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Correspondence to: Ilse J.E. Kouijzer, MD, PhD, Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands
For surgical treatment of primary aortic infection and aortic graft infection, in situ reconstruction with autologous vein(s) has the lowest rates of re-infection and of graft thrombosis. In this study, we have assessed the outcome after autologous femoral vein reconstruction in patients with aortic (graft) infection and we provide insights into the specific technical surgical considerations of the procedure.
Methods
In this retrospective single-center study, all patients who underwent autologous femoral vein reconstruction because of primary aortic infection or aortic graft infection between January 2012 and January 2020 were included. The primary outcome parameter was 30-day mortality.
Results
Twenty-nine patients with autologous femoral vein reconstruction for a primary aortic infection (n = 3) or aortic graft infection (n = 26) were included. An aorto-enteral fistula was detected in 13 patients (49%). Venous reconstruction of the aorta was performed with a single femoral vein in 17 patients (59%), and two femoral veins in 12 patients (41%). Thirty-day mortality was 17%. Relapse of infection occurred in two patients (7%) and no amputations were needed. One year after surgery, only three patients (10%) still needed stockings and after 2 years none of the patients used stockings.
Conclusions
Central aortic reconstruction with femoral veins is a durable solution for primary aortic and aortoiliac graft infections with a low incidence of reinfections, amputations, and venous hypertension.
INTRODUCTION
Primary aortic infection and aortic graft infection are major clinical challenges in vascular surgery. The incidence of aortic vascular graft infection is around 1–5%,
Editor's Choice - European Society for Vascular Surgery (ESVS) 2020 clinical practice guidelines on the management of vascular graft and endograft infections.
Editor's Choice - European Society for Vascular Surgery (ESVS) 2020 clinical practice guidelines on the management of vascular graft and endograft infections.
and the choice for a specific therapeutic strategy should be individualized for each patient. The mainstay of medical therapy is the use of well targeted antimicrobial therapy. The most preferred surgical technique in aortic infection is removal of the infected graft material or infected native aorta, aggressive debridement, followed by an in situ reconstruction.
Editor's Choice - European Society for Vascular Surgery (ESVS) 2020 clinical practice guidelines on the management of vascular graft and endograft infections.
Options for in situ reconstructions are autologous vein grafts, implantation of a rifampicin-soaked prosthesis, cryopreserved allografts, and silver coated grafts. Autologous veins have the lowest infection rates and lowest graft thrombosis rates.
Editor's Choice - European Society for Vascular Surgery (ESVS) 2020 clinical practice guidelines on the management of vascular graft and endograft infections.
A disadvantage, particularly in an emergency setting, is the longer operation time due to harvesting of the vein, which may be contraindicated in the elderly comorbid patient.
Editor's Choice - European Society for Vascular Surgery (ESVS) 2020 clinical practice guidelines on the management of vascular graft and endograft infections.
At our institute, there is broad experience of in situ autologous femoral vein reconstruction. In this study, we have analyzed the outcome after autologous femoral vein reconstruction in patients with primary aortic infection and aortic graft infection. We further aim to provide insights into the peri-operative antibiotic regimes in these diverse patients. We also present details regarding specific technical surgical considerations of the procedure, such as number of veins, graft configuration, and clamp and landing zones.
MATERIAL AND METHODS
Study Design
In this single-center retrospective case series, all consecutive patients who underwent autologous femoral vein reconstruction because of primary aortic infection or aortic graft infection between January 2012 and January 2020 at the Radboudumc were included. For diagnosis of aortic graft infection, the Management of Aortic Graft Infection Collaboration (MAGIC) criteria were used.
The regional institutional ethics committee approved this study and the requirement to obtain informed consent was waived (no. 2020-6596, Radboudumc, the Netherlands). This case series has been reported in line with the PROCESS criteria.
We retrieved the following data from medical charts: demographic characteristics, medical history and estimated prognosis of preexisting underlying disease and comorbidity according to the Charlson Comorbidity Index (CCI),
microbiological and imaging results, surgery details, antimicrobial therapy, and outcome. For the timing of surgery, urgent surgery was defined as surgery scheduled within 48 hours after indication, all other surgery was considered elective.
Surgical Technique and Postoperative Care
The whole surgical procedure is done with two vascular surgeons, in a theatre booked for a whole day only for the case. Harvesting of the femoral vein is performed via an anteromedial incision.
The common femoral vein, the deep femoral vein, and the greater saphenous vein are preserved to prevent venous outflow obstruction. The femoral vein is transected caudally at the level of the knee joint keeping the popliteal collateral veins to the deep system intact. The femoral vein is transected cranially at the junction of the deep femoral vein. Wound closure is performed prior to the laparotomy to avoid contamination. Mid-line laparotomy is performed followed by a thorough debridement of macroscopically infected tissue. When present, an infected vascular graft is removed after safe surgical control of the aorta and iliac arteries. Multiple samples of the aortic wall, graft and fluids are taken for culture. On the backbench, the femoral vein is reversed and reconstructed into a tube or bifurcated graft in a fashion suitable for implantation (Fig. 1). Proximal anastomosis is performed in an end-to-end fashion, whereas distal anastomosis are performed in an end-to-end or end-to-side fashion depending on the target artery (Fig. 2). An omentum plasty may be used to cover the autologous graft. In an acute setting, median laparotomy is performed first to control the bleeding, followed by the harvesting of the femoral vein. All patients require postoperative intensive care. Thrombocyte aggregation inhibitors and prophylactic low molecular weight heparin are prescribed. Elastic stockings are not distributed routinely. Patients are treated with intravenous antimicrobial treatment for a minimum of 6 weeks, either tailored to the outcome of previous or obtained cultures. In case of negative cultures, antimicrobial treatment plan is made multidisciplinary based on patient characteristics. Before surgery or before cultures are known, empirical antimicrobial treatment is given only in case of an acutely ill patient. Antifungal treatment is not a part of empirical treatment, but is only administered in case of Candida is cultured. Follow-up after discontinuation of antimicrobial treatment is at least 6 months in all patients.
Fig. 1A femoral vein is meticulously inspected for damage and leakage by insufflating the vein with heparin saline solution. In this case a double system is present in the mid-section of the vein and is left intact (A). A bifurcated venous graft is constructed by attaching the end of each vein in a side-to-side fashion. Reversal of the vein is important for the correct flow direction (B). The anterior side of both legs of the venous bifurcation graft was marked with a sterile marker to help to surgeon in assuring no torsion occurred.
Fig. 1A femoral vein is meticulously inspected for damage and leakage by insufflating the vein with heparin saline solution. In this case a double system is present in the mid-section of the vein and is left intact (A). A bifurcated venous graft is constructed by attaching the end of each vein in a side-to-side fashion. Reversal of the vein is important for the correct flow direction (B). The anterior side of both legs of the venous bifurcation graft was marked with a sterile marker to help to surgeon in assuring no torsion occurred.
Fig. 2An in situ autologous bifurcation graft constructed from two femoral veins. Proximal anastomosis is infrarenal (red vessel loop was looped around the left renal vein). The right distal anastomosis is end-to-side onto the distal common iliac artery; the left distal anastomosis is end-to-side onto the external iliac artery dorsally from the ureter and sigmoid.
The primary outcome parameter was 30-day mortality. Secondary outcome parameters were relapse of infection, length of hospital stay, and surgical related variables as usage of one or two femoral veins, reoperation, operating time, and complications. Antimicrobial treatment after surgery was also evaluated. Relapse of infection was defined as a new episode with the same micro-organism after discontinuation of antimicrobial treatment. Re-infection was defined as a new infection with another micro-organism after discontinuation of antimicrobial treatment.
Statistics
SPSS (Version 25.0; SPSS, Inc.) was used to perform statistical tests on the retrieved anonymized data. For representation of continuous data medians were used, including interquartile ranges (IQRs).
RESULTS
Baseline Characteristics
From 2012 to 2020, 29 patients underwent an autologous femoral vein reconstruction for a primary aortic infection (n = 3) or aortic graft infection (n = 26) (Table I). All patients but two were male (93%), median age was 69 years (IQR 9), and median BMI was 25 kg/m2 (IQR 4). At diagnosis, 10 patients (35%) had fever, 19 patients had abdominal (n = 13, 45%) or back pain (n = 6, 21%), 20 patients (70%) complained of malaise, and five patients presented with hematemesis (n = 2, 7%) or rectal bleeding (n = 3, 10%). Fifteen patients (51.7%) had an acute onset of symptoms. One patient (3%) had an active wound infection in the groin after previous surgery for a mycotic anastomotic aneurysm of the common femoral artery. Median hemoglobin was 7.1 mmol/L (IQR 2) at the time of diagnosis, median C-Reactive Protein (CRP) at diagnosis was 55 mg/L (IQR 128). Imaging was performed in all patients: 20 patients (69%) underwent both CT angiography and [18F]FDG-PET/CT and in 9 patients only one imaging modality was performed, that is either [18F]FDG-PET/CT (n = 3, 10%) or CT angiography (n = 6, 21%). Median time interval between aortic graft placement and diagnosis was 20 months (IQR 69) in the 26 patients with aortic graft infection.
Previous primary aortic surgery was performed in 26 patients: 11 open reconstructions (five aortic tube grafts, four bifurcated grafts, two aorto-femoral grafts), 12 endovascular reconstructions (one covered aortic stent, 10 standard endovascular aneurysm repair [EVAR], one EVAR with iliac branch device [IBD]), and three patients with both types of procedures (Table I). Initial indication for primary aortic surgery was aneurysmal disease in 83% (n = 24) and central occlusive disease in 17% (n = 5). Twenty-one patients (72%) underwent elective surgery and 8 patients (28%) underwent urgent surgery within 48 hours after indication. Reasons for urgent surgery were bleeding from an aorto-enteral fistula (n = 3, 38%), rapid growth of the aneurysm (n = 2, 25%) and uncontrolled infection (n = 3, 38%). Median time interval between diagnosis of the aortic (graft) infection and surgery was 16 weeks. An aorto-enteral fistula was detected in 13 patients (49%): six after EVAR, five after open reconstruction, and two after previous hybrid surgery. None of the patients with an open reconstruction for central occlusive disease presented with a fistula. Median CRP level at the time of surgery was 27 mg/L (IQR 84) of which 10 patients had normal CRP level (<10 mg/L). Median BMI prior to surgery was 26 kg/m2 (IQR 5).
Surgical Reconstruction
All patients received an autologous vein reconstruction using the femoral vein as initially planned (Table II). Venous reconstruction of the aorta was performed with a single femoral vein in 17 patients (59%), and two femoral veins in 12 patients (41%). A single femoral vein was used in the reconstruction of aortic tubes (n = 4), mono-iliac/femoral grafts (n = 5) and aorto-bi-iliac grafts all anastomosed on the common iliac artery (n = 8). Two femoral veins were used to reconstruct aortic graft (spliced, n = 2), aorto-femoral graft (n = 1), aorto-bi-iliac graft to both common iliac arteries (n = 1) and other bifurcated grafts where it was necessary to anastomose at least one leg more distal than the common iliac artery (n = 8). In two patients, an additional rifampicin soaked Dacron proximal cuff was required because of total length shortage of both femoral veins for an aorto-bifemoral graft in one patient and due to poor venous quality leading to disruption of the proximal anastomosis in the other patient. Overall median operation time was 377 minutes (IQR 173). Intraoperative blood loss was 2,500 mL (IQR 2650). Using two femoral veins for an autologous reconstruction compared to one femoral vein resulted in a higher mortality rate (50% vs. 35%), longer operating time (446 minutes vs. 347 minutes), and more blood loss (3,500 mL vs. 1,800 mL). Coxiella burnetii was the causing micro-organism in 14 patients (48%) of which the majority (n = 13) needed an autologous reconstruction with two femoral veins. Seventeen complications after surgery were reported in 16 patients (55%): deep vein thrombosis (n = 1), wound infection (n = 2), postoperative bleeding requiring urgent relaparotomy (n = 5), fatal postoperative bleeding (n = 2), multi-organ failure (n = 1), arterial thrombosis requiring thrombectomy (n = 3), intestinal ischemia requiring resection (n = 2), and acute tubular necrosis for which dialysis was temporarily needed for several months (n = 1). Compression stockings for edema were prescribed in seven patients (24%) after discharge. One year after surgery, only three patients (10%) still needed stockings and after 2 years none of the patients used stockings. Seroma and wound infection after removal of the deep veins were reported in eight (28%) and two patients (7%), respectively. No amputations were performed in any of the patients.
Aorto-bi-femoral (LCFA, RFBif) with proximal 5 cm Rifamp Dacron and 2 FV (proximal dacron due to bilateral length shortage of FV)
Infrarenal
413
4000
No
171
-
7
EVAR: aorto-bi-iliac (CIA)
Aneurysm
No
Aorto-bi-iliac (RCIA, LCIA) with proximal 4 cm Rifamp Dacron mini-bif and with 2 FV (proximal anastomic venous graft tear during OR requiring prosthetic material proximal)
The 30-day mortality was 17% (n = 5) (Table II). Three deaths were surgically related (hemorrhage related to graft blowout) and two were infection related (abdominal sepsis). Two patients died within 30 days after urgent surgery (38%) and three patients died who were treated electively (14%). Seven deaths after the 30-day period with a median time interval after surgery of 119 weeks (IQR 251), were due to late fatal bleedings caused by ongoing infection (n = 2), intracerebral hemorrhage (n = 2), myocardial ischemia (n = 2), and one unknown. Median postoperative ICU stay was 3 days (IQR 3). Patients were discharged after a median of 13 days (IQR 8). Median follow-up in all surviving patients after 30 days was 33 months (IQR 28) after surgery. Reasons for loss of follow-up were death (n = 12), emigration (n = 1), and unknown (n = 2). One patient (no. 29) had a relapse of infection of chronic Q fever with increased Q fever serology titers and restarted antibiotic therapy 1 year after discontinuation. Another patient (no. 11) developed a new fistula for which he received an endovascular salvage stent which became infected 5 years later, again a polymicrobial infection due to the fistula.
Infection and Antimicrobial Treatment
Post-surgical antimicrobial treatment for all patients is shown in Table III. Of all 29 patients with aortic (graft) infection, blood cultures were only positive in three patients. Nine out of 29 patients (31%) had aortic infection due to chronic Q fever (Coxiella burnetii) which is known for its difficult and long-term antimicrobial treatment. Fifteen patients were positive for micro-organisms other than Q fever and in seven of these patients (47%) antimicrobial treatment was discontinued 6 weeks post-surgery. None of these patients had relapse of infection. Of all 29 patients, only four patients (15%) are still on antimicrobial treatment, whereas 18 patients (62%) have been cured after surgical and antimicrobial treatment for a primary or vascular graft infection.
This study demonstrates that autologous femoral vein reconstruction for primary aortic (graft) infection, in conjunction with antimicrobial treatment, is a durable option for treatment. In 66% of the cases patients were completely recovered, whereas only 15% still need antimicrobial therapy after surgery. One relapse of infection was reported after 12 months. Thirty-day mortality rate was 17% reflecting the gravity of the underlying disease and treatment. Previous case series on aortic graft infections reported mortality rates between 8 and 48%.
Editor's Choice - Treatment of aortic prosthesis infections by graft removal and in situ replacement with autologous femoral veins and fascial strengthening.
A recent meta-analysis on 1,365 patients with aortic graft infection showed similar mortality rates between extra-anatomical reconstructions and in situ reconstruction (both prosthetic and autologous material), but a good comparison was limited due to the heterogenicity of the data from all 22 included studies.
A distinct finding in this study was the use of either one or two femoral veins for the vascular reconstruction and its concomitant outcome. In general, aorto-iliac reconstruction with one single femoral vein can be performed when only an aortic tube graft or mono-iliac graft is needed, or a bifurcated graft that extents to the proximal common iliac arteries. If the distal anastomosis zone for a bifurcated graft is located more distally than the mid common iliac artery or extents to the common femoral artery in case of a mono-femoral graft, then two femoral veins are required. This difference has its implications in outcome since we report a longer operating time, more blood loss, and a higher mortality in cases where two veins were needed. In nearly all patients with Coxiella burnetii infections, two femoral veins were needed for the vascular reconstruction. This reflects our experience that in chronic Q fever, vascular infection is often extended to a major part of the aorto-iliac system and more venous material is needed for reconstruction. These findings will help the vascular surgeon in the preoperative surgical planning for these patients.
Amputation rates after an autologous central repair are low and range from 2 to 10%.
Editor's Choice - Treatment of aortic prosthesis infections by graft removal and in situ replacement with autologous femoral veins and fascial strengthening.
Despite three acute thrombectomies, no amputations were performed in this study resulting in an excellent limb salvage rate of 100% during follow-up. This could be explained by the fact that initial reason for reconstruction was foremost aneurysmal aortic disease (83%), where most other series had a case mix that also contained a considerable amount of occlusive vascular disease. Careful selection of suitable distal landing zones is essential in an infected area. Avoiding infected and calcified target arteries will improve patency of the venous graft. Another possible reason is the use of a reversed femoral vein in this study, where in other series a non-reversed technique with valvulotomy has been used. Possible iatrogenic damage could lead to a higher risk of thrombosis of the conduit leading to an acute thrombosis or chronic stenotic segments with acute-on-chronic occlusion later in follow-up.
Possible mismatch problems of the conduit after reversal are easily solved by a pantaloon configuration (partially spliced side-to-side) or proximal widening of the conduit by a venous wedge. Good autologous vein quality is mandatory for the surgical reconstruction and the longevity of the graft, but is difficult to assess preoperatively. We recommend duplex ultrasound screening of both femoral veins before surgery to evaluate vein diameter, possible vein length, presence of a double vein system, venous webbing, or partial thrombosis. Nevertheless, in two cases, vein quality and length were inadequate which was solved by using a short rifampicin soaked Dacron graft material to complete reconstruction.
Venous hypertension after removing the femoral vein is reported in 4–15%.
Editor's Choice - Treatment of aortic prosthesis infections by graft removal and in situ replacement with autologous femoral veins and fascial strengthening.
In this study, we report the use of stockings as preventative measure in 10% after 1 year. After 2 years, none of the patients were on stockings and all were able to mobilize normally without complaints of swelling.
All but one patient had a proven infection according to the MAGIC criteria.
Median time interval between diagnosis of infection and surgery was 16 weeks. This delay in surgery could be explained by an initial conservative treatment in some patients or by improving the condition of the patients as a bridge-to-surgery. As our center was localized in the center of a large Q fever outbreak between 2007 and 2020,
Primary aortic (graft) infection is not easily diagnosed; pathogens are heterogenous, and clinical presentation of patients is characterized by diverse and often non-specific symptoms. Structure in the diagnostic work-up
Editor's Choice - European Society for Vascular Surgery (ESVS) 2020 clinical practice guidelines on the management of vascular graft and endograft infections.
Whether patients are eligible for autologous femoral vein reconstruction in aortic (graft) infection, should be decided multidisciplinary and accurate patient selection in a centralized environment is recommended.
CONCLUSIONS
Our results demonstrate that central aortic reconstruction with femoral veins is a durable solution for primary aortic and aortoiliac graft infections with a low incidence of reinfections, amputations, and venous hypertension.
REFERENCES
Chakfe N
Diener H
Lejay A
et al.
Editor's Choice - European Society for Vascular Surgery (ESVS) 2020 clinical practice guidelines on the management of vascular graft and endograft infections.
Editor's Choice - Treatment of aortic prosthesis infections by graft removal and in situ replacement with autologous femoral veins and fascial strengthening.
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