**3.1 Early failure/complications**

Early failure of an AVF is defined as a fistula which never matures or is unable to be used by three months of time. It is well known from several studies that there is a significant primary failure rate for all AV fistulas that are placed (Schild,2004; Biuckians,2008; Dember 2008). Causes of early fistula failure are due to inflow problems from inadequate arterial supply, anastamotic stenosis which may result from trauma during creation, or outflow

traumatic post-phlebitic changes when compared to the cephalic vein. When the BBF is placed more surgical skill is required with an initial anastomosis deep between the brachial artery and basilic vein (Fig 3). The BBF is left to mature for two months and then a second surgical procedure is preformed to "lift" the vein to allow ease of cannulation. The anatomic location of this fistula is often located in a position which is difficult to cannulate. Overall,

Fig. 3. Brachial-basilic fistula. Figure reprinted by permission from Macmillan Publishers

Even though complications of fistula access are far less than a graft or a catheter, they do occur and need to be addressed. Complications occur in approximately one-third of fistulas and include: aneurysms, infection, stenosis, thrombosis, steal syndrome and heart failure. These complications have historically been classified as early and late failure. The etiology of both early and late are somewhat similar because if the cause is not diagnosed early on it may progress and lead to late access failure. Fistula failure may also be classified as primary defined as a fistula which fails prior to cannulation or secondary defined as failure after a

Early failure of an AVF is defined as a fistula which never matures or is unable to be used by three months of time. It is well known from several studies that there is a significant primary failure rate for all AV fistulas that are placed (Schild,2004; Biuckians,2008; Dember 2008). Causes of early fistula failure are due to inflow problems from inadequate arterial supply, anastamotic stenosis which may result from trauma during creation, or outflow

radiologic intervention such as angioplasty or stent or surgical revision.

Ltd: Kidney International, 62, 2002

**3.1 Early failure/complications** 

**3. Complications of fistula access** 

the failure rate of the BBF is worse than BCF or RCF (Taghizadeh, 2003).

problems of the venous segment. Outflow problems may occur because of underlying fibrosis of the vein. Other factors which contribute to the primary failure of fistulas include demographic factors such as age, obesity, non-white ethic group, female sex , history of diabetes or peripheral vascular disease (Lok, 2006; Huijbregts, 2008) The size of the underlying vein may also influence the ability of a fistula to mature. A cephalic vein diameter of less than 2.0 mm on ultrasound in the forearm and less venous distensibility increases the risk of primary failure (Silva, 1998).

A cause of poor maturation is the development of collateral circulation. Often times a fistula is placed and when developing, collateral vessels may form which decrease the amount of flow through the designated vein to be used for cannulation. The physical exam may often help diagnosis this problem as you may palpate extra accessory vessels with an apparent augmentation in the vein when it is occluded. Small assessory vessels less than one-forth the diameter of the main AVF are likely to be insignificant. If a fistula is not maturing by 6 weeks, many algorithms suggest a vengram by 6 weeks. If collateral vessels are identified they may be coiled by interventional radiology techniques or ligated by surgical techniques (Rodriguez, 2000).

Prevention of early fistula thrombosis with pharmacologic intervention has been the subject of several recent trials, which have shown only minimal effect. The Dialysis Outcomes –Practice Patterns Study (DOPPS) noted a lower risk of failure of established fistulas in patients who used aspirin consistently over a year (Hassegawa, 2008). The Dialysis Access Consortium Fistula Trial (DAC) was a multi-center trial which compared the effects of the anti-platlet agent Clopidrogrel with placebo on early fistula failure. The proposed sample size was 1284, but the study was terminated after enrollment of 877 patients as interim data analysis showed that Clopridrogel reduced the risk of fistula thrombosis by 37% (Dember, 2008). In the DAC study 61% of newly created fistulas failed. These findings and others have shown a primary failure rate of 31-61% (Schild,2004; Biuckians,2008; December 2008). This suggests that failure of the fistula to mature is the main obstacle to successful fistula use.

#### **3.2 Late failure/complications**

Late failure of the fistula is defined as occurring greater than three months after creation and is often due to outflow stenosis. Venous stenosis occurs less frequently in AVF when compared to AVG, but nonetheless it is a common cause of AVF failure. Venous stenosis is usually detected clinically by symptoms of swelling of the extremity, prolonged bleeding post dialysis, difficulty cannulation or poor clearance. When these symptoms develop, the patient may be sent for an ultrasound for diagnosis or more commonly an interventional venogram. The venogram is desirable as a patient may have the venogram/angioplasty as a treatment option during the same procedure.

The most common anatomic location for an outflow stenosis in a RCF is 3 cm from the arteriovenous anastomaosis (Rajan, 2004). Outflow stenosis in RCF may be treated successfully by angioplasty with favorable primary and secondary patency rates (Rajan, 2004). Inflow lesions from inadequate arterial flow are often detected by a negative arterial pressure during hemodialysis and by physical examination using pulse augmentation. An arterial lesion may be present in 15-30% of fistulas (Leon, 2008). This type of lesion also is successfully treated by angioplasty or surgical revision (Turmel-Rodrigues, 2000).

One of the leading causes of failure of BCF is due to stenosis in the cephalic arch, which is the final bend in the cephalic vein prior to entry into the axillary vein (Fig 4). Cephalic arch stenosis (CAS) is found to occur in up to 77% of patients with BCF compared to 30% of

Hemodialysis Access: The Fistula 23

of the feeding artery. Symptomatic steal occurs when there is a failure of adequate collateral flow and/or excessive blood flow. This problem complicates approximately 3-5% of fistulas and grafts. It is likely to occur more frequently with BCF (6%) verses RCF. Hand ischemia from steal syndrome may require distal revascularization with interval ligation (DRIL) procedure or complete ligation in severe cases. The DRIL procedure was first proposed by Harry Schanzer in 1988 (Schanzer, 1988). A short distal bypass is created and the artery just distal to the AV anastomosis is ligated. The DRIL procedure has been used successfully to relieve the ischemic symptoms in a significant number of patients with steal syndrome

The incidence of infection of an AVF is relatively low given that the native vein is used as a conduit. Predisposing factors to infection include: inadequate skin disinfection prior to cannulation, pseudo aneurisms, perifistular hematomas (often due to inappropriate cannulation), puritis with skin excoriation over needle sites, or the use of the fistula for IV drug use. Infection occurring in native fistulas can usually be treated with intravenous

AVF creation causes an increased blood flow and resultant cardiac output, Creation of a fistula is associated with a 15% increase in cardiac output and 4% increase in left ventricular end-diastolic diameter There is also an observed increase in ANP and BNP (Iwashima, 2002). These changes often go unnoticed, however high output failure from fistula access occurs in less than 1% of cases. The decision for permanent access placement in patients with category III or IV heart failure is challenging. Patients with ESRD in this subset should be considered for peritoneal dialysis. If this is not possible a lower arm fistula could be considered (decreased blood flow when compared to an upper arm fistula) with close

Venous hypertension in an extremity occurs because of incompetent venous valves or central venous stenosis. This problem may cause severe swelling in an extremity with associated complications of skin discoloration and thickening predisposing to infection. Doppler exam is used for diagnosis to demonstrate reversal of blood flow. Diagnosis and treatment with a venogram by an interventional radiologist may also be preformed. Treatment is aimed at correcting the underlying problem if present. Careful clinical practice includes obtaining a central venograms prior to fistula placement if there are clinical clues of venous hypertension such as, a history of ipsilateral catheter placement or

A very difficult problem with AVF access is median nerve injury. It may occur from ischemic injury from steal, compression of the nerve if there is extravasation of blood or local amyloid deposition in long term dialysis patients. The treatment is first to rule out vascular compromise and confirm diagnosis with an EMG. If traditional therapy to treat

neuropathy does not resolve the pain, the fistula may need to be ligated.

(Waltz, 2007).

**3.2.3 Infection** 

**3.2.4 Cardiac failure** 

antibiotics and, if necessary surgical drainage.

monitor for worsened heart failure.

**3.2.5 Venous hypertension** 

dialated chest wall veins.

**3.2.6 Median nerve injury** 

patients with RCF with an average clinical significance at 2 years necessitating a venogram with intervention. The risk of development of CAS is less in diabetics for unclear reasons (Hammes, 2008). The BCF has been shown to be a superior access in older diabetic patients (Papanikolaou, 2009). Once CAS occurs it leads to head and neck swelling, high venous pressures and resultant thrombosis with complex treatment options. The arch is elastic, resistant to repeated angioplasty and often requires stent placement resulting in further stenosis (Hammes, 2008).

#### **3.2.1 Aneurysms**

The incidence of aneurysm formation in fistulas varies in studies from 5-7% (Lo, 2007). A traditional definition of an aneurysm is that it is considered true if it involves all layers of a venous wall or false if the wall is lined by thrombus or fibrous tissue. Aneurisms form for many reasons which include repeated cannulation at repetitive sites or altered turbulent blood flow from stenosis. As aneurysms are both a physiologic and cosmetic complication that may lead to the need for surgical revision and subsequent failure an approach to address aneurysms should be developed. Moreover, if a thrombosis occurs and significant aneurysm is present, the clot burden may be large and the thrombectomy procedure may be difficult. Aneurysms may also lead to an increased infection risk and prolonged bleeding post dialysis.

The treatment of aneurysms is prevention and if they form surgical correction. Preventative measures start with careful cannulation techniques (see cannulation techniques). Surgical options for correction include longitudinal stapling to reduce the lumen, open placation, excision with primary anastomosis, excision with interposition of prosthetic graft, and ligation (Pierce, 2007; Lo, 2007; Georgiadis, 2008). All of these techniques have been used with success and a decision for surgical treatment should be made on a case-by-case basis.

#### **3.2.2 Steal syndrome**

Steal syndrome is defined as distal hypoperfusion of the extremity in patients with severe peripheral vascular disease due to shunting of arterial blood flow into the fistula (Leon 2007). Reverse flow occurs if the diameter of the fistula opening is greater than the diameter of the feeding artery. Symptomatic steal occurs when there is a failure of adequate collateral flow and/or excessive blood flow. This problem complicates approximately 3-5% of fistulas and grafts. It is likely to occur more frequently with BCF (6%) verses RCF. Hand ischemia from steal syndrome may require distal revascularization with interval ligation (DRIL) procedure or complete ligation in severe cases. The DRIL procedure was first proposed by Harry Schanzer in 1988 (Schanzer, 1988). A short distal bypass is created and the artery just distal to the AV anastomosis is ligated. The DRIL procedure has been used successfully to relieve the ischemic symptoms in a significant number of patients with steal syndrome (Waltz, 2007).

#### **3.2.3 Infection**

22 Technical Problems in Patients on Hemodialysis

patients with RCF with an average clinical significance at 2 years necessitating a venogram with intervention. The risk of development of CAS is less in diabetics for unclear reasons (Hammes, 2008). The BCF has been shown to be a superior access in older diabetic patients (Papanikolaou, 2009). Once CAS occurs it leads to head and neck swelling, high venous pressures and resultant thrombosis with complex treatment options. The arch is elastic, resistant to repeated angioplasty and often requires stent placement resulting in further

Fig. 4. Radiograph of Cephalic arch represented by arrow; C is the cephalic vein;A is the

The incidence of aneurysm formation in fistulas varies in studies from 5-7% (Lo, 2007). A traditional definition of an aneurysm is that it is considered true if it involves all layers of a venous wall or false if the wall is lined by thrombus or fibrous tissue. Aneurisms form for many reasons which include repeated cannulation at repetitive sites or altered turbulent blood flow from stenosis. As aneurysms are both a physiologic and cosmetic complication that may lead to the need for surgical revision and subsequent failure an approach to address aneurysms should be developed. Moreover, if a thrombosis occurs and significant aneurysm is present, the clot burden may be large and the thrombectomy procedure may be difficult. Aneurysms may also lead to an increased infection risk and

The treatment of aneurysms is prevention and if they form surgical correction. Preventative measures start with careful cannulation techniques (see cannulation techniques). Surgical options for correction include longitudinal stapling to reduce the lumen, open placation, excision with primary anastomosis, excision with interposition of prosthetic graft, and ligation (Pierce, 2007; Lo, 2007; Georgiadis, 2008). All of these techniques have been used with success and a decision for surgical treatment should be made on a case-by-case basis.

Steal syndrome is defined as distal hypoperfusion of the extremity in patients with severe peripheral vascular disease due to shunting of arterial blood flow into the fistula (Leon 2007). Reverse flow occurs if the diameter of the fistula opening is greater than the diameter

stenosis (Hammes, 2008).

axillary vein

**3.2.1 Aneurysms** 

prolonged bleeding post dialysis.

**3.2.2 Steal syndrome** 

The incidence of infection of an AVF is relatively low given that the native vein is used as a conduit. Predisposing factors to infection include: inadequate skin disinfection prior to cannulation, pseudo aneurisms, perifistular hematomas (often due to inappropriate cannulation), puritis with skin excoriation over needle sites, or the use of the fistula for IV drug use. Infection occurring in native fistulas can usually be treated with intravenous antibiotics and, if necessary surgical drainage.

#### **3.2.4 Cardiac failure**

AVF creation causes an increased blood flow and resultant cardiac output, Creation of a fistula is associated with a 15% increase in cardiac output and 4% increase in left ventricular end-diastolic diameter There is also an observed increase in ANP and BNP (Iwashima, 2002). These changes often go unnoticed, however high output failure from fistula access occurs in less than 1% of cases. The decision for permanent access placement in patients with category III or IV heart failure is challenging. Patients with ESRD in this subset should be considered for peritoneal dialysis. If this is not possible a lower arm fistula could be considered (decreased blood flow when compared to an upper arm fistula) with close monitor for worsened heart failure.

#### **3.2.5 Venous hypertension**

Venous hypertension in an extremity occurs because of incompetent venous valves or central venous stenosis. This problem may cause severe swelling in an extremity with associated complications of skin discoloration and thickening predisposing to infection. Doppler exam is used for diagnosis to demonstrate reversal of blood flow. Diagnosis and treatment with a venogram by an interventional radiologist may also be preformed. Treatment is aimed at correcting the underlying problem if present. Careful clinical practice includes obtaining a central venograms prior to fistula placement if there are clinical clues of venous hypertension such as, a history of ipsilateral catheter placement or dialated chest wall veins.

#### **3.2.6 Median nerve injury**

A very difficult problem with AVF access is median nerve injury. It may occur from ischemic injury from steal, compression of the nerve if there is extravasation of blood or local amyloid deposition in long term dialysis patients. The treatment is first to rule out vascular compromise and confirm diagnosis with an EMG. If traditional therapy to treat neuropathy does not resolve the pain, the fistula may need to be ligated.

Hemodialysis Access: The Fistula 25

straight regions of vessels, blood flow is in the same direction (laminar) and EC are quiescent with high laminar shear stress and resultant low oxidative stress, cell turnover and permeability. When a fistula is created blood vessels divide or curve and complex flow patterns may develop. When this happens EC are subjected to disturbed shear stress with higher levels of oxidative stress and inflammation which may result in vascular remodeling

The anastomosis of the fistula is also important to the development of intimal hyperplasia. The primary mode of failure of a fistula access relates to outflow stenosis caused by anastomotic intimal hyperplasia. When an anastomosis is created, the trauma causes activation of chemotactic factors which result in smooth muscle migration from the media to the intima. The resultant EC dysfunction with abnormal NO production may cause dysregulation of vascular tone. Smooth muscle cells continue to migrate and proliferate with resultant intimal hyperplasia. The end result may be decreased anastomotic compliance (Lin

This schematic of this process eventually leading to fistula failure is depicted in Figure 5. When a fistula is placed there is a bend or curve created at the anastomosis. This causes a turbulent blood flow, injury to EC, decreased WSS and resultant intimal hyperplasia. There is flow restriction that results and eventual worsened intimal hyperplasia that leads to further flow restriction with the end result of stenosis. The stenotic surface leads to heamostasis and further thrombus formation. Ultimately the fistula fails as a consequence of

> High WSS

Fig. 5. Proposed cycle of fistula creation which eventually leads to intimal hyperplasia and

EC Denudation

Fistula Creation Anastomosis

Decreased WSS

> Flow Recirculation

> > Intimal Hyperplasia

Stenosis

(Hahn, 2009).

2005).

the stenosis.

fistula failure

Fistula Failure

Thrombus
