 4°C for 24 hours. This is done for 48 hours when the donor has been on artificial ventilation for more than 2 days.
After this, cryopreservation, which consists of the following steps, is performed. All vessels are first dipped in an ice-cold cryoprotective solution (10% DMSO [dimethylsulfoxide]) and sealed in double pouches, then frozen in liquid nitrogen vapor to -100°C, according to an electronically monitored program, and stored in the vapor phase of liquid nitrogen at -180°C. The time, temperature of incubation, freezing rates, and control-rate freezing end points are noted. The pouches are transported in a cryogenic dry shipper that maintains the temperature of the frozen tissue below -130°C. The grafts are thawed and washed immediately before implantation in accordance with a well-defined protocol.
Operative Technique
ASCENDING AORTA AND TRANSVERSE ARCH.
To place a homograft in the ascending aorta and transverse arch, a median steronotomy is made and then cardiopulmonary bypass is instituted through a femoral artery and a right atrial venous cannula. Cold retrograde blood cardioplegia and, for deep hypothermic circulatory arrest, retrograde cerebral perfusion are used. The mycotic aneurysm or the infected grafts are excised with minimal periaortic debridement. The homograft is inserted end-to-end to the normal aorta, using a single, nonabsorbable running polypropylene suture. In the event of aortic arch replacement, each arch vessel is anastomosed separately end to end to the homograft.
DESCENDING AORTA.
To place a homograft in the descending aorta, first partial cardiopulmonary bypass is instituted through the left groin vessels with a heparin-coated oxygenator and moderate hypothermia (30°C). A left-sided posterolateral thoracotomy is made, and then the aneurysm is opened longitudinally and resected. The posterior aortic wall is tailored to preserve the most important intercostal arteries. A tube homograft is inserted end to end to the normal aorta using a single, nonabsorbable running polypropylene suture.
ABDOMINAL AORTA.
A standard midline incision is made in patients with mycotic aneurysms in the abdominal aorta. All the infected aneurysmal tissue is resected, except the posterior wall, which is left in situ. A tube or bifurcation homograft is inserted, and anastomoses are performed in an end-to-end fashion using a nonabsorbable running polypropylene suture (Fig 1
). In the event of an infected juxtarenal inflammatory aneurysm, the proximal anastomosis is sutured directly at the ostia of the renal arteries. The thick inflamed aortic wall containing parts of the retroperitoneal duodenum is only minimally debrided.
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Microbiology and Postoperative Antibiotic Treatment
Aspirates of pus, perigraft exudates, and tissue specimens are collected intraoperatively. Rapid Gram's staining and examination for aerobes and anaerobes are then performed. Appropriate culture media and conditions, especially for anaerobes, fungi, and mycobacterias, are readied in advance. The responsible infectious agents were identified in 89% of the patients and comprised the following:
The vascular infection in 3 patients was caused by more than one microorganism: 1 patient had M tuberculosis, S aureus, and A fumigatus; 1 patient had S aureus and C parapsilosis, and 1 patient had S aureus and C albicans.
The postoperative intravenous antibiotic treatment chosen was determined on the basis of the microbiologic findings, including the results of antimicrobial susceptibility testing. The duration of antibiotic treatment was decided for each patient and was influenced by the type of infectious agent and the extension of the infection, as determined intraoperatively. None of the patients received long-term or indefinite antibiotic treatment.
Follow-up
Early and medium-term follow-up information was obtained from the referring hospital or from the primary care physician. Computed tomography, magnetic resonance imagingangiography, transesophageal echocardiography, or intravenous digital subtraction angiography, or a combination of these, was performed routinely at the end of the follow-up period. The average duration of follow-up was 18.6 ± 13 months (range, 760 months).
| Results |
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The mean hospital stay was 27 ± 26 days (range, 784 days). Hospital stays of more than 21 days were due to the need for prolonged intravenous antibiotic treatment. Neurologic complications were not observed. Reoperations were necessary in 4 patients and consisted of placement of a femoropopliteal vein graft for associated peripheral vascular disease placement of an iliaofemoral vein graft for ongoing infection of an external iliac artery segment, splenectomy necessitated by delayed spleen rupture on the second postoperative day, and stabilization for accidental hip fracture. Delayed wound healing was observed in 4 of the 18 survivors (22%). No delayed operative wound closure was necessary.
The mean duration of the postoperative antibiotic treatment was 30 ± 12 days (range, 484 days). Antibiotic treatment lasting for more than 6 weeks was carried out only in the event of fungal infection. Neither septic nor homograft-related complications were observed postoperatively. There were two late deaths (11%), of which only one (5.5%) was homograft related. This occurred in an 85-year-old patient with an aortobifemoral homograft who died 7 months later as the result of acute upper gastrointestinal tract bleeding. An inferior mesenterio (homograft)duodenal fistula without any evidence of infection and intact suture line were found at autopsy. The second death occurred in a 41-year-old man who died 9 months later from severe diabetes-related complications; the homograft reconstruction was intact and he was free from infection at the time of death. Postoperative magnetic resonance imaging findings in 8, computed tomographic findings in 9, angiographic findings in 8, and transesophageal echocardiographic findings in 4 patients were normal. There was no false aneurysm formation or homograft leakage. Perihomograft exudation, unusual scar formation and intraluminal mural thrombi of the homografts also could not be detected by magnetic resonance imagingangiography or computed tomography. All surviving patients had normal peripheral circulation and were free of infection with normal hematologic findings.
| Comment |
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Extraanatomic bypass graft techniques allow complete removal of all infected prosthetic material and have been recommended for the management of severe sepsis when significant hemorrhage would be associated with the aortic anastomosis and when there are pangraft infections with virulent organisms such as Pseudomonas or fungi [6]. Despite the improvements in treatment, several distinct disadvantages remained: (1) depending on the site of infection (eg, transverse aortic arch or paravisceral aorta), extraanatomic reconstruction may be impossible; (2) extraanatomic grafts may become infected [7]; (3) these latter grafts have lower overall patency rates than aortoiliac or aortofemoral grafts [8], necessitating multiple reoperations in the axilla, the groin, and the retroperitoneum; (4) total graft excision carries a high mortality [7] and amputation rate [9]; and (5) aortic stump blowout is associated with up to 43% of the early deaths and 71% of the late deaths [10].
The in situ interposition of a vascular prostheses may prevent the complications associated with an extraanatomic bypass and yield satisfactory long-term results, with early mortality rates as low as 14% to 17% [9]. Nevertheless, suture line complications and secondary graft infections may occur. Prolonged antibiotic treatment is necessary, and lifelong therapy is sometimes recommended [11].
The use of arterial homografts in vascular surgery is not new and has been reported by Dubost [12], Oudet [13], Szilagyi [14], Barner [15], Halpert [16], and Humphries [17] and their colleagues. Because of the spontaneous rupture, thrombosis, and inevitable late aneurysm formation associated with the use of homografts, Szilagyi and associates [14] confirmed their "unsuitability to serve as vascular substitutes." Humphries and associates [17] reported their failure when used to treat vascular infections. Arterial homografts were therefore abandoned as treatment for mycotic aneurysms and arterial graft infection, and replacement with a vascular prosthesis became the method of choice. Renewed interest in the implantation of homografts for the management of these problems was sparked by Kieffer and associates [18], who used fresh allografts, stored at 4°C for 48 hours. Their operative mortality rate was 13.8%, and after a mean follow-up of 19.6 ± 14.0 months (range, 153 months), 24% of their patients had had pathologic changes in their allograft and 9% required reoperation. The use of cryopreserved homografts allows safe in situ repair and limits the need for extended debridement at the site of infection. Local antibiotic treatment, which risks producing resistant strains, is unnecessary. Impressive results may be achieved with cryopreserved homografts, as demonstrated by our 55-year-old patient, whose 7-year-old aortobifemoral Dacron graft became infected and who underwent ten subsequent reoperations during the following 2 years. Finally, he presented with a massive purulent S aureus and C parapsilosis infection of a graft that extended from the infrarenal aorta to the distal superficial femoral artery on the right as well on the left side. In this case, we think that the total graft replacement with homografts done in one stage, combined with limited antibiotic treatment, has been livesaving.
Reliable eradication of aortic infection was observed even in the presence of virulent or traditionally difficult-to-treat organisms such as P aeruginosa, M tuberculosis, C albicans, and A fumigatus.
In this difficult-to-treat patient population, the use of cryopreserved homografts is associated with a mortality rate that compares favorably even with the results of primary replacement of noninfected abdominal aortic aneurysms [19]. In addition, there was no early or late amputation, a finding that has been clearly confirmed by Kieffer and colleagues [18]. We believe that the placement of cryopreserved homografts can be used in lieu of many complex techniques, such as extended perigraft, mediastinal, and chest wall debridement and the mobilization of viable tissue such as omentum or flaps of muscle as well as the sacrifice of arteries and veins as autografts, in the management of mycotic aneurysms and graft infections [20].
Postoperatively, homografts are not a source of the diagnostic problems associated with other vascular prostheses, such as prolonged postoperative pyrexia or unusual perivascular inflammatory responses such as fluid accumulation and scar formation around the graft [21]. As a result, the need for troublesome investigations for presumed persistent or early recurrent infection is eliminated.
For all of these reasons, vascular reconstruction with cryopreserved arterial homografts is indicated for the management of mycotic aneurysms and arterial infection of the thoracic and abdominal aorta and of iliac and femoral vessels. Vascular prosthesis infection at any site in the arterial tree, aortoenteric fistula, and contamination of the retroperitoneal space by intestinal contents also represent ideal indications for the use of these grafts. Even aortobronchial fistula, a highly lethal condition [22], can be treated safely by homograft interposition. Our use of extraanatomic bypass graft reconstruction and conventional in situ repair for the treatment of aortic infection has been limited to situations in which an appropriate cryopreserved homograft has not been available.
Regarding the long-term behavior of these grafts, we believe that cryopreserved homografts do not follow the same course as fresh homografts were earlier observed to follow [1417]. The degeneration of fresh biologic grafts is accompanied by an immunologic rejection reaction, which leads to intimal hyperplasia, medial thinning, and necrosis, as well as to progressive degeneration of the elastic fibers and the fibrous connective tissue [23]. This reduces the mechanical strength of the homograft, leading to dilation and aneurysm formation, and ultimately to spontaneous rupture. Homografts stored at 4°C demonstrate the same, albeit diminished, reaction [3, 18, 24]. Cryopreservation of homografts preserves their collagen network, the elastic lamina, and the amorphous extracellular matrix; reduces their antigenicity; and limits the immune response of the host [2426]. Cryopreservation seems to cause a cross-linking reaction such as that caused by glutaraldehyde, used for the pretreatment of the porcine heart valve bioprosthesis [27]. It produces an autolysis-resistant collagenous skeleton, protects the graft from autogenic digestion, and makes the homograft relatively immunologically inert [28], resulting in mechanical properties superior to those of freshly implanted homografts [26].
As the cryopreserved allograft heart valve is superior to the 4°C-stored valve in terms of valve competence, freedom from reoperation, and structural degeneration [3], so do we consider the same may be true for our arteries, although we have no proof so far that the long-term outcome in patients with cryopreserved homograft arteries is superior to that in patients with fresh grafts or grafts stored at 4°C. However, even if the patients with cryopreserved homografts require late reoperation, the grafts may have had some value as a stopgap measure in the treatment of aortitis or synthetic infections.
It is also not evident why cryopreserved homografts appear to be more resistant to bacterial infection than other conduits. Viability early after implantation may be an important factor, possibly by allowing the antibiotic drug to diffuse into the homograft. The limited rejection phenomena, combined with allurement of immunocompetent cells, provoked by the implanted homograft, may support eradication of the infection. These are interesting hypotheses but, as of now, are entirely speculative. Culture-specific antibiotic treatment, based on the results of perioperative microbiologic investigations, is an important component in the treatment of vascular infections. On the basis of the experience with cryopreserved homografts in the treatment of aortic valve endocarditis, the duration of antibiotic treatment has been consistently shortened, but the exact duration of optimal treatment has not yet been determined.
Although larger clinical series and longer follow-up are necessary to determine the true potential of cryopreserved arterial homografts in the surgical treatment of mycotic aneurysms and infected vascular prostheses, our early results have been very satisfactory. Not only are homograft vascular replacements associated with a low early and medium-term mortality, but they also allow safe in situ repair, shorten the hospitalization, reduce postoperative antibiotic requirements and obviate the need for early or medium-term reoperations. Our results encourage the use of vascular homografts as the conduit of choice in the surgical treatment of mycotic aneurysms and infected prosthetic grafts.
| Footnotes |
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Address reprint requests to Dr Vogt, Clinic for Cardiovascular Surgery, University Hospital, Rämistrasse 100, CH-8091 Zurich, Switzerland.
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