Complications of arteriovenous hemodialysis access: Recognition and management

Article Outline

• Abstract
• Dysfunctional hemostasis
  • Clinical features
  • Pathophysiology and restoration of coagulability
    • Cryoprecipitate
    • Vasopressin
    • Erythropoietin and restoration of red cell volume
    • Estrogen therapy
    • Dialysis—antiplatelet and anticoagulant therapy
  • Intraoperative and postoperative bleeding diathesis
    • Recommendations
  • Needle puncture sites and high pressures on dialysis
    • Recommendations
• Infection
  • Clinical presentation
  • Pathophysiology and diagnostic evaluation
    • Bloodstream infections: bacteremia and septicemia
    • Adjuncts to clinical diagnosis: duplex imaging, nuclear medicine
    • Organisms
  • Management and treatment options
    • Autogenous
    • Prosthetic grafts
  • Results and recommendations
• Noninfectious fluid collections
  • Hematoma
  • Seroma
  • Lymphatic
• Pseudoaneurysm
  • Clinical features and pathophysiology
  • Management and treatment options
    • Puncture site pseudoaneurysm
    • Anastomotic pseudoaneurysm
    • Diffuse enlargement of an autogenous AV access
• Venous hypertension
  • Clinical features of V-HTN
  • Pathophysiology
  • Central venous stenosis or occlusion
    • Endovascular: angioplasty and stenting
    • Open surgical management: bypass and interposition grafts
    • Results of treatment
  • Valvular insufficiency
    • Results of treatment
  • Regional outflow obstruction
    • Results of treatment
  • Recommendations
• Arterial steal syndrome
  • Clinical features of symptomatic and asymptomatic arterial steal syndrome
  • Pathophysiology and diagnostic testing
  • Management, treatment, and results
    • Ligation or deconstruction of the access
    • Restriction of flow: banding or tapered conduit
    • Rerouting of arterial inflow: DRIL, RUDI, and PAI
  • Recommendations
• High-output cardiac failure
  • Clinical features of access-related high-output cardiac failure
  • Pathophysiology: role of AV access flow and cardiac output measurements
  • Management and treatment options
• Neuropathy
  • Ischemic monomelic neuropathy (ischemic neuropathy?)
    • Clinical features of IMN
    • Pathophysiology and electrodiagnostic studies
    • Recommendations
  • Peripheral nerve compression syndromes
    • Clinical features of median nerve entrapment (carpal tunnel)
    • Clinical features of ulnar nerve entrapment (cubital and ulnar tunnels)
    • Role of electrodiagnostic studies
    • Pathophysiology: compartment pressures and β-amyloid
    • Management: release of median or ulnar entrapment; tourniquet
    • Results of treatment
    • Recommendations
  • Polyneuropathy: uremic and diabetic
    • Clinical features of uremic neuropathy
    • Pathophysiology and electrodiagnostic studies
    • Results of treatment
    • Clinical features of diabetic neuropathy
    • Pathophysiology and electrodiagnostic studies
    • Results of treatment
    • Recommendations: uremic and diabetic neuropathy
• Author contributions
• References
• Copyright

English language citations reporting complications of arteriovenous access for hemodialysis are critically reviewed and discussed. Venous hypertension, arterial steal syndrome, and high-output cardiac failure occur as a result of hemodynamic alterations potentiated by access flow. Uremic and diabetic neuropathies are common but may obfuscate recognition of potentially correctable problems such as compression or ischemic neuropathy. Mechanical complications include pseudoaneurysm, which may develop from a puncture hematoma, degeneration of the wall, or infection. Dysfunctional hemostasis, hemorrhage, noninfectious fluid collections, and access-related infections are, in part, manifestations of the adverse effects of uremia on the function of circulating hematologic elements. Impaired erythropoiesis is successfully managed with hormonal stimulation; perhaps, similar therapies can be devised to reverse platelet and leukocyte dysfunction and reduce bleeding and infectious complications.

Management of complications associated with arteriovenous (AV) access is an integral part of planning individual hemoaccess procedures. These comments are formulated as a separate but complimentary document to the Society for Vascular Surgery Clinical Practice Guidelines for the Surgical Placement and Maintenance of Arteriovenous Hemodialysis Access.

Literature citations in the English language are critically reviewed and discussed. Recent data collated from large surveys and revised practice recommendations are incorporated.¹, ², ³ Relevant randomized controlled trials, meta-analyses, or systematic reviews are noted in the reference section with an asterisk [*]. However, due to the infrequency of many of these morbidities, much of the information is derived from clinical series. Because this is not a systematic review, the evidence is not rigorously classified and graded as in the Clinical Practice Guidelines.

The text outline follows that introduced in the reporting standards; grading of severity estimates, the extent of treatment required, or the morbidity incurred.⁴ Nomenclature is standardized to AV access throughout the text to retain consistency with these standards; reference citations, however, frequently retain terms such as fistula (autogenous arteriovenous fistula) and hemoaccess (an alternate term for AV access).

The format incorporates a brief initial outline summarizing the major points discussed in each section. Consideration of each complication commences with a description of its characteristic clinical features and pathophysiology. Presentation of recognized treatment options is followed by current recommendations for management.

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Dysfunctional hemostasis 

A clinically significant bleeding tendency is a frequent complication of uremia, and its risk is assessed by template bleeding time. Hemorrhage into deep organs (subdural hematoma, arthrosis, gastrointestinal bleeding, and pericardial hemorrhage) and superficial bleeding (bruising, puncture sites, catheter entry sites) are both common. A recent randomized clinical trial focused on pharmacologic intervention for graft thrombosis observed a 24% incidence of bleeding events in the placebo group ≤6 months.⁵ The hazard rate for bleeding in the placebo group was 0.5 per year (95% confidence interval [CI], 0.32-0.75).⁵ Gastrointestinal hemorrhage is the second leading cause of death in acute renal failure and was the most frequent bleeding event in the trial.⁵, ⁶

Clinical features 

Specifically, the vascular surgeon will encounter dysfunctional hemostasis in two common clinical situations. The first is intraoperative, characterized by diffuse oozing throughout the wound and prolonging both the dissection and closure. The second is after dialysis, characterized by a failure of hemostasis at the puncture sites in a reasonable time. This may manifest as external bleeding, hematoma, or pseudoaneurysm.

In more general terms it would be advantageous if uremic patients with a higher risk of clinically significant bleeding could be identified before any major invasive procedures (ie, renal biopsy, catheterization, surgery, access placement, etc). What specific therapy could be administered before these invasive interventions?

Pathophysiology and restoration of coagulability 

The increased bleeding tendency in the uremic patient is multifactorial, but is attributed to platelet dysfunction. Normal results on coagulation studies and normal platelet counts with abnormal bleeding times are characteristic.⁷, ⁸ Uremic patients with hemorrhagic problems often have bleeding times of >15 to 30 minutes.⁷, ⁹, ¹⁰, ¹¹, ¹² Although the exact mechanism has not been elucidated, clinical and basic research has begun to unravel this clinical puzzle during the past several decades. Defective aggregation, defective thromboxane-A2 production, nitric oxide, fibrinogen, von Willebrand factor (vWF), glycoprotein (GP), and the GPIIb-IIIa complex are implicated in abnormal platelet-to-platelet and platelet-to- vessel wall interactions.⁶, ⁸, ⁹, ¹³

Recognition and acceptance of the template bleeding time as the best method for identifying uremic patients at risk for bleeding provided a reproducible end point for clinical studies.⁹ Platelet aggregation studies, glomerular filtration rate (GFR), blood urea nitrogen/creatinine level, and bleeding times were significantly correlated, but only the bleeding time discriminated patients affected by clinical bleeding problems. The clinical studies described subsequently have used this end point to evaluate delivery of dialysis, anemia and epoetin alfa, estrogen, cryoprecipitate, vasopressin, and antiplatelet agents (clopidogrel). These investigations have defined effective therapy for acute and prolonged hemorrhage associated with uremia.

Results from a series of six patients were used to advance cryoprecipitate acute therapy for uremic bleeding.¹⁰ The patients responded to the infusion with a shortened bleeding time or resolution of major bleeding episodes, or both. Its mechanism of action remains undefined. Potency may vary between different preparations. Cryoprecipitate is a plasma derivative containing vWF, fibrinogen, and fibronectin.⁶ The typical dose is 10 U infused during 30 minutes.¹⁰, ¹⁴ The total dose is guided by the clinical response (ie, bleeding time and cessation of bleeding). It offers the advantage of an immediate effect; however, its duration of action is short, the hemostatic effects are lost ≤24 hours, and exposure to blood-borne infectious disease exists. Although still widely used, subsequent authors have found a less consistent response to this therapy.¹⁴ Because of these factors, cryoprecipitate is most appropriate when the need for hemostasis is immediate.

In randomized, double-blinded, placebo-controlled trials, the effectiveness of vasopressin (DDAVP), was confirmed by a reduction in template bleeding time and achievement of normal periprocedural hemostasis.⁷, ¹⁵ A synthetic analog of antidiuretic hormone, DDAVP is hypothesized to induce the release of autologous vWF from storage sites.¹⁶ The initial dose is 0.3 μg/kg administered intravenously with a 50 mL bolus of saline during 30 minutes. The hemostatic effect is maximal after 1 hour and is retained for up to 4 to 6 hours.⁷ Repeat doses appear to be less efficacious.¹⁷ Alternatively, it may be administered subcutaneously (dose, 0.3 μg/kg) or intranasally (dose, 2 μg/kg); equivalent efficacy was demonstrated in similar controlled clinical trials.¹⁵, ¹⁸ Side effects are generally minimal. DDAVP provides immediate off-the-shelf treatment, but its effect is of short duration.

Restoration of a hematocrit >30% effectively reduces bleeding time, and randomized trials have confirmed that packed red cell transfusions or erythropoietin effectively reduce clinically significant bleeding in the uremic patient.⁸, ¹¹, ¹⁹ An inverse relationship exists between rising packed cell volume and decreasing bleeding time.⁸, ¹⁹ The effect is achieved with a hematocrit of >30% but no relationship to change was noted in platelet count.¹⁹ The effectiveness of increased red cell mass is hypothesized to be a rheologic effect, by directing more of the platelet elements toward the endothelial wall facilitating platelet–vascular wall interactions.⁸, ¹⁹ Thus, erythropoietin provides the double advantage of correcting anemia and diminishing the risk of bleeding over the long term.

Bleeding time in von Willebrand disease is often corrected during pregnancy, and randomized, placebo-controlled trials have confirmed that estrogen administration shortens the bleeding time in uremic patients, both women and men.¹², ²⁰ The major advantage of this modality is the duration of hemostatic effect of up to 14 days; the maximum reduction in bleeding time was between 5 and 7 days, and the initial effect was evident ≤6 hours.¹² Infusions of conjugated estrogen were effective for this time frame with a dose of 0.6 mg/kg for 4 to 5 days.¹², ²⁰ The most active agent in the conjugated estrogen infusion was 17β-estradiol.²¹ The transdermal application of 17β-estradiol (50 to 100 μg/24 h) reduced bleeding time, reduced transfusion requirements, and resulted in cessation of active clinical bleeding in six patients with recurrent gastrointestinal hemorrhage.²² The efficacy of the lower dose was hypothesized to reflect the constant steady-state levels. The mechanism of the estrogen effect remains under investigation. Exuberant nitric oxide production in the wall of the vascular endothelium is implicated by studies relating L-arginine to defective platelet adhesion to subendothelium in uremic patients.¹³, ²³, ²⁴ Estrogen therapy is quickly effective, and its effects are maintained for approximately 2 weeks after a series of doses.

In addition to the measures described previously, it is assumed that bleeding patients have received adequate dialysis. If not, intensification of dialysis may also be beneficial in the bleeding patient. Heparin, used to prevent clotting in the dialysis circuit, can also be avoided in patients with active bleeding or elevated bleeding times.

Evidence from randomized, prospective clinical trials shows no role for clopidogrel or warfarin as an adjunct to patency of prosthetic or autogenous AV access. Prosthetic access thrombosis was not reduced by 75 mg of clopidogrel plus 325 mg of acetylsalicylic acid (ASA), and the trial was terminated prematurely because the risk of bleeding (gastrointestinal, hematoma, hematuria, and prolonged needle site bleeding) doubled in the clopidogrel group. The bleeding hazard rate for the treatment group was 0.99 per year (95% CI, 0.73-1.34).⁵

Similarly, another randomized controlled trial with low dose warfarin (international normalized ratio, 1.4-1.9) reported no improvement in prosthetic graft function and an increase in major bleeding events with warfarin.²⁵ Clopidogrel (75 mg) demonstrated no benefit for autogenous access either. An improvement in patency did not translate into an increase in autogenous AV accesses suitable for dialysis; bleeding events did not increase, but duration of follow-up was limited to 30 days of access use.²⁶

Myocardial complications remain a major source of morbidity and mortality in the patient with ESRD.²⁷, ²⁸ As the evidence supporting medical interventions for these diseases grows, more renal patients are likely to be treated with ASA, clopidogrel, warfarin, and other potent antithrombotic agents for concomitant medical problems related to coronary artery disease and atrial arrhythmias. Although these therapies are supported by level I evidence, the subpopulation of patients with ESRD appears to have a different level of risk for bleeding. In addition, increasing use of percutaneous arterial and venous therapeutic interventions is accompanied by the introduction of more potent agents such as GPIIb-IIIa inhibition and clopidogrel. Intuitively, all of these therapies will create increased bleeding problems in the dialysis population. Therefore, the risks and benefits of warfarin and antiplatelet medications should be seriously considered before prescribing them for uremic patients.

Intraoperative and postoperative bleeding diathesis 

Patients scheduled for elective surgical interventions or other common invasive procedures (ie, renal biopsy) should be adequately evaluated and prepared for these events. This may include a determination of the bleeding time and appropriate intervention, as previously described. Although heparin is not used routinely for construction of an AV access, its use may increase intraoperative and postoperative bleeding. Because the arterial clamp time is generally short and the arteries are fairly normal, but primarily because of the underlying platelet abnormalities in uremic patients, adjunctive heparin is usually not necessary for most patients. Scheduling AV access procedures on the day between dialyses will decrease exposure of fresh surgical incisions to the heparin used during hemodialysis.

Preparation for invasive interventions should include assurance of adequate dialysis, correction of anemia with hematocrit to >30%, discontinuance of medications promoting bleeding, and reasonable correction of abnormal bleeding times. If this cannot be accomplished with these routine procedures, estrogen should be considered to promote correction of the bleeding time. If a reasonable bleeding time cannot be achieved, DDAVP may be administered at the time of the intervention. Although repetitive dosing may not achieve the same degree of hemostatic efficacy, it is probably worth repeating. If the bleeding is still not controlled, another short-acting hemostatic agent, cryoprecipitate, may be administered.

Needle puncture sites and high pressures on dialysis 

Patients will often appear in the emergency department after discharge from the dialysis center with persistent or delayed access site hemorrhage. Such bleeding associated with an AV access usually occurs due to needle puncture during hemodialysis, but may be the result of skin erosion overlying superficial conduits when infection is not the cause. If limited to a needle puncture, direct digital pressure over the site will usually achieve hemostasis. While maintaining direct digital pressure, a bleeding time can suggest the severity of the individual's bleeding tendency. If the bleeding cannot be stopped, a suture may be sufficient.

Insertion of an endograft through a separate percutaneous puncture site is another option for managing hematomas associated with AV access conduits, especially for rapidly expanding hematomas or when the skin is intact over the bleeding site. This option avoids the need to make an incision directly in the hematoma and also allows the option of controlling the bleeding by temporarily inflating an occluding balloon in the conduit until an endograft is placed across the bleeding site. This option is discussed in greater detail in the subsequent section on pseudoaneurysm.

Rapidly expanding hematomas should be temporarily controlled by continuing direct pressure to the bleeding site for 30 to 40 minutes. If necessary, compression may be applied to the arterial inflow part of the access. However, if the skin has eroded over the conduit and a hematoma has resulted, then the situation should be handled much like an infected AV access. Often an emergency intervention is required. A new graft should be tunneled subcutaneously beneath intact skin lateral or medial to the exposed site so that the new segment of graft is covered with healthy tissue, and the exposed segment of graft should be excised.

A well-functioning AV access is characterized by a low-resistance venous outflow, which may be altered by outflow stenoses or obstruction. Elevated outflow venous pressures would predispose to access site bleeding. Thus, although most needle puncture site bleeding can be managed medically, underlying causes that should be considered include outflow obstruction, graft infection, and pseudoaneurysm, any of which may require more urgent operative intervention. A duplex examination will help define these complications.

Emergency onset of persistent bleeding requires rapid acting interventions to achieve hemostasis and preserve the AV access. Direct digital compression is effective for needle hole bleeding and may often require an adjunctive suture. If still uncontrolled, a covered stent may be deployed at the site. If the skin is eroded at the bleeding site, a short jump graft through clean tissue planes is appropriate.

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Infection 

Infection is the second leading cause of failure of prosthetic AV accesses and autogenous AV accesses and is a frequent complication of AV access surgery requiring hospitalization. Infection ranks second to cardiovascular disease as a cause of death in hemodialysis patients.¹ Infection associated with AV access in hemodialysis patients is multifactorial. It has long been recognized that immune function is compromised in uremic and dialysis-dependent individuals. Although transcutaneous catheters are the most frequent source of these infections, the main focus of this document is infection at peripheral access sites.

Access infections can begin during the initial access placement and during frequent breaches of the skin and access conduit by dialysis needles. As a result of this interrelationship between skin flora and the necessity for transcutaneous access to the circulation, Staphylococcus spp are the most frequent causative organisms, with an increasing frequency of antibiotic resistance in these and enterococcal species. Discussion will focus on options for preservation of the access site, recognizing that complete resolution of infection will require sacrifice of some sites.

Clinical presentation 

Diagnosis of peripheral AV access site infection is usually clinically obvious and manifested by localized findings such as tenderness, erythema, cellulitis, induration, masses, drainage, exposed access, and sinus tracts. These findings may develop long after implantation, or as a consequence of hematoma from a recent puncture or an incision from a surgical intervention. Systemic manifestations such as fever, bacteremia, and septicemia are more commonly associated with catheter access; these infections are associated with considerably greater morbidity and mortality. However, many reports on infection in the dialysis population focused on septicemia or bacteremia, or both, but did not distinguish between bloodstream infection and those related to peripheral AV access sites. Likewise, infections originating from the access must be distinguished from other sources such as pneumonia, osteomyelitis, septic arthritis, and endocarditis.²⁹

The mortality rate at the commencement of dialysis is 12%; this increases to 15% during the third month after the first dialysis. Infection-related mortality rates during this same interval rose from 25% to 48% per 1000 patient-years.¹ According to a survey sponsored by the Centers for Disease Control and Prevention (CDC), an average of 3.2% of patients per month (range, 0.31%-3.98%) at United States dialysis centers will experience a vascular access–related infection; fully 55% were associated with bacteremia.³⁰

The prosthetic AV access conduit is intentionally placed in a superficial tunnel; thus, the distinction between subcutaneous inflammation and graft involvement may be difficult because erythema, tenderness, and induration may be present for a variable length of time postoperatively. Accurate determination of the extent of graft infection is critical to successful management but may not be clarified until operative exploration. It is particularly important to recognize infection involving the arterial anastomosis.

Pathophysiology and diagnostic evaluation 

Patients with ESRD are prone to infection from uremia-induced immunologic dysfunction, including impaired lymphocyte-mediated cellular immunity, neutrophil chemotaxis, phagocytosis, bacterial killing, and metabolic function.³¹, ³², ³³, ³⁴, ³⁵, ³⁶ Recent data suggest that resistance to platelet microbicidal protein is a permissive factor in the development of infection with intravascular devices.³⁷ Other mechanisms of altered polymorphonuclear neutrophil function include malnutrition, iron overload, increased intracellular calcium, the dialysis treatment, and circulating plasma factors.³¹ Although septicemia may originate from many different sites (pneumonia, foot sepsis, urinary tract infection, decubitus ulcers, endocarditis), an established intravascular focus is usually responsible for satellite infection in the spine, septic joints, endarteritis, or endocarditis.³⁴, ³⁸

An increasing international body of data implicates catheter access as the leading source of these bloodstream infections. Epidemiology of Bacteremia in Dialysis Patients (EPIBACDIAL), a prospective, French multicenter cohort study, compared bloodstream infections with peripheral site infections and found a relative risk of 7.6 between catheter and autogenous AV access; 81% of their patients were dialyzed through an autogenous AV access.³⁸ In the United Kingdom, tunneled catheters had a 5.43 hazard ratio for bacteremia (95% CI, 2.67-11.0, P < .001) compared with autogenous AV access, and the hazard ratio was 3.39 (95% CI, 1.67-6.87, P < .001) when analyzed for mortality; however, the number of grafts at this center was too low for reasonable comparison.³⁹

An integrated nephrology network in the western United States conducted a prospective cohort study of access-related infections; 62% of the encounters were with prosthetic AV access. There was no significant difference between autogenous and prosthetic AV access, but tunneled catheters, accounting for 20% of the encounters, had a relative risk of 33.0 (95% CI, 10.5-103.8, P < .0001) for bacteremia and sepsis.⁴⁰

Tokars et al,³⁰ from the CDC, recruited 109 centers in 30 states to form the Dialysis Surveillance Network in the United States. Overall, there were 3.22 access-related infections per month, of which 1.78 per month were bacteremias. As expected, the rate ratios for access-related bacteremia were less with autogenous AV access (0.48 [95% CI, 0.35-0.65]), or prosthetic graft (1.0 [reference]) than with a cuffed catheter (9.2 [95% CI, 7.7-10.8]). Independent risk factors for access-related infection were catheter access, low albumin, urea reduction ratio, and hospitalization ≤90 days.

A unique contribution from Tokars' investigation demonstrated the magnitude of the difference in infection rates between dialysis centers. These findings were consistent with a pilot study suggesting that an increase in peripheral site-related bacteremia was associated with an inner city location.⁴¹ Although personal hygiene as a risk factor was implicated by a previous study,⁴² this was only significant in the univariate analysis of the pilot data.⁴¹ Mean access-related infection events per month in the different centers ranged from 0.31 to 3.98. The infection rate was significantly reduced in 11 centers and was significantly increased in 14 centers.³⁰

Despite intensive programs to curb their use, 81% of United States ESRD patients initiate dialysis with a catheter, and only 26% have an autogenous or prosthetic AV access already in place. Although the most likely reason for the increase in 1-year mortality was attributed to catheter access and infection, overzealous treatment of anemia, intravenous iron, and intravenous vitamin D were also associated with this increase.¹

Because the peripheral AV access is punctured thrice weekly for maintenance hemodialysis, bleeding and hematoma will occasionally complicate this process. Surgical incisions and recently implanted prosthetic grafts require several weeks to heal and become fully incorporated into the surrounding tissues. Failure of this process may result in seromas or perigraft fluid collections. Appropriate perioperative antibiotic prophylaxis is the best preventive measure during this critical early implantation phase.

Duplex ultrasound imaging may be helpful in resolving the diagnosis. Perigraft fluid collections can be distinguished from pseudoaneurysm. Serial examinations may be performed to monitor the progress or resolution of hematomas and fluid collections. A reasonable prediction of the extent of a perigraft fluid collection using duplex ultrasound imaging has direct bearing on preoperative planning when infection is actually present. The functional status of the access becomes important when considering procedures to salvage an access with localized infection.

Occasionally, the diagnosis of infection and the clinical findings are nonspecific, such as patients with positive blood cultures, leukocytosis, or fever. Localization of prosthetic graft infection with ¹¹¹In-tagged leukocyte scanning is highly sensitive, but not necessarily specific, because any inflammatory response may suggest infection.⁴³, ⁴⁴, ⁴⁵ However, false-negative reports may be relatively frequent, the most common of which is hematoma. The accuracy of ¹¹¹In scans with the functional access punctured thrice weekly is unknown.

Subcutaneous prosthetic AV accesses account for most peripheral access site infections, with a small percentage contributed by autogenous AV access. Because they have the lowest incidence of infection, autogenous AV access is often used as the reference value for estimates of relative risk.³⁸, ³⁹, ⁴⁰

Most peripheral access site infections are caused by gram-positive cocci. S aureus accounts for 50% to 70% of these infections.³⁰, ⁴³, ⁴⁶, ⁴⁷, ⁴⁸ Coagulase-negative staphylococci are usually second in frequency, followed by polymicrobial infections with multiple gram-negative bacteria. S aureus is more common with prosthetic or autogenous AV accesses (54%) than with bacteremias (32%).³⁰ In the surveillance study by Tokars et al,³⁰ only 12% of bacteremic isolates originated from peripheral access infections: 53% S aureus, 20% coagulase-negative staphylococci, 10% other gram-positive organisms, 10% gram-negative rods, and 15% other organisms. The majority (66%) of bacteremic isolates were from patients with catheters: 32% S aureus, 32% coagulase-negative staphylococci, 18% gram-negative rods, and 12% other gram-positive organisms (predominantly Enterococcus spp). The remaining 23% consisted of 19% secondary bacteremias (wounds unrelated to the access, urine, osteomyelitis, pneumonia) and 4% contaminants. Fungal infection with a prosthetic or autogenous AV access was unusual.³⁰

Antibiotic resistant organisms are common: S aureus, 38%; coagulase-negative staphylococci, 6.5%; and Enterococcus spp, 4.6%.³⁰, ³⁷, ³⁹ Arterial dissolution with aneurysm formation is more frequently encountered in infections with virulent organisms such as Pseudomonas or S aureus.⁴⁹, ⁵⁰, ⁵¹ Grafts with convincing clinical findings of infection that produce no growth with standard culture techniques may occur as frequently as 25%.⁴⁷, ⁴⁸ This inconsistency is often attributed to preoperative antibiotic administration. Enhanced microbiologic techniques with gentle sonication of explanted prosthetic AV access may improve the yield, particularly for late AV access graft infections and organisms with a high adherence to graft material.⁴⁷

The chronically thrombosed prosthetic or autogenous AV access may be considered a source of otherwise unexplained systemic infection. Removal of these prosthetic grafts can require an extensive dissection and may be associated with nerve injury, bleeding, and significant patient discomfort. However, Ayus and Sheikh-Hamad⁴³ identified subclinical infection in a number of otherwise asymptomatic dialysis patients with ¹¹¹In-tagged leukocyte scans.

The threshold for evaluating these grafts for clinical investigation has been lowered, but there are no clear guidelines for management of the otherwise asymptomatic patient. This limited experience indicates that in patients with no other identifiable source of infection, it may be prudent to remove the nonfunctional ¹¹¹In-positive graft.

Management and treatment options 

The choice of conduit has a profound effect on the incidence and treatment of AV access infection. Access site infections should be reported as early (<30 days) or late (>30 days), culture-positive or culture-negative, and identify the site of the infection, whether para-anastomotic, mid-AV access, or outflow veins.⁴

Surgical intervention is usually required for true AV access infections. The recommended therapy for these complications depends on the (1) extent of infection, (2) type of AV access conduit (autogenous vs prosthetic), (3) bacterial etiology, (4) functional status of the AV access (patent or occluded), and (5) type of presentation (bleeding, purulent drainage, cellulitis, fever of unknown origin). Management includes total, subtotal, or segmental AV access excision or (rarely) complete AV access preservation.

The low incidence of infection with the autogenous AV access is one of its major clinical advantages. Autogenous AV access infections are usually related to puncture site hematoma, pseudoaneurysm, or incisional complications. The reported frequency is 0.56% to 4.5%.⁴⁰, ⁵², ⁵³, ⁵⁴ Because the rate of infection for the autogenous AV access is so low, it is frequently assigned the reference value of 1.0 for investigations assessing comparative risk.³⁸, ³⁹, ⁴⁰ Broad-spectrum antibiotics should be administered if AV access infection is suspected, such as β-lactam antibiotics or vancomycin and gentamicin. Intact autogenous AV access infections have occasionally resolved with 4 to 6 weeks of parenteral antibiotics.⁵⁵ Infections that originate at a puncture site should be observed for subsequent reinfection.⁵⁶

Local manifestations of cellulitis, abscess, pseudoaneurysm, or hematoma are the usual findings with infection involving autogenous AV access. However, thrombus within the aneurysmal AV access may become a source of endarteritis.⁵⁷ Owing to its infrequent occurrence, there is a paucity of published experience.⁴⁶, ⁵², ⁵³, ⁵⁴, ⁵⁵, ⁵⁶, ⁵⁷ The combined presence of bleeding, proximity to an anastomosis, and local site infection is more likely to result in sacrifice of the access.⁴⁶, ⁵³ However, if not localized at an anastomosis, the infected area may be ligated and a new anastomosis constructed in a clean field.⁴⁶, ⁵⁶

Prosthetic grafts, predominantly polytetrafluoroethylene (PTFE), have until recently accounted for most AV access sites in the United States. With the success of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) and Fistula First initiatives, autogenous access is replacing prosthetic grafts in United States practice.⁵⁸ The advantages of the prosthetic graft include ready availability of a standard size conduit that is easily punctured and has a short maturation time. In addition to infection, disadvantages of prosthetic grafts include a short life expectancy and fibrointimal hyperplasia. A recent randomized controlled trial comparing an autogenous brachiobasilic AV access with a prosthetic forearm loop configuration found in favor of the autogenous AV access due to a significantly decreased intervention and complication rate.⁵⁹

The reported incidence of infection with prosthetic AV access ranges from 3.5% to 19%.⁴⁶, ⁴⁸, ⁵², ⁵³, ⁵⁴, ⁵⁵, ⁵⁹ If infection truly involves the AV access conduit and is not simply cellulitis, systemic antibiotics alone are usually inadequate as the sole treatment.

Total or subtotal AV access excision should be performed for infected conduits when the (1) access is causing septicemia, (2) access is occluded, (3) infection is due to Pseudomonas spp or other aggressive bacteria, or (4) the entire AV access is involved with infection as manifested by pus or fluid surrounding the entire conduit or when the conduit is completely unincorporated. Occasionally, total or subtotal AV access excision is necessary in patients with persistent or recurrent bacteremia even when there is no overt evidence of access infection.

The venous end of the prosthetic graft should be removed and the vein oversewn or ligated. If the arterial anastomosis is intact, a small cuff of the AV access graft can be oversewn to maintain patency of the underlying artery.⁴⁸, ⁶⁰ If the arterial anastomosis is involved, or infection recurs in the retained cuff, débridement of the infected arterial wall is needed. Reconstruction with autogenous patch angioplasty has had inconsistent success, and arterial ligation or bypass through clean tissue planes may be required.⁴⁶, ⁵² When required, radial or distal brachial ligation (below the profunda brachii) is well tolerated in the presence of functioning collateral circulation.⁵²

Segmental access excision with placement of a new jump graft through a sterile field should be considered if infection is localized to one part of the conduit. In more than half of infected prosthetic AV accesses, infection is confined to a focal segment of the graft ⁵⁵ An infected, disrupted anastomosis must be managed by excision of at least that segment of the AV access. To perform partial AV access excision with a jump graft, the infected site should first be covered and isolated with sterile adhesive dressing after the arm is prepared. Through separate, clean incisions proximal and distal to the infected area, sterile segments of the patent AV access or native arteries are exposed. A short new bypass graft is tunneled subcutaneously through a sterile field and anastomosed to the divided ends of the original AV access or to an uninvolved artery, depending on the extent of the infection. Once the new incisions are closed primarily and isolated with sterile adhesive dressings, the infected segment is excised through a separate incision.

Complete AV access preservation may be attempted when a small segment of the conduit is involved. However, this strategy using delayed secondary-intention wound healing is usually less successful than for lower extremity arterial bypasses because an AV access is usually very superficial and located immediately under the skin. Placement of a muscle flap can be considered, but again, this is usually not possible because of the superficial position of the bypass and unsuitability of adjacent muscles.

Results and recommendations 

Infected prosthetic AV accesses treated by total, subtotal, or partial graft excision (51 graft infections in 45 patients) were managed using the above strategies at Pennsylvania Hospital.⁴⁸ Thirteen patients underwent total graft excision in the presence of systemic sepsis. Fifteen patients with infection involving a patent graft without sepsis required subtotal graft excision involving a small, oversewn cuff of prosthetic graft adjacent to the arterial anastomosis. Twenty-three patients with localized infection in one segment of the graft and absence of fluid around the remaining uninfected portion of the graft as documented by preoperative ultrasound and intraoperative findings underwent segmental graft excision with placement of a new jump graft through a sterile field. None of the 45 patients died.

Palder et al⁵⁵ reported a similar experience in 22 grafts. The wounds healed in all patients treated with total or subtotal graft excision, although patients required insertion of a temporary dialysis catheter and placement of a new permanent AV access at a different site at a later time. In patients treated with segmental graft excision, graft patency was maintained and wound healing was achieved in 74%, whereas failures ultimately required total graft excision.

Schwab et al⁶¹ reported a 94% success rate when 17 patients were treated with segmental graft excision. Preservation of a significant part of the incorporated graft was possible in many of these patients, and the graft was used for immediate dialysis, avoiding the need for temporary catheters or new permanent dialysis access. These results suggest that subtotal and segmental graft excision can be safely used in selected patients with infected prosthetic AV grafts.

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Noninfectious fluid collections 

Localized noninfectious fluid collections representing hematomas, seromas, lymphoceles, or lymphedema will occasionally complicate peripheral access sites. The initial presentation may be similar, but it is critically important to distinguish these from infection, abscess, or pseudoaneurysm because the implications for management vary significantly.

Although recognized as a noninfectious problem initially, each of these collections can be secondarily complicated by infection. Duplex scan examination is helpful for both diagnosis and guidance for aspiration of the fluid.

Hematoma 

Identification of a hematoma is usually obvious if the immediate history is known. Bleeding from needle puncture sites may be prolonged after a dialysis session. In particular with a newly matured autogenous AV access, posterior wall puncture may not be well controlled, leading to hematoma and diffuse infiltration of tissue planes. This low-frequency complication may occur with any peripheral access configuration. The incidence ranges from 0.073 to 0.2 per patient-year in recent studies.⁵⁹, ⁶²

Clinically significant bleeding is a frequent complication of uremia. This section will focus on the mechanical aspects of contained, nonexpanding hematomas because medical corrective measures and the approach to active surgical bleeding were discussed previously.

Hematomas associated with AV accesses usually arise from needle punctures during hemodialysis. In the absence of infection, a persisting nonexpanding intraluminal communication, or pseudoaneurysm, the bleeding will usually stop and the extravasated blood will diffuse into local tissue planes. These are usually reabsorbed and can be observed through the ecchymotic stage until they have resolved.

Seroma 

Seromas are sterile fluid collections that can develop around prosthetic AV grafts and almost never involve autogenous AV accesses. These collections occur due to transudation of sterile serum-like fluid and are confined within a nonsecretory fibrous pseudomembrane surrounding the graft.⁶³ Although the etiology is unclear, they have been reported with Dacron, bovine, and PTFE prostheses.⁶⁴, ⁶⁵ Seromas usually appear within the first month after placement, are often close to the arterial anastomosis, and may simulate a pseudoaneurysm.⁶⁶

Ultrasound-guided needle aspiration of the fluid yielding serous or gelatinous material is consistent with a seroma and can be both diagnostic and possibly therapeutic. This strategy facilitates diagnosis by submitting the fluid for white blood cells and bacteria evaluation, which may suggest an infectious or lymphatic etiology. Treatment options include serial aspirations, wrapping the graft with microfibrillar collagen (Avitene, Davol/Bard, Cranston, RI), surgical excision of the entire seroma with débridement of inflammatory tissue from around the graft while leaving the graft in situ, and replacing the graft with a conduit different from the original one.⁶⁴ Aspiration may be as successful as observation alone (about 68%) but was associated with infection or graft thrombosis in 8% of cases in one series.⁶⁵ Drainage of the seroma and excision of the pseudomembrane was associated with a 72% success rate, but infection or thrombosis occurred in 12% of cases in a different series.⁶³ In situ graft replacement resulted in the highest success rate (92%) in a series of 279 cases compiled from a survey of American vascular surgeons.⁶⁵ The most worrisome concern about this strategy is whether the fluid is infected, but the clinical presentation, Gram stains, and cultures usually help determine the true etiology of the fluid. Although recognized as a noninfectious problem initially, repetitive interventions can still be secondarily complicated by infection and loss of the access.

Lymphatic 

A lymphocele, lymphorrhea, or lymphedema can occur as a result of disrupted small lymphatics during dissection to expose the arterial or venous structures or during tunneling through the subcutaneous tissue. Lymphatics and lymph nodes concentrated along the medial aspect of the extremity may be disrupted or become inflamed as a result of surgery. Accurate distinction between lymphocele and other localized collections may be difficult, but the management is similar to that for perigraft seroma. Fortunately, this is a very infrequent complication of hemoaccess procedures.

Lymphorrhea or a discrete lymphocele in an extremity is characterized by clear fluid. A small, nonenlarging lymphocele may resolve with simple observation. External lymphatic drainage and lymphoceles in communication with the access will usually respond to surgical exploration. Extrapolating from the experience with arterial reconstruction, identification and obliteration of leaking lymphatic tissue may be the key.⁶⁷ Diffuse lymphedema of the extremity is treated nonoperatively. Generally, the edema will resolve after a few days or weeks with elevation. Management of recalcitrant edema may require localized compression of the extremity with careful attention to the access site. Each of the noninfectious fluid accumulations is distinct from infection, which must be excluded before proceeding to treat these. Unfortunately, intervention for correction of the problem is also a risk factor for introducing infection.

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Pseudoaneurysm 

A localized mass is the primary manifestation of a pseudoaneurysm, which may occur at the anastomosis or along the course of the access. Diagnosis is confirmed by duplex examination localizing the neck of the aneurysm. Perianeurysmal inflammation or fluid collections suggest infection. Sterile pseudoaneurysms usually occur after needle puncture, whereas anastomotic pseudoaneurysms are more likely to have an infectious etiology.

Clinical features and pathophysiology 

An incidence of access-related pseudoaneurysms has been reported to be 0.049 to 0.1 per patient-year reported from two Dutch randomized trials, which probably underestimates this problem because it was limited to a single year of observation after construction of a new access.⁵⁹, ⁶² Previous case series with longer observation periods report pseudoaneurysms in 2% to 10% of PTFE grafts,⁵³, ⁵⁵, ⁶⁸ which is a higher incidence than in autogenous access.⁵⁰, ⁵³, ⁶² Pseudoaneurysm tends to occur in that portion of the access closest to the arterial inflow, and it has been suggested that reductions of intragraft pressures or venous outflow obstruction, or both, contribute to their formation.⁶⁹ Although not a pseudoaneurysm, diffuse aneurysmal dilation and elongation of the autogenous AV access is also described here because the two are often confused clinically.

Management and treatment options 

Management of an AV access pseudoaneurysm depends on the etiology (puncture site vs anastomotic vs diffuse dilation, sterile vs infectious) and the location (endovascular vs surgical management) of the lesion.

A small puncture site pseudoaneurysm can often be observed and may resolve without further treatment; however, surgical intervention may be necessary if it is enlarging or acutely expanding.

Diffuse involvement of a prosthetic conduit may herald a loss of integrity in the anterior wall structure of the graft. Depending upon the extent of this destruction, segmental resection may be used with anastomosis to the residual arterial and venous ends of the graft as inflow and outflow sites.⁵⁰, ⁵³, ⁵⁵

A covered stent offers an endovascular alternative to surgical management.⁶⁸, ⁶⁹, ⁷⁰ Deployment of a short covered stent (endograft) will control an actively communicating puncture site and is also valuable for lesions that are difficult to repair with open surgical exposure, such as sites that have undergone repeated punctures, sites with extensive scarring due to past surgery or repeated punctures, or sites located near the axilla. Vesely⁶⁹ notes that this represents an off-label indication and reported a 6-month patency of 20% in 11 PTFE-covered stents. Dialysis through the area of the covered graft should be avoided for some time because the aneurysm may recur and the supporting covered stent may also be disrupted. Also, similar to endovascular therapy for abdominal aortic aneurysm, the aneurysm sac may not regress rapidly if filled with organized thrombus.⁶⁸, ⁶⁹, ⁷⁰

Anastomotic disruption resulting in pseudoaneurysm should always be managed by surgical or endovascular revision. The most common cause of an anastomotic pseudoaneurysm is infection, and it should be treated as outlined previously.

Although it is possible for sutures to erode through the arterial wall because of arterial wall degeneration, undue tension, or inadequate depth of suture bites, these causes are uncommon in the AV access population. If infection is not the cause, oversewing a small anastomotic defect may suffice. However, a patch or short jump graft may need to be placed from the original graft to a new segment of uninvolved artery.⁵⁰, ⁵⁵

Aneurysmal dilation and tortuosity is a unique feature that may develop in an autogenous AVF that has functioned for many years. Because these develop with expansion of the autogenous AV access lumen, all layers of the access walls are dilated. Although not a pseudoaneurysm, these are often mislabeled as such. These AV accesses function extremely well for the purpose of hemodialysis as long as the lumen is not filled with layered thrombus and the cutaneous envelope remains intact. An aneurysmal AV access may raise concern from the staff, but there is no reason to intervene as long as the AV access is functioning well for dialysis and the dilatation is not steadily and rapidly enlarging.

The usual indication for intervention is compromise of the overlying skin. In addition, obstructive kinks and intraluminal thrombus may compromise dialysis exchanges. Constructing a more proximal AV access using the arterialized vein end-to-end anastomosis after excision of redundant aneurysm, or a prosthetic graft, can restore a functional access.

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Venous hypertension 

Symptoms of V-HTN were recognized in its complete clinical form within a decade of the initial reports advocating AV access for hemodialysis.⁷¹, ⁷², ⁷³ The most common manifestation of V-HTN is regional edema, although other typical signs and symptoms such as pigmentation, induration, dermatosclerosis, and ulceration may be produced. The pathophysiology is straightforward but is frequently misunderstood or misdiagnosed. The essential concept pairs a functioning AV access, which increases arterial blood flow to an extremity, with an obstruction to venous outflow.

Pre-existing venous obstruction may not be readily recognized. To produce V-HTN, the obstruction must be located close enough to the AV access outflow to permit filling of branch veins. If there were no intervening branches between the access and the obstruction, thrombosis would occur; thus, obstruction may produce a localized V-HTN or affect an entire extremity. Central vein obstruction may affect one or both extremities. Normal blood flows are generally accommodated by the development of extensive collateral drainage beds. A slightly different variant is seen with the valvular incompetence that occurs with the less frequently constructed side-to-side autogenous AV access; dilation of the vein may render the valves in the branches incompetent, permitting high-volume retrograde flow to be redirected distally. Progressive intimal hyperplastic stenosis in an outflow vein may produce similar volume redirection.

Clinical features of V-HTN 

Liberal use of central venous catheters, and the resulting venous obstruction, makes this the most common complication limiting venous access options in the upper extremities.², ³ In the absence of AV access flow, central vein stenosis or obstruction is often asymptomatic. Recognition may be difficult since the standard preaccess duplex ultrasound workup may not visualize this area well.

Clinical and noninvasive “hints” may suggest central vein stenosis or obstruction before AV access construction. Although the history should inquire about prior catheterization, not all patients will recall this treatment. Typical scars accompany the insertion sites for tunneled catheters, pacemaker leads, defibrillator leads, parenteral nutrition, triple lumen, and PICCs. All of these central venous devices have a high incidence of thromboses in the axillary, subclavian, innominate, jugular veins, and vena cavae that will compromise the options for subsequent AV access.⁷⁴, ⁷⁵, ⁷⁶, ⁷⁷, ⁷⁸, ⁷⁹ A PICC directly damages the cephalic and basilic veins, but may also impede recognition of central obstruction because of its peripheral insertion site.⁷⁸, ⁷⁹ Central vein catheterization is now the most common primary cause of central vein thrombosis.⁸⁰ The actual incidence of central vein thrombosis may be under-appreciated, however, because ultrasound transmission is limited by the clavicle and sternum in these anatomic distributions.⁸¹

Once the access has been constructed, obstruction may produce clinical findings of regional edema and high venous pressures. In addition to the inconvenience of persistent edema, AV access use may be compromised by difficulty with needle access and the potential for recirculation. Axillary, subclavian, and innominate vein obstruction are associated with unilateral findings; vena caval obstruction produces bilateral findings. If the superior vena cava (SVC) is occluded, this generally means the loss of both upper extremities for subsequent AV access placement.

A strong pulse (vs a palpable thrill) in the AV access conduit may suggest outflow obstruction. Inspection of the extremity and the central outflow anatomy may identify an extensive collateral pattern located across the anterior chest, shoulder, and along the flank. SVC obstruction or stenosis can produce a large swollen head, neck, and shoulder, with large chest wall collateral veins, and a feeling of head and neck fullness and dyspnea. Airway compromise, dizziness, mental changes, and visual problems including blindness may supervene.⁸², ⁸³, ⁸⁴, ⁸⁵

The severe V-HTN produced with a functioning AV access may also produce the typical extremity findings associated with chronic venous insufficiency, including pigmentation, thickening, induration, and even ulceration of the skin.⁷², ⁷³, ⁸⁶, ⁸⁷, ⁸⁸, ⁸⁹, ⁹⁰, ⁹¹ Patent side branches between the anastomosis and an outflow stenosis in an autogenous AV access,⁹², ⁹³ or a radiocephalic side-to-side anastomosis,⁸⁹, ⁹⁰ divert the AV access flow into the patent collateral venous bed, resulting in distal edema. Persistence of V-HTN will typically produce these symptoms in the first through fourth digits of the hand. The distribution localizes to the pressurized venous bed. This may be mistaken for infection, but will only resolve with correction of the V-HTN.⁸⁸, ⁹⁰, ⁹³

Pathophysiology 

Flow in the radial artery increases from 30 to 300 mL/min after construction of a radiocephalic AV access.⁹⁴ Mean flow using ultrasound-detected indicator dilution is 645 mL/min for radiocephalic and 1336 mL/min for brachiocephalic autogenous AV accesses.⁹⁵ Even well-developed collaterals may have difficulty managing this 10-fold increase in arterial volume flow.

The most frequent cause of upper extremity venous thrombosis is now central venous catheters or cardiac devices; the most powerful predictor is the presence of these devices, with an odds ratio of 7.3 (95% CI, 5.8-9.2).⁸⁰, ⁸¹ Approximately 50% of dialysis patients had a history of subclavian catheterization, and 50% of those exposed had stenoses that were considered significant.⁹⁶ A Belgian study detected significant subclavian vein stenosis or obstruction by venography in 19% of patients who had received dialysis through a subclavian catheter.⁷⁴ A 10-year review of pacemaker insertions at one institution found a 71% incidence of significant subclavian vein obstruction; ligation of an ipsilateral AV access was required in 10 of 14 dialysis patients.⁷⁵ A review of defibrillator lead placements found 14 of 30 had >50% subclavian stenosis.⁷⁶

Although most thrombi were peripheral in venographic reviews of PICCs, the overall incidence of 38% has direct implications for all dialysis patients.⁷⁸, ⁷⁹ Thrombus was occlusive in 86%, 38% were basilic or cephalic vein, and 12% central vein thrombi.⁷⁸ A 29% incidence of unsuspected central venous stenosis was prospectively observed in patients with functioning prosthetic AV access who had venography for evaluation of a known anastomotic outflow stenosis.⁹⁷ These stenoses are often short, web-like, and focal.⁹⁵

There is minimal literature comparing the cutaneous effects of V-HTN with that of lower extremity chronic venous insufficiency.⁹¹ Pericapillary cuffs, dermal edema, and intimal proliferation were observed in biopsy specimens taken from the index finger or first web space of patients with upper extremity access grafts and signs of venous hypertension.⁸⁹, ⁹⁰ Peroxidase-antiperoxidase staining confirmed the presence of fibrin.⁹⁰ Monoclonal antibodies and immunofluorescence studies confirmed the presence of fibrin in the cuffs as well as plasminogen activator inhibitor-1; the latter is suggestive of impaired breakdown of fibrin. Less extensive fibrin cuffs were also observed in two side-to-side autogenous AV accesses, but none in three end-to-end autogenous AV accesses or controls.⁸⁹

Central venous stenosis or occlusion 

Because clinical and duplex ultrasound assessments may not accurately reflect subclinical central vein obstruction, identification and correction may require complete visualization of the anatomy of the proposed AV access site and its outflow veins. Venography is essential to determine whether the vein is occluded or stenotic; even if it is occluded, passage of a guidewire opens up therapeutic options. Recognition of central vein stenosis before access placement is generally a contraindication to use of that extremity, unless the venous stenosis can be corrected. If it develops after construction of the AV access, the focus is on resolution of the symptoms of V-HTN as well as preservation of the AV access site.

Endovascular approaches to treat venous outflow stenosis offer minimal risk and a reasonable initial technical success rate; however, durability has only been mediocre, and continued function may require repeat intervention. The SVC is amenable to thrombolysis, angioplasty, and stenting.⁸², ⁸³, ⁸⁴, ⁹⁸, ⁹⁹ Stenting SVC obstruction produced a more durable patency than open repair for benign etiologies, such as catheters, and pacemakers, in the most recent report from the Mayo Clinic.⁹⁹ A 12-month patency of 67% with an assisted patency of 100% was achieved by stenting to a diameter of 8 to 12 mm in the SVC.⁸³ The purpose of the stent is to prevent elastic recoil associated with the need for repeat percutaneous transluminal angioplasty (PTA).

The same interventions are available for treatment of the innominate vein.⁸³, ⁸⁴, ⁹⁸, ¹⁰⁰ Results of these procedures in the subclavian and internal jugular veins are satisfactory, but subclavian stents may be complicated by the scissoring effects of the first rib and the clavicle, resulting in permanent deformation. A summary of these interventions over the past decade reported a 12-month patency ranging from 11% to 68% for central venous stents and 11% to 35% for PTA alone.⁸³

Surgical management options include a direct approach to the site of obstruction, bypass of the obstruction, construction of the access in another extremity, and conversion to peritoneal dialysis. The direct approach includes a number of creative surgical options: jugular turndown, axillary–jugular bypass, axillary to contralateral venous outflow, and even atrial bypass.¹⁰¹, ¹⁰², ¹⁰³, ¹⁰⁴ The best results with SVC and innominate vein procedures have been with autogenous vein–spiral saphenous and femoral veins.⁸², ⁸⁴, ¹⁰⁵ With moderately reduced long-term patency, PTFE is acceptable in this anatomic site. At 4 years, secondary patency for spiral saphenous vein graft was 90% and 50% for PTFE. Both reflect secondary patency achieved by initial surgery with additional endovascular interventions.⁸², ⁹⁹

Although not optimal, the physician can justify continued use of the extremity with moderate venous obstruction in some situations. These include a paucity of reasonable options for new AV access and relatively mild symptoms from the V-HTN. In patients who have few AV access alternatives, the burden of a chronically swollen extremity may become relatively acceptable.

Clearly, avoidance of the central venous catheterization in the first place is the most effective method of eliminating this problem. Patients with impending chronic renal failure constitute a relatively small population of those requiring pacemakers or defibrillators. When these choices are elective, consideration of the subsequent need for access should be considered before the devices are placed on the nondominant upper extremity, which is usually the left.⁷⁵, ⁷⁶, ⁷⁷, ⁷⁹ This has been emphasized by the Fistula First initiative and is strongly supported by data demonstrating a significant increase in the morbidity associated with patients commencing dialysis with a catheter.³, ¹⁰⁶

The literature on this complication is based on small case series and thus is limited. The best results have been obtained when the AV access is constructed and matured before hemodialysis commences. When this program is successful, catheter complications can be largely eliminated.

Endovascular options offer a minimally invasive approach with relatively low risk and immediate restoration of functional AV access. Although durability is only mediocre, these factors favor this as an initial approach, with the caveat that repeated intervention is frequently necessary to maintain the result. Surgical approaches are more invasive, but provide greater durability. However, the prolonged patencies that were described were only achieved with adjunctive secondary endovascular interventions. The durability of these solutions depends on the reconstruction used: Autogenous reconstructions have the best track record, with PTFE as an acceptable second choice.⁸², ⁸⁴

Valvular insufficiency 

When the autogenous AV access was initially introduced, considerable debate ensued about the best method of construction. Technically, a side-to-side anastomosis was more straightforward, had higher flows, and was less prone to early thrombosis.⁸⁷ It was assumed that the valves in the distal venous limb would remain functional, preventing retrograde flow into the distal, superficial veins. This did not always occur, however, and some limbs with side-to-side anastomosis developed high-volume retrograde flow resulting in the typical findings of chronic venous insufficiency (edema, pigmentation, induration, and ulceration). Unless the practitioner is familiar with the findings of distal V-HTN, the symptoms may be mistaken for infection or allowed to persist until infection supervenes.⁸⁸, ⁹⁰, ⁹³

With a side-to-side radiocephalic AV access, these findings were most commonly seen on the thumb and index finger, presumably because the incompetent valves producing the V-HTN were in the distal drainage pattern of the cephalic vein.⁷², ⁸⁷ The appropriate management is to convert the side-to-side configuration to a functional end-to-side by ligation of the incompetent, distal outflow vein.⁷², ⁸⁷

For a new autogenous AV access, end-to-side construction is now standard procedure. However, V-HTN may still occur when the outflow from an end-to-side radiocephalic fistula is obstructed proximally and the branch veins conduct the same retrograde pressure pattern. In this setting, the distribution is more likely to occur in the index, middle, and ring fingers because the retrograde flow is transmitted through the remaining superficial veins.⁸⁸, ⁹², ⁹³ Management options include ligation of the incompetent branch vein feeding the distal superficial veins or relief of the obstruction, or both.⁷³, ⁸⁷, ⁹² Alternatively, if the access site can be sacrificed, the AV access can always be ligated.⁷², ⁸⁸, ⁹², ⁹³ A similar syndrome may develop with an prosthetic AV access when intervening branches are present between the outflow anastomosis and a more proximal obstruction in the outflow vein.

Resolution of venous outflow obstruction can often be achieved. Construction of a side-to-side AV access should generally be avoided. Clinical recognition is the key to successful treatment. When accurately characterized anatomically, ligation of the incompetent branch vein results in resolution of symptoms.

Regional outflow obstruction 

Prosthetic AV accesses are commonly found to have intimal hyperplasia at the outflow anastomosis. Rather than producing edema and V-HTN, outflow anastomotic stenosis results in high venous pressures, poor dialysis from recirculation, and ultimately, thrombosis. However, when outflow obstruction occurs in a more proximal vein, a functioning autogenous or prosthetic AV access may also produce V-HTN with complicated drainage patterns that are difficult to visualize and correct. Rising venous pressure is considered a sensitive indicator of outflow obstruction. Venography may be required to identify these flow patterns and to accurately localize the site and extent of the obstruction.

The KDOQI guidelines hypothesize that a stenosis of >50% in an autogenous or prosthetic AV access outflow predisposes to early thrombosis with permanent loss of the AV access.² Accordingly, serial surveillance is recommended for the purpose of identifying these stenoses, with the expectation that treatment of the stenosis will prevent thrombosis and improve the functional life of an autogenous or prosthetic AV access. Surveillance includes measurement of recirculation, dialyzer flows during treatment, duplex Doppler imaging, and derived AV access flow.² The more accurate ultrasound-detected indicator dilution method has recently been introduced to observe serial AV access flows.⁹⁵, ¹⁰⁷, ¹⁰⁸, ¹⁰⁹, ¹¹⁰

Supporting the concept of surveillance, Schwab et al¹¹¹ measured elevated venous pressure in 73 patients for further evaluation: 15 declined, eight had no stenosis, and venography showed 50 had >50% lumen diameter reduction. Initial treatment with PTA was followed with repeat PTA or surgical revision. Stenoses were located at the outflow anastomosis, the outflow vein, and the subclavian vein in this group of predominantly prosthetic AV accesses. In comparison with a historical control group and the concurrent nontreatment (refused intervention) group, the authors concluded that elective intervention reduced the rate of thrombosis or loss of access.¹¹¹

Four completed randomized trials with similar conclusions assessed the concept of elective, preemptive intervention for venographically confirmed >50% venous stenosis.¹¹², ¹¹³, ¹¹⁴, ¹¹⁵ After angiographic confirmation of >50% stenosis, 64 patients with prosthetic AV accesses were randomized to PTA or observation. Repeat PTA was performed (up to 6 PTA procedures) in the intervention group if >50% stenosis recurred. The two groups did not differ significantly in terms of thrombosis or functional access failure.¹¹²

In another trial, 58 patients with prosthetic AV accesses and venous anastomotic stenosis of >50% were randomized to PTA or PTA with an adjunctive stent. No significant difference was noted in access thrombosis, need for surgical revision, or need for a repeat PTA.¹¹³ In yet another trial, 34 patients with stenoses of >50% at or ≤3 cm of the outflow vein–prosthetic graft junction or in the peripheral outflow vein were randomized to PTA or PTA with an adjunctive stent. The authors concluded that stent placement offered no advantage.¹¹⁴ The fourth trial randomized 43 patients with venous anastomotic stenosis of >50% to PTA or surgical revision (patch angioplasty or an interposition graft). Surgical median patency of 12 months differed significantly (P < .01) from the PTA median patency of 4 months.¹¹⁵ The results of these randomized trials are difficult to interpret but suggest that prophylactic intervention may not be helpful, that stenting offers no advantage, and that surgical revision is better than PTA.

Stenosis at the arch of the cephalic vein outflow into the axillary vein is problematic. The vein is fragile, has a greater incidence of rupture, is most frequently involved with brachiocephalic AVFs, and is anatomically inhospitable to stent therapy.¹¹⁶, ¹¹⁷ In this setting, a direct surgical transposition procedure to reroute the cephalic vein outflow to the more distal axillary or brachial vein performed well.¹¹⁷, ¹¹⁸ Outflow transposition is also effective for basilic vein stenosis.¹¹⁸

Two randomized trials with similar conclusions address the role of surveillance monitoring of AV access flow.¹⁰⁹, ¹¹⁰ Both used ultrasound-detected indicator dilution in an experimental group compared with observation or clinical monitoring alone. Both randomized >100 subjects, and surveillance was conducted monthly or every fourth month. Both found that the frequency of intervention with angioplasty was significantly higher in the experimental group, but that it had no effect on the end points. Neither protocol resulted in an improved interval to thrombosis or to permanent prosthetic access failure. Both concluded that surveillance increased interventions but without demonstrable efficacy.¹⁰⁹, ¹¹⁰ These findings are consistent with those focused on anatomic stenoses as described previously. The utility of surveillance monitoring is discussed in detail in the Clinical Practice Guideline.¹¹⁹

Recommendations 

The available data demonstrated no clear advantage of angioplasty with or without stenting compared with observation; thus, there is no mandate for elective intervention to correct >50% stenosis in the absence of other abnormalities. However, because functional use of the access may be compromised by stenosis, PTA may still have a role as a bridge to more definitive therapy. Surgical intervention with patch angioplasty, interposition grafting, or transposition will resolve the symptoms of V-HTN and preserve a functional access. A systematic review is in progress at the Cochrane Collaboration.¹²⁰ Numerous authors contributing written opinions on the topic have advocated a randomized prospective trial to evaluate preemptive therapy for stenosis or flow reduction identified during the recommended surveillance.¹²¹

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Arterial steal syndrome 

Within 5 years of the introduction of the Brescia-Cimino-Appel AV access, disabling neurologic symptoms in the forearm and hand were attributed to arterial steal syndrome from radial and brachial AV accesss.⁷¹, ¹²², ¹²³ The clinical findings of ischemic neuropathy (ie, severe pain, motor and sensory impairment, and involvement of multiple nerve trunks) were accurately described by Bolton,¹²⁴ a clinical neurologist with an interest in neurologic dysfunction in patients with uremia.

Clinical features of symptomatic and asymptomatic arterial steal syndrome 

The clinical spectrum of arterial steal is wide because most patients are not symptomatic but have laboratory evidence of abnormal flow. Asymptomatic “steal,” manifested by pulse deficits, Doppler signal attenuation, and distal flow reversal, may be present with AV access but only becomes symptomatic when blood flow is shunted (stolen) from tissue beds distal to the arterial anastomosis.

Mild ischemia produces slight coldness and numbness that occurs only during dialysis, may be self-limited, and may resolve without treatment.

Severe ischemic symptoms of arterial steal syndrome can be permanent and may be associated with constant pain, severe numbness, digital cyanosis or gangrene, finger contracture, or amputation of a digit, hand or forearm. Symptomatic arterial steal syndrome is uncommon, but usually requires surgical intervention. Although symptomatic steal can occur with a forearm AV access, the incidence is low, ranging from 0.25% to 1.8%.⁵³, ⁷², ¹²⁵, ¹²⁶ Severe symptomatic arterial steal syndrome is most frequently associated with a brachial arterial source, with a frequency of 4% to 9%.⁵³, ⁷², ¹²³, ¹²⁵, ¹²⁷, ¹²⁸, ¹²⁹, ¹³⁰, ¹³¹, ¹³² Diabetes mellitus⁵⁰, ¹²⁵, ¹²⁷, ¹²⁹, ¹³⁰, ¹³¹ and female gender⁷², ¹²⁸, ¹³⁰, ¹³² are present in more than half of the reported cases. Other associated risk factors include previous ipsilateral AV access, peripheral atherosclerosis, and age.¹³⁰ Gender and diabetes cannot be altered, but the need for anastomosis to the brachial artery can be reduced by preferential use of proximal radial artery inflow for the initial procedure or as treatment for steal.¹³³, ¹³⁴

Between 50% and 66% of patients who develop steal do so ≤1 month of surgery.¹³⁵ Steal syndrome may occur immediately or evolve over several weeks and is often exacerbated during dialysis.¹²⁷, ¹²⁸, ¹³¹, ¹³⁶, ¹³⁷ The diagnosis is predominantly clinical and confirmed by unilateral neurologic complaints associated with digital tissue necrosis, pallor/cyanosis of the distal extremity, reduced arterial flow distal to the anastomotic site, and reversal of flow in the distal artery.

Complicating an accurate diagnosis in these patients is the recognition that digital gangrene is probably due as much to advanced atherosclerosis in the hand and forearm as to arterial flow diversion.¹³⁸ Yeager et al¹³⁸ found an equal distribution of digital gangrene in extremities contralateral to the access and confirmed the severity of radial, ulnar, and digital arterial occlusions. Thus, arteriography is useful to define the problem and may identify an unexpected proximal stenosis.

The diagnosis of steal is less likely when AV access flow is lower than expected or necrosis is present without other characteristics of steal. When ulceration and localized edema are present, steal must be differentiated from regional venous hypertension. When the complaints are only neurologic, consideration should be given to IMN and entrapment.

A critical but infrequent and easily overlooked problem associated with steal syndrome is proximal arterial stenosis.¹³⁹, ¹⁴⁰, ¹⁴¹ Just as exercise brings on symptoms of claudication with subcritical stenoses, increased flow demand associated with an AV access may unmask arterial stenoses that were not significant at resting flows. Although upper extremity occlusive disease is generally uncommon, it should be suspected more frequently in patients with ESRD. Contrast arteriography may be beneficial in planning treatment and an endovascular approach may simplify correction.¹³⁹, ¹⁴⁰, ¹⁴¹ A preoperative evaluation of adequate proximal inflow is a familiar consideration when a lower extremity access is constructed.¹⁴⁰

An important differential diagnosis to consider in a patient with severe symptoms despite normal physical findings and a palpable pulse distal to the access is IMN.¹⁴², ¹⁴³ This diagnosis can be very difficult to make, because this form of steal affects only the median, radial, and ulnar nerves but not the skin or muscles.

A thorough physical examination before an AV access is performed includes a blood pressure examination of both upper extremities and an Allen test to confirm the presence of an intact palmar arch. Routine testing beyond a physical examination is not necessary unless the results are abnormal.¹⁴⁴

Pathophysiology and diagnostic testing 

Clinical evidence of flow diversion is observed in >90% of upper extremity AV access when evaluated by Doppler augmentation or pressure studies. Approximately one-third of a prospective study cohort had no radial pulse after brachial AV access was constructed.¹²⁸ About 73% of radiocephalic AV access and 91% of brachial-axillary, prosthetic AV access (8 mm) demonstrated reversed flow in the distal artery grafts.¹⁴⁵

Supporting the clinical observation that brachial inflow is associated with flow-related steal are studies with ultrasound dilution and electromagnetic flowmetry in newly constructed AV access.⁹⁵, ¹⁴⁵ Both methods consistently reported that brachial-based AV access had twice the flow of radial-based AV access.⁹⁵, ¹⁴⁵ Arterial steal has been more pronounced with lower extremity AV access and was once considered a major negative factor to their use.¹⁴⁶

Attempts to predict symptomatic arterial steal syndrome preoperatively are confounded by the high incidence of flow diversion after an AV access is constructed. Various investigators have used digital plethysmography in an attempt to characterize a critical threshold for ischemia. Although not always predictive, these thresholds offer some guidance for flow-adjustment therapies. The proposed criteria are pressures of 50 to 60 mm Hg or an index of 0.4 to 0.6 measured with a digital or forearm cuff after AV access construction.¹²⁶, ¹²⁸, ¹³², ¹⁴⁷

In patients with unrecognized or uncorrected steal, persistence of severe ischemia may produce devastating results, such as a nonfunctional extremity with unremitting chronic pain or gangrene with loss of digits or limbs.⁵³, ⁷², ¹²⁷, ¹³⁰, ¹³⁵, ¹⁴⁸

Management, treatment, and results 

When severe hemodynamic steal syndrome occurs or IMN is diagnosed, immediate ligation or physiologic restoration of flow is appropriate. If intervention is delayed ≥1 week, reported results are poor and intervention is likely to produce little change or improvement.³, ¹²⁴, ¹²⁷, ¹³¹, ¹³⁶, ¹³⁷, ¹⁴² In a small series of four patients, the AV access was deconstructed in each patient but only after 8 weeks. The pain syndrome improved after 12 months, but motor function did not improve.¹³⁶ Redfern and Zimmerman¹²⁷ reported partial or complete recovery of motor and sensory findings in seven of eight subjects when intervention occurred between 1 day to 6 months after AV access construction.¹²⁷ Although the symptoms appeared to be less severe, two of six subjects who were treated ≤2 weeks of access construction achieved better resolution of symptoms.¹³¹ Claw hand with severe persisting pain may result when corrective surgery is unsuccessful.³, ¹³⁷

The simplest and most reliable method for treating dialysis access–induced ischemia is ligation of the conduit. However, in addition to sacrificing the access site, this strategy requires placement of a new AV access and is of particular concern for those with limited availability of access sites. Occasionally, angioplasty of a proximal arterial stenosis or coil embolization of distal reversed inflow may effectively address symptoms of steal.¹³⁹, ¹⁴⁰, ¹⁴⁹

Banding of an AV access can provide improved native arterial flow by deliberately narrowing the venous outflow to increase resistance through the access and thus increasing perfusion to ischemic distal tissue beds. Reducing the flow into the access is the goal of banding. Although this is more likely to succeed with a high-flow access, it may lead to thrombosis in those with a low-flow access. Some centers have successfully used controlled reduction of autogenous AV access flow by banding, but objective criteria measuring the amount of banding necessary to eliminate distal ischemia while maintaining a functional access is lacking.¹²⁶, ¹⁵⁰, ¹⁵¹ As a result, thrombosis of the access is common after banding. Although flow restriction has offered little advantage in upper extremity access, a controlled intraoperative anastomotic taper may revitalize consideration of lower extremity access procedures for individuals whose upper extremity sites are exhausted. In consecutive case series, this technical innovation successfully controlled steal with transposition of the larger diameter femoral vein.¹⁴⁶, ¹⁵²

Schanzer et al¹⁵³ in 1988 described a novel technique termed distal revascularization and interval ligation (DRIL), which offers preservation of the access with physiologic restoration of flow to the hand. A DRIL procedure involves two parts: a bypass and interval ligation of the native artery. The bypass graft is connected to the artery proximal to the access anastomosis and its outflow directed to the native artery distal to the access anastomosis. The reversal of blood flow is eliminated by ligation of the artery distal to the AV access, providing the distal vascular bed with normal perfusion pressure and flow.

Schanzer et al¹⁵⁴ reported their updated experience with DRIL procedure in 2004. Complete relief of symptoms was achieved in 34 of 42 patients. Only partial improvement was seen in the remaining eight patients due to irreversible ischemic neuropathic changes at the time of the procedure. The cumulative patency rate at 1 year was 96% for bypasses, 100% for autogenous AV access, and 73% for prosthetic AV access.

Lazarides et al¹²⁸ reviewed 180 AV accesses originating from the brachial artery in an effort to better characterize the relationship between steal and permanent neurologic dysfunction. Those with severe sensorimotor symptoms, as described earlier, were treated ≤24 hours with a DRIL procedure, with complete resolution of ischemic symptoms. An attempt was made to select those with greater severity of ischemia on the basis of a wrist/brachial index combined with selective performance of nerve conduction studies. Repetitive nerve conduction studies improved in most of the treated limbs.

The DRIL procedure is generally effective but is significantly more involved and morbid than banding. Although symptomatic steal from a distal radiocephalic AV access is uncommon, bypass and ligation is a less attractive option with these smaller arteries. Simple interruption of the distal radial artery to arrest the reverse flow is straightforward and may be approached surgically or with endoluminal coil embolization.¹⁴⁹ A major consideration with the DRIL procedure is loss of the native artery.

Other novel solutions have focused on the basic concept of rerouting the arterial inflow. Recognizing that brachial arterial origin was a common feature of symptomatic steal, others have reported success with extending the arterial end of the access distally to smaller arteries with revision using distal inflow (RUDI) and proximally to larger arteries with proximalization of arterial inflow (PAI).¹³⁴, ¹⁵⁵ Each of these management solutions is based on small case series involving an uncommon but clinically significant complication of AV access. More experience is needed before an appropriate solution can be recommended.

Recommendations 

When severe neurologic findings occur, physiologic ischemia should be addressed immediately because neurologic injury may not be reversible once it has occurred. The only treatment associated with neurologic improvement was correction of the ischemia at the earliest opportunity after recognition. Prevention is an even better approach; although it is impossible to avoid diabetic patients or women with ESRD, brachial arterial anastomoses should be avoided whenever possible. Although this is again subject to anecdotal evidence, alternative placement of the arterial anastomosis on the proximal radial artery is thought to reduce development of arterial steal syndrome and IMN.¹³³, ¹⁵⁶

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High-output cardiac failure 

Autogenous AV access for maintenance hemodialysis was usually well tolerated, but high-output cardiac failure was reported within a decade of its introduction.¹⁵⁷ Symptoms of heart failure have multiple etiologies and are very common in the ESRD population. This rare complication accounts for a minimal proportion of these.

High-output cardiac failure is primarily associated with autogenous AV access because no known report implicates a prosthetic conduit. Excessive AV access flow should raise reasonable suspicion, but this rare morbidity may still occur with normal AV access flows. As a result, delay in diagnosis is common.

Although high output cardiac failure remains uncommon, the current sparse literature attempts to address recognition using new and better physiologic measurement techniques. To date, the only convincing evidence that these symptoms are not from intrinsic cardiac disease or other correctable conditions is resolution of the complaints by ligation or banding of an AV access. Resolution of symptoms remains the sine qua none of diagnosis.⁹⁴, ¹⁵⁷, ¹⁵⁸, ¹⁵⁹, ¹⁶⁰, ¹⁶¹, ¹⁶²

Clinical features of access-related high-output cardiac failure 

High-output cardiac failure is defined as “symptoms of cardiac failure in the presence of an above-normal cardiac index (2.3 L/min/m²).”¹⁵⁸ The typical symptoms and findings are those of right heart failure: dyspnea at rest, dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea, reduced exercise tolerance, peripheral edema, pulmonary edema, cardiomegaly, increased blood volume, tachycardia, and a hyperdynamic cardiac output.¹⁵⁸ Although not very accurate for the diagnosis of high-output cardiac failure, temporary occlusion of the high-flow AVF may produce a reduction in pulse rate—the Nicoladoni-Branham sign. The decrease in pulse rate is a baroreceptor reflex mediated by the vagus.¹⁶⁰, ¹⁶³ One report estimated that the mean slowing of the pulse rate in recognized high-output cardiac failure was approximately 7 beats/min.¹⁶³

Because 31% to 36% of dialysis patients have cardiac failure at the initiation of dialysis therapy, the clinical distinction between high-output cardiac failure and intrinsic cardiac disease remains difficult.²⁷, ²⁸ Further complicating recognition is that heart failure subsequently develops in an additional 25% during their dialysis lifetime.²⁸ An abnormally elevated cardiac output that decreases with temporary occlusion of the AV access would help differentiate this condition from intrinsic cardiac insufficiency.

The more difficult diagnostic dilemma arises, however, when the cardiac output is relatively low. The poorly functioning heart may be unable to increase output when a large proportion of output is obligated to AV access flow. Thus, it is difficult to validate a specific diagnostic criterion for high AV access flow or an abnormal cardiac index due to the inherent variation between individuals. At one extreme, a young, trained athlete was able to compensate until autogenous AV access flow reached 19.4 L/min when symptoms of failure developed.¹⁶³ In contrast, others have reported high-output cardiac failure with AV access flows as low as 0.8 to 1.0 L/min.⁹⁴, ¹⁵⁷ According to the existing literature, the prognosis for high-output heart failure is excellent, as long as the cause is recognized and treated.⁹⁴, ¹⁵⁷, ¹⁵⁸, ¹⁵⁹, ¹⁶⁰, ¹⁶³ These guidelines attempt to define which ESRD patient is at risk of high-output cardiac failure.

Because high-output cardiac failure is rarely encountered in most dialysis units, diagnosis is likely to remain elusive. Although literature citations for this are exceptionally uncommon, if the problem is an obligate increase in cardiac output, it would be logical to expect that the pulmonary circulation would also be compromised in susceptible individuals. Indeed, several recent reports have now appeared demonstrating pulmonary hypertension that has responded to adjustments in the autogenous access.¹⁶¹, ¹⁶²

Improved methods for noninvasive characterization of AV access flow and cardiac output will distinguish AV access–related high-output cardiac failure from other common causes of these symptoms, such as anemia, hypertension, inadequate dialysis, and fluid/electrolyte retention.¹⁵⁷, ¹⁶⁰ Recent advances in medical management of these problems have addressed these issues with erythropoietin, better antihypertensive therapy, and improved dialysis techniques.

Pathophysiology: role of AV access flow and cardiac output measurements 

Development of validated methods for the minimally invasive determination of accurate AV access flow rates should help to define this major risk factor for high-output cardiac failure. The indicator-dilution technique with ultrasound detection was introduced in 1996 and measures flow in the access during the time of dialysis. The mean absolute error between duplicate access flow measurements was 5.0% ± 3.8%; the mean absolute error compared with duplex Doppler (off of the dialysis machine) was 9.2% ± 7.2% in seven subjects.¹⁰⁷ The technique has subsequently been validated by correlation against two other techniques: magnetic resonance arteriography (r = 0.91, P < .001), and intra-access flow pressure curves (r = 0.84, P < .001).¹⁰⁸ Serial ultrasound dilution measurements are now recommended for monthly surveillance of hemoaccess flows and have been used in randomized and prospective trials.², ¹⁰⁹, ¹¹⁰

Early reports describing this rare and unusual complication were summarized in a 1976 review that measured access flow with an electromagnetic flowmeter.¹⁵⁷ By 1995 “invasive measurements” were used to describe improvement in cardiac function before and after ligation¹⁵⁹ and duplex-derived AV access flows were described in 1998.¹⁶³ Subsequently, the ultrasound dilution method for measurement of AV access flow, a more accurate examination, has been used to attempt to define what constitutes “too much flow.”⁹⁴, ¹⁵⁸, ¹⁶⁴ But AV access flows as low as 0.8 to 1.0 L/min measured with the earlier techniques were believed to have produced high-output cardiac failure by the standard of clinical resolution of symptoms of failure.⁹⁴, ¹⁵⁷ Thus, the relationship between AV access flow and cardiac output probably involves more parameters than flow alone.

Physiologic changes accompanying an AV access become more pronounced as the volume of AV access flow increases, including increased heart rate, increased cardiac output, and increased blood volume. A strong relationship between access flow and cardiac output (r = 0.62, P < .01) was defined by the equation: AV access flow = 0.20 × cardiac output + 0.06.¹⁶⁴

Previous attempts to correlate clinical cardiac failure with AV access flow rates faltered because of the wide variation between individuals. On the basis of these findings, the ratio between autogenous AV access flow and cardiac output of >30% to 35% has been suggested as a screening threshold for serial surveillance for high output cardiac failure.¹⁵⁸, ¹⁶⁴

A summary of the findings from numerous reports indicates that “normal” autogenous AV access flows range from 1126 to 1922 mL/min; however, >15% to 23% were still >2.0 to 2.5 L/min.¹⁵⁸ Using serial ultrasound dilution in a prospective study of access flows between 6 and 28 weeks after construction, a study documented higher flows (mean, about 1300 mL/min) in both male sex and brachial vs radial, AV access. A trend toward lower flows was noted in diabetic patients.⁹⁵ Because a brachial AV access has almost twice the flow of a radial, one would expect these higher AV access flows to predispose to high-output cardiac failure.¹⁵⁸ MacRae et al¹⁵⁸ suggested that the diagnosis be entertained when the AV access flow rate >3 L/min or ≥30% of the ratio of AV access flow to cardiac output.

Management and treatment options 

Reduction of flow through the conduit or ligation of the AV access is appropriate management once the diagnosis is convincingly established. Although flow reduction procedures have had little success in relation to the more common problem of arterial steal, revision of an enlarged anastomosis or banding of a dilated autogenous access has been a more useful alternative for treatment of high-output cardiac failure. A German group commented that they had successfully managed this complication with banding and, therefore, never needed to ligate an AV access for high-output cardiac failure.⁹⁴ Successful resolution of the symptoms of failure by banding or anastomotic revision has been reported by several authors, with continued functional utility of the hemoaccess site.⁹⁴, ¹⁰⁷, ¹⁵⁷ Deconstruction of the AV access by ligation also resolves the symptoms of cardiac failure at the price of loss of the site; ligation may be the most appropriate treatment when no further need exists for the access—such as successful transplantation.¹⁵⁷, ¹⁵⁹, ¹⁶⁰, ¹⁶¹, ¹⁶², ¹⁶³ In one report, renal allograft function also improved.¹⁵⁹

Literature on this rare and unusual complication remains sparse and characterized by clinical case analysis. High-output cardiac failure is uncommon, but enough detailed reports have described resolution of the clinical findings with physiologic adjustment of AV access flow to justify consideration of the diagnosis in appropriate clinical situations. Because of the prevalence of cardiac failure in the dialysis population, consideration of high-output failure must be individualized. Currently, no specific threshold of AV access flow or cardiac output defines high-output cardiac failure. Although 2.5 L/min is the upper limit of flow in most AV access, this value exceeds that required to produce remediable symptoms in some reported cases. Further evaluation of the flow/cardiac output ratio may be beneficial. Response to treatment remains the sine qua none of this diagnosis.

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Neuropathy 

Neuropathic findings are generally more common than not in patients with ESRD. This section will focus on those neurologic symptoms relating to the management of the AV access. Most patients with ESRD have chronic, symmetrical polyneuropathy that responds to little besides transplantation. However, an astute clinician will also be alert for two other etiologies that may respond to intervention. Ischemic neuropathy related to AV access involves multiple nerves in a single extremity (monomelic) and is most likely to improve when corrected immediately. Entrapment neuropathy is a mononeuropathy amenable to focal surgical intervention.

Accurate diagnosis of postoperative sensorimotor complaints requires a satisfactory preoperative neurologic examination in addition to the obvious arterial and venous assessment. Although it would seem that these etiologies are relatively distinct, in practice, even experienced clinicians have found it difficult to differentiate between these neuropathic syndromes. Electrodiagnostic studies have a wide range of normal values, but may localize specific site dysfunction or confirm a difference between extremities when systemic neuropathy is present. By facilitating differential diagnosis, electrodiagnostic examination may reduce the delayed recognition associated with adverse outcome.

Ischemic monomelic neuropathy (ischemic neuropathy?) 

The rare but devastating complication of IMN is distinguished by dysfunction of multiple peripheral nerve trunks in a single extremity in the apparent absence of arterial insufficiency. Initial descriptions of IMN reported neurologic abnormalities in clinical situations where acute arterial ischemia was prolonged, but subsequently corrected. In practice, symptoms may begin within hours.

The term IMN was introduced by Wilbourn in 1983, a neurologist at the Cleveland Clinic, and was intended to distinguish isolated ischemia of the arterial supply to multiple nerves of a single extremity.¹⁴² The term refers to the combination of ischemia and neuropathy in a single limb (melos is Greek for limb). Descriptive and treatment recommendations are both derived from observational data.

Neurologic symptoms may become manifest immediately after construction of hemoaccess and should be specifically assessed.¹²⁷, ¹²⁸, ¹³¹, ¹³⁶, ¹³⁷ A major diagnostic feature of IMN is the absence of findings to suggest reduction or diversion of arterial flow. Another confounding factor delaying recognition is the high incidence of diabetic neuropathy in this population.¹²⁹, ¹³⁰, ¹³¹, ¹³⁶ When the clinical neurologic examination is equivocal, electrodiagnostic studies may facilitate diagnosis.

A deep, burning discomfort in the hand (or foot) dominates the sensorimotor features of IMN that is continuous and persists for months. Sensory impairment is most prominent distally, with pain, paresthesias, and numbness in the distribution of all three forearm nerves.¹²⁴, ¹²⁹, ¹³¹, ¹³⁷, ¹⁴² Sensory symptoms are usually more prominent than the physical findings, misleading the clinician to consider a psychogenic or radiculopathic etiology.¹⁴²

The motor features include weakness or paralysis of the muscles innervated by the three forearm nerves: radial (wrist and finger extension), ulnar (abduction and adduction of extended fingers), and median (thumb opposition, flexion, abduction). The thumb is unable to oppose the fingers (pinch). The end result is a claw-hand deformity with profound loss of function and severe neuropathic pain.¹³⁷

Wilbourn et al¹⁴² described multiple axonal-loss mononeuropathies that developed abruptly, simultaneously, and without evident muscle necrosis. In one of their three patients, IMN developed as a consequence of an autogenous AV access constructed for hemodialysis, and in the others, IMN was related to arterial ischemia that was usually corrected by the time the neurologic symptoms were recognized. In two of three patients in the Kaku et al¹⁴³ report, IMN was access related. Subsequent reports have focused on IMN encountered in hemoaccess patients. The major risk factors (brachial arterial inflow, diabetes, and usually female gender) are essentially those associated with arterial steal syndrome.⁵⁰, ⁵³, ⁷², ¹²⁵, ¹²⁷, ¹²⁸, ¹²⁹, ¹³⁰, ¹³¹, ¹³², ¹³⁶

It is hypothesized that IMN results from transient or localized diversion of the blood supply to the nerve trunk. Evidence from animal and human studies supports the selective loss of flow through the vasa nervorum.¹⁶⁵, ¹⁶⁶ Thus, although arterial flow diversion may be transient with minimal evidence of persisting ischemia, the sensitivity of neural tissue to ischemia (even though transient) may render it at greater risk for prolonged or permanent injury. IMN thus most likely represents the residual effects of a severe but subsequently collateralized arterial steal syndrome, with its effects manifested in the peripheral nerves.

Bolton et al¹²⁴ described restoration of radial pulses, but no neurologic improvement, when flow was reduced 6 weeks after construction of the AV access. In the AV access patient reported by Wilbourn et al,¹⁴² a radial pulse was absent for 11 days before autogenous AV access ligation and 3 weeks before neurologic consultation. In clinical practice and in the sparse literature on this topic, the identification of arterial flow disturbances are not clearly distinguished. Thus, IMN may be more simply conceived as a particularly severe, focal neurologic consequence of arterial steal syndrome and treated accordingly.

“EMG [electromyography] findings are suggestive of axon-loss lesions of motor and sensory nerves supplying the distal portion of one limb.”¹⁴² Reduced amplitudes of nerve conduction are observed in the forearm and hand, with the greatest reduction in the sensory fibers. Denervation is more severe distally, and the needle examination gradually reverts to normal as one progresses proximally, suggesting there is not a single site of infarction of a proximal nerve trunk.¹⁴² Large and small axonal injury is present without predilection for one size.¹⁴² Electrodiagnostic studies have been advocated to clarify the differential diagnosis.¹²⁷, ¹²⁸, ¹³¹, ¹⁴³

Recognition of IMN is difficult because it occurs so infrequently. A delay in diagnosis is common and may compromise outcome.¹²⁸, ¹³¹, ¹³⁶, ¹⁴² The symptoms are commonly attributed to anesthesia (such as axillary block), positioning, or surgical trauma.¹³¹, ¹³⁶ The distinction between IMN and arterial steal is probably artificial. Limbs manifesting clinical symptoms of IMN should be managed aggressively in the presence or absence of hemodynamic steal.

Recognition of IMN is the indication for deconstruction or revision of the AV access. IMN is best managed with immediate sacrifice of the AV access or rerouting of arterial inflow as described in the previous section on arterial steal syndrome.³, ¹²⁸, ¹³¹, ¹³⁶, ¹³⁷ The KDOQI Clinical Practice Guideline 5.6.2 recommends emergency vascular access surgical consultation for these symptoms.²

Peripheral nerve compression syndromes 

Peripheral nerve compression syndromes in the chronic hemodialysis patient may be amenable to surgical intervention. The most common of these is median nerve compression at the wrist from carpal tunnel syndrome; less frequently encountered is ulnar nerve compression in the cubital or ulnar canal. The differential diagnosis is complicated by the high incidence of concomitant uremic or diabetic polyneuropathy. Outcome is compromised by delayed recognition and treatment.

Median nerve compression in hemodialysis patients was reported ≤10 years of the introduction of the autogenous AV access.⁷¹, ¹⁶⁷ Clinical features of median nerve entrapment consist of pain, numbness, and tingling in the median nerve distribution to the palm. The pain component is often greatest in the nocturnal hours and usually worsens during dialysis.¹⁶⁸, ¹⁶⁹, ¹⁷⁰, ¹⁷¹, ¹⁷² Atrophy and weakness of the thenar muscles are clinically manifest as inability to pinch between the thumb and index finger; motor dysfunction is a late but more specific finding and suggests a less complete or prolonged recovery. Even in nonrenal populations, clinical diagnosis is difficult.¹⁷³, ¹⁷⁴ In the general population without renal failure, approximately 15% of patients offer appropriate complaints, but only 2% to 3% are confirmed to have median nerve entrapment.¹⁷³ Diagnosis and treatment decisions are often made on a clinical basis alone; however, electrodiagnostic studies are the most accurate adjunctive test despite recognized false-negative and false-positive results.¹⁷³, ¹⁷⁴ They are particularly useful when symptoms are suggestive—but not classic—and coexisting neuropathy is present.

Substantive differences probably exist between median nerve compression in the population at large and that on hemodialysis. A 10-fold increase in incidence occurs, the nondominant hand is more often symptomatic, male gender is more predominant, outcomes are less complete, and postoperative recurrence is a real issue.¹⁶⁷, ¹⁶⁸, ¹⁷² Although compression neuropathy may occur earlier, symptoms are most frequently manifest after 6 to 8 years on hemodialysis.¹⁷⁵, ¹⁷⁶ The probability increases with the length of time on dialysis; for example, compression neuropathy was diagnosed in >35% of individuals who have received >5 years of hemodialysis compared with 10% of those on dialysis <5 years.¹⁶⁸, ¹⁶⁹ The probability is >60% if the patient has been on dialysis for >10 years. If neuropathy was already present, the incidence was 59% at 5 years; overall, 31% of a hemodialysis population had findings of carpal tunnel syndrome.¹⁶⁸

The differential diagnosis is significantly less distinct in the ESRD patient, and even well-trained examiners have had difficulty distinguishing nerve compression symptoms from diffuse systemic neuropathy and arthropathy.¹⁷¹ As might be expected, the incidence of entrapment neuropathy is higher when electrodiagnostic studies are used for the diagnosis.¹⁶⁸, ¹⁷⁵, ¹⁷⁶

Enlargement and calcification of the median artery, which accompanies the median nerve through the carpal tunnel into the palm, is an unusual etiology of carpal tunnel syndrome.¹⁷⁷, ¹⁷⁸ Diffuse calcification of the media results in enlargement of the external diameter of the artery that exceeds a critical threshold in this unyielding restricted space. The diagnosis may be suspected on review of plain hand films when the bony structure is assessed for osteoarthropathy.¹⁷⁷ Resection of the enlarged calcified median artery is preferred; however, if a tourniquet is used, it must be released to assess whether median artery resection results in circulatory compromise to the hand.¹⁷⁷, ¹⁷⁸ If the artery is thrombosed, resection is uncomplicated; however, dissection and reimplantation may be required if it is the sole blood supply to the index or middle fingers.¹⁷⁸

Ulnar nerve entrapment neuropathy has also been reported in hemodialysis patients.¹⁶⁸, ¹⁷⁰, ¹⁷¹, ¹⁷⁹, ¹⁸⁰, ¹⁸¹ The clinical features of ulnar nerve entrapment include pain, paresthesia, and sensory loss to the ulnar aspect of the fourth and the entire fifth digit; weakness of the dorsal and volar interosseous muscles (abduction and adduction of the extended digits) and hypothenar muscles (atrophy and weakness of forceful grasping).¹⁶⁸, ¹⁷⁹ Compression of the ulnar nerve in the ulnar tunnel at the wrist (Guyon's syndrome) is characterized by a similar distribution of symptoms. The cubital and ulnar tunnels are both managed by decompression. Although entrapment is usually considered as a mononeuropathy, median and ulnar entrapment may occur together—a difficult diagnosis indeed.¹⁶⁸, ¹⁷⁰, ¹⁷⁹, ¹⁸⁰, ¹⁸¹

Electrodiagnostic studies may include ulnar, median, and peroneal nerve conduction studies and electromyography; two abnormal nerves in a single extremity or symmetrical dysfunction suggest a diagnosis of polyneuropathy.¹⁶⁸, ¹⁷¹, ¹⁷³, ¹⁷⁴, ¹⁷⁵ However, results of electromyography and nerve conduction studies are abnormal in many more patients than those exhibiting clinical findings. When the diagnosis is based on electrodiagnostic studies, peripheral nerve dysfunction is identified with equal frequency in the extremity contralateral to the AV access.¹⁷⁵, ¹⁷⁶ Some authors have recommended annual lower extremity electrodiagnostic studies because the role of entrapment is obfuscated by the frequency of coexistent polyneuropathy.¹⁷¹, ¹⁷⁵ Although earlier KDOQI guidelines specifically state that there is compelling indication for electrodiagnostic studies in asymptomatic patients, most hemodialysis patients do have some peripheral symptoms.¹⁸² Delay in diagnosis is common and can be partly attributed to patient reluctance and to both steal syndrome and coexisting neuropathy.

Although entrapment neuropathy is often assumed to be directly related to the access, this cannot be clearly discerned from the available data. Some reports have suggested that the equivalency of electrodiagnostic study findings in both upper extremities is evidence against this.¹⁶⁸, ¹⁷¹, ¹⁷⁵ The occurrence of carpal tunnel syndrome in patients with chronic peritoneal dialysis also suggests that a systemic pathophysiology underlies carpal tunnel syndrome.¹⁷⁵, ¹⁸³, ¹⁸⁴

Localized pressure elevation within the carpal tunnel is considered the primary pathophysiologic mechanism.¹⁶⁹, ¹⁷³, ¹⁸⁵ Normal pressures are 2.5 mm Hg in the neutral, relaxed position and rise to 30 to 31 mm Hg with flexion and extension.¹⁸⁵ The complete elimination of electrodiagnostic impulses when tissue pressure thresholds reached a critical value of 40 to 50 mm Hg suggest that localized neural ischemia is responsible for entrapment neuropathy; Semmes-Weinstein filaments and 256 cps vibratory stimulus were also found to correlate more closely with electrodiagnostic study findings than the traditional, widely accepted 2-point discrimination.¹⁸⁶ Abnormal, chronically elevated pressures in the carpal tunnel (24 and 32 mm Hg) were documented intraoperatively in patients with the clinical diagnosis of carpal tunnel syndrome.¹⁶⁹, ¹⁸⁵ Accumulation of β-amyloid is one postulated etiology that is consistent with the 6- to 8-year latency for development of compression neuropathies. Thickening of connective tissues is attributed to deposition of amyloid in the form of serum β₂-microglobulin.¹⁷¹, ¹⁸¹ This protein is normally found in the walls of leukocytes and is excreted by the kidneys; it accumulates in periarticular structures and is also associated with osteodystrophy and crippling arthropathy.¹⁶⁹, ¹⁸⁷

In patients without renal failure, mild symptoms of median or ulnar nerve entrapment are initially managed with splints, anti-inflammatory medication, and corticosteroid injection.¹⁷¹, ¹⁷³ Surgical decompression of the median nerve consists of transection of the transverse carpal ligament, which may be done as an open or endoscopic procedure. Although a reduction in the duration of pain from the scar was demonstrated with the endoscopic procedure, a randomized trial demonstrated no other differences between the two techniques, including return to work.¹⁸⁸

Ulnar nerve entrapment is relieved by surgical decompression of the cubital or ulnar tunnels. Surgical intervention is recommended for symptoms suggestive of axonal loss, such as persistent numbness, symptoms >1 year, weakness, or muscular atrophy.¹⁷³ It has been repeatedly emphasized that early recognition and treatment is associated with improved outcomes.¹⁶⁸, ¹⁶⁹

Vascular surgeons may be asked to approve use of a tourniquet for release of the flexor retinaculum. Although one author reported no autogenous AV access loss when tourniquet times were <45 minutes, the tourniquet was not advocated for prosthetic AV accesses.¹⁶⁹ However, two of 14 autogenous AV accesses thrombosed in another report.¹⁷⁰ If recognized after release of the tourniquet, revision and thrombectomy may be performed while in the operating room.¹⁷⁰ The procedure itself is quite rapid, but surgical consultants will have to determine whether the risk of thrombosis justifies adjunctive use of the tourniquet on an individual basis. When the use of a tourniquet on the arm bearing the AV access is being considered, a preprocedural duplex ultrasound examination should be obtained to determine whether the AV access is at risk due to stenoses or reduced flow.

Patients in the general population with median nerve decompression experience pain relief immediately. More than 70% reported complete satisfaction with surgical treatment, but return of muscular strength was usually delayed for months.¹⁷³ The results with AV access patients are less satisfying but follow a similar sensory-to-motor progression.¹⁶⁸, ¹⁸⁹ Prolonged symptoms may not respond, particularly when weakness and atrophy are advanced.¹⁶⁹, ¹⁷¹, ¹⁷² A “good” result was reported in 76%; those with preoperative symptoms for >2 years improved the least, recovering some sensation but little motor function.¹⁶⁹ A more detailed assessment described “good” relief of pain in 81%, relief of paresthesia in 51%, and improvement of grip strength of 8%.¹⁷² Carpal tunnel syndrome is particularly disabling for those performing self-dialysis, in whom compression release restored this capability.¹⁶⁷

Because almost all ESRD patients have some evidence of polyneuropathy, the symptoms suggesting entrapment will tend to be more advanced at the time of presentation; this combined with the difficulty of diagnosis and separation of symptoms between entrapment and other neuropathies may explain these disparate results. Despite this, once recognized, release of entrapped neural trunks is appropriate, with the caveat that those with motor findings or prolonged untreated symptomatic nerve compression will fare less well. The role of splints or injections has not been well addressed in the hemodialysis patient.

Unlike carpal tunnel syndrome in the general population, repeat surgical decompression is occasionally necessary for recurrent symptoms. Unfortunately, the result of repeat surgical release is less encouraging; even pain was not always relieved, and the duration of improvement was decreased.¹⁷⁰, ¹⁷¹, ¹⁷² The incidence of recurrent carpal tunnel syndrome varies with the institution but may be as high as 19% in a given hemodialysis population.¹⁷²

Entrapment neuropathy results in significant disability. The clinical distinction between median or ulnar nerve compression syndromes, steal, and polyneuropathy is often not easy. Ulnar compression syndromes are less commonly recognized, may occur in conjunction with carpal tunnel syndrome, and make differential diagnosis more difficult. Surgical decompression is a rapid, well-tolerated procedure that usually results in immediate pain relief. However, when motor dysfunction is present, recovery is slower and may never recover completely, particularly if compression symptoms have been present for a prolonged time or when there is pre-existing neuropathy. Electrodiagnostic studies may identify a focal nerve dysfunction but have not been a good predictor of success from release of the compression.¹⁷⁰, ¹⁷⁴

Polyneuropathy: uremic and diabetic 

Complicating the assessment of surgically treatable neuropathy is the high incidence of diffuse polyneuropathy in patients with advanced chronic renal failure. Fully 50% to 70% of patients with ESRD will have polyneuropathy.¹⁸³, ¹⁹⁰, ¹⁹¹ More than 60% of diabetic patients will have some form of neuropathy, the most common of which is polyneuropathy.¹⁹² The combination of diabetes and chronic uremia may be expressed as a more acute or more severe form of polyneuropathy.¹⁹³, ¹⁹⁴, ¹⁹⁵

The clinical and histopathologic findings of uremic neuropathy were recognized and described just before widespread application of transplantation or hemodialysis.¹⁹⁶ Before the advent of modern renal replacement therapy, insoluble metabolic abnormalities and coma generally dominated the care of the patient in terminal renal failure. As survival lengthened with dialysis therapy, these findings became more prevalent and the adverse effect on quality of life more apparent. Symptoms from uremic neuropathy are rare until the GFR is <12 to 20 mL/min (class 5 chronic renal failure).¹⁸³, ¹⁸⁹

The typical clinical findings usually begin in the lower extremity, but eventually may involve all four extremities.¹⁸⁹, ¹⁹⁶ Symptoms initially manifest as a burning pain in the sole of the foot with sensations of numbness or tingling; this is followed by loss of peripheral reflexes and vibration sense. The earliest motor complaint is usually weakness of ankle or toe dorsiflexion.¹⁸⁹ Symptomatic uremic polyneuropathy develops insidiously in most individuals; however, occasionally it will develop in a fulminant acute form.¹⁹⁷ Consistent with the systemic nature of uremic polyneuropathy, autonomic fibers are involved but usually produce minimal, clinically insignificant symptoms.¹⁹¹

The typical clinical findings result from axonal degeneration, with a particular predilection for large-diameter axons in the most distal nerve trunks of the extremities.¹⁸⁹, ¹⁹⁶, ¹⁹⁷, ¹⁹⁸ Distal segmental demyelination and axonal degeneration have been confirmed, but the mechanism remains unknown.¹⁸⁹, ¹⁹¹, ¹⁹⁷ Although frequently asymptomatic, slowing of sensory nerve conduction is the earliest neurophysiologic abnormality.¹⁸³

The symptoms of uremic polyneuropathy are rarely reversed by dialysis; occasionally they become worse, but the usual outcome is stabilization. Attempts to alter the progression with dietary therapy or manipulation of the mechanics and scheduling of dialysis, or both, have no effect in reversing uremic neuropathic symptoms.¹⁹¹, ¹⁹⁹ In contrast, the symptoms are often dramatically reversed after renal transplantation.¹⁸⁹, ¹⁹¹, ¹⁹⁸ After successful renal transplantation, reversal of wasting and weakness occur more slowly, with deep tendon reflexes recovering last during 9 to 12 months.¹⁸⁹

Other neurologic abnormalities (ie, dementia, disequilibrium syndrome, Wernicke's encephalopathy, etc) that may be seen in patients with renal insufficiency are beyond the scope of this review.¹⁸⁹

Diabetic polyneuropathy has been recognized in many forms and is generally thought to be the most common etiology of polyneuropathy. Mononeuropathy and autonomic dysfunction occurs in 50% to 60% of diabetic patients.¹⁹² The incidence increases with the duration of diabetes.¹⁹² Several forms are known. The most prevalent manifestation is a distal, symmetrical, sensory neuropathy, often described as having a stocking or glove distribution; the more debilitating form consists of burning or lancinating pain. It usually develops insidiously, continues to progress, and rarely improves. Sensory and autonomic findings are more prominent than motor impairment.²⁰⁰ Cranial nerve involvement most commonly affects the muscular innervation of ocular movement and will frequently improve on its own. The more central neuropathies are more likely to resolve and return to normal. Unlike the uremic form, diabetic autonomic neuropathy is likely to be symptomatic and is manifested as gastroparesis, impotence, nocturnal diarrhea, loss of sphincter control, or postural hypotension¹⁹², ¹⁹⁴; this too has a low expectation for improvement.

In a prospective, population based cohort, Dyck et al¹⁹² performed a longitudinal study using standardized and validated assessments of the type and stages of polyneuropathy. When evaluated by sensitive and comprehensive diagnostic methods, the incidence of neuropathy was 66% in insulin-dependent diabetes mellitus (IDDM) and 59% in noninsulin-dependent diabetes mellitus (NIDDM).¹⁹² The most common type was a polyneuropathy in 45% to 54% and visceral autonomic neuropathy in 5% to 7%. However, symptomatic neuropathy was observed in only 15% patients with IDDM and 13% with NIDDM. Severe neuropathic symptoms were significantly more common in those with IDDM (6% vs 1%). Interestingly, 10% of neurologic symptoms were not of diabetic etiology, and 7% had symptomatic carpal tunnel syndrome.¹⁹²

Despite its prevalence, the etiology of diabetic polyneuropathy remains unknown.²⁰⁰ Suggested etiologies include metabolic abnormalities, local hypoxia, thickened basement membranes, or perivascular inflammation.²⁰⁰, ²⁰¹ The range of histologic findings include axonal degeneration, segmental demyelination, remyelination, and hypertrophy of basal lamina.¹⁹⁴ In the fulminant acute form, this may advance at the rate of a few hundred micrometers per day.¹⁹⁴ Dying back fibers are a characteristic of centripetal degeneration of peripheral axons. Mild slowing of motor and sensory conduction is a common finding in the diabetic patient, with or without diabetic symptoms; more severe symptoms are associated with further decreases or absence of conduction.¹⁹²

Once diabetic neuropathy has developed, there is rarely a specific remedy. Level I data have demonstrated that tightly controlled glucose monitoring reduces the likelihood of developing neuropathy in IDDM.²⁰² The effect of pancreatic transplantation on diabetic neuropathy has not been clarified; however, one long-term study observed continued, slow improvement in neurophysiology in patients observed for up to 10 years.²⁰³

Symmetrical distal sensory findings are common to both uremic and diabetic etiologies. Acute onset and rapid progression of severe neuropathy has been reported for both diabetic and uremic etiologies.¹⁹³, ¹⁹⁴, ¹⁹⁵ When both occur together, however, functional deterioration can be accelerated even further. Beginning with the typical distal sensory dysfunction, this form may progress within months or years, leaving patients with an inability to stand or walk.¹⁹³, ¹⁹⁵

The clinical effects of uremic or diabetic peripheral polyneuropathy are essentially indistinguishable; however, symptomatic autonomic neuropathy is more likely to result from diabetes. The severity of the typical distal, symmetrical sensory neuropathy correlates with the duration of the diabetes and with the duration of dialysis-dependent chronic renal failure. Diabetic patients who require dialysis are subject to greater severity of clinical symptomatology. Recognition of uremic or diabetic polyneuropathy confounds the recognition and may delay intervention of surgically amenable compression or ischemic neuropathy. Electrodiagnostic studies may help to distinguish these etiologies in symptomatic patients.

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Author contributions 

References designated with * are relevant randomized controlled trials, meta-analyses, or systematic reviews.

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