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. Locatelli F, Andrulli S, Pecchini F, et al. Effect of high- \202 ux dialysis on the anemia of haemodialysis patients. Nephrol Dial Transplant 2000; 15: 1399 \200\2231409. Locatelli F, Pozzoni P, Di Filippo S. What are we expecting to learn from the MPO study? Contrib Nephrol 2005; 149: 83 \200\22389. Lowrie EG, Parker TF, Parker TF, Sargent JA. Effect of the hemodi- alysis prescription on p atient morbidity: report from the National Cooperative Dialysis Study. N Engl J Med 1981; 3 05: 1176 \200\2231181. Macleod AM, Campbell M, Cody JD, et al. Cellulose, modi \201 ed cel - lulose and synthetic membranes in the haemodialysis of patients with end-stage renal dise ase. Cochrane Database Syst Rev 2005(3). Mactier RA, Madi AM, Allam BF. Comparison of high-ef \201 ciency and standard haemodialysi s providing equal urea clearances by partial and total dialysate quanti \201 cation. Nephr ol Dial Transplant 1997; 12: 1182 \200\2231186. Incidence and prevalence of comorbid medical conditions The incidence and prevalence of a w ide range of comorbid medical conditions is higher in chronic HD patients: \200 \200 \200 \200 \200 \200 Marshall MR, Byrne BG, Kerr PG, McDonald SP. Associations of hemodialysis dose and session length with mortality risk in Australian and New Zealand patients. Kidney Int 2006; 69: 122 9 \200\223 1236. myocardial infarction; cerebrovascular disease; peripheral vascular disease; falls and frac tures; infective endocarditis; metastatic staphylococcal infections. Owen WF, Lew NL, Lowrie EG, et al. The urea reduction ratio and serum albumin concentration as predictors of mortality in patients undergoing haemodialysis. N Eng J Med 1993; 329: 10 01 \200\223 1006. Penne EL, Blankestijn PJ, Bots ML, et al. Effect of increased convective clearance by on-li ne hemodia \201 ltration on all cause mortality in chronic hemodialysis patients \200\223 the Dutch CONvective transportation STudy (CONTRAST): rationale and design of a randomized con- trolled trial. Curr Control Trail Cardiovasc Med 2005; 6: 8. The management of these medical complications is akin to standard clinical practice but nee ds to take account of a reduction in the dosage of drugs excreted by the kidneys and the pa tient \200\231s ongoing dialysis therapy. Pierratos A. Nocturnal home haemodialysis: an update on a 5-year experience. Nephrol Dial Transplant 1999; 14: 2835 \200\2232840. Rabindranath KS, Strippoli GF, Roderick P, et al. Comparison of hemodialysis, hemo \201 lt ration, and acetate free bio \201 ltration for ESRD:systematic review. Am J Kidney Dis 200 5; 45: 437 \200\223447. Further reading Astor BC, Eustace JA, Powe NR, et al. Type of vascular access and survival among incident hemodialysis patients: the Choices for Healthy Outcomes in Caring for ESRD ( CHOICE) Study. J Am Soc Nephrol 2005; 16: 1449 \200\2231455. Reddan DN, Szczech LA, Hasseblad V, et al. Intradialytic blood vol- ume monitoring in ambul atory hemodialysis patients:a ran- domised trial. J Am Soc Nephrol 2005; 16: 2162 \200\2232 169. Canaud B, Bragg-Gresham JL, Marshall MR, et al. Mortality risk for patients receiving haemo diafiltration versus hemodialysis: European results from the DOPPS. Kidney Int 2006; 69: 20 87 \200\223 2093. Roberts TL, Obrador GT, St Peter WL, et al. Relationship among catheter insertions, vascula r access infections and anemia man- agement in hemodialysis patients. Kidney Int 2004; 66: 2429 \200\2232436. Saran R, Bragg-Gresham JL, Levin NW, et al. Longer treatment time and sl ower ultra \201 ltration in hemodialysis: associations with lower mortality in the DOPPS. Kidney Int 2006;69:1222 \200\2231228. Charra B, Calemard E, Ruffet M, et al. Survival as an index of ade- quacy of dialysis. Kidney Int 1992; 41: 1286 \200\2231291. Chauveau P, Nguyen H, Combe C, et al. Dialyser membrane perme- ability and survival in hemo dialysis patients. Am J Kidney Dis 2005; 45: 564 \200\223571 Schif \202 H, Lang SM, Fischer R. Ultrapure dialysis \202 uid slows loss of residual ren al function in new dialysis patients. Nephrol Dial Transplant 2002; 17: 1814 \200\2231818. Cheung AK, Levin NW, Greene T, et al. Effects of high- \202 ux hemodi- alysis on clinical outcomes: results of the HEMO study. J Am Soc Nephrol 2003; 14: 3251 \200\2233263. Selby NM, McIntyre CW. A systematic review of the clinical effects of reducing dialysate \202 uid temperature. Nephrol Dial Transplant 2006; 21: 1883 \200\2231898. Eknoyan G, Beck GJ, Cheung AK, et al. Effect of dialysis dose and \202 ux on mortality an d morbidity in maintenance hemodialysis patients: primary results of the HEMO study. N Engl J Med 2002; 347: 2010 \200\2232019. Shinzato T, Nikai S, Akiba T, et al. Survival in long-term haemodialy- sis patients results from the annual survey of the Japanese Society of Dialysis Therapy. Nephrol Dial Transplan t 1997; 12: 884 \200\223814. Stevenson KB, Adcox MJ, Mallea MC, et al. Standardized surveil - lance of hemodialysis vascular access infections: 18-month expe- rience at an outpatient, multi-facility, hemodialysis center. Infect Control Hosp Epidemiol 2000; 21: 200 \200\2232 03. Goldfarb-Rumyantzev AS, Leypoldt JK, Nelson N, et al. A crossover study of short daily haem odialysis. Nephrol Dial Transplant 2005; 21: 166 \200\223175. Grooteman MPC, Nube MJ. Impact of the type of dialyser on clini- cal outcome in chronic hae modialysis patients: does it really mat- ter? Nephrol Dial Transplant 2004; 19: 2965 \200 \22329701. Termorshuizen F, Dekker FW, van Manen JG, et al. Relative contri- bution of residual renal function and different measures of ade- quacy to survival in hemodialysis patients: an anal ysis of the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD)-2. J Am Soc Nephrol 2004; 15: 1061 \200\2231070. Held PJ, Levin NW, Bovbjerg RR, et al. Mortality and duration of hemodialysis treatment. J Am Med Assoc 1991; 265: 871 \200\223875. R. MACTIER 504 Internet resources Renal Association Clinical Practice Guidelines for HD: http://www.hdintl.org/ Australia and New Zealand Dialysis and Transplant Registry: http://www.renal.org/pages/pages/clinical- affairs/guidelines.php The Renal Registry: http://www.anzdata.org.au/ National Institute for Clinical Excellence: http://www.renalreg.org National Kidney Federation Dialysis Outcomes Quality Initiative: http://www.nice.org.uk/ Association of Renal Technologists: http://www.artery.org.uk/site/ART/home http://www.kidney.org/professionals/kdoqi/ European Best Practice Guidelines: See also Renal replacement therapies in acute kidney injury, p. 328 Dialysis and hemoperfusion treat ment of acute poisoning, p. 336 Dialysis strategies, p. 480 Vascular access, p. 488 Adequac y of dialysis, p. 518 Medical management of dialysis patients, p. 528 http://www.ndt-educational.org/guidelines.asp Frequent hemodialysis clinical trials: www.niddk.nih.gov/patient/hemodialysis/hemodi- alysis.htm Cochrane Renal Group: http://www.cochrane-renal.org/ International Organization for Standardization (standards fo r concentrates and water for HD): www.iso.org European Pharmacopeia: http://online.pheur.org/entry.htm Association Instrumentation: for the Advancement of Medical http://www.aami.org/ International Society for Haemodialysis: This page intentionally left blank G. WOODROW 506 Peritoneal dialysis Introduction Since the initial description of continuous ambulatory peri- toneal dialysis ( CAPD) to treat ESRD in the 1970s, perito- neal dialysis (PD) has become established as a ma jor option for long-term renal replacement therapy. PD now offers a variety of modalities t o allow treatment to be tailored to the individual patient \200\231s requirements. The membrane is lined by mesothelial cells which are attached to a submesothelial connectiv e tissue layer con- taining the peritoneal capillaries and lymphatics. The peritoneal vascu lature is central to the physiology of PD. The peritoneal capillary endothelium provides th e major barrier to solute and \202 uid removal between patient and dialysis \202 uid. F actors affecting peritoneal capillary blood \202 ow alter peri- toneal membrane function. Peritoneal lymphatics contribute to \202 uid removal from the peritoneal cavity. The place of PD in the integrated care of the patient with ESRD The relative merits of diff erent dialysis modalities have been debated but no evidence clearly shows one to be superio r. Rather than debating whether any mode of dialysis is supe- rior, it is better to conside r that most patients will receive a variety of renal replacement modalities (including tran s- plantation) and these should be used in combination over the patient \200\231s life to a chieve the optimal patient outcomes and quality of life. It may be advantageous to use PD a s the initial mode of dialysis therapy as part of an integrated care concept: \200 The three-pore theory of movement of solutes and water This theory describes movement of so lutes and water between patient and peritoneal dialyzate. It describes the barrier between capillary blood and dia- lyzate according to three different sizes of pores in the capillar y endothelium: Large pores: \200 \200 \200 possibly interendothelial cell clefts; are few in number; allow passage of macromolecules s uch as proteins into the dialyzate. PD may be associated with better preservation of resid- ual renal function and this may acc ount for superior early outcomes on PD compared to HD. Initial PD use preserves possible si tes for vascular access, which will be available later if a transfer to HD is required. Som e evidence suggests that initial treatment with PD and subsequent transfer to HD has a supe rior outcome than treatment with a single dialysis modality. Small pores: \200 \200 \200 the gaps between endothelial cells; represent the majority of the total pore area; allow sm all solute diffusion between blood and dialyzate (removal of urea and creatinine, and absor ption of solutes from dialyzate such as glucose); account for part of \202 uid removal by ultra \201 ltration. In most cases there are no contraindications to either dialysis mode, leaving patients to c hoose according to per- sonal preference and social/lifestyle factors. Contraindications to PD include: \200 Ultra-small pores: \200 \200 \200 \200 transcellular aquaporin water channels; allow passage of water; impermeable to solutes; acc ount for 50% of water removal by the osmotic effect of dialyzate glucose. psychosocial factors preventing patient or carer per- forming PD; abdominal stomas; morbid obesity. \200 PD catheters and exit site care Permanent peritoneal access is crucial to successful PD. Ca theter-related problems are a major cause of treatment interruption and transfer to HD. PD catheters should pro- vide fast, reliable \202 ow of dialysis \202 uid in and out of th e peritoneal cavity, and avoid leaks and infection. Catheter types Most catheters are made from silicone or polyurethane. They have either one or two subcutaneous cuffs which anchor the catheter in position. There is some evidence that single-cuffed catheters have a shorte r time to the \201 rst episode of peritonitis and more exit site complications. However, they may produce equiv- alent outcomes to double-cuffed catheters, if the cuff is placed in a deep rather than super \201 cial position. There are various designs for the intraperit oneal portion of the catheter. The commonest is the straight Tenckhoff design. A coiled cat heter design provides increased size of cathe- ter tubing to separate catheter tip from the peritoneum and may provide better dialyzate \202 ow, less in \202 ow pain and Previous abdominal surgery is not usually a contraindica- tion, although in some cases intr a-abdominal adhesions may limit its success. PD may be speci \201 cally indicated in patie nts where HD is difficult due to limited options for vascular access or hemodynamic instabi lity. Anatomy and physiology of the peritoneal cavity PD involves infusion of dialysis \202 uid into the peritoneal cav- ity, with movement of solutes between the patient \200\231s blood and dialysis \202 uid across the semipermeable peritoneal membrane. The peritoneal cavit y represents the space between the abdominal viscera and abdominal wall. It is lined by the peritoneal membrane which comprises the parietal peritoneal membrane lining the abdominal wall, and vis- ceral peritoneal membrane covering the intra-abdominal viscera. The anatomic al surface area of the peritoneal membrane in adults is typically 1.7 \200\2232 m2 but effe ctive surface area var- ies with anatomical factors and peritoneal blood \202 ow. CHAPTER 13.4 Peritoneal dialysis 507 less risk of migration or omental obstruction, though evi- dence for this is inconclusive. The Toronto \200\223Western Hospital catheter has two disks near the catheter tip, perpendi cular to the catheter, which separate drainage holes from the peritoneum and viscera. A T- \202 uted catheter has a T-shaped terminal portion with grooves designed to improve dialyz ate \202 ow. A presternal catheter has a long subcutaneous tunnel, with the exit site on the chest wall in the presternal region. This may be used for patients with: \200 \200 \200 \200 The bladder should be emptied prior to surgery to reduce the risk of accidental perforation during the procedure. Antibiotic prophylaxis prior to catheter insertion may reduce the ri sk of developing exit site or wound infections postoperatively. Antibiotic choice depends o n local pat- terns of infection. There is some evidence supporting the use of vancomycin, b ut this needs to be balanced against risk of development of antibiotic resistance. Postinsertion care Postinsertion management aims to allow healing and mini- mizing any risk s of infection or leakage. Dressings should be gauze or similar to avoid pooling of dischar ge around the exit site. Dressing changes should be minimized in the initial period after i nsertion, with the initial dressing left unchanged for a week unless there is suspicion of infection. The catheter should be immobilized with tape or dressings to reduce trauma due t o movement. It is desirable to delay commencing PD for 1 \200\2233 weeks after catheter ins ertion to promote healing, although there is increasing evidence that it is safe to use low volume APD immediately after insertion when the catheter has been placed using a percutane ous technique. If early dialysis is required, this should be done with small dialyzate volu mes (1 \200\2231.5 L) in a recumbent position, to reduce intra-abdominal pressure and the r isk of leaking. A 1 year catheter survival of 80% has been suggested as a desirable cathete r outcome target. abdominal stomas; fecal incontinence; no suitable abdominal site for an exit site; severely obese subjects. The subcutaneous portion of the catheter may be straight or have a preformed bend (e.g. Swa n-necked catheter) designed to ensure a downward-pointing exit site. This can also be achie ved by appropriate tunneling of a straight catheter. Exit site infection rates are signi \201 cantly lower when the exit site is formed in a downwards direction. Catheter insertion techniques \200 \200 surgical dissection and placement under direct vision; blind placement by Tenckhoff trocar or Seldinger tech- nique; peritoneoscopic placement; laparoscopic placement. \200 There are various potential advantages and disadvantages to the different techniques, often with bene \201 ts at the expense of greater complexity. Laparoscopy allows visualization of the catheter tip posi- tion, and other procedures can be performed at the same time (e.g . suturing the catheter tip in position, division of adhesions, omentectomy and hernia repa ir) but may be accompanied by greater surgical complications. There is no clear evidence fa voring any of the options. The experience and skill of the operator inserting the catheter and procedures for planning and preparing for the proce- dure are the most important factor s affecting catheter insertion outcome. Exit site care Chronic exit site care involves regular assessment and cleaning. There are n o trials showing superiority of any particular cleansing agent or dressings. Frequent clean ing is necessary to prevent the build-up of bacteria at the exit site, and most units recom mend that this is done daily. Cleaning should also be performed if the exit site becomes di rty or wet. Patients should be taught to undertake hand washing and appropriate sterile tec hnique, to assess their exit site and to detect the presence of infection or other problems . Various cleansing agents are used, including povidone iodine, chlorhexidine solution and antibacterial liquid soap products. There is no evidence in adults for superiority of any p ar- ticular dressing and many types are used. Some patients and centers may not use a dress ing, and again there is no evidence of any adverse effect on out- comes. Antibiotic or anti bacterial preparations such as mupirocin cream may be used at the exit site (mupirocin oint ment should be avoided with polyurethane catheters due to reports of resulting damage to th e catheter). Preinsertion preparation Preparation before catheter insertion is important. The presence of hernias and abdominal w all weakness should be sought, with defects being repaired either before or at the time of catheter insertion. The position of the exit site should be determined and marked prior to surgery. Areas of pressure should be avoided (e.g. it should be above or below the patient \200\231s belt- line). Preoperative skin preparation includes washing with soap or detergen t on the morning of surgery, and if necessary, clipping of abdominal wall hair. Bowel prepa ration and avoidance of constipation is impor- tant. Patients should be started on laxative s prior to cath- eter insertion, and these should continue postoperatively. An enema on the day prior to surgery is sometimes admin- istered. Different modalities of peritoneal dialysis CAPD CAPD was the original modality allowing wi despread uptake of PD for the treatment of ESRD. It consists of manual exchanges of dialyza te, with spent dialyzate drained G. WOODROW 508 increasing the ease of performing dialysis (e.g. for patients with reduced manual dexterity or visual impairment). A major development in CAPD was the introduction of disconnect Y-sy stems which resulted in a major reduction of peritonitis. Mechanical devices exist which ai d connection, including those incorporating a UV light sterilization component to the conne ction procedure. by gravity from the peritoneal cavity and replaced by fresh \202 uid for a dwell period u ntil the next exchange. Typical CAPD regimes involve four exchanges per day. Some patients may perform fewer exchanges where clear- ances allow, and occasional patients perform \201 ve exchanges per day. Automated peritoneal dialysis (APD) An automated dialyzate cycling machine performs a numbe r of dialysis cycles overnight while the patient is asleep. A number of variants of APD hav e been developed. Peritoneal dialysis solutions Peritoneal dialysis \202 uids consist of solutions of elect rolytes, a buffer to correct metabolic acidosis and an osmotic agent to achieve net \202 uid removal (Table 13.4.1). Continuous cycling peritoneal dialysis (CCPD) This comprises a series of automated dialysis exchanges performed overnight, with a long \202 uid dwell remaining in the peritoneal ca vity during the day, which drains out at the start of next overnight session. Variations in clude having a shorter daytime dwell \200\223 either by drainage of the day exchange befor e the night, with a subsequent dry period, or by leaving the peritoneum dry after the night cycles and draining in a day dwell later in the day. Electrolytes Sodium Dialyzate sodium concentration is slightly below the nor- mal plasma ra nge. This prevents sodium diffusion into patients with hyponatremia, but achieves minimal s odium removal by diffusion. Some studies have investigated the use of lower sodium concentr ations in dialyzate to enhance sodium removal and improve BP control. Optimized cycling peritoneal dialysis (OCPD) This involves two daytime dwells, with \202 uid left in the peri- toneal cavity after the night-time cycles and an additional exchange performed at some time during the day. It is used particularly to enhance solute clearances , or to improve daytime ultra \201 ltration. Potassium Potassium is absent from dialyzate, facilitating removal from the patient. Calcium Solutions are available with varying calcium concentrations. Previously, standard s olutions had a calcium concentration of 1.75 mmol/L (greater than the ionized calcium conce n- tration in blood). This allowed correction of hypocalcemia but frequently resulted in hy percalcemia when used in conjunction with calcium-containing phosphate binders or vitamin D ana- logues to control hyperparathyroidism. The majority of patients now receive lower cal cium con- centration dialyzate (e.g. 1.25 mmol/L), with choice of solu- tion according to i ndividual biochemistry parameters. Nocturnal intermittent PD (NIPD) This involves overnight automated cycles, with subsequent dry peritoneal cavity during the day. It avoids peritoneal \202 uid during the day which may help patients with problems due to intra-abdominal pressure, but clearances are infe- r ior to other APD regimes. Tidal APD The cycler is programmed to leave a percentage of the preceding dwell in the peri toneal cavity before the next \202 uid instillation during night-time cycles, so that the perito- neal cavity never completely empties. It is useful for patients with abdominal pai n between cycles and those with frequent \200\230low drain \200\231 alarms overnight, but generally does not improve clearances, which was the original aim of its development. Correction of acidosis by dialyzate buffer content Correction of acidosis in PD is achieved by absorption of buffer contained within the dialyzate. Standard solutions contain lactate which is absorbed by the patient and undergoes hepatic conversion to bicarbo- nate, thereb y correcting the acidosis. Solutions with differing buffer content are available which may result in differing degrees of correction of acidosis or even development of alkalosis. Use of bicarbonate as a buffer had been precluded due to instability and reaction with metal i ons such as calcium and magnesium during storage. Newer twin-chamber design bags for dialyz ate have over- come this problem, with bicarbonate separated from diva- lent metal ions dur ing storage, being mixed shortly prior to infusion. To achieve serum bicarbonate levels in the normal physio- logical range, higher concentrations of buffer need to be present in the dialysis \202 uid, typically 35 \200\22340 mmol/L. Choice of PD modality A number of features determine choice of PD modality. Social and life style reasons are important. CAPD is simpler, not requiring a cycling machine or connection to it over- night. However, APD, with few or no exchanges during the day, suits many patie nts, including individuals where employment would make CAPD dif \201 cult, or where a care r performs the dialysis, since it allows freedom from under- taking dialysis exchanges duri ng the day. Lower intraperitoneal pressure in the supine position means that APD is useful where problems arise from raised intra-abdominal pressure such as hernias and \202 uid le aks. It allows larger dwell volumes to be instilled at night, which may help to obtain targ et small solute clearances. Shorter dwell periods overnight on APD enhance ultra \201 ltra tion in higher peritoneal membrane transportation status patients, due to reduced time for loss of osmotic agent during the dwell. Osmotic agents Glucose Glucose has been the standard osmotic agent in PD solu- tions, but h as several limitations. PD equipment design A variety of designs of PD equipment have been devel- oped, with the ai ms of reducing peritonitis rates and CHAPTER 13.4 Peritoneal dialysis 509 Table 13.4.1 Typical composition of peritoneal \202 uid Biocompatibility of PD \202 uid Biocompatibility of PD \202 uid can be de \201 ned as the ability to perform its role without inducing adverse effects in the patient \200\223 p articularly change in peritoneal membrane, and also immune cell dysfunction. Bioincompatibi lity of PD \202 uids is due to the toxicity of: \200 \200 \200 \200 \200 Solute Concentration Electrolyte Sodium Potassium Calcium Magnesium Chloride 132 \200\2233 mmol/L 0 ( \200\2232) mmol/L 1.0 \200\2231.75 mmol/L 0.25 \200\2230.75 mmol/L 95 \200\223102 mmol/L high glucose concentrations; high osmolality; acid pH; lactate buffer; glucose degradation products (GDPs) produced from heat sterilization of glucose solutions. Buffer 35 \200\22340 mmol/L Lactate or Lactate/bicarbonate or Bicarbonate 25/10 \200\22315 mmol/L Solutions have been developed to try to overcome these factors. Icodextrin and amino acid \202 uids have some biocompatible features. A variety of newer glucose-containing solution s are available which are low in GDPs, have neutral pH and use bicarbonate or a mixture of bicarbonate and lactate as a buffer. Neutral pH reduces symptoms of infusion pain. Long-ter m clinical bene \201 ts of these \202 uids are currently under investigation. 34 \200\22339 mmol/L Osmotic agent 1.36 \200\2233.86 g/dL Glucose (anhydrous) or Amino acids or Icodextrin 1.1 g/dL 7.5 g/dL It is absorbed from the peritoneum relatively quickly (espe- cially with higher peritoneal membrane transportation status). This leads to loss of its osmotic effectiveness and reduce d or negative ultra \201 ltration on longer dwell times. Absorbed glucose results in metab olic complications such as hyperglycemia, hyperinsulinemia, hyperlipidemia and weight gain. Exposure of the peritoneal membrane to high concentra- tions of dialyzate glucose adversel y affects peritoneal membrane structure and function. Peritoneal membrane function testing Peritoneal membrane function differs between individua ls. Variability occurs in the rate of movement of small solutes between the patient and the dialyzate. More rapid movement equates to the presence of a greater number of small pores, or effective vascular surface area (higher trans- porters). Peritoneal equilibration test (PET) This is the common test of peritoneal membrane function . Two litres of 2.27% glucose dialyzate is infused into the peritoneal cavity for a 4 h per iod. Dialyzate samples are taken after infusion, and at 2 and 4 h and analyzed for creatini ne and glucose. A blood sample is taken at 2 h. Graphs are plotted of the ratio of dialyzat e to plasma (D:P) creatinine concentrations and the ratio of dialyzate glucose concentratio ns at sample time to that at time zero. Comparison with standard curves derived from popula tion studies allows classi \201 cation of the patient \200\231s solute trans- porter statu s as: \200 \200 \200 \200 Amino acids Amino acid dialyzate solutions contain amino acids instead of glucose as the os motic agent. An exchange of 1.1% amino acid solution achieves equivalent ultrafiltration to 1.36% glucose solution and typically provides 20 \200\22325% of the patient \200\231s dai ly nitro- gen requirements by absorption of amino acids from the dialyzate. Usually only on e exchange is used per day as more can result in the development of uremia and acidosis. Icodextrin Icodextrin is a large glucose polymer and acts as a colloid osmotic agent (simil ar to large molecules such as albu- min). It acts at the small intercellular pores and is o nly slowly lost from the peritoneal cavity. Unlike glucose, it produces gradual and sustain ed ultra \201 l- tration over long dwell periods and may be more effective in achieving ul tra \201 ltration in higher transporters. It is used for a single long dwell daily \200 \223overnight in CAPD or the day dwell in APD. Being glucose free, it may avoid the adverse peritoneal membrane and metabolic effects of glucose. Some icodextrin metabolites are abso rbed. This leads to a small fall in serum sodium and increase in osmolality or osmolar gap in plasma, which is not of clinical signi \201 cance. These absorbed metabolites can cause overestimation of blood glucose by some patient glucometers (with risk of undiagnosed hypo glycemia). low; low average; high average; high. Increasing transportation state is associated with more rapid rise in dialyzate creatinine and fall in dialyzate glucose con- centrations over time. The net ultra \201 ltration at 4 h is also useful, with a value <100 mL suggesting ultra \201 ltration failure. Standardized permeability analysis (SPA) The test is similar to the PET, but: \200 uses 3 .86% glucose dialyzate; \200 has an additional sample of dialyzate extracted at 1 h; \200 dialyzate samples also analyzed for sodium. G. WOODROW 510 SPA classi \201 es transportation status in the same way as PET. The fall in dialyzate sod ium at 1 h (sodium dipping) re \202 ects aquaporin function. Net UF <400 mL at 4 h with 3. 86% glucose is a more robust de \201 nition of ultra \201 ltration failure than that with PET. Thus patients with low ultra \201 ltration will develop sodium overload and hypertension. Sodium sieving Part of the ultra \201 ltration induced by glucose is water passage without accompanying solutes, through the ultra- small pores. This water transportation without so dium is termed sodium sieving. The measured fall in dialyzate sodium at 1 h in the SPA re \202 ects sodium sieving and aquaporin function. Over a 4 h dwell, sodium concentrations wi ll equilibrate between dialyzate and plasma by diffusion. With hypertonic glucose exchanges and very short dwell times (e.g. in APD), sodium removal may be low relative to ultra \201 ltration volume (i.e. sodium sieving greater), as there is less time for dialyzate sod ium concentration to equili- brate with plasma by diffusion. Fluid balance management Maintaining normal \202 uid balance is a primary role of PD. Hyd ration depends on a balance of intake and input. Determining correct dry weight is a dif \201 cult and imprecise process. Clinical assessment can be insensitive to signi \201 cant \202 uid imbalance. Fluid overload is associated with adverse cardiovascular effects suc h as hypertension, and development of left ven- tricular hypertrophy and dysfunction. Hyper tension in the absence of other evidence of \202 uid overload may be due to \202 uid ex cess and respond to \202 uid removal, but care is necessary to avoid dehydration and loss of residual renal function in patients who still pass urine. Appropriate individualized in structions should be given to patients with regard to their \202 uid and sodium intake al low- ances. Water and sodium loss occur through dialysis and also residual renal function. Urine volume (but not clearance) may be enhanced by prescription of high doses of loop diur etics. Assessment of \202 uid overload in PD Fluid overload has many potential causes and carefu l sys- tematic assessment is essential to make the correct diag- nosis and institute correc t treatment. The majority of cases are not due to primary peritoneal membrane failure. Excessive \202 uid intake Fluid overload from excess \202 uid intake can result from: \200 thirst due to high sodium intake or hyperglycemia in poorly controlled diabetes; inadequate education or instruction about intake; nonconcordance. \200 Ultra \201 ltration with PD Dialyzate \202 uid removal is dependent on: \200 \200 \200 It is important to recognize these as they are reversible.