Modi \201 ed cellulose (e.g. Hemophan ) More biocompatible. Synthetic membranes (e.g. Polysulfone , polyamide, polyacrylnitrile) \200 More recentl y developed. \200 Most biocompatible. \200 More permeable than cellulose membranes: Solute clearance similar to cellulose membranes. \200 i B 2 microglobulin clearance. High vs low \202 ux High- \202 ux membranes are usually synthetic membranes with a large pore size l enhanced clearance of middle and large molecules. X May lead to better outcome s. Surface area i dialyser surface area (usually 0.5 \200\223 2.1m 2 ) l i delivered dialysis . See Fig. 4.5. DIALYSERS AND MEMBRANES 285 Mixed, heated, and deaerated dialysate To waste Balancing chamber From patient Ultra filter Arterial Venous To patient Dialyser Ultra filter Fig. 4.5 Haemodia \201 ltration circuit using online ultra \201 ltration for production o fultra-pure dialysate and replacement \202 uids. CHAPTER 4 Dialysis 286 Dialysis prescription and adequacy Introduction Intermittent HD places exacting demands on a patient. As it only partially replaces renal function, \202 uid and dietary restriction s remain signi \201 cant and burdensome. Dialysis can be considered adequate if it provides relief of uraemic symptoms and controls acidosis, \202 uid balance, and serum K + . It should also allow a feeling of physical an d psychological well-being. Aspects of dialysis adequacy \200 Solute clearance . Small molecule clearance is relative ly easy to measure ( b p. 287). Aim to achieve a target Kt/V of >1.2 or URR >65% (see box b elow). Blood pressure and \202 uid balance . As a general rule, i BP in a dialysis patient shoul d be treated by d \200\230 dry weight \200\231 (i.e. post-dialysis weight). This should b e the weight at which salt and water balance is optimal. Oligo-anuric patients (majority of long-term HD patients) need to restrict their interdialytic salt and \202 uid intake in order to achieve this, aiming for weight gains of 1 \200\223 2.5kg (maximum) between sessi ons. It is dif \201 cult to be achieve prescriptive BP targets in the HD population (lack of evidence and a heterogeneous population). However, pre- and post- dialysis BP <140/90mmH g is desirable. This would preferably be achieved without anti-hypertensive medication. Int er- or intra-dialytic hypotension should be avoided. Nutrition. Blood Ur levels depend on rate of production as well as rate of excretion. (cid:2) A low pre-dialysis Ur may re \202 ect poor nutrition, rather th an good dialysis. Targets: \200 Serum albumin >35g/L. \200 Normalized protein catabolic rate (nPCR) >1.0g/kg/day ( b p. 287). \200 Acceptable anthropometric measures. Clearance of other molecules: \200\230 Middle \200\231 molecule clearance thought to be important to prevent the long-t erm complications of dialysis. B 2 microglobulin is the most used marker. Phosphate clearance is also important and appears to correlate more with hours of dialysis than rate of small molecule clearance. \200 Quality of life a nd life expectancy . There is a potential trade-off to be made between the number of hours spent on the machine ( i dialysis dose) and quality of lif e. For patients with a limited life expectancy, the latter may be a more important consider ation (although reducing hours below 4h 3x week is only rarely indicated). DIALYSIS PRESCRIPTION AND ADEQUACY 287 Measuring dialysis adequacy In the 1980s, the National Cooperative Dialysis Study (NCDS) es tab- lished timed average Ur concentration as a determinant of morbidity and mortality on H D. Subsequent mathematical analysis of these data has led to the development of urea kineti c modeling (UKM) as the accepted method of measuring small solute clearance. Kt/V is a measure of Ur clearance where: K = dialyser urea clearance. \200 t = time on dialysis. \200 V = volume of distribution of Ur (estimated from patient size). The single pool Kt/V assumes that, at the end of dialysis, the concentra- tions of intracel lular and extracellular Ur are equal: = \210\222 \210\222 + \210\222 4 3 5 . spKt V/ ln[ Upost/Upre 0 008 . t ] [ Upost/Upre ] \227 UFvol/wtp oost (Upre, urea pre-dialysis; Upost, urea post-dialysis; UFvol, volume removed on dialysis) The two compartment model acknowledges that, in reality, it takes time for Ur to be redistr ibuted post-dialysis and that the extracellular Ur concentration is lower than intracellula r. An equilibrated Kt/V or eKt/V can be calculated from the spKt/V. A simpler measurement of Ur clearance is the urea reduction ratio (URR), which does not tak e account of the amount of \202 uid removed by ultra \201 ltration. It is thus less accu rate but has been shown to correlate with outcome: \210\222 \227 URR =(1 Upre/Upost) 100 Normalized protein catabolic rate (nPCR) A measure of Ur generation, which re \202 ects nu tritional status. It can only be reliably used in patients who are \200\230 stable \200 \231 so Ur generation will broadly re \202 ect protein intake. It is felt that patients re quire an nPCR >1.0g/kg/ day. nPCR of <0.8g/kg/day is associated with higher mortality. Residual function When HD is \201 rst commenced, residual renal function may contribute g reatly to the total amount of solute clearance (Kru). This is usually calculated with a 24h urine collection. Residual function tends to dimin- ish quickly on HD (secondary to repeti tive d BP 9 bio-incompatibility) ( b p. 284). CHAPTER 4 Dialysis 288 Ensuring adequacy Kt/V UK and US guidelines suggest a single pool Kt/V >1.2 for patients di a- lysed x 3/week, equating to a URR of 7 65%. The landmark HEMO study compared two target Kt/V levels. Patients with a target Kt/V of 1.2 had no difference in mortality or cardiac e vents, compared to those with a Kt/V of 1.6. 2 Residual renal function should always be taken into account. Prescribed vs delivered Kt/V \200\224variables in the dialysis prescription Most guidelines suggest monthly measurement of Kt/V. Online meth- ods of measuring Kt/V are provided on mo dern dialysis machines (often using Na + clearance to estimate urea clearance). If Kt/V fai ls to meet target, options are to: Improve vascular access \200\224 if \202 ows are poor or if there is access recirculation, it will be hard to improve clearances. Increase blood \202 ow/larger needles \200\224 bene \201 cial if access reasonable. \200 Increase dialyser size \200\224 modest impact. \200 Increase dialysate \202 ow. \200 Increase dialysis time/frequency \200\224 major bene \201 t. \200 Consider HDF. Computer modeling software can help decide which elements of the prescription require modi \201 cation to improve Kt/V. (cid:2) HD adequacy is multifaceted. Achieving a desired Kt/V does not nec- essarily equate to optimal dialysis. DIALYSIS PRESCRIPTION AND ADEQUACY 289 Management of dialysis patients on non-renal wards - For elective procedures, inform your r enal team at the pre- assessment stage. On the day of admission contact them again (arrangements for routine dial ysis will need to be made). 1 Many dialysis patients are oligo-anuric, so DO NOT routinely administer IV \202 uids (u nless the patient is haemodynamically compromised \200\224if so, use small boluses, assess volume status regularly and call for expert help). 1 DO NOT give K+ supplementation. Discuss with renal team if being considered. DO NOT place a urinary catheter unless there is a clear urological indication. Oligo-anuria is virtually universal in this patient group! If the patient is clinically overloaded inform the renal team immediately, as the patient m ay require urgent dialysis. Check U+E on admission. If K+ >5.5 mmol/L inform renal team. - 1 When considering any new m edication, check whether the drug is safe in ESRD and if a dose adjustment is required. Be particularly cautious with opiate analgesia and sedatives (accumulation!). 2 See b p. 271 a nd discuss with the renal drugstore team. Check (and document) daily weight. - Does the patient have an AVF? NEVER insert an IV cannu la into a \201 stula arm. The back of the hand on the non- \201 stula arm is the best site. - If p atient has a dialysis central venous catheter (CVC), it should not be used for anything else but HD. If a dialysis patient undergoes a general anesthetic, their K+ must be checked immediately on return to the ward. This K+ check cannot wait until the following morning, even if the G A procedure is performed late in the day or out of hours. If K+ >5.5mmol/L inform the renal team - the patient may require dialysis. Peritoneal dialysis (PD) patients should ideally continue their own dialysis throughout their hospital admission. Ocassionally this may be with the assistance of a relative or carer. Liaise with their PD team. - If there is any concern that a patient will not be able to undertake their own PD (e.g. confusion, neurological event, etc.), inf orm the renal team ASAP, so that alternative arrangements can be made. CHAPTER 4 Dialysis 290 Anticoagulation Blood exposed to dialysis lines and membranes in an extracorporeal circuit rapidly sees the induction of the extrinsic coagulation cascade. In order to ensure ef \201 cient and adequate dialysis, regular anticoagulation throughout the duration of each d ialysis session is required. Historically, this was pro- vided by the use of unfractionated heparin (UFH) and, indeed, this is still the case in many parts of the world, including th e USA. There has been a trend, in Europe, however, to adopt the low molecular weight hepari ns (LMWHs) for standard anticoagulation. A 2004 meta-analysis of the safety and ef \201 ca cy of the LMWHs vs UFH concluded that there was no difference in the num- ber of bleeding e vents, post-dialysis vascular access compression time, or thrombosis of the extracorporeal circuit between the two. Unfractionated heparin \200 Mixture of glycosaminoglycans between 3 and 30 kDa. \200 Hi ghly negatively charged. \200 Indirect thrombin inhibitor. \200 Narrow therapeutic wind ow and highly variable dose response. \200 Metabolized in the liver and by vascular endot helial heparinases. \200 No single dosing protocol but usually single bolus 1,000 \200 \223 2,000 IU, followed by infusion of 1,000 \200\223 1,500IU/h. Adjust if weight <50kg or >90kg. \200 Monitor using activated clotting time (ACT) at the bedside. \200 Short half-life and fully reversible with protamine. Low molecular weight heparin \200 Smaller molecules, typically 4 \200\223 5kDa. \200 D ifferent preparations have variable lengths, weights, and charges (enoxaparin least \200\230 heparin-like \200\231 , tinzaparin most). Primarily work through inhibiting factor Xa. \200 Predominantly renally clearly \210 i half-life in ESRD. \200 Tinzaparin, commonly used at doses of 2,500IU or 3,500IU, is considered safe and effective. Enoxaparin (e.g. 10 \200\22340mg) is used in many centers. Monitor using anti-Xa activity, aiming <0.4IU/mL (historically slow turnaround in results, but now usually available in 90 \200\223120mins. Heparin-induced thrombocytopenia (HIT) see p. 184 This is a signi \201 cant complication o f heparin use (both UFH and LMWH), associated with major morbidity and mortality. Platelet activation and aggregation results in thrombocytopenia, thrombosis, and infarction. There a re wide-ranging reports as to the prevalence of HIT antibodies in dialysis patients, with \201 gures varying between 0 and 18%. ANTICOAGULATION 291 Other Other options for anticoagulation include regional anticoagulation (UFH/ protamine, c itrate, epoprostenol), heparin-coated dialyser, heparinoids (danaparoid or dermatan sulfate ), or direct thrombin inhibitors (arga- troban or hirudin). Some of these may be useful in those patients who develop HIT or those with a high bleeding risk. Bleeding 2 Patients with ESRD have an increased incidence rate of major bleed- ing. This ha s been quoted as 2.5% per person-year for patients on hae- modialysis. A recent study sugge sted that this increased to 3.1% with warfarin use, 4.4% with aspirin, and 6.3% with warfar in and aspirin. (cid:2) Caution when prescribing these agents in patients on haemodialysis. CHAPTER 4 Dialysis 292 Dialysis access: AVF/PTFE Reliable vascular access is the cornerstone of HD therapy, and ti mely plan- ning of access creation is a major facet of CKD care (see Fig. 4.6). 7 25% of al l admissions in the dialysis population relate to access failure or other complication and remain an important source of morbidity and mortality. AV \201 stula The optimal form of vascular access. Requires surgical anastomosis of an ar tery and a vein (under LA or GA), either at the wrist (radiocephalic) or elbow (brachioceph alic, brachiobasilic). If the suitability of veins is in doubt, then vascular mapping with USS is desirable. Maturation for 6 \200\223 8 weeks (minimum) is required prior to needlin g ( 6 advance planning crucial). PTFE graft Second best. A synthetic graft is interposed between an artery and a vein. A lar ger operation than AVF creation. Necessary if veins inadequate to fashion an AVF (e.g. DM, previous phlebotomy/cannulation). Lower limb sites possible (e.g. femoral loop), in additio n to upper limb. Useable within days, but thrombosis and infection (usually necessitating r emoval) are problematic. Half-life shorter than an AVF. Forearm straight PTFE graft Forearm loop PTFE graft Graft Brachial artery Brachial artery Graft Radial arteriovenous fistula Cephalic vein Radial artery AVF Fig. 4.6 Permanent vascular access for haemodialysis. Reproduced with permission from Levy J, Morgan J, and Brown E (2004). Oxford Handbook of Dialysis , 2nd edn. Oxford: Oxford Univ ersity Press. DIALYSIS ACCESS: AVF/PTFE 293 Planning UK Renal Association guidelines suggest that 85% of prevalent haemodi- alysis pati ents should be dialysing through either a native arteriovenous \201 s- tula or a PTFE gra ft. At the start of their dialysis career, all patients should have a lifelong vascular acc ess strategy; i.e. a planned approach to vascular access that preserves potential sites for as long as possible. Many centers have a multidisciplinary vascular access team for this p urpose. Clinical examination and vessel mapping (duplex Doppler) help to plan the site of \201 st ula formation. A native \201 stula takes at least 6 \200\223 8 weeks to mature. A PTFE g raft can often be used within 2 weeks. Primary failure rates for AV \201 stulae (unusable at 3 months) remain high (up to 50% in some centers). In addition to technical factors, or poor AVF care, this may be caused by a vascular stenosis, either at the AV anastomosis or in the downstream vein. These may be amenable to angioplasty. Grafts have a lower primary f ailure rate, but are more likely to develop late stenoses \200\224 either at the venous ana stomosis or in the out \202 ow vein. Fistula care: what every doctor and patient should know \200 Dialysis access is extremely precious. \200 Arm veins should be preserved in pre-dialysis patients (no IV cannulae between elbow and wrist). Needling should only be carried out by a trained operator (usually a dialysis nurse, ideally the patient). Technique: avoid using the same site repetitively ( l false aneurysm formation). Never put a tourniquet or BP cuff on a \201 stula arm. \200 Do not use a \201 stula t o take blood. \200 Hypotension (and volume depletion) l i thrombosis risk. \200 i Hct ( too much ESA) predisposes to thrombosis. Keep within recommended guidelines and at the lower end of these, if at risk. A clotted \201 stula or graft requires immediate attention (time to declotting is a major determinant of success). Surveillance Alongside clinical monitoring of signs that may indicate stenosis (dif \201 c ult can- nulation, prolonged bleeding post-needle removal), KDOQI have published guidelines for regular access screening. The rationale is that regular surveil- lance of vascular acc ess should identify a stenosis and allow pre-emptive intervention to prevent thrombosis. Th e recommendations are that a refer- ral for intervention should be triggered when blood \202 ow < 600mL/min in a PTFE or <400 \200\223 500mL/min in an AVF. While these guidelines are controver- sial (as they may potentially lead to a high number of unnecessary interven - tions), they can be helpful when correlated with clinical \201 ndings such as access ve nous pressures and post dialysis bleeding times. If a stenosis is suspected, investigate further by duplex or angiography ( \200\230 \201 s tulogram \200\231). The advantage of angiography is the potential ability to pro- ceed imme diately to an angioplasty ( \200\230 \201 stuloplasty \200\231). CHAPTER 4 Dialysis 294 Clotted AVF/PTFE No thrill or buzz in \201 stula = thrombosis (ensure patients are aware of this) \210 seek immediate medical opinion. Swift intervention (within 48h) either via interventional radiology (local thrombolysis), or surgery, may be able to salvage the \201 stula. The longer the time to intervention, the less likely it is to be successful. Th ere is no clear evidence for anticoagulation in the interim. Check U+E and volume status, a nd insert a temporary dialysis line, if required. Other complications of \201 stulae and grafts \200 Infection: \201 stulae rarely beco me infected beyond a super \201 cial cellulitis. PTFE infection is not uncommon. May be occult, causing weight loss, ESA resista nce, and failure to thrive. Antimicrobials rarely successful, and management usually involv es surgical removal. Aneurysm or pseudoaneurysm formation: may occur at needling sites, especially if sites not rotated. Surgery may be necessary. \200 Bleeding from an infected or aneurysmal AVF or gr aft is a much feared complication (proceeds under arterial pressure!). 2 Wear a gown, gloves, and goggles. Seal the bleeding site with the lid of a universal cont ainer, and secure with a tight bandage. Establish wide-bore IV access; check clotting; cros s-match blood, and inform a surgeon. Distal ischaemia or steal syndrome: \202 ow through the \201 stula or graft may comprom ise distal blood supply. Cold or numb peripheries are common but may l infarction or ischae mic pain. Other features include paraesthesia, cyanosis, loss of distal pulses. Patients of ten elect to wear a glove on the affected hand. AVF ligation or graft removal may be necess ary in severe cases. Excess \202 ow: may l large i in cardiac output with cardiac decompensation. Surgical \200\230banding \200\231 (plication) of an AVF can d \202 ow. Extravasation: blood leakage into the soft tissues. Can cause rapid limb swelling, haemodynamic compromise, compartment syndromes, s infection, access thrombos is. DIALYSIS ACCESS: AVF/PTFE 295 The golden rules of vascular access formation - Assess the patient for vascular access when dialysis is expected within 12 months. Make sure the patient resists venepuncture in the selected limb. - Use upper limbs before l ower limbs. - Non-dominant arm before dominant. - Use distal sites (e.g. radiocephalic) bef ore proximal (e.g. brachiocephalic) whenever possible. See Fig. 4.7. Use a native vein before prosthetic graft. - Aim for formation >6 months prior to dialysis. This will give adequate time for maturation (and for repeat intervention in cases of primary non-function) . Ensure all access procedures and interventions (successful or unsuccessful) are adequately documented. Plan ahead \200\224what next? Is peritoneal dialysis an option? Fig. 4.7 A mature radiocephalic AVF used for hemodialysis. CHAPTER 4 Dialysis 296 Haemodialysis access: lines If a patient has neither an AVF nor a PTFE, the remaining optio ns are: Temporary dialysis catheter ( b p. 180) For immediate use; e.g. AKI, or in a patien t with unresolved sepsis. Internal jugular, subclavian and femoral are possible routes. Ide ally leave in situ for \211 2 weeks (femoral <5 days). These have much higher infection ra tes than other forms of dialysis access. Tunneled (and cuffed) dialysis catheter A dual-lumen (or two single-lumen) venous catheter is placed in a central vein (internal jugular or subclavian; femoral less common). Availabl e for immediate use and usually left in situ for 1 \200\223 3 months (occasionally longer) . Blood \202 ows 300 \200\223 450mL/min achievable. The use of tunneled central venous haemodialysis catheters (CVC) is common. They are freque ntly used as a \200\230 bridging \200\231 step in those who are waiting for a \201 stul a or in those in whom access surgery has been unsuc- cessful. They should generally be view ed as a short-term solution, as they are associated with a 3-fold increased mortality, comp ared with AVFs. In addition, sepsis-related death is 100-fold greater in HD patients than t he general population, and infection-related death and all-cause mortality is highest in th ose dialysing through a CVC. Malfunction Catheter malfunction is common. 50% of lines fail within the \201 rst year of insertion. Catheter malfunction is de \201 ned as one of the following: \200 Peak blood \202 ow \211 200mL/min for 30min in an HD session. \200 Mean blood \202 ow \211 200mL/min for two consecutive HD sessions. \200 No \202 ow, unable to initiate HD. Malf unction may be positional (usually \211 7 days post-insertion) or mechani- cal. Mechanica l malfunction may be intraluminal (thrombosis), extralumi- nal ( \201 brin sheath), or int rinsic to the catheter material/properties. Fibrin sheaths will start to form within 24 hours of insertion and may eventually completel y enclose the catheter. Can cause a one-way valve, manifesting in dif \201 cult aspiration despite easy injection. Primary prevention Strategies include heparin, rtPA, or trisodium citrate catheter lumen lo ck between sessions. The PreCLOT trial showed that rtPA for pri- mary prevention of cathete r malfunction (1mg/lumen once/week + hepa- rin for the other two sessions) vs standard hepa rin (5,000U/mL to \201 ll lumen) was associated with signi \201 cantly less catheter mal function and bacteraemia, with no increase in bleeding events. Trisodium citrate (4, 30, or 46.7%) has also been shown to be more effective than heparin and causes less bleeding, les s bio \201 lm formation, and a signi \201 cant reduction in catheter-related bacteraemia. There are no convincing data for low-dose warfarin, ticlopidine, or other antiplatelet age nts with respect to primary prevention. HAEMODIALYSIS ACCESS: LINES 297 Treatment \200 Initial attempts to restore \202 ow: \202 ush catheter with 10mL syrin ge of saline; reposition patient; reverse lines. Beware recirculation (repetitive dialysis of the same small volume of blood) and inadequate dialysis. \200 Thrombolytic agents: streptoki nase/urokinase have largely been replaced by rtPA (alteplase, reteplase, tenecteplase). Dif fering regimens have been studied: \200\230 push \200\231 , short dwell (30 \200\223 60m in), long dwell (>2 hours, interdialytic), or infusions. These methods are associated with short-term success of between 40 and 90%, with median patency 14 \200\223 30 days. Fibrin sheath disruption: mechanical disruption of sheath from catheter wall. Published out comes variable, presumably related to catheter type and operator technique. Exchange over guidewire: if previously listed measures unsuccessful, then consider a cathet er exchange. Comparable infection rates to de novo insertion and preserves vascular access, particularly if a central venous stenosis has developed. Caution \200\224do not use this t echnique when replacing fractured or \200\230split \200\231 lines due to risk of bacteraem ia. Catheter-related bacteraemia Catheter-related bacteraemia (CRB) is a serious complication o f CVC use. Catheters are associated with a 10-fold increase in bacteraemia rates vs AVF. In cidence of CRB used to range from 2.5 to 6.5 episodes/1,000 catheter days for tunneled line s and higher for temporary uncuffed lines. Since the advent of antimicrobial catheter locks , most units aim for <1 bacteraemia/1,000 patient days at risk. \200 Fever in an HD patie nt with a line = line sepsis until proven otherwise. \200 Causes: 7 70% l Staph. aureus ( (cid:2) MRSA) or Staph. epidermidis . Gram \200\223 ve organisms more common with femoral catheters. Risk factors: poor patient hygiene, previous CRB, recent hospitalization, d albumin, durati on of catheter use, Staphylococcus nasal carriage or skin colonization, DM, immunocompromis ed. Clinical features \200 Usually presents with fever, rigors 9 d BP whilst on dialysis. Als o N+V, diarrhea, confusion. Examination and investigation: The line: often appears innocent, but check for erythematous or purulent exit site ( l swab for C+S). Is there a tunnel infection? \200 General exam: stigmata of endocarditis, ches t signs, other sources of infection; e.g. spinal tenderness (?discitis). Blood cultures: from line and peripheral vein (see Table 4.1 ). \200 CRP. \200 CXR if c hest signs. CHAPTER 4 Dialysis 298 Table 4.1 De \201 nitions De \201 nite Con \201 rmation of septic thrombophlebitis with single positive blood culture (BC), OR Si ngle positive BC + positive culture of catheter segment with identical organism, OR 10-fold difference in colony count in BC from catheter vs peripheral, OR Single positive BC + posi tive culture from discharge/aspirate from exit site or tunnel with identical organism \211 2 positive BC with no other obvious source, OR Single positive BC from Staph. aureus /Candida with no other obvious source, OR Single positive BC for coagulase-negative staph / Bacillus / Corynebacterium jeikeium / Enterococcus / Trichophyton or Malassezia in immunoc ompromised/neutropenic patient Probable Adapted from Prevention of catheter lumen occlusion with rT-PA versus heparin (PreCLOT): st udy protocol of a randomized trial. Hemmelgarm et al. BMC Nephrol 2006;7:8 Treatment \200 Start antibiotics empirically if fever >38 * C, rigors, or d BP. \200 Co ver for both Gram +ve and Gram-ve organisms. \200 For Gram +ve cover use either vancomyci n (10 \200\22320mg/kg IV \200\224usually 1g) or teicoplanin (see b p. 882). For Gram \200\223ve cover use either gentamicin (see b pp. 881 \200\2232) or third-generation Cephalosporin. \200 Tailor therapy to culture results. \200 Vancomycin is not removed by HD; gentamicin is. Measure gent levels daily (levels will decrease soone r in patients with signi \201 cant residual function). Continue 4 weeks for Staphylococcus (6 \200\2238 weeks if complicated by metastatic infecti on), Minimum 2 weeks if Gram \200\223ve or Candida. \200 If fever still present after 12 \200\223 24h l remove line, earlier if severe sepsis or deteriorating patient. Remove in all cases of Staph. aureus , tunnel infection, or if infection seeded elsewhere. Patients with CRB are at risk of developing osteomyelitis, discitis, epidural abscess, sept ic arthritis, or endocarditis, regardless of whether the CVC is removed or exchanged \200 \224 consider if ongoing fever or CRP. Prevention \200 Consider IV antibiotics at insertion for patients with Staphylococcal skin colonization. Sterile placement technique ( b p. 936). Meticulous nursing care (KDOQI guidelines: mask and sterile gloves; clean exit site with chlorhexidine each use). Eradication of Staphylococcus carriage may d incidence (e.g. nasal mupirocin cream). Topical antimicrobial ointment: d CRB by 75 \200\223 93% (e.g. mupirocin). HAEMODIALYSIS ACCESS: LINES 299 Antimicrobial locks: the cornerstone of preventing catheter-related bacteraemia ( d by 51 \200\223 99% over 25 trials) though microbial resistance and long te rm ef \201 cacy are concerns. The application of chlorhexidine-impregnated foam dressings to catheter exit sites has become popular in many units. Long-term complications \200 Catheters may l central venous stenosis, preventing subseque nt catheter placement and compromising AVF maturation and \202 ow. May lead to SVC obstru ction, with swollen arms, chest wall, and face. Multiple collateral veins may be visible. B alloon angioplasty 9 stent insertion may be successful but recurrence common. CHAPTER 4 Dialysis 300 Fluid balance on dialysis Fluids gains between dialysis depend on: \200 Fluid intake duri ng the interdialytic interval ( (cid:2) the long interdialytic interval, or the 3-day break that occurs once a week on a standard thrice weekly dialysis r egime, is usually associated with the largest \202 uid gains). Residual renal function or urine output. \200 Other \202 uid losses (stoma output, stoo l losses, etc.). As a general rule, HD patients should gain no more than 2% of their body weight in \202 u id between sessions (1.4kg in a 70kg adult). Gains of >4% (2.8kg in a 70kg adult) are descr ibed as large interdialytic weight gains. But, as most HD patients will con \201 rm, this is easier said than done. Patients require encouragement and regular tailored advice regard ing \202 uid (and salt) intake. Dry weight (DW) \200 It is the end-dialysis weight thought to best represent a euvolaemic state. It is the body weight in kg against which the ultra \201 ltration volume is set at each session. For example: \200 HD patient with a dry weight of 70kg. \200 Pre-dialysi s weight 72.7kg. \200 Target UF volume = 2,700mL over 4h to achieve DW. Assessing DW Can be achieved in a number of ways but should always include clinical assessm ent. The point at which a patient experiences intradialytic hypo- tension (or unpleasant cr amp) ( b p. 302) is a crude (and not always correct) indication that further \202 uid rem oval will not be advantageous: \200 Examination: to include presence or absence of ankle oedema, lying and standing BP, JVP, and examination of the chest. Hypertension, oedema, and an elevated JVP suggest overload. Fluid gains between dialysis sessions. \200 Continuous blood volume monitoring (BVM, on-l ine measurement of the haematocrit on HD where sudden haemoconcentration suggests vascular re \201 ll is failing and dry weight has been reached). Biofeedback control, a combination of BVM, conductivity, BP, and UF rate, analyzed in real time to predict impending hypotension. \200 Bioimpedance where res istance to alternating current is used to determine lean body mass and body \202 uid volume. IVC:aorta ratio on ultrasound (predominantly a research tool). (cid:2) Of these, only the \201 rst two have entered routine practice \200\224 trials of the other techniques have e ither been inadequate or results have been inconsistent. A widely applicable, and clinicall y useful, tool that accurately assesses \202 uid status is awaited. FLUID BALANCE ON DIALYSIS 301 Sodium and dialysis Any individual has a (remarkably stable) \200\230 sodium set-point \200\231 : if their plasma Na + rises above their set-point, osmoreceptors trigger thirst u ntil Na + returns to this point. The reverse is also true: if plasma Na + falls with total body Na + depletion, salt craving increases Na + ingestion to regain the \200\230 set-poin t Na + \200\231 . So it follows that: \200 (cid:2) Dietary salt intake is a vital part o f haemodialysis patients \200\231 salt balance ! Achieving <100mmol/day intake (equivalent to 6g NaCl) is dif \201 cult on a western diet. The more salt ingested, the more water will be drunk, and the more \202 uid weight gained between sessions. During dialysis, ultra \201 ltration (convection) removes Na + , as does diffusion down a plasma/dialysate gradient. This gradient is not as simple as a patient \200\231 s measured serum Na + , compared to the prescribed dialysate Na + : \200 Plasma Na + is reported in mmol/L, but only 93% of plasma is free water (so the true Na + in that fraction of dialysable water is higher ). Negatively charged plasma proteins \200\230 resist \200\231 movement of Na + from plasma into dialysate (Gibbs \200\223 Donnan effect), affecting true diffusion. As long as dietary salt intake is controlled to <100mmol/day \200 Lowering the dialysate Na + will lead to a negative Na + balance over time. BUT may be associated with more intradialytic haemodynamic instability over the short term. Higher dialysate Na + l increased \202 uid intake and larger interdialytic weight gains over time. BUT may be associated with better haemodynamic control during any one session (allows for better capillary re \201 lling during ultra \201 ltrat ion). CHAPTER 4 Dialysis 302 Intradialytic hypotension A sudden and symptomatic fall in BP during a dialysis session is called intradialytic hypotension (IDH). During ultra \201 ltration, \202 uid is removed from the vascular space. This requires prompt re \201 lling from the ECF to maintain blood volume. Healthy adults will tolerate up to 25% reduction in blood volume, but, amongst pat ients on dialysis, there is large inter- and intrapatient variability. IDH is de \201 ned as a fall in SBP >20mmHg (or MAP >10), associated with symptoms, or a f all to SBP <100mmHg. Symptoms associated with IDH include: \200 Cramps, abdominal pain, o r nausea (reduced gut perfusion). \200 Yawning, sighing, anxiety, or dizziness (reduced c erebral perfusion). \200 Chest pain or arrhythmias. IDH occurs in around 10% of all HD patients and in around 5 \200\223 30% of these patients \200\231 sessions. IDH is always related to the rate of ultra \201 ltration (i.e. the sp eed of \202 uid removal). It is less usual at UF rate <0.3mL/min/kg and common if UF rate >0.6mL/min/kg. IDH is more likely in: \200 Elderly (esp. if with wide pulse pressure and isolated systolic hypertension). \231\200. \200 Diabetic patients ( 2 with autonomic neuropathy). \200 Cardiomyopathies . \200 Occult sepsis. Immediate management of IDH: \200 Stop ultra \201 ltration (UF). \200 Place patient in Trendelenburg position. \200 Administer 0.9% NaCl as a 250mL bolus. \200 Recheck BP. \200 Undertake thorough clinical review (including medications) to prevent future episodes! Prevent IDH by identifying those most at risk \200 Large interdialytic weight gains. \200 High salt intake. \200 Anuric (no residual renal function). \200 Valvular heart d isease (aortic valve disease), known systolic dysfunction, or untreated coronary artery disease. Those taking dialysis-day antihypertensives (particularly vasodilators). \200 Malnourishe d or hypoalbuminaemic, or those losing \202 esh weight. \200 Large arteriovenous \201 stulae ( \202 ows >2L/min). INTRADIALYTIC HYPOTENSION 303 Management: preventing IDH \200 Maintain residual renal function where possible. \200 C on \201 rm cardiac function (ECG, echo) and exclude valvular heart disease. \200 Give go od dietary salt and \202 uid intake advice. Patients who do not understand the importance of salt restriction on HD will \201 nd controlling thirst a nd \202 uid very dif \201 cult. Avoid eating during HD. \200 Stop dialysis-day antihypertensives (but try to continue B - blockers if prescribed). Control blood sugars in diabetic patients. \200 Correct anemia, if present, and arrange n utritional input for those who are malnourished. Increase dialysis hours or increase number of weekly sessions (i.e. reduce the UF rate or the UF volume per session). Cooling the dialysate Dialysis is often a \200\230 warming \200\231 event \200\224 if th e dialysate temperature were set at 37 * , the metabolic consequences of the process and of pyrogens and cytokines released through blood \200\223membrane interaction would l a gain in energy. Warming l peripheral vasodilatation \200\224 BP will then only be main- tained if heart rate or stroke volume increases (or both). Patients on dialysis often have a multifactorial uraemic cardiomyo- pathy \200\224 during dialysis, ischaemic regional wall motion abnormalities (RWMAs) are visible on echocardiogra phy in a signi \201 cant subgroup of patients prone to IDH (as O 2 delivery fails to meet cardiac work). Reducing the dialysate temperature to 36 * or even 35.5 * l cooler returned blood during an y session, with vasoconstriction, then sustaining or raising blood pressure without tachyca rdia or increased myocardial contractility. 2 Cooled dialysate reduces IDH and prevents RWMAs. Sodium pro \201 ling Sodium \200\230 ramping \200\231 , or \200\230 pro \201 ling \200\231 , has not become widely adopted to control IDH \200\224 although a higher dialysa te Na + during the \201 rst hour of dialysis, which then falls on an hour-by-hour (or sho rter) basis, should improve haemodynamic stability. The total Na + load tends to be higher than with \201 xed concentration (standard) dialysate Na + . So a higher load then drives intradialytic thirst and \202 uid gains, setting up a cycle of large intradialytic weigh t gains requiring ever higher ultra \201 ltration volumes and more frequent IDH. CHAPTER 4 Dialysis 304 Extended hours HD treatments Background Dialysis frequency and duration - For >3 decades in Tassin, France, patients with ESRD have received 8h in-center dialysis sessions 3x/wk. Pat ient outcome data with this regime are amongst the best in the world. This improved survival (compared to shorter dialysis schedules) is mainly due to lower CV m ortality. Other reported bene \201 ts include improved nutritional status, better anemia p arameters (with lower ESA requirement) and superior BP control. In addition, the 2-day interval between conventional HD sessions is well recognized as a time of heightened risk for CV events. In view of these observations, it has been proposed that modern dialysis care should focus on: - - i dialysis frequency - i dialysis duration - Or both of these. Strategies to increase the intensity of dialysis include short daily haemodialysis (SDHD), in-hospital nocturnal haemodialysis (INHD) and nocturnal home haemodi alysis (NHHD). SDHD - 6-7 days/week, 1.5 \200\2233 hours/session - Bene \201 ts: improved BP control, dLV mass, variable reports on quality of life, anemia, dPO4, dmortality. INHD - 3 nights/week, 8 hours/session - dMortality, dhospitalisation, dESA requirements, dI DH, dPO4 NHHD - 5 \200\2236 nights/week, 6 \200\2238 hours/session - Improved BP control, d ESA requirements, dLV mass, No current RCT data on mortality. Frequent Haemodialysis Network (FHN) - The FHN, formed in 2005, is responsible for the two most recent RCTs that have examined daily and nocturnal dialysis. The trials (short daily haemodialysis (SDHD) v conventional HD (2010) and nocturnal haemodialysis (NHD) v conventional HD (2011)), were designed to test t he hypothesis that signi \201 cant modi \201 cations to HD treatment time and/or frequenc y would have a signi \201 cant impact on patient outcomes. Outcome measures included mortality, change in LV mass, and change in self-reported physical functioning. Unfortunately neither of the studies was powered suf \201 ciently to examine the effects o f either mortality or risk of hospitalization. However, they did demonstrate that frequent or long duration dialysis schedules could improve certain clinical parameters and quality o f life scores. Bene \201 ts of increased hours dialysing may, however, be at the expense of vascular access longevity in some patients.