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Hemodialysis Access: Nonthrombotic Complications
The National Kidney Foundation Kidney Dialysis Outcomes Quality Initiative (KDOQI) has updated guidelines for 2019. Recognized complications are: bleeding, infection, aneurysm/pseudoaneurysm, seroma, access-related hand ischemia (ARHI) or steal syndrome, venous hypertension, neuropathy, and cardiopulmonary complications.
Bleeding
The most frequent bleeding complications are prolonged access-site bleeding and easy bruising. Needle dislodgement is extremely rare. End-stage renal disease (ESRD) is associated with increased gastrointestinal bleeding, spontaneous retroperitoneal bleeding, and hemorrhagic transformation of stroke. Contributing factors include anemia, acquired defects of primary hemostasis, thrombocytopenia, repeated procedures, and medications.
Etiology
At normal hematocrit levels, platelets and plasma reside at the vessel periphery, facilitating activation and aggregation at injury sites. In anemia, rheology changes. As hematocrit declines, nitrous oxide (NO) activity increases, causing vasodilation and platelet inhibition. ,
Moderate thrombocytopenia is common in ESRD. Increased bleeding is predominantly due to uremia-induced platelet dysfunction. Risk increases markedly when BUN is >100 mg/dL (35.7 mmol/L). Uremia is associated with multiple defects of platelet function. ,
Many medications increase chronic kidney disease (CKD) bleeding risk. Beta-lactam antibiotics cause platelet dysfunction at high levels, and are only partially cleared by dialysis. At extremely high levels, penicillins alter antithrombin III activity, causing heparin-like abnormalities. Antiplatelet agents are common among HD patients due to high rates of cardiovascular disease (CVD). Su et al.’s meta-analysis of antiplatelet effect on major cardiovascular events in patients with CKD noted a beneficial effect on prevention of access failure (OR 0.52; 95% CI, 0.31–0.73), 15% reduction of odds of cardiovascular events, 23% reduction of MI. Antiplatelets are recommended for high risk patients by the National Kidney Foundation. A recent meta-analysis showed increased bleeding risk (RR = 2.78; 95% CI 1.63–4.76) with dual antiplatelet agents, but no increased risk with monotherapy (RR = 1.08; 95% CI 0.53–2.19), suggesting reserving dual antiplatelet therapy for secondary prevention of CVD following intervention.
Oral anticoagulation is also common in CKD, as almost 20% have atrial fibrillation. Most receive warfarin, however novel oral anticoagulation (NOAC) use is increasing. NOACs are renally cleared in varying degrees, and initial trials excluded dialysis patients. Fresenius Medical Care North America ESRD database demonstrated that dabigatran and rivaroxaban are associated with higher risks of bleeding than warfarin and can result in hospitalization or death. Apixaban (5 mg BID) has the same , or decreased bleeding risk, , decreased embolism/stroke risk, and decreased mortality in comparison to warfarin.
Persistent or recurrent access-site bleeding requires evaluation for causes other than coagulopathy. At least 40% of fatal vascular access hemorrhages are preceded by a herald bleed or access infection within the prior 6 months.
Treatment
Active Bleeding and Emergent Surgery
Rapid and short-term treatments include platelet transfusion and desmopressin (1-desamino-8- d -arginine vasopressin, DDAVP). Platelet transfusions work immediately, lasting 4 to 5 hours. DDAVP (0.3–0.4 μg/kg administered intravenously or subcutaneously) induces rapid release of autologous vWF and factor VIII transiently decreasing protein C activity. Tachyphylaxis typically develops after a second dose.
Prolonged effects occur with cryoprecipitate, a plasma derivative rich in fibrinogen, vWF, and factor VIII, works within minutes, maximal effects 4–12 hours, lasting up to 24 hours. , Anaphylaxis and hemolysis are rare. If ACT is elevated, protamine (up to 1.5 mg/100 units of heparin) can be administered. Recombinant factor VIIa may be used “off label” as rescue, but carries risk of systemic thromboembolic complications.
Elective Surgery
Preoperative planning should minimize platelet dysfunction and correct anemia. Hemoglobin <10 g/dL is present in at least 20% of ESRD patients. Adequate hematocrit facilitates platelet function. Recombinant human erythropoietin induces erythropoiesis, but takes several weeks. Erythropoietin increases expression of GP-IIb/IIIa and enhances platelet aggregation. , Platelet function can also be improved by scheduling surgery 24 hours after dialysis. Aspirin should be continued, but other antiplatelet medications held 1 week prior.
Conjugated estrogens, transdermal estrogen administered 2 weeks prior (50 μg/24 hours) for elective, 25–50 mg orally, or 0.6 mg/kg per day IV for 5 consecutive days for urgent interventions decrease bleeding by increased vWF synthesis, protein S and NO reduction, and bleeding time correction. , , Transdermal estradiol can be used long term in patients with chronic uremic bleeding as well, with less incidence of VTE than oral estrogens.
Postoperative Bleeding
Postoperative bleeding warrants prompt re-exploration for surgically correctable causes. Pharmacologic adjuncts, particularly protamine sulfate, should be considered if the procedure involved heparin. DDAVP may also be useful.
Infection
Infections are the second most frequent cause of death and access loss (20%), more commonly with prosthetics. Risk of sepsis-related death is markedly increased in CKD. The Society for Vascular Surgery reporting standards recommend classifying infections as early (<30 days) or late (>30 days), culture-positive or culture-negative, and by site of infection. Local signs include: erythema, skin breakdown, purulence, and exposed graft material.
Bacteriology
Most access-related infections are single-organism Gram-positive bacteria, predominantly Staphylococcus aur eus, with up to 40% methicillin resistant, followed by solitary Gram-negative organisms, and fewer polymicrobial. ,
Catheter Related
Temporizing catheters are associated with higher mortality and infection and lower patency. Catheters are the source of two-thirds of all infections and more than 80% of all bloodstream infections in hemodialysis patients. , In a Centers for Disease Control and Prevention study, use of a catheter, specific dialysis units, and malnutrition (albumin <3.5 g/dL) were independent risk factors for sepsis. Multiple trials have attempted to identify specific lock solutions to decrease infection risk but results are varied. Some show improved results, , while others show similar infection rates, but increased antibiotic-resistant species.
Epidemiology
Most infectious complications are local (61%). Access type is the most important factor with infections occurring in 11% of catheters, highest with temporary (RR 32.6), 9.3% of grafts, and 5.5% of fistulas. , , More recently Dialysis Outcomes and Practice Patterns Study showed HR for systemic infections of graft to fistula, 1.36, and catheter to fistula, 2.47.
Other factors include repeated cannulation, cannulation technique, poor hygiene, repetitive hospitalizations, duration of prosthetic AV access use, increased age, lower extremity location, and diabetes mellitus. , Gram-negative bacteria and associated remote infections or complications are more common with lower extremity prosthetic accesses. , The buttonhole technique is also implicated in higher infection rates.
Treatment
Suspicion of AV access infection can be evaluated with duplex, CT, PET and nuclear medicine scans, but does not replace physical exam. Broad-spectrum antibiotics should be initiated and tailored to appropriate organisms. Most commonly, vancomycin and gentamicin are chosen because of dosing ease and spectrum. In centers with a low prevalence of methicillin-resistant S. aureus , nafcillin, oxacillin, or cefazolin may be used. ,
Autogenous Access
Most autogenous AV access infections are associated with cannulation issues or hematomas, with bacteriology similar to prosthetic infections. They may present with cellulitis or abscess. Most respond to 2–4 weeks of antibiotics, rarely requiring surgery. Fistulas with intraluminal endovascular devices requires a prolonged course (4–6 weeks) of parenteral antibiotics and/or resection of prosthetic material.
Prosthetic Access
Prosthetic access infections are more complex. Greater than 50% of such infections involve only a discrete portion of the access. Attempts at salvage are reasonable for limited infections, allowing uninterrupted dialysis, site preservation, decreased catheter days and surgical complexity. Failure to improve with local resection may necessitate full graft excision. Thigh graft infections are more likely to involve Gram-negative bacteria (OR 10.22) and distant seeding (OR 5.24) including endocarditis, spinal abscess and septic arthritis.
Graft salvage is feasible when infection involves the mid-graft, allowing segmental resection following exposure of uninfected graft, tunneling through clean tissue planes and resection of involved segment. Early success is 90%. Unfortunately, recurrent infection occurs in up to 20%. Vacuum-assisted closure after open surgical debridement is an alternative.
Anastomotic Infection
Anastomotic infections require prompt complete graft excision to prevent disruption and hemorrhage. Low-virulence organisms may be amenable to subtotal graft excision, leaving a small arterial cuff to decrease dissection and complexity, but risks recurrent cuff infection (17%). In critically ill patients with grossly infected grafts, brachial artery ligation is a last resort. Cryopreserved grafts may allow site preservation with 1-year primary patency (PP) and secondary patency (SP), 42%% and 68%, and recurrent infection rates of 2.3%. Early infections, within days of access creation, require complete graft excision. ,
Thrombosed Grafts
Although removal of thrombosed AV grafts is usually unnecessary, several studies demonstrate the potential infectious source. , Thrombosed AV graft removal decisions should be based on signs of inflammation combined with absence of alternate sources.
Pseudoaneurysm and Aneurysm
While some dilation is expected with fistulas, >18 mm or 3× the matured diameter is considered aneurysmal. Both pseudoaneurysms and true aneurysms create issues with cannulation and cosmesis, as well as increased risk of thrombosis, pain, bleeding, and infection. Progressive enlargement can compromise overlying skin, which may lead to rupture ( Fig. 178.1 ).
Pseudoaneurysm
Pseudoaneurysms occur in 2%–10% of polytetrafluoroethylene (PTFE) grafts. They develop from repeated punctures, with perigraft hematoma formation. They are associated with outflow stenosis, with increased intragraft pressures, often in older grafts. Surrounding tissue ingrowth limits development, with poorly incorporated grafts at higher risk. Autogenous fistula pseudoaneurysms are less frequent, mostly related to cannulation. Asymptomatic pseudoaneurysms should prompt a change in cannulation, but is not a reason for intervention.
Treatment
Open
Open repair is recommended. Prosthetic graft pseudoaneurysm requires resection of involved segments with interposition graft or bypass with tourniquet for control. While new segments become incorporated, dialysis continues in preexisting incorporated segments. Extensive degeneration requires near-complete excision while maintaining anastomoses, with temporary catheter placement. Staged, segmental replacement is an option to avoid catheter placement, but requires two procedures.
Treatment of autogenous fistula degeneration options include conversion to a graft, maintaining only the arterial anastomosis or fistula reduction surgery (“aneurysmorrhaphy”). This involves resection of excess skin and a portion of the vein wall. Anastomosis is typically performed along lateral wall to prevent issues with cannulation along the suture line.
Endovascular
Endoluminal repair avoids use of catheters and allows identification and treatment of concomitant venous stenosis, present in up to 73%. , Cannulation difficulty may occur due to need to puncture stent graft through the pseudoaneursym and persistent cosmetic issues. Although minimally invasive techniques are appealing, higher cost, risk of infection (7%–37%), skin erosion (OR 5.0), thrombosis (17%–35%), and potential difficulty with access without good long-term patency remain concerns.
True Aneurysm
Aneurysm formation occurs adjacent to the anastomosis associated with hemodynamically significant stenosis, within cannulation areas, adjacent to mid-access stenoses, next to vein junctions and valves, or scarring from prior catheters.
Treatment
The preferred treatment for post-anastomotic aneurysms is relocation of the anastomosis. Comparable SP has been achieved for small dilations with angioplasty of stenotic anastomosis, but increases resolution time and may necessitate a catheter. Partial resection and patch angioplasty are alternatives. For mid-access aneurysms, fistulogram and treatment of associated stenoses are recommended. For diffuse degeneration partial aneurysmectomy is preferred, , with 6–10 mm catheter used as a dowel. Stapled repair has also been described, with good technical success. A modified technique is dissecting and resecting only the lateral wall and preserving an incorporated area to access which decreases the need for catheters. Treatment for aneurysms along the venous outflow tract is angioplasty, with selective stenting.
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