**3. Classification of vascular access**

Aubaniac [18], in 1952, described the puncture of subclavian vein as a VA, while, in the 1960s, Dillard, Quinton, and Scribner [19], based on Alwall's experience, developed arteriovenous Teflon shunt inserted into radial artery and cephalic vein. Flexible silicon rubber replaced later Teflon. Based on Seldinger's technique, Shaldon inserted catheters into femoral artery and vein for dialysis sessions in 1961 [20, 21]. Vessels in different sites were used, over time, including

Cimino and Brescia [22] described, in 1962, a "simple venipuncture for hemodialysis." Fogarty et al. [23] invented, in 1963, a special designed catheter for thrombectomy and embolectomy with an inflatable balloon at its distal tip. In 1965, the first AVF was created, and 14 more in 1966 when Brescia, Cimino, Appel, and Hurwich published their paper [24]. Sperling [25], in 1967, created an end-to-end anastomosis in the forearm, between radial artery and cephalic vein, in 15 patients, whereas Appell did side-to-side anastomosis. End-to-end anastomosis usually is not the first choice of AVF due to high risk of steal syndrome in aging, diabetic patients of dialysis, but it remains a useful option in revision procedures, although it is

Nowadays, artery side-to-vein anastomosis seems to be a standard procedure [27], which began from Rohl et al. [28] in 1968. Girardet et al. [29] and Brittinger et al. [30] in 1970 described their experience with AVG between femoral vein and artery and subcutaneously fixed superficial femoral artery for chronic HD. Brittinger et al. [31] were the first to implant a plastic valve as a vascular access in an animal model, but unfortunately, their efforts did not proceed to a human one. In the early 1970s, Buselmeier et al. [32] developed a U-shaped silastic prosthetic AV shunt with either one or two Teflon plugged outlets, which communicated to the outside of the body. The U-shaped portion could be totally or partially implanted subcu‐ taneously. Subsequently, pediatric hemodialysis patients were extremely favored by this procedure. In 1976, Baker [33] presented expanded PTFE grafts in 72 hemodialysis patients. In the subsequent years, several publications indicated the benefits and the shortcomings of the prosthetic material in question, remaining the primary choice of graft for hemodialysis VA to date. The same year, two authors, Mindich and Dardik, had worked with a new graft material: the human umbilical cord vein [34, 35]. Regrettably so, this material did not succeed in becoming a revolutionary graft material due to its inadequate resistance against the trauma of repeated cannulations and their complications (aneurysm and infection). After the subcla‐ vian route for hemodialysis access was firstly introduced by Shaldon in 1961, it was further processed in 1969 by Josef Erben, using the intraclavicular route [36]. In the next 20 years or so, the subclavian vein was the preferred access for temporary vascular access by central venous catheterization. Today, due to phlebographic studies revealing a 50% stenosis or occlusion rate at the cannulation site, subclavian route has been discarded. Subclavian stenosis and occlusion predispose to edema of the arm, especially after creation of an AV fistula [37]. The first angioplasty described by Dotter et al. [38], who introduced a type of balloon, was immensely conducive to the resolution of one of the most significant predicaments in vascular

In 1977, Gracz et al. [39] created the "proximal forearm fistula for maintenance hemodialysis," a variant of an AV anastomosis. An adjustment of this AVF became quite significant in the old,

the subclavian, jugular, and femoral vein.

246 Updates in Hemodialysis

surgery and vascular access surgery.

correlated with higher mortality risk from infections [26].

Nowadays, and thanks to all above efforts, nephrologists have the ability to choose the most suitable VA for their patients depending on special needs of each one. Based on expected halflife, the first demarcation is of permanent and temporary VAs [43]. Long-term or permanent VAs are called the ones with an expected half-life of more than 3 years, and mainly include AVF [13] and PTFE AVG. VAs with expected half-life of less than 90 days are called temporary VAs and basically are noncuffed double lumen catheters and arteriovenous shunts. The VAs with half-life between the above categories (90 days to 3 years) are the mid-term VA containing tunneled cuffed catheters, port devices and external and internal shunts.

#### **3.1. Acute hemodialysis vascular access**

Acute hemodialysis is a lifesaving treatment, which needs a VA in order to be carried out. When a permanent VA is not available, the preferred and currently available VA for acute hemodialysis is cuffed tunneled and noncuffed nontunneled hemodialysis catheters (Figures 1–5). The reason is that they can be used immediately and placed relatively easily. For catheter insertion, a modified Seldinger guide wire technique is used, preferably with ultrasound guided assistance for minimizing acute placement complications [44, 45].

**Figure 1.** Noncuffed in jugular double lumen catheter.

**Figure 2.** Cuffed tunneled in jugular double lumen catheter.

**Figure 3.** Permanent cuffed jugular catheter.

**Figure 4.** Acute noncuffed jugular catheter.

**Figure 5.** Femoral noncuffed catheter.

**Figure 2.** Cuffed tunneled in jugular double lumen catheter.

248 Updates in Hemodialysis

**Figure 3.** Permanent cuffed jugular catheter.

**Figure 4.** Acute noncuffed jugular catheter.

The most used and feasible are the noncuffed nontunneled catheters with easy insertion and availability for immediate use. They have some specific technical characteristics; they are made of polymers inelastic at room temperature, facilitating the insertion, but unstiffening at inner body temperature in order to be atraumatic for the vessels. The distance between the inflow and the outflow tip of the catheter must be at least 2 cm to lessen recirculation [46].

Central veins such as jugular or femoral can be used as insertion routes of these catheters [47]. Subclavian typically is an option, but due to its higher incidence of complications, such us lung injury, it is used when the others insertion sites are not feasible.

The National Kidney Foundation Dialysis Outcomes Quality Initiative (K/DOQI) 2006 guidelines recommend the radiographical identification of tip placement and any potential complications before catheter use or anticoagulation treatment [48]. Subclavian vein should be avoided for catheter insertion due to high frequency of stenosis and thrombosis.

There are restrictions concerning the use of these catheters such as the blood flow with a maximum pump speed of 300 ml/min, although actual blood flow tops at 250 ml/min, catheters for insertion in femoral vein should be no less of 18 to 25 cm long to minimize recirculation [49, 50]. Their insertion site determines their life use, with the ones in internal jugular vein be suitable for use for about 2 to 3 weeks, while in femoral vein are used for 3 to 7 days in bedridden patients and for a single treatment in ambulatory patients [51]. Nevertheless, according to KDOQI guidelines, the life use of noncuffed, nontunneled catheters must be of a week or less; when hemodialysis treatment will be required for a longer period, the placement of cuffed, tunneled catheters is suggested [48]. Especially in hospitalized patients, triple lumen catheters are placed, using the third lumen for intravenous drugs and fluid administration and for blood drawing. It seems that two and three lumen catheters have similar blood flow and inflections incidence [52]. The leader cause for catheter removal is infectious complications.

#### **3.2. Permanent vascular access**

Taking patient-dependent factors into consideration, such as life expectancy, comorbidities, the status of the venous and arterial vascular system, is very important in order to prescribe the appropriate access. Each type of access, such as arteriovenous fistula (AVF), arteriovenous graft (AVG) or TC, has a different effect on circulatory system, and this should be taken into consideration. Also, the duration of their functionality and the risk for infection and thrombosis are important factors to consider. Each type of surgical anastomosis has advantages and disadvantages [53]. Also, it seems that the advantages of an AVF attempt strategy lessened considerably among older patients, particularly women with diabetes, reflecting the effect of lower AVF success rate and lower life expectancy, suggesting that vascular access-related outcomes may be optimized by considering individual patient characteristics [54]. The American Association for Vascular Surgery and the Society for Vascular Surgery, in 2002, for better consultation and understanding between physicians and registration of VA set VA reporting standards in which three components should be listed, structure (autogenous, prosthetic), position and alignment (loop, direct, etc.) [55]. Risk factors such as female gender, age, diabetic nephropathy, dialysis initiation via CVC and inability of VA maturation before HD initiation are responsible for the majority of VA failure. Repetitive VA failures are risk factor for mortality [56]. It seems that early referral to nephrologist and patient's education leads to initiation of dialysis with permanent VA, better metabolic and clinical situation, lower long-term morbidity and higher 2-year survival [57–61]. It is of benefit to the patient to begin hemodialysis treatment via a functional AVF than with a TC [62–64]; however, grafts are a better alternative to TCs, when AVF is not feasible [65]. Patients with bilateral central vein stenosis often require more than one vascular access modality to achieve a "personal access solution." Native long saphenous vein loops provided the best long-term patency. Expedited renal transplantation with priority local allocation of cadaveric organs to patients with precarious vascular access provides a potential solution [66]. Patients who received either femoral AVG or HeRO VA device experience poor access patency. ESRD patients who receive either of these procedures appear to be at the end stage of available access options [67].

#### *3.2.1. Arteriovenous fistula*

The first choice of VA is AVF, for its longevity and low morbidity and mortality rates [68, 69], low complication incidence for infection (one-tenth of AVGs) and thrombosis (one-sixth of AVGs) [70, 71]. AVFs' primary patency rates at 1 year vary considerably between USA and Europe, with reports from the USA that include diabetic patients be as low as 40–43% [72, 73]. From the study of 748 AVFs in diabetic patients over 5 years, Konner et al. showed a primary patency rate of 69–81% [74], while Chemla et al. had a rate of 80% at 22 months in 552 radio‐ cephalic AVFs in 153 patients over a 4-year period [75]. Hemodialysis patients with AVF have lower mortality and that seems to be attributed not only to decreased incidence of infections and VA dysfunctions but also to other factors, such as LVEF increase and blood pressure and arterial stiffness reduction, as Korsheed et al. [76] showed.

Based on the way of their creation, three types of AVFs can be identified. The first type belongs to the AVFs where an artery and a vein are connected in their natural position, with a side-toside or side-artery-to-vein-end anastomosis. In the second type, a vein is connected to an artery in end-to-side form, after its metathesis, to connect a further distance or surface the vein to facilitate cannulation; a tunnel creation is required for vein's new positioning. When a vein is connected to an artery end-to-end after it is removed from its anatomical location, we have the third type of AVF [77] (Figures 6–9). The end-to-end technique is abandoned nowadays since it leads to advanced risk for ischemia and thrombosis. Vein end to artery side anastomosis is the most common technique. The first option for the primary AVF is the radial-cephalic. Distal forearm ulnar-basilic has similar secondary patency rate to it and is the best alternative when the first one is not feasible [78]. Stenosis due to technical problems like false surgical cut of vein leads to dysfunctional VA. Complications such as heart failure or steal syndrome may result from a more proximal, big arterial anastomosis [77]. Local anesthesia is usually effective for AVF creation, and the morbidity of the procedure is low. AVF requires time after its creation for maturation before cannulation for at least 14 days according to DOPPS (Data from the Dialysis Outcomes and Practice Patterns Study). During the period of maturation, the blood flow and the vessel size increase over time in 8–12 weeks, and the initial blood flow is in a range of 200–300 ml/min [64].

**Figure 6.** Forearm AVF.

**3.2. Permanent vascular access**

250 Updates in Hemodialysis

*3.2.1. Arteriovenous fistula*

Taking patient-dependent factors into consideration, such as life expectancy, comorbidities, the status of the venous and arterial vascular system, is very important in order to prescribe the appropriate access. Each type of access, such as arteriovenous fistula (AVF), arteriovenous graft (AVG) or TC, has a different effect on circulatory system, and this should be taken into consideration. Also, the duration of their functionality and the risk for infection and thrombosis are important factors to consider. Each type of surgical anastomosis has advantages and disadvantages [53]. Also, it seems that the advantages of an AVF attempt strategy lessened considerably among older patients, particularly women with diabetes, reflecting the effect of lower AVF success rate and lower life expectancy, suggesting that vascular access-related outcomes may be optimized by considering individual patient characteristics [54]. The American Association for Vascular Surgery and the Society for Vascular Surgery, in 2002, for better consultation and understanding between physicians and registration of VA set VA reporting standards in which three components should be listed, structure (autogenous, prosthetic), position and alignment (loop, direct, etc.) [55]. Risk factors such as female gender, age, diabetic nephropathy, dialysis initiation via CVC and inability of VA maturation before HD initiation are responsible for the majority of VA failure. Repetitive VA failures are risk factor for mortality [56]. It seems that early referral to nephrologist and patient's education leads to initiation of dialysis with permanent VA, better metabolic and clinical situation, lower long-term morbidity and higher 2-year survival [57–61]. It is of benefit to the patient to begin hemodialysis treatment via a functional AVF than with a TC [62–64]; however, grafts are a better alternative to TCs, when AVF is not feasible [65]. Patients with bilateral central vein stenosis often require more than one vascular access modality to achieve a "personal access solution." Native long saphenous vein loops provided the best long-term patency. Expedited renal transplantation with priority local allocation of cadaveric organs to patients with precarious vascular access provides a potential solution [66]. Patients who received either femoral AVG or HeRO VA device experience poor access patency. ESRD patients who receive either of these procedures appear to be at the end stage of available access options [67].

The first choice of VA is AVF, for its longevity and low morbidity and mortality rates [68, 69], low complication incidence for infection (one-tenth of AVGs) and thrombosis (one-sixth of AVGs) [70, 71]. AVFs' primary patency rates at 1 year vary considerably between USA and Europe, with reports from the USA that include diabetic patients be as low as 40–43% [72, 73]. From the study of 748 AVFs in diabetic patients over 5 years, Konner et al. showed a primary patency rate of 69–81% [74], while Chemla et al. had a rate of 80% at 22 months in 552 radio‐ cephalic AVFs in 153 patients over a 4-year period [75]. Hemodialysis patients with AVF have lower mortality and that seems to be attributed not only to decreased incidence of infections and VA dysfunctions but also to other factors, such as LVEF increase and blood pressure and

Based on the way of their creation, three types of AVFs can be identified. The first type belongs to the AVFs where an artery and a vein are connected in their natural position, with a side-to-

arterial stiffness reduction, as Korsheed et al. [76] showed.

**Figure 7.** Side-to-side forearm AVF.

The placement of AVFs should be initiated when the patient reaches CKD stage 4, or within 1 year of the anticipated start of dialysis. In their recent study, Hod et al. [79] suggested that

**Figure 8.** End-to-end forearm AVF.

**Figure 9.** Side-to-end forearm AVF.

creating AVF more than 6 to 9 months before initiating dialysis in elderly may not associate with better AVF success rate. In order to increase the possibilities of a well-functioning AVF's creation and to minimize the complication, a physical examination must be done prior to procedure to identify any differences in blood pressure between the upper extremities [80] and the presence or lack of a well-developed palmar arch to avoid steal syndrome in case of using the dominant artery for AVF creation [81].

Additional information before the creation of AVF can be given with ultrasound of the vessels; their diameter is closely correlated with surgery success with a size of 2 mm and more leads with fruitful maturation [80], in contrast of a size of 1.6 mm and less, which predispose to failure [82]. The upper extremity AVF is the preferred access for hemodialysis, the duplex ultrasound identifies suitable arteries and veins for its successful creation, while early detection and intervention can save the fistula when complications occur [83]. Uzun et al. [84] showed that autologous saphenous vein can be preferably chosen as a prosthetic hemodialysis access graft due to its higher primary and secondary patency and lower complication rate and cost when compared with PTFE grafts. According to the vascular access guidelines of KDOQI, a well-functioning AVF has blood flow over 600 ml/min, with a diameter greater than 6 mm, and is lying less than 6 mm from the surface in a depth between 5 and 10 mm. When an AVF's maturation progresses successfully, then rapidly after surgery blood flow increases from baseline values of 30 to 50 ml/min, reaching 200 to 800 ml/min within 1 week; after 8 weeks, blood flow is over 480 ml/min [85, 86]. The AVFs must be evaluated 4–6 weeks after placement; experienced examiners (e.g., dialysis nurses) can identify nonmaturing fistulas with 80% accuracy [87]. Patients with newly placed AVF are advised for hand squeezing exercises to increase the rate of fistula maturation, such as squeezing a ball, bicep curls, and finger tips touches resulting to fistulae dilation [88, 89]. Far Infrared therapy, which is a form of heat therapy, has been implicated in improvement of endothelial function and hemodynamics in coronary arteries, probably through up-regulating endothelial nitric oxide synthase (eNOS) expression in arterial endothelium, leading to improved cardiac function in patients with chronic heart diseases. Repeated leg hyperthermia using FIR has been shown to reduce oxidative stress in bed-ridden type II diabetics and may positively influence the complex process of AVF maturation, improving both primary and secondary patency rates [90, 91]. Jennings et al. [92] published a trial, which showed that Venous Window Needle Guide, a subcutaneously placed hemodialysis cannulation device, is safe and effective in facilitating AVF cannulation for patients with an otherwise mature but noncannulatable access. Strozecki et al. described a case report of a 65-year-old female patient who had several hemodialysis sessions by cannulation of dilated collateral abdominal veins with dialysis needles, as an unconventional vascular access for HD in case of central vein occlusion [93]. Humerobasilic and radiocephalic AVF are the two VA types with the most functioning longevity, although in radiocephalic AVF, there is high initial failure rate [94]. It is the preferable VA due to its longevity, low incidence of complications, and easy cannulation [95–97]. In case of failure of radiocephalic AVF creation, the second most preferable VA is brachiocephalic AVF, which comes first in diabetic patients, in whom the inadequacy of vessels for radiocephalic AVF is usually found [98] with a reported 4-year patency of 80% [99]. According to a study of Rondriguez et al., brachiocephalic AVF has a lower survival than radiocephalic. Four years after its creation, just over 50% of the patients have patent AVF and about 30% after 8 years. Failure at first VA increases the risk for following failure, while successful development of the first VA, at about 60% of patients, does not lead to subsequent failure. Diabetes and female gender seem to be risk factors to VA failure [94].

#### *3.2.2. Arteriovenous graft*

creating AVF more than 6 to 9 months before initiating dialysis in elderly may not associate with better AVF success rate. In order to increase the possibilities of a well-functioning AVF's creation and to minimize the complication, a physical examination must be done prior to procedure to identify any differences in blood pressure between the upper extremities [80] and the presence or lack of a well-developed palmar arch to avoid steal syndrome in case of using

Additional information before the creation of AVF can be given with ultrasound of the vessels; their diameter is closely correlated with surgery success with a size of 2 mm and more leads with fruitful maturation [80], in contrast of a size of 1.6 mm and less, which predispose to failure [82]. The upper extremity AVF is the preferred access for hemodialysis, the duplex ultrasound identifies suitable arteries and veins for its successful creation, while early detection and intervention can save the fistula when complications occur [83]. Uzun et al. [84] showed that autologous saphenous vein can be preferably chosen as a prosthetic hemodialysis access graft due to its higher primary and secondary patency and lower complication rate and cost when compared with PTFE grafts. According to the vascular access guidelines of KDOQI, a well-functioning AVF has blood flow over 600 ml/min, with a diameter greater than 6 mm, and is lying less than 6 mm from the surface in a depth between 5 and 10 mm. When an AVF's maturation progresses successfully, then rapidly after surgery blood flow increases from baseline values of 30 to 50 ml/min, reaching 200 to 800 ml/min within 1 week; after 8 weeks, blood flow is over 480 ml/min [85, 86]. The AVFs must be evaluated 4–6 weeks after placement; experienced examiners (e.g., dialysis nurses) can identify nonmaturing fistulas with 80% accuracy [87]. Patients with newly placed AVF are advised for hand squeezing exercises to increase the rate of fistula maturation, such as squeezing a ball, bicep curls, and finger tips

the dominant artery for AVF creation [81].

**Figure 8.** End-to-end forearm AVF.

252 Updates in Hemodialysis

**Figure 9.** Side-to-end forearm AVF.

In the USA, AVGs (Figures 10–12) are the most common type of VA that is used for hemo‐ dialysis [100]. However, they last less than AVFs and have more complications such as infections and thromboses [70]. Recent technological advances using tissue-engineered AVGs have shown promise for patients receiving hemodialysis and their potential to provide an attractive, viable option for vascular access [101]. Grafts present a second choice of VA when AVF is not possible to be performed because of vascular problems [102]. AVGs have lower risk of nonmaturation in lower time [103]. They can be placed in the forearm, the upper arm and the thigh, when upper-extremity options are exhausted [104] and they can have a straight, curved or loop configuration. Axillary loop arm graft yields acceptable early patency rates in specific patients with vascular problems [105]. Another advantage is that AVGs may offer a large surface for cannulation. Some types of AVGs such as PTFE AVGs can be cannulated immediately after their placement, according to some studies, although it is preferable to wait for about 2 to 3 weeks for the first cannulation [106, 107]. However, the usual time for a functional graft is 2 to 3 weeks in order to reduce the post surgical edema and the perigraft hematoma and seroma [108]. Karatepe et al. [109] presented a novel polycarbonate urethane nanofabric graft, produced by electrospinning technology, which had self-healing features that avoid seroma formation and allow puncturing within 48 hours. It had good 12-month primary and secondary patency rates and substantially lowers infection rates. Early experience with GORE Acuseal is encouraging with patency and bacteremia rates at least comparable to standard polytetrafluoroethylene grafts, permitting cannulation within 24 hours of insertions and line avoidance in the majority of patients [110].

**Figure 10.** Upper arm AVG.

**Figure 11.** Looped forearm AVG.

**Figure 12.** Straight femoral AVG.

### *3.2.3. Tunneled hemodialysis catheter*

and secondary patency rates and substantially lowers infection rates. Early experience with GORE Acuseal is encouraging with patency and bacteremia rates at least comparable to standard polytetrafluoroethylene grafts, permitting cannulation within 24 hours of insertions

and line avoidance in the majority of patients [110].

**Figure 10.** Upper arm AVG.

254 Updates in Hemodialysis

**Figure 11.** Looped forearm AVG.

**Figure 12.** Straight femoral AVG.

TCs (Figures 2 and 3) have higher mortality risk than AVFs or AVGs; thus, they are used when the creation of the latter is not feasible [111]. There are several reasons that lead to the inability for AVF or AVG creation, such as multiple vascular surgeries, which lead to vascular thrombosis, or when patients have severe peripheral vascular disease or very low cardiac output. TCs are more frequently encountered in pediatric and very old patients. They can also be used as a bridge until AVF or AVG maturation [111]. Their use remains very high during the first year of HD care and is associated with high mechanical and infection rates [112]. The incidence of AVFs has been effectively increased since the "fistula first" has been developed [113], although it is accompanied with an increase in TCs, especially those used as a bridge until the maturation of an AVF [100]. Nonetheless, DOPPS shows an increasing use of TCs for the period 1996 to 2006 in many countries [114], which is in accordance with our data of 2011, which showed increased prevalence of TCs in female hemodialysis patients [115]. It is also signified that it is more likely for a patient to have permanent VA (AVF or AVG) than TC if he is at a center with experienced vascular surgery department successfully creating permanent VA in diabetic, older women and early AVF cannulation practice (within 4 weeks from its formation) [114].

They do not last as much as the others types of VA, and they have higher complication rates such as infections. There are studies revealing that CVCs are colonized within the first 10 days of placement; however, the catheter's lumen colonization does not equal to positive blood cultures or clinical signs of bacteremia [116]. The guide-wire change or the complete removal of catheter does not affect the outcome of the infection treatment [117]. Power et al. [118] with their study of 759 TCs showed that the appropriate management of catheters can give functional and complication results similar to AVGs. In their study, survival rates were 85%, 72%, and 48% at 1, 2, and 5 years, respectively, while the infection rate was 0.34 per 1000 catheter-days. Although earlier studies showed a lower risk of catheter-related bloodstream infections with internal jugular TCs compared to femoral, recent studies show no difference between the three sites [119, 120].

Transhepatic hemodialysis catheters seem to be a viable alternative option with low morbidity rates [121]. Another safe and effective long-term access is translumbar inferior vena cava [122]. Retrograde femoral vein catheter insertion is a newly applied lifesaving HD vascular access approach for selected ESRD patients with no available HD vascular access at the ordinary sites with accepted HD adequacy, but it needs more evaluation and studies [123].
