Recommendations

Rationale

There are numerous circumstances associated with ACKD patient comorbidity that can influence the correct development of the VA, which requires prior awareness of all factors involved. During the review of the medical record, all the pathological antecedents that may increase the risk of AVF failure in some way or predispose to the appearance of morbidity related to its creation must be considered.10

Regarding the antecedents related to the risk of VA failure, firstly, there are the comorbidities associated with a bad prognosis of the VA in general (Table 1): advanced age, diabetes mellitus, peripheral arterial disease, smoking or obesity; and secondly, it is important to consider factors that will determine the optimal location of the arteriovenous fistula (Table 2): previous history of CVC or pacemaker (PM), previous VA, trauma or previous surgery in the arm, shoulder girdle or chest, and previous venous cannulations.10

Likewise, a particular underlying pathology, which may be aggravated by the presence of the new AVF, such as heart failure, or prosthetic valves, which may be infected if CVC is used, must be taken into consideration. Moreover, it is important to bear in mind the dominance of the upper limbs to minimise the impact on daily activity, as well as factors like anticoagulant therapy.

Finally, other factors which may affect the election of a given type of AVF should be considered (Table 3). These include life expectancy associated with the patient’s comorbidity, which may advise a more conservative approach by using a CVC, or patients eligible for transplant from a living donor, where a CVC may also be highly recommended.

The high prevalence of ischaemic heart disease in HD patients in our setting11 means bearing in mind that both the entire systemic situation and vascular tree of patients undergoing HD is significantly worse than the general population’s. Therefore, strategies must be established to choose the best territory in which to create the VA, taking into consideration the future of the VA and, of course, the patient.

→ Clinical question I Does the preservation of the venous network prevent complications/facilitate the creation of the arteriovenous fistula?

(See fact sheet for Clinical question I in electronic appendices)

Evidence synthesis development

In order to create an AVF, a suitable vascular bed must be available, both arterial and venous, and the anatomical and functional integrity of both beds is required. Given its deeper location, the arterial bed mainly depends on the patient’s comorbidity and is less exposed to external forms of aggression than the venous bed. As the superficial venous bed may deteriorate and this may have repercussions on the success of the future AVF, the need for measures of protection has to be addressed. The absence of these measures explains why many patients do not have a mature nAVF when they need it to start HD.

The superficial veins of the upper limbs are the most common venous access point in the hospital setting, given the ease of access and safety of the technique. In patients with multiple hospital admissions, this is precisely what causes the venous network to become impaired, as repeated and multiple cannulations produce trauma and the administration of medication provokes an inflammatory response at the vein level (chemical phlebitis).

Despite this, there is no available evidence in the form of observational studies or randomised controlled clinical trials which answers the question of whether the preservation of the venous network prevents complications or facilitates the creation of the VA. Thus, the recommendations made by both clinical practice guidelines (CPG) and the literature are based on the opinions of different groups of experts.12

Most of the CPG in use today,10,13-15 and the literature,16 recommend an aggressive policy aimed at preserving the venous network in HD candidates, through a series of measures prepared to this end (Table 4) and summarised in 2 directives:

• 1.

  Patient education related to the importance and the measures required to preserve veins in the upper limb.

• 2.

  Information and commitment on the importance of vein preservation among healthcare professionals.

From evidence to recommendation

There is no quality scientific evidence to back up an evidence-based recommendation. Therefore, based on good clinical practice criteria, after voting on the recommendation, GEMAV unanimously agreed to formulate a strong recommendation in favour of a strict preservation strategy to preserve the vascular bed, given the clear relationship between its preservation and the viability of the future VA.

Informing the patient about vascular access: when and how should it begin?

Information on HD should include details relating to the VA, the need for its creation, its importance, care and complications. This information must be reinforced in subsequent ACKD check-ups and should be continued when the VA has been created and during the HD programme.17 If a patient has to start HD urgently, he must be informed that a VA is required when this situation is detected. This information will be completed in accordance with their evolution and needs.

Time to start giving information about renal replacement therapy

The optimal time to start RRT requires adequate planning. There is an increased risk of mortality associated with inadequate nephrological care in pre-dialysis and to the use of a CVC as the first VA.18 A lack of organisation at this stage causes greater incidence of starting HD through a CVC with its associated morbidity. If the patient is referred to the nephrologist with enough time, he will receive adequate treatment and preparation from the pre-dialysis phase, as well as information on different RRT techniques: HD, peritoneal dialysis (PD) and kidney transplant (KT). In the Sociedad Española de Nefrología (Spanish Society of Nephrology) agreement document for managing ACKD, the preparation of patients for RRT is based on estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2, if applicable. At this time, in addition to the information about different RRT techniques, the patient should receive VA-related information.19 This appropriate referral implies a lower incidence of complications, especially infections and cardiovascular complications.

RRT should be considered when GFR is < 15 mL/min/1.73 m2 and, in general, dialysis is initiated with an eGFR between 8 and 10 mL/min/1.73 m2, the limit being around 6 mL/min/1.73 m2.19 Expectation of entry into HD is related to the time when detailed information about VA preparation has to be given to the patient. However, the nephrologist’s ability to predict the dialysis commencement is not totally precise and there is a tendency to underestimate the patient’s renal function, which means that HD may begin later than the time estimated.20 This delay is more common in elderly patients, primarily over 85. A number of unnecessary surgical procedures has been shown in this patient group, as they may die before starting dialysis.21 Thus, eGFR on its own may not be sufficient to decide on timing for VA creation.

Informing the patient about ACKD and the various RRT options needs to be coordinated with VA creation. The very creation of the VA may determine the decision to choose HD to the detriment of other techniques, like PD or even conservative management. A systematic review of the timing of the decision-making process of patients and caregivers on RRT22 shows that, from the patient’s perspective, waiting until the final phase of ACKD may not be appropriate. This has important implications, as an unwanted surgical procedure may be performed or the patients perceive that a decision has been taken for them regarding RRT, without their participation. Once the AVF has been created, the patient tends to reject another type of RRT, due to the preference for maintaining the status quo, so this type of treatment is not changed. Therefore, information related to VA creation should be given after the patient has been informed of the various options for RRT and has specifically chosen HD.22

Content and manner of providing the information

At the time of providing information to the patient about the VA, it should be borne in mind that from their perspective, in addition to renal disease and RRT options, the VA is among the main concerns.23 For the patient who needs one, living with an AVF is an important issue as they depend on it and have to provide the necessary care to maintain the access viable. This may generate the feeling of vulnerability, dependence, distrust and it may even become a stigma. Therefore, informing the patient about the need for a VA may generate a pronounced emotional response that should be taken into account.24 Indeed, one of the largest barriers to the creation of the AVF is the actual patient’s refusal.25

Because of all of this, the nephrologist must show particular sensitivity when informing the patient. There are studies which highlight that rejection of AVF creation may be explained by a previous negative experience and the information they receive from other patients and carers may not be well expressed. In addition, it is possible that the information has not been adequately assimilated as it is given at the same time as all the other details relating to entry into HD. Likewise, it is worth pointing out that patients are not usually aware that the use of CVC for HD carries a risk of mortality with it.26 Programmes aimed at helping patients decide which RRT technique to choose mean that patients opting for HD have a significantly higher likelihood of beginning treatment with an AVF.27 This is accomplished by motivating both patient and family from the creation phase to subsequent care. Moreover, the participation of other patients in the orientation of new patients can be of benefit. It has been shown that more patients with AVF recommend this VA than those who use a tunnelled CVC.28

Finally, when providing the patient with all the necessary information on VA, as well as the different forms of RRT, the nephrologist should give information about the different types of definitive VA and their characteristics (nAVF, pAVF and tunnelled CVC). The advantages and drawbacks of each one should be explained, highlighting the fact that the tunnelled CVC is not an acceptable alternative to AVF, if the latter is possible, given its high association with morbidity and mortality (section 6). The risks of tunnelled CVC should be systematically explained, making it clear that CVC is only indicated as a temporary measure pending AVF creation or when it is impossible to create one.

Ethical-legal considerations

Some literature reviews propose that there may be legal implications, in addition to ethical issues, if severe complications of tunnelled CVC arise in a patient who may be eligible for an AVF. In this context, in the same way as the patient signs a consent form before the surgical procedure, some groups suggest that this should be done before inserting the tunnelled CVC, and all the risks agreed to.29

Recommendations

→ Clinical question II In patients with chronic kidney disease, what are the demographic, clinical and analytical parameters in order to determine when the arteriovenous fistula (either native or prosthetic) should be created?

(See fact sheet for Clinical QUESTION II in electronic appendices)

Evidence synthesis development

For the patient with ACKD it is very important to have a functional AVF when starting HD to avoid the use of CVC and its associated comorbidity. This requires careful planning of its creation.

There are no clinical trials, only observational studies designed to determine when a definitive VA should be created. Recommendations in clinical guidelines are based on this type of studies and experts’ opinions and the proximity of HD is established according to levels in the decline in renal function. They highlight the importance of using these parameters adjusted for age, gender and body surface area. There are 6 CPG that assess the appropriate timing for VA creation in the literature review.6,10,13-15,30

Clinical practice guidelines recommendations

The previous edition of this guide, as well as the Japanese and Canadian guidelines, consider that the VA should be created when eGFR is less than 20 mL/min/1.73 m2. KDOQI (Kidney Disease Outcomes Quality Initiative), European and British guidelines recommend VA planning when eGFR falls below 30 mL/min/1.73 m2. The recommended minimum time elapsed between the creation of VA and the beginning of dialysis varies. The Spanish guidelines recommend 4 to 6 months; KDOQI and European guidelines, between 2 and 3 months; British guidelines, between 3 months to one year and Japanese guidelines, between 2 and 4 weeks. They all recommend assessing the earliest possible VA creation when ACKD evolves rapidly, there is VA failure and in patients with a CVC. They all agree that as the pAVF takes around 3 weeks to mature, it has to be created at least 3 weeks before initiation of HD. Finally, CVC does not require specific preparation, except that needed for the placement procedure itself, as it is for immediate use.

Available evidence

The latest review of clinical guidelines still fails to bring to light clinical trials, only observational studies. These publications emphasise the need for early referral to the nephrologist to guarantee adequate information on the various aspects of RRT and the possibility of starting HD with an AVF. Different observational studies made in recent years present data on how influential and important the time taken to refer the patient to the nephrologist and surgeon is regarding the appropriate moment to construct the VA.10,13-15,30

These observational studies show there is a direct relationship between the length of time in the care of a nephrologist and the significantly higher number of AVF created prior to the initiation of HD. This time period ranges from 431,32 to 12 months33,34, passing through 6 months.35,36

However, there have been changes in the latest recommendations for starting RRT. In recent years these criteria have evolved from higher levels of eGFR, > 15 mL/min, to much lower values approaching 5 mL/min. After the publication of clinical trials showing not only the lack of benefit, but even a higher morbidity with the early initiation of dialysis,37-39 the KDIGO guidelines40 (Kidney Disease Improving Global Outcomes) suggest that HD should be started when clinical symptoms of terminal CRF (chronic renal failure) are visible, seen with eGFR ranges between 5 and 10 mL/min/1.73 m2. In the agreement document for managing ACKD produced by the Sociedad Española de Nefrología (Spanish Society of Nephrology), RRT is considered when GFR is < 15 mL/min/1.73 m2, although an earlier start may be considered if there are symptoms of uraemia, hyperhydration, hypertension difficult to control, or a worsening nutritional status. In general, dialysis is initiated when GFR is between 8 and 10 mL/min/1.73 m2 and would be mandatory if eGFR was < 6 mL/min/1.73 m2, even in the absence of uraemic symptoms.19 However, in patients at risk, an early start for HD should be considered on a case-by-case basis.

From evidence to recommendation

In the absence of clinical trials or observational studies addressing criteria related to timing for VA creation and clinical trials addressed to HD commencement, GEMAV put this recommendation to the vote. It was thought appropriate to consider 2 options. For the first option—when eGFR drops below 15 mL/min and/or estimation of entry at 6 months—there were 15 votes, and for the second option < 20 mL/min and/or estimation of entry at 6 months there were 2 in favour and 3 abstentions. Therefore, considering that three quarters were clearly in favour of one of the options, the working group decided to formulate as a strong recommendation that the creation of the definitive VA should be requested when eGFR ≤ 15 mL/min, or with an estimation of entry into dialysis lower than 6 months.

Patients with rapid CKD progression, with a non-matured AVF or a non-tunnelled CVC should be given priority.

As pAVF take between 3 to 6 weeks to mature (except in those with immediate needling), we suggest this be the time period required for creation prior to the planned HD commencement (section 3).

Recommendations

Rationale

An important factor to consider in choosing the ideal VA location is the influence that this location will have on subsequent accesses. The surgeon must plan a long-term strategy for possible future access locations. Despite the absence of randomised clinical trials (RCTs) on the order to be followed in access creation, there is general consensus among different groups10,23,24 that access location should be as distal as possible, thereby allowing the creation of further VA in the same limb in the future. The VA should preferably be created in the non-dominant limb to maintain patient’s comfort. Furthermore, the creation of nAVF with preference to pAVF is recommended, although individual conditions may suggest a different approach.

Patient assessment must include a detailed clinical history to identify risk factors for early failure and lack of maturation of the nAVF. It is also necessary to perform a physical examination to detect limitations in joints, motor or sensory deficits, thickness of the skin and subcutaneous fat, limb oedema, presence of collateral circulation in the arm or shoulder, scars or indurated veins.

Physical examination must include pulse palpation to assess presence and quality, including the Allen test, measurement of blood pressure in both upper limbs and the examination of the venous system by palpation with and without tourniquet41 (Table 5).

Complementary examinations should be performed as a necessary and indispensable aid to define what strategy to follow when deciding which order to choose for VA creation.

→ Clinical question III What criteria are required for arteriovenous fistula planning (based on different types of fistula)?

(See fact sheet for Clinical question III in electronic appendices)

Evidence synthesis development

1.3.1 The role of Doppler ultrasound in arteriovenous fistula planning

Since its incorporation into daily clinical practice, different publications have attempted to determine the usefulness of Doppler ultrasound (DU) in the pre-operative assessment of VA candidates.

According to a review by Ferring et al.,42 in order to assess a suitable place for AVF surgery, physical examination must initially be performed in all patients, reserving pre-operative (DU) for certain cases: patients with poor physical exam (obese, no pulses, multiple previous surgeries on the limb), patients with possible arterial disease (elderly, diabetes, cardiovascular diseases) or in patients with possible venous disease (previous cannulation).

Later, Wong et al.43 published a systematic review of the literature, based on the three RCTs published to date on the systematic use of pre-operative ultrasound mapping.44-46 Two of the articles showed the systematic use of pre-operative DU was significantly beneficial, while in the third no benefit in terms of effective access use was shown to carry out HD. The authors conclude that the review suggests positive results in patients who underwent ultrasound mapping prior to VA creation, which may improve long-term patency rates.

Besides the reviews assessed while preparing the recommendations in this section, other more recently published systematic reviews have shown non-uniform results. Although a meta-analysis of five clinical trials suggests that the routine preoperative use of DU is beneficial47 in line with the publication by Wong et al.,43 a systematic Cochrane review48 emphasises that using preoperative imaging does not improve AVF outcome and that new studies with a better design are needed to confirm the result.

1.3.2 Vessel diameter as a criterion for arteriovenous fistula planning

Several studies have tried to determine the ultrasound parameters that may predict AVF outcome.16,42,49-51 Some degree of correlation has been found between the following ultrasound parameters and AVF function: diameter of the artery, presence of arteriosclerosis (measurement of intima/media thickness), flow characteristics at artery level (resistance index after reactive hyperaemia, peak systolic velocity), vein diameter and venous compliance.52

Among these, the parameter most widely documented and in which a higher level of evidence has been found as predictor of AVF function is the inner diameter of artery and vein measured by DU.53-59

Several articles have published series trying to document the minimum diameter of the artery and the vein associated with good AVF prognosis (Tables 6 and 7).49,53-58,60-63

1.3.3 Patient comorbidity as a criterion for arteriovenous fistula planning

There is considerable evidence of the influence of underlying pathology, comorbidities and the patient’s own parameters on the prognosis of the VA to be created.42,49,59

Advanced age

The available evidence suggests VA prognosis is considerably worse in older patients.64 The authors suggest that distal AVF should be avoided in the elderly.

Female gender

Contrary to general opinion and to some authors,65 the best available evidence does not demonstrate that female gender is a risk factor for AVF prognosis66; this is attributed to the small diameter of vessels found in female patients.

Diabetes

Different prospective series show the negative effect of diabetes on AVF prognosis, having less impact in proximal AVF.67,68

Hypotension

Evidence from prospective series suggests a negative effect of sustained hypotension in the prognosis of AVF due to an increased risk of access thrombosis.69,70

Smoking

Smoking has been associated with a worse AVF prognosis in published prospective studies.71-73

Obesity

While a worse prognosis in obese patients with Body Mass Index (BMI) > 30 has not been proved, the evidence available suggests that obesity with a BMI > 35 is a risk factor in AVF prognosis.74

Other factors

Several studies have tried to determine the influence of other factors in access prognosis. These factors are considered to have a minor impact, either due to the lack of clinical evidence (use of systemic heparin during surgery, type of anastomosis, suture technique), or because despite the importance they have shown in limited studies, there is a need for further studies to demonstrate their usefulness in clinical practice (intra-operative heparin dose, use of transdermal nitrates, range of distribution of red blood cells).42,49,59,75-77

1.3.4 Models/rules to predict arteriovenous fistula failure

Using data from 422 patients, Lok et al.78 developed a rule for predicting the risk of AVF failure. They found that poor prognosis factors include age ≥ 65 years, peripheral vascular disease and coronary heart disease, while being Caucasian was a good prognostic factor. These data were used to elaborate a classification of risk of AVF failure.

Despite the acceptable predictive capability shown in this study, there have been no subsequent studies to confirm its clinical usefulness; in fact, it has been questioned by other studies.79

1.3.5 Determining factors for the success of a prosthetic arteriovenous fistula

Rosas et al.80 found some factors of poor prognosis: presence of vascular claudication, number of previously implanted grafts, dialysis dependence at the time of surgery and the use of vascular clamps during the procedure. On the other hand, the use of the brachial artery and the axillary vein, acute-angle anastomosis and grafts of a specific brand (Gore-Tex®) were factors suggesting favourable prognosis.

From evidence to recommendation

The introduction of portable DU in the pre-operative examination of AVF candidates has undoubtedly helped professionals to decide when to create an AVF.

DU has proved to be an essential tool in those units where it is available because it provides a reliable image plus haemodynamic information on the vessels in the pre-operative evaluation.

The progressive increase in the age of patients candidates to arteriovenous fistula creation, with the resulting increase in associated comorbidities, as well as the high prevalence of obesity, often make it difficult to carry out a complete physical examination in these patients, so essential information required to create the AVF is missing (Table 5). In these cases, both clinical practice and the available evidence unanimously recommend the use of DU as the imaging test of choice, before requesting other radiological examinations (phlebography, magnetic resonance imaging).16,42,81,82

However, there is no unanimity in the available literature regarding DU use in patients with a favourable physical examination. There are studies documenting that routine pre-operative ultrasound increases VA patency.10,44,46,47,49,65,83 However, in most of these reports the benefit does not reach the level of significance needed to make a recommendation about the generalised use of DU.42,43,45 Thus, in fact, these authors do not recommend the routine use of DU because it has no proven benefits, both because of the delay other tests may cause and because of the possibility of ruling out AVF creation in vessels with borderline diameter. In contrast, the reasons given in favour of its routine use include the reduction in the number of unnecessary surgical interventions due to low vessel size, no creation of AVF with poor venous drainage, the detection of subclinical arterial disease and the better use of the available vascular bed.

This last point, together with the trend described in the literature, was the main argument which led GEMAV to unanimously decide to recommend the systematic use of DU in the pre-operative examination of all candidates for AVF. It allows physicians to non-invasively obtain a map of a patient’s entire venous capital during the pre-operative evaluation, thus allowing them to decide on the location of the VA bearing in mind the real options for future accesses.

During this examination, the diameter and quality of the arterial wall, as well as the anatomy and patency of the limb’s superficial and deep venous system, must be assessed by creating a map of the aforementioned venous capital of the patient.16,42,52,81,82,84

Current evidence does not allow for a recommendation regarding the minimum diameter of vessels to be used for the AVF; the decision whether the vein or artery should be considered apt for AVF creation must be taken in accordance with diameter – basically, the bigger the diameter, the better the prognosis – and with the available VA alternatives. In any case, in accordance with published articles, arteries < 1.5 mm and veins < 1.6 mm in diameter, following placement of a proximal tourniquet, are considered of dubious feasibility.

Finally, although the prognostic factors in each case should be taken into consideration, it is suggested that the VA location not be decided by taking into account any isolated clinical or socio-demographic factor, or any specific multivariate risk prediction model. It is recommended that the decision be based on a global assessment of each patient’s medical history, physical vascular examination, pre-operative DU and on their individual preferences.

→ Clinical question IV What risk factors have been shown to influence the development of limb ischaemia after arteriovenous fistula creation?

(See fact sheet for Clinical question IV in electronic appendices)

Evidence synthesis development

AVF creation in an upper limb determines significant changes in the limb’s haemodynamics. The direct communication created between the arterial and venous system, which avoids passing through the capillary bed, causes a shunt with a large flow rate that may compromise the vascularisation of the arterial bed distal to the access. In many cases of ischaemia, the situation is aggravated by the presence of previous arterial disease in the proximal or distal territories.

This can lead to the development of distal hypoperfusion ischaemic syndrome in the limb, known as “fistula steal”. This is an uncommon complication after the access creation, with an incidence ranging between 1% and 20%,85-87b but it may have serious consequences and could lead to important tissue loss and amputation.

That is why various authors have tried to identify epidemiological and clinical factors which may be associated with the development of this syndrome so that patients at risk of ischaemia following VA creation can be detected.

Type of arteriovenous fistula

The main prognostic factor, accepted by all authors, is the type of VA.10,85-89 Accesses with increased risk of ischaemia are nAVF created in the brachial artery (brachiocephalic, brachiobasilic and brachioperforating); 10-25% of patients with these VA present clinically relevant ischaemia. This percentage drops to 4.3-6% in pAVF, while nAVF created in the forearm and wrist are those with the lowest risk of ischaemia (1-1.8%).87 These authors associate this difference with the greater flow present in proximal AVF and the presence of collateral circulation through the ulnar artery, which decreases the severity of ischaemia in AVF in the wrist and forearm.

Peripheral arterial disease

The great prevalence of cardiovascular risk factors in the HD population implies a high incidence of patients with symptomatic peripheral arterial disease. Although this disease usually affects the upper limbs less than other territories, the presence of haemodynamically significant lesions has been reported in up to 62-100% of patients with distal hypoperfusion syndrome.86 The prior existence of these lesions, both in the proximal artery and distal trunk territories, is an important predisposing factor to the onset of ischaemic symptoms in the limb upon creation of the VA.86-88,90

Diabetes mellitus

The presence of DM is, for all authors, one of the main risk factors for developing ischaemia.86-88,90,91 Observational studies show that the presence of diabetes is a predictor for developing ischaemia.85,92 The effect on the distal arterial bed determines the lack of vasodilation capacity in that territory and the appearance of distal tissue hypoperfusion.

Advanced age

Advanced age, which is considered to be > 60 years, is widely accepted as a predisposing factor in the onset of ischaemia, due to a mechanism similar to the one in diabetic patients.87,88,90,91

Female gender

Female gender is unanimously considered in the literature to be an isolated risk factor for presenting ischaemia.85,87,88,90,91 The authors do not deter mine the mechanisms involved, although hormonal and vessel size factors are suggested.

Other factors

Different publications describe the influence of other factors on the development of ischaemia, such as time on dialysis,73 end-to-side anastomoses,85 previous VA in the same limb87,88,90 and racial factors.92 However, the potential influence they have in these cases is not unanimously accepted.

Regarding the drainage vein used in elbow nAVF, a direct comparison between brachiocephalic and brachiobasilic nAVF has not shown a difference in terms of incidence of ischaemia.85

Finally, despite the evident relationship between the blood flow in the AVF and the development of ischaemia, no direct relationship has been shown, probably due to the intervention of other factors in the physiopathology of the disease. Nevertheless, some authors recommend anastomosis creation < 7 mm to limit excessive flow rate to the VA.87

From evidence to recommendation

There are no systematic reviews or clinical trials on this subject. The level of evidence is limited to published observational articles and to experts’ opinion stated in the various clinical guidelines.

While there are well defined ischaemia risk factors, whose influence is unanimously taken into consideration (type of access, peripheral arterial disease, diabetes mellitus, advanced age and female gender), there are other factors whose role has not been well defined.

Furthermore, there are no published recommendations regarding the strategy to follow in daily clinical practice in the presence of these risk factors, which are highly prevalent in HD patients.

There is, however, widespread agreement among authors regarding the need for close post-operative monitoring of those patients considered high risk (diabetics, aged > 60, presence of peripheral arterial disease, female), so distal ischaemia can be detected and treated as soon as possible to avoid serious consequences. Authors also agree on the need to prioritise the creation of distal accesses in these patients over an access on the brachial artery.10,85-88,92

For all these reasons, although there are no systematic reviews or clinical trials on the subject, based on the published studies, the opinion of experts and good clinical practice, GEMAV suggests that firstly, surgical techniques aimed at minimising the risk of ischaemia be promoted; and secondly, that there must be close clinical monitoring of patients considered high risk after VA creation, in order to prevent the appearance of irreversible complications.

Recommendations

Rationale

Prioritising nAVF over pAVF is a basic recommendation in numerous clinical guidelines and among experts, given the low rate of complications and excellent long-term patency it presents once the nAVF has matured.

Arteriovenous fistula patency

Primary patency rates for nAVF at 6 and 18 months is 72% and 51%, while secondary patency is 86% and 77% respectively. In pAVF, however, primary patency at 6 and 18 months is 58% and 33% and secondary is 76% and 55%, respectively.93 The main disadvantage of nAVF versus pAVF lies in the high risk of primary failure, due to the high rate of immediate thrombosis (5-30% for radiocephalic nAVF) and in maturation failure (28-53%), compared to only 0-13% primary failure for pAVF in the forearm and 0-3% for pAVF in the arm.8

In addition, there has been a demographic change in incident patients starting renal replacement therapy (RRT) in recent years. This means that there has been a progressive trend towards a decrease in patency rates reported in the literature.94 Thus, the analysis of results from 46 articles between 2000 and 2012 provided by Al-Jaishi et al.94 estimate a primary failure rate for nAVF of 23%—significantly higher in distal nAVF (28%) than in proximal (20%). They found a primary patency (including primary failures) of 60% after 1 year and 51% after 2 years, with a significant difference depending on the location of the nAVF (distal or proximal) after 1 year, but not after 2 years. These same authors found a secondary patency rate of 71% after 1 year and 64% after 2 years, with no difference in the location of the nAVF.94 It has also been reported that the routine use of a preoperative ultrasound study may reduce immediate nAVF failures.46

Rate of complications

nAVF are associated with a decreased morbidity and mortality compared to pAVF and catheters (CVC).95 According to Ravani et al.,96 the use of pAVF and CVC versus nAVF is associated with an increased mortality of 18% and 53%, respectively. In addition, nAVF have a lower rate of infections than pAVF, which is lower than CVC.96,97

As a result of all this, when compared with nAVF, the risk of hospitalisation increases by 26% with pAVF and by 68% with CVC.96

Another advantage of nAVF is that they have a lower rate of re-intervention than pAVF, which implies a lower maintenance cost.98

Thus, in any patient who requires RRT using HD, the ideal VA must be created, one which allows appropriate dialysis, has greater patency and a lower rate of complications. The VA that brings all of these characteristics together is nAVF10,99-102 and, therefore, this must be the first VA to be considered. When nAVF cannot be constructed because there is no venous capital or venous capital is damaged, pAVF should be used99-101, while CVC placement must only be considered when neither of the above are possible or when HD treatment must be initiated without a mature VA.103,104

Permanent VA should be indicated on a case-by-case basis, depending on vascular examination, the patient’s previous VA, as well as other factors such as age, comorbidity and the urgency for VA use.10,82,99-101,105-108

In the case of nAVF, the most distal location possible should be chosen as first option when planning VA creation, in order to preserve the maximum peripheral venous network for future VA. All things being equal, the non-dominant limb should be prioritised to help facilitate patient comfort both during HD sessions and in their daily activities.109

2.2.1 Native arteriovenous fistula in wrist and forearm

Radiocephalic native arteriovenous fistula at the wrist (Brescia-Cimino arteriovenous fistula)

The radiocephalic AVF at the wrist, described by Brescia-Cimino in 1966, is still the VA reference for HD.10,110,111 It preserves proximal venous capital for future VA, has a low rate of complications, especially VA-induced ischaemia and infections, and those that mature correctly have an excellent patency rate.99-101,109 The main limitation of this technique is the relatively high immediate failure rate, which ranges between 10% and 30%, but reaches almost 50% in some groups, especially in diabetic, elderly and female gender.100,112,113 A further disadvantage of the radiocephalic AVF is its high incidence of maturation failure, so that approximately 30% of these AVF have not matured enough for use at 3 months.100,102,105 Primary patency at 6 months ranges from 65% to 81%; this is lower than the 79-89% found in pAVF, although they equal out after the first year, with fewer complications.100,101

Arteriovenous fistula in the anatomical snuffbox

The anatomical snuffbox AVF, using the posterior branch of the radial artery located between the tendons of extensor pollicis brevis and extensor pollicis longus as a donor, is used less frequently due to its greater surgical complexity. Despite this, results in units where it is normally performed are good114: 11% immediate thrombosis, 80% maturation at 6 weeks and cumulative patency at one and five years of 65% and 45%, respectively. In this case, its greatest benefit is that it does not exclude the possibility of performing a radiocephalic nAVF in the same limb if the access fails. Both sites allow proximal reconstructions in the forearm when either juxta-anastomotic stenosis or thrombosis appears.

Radiocephalic arteriovenous fistula in forearm

This technique differs from the previous one in that it is performed in a more proximal area; it is indicated as surgical treatment in AVF juxta-anastomotic stenosis in the wrist, and in cases of non-viability of the cephalic vein in the wrist, usually due to early bifurcations.

Radiobasilic transposition

When the cephalic vein in the forearm is not adequate for a radiocephalic AVF, a possible option before using more proximal veins is radiobasilic transposition.115,116 The basilic vein must be transposed from the wrist proximally towards the antecubital fossa and subcutaneously tunnelled as far as the radial artery to create anastomosis. The antebrachial basilic vein is usually free of previous vein cannulations. However, its lower consistency makes it more vulnerable to possible lesions during the transposition process, with a greater tendency to torsion, so its use in clinical practice is limited by the vein’s development and by the experience of the surgical team.

Other venous transpositions

When the radial artery is not suitable for radiocephalic AVF, other possible venous transpositions in the forearm include the cephalic or basilic vein, placed in the shape of a loop in the palmar face of the forearm, towards the proximal radial artery in the antecubital fossa.117 This is how different ulnar-basilic transposition options in the forearm, as well as brachiobasilic in the shape of a loop, and different configurations using the great saphenous vein have been reported.111 Its use is limited in practice to specific anatomical situations in certain patients.

2.2.2 Native arteriovenous fistula in the antecubital fossa (elbow)

According to the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines10 radiocephalic and brachiocephalic AVF are the first and second options for creating a VA, respectively.10 The antecubital fossa contains larger vessels, which usually provide higher flow and have lower rates of primary failure and alterations in maturation, while their main drawback is the shorter needling segment available and the fact that they limit subsequent use of a more distal access.

Brachio-cephalic arteriovenous fistula

The brachiocephalic AVF is the vascular access of choice for this location.6,10,109 It has the advantage over radiocephalic AVF of achieving higher flow and the cephalic vein in the arm is usually more accessible for needling and aesthetically more discrete than in the forearm. However, it may cause greater oedema in the limb and it has an increased risk of causing VA-induced distal ischaemia.

Brachioperforating arteriovenous fistula (Gracz arteriovenous fistula)

A widely used variant of the previous technique consists of creating the AVF between the brachial artery and the perforating vein in the antecubital fossa (brachioperforating AVF), using the technique described by Gracz118 and subsequently modified by Konner et al.67,119 in order to obtain arterialisation of both the cephalic and the basilic vein.120

Arteriovenous fistula using the proximal radial artery

As an alternative to the brachial artery, the proximal radial artery in the antecubital fossa can be used as a donor.113,119,121-123 This technique has certain functional advantages. The risk of VA-related distal ischaemia is lower when the donor artery is the radial, compared to procedures performed with the brachial artery. As this anastomosis is constructed on the radial artery, its smaller size favours the appropriate resistance of the new VA and minimises the risk of distal ischaemia. Likewise, as a lower flow in the AVF is obtained, it limits the cardiological impact in patients at risk. Moreover, venous confluence in this location allows the possibility of setting up a two-way flow in the venous drain.

In cases where few veins are available for needling, technical variations have been proposed to promote two-way flow in the veins distal to the AVF, mainly in the elbow, in order to increase the segment available for cannulation,124 by retrograde valvotomy of the drainage veins.125

The antecubital fossa presents multiple anastomoses between veins that may allow the intervention to be performed. Although short case studies are described in the literature, there is not enough documented evidence to determine its usefulness in practice and to assess the clinical significance of venous hypertension arising from this technique. As a result, its use is limited to cases with short needling trajectory in which this is anatomically feasible.111

Brachiobasilic arteriovenous fistula

Those patients who cannot have a radiocephalic or brachiocephalic AVF created may opt for a brachiobasilic AVF with venous superficialisation or transposition as an alternative to vascular prosthetic implants.126

The depth of the basilic vein protects it against repeated venipunctures so it tends to be preserved in HD candidates; however, this greater depth may cause difficulty when needling, requiring superficialisation. In addition, the trajectory of the basilic vein is adjacent to the neurovascular bundle in the limb, which leaves these structures vulnerable to potential cannulation lesions during dialysis. Therefore, as well as being superficialised, it can be transposed to an anterior and lateral location in the arm to move away from these structures and to improve patient comfort during dialysis.

Given that two surgical procedures are usually required, in clinical practice they can either be carried out in the same intervention, or in two procedures separated in time.

When the surgery is performed, the basilic vein is dissected and transposed; thus the new trajectory is created and finally the arteriovenous anastomosis constructed. The advantage of performing the two procedures in one session is that it shortens the time required before being able to cannulate the VA; the disadvantage is that it increases the likelihood of mechanical complications during surgery, as the mobilisation and/or transposition of the vein has to be performed with a vein without the necessary prior arterialisation.

When performed in two procedures, the anastomosis is firstly constructed between the basilic vein and the brachial artery, and from day 30-90, after using a Doppler ultrasound to check the correct maturation of the AVF and the absence of stenosis, the second procedure is performed and the vein is superficialised and/or transposed.127

Three superficialisation techniques are described in order to allow cannulation in this type of access128: a) anterior transposition in the arm, by creating a new subcutaneous tunnel; b) anterior transposition in the arm, by creating a lateral flap of skin and subcutaneous tissue, and c) simple superficialisation without transposition.

Brachiobrachial fistula

When there are no available superficial veins, a suggested alternative is to create an arteriovenous fistula between the brachial artery and the brachial vein.129-131

The brachial vein lies next to the artery and can be single or double. As this vein corresponds to the deep venous system, it is well preserved from prior needling. As a result, despite being a complex operation, if the vein develops well, it may be technically feasible.

The surgical procedure is the same as brachiobasilic AVF: the anastomosis is created in the antecubital fossa, mobilising the brachial vein with collaterals ligation, and performing superficialisation and/or transposition.129

Once the VA has matured, the results in terms of patency and complications are similar to those of the brachiobasilic AVF. However, the severe limitation of this technique is the high rate of primary failure, which may reach 53%, and its low primary patency after one year (35-40%),129,131 probably related to the increased technical complexity of mobilising and transposing the brachial vein. Therefore, given the lack of broader studies, this technique is not usually considered as a valid alternative option to using synthetic prostheses in the arm.128

Other venous transpositions

As in the forearm, there are also various possibilities for venous transpositions; their use is limited to certain clinical situations with particular anatomical layouts.111

Recommendations

Rationale

2.3.1 Rationale for prosthetic arteriovenous fistulae

The use of prosthetic material to create VA for HD has been shown to be a viable and effective solution to achieve a permanent VA.93,99,132,133

However, the high economic cost involved and the associated morbidity and deterioration in the patient’s quality of life, due to the need for procedures to maintain VA usefulness, mean that it is not considered a first choice technique when planning the VA, a role reserved for nAVF.10,93,98,109,132-135

As it is technically less complex to perform, this may help surgeons who have little expertise in creating VA lean towards this procedure from the onset.99

Despite not being the first-choice VA, nowadays this access plays a highly relevant role because an ever increasing number of patients require HD for very long periods of their lives, consequently putting the vascular bed at risk, and there is also a progressive increase in the average age of the patients on a HD programme. In addition, pAVF offer some theoretical advantages, such as a shorter maturation time and greater ease of needling in certain cases, as in the case of obese patients. They may also make it easier to create a secondary native VA, by helping to dilate previously unsuitable veins in the arms to create an AVF.132

2.3.2 Prosthetic arteriovenous fistula planning and creation

Arteries or veins with a diameter suitable for pAVF placement should first be identified (not less than 4 mm).63,116,133 In most cases, with an already exhausted distal venous bed, arterial anastomosis should be as distal as possible; venous anastomosis should also be as distal as possible, whenever correct drainage towards central venous trunks can be ensured.

It should be noted that the use of antecubital fossa veins for anastomosis involves the integrity of that territory and its respective drainage veins. Therefore, in these cases, the priority indication would be nAVF creation using these veins. For this reason, there are authors136 who recommend avoiding prosthetic loops in the forearm, since they consider that in these cases a native AVF can be created.

Expanded polytetrafluoroethylene

The material recommended for the prosthesis is ePTFE, given that it offers better rates of infection and integration than Dacron.10 Apart from this standard material, there are other prostheses which may be used in special circumstances.137,138

Immediate puncture prosthesis

Immediate needling prostheses are bilayer ePTFE prostheses reinforced with a third elastomer layer between the two, which means it does not need to be integrated in the tissues for needling. It provides similar results to conventional prostheses with the advantage of allowing cannulation after 24 hours, if necessary.139

Biosynthetic prostheses

Good results have also been published in relation to bioengineered prostheses. This is a prosthesis manufactured from a polyester matrix in which collagen from sheep is cultivated. It has a potential benefit in terms of presenting a lower incidence of infections when it is not possible to create an nAVF.140 The main evidence regarding the use of this type of prosthesis is that published by Morosetti et al., comparing the prosthetic access with the brachiobasilic AVF access in patients without other alternatives; although results with autologous access were more favourable, patency results and complication rates were similar to those of other studies with ePTFE.135

Surgical technique

The prosthesis can be implanted in a straight line or in the shape of a loop, the latter being the preferred layout in the forearm.141 These layouts are determined by the characteristics of the patient.

The order of preference for arterial anastomosis location is the brachial artery in antecubital fossa, brachial artery in arm, brachial artery close to axilla and axillary artery. However, because a pAVF is usually created after several failed nAVF, the location will depend on the well preserved vascular bed. Venous anastomosis can be performed on the veins in the antecubital fossa or above the elbow, as well as in the cephalic, basilic, axillary, subclavian and jugular vein.

Arterial anastomosis of the prosthesis should preferably be end to side. There are no studies showing differences depending on the anastomosis type between the vein and the prosthesis. The prosthesis should be between 20 and 40 cm in length to ensure a large needling segment. Prosthesis diameter must range between 6 and 8 mm. According to some authors,142 bigger diameters are associated with better long-term outcomes in this type of VA.

Patients who have exhausted all their venous capital for VA in the upper limbs, including nAVF and pAVF, are a small, but growing, percentage of patients on HD.

In view of the greater morbidity and mortality discussed when performing HD through CVC, surgical techniques known as “fall-back” techniques have been described. These allow permanent access when there are no viable veins in the upper limbs. These techniques make it possible to avoid the use of CVC despite the higher level of complications, the greater operative morbidity and lower patency than conventional VA.93,97,122,132,133,143

2.4.1 Vascular access at lower limbs

There is widespread evidence regarding VA creation in the lower limbs, using a vascular prosthesis (proximal in the thigh or mid-thigh section) or else using nAVF (AVF in femoral vein with transposition). pAVF creation in the lower limb is the most widely used of all the fall-back techniques described, since it offers acceptable patency rates and is the least complex surgical technique.111,122,132,133

2.4.2 Prosthesis-tunnelled catheter device

The hybrid prosthesis-tunnelled catheter device Haemodialysis Reliable Outflow (HeRO-device) is indicated in cases where there is a central venous obstruction which prevents the creation of any other VA in the upper limb. It consists of a VA that is created in a mixed way. On the one hand, it is a tunnelled catheter which is inserted through the internal jugular vein to the atrium; on the other, it is connected to an ePTFE prosthesis that is anastomosed at the level of the brachial artery. This means that the needling area is the prosthesis which is subcutaneously tunnelled and distal drainage is carried out directly in the atrium. The objective is to go through the stenosis and central vein occlusions which would prevent AVF creation.

The advantage of using this in clinical practice is that it is a VA that can be implanted in patients without adequate central venous drainage, in which all nAVF and pAVF options have been depleted, without compromising future accesses; main disadvantages include the technical complexity of the operation and its high cost.

2.4.3 “Exotic” vascular access

“Exotic” VA are those considered when there are extensive occlusions of venous trunks, both in upper and lower limbs. They have two great advantages: firstly they allow a new VA to be created in a theoretically exhausted territory; secondly, they can sometimes be used to salvage VA which have failed due to occlusion in the drainage veins and where endovascular therapy has not been effective.144,145

Given the exhaustion of the venous bed in these patients, these accesses are created using ePTFE prosthetic grafts, in the form of artery bypass between the donor artery and recipient vein.

Unfortunately, despite the initial advantage of providing access when the venous bed is depleted, there is a higher incidence of complications than in nAVF, because they are made of heterologous material. This is particularly serious in infection, because it involves central vessels which are difficult for the surgeon to access.

Furthermore, they are complex surgical procedures which are not exempt from morbidity and mortality and are performed on patients with significant associated comorbidities, who frequently have a history of multiple failed VA.

Therefore, as a general rule, the benefit/risk of the surgical intervention should be assessed on a case-by-case basis, the intervention required and the existing access options.

Prosthetic accesses in the anterior chest wall

These VA are created either as a loop, placing a prosthesis between the vein and axillary artery on the same side, or in a straight line, placing the prosthesis between the vein and contralateral axillary artery. These VA can be considered for patients with an exhausted venous bed but with central vein patency; they especially benefit those patients at high risk of ischaemia in the limb. Results report patency rates similar to more conventional pAVF in the arm.146,147

Bypass to central veins

In the case of distal axillary vein thrombosis, the technique consists of creating a bypass between the brachial artery and proximal axillary vein, while in cases of extensive axillosubclavian thrombosis with internal jugular vein and brachiocephalic trunk patency, the technique of choice is to perform a bypass between the brachial artery and internal jugular vein.144

Bypass to leg veins

If the two brachiocephalic venous trunks or the superior vena cava are occluded, the surgical alternative is to perform a bypass between the axillary artery and iliac vein144,148 or else to the popliteal vein.145,149

Other derivative techniques

Other alternative derivative techniques have been described, such as bypassing to the right atrium,150 femorofemoral crossover bypass,145 axillo-renal bypass,151 or axillo-inferior vena cava bypass.144 In all cases, these are techniques which are considered extraordinary, and evidence is restricted to a few documented cases.

Types of vascular access

• •

  nAFV at wrist and in forearm.

  • –

    Radiocephalic AVF in the wrist (Brescia-Cimino AVF).

  • –

    AVF in the anatomical snuffbox.

  • –

    Radiocephalic AVF in forearm.

  • –

    Radiobasilic transposition.

  • –

    Other venous transpositions.

• •

  nAVF in antecubital fossa (elbow) and arm.

  • –

    Brachiocephalic AVF.

  • –

    Brachioperforating AVF (Gracz AVF).

  • –

    AVF using the proximal radial artery.

  • –

    Brachiobasilic AVF.

  • –

    Brachiobrachial AVF.

  • –

    Other venous transpositions.

• •

  pAVF in upper limbs.

  • –

    Radioantecubital Straight graft.

  • –

    Brachio/radioantecubital loop.

  • –

    Brachiobrachial/axillary straight graft.

  • –

    Brachiobrachial/axillary loop.

• •

  Fall-back techniques.

  • –

    VA in lower limbs.

  • –

    Proximal femorofemoral (groin) graft.

  • –

    Femorofemoral graft in the middle third of the thigh.

  • –

    Transposition of femoral vein.

  • –

    Prosthesis tunnelled catheter device (HeRO).

  • –

    “Exotic” vascular access.

• •

  Central venous catheter.

Recommendations

→ Clinical question V Can an order of preference be recommended when performing the arteriovenous fistula?

(See fact sheet for Clinical question V in electronic appendices)

Evidence synthesis development

Preferred arteriovenous fistula location

Experts and guidelines both indicate that the procedure should be started by placing an AVF as distally as possible to preserve the option of future, more proximal accesses if necessary.6,10,109,111 However, no study has been found comparing the results of different AVF locations for HD in patients where any of these options would initially seem viable.

According to published clinical guidelines,6,10,111 arteriovenous radiocephalic and brachiocephalic nAVF are the first and second choice for VA, respectively. If these options are not possible, they recommend the creation of an autologous brachiobasilic nAVF in the upper arm or a radioantecubital pAVF in the forearm.

Using the non-dominant limb

Although the first VA is generally recommended in the non-dominant upper limb, no studies have been found which explicitly compare the option of prioritising the dominant or the contralateral hand.

In this respect, Koksoy et al.152 document, in an RCT on efficacy and safety in brachiocephalic and brachiobasilic nAVF, that the use of the dominant arm may increase the risk of fistula failure. However, this trend could not be confirmed in any other study conducted to date.

Distal versus proximal location

Moreover, no studies have been found specifically comparing whether it is more effective or safer to prioritise the most distal locations possible, alternating between non-dominant limb and dominant, or, on the other hand, to continue using the same limb until all other surgical options have been exhausted. Given the lack of solid evidence clearly favouring either of the options, it seems reasonable to leave the decision on a future AVF proximally in the same limb or distally in the contralateral limb to the patient, with professional advice.

Reinhold et al.8 point out that the first VA should be placed as distally as possible. The main disadvantages of a distal radiocephalic nAVF in the anatomical snuffbox or wrist are the relatively high rates of occlusion and non-maturation, which are affected by patient risk factors such as age, diabetes mellitus and cardiovascular disease.

A previous review with meta-analysis66 based on 38 observational studies estimated a primary failure rate of 15.3%, and primary and secondary patency rates of 62.5% and 66.0%, respectively, for radiocephalic fistula in the wrist.

Options prior to placing a prosthetic arteriovenous fistula: role of the brachiobasilic native arteriovenous fistula

As an option prior to pAVF use, a brachiobasilic nAVF with superficialisation or venous transposition in the arm is indicated.

Brachiobasilic arteriovenous fistula. Results

The systematic review of Dukkipati et al.128 analyses the results of brachiobasilic nAVF, based on several observational studies and an RCT.134 This review finds acceptable rates for primary failure (15% to 20%), and primary patency after one year (72%) and 2 years (62%).

Brachiobasilic arteriovenous fistula versus prosthetic arteriovenous fistula

2 RCTs and 2 retrospective studies compare results between the two procedures.134,135,153,154 All of them report similar results, with significantly better primary patency rates and primary assisted patency rates in the group of brachiobasilic AVF patients. However, when secondary patency results are analysed, these differences disappear, although the number of surgical interventions required to maintain this secondary patency is markedly greater in the case of pAVF.134

Complications are more frequent in pAVF,134,135,153 especially those with infection; however, maturation time is higher in brachiobasilic AVF.154

Brachiobasilic versus brachiocephalic arteriovenous fistula

The RCT conducted by Koksoy et al.152 comparing the efficacy and safety of brachiocephalic AVF versus brachiobasilic AVF found no differences in relation to mortality, wound complications, immediate thrombosis, post-operative bleeding, AVF maturation and time to AVF maturation, and there were no significant differences regarding patency rates. Other authors155,156 reported similar results. In the aforementioned studies, brachiobasilic AVF also show a tendency to present better VA maturation rates, albeit with no statistically significant differences. This may be due to the better preservation of the basilic vein than the cephalic vein in most patients.

All these results make the brachiobasilic fistula a safe technique with good results when considering permanent VA.

Brachiobasilic arteriovenous fistula versus brachiocephalic arteriovenous fistula versus prosthetic arteriovenous fistula

There are also several published studies which analyse the results by comparing the three main types of AVF in the arm.156-159 All of them concur in describing better statistically significant patency in autologous VA, even though they present a greater primary failure rate.

Likewise, they also find a higher rate of complications and number of interventions needed to maintain patency in pAVF, but no significant differences between both types of nAVF.

There is no consensus between the different groups on the suitability of transposing the basilic vein during the same surgical procedure or after dilatation and arterialisation. Nor do they agree on which the technique of choice should be (transposition with subcutaneous tunnel, transposition with flap or simple superficialisation).128

One-stage procedure versus two-stage surgeries

In El Mallah’s RCT,160 which offers the best evidence to date, significantly better primary patency is described after two-stage surgery (50% versus 80%), although the number of patients is not high (n = 39). Similar results are subsequently described by Ozcan et al.,161 who found a higher rate of maturation and lower number of complications when surgery is performed in two stages. Finally, the case series published by Pflederer et al.158 highlighted that most complications in two-stage surgery occurred in the interval between both stages, so the authors recommend this technique to minimise surgical aggression.

Superficialisation versus transposition

There is agreement among authors that transposition through a subcutaneous tunnel is associated with a lower rate of complications,117,162 but not a better maturation rate. Finally, Hossny117 describes a greater level of satisfaction among nursing staff responsible for needling in the cases where transposition is performed by creating a subcutaneous tunnel.

Prosthetic arteriovenous fistula in an upper limb

Results of prosthetic arteriovenous fistula

The primary patency of prostheses is between 20% and 50% at 24 months and, through successive surgical interventions, can reach a level of assisted patency of between 45% and 70% at 2 years.163-167

The best available evidence comes from Huber’s systematic review with meta-analysis,93 which found thirt y-four studies, mostly case studies and some non-randomised controlled studies, comparing outcomes in nAVF and pAVF in the upper limb. Primary patency rates for nAVF were 72% at 6 months and 51% at 18 months, and for pAVF 58% and 33%, respectively. Secondary patency rates for nAVF were 86% and 77%, and for pAVF, 76% and 55%, respectively. It must be noted that there is significantly much greater patency in nAVF across all categories analysed (arm/forearm and primary/secondary patency).

To improve this patency, technical improvements, such as the inclusion of bioactive surface with heparin, have been introduced in the prostheses. So far, it has not been possible to demonstrate improvements in patency or in the need for fewer re-interventions.168,169

Prosthetic arteriovenous fistula indication

There is overall consensus among authors that nAVF are superior to pAVF,93 and this is reflected in the various clinical practice guidelines published.6,10,111 Thus, there is currently no controversy regarding pAVF indication in cases where venous capital in the patient has been exhausted and no other nAVF can be created.93,132,136

However, there is debate among authors related to the possible use of pAVF as the first choice in patients where the venous bed has not been exhausted.132,136,170

In recent years there has been a progressive increase in the average age of patients starting RRT with HD, and underlying pathology, which has meant there is a growing percentage of nAVF with impaired maturation and of nAVF which do not become functional.78 In some studies these have reached 60%.171 Inevitably, this results in a growing dependence on CVC in these patients, thus increasing the risk of sepsis and related complications.132

This has made several authors re-assess the suitability of prioritising nAVF in all cases over pAVF.78,132,136,170 They have also proposed assessing clinical situations in which a pAVF may be indicated as the technique of first choice, where the potential benefits of pAVF (shorter maturation time, lower rate of primary failure) would outweigh the advantages of nAVF (higher patency, lower rate of complications).

According to Sgroi et al.,136 clinical situations in which a pAVF would be the VA of first choice would be the absence of anatomically appropriate veins in the forearm or arm, a patient with end-stage kidney disease with limited life expectancy, the urgent need to start HD and patients with clinical risk factors for nAVF failure.

Urbanes132 recommends deciding on a case-by-case basis approach, and considering pAVF in cases of limited life expectancy, absence of suitable vessels in forearm and previous failed nAVF. He also considers the possibility of constructing “bridge” pAVF in patients with an urgent need for HD to avoid CVC placement.

Other authors170,172 propose an algorithm that decides between nAVF and pAVF based on the calculation of the likelihood of primary failure on the basis of three basic parameters: if HD has commenced, life expectancy of above or below 2 years, and a history of previous failed VA.

Fall-back techniques

As mentioned previously, once “conventional” VA have been exhausted, other fall-back VA may be performed. There is limited evidence available on the results of these techniques, so their role remains uncertain in VA choice in clinical practice.

Vascular access in the lower limb

The main recorded evidence comes from the systematic review carried out by Antoniou et al.173 in 2009. Patency and complications of the following types of AVF were assessed: pAVF in the upper thigh (inguinal region), pAVF in mid-thigh and nAVF with femoral vein transposition. These studies obtained acceptable results in terms of patency of these techniques, with a primary patency at 12 months of 48%, 43% and 83%; and a secondary patency at 12 months of 69%, 67% and 93%, respectively. The patency study found greater patency in the nAVF with femoral vein compared to the pAVF, with statistically significant differences, while there were none between both types of pAVF. Infection-related complications are described with more frequency in pAVF while femoral vein nAVF present the highest rate of ischaemia in the limb.

Other observational studies published compare the patency and complications of pAVF in the lower limbs with those created in the upper limbs. Miller et al.174 also show similar patency rates between both territories but with a higher incidence of primary failure and of infectious complications in lower limb VA. In turn, Harish and Allon175 report more serious infections arising from pAVF in these lower limbs.

Prosthesis-tunnelled catheter device

The first study published176 described a reduced incidence of infection compared to tunnelled CVC, obtained via a review of the literature conducted by the same authors (0.7 VA-associated bacteraemias per 1000 days versus 2.3 VA-associated bacteraemias per 1000 days).

Steerman et al.143 conducted a comparative study between this device and pAVF in the thigh, but found no differences in terms of secondary patency, infection and mortality rate. The main advantage of this device is therefore considered to lie in the use of the arm, which allows the thigh to be preserved for future accesses, and in possible use in patients with peripheral arterial disease.

Currently, the best available evidence refers to a meta-analysis published by Al Shakarchi et al.177 in which various published case series are referenced. Likewise, in two studies the results of this device are compared versus pAVF in lower limbs.143,178 Overall VA patency results described show a 1-year primary patency of 21.9% and a secondary patency of 59.4%, while in the comparison of pAVF there were no significant differences in patency. With regard to infection rate using the device, the authors report an incidence of 0.13 - 0.7 VA-associated bacteraemias per 1000 days, which is significantly better than the rates associated with CVC.177

“Exotic” vascular access

As mentioned previously, once “conventional” VA have been exhausted, fall-back VA may be constructed. These include pAVF in the anterior chest wall, central vein bypasses, lower limb vein bypasses, and other derivative techniques.

In all cases, the available evidence refers to the publication of case series.144-151 They all provide acceptable results considering that these are fall-back techniques, but there are no studies with a sufficient level of evidence showing what the first choice is in each case.

Assessment of the preferred vascular access in the elderly patient

As mentioned previously, the VA of choice is nAVF, due mainly to much higher primary, primary assisted and secondary patency rates than pAVF and CVC.93 Likewise, they have a lower complication incidence than other accesses, especially in terms of infections and thrombosis. In contrast, the major drawback of nAVF lies in their low maturation rate and in the lengthy period required for them to mature, especially in cases where secondary procedures are needed to induce them.

This high incidence of primary failure offered by nAVF, which in some studies reaches 60%,171 is considered its real Achilles’ heel. Moreover, it is even more pronounced in elderly patients, where there is an increased risk of primary failure (OR = 1.79) compared to non-elderly patients.64

Added to this is the low survival of this type of patient, due to their age and the frequent presence of significant comorbidities, with a mortality rate > 50% at 2 years for patients older than 75 when starting HD.179 A mortality rate of 30% is described in octogenarians even before they started RRT.180

In the light of these facts, it is the common opinion among several authors that the suitability of nAVF in the geriatric patient and/or with limited life expectancy should be reconsidered, as in these cases, attempting to start RRT through nAVF can lead to a greater dependency on CVC, with their associated complications.64,128,132,136,170,180

As a result, one of the major issues being debated today, due to the increased average age in the population in HD, is whether nAVF should be created in elderly patients, despite potential maturation issues, or pAVF, despite problems related to infection and medium-term patency. Direct placement of a tunnelled CVC is even considered in patients with limited life expectancy.

When performing a systematic search, no randomised controlled studies have been found regarding this issue. The best available evidence currently consists of a meta-analysis,64 a retrospective study with a cohort of patients from the United States Renal Data System,181 as well as several literature reviews and expert opinions.132,136,170

In a retrospective study of a cohort of 82,202 patients aged 70 and older when starting HD and whose data were collected in the United States Renal Data System, DeSilva et al.181 analysed the global mortality and survival of these patients. They found a lower mortality rate and better survival in patients who started HD with nAVF. He also highlights that pAVF results are better than CVC. Only in the group of patients over 90, although the trend described is maintained, the differences between nAVF and pAVF did not reach statistical significance. This leads to the consideration that, in general terms, nAVF is also valid as the VA of first choice for most elderly patients, even for those with comorbidities.

With regard to nAVF of choice in the elderly, the review with meta-analysis conducted by Lazarides et al.,64 based on retrospective cohort studies, finds a higher risk of failure for radiocephalic nAVF in elderly patients compared to younger patients. When comparing the results according to nAVF location, they notice a lower failure rate in brachiocephalic nAVF than in radiocephalic nAVF. They consider that the advantage of conserving proximal access sites for possible future accesses found in distal nAVF has minimal importance in patients with a short life expectancy. Therefore, the authors consider that brachiocephalic nAVF should be the first choice in elderly patients with short life expectancy or with a late start in HD. The main limitation of this study is the heterogeneous definition of old age, ranging between 50 and 70 years, depending on the study in question.

Finally, articles based on the literature review and expert opinion concur in considering a patient’s life expectancy as a main parameter rather than specific age as a criterion for the VA of choice. In this respect, they recommend pAVF in cases of patients with a life expectancy of less than 2 years, since this is the average accumulated patency for pAVF for HD.132,136,170

From evidence to recommendation

Preferred arteriovenous fistula location

Using the non-dominant limb

Although there are no studies in this respect, it is widespread practice to create nAVF as the first VA in the non-dominant limb, based on the reasonable assumption that the patient will prefer to have the dominant hand free during the HD session, and also because an AVF in the non-dominant limb will interfere less in daily activities.

Distal versus proximal location

As mentioned above, there are currently no studies that allow an unequivocal indication of which VA should be the first to be taken into consideration. Nevertheless, experts and guidelines unanimously agree on recommending the most distal AVF possible to preserve the option of future, more proximal VA if necessary.6,10,109,111 This broadly accepted criterion, based on good clinical practice, has prevailed in the recommendation put forward. However, clinical situations may occur in which other considerations could take priority (elderly patient, patients with short life expectancy in HD).

As a logical exception, in cases where the matured venous bed previously developed for a former, more distal AVF could be exploited to create a proximal AVF, the use of the aforementioned bed must be prioritised.

Vascular access of choice in the arm

After all nAVF options have been used up in the forearm, the next access to consider is the AVF in the arm/antecubital fossa. There are three conventional options: brachiocephalic nAVF, brachiobasilic nAVF or pAVF.

There is currently no discussion among authors on the suitability of nAVF (brachiocephalic AVF and brachiobasilic AVF) over pAVF, given their greater patency and their lower rate and severity of complications. However, there is currently a debate on specific cases in which pAVF may be a reasonable first indication. In accordance with the literature review and the majority opinion of the authors, GEMAV has decided to consider the recommendation to propose pAVF in cases of:

• 1.

  Patients without anatomically appropriate veins in the arm or forearm.

• 2.

  Patients requiring urgent HD (placement of immediate needling pAVF).

The first assumption is the main indication for pAVF, given the greater patency and the lower rate of complications versus CVC. For patients who require urgent HD without a mature nAVF, the indication of pAVF is restricted to those cases where the patient’s overall status does not allow for the consequences of potential CVC complications to be accepted. In this case, an immediate cannulation pAVF may be indicated, although the patient’s status should be carefully assessed, since pAVF placement without having used up the venous bed may lead to the early exhaustion of the limb’s veins.

Where life expectancy is short (as described above) some experts are of the opinion that an elective pAVF may be suitable. The choice should also be made carefully, as the available evidence does not allow for a minimum value of life expectancy from which to indicate pAVF to be established. In other words, the appropriateness of such a choice must be considered on a case-by-case basis. In any case, pAVF should not be indicated to the detriment of nAVF when life expectancy is over 2 years, as this is the average secondary patency of pAVF.

With regard to the convenience of prioritising brachiocephalic nAVF over brachiobasilic nAVF, the available evidence detects no significant differences in patency, so the decision to propose brachiocephalic AVF as first choice has been based on its lower surgical aggressiveness, greater comfort for the patient and the shorter maturation period required, especially when compared to those brachiobasilic AVF created with two-stage surgery.

Finally, concerning second-choice access in the arm (after brachiocephalic AVF), published studies are clear that there are better rates of primary and primary assisted patency for brachiobasilic AVF, as well as a lower incidence and severity of infections. Thus, although some groups have not documented differences in secondary patency and it takes longer to mature, the evidence recommends prioritising the use of brachiobasilic AVF over pAVF.

Fall-back techniques

After having exhausted access options in the forearm and arm, a fall-back VA can be considered as an alternative to tunnelled CVC. Except in the case of AVF in the thigh, the other techniques lack the casuistry to provide sufficient evidence to support their usefulness and safety in practice. Consequently, their use is recommended selectively, on a case-by-case basis.

Vascular access at the lower limbs

As discussed, AVF use in the thigh is a valid alternative to CVC, supported by the available evidence, with patency results comparable to pAVF in the upper limb.

From the three techniques described (transposition of femoral vein, prosthetic loop in groin and prosthetic loop mid-thigh), the transposition of the superficial femoral vein offers better patency at the expense of an increased risk of ischaemia and greater technical complexity, while the mid-thigh loop shows a non-significantly lower rate of infections in pAVF. In any case, as each technique has different advantages and disadvantages, no recommendation as to the technique of choice has generally been made; it is the patient’s clinical condition and individual preferences which advise their use.

Prosthesis-tunnelled catheter device

As this is a relatively new technique, there are no RCTs supporting its usefulness and safety. Existing evidence reports lower rates of complications than CVC. For this reason, its indication should be assessed after all AVF options have been exhausted prior to the catheter placement.

The only published meta-analysis to date describes rates of complications without significant differences compared to pAVF in the lower limbs, so it can be considered an alternative indication.

However, as with other fall-back techniques, there is currently insufficient evidence to be able to indicate its general use.

The order of sequence for creating VA in function of the location and type of VA is summarised in Figure 1.

Figure 1.

Order of creating vascular access. CVC, central venous catheter; nAVF, native arteriovenous fistula; pAVF, prosthetic arteriovenous fistula. In black, the primary sequence.

(0.15MB).

Preferred vascular access in elderly patients

As mentioned in the evidence synthesis development, there is a debate on the VA of first choice in elderly patients. As a result, the high primary failure rate of autologous fistulae in wrist and the older patient’s limited life expectancy, the advisability of prioritising the use of pAVF over nAVF, and of nAVF in arm over nAVF in wrist, are being discussed.

A priori, pAVF is considered as a good option in these patients, since it has a low primary failure rate and drastically shortens the complex process of maturation. The disadvantage to be found in their worse patency rates and higher incidence of complications would be minimised because these are patients with low or very low life expectancy; for this reason, it has been included in the proposals put forward by several authors. Despite this, the studies which validate them have a small number of patients, and studies with a large number of elderly patients continue to confirm the benefits of nAVF across all age groups compared with pAVF and CVC, even in cases with significant comorbidities, with the possible exception of nonagenarian patients. For this reason, GEMAV believes it is important to put forward carefully thought-out indications for this group of patients, while highlighting that the main aim is still the need to achieve HD through nAVF, even in the advanced age group.

Available evidence on the possibility of considering VA in the arm from the outset confirms the worse prognosis for nAVF in the forearm compared to the general population. However, it is difficult and subjective to assess whether this justifies a general recommendation in this regard. In contrast, GEMAV suggests a careful assessment of the elderly patient, including ultrasound mapping, before deciding on the type of nAVF to be created. We consider there is insufficient evidence to be able to recommend constructing nAVF in the arm as a first option in all cases for this group, although in the same way we advise not creating AVF of dubious feasibility where possible, given the greater importance that morbidity/mortality associated with primary VA failure has in this group of patients. As already mentioned, ultrasound mapping is considered to be the most useful tool in this regard.

Finally, GEMAV considers that no time limit can be established to be able to classify patients as elderly. This is due, on the one hand, to the great heterogeneity of inclusion criteria in the main studies, which range from 50 to 90 years of age, and on the other, to the subordination of age criterion to life expectancy. The latter is the factor that will be most important when indicating VA.

Recommendations

Rationale

Infection is one of the most significant complications associated with VA and in many cases leads to VA loss. Added to this, as these are superficial structures, infection of the surgical wound can lead to infection of the whole AVF relatively easily.

However, nAVF have a very low rate of peri-operative infection, so there is no evidence to justify systematic preoperative prophylaxis in these patients.

In contrast, a higher incidence and greater severity of infections is reported in pAVF, which in many cases necessitate their withdrawal in a patient who has very limited options for creating further VA. The micro-organisms that most often colonise or infect the pAVF are usually part of the cutaneous microbiota (staphylococci, streptococcus and corinebacterias), the most common being Staphylococcus aureus. For this reason, numerous studies advocate the pre-operative administration of prophylactic antibiotics, the most commonly accepted being a single dose of vancomycin.133,182

Recommendations

Care in the immediate post-operative period. Prevention and early diagnosis of complications

Strict monitoring of the patient with a newly-created AVF must allow for any possible complication that may arise to be prevented and diagnosed in the early stages and be treated appropriately. The main complications associated with VA creation include haemorrhage, seroma, infection, distal ischaemia, neuropathy and thrombosis.

In the operating theatre, once the AVF has been performed, before concluding the surgical procedure, the surgeon must check the presence of peripheral pulse and AVF function by palpating the thrill.183

A functioning AVF has a palpable thrill and an audible bruit on auscultation at the level of the anastomosis. If there is any doubt about functioning, a Doppler ultrasound (DU) can be performed183 to demonstrate its permeability. To this end, some authors have proposed intra-operative flowmetry.184 The absence of bruit at the end of the procedure in conjunction with end-diastolic velocity values under 24.5 cm/s, obtained by intraoperative DU, represent an effective predictive test for AVF thrombosis, which is better than the absence of thrill.185

It is important that the surgeon includes a clear diagram of the newly-created AVF in the patient’s medical record. The more information the nursing staff have about the AVF, the greater the likelihood of successful cannulation and improved VA patency.184

Most AVF can be created in major outpatient surgery without the need for hospital admission. During the time that the patient remains in the health centre, the AVF must be observed carefully in case any of the three major complications, i.e. bleeding, ischaemia and thrombosis, appear.

Care in the immediate post-operative period

• 1.

  Monitor vital signs. Blood pressure (BP), heart rate, and body temperature should be checked. BP must never be taken in the arm with the AVF.183,186 The patient’s haemodynamic stability must always be maintained, minimising the risk of AFV thrombosis.183,186.

• 2.

  Physical examination of the AVF (see section “Monitoring and surveillance of arteriovenous fistula”). The existence of bruit and thrill in the AVF should be checked in order to detect early failure and thrombosis. There are various pre-operative factors related to lower patency immediately after nAVF creation, associated with age over 65, female gender, diabetes, coronary disease and the patient’s peripheral vascular disease history, which are discussed in section 1 of this guide.58,185,187,188

  In the case of pAVF, Monroy-Cuadros et al. observed lower patency in patients with the aforementioned clinical history and an access flow (QA) < 650 mL/min when starting needling.189 QA values < 500 mL/min in the nAVF represent an independent risk factor associated with lower primary patency.71

• 3.

  Monitor the dressing for signs of bleeding. No compression dressings should be placed on the arm with the AVF.

• 4.

  The limb with the arteriovenous fistula should be raised, resting on a pillow to promote venous return and prevent oedema.183,186

• 5.

  Examine the limb where the AVF has been created and check the patient’s blood flow. Distal pulses of the AVF limb must be palpated and the capillary refill checked. Distal areas of the limb should be observed to rule out signs of ischaemia, such as the occurrence of pain, coldness, pallor and motor and sensory changes in the affected hand.

  The distal hypoperfusion syndrome (steal syndrome) associated with AVF during the post-operative period is an uncommon but important complication. It is caused by a sudden drop in distal perfusion pressure, due to the occurrence of a preferred flow or diversion of arterial blood flow through the VA, causing symptomatic ischaemia in the affected limb. It occurs more frequently in arm nAVF with an incidence of between 1% and 20%, which is higher than in forearm or radiocephalic AVF85,87,87a,87b (see section “Complications of arteriovenous fistula”). Although less common, it may also be caused by an obstruction of the artery proximal to the anastomosis due to a technical failure.

  If a distal pulse to the AVF is observed, a differential diagnosis should be made with ischaemic monomelic neuropathy (IMN). This is a neurological pathology that affects the three nerves in the forearm: the radial, ulnar and median nerve, without other signs that suggest arterial ischaemia. The main risk factors for steal syndrome and IMN are common (diabetes, female gender and brachial artery flow). In any case, the ischaemic hand of an AVF, whether due to arterial steal syndrome or the existence of IMN, may necessitate a revascularisation procedure or the complete ligation of the AVF.190

• 6.

  Post-operative bleeding and/or haematoma should be checked (see section 5) and whether an immediate surgical review is required assessed. Although bleeding complications are uncommon, we should not forget that this is a surgical procedure which involves a vascular anastomosis and, therefore, it is important to check there is no haematoma in the surgical area which might necessitate an urgent review of the VA before discharge.191

Initial care during the outpatient follow-up

The first outpatient check-up should be carried about 7 days after the procedure. Depending on the status of the wound, the suture may be substituted by adhesive strips for some more days, or half of the stitches removed alternately. Antihypertensive medication should be reviewed and adjusted in order to avoid hypotensive episodes and minimise the risk of thrombosis of the AVF.191

This check-up should assess AVF patency and rule out the presence of complications. Skin and subcutaneous tissue should be examined to rule out any signs of infection, which can occur in between 1% and 5% of cases.192 If swelling, erythema, cellulitis or skin induration is observed, DU can help us to diagnose the specific existing pathology. Treatment of complications is discussed in section 5.

In the case of oedema in the AVF arm, venous hypertension should be ruled out. This complication occurs in 3% of patients and is usually associated with a central venous stenosis secondary to a previous CVC placement.190

Moreover, in pre-dialysis patients with ACKD, episodes of decompensated heart failure are not uncommon following nAVF creation. Up to 17% of cases of heart failure in patients with stage 4-5 CKD have been reported after AVF surgery related to an increase in cardiac output.10,193 It should be suspected when the AVF flow is > 2 L/min or ≥ 30% of the cardiac output.190,194 This is described in detail in section 5.

Medical and nursing staff are responsible for informing the patient about the characteristics of the AVF, its importance for their future haemodialysis (HD) treatment and the self-care that they should give their newly-created AVF (see self-care plan in point 3.4 of this section).191

Rationale

Inadequate nAVF maturation may increase the incidence of complications associated with needling (haematoma, thrombosis) and reduce patency. In addition, when needling begins, a non-matured nAVF may require CVC placement in the incident patient in order to start the HD programme or CVC withdrawal should be delayed in the prevalent patient. Therefore, it is important to establish strategies that encourage the maturation process so that the nAVF can be cannulated at the right time.

Recommendations

→ Clinical question VI Are exercises useful for developing arteriovenous fistulae?

(See fact sheet for Clinical question VI in electronic appendices)

Evidence synthesis development

The study by Leaf et al.195 showed that the performance of a simple programme of exercises can cause a significant increase in cephalic vein diameter prior to the creation of the VA (n = 5). The diameter of the cephalic vein in the exercised arm increased significantly compared with the control arm when measured, both without (0.048 ± 0.016 versus 0.024 ± 0.023 cm2) and with a tourniquet (0.056 ± 0.022 versus 0.028 ± 0.027 cm2).

Order et al.196 analysed the impact of physical exercise in 20 patients prior to surgery. The mean change seen in the diameter of the nAVF was 0.051 cm or 9.3% (p < 0.0001).

The study by Uy et al.197 included 15 patients with small cephalic vein diameter (< 2.5 mm). After four weeks of exercise, the average diameter of the vein increased significantly, both proximally (1.66 to 2.13 mm) and distally (2.22 to 2.81 mm).

The prospective randomised study by Salimi et al.198 analysed the influence of a regulated scheme of exercises on nAVF maturation in 50 patients in a HD programme (25 patients in control group). Checks were performed by DU at 24 h and 2 weeks after AVF creation. Significant increases in the diameter of the efferent vein, wall thickness, venous area and QA were observed in the study group after exercise. Although there were no significant differences with regard to criteria of ultrasound maturation, significantly higher maturation was observed by clinical criteria. Its beneficial effects include the increase in venous diameter, as well as the increase in muscle mass and the decrease in the amount of fat tissue.

Fontseré et al.199 carried out a prospective randomised controlled study on the effect of a post-operative programme on nAVF maturation 1 month after creation in 69 patients with CKD in the pre-dialysis stage (65.2%) and in chronic HD programme. After 1 month, an assessment was made using criteria of adequate clinical maturation (specialist nursing staff) and ultrasound (QA > 500 mL/min, diameter > 5mm and depth < 6mm) in all patients. The rates of clinical and ultrasound maturation 1 month after nAVF construction were 88.4% and 78.3% respectively (Kappa coefficient = 0.539). The exercise group showed a non-significant trend towards better clinical and ultrasound maturation compared with the control group (94.7% versus 80.6%, p = 0.069; 81.6% versus 74.2%, p = 0.459). Logistic regression analysis identified nAVF location as a confounding factor so that, in distal nAVF, the exercise group showed significantly higher clinical maturation, but not in ultrasound (odds ratio [OR]: 5.861, 95% confidence interval [CI], 1.006-34.146, and OR: 2.403, 95% CI, 0.66-8.754, respectively).199

From evidence to recommendation

Although there are few studies on this subject, performing isometric exercises on the limb, before and/or after AVF construction, may promote the maturation process of the nAVF.

GEMAV suggests advising patients with ACKD to do exercises before and after nAVF creation in order to promote muscle and vascular development, and, consequently, to accelerate the maturation process, increase nAVF patency and development, and reduce morbidity associated with lack of maturation.

However, further clinical research is needed to analyse the advantages of doing exercises as a factor promoting the correct nAVF maturation process.

→ Clinical question VII What is the minimum maturation time required for a native or prosthetic arteriovenous fistula to be mature enough for needling?

(See fact sheet for Clinical question VII in electronic appendices)

Rationale

The maturation period for the VA is the time needed from the creation of the AVF until the moment when the first HD session can be carried out with the minimum risk of complications arising from needling. Although timing to begin needling is a controversial issue, both in nAVF and pAVF, it is accepted that excessively early use of any AVF may lead to a significant reduction in patency in relation to associated complications. Therefore, it is very important to determine the ideal time to initiate AVF cannulation.

The criteria for mature AVF are discussed in section 2. The lack of nAVF maturation has been associated with: a) insufficient arterial dilatation, present in patients with severe vascular disease and diabetes mellitus in the context of accelerated arteriosclerosis; b) deficiency in venous vasodilation secondary to the existence of collateral venous circulation; c) presence of a central stenosis, and d) development of accelerated neointimal hyperplasia secondary to juxta-anastomotic stenosis after the surgical procedure in areas of low tangential force.58,187,188

Evidence synthesis development

There are only two observational studies that deal with this question.200,201 The first, based on data provided by the DOPPS study (Dialysis Outcomes and Practice Patterns Study), showed that the first nAVF puncture was performed within 2 months of construction in 36% of North American patients, 79% of European patients and 98% of Japanese patients.200 In the study by Rayner et al.,201 nAVF cannulation within 2 weeks after creation was associated with a significant decrease in patency, with a relative risk of 2.27 (p = 0.02). DOPPS studies200,201 suggest that, while nAVF cannulation is not recommended within 2 weeks of creation, first cannulation between 2 and 4 weeks afterwards may be considered following close clinical evaluation without it necessarily increasing the risk of nAVF failure.

In the case of pAVF, according to the data provided by the DOPPS study,200 needling starts between 2 and 4 weeks in 62% of North American patients, 61% of European patients and 42% of Japanese patients. No significant reductions in pAVF patency were observed in this study when cannulation started before 2 weeks or after 4 weeks following surgical placement, taking the 2-3-week subgroup as reference. However, needling a polytetrafluoroethylene pAVF within 2 weeks of its construction is not recommended due to the high risk of haematoma. Except those immediate cannulation pAVF, the remaining pAVF may usually be cannulated 2-4 weeks after construction once the subcutaneous oedema has disappeared and the graft can be easily palpated along its entire length.

From evidence to recommendation

In the case of nAVF, we recommend that needling not be started within the first 2 weeks after creation. From this date onwards, risks must be studied on a case-by-case basis in order to decide the ideal moment to perform the first cannulation.

For those patients with pAVF, we recommend that needling starts between two to four weeks after construction, except immediate cannulation pAVF. In this subgroup of patients, it is important to be familiar with the type of prosthetic material used.

Recommendations

Rationale

A direct relationship has been described between a premature start to needling in nAVF and shorter patency.202,203 An AVF should only be cannulated when an optimal level of maturation has been reached. Therefore, nAVF must be monitored in all ACKD check-ups and, if insufficient development is observed, the nAVF must be examined using DU for diagnosis and the corrective treatment applied using percutaneous transluminal angioplasty (PTA) and/or surgery.

Basic examination to be performed prior to the first arteriovenous fistula cannulation

Physical examination is the most commonly used method for nAVF monitoring in the ACKD outpatient check-up to detect a deficiency in maturation and to attempt to identify its cause at the earliest possible moment. Different studies have shown that where this is done exhaustively, there is an increased diagnostic capability and an extraordinary cost-benefit relationship in the detection of significant stenosis and collateral venous circulation.204,205 The procedure for physical examinations is described in section 4.

DU is an essential tool in ACKD outpatient clinics and should be used both to perform pre-operative vascular mapping and to identify the cause of any post-surgical maturation deficit observed in physical examination. In the presence of any nAVF with insufficient clinical maturation, which is highly unlikely to be ready to use in the first HD session, GEMAV considers it necessary to carry out a DU to diagnose the precise cause of the lack of maturation. The objective is to repair any non-matured nAVF using an endovascular and/or surgical procedure in the pre-dialysis stage so that it can be cannulated in the first HD session.

Asepsis during arteriovenous fistula cannulation. Use of local anaesthetics

It must not be forgotten that AVF cannulation is an invasive procedure and, therefore, extreme care must be taken with asepsis measures. Before placing the sterile field and disinfecting the needling area, the arm or the needling area in the leg must be washed with soap and water, taking particular care where patients have used anaesthetic cream and if there are highly prominent aneurysms. Alcoholic chlorhexidine, alcohol 70% or povidone-iodine can be used to disinfect the area. The first takes effect after 30 seconds and lasts for up to 48 h. Alcohol has a shorter bacteriostatic effect and should be applied 1 min before needling. Povidone requires 2-3 min to fully develop its bacteriostatic capability. In an international survey conducted at 171 HD centres on 10,807 cannulations with two needles in patients mainly dialysed with nAVF (91%), an alcohol-based disinfectant was used for most cannulations (69.7%) and certain specific preferences were observed depending on the country: chlorhexidine in the United Kingdom, Ireland, Italy and South Africa, and povidone-iodine in Spain.206

Some patients with hypersensitivity to pain on needling the AVF may benefit from topical local anaesthetics. The most commonly used are the combination of lidocaine with prilocaine (cream) and ethyl chloride (spray) which need to be applied at least 1 hour before and 20 seconds before needling, respectively. In the same study by Gauly et al., the use of local anaesthetics was uncommon (overall, in 8.5% of cases), except in the United Kingdom, Ireland and Spain, where 29.4%, 31.7% and 27.2%, respectively, of cannulations were performed with their prior application.206

Characteristics of the dialysis needles

Types of needles

HD needles may have a sharp or a blunt tip. They have a silicone coating to facilitate insertion and reduce their resistance to QA.207 The bloodstream can be accessed through AVF via 2 needles with a different structure to carry out the HD session207: a) conventional stainless steel needle; this type of needle is the most commonly used, and b) catheter-fistula; made up of a polyurethane cannula and an internal metal needle designed to cannulate nAVF. Upon withdrawal of the needle, the cannula remains inside the arterialised vein for the entire HD session.208-210 This type of cannula can reduce pain both cannulating and removing the needle,209 besides decreasing the risk of extravasations and haematoma,208 especially in the case of nAVF in the elbow flexure in elderly patients.

Gauge and length of needles

HD prescription should be adapted to the needle type used.211 As a general rule, the smallest gauge and shortest needle which allows an adequate blood flow (QA) must always be chosen to suit the specific needs of each individual patient.212

With regard to needle gauge, these are available from 17 G up to 14 G, with the numbering being inverse to the gauge, i.e. a 17 G needle is the smallest and, on the other hand, a 14 G needle is the largest.213 After the first nAVF cannulations without complications, the choice of a higher-sized needle (lower number) depends on the diameter of the arterialised vein and the existing QA.213 In the study by Gauly et al., the needle gauge most commonly used was 15 G (61.3%), followed by 16 G in one-third of cases. 14 G and 17 G needles were used in less than 3% of cases.206

Moreover, the needle length chosen should be the shortest possible to reach the centre of the AVF lumen and thus reduce the risk of perforating the posterior wall.213

Only if we consider the relationship between a particular needle gauge, the maximum blood pump velocity and the duration of the HD session will we be able to adequately use nAVF without causing haematoma.211 Again, in the survey by Gauly et al., when larger needles were used (14 G) most patients were dialysed using a high pump flow (QB) (> 400 mL/min) and, on the other hand, when small needles were used (17 G) more than 80% of patients were dialysed with a QB ≤ 300 mL/min.206

Arterial needle backeye

In the study by Gauly et al., the arterial needle with backeye was used in most cases (65%).206 An arterial needle with backeye should always be used to maximise the flow aspirated through it and to prevent the adhesion of the bevel to the vessel wall due to negative pressure, which could cause damage.10,212

First cannulations of a new native arteriovenous fistula

Use the needle with the smallest gauge available (usually, 17 G)10. The selection of this “arterial” needle gauge ensures a sufficient blood flow to meet a demand for 200 mL/min from the blood flow pump of the HD machine and, simultaneously, minimises resulting haematoma if extravasation occurs during the HD session.213 Pre-pump arterial pressure monitoring (–250 mmHg or less) is recommended to ensure that the blood pump velocity does not exceed what the “arterial” needle can provide.10

Arteriovenous fistula cannulation. Methodology

Arteriovenous fistula cannulation

All professionals involved in a kidney patient’s care are aware of the existing difficulty in ensuring that the incident patient is dialysed through a mature nAVF from the very first HD session.214 Perhaps the main barrier lies in the maturation period but, undoubtedly, the final crucial hurdle that must be overcome for the nAVF to be usable for HD is its cannulation.214 Inadequate cannulation of the nAVF may require the placement of a CVC to carry out the first HD session and, therefore, all the previous work done in the pre-dialysis phase to achieve the best VA to start the HD programme will have been lost.

There is a relationship between cannulation practices (technique used, needle gauge, direction of the arterial needle), patient factors (age, comorbidity) and centre factors (QB, duration of the session), all of which may influence one of the key issues in any HD programme in a prevalent patient: the AVF patency.215,216 In this respect, Parisotto et al.,217 applying a Cox multivariate regression model on the results of an international survey on cannulation practices (n = 7058, majority nAVF), showed that AVF patency was significantly lower in the case of HD through pAVF, small-gauge needle (16 G), which may have been due to the endothelial damage caused by the increased velocity of the blood return, retrograde direction of the arterial needle and cannulation with the bevel down, QB < 300 mL/min, venous pressure < 100 mmHg (perhaps due to inflow stenosis) or progressively increasing pressure (perhaps due to outflow stenosis) and, finally, without compression of the arm at the time of cannulation or with compression using a tourniquet (versus compression of the arm by the patient). In addition, AVF patency was significantly greater if needling was performed using the rope ladder or the buttonhole technique compared to the area method.217

Repeated venous cannulation itself may damage the AVF due to direct trauma of the needle and/or to increased endothelial damage by shear forces created during blood return.207,211,212,218 These factors may stimulate the development of intimal hyperplasia, which could decrease patency of the AVF and, probably, also the survival of the patient.207,211,212,218 In this respect, the Frequent Hemodialysis Network Trial Group has conducted two controlled randomised trials: a) diurnal trial, comparing patients in in-centre HD during the day (6 days a week) and patients in conventional HD (3 days per week) for 1 year, and b) nocturnal trial, comparing patients in nocturnal home HD (6 nights per week) and patients in conventional HD (3 days per week) for 1 year.218 In both diurnal and nocturnal trials, the HD regimen of 6 times per week significantly increased the risk of AVF complications compared to the HD regimen performed 3 times per week. The authors concluded that frequent HD increases the risk of VA complications, largely because of the need for more repair procedures in patients with AVF. In other words, the more frequent nAVF use itself causes VA dysfunction.218

Cannulation practices are key factors in the process of AVF care and attention. An inadequate AVF cannulation technique could lead to short and long-term complications, such as infiltration-haematoma, infection, formation of aneurysms and pain at the cannulation site, resulting in situations of anxiety and fear in the patient, which often lead to a refusal to remove the CVC.207,211,212 These complications have a number of direct consequences, such as the need for additional needling, suboptimal or missed HD sessions, patient discomfort due to interruption of their regular treatment regimen and the need for longer sessions, the need to use CVC to bridge the gap between the creation and maturation of a new AVF, increase in hospital admissions and interventions, as well as higher HD treatment costs.207,211,212 These complications and their consequences can reduce VA patency and patient survival.207,211,212

Lee et al. analysed the risk factors and consequences of extravasations caused by needling the nAVF comparing 47 patients with a sufficiently significant nAVF infiltration to prolong CVC dependence for HD with 643 patients in the control group without nAVF infiltration.208 These authors showed that nAVF infiltration caused by needles is more common in elderly patients (aged 65 years or above) and those with recent nAVF (less than 6 months).208 In addition, as a result of these infiltrations, numerous diagnostic studies and interventions on the nAVF were carried out. There was a notable percentage of thrombosis (26%) and CVC dependence for HD was prolonged for more than 3 months.208 Finally, the financial impact of CVC-related bacteraemia, linked to the increase in the days of CVC dependence secondary to major nAVF infiltration, was estimated at US $ 8 million per year.208

Van Loon et al. published two prospective observational studies in 2009 (from the first cannulation until 6-months follow-up) on incident HD patients with nAVF and pAVF using the rope ladder technique.219,220 In most patients miscannulations (defined as the need to use more than one needle for the arterial and venous connection) were recorded between 1 and 10 times, being always greater the percentage of miscannulations for nAVF than for pAVF219. Although miscannulations were recorded on over 10 occasions for 37% of patients with nAVF and 19% of patients with pAVF, ultrasound-guided needling of the AVF was only used in 4% of patients.219 The percentage of patients with haematoma secondary to inadequate cannulation was always higher for nAVF than for pAVF, and it was higher for AVF in the arm than in the forearm.219 In the multiple regression model applied, complications associated with cannulation (need to use a CVC or carry out the HD session using single needle) were predictive of AVF thrombosis.219 In addition, these authors showed that these complications depend on the type of existing AVF so the percentage of AVF without complications was always significantly lower for pAVF than for nAVF.220

The use of the portable DU has been recommended in all HD Units in Spain for several years.216 There is no doubt that ultrasound guided cannulation is a tool of invaluable assistance for successful cannulation in difficult nAVF and, therefore, it can reduce errors in needling.221,222 In a national study covering 119 examinations using portable DU performed by the same nephrologist on 67 AVF, 31 previously unsuspected stenoses were identified in 44 cases where needling was difficult.223

Methodology of arteriovenous fistula cannulation

• •

  The AVF must be used exclusively to carry out HD treatment.

• •

  Cannulation of any AVF must be performed exclusively by specialised nursing staff in HD units who have demonstrated a high level of knowledge and specific skills.222

• •

  The initial cannulation of all new AVF should be performed exclusively by experienced nursing staff members of the HD Unit.212,213,222,224,225

• •

  All needling incidents should be recorded for investigation and for appropriate corrective measures to be adopted in order to ensure that the patient will receive the best nephrological care possible.213,225

• •

  Multiple unsuccessful needling attempts made by the same cannulator represent unacceptable practice.213

• •

  Prior to AVF cannulation, it is essential to know type, anatomy and the direction of QA in order to plan the location of the needling areas. For this purpose, it is extremely useful to have an AVF map in the patient’s medical record. All nursing staff needling an AVF for the first time should have prior knowledge of the map to correctly needle the area.

• •

  Before starting each HD session, an exhaustive physical examination of the AVF is needed, as detailed in section 4.

• •

  Needling should not be performed without first checking whether the AVF functions properly.225

• •

  Needling must be avoided at all times in areas of redness or areas with signs of infection, in areas with haematoma, crusting or altered skin and in apical areas of aneurysms.

• •

  In difficult or first cannulations, it is advisable to check for correct AVF cannulation using a syringe with physiological saline solution to avoid blood extravasations and the subsequent formation of a haematoma.

• •

  Topography of the needles. The “venous” needle should always be inserted proximal to the “arterial” needle to avoid recirculation.

• •

  Direction of the needles. The tip from the “venous” needle should always point in the same direction as QA (anterograde direction) to ensure optimal venous return.222 Whether the “arterial” needle tip should be oriented in the same direction (anterograde direction) or in the opposite direction to QA (retrograde direction) has been the subject of debate.213 In the Gauly et al. study, the “arterial” needle was placed in an anterograde direction in most cases (63%),206 but this situation does not necessarily increase the risk of recirculation as long as QA in the AVF is significantly higher than QB.222 According to recent data, anterograde direction of the “arterial” needle is associated with higher AVF patency217 as it leads to a lower turbulent QA and, probably, less intimal vascular damage.212

• •

  Orientation of the needle bevel. In the Gauly et al. case series, the bevel pointed upwards in most cases (72.3%).206 Although the upward or downward orientation of the bevel has been associated with the degree of pain at the time of needling,226 it has recently been shown that the bevel-up orientation is associated with higher AVF patency.217

• •

  Rotation of the needle (180º) at the time of cannulation. In the survey by Gauly et al., this manoeuvre was performed in around 50% of cases206 but nowadays it is discouraged since it enlarges the needle entry hole. It may also tear the body of the pAVF or damage the endothelium of the arterialised vein, and give rise to blood infiltrations in the lateral wall of the arterialised vein during the HD session.212,213 In addition, performing this rotation is unnecessary if backeye needles are used.10,213

Process of native arteriovenous fistula cannulation

• •

  After preparing the skin, proximal compression (manual, tourniquet) should be performed to cause venous stasis, and to stretch the skin in the opposite direction from the cannulation in order to fix but not obliterate the arterialised vein. The vein should always be compressed even if it is very well developed and/or the buttonhole method is used.213,217 In the study by Parisotto et al., compression by the patient at the time of nAVF cannulation had a favourable effect on its patency compared with no compression or the use of a tourniquet.217

• •

  Using the rope ladder method, the insertion angle of the needles in the nAVF must be approximately 25°, although this may vary according to the depth of the arterialised vein. The needles should be located at a distance of at least 2.5 cm from the anastomosis and should maintain a distance of at least 2.5 cm between their tips.207,212 In an international survey covering more than 10,000 cannulations with two needles in patients undergoing dialysis, mostly by nAVF (91%), the average distance between the two needles was 7.0 ± 3.7 cm and very similar to the distance recorded in a national study (7.3 ± 3.1 cm).206,227

Prosthetic arteriovenous fistula cannulation process

• •

  The angle of insertion of the needles in pAVF should be approximately 45°, although this may vary depending on their depth. The needles should be located at a distance of at least 5 cm from the anastomosis and should maintain a distance of at least 2.5 cm between tips.207,212 Rotation of needling sites for each HD session is particularly important in pAVF and consequently new needling sites should be selected between 0.5 cm and 1.25 cm from the previous sites to preserve the fullest integrity of the pAVF wall.212

• •

  Once the pAVF is needled, the angle must decrease to avoid needling the posterior wall, and it is then cannulated, making sure the tip of the needle is located in the centre of the pAVF lumen.

• •

  The area should not be proximally compressed when needling.

Fixing the needles and haemodialysis blood lines

• •

  Needles must be securely fixed on the skin of the limb to prevent accidental dislodgement and should remain visible for the entire treatment. The needle tip must be checked so that it does not damage the vessel wall.

• •

  The lines can be fixed onto the VA limb. It is not recommended that they be attached to anything mobile (armchair, bed or pillow). The main aim is to prevent extravasations as the patient moves.

• •

  Accidental needle dislodgement during HD session.228-230 This is a serious complication that may have catastrophic results.228 The reasons why needles may accidentally be dislodged are the following: poor fixation of the needles to the skin, defective adhesive tape, traction on any of the circuit lines or sudden movement of the AVF-bearing arm.230 To prevent needle dislodgement, the needles and blood lines must be properly secured with enough space so as to avoid dangerous traction.230 The limb must always be kept in view and, if necessary, kept still. If one of the needles is dislodged, the bleeding exit site must be immediately compressed, the blood pump stopped if this has not happened automatically, and the corresponding line clamped.230 The volume of blood lost must always be estimated and the patient’s haemodynamic stability must be checked.

→ Clinical question VIII What is the needling technique of choice for the different types of arteriovenous fistula: the 3 classical ones and self-cannulation?

(See fact sheet for Clinical question VIII in electronic appendices)

Rationale

Three different types of AVF cannulation techniques have been described.207,211-213,231

Rope ladder or rotating needling technique (sharp needle tip)

This is the needling method of choice for most patients. The needling sites are distributed regularly throughout the length of the arterialised vein for nAVF or pAVF body. In each HD session, two new sites are chosen for needle placement, thus allowing the skin to heal between HD sessions. With this technique, there is a moderate increase in diameter over the entire length of the arterialised vein with no or very little development of aneurysms (this avoids progressive weakening of the vein wall secondary to the blood return flow when this always occurs at the same point). The main problem is that it requires an arterialised vein which has a long enough trajectory to allow needling to rotate.

Area technique or needling circumscribed to the same area (sharp needle tip)

The main reasons for the use of this method are: short length of the arterialised vein, difficult trajectory for cannulation, nursing assessment that needling in another area will fail and patient refusal to be needled in another area. This technique involves repeated needling in a very restricted area of the arterialised vein, which causes damage to the venous wall and forms aneurysms in nAVF, as well as causing risk of pseudoaneurysms and thrombosis in pAVF. Therefore, this method is to be avoided whenever possible. However, the current situation in the “real world” is disappointing: according to an international survey mentioned above, the most commonly used technique (61%) was the area needling method.206

Buttonhole technique or constant needling at the same site (blunt needle tip)

This method must be used exclusively in nAVF and never in pAVF. The same hole is used to needle vessels in all HD sessions (the same entry into the skin, same angle of entry and same depth of entry into the vein). Following the creation of a subcutaneous tunnel of fibrous scar tissue, access to blood circulation is obtained with a blunt needle tip which eliminates the risk of internal tearing and bleeding.

The technique is based on repeatedly inserting a sharp needle tip into the same site and at the same angle of entry, preferably by a single cannulator, over six to ten HD sessions. This strategy allows a tunnel of fibrous scar tissue to be built up to the vein wall, which can then be cannulated with blunt-tipped needles. An arterial and a venous buttonhole are created. Once the tunnel is well formed, any trained member of the nursing staff or the patients themselves can needle the nAVF. In addition to the conventional sharp needle tip, the construction of the subcutaneous tunnel by other methods has been reported.232,233

It is very important to follow strict aseptic protocol. Before inserting the blunt-tipped needle into the subcutaneous tunnel, the two buttonhole sites must be carefully disinfected both before and after every HD session (double aseptic method), making sure that the scar crusts are completely removed from the previous session. The scab should never be removed with the same blunt needle which will subsequently be used for cannulation. Most blunt needles have a specially designed cap for removing the scab safely, without the need to use an additional needle and without damaging the walls of the hole.

All highly motivated patients with sufficient capability, treated in an HD unit or else in home HD, are offered the option to self-needle using the rope ladder method and, in some selected cases, using the buttonhole method.213,224

Evidence synthesis development

The initial enthusiasm generated by the buttonhole method, which was even reflected in some clinical guides,13 has been curbed by the evidence which subsequently appeared.234,235 For example, regarding the degree of pain perceived by the patient using the buttonhole method, studies have been published which report less pain,236-238 greater pain239,240 and the same amount pain versus rope ladder technique.241,242 In other words, there is equivocal evidence regarding the degree of pain using the buttonhole method, so taking all combined observational studies into account, buttonhole method is associated with a significant reduction in pain but this benefit disappears when analysing the randomised controlled trials.235 Therefore, with the currently available evidence, we cannot state that the pain produced by needling is significantly reduced using the buttonhole method, either in in-centre HD or in home HD with self-cannulation.235

Van Loon et al. published a prospective observational study with a 9-month follow-up in 2010 comparing 145 prevalent patients on HD using rope ladder technique (n = 70) and buttonhole method (n = 75).240 Despite seeing a significantly greater number of miscannulations in the buttonhole group compared with the rope ladder group, the number of haematomas was significantly lower in the buttonhole group, probably because an unsuccessful cannulation with a blunt-tipped needle causes less tissue damage than a sharp-tipped needle.240 In addition, the buttonhole group required significantly fewer interventions on the nAVF at the expense of fewer PTA; no differences were noted in the number of thrombectomies and surgical procedures between both groups of patients.240 The formation of aneurysms was significantly lower in the buttonhole group but, on the other hand, this group of patients received antibiotic treatment for nAVF-related infection significantly more frequently.240 Finally, patients in the buttonhole group experienced significantly greater pain and fear compared to the rope ladder group, although the application of local anaesthetic cream was significantly more frequent in this latter group.240

MacRae et al. carried out a randomised controlled trial in 2012 comparing 140 prevalent patients on HD using the standard (rope ladder, n = 70) and buttonhole needling (n = 70) methods. There was no difference in the perception of pain on needling between both groups of patients241. In the same study, although haematoma was significantly higher in the standard group, the signs of local infection and episodes of bacteraemia were significantly higher for the buttonhole group; no differences were found in post-dialysis bleeding between both groups241. Finally, the degree of difficulty in needling by the nursing staff was significantly higher in the buttonhole group (for both the arterial and the venous needle) compared with standard needling from 4 weeks, which coincided with the use of the blunt needle by multiple nurses.241

Subsequently, in 2014 MacRae et al. published the follow-up results of these patients (17.2 months with standard and 19.2 months with buttonhole needling): no differences were found in nAVF patency between HD patients using standard (rope ladder, n = 69) and buttonhole technique (n = 70).243 However, the total number of infections, both local and Staphylococcus aureus bacteraemia, was significantly higher in the buttonhole group.243 They found no differences in thrombosis rates, fistulography, PTA and surgical procedure when comparing the two groups of patients.243 The conclusions of this RCT were that the lack of patency benefit in nAVF and the increased risk of infection should be taken into careful consideration when promoting buttonhole technique.243

In 2013 Vaux et al. carried out a prospective randomised clinical trial comparing 140 prevalent patients on HD using the standard method (n = 70) and buttonhole technique (n = 70) with 1 year follow-up. They showed a significantly higher nAVF patency rate, significantly fewer procedures to maintain nAVF function (due to a lower number of PTA in stenosis) and no episodes of nAVF-related bacteraemia in the buttonhole group.233 The beneficial effects of the buttonhole method seen in this study may be explained by the different methodology used in constructing the subcutaneous tunnel, as a polycarbonate peg was used as a tutor inserted into the tunnel between HD sessions during the tunnel creation stage using a sharp-tipped needle.233,241,244

Muir et al. conducted a retrospective review of 90 consecutive patients in home HD comparing rope ladder (n = 30) and buttonhole needling (n = 60). No difference was found between the two groups with regard to definitive nAVF loss or the need for surgical intervention (any surgical revision or event requiring the definitive loss of the nAVF and/or the creation of a new nAVF).245 However, the total number of infections was significantly lower for rope ladder compared to buttonhole: 0.10 versus 0.39 events per 1000 days of nAVF use, respectively245. In addition, these authors also conducted a systematic review of 15 studies (4 randomised controlled trials and 11 observational studies) and found that, compared to the rope ladder method, the risk of infection was approximately three times greater using the buttonhole method.245

The rate of total recorded infections in the group of patients on dialysis using buttonhole in the study by Muir et al.245 was very similar to the rate of CVC-related bacteraemia (0.40 episodes of bacteraemia/per 1000 days CVC) recorded in HD units with optimal CVC management.246 Therefore, one of the main benefits of nAVF compared to CVC, i.e. its low infection rate, is thrown into serious doubt when using the buttonhole method.244

This increased risk of local and systemic infection when using buttonhole has been confirmed in other studies and systematic reviews234,235,239,247,248 and calls into question the use of this method in routine clinical practice.245 Favourable results have been reported in the prevention of bacteraemia caused by Staphylococcus aureus via the application of topical mupirocin in each buttonhole after performing haemostasis.249 However, the fundamental cornerstone for reducing infectious episodes using this technique is the continuing education of nursing staff and/or the patient through periodic step-by-step review of the asepsis protocol used.248

In 2013, Grudzinski et al. carried out a systematic review of 23 full text articles and 4 abstracts on the buttonhole method: 3 were open-label trials and the rest were observational studies of different methodological design and quality.234 The main conclusions of these authors were as follows: a) there were no qualitative differences in the results obtained between home HD patients and those who were dialysed using this method in HD centres; b) studies which considered nAVF patency, hospital admission, quality of life, pain and the formation of aneurysms had serious methodological limitations with an impact on the analysis of the results considered; c) bacteraemia rates were generally higher when using buttonhole cannulation, and d) the buttonhole method may be associated with an increased risk of infection.234

More recently, Wong et al. published another systematic review of 23 articles, 5 randomised trials and 18 observational studies on the buttonhole method, in which they highlighted the following main aspects235: a) this method does not significantly reduce pain during cannulation and appears to be associated with an increased risk of local and systemic infections; b) considering nAVF patency, interventions in the nAVF, hospital admissions or nAVF-related mortality, haemostasis, and hospital admission or mortality for any other cause, there are no data that enable us to impose one needling technique over the other, and c) the buttonhole method is only beneficial in reducing the formation of haematomas and aneurysms. The final conclusion of these authors235 was that: a) the evidence does not support the preferred use of the buttonhole method over rope ladder, either in a conventional in-centre HD or in home HD, and b) the evidence does not exclude buttonhole cannulation as appropriate for some patients with nAVF which are difficult to cannulate.

Although experience is limited, there is a surgical placement device250 which allows deep nAVF, at a depth of up to 15 mm, to be needled using the buttonhole method without the need for surgical superficialisation. This is a funnel-shaped titanium guide sutured over the vein. Its use is also indicated in nAVF which have a very limited space for needling and are difficult to cannulate. This device can only be used with the buttonhole technique.

From evidence to recommendation

According to the scientific evidence reviewed, there are no conclusive data to recommend one cannulation technique for all HD patients. However, rope ladder technique has been proven to offer fewer complications in both nAVF and pAVF. Buttonhole technique results in terms of reduction in the number of aneurysms, duration of AVF, local and systemic infections, pain on needling and post-dialysis bleeding time vary from one study to another. These data reinforce the idea that it is a “centre and cannulator-dependent” needling technique. However, the incidence of infections reported in controlled studies contraindicates its systematic use in the AVF, and hence GEMAV considers that the buttonhole method should be reserved exclusively for selected nAVF with great tortuosity and/or a short vein segment available for needling.

Single needle cannulation

The single needle cannulation technique is occasionally used in routine clinical practice when nAVF cannulation with two needles is impossible. It is a transitory fall-back puncture technique in order to avoid CVC placement, when the arterialised vein only presents a very short segment for double needling, as there has been some kind of complication during cannulation and/or withdrawal of the needles (haematoma) in the preceding HD session, or to attempt to continue the development of an incomplete arterialised vein, especially in a brachial location. A Y-shaped dual-exit bevel 14G or 15G needle and a double pump system in the HD monitor are required. HD adequacy should be monitored strictly, increasing the surface of the dialyser and/or duration of the HD session if necessary.

Needle withdrawal

The technique used to withdraw needles is just as important as cannulation as it must protect the AVF, avoid any additional injury (tears) and facilitate appropriate haemostasis.207 Each needle should be removed at approximately the same angle as it was inserted.10 No pressure should be placed on the exit site until the needle has been completely withdrawn in order not to damage the AVF.207

At the time of cannulation, 2 holes are created for each needle: one that goes through the skin (external) and another through the arterialised vein wall of the nAVF or of the pAVF body (internal).207 Therefore, even though they are not on the same plane, both external and internal holes should be compressed after removing the needle to ensure that there is no bleeding.207 If the internal orifice is not adequately compressed, bleeding will occur in the subcutaneous tissue with subsequent haematoma development.207,251 As previously mentioned in AVF cannulation methodology,208 this haematoma may jeopardise the AVF as it may hinder subsequent cannulation, limit the options for future cannulations and cause thrombosis due to increased extrinsic pressure or the development of stenosis.207 Therefore, 2 fingers should always be used for haemostasis after removing the needle, one intended to compress the outer hole and the other the inner hole.207 During haemostasis, the pressure exerted must be constant, without interruption and intense enough to stop bleeding at the exit sites but without interrupting the QA in the AVF.207,251 To minimise the risk of re-bleeding through the “arterial” needle hole once haemostasis has been achieved at this point (due to a sudden backward increase in pressure inside the AVF secondary to compression of the “venous” needle hole), it is preferable to first remove the “venous” needle, carry out the corresponding haemostasis at this level and then remove the “arterial” needle.251

Manual compression must be maintained for at least 10 min before checking if there is still bleeding at the needling site.252 In general, the time of haemostasis is higher for pAVF than for nAVF.207 When there is no excessive anticoagulation, a prolonged haemostasis time (more than 20 min) may indicate increased pressure inside the AVF secondary to a stenosis as detailed in section 4.251-253 If there are problems of bleeding and/or patients with a prolonged bleeding time, haemostatic dressings may be effective.251 A transparent micro-perforated dressing, which significantly reduces haemostasis time in both “arterial” and “venous” holes compared with conventional manual compression, has recently been introduced.254

Haemostasis in the first needling sessions must always be carried out by an expert member of the nursing staff. Subsequently, if the patient characteristics and AVF allow it, the patient himself should be taught how to perform haemostasis with a non-sterile glove.251 If this is not possible, a staff member of the HD Unit must be responsible for haemostasis.251 Clamps should not be used to perform haemostasis on pAVF and their use is discouraged in nAVF.207 If their use is necessary, they should only be applied to a well-developed nAVF with an adequate QA and the continuing nAVF function should be continually checked while the clamp is placed.207

Adhesive dressings or bandages should be applied to needling sites but never before haemostasis has been fully achieved.252 The bandage should never cover the whole circumference of the limb.207 AVF patency should always be checked after applying the dressing.207 The patient will be instructed to remove the dressing 24 h after application.207

Rationale

The self-care plan involves fully training the patient to take all the actions needed to help maintain a correctly functioning AVF, prolong its patency and acquire the necessary habits to allow them to detect, avoid and prevent AVF complications.

Training the patient to look after the arteriovenous fistula

This section describes the AVF self-care plan from its creation and the steps to be taken in the interdialytic period.10,255

Monitoring arteriovenous fistula function

Where possible, depending on their characteristics, patients must be taught to perform a daily physical AVF examination as detailed in Figure 2 of section 4.

Figure 2.

Systematics for physical examination of arteriovenous fistula according to examiner and frequency. The different aspects of physical exploration that should be performed by each examiner are highlighted in blue. Modified from reference 302.

(0.13MB).

Detection of possible complications

• •

  Signs and symptoms of infection such as redness patches/irritations, warmth, pain and suppuration.

• •

  Signs and symptoms of ischaemia on the AVF-bearing arm such as coldness, pallor and pain.

• •

  Signs and symptoms of thrombosis such as the appearance of hardening or pain, and absence of bruit and thrill.

• •

  Signs and symptoms of decreased venous return such as the presence of oedema.

Local care

• •

  From the first 24-48 h after AVF creation, gentle movements should be made with the fingers and arm of the AVF to promote blood circulation, but no brusque movements should be made when doing the exercises as they are likely to lead to bleeding from the wound or hinder venous return. In elbow nAVF and in pAVF created in the flexure, the arm must not be flexed.

• •

  The dressing should be kept clean and dry at all times and changed if dirty or wet.

• •

  In these early stages, situations that may contaminate the surgical wound are to be avoided and, if necessary, adequate protective measures should be taken (work in the countryside, work with animals.).

• •

  After the surgical stitches have been removed, the whole arm of the AVF should be thoroughly cleansed with warm water and soap on a daily basis. Skin should be kept hydrated to prevent the appearance of wounds.

• •

  When the patient has started HD therapy, the dressing covering the needling sites must be removed the day after the HD session. If the dressing is stuck to the skin, it is advisable to wet it with saline solution to prevent any injury which might lead to bleeding or infection of the AVF. The scab covering the wound must never be lifted.

• •

  If bleeding occurs through the needling hole in the skin, a gauze should be applied and compressed gently with the fingers as in the HD session. If bleeding does not stop in a reasonable amount of time, the patient should attend a healthcare facility for assessment. A circular compression bandage should never be used.

Acquiring certain habits in order to preserve arteriovenous fistula function

• •

  Blood pressure must not be taken or venipunctures be performed on the same arm as the AVF.

• •

  The AVF must not be knocked or compressed. Tight clothing, watches, bracelets and occlusive bandages should not be worn and the patient should not sleep on the arm of the AVF.

• •

  Weights must not be lifted or brusque movements made during exercise with this arm.

• •

  Sudden changes of temperature must be avoided.

If complications are detected, the nearest medical centre of reference must be contacted.

Recommendations

Rationale

AVF failure may be early or late. Early AVF failure is common, with an incidence of 9 to 53%.94,256 Late failure is associated with acquired stenosis in the arterial and mainly venous territory. The physiopathology of the failure is not at all well-defined, but it has been associated with different triggers that initially cause a stenosis that can lead to thrombosis and VA loss.257 Thrombosis is therefore the common factor in both early and late failure.

There are vascular diseases where the territory affected by a thrombosis has severe clinical repercussions, such as coronary or cerebral arteries.258 As antithrombotic medication may be beneficial in these diseases, for this reason it has been suggested that it could also reduce AVF thrombosis and, therefore, VA loss.

The first time this type of drug was proposed for VA thrombosis prevention was with the Scribner cannula in 1967.259 This cannula connected vessels in the wrist (radial artery and cephalic vein or ulnar artery and basilic vein) or in the lower third of the leg (posterior tibial and internal saphenous), through a permanently installed external bridge made of synthetic material (external AVF), so that the artificial kidney might be connected as often as necessary. Since then the result of the use of antiplatelet agents to reduce AVF failure has not been conclusive. Salicylates have been linked to a decrease in early failure, but observational studies such as the DOPPS found no increase in the proportion of usable AVF for HD.260 A clinical trial comparing clopidogrel with placebo demonstrated a reduction in early thrombosis in incident AVF but the proportion of AVF useful for HD did not change.171 Moreover, another DOPPS review found a lower risk of AVF failure in patients taking acetylsalicylic acid for at least one year261 and a meta-analysis including studies with the short-term use of different antiplatelet drugs also demonstrated a reduction in thrombosis in nAVF and pAVF.262

However, the follow-up period of these studies is limited, usually less than one year, and they fail to clearly show the benefit on patency without showing an increased risk of bleeding.

The HD patient presents a higher risk of bleeding as a result of multiple factors, including platelet dysfunction, anaemia or heparin use during HD. Added to this is the uncertainty of the extra risk due to the use of antiplatelet agents or oral anticoagulants, knowing that bleeding risk scores developed for the general population have not been validated for patients on HD.

This greater tendency towards haemorrhage has been observed in one of the DOPPS study reviews in patients with specific antiplatelet indications, such as rhythm disorders, in which the use of both antiplatelet agents and anticoagulants was associated with an elevated risk of mortality, both from cardiovascular and all-cause mortality.263 In a retrospective study that included a 5-year follow-up of 41,000 patients, there was also a higher association with a higher mortality with antiplatelet or anticoagulants in HD patients, although the confounding factor of the treatment indication could not be totally ruled out.264 When studies assessing the risk of bleeding are analysed using the results of antiplatelet therapy in AVF patency, these are limited and without conclusive results. Although appearing to show a decrease in the risk of thrombosis in nAVF and not in pAVF, a systematic review assessing the risk of bleeding in HD patients cannot find agreement on an indication in antiplatelet therapy in the presence of increased risk of bleeding in kidney patients.265

It is therefore considered necessary to assess whether antithrombotic therapy can be indicated in the prevention of AVF dysfunction.

→ Clinical question IXa In which situations is it necessary to indicate antithrombotic prophylaxis after creating/repairing the arteriovenous fistula?

(See fact sheet for Clinical question IXa in electronic appendices)

→ Clinical question IXb Does the use of antiplatelet agents prior to arteriovenous fistula creation have an impact on patency and reduce the risk of thrombosis?

(See fact sheet for Clinical question IXb in electronic appendices)

Evidence synthesis development

In which situations is it necessary to indicate antithrombotic prophylaxis after creating/repairing the arteriovenous fistula?

The systematic review of Palmer et al.266 (arising from the Cochrane review of Palmer et al.267) analyses the effect of antiplatelet therapy on the rate of thrombosis and patency of the VA in HD patients, including both nAVF and pAVF. In 12 trials (with 3118 participants), antiplatelet therapy started at the time of surgery; in 6 trials, 1-2 days before; in 2 trials, 7-10 days before; in 2 trials, 1-2 days after; in 1 trial 1 month after, and was not specified in another. The median of intervention was 3 months (interquartile range, 1.25-6). Ticlopidine, acetylsalicylic acid and clopidogrel were the most commonly used antiplatelet drugs.

Limitation: risk of high or unclear bias in most trials and limited data for analysis of some effects, especially in pAVF and VA adequacy for HD.

Results

• •

  AVF failure due to thrombosis or loss of patency. Antiplatelet therapy reduced the thrombosis or loss of patency in nAVF to half (6 trials, 188 events, 1242 participants; relative risk [RR]: 0.49; 95% CI, 0.30-0.81; I2 = 29%). In absolute terms, the treatment of 100 individuals with antiplatelet agents for 1-6 months (acetylsalicylic acid, ticlopidine or clopidogrel) would prevent failure of the fistula in between 6 and 21 individuals, assuming a baseline risk of 30% of one or more events.

  However, antiplatelet therapy had little or no effect on pAVF thrombosis or patency (3 trials, 374 events, 956 participants; RR: 0.94; 95% CI, 0.80-1.10).

• •

  AVF failure due to thrombosis or early loss of patency. VA failure was assessed in 5 trials (1105 participants) in the 8 weeks after surgery. In this subgroup, treatment with antiplatelet drugs significantly reduced early thrombosis or failure in AVF patency in 57% compared with placebo treatment or no treatment (177 events, RR: 0.43; 95% CI, 0.26-0.73; I2 = 25%). There were no data in the review on patients with pAVF.

• •

  Failure to achieve a suitable VA for HD. The effect of antiplatelet therapy on the adequacy of VA for HD was investigated in 5 trials (1503 participants). The differences were not statistically significant, either in nAVF (2 trials, 470 events, 794 participants; RR: 0.57; 95% CI, 0.13-2.51) or in pAVF (1 trial, 12 events, 649 participants; RR: 0.51; 95% CI, 0.16-1.68).

• •

  Need for intervention to maintain AVF patency or maturation. There were no statistically significant differences in the need for intervention to maintain patency or maturation of the AVF, in nAVF (1 study, 17 events, 866 participants; RR: 0.69; 95% CI, 0.26-1.83) or in pAVF (1 study, 196 events, 649 participants; RR: 0.89; 95% CI, 0.64-1.25).

• •

  Risk of bleeding. Information is provided on bleeding events in 10 trials (3930 participants). There were no statistically significant differences in severe bleeding—retroperitoneal, intraocular, intra-articular, cerebral or gastrointestinal—(10 studies, 3930 participants; RR: 0.93; 95% CI, 0.58-1.49) or minor bleeding (4 studies, 237 participants; RR: 1.22; 95% CI, 0.51-2.91).

• •

  Abandonment of treatment. There were no statistically significant differences in abandoning treatment compared with the control group (8 studies, 1973 participants; RR: 1.01; 95% CI, 0.84-1.20).

• •

  Antithrombotic prophylaxis after VA repair. No studies have been found that analyse the effects of antithrombotic prophylaxis after VA repair.

Does the use of antiplatelet agents prior to arteriovenous fistula creation have an impact on patency and reduce the risk of thrombosis?

No studies were found on the use of antiplatelet agents prior to VA creation and the impact it has on patency and the risk of thrombosis in the publications by Palmer et al.,266,267 so there is no comparison of antiplatelet use prior to or post VA creation, or prior and post versus only post VA creation. Since the studies found analyse peri-operative, i.e. both prior to and post, treatment in all cases, the evidence available is considered to be indirect.

Results

• •

  AVF failure (due to thrombosis or loss of patency). Reviews provide information on 5 RCTs in which antithrombotic therapy begins before AVF creation and continues for up to four or six weeks after creation; however, there is a great deal of variability in the number of days the drug is received prior to the operation in each study. In one study, the drugs were given one day before and for 28 days after creation; in another, 2 days before and for one month afterwards; in another two, 7 days before and then for 28 days; in yet another, 7 to 10 days before and then for 6 weeks. This meta-analysis also includes another study in which drugs are administered on day 1 of the operation and continue for 6 weeks.

  Antiplatelet therapy reduced the risk of thrombosis or patency failure by almost 50% (6 trials, 218 events, 1365 participants; RR: 0.54; 95% CI, 0.39 to 0.74; I2 =10%).

• •

  Early thrombosis of the VA (within 8 weeks) in AVF. Antiplatelet therapy reduced the risk of early VA thrombosis by close to half (6 trials, 218 events, 1365 participants; RR: 0.54; CI: 95%, 0.39 to 0.74; I2 = 10%).

  There were no significant differences between treatments relating to: all-cause mortality; cardiovascular-related mortality; fatal or non-fatal infarcts; fatal or non-fatal strokes; minor, major or fatal bleeding; loss of primary patency; need to perform any intervention to maintain patency and hospital admission.

• •

  pAVF. No differences were found between treatments for any outcome measure in patients who undergo VA creation using pAVF.

• •

  pAVF failure (due to thrombosis or loss of patency). No significant differences were found between treatments (2 trials, 266 events, 756 participants; RR, 0.94; 95% CI, 0.79 to 1.11; I2 = 0%).

In a systematic Cochrane review on the use of medical treatment to improve nAVF and pAVF patency,268 the antiplatelet ticlopidine showed a significant reduction in the risk of failure of nAVF due to thrombosis compared with placebo, which in relative terms was 48% (3 clinical trials, 339 participants; OR: 0.45; 95% CI, 0.25 to 0.82). No significant differences were seen when comparing other treatments such as acetylsalicylic acid, clopidogrel or warfarin with placebo. According to the authors of the review, the quality of evidence was low due to the limited follow-up of the studies and the low availability of studies to test the efficacy of the treatment.

From evidence to recommendation

VA thrombosis is the consequence of both early and late failure leading to the loss of the vascular access. Based on other vascular territories, where antiplatelet therapy is effective in reducing risk of thrombosis, it has been proposed that this benefit might even be applied to improve AVF patency. However, patients on HD present a greater risk of multifactorial component bleeding, meaning the introduction of antiplatelet therapy could potentially increase this risk.

The evidence review shows that in HD patients with nAVF antiplatelet therapy reduces the risk of thrombosis, and there are no differences in the effects on maturation and use of the nAVF for HD. It must be noted that bleeding risk analysis gives uncertain results. The authors point out that not every adverse effect was reported accurately, because the number of events identified in both groups was limited. In addition, episodes of serious haemorrhaging events were defined a priori and systematically described in only 2 out of 21 trials. Therefore, GEMAV interpreted that the use of antiplatelet therapy should be studied on a case-by-case basis, due to the potential side effects in this population.

On the other hand, in HD patients with pAVF, antiplatelet treatment is not effective in preventing thrombosis or maintaining VA patency.

Recommendations

Several obstacles have to be overcome to obtain a valid AVF which can be used to start a chronic haemodialysis (HD) programme.214 The biggest of them is to achieve an adequate maturation, particularly in the case of nAVF, since the current percentage of maturation failures is about 40%.214 Once this difficult objective has been achieved, we must remain in a state of alertness and use all available means at our disposal to prevent thrombosis and to maintain AVF patency in the prevalent patient.

Irreversible thrombosis of the AVF results in a series of negative consequences for the prevalent patient included on an HD programme269: reduction in venous capital, need for central venous catheter (CVC) placement, lower HD efficacy, possible central vein stenosis or thrombosis, chronic inflammation in the case of pAVF, and construction of a new AVF. All of this increases the frequency of hospital admission, morbidity and mortality and healthcare spending for the chronic HD patient.270 Therefore, preventing thrombosis of the AVF is paramount for these patients.

Regarding AVF thrombosis, it must be taken into account that:

• •

  It is not always technically possible to restore AVF patency in all cases of thrombosis of the AVF, even in the hands of experienced specialists.271

• •

  Secondary AVF patency is significantly lower after restoring AVF patency post-thrombosis when compared with elective repair of AVF stenosis before thrombosis (see section 5 “Complications of arteriovenous fistula”, recommendation 5.2.6).272,273

Therefore, it is very important to note that thrombosis should preferably be prevented through early diagnosis and treatment of significant stenosis rather than be salvaged via interventional radiology or vascular surgery.

The most common cause of thrombosis is severe stenosis of the AVF.10,253 Currently, in order to qualify a stenosis as significant, it is necessary to demonstrate a reduction in the vascular lumen greater than 50% using ultrasound and/or angiography together with the repeated alteration of one or several parameters obtained by monitoring and/or surveillance methods.10 The diagnosis of significant stenosis is an indication that corrective treatment by percutaneous transluminal angioplasty (PTA) and/or surgery should be performed electively or preventatively to avoid thrombosis.10

AVF follow-up programmes comprise two key aspects: a) the early diagnosis of significant stenosis using different screening methods or techniques, and b) its elective or preventive correction to prevent thrombosis and improve AVF patency.10

The philosophy of these programmes is based on the fact that, in the vast majority of cases, AVF stenosis develops over varying time intervals and, if diagnosed and corrected in time, sub-dialysis can be avoided and the rate of thrombosis reduced by between 40% and 75%.10,274 These follow-up programmes should be developed in every HD unit systematically, protocolised and with multidisciplinary participation involving nursing staff, nephrology, radiology and vascular surgery.253Table 8 shows the AVF follow-up programme objectives for both nAVF and pAVF.275-277

According to DOPPS (Dialysis Outcomes and Practice Patterns Study I and II, 1996-2004) study data, the likelihood that a prevalent patient be dialysed through a CVC is directly related to the number of permanent AVF previously placed.32 It is likely that if AVF follow-up programmes had previously been introduced in these DOPPS centres, many cases of thrombosis could have been avoided; therefore, the prevalence of patients on HD with CVC would have been reduced.32 In this respect, an inverse relationship between the rate of preventive intervention and the rate of AVF thrombosis has been demonstrated in Spain for both nAVF and pAVF.278

The screening methods or techniques for the early diagnosis of significant stenosis are classified in 2 major groups279 (Table 9):

• 1.

  First-generation methods.

  • •

    Clinical monitoring:

    • –

      Physical examination.

    • –

      Problems during the HD session.

    • –

      Blood pump (QB) stress test for nAVF.

  • •

    Monitoring and surveillance of AVF pressure: dynamic venous pressure (DVP), intra-access pressure (IAP) in its normalised static version.

  • •

    Determining the percentage of recirculation.

  • •

    Unexplained decrease in HD adequacy: Kt/V index, urea reduction ratio (URR), Kt index.

• 2.

  Second-generation methods. These allow the calculation of AVF blood flow (QA).

  • •

    Dilution screening methods.

  • •

    Doppler ultrasound (DU).

In addition, these techniques can also be classified as “monitoring methods” and “surveillance methods” depending on whether special instrumentation is not or is required, respectively. All first-generation methods, except static venous pressure, fall within monitoring methods.274 Static venous pressure (see section 4.3.2.) and second-generation methods are considered to be surveillance methods. With regard to periodicity of determination, although these methods should be applied monthly,10 it is acceptable to measure QA in the nAVF every 2-3 months.14,15

Regarding the different monitoring and surveillance techniques used, it is important to consider that:

• •

  The prospective analysis of any monitoring or surveillance parameter used has greater predictive power to detect AVF dysfunction than any isolated values.10 In this respect, it is essential to have a record of each AVF in the HD unit to allow it to be assessed over time.

• •

  They are not exclusive but complementary. The application of several monitoring or surveillance methods simultaneously increases the performance of the follow-up programme.280,281 In addition, it has been demonstrated that the precision of each AVF monitoring and surveillance technique is related to stenosis location.282

Many of the screening methods described, both first- and second-generation, can be used to non-invasively assess the functional outcome of elective procedure performed on the AVF stenosis.282-284 In this regard, QA measurement has also been used in situ immediately after performing PTA on the AVF stenosis to check the functional outcome of the elective treatment.285

Although clinical monitoring lost a certain amount of importance when dilution methods were introduced for non-invasive QA determination and DU use became more widespread, its central role in AVF monitoring is currently undisputed.282,286,287 The AVF’s clinical monitoring takes into account two key aspects253,270,282,286-293: physical examination and problems during the HD session. The stress test for nAVF according to QB (QB stress test) has recently been described, and seems to be effective in diagnosing so-called inflow stenosis.294

4.2.1 Physical examination

This should be carried out regularly using inspection, palpation and auscultation10,282,286,293 (Table 10). This is an easy method to learn and perform; it takes very little time, does not require any special instrumentation or additional staff and, therefore, is a low cost test. In addition to nursing staff and the nephrologist, it is advisable that this examination should be partially carried out by the patients themselves daily (Figure 2).295 The detection of changes in the characteristics of the pulse, bruit and thrill of the AVF, compared with prior checks, makes it possible to diagnose a stenosis and specify its location.282,286,293 Unlike other AVF follow-up methods, physical examination also allows the identification of pathologies other than stenosis, such as aneurysms or infection.286

Table 11 summarises the findings obtained by physical examination for the differential diagnosis between inflow stenosis (located in the feeding artery, in the anastomosis itself or in the initial segment of the arterialised vein up to 5 cm post-anastomosis), outflow stenosis (located in the arterialised vein segment from the needling area to the right atrium) and nAVF thrombosis. Central venous stenosis is an outflow stenosis which is located in the venous segment from the cephalic vein arch at the level of the first rib to the right atrium. The nAVF without stenosis has a smooth or soft, easily compressible pulse, a predominant thrill over the anastomosis and a continuous bruit (systolic and diastolic) of low intensity (Table 11).

• •

  Inspection. Table 10 summarises the basic information to be taken into account during AVF examination. It is very important to observe the entire limb where the vascular access (VA) is located. In the case of AVF in the upper limbs, oedema and collateral circulation are signs that suggest total or partial central venous stenosis. The extension of an oedema can help us to locate the level of the central stenosis: if the oedema only involves the arm, this suggests that the stenosis is in the subclavian vein; if the oedema includes the chest, breast and/or ipsilateral face, stenosis is more likely in the brachiocephalic vein; bilateral oedema (chest, breasts, shoulders and face) suggests a superior vena cava stenosis.286 The distal areas of the limb must be assessed for signs of ischaemia (coldness, pallor and ischaemic digital ulcers) and signs of venous hypertension (hyperpigmentation and stasis digital ulcers).286,296-298 The entire AVF segment must be inspected to detect the presence of haematomas, aneurysmal dilatations and signs of swelling.299,300 Any arterialised vein which does not collapse, at least partially, after lifting the arm, probably has a proximal stenosis (Tables 10 to 12).10,282,286,293

  Table 12.

  Main tests used for physical examination of arteriovenous fistula (AVF)

  Arm elevation test

  • It consists of raising the arm where the nAVF is located, above the heart level, and then observing whether the arterialised vein collapses • The test is considered normal when the nAVF collapses after arm elevation, thus ruling out an outflow stenosis • In the case of a venous stenosis, only the segment of arterialised vein proximal to the lesion will collapse during the test, while the segment distal to the stenosis will remain distended without collapsing

  Pulse augmentation test

  • This test allows assessment of the inflow segment of the arteriovenous access • It consists of transient arterialised vein occlusion several centimetres above the arterial anastomosis with one hand and, simultaneously, the evaluation of the pulse intensity at the anastomosis level with the other • This test is considered normal when the arterialised vein segment distal to the occlusive finger (between the finger and the anastomosis) presents an increase in pulse rate • This test is based on the fact that if the vascular access is completely occluded at a distance from the arterial anastomosis, the soft pulse intensity will increase. The degree of this increase is directly proportional to the QA in the inflow segment of the nAVF • The presence of arterial system pathology retrograde to the anastomosis (feeding artery stenosis) conditions the degree of pulse increase obtained when using this test

  Sequential occlusion test

  • It is similar to the Pulse Augmentation Test but focuses on the thrill disappearance with the arterialised vein occlusion of the nAVF • Its purpose is to detect the collateral venous branches that arise from the arterialised vein. Often, a collateral vein may be visible and, therefore, previously detected by examination • This test is based on the relationship between the thrill and the QA of the arterialised vein • It involves occluding the arterialised vein close to and proximally to the anastomosis with one hand, while the normal thrill is palpated over the anastomosis with the other. The thrill, usually palpable in the arterial anastomosis, indicative of QA, disappears when the arterialised vein is manually obstructed proximally by causing a transient QA interruption. Next, the entire arterialised vein segment should be examined by progressively changing the occlusion point proximally. If the thrill does not disappear at any point along the venous pathway, it means that a collateral vein is present below the occlusion point

  nAVF, native arteriovenous fistula; QA, blood flow.
• •

  Palpation.282,286,293,301 Pulse is observed more correctly using the finger tips. Under normal conditions, the nAVF pulse is of low intensity, soft and easily compressible. Usually, an increased nAVF pulse is indicative of proximal stenosis (hyperpulsatile nAVF) and the amount that this increases is directly proportional to the existing degree of stenosis. In contrast, a pulse which is excessively weak (hypopulsatile nAVF, flat access), with little increase through transitory manual occlusion, suggests the presence of inflow stenosis (pulse augmentation test, Table 12).

  Thrill is a palpable nAVF vibration, which is more easily explored using the palm of the hand, and reflects the QA circulating along the arterialised vein.282,286,293 The absence of thrill indicates a deficit of QA. This sign, together with the absence of pulse, is characteristic of AVF thrombosis. Two different types of thrill can be palpated:

  • –

    A diffuse basal thrill in a normal AVF. This is gentle, continuous (systolic and diastolic), palpable throughout the whole AVF segment but more intense at the level of the venous anastomosis.

  • –

    A locally increased thrill. This reflects the presence of turbulent flow located at a stenosis area in the arterialised vein. As the degree of stenosis progressively increases, with a concomitant increase in resistance to the QA, thrill shortens and loses its diastolic component. The whole trajectory of the arterialised vein should be examined to detect the presence of abnormal thrill. In the event of a stenosis in the subclavian vein or cephalic vein arch, thrill can be detected below the clavicle.286

• •

  Auscultation. The normal AVF bruit and the temporary changes that may occur in this bruit, as well as the occurrence of abnormal bruits,282,286,293 must be assessed. This is the auditory manifestation of thrill. Two different types of bruit can be heard:

  • –

    A diffuse basal bruit in a normal AVF. This has a low tone, like a soft and continuous murmur (systolic and diastolic).

  • –

    An abnormal bruit associated with stenosis. The increased resistance caused by a progressive stenotic lesion will lead to the gradual loss of the diastolic component of the bruit and a simultaneous increase in its tone. The whole trajectory of the arterialised vein, including the area below the clavicle, should be examined to assess the presence of an abnormal bruit.286

Juxta-anastomotic or peri-anastomotic nAVF stenosis, i.e. the stenosis located in an area of 2-3 cm immediately adjacent to the anastomosis, which can affect both the afferent artery and the efferent vein, behaves like an inflow stenosis and may be diagnosed easily by exploring the anastomosis and the most distal segment of the arterialised vein286. At anastomosis level, thrill is only palpated during the systole and the pulse is greatly increased (defined as “water-hammer” according to English-speaking authors) but it suddenly disappears when the examiner’s finger moves proximally along the trajectory of the vein and finds the precise location of the stenosis; proximally to the stenosis, the pulse is very weak and may be difficult to detect. On occasions, the stenosis can be seen as a gap related with a sudden decrease in vein size.

Several prospective observational studies have shown that physical examination diagnoses stenosis with a high degree of sensitivity and specificity, as well as precision, and therefore, it should have a prominent position among AVF screening methods.204,286,287,301-308 The efficacy of physical examination carried out by qualified staff is equivalent to other more sophisticated screening methods287,301,302; the key lies in the examiner’s judgement.302 In this respect, in the study by Coentrão et al., conducted on 177 consecutive prevalent patients with nAVF dysfunction, diagnostic agreement of physical examination with fistulography for diagnosis of stenosis at all locations was always higher when a resident nephrology doctor with six months’ training performed the study compared with several general nephrologists without any specific training in nAVF examination (overall agreement 86% versus 49%, respectively).302

4.2.2 Problems during the haemodialysis session

These could be indirect signs of AVF stenosis if they appear persistently (three consecutive HD sessions), compared with the previous HD sessions253:

• •

  Difficulty in AVF needling and/or cannulation.

• •

  Aspiration of clots during needling.

• •

  Increase in negative pre-pump arterial pressure.

• •

  Failure to reach prescribed QB.

• •

  Increase in the return or venous pressure.

• •

  Prolonged haemostasis time, without excessive anticoagulation.

4.2.3 Native arteriovenous fistula stress test according to the pump flow

This test has proved effective in diagnosing inflow nAVF stenosis (positive predictive value of 76.3%) and is based on the decrease that occurs in QA when raising the upper limb from 0° to 90° for 30 s and QB of 400 mL/min.294 To carry it out, with the arm in this raised position, QB is reduced progressively to 300, 200 and 100 mL/min and the test is considered positive when the alarm on the HD machine is triggered because negative arterial pressure falls below -250 mmHg. The existence of a positive test with low QB values (100-200 mL/min) involves the presence of decreased QA and, therefore, high probability of relevant stenosis.

The presence of significant AVF stenosis may cause a retrograde increase in pressure inside it and can be detected by monitoring and surveillance of AVF pressure.10,274,283,303,309-315Table 13 provides details of how to determine AVF pressure.

These methods are preferred for the follow-up of proximal nAVF and, especially, pAVF.10,283 Collateral veins of a radiocephalic nAVF can cause decompression and a decrease in the sensitivity of these techniques when used for detecting distal nAVF stenosis.10,283

The pioneering work of Besarab et al.309 showed that the sensitivity to diagnose significant pAVF stenosis by determining normalised static pressure (see section 4.3.3.) was 91%. In the presence of the most common stenosis diagnosed in pAVF, i.e. the stenosis located in the anastomosis between the venous end of the graft and the efferent vein, there is a retrograde increase in pressure throughout the whole pAVF and the pressure level reached is directly related to the existing degree of stenosis.316

4.3.1 Dynamic venous pressure

DVP is the pressure needed to return the dialysed blood into the AVF through the venous needle recorded by the venous pressure transducer of the HD monitor. In fact, it is the sum of the pressure required to overcome resistance exerted by the venous needle and the pressure existing inside the AVF (Table 13).10

There are contradictory results in the literature with regard to DVP efficacy in detecting AVF with significant stenosis and high risk of thrombosis.311,312,317-321 In the classic Schwab et al.312 study, the incidence of thrombosis obtained when comparing AVF with electively corrected significant stenosis (previous DVP > 150 mmHg) and AVF with normal DVP with no suspected stenosis was similar (0.15 versus 0.13 episodes/patient/year). Smits et al.311 showed a significant reduction in the incidence of pAVF thrombosis by the application of a follow-up programme which included DVP measurements, static venous pressure and QA. However, this same Dutch group failed to previously demonstrate the efficacy of DVP in predicting pAVF thrombosis.322

To sum up, the current available data suggesting the usefulness of DVP to diagnose stenosis and predict thrombosis are limited and inconclusive. It is not acceptable to use DVP as a screening method for AVF stenosis in a non-standardised way.

4.3.2 Intra-access pressure or static pressure

This is determined by the presence of QB = 0 mL/min (pump stopped). Unlike DVP, IAP is not influenced by the type of needle used, QB or blood viscosity.

The simplified determination by Besarab et al. is used to calculate it. This takes into account the pressure obtained by the pressure transducer connected to the venous or arterial line of the HD monitor (mmHg) and the height between the venous or arterial needle (or the arm of the patient’s armchair) and the level of blood in the venous or arterial chamber (cm).10,314

In a national study, referring to 24 brachial pAVF, the VA with stenosis had a significantly higher IAP than the other AVF (48.7 ± 22.2 versus 27.6 ± 0.1 mmHg).283 It is considered that a DVP ≥ 150 mmHg with a QB = 200 mL/min (PV200) corresponds to an IAP > 60 mmHg.313 In the aforementioned study by Besarab et al., pAVF surveillance using static pressure achieved a 70% decrease in the incidence of thrombosis.309

4.3.3 Equivalent or normalised static intra-access pressure

As IAP relates to mean arterial pressure (MAP), the results are expressed in an equivalent or normalised form using the IAP/MAP ratio.10 In the absence of significant stenosis and because of existing collateral circulation, the IAP/MAP ratio will always be lower in nAVF than in pAVF. In another study by Besarab et al.,315 the IAP/MAP ratio in cases without stenosis was higher in pAVF (0.43 ± 0.02, n = 414) compared with nAVF (0.26 ± 0.01, n = 286), but without significant differences in relation to QA.

Normalised intra-access pressure profiles have been described according to the situation of the stenosis in the pAVF at the level of the arterial anastomosis, body (between the 2 needles) or venous anastomosis. It is considered that, when faced with a stenosis located in the venous anastomosis of the pAVF, the IAP/MAP ratio at the level of the venous and arterial needles is > 0.5 and 0.75, respectively.10,315 In the aforementioned study by Caro et al.,283 there was a significant difference between the IAP/MAP ratio determined in pAVF with and without stenosis: 0.5 ± 0.2 and 0.3 ± 0.1, respectively.

When there is a significant stenosis located in the venous anastomosis of a pAVF, there is an inverse relationship between normalised IAP and the QA of AVF.315,323 In this functional situation of raised normalised IAP and low QA, the AVF comes fully within the area of high risk for thrombosis.274

When significant stenosis is present, the QA of AVF decreases and the percentage of already dialysed blood re-entering the dialyser through the arterial needle increases. In the absence of technical errors, recirculation occurs as a consequence of a severe AVF stenosis when QA is close to or decreases below the planned QB (300-500 mL/min).10,313,315

Therefore, the measurement of recirculation is not the best method for early detection of stenosis.279,324 Above all, it is not recommended that it be applied to monitoring pAVF.10,274 In this type of AVF, recirculation occurs late when there is severe stenosis and a very high risk of thrombosis.274 In addition, we must remember that the presence of a localised stenosis between the two AVF needles does not cause recirculation.324

The recirculation percentage can be determined using the following two methods10:

• •

  Determination of urea recirculation.325 This is described in Table 14. The presence of a percentage of urea recirculation > 10% is a criterion for investigating a possible AVF stenosis by means of an imaging test.10

  Table 14.

  Determination of urea recirculation

  • This should be performed at the start of the haemodialysis session—HD—(during the first 30-60 min), provided that the haemodynamic stability of the patient is checked. • In order to calculate it, the ultrafiltration (UF) rate should be decreased to zero. If the online haemodiafiltration technique is being used, it must be disabled. • To obtain the samples, withdraw blood simultaneously from the dialyser entry in the arterial line and at the exit of the dialyser in the venous line at the programmed pump flow (QB). Immediately afterwards, reduce the QB to 50 mL/min, wait 20 seconds and take another sample from the arterial line to determine peripheral or systemic urea (low-flow method). Then, continue with the scheduled HD. • The recirculation percentage calculation (R) is performed according to the following formula:R=( UREAp−UREAa / UREAp−UREAv)×100

  UREAa, urea of the arterial line; UREAp, peripheral urea; UREAv, urea of the venous line.
• •

  Determination of recirculation using dilution screening techniques (Table 15).326-330 These methods present higher sensitivity and specificity than the urea recirculation method.328,329 There are published studies using the ultrasound dilution method, the thermodilution method with BTM (blood temperature monitor) sensor and the glucose perfusion method.327,328,330 In this respect, Wang et al.330 demonstrated that recirculation values higher than 15% obtained using the BTM sensor provided a high sensitivity (81.8%) and specificity (98.6%) in the detection of nAVF requiring elective intervention. The presence of AVF stenosis should be investigated in the case of a recirculation percentage greater than 5% and 15% using the ultrasound dilution and thermodilution methods, respectively.10,330

  Table 15.

  Main dilution screening techniques for the indirect determination of arteriovenous fistula blood flow (QA)

  Reversing the haemodialysis blood lines

  • Ultrasound dilution method335 • Haematocrit dilution or ultrafiltration or Delta-H method336 • Differential conductivity method337 • Ionic dialysance method338 • Thermodilution method339 • Temperature gradient method340 • Haemoglobin dilution method341

  Without reversing the haemodialysis blood lines

  • Transcutaneous optical method342 • Glucose pump test343

The decrease, for no apparent reason, in HD adequacy assessed by the Kt/V index or PUR may be an indirect sign of AVF dysfunction.279,331 In one study, patients with significant nAVF stenosis (n = 50) presented a Kt/V index lower (1.15 ± 0.20) than the remaining patients (1.33 ± 0.16) (p < 0.0001).303 It is considered that HD efficacy is affected at a late stage during the natural development of AVF stenosis when a high percentage of recirculation becomes evident.279

However, it has been published that the persisting decrease in the Kt index, determined online using the ionic dialysance method in each HD session, makes it possible to detect early recirculation caused by significant nAVF stenosis.332

Rationale for dilution methods

The objective follow-up of AVF function should be carried out regularly by determining its QA.14 In the presence of a significant stenosis, QA always decreases irrespective of the AVF type (nAVF or pAVF), its location (upper or lower limb) or the topography of the stenosis (feeding artery, anastomosis, arterialised vein, central vein) .10,279,333,334 This is very important and is a notable advantage compared with first-generation methods. For example, in the presence of a significant nAVF stenosis in the arterialised vein, QA will decrease but, depending on the venous needle position in the arterialised vein, it is possible that the venous pressure (determined by DVP) does not increase.279

The introduction of the ultrasound dilution method by Nicolai Krivitski in 1995 meant a qualitative change in the field of AVF study as, for the first time, it was possible to perform non-invasive QA estimation.335 Since then, several dilution techniques that allow the indirect determination of QA during HD and, therefore, the functional follow-up of the AVF have been described (Tables 15 and 16).336-343

QA is calculated by quantifying the difference in recirculation before and after the dilution of a particular indicator (haematocrit, temperature), with or without inversion of the HD blood lines. If both arterial and venous needles have been inserted into the same arterialised vein, artificial recirculation is created when reversing the blood lines, with the dilution of the indicator that enables us to calculate QA according to the formulae shown in Table 16.

The dilution methods requiring the HD blood lines to be reversed are those most commonly used today. However, in some cases, they cannot be applied: when we insert the venous needle through which blood returns into a vein other than the AVF-bearing arterialised vein, AVF recirculation is zero and, therefore, QA calculation is impossible.338,344

Dilution techniques that calculate QA during HD should be performed within the first hour of the session to avoid haemodynamic changes secondary to ultrafiltration.270

According to the European guidelines, there is no clear preference for any of these methods14 and most studies have shown similar results for QA after applying different dilution techniques.345-348 Indeed, all of them have advantages and disadvantages when used. For example, the time required to determine QA using the Delta-H method is long (more than 20 min) but, in contrast, it is a completely examiner-independent method and QA value automatically displays on the Crit-Line monitor screen immediately after the completion of the examination.270,348 Other methods, like thermodilution and temperature gradient, have an advantage over those previously mentioned, as the sensor (BTM) is already incorporated into the HD machine, but QA value is not obtained automatically and needs to be calculated subsequently345,348; both methods are only validated for high-flux HD with QB of 300 mL/min.349 The use of certain devices allows the instant inversion of the HD blood lines and, therefore, the time required to obtain QA value is significantly reduced.348

Interpreting the results

When any functional AVF alteration is detected by any of these screening methods, an imaging test should be carried out in the event of suspected AVF stenosis. The functional criteria for this are as follows10,15,350:

• •

  Absolute QA value. The threshold value or cut-off point of QA which indicates the need for an imaging test varies according to the ROC curves of sensitivity-specificity obtained in several studies: < 500, 650, 700 or 750 mL/min.269,288,327,350,351 The KDOQI guide considers a QA < 600 mL/min for pAVF and < 400-500 mL/min for nAVF,10 whereas the European Guide indicates elective intervention in the case of a QA < 600 mL/min in pAVF or < 300 mL/min in nAVF of the forearm.14

• •

  Temporary decrease in QA > 20-25%, regardless of whether nAVF or pAVF, in relation to the baseline QA.10,15,227,352,353

As mentioned previously, prospective analysis of QA evolution over time is of higher value for diagnosing AVF stenosis than isolated determinations.10 In a longitudinal study by Neyra et al.,353 involving 95 AVF, QA decrease over time was a powerful predictive variable of thrombosis, so that the relative risk (RR) of thrombosis increased when there was a drop in QA higher than 15% and was maximum (34.7%) when the decrease in QA was > 50%. Paulson et al.354 consider that a 20% to 25% decrease in QA percentages may be secondary only to haemodynamic changes and that only a decrease in QA greater than 33% should be considered significant.

It has been demonstrated that QA is related to AVF type (for example, radiocephalic versus brachiocephalic nAVF) as well as various demographic and clinical factors of the patient345,349,352,355,356. An inverse relationship between QA of the AVF and patient age has been demonstrated269,349 so that the application of a multiple linear regression model showed a reduction of 11.6 mL/min in baseline QA of the AVF for every year of the patient’s life, with the rest of the variables considered remaining constant.269 The functional AVF profile also depends on its location, as demonstrated in a case series by Treacy et al.,356 referring to 53 nAVF studied using the thermodilution method: the functional result obtained differed depending on the nAVF topography in the snuff box, distal forearm, proximal forearm, brachiocephalic and brachiobasilic, from the lowest to the highest QA.

In some studies, better AVF function, that is to say, a higher QA, has been shown in patients with a history of some previous ipsilateral AVF.345,357 The existence of previous venous arterialisation may explain this functional difference. In other words, a previous functional distal AVF in the same limb may determine the function of a secondary nAVF of proximal location. In this respect, in a study by Begin et al.,357 referring to 45 patients with nAVF, QA of patients with brachiocephalic nAVF, measured by the ultrasound dilution method, was higher in cases of a previously functioning radiocephalic nAVF in the same arm compared with the remaining patients (1800 ± 919 versus 1167 ± 528 mL/min).

Functional AVF surveillance through QA determination has allowed a higher incidence of pathology to be shown in the feeding artery than that reported in historical studies and currently estimated at around 30% of all dysfunctional AVF cases.333,358,359 In addition, through this AVF surveillance, the radial artery pathology in radiocephalic nAVF could be classified in 3 differentiated groups.333

In addition to diagnosing AVF stenosis, AVF surveillance through periodic QA measurements allows the identification of hyperdynamic AVF with excessive QA which may cause heart failure.360,361 There is increased risk of heart failure secondary to AVF when its QA is ≥ 2000 mL/min or 20% of cardiac output.194 In such cases, it is reasonable to perform strict cardiological follow-up by periodic echocardiograms. On the other hand, cardiac decompensation can also occur with a QA< 2000 mL/min in patients with a reduced myocardial reserve.360

In some cases, the estimation of both QA of the AVF and the systolic pulmonary artery pressure jointly using non-invasive methods (Delta-H method and Doppler echocardiogram, respectively) has allowed a diagnosis to be made, surgical indication to be established (banding) and post-operative follow-up of the AVF with haemodynamic repercussions to be carried out.361

Recommendations

DU is an imaging technique that allows examination of both nAVF and pAVF using a linear sender and receiver ultrasound transducer applied on the different AVF planes (Table 17). Despite some drawbacks (operator-dependent technique, impossible to use in case of bandages and/or wounds and difficulties in assessment in the case of vascular calcification), the use of ultrasound image together with Doppler is growing as an AVF surveillance method since this is a second-generation non-invasive method which does not use ionising radiation or iodinated contrast media and which, in addition, is inexpensive and readily available.362 In Table 18 other imaging methods for studying AVF are described.

DU has the following benefits in AVF surveillance52,363,364:

• •

  Method for quick diagnosis that can be used in situ in the HD room (portable ultrasound machine) when any change in the AVF is detected by a first-generation method or by a decrease in QA recorded by a dilution method.223 In a Spanish study referring to 119 portable DU examinations carried out by the nephrologist on 67 AVF, 31 stenoses were diagnosed in 44 cases of needling difficulty with no other warning signs for stenosis,223 demonstrating the usefulness of DU in the hands of a well-trained professional.

• •

  Regulated surveillance method for periodic AVF assessment. DU allows direct visualisation of the AVF and, therefore, makes it possible to perform morphological surveillance.365-368

• •

  Haemodynamic information related to the AVF. DU allows direct QA determination and, therefore, functional AVF surveillance.369 QA (mL/min), preferably in the brachial artery, is calculated using the following formula367:QA=Time-averaged mean velocity (m/s)× cross-sectional area (mm2)×60

  Various authors have found that QA determined by DU is significantly lower in AVF with stenosis compared with other AVF without stenosis.303,369 A positive correlation has been shown between QA of the arterialised vein in nAVF determined by DU and diameter and parameters of the feeding artery (diameter and arterial blood flow).369 A significant correlation has also been found between QA obtained by DU and by various dilution methods.369,370

• •

  Imaging test of choice to confirm, locate and quantify AVF stenosis detected by screening methods prior to elective treatment.303,371-373 In this respect, a linear correlation has been described between DU and fistulography to diagnose significant AVF stenosis.373,374 In addition, it allows for the surveillance of stenoses which are considered non-significant.375 The ultrasound criteria described for the diagnosis of significant AVF stenosis are shown in Table 19.52,84,376

  Table 19.

  Described ultrasound criteria for significant arteriovenous fistula stenosis

  Morphological criteria

  • Vascular lumen reduction ≥ 50%

  Functional criteria

  • Pronounced “aliasing” phenomenon as a sign of turbulent flow. It is a suspicion, not a diagnostic criterion • PSV > 400 cm/s. Not valuable in the AVF anastomosis zone • PSV ratio. This is the ratio between PSV in the stenotic and in the pre-stenotic area and is considered diagnostic when it is > 2 • Indirect characteristics in brachial artery: high resistive Doppler wave; resistive index: > 0.6 • QA values preferably obtained at brachial artery level: absolute < 500 (nAVF) or < 600 (pAVF) mL/min, or a decrease in QA > 25% over time

  nAVF, native arteriovenous fistula; pAVF, prosthetic arteriovenous fistula; PSV, peak systolic velocity; QA, blood flow.
• •

  It allows the morphological and functional assessment of other AVF dysfunctions which are not related to stenosis or thrombosis, such as aneurysms and pseudoaneurysms, haematoma, abscesses, etc.

→ Clinical question X How reliable is Doppler ultrasound in determining blood flow in the arteriovenous fistula in comparison to dilution screening methods?

(See fact sheet for Clinical question X in electronic appendices)

Evidence synthesis development

Doppler ultrasound versus ultrasound dilution

The study by Weitzel et al.377 evaluated the comparability of QA measurements through DU with those taken by ultrasound dilution method in 24 patients with pAVF. In this study the reproducibility in 54 pairs of DU measurements was also assessed. Measurement variations by DU were 4% for pAVF with QA < 800 mL/min (n = 17), 6% for pAVF with QA flow between 801 and 1600 mL/min (n = 22), and 11% for pAVF with QA > 1600 mL/min (n = 15). The mean variation coefficient of measurement was 7% for DU compared with 5% for ultrasound dilution method. Correlation coefficients (r) between QA measurements by DU and by ultrasound dilution were 0.79 (n = 24, p < 0.0001), 0.84 for pAVF with QA < 2000 mL/min (n = 20, p < 0.0001), and 0.91 for pAVF with QA < 1600 mL/min (n = 18, p < 0.0001). They concluded that DU gives reproducible QA measurements which correlate with ultrasound dilution measurements.377

The study by Schwarz et al.378 compared both techniques using fistulography as a reference. They assessed 59 HD patients with forearm nAVF using ultrasound dilution, DU and fistulography, in that order, and diagnosed nAVF stenosis in 41 patients, who were treated with PTA. The accuracy of both techniques, assessed by ROC curves, was similar: average areas under the curve were 0.79 (95% CI, 0.66 to 0.91) for ultrasound dilution and 0.80 (95% CI: 0.65 to 0.94) for DU. The correlation between QA values obtained by ultrasound dilution and by DU measurements was 0.37 (Spearman = 0.004). The optimal cut-off value calculated for stenosis prediction was 465 mL/min for ultrasound dilution and 390 mL/min for DU. Both ultrasound techniques were valid for predicting nAVF stenosis (p < 0.01). In 13 patients restenosis occurred in the first 6 months after PTA. QA obtained by ultrasound dilution after PTA was significantly lower in these 13 patients, compared with the other 21 patients. The authors concluded that QA surveillance of nAVF for HD using ultrasound techniques provides a reasonable prediction of stenosis and restenosis.378

The study by Lopot et al.379 provided measurement comparative data for DU and dilution ultrasonography, which was used as the reference technique in 27 patients, and found a good correlation between both techniques (r = 0.8691).

The study by Lin et al.380 compared the reproducibility and correlation of QA measurements using a variable QBbased Doppler method combined with spectral analysis of Duplex Doppler images (VPFDUM), with the ultrasound dilution method, and conventional DU method, in 73 HD patients, 70 with nAVF and 3 with pAVF. The mean value of QA by VPFDUM (870.8 ± 412.0 mL/min) showed a high degree of similarity to that of measurements by ultrasound dilution (868.6 ± 417.9 mL/min) but was higher than measurements by conventional DU (685.1 ± 303.6 mL/min; p < 0.005). The mean coefficient of variation values was similar using VPFDUM (1.6%) and ultrasound dilution (1.4%) but lower than conventional DU (6.8 %, p < 0.01). The correlation coefficient and the intra-class correlation coefficient (ICC) of repeated QA measurements by VPFDUM (0.985 and 0.993, p < 0.001) were also similar to those by ultrasound dilution (0.992 and 0.995, p < 0.001), but slightly higher than those of conventional DU (0.917 and 0.948, p < 0.005).The reproducibility of the VPFDUM technique (r = 0.98, p < 0.0001) and the correlation between VPFDUM and ultrasound dilution (r = 0.99, p < 0.0001) for QA measurements were good. Unassisted AVF patency at 6 months was significantly lower in patients with a QA < 500 mL/min than in those with a QA > 500 mL/min (13.6 % versus 92.2 %, p < 0.0001). They concluded that the VPFDUM technique is a non-invasive, accurate and reliable procedure for measuring QA and has predictive power regarding AVF patency.380

Doppler ultrasound versus other dilution methods

Roca-Tey et al.369 carried out a functional study comparing DU and Delta-H methods for QA determination in AVF (84.8% of nAVF) in 33 prevalent patients on chronic HD. In diagnostic concordance analysis, the ICC between QA values of the AVF obtained using both methods was 0.74 (p < 0.0001). The authors concluded that DU and Delta-H methods are super-imposable for QA determination of the AVF.369

Fontseré et al.381 compared thermodilution and DU, which they used as the reference technique, to measure QA in a cross-sectional study conducted in 64 HD patients using nAVF (54) and pAVF (10). The mean QA obtained by DU was 1426 ± 753 mL/min for nAVF and 1186 ± 789 mL/min for pAVF. The values obtained by thermodilution were 1372 ± 770 for nAVF (bias: 54.6; ICC: 0.923) and 1176 ± 758 for pAVF (bias: 10.2; ICC: 0.992). In the subgroup of 28 patients with end-to-side radiocephalic nAVF, the QA obtained by DU was 1232 ± 767 mL/min.; in the radial artery, 942 (ICC: 0.805); radialulnar artery, 1103 (ICC: 0.973); cephalic vein, 788 (ICC: 0.772) and with thermodilution, 1026 (ICC: 0.971). They concluded that thermodilution is a useful indirect method for QA measurement. In the subgroup of patients with radiocephalic nAVF the sum of QA obtained in radial and ulnar arteries was more accurate. However, thermodilution also had an excellent correlation with the brachial artery.381

Sacquépée et al.382 studied the correlation of QA values obtained using thermodilution and DU in 15 patients dialysed through nAVF (14) and pAVF (1). The QA mean was 1088 ± 576 mL/min measured by DU and 1094 ± 570 measured by thermodilution. The comparison of QA values obtained with both techniques showed a strong linear relationship.

From evidence to recommendation

Due to their high concordance for determining QA of AVF, dilution screening methods such as ultrasound dilution, Delta-H and thermodilution are equivalent to DU.369,370,377-382

→ Clinical question XI Can regulated Doppler ultrasound performed by an experienced examiner replace angiography as the gold standard to confirm significant arteriovenous fistula stenosis?

(See fact sheet for Clinical question XI in electronic appendices)

Evidence synthesis development

In order to formulate the recommendations in this guide, a meta-analysis was carried out (using the program MetaAnalyst, 11-11-2013) on four studies conducted in the last ten years. These studies provide complete data, thereby making it possible to calculate the sensitivity and specificity of regulated DU compared with fistulography to confirm diagnosis of significant AVF stenosis in patients with clinically suspected stenosis.364,374,383,384 Using data from 755 patients, of which 319 were diagnosed with significant stenosis by fistulography (prevalence: 42.3%), the meta-analysis provided high overall values of sensitivity of 89.3% (95% CI, 84.7-92.6) and a specificity of 94.7% (95% CI, 91.8-96.6) for DU (Figures 3 and 4). These levels are high, but they are insufficient to consider DU as a substitute for fistulography as the “gold standard” for confirming diagnosis of significant AVF stenosis. No diagnostic test which leaves 10% of cases undetected can be considered as a “gold standard”.

Figure 3.

Sensitivity of Doppler ultrasound versus fistulography to confirm significant stenosis in arteriovenous fistula in patients with clinical suspicion of stenosis obtained in a meta-analysis of 4 studies: 89.3% (95% confidence interval, 84.7-92.6).

(0.14MB).

Figure 4.

Specificity of Doppler ultrasound versus fistulography to confirm significant stenosis in arteriovenous fistula in patients with clinical suspicion of stenosis obtained in a meta-analysis of 4 studies: 94.7 (95% confidence interval, 91.8-96.6).

(0.14MB).

However, the answer to this clinical question leads us to ask other questions: Which test should patients initially be assessed with in cases of suspected AVF stenosis: DU or fistulography? Are DU findings enough to indicate elective intervention in patients with suspected stenosis, a suspicion arising from the use of other screening methods?

Clinical decisions are not solely dependent on the sensitivity and specificity of DU to correctly diagnose significant stenosis, but they also depend heavily on real prevalence of significant stenosis among patients with suspected stenosis that arise after applying methods of AVF monitoring and/or surveillance. For fixed sensitivity and specificity, incorrect and accurate diagnoses will be heavily influenced by the prevalence of the pathology being studied. As can be seen in Table 20, the positive predictive value of DU, i.e. the percentage of patients who really present a significant stenosis among those diagnosed by DU, progressively increases as prevalence of significant stenosis rises among patients who are suspected of having one. Thus, when the prevalence of significant stenosis is 50%, the positive predictive value of DU is 94.4%, and this percentage increases as higher prevalence is reached.

The option of using DU as an initial diagnostic test to assess possible significant stenosis would have a significant impact from the start: angiography would no longer be performed on all patients, as it is an invasive test, with potential side effects, and is more expensive for health services.

There is no doubt that there are two patient groups which clearly benefit from using DU without fistulography, because the same conclusion would be reached as in fistulography, patients would be exposed to lower risks and it is economically cheaper. On the one hand, there would be true positives: patients with significant stenosis, for whom preventive intervention of the stenosis would be directly indicated. On the other, there would be true negatives: patients without any stenosis who would be kept on the routine follow-up programme.

It is especially important to consider the false-negative cases, i.e. AVF with significant stenosis in which DU has been unable to establish the diagnosis. In these particular cases, the suspicion will persist despite the DU result and therefore, it seems reasonable to then carry out fistulography, which will end up providing the definitive diagnosis of the stenosis.

Therefore, the use of DU as a first choice diagnostic imaging test for patients with suspected significant stenosis seems to be a sensible decision, both clinically and economically. Given that false-positive rates are low, those who showed positive on the DU could be treated electively, without the need to undergo fistulography for confirmation. In patients with persisting suspected significant stenosis in whom a previous DU was not conclusive, it is advisable to perform fistulography and preventive treatment if the stenosis is then confirmed.

There are no controlled studies which have assessed the clinical consequences of testing patients with AVF dysfunctions that may make us suspect the possible presence of significant stenosis, by means of only DU or angiography.

No relevant studies have been identified regarding patient preferences. It seems logical to think that if there were equal clinical performances, patients would prefer the non-invasive techniques which do not imply exposure to radiation.

No relevant studies have been identified related to the use of resources and costs, either. DU is a less expensive technique than fistulography. The diagnostic approach of using DU at the beginning of the study and keeping fistulography for cases where stenosis is repeatedly suspected, but with a negative result in DU, is more cost-effective than performing fistulography on all patients with suspected stenosis.

From evidence to recommendation

Although it cannot replace fistulography as the “gold standard”, DU is a non-invasive imaging diagnostic method, does not harm the patient, and is highly sensitive and specific for the diagnosis of significant stenosis. Furthermore, it provides valuable additional functional information, its portable version can be used in situ in the HD room and, in addition, it offers a favourable cost-effectiveness profile. For all these reasons, GEMAV unanimously considers that the best diagnostic approach is to perform DU as the initial imaging examination if there is any suspicion of stenosis and keep fistulography for cases of negative outcome and persisting suspicion of stenosis.

Recommendations

→ Clinical question XII Which non-invasive monitoring or surveillance screening method for haemodialysis arteriovenous fistula presents predictive power of stenosis and thrombosis and increased patency of the prosthetic arteriovenous fistula in the prevalent patient and what is the frequency?

(See fact sheet for Clinical question XII in electronic appendices)

Evidence synthesis development

Two systematic reviews with meta-analysis have been found, both published in 2008, which address the clinical effects of pAVF monitoring and surveillance.385,386 The review by Tonelli et al.385 includes only randomised clinical trials (RCTs), whereas the Casey et al review386 also includes non-randomised studies. Both studies found the same clinical trials and come to similar conclusions. For this Guide, the Tonelli et al. meta-analyses were used as they provide more complete data in the stratified analysis for patients with pAVF.385

Clinical benefit of screening compared with usual practice

The systematic review with meta-analysis by Tonelli et al.385 included 6 clinical trials comparing active pAVF screening (using QA or DU measurements) versus usual follow-up by monitoring methods in 446 patients. In this study, there were no significant differences in the rate of pAVF thrombosis between active methods of surveillance and regular monitoring (RR 0.94, 95% CI, 0.77 to 1.16). Using data from 1 clinical trial and 126 patients, there were no statistically significant differences in the time to pAVF thrombosis between the two follow-up options (hazard ratio [HR]: 1.13; 95% CI, 0.71 to 1.80). Meta-analysis with data from 4 clinical trials and 381 patients did not show statistically significant differences in pAVF loss between the active methods of surveillance and those of usual monitoring (HR: 1.08; 95% CI, 0.83 to 1.40). Data from 2 clinical trials and 315 patients also showed no differences in the time to pAVF loss (HR: 0.51; 95% CI, 0.15 to 1.74; high statistical heterogeneity I2: 85%).

Some causes have been reported which may explain these disappointing results obtained by clinical trials in pAVF surveillance316,354,387-394:

• •

  Diameter of the artery and the vein involved in anastomosis. This diameter controls the relationship between QA (or venous pressure) and the stenosis. In the event of a low artery/vein ratio, progression of the stenosis is so fast that regular surveillance is unable to detect a decrease in QA (or an increase in venous pressure) before thrombosis.

• •

  MAP. The significant decrease in blood pressure can play a central role in some cases of pAVF thrombosis without prior suspicion of stenosis.

• •

  Preventive intervention by PTA. In a stable stenotic lesion or slow growth PTA can stimulate intimal hyperplasia, lead to rapidly developing restenosis and have a negative impact on pAVF patency.

• •

  Sample size. An insufficient sample size in the published studies could explain the results obtained.

From evidence to recommendation

There are no significant differences in the risk of thrombosis or in survival of the pAVF if surveillance methods are added to usual methods of monitoring. Therefore, according to the current concept of significant stenosis included in the KDOQI guide,10 we cannot recommend pAVF surveillance using second-generation screening methods, whether they be dilution techniques to estimate the QA or DU. The application of these methods in pAVF is not predictive of thrombosis and will not help increase their patency compared with first-generation methods, based on current criteria for significant stenosis. It is recommended that pAVF monitoring be performed using first-generation screening methods.287

→ Clinical question XIII Which non-invasive monitoring or surveillance screening method for haemodialysis arteriovenous fistula presents predictive power of stenosis and thrombosis and increased patency of the native arteriovenous fistula in the prevalent patient and what is the frequency?

(See fact sheet for Clinical question XIII in electronic appendices)

Evidence synthesis development

First-generation methods

A prospective study by Asif et al.204 of 142 patients with nAVF analysed the accuracy of physical examination in detecting stenotic lesions in comparison with fistulography, which is considered the gold standard test. The sensitivity and specificity of physical examination was 92% and 86%, respectively, for outflow stenosis and 85% and 71% for inflow stenosis.

A study by Campos et al.303 analysed the accuracy of physical examination and pressure measurement in detecting stenotic lesions in comparison with DU, which they used as the reference technique. Out of the 84 patients analysed, 50 of them, i.e. 59%, showed positive for stenosis by DU. Upon physical examination 56 patients showed positive, representing a sensitivity for the test of 96%, a specificity of 76%, a positive predictive value of 86% and a negative predictive value of 93%. Intra-access pressure measurement for 34 patients showed positive, i.e. 40%, representing a sensitivity for the test of 60%, a specificity of 88%, a positive predictive value of 88% and a negative predictive value of 60%.

Second-generation methods

With respect to second-generation methods, several published meta-analyses should be highlighted.385,386,395 On analysing data from four controlled clinical trials and 360 patients, Tonelli et al.385 describe that active screening by ultrasound causes a statistically significant decrease in the risk of nAVF thrombosis (RR: 0.47; 95% CI, 0.28-0.77). In addition, the time to reach nAVF thrombosis was significantly higher in the “surveillance” group compared to the “control” group (HR: 0.30; 95% CI, 0.16-0.56). Regarding AVF loss, when carrying out a meta-analysis with data from 2 RCTs and 141 patients, no statistically significant differences were found (RR: 0.65; 95% CI, 0.28 to 1.51), and, finally, with data from 1 RCT and 60 patients, slightly statistically significant differences were found with respect to time to access loss (HR: 0.38; 95% CI, 0.14 to 0.99).385

Moreover, after analysing the functional criteria selected for the diagnosis of stenosis in various controlled and uncontrolled clinical trials as well as observational studies, Tessitore et al.395 concluded that nAVF surveillance through QA determination significantly reduces the risk of thrombosis. In this respect, a case-control study from Spain demonstrates a significantly lower incidence of AVF thrombosis (mostly nAVF) in patients dialysed in a hospital HD unit and under QA surveillance compared with patients dialysed at a satellite HD centre without QA measurements352. Salman et al.396 analysed 4 RCTs (n = 395) to assess the benefit of nAVF surveillance using QA determination and the result was positive for the 3 trials in which the main aim was to reduce the rate of thrombosis.396 Muchayi et al.397 performed a meta-analysis on these same 4 studies and showed a non-significant reduction of 36% in thrombosis risk by nAVF surveillance.

Concerning nAVF patency, the meta-analysis by Tessitore et al.,395 carried out on two controlled clinical trials, demonstrated a 50% reduction in risk of nAVF loss using screening with QA determination, but the difference was not statistically significant given that they are two single-centre studies (Verona, Italy) with a limited sample size and follow-up.276,398 Recently, the preliminary results have been published from a controlled, multicentre clinical trial carried out in Spain (METTRO) on the effect of second-generation methods compared with conventional monitoring on the incidence of thrombosis and patency of nAVF. These results show a significantly lower rate of thrombosis and better primary assisted patency after 1 year of follow-up.399

The implementation of second-generation screening techniques for nAVF surveillance makes it possible to reduce the incidence of thrombosis and, therefore, decrease the rate of CVC placement and its associated morbidity/mortality.269,368,385

Use of resources and costs

No specific cost-effectiveness studies were found when these interventions were analysed for the setting in which this Guide is to be applied. Neither are there studies on the budget impact that the generalisation of continued and regular use of active screening techniques by DU would suppose on nAVF patients in our setting.

From evidence to recommendation

The regular application of second-generation screening methods (both dilution techniques to estimate AVF flow or QA and DU) is recommended for nAVF surveillance as existing evidence indicates a beneficial effect with relation to the reduction in thrombosis incidence and CVC placement rate. There are no arguments against such methods in relation to the rate of nAVF thrombosis and patency.

Recommendations

→ Clinical question XIV What are the demographic, clinical and haemodynamic factors and variables with predictive power of thrombosis in an arteriovenous fistula that presents stenosis?

(See fact sheet for Clinical question XIV in electronic appendices)

Evidence synthesis development

The application of various methods of AVF surveillance in routine clinical practice has shown cases of AFV thrombosis preceded by a QA value > 600 mL/min without apparent stenosis, as well as cases of stenosis > 50% which are stable over time and never actually become thrombosed.400-403 Therefore, in the case of any vascular reduction > 50% in nAVF or pAVF, it is necessary to know its thrombosis risk. It is important to identify whether this stenosis involves a high risk of thrombosis, i.e. a high likelihood of progressing over time and leading to total vascular lumen occlusion of the AVF if an early elective intervention through PTA or surgery is not carried out. However, if we perform preventive treatment when there is a vascular lumen reduction > 50% of nAVF or pAVF with a low thrombosis risk, in addition to this being an unnecessary procedure with a noteworthy financial cost, we may cause an unwanted accelerated restenosis and AVF thrombosis which would not have occurred with therapeutic abstention.

It is necessary to identify factors or variables (demographic, clinical, haemodynamic) which are predictive of thrombosis in any AVF with stenosis. The presence or absence of these will define the existing risk of thrombosis and, therefore, make it possible to distinguish if any vascular lumen reduction > 50% in nAVF or pAVF has a high or low risk of thrombosis.

In this respect, Paulson et al.403 demonstrated in a prospective study in 2000, through ROC curve analysis, that the functional variable QA did not provide enough predictive value of pAVF thrombosis on its own for it to be used as an isolated criterion in decision-making. They thus concluded that the inclusion of other predictive variables in association with QA could provide the predictive value required.

In 2005, Malik et al.367 published a randomised clinical trial in 192 patients with pAVF comparing pAVF patency (mean follow-up 392 ± 430 days) between two subgroups of patients who were categorised according to the different monitoring and surveillance strategy applied: group 1 (n = 97) using traditional screening (clinical monitoring, venous pressure, and QA) associated with DU surveillance every 3 months and group 2 (n = 95) only by traditional screening. Cumulative pAVF patency was significantly higher in group 1 compared to group 2, which the authors attributed to the early diagnosis of stenosis and, therefore, more common elective procedures on the pAVF stenosis.367 Unlike other clinical trials on pAVF with negative results,404 why was this positive result obtained in this study? The answer lies in the methodology, as DU indications for carrying out fistulography and/or a therapeutic procedure using PTA or surgery were as follows:

• •

  Finding a significant stenosis, defined by the presence of a peak systolic velocity (PSV) ratio > 2 with or without decrease in QA.

• •

  Finding a non-significant stenosis in appearance but associated with a decrease in QA > 25% over time.

In the case of uncertainty over significant or non-significant stenosis, the existence of a residual diameter of less than 2.0 mm was an additional indication for fistulography. Patients that only met one of the above-mentioned criteria were examined after 4-6 weeks by DU.367 In other words, in this study a series of additional ultrasound factors were introduced which allowed preventive action to be taken on significant stenoses with the risk of thrombosis and pAVF patency to be prolonged.

In 2009 the same group published a retrospective study in which pAVF stenoses were classified by DU into 2 distinct groups375:

• •

  Significant pAVF stenosis or high risk of thrombosis defined by a combination of the following criteria: reduction > 50% in the vascular lumen + PSV ratio > 2 + at least 1 additional criterion (residual diameter < 2 mm or QA < 600 mL/min or decreased QA > 25%).

• •

  Borderline pAVF stenosis or low thrombosis risk (n = 102): defined with the same criteria but without any additional criteria.

The first group of stenoses was treated electively by PTA and the second underwent a strategy of “wait and see” with repeated DU after 6 – 8 weeks. After 14 ± 6 weeks, the follow-up of the 102 borderline stenoses was as follows: 55 without stenosis progression, 38 with an increase in the degree of stenosis, 8 treated using PTA because of clinical indication and 1 single case of thrombosis375; in other words, at the time of the next DU (14 ± 6 weeks), more than half of the borderline stenoses remained stable over time with a risk of thrombosis < 1%. The significant risk factors for progression of borderline stenosis to significant stenosis were a history of previous PTA and female gender. The authors concluded that delaying PTA in asymptomatic borderline stenosis is safe using this expectant management and stenoses remain stable, at least in the short term, but with a high risk of progression, especially if there is a history of previous PTA.37 In Spain, when a similar protocol for selecting AVF with a greater risk of thrombosis was implemented, a thrombosis rate < 0.05/patient/year was achieved.52

To sum up, according to current data, AVF surveillance methods could be optimised for both nAVF and pAVF by redefining the concept of significant stenosis, which would include only those AVF with an increased risk of thrombosis and, therefore, really require elective intervention (Figure 5).405 In this way, in addition to the criteria of stenosis according to the current KDOQI Guide, the haemodynamic repercussion of the stenosis should be assessed and some additional criteria added, both morphological and functional, that have enough predictive power to discern whether nAVF or pAVF with stenosis has a high or low risk of thrombosis.394 These criteria are:

Figure 5.

Algorithm proposed by GEMAV for the diagnosis of significant stenosis and its elective treatment. DU, Doppler ultrasound; PVS, peak systolic velocity; QA, blood flow.

(0.34MB).

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  Two main criteria: vascular lumen reduction percentage > 50% + PSV ratio > 2.

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  At least one of the following additional criteria: morphological criterion (residual diameter < 2 mm) or functional criterion (QA [mL/min] < 500 [nAVF]-600 [pAVF] or ∇QA > 25% if QA < 1000 mL/min).

From evidence to recommendation

Optimising AVF surveillance methods requires redefining significant stenosis. Some ultrasound variables, both morphological and functional, have been described that allow the risk of thrombosis of stenosis to be clarified and therefore, whether this stenosis really requires elective intervention. The new concept of significant stenosis would only include stenosis with high risk of thrombosis. As a result, some criteria were established to define it (Figure 5): some main criteria (reduction of vascular lumen > 50% + PVS ratio > 2) and some additional criterion should be added (residual diameter < 2 and/or QA < 500 mL/min in nAVF/< 600 mL/min in pAVF and/or reduction in QA > 25% if QA < 1000 mL/min). This redefinition of significant stenosis would result in a series of benefits over AVF, such as the decrease in unnecessary procedures that may endanger the AVF itself, the reduction in the thrombosis rate and the increase in patency (Table 21).

Recommendations

Rationale

The aim of correcting stenosis requiring elective treatment is to ensure sufficient QA, proper haemodialysis (HD) adequacy, to prevent the occurrence of thrombosis and to increase AVF patency. Only significant stenosis should be treated electively as described in section 4.

Types of stenosis

Anatomically and functionally, vascular stenosis with haemodynamic repercussion in the AVF function can be located in the segment prior to the arteriovenous anastomosis (arterial stenosis), in the anastomosis itself or in the outflow vein of the AVF (venous stenosis).

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  Arterial stenosis. Vascular lesions located in the arterial tree that feeds the vascular access (VA). The haemodynamic alteration they cause is a decrease in AVF flow. It is mainly due to the presence of stenosing or occlusive lesions arising from the progression of an existing underlying atherosclerosis.

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  Stenosis in the arteriovenous anastomosis. They are usually due to a technical problem during anastomosis creation. Clinically, they present as immediate or early thrombosis of the access or as alterations in maturation (non-mature fistula).

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  Venous stenosis. It is the most common cause of access dysfunction. Depending on location along the venous pathway, aetiology, frequency and response to treatment vary. Therefore, it is usually classified into four groups:

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    Juxta-anastomotic or peri-anastomotic stenosis. This is the one located in an area covering the zone immediately adjacent to the anastomosis and up to 5 cm post-anastomosis. It is of complex aetiopathogenesis, involving haemodynamic factors and alterations in the inflammatory response of the endothelium.

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    Stenosis of the cannulation segment. Stenosis located in needling areas. It usually occurs in response to mechanical trauma caused by cannulation of the vessel.

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    Stenosis of the cephalic vein arch (CVA). Stenosis located in the cephalic vein segment immediately adjacent to its confluence in the axillary vein. Like stenosis located in the juxta-anastomotic region, it is usually due to haemodynamic factors, presenting a poor response to percutaneous treatment.

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    Central venous stenosis. Stenosis located in the venous sector from the subclavian vein to its drainage in the right atrium, and covers the subclavian vein, brachiocephalic trunk and superior vena cava. It is usually associated with endothelial trauma caused by the presence of venous catheters inside the vessel.

Another classification used in different publications prioritises a criterion of functionality in relation to the cannulation point, classifying them between inflow stenosis (arterial stenosis, arteriovenous anastomosis and the juxta-anastomotic venous segment) and outflow stenosis (venous stenosis of the cannulation segment, CVA, and central venous stenosis).374,406

As described, stenosis location is the main determining factor when considering therapeutic option. In this context, the success of the results should weigh up not only the efficacy of the treatment, but also any possible associated comorbidity and complications.

There are several examples that can demonstrate this factor, as will be seen below. There is consensus that central vessel (arterial or venous) stenosis be given endovascular treatment as it is difficult to access these vessels in surgery and there is high morbidity and mortality.10,407 Venous stenosis of the needling segment has traditionally been treated by percutaneous transluminal angioplasty (PTA) because HD can be continued using the same VA and without the need for CVC placement. On the other hand, there has arisen more controversy in the treatment of juxta-anastomotic stenosis, which entails most AVF stenosis, in both native arteriovenous fistula (nAVF) and prosthetic arteriovenous fistula (pAVF), since they can be approached from both a surgical and an interventionist point of view, although the first usually offers better overall results than percutaneous treatment.

Types of treatment

Stenosis can be treated either by an endovascular procedure consisting of PTA and/or endoprosthesis placement or by surgical review.

In general terms, percutaneous treatment is the least invasive alternative, has lower morbidity and does not require CVC placement to continue HD. However, a significant disadvantage is that it presents a high rate of restenosis which determines the need to periodically perform additional interventional procedures to maintain access patency.

On the other hand, surgical treatment usually has better primary patency in the medium and long term, although, in terms of drawbacks, it is more invasive and sometimes requires the use of venous capital and CVC placement for HD after the intervention. Thus, even though the technique provides better results overall, in daily clinical practice treatment must be decided on a case-by-case basis, precisely delimiting if the greater patency of the procedure justifies the possible consumption of venous segment and the possibility of CVC placement.

Percutaneous transluminal angioplasty

PTA is a percutaneous technique of intravascular dilation using a balloon that allows the treatment of vascular stenosis. In addition to the use of the conventional balloon, the technical improvements that have arisen in recent years for the treatment of stenosis have allowed the development of high-pressure balloons, cutting balloons and drug-coated balloons.

The advantages of PTA include the fact that it can be performed during diagnosis by fistulography, especially in the case of central venous stenosis, and preserves the vascular tree, unlike surgery. On the other hand, it has a higher recurrence rate versus surgery. The success of the procedure can be considered from the anatomical and functional perspective: anatomically, when residual stenosis is < 30% after balloon removal and, functionally, with the improvement of AVF haemodynamic parameters and the restoration of flow (QA).

The only absolute contraindication for this procedure is the active AVF infection. Relative contraindications would include allergy to the contrast, a shunt from pulmonary to systemic circulation and severe pulmonary disease.

High pressure balloons

High pressure balloons are those that bear an inflation pressure higher than 25-30 atm. Their use is indicated in the treatment of symptomatic stenosis that has not responded to dilation with conventional semi-compliance balloons. The use of high pressure balloons does not initially provide better patency results when compared to conventional balloons.408 High cost, the need to use thicker introducers, emptying difficulty and lower compliance and flexibility make it advisable not to use them as first choice in the treatment of stenosis

Cutting balloon

When small blades or atherotomes are incorporated into a conventional balloon, they are called cutting balloons. Its use is controversial and is not justified as initial treatment for stenosis. In a recent randomised study,409 no significant differences were found in the treatment of stenosis between cutting balloon and conventional balloon except for a greater primary assisted patency at 6 and 12 months, in favour of the cutting balloon, when treating juxta-anastomotic venous stenosis of pAVF (86% and 63% versus 56% and 37%). However, higher cost, management difficulties (they need finer guides) and the larger size of the introducer make them less indicated for the initial treatment of a dysfunctional access.

Eighty-five per cent of stenosis responds satisfactorily to conventional balloon angioplasty.410 In the rest, which do not have an appropriate response, both high pressure and cutting balloons would be useful. Existing studies comparing both procedures find no significant difference in immediate outcomes410-413 but there was an increase in the 6-month assisted patency of stenosis treated with cutting balloon versus high-pressure balloon (66.4% versus 39.9%).410-413

Angioplasty with pharmacoactive balloon

Drug coated balloons impregnated with paclitaxel have recently appeared as an alternative in the treatment of arterial stenosis. Application in nAVF stenosis is very low, though some randomised clinical trials (RCTs) with satisfactory results at 6 months414 and at 1 year follow-up415 have been reported.

Stents

Indications for stent placement are limited given the lack of evidence regarding improvement of secondary VA patency after their use. This controversial use is relegated to the treatment of stenosis with recoil, vascular ruptures after PTA or in dissections that condition stenosis > 30%.

It can be considered for use with refractory AVF following early recurrence (< 3 months) after several PTA and due to vascular recoil (elastic stenosis) following PTA.416 However, stent use is highly controversial in these two indications, given that on the one hand, a certain number of AVF maintain an adequate function even if there is residual post-PTA stenosis up to 50%, and on the other, there are early recurrences (< 3 months) in angioplasties with good immediate outcomes.417,418

Regarding stent use for vessel rupture treatment, it should be noted that this is the most frequent PTA complication. The initial treatment is tamponade with prolonged inflation at low pressure and external manual compression at the point of rupture. After three failed attempts, the placement of covered prostheses is considered indicated.417,418

Vascular endoprosthesis

Recently stent graft has been increasingly used in an attempt to improve outcomes. A controlled multicentre study found a patency of covered stents at 6 months that was significantly higher (51% versus 23%) than simple PTA in the treatment of venous anastomotic stenosis in pAVF.419 Use in other locations has been reported on several occasions,420,421 with better outcomes than those obtained with PTA alone or with placement of uncovered metal stents.422,423 In the most recent study of Schmelter et al.,424 conducted on 66 AVF (41 pAVF and 25 nAVF), found good initial results but with no increase in overall patency. They observed a high rate of restenosis and thrombosis, although not associated with the stent graft, which were responsible only for a minority of the new cases of dysfunction. The authors conclude that the placement of covered stents can be used to solve local problems but they do not improve the average patency of the VA because they are associated with lesions situated in other locations.

Regarding endoprosthesis-related disadvantages, it is important to emphasise that there is great difficulty in creating new accesses in the treated vein segment and can be associated with a not insignificant percentage of complications.420,425 Although stent placement may increase the interval between first dilatation and stenosis recurrence, once intra-stent neointimal hyperplasia stenosis is established, it is very difficult to treat. Recent studies must be added here, in which a high percentage of post-stent complications are observed (28.9%),426 as well as others describing migrations,427 fractures428 and infections.429,430

Ultimately, it can be concluded that further multicentre, randomised, prospective, multidisciplinary studies are required to adequately rate the advantages of the new versus traditional materials when performing PTA, the usefulness of stents and their benefit or disadvantages versus surgical treatment.

Surgical treatment

There are multiple surgical techniques described for AVF stenosis correction. The major advantage of this type of treatment is that it tends to have better patency rates than endovascular, but has higher morbidity, depletes the venous segment, may require CVC placement and is technically more complex, especially in central vessels.

Arterial stenosis

In the case of stenosis located in the arterial segment prior to the arteriovenous anastomosis, endovascular treatment through PTA presents low morbidity and acceptable results, which is why surgery is considered as a fall-back technique. Surgical revascularisation is performed through the interposition of a bypass of autologous material, presenting excellent patency in the medium and long term.

Anastomotic stenosis

In the case of stenosis located in the arteriovenous anastomosis (related to the surgical procedure to create the access), surgical review of the anastomosis, as well as the correction of the underlying technical defect, are indicated.

Juxta-anastomotic stenosis

In many cases, reanastomosis between the artery and the outflow vein in the area immediately proximal to the AVF is the surgical technique of choice. Likewise, the interposition of a bypass made of prosthetic material has been reported between the artery and the proximal sector of the outflow vein.

Stenosis of the cannulation segment

In the event of stenosis of the venous cannulation segment, the surgical treatment of choice consists of interposing a bypass made of prosthetic material, which can be placed in the shape of a loop, to allow the newly implanted segment to be cannulated.

Stenosis of the cephalic arch

As discussed below, the technique of choice consists of transposing the cephalic vein and its anastomosis with the proximal brachial or axillary vein. The surgical re-implantation of this cephalic arch has also been described.

Central venous stenosis

As surgery in central veins is complex and aggressive, it is considered a fall-back technique. Interventions using extra-anatomical derivative techniques to allow drainage to central venous trunks have been reported.

→ Clinical question XV Is there a treatment with better outcomes (percutaneous transluminal angioplasty versus surgery) in juxta-anastomotic stenosis, assessed in terms of patency and/or thrombosis and cost/benefit?

(See fact sheet for Clinical question XV in electronic appendices)

Evidence synthesis development

Native arteriovenous fistula

No clinical trials comparing PTA versus surgery for the treatment of stenosing AVF in patients with nAVF have been identified. Two publications comparing series of patients treated with surgery and patients treated with PTA have been identified.

In the study of Napoli et al.,432 conducted on 66 PTA and 68 surgical procedures with juxta-anastomotic stenosis of the AVF, the efficacy of the interventions was evaluated by measuring the brachial artery flow. The comparative analysis between the two options showed a significantly better primary patency for surgery, but with no difference in primary assisted patency, although PTA showed a greater tendency to restenosis.

Tessitore et al.431 conducted a retrospective analysis of clinical data of 64 patients with juxta-anastomotic stenosis of the fistula in the distal part of the forearm, of which 43 were treated with PTA and 21 with surgery. The restenosis rate was 0.168 and 0.519 events per year of fistula follow-up for surgery and PTA, respectively (p = 0.009), with an adjusted relative risk 2.77 times higher for PTA than for surgery. The cost profile was similar for both procedures. Both procedures show similar primary assisted patency and costs.

The other studies evaluate the two techniques individually. Thus, in an article from 2012435 evaluating the medium-and long-term results of surgery in juxta-anastomotic stenosis in 96 radiocephalic nAVF, the authors found very high results for immediate patency, without the need for CVC. Primary patency was higher than that recommended in international guidelines (89% versus 50%) with a low rate of maintenance procedures (0.035 procedures/patient/year). These patency data are superior to those shown in the study by Mortamais et al.,436 where the results of angioplasty are evaluated in 147 procedures performed on 75 radiocephalic nAVF. They obtained a primary patency at 1 and 3 years of 46.6% and 25.5%, respectively, with assisted patency in the same periods of 81.3% and 63.2%. They associate worse outcomes and early relapse of stenosis to the presence of post-PTA residual stenosis > 50%. They consider that in these cases evaluation and surgical repair would be indicated.

Although neither study conducted a comparative analysis with the other repair technique, their results support the use of surgery as an initial technique in the treatment of juxta-anastomotic stenosis, provided that there is a surgical team which has 24-hour availability and repair can be executed without the use of CVC.

Recently, a meta-analysis including the clinical series discussed in this section has shown results similar to those of the original studies. The combined results from the case study data showed significantly better primary patency of the AVF in patients treated with surgery at 12 (odds ratio [OR]: 0.42) and 18 months (OR: 0.33), an effect that seems to become moderate at 24 months of follow-up (OR: 0.53).433

Prosthetic arteriovenous fistula

Only one RCT has been identified in the literature comparing surgery and PTA in patients with pAVF and juxta-anastomotic stenosis.434 This is the RCT of Brooks et al.,434 which included 43 patients with venous stenosis at the pAVF access in the forearm, 19 of which were treated with surgery and 24 with PTA. Those treated with surgery obtained greater median long-term patency (12 months) versus PTA (4 months) (p < 0.01). It is not mentioned whether CVC was needed to perform any of the procedures.

No more recent studies comparing both procedures have been found, although there are several studies in the literature that support PTA use in the treatment of these lesions437 versus surgery167 as it allows proximal venous capital to be preserved, is more widely accepted by the patient and it is difficult to treat proximal anastomoses located on brachial and axillary veins surgically.8 Surgery is reserved for failed PTA treatment and prior to stent placement as well as in cases of recurrence.167,438

Stent use with stenosis recurrence has not improved patency439 in the same way as other technical improvements such as high pressure408 or cutting440 balloons, among others, have. Recently, however, a multicentre controlled study found significantly greater patency in the treatment of anastomotic venous stenosis at 6 months using covered stents versus simple PTA (51% versus 23%).419 The study is limited as long-term follow-up was not performed. In a more recent article424 where a retrospective study was conducted on 41 patients with complex pAVF stenosis (defined as rigid and resistant stenosis, stenosis with recoil or intra-stent stenosis) treated with vascular endoprosthesis (stent graft), good results in primary patency, but elevated restenosis and thrombosis rates, are obtained. Restenosis, however, is not located in the stent graft in place and is only responsible for a few cases of new dysfunctions. The authors conclude that the placement of stent grafts can be used to solve local problems but they do not improve the average patency of the access because it is associated with lesions in other locations.

The use of stents is controversial, though there seems to be agreement on the use of stent graft versus uncovered stents. Several articles in the literature have found an improvement in the primary patency rates of these devices versus PTA and uncovered stents.420,421,441,442 The increase in primary patency, according to some authors, seems to be related to a lower presence or absence of neointimal hyperplasia inside the stent graft.442,443

From evidence to recommendation

In the case of nAVF, and although observational studies report no differences between both techniques, as there are no randomised cost-benefit studies, and despite the advantages and drawbacks of using both (PTA does not deplete the bed, but requires procedures to be repeated, and surgery depletes the vessel, but may still allow cannulation and has better primary patency), studies coincide that there is better patency with surgery, though assisted patency is similar. Surgery, therefore, can be considered the initial indication if it is technically possible, as it requires fewer procedures to maintain patency. However, if surgery requires catheter placement, the endovascular technique should be considered as the first option.

This recommendation was submitted to a vote by GEMAV. The wording of the recommendation was unanimously accepted. However, the number of members of the working group who felt that the recommendation should be strong (one third) was not sufficient to award it this category. The remaining members felt that it was weak, or abstained in the vote.

In pAVF, endovascular therapy is more advantageous as it is less invasive than surgery; it does not deplete the venous bed and does not exclude surgical procedure. Thus, despite its higher cost and lower primary patency rate, it can be considered an equally valid therapeutic option to surgery. However, until the publication of comparative studies with surgery, a degree of evidence cannot be established in favour of either technique.

The use of covered stents (stent graft) to treat early recurrence of venous stenosis in prosthetic fistulae seems to provide an improvement in medium-term survival but more studies and longer-term assessment are needed to recommend use.

Treatment of non-perianastomotic stenosis

Non-perianastomotic venous stenosis, i.e. those located proximally to the juxta-anastomotic area, also referred to as the middle segment or needling area, are usually caused by mechanical trauma during AVF cannulation, and can be associated with the aneurysmal degeneration of the vein,444 with risk of skin necrosis, and with bleeding after HD sessions.445 They might not be associated with alterations during HD or to pump flow (QB) problems and, as a result, they may remain undetected if there is no careful clinical assessment or follow-up.

Treatment options include surgical repair by performing a prosthetic bypass or percutaneous repair using PTA. Although there are studies in the literature comparing both techniques, there are no randomised studies and they are unable to establish a better treatment option. Despite showing that the results of surgery are better in terms of patency,446 most support the initial use of percutaneous AVF treatment since they treat dysfunctional AVF less aggressively.

Although endovascular treatment is not a permanent solution, it is effective in increasing patency; it is a relatively non-invasive, repeatable technique that rarely requires CVC placement and preserves vascular bed integrity without compromising subsequent surgical procedures.

Surgical treatment of stenosis in this location includes creating a bypass excluding the stenotic segment; likewise, its placement in the shape of a loop may be considered, thereby lengthening the cannulation area. Surgery in the access cannulation area may cause the need for temporary HD through CVC, which is the main limitation of the technique. In contrast, when stenosis is associated with aneurysmal dilatation with cutaneous disorders, surgery can treat both during the same intervention.

In studies in the literature, results of surgery versus endovascular treatment are better in terms of the primary patency rate,446 but similar in assisted patency. These same studies support the initial use of percutaneous treatment because it is relatively non-invasive, can be performed in an outpatient’s clinic, avoids CVC and preserves the vascular bed, allowing new surgical procedures. However, PTA and surgery should be considered complementary and uncompetitive techniques.

There is no evidence to support the use of stents in the treatment of stenosis and it is recommended they not be used except in early and repeated recurrences after PTA of middle segments of nAVF and in vein ruptures that do not respond to balloon compressions.

It is advisable to keep in mind that heart failure or distal ischaemia after PTA should be prevented in patients at risk, especially if the flow is high.194,447 In these cases it is important not to over-dilate the stenosis, mainly in the first PTA and in those located in the arm, to avoid an excessive increase in QA. In patients at risk, such as diabetics or the elderly, caution should be exercised, and it is advisable to avoid using balloons with a diameter > 7 mm. If there is recurrence and there are no signs of ischaemia, the stenosis may be over-dilated 1 mm more.425 For this reason, it is imperative to know the QA of the AVF to indicate therapy.

If post-HD haemostasis problems are important, stenosis dilation is indicated by under-dilating and assessing risk-benefits. In this respect, a double dilation technique associated with surgical reduction of QA has been proposed.448

To sum up, both surgical and endovascular treatment have proven to be safe techniques in stenosis of the needling segment, with good rates of technical and clinical success. However, although there is a better rate of primary patency with surgery, and although assisted patency is similar, the majority opinion of experts, as well as of GEMAV, suggests that percutaneous treatment should be introduced at the outset because it is less aggressive as a technique. In AVF that require an additional surgical procedure, such as in aneurysmal AVF, which have a large mural thrombus or are associated with trophic lesions, surgery is suggested as the first repair technique. Despite the possibility of using endovascular techniques with endoprosthesis placement, there is no experience that can endorse this indication at the present time.

Treatment of cephalic arch stenosis

The cephalic vein is part of the superficial venous system of the upper limb, and follows an anterolateral subcutaneous trajectory along the arm; proximal to the arm it continues in a superficial position in the deltopectoral groove until it flows into the deep venous system in the axillary vein just before the clavicle. This confluence occurs in the anatomical region known as the cephalic vein arch (CVA), which is the segment in which this vein changes direction through the clavipectoral fascia. It then moves from a superficial position to a deeper level, eventually flowing into the axillary vein, which is the venous drainage trunk of the upper limb.449,450

As it is an anatomical transition segment between the superficial and deep venous systems, its access stenosis presents a series of particular characteristics that force it to be considered separately from stenosis that occurs in the trajectory of the cephalic vein in the arm.

First, it is one of the most common causes of nAVF dysfunction,451-453 and this dysfunction usually presents with significant haemodynamic changes334 and a marked association with arm nAVF (39%) versus nAVF in the forearm (2%).451,452

Likewise, in comparison to stenosis in other locations, these are lesions with a significantly poorer response to treatment using PTA, with greater resistance to dilation (4.8% versus 1.3%), higher rate of vascular rupture (14.9% versus 8.3%) and shorter free interval between angioplasties (10.6 versus 18.3 months).449,451 Finally, a higher rate of thrombosis has been found in patients with stenosis in CVA.334,454

Several possible pathophysiological mechanisms for the development of this type of stenosis have been put forward, such as lack of adaptation to the high-flow situation, presence of valves in the cephalic-axillary confluent, alterations due to the angle of the confluent, absence of elasticity at the level of the clavipectoral fascia or intrinsic alterations in the venous wall due to uraemia.449,454-456 The sequence of mechanisms that leads to the development of stenosis has not been identified to date, leading some authors to consider the possibility that all the indicated agents could be involved in a variable way.453

Therapeutic options of cephalic arch stenosis

As mentioned, the management of this type of stenosis involves greater complexity, given its poor response to treatment and the higher rate of recurrence and complications.

Percutaneous transluminal angioplasty

It is the most widely used therapeutic technique, in many cases due to the unavailability of other technical options in practice. The study by Rajan et al.452 reports a technical success rate of 76%, having required the use of high pressure balloons (> 15 atm) in 58% of cases, with 6% ruptures of the target vessel. Primary patency at 6 months was 42% and 23% at 12 months, with primary assisted patency of 83% and 75% at 6 and 12 months, respectively, requiring an average of 1.6 procedures per year to achieve this, results similar to those later published by Vesely and Siegel.440 Dukkipati et al.,457 in a study on the results of PTA in the CVA, describe an average of 91.5 days between PTA to maintain VA patency.

Thus, results of PTA on CVA stenosis demonstrate a markedly lower effectiveness than in other venous territories, with a higher rate of complications and with lower primary patency than the standards recommended by some clinical practice guidelines.10 However, it is a minimally invasive and widely available treatment mode, justifying its extensive use in clinical practice. Despite this, new treatment options have been proposed in different studies which have been published.

Percutaneous transluminal angioplasty with stent placement

In order to improve the clinical success and patency of the procedure, placement of an intravascular stent has been proposed.449,453 As already mentioned, it is a technique commonly used in clinical practice for the treatment of PTA complications, in cases of vessel rupture, and also for recurrent stenosis, as it is a safe and minimally invasive procedure. On the other hand, it is a technically complex procedure, since it requires placement adjacent to the cephalic-axillary venous confluent, which means there is a risk of compromising axillary vein permeability with stent deployment or with posterior migrations of the stent, thereby limiting the creation of new accesses in the limb.453 In addition, in the case of peripheral veins, stent placement has not been shown to increase VA patency.458

Currently available evidence on stent placement in the CVA comes from two published studies, in comparison to simple PTA457and stent versus the deployment of endoprosthesis,442 with 39% primary patency of the procedure at 6 months. The study of Dukkipati et al.,457 which compares simple PTA versus PTA with stent placement, found an association between stent deployment and an increase in patency, reducing the number of PTA needed after the procedure to maintain it.

Despite providing a modest improvement in primary and primary assisted patency for simple angioplasty, the overall results of stent deployment in the CVA hardly justify the cost/benefit of its use in a systematic way, except in cases of technical complication during PTA.442

Cutting balloon

As this is a stenosis with poor response to simple PTA, the possibility of treatment using PTA with cutting balloon has also been proposed.

Despite the theoretical benefit that this technique might offer, evidence from a prospective randomised study of 340 patients (including stenosis at various sites)440 found no benefit in relation to the primary patency of the procedure, and a higher complication rate (5.2%) was observed versus PTA with conventional balloon. Subsequently, another study459 also failed to find better patency of cutting balloon versus simple PTA.

Endoprosthesis

Placement of a vascular endoprosthesis—stent covered with prosthetic material (polytetrafluoroethylene [ePTFE])—may prevent the development of endothelial hyperplasia present in the recurrence of CVA stenosis. It is, however, a technique with a high medical cost.449

The RCT conducted by Shemesh et al.,442 comparing stent and endoprosthesis placement, describes a technical success rate of 100%, with 82% primary patency at 6 months, significantly greater compared to that reported in uncovered stents. Similar results have been reported by Shawyer et al.,460 who found primary patency at 6 and 12 months of 82% and 73%, respectively, and a secondary one of 91% at 6 months.

Despite the improvement found with this technique, given the high financial cost of the procedure, new studies are needed to confirm the results in order to recommend its widespread use in clinical practice.

Surgical transposition

Given the suboptimal results obtained by PTA in this type of stenosis, the surgical transposition of the cephalic vein into the brachial or basilic vein has been proposed by different authors.449,453 The described technique consists of disconnecting the cephalic vein arch with ligation of the proximal vein and reanastomosis in the basilic or brachial vein in the axillary cavity, by subcutaneous tunnelling, so that drainage to the deep venous system occurs at this level. This surgery is of a moderate technical complexity, and can be performed with locoregional anaesthesia.

The evidence currently available is from several published case studies,461-463 and there are no direct comparisons with other types of treatment. The results show primary procedure patency of 70-79% at 6 months and 60-79% at 12 months, with a complication rate of 8%.453-463

Likewise, significantly better patency has been reported in PTA procedures performed after surgery, so there are authors462 who recommend their use in combination.

Thus, the surgical transposition of the CVA is a safe therapeutic option that offers superior patency results to PTA with or without stent placement, presenting the disadvantage of being an invasive technique of intermediate complexity. Large-scale studies that can confirm its usefulness in clinical practice are therefore necessary.

Other techniques

Given the association between turbulent flow and development of endothelial hyperplasia, the indication of flow reduction techniques has been put forward to reduce this turbulence. In the retrospective study of Miller456 on a group of patients with intervention (minimally invasive limited ligation endoluminal-assisted revision [MILLER]) to reduce the flow for other reasons (distal hypoperfusion syndrome (DHS) or high flow), there is a significant improvement in PTA patency after reducing access flow. However, there are no further studies on the role that flow reduction may play in the treatment of these lesions.

Finally, the possibility of performing a surgical procedure through surgical angioplasty with patch through a direct approach of the CVA has also been proposed.464 While it is a technically relatively complex technique, further studies are necessary to determine its role in clinical practice.

Cephalic arch stenosis: therapeutic management

Only a relatively small number of studies supporting the use of the different treatment methods in a clinical setting are available for CVA stenosis, despite their significant prevalence. Consequently, the available evidence is based, in most cases, on a small number of published cases that do not compare different techniques. Therefore, the recommendations made are essentially based on the opinion of GEMAV members, taken on the basis of currently available studies and criteria for good clinical practice (Table 22).

PTA has been the treatment of choice in cases of CVA stenosis, as it is a safe technique, with low complexity and acceptable results in other venous sectors.453 It is, in addition, a widely available procedure in practice that, in many cases, has no feasible therapeutic alternatives. We realise that both expert opinion and studies confirm the suboptimal result, with poor patency and higher rate of complications than in other locations.452,462 Despite this, PTA is still considered as a first-line technique for treating these lesions, given its good cost/benefit ratio, its minimally aggressive nature and the acceptable rates of both assisted patency and number of procedures required to maintain it.

In contrast, the use of stents has not shown a parallel increase in the effectiveness of the technique442; therefore, its use is not justified in a generalised and systematic way given its greater cost. Their placement would be reserved for cases of technical failure in simple PTA (vessel rupture or persistent stenosis).

Along the same lines, incorporating the cutting balloon device, one study has not shown better patency than simple PTA,459 and the results of the largest study to date (340 patients in all sites along the whole AVF segment)440 do not show an improvement in results and even have a higher rate of complications, so its widespread use raises doubts regarding the cost of the procedure and its safety.

The results of studies on endoprosthesis placement have actually shown better results versus simple PTA.442,460 Although this is a recently introduced technique with little available evidence to support it and it is a procedure with far higher costs than the rest, its routine use is determined by evidence that may arise from new studies.

With regard to surgical techniques, although there is relatively limited evidence, transposition of the cephalic vein has also proved to be a useful treatment as it both increases primary patency and decreases the need for angioplasty after surgery.461-462 Therefore, it can also be considered a first-line treatment in the treatment of CVA stenosis.

Finally, it was considered that the very limited evidence on flow reduction techniques and surgical angioplasty do not allow us to make any recommendation regarding use, as future studies must be conducted in order to determine their usefulness in clinical practice.

→ Clinical question XVI Are there any criteria that indicate in which cases, when and how to treat central vein stenosis, assessed in terms of usable arteriovenous fistula patency and/or thrombosis?

(See fact sheet for Clinical question XVI in electronic appendices)

Rationale

Central veins are considered to be the subclavian vein, the brachiocephalic vein (also called the innominate vein) and the superior vena cava. The subclavian vein is a continuation of the axillary vein and starts on the lateral edge of the first rib. Due to their intra-thoracic location, i.e. protected by rib arcs, clavicle and sternum, central veins are less accessible to surgery than the peripheral veins of the arm, and are also larger, support more flow and are more elastic.465,466

Stenosis or occlusion in the central veins of an upper limb in which VA has been created may lead to venous hypertension that is symptomatic, secondary to progressive oedema of the arm that may become refractory, VA dysfunction, trophic disorders of the limb and increase in collateral circulation in the neck and thorax. This may appear in 15-20% of patients on HD, often with previous history of handling and cannulation of the central, subclavian or jugular vein.427,428 Regardless of CVC location, the greater the number and duration of the CVC, the greater the risk of developing stenosis. A higher prevalence of stenosis is also described in CVC placed on the left side because of the longer and more tortuous trajectory of the central veins on this side.466 In patients with defibrillators or pacemakers requiring AVF, this should be created in the arm opposite the location of the cardiac device. In the HD patient, central stenosis usually remains asymptomatic until an AVF is made in the ipsilateral limb, at which point, the stenosis becomes symptomatic as QA increases.466

The main cause of central venous stenosis in patients on HD is the development of intimal hyperplasia secondary to chronic trauma caused by a CVC, plus high flow and secondary turbulence in patients with AVF in the arm.467 Ninety percent of patients with stenosis have had a central venous catheter.468 Forty percent of CVC in the subclavian vein and 10% of CVC implanted in the jugular vein cause central vein stenosis.14

When central venous stenosis is suspected, the imaging test of choice is fistulography or venography. If the patient already has an AVF, the study can be performed by direct vein needling of the AVF (outflow segment). As it is impossible to directly view central vessels with US, this imaging test is relegated to a secondary place, although it must be performed before fistulography to rule out stenosis in any other segment of the access that is accessible to ultrasound waves. Fistulography also allows the VA to be treated during the procedure, if indicated.

Other diagnostic means for the study of central veins are Computed Tomography angiography (CT angiography) and Magnetic Resonance angiography (MR angiography). CT angiography has an advantage over MR angiography in that it provides better image resolution, but both techniques have disadvantages (see section “Monitoring and surveillance of arteriovenous fistula”), as they have a high cost and will not prevent fistulography if there is central stenosis. In cases of iodinated contrast allergies, MR angiography may be indicated, although there is a risk of nephrogenic systemic fibrosis.

Evidence synthesis development

The literature unanimously agrees that only symptomatic cases should be treated.14,15,466,469 In the review of Levit et al.469 of asymptomatic patients in HD with central stenosis > 50%, in 28% of them angioplasty was not performed and none developed symptoms later. However, in 8% of patients treated the stenosis worsened and became symptomatic which, according to the author, would be the result of endothelial damage produced by the balloon. Chang et al.470 described similar findings.

The treatment of choice in central vein stenosis is dilation with balloon catheter.14,15,466 PTA in central veins has a high technical success rate ranging from 70% to 90% depending on the studies.466 Buriankova et al.471 obtained a 96% success rate in stenosis and only 50% in occlusions. Results of patency after PTA vary (according to authors) between primary patency of 12% to 50% at one year and secondary patency of 13% to 100%,466 although these results can be improved with the systematic and increasingly widespread use of larger diameter and high pressure balloons.466,471 The most serious complication following central venous PTA is vein rupture, which, although exceptional, should be immediately identified and initially treated by low pressure balloon compression for 6 min, three consecutive times. If it is not possible to stop the bleeding, the other option is to implant a covered stent.465

The different guidelines and recent bibliographic reviews recommend stent implantation in dilation-resistant elastic stenosis and in recurrence under three months following the last PTA.14,15,466 When a stent is placed, it is very important not to occlude areas of venous confluence such as the internal jugular ostium and the contralateral brachiocephalic trunk, to prevent problems during the placement of future VA.

Outcomes of stents, the same as with PTA, vary according to the authors, with primary patency rates at one year which fluctuate between 14.3% and 100% and secondary patency between 33% and 91%.466 In some comparative studies between PTA and stent implants, there appears to be no significant differences in primary and secondary patency.472,473 In the future, the development of new specific stents for veins which have adequate diameters and high radial strength may make these outcomes improve. Covered stents may be another option, and show promising initial results, although there are no prospective and randomised studies.467

Theoretically, covered stents cause less intimal hyperplasia than uncovered ones. As a factor against, as they are covered, they can more easily occlude venous confluence areas that prevent CVC placement in the future. With regard to complications, the most common ones are shortening, fracture and migration of the stent.467 Shortening and migration are less common since nitinol stents are used; due to their thermal memory, these best adapt to tortuous venous areas.418

From evidence to recommendation

If central venous stenosis is clinically suspected during VA follow-up in HD patients, fistulography is required to confirm the diagnosis. Fistulography is the diagnostic method that locates the lesion and prepares the therapeutic approach.

In central stenosis processes where collateral circulation has developed to compensate the stenosis and there is no clinical significance, treatment would not be necessary given there is no positive risk-benefit balance. Therefore, it is only recommended to treat the stenosis with clinical repercussions.

Should stenosis require treatment, the approach of choice would be endovascular treatment by means of balloon PTA, reserving stent placement for cases of stenosis that present resistance to dilation or frequent or early recurrence of the stenosis, within 3 months. While placing the stent, occluding areas of venous confluence should be avoided to prevent problems with future VA.

Recommendations

Rationale

Thrombosis is suspected when physical examination fails to detect murmur or thrill through AVF auscultation and palpation, and must be confirmed with an image test.

Thrombosis is the main AVF complication. The main predisposing factor is the presence of venous stenosis and accounts for 80% to 90% of thromboses.291,474 Most stenosis are usually located in the proximal segment of arteriovenous anastomoses in the nAVF and in the venous anastomosis of pAVF.14 Any thrombosed VA should be evaluated urgently, and access patency restored when indicated, within the first 24-48 h after the event. Whether the salvage procedure performed is endovascular or surgical, once the thrombus has been removed, fistulography should be performed to locate the stenosis and, in the same procedure, resolve the underlying cause to prevent episodes of rethrombosis.475,476 Other causes of thrombosis are arterial stenosis and non-anatomical factors such as excessive VA compression after HD, hypotension, elevated levels of haematocrit, hypovolaemia and states of hypercoagulability.477-480

Due to the importance of VA for the patient’s clinical evolution, the morbidity associated with CVC and the anatomical limitation for multiple VA creation, the salvage of every potentially recoverable AVF should be attempted. The only absolute contraindication is the active infection of the VA. Relative contraindications include allergy to iodinated contrast, unstable or life-threatening clinical situation; biochemical or hydroelectrolytic alterations requiring treatment with urgent dialysis such as pulmonary oedema, hyperkalaemia or severe metabolic acidosis; right-to-left heart shunt; severe pulmonary disease and aneurysmal AVF with thrombosis of a great length of the VA.

Thrombosis of the VA for HD should be regarded as a therapeutic emergency requiring immediate solution. Strategies must be established to take this into account so that in each centre, all the professionals involved participate in a multidisciplinary approach to the problem. Urgent restoration of VA patency allows, in the first place, temporary CVC placement to be avoided, with the morbidity that this implies. However, prior to any therapeutic procedure, a clinical assessment of the patient and an analytical study should be performed to rule out situations of potential risk or severity (pulmonary oedema and severe hyperkalaemia). If the patient requires urgent HD, a CVC should be placed, and the thrombectomy procedure delayed. This delay should be less than 48 h after thrombosis occurred.14,481 The thrombi become progressively fixed to the vein wall or the ePTFE prosthesis making thrombectomy more difficult the later the unblocking procedure is attempted.14 However, the “time” factor is not necessarily restricted, given that thrombosed accesses have been salvaged even after several weeks following thrombosis.271

Endovascular thrombectomy

The main objective of the endovascular technique is to re-cannulate the thrombus, using hydrophilic guides, preferably with an angled tip, as they are less traumatic and avoid venous dissection. Thrombus aspiration is performed with manual thromboaspiration systems with negative pressure271,482 with a thick catheter of 7 to 9 Fr or thromboaspiration by suction. To avoid any procedure-related complications, it is advisable to administer sodium heparin. At the end of the procedure there is no standardised indication for pharmacological treatment, although some authors recommend low molecular weight heparin on alternate days to HD to prevent AVF rethrombosis,271 and other anti-aggregants with acetylsalicylic acid or clopidogrel during 72 h post-thrombectomy.475

Wen et al.475 review their results using the AngioJet thrombus aspiration system in 109 patients with nAVF thrombosis. They obtain a technical success score of 76% (80% before three days and 63% after three days) with primary patency rates of 67%, 57% and 39% at 30, 90 and 180 days, respectively. These results are similar to those obtained with other thromboaspiration devices (Arrow-Trerotola, Hydrolyser and thrombectomy with balloon) and pharmacological thrombolysis.475,483 These same authors considered nAVF revascularisation more difficult than in pAVF, since, in their experience, native veins are more susceptible to lesion or breakdown, and have a more complex anatomy with occasional onset of multiple stenosis and/or aneurysmal formations. In conjunction with these data, several authors recommend the use of manual thromboaspiration with catheter in nAVF as the catheters are more flexible, are pre-shaped, are smaller in size than other thrombectomy devices, and are therefore less damaging to the vascular endothelium.271,484

The complications described during the procedure are pulmonary thromboembolism, arterial embolism, rupture or dissection of the vein and haematoma at the needling site, which can become anaemic.271,475 The use of stents in cases of thrombosis is poorly documented but could be useful in aneurysmal dilatations with residual thrombi after thromboaspiration.271

Surgical thrombectomy

Traditionally, nAVF thrombosis has been treated surgically,485,486 and it is still performed in many HD units487 through embolectomy catheter, early surgical review of the access and its afferent and efferent vessels. Intra-operative radiological evaluation is also used to treat the underlying lesions found with good results and at a low cost. Treatment includes repair with the reconstruction or creation of a new anastomosis a few centimetres more proximal, or bypass of the stenotic area by interposing an ePTFE segment. If the thrombosis is located in the area adjacent to the anastomosis of radiocephalic and brachiocephalic AVF, the vein may be preserved and the creation of a new anastomosis is recommended, even if several days have elapsed.291,485 In addition to the surgical technique normally used to perform a proximal reanastomosis, there are authors who have proposed the interposition of an ePTFE segment, in order to avoid depleting the venous pathway inherent to surgery. The results published by these authors show similar patency rates to proximal reanastomosis, although as a drawback, they introduce prosthetic material in the VA.273,488

New surgical techniques that have been proposed via manual thrombus extraction followed by PTA of stenotic lesions show good results (technical success in 87% of procedures). The authors consider that this is a simpler and cheaper procedure than percutaneous thrombectomy or thrombolysis, and also allows acute and chronic thrombus to be eliminated as well as that in aneurysmal segments.489

Finally, one of the indications for review and surgical treatment is in early nAVF thrombosis (first hours or days), which is mainly related to technical problems.

Pharmacomechanical fibrinolysis

Percutaneous pharmacomechanical fibrinolysis is a minimally invasive method that uses thrombolytic drugs and a PTA balloon for the treatment of thrombosis. The commonly used thrombolytic drugs are urokinase and the recombinant tissue plasminogen activator (rt-PA). The procedure combines releasing fibrinolytics locally, which can be performed in several ways, and PTA of the thrombus. The fibrinolytic drug is released after breaking through the thrombus and the stenotic area responsible for the thrombosis with the hydrophilic guidewire; pulse-spray is the most commonly used system.490 After patency is partially restored, a thrombectomy and PTA of the thrombus,491,492 using balloon catheter, and the treatment of lesion(s) responsible for the occlusion are also carried out, in the same procedure.

The literature contains four RCTs493-496 and a retrospective study497 comparing fibrinolysis with urokinase and percutaneous mechanical thromboplasty. No statistically significant differences were observed between either technique in relation to technical success, patency and complications493-495,497 with the exception of a study conducted by Vogel,496 where the authors found a higher percentage of bleeding complications, primarily at the needling site, with the use of fibrinolytics. The impossibility of lysing the entire thrombus should be added to this drawback.

On the other hand, although most studies found the longer procedures to be a disadvantage of fibrinolysis, in the study conducted by Vashchenko in 2010, where 563 procedures were studied comparing fibrinolysis of thrombosed access by the technique of “urokinase injection and wait” versus mechanical thrombectomy with mechanical device,497 they found the lower cost of fibrinolysis to be an advantage, given the high price of mechanical thrombectomy devices. There is no study comparing the financial cost of VA fibrinolysis to thrombectomy with catheter.

In the review conducted by Bush et al. in 2004,498 comparing different techniques of both endovascular and surgical revascularisation, including fibrinolysis, they also found no differences between the different methods used.

Even with its drawbacks, fibrinolysis is a therapeutic tool that may be useful in certain cases when mechanical or aspiration thrombectomy is not sufficient for the complete removal of thrombi.14 Its greatest usefulness is in combination with mechanical thrombectomy, allowing the use of lower dose of fibrinolytic drugs and reducing the systemic complications derived from its use.

5.2.1 Treatment of native arteriovenous fistula thrombosis

→ Clinical question XVII In native arteriovenous fistula thrombosis, what would be the initial indication (percutaneous transluminal angioplasty versus surgery) assessed in terms of patency of the native arteriovenous fistula and/or thrombosis? Does it depend on location?

(See fact sheet for Clinical question XVII in electronic appendices)

Evidence synthesis development

So far there have been no RCTs comparing the results obtained with surgical treatment and endovascular therapy. There are, however, recent retrospective studies. Ito et al.476 compare both techniques in a sample of 587 patients of which 25% had nAVF. In this subgroup, a patency of 33.7% at 2 years with endovascular treatment stands out compared to 37.5% with surgical thrombectomy and 59.8% if surgery is performed with an additional graft or a new VA (p = 0.0005).

In the review of Tordoir499 in which there are only observational studies to describe the behaviour of both techniques in the nAVF, surgery maintains better results in primary patency at 1 year (74% versus 40%) and secondary patency (87% versus 72%), with the results being similar in technical success (90% versus 89%).

In forearm nAVF, there is a slight advantage of surgical treatment over PTA when comparing long-term primary and secondary patency. The study does not establish a separation between stenosis in different locations, so the best results in the forearm may be related to the treatment of the juxta-anastomotic stenosis.

Similar findings regarding outcomes by location have been found in two studies analysing endovascular treatment in the arm and forearm500,501 and in one study with patients treated with surgery.502 All of them report a greater primary patency for AVF located in the forearm.

From evidence to recommendation

The results obtained from retrospective studies, and in the absence of RCTs, indicate a moderately better primary patency of surgery versus endovascular treatment. When results are analysed in the thrombosed fistulae secondary to juxta-anastomotic stenosis, better long-term primary and secondary patency rates are found, which allows surgical treatment to be recommended at this location, given the better results in the treatment of this stenosis. This decision should be associated with the priority of avoiding CVC placement, so if surgery does not guarantee it, endovascular procedure can be contemplated.

In the treatment of thromboses not associated with juxta-anastomotic stenosis, both endovascular and surgical treatment has a high clinical success rate, with no evidence currently available to recommend a specific therapeutic alternative. Therefore, the technique of choice should be decided in accordance with the patient’s clinical context, and the avoidance of CVC placement made a priority whenever possible.

In any case, existing evidence on the treatment of thrombosis of nAVF is difficult to interpret since not only are there no studies that directly compare the procedures, but these studies present considerable technical heterogeneity, both in the endovascular and surgical approach. It cannot be ruled out that the use of different devices in different circumstances may play a role in this variability. Therefore, the limited available evidence also allows a partial therapeutic orientation with these recommendations being based on the interpretation of GEMAV.

5.2.2 Treatment of prosthetic arteriovenous fistula thrombosis

Treatment of prosthetic arteriovenous fistula thrombosis

Rationale

Despite having a higher rate of complications than nAVF, pAVF is a good solution for patients with an exhausted venous vascular bed and in elderly patients, with thrombosis being the main complication. In these cases, thrombosis is located mostly in the venous anastomosis.14 and is secondary to intimal hyperplasia derived from haemodynamic mechanisms due to lack of adjustment between the vein and the ePTFE prosthesis.503,504

As in nAVF, urgent assessment with subsequent thrombectomy in recoverable pAVF is indicated, if possible, in the first 24-48 h after the event, in order to avoid CVC placement and associated morbidity. The same strategies mentioned in the previous section are established (section 5.2.1). Imaging studies (DU or fistulography) should be performed after restoring patency to locate stenosis, and in the same procedure to perform treatment of the lesions conditioning episodes of rethrombosis.475,476

Stenosis and thromboses can be treated endovascularly or surgically. Numerous studies have evaluated both methods, concluding that a combination of both can be highly beneficial. At the end of the 1990s, thrombosed prosthetic accesses were primarily treated surgically followed by angiographic assessment to identify the cause of thrombosis and the presence of residual thrombus. The development of new endovascular devices and the lower invasiveness of this type of procedure have resulted in a predominance of the latter. In any case, the aim of both types of treatment in the detection and treatment of underlying stenosis is always to ensure their ongoing long-term patency.

→ Clinical question XVIII In prosthetic arteriovenous fistula thrombosis, what would be the initial indication (percutaneous transluminal angioplasty versus surgery versus fibrinolysis) assessed in terms of patency of the arteriovenous fistula and/or thrombosis? Does it depend on location?

(See fact sheet for Clinical question XVIII in electronic appendices)

Evidence synthesis development

Traditionally, surgical thrombectomy has been used in pAVF thrombosis, followed by repair with bypass by interposing a graft or associating reanastomosis in a proximal segment of vein without stenosis. Percutaneous treatment of VA thrombosis is a therapeutic option that is less invasive than surgery475 and allows the preservation of proximal venous territory. As a disadvantage, there is a need for a greater number of procedures to maintain pAVF patency.451,474

A meta-analysis by Green et al.474 concluded in 2002 that surgery was superior, both in terms of technical failures and in primary patency. However, in a recent meta-analysis performed by Kuhan et al.,505 analysing 6 RCTs comparing endovascular therapy and surgery in thrombosis of pAVF, the results were comparable between both techniques. Technical success rates were, on average, 74.5% with endovascular treatment versus 80.3% with surgery (p = 0.13); primary patency at 30 days was 64.6% for endovascular therapy and 66.8% for surgery (p = 0.46); at one year, 14.2% with the endovascular approach versus 23.9% with surgery (p = 0.06). Primary assisted patency at one year was analysed in a single study, with 20.5% with endovascular treatment versus 43.9% with surgery (p = 0.03); however, secondary patency at one year, also analysed in a single study, was 86% for endovascular treatment versus 62.5% for surgical (p = 0.14).

Unlike the meta-analysis conducted by Green et al.,474 in which results were clearly favourable for surgery, the study of Kuhan et al.505 placed endovascular therapy on a par with surgical, with the former being less aggressive. Endovascular techniques, using mechanical and aspiration thrombectomy devices, and the incorporation of new angioplasty balloons with more technical features, have levelled the balance between surgery and endovascular treatment, the latter having the advantage of being less invasive. The comparison of percutaneous mechanical techniques with pharmacological fibrinolysis in three RCTs493-495 shows no significant differences in patency results.

In this respect, however, despite its invasiveness, urgent surgery avoiding CVC placement with subsequent assessment and endovascular treatment has recently been reported with very good results.167 The authors obtained a patency rate of 67% at three years and a thrombosis rate of 0.45 events per patient per year.

Finally, the use of uncovered metallic prostheses is highly controversial, and results similar to those described for the treatment of non-thrombosis-related VA stenosis have been reported (section 5.1). With regard to the use of covered metallic prostheses (stent graft), in the study by Nassar et al.505a where the results of 66 patients with thrombosed pAVF are analysed, the authors find poorer outcomes than those observed in other studies referring to treatment of venous stenosis without thrombosis,419-421 with poor primary patency (47% and 21% at 3 and 12 months), similar to that observed following thrombectomy without stenosis treatment.498 The thromboses were not associated with the development of an intra-stent stenosis, and so the authors concluded that there must be other factors that determine VA thrombosis different to stenosis in the venous anastomosis, and do not recommend its use in case of thrombosed pAVF.

From evidence to recommendation

The reviewed studies and clinical trials show no significant differences in patency results between surgery and endovascular treatment, being lower in all cases than those obtained in nAVF. Surgical treatment has better rates of technical success, primary and assisted primary patency (although not significantly), while on the other hand, percutaneous treatment is less aggressive and avoids CVC placement.

Therefore, the approach to thrombosed pAVF can be therapeutically oriented indistinctly, either using the endovascular or surgical approach. The choice of technique should take the patient’s clinical context into consideration, and CVC placement be avoided where possible.

Thrombosis due to stenosis in the axillary vein territory warrants separate consideration, as the technical complexity of exposing a proximal venous segment in surgery makes percutaneous treatment the treatment of first choice.

Finally, similar to nAVF, the heterogeneity, both of the studies and the technical conditions, means that the opinion of GEMAV has contributed to the interpretation of the evidence.

5.2.3 Elective treatment of arteriovenous fistula stenosis versus post-thrombosis

Elective treatment of arteriovenous fistula stenosis versus post-thrombosis

Rationale

As mentioned, thrombosis is the main AVF complication and the main cause of its definitive loss. The main predisposing factor is the presence of venous stenosis which accounts for 80 to 90% of thromboses.291,474 Most stenosis is usually located in the segment proximal to arteriovenous anastomoses in nAVF and in the venous anastomosis in pAVF.14

Irreversible AVF thrombosis will have a series of negative consequences on the prevalent HD patient,269 increasing morbidity and mortality, frequency of hospital admissions and healthcare costs.270 In relation to the access thrombosis, it should be noted:

• •

  It is not always possible to restore all thrombosed AVF.271

• •

  Several studies indicate that the secondary AVF patency after post-thrombotic restoration is lower than elective AVF stenosis repair prior to thrombosis.272,273

These data suggest that it is appropriate to perform elective stenosis treatment prior to AVF thrombosis and this means it is important to conduct surveillance and monitoring of both nAVF and pAVF.

→ Clinical question XIX In the presence of stenosis in the native arteriovenous fistula, is there a significant difference between elective intervention or performing treatment after thrombosis?

(See fact sheet for Clinical question XIX in electronic appendices)

Evidence synthesis development

Two retrospective studies compared results of elective surgery of nAVF with stenosis but without occlusion versus thrombosed AVF surgery.273,506

The retrospective study of Lipari et al.273 provided results of 64 patients with forearm AVF stenosis, treated 32 with elective surgery and 32 after thrombosis. It did not find differences in the restenosis rate of access: 0.189 per AVF year, the same for both types of surgery, but there were differences in VA loss: rate of 0.016 per AVF year for the elective surgery group and 0.148 for surgery after thrombosis (p = 0.048). Technical success was 100% for elective surgery and 84% for surgery after thrombosis.

The retrospective study of Cohen et al.506 reports on 43 patients with AVF in arm who had received 48 interventions in stenosed AVF and 15 in already thrombosed AVF. They did not find significant differences in terms of patency of the access at 12 months:

• •

  Primary patency of the access at 12 months: 56% for AVF with stenosis and 64% for already thrombosed AVF (p = 0.22).

• •

  Secondary patency of the access at 12 months: 64% for AVF with stenosis and 63% for already thrombosed AVF (p = 0.75).

Technical success of the surgery was 95% overall (60 of 63; two failures in thrombolysis and one in the primary surgery for the stenosis).

In one prospective study elective surgery to correct the AVF stenosis versus waiting and operating when thrombosis of the AVF develops272 are compared. Researchers describe a greater patency in AVF salvaged following dysfunction than following thrombosis, both as a whole and when analysed in a disaggregated way by type (native or prosthetic). In this prospective study with a 5-year follow-up, 317 AVF were evaluated (73% nAVF and the rest pAVF [ePTFE]), on 282 patients. 88 thromboses occurred, corresponding to a rate of thrombosis/access/year of 0.06 for nAVF and 0.38 in pAVF. In total, 66.6% of AVF salvage repairs were elective, with emergency surgery in 76% of thromboses. The added patency of all incident AVF repaired after dysfunction was 1062 ± 97 days versus 707 ± 132 in those repaired for thrombosis (p < 0.02). The increased risk for AVF loss in those repaired post-thrombosis versus dysfunction was 4.2 (p < 0.01).

From evidence to recommendation

Despite the lack of randomised studies and their scarcity and methodological limitation, studies analysing the evolution of elective versus post-thrombotic treatment show a preference for elective therapy in their results, with both lower AVF loss and better patency.

At the same time, the outlook of a patient with a thrombosed access must be taken into account regarding elective procedure. The greater likelihood of there being less controllable factors, such as patient clinical situation, extent of the thrombosis or CVC requirement, means that the guarantees of success may be compromised.

Therefore, GEMAV recommends performing an elective or preventive intervention of the stenosis rather than post-thrombosis salvage, following the criteria presented in section 4, associated with the high risk of thrombosis.

5.2.4 Thrombosis: salvage versus new vascular access

Thrombosis: salvage versus new vascular access

Rationale

AVF thrombosis results in a substantial number of hospital admissions, the use of CVC and, consequentially, an increase in healthcare expenditure. In addition to this, CVC-associated morbidity and mortality and anatomical limitation for multiple accesses must be considered, which is why clinical guidelines currently in force consider AVF thrombosis to be a medical emergency.6

When an AVF is thrombosed, the possible options are:

• •

  Place a CVC to dialyse the patient and then refer him/her for a new AVF;

• •

  Attempt to urgently salvage the AVF for later use, to avoid hospital admission and CVC placement.

Both procedures imply healthcare costs and expenditure, and cost analysis studies should be conducted on these procedures.

With regard to pAVF treatment, there appears to be an agreement in the literature on a major advantage of urgent thrombectomy, either surgical or endovascular, versus a new VA.272,507 That is not the case in native accesses. While nAVF are considered superior to pAVF as VA, they are not problem-free. Over the last decade, thrombosed nAVF have been managed surgically or endovascularly. Despite this, attempts to salvage them have not been widely established. Although the percutaneous management of a thrombosed nAVF is highly successful, repeated interventions are usually required to sustain long-term patency.507 Data published in relation to the healthcare expenditure involved in the surveillance and elective treatment of stenosis to prevent thrombosis of VA are controversial281,508 with few cost-effectiveness studies.

However, there are several studies on the significant healthcare costs caused by VA in prevalent patients undergoing HD.509 The study of Manns et al.510 shows the high cost of HD incident patients with primary failure in their AVF due, in part, to the increase in the number of diagnostic procedures: image and interventional procedures. For health systems which strictly control financial expenditure, this is extremely relevant.

After conducting a financial analysis of expenditure on AVF maintenance, Bittl et al.508 conclude that this is higher than the cost of creating a greater number of nAVF in the prevalent population (with lower percentage of thrombosis and dysfunctions). The article does not refer to what would happen with a prevalent population with a very high percentage of nAVF.

On the other hand, in the study by Coentrao,511 a retrospective analysis of healthcare costs and expenses was conducted comparing the treatment of thrombosed nAVF and the subsequent follow-up with the creation of a new AVF. They observed that percutaneous thrombectomy and treatment of stenosis versus creation of a new VA and waiting for its maturation is associated with a reduction in costs. The group where this procedure was conducted is associated with a higher number of hospital admissions and problems with AVF management (4 times greater), with shorter patency of the new AVF and the consequent comorbidity associated with the CVC.

Finally, in a very recent study where urgent surgical treatment of 268 AVF thrombosis episodes versus scheduled surgery was tested retrospectively and over a period of 11 years,487 the authors obtain a financial saving of €5397 in favour of urgent AVF repair versus creation of a new access. This benefit is derived from the greater hospital expenses associated with creating a new AVF (CVC complications), and the need to perform interventions to achieve maturation. Extrapolation of savings to the entire Spanish population with 23,000 patients undergoing HD would be €9,930,480/year. The study does not analyse, however, the differences between nAVF and pAVF; nor does it include endovascular therapy of the thrombosed AVF.

Therefore, although no prospective studies or clinical trials comparing both of these procedures have been found, the data obtained from the literature seem to suggest that the creation of a new VA results in higher expenditure and morbidity associated with CVC placement than by urgent restoration of the thrombosed AVF.

Recommendations

Rationale

It is estimated that between 28% and 53% of AVF do not mature enough for use in HD.512 In general, QA of 500 mL/min and a diameter of at least 4 mm are required for nAVF to be suitable for dialysis. In successful fistulae, these parameters are met in 4 to 6 weeks. In other cases, from 4–6 months must be waited to conclude that the AVF has failed. In the interval, if HD is needed, a tunnelled CVC is inserted exposing the patient to the morbidity and mortality associated with the use of this VA.

This problem could hypothetically be resolved through the early detection of cases of lack of maturation and treated using surgical or endovascular methods to induce VA maturation.

Two factors, separately or combined, tend to cause most cases of lack of nAVF maturation: venous stenosis and the presence of a significant accessory vein (a venous branch that leaves the primary venous channel which forms the AVF). Both problems can be suspected during clinical check-ups and, after being confirmed with DU, therapeutic intervention could be considered.

The increase in QA and the diameter of the outflow vein occur soon after nAVF creation.513-515 These studies have shown that fistulae that are definitively going to mature do so in the first 2-4 weeks. Thus, good medical practice would advise VA assessment after 4-6 weeks from creation.512,516 The recommendation for early monitoring is based on the fact that most nAVF with delay or no maturation have stenotic lesions in the AVF circuit, which, because vascular stenoses are usually progressive, will lead to thrombosis and VA loss over time.

In most cases, potential patients with non-matured nAVF can be detected through careful physical examination, as indicated in section 4, which can provide orientation on the cause of the dysfunction (Table 23).