Types of graft \201 stula Upper limb Forearm straight graft Run from radial artery to ant ecubital vein. Types of autogenous AVF Upper limb \201 stulae Radio-cephalic This is eponymously known a s the Cimino \200\223Brescia AVF. The cephalic vein is joined to the radial artery at the w rist (Fig. 13.2.1). Forearm loop graft Run from brachial artery to antecubital vein in a U-shaped loop. CHAPTER 13.2 Vascular access 489 Disadvantages of autogenous AVF There is an early failure rate of up to 30% for radio-cepha lic AVFs, but less for others. Often suitable veins are not available due to prior usage fo r IV infusions. They need a maturation time of several weeks before usage. Fistula vein may need transposition to a super \201 cial position in obese patients. Cosmetically less sat isfactory, especially if they develop aneurysmal dilatation. Advantages of prosthetic or biological grafts Good quality grafts are easily available \200\230off the shelf \200\231 in appropriate lengths. They allow earlier needling for dia lysis, particularly the prosthetic grafts. In an emergency, the graft can be needled almost immediately although there is greater risk of infec- tion and bleeding at this early stage . Biological grafts are easy to handle and anastomose com- pared to prosthetic grafts. They are cosmetically more acceptable. Fig. 13.2.1 A mature radio-cephalic AVF used for hemodialysis. Arm graft Run from brachial artery to axillary vein. Lower limb Thigh loop graft Run from femoral artery to saphenous or femoral vein in the gro in. Disadvantages of prosthetic or biological grafts There is a lower long-term patency (Figs 1 3.2.3 and 13.2.4). The risk of thrombosis due to the development of neointi- mal hyperplasi a at the venous anastomosis is signi \201 cantly greater. There is a greater risk of infec tion requiring excision of the graft. Biological grafts are susceptible to aneurysm formati on. The cost is high. Thigh straight graft Run from the distal super \201 cial femoral artery to the saphe- nous or femoral vein in the groin. Advantages of autogenous AVF Biological tissues generally handle better than prosthetic. Th e long-term patency is better (Figs 13.1.3 and 13.1.4). There is resilience to thrombosis i n hemodynamically unstable patients. There are low rates of septic complications which gene r- ally respond to antibiotic therapy. There is ease of needling for dialysis except in obe se patients Low cost. Complications of \201 stulas Thrombosis This is the greatest risk, requiring radiological or surgical intervention to re-establish the \201 stula. Infection This is less with autogenous \201 stulas and usually responds to appropriate an tibiotic therapy but grafts frequently have to be removed when infection develops. Fig. 13.2.2 Complications of AVF formation: central venous occlusion following previous cen tral venous catheter insertion. Right arm swelling following brachio-cephalic AVF formation due to a right subclavian vein occlusion following a previous right subclavian vein cathet er. Note the occluded subclavian stent previously inserted to open up the vein. The AVF had to be ligated eventually. A. BAKRAN 490 It may present even more dramatically as complete anesthe- sia of the \201 ngers, pain in the hand or forearm, loss of move- ment, and eventually with ulceration and gangrene. This presentation is a surgical emergency and is due to ischemia of the hand and forearm, with loss of sensory and motor nerve function. Unless the \201 stula is taken down or revised rapidly, it will lead to long-term loss of hand/fore- arm function. No patient should devel op pain in the hand after proximal \201 stula surgery and so the operating surgeon should be noti \201 ed to assess the possibility of a steal syndrome. Steal syndrome See below. Aneurysm formation The risk is greatest with biological and autogenous \201 stulas. High output cardiac failure This occurs when \201 stula blood \202 ow becomes excessive . One extraordinary case report revealed a blood \202 ow of >30 L/min before the surgeon banded the \201 stula down to a \202 ow of 600 mL/min. Venous hypertension This may develop in the \201 stula limb and be exacerbated by central vein stenoses from previous central venous cathe- ters (Fig. 13.2.2). If it fails to settl e as venous collaterals open, options include central vein angioplasty with or without sten t insertion or ligation of the AVF. Physiological changes after graft surgery Usually 6 mm PTFE grafts are implanted and the gr afts should not change in size with time. The principle problem with grafts is neointimal h yperplasia which causes a gradual narrowing of the venous anastomo- sis leading to \201 s tula thrombosis. Flow monitoring has been suggested as a means of detect- ing risk of graft thrombosis although evidence from the lit- erature is mixed. Percutaneous thrombectomy and angioplasty of the venous stenosis is the procedure of choice to re-establish patency with surgery as an alternative. Revision of the venous anastomosis may be required. Seroma This may occur with prosthetic \201 stulas. Physiological changes after \201 stula surgery Creation of an AVF or graft produces a new low pressure circuit through which blood \202 ows preferentially. The limb with a \201 stula attracts increased blood \202 ow com- pared to the other limb. The \201 stula ve in dilates rapidly over the \201 rst 2 \200\2233 weeks after surgery and then at a slower rate subsequently. The artery also remodels and dilates although less than the vein. Howev er, in some patients the artery can become huge over time. Major hemodynamic changes take p lace at the \201 stula anas- tomosis due to changes in \202 ow patterns. The normal lam inar blood \202 ow becomes turbulent with changes in wall shear stress, leading to variab le degrees of intimal hyperplasia and \201 stula vein stenosis. Percutaneous angioplasty or surgical revision of the \201 stula will be necessary in severe cases. Vascular access in special groups Diabetics Pose problems due to poor vessels. Often veins have already been used and arteries are calci \201 ed. Are more likely to need a proximal \201 stula hence greater risk of steal syndrome. Similar principles for vascular access p lanning apply in diabetics but there is a greater necessity for preoperative vessel imaging . Elderly patients Need to be evaluated more carefully before access per- formed. If survival prospects are poor then a long-term tunneled catheter may be appropriate, but if the progn osis is good then an AVF/graft should be considered. Failure of AVF maturation The radio-cephalic AVF has a high incidence of nonmatura- tion (u p to 30%) but when successful can survive >20 years without thrombosis. The causes of nonma turation can be related to: \200 \200 \200 Children PD is the preferred treatment but an AVF remains an option. small size and quality of vein or artery; raised blood viscosity; intimal hyperplasia in th e segment just distal to the anas- tomosis. When to needle a \201 stula AVFs can be needled mostly between 4 and 6 weeks (occa- siona lly earlier if well-developed). Needling is too often delayed in the UK compared to other E uropean countries. Grafts can be needled within 2 weeks after the pain of the tunneling has settled and a pseudointima allowed to develop. More proximal fistulas using the brachial artery as in \202 ow have less risk of failure a nd a higher blood \202 ow. However, there is a potential for development of a \200\230st eal syndrome \200\231. Steal syndrome A steal syndrome typically presents with: \200 \200 \200 \200 \200 Central venous catheters Types of catheters Catheters are generally made of polyurethane an d may be single lumen, double lumen or two separate single cathe- ters inserted for drawing and returning blood. a cool/cold hand; paresthesia; numbness in the \201 ngers; loss of the radial pulse; cyan osis of \201 nger tips. Temporary catheters Used for emergency dialysis and short-term access. If the patient starts to wear a glove on the \201 stula hand then suspect steal syndrome. CHAPTER 13.2 Vascular access 491 1 Fistula, Europe 0.8 e r u l i a f 0.6 t u o h t i Fistula, US w n o i t c a r F 0.4 Grafts, US 0.2 0 0 100 200 300 Days 400 500 600 Fig. 13.2.3 Fistula versus graft survival in patients starting hemodialysis with permanent vascular access. Data kindly provided by DOPPS 2005; adjusted for differences in age, gende r, diabetes, peripheral vascular disease and body mass index. 1 AVF, EUR (no prior temp VA) 0.8 e r u AVF, EUR (with prior temp VA) l i a f 0.6 t u o h t i AVF, US (no prior temp VA) w n o i t c a r F AVF, US (with prior temp VA) 0.4 0.2 0 0 200 400 600 Days Fig. 13.2.4 Survival of \201 rst AVF in incident patients with or without prior temporary vascular access (VA). Data kindly provided by DOPPS 2002; adjusted for differences in age, gender, diabetes, peripheral vascular disease and body mass index. Tunneled or \200\230permanent \200\231 catheters Used for long-term dialysis. They have a subcutaneous Dacron cuff into which tissue grows, \201 xing the catheter in position and reducing passage of organisms up around the catheter. They are generally of larger bore tha n temporary cathe- ters. vein will cause severe arm swelling if an ipsilateral \201 stula is created (Fig. 13.2.2) . The inferior vena cava may be used in extremis when there is no other access site. Bene \201 ts of central dialysis catheters They can be inserted quickly for emergency dial ysis, as in late presenters. They offer painless dialysis once catheter inserted, hence are popular with patients. They are useful as permanent dialysis for patients with poor cardia c output and poor prognosis. Insertion of catheters Catheter placement is usually performed under local anes- thetic, in a clean area, using strict aseptic technique, prefer- ably with radiological screening. Ca theter tip placement ideally should be in the right atrium for maximum blood \202 ow. Sit es of insertion: \200 \200 \200 Disadvantages of central dialysis catheters There is a much greater infection risk compared to AVFs (5 \200\2238 \227 that of a \201 stula according to DOPPS data), including a hig h rate of MRSA infection. There is a risk of central vein stenosis, especially with sub- cl avian vein catheters. Vein thrombosis can occur, especially the iliac veins when using femo ral catheters. internal jugular vein; femoral vein; subclavian vein. The subclavian vein should be avoided unless there is abso- lutely no other option since su bsequent stenosis of the A. BAKRAN 492 Further reading Bakran A, Mickley V, Passlick-Deetjen J (eds). Management of the renal pati ent: clinical algorithms on vascular access for haemodialy- sis. Berlin: Pabst Science Publ ishers; 2003. Catheter use is associated with: \200 higher rate of hospitalization: 50% greater in centers where >20% of patients dialyze throu gh catheters com- pared to AVFs; higher mortality rate: 20% higher in centers with >28% cat heter use versus centers with <7% catheter use. Davies AH, Gibbons CP (eds). Vascular access simpli \201 ed, 2nd edn. Shrewsbury: TFM Publishing; 2007. Fluck R, Rao R, van Schalkwyk D, Ansell D, Feest T. The 9th Renal Registry Report, 2005. So uthmead Hospital, Bristol: UK Renal Association Renal Registry. Data from the DOPPS study suggest prior central vein catheters reduce the long-term patency of subsequent autogenous and graft \201 stulas. Pisoni RL, Young EW, Dykstra DM, et al. Vascular access use in Europe and the United States : results from the DOPPS. Kidney Int 2002;61:305 \200\223316. Complications of central venous catheterization \200 \200 \200 \200 \200 Carotid artery/femoral artery injury. Hemo-/pneumothorax. Lymphatic injury. Cardiac tampona de. Nerve injury. Pisoni RL, Albert JM, Elder SE, et al. Lower mortality risk associated with native arteriov enous \201 stula (AVF) vs graft (AVG) use in patient and facility-level analyzes: results from the DOPPS. J Am Soc Nephrol 2005;16:259A. Internet resources Vascular Access Society: Current problems in vascular access Vascular access is fundamental to enable good dialysis and sustain the quality of life of patients. More effort needs to be made to preserve the v eins in renal patients to facilitate autogenous \201 stula formation. Venepuncture can be performed using veins on the dor- sum of the hand. Use of the cephalic vein in the nondomi - nant hand should be avoided since this potentially is the best resource for long-term dia lysis. Early placement of vascular access ( \211 6 months before dialysis is necessary) is recommended by the UK National Service Framework. Patients are frequently not referred earl y enough to surgeons for timely \201 stula creation. There is frequently a long delay fro m referral to preopera- tive investigations and surgery. Hence too many patients start hemo dialysis with central venous dialysis catheters, with all their known complications. Increa sing the number of patients dialysing through an autogenous AVF or graft, and reducing the number dialyz- ing through tunneled or nontunneled dialysis central venous catheters, will improve morbidity and mortality of patients on hemodialysis. www.vascularaccesssociety.com The Renal Registry: http://www.renalreg.org National Kidney Federation Dialysis Outcomes Quality Initiative: http://www.kidney.org/professionals/kdoqi/ European Best Practice Guidelines: http://www.ndt-educational.org/guidelines.asp Dialysis Outcomes and Practice Patterns Study (DOPPS): http://www.dopps.org/Dopps_Default.aspx See also Dialysis strategies, p. 480 Hemodialysis, hemofiltration, and hemodiafiltration, p. 494 Psy chological aspects of treatment for renal failure, p. 538 This page intentionally left blank R. MACTIER 494 Hemodialysis, hemo \201 ltration and hemodia \201 ltration Principles of hemodialysis Hemodialysis (HD) is the default therapy for all forms of renal replacement therapy (RRT). HD requires an integrated machine with the following essential c omponents: \200 The reported bene \201 cial biological effects of the more bio- compatible membranes inclu de: \200 \200 \200 \200 lower activation of complement and leukocytes; greater adsorption of cytokines; greater ads orption of 2-microglobulin; higher \202 ux and removal of middle molecules e.g. 2- mi croglobulin. a pump to deliver blood from the vascular access to the dialyzer; a dialyzate concentrate p roportionating system to pre- pare dialysis \202 uid from treated water and then deliver the dialysis \202 uid to the dialyzer; a volumetric control system for \202 uid removal (ultra \201 l- tration); a range of patient safety monitors and alarms. A systematic Cochrane review showed no evidence of bene \201 t either in reduced mortality or reduction in dialysis- related adverse symptoms when synthetic membranes were compared with cellulose/modi \201 ed cellulose mem- branes. A comparison of unmodi \201 ed cellulo se and modi- \201 ed cellulose membranes was not performed. Despite the lack of evidence of improved patient outcomes the use of more biocompatible dialyzers instead of unmodi- \201 ed cellulose seems justi \201 able on the basis of the evidence for their biological bene \201 ts and equivalent costs. HD employs the use of countercurrent \202 ow of the blood and dialyzate pathways in the d ialyzer to maximize the con- centration gradient for diffusive transportation. Diffusive tr ansportation is greater for smaller and uncharged solutes. HD also employs the use of a hyd rostatic gradient across the dialyzer membrane to induce ultra \201 ltration (UF) of water and convective transportation of solutes by solvent drag. The permeability of the membrane to larger solutes, such as vitamin B12 or 2-microglobulin, is used to categorize dialyze r membranes into low, mid or high \202 ux. Dialyzer membranes have widely different capac ities to permit \202 ow of water across the membrane and the ultra- \201 ltration coef \201 cient (Kuf) of dialyzers ranges from 3 to >60 mL/min/h per mmHg transmembrane hydrost atic pressure. High or low \202 ux biocompatible dialyzers Most of the currently used dialyzers are manu factured from modi \201 ed cellulose or synthetic materials which are more biocompatible t han unmodified cellulose mem- branes. The key decision when using these more biocompatible membranes is whether to prescribe a low, mid or high \202 ux dialyzer. Removal of middle molecules The proven bene \201 ts of high \202 ux synthetic membranes in randomized trials are limited to advantages arising from improved biocompatibility and e nhanced removal of mid- dle molecules, such as 2-microglobulin, rather than better patien t survival rates. A systematic review of 27 randomized trials comparing cellulose, modi \201 ed cellulose and synthetic membranes showed a significant reduction in end-of-study 2- microglobulin values when high \202 ux synthetic membranes were used and one small stu dy showed that dialysis-related amyloid occurred less frequently with this treatment. Prescription of hemodialysis Small solute clearance rates The urea clearance rate (K) will depend on whichever of the following prescription variables is the lowest: \200 \200 \200 blood \202 ow rate (200 \200\223500 mL/min) dialyzer urea mass transfer coef \201 cient (>300 mL/min) dialyzate \202 ow rate (500 \200\223800 mL/min) The HEMO study There has been a trend to prescribe higher blood \202 ow rates (300 \200\223450 mL/min) a nd use dialyzers with higher urea mass transfer coef \201 cients to provide higher ef \201 ciency HD than in the past. The commonest rate-limiting factor for urea clearance is t he blood \202 ow rate that can be achieved from the patient \200\231s vascular access. In creasing the dialyzate \202 ow rate results in a relatively small increase in urea cleara nce rates, e.g. a 60% rise in dialyzate \202 ow rates from 500 to 800 mL/min increases th e rate of urea clearance by only 5 \200\22310% when a high ef \201 ciency dialyzer is used and the blood \202 ow rate is 350 mL/min. This is the only large prospective randomized trial to study the effect of dialyzer membran e \202 ux on patient outcomes (Table 13.3.1). The study was designed to detect a 25% redu ction in the predicted baseline all-cause mortality rate. The limited benefit observed with high flux membranes has been attributed to several factors in its design: \200 \200 \200 enrolment of prevalent rather than incident patients; exclusion of patients with major como rbidity; failure to use ultrapure water whilst using dialyzer reuse; the high and low \202 ux groups may have been separated inadequately since pre-dialysis 2-microglobulin le vels were only 19% lower in the high \202 ux group; Ultra \201 ltration The interdialytic \202 uid (weight) gain is removed under volu- metr ic control by the HD machine which adjusts the trans- membrane pressure to achieve the pres cribed UF rate. The MPO study Most of the confounding factors listed above have been addressed in the Membr ane Permeability Outcome (MPO) study. This study is a randomized, multicenter European stud y of high \202 ux membranes in incident HD patients who have few Choice of dialyzer Biocompatible dialysis membranes Synthetic and modi \201 ed cellulose m embranes have been shown to be more biocompatible than unmodi \201 ed cellu- lose membrane s. CHAPTER 13.3 Hemodialysis, hemo \201 ltration and hemodia \201 ltration 495 Table 13.3.1 Summary of the HEMO study \201 ndings Prospective randomized controlled trial of 1846 prevalent HD patients. Patients were on dia lysis for a median of 3.7 years at the time of recruitment to the study. 2 \227 2 factoria l study design: high and low \202 ux; high and standard dialysis dose. Study design 871 of the 1846 randomized patients died during the study after a mean follow-up period of 2.8 years. Ten-fold increase in 2-microglobulin clearances in the high \202 ux group ( 2-microglobulin clearances of \211 20 mL/min) versus low \202 ux group. No difference i n: Outcomes primary outcome of all cause mortality; \201 rst cardiac hospitalization or all cause mor tality; \201 rst infectious hospitalization or all cause mortality; \201 rst 15% decrea se in serum albumin or all cause mortality; all nonvascular access-related hospitalizations . For the patient subgroup which had been on HD for median of >3.7 years before enrolment: Secondary analysis use of high \202 ux dialysis membranes was associated with a 32% reduction in all cause m ortality; use of high \202 ux dialysis membranes was associated with a 37% reduction in c ardiac death. When the number of prevalent years on HD was analyzed as a continuous variable, the interac tion of \202 ux and years of dialysis on patient survival was not signi \201 cant. exclusion criteria and do not reuse dialyzers. This study has now \201 nished recruitment . These patients are at the greatest risk of developing dialysis- related amyloidosis. Report of the French Group for Nutrition in Dialysis A multivariate Cox proportional hazard s analysis of a pro- spective nonrandomized study of 1610 prevalent HD patients from 20 cen ters in France showed that the follow- ing were associated with poorer survival: \200 \200 \200 \200 Treatment time on hemodialysis per week Weekly solute removal rates may be increased by eit her increasing the frequency and/or duration of HD sessions. Frequency of hemodialysis HD frequency is a more powerful determinant of weekly solute remo val than the duration of each session. HD twice per week is not regarded as an adequate lon g- term form of chronic RRT and should be avoided. The frequency of twice-weekly HD has dec reased world- wide, including in the USA where it fell from 12.9% to 3.6% of incident patie nts between 1990 and 1996. Twice-weekly HD may be acceptable provided that: \200 increasing age; diabetes; lower serum albumin; use of low \202 ux dialyzer membranes. Patients on high \202 ux dialyzers had a 38% lower risk of death (P = 0.01) than patients on low \202 ux membranes. Effect of high \202 ux dialysis on control of anemia A multicenter, randomized controlled trial has failed to show a bene \201 cial effect on anemia in stable HD patients treated over a 12 week study period with high \202 ux biocom- patible membranes instead of conven tional cellulose mem- branes. the patient has a signi \201 cant level of residual renal func- tion (e.g. mean of combine d urinary urea and creatinine clearance >5 mL/min/1.73 m2); the patient \200\231s residual renal function is monitored at least every 3 months; the frequency of dialysis is increased when renal function decreases. Effect of high \202 ux dialysis on residual renal function One small prospective study ha s shown better preserva- tion of residual renal function when using high \202 ux mem- bra nes combined with ultrapure water. Preservation of residual renal function is desirable as resid- ual renal function is a predictor of survival in HD patients, decreases 2-microglo bulin levels and lessens the need for ultra \201 ltration. A thrice-weekly HD schedule evolved from the belief that it reconciled adequate treatment w ith adequate breaks between treatments to provide the patient with a reasonable quality of life within a 7 day treatment cycle. It is common practice to prescribe daily HD in the sho rt term when patients with ESRD develop an acute intecur- rent illness or pericarditis. Conclusions The French study and post hoc analysis of the HEMO study provide some evidence that long-term HD patients may have better survival from the use of high \202 ux dialyzer s but this observation needs to be con \201 rmed in a large prospective randomized study, such as the MPO study. As long as high \202 ux membranes cost signi \201 cantly more tha n low \202 ux synthetic and modi \201 ed cellulose membranes, the use of high \202 ux membranes should be a higher priority in patients who are: \200 \200 Daily dialysis strategies Two forms of more frequent, long-term HD have been advocated rece ntly: Short daily HD \200 usually prescribed as 6 \200\230daily \200\231 sessions of dialysis of 2 \200\2233 h with one rest day per week. Nocturnal daily HD \200 likely to remain/have been on HD for \211 3.7 years; have no residual renal function at th e start of dialysis. usually prescribed as slow overnight treatment for 5 \200\2237 nights per week while the pa tient is sleeping.