Overview of hemodialysis arteriovenous fistula maintenance and thrombosis prevention

INTRODUCTION — This topic provides an overview of general issues regarding arteriovenous (AV) fistula maintenance, including measures to prevent AV fistula thrombosis and management of the high-risk fistula. These same considerations with respect to AV grafts are reviewed separately. (See "Overview of hemodialysis arteriovenous graft maintenance and thrombosis prevention".)

RISK FACTORS FOR AV FISTULA THROMBOSIS — Many factors influence the choice of type and location for AV fistula creation and should be taken into account during patient selection and surgical creation of the fistula [1]. Although some of these factors affect outcomes, once the access has been placed, they cannot generally be modified.

Other factors that can lead to AV fistula dysfunction and thrombosis include:

●Preexisting stenotic lesions

●Cannulation injury/more frequent cannulation (ie, daily hemodialysis)

●Infiltration/hematoma formation

●Thrombosis of a pseudoaneurysm [2]

●Recurrent stenosis

●Prior stenting

ROUTINE FISTULA MAINTENANCE AND CARE — Proper fistula maintenance and care can help prevent injury to the fistula that might lead to problems. Proper cannulation technique is paramount for preventing injury to the fistula that might cause infiltration/hematoma formation that might lead to thrombosis or intimal injury that might lead to future stenosis.

Monitoring — All AV fistulas should be evaluated after their creation for appropriate fistula maturation and, once matured, examined at each dialysis session and monitored for any problems with dialysis. (See "Physical examination of the mature hemodialysis arteriovenous fistula" and "Clinical monitoring and surveillance of the mature hemodialysis arteriovenous fistula".)

Patients should be taught to examine the AV fistula between dialysis sessions for a thrill. If a thrill cannot be felt or there is a change from the prior examination or there is redness or swelling of the arm, the patient should inform the staff at the dialysis unit [3,4]. Patients with a functioning fistula who are not yet on dialysis therapy should also be taught to examine the access.

Cannulation and decannulation — Proper cannulation and decannulation are important for preventing complications that can reduce the survival of the AV fistula. Hemodialysis staff should be appropriately trained, and only those with technical mastery should be allowed to cannulate a newly created fistula [3].

Inspection prior to initial cannulation — The newly created AV fistula should be examined by an experienced clinician no later than four to six weeks after creation to determine if the AV fistula is clinically usable [5]. The AV fistula must be physiologically mature with an appropriate depth, length, and location that allows cannulation with a minimal risk for infiltration and the ability to deliver adequate blood flow [6]. The physical examination measures of maturation are reviewed separately. (See "Early evaluation of the newly created hemodialysis arteriovenous fistula".)

If the AV fistula is judged to be ready, cannulation and hemodialysis can be initiated. (See 'General procedure' below.)

Standard versus buttonhole technique — The standard technique for repeatedly cannulating an AV fistula is using the "rope-ladder" technique. Another technique is the buttonhole technique, also referred to as the constant-site technique. For patients undergoing standard dialysis at outpatient centers (three times weekly), we suggest the standard technique. The buttonhole technique may improve fistula survival but may be associated with more pain and an increased risk for bloodstream infection.

The rope-ladder technique simply involves rotating the cannulation sites between hemodialysis sessions, whereas the buttonhole technique deliberately cannulates the same site each time [7-10]. It takes up to 10 cannulations (more for patients with diabetes) to develop an epithelialized track that allows the use of a dull bevel (antistick) needle [9]. Once this occurs, standard sharp needles are avoided, though the ideal approach is still under study [11,12]. More pressure and more needle manipulation are needed to cannulate the AV fistula using antistick needles, which can lead to bleeding from the needle site during hemodialysis.

Although it had been suggested that the buttonhole technique may improve fistula survival, it may be associated with an increased risk for bloodstream infections [13-21]. Thus, it is not generally used among patients undergoing standard dialysis at outpatient centers. The more common practice in such units is to cannulate the AV fistula at different sites or rotating sites each dialysis session. An exception would be a short AV fistula that has insufficient length to permit rotation of cannulation site [13,22,23]. (See 'General procedure' below.)

Systematic reviews have compared standard with buttonhole cannulation [13,14]. Although observational trials have suggested a difference between the techniques for perceived pain with cannulation, among the randomized trials, there was no difference. Studies evaluating infection have reported a trend toward an increase in infectious events for those using buttonhole cannulation. The results of the two largest trials are briefly summarized.

●One trial compared AV fistula survival among 127 patients randomly assigned to standard or buttonhole technique at three outpatient dialysis sites [15]. At one year, AV fistula survival was lower for patients using the standard compared with buttonhole technique (86 versus 100 percent). Fewer patients using the standard technique were free from any intervention to maintain patency (49 versus 74 percent). However, 14 patients assigned to the buttonhole technique switched to the standard technique (eight patients who had pain associated with the technique, four in whom the buttonhole could not be established, and two who transferred out of the study center).

●In another trial of 140 hemodialysis patients randomized to either the standard or buttonhole technique, the rate of localized infection was higher for the buttonhole group (50 versus 22.4 per 1000) at eight weeks [19]. At 12 months, the number of needling-site abscesses requiring intravenous antibiotics was also higher in the buttonhole group (nine versus none). In a later follow-up of this trial, buttonhole cannulation was not associated with improved AV fistula survival [20].

The use of the buttonhole technique among patients who undergo short daily hemodialysis or nocturnal hemodialysis is discussed separately. (See "Short daily hemodialysis", section on 'Vascular access' and "Technical aspects of nocturnal hemodialysis", section on 'Fistulas and grafts'.)

General procedure — Regardless of which cannulation method is used, appropriate technique should be used. We recommend wearing gloves and masks during cannulation and appropriate hand cleansing and antiseptic cleansing of the cannulation site [24]. Full barrier precautions (gowns, drapes) are generally not needed. Dialysis unit personnel should wear a gown if there is risk of contamination of field (eg, uncontrolled diarrhea or wound drainage not contained by a dressing) [25].

These minimal standards reduce the transmission but are variably used in observational studies that have compared different dialysis facilities [26]. Preventing disease transmission is important, particularly given the increasing microbial resistance to mainstream antibiotics [25].

We generally cannulate a new AV fistula with a 17 gauge needle and limit dialysis blood flow to 200 mL/min, although there are no good studies that have shown a benefit to this approach. If successful, at subsequent dialysis sessions, the needle gauge can progressively be increased to 16 g and then 15 g, and the dialysis blood flow progressively increased from 200 to 450 mL/min. In general, a dialysis blood flow of 300 mL/min requires a 16 g needle, and a blood flow of 400 mL/min requires a 15 g needle. Each dialysis unit should have an established protocol for increasing the needle size and blood flow when initiating cannulation of new AV fistulas.

Cannulating a fistula — Our approach for cannulating an AV fistula is as follows [3]:

●Locate, inspect, and palpate the needle cannulation sites prior to skin preparation.

●Wash the access site using an antibacterial soap or scrub and water.

●Cleanse the skin using 2% chlorhexidine gluconate/70% isopropyl alcohol. Although less preferred, alternatives are 10% povidone iodine and/or 70% alcohol.

●If the skin is touched by the patient or staff after the skin prep has been applied but the cannulation has not been completed, repeat the preparation.

●Once the preparation is completed, apply tourniquet above the puncture site to increase venous pressure.

●The use of a wet needle is safer and also prevents the risk for a blood spray or spill, especially for the initial AV fistula cannulation. Attach a 10 mL syringe filled with 8 mL of normal saline solution to prime the AV fistula needle immediately before use, then clamp the needle.

●Apply traction to the skin in an opposite direction to the direction of needle insertion, avoiding excessive pressure that can flatten the vein.

●Insert the needle bevel up at an approximately 15 degree angle. Arterial needle direction can be antegrade or retrograde to direction of blood flow; venous needle should be antegrade to direction of blood flow.

●Once the vein has been penetrated, blood flashback will be visible (the needle may need to be unclamped to see the blood flashback); flatten the angle of the advance of the needle slowly. Remove the tourniquet, and tape the needle onto the skin.

●Confirm needle placement with a normal saline flush before connecting the needles to the blood pump and starting the pump. Blood return alone is not enough to show good needle placement. After flashback is visible, aspirate 1 to 5 mL with the 10 mL syringe, then flush the needle with the normal saline solution, looking for any signs of infiltration, then clamp the needle.

Decannulating a fistula — Proper needle removal prevents postdialysis infiltrations. Our approach to decannulating a fistula is as follows [3]:

●Remove the needle at approximately the same angle used for insertion. Using too steep an angle during needle removal may cause the tip to puncture the back wall.

●Apply the gauze dressing over the needle site, but do not apply pressure.

●Apply pressure only after the needle has been completely removed. Take care to properly clot the needle tract and not the fistula.

Cannulation difficulty or failure — As noted, veins that are difficult to see and feel should be identified with a duplex ultrasound and marked with an indelible marker prior to dialysis. (See 'Inspection prior to initial cannulation' above.)

If cannulation is unsuccessful, recannulation should not be attempted again until the site has healed.

Infiltration associated with cannulation sites can occur at any time during dialysis. The patient should be monitored closely during the dialysis procedure for signs and symptoms of infiltration (pain, bruising, oozing). If infiltration occurs, application of ice can help decrease the pain and size of the infiltration and may decrease bleeding time [3]. A quick response to a needle infiltration can help minimize damage to the access.

●Avoid lifting up on the needle after it is in the vein, and use care when taping needles in place. Improper needle placement or taping procedure can cause infiltration, as can improper decannulation.

●For infiltration occurring during the initial cannulation, release the tourniquet immediately.

●If the fistula has infiltrated, it is best to rest the fistula for at least one treatment, but, if this is not possible, the next cannulation should be above the site of the infiltration. If the patient still has a catheter in place, restart use of the fistula with one needle.

●For infiltration that occurs after the administration of heparin, leaving the needle in place and cannulating at another site may be appropriate.

Care between dialysis sessions — In between dialysis sessions, patients are instructed to keep the fistula clean and avoid wearing any clothing, jewelry, or other activities that restrict flow to or from the access. Bathing and other activities can be resumed as normally tolerated.

HIGH-RISK AV FISTULAS — (See 'Risk factors for AV fistula thrombosis' above.)

Nonmaturing AV fistula — For patients who have a newly created AV fistula that has not matured, an imaging study should be obtained. A postoperative ultrasound is frequently used first to determine the cause. The most common abnormality is a juxta-anastomotic stenosis (within 2 cm of the anastomosis), which can be treated with balloon angioplasty. Occasionally, ligation of collateral veins can help mature the fistula by redirecting all the arterial blood into a single venous channel. (See "Primary failure of the hemodialysis arteriovenous fistula" and "Endovascular intervention for the treatment of stenosis in the arteriovenous access".)

There are no proven pharmacologic therapies for improving AV fistula maturation, although some are under investigation and may prove useful. (See 'Ineffective and investigational therapies' below.)

Venous stenotic lesions — As with the developing AV fistula, stenotic lesions responsible for the failure of a matured AV fistula are predominantly related to a juxta-anastomotic lesion. Many therapies have been used in an attempt to reduce AV fistula thrombosis, including antiplatelet agents and fish oil [27]. None of these have proven effective for improving AV fistula survival or other clinically meaningful outcomes. (See 'Ineffective and investigational therapies' below.)

Treatment of stenotic lesions is balloon angioplasty; however, the need for angioplasty to correct a venous stenotic lesion is, in itself, a risk factor for future AV fistula failure. The AV fistula with recurrent stenosis has even higher failure rates. (See "Failure of the mature hemodialysis arteriovenous fistula" and "Endovascular intervention for the treatment of stenosis in the arteriovenous access".)

Thrombosis without identified stenotic lesion — On rare occasions, AV fistula thrombosis can occur in the absence of an identified stenotic lesion. The cause is unclear. A hypercoagulable condition is rarely the cause of AV fistula thrombosis [28].

AV fistula with aneurysm — Excessive dilation of the vein under pressure can thin the vessel wall and lead to focal aneurysm formation. Aneurysms uncommonly cause AV fistula failure unless they are very large. By contrast, pseudoaneurysms, which may result from repeated cannulation at one site (not to be confused with the constant-site or buttonhole technique), may rupture or become infected. The clinical features and management of aneurysms and pseudoaneurysms associated with AV hemodialysis are reviewed separately. (See "Arteriovenous graft creation for hemodialysis and its complications" and "Arteriovenous fistula creation for hemodialysis and its complications", section on 'Aneurysm/pseudoaneurysm/megafistula'.)

Secondary AV fistula — Among patients with a prior failed AV fistula, a secondary fistula is often possible (algorithm 1). The risk factors for AV fistula failure are likely similar to those for failure of the initial access; however, the fact that the first access has failed may compound the risk. (See "Hemodialysis access following a failed arteriovenous access".)

Failure of maturation and stenotic lesions associated with secondary AV fistulas are treated in an analogous manner as with the initial fistula. (See 'Nonmaturing AV fistula' above and 'Venous stenotic lesions' above.)

No pharmacologic therapies are known to increase the likelihood of secondary fistula success or improve long-term secondary AV fistula survival. Although these patients are at risk for AV fistula failure, assisted patency rates are similar to those of the initial access; however, as noted in the linked topic, these results reflect a selected group. (See "Hemodialysis access following a failed arteriovenous access", section on 'SAVF series results'.)

INEFFECTIVE AND INVESTIGATIONAL THERAPIES — Most pharmacologic therapies studied are aimed at preventing neointimal hyperplasia. None have proven useful for preventing thrombosis of AV fistulas.

Similarly, there are no proven pharmacologic therapies for improving AV fistula maturation, and none can be recommended. However, emerging evidence suggests that inadequate outward remodeling (ie, suboptimal sustained dilation of the AV fistula) is an important factor in nonmaturation. Some degree of neointimal hyperplasia is observed in almost all AV fistulas, and many AV fistulas mature in spite of the presence of a stenosis, provided there is adequate outward remodeling. Some research suggests that chronic kidney disease may reduce nitric oxide (NO) signaling [29]. Whether targeting NO resistance with novel agents will prove beneficial remains to be seen.

Antithrombotic therapies — In randomized trials, systemic anticoagulation at the time of AV fistula creation is associated with increased bleeding complications with no benefit in terms of AV fistula patency [30,31].

Many antiplatelet agents have also been used in an attempt to reduce AV fistula thrombosis, but none have been shown to reliably reduce the rate of AV fistula failure [27]. Among the many available agents, predominantly those that block cyclo-oxygenase (aspirin, sulfinpyrazone) and the platelet P2Y12 receptor blockers (clopidogrel, ticlopidine) have been studied for reducing AV fistula thrombosis. Other antiplatelet therapies, including the protease-activated receptor-1 antagonists (vorapaxar) and the glycoprotein IIb/IIIa receptor blockers, have not been evaluated for this clinical indication.

●Aspirin therapy does not appear to improve AV fistula patency rates. A large multicenter trial randomly assigned 407 of 567 patients (concurrent fish oil trial) with newly created AV fistulas to receive aspirin (100 mg/day) or placebo starting one day prior to AV fistula creation and continued for 12 weeks [32]. At 12 months follow-up, the risk of fistula failure was similar between the aspirin and placebo arms (45 versus 43 percent; relative risk [RR] 1.05, 95% CI 0.84-1.31) [32]. In an earlier trial, 92 patients were assigned to placebo or aspirin (Colfarit) starting the day before AV fistula creation and continued to 28 days afterwards [33]. In this study, aspirin did reduce the rate of AV fistula thrombosis (2 of 45 versus 11 of 47; 4.4 versus 23.4 percent). However, more patients in the placebo group had diminished arterial flow (six versus one), which may reflect use of inadequate vessels. The criteria for creation of an AV fistula have since been standardized, and the relevance of this trial in contemporary practice is questionable.

●Two small trials have compared clopidogrel with placebo in newly created AV fistulas [34,35]. In the larger of the two (n = 877), the rate of early thrombosis was reduced for patients who received clopidogrel (300 mg load, followed by 75 mg daily), but there was no difference in the proportion of fistulas that became suitable for dialysis (>300 mL/minute during 8 of 12 dialysis sessions) [34]. In the other, a smaller trial of 93 patients, the rate of primary fistula failure trended lower for clopidogrel (5.2 versus 21.6 percent; hazard ratio 0.72, 95% CI 0.41-1.01). The attempt at first hemodialysis using the newly created AV fistula was more successful in the clopidogrel compared with placebo group (92.3 versus 70.5 percent), though success rates through multiple sessions were not reported [35]. Clopidogrel was discontinued prematurely in 19.4 percent of patients primarily due to side effects (11 of 18 who discontinued).

●The results of small studies using ticlopidine have been mixed [36-38]. In a multicenter, randomized trial of 250 patients, ticlopidine did not significantly reduce AV fistula thrombosis compared with placebo (12 versus 19 percent; odds ratio [OR] 0.60, 95% CI 0.30-1.18) [36]. In another small trial of 42 patients, AV fistula thrombosis occurred in fewer patients who received ticlopidine compared with placebo (11 versus 47 percent, OR 0.13, 95% CI 0.02-0.76) [37].

Fish oil — A benefit for fish oil (omega-3-acid-ethyl esters) with respect to access survival as seen with AV grafts has not been demonstrated for AV fistulas, and we suggest not administering fish oil for the sole purpose of preventing thrombosis. Nevertheless, the administration of fish oil may be indicated for other clinically relevant cardiovascular benefits (eg, blood pressure lowering, reducing adverse cardiovascular events), particularly among individuals with coronary heart disease and its risk equivalents [39]. (See "Chronic kidney disease and coronary heart disease" and "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)

Omega-3-acid-ethyl esters inhibit cyclo-oxygenase (thereby prolonging bleeding times) and may reduce intimal hyperplasia, which is an important cause of hemodialysis AV access failure. While the majority of trials evaluating the effectiveness of fish oil for reducing AV access failure have been performed in the setting of AV grafts, one large multicenter trial randomly assigned 567 patients with newly created AV fistulas to receive fish oil (4 g/day) or placebo for 12 weeks [32]. At 12 months follow-up, no differences between the groups were observed for the primary composite outcome of AV fistula failure (47 percent in each group) or for any of the individual outcomes (fistula thrombosis, fistula abandonment, cannulation failure).

Phosphodiesterase inhibitors — The phosphodiesterase inhibitor, cilostazol, has been studied for maturation of fistulas. In a small nonrandomized study, 33 patients received cilostazol for ≥30 days prior to creation of a dialysis access, continuing cilostazol therapy for ≥60 days after surgery [40]. The matched control group included 116 patients who underwent the same procedure but did not receive cilostazol before or after surgery. The cilostazol group was more likely to experience fistula maturation compared with controls (88 versus 66 percent; RR 3.8, 95% CI 1.3-11.6). Additional controlled studies are need to confirm this effect.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Dialysis" and "Society guideline links: Hemodialysis vascular access".)

SUMMARY AND RECOMMENDATIONS

●Many factors predispose to primary failure or failure of the mature arteriovenous (AV) fistula. Proper routine AV fistula care and maintenance can help prevent injury to the fistula that can lead to dysfunction and thrombosis. (See 'Risk factors for AV fistula thrombosis' above.)

●The newly created AV fistula should be examined by an experienced clinician no later than four to six weeks after creation to determine if the AV fistula is clinically usable. If the AV fistula is judged to be ready, cannulation and hemodialysis can be initiated. If successful, the needle gauge and blood flow rate can be progressively increased at subsequent sessions. (See 'Inspection prior to initial cannulation' above.)

●Proper cannulation and decannulation are important for preventing complications, and only those with technical proficiency should be allowed to cannulate an AV fistula. (See 'Cannulation and decannulation' above.)

●In addition to routine monitoring in the dialysis unit, patients should be taught to examine their AV fistula routinely, and, if a thrill cannot be felt or if there is redness or swelling of the arm, the patient should inform the staff at the dialysis unit. Patients are instructed to keep the fistula clean and to avoid wearing any clothing, jewelry, or other activities that restrict flow to or from the access. (See 'Monitoring' above and 'Care between dialysis sessions' above and "Early evaluation of the newly created hemodialysis arteriovenous fistula" and "Clinical monitoring and surveillance of the mature hemodialysis arteriovenous fistula".)

●Two techniques are used for repeatedly cannulating the AV fistula: the standard, "rope-ladder" technique and the "buttonhole," or constant-site, technique. The rope-ladder technique uses a different cannulation site for each dialysis session, whereas the buttonhole technique deliberately cannulates the same site each time. For patients undergoing standard dialysis at outpatient centers, we suggest the standard technique (Grade 2B). The buttonhole technique may improve fistula survival, but it appears to be associated with more pain and an increased risk for bloodstream infection. (See 'Standard versus buttonhole technique' above.)

●Regardless of which cannulation method is used, sterile precautions should be used including appropriate hand cleansing, antiseptic cleansing of the cannulation site, and the use of gloves and masks during cannulation. Full barrier precautions (gowns, drapes) are generally not needed. (See 'General procedure' above.)

●The technique for properly cannulating and decannulating an AV fistula and techniques to manage common problems are described above. (See 'General procedure' above and 'Cannulation difficulty or failure' above.)

●For patients who have an AV fistula that has not matured, has matured but is dysfunctional, or has thrombosed, further evaluation should be undertaken to identify any stenotic lesions (juxta-anastomotic stenosis is most common), which can be treated with balloon angioplasty. (See 'Nonmaturing AV fistula' above and 'Venous stenotic lesions' above.)

●Although there is some support for use of pharmacologic therapies for the prevention of thrombosis in AV grafts, data for any benefit with AV fistulas are lacking. Thus, for patients with newly created AV fistulas, we suggest not using aspirin (Grade 2B), other antiplatelet agents (Grade 2C), or fish oil (Grade 2B) for the sole purpose of preventing thrombosis. Further, we recommend not using systemic anticoagulation given the increased risk of bleeding without demonstrated benefit (Grade 1B). Nevertheless, the administration of antiplatelet therapies and fish oil are associated with clinically relevant cardiovascular benefits (eg, blood pressure lowering, adverse cardiovascular events) and may be indicated, particularly among individuals with coronary heart disease and its risk equivalents. (See 'Ineffective and investigational therapies' above and "Chronic kidney disease and coronary heart disease" and "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)