R. MACTIER 496 Thus, when short and standard duration HD provide equal urea clearances, delivered dialysis therapy should not be regarded as equivalent. Both forms of daily HD have been shown to provide a number of medical advantages compared w ith standard duration, thrice-weekly HD: \200 \200 \200 \200 \200 \200 improved well-being and better quality of life; regression of left ventricular hypertrophy; improved \202 uid balance and BP control; reduced need for erythropoetin; lower hospital admission rate; higher dietary protein intake and better nutritional status. Clinical impact of dialysis duration There has been a gradual reduction in the average leng th of HD sessions in many areas of the world during the last two decades. This trend was mo st likely due to better patient tolerance of higher ef \201 ciency HD arising from the rou tine use of bicarbonate dialyzate, more biocompatible dialyzers and machine improvements, s uch as volumetric control of UF, combined with patient preference for shorter times and eco nomic constraints. However, several observational studies have shown an association between risk of death and shorter dialysis duration: \200 Short daily HD offers the additional bene \201 t of: \200 higher weekly removal of small and large molecu- lar weight solutes (e.g. potassium, phosph ate, urea, 2-microglobulin) for the same total time on HD per week. Daily nocturnal HD provides: \200 very low mortality rates were observed in patients treated with long duration thrice-weekly HD with mean spKt/V of 1.67 + 0.41 in Tassin, France; increments in dialysis duration up t o 5.5 h were associ- ated with improved patient survival rates in a large Japanese populati on after adjusting for dialysis dose; patients in the USA who received dialysis for <3.5 h per session three times per week had approximately twice the risk of death of patients on H D for >4 h three times per week; data from the Dialysis Outcomes and Practice Patterns Stud y (DOPPS) have shown that patient survival, inde- pendent of dialysis dose, was greater in patients with treatment times >4 h; data from the Australian and New Zealand Dialysis and T ransplant Registry have shown that patient survival, independent of dialysis dose, was grea ter in patients with treatment times >4.5 h. very large doses of dialysis (weekly Kt/V of almost 6 and much greater removal of middle mo lecules); greatly reduced need for phosphate binders; reduction in sleep disturbance and sl eep apnea. \200 Based on the above medical advantages the NHS in the UK has included daily HD as a treatmen t option in planning future renal services. During the past few years a small number of pat ients have commenced daily home HD, and these patients and their helpers continue on daily HD in spite of the potential inconvenience arising from the long-term need for set-up, trea tment, and disconnect time on a daily basis. Clinical trials evaluating impact of frequency of HD Randomized prospective trials thus far have compared outcome data only in patients receiving thrice-weekly HD. On the basis of ob servational studies of the clinical bene- \201 ts of short daily and nocturnal daily HD t he National Institutes of Health (NIH) has commenced two prospec- tive randomized studies ( Frequent Haemodialysis Network Studies) of 250 patients comparing each form of frequent HD with standard thrice-weekly HD. These observations suggest that the duration of thrice- weekly HD should not be reduced to <4 h unless the patient has signi \201 cant residual renal function and indicate that a ra ndomized controlled study of longer dialysis ses- sions in thrice-weekly HD is needed. Duration of hemodialysis It is dif \201 cult to separate the in \202 uence of dialysis du ration and dose on patient outcomes. The National Co-operative Dialysis Study (NCDS), a his - torical US randomized trial where cellulose membranes and acetate dialyzate were used, is the only randomized study so far to address the issue of optimal dialysis time. This 2 \227 2 factorial design study randomized nondiabetic patients into one of four dialysis reg imens: \200 two with short (2.5 \200\2233.5 h) dialysis times; \200 two with longer (4. 5 \200\2235.0 h) dialysis times; \200 two with different time-averaged urea concentration s. Longer dialysis gave a better but statistically insigni \201 cant outcome. A crossover study of standard and higher ef \201 ciency HD prescriptions delivering equal dialysis dos e (urea removal) measured by direct dialyzate quanti \201 cation has shown that shorter du ration, higher ef \201 ciency dialysis is associated with: \200 \200 Ultra \201 ltration on hemodialysis Ultra \201 ltration of \202 uid is required to main tain the patient at estimated dry body weight. Treatment time and UF rates are related inve rsely in HD. Patients with excessive interdi- alysis weight gain or hemodynamic instability may require isolated ultra \201 ltration. Long-term observational data from Tassin, Franc e have demonstrated that target \200\230dry \200\231 body weight and good con- trol of BP without antihypertensive medication are more likely to be achieved with long duration HD se ssions and lower rates of UF. Higher rates of UF may be poorly tolerated and associated wit h a greater risk of death. The Dialysis Outcomes and Practice Patterns Study This was an international observational s tudy of the risk of death in 22 000 HD patients. It adjusted for demographics, comorbidity, dialysis dose (including RRF) and body size and showed that: \200 lower phosphate and 2-microglobulin removal; less bicarbonate absorption. UF rate >10 mL/h/kg was associated with a higher risk of intradialytic hypotension; UF rate >10 mL/h/kg was associated with a higher risk of death. Improved clearance of iohexol has also been observed on longer duration HD with similar Kt/ V. CHAPTER 13.3 Hemodialysis, hemo \201 ltration and hemodia \201 ltration 497 Factors affecting patient safety on HD Hemodialysis machine monitors and alarms HD machines must be serviced and maintained in full working order at all times to ensure that all of t he safety monitors and alarms are functional: \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 Reuse of dialyzers Dialyzers are generally marked for \200\230single use only \200\231 alt hough some are now designed for multiple use in an individual patient. Reprocessing of dial yzers for reuse requires a combination of cleaning, disinfection and sterilization processe s. It is standard practice to discard the dialyzer whenever the hollow \201 ber volume (t otal cell volume) is <80% of the ini- tial measured value but this method may not always be reliable in detecting dialyzer dysfunction. Changing from multiple to single use of dialyz ers has been reported recently to result in a reduction in the mortality rate in a large po pulation in the USA. The cost of high \202 ux dialyzers has fallen gradually and the use of high \202 ux biocompatible dialyzers is now cost-effec- tive without reuse. blood pump speed (nominal dialyzer blood \202 ow rate); ultra \201 ltration rate and vol ume; heparin infusion pump; dialyzate conductivity monitor and alarm; dialyzate temperature monitor and alarm; arterial pressure monitor and alarm; venous air detect alarm and air tr ap; venous pressure monitor and alarm; dialyzate blood leak detector and alarm; BP monitor (optional); ionic dialysance or online urea clearance for dialysis dose (optional). Water quality for hemodialysis Quality assurance of the water used in the preparation of di alysis \202 uid is of paramount importance. HD exposes the blood of the patient to >300 L of water per week through a nonselective dialyzer membrane in contrast to an average of 12 L per week through a highly selective membrane (intestinal tract) in healthy individuals. Intact dialyzer membranes are permeable to bacterial con- taminants, and permit back-diffus ion and filtration of chemical contaminants from the dialyzate. A subset of contaminants th at should always be included in routine testing are listed in Table 13.3.2. This is because they occur in relatively high levels and are not restricted in drinking water (chlorine, c alcium, magnesium and potassium), or where the drinking water limit is more than five times the recommended limit for water for dialysis. Sodium is included in the \200\230mandatory \200\231 group because, although the drinking water limit is 200 mg/L, additional sodium i s introduced by softening. In water treated by reverse osmosis, these contaminants will onl y exceed the limits in Table 13.3.3 if they occur at relatively high levels in the water su pplied to the unit. These contaminants can be omitted from routine tests if data are availa ble to show that the levels in the water supplied to the unit rarely exceed the limit in th e table. These data should be obtained from the municipal water supplier or from tests on t he raw water if it is obtained from a private source. Routine testing is not required for o ther contaminants (barium, beryllium, silver, thallium, tin and zinc) for which limits are de \201 ned for the water used for dialysis as these trace elements are not considered to occur in levels that give cause for concern and, if low levels are present, they are remove d effectively by reverse osmosis. Testing is only required if there is evidence of high lev els in the local water supply (zinc, for example, can be introduced in the pipe- work). The tests used for monitoring microbial contamination of water for dialysis should be appropri ate to the type of organisms found in water. A low nutrient agar, such as Tryptone Glucose Extract Agar or Reasoner \200\231s 2A, should be used and samples should be incubated for \211 7 days at 20 \200\22322 C. Vascular access Integrity of the extracorporeal blood circuit is paramount for patient safe ty on HD. Dislodgement of vascular access needles or catheters and disconnection of the HD lines should be very uncommon complications of HD and should be detected promptly if they d o occur. Patients are at greater risk of exsanguination following dislodgement of the venou s needle or line as the patient will continue to lose blood at the rate of the blood pump s peed unless the HD venous pressure alarm is activated. The venous alarm may only activate a fter venous line dis- connection when the venous pressure alarm is set close to the prevail ing venous pressure of the HD circuit. Anticoagulation during hemodialysis Extracorporeal anticoagulation is usually required to p re- vent thrombosis of the dialyzer and extracorporeal circuit. Unfractionated heparin This may be used as the standard anticoagulant in view of its proven ef \201 cacy, ease of use and safety record. It is best administered as a loading dose fo llowed by a continuous infusion of 500 \200\2231500 units/h that is discontin- ued 30 min before the end of the dialysis session in patients using an arteriovenous \201 stula or g raft (mean half-life 1.5 h). The dosage of heparin may need to be increased if there has be en a substantive rise in the hematocrit after correc- tion of renal anemia or reduced if th e patient is on warfarin or antiplatelet drugs. Low molecular weight heparin This is an alternative agent that has been associated with a l ower risk of bleeding, less frequent episodes of hyper- kalemia, and an improved lipid prof ile than standard heparin. A systematic review of 11 trials comparing the use of low molecu lar weight heparin and unfractionated heparin in HD patients concluded that there was no di fference in the incidence of bleeding complications, bleeding from the vas- cular access af ter HD or thrombosis of the extracorporeal circuit. For patients with heparin-induced throm bocytopenia either heparinoids (danaparoid) or hirudin should be used instead of heparin. R. MACTIER 498 Table 13.3.2 Maximum recommended concentration of chemical and microbial contaminants in wa ter for dialysis for which routine testing is mandatory Contaminant Maximum recommended concentration (mg/L = ppm) Standards on which limit is based Initial test frequency Aluminum 0.01 EP, AAMI, ISO 3-monthly Calcium 2 (0.05 mmol/L) EP, AAMI, ISO 3-monthly Total chlorine 0.1 EP Not less than weekly Copper 0.1 AAMI, ISO 3-monthly Fluoride 0.2 EP, AAMI, ISO 3-monthly Magnesium 2 (0.08 mmol/L) EP 3-monthly Nitrate (as N) 2 (equates to 9 mg/L NO3) AAMI, ISO 3-monthly Potassium 2 (0.05 mmol/L) EP 3-monthly Sodium 50 (2.2 mmol/L) EP 3-monthly Bacteria (total viable count) 100 cfu/mL EP, ISO Not less than monthly Endotoxin 0.25 IU/mL EP Not less than monthly Table 13.3.3 Chemical contaminants in water for dialysis which only require routine testing if the concentration in the water supply exceeds the maximum recommended concentration for treated water Table 13.3.4 Summary of water standards adopted by the UK Renal Association Limits for chemical contaminants derived from: Association for the Advancement of Medical Instrumentation International Organization for S tandardization European Pharmacopeia Initial test frequency Standards on which limit is based Contaminant Maximum recommended concentration (mg/l = ppm) Limits for bacterial counts (100 cfu/mL) and endotoxin (0.25 IU/mL) based on: European Pharmacopeia European Renal Association Best Practice Guidelines With exception of nitrate, where standards differ in their recommendations, the most stringent limit has bee n adopted. Ammonium 0.2 EP 3-monthly Arsenic 0.005 AAMI, ISO 3-monthly Cadmium 0.001 AAMI, ISO 3-monthly Chloride 50 EP 3-monthly Achieving this standard of purity usually requires: Chromium 0.014 AAMI, ISO 3-monthly softening \200 carbon \201 ltration \200 reverse osmosis \200 effective disinfectio n program for pipework between the Lead 0.005 AAMI, ISO 3-monthly Mercury 0.0002 AAMI, ISO 3-monthly Sulfate 50 EP 3-monthly treatment plant and dialysis machines Water quality limits should not be dif \201 cult to meet with a correctly speci \201 ed a nd maintained water plant. EP, European Pharmacopeia; AAMI, Association for the Advancement of Medical Instrumentation ; ISO, International Organization for Standardization. If routine monitoring of treated water demonstrates contamination in excess of the desired levels a program to improve this should start immediately. The water quality standards in Tables 13.3.2 and 13.3.3 have been endorsed by the Associati on of Renal Technologists and UK Renal Association Clinical Practice Guidelines on HD (Tabl e 13.3.4). Hemo \201 ltration and hemodia \201 ltration Reinfusion \202 uid, used in hemo \201 lt ration and hemodia \201 ltra- tion, must be sterile (<1 cfu/1000 L) and, particularly wher e large exchange volumes are required, have an endotoxin level of <0.03 IU/mL. Even with ul trapure water, this standard of purity can only be achieved with \200\230online \200\231 \202 uid production with multiple \201 ltration of the dialysis \202 uid. Machines des igned to produce reinfusion \202 uid usually require a water supply which can produce ult rapure water. Clinical impact of water quality The use of ultrapure water in a randomized study of 30 inc i- dent HD patients was associated with a reduction in both CRP levels and the rate of loss of residual renal function. Impure dialysis \202 uid has also been implicated in the pat ho- genesis of dialysis-related amyloidosis. While this hypothesis has not been tested in c linical practice it would seem pru- dent to ensure that water is as pure as reasonably poss ible. Ultrapure water Ultrapure water (defined as <0.1 cfu/mL and bacterial endotoxins <0.03 IU/m L) is readily achievable using modern water treatment techniques and should be regarded as the standard for all newly installed water treat- ment plants. The European Best Practice G uidelines recom- mend the use of ultrapure water for conventional as well as high \202 ux HD. Modi \201 able factors affecting clinical outcomes on hemodialysis Mode of vascular access A native arteriovenous \201 stula is the preferred access in the great majority of HD pa tients as it provides the highest CHAPTER 13.3 Hemodialysis, hemo \201 ltration and hemodia \201 ltration 499 Table 13.5.5 Biochemical and hematological factors predictive of improved survival in patie nts on hemodialysis Blood sampling for biochemical and hematological meas- urements in HD patients needs to be standardized and should be performed before a mid-week HD session using a dry needle or syr inge. Pre-dialysis serum: bicarbonate: 20 \200\22326 mmol/L Interdialytic weight gain and blood pressure The impact of BP control and interdialytic wei ght gain on HD patient survival is uncertain. Observational studies have shown an associati on between excessive interdialytic \202 uid gains and reduced survival rates whereas pati ents with hypotension rather than uncon- trolled hypertension have the lowest life expectan cy. In particular the frequency of dialysis-related hypotension, de \201 ned as an acute s ymptomatic fall in BP during dialysis requiring immediate intervention to prevent syncope, is an indicator of poor prognosis for survival in HD patients. This may re \202 ect underl ying overt or occult cardiac disease in patients with dialysis-related hypotension. (measured with minimum delay after venepuncture) <6.5 mmol/L 1.1 \200\2231.8 mmol/L within normal range for local laboratory (adjusted for serum albumin) \211 4.8 mmol2/L2 (serum al bumin-corrected) potassium: \200 phosphate: \200 calcium: Ca \227 P: Pre-dialysis: hemoglobin <12.5 g/dL (in patients receiving erythropoietin-stimulating agents) blood \202 ow rates, minimizes the risk of sepsis and has the greatest longevity. The rat e of vascular access-related infection has been reported as: \200 Dialyzate composition Recognition of the adverse effects of acetate intolerance led to the introduction of bicarbonate in the early 1980s as the standard dialysis \202 uid buffer. A systematic review of 18 randomized trials indicated a reduction in the number of treatmen ts complicated by headaches, nausea, vomiting and symptomatic hypotension when bicarbonate was used. It should be noted, however, that \200\230bicarbonate \200\231 dialyzate still c ontains moderate amounts of acetate. There are no set standards for the other components of the dialyzate. HD treatment in nondiabetic patients using glucose- free dialyzate may resu lt in asymptomatic hypoglycemia without inducing an associated counterregulatory response. The potential for adverse long-term effects from repeat episodes of dialysis-induced hypogl ycemia can be avoided if the dialyzate contains glucose. Individualization of dialyzate pot assium concentrations may be required in patients with hypokalemia, and adjust- ment of dia lyzate sodium concentrations during HD (sodium pro \201 ling) may be bene \201 cial in pa tients with hemo- dynamic instability. 2.5 per 1000 dialysis sessions with native \201 stulae or grafts; 13.6 per 1000 dialysis sessions for tunneled central venous catheters; 18.4 per 1000 dialysis sessions with tempor ary central venous catheters. The CHOICE study of 616 incident patients showed that the adjusted relative risk of death c ompared with a refer- ence group with an arteriovenous \201 stula was: \200 \200 1.2 for an arteriovenous graft; 1.5 for a central venous catheter. Adequacy of dialysis A global assessment of the adequacy of the delivered rather than the p rescribed HD treatment is required to optimize patient outcomes. The assessment of dialysis adequacy should include: \200 Clinical assessment of patients, including: general well-being; nutritional status; quality of life; BP; \202 uid status. Measures of clearance of putative uremic toxins by the dia lysis process. Monitoring of biochemical and hematological parame- ters. Relative importance of modi \201 able factors on hemodialysis patient survival Data from D OPPS have evaluated the relative risk of death of HD patients who fail to meet clinical pra ctice guidelines for \201 ve modi \201 able clinical variables. This observational data suggests that the use of central venous catheters for vascular access and nutrition/in \202 am- mation are at least as important as adequate dialysis dose or control of hyperphos phatemia in in \202 uencing patient survival rates (Table 13.3.6). Dialysis dose Prospective randomized controlled trials of thrice-weekly HD have indicated t hat the minimum \200\230dose of dialysis \200\231 should be: \200 \200 Hemo \201 ltration Hemo \201 ltration (HF) is an alternative form of extracorpor- eal dia lysis which removes solutes by convection rather than diffusion as in HD. The highly permea ble membrane in the hemo \201 lter allows UF of large volumes of \202 uid which is measu red gravimetri- cally and replaced by infusion of the substitute \202 uid either into the arterial line (predilutional HF) or the venous line (postdilutional HF). urea reduction ratio (URR) of 65%; or eKt/V of 1.2. A target URR >70% or eKt/V >1.4 is required if this \200\230dose of dialysis \200\231 is t o be achieved consistently (see Chapter 13.5). Large observational studies have shown that survival in patients on thrice-weekly HD is highest when predialysis biochemical and hemato logical measurements are within set target ranges (Table 13.3.5). R. MACTIER 500 HF is not commonly used as a mode of chronic RRT because adequate intermittent HF requires: \200 A randomized study of extended daily HD and continuous HD in intensive care patients with A KI showed no differ- ence in hemodynamic stability. The ongoing prospective, multicenter, V eterans study in the USA may clarify which modality of RRT should be used in AKI. large exchange volumes (40% of body weight three times per week); high blood \202 ow rate s (350 \200\223450 mL/min); additional costs. \200 Continuous or daily HF is often performed instead of daily HD for management of AKI in many critical care settings since continuous HF can maintain \202 uid balance and may promote cardiovascular stability. The introduction of online production of substitution \202 uid in the new range of HF machines has obviated much of the extra cost of this form of therap y. Frequency of HD in AKI There is evidence that survival in patients with AKI is bet- ter wit h daily than alternate day RRT. In a randomized pro- spective study of 160 critically ill p atients with AKI the mortality rate using an intention-to-treat analysis was 28% with daily HD and 46% with alternate day HD (P < 0.01). Choice of dialyzer Hemodia \201 ltration Hemodia \201 ltration (HDF) is a hybrid of HD and HF and can be use d to increase middle molecule clearances without the need for an increase in treatment time . HDF superimposes convective removal of middle mole- cules onto the diffusive removal of t he HD technique. As well as removal of \200\230unwanted \200\231 larger solutes, such as 2- microglobulin, HDF removes other \200\230wanted \200\231 solutes, such as amino acids and small proteins. Vitamin B12 supplements are often required in patients receiving long-t erm HDF. Usually 20 L of \200\230extra \200\231 \202 uid, over and above the patients \200\231 interdialytic \202 uid gain, is removed through the hemodia \201 l- ter and an equal volume of physiological \200\230replacement \200\231 \202 uid is returned to the b lood before (predilutional) or after (postdilutional) the hemodia \201 lter. Initial randomized studies showed that the use of high \202 ux biocompatible membranes wa s associated with improved patient survival rates in AKI but this has not been con- \201 rmed in follow-up studies. In one study 58% of the 90 patients randomly assigned to bioinco mpatible Cuprophan dialyzers survived compared with 60% of the 90 patients assigned to poly methylmethacrylate membranes. Dialysis dose A randomized study of continuous venovenous HF in AKI has shown improved patient survival i n patients prescribed an UF rate of \211 35 mL/h/kg body weight. Conclusions Both daily treatment and dialysis dose have been shown to improve patient survival. Extende d daily HD and postdilutional CVVHD are widely utilized in the management of AKI and both p rovide long duration therapy to help maintain adequate \202 uid balance whilst keeping ad verse hemodynamic effects to a minimum in this critically ill patient group. Outcomes with HD, HF and HDF A recent systematic review of 18 small, randomized trials show ed no difference between HD, HDF and HF on the outcomes of patients on long-term RRT. Hemod ynamic stability was found to be similar in a study comparing HDF and low \202 ux HD with equivalent dialysis dose, UF volume and core temperature. A large retrospective observatio nal study has shown a sur- vival advantage for patients treated with high ef \201 ciency H DF (Table 13.3.7). In view of the potential in \202 uence of selection bias and other conf ounding factors the authors of this study concluded that evidence of the bene \201 ts of H DF from a controlled clinical trial was required before HDF could be recommended instead of low \202 ux HD in the management of ESRD. The Dutch CONvective transportation STudy (CON TRAST) is a 3 year randomized study in progress that addresses whether all-cause mortality and/or fatal and nonfatal car- diovascular events differ between HDF and low \202 ux HD i n almost 800 HD patients. Center HD versus home HD The National Institute for Clinical Excellence (NICE) has recommended that all suitable pat ients should be offered the opportunity to perform HD at home. This statement is based on o bservations that patients on home HD have better survival than center HD patients after adj ustment for comorbidity and that annual treat- ment costs are signi \201 cantly less on ho me than center HD. These comparisons are based on patients receiving three sessions of HD p er week. Home HD vs peritoneal dialysis In most countries, patient choice of dialysis modality is li m- ited to patients who are able to perform dialysis at home. Observational studies have sh own that short-term survival rates of patients on home HD and peritoneal dialysis are simil ar but technique survival is much poorer on perito- neal dialysis, mainly because of cathet er-related infections and inadequate dialysis. The relative advantages and disadvantages of home HD are summarized in Table 13.3.8. Home HD may be considered more suitable for patien ts with: \200 \200 \200 \200 Renal replacement therapy for AKI Modality of renal replacement therapy At present there is no evidence to show whether continu- ous or intermittent renal replacement therapies, or H F or HD provide better survival in patients with AKI. In a randomized, risk strati \201 ed , dose equivalent prospec- tive comparison of continuous venovenous HD (CVVHD) versus inter mittent HD in 80 intensive care unit patients with AKI, the CVVHD group had greater daily \202 uid volume removal but no improvement in patient sur- vival, preservation of urinary output or recovery of renal function. large body weight or body mass index; low residual renal function; heavy proteinuria and/or hypoalbumemia; previous major abdominal surgery. CHAPTER 13.3 Hemodialysis, hemo \201 ltration and hemodia \201 ltration 501 Table 13.3.6 Adjusted relative risk of mortality of patients who fail to achieve clinical p ractice guidelines (DOPPS I and DOPPS II) and percentage of British patients outside each g uideline or practice pattern Modi \201 able practice pattern Level at which clinical practice guideline parameter was achieved Relative risk of mortalitya P-value % British patients outside each parameterb Dialysis dose Single pool Kt/V <1.2 1.13 0.0023 17.8% Anemia management Hemoglobin <10 g/dL 1.21 <0.0001 21.5% PO4 >1.8 mmol/L Albumin <35 g/L 1.11 0.001 41.6% Mineral metabolism Nutrition/in \202 ammation 1.48 <0.0001 36.6% Vascular access Facility catheter use >10% 1.20 <0.0001 76.8% aDOPPS I and DOPPS II. bUK DOPPS II data only. Table 13.3.7 Mortality risk for patients receiving HDF versus HD: European results from the DOPPS Patients with central venous dialysis catheters and a conse- quent risk of catheter-related infection have been shown to require higher doses of erythropoiesis-stimulating agents (ES As) to maintain similar or slightly lower mean hemoglobin values. Vascular access using cen tral venous dialysis catheters is also associated with a higher risk of central venous sten - oses and lower blood \202 ow rates. Loss of patency of central venous catheters is comm on. Multicenter study of 2165 patients from 1998 \200\2232001 in \201 ve European countries p atients strati \201 ed into four groups: low \202 ux HD \200 high \202 ux HD \200 low ef \201 ciency HDF \200 high ef \201 ciency HDF High ef \201 ciency HDF group had a 35% lower mortality risk than patients on low \202 u x HD (after adjusting for the dialysis dose and comorbidity). No signi \201 cant differenc es observed between high \202 ux HD and HDF. Nontunneled versus tunneled central venous catheters The incidence of bacteremia in a prosp ective study of non- tunneled HD catheters was 5% after 3 weeks of placement in the interna l jugular vein. Cuffed, tunneled rather than nontunneled central venous catheters are prefe rred if vascular access is likely to be required for >3 weeks since tunneled catheters are associ- ated with a lower rate of infections and can provide higher blood \202 ow rates. Table 13.1.8 Comparison of home hemodialysis (HD) with peritoneal dialysis Advantages of home HD Disadvantages of home HD Acute hemolysis This uncommon complication should be suspected if: \200 Need for vascular access \200 Need for anticoagulation and risk Higher doses of therapy the patient develops backache, chest tightness or breath- lessness; the blood in the venous line has a port-wine appearance; there is pink plasma in the venous chamber. per unit time \200 of bleeding Ability to prescribe ultra \201 ltration volume \200 No need for peritoneal Need for a designated treatment room or portacabin at home \200 Most home HD training centers require that the patient ha s a helper at home This complication may be due to: \200 \200 \200 access excessive dialyzate temperature; kinking of the venous line; water contamination with chlor amines, nitrates or copper. Quality control of the dialyser membrane as well as the dialysis \202 uid and so no loss of dialysis ef \201 ci ency with time Training of the patient is more dif \201 cult and requires more time \200 Unphysiologica l unless performed Lower daily protein losses Air embolism This life-threatening complication should be prevented by the machine alarms i f a disconnection of the arterial line or arterial access occurs. Foam is often seen in the dialysis lines and the commonest symptoms are chest tightness if the patient is recumbent, and impaired conscious level or seizures if the patient is sitting upright. If suspected t he blood pump should be stopped, the venous line clamped immediately and the patient placed in the recumbent position on their left side and with their head tilted downwards. daily Complications of hemodialysis, hemo \201 ltration and hemodia \201 ltration Access-relate d infections The relative risk of bacteremia in a large prospective cohort of incident HD p atients compared to patients with an arteriovenous \201 stula was: \200 \200 1.95 for HD with tunneled catheters; 1.05 for HD with grafts. Infection-related hospitalization in the HEMO study was also shown to be more frequent in p atients relying on central venous catheters for vascular access but was not reduced by the use of high \202 ux dialyzers or a higher dialysis dose. Dialyzer reactions Chemical sterilization of dialyzers and tubing with ethylene oxide has b een associated with anaphylactoid reactions. R. MACTIER 502 This can be avoided by routinely using either steam- or -radiation-sterilized dialyzers. The concurrent use of AN 69 dialyzer membranes in patients on ACEIs has been reported to ca use hemody- namic instability attributable to bradykinin. This interaction is preventable b y changing the ACEI to an ARB or changing to a different dialysis membrane. For patients with an increased risk of bleeding, anticoagula- tion should be avoided or kep t to a minimum by using a high blood \202 ow rate and regular \202 ushing of the extrac or- poreal circuit with saline every 15 \200\22330 min. Alternatively heparin may be replac ed by a prostacyclin infusion or regional citrate anticoagulation. The former may induce hy potension and is expensive whereas the lat- ter requires careful replacement of calcium, mo nitoring of serum calcium levels during HD and is too complex for routine use. Dialysis dysequilibrium Nausea, vomiting, restlessness, headache, confusion, som- nolence a nd, more rarely, seizures may occur during or shortly after dialysis when patients with adv anced ESRD receive high intensity dialysis. As the symptoms result from cerebral edema, pre sumed due to disequilibrium between cerebral water and blood water solute or H+ concentrati ons, this syndrome can be avoided by increasing the dialysis dose gradually in patients sta rting RRT, e.g. 2 h, 3 h and then 4 h treatment for the \201 rst three dialysis sessions. Dialysis-related symptomatic hypotension Hypotension is the most frequent complication of H D and can shorten treatment times, thus reducing the delivered dialysis dose. It is importa nt to exclude a range of uncom- mon alternative causes when a patient develops hypoten- sio n on dialysis: \200 cardiac disease (arrthymias, myocardial infarction, peri- cardial tamponade); autonomic neu ropathy; occult hemorrhage; septicemia; dialyzer reactions; air embolism; acute hemolysis. \200 \200 \200 \200 \200 Dialysis-related amyloidosis Dialysis-related amyloidosis is a disabling, progressive con- dition caused by the polymerization of 2-microglobulin within tendons, synovium, and othe r tissues. 2-Microglobulin is a large molecular weight molecule (MW 11 600), which is rel eased into the circulation as a result of normal cell turnover but is not excreted in renal failure and is not removed by cellulose membranes. Exposure to bioincompatible membranes m ay increase 2- microglobulin generation. Symptoms are typically \201 rst reported 7 \200\22310 years after commencing HD although tissue accumulation of dialysis- related amyl oid in the joints and bone can be demon- strated much earlier. The most common clinical pre sentations of dialysis-related amyloid are: \200 \200 Dialysis-related hypotension is an independent predictor of poor patient survival and patie nts experiencing frequent dialysis-related hypotension are at higher risk of death probably because dialysis-related hypotension is a marker of severe cardiac disease. The frequency of dialysis-related hypotension is, therefore, an important indicator of the quality of dia lysis. The risk of dialysis-related symptomatic hypotension can be reduced by: \200 increase in postdialysis target weight if the patient is assessed as below \200\230dry \200\231 weight; reduction in interdialytic weight gain; decrease in the rate of \202 uid removal; reduction in dialyzate temperature during dialysis; increase in dialyzate sodium concentration; avoiding the administration of BP-lowering medication before dialysis; reduc tion in food intake during dialysis. carpal tunnel syndrome (usually after \211 7 years of HD); joint pains and stiffness espec ially in hands, arms and shoulders (usually after \211 10 years of HD); tenosynovitis of t endons in the hands; pathological fractures due to amyloid bone cysts; destructive spondyla rthropathy. \200 \200 \200 \200 \200 \200 Symptoms from dialysis-related amyloidosis may occur earlier if patients have no signi \201 cant residual renal function or are elderly at the onset of dialysis. High flux HD mem branes remove 2-microglobulin by a combination of diffusive clearance and adsorp- tion; H DF removes substantially more as a result of additional convective clearance. Both treatmen ts are thought to reduce the risk of developing dialysis- related amyloid and have been rec ommended for use in patients who are predicted to remain on dialysis for at least 3.7 years . Renal transplantation usually results in improvement in amyloid-related symptoms. Dialyzate sodium modeling or \200\230ramping \200\231 can reduce intradialytic cramps and hypotension but may increase thirst, weight gain and hypertension between dialysis sessions . A recent randomized trial of intradialytic blood volume monitoring demonstrated no differ ence in weight, BP or frequency of dialysis-related complications although hospi- talizatio n and mortality rates were lower in the control group assigned to conventional monitoring. A recent systematic review of 22 studies has concluded that a reduction in dialyzate temper ature is effective in decreasing the incidence of intradialytic hypotension with- out affec ting dialysis adequacy. An increase in the dialysis treatment time combined with a reductio n in the \202 uid UF rate or a decrease in the dialyzate \202 uid temperature are the m ost reliable methods of reduc- ing intradialytic hypotension without causing adverse sequel ae. Dialysis-related hemorrhage Bleeding from an arteriovenous \201 stula, graft or the GI tr act is not uncommon in HD patients and should be treated as an emergency. Great care is req uired with the use of anticoagulants dur- ing HD and heparin-locking solutions in patients with cen- tral venous catheters. CHAPTER 13.3 Hemodialysis, hemo \201 ltration and hemodia \201 ltration 503 Hyperkalemia Hyperkalemia is a common indication for emergency dialy- sis among patients al ready on HD and hyperkalemia is the probable cause of death in 3 \200\2235% of HD patients. Nonconcordance with the dialysis prescription and diet are the commonest contributory fact ors but medications such as ACEIs, ARBs, NSAIDs, -blockers and potassium supplements may be implicated. Performing an urgent electrocardiogram is of proven use in guiding managemen t of patients with serum potassium concentrations >6 mmol/L and can be used to dictate whic h patients should receive emergency administration of intravenous calcium chloride. HD is t he most appropriate emergency treatment for hyperkalemia in the dialysis patient. Serum pot assium levels usually fall by 1 mmol/L during the \201 rst hour of treat- ment and by a f urther 1 mmol/L during the next 2 h. The rate of potassium removal is increased by using a higher dialyzer blood \202 ow rate, higher dialyzate bicarbo- nate concentration or lower dialyzate potassium concen- tration. Ishani A, Collins AJ, Herzog CA, Foley RN. Septicaemia, access and cardiovascular disease i n dialysis patients: the USRDS Wave 2 study. Kidney Int 2005; 68: 311 \200\223318. Karamperis N, Sloth E, Jensen JD. Predilution hemo \201 ltration dis- plays no hemodynamic advantage over low- \202 ux hemodialysis under matched conditions. Kidney Int 2005; 67: 1 601 \200\2231608. Lim W, Cook DJ, Crowther MA. Safety and ef \201 cacy of low molecu- lar weight heparins fo r hemodialysis in patients with end-stage renal failure: a meta-analysis of randomized tria ls. J Am Soc Nephrol 2004; 15: 3192 \200\2233206.