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Abstract
The main problems affecting vascular access in patients are infection, thrombosis, steal syndrome, pseudoaneurysms, and central vein stenosis. Complications of vascular access account for 20 % of hospitalizations among hemodialysis patients and can result in loss of access, significant morbidity, and mortality. This article provides an update on the management of patients with problematic vascular access. The functioning native arteriovenous (AV) fistula is the ideal access. To achieve the ideal standard, pre-dialysis care, pre-dialysis access surgery, adequate fistula maturation, and successful fistula cannulation by dialysis staff must be improved. The risk for infection is highest with temporary catheters, high with cuffed tunnelled catheters, medium with AV grafts, and lowest with native AV fistula. Percutaneous strategies are successful in declotting thrombosed access in 6795 % of patients. Complex access surgery may be required in patients with exhausted conventional access sites. Vascular access management must be given more prominence to ensure trouble-free functional longevity through access monitoring, surveillance, and early therapeutic intervention when necessary.
Keywords
Angioplasty, arteriovenous (AV) fistula, AV grafts, central venous catheter, hemodialysis, infection, primary failure, pseudoaneurysm, steal syndrome, thrombosis, vascular access
Disclosure: The author has no conflicts of interest to declare. Received: November 25, 2010 Accepted: January 16, 2011 Citation: US Nephrology, 2011;6(1):4855 Correspondence: Jacob A Akoh, FRCSED, FRCS(Gen), Consultant General and Transplant Surgeon, Level 04, Derriford Hospital, Plymouth PL6 8DH, UK. E: jacob.akoh@phnt.swest.nhs.uk
The commonly used types of vascular access include native arteriovenous (AV) fistulas, prosthetic AV grafts, and central venous catheters (CVC). Complications of vascular access account for 20 % of hospitalizations among patients on hemodialysis (HD) and can result in loss of access, significant morbidity, and mortality. The limited number of available sites makes the preservation of existing access sites important. The longer a patient remains on HD, the greater the challenge to find and maintain access sites. Every vascular access that is lost brings the patient one step closer to a terminal access problem and ultimate death. Problematic access prevents many patients on HD from receiving optimal care. Low access flow rates limit dialysis delivery, extend treatment times, and can result in underdialysis, which, in turn, leads to increased morbidity and mortality.1 Several lessons have been learnt recently in terms of the management of vascular access (see Table 1).2 Despite these lessons, the proportion of patients on HD who have had multiple access procedures, failed transplant(s), or who have exhausted sites of conventional AV fistula or graft is increasing. Consequently, an increasing proportion of such patients are requiring more complex vascular access modalities for long-term HD. This article provides an update on the management of patients with problematic vascular access.
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for access, acute presentation, delayed maturation of AV fistula, and the primary failure of AV fistula.6,7 In addition to insertion complications, the use of CVC is associated with higher morbidity, hospitalization rates, and mortality in patients on HD.6,810 AV fistulas have advantages over AV grafts11 and CVC, but whether they are associated independently with better survival is still unclear. The Choices for healthy outcomes in caring for ESRD (CHOICE) study, which included 1,084 accesses in 616 incident patients, reported an adjusted relative hazard of death of 1.5 (95 % confidence interval [CI] 12.2) for CVC and 1.2 (0.81.8) for AV grafts compared with AV fistula.12 The use of venous catheters should be minimized to reduce the frequency of access complications and to improve patient survival.
complications, such as osteomyelitis and infective endocarditis, and also is an independent risk factor for recurrence of infection.37 In a study involving 2,230 permanent silicone CVC implanted in 1,749 patients, Lemaire and coworkers16 found an overall incidence of bacteremia of 0.51/1,000 catheter days, identifying a previous history of a bacteremia, type 2 diabetes, a duration of catheter use of >90 days, and hypertension as significant factors. Bacteremia is more probable in patients with nasal carriage of S. aureus and catheter exit-site infections. Diagnosis of CVC-related infection is confirmed by a positive blood culture from the CVC and a peripheral vein with a four-fold quantitative differential colony count or differential time to positivity.38 It is important to draw blood before commencement of dialysis and, in the absence of accessible peripheral veins, blood can be drawn from both catheter lumens.39
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Management of Thrombosis
The options for managing AV fistula or graft thrombosis include: surgical thrombectomy performed soon after diagnosis52 and combined with either patch angioplasty to widen the outflow vein or a jump graft to bypass a long stenotic segment,5355 pharmacologic thrombolysis with or without angioplasty and/or stenting,53,54,56,57 and revision access surgery, for example, refashioning of AV fistula in the case of a juxt-anastomotic stenosis not responding to angioplasty. Two randomized trials comparing surgery versus mechanical thrombolysis showed superior success rates with surgery and revision (94 and 83 % compared with 67 and 72 % for thrombolysis, respectively).52,53 Pharmacologic thrombolysis is performed using either urokinase or recombinant tissue plasminogen activator (rt-PA) and can be combined with angioplasty when necessary.54,58 Percutaneous strategies are successful in declotting access in 6795 % of cases52,57,59,60 and, when combined with prompt endovascular management of subsequent thrombosis, significantly improves secondary patency rates (62 and 47 % one- and two-years, respectively).61 Post-thrombolysis angiography or CDUS is necessary to clarify anatomic stenosis and enable targeted radiologic or surgical correction. The role of stenting of the venous anastomoses following thrombectomy in extending access life was studied by Maya and Allon.62 They compared 14 patients with thrombosed AV grafts treated by thrombectomy and stenting with 34 sex-, age-, and date-matched controls treated by thrombectomy and angioplasty alone. The secondary patency (time from thrombectomy to permanent graft failure) was longer for the stent group (median survival 1,215 versus 46 days). The benefit of angioplasty alone is short lived as stenosis appears to develop faster than de novo access stenosis. This is probably because the vascular injury caused by the angioplasty accelerates the underlying proliferative process.63 Use of expanding nitinol stents placed at the venous anastomosis following graft thrombectomy and angioplasty improves the outcome of recurrent graft stenosis significantly and can rescue some AV grafts.64 Where the technology is available, pharmacomechanical thrombolysis with or without percutaneous transluminal angioplasty (PTA) and stenting is preferred over surgical thrombectomy. Systemic complications are rare with rt-PA, provided that patients who are at risk for bleeding are excluded.60 Local bleeding is easily controlled by digital pressure and it is rarely necessary to stop the thrombolysis infusion. Other new techniques to complement angioplasty include application of vascular radiotherapy.65
Thrombosis
Thrombosis, the main cause of AV fistula and/or graft dysfunction and failure, is usually the result of outflow tract obstruction.3,40,41 Although stenosis is commonly thought to affect the access outflow tract, inflow stenosis is not uncommon in dysfunctional HD accesses and radiologic evaluation should also include the arterial inflow.42,43 Native AV fistulas are associated with two major problems: initial failure to mature (primary failure) and a later venous stenosis followed by thrombosis.40 Causative factors include a small artery (<1.52 mm), a small vein (<22.5 mm), poor surgical technique, hemodynamic stressors, and a predisposition to vasoconstriction and neointimal hyperplasia.40 In terms of AV grafts, the etiologic factors include hemodynamic stress at the graftvein anastomosis, the type of graft material, and injury owing to repeated needling. In predisposed AV access, thrombosis might be heralded by dehydration, hypotension, compression during sleep, and excessive pressure required to stop hemorrhage following dialysis.
Diagnosis
Access dysfunction can be identified by: physical examination pre-dialysis, limb swelling, prolonged bleeding following needle withdrawal, dynamic venous pressure >140 mmHg,44 re-circulation >15 %, transonic access flow measurements, and colour Doppler ultrasound scan (CDUS) to assess both access inflow and outflow.45
Pharmacologic Prophylaxis
The Dialysis access consortium (DAC) fistula trial involving 877 participants showed that clopidogrel reduced the risk for native AV fistula thrombosis by 37 %, but had no beneficial effect on fistula suitability for dialysis. Sixty-one per cent of newly created fistulas failed to reach suitability for dialysis.7,46 To reduce the risk for AV graft thrombosis, some clinicians have used prophylactic warfarin or antiplatelet agents (e.g. aspirin, dipyridamole or clopidogrel). However, warfarin does not appear to have any beneficial effect in preventing thrombosis in patients on HD and could increase the risk for bleeding.4749 Antiplatelet drugs have a mixed effect on thrombosis of AV grafts. Whereas dipyridamole is effective in reducing the rate of thrombosis in patients with AV grafts, aspirin is associated with a high risk for thrombosis.50 Aspirin has also been demonstrated to enhance
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This may present as low flow rates during dialysis or high negative arterial pressures causing dialysis machine alarms. In severe cases, there is inability to aspirate blood from the catheter lumens. Blockage of CVC lumen is prevented by the instillation of a lock solution. Using 30 % citrate solution or 4 % trisodium citrate has advantages over heparin (5,000 units/ml), including a reduced risk for hemorrhage and avoidance of heparin-induced thrombocytopenia.66,67 Low-dose warfarin (1 mg/day) produces no difference in CVC thrombosis rates, whereas therapeutic doses (International Normalized Ratio [INR] 1.82.5) in conjuction with ticlopidine produce a dramatic reduction in thrombosis rates.68 Management involves a step-wise gradation of measures until either catheter function is restored or the catheter is replaced. These options include forceful aspiration and/or flushing, instillation of a thrombolytic agent for CVC clearanceurokinase 5,000 units/ml or rt-PA 2 mg per lumen over 3060 minutes (successful in 6595 % of cases),6971 low- and high-dose streptokinase or urokinase infusion, 70,72 improvement of catheter patency and blood flow rates through disruption of fibrin sheaths by angioplasty and/or stripping,73,74 and catheter exchange over a guidewire or a new CVC.
Figure 1: Examples of Complex Vascular Access Procedures Used in Patients with Exhausted Conventional Access Sites
Necklace graft Right atrium Brachial artery to contralateral jugular vein bypass graft
Axillo-axillary graft Femoral artery to right atrium bypass graft Bikini graft
Steal Syndrome
A less common, but challenging, complication of AV grafts and/or AV fistulas is extremity ischemia caused by diversion of arterial flow through the access site. It is thought that the presence of significant peripheral vascular disease (particularly in the elderly and patients with diabetes) and high fistula flow in addition to calcification of the arteries does not allow the vessel to dilate and supply the extremity and the fistula with more blood.7577 Patients can present immediately following AV fistula or graft formation with mild digital paresthesia or acute arterial insufficiency (i.e. cool, pale, numb, or painful digits) or insidiously (months to years later) with finger necrosis and/or permanent nerve damage. Steal syndrome, whether acute or late onset (>30 days), is more common with AV grafts (4.2 %) compared with AV fistulas (2.4 %), previous operations on the same limb and use of a brachial instead of radial artery.77,78 Ischemia can affect upper limb nerves predominantly or exclusively and result in ischemic monomelic neuropathy.79 Some patients may present with dialysis treatment-related ischemia, owing to a drop in blood pressure during dialysis, which severely reduces the perfusion pressure in an already compromised vascular bed. Diagnosis of vascular steal is usually made on clinical grounds: manual occlusion of the venous limb of the access resulting in immediate relief of symptoms, supplemented by CDUS, which confirms severe flow reversal; or by digital plethysmography revealing digital finger pressures <50 mmHg, digital-brachial indices <0.47 associated with symptom augmentation and reversal of pressures on manual compression, and transcutaneous oxygen saturation measurements.80,81 In severe cases, fistulography can confirm athero-occlusive disease amenable to correction. Complete imaging of the arterial circulation by digital substraction angiography (DSA), contrast enhanced-magnetic resonance angiography (CE-MRA), or computed tomography (CT) angiography with
Table 3: General Principles for the Comprehensive Management of Patients with Vascular Access
Pre-dialysis care to ensure advice is given in terms of venipuncture sites and early referral for access surgery Comprehensive assessment including vessel mapping with detailed information on both inflow and outflow tracts Early creation of native AV fistula in the pre-dialysis phase Improving maturation of native AV fistula, reducing stenosis and thrombosis of AV fistula and grafts Prevention, diagnosis, and appropriate treatment of vascular access infection Judicious use of AV grafts Avoidance of central venous catheters Monitoring and surveillance of accesses to ensure early detection and appropriate pre-emptive intervention before access thrombosis Appropriate pharmacologic, radiologic, and surgical intervention Encouragement of clinically oriented research into vascular access problems and adoption of novel therapies into clinical practice
AV = arteriovenous.
multidetector-row technology is the most important diagnostic tool and helps in planning the treatment strategy.82,83 The challenge of treatment is to resolve distal ischemia while preserving uninterrupted vascular access. The best way to avoid steal syndrome is to construct a narrow caliber AV anastomosis after full assessment of the vascular tree. Mild cases of steal syndrome can be observed,
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Native AV fistula
AV fistula functioning
Primary failure Failing transplant Physical examination and vessel mapping (Doppler ultrasound venography)
New acute patient Not suitable for AV graft Tunnelled central venous catheter
AV = arteriovenous.
but frequent follow-up is required. The options for treatment for more severe forms include both percutaneous and surgical techniques and are shown in Table 2.78,79,8496 Percutaneous approaches have the advantage of an inherent, clear demonstration of the anatomy and clarification of the cause of distal ischemia. They are performed as day-case procedures under local anesthesia and the effect of the procedure can be monitored synchronously. A new addition to the armamentarium is the Amplatzer Vascular Plug Type II (AVP II), a self-expandable nitinol wire-mesh device that is a promising tool for the management of problematic vascular access, including steal syndrome and high-flow tributaries.97,98
ipsilateral AV fistula has been described.102 More severe forms can be managed by ligation of the AV graft or fistula or use of the Hemodialysis Reliable Outflow (HeRO) device. This device consists of a 6 mm expanded polytetrafluoroethylene graft attached to a 5 mm nitinol-reinforced silicone outflow component designed to bypass venous stenoses and enter the internal jugular vein directly. The HeRO device was studied in a multicenter clinical trial demonstrating a statistically significant reduction in bacteremia rates compared with a CVC.103 Selection of the appropriate option should be based on perceived life expectancy, dialysis access longevity and other comorbid factors.104
Pseudoaneurysm
A large pseudoaneurysm causes turbulent flow in the AV fistula or graft and can lead to thrombosis of the access. Pseodoaneurysms may also become unsightly and painful. Pseudoaneurysms develop in response to repeated needling in the same segment of the access and can be avoided by careful rotation of needling sites. Traditionally, these lesions were treated by surgical excision, refashioning using a gastrointestinal anastomosis stapler,99 or abandonment of the fistula. Ryan and coworkers100 successfully treated four patients with large pseudoaneurysms by inserting a covered stent (Wallgraft, Boston Scientific/Meditech, Newton, MA). The type of stent used allows needling through the access segment containing the stent, which is especially useful for short-length accesses.
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CVC in patients with exhausted access sites. In selected patients, insertion of cuffed tunneled femoral catheters may provide a safe and effective access for long-term HD and obviate the need for complex access procedures.18,112
Prevention Strategies
Prevention is better than cure and this is especially true in the management of vascular access problems. The principles of a comprehensive access management are presented in Table 3. Most vascular access problems can be managed as day cases and efforts must be made to avoid unnecessary hospitalizations.113
of 12 randomized controlled trials examining the effect of access screening on thrombosis, access loss, and resource use found that screening significantly decreased the risk for access thrombosis for AV fistulas, but not the risk for fistula loss or resource use. In terms of AV grafts, no decrease in the risk for thrombosis or access loss was identified.129 Further research into ways of preventing or treating access stenosis is therefore required. Based on the observation that progression of stenosis is a precursor to thrombosis, pre-emptive angioplasty has been recommended.130 The results of a prospective controlled trial to evaluate the effect of prophylactic PTA of stenosis not associated with access dysfunction offers strong support for access surveillance.128 Kaplan-Meier analysis of the data showed that PTA improved AV fistula functional failure-free survival rates (p=0.012) with a four-fold increase in median fistula survival and a 2.87-times decrease in risk for failure. Several imaging modalities are available for the evaluation of dysfunctional HD access. Blood flow measurements using Doppler ultrasound did not reduce the risk for thrombosis,129 but clinical assessment readily identified problems leading to intervention.131 In a well-constructed, prospective study, Doelman et al.45 compared CDUS and CE-MRA with DSA for the detection of significant (50 %) stenosis in failing dialysis accesses (49 AV fistula and 32 AV grafts). Their findings suggest that CDUS is the initial imaging modality of choice but that CE-MRA should be considered before angioplasty if DSA is inconclusive.45
Comprehensive Assessment
Robust assessment, including a comprehensive review of previous access procedures, full physical examination, and vessel mapping using CDUS before access placement, is the best way to ensure that the first access and/or subsequent accesses are appropriate (see Figure 2). Vessel mapping should answer questions in terms of the condition of the arterial tree and the venous circulation (i.e. size, depth, and flow properties through the vein). Such assessment has been shown to increase the use of native AV fistulas114117 and lead to a higher maturation rate (90 versus 68.5 %) and mean duration of patency (14.716.8 versus 11.99.4 months) than those created without.118 In addition, it has the potential to reduce the overall necessity for multiple access procedures and, by unearthing problems such as CVS, enable percutaneous intervention, which could help avoid early use of secondary access procedures.
Conclusion
Local Therapy
Another strategy is the perivascular delivery of antiproliferative agents to achieve high local drug levels while avoiding systemic toxicity. Two studies in porcine AV graft models have shown promising results in reducing neointimal hyperplasia and graft stenosis by local delivery of paclitaxel.119,120 This article highlights the need for vascular access management to be given more prominence in the same manner as other major problems that affect patients on HD. An integrated vascular access management strategy encompassing evidence-based practice and a multidisciplinary team that includes committed and trained vascular access surgeons and interventionalists is required to ensure best quality of patient care. The requirement for new ways of treating old problems affecting vascular accesses is higher than ever. The dynamics of the dialysis population has resulted in more elderly, long-term patients with multiple comorbidities and multiple vascular access procedures, who are unsuitable for peritoneal dialysis and transplantation. The drive to achieve native fistula at all costs might increase the problem of primary failures and paradoxically increase CVC use. The two big players must continue to be native AV fistula and prosthetic AV grafts. Apart from introducing novel techniques to improve these, there is a need to optimize choice of access for individual patients. Once that choice is made (and increasingly by the multidisciplinary team), then efforts to ensure trouble-free functional longevity through access monitoring and surveillance are required to ensure early therapeutic intervention when necessary. n
Kidney Int, 2002;62(2):6206. Moist LM, Hemmelgarn BR, Lok CE, Relationship between blood flow in central venous catheters and hemodialysis adequacy, Clin J Am Soc Nephrol, 2006;1(5):96571. Wasse H, Catheter-related mortality among ESRD patients, Semin Dial, 2008;21(6):5479. Huber TS, Carter JW, Carter RL, Seeger JM, Patency of autogenous and polytetrafluoroethylene upper extremity arteriovenous hemodialysis accesses: a systematic review,
Surveillance
Early access surveillance duplex scanning at six to eight weeks post-operatively helps to identify AV fistula with potential problems early, allowing either intervention to prevent primary failure or the creation of a new access so as to limit use of CVC.116,121 Access surveillance coupled with radiologic or surgical intervention has been known to prolong access life.122125 Cayco et al.126 introduced a vascular access surveillance protocol (using dynamic venous pressure >140 mmHg, re-circulation >15 %, limb swelling, and prolonged bleeding post-dialysis) to decide which patients to refer for angiography with or without angioplasty; the authors demonstrated a reduced thrombotic episode per graft year of 0.29 compared with 0.49 for a historical, controlled group in their center. Additional benefits of this strategy are reduced hospitalization and decreased use of CVC.127,128 However, a systemic review and meta-analysis
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