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Eur J Vasc Endovasc Surg 14 (Supplement A), 102-107(1997) In situ Arterial AIIografts: a New Treatment for Aortic Prosthetic Infection C. Ruotolo, D. Plissonnier, A. Bahnini, F. Koskas and E. Kieffer* Department of Vascular Surgery, Piti~-Salp~tri~re University Hospital, Paris, France Introduction During the last decade the most widely favoured management for aortic graft infection required a rad- ical approach with total graft removal, aortic stump closure, and extra-anatomic grafting through un- infected tissues. 14 Staging of the procedures - initial extra-anatomic bypass followed by either immediate or interval graft excision vs. the more traditional single operation of graft excision followed by lower extremity revascularisation - seems to give the best results. 3 Unfortunately, this management strategy results in several significant problems. Extra-anatomic bypass patency rates can be very disappointing, in particular in patients with extensive vascular occlusive disease who require axillounilateral profunda or popliteal by- passes. In addition to the high rate of thrombosis, recurrence of infection in an extra-anatomic bypass graft occurs in about 20% of cases. 9 Aortic stump blowout is still an unresolved issue. Although recent studies have shown that the risk of disruption of the aortic closure is minimised by careful surgical technique, 7 it continues to be a much feared and fre- quently quoted early and late problem, with an in- cidence of 20% or more. 3'1° Stump blowout is almost always fatal and reinfection of extra-anatomic pros- thetic grafts often causes limb loss or death. In situ graft reconstruction has been reported as an attractive treatment alternative because of its relative technical ease, theoretically better long-term patency rates, and potential avoidance of aortic stump blow- out.~ ~aAlthough it can be a rational treatment option for localised or circumscribed aortic infection, it does not seem reasonable in the case of diffusely infected *Please address all correspondence to: E. Kieffer, Service de Chi- rurgie Vasculaire, Groupe Hospitalier Piti6-Salp@tri6re, 47-83 bou- levard de I'H6pital, 75013Paris, France. abdominal aortic prosthetic grafts, where graft re- moval and extra-anatomic grafting are required. 13Fur- thermore, placing a prosthesis in a contaminated field surely risks reinfection of the graft, with early recurrent rupture or false aneurysm of the proximal aortic anastomosis. 12 Towne et al. 14 have emphasised the subtle clinical presentation of patients with Staphylococcus epidermidis graft infections. The low virulence of this organism permits treatment by partial excision of the grossly involved graft segments, debridement of perigraft tis- sue and adjacent artery, and in situ replacement of another prosthesis. Conversely, according to these au- thors in situ replacement for Gram-negative infection and for coagulase-positive staphylococcus infections is not recommended, and subsequent infection of pre- viously uninvolved graft segments may be expected. Experimental studies 1~ have shown that collagen rifampicin-bonded grafts reduce the incidence of graft colonisation after in situ replacement of an infected graft. Based on these excellent results, gelatin-sealed grafts soaked with rifampicin were implanted in situ in five patients with aortic prosthetic infection not suitable for graft excision and extra-anatomic bypass. ~6 Despite promising early results, further observation of the patients is necessary to exclude recurrent graft infection. Also, grafts infected with bacteria resistent to rifampicin remain an unresolved issue. A controversial strategy including complete graft preservation to treat selected aortobifemoral prosthetic graft infection has been recently reported. ~7 Pre- servation of the entire graft is only recommended when the graft is patent, the anastomoses are intact, the patient does not have sepsis, and cultures of the wound do not yield pseudomonas. Treatment adjuncts include repeated, radical operative wound de- bridement and rarely rotational muscle flaps. Once again, in case of anastomotic haemorrage, graft throm- bosis, or persistent drainage of purulent material the 1078--5884/97/SA0102 + 06 $12.00/0 © 1997W.B.Saunders Company Ltd.

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Eur J Vasc Endovasc Surg 14 (Supplement A), 102-107 (1997)

In situ Arterial AIIografts: a New Treatment for Aortic Prosthetic Infection

C. Ruotolo, D. Plissonnier, A. Bahnini, F. Koskas and E. Kieffer*

Department of Vascular Surgery, Piti~-Salp~tri~re University Hospital, Paris, France

Introduction

During the last decade the most widely favoured management for aortic graft infection required a rad- ical approach with total graft removal, aortic stump closure, and extra-anatomic grafting through un- infected tissues. 14 Staging of the procedures - initial extra-anatomic bypass followed by either immediate or interval graft excision vs. the more traditional single operation of graft excision followed by lower extremity revascularisation - seems to give the best results. 3 Unfortunately, this management strategy results in several significant problems. Extra-anatomic bypass patency rates can be very disappointing, in particular in patients with extensive vascular occlusive disease who require axillounilateral profunda or popliteal by- passes. In addition to the high rate of thrombosis, recurrence of infection in an extra-anatomic bypass graft occurs in about 20% of cases. 9 Aortic stump blowout is still an unresolved issue. Although recent studies have shown that the risk of disruption of the aortic closure is minimised by careful surgical technique, 7 it continues to be a much feared and fre- quently quoted early and late problem, with an in- cidence of 20% or more. 3'1° Stump blowout is almost always fatal and reinfection of extra-anatomic pros- thetic grafts often causes limb loss or death.

In situ graft reconstruction has been reported as an attractive treatment alternative because of its relative technical ease, theoretically better long-term patency rates, and potential avoidance of aortic stump blow- out.~ ~a Although it can be a rational treatment option for localised or circumscribed aortic infection, it does not seem reasonable in the case of diffusely infected

* Please address all correspondence to: E. Kieffer, Service de Chi- rurgie Vasculaire, Groupe Hospitalier Piti6-Salp@tri6re, 47-83 bou- levard de I'H6pital, 75013 Paris, France.

abdominal aortic prosthetic grafts, where graft re- moval and extra-anatomic grafting are required. 13 Fur- thermore, placing a prosthesis in a contaminated field surely risks reinfection of the graft, with early recurrent rupture or false aneurysm of the proximal aortic anastomosis. 12

Towne et al. 14 have emphasised the subtle clinical presentation of patients with Staphylococcus epidermidis graft infections. The low virulence of this organism permits treatment by partial excision of the grossly involved graft segments, debridement of perigraft tis- sue and adjacent artery, and in situ replacement of another prosthesis. Conversely, according to these au- thors in situ replacement for Gram-negative infection and for coagulase-positive staphylococcus infections is not recommended, and subsequent infection of pre- viously uninvolved graft segments may be expected.

Experimental studies 1~ have shown that collagen rifampicin-bonded grafts reduce the incidence of graft colonisation after in situ replacement of an infected graft. Based on these excellent results, gelatin-sealed grafts soaked with rifampicin were implanted in situ in five patients with aortic prosthetic infection not suitable for graft excision and extra-anatomic bypass. ~6 Despite promising early results, further observation of the patients is necessary to exclude recurrent graft infection. Also, grafts infected with bacteria resistent to rifampicin remain an unresolved issue.

A controversial strategy including complete graft preservation to treat selected aortobifemoral prosthetic graft infection has been recently reported. ~7 Pre- servation of the entire graft is only recommended when the graft is patent, the anastomoses are intact, the patient does not have sepsis, and cultures of the wound do not yield pseudomonas. Treatment adjuncts include repeated, radical operative wound de- bridement and rarely rotational muscle flaps. Once again, in case of anastomotic haemorrage, graft throm- bosis, or persistent drainage of purulent material the

1078--5884/97/SA0102 + 06 $12.00/0 © 1997 W.B. Saunders Company Ltd.

In situ Arterial AIIografts 103

authors advocate graft excision and extra-anatomic bypass. The limited number of patients with aortic prosthetic infections so treated does not allow any firm conclusions to be drawn.

In order to avoid the risk of persistent or recurrent graft infection and the hazards of aortic stump com- plications, different types of autogenous recon- structions have been reported. ~8-22 The autogenous approach was originally advocated by Ehrenfeld et al., TM who reported reconstructing the aortoiliac seg- ments by disobliterating occluded aortoiliac segments, coupled with arterial and venous autografts, after extensive debridement of the infected area. However, the presence of degenerative or aneurysmal changes in the native arterial segments contraindicating end- arterectomy and the lack of suitable greater saphenous veins (GSV) limit the use of these procedures, which are always technically demanding. The risk of sec- ondary failure of disobliterated arterial segments and GSV is also a major concern. 2°'2~ More recently, the use of GSV alone, 19 lower extremity deep veins (DV) alone, 22 or both GSV and DV 21 has been reported. Harvesting of DV was well tolerated, without disabling chronic venous stasis, although it is obviously contra- indicated in cases of previous deep venous thrombosis. Furthermore, the use of GSV has been associated with development of focal stenoses and diffuse neointimal hyperplasia. 21 The possibility of future dilatation of thin wall DV in an aortic position can also be expected.

Arterial allografts

Allograft aortic replacement is not a new technique. Experimental studies were carried out by Carrel 23 early in this century and the first clinical use goes back to the early years of vascular surgery. 24"25 Although clinical results were encouraging, several drawbacks were soon recognised.

Despite the organisation of arterial banks, pro- curement and preservation of human allografts were fraught with difficulties. The available methods of sterilisation and storage were certainly a major con- tributing factor to the secondary dilatation and cal- cification observed in a significant number of patients. 26'27 Finally, the development of suitable ar- terial prostheses led to abandonment of arterial allografts in the early 1960s. Prosthetic infection soon appeared, however, as a rare but dreadful complication.

During the last two decades our policy for the treatment of this devastating complication shifted from partial graft removal to total graft removal, associated

with lower limb revascularisation by either extra-ana- tomic bypasses or in situ autogenous reconstructions. Despite a progressive decrease in mortality and mor- bidity, our experience of these conventional methods of treatment was disappointing. Encouraged by the excellent long-term results reported by cardiac sur- geons following allograft replacement for management of infections involving the ascending aorta 23'29 and from a very active local multi-organ transplant tissue retrieval program, we decided to investigate allograft replacement in the management of arterial infections.

Our first patient was operated upon in October 19883o and a series of 43 consecutive patients was reported in 1993. 31 As of October 1995, 100 consecutive patients with infected infrarenal aortic prosthetic grafts underwent in situ replacement with preserved al- lografts in our department. 32 Twenty-seven patients had a graft-enteric fistula. Twenty-six patients needed emergency procedures because of acute bleeding, sep- tic complications and/or lower limb ischaemia, while 74 patients had planned operations.

Technique

Our technique of procurement and preservation of allografts has been previously described. 31 Arterial allografts were harvested from cadavers as part of a multi-organ transplant tissue retrieval program. Bac- teriology and virology tests were routinely performed among donors. The whole length of the descending thoracic aorta, aortic bifurcation, iliac and femoral arteries were obtained. Hypogastric and deep femoral arteries were transected 2-3 cm distal to their origins in order to allow revascularisation of the corresponding arteries of the recipient. A fragment of the retrieved arterial allograft was routinely cultured for bac- teriological control. Allografts were stored in 500 ml of preservation medium containing heparin and anti- biotics. Allografts were implanted after a minimum interval of 48 h, to decrease cellular antigenicity and a maximum interval of 21 days, to avoid late de- generative changes. Because of the limited number of available allografts, matching blood and tissue com- patibility between recipient and donor was not attempted.

Before implantation a fragment of allograft and a few millilitres of the preservation medium were sent to the bacteriology laboratory. The aortic stump and periprosthetic infected tissues were carefully debrided. The periprosthetic fluid and part of the infected pros- thetic graft were sent for bacteriological culture. The allograft was implanted in situ, using polypropylene

Eur J Vasc Enctovasc Surg Vol 14 Supplement A, December 1997

104 C. Ruotolo et aL

Fig. 1. Postoperative aortography showing an aortobifemoral al- lograft and a retrograde saphenous vein graft to the superior mes- enteric artery.

running sutures for proximal and distal anastomoses. All infected prosthetic material was usually removed at the same operation. Associated reconstructions of lower limb and/or visceral arteries were performed in a significant number of patients (Figs. 1 and 2). Retroperitoneal and inguinal drainage were used routinely.

All patients received broad-spectrum antibiotics perioperatively that were replaced by selective anti- biotics according to culture results. Antibiotics were maintained for at least 6 weeks. None of the patients received long-term or indefinite antibiotic therapy.

Results

Twenty-four patients died during the early post- operative period. More than half of deaths were due to septic complications. The overall mortality of the present series (24%) is quite disappointing, compared to the 12% mortality among the 43 patients we reported in 1993. However, in the present series mortality rate was 38% in patients with aortoenteric fistulas, and 19% in patients with isolated prosthetic infection. Even

Fig. 2. Postoperative aortography showing an aortobifemoral al- lograft, with direct reconstruction of the left internal iliac artery.

more striking was the difference of mortality rates among patients undergoing emergency operations be- cause of haemorragic, septic or ischaemic com- plications, and patients undergoing planned operations (46% vs. 16%, respectively). All surviving patients had postoperative arteriography before dis- charge. Routine follow-up included duplex scanning at 3-monthly intervals. Late computed tomography (CT) scanning and/or aortography were performed depending upon the results of duplex scanning. There were 13 late deaths, of whom two were due to aortic rupture. During follow-up 20 occlusive lesions were observed and 15 required reoperation which was al- ways successful. Ultrasonography and CT scanning showed aortic dilatation with mural thrombosis in five patients. In all of these cases descending thoracic aortic allografts had been used for replacement of the infrarenal aorta. As of yet, none have had to be reoperated upon. Three patients had major am- putations because of pre-existing irreversible ischemia. No patients had secondary amputations.

Eur J Vasc Endovasc Surg Vol 14 Supplement A, December 1997

In situ Arterial AIIografts 105

Discussion

Although the overall survival rates of our series are less promising than our preliminary experience, 31 in situ allograft replacement has several undeniable ad- vantages in the management of infected infrarenal aortic prosthetic grafts. Experimental studies 33 sug- gested that fresh allograft arteries are suitable materials for arterial reconstruction in infected fields because they function as a vascular conduit and allow res- olution of infection by conventional antibiotic therapy. This avoids complications related to aortic stump path- ology as well as occlusion or infection of prosthetic extraanatomic bypasses. 34 The risk of persistent or recurrent infection of in situ prosthetic replacement is also significantly reduced, even though not completely eliminated. Furthermore, availability of long bi- furcated grafts makes the procedure feasible in all cases and technically much easier than autogenous in situ reconstructions using endarterectomy, venous or arterial autografts or a combination of these. 18 As- sociated visceral reconstructions, if indicated, are also feasible. More importantly, there were no early or late amputations in our patients secondary to failure of arterial allograft reconstruction, an outcome not matched by any of the conventional methods. Never- theless, arterial allograft replacement raises several theoretical as well as practical problems:

1) Availability of arterial allografts is rather limited at present, because of donor shortage and legal problems. The organisation of arterial banks has just begun and will probably develop in the next years. However, according to experimental as well as clinical studies, there is no hard evidence to choose between fresh allografts stored at 4°C in a preservation medium, which we used to reduce allograft antigenicity, and cryopreserved grafts, which have the distinct ad- vantage of avoiding all risks of viral contamination. 2) Perioperative mortality of in situ arterial allograft replacement remains high and is by far greater than mortality of prosthetic aortic replacement in a non- infected field. Aortic allograft replacement can be a rather aggressive operation, entailing a repeat lap- arotomy, the possibility of significant blood loss and long operative times along with the necessity of sup- rarenal clamping in a significant number of cases. Unfortunately, patient selection is difficult due to the unfavourable outcome of spontaneously evolving prosthetic infections and the need for emergency oper- ation in case of haemorragic, ischaemic or septic com- plications. Some of our patients, in poor general condition, without emergency indications might have benefited from a two-stage operation, including local

treatment of the main complications (drainage of closed collections, direct suture of leaking ana- stomoses, direct suture repair of enteric fistulas), with allograft aortic replacement and removal of all pros- thetic materials performed as a secondary procedure after adequate preparation of the patient. Septic shock was the leading cause of mortality in our series. Patients usually had long-standing infections sec- ondary to multiple multi-resistant organisms, in- cluding mycobacteria and fungi, and had undergone multiple redo palliative operations. Of the utmost importance, therefore, is early treatment of the patient as soon as signs of prosthetic infection appear, and replacement of broad-spectrum antibiotics by selective antibiotics, according to cultures from blood, perigraft collections, and infected graft fabric. 3) Resistance of allograft to infection cannot be con- sidered complete, especially when dealing with highly virulent organisms and incompletely debrided infected tissues. In our series one patient died 13 days post- operatively from septic rupture of his native aorta proximal to the allograft anastomosis, probably be- cause of highly virulent infection and insufficient de- bridement of the infected aorta. Besides appropriate antibiotic therapy, coverage of the aortic allograft with viable tissue such as omentum or rotational muscle flaps as well as drainage or even continuous irrigation of contaminated fields with antibiotics or povidone- iodine solution, are all important adjuncts to eradicate infection. 4) Long-term results of arterial allografts are still a cause for concern. Although the methods of allograft procurement and storage are at present totally different from those utilised in the 1950s, the risks of allograft degenerative changes cannot be overlooked. All of our patients had routine duplex scanning during the follow-up. CT scanning and/or aortography were per- formed depending on the results of ultrasound studies. Dilatation of the allograft was observed in only a few patients in whom thoracic aortic allografts (elastic arteries), had been used for replacement of the in- frarenal aorta. None has yet been reoperated upon. However, at 2 years of follow-up, occlusive lesions were observed in about 25% of external iliac and femoral arterial allografts (muscular arteries), re- quiring redo operations for ischaemic symptoms. Al- though the cause was probably intimal hyperplasia in the majority of cases, typical histological signs of chronic rejection were observed, i.e. intimal pro- liferation of myofibroblastic cells, medial smooth muscle necrosis and adventitial inflammatory cells infiltration. Secondary and late deterioration of al- lografts, therefore, are probably partly immunological

Eur J Vasc Endovasc Surg Vol 14 Supplement A, December 1997

106 C. Ruotolo et al.

in origin. 3536 Matching of blood and histocompatibility between recipient and donor was not attempted in our series because of the lack of available allografts. The development of arterial banks should make this possible in the near future. Although immuno- suppressive treatment can delay intimal thickening s6 and improve long-term patency of arterial allografts, 37 it is obviously contraindicated in infected patients.

Conclusions

The use of arterial allografts is certainly not the "ideal" solution for the treatment of aortic prosthesis infection. In situ reconstructions with either autogenous DV or antibiotic-bonded grafts may be valuable alternatives, even though further evaluation of these materials is needed. Nevertheless, arterial allografts deserve on- going research, regarding their resistance to infection, antigenicity, mechanical properties and preservation techniques, in order to better understand their bio- logical behaviour and better define the indications and modalities for their clinical use. Our results have encouraged us to continue to offer in situ allograft replacement to patients with abdominal aortic infected grafts.

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