EXTENDED HOURS HD TREATMENTS 305 Survival Studies - RCT design, particularly when studying a therapeutic intervention such a s HD, can be challenging - as has proved to be the case for the FHN. - Recruitment of signi \201 cant numbers of dialysis patients to RCTs is often dif \201 cult. It took 10 years and millions of dollars to recruit 245 patients to the SDHD v conventional HD FHN study (20 10). However, there are large cohorts of patients undergoing various dialysis schedules and these can provide highly informative data. Table 4.2 summarizes some of the recent survival studies (USA and Canada based) with respect to different extended h ours modalities. Home haemodialysis - Extended hours treatments are associated with certain barriers (both p erceived and actual) for patients and these should be balanced against potential bene \201 ts. Some barriers may be overcome through the greater \202 exibility of a home-based the rapy. Improving the patient \200\231s understanding of the bene \201 ts of intensive treatment is fundamental to successful implementation. Meticulous attention to care of vascular access is essential for longevity and reduced infection/hospitalization. CHAPTER 4 Dialysis 306 n e e w t e b t a e r t - o t - n o i t n e t n d e r a p m o c % 2 9 1 ) 1 9 0 \200\223 1 6 0 = C % 5 9 % 5 9 . ; s i s y l a d o m e a h k w / x 3 d e d e e n n o i s s i D H C n a h t ; 1 5 1 \200\223 0 5 0 . % 3 1 d e t a e r t . g n i r u d r o r o s a w . ; d n a 5 5 0 = R H i f s a w h t a e d f 5 0 1 D H C r o k s i r a % 7 1 2 . . l a v v r u s . ) 1 9 0 \200\223 8 2 0 = C % 5 9 l a v v r u s X T L . h t i . , , s t n e i t a p M B . d e d i D H N i s u s r e v e h t l w d e t a c o s s a . l m r e p \200\223 3 1 3 4 \200\223 7 0 3 4 y t i l a t r o m e s u a c - l l a C % 5 9 i d n a , e g a . ) 7 9 0 \200\223 8 7 0 = C % 5 9 ; s r a e y - s n o s r e p n f s t n e i t a p i d e t s u d a i I % 3 7 f e h t . o e c n e d c n n o i t c u d e r % 5 2 r o 1 6 ( s t n e i t a p . i r o l a n o i t n e v n o c d e t a e r t . , , 5 7 0 = R H 7 8 0 R H f l n f h t i j ; ) p u o r g % 1 8 I . t n e m . ; p u w o . t n e i t a p . w d e r a p m o c d e t a e r t e h t s a w D H D S i s a w d e t a e r t l D H C t s u d a ( , i : 1 5 0 = R H n ( 7 2 e c n e r e f e r l l X T D d n a D H N e v i t a l u m u c , i 0 0 1 D H C . ) 7 8 0 \200\223 4 3 0 = C e g a t n v j o l a v v r u s . e c n e r e f f i r o ) 2 1 0 2 ( d e t a e r t f D H N a r a e y f i s e m o c t u O f o % 1 2 r e t f a . r e p d a h D H N D H D S , k s i r 7 8 0 = R H ; l a v r e t n i . s t n e i t a p , s i s y l a n a s t n e i t a p t n a l p s n a r T ( . s i s y l a d 8 1 f s h t a e d r a e y - 2 r e t t e b o % 3 1 r e w o . h t a e d D H N . D H C d o N h t i e h T i e h t r o e c n e d \201 n o c l i w ( f I l l a D i w o l o r h p e N m o r f , I C l l o F n a i d e M ; ) s r a e y ( o i t a r d r a z a h 5 5 9 2 8 3 8 1 . 8 1 3 3 1 5 6 4 . 3 4 . . . . . . . : : D H D S D H N : : : : : D H N D H N : D H C D H C D H C X T D : X T L d e \201 d o M p u i I , R H ; t n a l p s n a r t . s t n e m t a e r t t a e r t - o t - n o i t n e t n . s i s y l a d o m e a h y l i a d t r o h s n g i s e d y d u t S e v i t c e p s o r t e r e v i t c e p s o r t e r e v i t c e p s o r t e r e v i t c e p s o r t e r i n o i t n e t n r o n o d e v i l d e h c t a M d e h c t a M d e h c t a M d e h c t a M t a e r t - o t t r o h o c t r o h o c t r o h o c t r o h o c s i s y l a d i i , X T L i 3 3 5 , s r u o h ; t n a l p s n a r t D H D S t n a l p s n a r T v D H N : X T L D H C v D H D S D H C v D H N r o t a r a p m o C D H C v D H N s r e b m u N & 3 7 8 1 ; x e d n e v i s n e t n 8 8 3 1 2 6 0 2 5 6 3 9 6 4 7 7 7 1 8 3 3 , 3 3 5 r o n o d d e s a e c e d i : s s a m y d o b : D H D S D H N : : : : : D H N D H N : D H C D H C D H C X T D i g n v l o v n I I i , I M B , X T D , l a l , l a ; s i s y l a d o m e a h d n a h n e & r o h t u A 2 1 0 2 2 1 0 2 t e h a l l a r s e N i t e ; s i s y l a d o m e a h s e d u t S n o s c a L i y l u a P , l a , l a 9 0 0 2 2 1 0 2 r a e y i i i W t e t e l a n r u t c o n e r t n e c n l a v v r u S l a n r u t c o n e m o h i s i s y l a D s i s y l a D s i s y l a D i i i 2 4 y l i a D ) e r t n e c - n I ( l a n r u t c o N l a n r u t c o N l a n r u t c o N . y t i l a d o M s i s y l a D e l b a T i , t r o h S D H N , D H N i I EXTENDED HOURS HD TREATMENTS 307 CHAPTER 4 Dialysis 308 Other HD complications Acute complications Cramps - Very common \200\224usually towards the end of treatment. - Associated with d BP, dNa+, hypovolaemia and hypoxia. - More common wi th high UF volumes. - Management: minimize interdialytic weight gains, reduce intradialytic hypotension, increase dialysate sodium (or sodium pro \201 le b p 303). Acutely, IV saline or 50% glucose is usually effective. Massage the affected area. Regular quinine sulfate can be helpful for some. Carnitine de \201 ciency i s present in some intractable cases and supplementation can be given (usually IV post dialy sis). Nausea and vomiting - Often associated with dBP. - Management: administer an anti-emetic. O bserve patient through treatment and reassess at completion. Headache - May be s to dBP, iBP, disequilibrium syndrome or large \202 uid shifts during dialysis. Management: analgesia. Reassure. Review ultra \201 ltration volumes. Investigate if persistent. Fever - Often s to dialysis access infection, particularly CVCs (b XXX). - Patient often ri gors prior to temperature rise. - Management: 2 the patient requires a detailed clinical re view. Reassure, paracetamol, blood cultures, antibiotics according to local policy. Haemolysis - Rare, but potentially serious. - Causes: overheating of dialysate, dialysate c ontamination, impure water supply, and dialysis machine malfunction. Multiple patients may be affected. Anemia and iK+ (1 can be severe) may result. Clotting of extracorporeal circuit (blood lines and dialyser ) - Causes: inadequate anticoagulation, low blood \202 ow rates, iHb levels (high viscosity), intradialytic blood transfusion, or clotted access. Warning signs: high (or increasing) venous pressure, the blood circuit darkens, i TMP. Action: disconnect the patient from the dialysis circuit and \202 ush their dialysis access with saline. Discard the old circuit and prime a new one. Recommence dialys is. Check FBC. Next session: titrate anticoagulation carefully. If anticoagulation is contraindicated, \202 ush the dialysis circuit at hourly intervals with 50-100mL of 0.9% sodium chloride (as permitted by the patient \200\231s volume status). OTHER HD COMPLICATIONS 309 Chest pain 2 Assume cardiac in origin until proven otherwise. Reduce blood \202 ow rate t o 200mL/min and stop UF. Check observations, perform ECG and commence cardiac monitoring. A dminister GTN if prescribed. Cardiac arrest in the dialysis unit - Manage as for any non-dialysis cardiac arrest. - Cons ider iK+ and other electrolyte imbalances early. - Ask dialysis staff to wash back and disc ontinue dialysis. - Consider the impact of witnessing an arrest on nearby patients. Disequi librium (see also b p. 177) - Cause: high blood urea levels being reduced too rapidly. Usua lly occurs during \201 rst dialysis session (with high blood \202 ows). Prevention: use a dialyser with small surface area, commence blood \202 ow rate at 150-200mL/min. Limit \201 rst session to 2h. Clinical features: nausea and vomiting, agitation, headache, seizures, loss of consciousness. First use syndrome/dialyser reaction - Cause: a reaction to the dialyser membrane or dialys is lines (s to either sterilizing agents; e.g. ethylene oxide, bacteria, or endotoxins). 2 Reactions range from severe immediate anaphylaxis, through to milder delayed reactions. Clinical features: pruritus, urticaria, breathlessness, cough, nausea, vomiting, \202 ushing, rigors, 2 laryngeal oedema, collapse. Prevention: careful circuit priming with saline and initial low blood \202 ow (e.g. 100mL/min). Management: depends on severity. Summon help. Disconnect the patient immediately without wa sh back. 2 Treat severe cases as anaphylaxis. For milder cases: O2 and other supportive mea sures (e.g. antihistamines), close observation. Exclude other potential causes; e.g. drug reaction. Send blood cultures, CRP and U+E. Check dialysate visually for contamination and send sample for microbiological testing. Inform t he dialysis technical staff. Prior to next dialysis, prime the circuit with 2L saline and r e-circulate before patient connection. Accidental disconnection - Prevention: ensure all connectors are secured on needle, dialyse r and dialysis catheters. Check CVC for evidence of deterioration. - Needles should be \201 xed securely on the pat ient \200\231s arm and lines taped so that they cannot pull. Do not tape lines to beds or chairs. 2 Connections should b e visible, do not cover with clothing or blankets. Action: if a needle dislodges stop the blood pump and clamp the arterial and venous lines. Apply direct pressure to the bleeding site. Check BP and initiat e appropriate treatment for hypovolaemia as dictated by amount of blood loss and the clinic al situation. Discard all lines and prime a new dialyser and circuit. Re-site needles and secure before recommencing dialysis. Check FBC. CHAPTER 4 Dialysis 310 If a temporary or tunneled CVC becomes dislodged: stop the blood pump and clamp arterial an d venous lines. Apply a dressing to the CVC exit site and call for assistance. 1 Never atte mpt to push a dislodged CVC back into place. Discard dialysis lines. Check FBC. Send tip of catheter for culture. Air embolism - Air detection systems should prevent air from anywhere in the extracorporeal circuit being returned to the patient. If an embolism occurs, air may enter the cerebral venous circulation or the heart and lungs, depending, partly, on the patient \200\231s position. Clinical features: loss of consciousness, seizures, cough, chest discomfort, breathlessness , patchy cyanosis, d BP, shock. - Management: clamp the venous line and stop the blood pump immediately. Do not wash back. Place the patient on their left side in the Trendelenburg po sition (hopefully trapping air in the right atrium). And administer 100% O2. Summon urgent assistance. Move the patient as little as possible. Check ABGs, ECG, CXR. Blood leak - Blood leak may occur due to a breach in the dialyser membrane (which may not be visible); e.g. excessive TMP in a dialyser with a low UF co-ef \201 cien t. Management: the dialysis machine should alarm if this occurs. The patient will need to cont inue dialysis on an alternative machine. Hard water syndrome - Cause: failure of the reverse osmosis (RO) machine or the water- softening plant. Clinical features: nausea and vomiting, headache, i BP, \202 ushing. Several patients may be affected simultaneously. Management: disconnect from dialysis immediately without wash back. Check observations, sen d U+E and bone pro \201 le. No further patients should be dialysed pending a technical rev iew of the water system. OTHER HD COMPLICATIONS 311 Long-term HD complications Cardiovascular Disease - Dialysis patients are 720x more likely to die a CV death than the general population. A cardiac cause is implicated in >40% of all deaths at ESRD. The cause in dialysis patients is multifactorial and not limited to classical Framingham risk factors (b p. 198). Vascular Calci \201 cation (b p. 242) Malnutrition (b p. 260) - Causes: inadequate dialysi s dose (lkanorexia, altered taste and reduced enjoyment of food), in \202 ammation, dietar y restrictions, nutrients lost via dialysate ( 4-8g amino acids lost per session), relative catabolic state, medications (e.g. unpalatable PO4 binders), impaired absorption of nutrie nts, gastroparesis. Management: early dietetic support, nutritional supplements, parenteral nutrition (intradialytic parenteral nutrition (IDPN) is available, is convenient and does not require additional IV access \200\224 but it may not provide suf \201 cient protein and calories to meet the needs of the patient), reduce in \202 ammation (l treat i nfection, use biocompatible HD membranes, review water endotoxin levels), Aluminum toxicity (b p. 247) Dialysis related amyloidosis (DRA) (b p. 632). Withdrawal of HD (see also b p 270) This is the second most common cause of death in RRT (1 5%). Several factors may contribute to a patient and/or their physician considering withdra wal, including advancing age, frailty, presence of multiple dete- riorating co-morbidities, malignancy, chronic pain, reduced mobility, dementia, dif \201 culties with vascular acce ss, repeated hospital admissions, problems during dialysis itself (e.g. recurrent hypotensi on) and poor overall quality of life. If considering withdrawal it is important to consider the following: Reversible factors (including depression). - Assessment of patient \200\231s decision-makin g capacity. - Identi \201 cation of any advanced directives. - Full family or care involve ment. - Involvement of the patient \200\231s general practitioner and local palliative services. 2 Post withdrawal supportive care Post withdrawal, patients typically survive 1-2 weeks, de pending on residual renal function. Palliative support (at home, if possible, depend- ing o n the patient \200\231s wishes) should include: relaxation of dietary restric- tions, conti nued \202 uid restriction to avoid distressing pulmonary oedema, appropriate analgesia (s ee p. 271), management of anxiety and dyspnoea (b p. 268). Advanced directives should be encouraged in dialysis patients. CHAPTER 4 Dialysis 312 Peritoneal dialysis (PD) Introduction PD is the dialysis modality of 11% of patients worldw ide ( 7 250,000 patients). The proportion varies dramatically, however, with <5% in Japan a nd >60% in Mexico. It is generally accepted that patient survival on PD is similar, compare d to HD; in fact, these modalities should be seen as complementary, offering different bene \201 ts for individuals at different times in their dialysis history \200\224 the so-cal led \200\230 integrated dialysis care \200\231 approach. Advantages of PD \200 Preservation of residual renal function. \200 No need for vascula r access. \200 Mobility (e.g. easy to transportation dialysis to holiday destinations). \200 Patient engagement in treatment. \200 Home-based therapy \200\224 maintains patien t independence. \200 Less expensive than HD. \200 Less risk of transmission of blood-bo rne viruses. Physiology and concepts The semi-permeable dialysis membrane of the peritoneum comprises th e capillary endothelium, supporting matrix, and peritoneal mesothelium. Fluid and solutes m ove between the \202 uid- \201 lled peritoneum and blood via, what is termed, the \200 \230 three-pore model \200\231 of PD. \200 Large pores (20 \200\223 40nm) : allow macro molecules, such as proteins, to be \201 ltered between compartments (effectively via venu lar or lymphatic absorption). Small pores (4 \200\223 6nm) : responsible for the transportation of small solutes, such as sodium, potassium, urea, and creatinine. Ultrasmall pores (<0.8nm) : transportation water alone (shown to be aquaporin 1). It is possible that the small and large pores represent different functional states of a si ngle entity, depending on the density of the glycocalyx. The net movement of solutes, such as urea, will depend on: Net diffusion through small pores and convection through large pores. \200 Total volume o f dialysate infused. \200 Net \202 uid ultra \201 ltration (or, under certain circumst ances, absorption). Effective peritoneal surface area Peritoneal capillary endothelium is the predominant barri er to peritoneal solute transportation. However, at any one time, not all capillaries are e qually perfused, and not all are close enough to the mesothelium (and thus dialysate) for e ffective dialysis. The \200\230 effective peritoneal surface area \200\231 then varies (e .g. with peritonitis or changing dialysate volumes). Increasing the effective peritoneal su rface area allows faster rates of small solute transfer but not necessarily better overall dialysis \200\224 by increasing dissipation of glu- cose, ultra \201 ltration might actua lly decrease ( b p. 318). PERITONEAL DIALYSIS (PD) 313 Ultra \201 ltration (UF) The net movement of water (UF) relies on the presence of a high i ntra- peritoneal osmotic gradient (generated by glucose) or oncotic gradient (generated by glucose polymers, such as icodextrin). Any absorption of dialysate via the lymphatics (esp. if i intraperitoneal hydrostatic pres- sure from patient posture or high instilled PD volu mes) will oppose this \202 uid movement into the peritoneum. The osmotic gradient is usually generated by glucose and depends on: The glucose concentration of the dialysate. \200 A patient \200\231 s blood glucose. \200 The rate of absorption of glucose itself from PD \202 uid. UF is optimized by: \200 Ensuring normoglycaemia (relevant for diabetic patients). \200 Adjusting the tonicity of the PD solution (glucose concentration). \200 Altering the dur ation of each dialysis dwell. \200 Adjusting dwell volumes; i volume often (but not alway s) leads to i UF (see next paragraphs). As an alternative to glucose-based solutions, glucose polymers (such as icodextrin) are poo rly absorbed and slowly metabolized \200\224 these PD solutions provide a sustained oncoti c gradient over longer dwells and permit i UF, particularly for patients designated as high transporters ( b p. 316). i dwell volumes of dialysate may maintain the glucose gradient for longer, but i intraperit oneal pressure may i lymphatic return. Also, i volume might increase effective peritoneal s urface area, with more rapid absorption of glucose, lessening the glucose gradient and redu cing UF. Contraindications to PD Absolute \200 Patient or carer unable to train adequately in the technique. \200 Inguinal, umbilical, or diaphragmatic hernias (esp. pleuroperitoneal leak). \200 Ileostomy or colostomy. \200 Abdominal wall infections or intra-abdominal sepsis, e.g. active diverticular disease. Relative \200 Abdominal surgeries (adhesions). The more extensive the surgery, the more likely PD will be unsuccessful. \200 Morbid obesity (inadequate clearance). \200 H uge polycystic kidneys (insuf \201 cient intraperitoneal space). \200 Severe gastropares is (worsening vomiting). \200 Severe lung disease (diaphragmatic splinting). CHAPTER 4 Dialysis 314 Types of PD Introduction Intermittent PD was originally developed for the treatment of AKI in situ- ations where HD facilities are not available ( b p. 188). Rapid exchanges over a 2 4-hour period are repeated twice or more times a week. The peritoneal catheters used for tr eatment of AKI are often different from those used for patients with ESRD (although standar d cuffed tubes can be used). See Fig. 4.8 for types of PD. PD regimens for ESRD Continuous ambulatory PD (CAPD) Consists of 3 \200\223 5 exchanges, w ith dwell times of 4 \200\223 10 hours over 24 hours. Usually performed by the patient con necting and disconnecting the PD catheter to dialysate bags. A night-time exchange can be p erformed with a machine (such as Quantum ). Advantages of CAPD include simplicity, ease of training, and \202 exibility \200\224 the timing of exchanges can be adjusted to time s of convenience for patients (although dwells <3 hours are gener- ally discouraged). Automated PD (APD) Uses an automated machine to perform exchanges at night whilst the patie nt is asleep. The machine is usually programmed to perform at least four exchanges over 8 h ours (can be more, depending on individual tolerance). At the end of the overnight exchanges, the machine can be programmed to leave the patient \200\230 dry \200\231 for the daytime (sometimes termed night-time intermittent peritoneal dialysis, NIPD). Alternatively, the machine can per- form a \200\230 last \201 ll \200 \231 , leaving PD \202 uid in the peritoneum. Patients may then perform a further exchang e during the day (either manually or using the APD machine (sometimes termed continuous cyc ling peritoneal dialysis or CCPD). Tidal APD Has the machine programmed to only partially drain out PD \202 uid at the end o f any dwell during the nightly cycles ( \200\230 75% tidal \200\231 indicates that the ma chine will stop draining \202 uid out when 75% of the expected drain has been extracted). Although ef \201 ciency of dialysis is reduced, it is useful for patients whose sleep is disturbed through the discomfort experienced when \200\230 dry \200\231 or near dry. Assisted APD Poor strength, limited dexterity, decreased vision, or cognitive impair- ment may mean that some patients are unable to perform PD themselves, although they may potentia lly bene \201 t from a home-based therapy. In this circumstance, a family member or traine d health care assistant can assist with lifting of the bags of dialysis \202 uid and the connection/disconnection of APD. TYPES OF PD 315 Daytime dwells Night-time dwell CAPD Night dwells \200\230Wet day \200\231 or long day dwell APD Night-time dwells TIDAL APD Fig. 4.8 Types of PD. Reproduced with permission from Levy J, Morgan J, and Brown E (2004). Oxford Handbook of Dialysis , 2nd edn. Oxford: Oxford University Press. CAPD technique Disconnect, \202 ush-before- \201 ll Y-systems are now the norm. The \200\230 connectology \200\231 has been re \201 ned over the years to minimize peritoniti s risk through touch contamination. At the time of an exchange, the patient connects a Y-sh aped set with a sterile drain bag and a fresh dialysate bag. Patients are taught to make th is connection using a sterile technique, although various assist devices are available to a id patients with dexterity or visual problems (e.g. UV Flash Compact ). After the waste dialysate is drained into the empty bag, the Y-connector is \202 ushed (theoretically, \202 ushing away any contaminating bac- teria in this portion of the giving set), using a s mall volume of fresh dialysate. The remaining dialysate is infused into the patient \200 \231 s abdomen. (See Fig. 4.9) Fresh dialysate Peritoneum Catheter Connector Adapter Connecting line* Drainage bag Changed 6-monthly Fig. 4.9 \200\230 Disconnect \200\231 PD system. Reproduced with permission from Levy J, Morgan J, Brown E (2004). Oxford Handbook of Dialysis , 2nd edn. Oxford: Oxford University Press. CHAPTER 4 Dialysis 316 PD \202 uids Introduction Peritoneal dialysate needs to remove uraemic toxins, normalize electro- lytes, correct acidosis, and remove \202 uid. Ideally, \202 uid should be comp at- ible with long-term peritoneal health. \200 Volume: usually 2L but 1.5, 2.5, or 3L al so available. \200 Glucose concentration: three standard concentrations, usually about 1. 5, 2.5, and 4.0% (roughly 25g, 50g, and 75g glucose per bag). Sodium: Na + 135mmol/L (although lower concentrations may improve salt, and thus water, removal). Electrolytes: Ca 2+ ranges from 1.25 to 1.75mmol/L (and 0.25mmol/L of magnesium). Buffer: bicarbonate is not compatible for storage with calcium and magnesium in PD bags, so lactate (which is rapidly converted to bicarbonate in the liver) is widely used instead, a t 35 \200\223 40mmol/L. Newer solutions may contain: Bicarbonate alone or in combination with lactate as buffer (using bags mixed immediately pre-infusion). Icodextrin (for an oncotic gradient), rather than glucose (as an osmotic gradient), to achieve UF. Amino acids as nutritional supplement. (cid:2) May cause systemic acidosis. Biocompatible solutions PD \202 uid is sterilized through heat treatment. During this pro cess, at the pH of lactate-based glucose solutions, glucose degradation products (GDP) and advanced glycation end-products (AGE) are formed. These are believed to damage the peritone al membrane: AGE exposure cor- relates with \201 brotic change. Thus, more \200\230 bioc ompatible \200\231 solutions have been developed in an attempt to ameliorate this. One such solution depends on a twin-bag system; heat sterilization of the compartment conta ining glucose (at very low pH) generates very low levels of GDP and AGE. The second compart ment contains the acid buffer, e.g. predominantly bicarbonate in the case of Physioneal or lactate in the case of Balance . Retrospective analysis of registry data suggested patient survival was better in the group treated with biocompatible solutions, while pro- spective trials have shown that biocompati ble \202 uids may preserve native urine output volumes (although not solute clearance) as well as reduce rates of peritonitis. However, de \201 nitive evidence to support their us e (and increased cost) is lacking. Solutions that rely on molecules, other than glucose, to provide the osmotic gradient have no GDP or AGE. In this respect, they can be considered biocompatible. PD FLUIDS 317 Commercially available PD solutions (UK) \200 Baxter: Dianeal \200\224 glucose-/lactate-containing (see Table 4.3). \200 Physioneal \200\224 glucose-/bicarbonate-containing. \200 Nutrineal \200\224 contains amino acid s. Osmotically equivalent to 1.36% glucose solutions. \200 Extraneal \200\224 (7.5%). Fresenius: Staysafe \200\224 glucose/lactate in single compartment (see Table 4.2). \200 Staysaf e Balance \200\224 glucose/lactate in twin-bag system. Gambro: Gambrosol trio 10 . Table 4.3 Range of glucose concentrations commercially available in the UK Baxter Fresenius \200\230 Light \200\231 1.36% 1.5% \200\230 Medium \200\231 2.27% 2.5% \200\230 Heavy \200\231 3.36% 4.25% CHAPTER 4 Dialysis 318 Prescribing PD Introduction Aim for \200\230 adequate \200\231 dialysis with as little im pact on the patient \200\231 s social or psychological well-being as possible. Dialysis ad equacy ( b p. 328) and UF failure ( b p. 332) are discussed separately. The choice of CAPD or APD will depend on patient choice, lifestyle, and peritoneal transportation status. \200 \200\230 High \200\231 transporters allow rapid movement of urea and other small The concept of \200\230transporter \200\231 status High concentrations of glucose generate an osmotic gradient across the peritoneal membrane. During the dialysis dwell, glucose is gradually absorbed, leading to a fall in glucose concentration and dialysate osmo- lality w ithin the peritoneal cavity. The rate of glucose dissipation correlates with the rate at which cre- atinine equilibrates across the peritoneal membrane and can change over time (termed the \200\230 transportati on \200\231 status of the patient). This can be measured during a peritoneal equilibration test (PET, b p. 330). molecules across the peritoneal membrane (through small pores, b p. 330). However, they als o absorb glucose rapidly, dissipating the osmotic gradient so that net UF at the end of a d well is likely to be low. This means that a high transporter often has dif \201 culty achieving adequate small solute clearance. High transporters are particularly suitable for APD, as frequent short dwells maximize UF and total solute removal. \200\230 Low \200\231 transporters bene \201 t less from very short dwells on APD. \200 Introducing a \201 fth PD exchange may be preferable (either manually or using an autom ated machine to deliver an additional exchange at night, b p. 314). Most patients start CAPD on four \200\230 light \200\231 (1.36 \200\223 1.5% dextrose) P D bags. \200 If this fails to provide adequate UF, one exchange is changed to a higher glucose concentration bag or icodextrin containing Extraneal . Further increases in glucose concentration may be necessary to achieve adequate dialysis and UF (but see b p. 319). With long-term PD, changes in the peritoneal membrane create a tendency for low transporter s to evolve into high transporters. Following characterization of a patient \200\231 s membrane transportation characteris- ti cs (via a PET, b p. 330), computer software can be used to predict small solute clearance a nd UF. These can be particularly useful when consider- ing the necessary changes to a PD pr escription in response to a reduction in UF or solute clearance. PRESCRIBING PD 319 (cid:2) Increasing the volume of a PD exchange can increase solute clear- ance, but the con sequent rise in intraperitoneal pressure may adversely affect UF. Avoiding peritoneal glucose exposure High peritoneal glucose exposure over time (often year s) predicts the development of UF failure, and causality has been suggested. An alternative to glucose-containing dialysis solutions dialysate is ico- dextrin (Extraneal ). Icodextrin is a 20-glucose polymer with potent colloidal effects (simi- lar to albumin). Icodextrin is particularly suited to high transporters. It acts at the small intercellular pores and is only slowly lost from the peritoneal cavity, meaning that the oncotic gradient is maintained. It 6 produces gradual and sustained UF over long dwell periods (overnight d well in CAPD or daytime dwell in APD). (cid:2) Ensure diabetics have glucose-speci \201 c monitors, as icodextrin may cross-react with some glucometers, showing falsely high reading s (i.e. there is a risk of undetected hypoglycaemia). CHAPTER 4 Dialysis 320 Peritonitis Introduction Peritonitis is the major complication of PD, leading to signi \201 cant mor- bidity and mortality. Repeated episodes of peritonitis will also accelerate peritoneal membrane failure, often necessitating a transfer of modality to haemodialysis. T he incidence of peritonitis has declined from about 3 episodes/patient/year in the 1980s to 0.6 \200\223 0.7 episodes/patient/year (or 7 1 episode every 18 months), attributed to im proved patient education and better catheter technology. The disconnect \200\230 \202 us h-before- \201 ll \200\231 system has also been an important advance. In addition, \200 \230 standard care \200\231 for all PD exit sites usually includes chlorhexidine-containin g disinfectant wiping of plastic and daily application of a topical antibiotic ointment (su ch as mupirocin). Risk factors \200 T2DM, other signi \201 cant comorbibity. \200 Catheter type and impl antation technique. \200 Connection systems. \200 Nasal carriage of Staphylococcus aure us . Clinical features \200 Abdominal pain, nausea, and vomiting. \200 \200\230 Cloudy \200\231 PD ef \202 uent is very highly suggestive. \200 High fever, systemic sepsis wit h signs of an ileus, and peritonism may be present. Diagnosis \200 PD \202 uid for microscopy and Gram stain: \200 Preferably after dwell time of 4h. \200 >100 WBC/mm 3 (>50% neutrophils). Microscopy and culture of PD \202 uid (discuss with microbiology) and blood. FBC ( i WCC) and i CRP. Patients should be taught to report cloudy ef \202 uent immediately. Abdominal pain can be severe. Rapid peritoneal \202 ushing can improve symptoms, but samples from the original cloudy bag should be sent for microbiology (and rapid \202 ushing should be avoided once IP antibiotics have been administered). 3 Always consider other causes of peritonitis (e.g. perforation, stran- gulated hernia, etc .). Bacteriology \200 Gram +ve cocci: 7 45 \200\223 75% (coagulase-negative staphylococci, S . aureus ), often introduced after touch contamination of the connections or following catheter exit si te infection. Colonization of catheter bio \201 lms can lead to recurrence of peritonitis and necessitate catheter exchange. PERITONITIS 321 Gram \200\223 ve organisms: 7 15 \200\223 25% ( Pseudomonas , coliforms). Usually of bowel origin. Air in the peritoneum is common and may not indicate bowel perforation. Suspe ct perforation if mixed organisms on culture, and arrange appropriate imaging and/or explor ation. Culture negative or \200\230 no growth \200\231 : ideally, cultures should be positive in >85% cases. Higher yields may be obtained by inoculating blood culture bottles with PD \202 uid. Mycobacterial infections: 7 1%. Consider in patients with culture-negative peritonitis not responding to empiric antibiotic therapy. Smears of PD ef \202 uent are rarely positive fo r acid-fast bacilli, and diagnosis is usually made on culture (6-week) or at laparoscopy/ot omy, with con \201 rmation on peritoneal biopsy. Fungal: 7 3%. Usually Candida spp. Peritonitis is infrequent but has a poor prognosis. It often follows antibiotic therapy in at-risk (e.g. malnourished) patien ts. PD catheter removal is mandatory. Allergic peritonitis is well described and often found following prescrip- tion of icodextr in solutions (although it can occur with glucose-based solutions). In general, the elevatio n of WCC is modest, and the pro- portion of eosinophils in PD ef \202 uent may be high (>1 0%). Does not respond to antibiotics. Withdrawal of icodextrin usually helps. Complications of peritonitis \200 Relapsing peritonitis . A second episode of peritonitis with the same organism within 4 weeks of completing antibiotic therapy. Prolonged antibiotics (particular ly for relapses secondary to Staphylococcus ) are required. Recurrent peritonitis refers to a second episode of peritonitis within 4 weeks with a different organism. Antibiotic treatment failure . Consider infected, encysted \202 uid collections and frank abscess formation if no response to protocol antibiotic therapy ( l C T abdomen and pelvis). (cid:2) PD catheters will generally require removal, and a laparotom y should be considered, especially if there is a suggestion of other intra-abdominal pathol ogy. Acute and chronic UF failure . In \202 ammation l vasodilatation l i glucose absorption, d glucose gradient, and impaired UF. Repeated bouts of peritonitis can lead to long-term changes in the structure and function of the peritoneal membrane, causing chronic UF failure. \200 Malnutrition . Peritoneal protein loss through the in \202 ame d membrane can be high. Anorexia and prolonged ileus can further impact on nutritional stat us. CHAPTER 4 Dialysis 322 Peritonitis: management 2 Empiric antibiotic therapy should always be initiated in cases of de \201 nite peritonitis without waiting for the results of cultures. Many therapeutic pr otocols are available and will be in \202 uenced by local experience \200\224 discuss wit h your microbiologist. The International Society of Peritoneal Dialysis (2010) recommends: Gram +ve cover with vancomycin or a cephalosporin, plus \200 Gram \200\223 ve cover with an aminoglycoside or third-generation cephalosporin. 2 IP administration is more effective than IV. In the UK, despite concerns surrounding the development of vancomy- cin resistance, most un its utilize vancomycin-based regimens. Protocols differ from unit to unit, but, as an examp le: \200 Vancomycin 2g IP on day 1, with a further dose on days 3 \200\223 7, depending on trough vancomycin levels (aim to keep trough level >15 micrograms/mL, plus Either gentamicin 0.6mg/kg IP daily (adjusted against trough gentamicin levels on days 3 \200\223 5; (cid:2) ototoxicity) or, alternatively, to spare potential aminoglycoside toxic ity, ceftazidime 1g IP daily. Once culture result and sensitivities known: \200 If Gram +ve: continue vancomycin accord ing to levels. If S. aureus , add in rifampicin 300mg PO bd. Stop gentamicin/ceftazidime. If Gram \200\223 ve: continue ceftazidime or gentamicin. Although concerns about aminoglyc osides affecting residual renal function exist, this is not borne out by current evidence. However, if the patient still has a signi \201 cant UO (e.g. >500mL), many centers may pre fer ceftazidime over gentamicin. Stop vancomycin. If culture negative: continue both Gram +ve and Gram \200\223 ve cover, doses adjusted according to trough levels. If mixed Gram \200\223 ve growth: add in metronidazole, and consider laparotomy ( 2 suspect bowel perforation). Treat for 14 \200\223 21 days. X PD programs with a high incidence of fungal peritonitis a fter antibi- otics may consider prophylaxis with oral \202 uconazole. Mupirocin ointment administered to the catheter exit site can prevent exit site infection and, potentially, S. aureus peritonitis. 3 Every episode of PD-related peritonitis should prompt a root cause analysis and review of aseptic technique. PERITONITIS: MANAGEMENT 323 Special considerations for APD Even in the absence of peritonitis, long day dwells may be \200\230 misty \200\231 . However, because cycling times are shorter, cloudy overnight dia lysate may not occur, even in the presence of peritonitis. Moreover, in some cases, PD ef \202 uent is drained directly into a sink. This means it is very important for APD patients to recognize poten- tial symptoms of perit onitis and to perform a dwell of at least 2 hours (for visual inspection and sampling of \202 uid for M, C+S). Treatment also requires some modi \201 cations to normal APD tech- nique. One option is to convert patients to CAPD for the duration of the episode. More preferable is to give antib iotics into the last dwell on the machine (sometimes called the \201 rst ambulatory dwell ). Indications for PD catheter removal during infection \200 2 Refractory peritonitis (cloud y bags persists after 5 days of appropriate antibiotic therapy). \200 Relapsing peritonitis ( b p. 321). \200 Fungal pe ritonitis. \200 Persistent exit site or tunnel infection. \200 Potential: Multiple episodes of peritonitis in an individual patient. \200 Mycobacterial peritonitis . \200 Peritonitis caused by multiple organisms of likely enteric origin. CHAPTER 4 Dialysis 324 Other PD complications Catheter exit site infection A purulent 9 bloody discharge from a PD catheter exit site, often associ- ated with erythema and pain. Crusting alone is not indic ative of an acute exit site infection. Scoring systems have been developed, including this one recommended by the ISPD (see Table 4.4). Table 4.4 Exit site infection scoring system 0 points 1 point 2 points Swelling No Exit only; <0.5cm >0.5cm and/or tunnel Crust No <0.5cm >0.5cm Redness No <0.5cm >0.5cm Pain No Slight Severe Drainage No Serous Purulent Reproduced from Piraino, B, Bailie, GR, Bernardini, J, et al . Peritoneal dialysis-related infections recommendations: 2005 update. Perit Dial Int 2005; 25 :107. Causes \200 Usually S. aureus , Pseudomonas . \200 The use of prophylactic topical exit site ointment (e.g. mupirocin) reduces such infections. Reducing nasal carriage of S. aure us is also helpful. Treatment \200 Swab for culture, and con \201 rm PD \202 uid is clear. \200 Empiric therapy: start \202 ucloxacillin 500mg PO qds or cipro \202 oxacin 500mg PO bd if there is a history of Gram \200\223 ve infection.