Chapter 64 Hemodialysis and Peritoneal Dialysis PDF

Wayne State University Access Provided by: DiPiro’s Pharmacotherapy: A Pathophysiologic Approach, 12th Edition Chapter 64: Hemodialysis and Peritoneal Dialysis Kevin M. Sowinski; Mariann D. Churchwell KEY CONCEPTS KEY CONCEPTS Hemodialysis (HD) involves the perfusion of blood and dialysate on opposite sides of a semipermeable membrane. Solutes are removed from the blood by diffusion and convection. Excess plasma water is removed by ultrafiltration. Native arteriovenous (AV) fistulas are the preferred access for HD because of fewer complications and a longer survival rate. Venous catheters are plagued by complications such as infection and thrombosis and often deliver low blood flow rates. Adequacy of HD can be assessed by the Kt/V and urea reduction ratio (URR). The National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative minimum goal Kt/V is greater than 1.2 per treatment and the URR is greater than 65%. During HD, patients commonly experience hypotension and cramps. Other more serious complications include infection and thrombosis of the vascular access. Peritoneal dialysis (PD) involves the instillation of dialysate into the peritoneal cavity via a permanent peritoneal catheter. The peritoneal membrane lines the highly vascularized abdominal viscera and acts as the semipermeable membrane. Solutes are removed from the blood across the peritoneum via diffusion and ultrafiltration. Excess plasma water is removed via ultrafiltration created by osmotic pressure generated by various dextrose or icodextrin concentrations. Patients on PD are required to instill and drain, manually or via automated systems, several liters of fresh dialysate each day. The more exchanges completed each day results in greater solute removal. Peritonitis is a common complication of PD. Initial empiric therapy for peritonitis should include intraperitoneal antibiotics that are effective against both grampositive and gramnegative organisms. Nasal carriage of Staphylococcus aureus is associated with an increased risk of catheterrelated infections and peritonitis. Prophylaxis with a topical antimicrobial agent (mupirocin 2% or polysporin triple ointment) applied to the catheter exit site after each dialysis session can reduce catheterrelated infections. BEYOND THE BOOK BEYOND THE BOOK Visit the National Institute of Diabetes and Digestive and Kidney Diseases Website. Review the information provided in the “Hemodialysis” and “Peritoneal Dialysis” links. Watch the video titled “What Is Dialysis?”. The video provides a brief description of hemodialysis and peritoneal dialysis. This Website and video are useful to enhance student understanding of and potential treatments for endstage kidney disease. Downloaded 2024923 10:41 P Your IP is 141.217.20.120 Chapter 64: Hemodialysis and Peritoneal Dialysis, Kevin M. Sowinski; Mariann D. Churchwell Page 1 / 43 INTRODUCTION ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility The three primary treatment options for patients with endstage renal disease (ESRD) are hemodialysis (HD), peritoneal dialysis (PD), and kidney reduce catheterrelated infections. Wayne State University Access Provided by: BEYOND THE BOOK BEYOND THE BOOK Visit the National Institute of Diabetes and Digestive and Kidney Diseases Website. Review the information provided in the “Hemodialysis” and “Peritoneal Dialysis” links. Watch the video titled “What Is Dialysis?”. The video provides a brief description of hemodialysis and peritoneal dialysis. This Website and video are useful to enhance student understanding of and potential treatments for endstage kidney disease. INTRODUCTION The three primary treatment options for patients with endstage renal disease (ESRD) are hemodialysis (HD), peritoneal dialysis (PD), and kidney transplantation. The United States Renal Data System (USRDS) is the national system that “collects, analyzes, and distributes” data relating to patients with ESRD or Stage 5 chronic kidney disease (CKD) in the United States and releases these data yearly.1 According to the 2020 USRDS, at the end of 2018, there were 785,883 patients in the United States with ESRD. Of whom, 62.7% were being treated with incenter HD, 1.6% home HD, 7.6% PD, and nearly 29.7% had a functioning kidney transplant. Each of these represents an increase in the actual number of patients in each treatment modality. In 2018, 131,636 new patients started therapy for ESRD. In 2018, the prevalence of ESRD was 3.4 times greater in Black patients than White patients. In addition, the percentage of Black patients treated with incenter HD is higher in Black people than White people.1 Since 1972, the cost of treating ESRD has been covered by Medicare. In 2015, Medicare feeforservice spending for patients with ESRD was $49.2 billion, which make up approximately 7% of all Medicare claim costs. ESRD consumes a vastly disproportionate amount of resources as only 1% of Medicare patients have the disease. Although total spending for ESRD treatment continues to climb by 2.1% each year, perpatient spending (after adjusting for inflation) increased by only 1.1% in 2018.1 The prevalence of ESRD continues to climb, reflective of reduced mortality and enhanced patient care. The two primary diagnoses and underlying etiologies of kidney disease for new patients with ESRD are diabetes and hypertension.1 Chapter 62 provides a thorough discussion on the epidemiology of chronic kidney disease. This chapter serves as a primer on the principles and practice of dialysis and the complications associated with the delivery of dialysis treatments. HD and PD as the modalities most commonly employed for the management of ESRD (see Chapter 61 for a discussion of the role of renal replacement therapies in the management of acute kidney injury). The pertinent factors that should be considered before the initiation of dialysis are described. The morbidity and mortality associated with HD and PD are compared, as these considerations may influence the dialysis method chosen by patients and clinicians. The variants of HD and PD are detailed, and the multiple types of vascular and peritoneal access used with each (ie, catheters and surgical techniques) are illustrated. The concept of dialysis adequacy for each modality is briefly reviewed. Finally, the clinical presentation of common complications of both dialytic therapies is presented, along with pertinent nonpharmacologic and pharmacologic therapeutic approaches. Information resources that describe the influence of CKD on patient’s quality of life, as well as the patient perspective on dialysis and dialysisrelated therapies, are presented to highlight the human consequences of chronic disease. Morbidity and Mortality in Dialysis Morbidity in patients receiving dialysis can be assessed in a number of different ways including the number of hospitalizations per patientyear, the number of days hospitalized per patientyear, or the incidence of certain complications. The number of allcause hospital admissions, 1.58 hospitalizations per patientyear, has fallen in recent years from greater than 1.82 hospitalizations per patientyear in 2009. Trends in hospitalization demonstrate an increase in hospitalization as a consequence of infection and cardiovascular disease and a decrease in hospitalizations as a consequence of vascular access problems. Patients with a functioning kidney transplant have a lower rate of hospitalization and shorter length of stay. Hospitalizations are more frequent in women than men, and in White people than Black people, and the frequency and duration increase with age in both dialysis modality groups.1 The life expectancy of US dialysis patients is markedly lower than that of healthy subjects of the same age and sex. In dialysis patients older than 75 years, the risk of dying is greater than fourfold higher when compared to all Medicare patients not receiving dialysis.1 Adjusted allcause mortality is greater for dialysis patients compared with agematched individuals. Greater than 50% of deaths in dialysis patients are cardiovascular related. In fact, those with CKD are more likely to die from cardiovascular disease before they reach ESRD. Infections, usually related to the dialysis access, are the secondmost common cause of death in dialysis patients. Although mortality remains high in this patient population, the overall patient mortality rate Downloaded 2024923 has fallen among dialysis10:41 P since patients Your 2009. IP is 141.217.20.120 The reductions are dependent on treatment type and are smallest for HD and greatest for Chapter 64: Hemodialysis and Peritoneal Dialysis, Kevin M. Sowinski; Mariann D. Churchwell Page 2 / 43 transplantation. In the United States, only 58% ©2024 McGraw Hill. All Rights Reserved. Terms of HD ofpatients and 68% Use Privacy of PD Policy patients Notice are alive 3 years after ESRD diagnosis and initiation of dialysis Accessibility treatment.1 Wayne The life expectancy of US dialysis patients is markedly lower than that of healthy subjects of the same age and sex. In dialysis patients State older University than 75 years, the risk of dying is greater than fourfold higher when compared to all Medicare patients not receiving dialysis.1 Adjusted allcause mortality Access Provided by: is greater for dialysis patients compared with agematched individuals. Greater than 50% of deaths in dialysis patients are cardiovascular related. In fact, those with CKD are more likely to die from cardiovascular disease before they reach ESRD. Infections, usually related to the dialysis access, are the secondmost common cause of death in dialysis patients. Although mortality remains high in this patient population, the overall patient mortality rate has fallen among dialysis patients since 2009. The reductions are dependent on treatment type and are smallest for HD and greatest for transplantation. In the United States, only 58% of HD patients and 68% of PD patients are alive 3 years after ESRD diagnosis and initiation of dialysis treatment.1 In addition to high morbidity and mortality, a dialysis patient’s quality of life is generally poor. For example, restrictions caused by thrice weekly HD and/or associated treatments have been shown to impact many areas of a patient’s life. These include, but are not limited to, physical endurance, sex, employment, social life, and diet. Patients often complain of fatigue and fear of the unknown related to their disease and its progression. The PD patient or the home HD patient may have some freedom from these restrictions, but this freedom comes with its own constraints. Indications for Dialysis Since first published in 2002, The National Kidney Foundation’s Kidney Disease Outcome Quality Initiative (KDOQI) has been the primary treatment guideline for CKD. Although the Kidney Diseases: Improving Global Outcomes (KDIGO) guidelines2 published in 2013, the updated 2015 version of the KDOQI guidelines serves as the most uptodate recommendations.3 Planning for dialysis initiation should occur when a patient’s kidney function declines to CKD stage 4 (estimated glomerular filtration rate [eGFR] below 30 mL/min/1.73 m2).3 Beginning the preparation process at this point allows adequate time for proper education of the patient and family and for the creation of a suitable vascular or peritoneal access. For patients choosing HD, a permanent arteriovenous (AV) access (preferably a fistula) should be surgically created when eGFR falls below 25 mL/min/1.73 m2, serum creatinine is greater than 4 mg/dL (354 µmol/L), or 1 year prior to the anticipated need for dialysis.4 The KDIGO and KDOQI guidelines provide recommendations for referral to a specialist in kidney care services and for planning for RRT. The recommendation for timely referral is for patients with progressive CKD in whom the risk of kidney failure within 1 year is greater than 10% based on validated risk prediction tools.2 The KDIGO guidelines and commentaries addressing them agree that the primary criterion for initiation of dialysis is the patient’s clinical status, rather than a specific level of kidney function.2,5 Namely, dialysis should be initiated when one or more of the following are present: signs or symptoms of kidney failure (eg, serositis, acidbase or electrolyte abnormalities, pruritis); inability to control volume status or blood pressure; a progressive deterioration in nutritional status or cognitive impairment. The guidelines suggest that these signs and symptoms are patient specific but tend to be evident once the patient’s eGFR is in the range of 5 to 10 mL/min/1.73 m2. The guidelines specifically indicate that RRT should be initiated to manage signs and symptoms and not to treat an arbitrary kidney function measurement.2 The advantages and disadvantages of HD and PD are depicted in Tables 641 and 642, respectively. These factors, along with the patients’ concomitant diseases, personal preferences, and support environments, are the principal determinants of the dialysis mode they will receive. The timing of dialysis initiation is a compromise between maximizing patient quality of life by extending the dialysisfree period while avoiding complications that will decrease the length and quality of dialysisassisted life.3 TABLE 641 Advantages and Disadvantages of Hemodialysis Advantages 1. Higher solute clearance allows intermittent treatment. 2. Parameters of adequacy of dialysis are better defined and therefore underdialysis can be detected early. 3. Technique failure rate is low. 4. Even though intermittent heparinization is required, hemostasis parameters are better corrected with hemodialysis than peritoneal dialysis. 5. Incenter hemodialysis enables closer monitoring of the patient. Disadvantages 1. Incenter hemodialysis requires multiple visits each week to the hemodialysis center, which translates into loss of patient independence. 2. Disequilibrium, dialysisinduced hypotension, and muscle cramps are common. May require months before the patient adjusts to hemodialysis. 3. Infections in hemodialysis patients may be related to the choice of membranes, the complementactivating membranes being more deleterious. 4. Vascular access is frequently associated with infection and thrombosis. 5. Decline of residual kidney function is more rapid compared to peritoneal dialysis. Downloaded 2024923 10:41 P Your IP is 141.217.20.120 Chapter 64: Hemodialysis and Peritoneal Dialysis, Kevin M. Sowinski; Mariann D. Churchwell Page 3 / 43 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility TABLE 642 Advantages and Disadvantages of Peritoneal Dialysis signs and symptoms and not to treat an arbitrary kidney function measurement.2 The advantages and disadvantages of HD and PD are depicted in Wayne State University Tables 641 and 642, respectively. These factors, along with the patients’ concomitant diseases, personal preferences, and support environments, are Access Provided by: the principal determinants of the dialysis mode they will receive. The timing of dialysis initiation is a compromise between maximizing patient quality of life by extending the dialysisfree period while avoiding complications that will decrease the length and quality of dialysisassisted life.3 TABLE 641 Advantages and Disadvantages of Hemodialysis Advantages 1. Higher solute clearance allows intermittent treatment. 2. Parameters of adequacy of dialysis are better defined and therefore underdialysis can be detected early. 3. Technique failure rate is low. 4. Even though intermittent heparinization is required, hemostasis parameters are better corrected with hemodialysis than peritoneal dialysis. 5. Incenter hemodialysis enables closer monitoring of the patient. Disadvantages 1. Incenter hemodialysis requires multiple visits each week to the hemodialysis center, which translates into loss of patient independence. 2. Disequilibrium, dialysisinduced hypotension, and muscle cramps are common. May require months before the patient adjusts to hemodialysis. 3. Infections in hemodialysis patients may be related to the choice of membranes, the complementactivating membranes being more deleterious. 4. Vascular access is frequently associated with infection and thrombosis. 5. Decline of residual kidney function is more rapid compared to peritoneal dialysis. TABLE 642 Advantages and Disadvantages of Peritoneal Dialysis Advantages 1. Hemodynamic stability due to slow ultrafiltration rate. 2. Higher clearance of larger solutes, which may explain good clinical status in spite of lower urea clearance. 3. Better preservation of residual kidney function. 4. Convenient intraperitoneal route for administration of drugs such as antibiotics and insulin. 5. Suitable for elderly and young patients who may not tolerate hemodialysis well. 6. Freedom from the “machine” gives the patient a sense of independence (for continuous ambulatory peritoneal dialysis). 7. Less blood loss and iron deficiency, resulting in easier management of anemia or reduced requirements for erythropoietin and parenteral iron. 8. No systemic heparinization required. 9. Subcutaneous versus intravenous erythropoietin or darbepoetin may reduce overall doses and be more physiologic. Disadvantages 1. Protein and amino acid losses through peritoneum and reduced appetite from continuous glucose load and sense of abdominal fullness predispose patients to malnutrition. 2. Risk of peritonitis. 3. Catheter malfunction, and exitsite and tunnel infection. 4. Inadequate ultrafiltration and solute clearance in patients with a large body size, unless large volumes and frequent exchanges are employed. 5. Patient burnout and high rate of technique failure. 6. Risk of obesity with excessive glucose absorption. 7. Mechanical problems such as hernias, dialysate leaks, hemorrhoids, or back pain are more common than HD. 8. Extensive abdominal surgery may preclude peritoneal dialysis. 9. No convenient access for intravenous iron administration. There is considerable debate in the literature regarding the mortality differences between HD and PD.68 Most observational trials suggest that PD is associated with a survival advantage early in therapy, which wanes with increased treatment time. Prospective trials have reported conflicting results Downloaded 2024923 10:41 P Your IP is 141.217.20.120 relative Chapterto64: efficacy of one modality Hemodialysis over another. and Peritoneal If there Dialysis, is aM. Kevin survival advantage Sowinski; Mariann forD. PD, the consensus is that the advantage is early in therapy Churchwell and4may Page / 43 not with continued therapy. Welldesigned studies are extremely difficult to conduct in ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibilitythis population, and thus the question of superiority of one modality over the other is controversial and continues to be debated. Differences in outcomes may be related to a wide array of confounding factors, such as the dose of dialysis, baseline patient health status, physician bias in modality selection, patient compliance with dialysis and medication 9. No convenient access for intravenous iron administration. Wayne State University Access Provided by: There is considerable debate in the literature regarding the mortality differences between HD and PD.68 Most observational trials suggest that PD is associated with a survival advantage early in therapy, which wanes with increased treatment time. Prospective trials have reported conflicting results relative to efficacy of one modality over another. If there is a survival advantage for PD, the consensus is that the advantage is early in therapy and may not with continued therapy. Welldesigned studies are extremely difficult to conduct in this population, and thus the question of superiority of one modality over the other is controversial and continues to be debated. Differences in outcomes may be related to a wide array of confounding factors, such as the dose of dialysis, baseline patient health status, physician bias in modality selection, patient compliance with dialysis and medication therapy, or other unknown factors. For example, healthier patients tend to be directed toward PD, and factors such as age, duration of dialysis, and comorbidities play an important role in the complex relationship between patient outcomes and mortality. Without clear distinction between modalities in terms of many important outcomes, the selection of the optimal therapy for a given patient is challenging. The selection of one modality over the other should be based upon patient motivation, desire, geographic distance from an HD unit, healthcare team preference, and patient education rather than survival advantages alone. HEMODIALYSIS Although HD was first successfully used in 1940, the procedure was not used widely until the Korean War in 1952. Permanent dialysis access was developed in the 1960s, which allowed routine use of HD in patients with ESRD. Subsequent decades brought advances in dialysis technology, including the introduction of more efficient and biocompatible dialyzer membranes and safer techniques. HD is the most common type of renal replacement therapy for patients with ESRD. Principles of Hemodialysis Hemodialysis consists of the perfusion of blood and a physiologic solution on opposite sides of a semipermeable membrane. Multiple substances, such as water, urea, creatinine, potassium, uremic toxins, and drugs, move from the blood into the dialysate, by either passive diffusion or convection as the result of ultrafiltration. Diffusion is the movement of substances down a concentration gradient. The rate of diffusion depends on the difference between the concentration of the solute in blood and dialysate, solute characteristics, that is, size, water solubility, and charge, the dialyzer membrane composition, and blood and dialysate flow rates. Diffusive transport is rapid for small solutes but decreases with increasing molecular size. Other important diffusive solute transport factors include the membrane thickness, porosity, and the steric hindrance between the membrane pores and solute. Ultrafiltration is the movement of water across the dialyzer membrane because of hydrostatic or osmotic pressure and is the primary means for removal of excess fluid. Convection occurs when dissolved solutes move across a membrane with water transport. This occurs only if the pores in the dialyzer are large enough to allow them to pass along with water. Convection can be maximized by increasing the hydrostatic pressure gradient across the dialysis membrane or by using a dialyzer that is more permeable to water transport. Diffusion and convection can be controlled independently, and thus, a patient’s HD prescription can be individualized to attain the desired degree of solute and fluid removal.9 Hemodialysis Access Obtaining and maintaining access to the circulation has been a challenge for longterm use and success of HD. Permanent access to the circulation may be accomplished by several techniques, including the creation of an AV fistula, an AV graft, or by venous catheters (Fig. 641).10 As shown in Fig. 64 1, the native AV fistula is created by the anastomosis of a vein and artery (ie, the radial artery to the cephalic vein or the brachial artery to the cephalic vein). The native AV fistula has many advantages including providing the longest survival time of all bloodaccess devices and the lowest rate of complications such as infection and thrombosis. Patients with fistulas have increased survival and lower hospitalization rates compared to other HD patients. Finally, AV fistulas are the most costeffective in terms of placement and longterm maintenance. Ideally, the most distal site (the wrist) is used to construct the first fistula; it is the easiest to create, and in the case of access failure, more proximal sites on the arm are preserved for later use. Unfortunately, fistulas require at least 1 to 2 months to mature before they can be routinely utilized for dialysis. Creation of an AV fistula, however, may be difficult in elderly patients and in patients with peripheral vascular disease, which is a particularly common comorbidity in patients with diabetes. FIGURE 641 The predominant types of vascular access for chronic dialysis patients are (A) the arteriovenous fistula and (B) the synthetic arteriovenous forearm graft. The first primary arteriovenous fistula is usually created by the surgical anastomosis of the cephalic vein with the radial artery. The flow of blood from the higherpressure arterial system results in hypertrophy of the vein. The most common AV graft (depicted in green) is between the brachial artery and the basilic or cephalic vein. The flow of blood may be diminished in the radial and ulnar arteries since it preferentially flows into the low pressure graft.2024923 10:41 P Your IP is 141.217.20.120 Downloaded Chapter 64: Hemodialysis and Peritoneal Dialysis, Kevin M. Sowinski; Mariann D. Churchwell Page 5 / 43 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Wayne State The predominant types of vascular access for chronic dialysis patients are (A) the arteriovenous fistula and (B) the synthetic arteriovenous University forearm Access Provided by: graft. The first primary arteriovenous fistula is usually created by the surgical anastomosis of the cephalic vein with the radial artery. The flow of blood from the higherpressure arterial system results in hypertrophy of the vein. The most common AV graft (depicted in green) is between the brachial artery and the basilic or cephalic vein. The flow of blood may be diminished in the radial and ulnar arteries since it preferentially flows into the low pressure graft. Synthetic AV grafts, usually made of polytetrafluoroethylene, are another permanent AV access option. These grafts require 2 to 3 weeks before they can be routinely used. Their primary disadvantages are shorter survival of the graft, and higher rates of infection and thrombosis. The leastdesirable and least permanent HD access option involves the placement of a central venous catheter. Venous catheters can be placed in the femoral, subclavian, or internal jugular veins. Their main advantage is that they can be used immediately, and they are often used in small children, diabetic patients with severe vascular disease, the morbidly obese, and patients who have no viable sites for permanent AV access. Late referrals to a nephrology specialist for HD initiation and delayed placement of a more appropriate longterm access contribute to the use of venous catheters in chronic HD patients. The major problem with all venous catheters is that they have shorter survival and are more prone to infection and thrombosis than either AV grafts or fistulas. Furthermore, some catheters are not able to provide adequate blood flow rates, which may limit the deliverable dose of dialysis.10,11 Regardless, tunneled dialysis catheters are used frequently because of the ease of insertion, painfree dialysis needle placement and availability for immediate use. They are, however, associated with increased morbidity, mortality, and cost. Hemodialysis Procedures The HD system consists of an external vascular circuit through which the patient’s blood is transferred in sterile tubing to the dialyzer via a mechanical pump (Fig. 642).10 The patient’s blood then passes through the dialyzer on one side of the semipermeable membrane and is returned to the patient. The dialysate solution, which consists of purified water and electrolytes, is pumped through the dialyzer countercurrent to the flow of blood on the opposite side of the semipermeable membrane. In most cases, systemic anticoagulation (usually unfractionated heparin in the United States) is used to prevent blood clotting in the HD circuit tubing. The process of dialysis results in the removal of metabolic waste products, medications, and water and replenishment of body buffers, such as acetate and bicarbonate. FIGURE 642 In hemodialysis, the patient’s blood is pumped to the dialyzer at a rate of 300 to 600 mL/min. An anticoagulant is administered to prevent clotting in the dialyzer. The dialysate is pumped at a rate of 500 to 800 mL/min through the dialyzer countercurrent to the flow of blood. The rate of fluid removal from the patient is controlled by adjusting the pressure in the dialysate compartment. Downloaded 2024923 10:41 P Your IP is 141.217.20.120 Chapter 64: Hemodialysis and Peritoneal Dialysis, Kevin M. Sowinski; Mariann D. Churchwell Page 6 / 43 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Hemodiafiltration (HDF), another variant of traditional HD, enhances convective solute and water transport in addition to diffusive clearance to a much 10,12,13 FIGURE 642 Wayne State University In hemodialysis, the patient’s blood is pumped to the dialyzer at a rate of 300 to 600 mL/min. An anticoagulant is administered to prevent clotting in the Access Provided by: dialyzer. The dialysate is pumped at a rate of 500 to 800 mL/min through the dialyzer countercurrent to the flow of blood. The rate of fluid removal from the patient is controlled by adjusting the pressure in the dialysate compartment. Hemodiafiltration (HDF), another variant of traditional HD, enhances convective solute and water transport in addition to diffusive clearance to a much greater extent than highflux HD.10,12,13 When fluid losses exceed those desired for the patient, an IV infusion referred to as replacement fluid may be administered. HDF may improve outcomes due to its ability to remove middle molecular weight uremic solutes more efficiently than the other HD variants. HDF improves survival compared to conventional HD.13,14 Preliminary information suggests that HDF enhances clearance of phosphate, beta 2 microglobulin, and proinflammatory solutes. This procedure is not used extensively in the United States. Barriers to its use are the high cost and logistic issues associated with providing the fluid replacement needs. Dialyzers are made up of a polyurethane container containing hollow fibers which are suspended in dialysate. These hollow fibers, or dialysis membranes, are made up of three substances, unmodified cellulose (cuprophan), substituted cellulose (cellulose acetate), and cellulosynthetic materials. The permeability of these membranes varies and the membranes are divided into three general types: low flux, high efficiency, and high flux. Lowflux and highefficiency membranes have small pores that limit clearance to relatively small molecules (size less than or equal to 500 daltons) such as urea and creatinine and are utilized for less than 20% of chronic HD procedures.10 Highflux membranes are now used in the vast majority of patients because they are capable of removing highmolecularweight endogenous substances, such as β2microglobulin, and medications such as vancomycin.10 The primary reason for using highflux membranes is that clearance of water as well as low and highmolecularweight substances is much greater, allowing for shorter treatment times. To maximize the clearance capacity of highflux dialyzers, the blood flow rates should be 400 to 600 mL/min, and dialysate flow rates greater than 500 mL/min, which necessitates strict controls and active monitoring of the rate of fluid removal. Typically, these dialyzers are composed of polysulfone, polymethylmethacrylate, polyamide, cellulose triacetate, and polyacrylonitrile.10 HD is usually prescribed as three sessions per week for 3 to 5 hours/session. These sessions are usually performed in “incenter” dialysis units. This is a large time commitment for any patient undergoing HD and results in substantial loss of control over their life. Several alternatives to this type of HD have been explored in an effort to balance dialysis adequacy with patient outcomes and quality of life. These alternatives include procedures that increase dialysis frequency, enhance dialysis duration, or both.1518 Examples are as follows: (1) frequent HD (57 sessions/week), which can be frequent short (less than 3 hours/session), frequent standard (35 hours/session), or frequent long sessions (longer than 5 hours/session); (2) long HD (more than 5 hours/session given 37 times/week, which can be long thrice weekly (administered either at night or during the day), long every other night (administered at night), and long frequent (administered at night 57 nights/week). Many of these alternatives are suggested to be associated with improved survival.1618 For example, incenter, thrice weekly HD was associated with a higher risk of the composite outcome of death, left ventricular mass, and change in health composite score than incenter six times per week HD.19 Intensive dialysis has been associated with reductions in leftventricular mass and improved blood pressure control, both surrogates for improved cardiovascular outcomes, and improved phosphate removal. Lastly, and perhaps most importantly, these procedures are associated with a reduction in dialysisrelated symptoms and improved quality of life.1618 Despite the perceived advantages and more frequent use in other countries such as New Zealand and Canada, the use of home HD is uncommon, albeit increasing in use in the United States, still less than 2% of dialysis patients receiving HD care at home at the end of 2018.1 Potential obstacles to home HD include patient factors (eg, lack of selfefficacy, fear of selfcannulation, fear of catastrophic event, and fear of lack of quality care) and a lack of awareness of the availability of this type of dialysis. Finally, there are suggestions that patients receiving intensive dialysis may be at higher risk of access infections and need for vascular access procedures. Further clinical trials are needed to elucidate the role of these types of Downloaded 2024923 dialysis therapy. The 201510:41 KDOQI P guidelines Your IP isprovide 141.217.20.120 suggestions and/or recommendations that all patients be offered short frequent HD as an Chapter 64: Hemodialysis and Peritoneal Dialysis, Kevin M. Sowinski; Mariann D. Churchwell Page 7 / 43 alternative ©2024 McGraw Hill. All Rights Reserved. Terms of Use with to standard HD in addition to providing patients information Privacy about the Policy Notice potential risk associated with them.3 Accessibility Adequacy of Hemodialysis removal. Lastly, and perhaps most importantly, these procedures are associated with a reduction in dialysisrelated symptoms and improved quality of life.1618 Despite the perceived advantages and more frequent use in other countries such as New Zealand and Canada, the use of Wayne homeState HD is University uncommon, albeit increasing in use in the United States, still less than 2% of dialysis patients receiving HD care at home at the end 2018.1by: of Provided Access Potential obstacles to home HD include patient factors (eg, lack of selfefficacy, fear of selfcannulation, fear of catastrophic event, and fear of lack of quality care) and a lack of awareness of the availability of this type of dialysis. Finally, there are suggestions that patients receiving intensive dialysis may be at higher risk of access infections and need for vascular access procedures. Further clinical trials are needed to elucidate the role of these types of dialysis therapy. The 2015 KDOQI guidelines provide suggestions and/or recommendations that all patients be offered short frequent HD as an alternative to standard HD in addition to providing patients with information about the potential risk associated with them.3 Adequacy of Hemodialysis The optimal dose of HD, the patient’s dialysis prescription, is that amount of therapy above which there is no costeffective increment in the patient’s qualityadjusted life expectancy. The two primary goals of the dialysis prescription are to achieve the patient’s dry weight and the adequate removal of endogenous waste products such as urea. Dry weight is the target postdialysis weight at which the patient is normotensive and free of edema. Measurement of urea removal, while imperfect, is the typical method used to quantify dialysis adequacy. Urea removal reflects the “delivered dose” of dialysis and is utilized as the surrogate for removal of other toxins. The delivered or desired dose of dialysis in terms of solute removal can be expressed as the urea reduction ratio (URR) or the Kt/V (pronounced “KT overV”). The URR is a simple concept and is easily calculated as follows: ‒ URR=Predialysis BUN‒Postdialysis BUNPredialysis BUN×100. The URR is frequently used to measure the delivered dialysis dose; however, it does not account for the contribution of convective removal of urea. The Kt/V is a unitless index based on the dialyzer clearance of urea (K) in L/h multiplied by the duration of dialysis (t) in hours, divided by the urea distribution volume of the patient (V) in liters.10 The Kt/V is thus the fraction of the patient’s total body water that is cleared of urea during a dialysis session. Urea kinetic modeling, using computer software, is the optimal means to calculate the Kt/V.10 An indepth discussion of the pros and cons of various methods of calculating and interpreting Kt/V is beyond the scope of this chapter. The reader is referred to other sources for more indepth information.10 For patients who receive thrice weekly HD, KDOQI recommends that the minimally adequate delivered dose of dialysis is a Kt/V of 1.2 (equivalent to an average URR of 65%).3 To achieve this goal, the recommended target prescribed Kt/V is 1.4 (equivalent to an average URR of 70%).3 For patients who receive HD on a schedule other than thrice weekly, the KDOQI suggests a target standard Kt/V of 2.3 volumes/week with a minimum delivered dose of 2.1. Lower doses of dialysis treatment are thought to be associated with increased morbidity and mortality. Many nephrologists believe that even greater doses of dialysis would have positive outcomes in dialysis patients, and so the average dose of dialysis has been increasing in the United States although the evidence for this is not strong. The results of HEMO study, a prospective, randomized trial that assigned patients to either standard (Kt/V = 1.25) or highdose (Kt/V = 1.65) dialysis with highflux or lowflux membranes, revealed that the risk of death was similar in both the standard and high dose therapy and the low and highflux groups. Thus, there is no benefit in increasing the dose of dialysis above the current recommendations. The HEMO study only enrolled patients who were on traditional thriceweekly dialysis, so the applicability of these findings to patients on more intensive regimens such as daily or nocturnal HD regimens remains to be determined. However, intensive HD regimens may result in better control of blood pressure, anemia, phosphate, and sleep apnea.15 In those relatively few patients who are below the adequacy goal, the deficiency may be related to patient compliance with the dialysis prescription (ie, ending dialysis early) or low blood flow rates caused by access stenosis or thrombosis, or due to the use of catheters. Adequate dialysis may not be achieved in some patients despite compliance and sufficient blood flow. For these patients, there are two options to increase urea clearance: use a larger membrane or increase the treatment time. Complications of Hemodialysis HD is a lifeextending therapy for patients with kidney failure but HD is associated with short and longterm complications. Complications associated with HD can decrease the efffectiveness of therapy, quality of life and life expectancy. This chapter discusses complications that occur during an HD session (intradialytic) and complications associated with vascular access. Hemodialysis Procedure Complications The most common complications that occur during HD include hypotension, hypertension, cramps, nausea and vomiting, headache, chest pain, back pain, and fever or chills.20 Table 643 lists these complications and their etiology and predisposing factors. TABLE 643 Common Complications During Hemodialysis Downloaded 2024923 10:41 P Your IP is 141.217.20.120 Chapter 64: Hemodialysis and Peritoneal Dialysis, Kevin M. Sowinski; Mariann D. Churchwell Page 8 / 43 ©2024 McGraw Hill. All Rights Reserved.Incidence Terms of(%) Use Privacy Policy Notice Accessibility Etiology/Predisposing Factors Hypotension 2030 Hypovolemia and excessive ultrafiltration Wayne State University The most common complications that occur during HD include hypotension, hypertension, cramps, nausea and vomiting, headache, chest pain, back Access Provided by: pain, and fever or chills.20 Table 643 lists these complications and their etiology and predisposing factors. TABLE 643 Common Complications During Hemodialysis Incidence (%) Etiology/Predisposing Factors Hypotension 2030 Hypovolemia and excessive ultrafiltration Antihypertensive medications prior to dialysis Target dry weight too low Diastolic dysfunction Autonomic dysfunction Low calcium and sodium in dialysate High dialysate temperature Meal ingestion prior to or during dialysis Hypertension 515 Plasma sodium concentration Intravascular volume Dialytic removal of antihypertensive medications Activation of the Renin Angiotensin Aldosterone system Cramps 520 Muscle hypoperfusion due to ultrafiltration and hypovolemia Hypotension Electrolyte imbalance Acid–base imbalance Nausea and vomiting 515 Hypotension Dialyzer reaction Headache 5 Disequilibrium syndrome Caffeine withdrawal due to dialysis removal Chest and back pain 25 Unknown Pruritus 5 Inadequate dialysis Skin dryness Secondary hyperparathyroidism Downloaded 2024923 10:41 P Your IP is 141.217.20.120 Abnormal skin concentrations of electrolytes Chapter 64: Hemodialysis and Peritoneal Dialysis, Kevin M. Sowinski; Mariann D. Churchwell Page 9 / 43 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Histamine Notice Accessibility release Mast cell proliferation Wayne State University Skin dryness Access Provided by: Secondary hyperparathyroidism Abnormal skin concentrations of electrolytes Histamine release Mast cell proliferation Fever and chills serum sodium Lower dialysate temperatures Bicarbonate dialysate Avoid food before or during hemodialysis Pharmacologic Midodrine 2.510 mg orally 30 minutes before hemodialysis (start at 2.5 mg and titrate) Droxidopa 100600 mg orally 1 hour before hemodialysis (start at 100 mg and titrate up to 600 mg) Other options (limited evidence): Levocarnitine 20 mg/kg IV after hemodialysis Sertraline 50100 mg daily Fludrocortisone 0.1 mg before hemodialysis DDAVP 12 intranasal sprays (150 µg/spray) Counsel patients Administer antihypertensive medications in the evening or after hemodialysis Minimize intradialytic weight gain by decreasing salt content in their diet Intradialytic or postHD hypertension can occur in 5% to 15% of patients receiving HD and may increase postHD fatigue and the risk of cardiovascular and allcause mortality.27 Underlying causes include, not achieving postHD dry weight goal, overestimation of dry weight, dialytic removal of antihypertensive medications, or the activation of the reninangiotensin system secondary to abrupt hypovolemia.28 Skeletal muscle cramps complicate 5% to 20% of HD treatments. Although the pathogenesis of cramps is multifactorial, plasma volume contraction and decreased muscle perfusion caused by excessive ultrafiltration are frequently the initiating events.10 Pruritus may increase in severity during the Downloaded 2024923 10:41 P Your IP is 141.217.20.120 HD treatment Chapter and is a complication 64: Hemodialysis of CKD.Dialysis, and Peritoneal The management Kevin M. of pruritusMariann Sowinski; is discussed in Chapter 63. D. Churchwell Page 11 / 43 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Vascular Access Complications Intradialytic or postHD hypertension can occur in 5% to 15% of patients receiving HD and may increase postHD fatigue and the risk of cardiovascular Wayne and allcause mortality.27 Underlying causes include, not achieving postHD dry weight goal, overestimation of dry weight, dialytic State removal ofUniversity Access Provided by: antihypertensive medications, or the activation of the reninangiotensin system secondary to abrupt hypovolemia.28 Skeletal muscle cramps complicate 5% to 20% of HD treatments. Although the pathogenesis of cramps is multifactorial, plasma volume contraction and decreased muscle perfusion caused by excessive ultrafiltration are frequently the initiating events.10 Pruritus may increase in severity during the HD treatment and is a complication of CKD. The management of pruritus is discussed in Chapter 63. Vascular Access Complications The most common vascular access complications in patients receiving HD are thrombosis and infection. The highest occurrence of complications is found in patients with a central venous catheter (CVC) compared with those with an AV graft or AV fistula.10,29 A majority of patients initiate HD with a CVC (80.8%), and of those patients 65.2% did so without a maturing AV fistula or graft. In prevalent patients receiving HD, 82.4% had either an AV fistula or graft.1 The maintenance of vascular access patency is critical for patients receiving HD. Predisposing factors are often described using Virchow’s triad of blood flow stasis, hypercoagulability, and endothelial injury. An aneurysm or stenosis of an AV fistula, graft or surrounding vasculature generally require a surgical intervention. Several pharmacologic therapies have been evaluated to maintain vascular access patency but results are conflicting.30 Vascular access stenosis can contribute to decreases in blood flow (blood flow 10 mm Hg either during or postHD may require a change in the delivery of an HD session, antihypertensive medications or Overall, the use of DDAVP increased postHD blood pressure and decreased the incidence of IDH.48 These medications have limited clinical evidence Wayne State University and should be used with caution in patients receiving HD with IDH. Overall, the best evidence for an oral pharmacological treatment of IDH is with Access Provided by: midodrine. Alternative agents have been studied but the evidence is limited for each of these agents as many of the studies had a small sample size and did not have a placebo control. Hypertension An elevated blood pressure in a patient prior to receiving HD is often attributed to volume expansion. A decline in blood pressure is expected during and after HD and improves survival, but a dramatic increase or decrease in blood pressure during or after HD decreases overall survival.49 An increase in blood pressure of >10 mm Hg either during or postHD may require a change in the delivery of an HD session, antihypertensive medications or adjustments to the timing of medication administration.28 Although the underlying mechanism may be multifactorial, antihypertensive medication dialyzability could play a role in HDrelated increases in blood pressure.50 HD enhances the clearance of metoprolol, atenolol, and angiotensin converting enzyme inhibitors (ACEIs). An angiotensin receptor blocker (ARB), carvedilol or amlodipine is minimally removed during HD and may be an option in patients experiencing a rise in blood pressure during or postHD. Antihypertensive medication regimes need to be individualized based on a patient’s comorbid conditions and risk of HDrelated blood pressure changes. A retrospective cohort examined patients with heart failure receiving HD and either taking a daily betablocker (carvedilol, bisoprolol, or metoprolol CR/XL) or those patients not taking a daily betablocker. Patients receiving either carvedilol, bisoprolol, or metoprolol had lower allcause mortality at 5 years.51 However, in patients at risk of IDH, a large retrospective study found an increased rate of IDH and risk of allcause mortality in patients taking carvedilol compared to metoprolol.52 Initiation of any antihypertensive medication in patients at highrisk should be followed with close monitoring pre and postHD in addition to during HD. One small study found an improvement in patients with intradialytic hypertension when lowdose carvedilol (6.25 mg twice daily) was initiated and titrated as tolerated. Muscle Cramps The cause of muscle cramps in patient receiving HD may be multifactorial and include aggressive removal of fluid and electrolyte imbalances. Nonpharmacologic interventions related to dialytic therapy may help alleviate muscle cramps. These measures include adjusting the ultrafiltration rate to avoid hypotension, volume contraction, or hypoosmolality. Other methods to reduce muscle cramps, including compression devices, moist heat, massage, exercise, stretching, or muscle flexing, should be considered first to minimize adverse consequences (Table 645).10,23 TABLE 645 Management of Cramps Acute treatment Give 100200 mL bolus of intravenous normal saline Give 1020 mL of intravenous hypertonic saline (23.4%) over 35 minutes Give 50 mL of 50% intravenous glucose (nondiabetic patients) Prevention Nonpharmacologic Accurately set “dry weight” Keep dialysate sodium >serum sodium Stretching exercises, massage, flexing, or compression devices Pharmacologic Vitamin E 400 international units at bedtime Quinine sulfate 324 mg daily (secondline therapy) Pharmacologic interventions include increasing the magnesium concentration in dialysate, supplementation with oral magnesium, vitamin E, or vitamin C or a trial of gabapentin or quinine. Vitamin E and quinine can reduce the incidence of muscle cramps.53,54 Quinine is associated with temporary sight and hearing disturbances, thrombocytopenia, or gastrointestinal distress. Quinine is FDAapproved for malaria only and the FDA has warned against the offlabel use of quinine for muscle cramps.55 In a small prospective Downloaded study 2024923 of patients 10:41 P Yourreceiving HD with at least six episodes of intradialytic muscle cramps in the 30 days prior to enrollment, patients IP is 141.217.20.120 Chapter received 64: Hemodialysis either and Peritoneal placebo or gabapentin Dialysis, 300 mg KevinaM. three times Sowinski; week Mariann administered D. Churchwell 5 minutes prior to HD. After 1 month, patients experiencedPage less 14 / 43 ©2024 McGraw Hill. All Rights Reserved. Terms 56 of Use Privacy Policy Notice Accessibility episodes of muscle cramps in the treatment arm. Both vitamin E (400 mg) and vitamin C (250 mg) reduced the frequency of cramps in patients receiving dialysis.57 The combination of these two drugs had an additive effect. Although these data further strengthen the case for vitamin E and Pharmacologic interventions include increasing the magnesium concentration in dialysate, supplementation with oral magnesium, vitamin E, or Wayne State University vitamin C or a trial of gabapentin or quinine. Vitamin E and quinine can reduce the incidence of muscle cramps.53,54 Quinine is associated with Access Provided by: temporary sight and hearing disturbances, thrombocytopenia, or gastrointestinal distress. Quinine is FDAapproved for malaria only and the FDA has warned against the offlabel use of quinine for muscle cramps.55 In a small prospective study of patients receiving HD with at least six episodes of intradialytic muscle cramps in the 30 days prior to enrollment, patients received either placebo or gabapentin 300 mg three times a week administered 5 minutes prior to HD. After 1 month, patients experienced less episodes of muscle cramps in the treatment arm.56 Both vitamin E (400 mg) and vitamin C (250 mg) reduced the frequency of cramps in patients receiving dialysis.57 The combination of these two drugs had an additive effect. Although these data further strengthen the case for vitamin E and vitamin C, longterm therapy must be used with caution. Doses of vitamin E greater than 400 U/day have been reported to increase mortality and high doses of vitamin C increase the risk of oxalate accumulation and developing oxalosis. Pharmacologic interventions to diminish muscle cramps are limited and vitamin E has the strongest evidencebased efficacy and safety profile. Vascular Access Thrombosis Vascular access patency is key to maintaining effective dialytic therapy for patients receiving HD. Multiple pharmacologic agents have been studied including oral and intravenous anticoagulant and antiplatelet agents and intravenous thrombolytic agents to assess their clinical value. The efficacy of oral antiplatelet therapy for the prevention of vascular access thrombosis has not been well established. Studies in patient receiving HD have shown an increased risk of bleeding with minimal benefit in maintaining vascular access patency. Therapy with antiplatelet agents should be individualized based on the patient’s risk factors and comorbidities.30 A metaanalysis of randomized controlled trials for the prevention of vascular access failure identified nine trials assessing antiplatelet therapy and dialysis access patency in AV fistula (n = 6) and graft (n = 3).58 This analysis found a lower rate of thrombosis or patency failure in patients with an AV fistula taking either aspirin, ticlopidine, or clopidogrel for up to 6 months (RR, 0.49; 95% CI, 0.300.81). In patients with an AV graft, there was no benefit with any of these antiplatelet therapies (RR, 0.94; 95% CI, 0.801.10). A posthoc analysis identified that patients receiving aspirin prior to AV graft placement had improved graft patency but not graft survival.59 An observational study in patients undergoing surgery for the creation of an HDrelated vascular access examined primary patency at 12 months and compared antiplatelet therapy (aspirin or a platelet adenosine diphosphate receptor [P2Y12] inhibitor) versus no antiplatelet therapy. There was no difference in primary patency between antiplatelet versus no antiplatelet therapy in patients receiving an AV fistula. There was a significant increase in primary patency in patients receiving an AV graft and antiplatelet therapy (P = 0.04). In hospital bleeding was assessed but longterm bleeding and bleeding risk were not reported and these results need to be interpreted with caution as previous studies have found an increased risk of bleeding with P2Y12 inhibitors.60 Overall, the studies have reported conflicting results, and patients with an AV graft taking antiplatelet therapy prior to a procedure may have some benefit but initiating aspirin postsurgery may increase the risk of thrombosis. The use of anticoagulation to maintain vascular access patency remains controversial with some trials suggesting an increase in morbidity and mortality.61,62 Patients receiving HD generally require a lower dose of anticoagulation and are at a much higher risk of a major hemorrhagic event.61,62 An examination of patients receiving a new AV fistula or graft from 2011 to 2019 were identified in the Vascular Quality Initiative database. Patients received either no anticoagulation or anticoagulation (warfarin, dabigatran, or rivaroxaban) postprocedure. At 6 months post procedure patients who received anticoagulation had a higher rate of wound infections (3.8% vs 2.3%) and a lower rate of access patency (84.3% vs 85.7%) compared to patients receiving no anticoagulation.63 The decision to initiate anticoagulation in patients receiving HD should be individualized for a patient’s comorbid diseases and bleeding risk. The effect of fish oil supplementation, a combination of eicosapentaenoic acid (EPA) 400 mg and docosahexaenoic acid (DHA) 200 mg, on AV graft patency for 12 months after graft placement revealed that the loss of patency was lower in the fish oil (48%) than the placebo (62%). Fish oil thus may benefit some patients with an AV graft since time to thrombus was longer and thrombus rates were about half that of placebo.64 Based on this evidence, the KDOQI guidelines are suggesting the use of fish oil supplements in patients with a newly created AV graft to reduce morbidity and the frequency of thrombosis. The guidelines state there is inadequate evidence to recommend fish oil supplementation in patients with an AV graft to prolong graft patency. Fish oil supplements were also studied in patients scheduled to receive surgery for an AV fistula. Patients were randomized to receive either placebo (olive oil) or fish oil 4 g/day (EPA 46% and DHA 38%) starting the day prior to surgery for 12 weeks. The patients receiving aspirin 100 mg/day were similar in each study arm. The AV fistula failure rate during the first 12 months postsurgery was 47% in both groups with similar rates of thrombus formation in patients receiving fish oil versus placebo (22% vs 23%) including those receiving aspirin or placebo (20% vs 18%).65 The KDOQI guidelines do not recommend the use of fish oil supplementation to prevent flow dysfunction in an AV fistula.30 Catheterlocking Downloaded solutions 2024923 havePbeen 10:41 Yourassociated with a reduction in catheter thrombosis. The instillation of unfractionated heparin (UFH), IP is 141.217.20.120 recombinant Chapter tissue plasminogen 64: Hemodialysis activator (rtPA), and Peritoneal Dialysis,orKevin sodium M.citrate in each Sowinski; HD catheter Mariann lumen between HD sessions have demonstrated efficacy D. Churchwell Page 15in/ 43 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility 66 reducing catheter thrombosis. Sodium citrate 4% is as effective as UFH but may offer a better safety profile at a reduced cost. A systematic review and metaanalysis of randomized controlled trials of HD locking solutions containing UFH and citrate found significantly fewer bleeding episodes in the 67 (olive oil) or fish oil 4 g/day (EPA 46% and DHA 38%) starting the day prior to surgery for 12 weeks. The patients receiving aspirin 100 mg/day were similar in each study arm. The AV fistula failure rate during the first 12 months postsurgery was 47% in both groups with similarWayne rates ofState University thrombus Access Provided by: formation in patients receiving fish oil versus placebo (22% vs 23%) including those receiving aspirin or placebo (20% vs 18%).65 The KDOQI guidelines do not recommend the use of fish oil supplementation to prevent flow dysfunction in an AV fistula.30 Catheterlocking solutions have been associated with a reduction in catheter thrombosis. The instillation of unfractionated heparin (UFH), recombinant tissue plasminogen activator (rtPA), or sodium citrate in each HD catheter lumen between HD sessions have demonstrated efficacy in reducing catheter thrombosis. Sodium citrate 4% is as effective as UFH but may offer a better safety profile at a reduced cost.66 A systematic review and metaanalysis of randomized controlled trials of HD locking solutions containing UFH and citrate found significantly fewer bleeding episodes in the patients receiving citrate. The analysis found no difference between citrate and UFH for catheter patency.67 Unfractionated heparin 5,000 units/mL twice weekly and recombinant tissue plasminogen activator (rtPA) 1 mg/catheter lumen once weekly were instilled in patients receiving HD with a CVC. Alternating the catheterlocking solution regimen with rtPA significantly decreased catheter malfunction compared to the patients receiving UFH only for catheter patency. The cost of catheter replacement and hospitalization may offset the cost of once weekly administration of rtPA. Based on their medical history, patients at high risk for catheter malfunction or bacteremia (n = 373) received postHD catheterlocking solutions of rt PA (1 mg/lumen) once weekly plus routine care with either sodium citrate 4% or UFH on the remaining postHD sessions. Catheter malfunction significantly declined with weekly rtPA treatment from 18.4 to 10.1 days/1,000 catheter days and the episodes of bacteremia declined from 0.28 to 0.25/1,000 catheter days. Most patients (96%) received routine care with sodium citrate 4%, which may account for the small decline in bacteremia episodes. Overall, the increased cost of weekly rtPA was not offset by the decline in catheter malfunction or bacteremia.68 Taurolidinebased catheter solutions were examined in patients with a tunneled catheter (n = 177). Patients were randomized to receive either taurolidine citrate with urokinase (Tauro/U) once weekly plus taurolidine citrate with heparin (Tauro/Hep) twice a week (n = 84) or Tauro/Hep (n = 93) three times a week. During the 6 month study, no patients in the Tauro/U group required catheter replacement compared with three patients in the Tauro/Hep group. The use of rtPA to restore catheter patency occurred at a lower rate with Tauro/U (n = 5) compared to Taurolock/Hep (n = 12). This was a shortterm study; therefore, it is difficult to extrapolate longterm benefits until further studies are completed.69 A catheter locking solution of taurolidine (1.35%), citrate (3.5%), and heparin (1,000 units) is seeking FDA approval for the prevention of CRBSI in patients receiving HD. A prospective cohort study in patients (n = 451) receiving HD with a tunneled or nontunneled catheter and either sodium bicarbonate 7.5% or 8.4%, or 0.9% normal saline as a catheter locking solution. Patients receiving the sodium bicarbonate locking solution had a significantly lower rate of thrombosis and blood stream infections compared the 0.9% NaCl group (P < 0.0001).70 UFH and citrate (concentrations less than 5%) are listed by KDOQI as catheter locking solution options. The KDOQI guidelines consider citrate and UFH to have similar efficacy for survival and maintaining patency. Catheter locking solutions to prevent infections with taurolidine, tinzaparin, or gentamicin are not recommended by KDOQI based on the current evidence. In patients with an indwelling catheter at high risk for a catheterrelated blood stream infection (CRBSI) defined as patients with multiple prior CRBSIs and/or an S. aureus nasal carriers may benefit from prophylactic instillation of rtPA once weekly.30 The therapeutic alternatives for the management of venous catheter thrombosis are listed in Table 646. If a catheterrelated thrombus is suspected, a forced saline flush should be used to clear the catheter, followed by installation of a thrombolytic. A number of studies have been published using alteplase and reteplase and initial reperfusion rates for both were approximately 90%, respectively.71 The efficacy, safety, and cost of alteplase, reteplase, and tenecteplase were compared, and venous catheter clearance rates were similar with reteplase (88% ± 4%) and alteplase (81% ± 37%), but markedly lower with tenecteplase (41% ± 5%).71 The cost analysis favored the use of reteplase, however, to attain these savings, reteplase must be batchprepared. Reteplase is not FDAapproved for this indication which may limit it use.71 The instillation of a tissue plasminogen activator once weekly in a catheter may reduce catheter dysfunction and could be considered in select patients at a high risk of thrombosis.30 TABLE 646 Management of Hemodialysis Catheter Thrombosis Nonpharmacologic therapy Forced saline flush Referral to vascular surgeon Pharmacologic therapy DownloadedAlteplase: instill10:41 2024923 2 mg/2PmL/catheter Your IP islumen port; attempt to aspirate after 30 minutes; may repeat dose if catheter function is not restored in 120 141.217.20.120 Chapter 64:minutes; Hemodialysis and Peritoneal Dialysis, Kevin longer durations of instillation have been M. Sowinski; Mariann D. Churchwell used. Page 16 / 43 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Reteplase: instill 0.4 U/0.4 mL in each lumen, attempt to aspirate after 2030 minutes, may repeat if necessary. reteplase, and tenecteplase were compared, and venous catheter clearance rates were similar with reteplase (88% ± 4%) and alteplase (81% ± 37%), Wayne but markedly lower with tenecteplase (41% ± 5%).71 The cost analysis favored the use of reteplase, however, to attain these savings, State University reteplase must be Access Provided by: batchprepared. Reteplase is not FDAapproved for this indication which may limit it use.71 The instillation of a tissue plasminogen activator once weekly in a catheter may reduce catheter dysfunction and could be considered in select patients at a high risk of thrombosis.30 TABLE 646 Management of Hemodialysis Catheter Thrombosis Nonpharmacologic therapy Forced saline flush Referral to vascular surgeon Pharmacologic therapy Alteplase: instill 2 mg/2 mL/catheter lumen port; attempt to aspirate after 30 minutes; may repeat dose if catheter function is not restored in 120 minutes; longer durations of instillation have been used. Reteplase: instill 0.4 U/0.4 mL in each lumen, attempt to aspirate after 2030 minutes, may repeat if necessary. Alteplase is available commercially and is the only agent that is FDAapproved, for venous catheter clearance, and is administered as a short dwell for 30 to 60 minutes, as a long dwell, or left in the catheter between treatments. No difference in patency rates between the short or long dwells has been demonstrated. Alteplase has also been given as a short infusion of 2 mg/h over 4 hours for a blocked catheter and 1 mg/h over 4 hours for sluggish blood flow. Infusions may theoretically be more efficacious than the dwell technique because the thrombus is only exposed to the thrombolytic at the tip of the catheter. Another consideration is dwell versus push techniques for thrombolytic therapy, with recent data indicating that a push protocol with alteplase is as effective and safe for managing HD catheter dysfunction and might be more practical than a dwell technique.72 A retrospective singlecenter study evaluated the dose of alteplase in patients receiving HD with a catheter requiring a thrombolytic for catheter dysfunction. Patients during the first 3 years of the study received alteplase 2 mg/lumen and during the last 3 years received alteplase 1 mg/lumen. Dwell time was 30 minutes and independent of dose. Patients receiving alteplase 2 mg dose had a lower rate of catheter removal due to dysfunction (10.2% vs 19.4%). Overall, the instillation of alteplase 2 mg compared to 1 mg resulted in a 89.2% success rate at resolving catheter occlusions versus 80.6% (P = 0.036).73 Infection Patients who develop a fever during dialysis should immediately be evaluated for infection; blood cultures should be collected prior to the administration of any antibiotics. When an AV fistula infection is suspected, empiric broadspectrum antimicrobial therapy must be initiated usually with vancomycin plus an aminoglycoside or extended spectrum betalactamase inhibitor. Antimicrobial therapy, if the infection is confirmed, should continue for a total of 6 weeks and should be tailored to culture sensitivities. Unfortunately, a suspected infection in an AV graft may require a surgical procedure to remove the infected graft material in addition to antimicrobial therapy. A suspected infection in a temporary catheter may warrant catheter removal and a culture of the catheter tip should be obtained.31,74 Catheterrelated infections are more common than infections of an AV fistula or graft; therefore, preventative care approaches are paramount. Preventative care includes minimizing the use and duration of catheters, proper disinfection and sterile technique, and the use of an antimicrobial ointment at the exit site (mupirocin 2%, povidoneiodine).75 Dialysis unit protocols that employ universal precautions, limit the manipulation of the catheter, and utilize an antiseptic wash (tincture of iodine, chlorhexidine, etc.) for skin preparation, and the use of facemasks by the patient and caregiver can significantly reduce the incidence of catheterrelated bacteremia.31,74,76 Topical application of 2% mupirocin ointment to a tunneled HD catheter exit site after each HD session can increase infectionfree days. Current recommendations are to apply either povidoneiodine antiseptic ointment or polysporin triple ointment (bacitracin/gramicidin/polymyxin B) to the exit site after each HD session. Longterm monitoring of infection rates of patients receiving HD with a catheter did not reveal an increase in antibiotic resistance with a onceaweek application of a topical polysporin triple ointment to catheter exit sites.77 The Infectious Disease Society of America (IDSA) and KDOQI guidelines address catheter care and the diagnosis and management of catheterrelated Downloaded 2024923 10:41 P Your IP is 141.217.20.120 infections. 30,76 Peripheral blood draws, although recommended by IDSA, are often avoided in patients receiving HD to protect potential or future HD Chapter 64: Hemodialysis and Peritoneal Dialysis, Kevin M. Sowinski; Mariann D. Churchwell Page 17 / 43 ©2024 McGraw vascular Hill. All access sites. Rights Blood Reserved. cultures Termsobtained are generally of Use from Privacy thePolicy blood tubing Noticeconnecting Accessibility the catheter to the HD machine. A prospective study examined blood cultures (n = 178) obtained from patients receiving HD suspected of a CRBSI. The blood cultures obtained from the HD circuit and venous catheter hub were the most sensitive, specific, and accurate for diagnosing CRBSI compared to blood cultures taken from a peripheral vein and bacteremia.31,74,76 Topical application of 2% mupirocin ointment to a tunneled HD catheter exit site after each HD session can increase infectionfree Wayne State University days. Current recommendations are to apply either povidoneiodine antiseptic ointment or polysporin triple ointment Access Provided by: (bacitracin/gramicidin/polymyxin B) to the exit site after each HD session. Longterm monitoring of infection rates of patients receiving HD with a catheter did not reveal an increase in antibiotic resistance with a onceaweek application of a topical polysporin triple ointment to catheter exit sites.77 The Infectious Disease Society of America (IDSA) and KDOQI guidelines address catheter care and the diagnosis and management of catheterrelated infections.30,76 Peripheral blood draws, although recommended by IDSA, are often avoided in patients receiving HD to protect potential or future HD vascular access sites. Blood cultures are generally obtained from the blood tubing connecting the catheter to the HD machine. A prospective study examined blood cultures (n = 178) obtained from patients receiving HD suspected of a CRBSI. The blood cultures obtained from the HD circuit and venous catheter hub were the most sensitive, specific, and accurate for diagnosing CRBSI compared to blood cultures taken from a peripheral vein and either catheter hub or HD circuit.78 A fullcourse of antimicrobial treatment is warranted if blood cultures are positive.31,76 Empiric therapy with coverage for both grampositive and gramnegative bacteria should be initiated after the blood cultures are obtained. The incidence of MRSA bacteremia warrants initial treatment for grampositive coverage with vancomycin or daptomycin. If gramnegative antimicrobial coverage is warranted, an aminoglycoside or thirdgeneration cephalosporin should be initiated depending on a center’s protocols and antimicrobial susceptibilities.31,76 Antimicrobial therapy deescalation should occur once blood cultures identify an organism and antimicrobial susceptibility. For example, if the isolated organism is methicillinsensitive S. aureus, administer IV cefazolin (20 mg/kg, rounded to the nearest 500 mg) after each dialysis session. Antibiotic selection should be based on bacterial coverage and the ability to optimize pharmacokinetics by administering a dose either during the last 30 to 60 minutes of HD treatment or during the rinse bath. This method minimizes additional dosages between HD sessions. Examples of antimicrobial agents that meet these objectives are vancomycin, cefazolin, ceftazidime, daptomycin, and aminoglycosides.76,79 The IDSA guidelines recommend removal of an infected catheter if S. aureus, Pseudomonas species, or Candida species are the infectious cause. Although removal of the catheter is warranted, this is not always possible in patients receiving HD because of limited vascular access options. Retaining an infected catheter significantly increases a patient’s risk of bacteremia recurrence after completing a course of antibiotics; therefore, other options need to be considered. Options such as replacing the catheter over a guidewire or using a catheterlock solution in conjunction with IV antibiotics are alternatives.31,76 The catheter salvage success rate when a catheterlock solution is used in addition to systemic antibiotics is highly variable and pathogen dependent.31,76 The IDSA guidelines recommend the use of catheterlock solutions as adjunctive therapy after each dialysis session for 10 to 14 days in a patient whose catheter was not removed and bacteremia symptoms resolved in 2 to 3 days. The IDSA recommendations for antibiotic therapy are listed in Table 647.76 TABLE 647 Management of Hemodialysis Access Infection 1. Primary arteriovenous fistula A. Treat as subacute bacterial endocarditis for 6 weeks. B. Initial antibiotic choice should always cover grampositive organisms (eg, vancomycin 20 mg/kg IV with serum concentration monitoring or cefazolin 20 mg/kg IV three times/week or after each dialysis session). C. Gramnegative coverage is indicated for patients with diabetes, human immunodeficiency virus infection, prosthetic valves, or those receiving immunosuppressive agents, gentamicin 2 mg/kg IV with serum concentration monitoring. 2. Synthetic arteriovenous grafts A. Local infection—empiric antibiotic coverage for grampositive, gramnegative, and Enterococcus (eg, gentamicin plus vancomycin then individualized after culture results available). Continue for 24 weeks. B. Extensive infection—antibiotics as above plus total resection. C. If access is less than 1monthold, antibiotics as above plus remove the graft. 3. Tunneled cuffed catheters (internal jugular, subclavian) A. Infection localized to catheter exit site. i. No drainage—topical antibiotics (eg, mupirocin ointment). ii. Drainage present—grampositive antibiotic coverage, vancomycin 20 mg/kg IV with serum concentration monitoring or cefazolin 20 mg/kg IV three times/week. B. Bacteremia with or without systemic signs or symptoms. i. Grampositive antibiotic coverage as above. ii. If symptomatic at 36 hours, remove the catheter. iii. If stable and asymptomatic, change catheter and provide culturespecific antibiotic coverage for a minimum of 3 weeks. Downloaded 2024923 10:41 P Your IP is 141.217.20.120 Chapter 64: Hemodialysis and Peritoneal Dialysis, Kevin M. Sowinski; Mariann D. Churchwell Page 18 / 43 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Data from References 76 and 80. The catheter salvage success rate when a catheterlock solution is used in addition to systemic antibiotics is highly variable and pathogen Wayne State University dependent.31,76 The IDSA guidelines recommend the use of catheterlock solutions as adjunctive therapy after each dialysis session for 10 to 14 days in Access Provided by: a patient whose catheter was not removed and bacteremia symptoms resolved in 2 to 3 days. The IDSA recommendations for antibiotic therapy are listed in Table 647.76 TABLE 647 Management of Hemodialysis Access Infection 1. Primary arteriovenous fistula A. Treat as subacute bacterial endocarditis for 6 weeks. B. Initial antibiotic choice should always cover grampositive organisms (eg, vancomycin 20 mg/kg IV with serum concentration monitoring or cefazolin 20 mg/kg IV three times/week or after each dialysis session). C. Gramnegative coverage is indicated for patients with diabetes, human immunodeficiency virus infection, prosthetic valves, or those receiving immunosuppressive agents, gentamicin 2 mg/kg IV with serum concentration monitoring. 2. Synthetic arteriovenous grafts A. Local infection—empiric antibiotic coverage for grampositive, gramnegative, and Enterococcus (eg, gentamicin plus vancomycin then individualized after culture results available). Continue for 24 weeks. B. Extensive infection—antibiotics as above plus total resection. C. If access is less than 1monthold, antibiotics as above plus remove the graft. 3. Tunneled cuffed catheters (internal jugular, subclavian) A. Infection localized to catheter exit site. i. No drainage—topical antibiotics (eg, mupirocin ointment). ii. Drainage present—grampositive antibiotic coverage, vancomycin 20 mg/kg IV with serum concentration monitoring or cefazolin 20 mg/kg IV three times/week. B. Bacteremia with or without systemic signs or symptoms. i. Grampositive antibiotic coverage as above. ii. If symptomatic at 36 hours, remove the catheter. iii. If stable and asymptomatic, change catheter and provide culturespecific antibiotic coverage for a minimum of 3 weeks. Data from References 76 and 80. Microbial colonization of a catheter could affect patency and a patient’s access to dialytic treatment. An examination of the catheterlock solutions, UFH 5,000 U/mL and tetrasodium EDTA, found an increased rate of microbial colonization with UFH but the tetrasodium EDTA solution had an increased rate of thrombosis.81 Alternative solutions to UFH and tetrasodium EDTA including catheterlock solutions containing ethanol 30% combined with sodium citrate 4% or ethanol 70% with UFH 2,000 U/mL have been effective at decreasing CRBSI and improving catheter survival.82 Catheterlocking solutions have been utilized to prevent infection and thrombosis in HD catheters. A metaanalysis of randomized control trials of catheterrelated bacteremia and antimicrobial lock solutions identified eight studies with 829 patients and more than 90,100 catheter days. Overall analysis found that the use of an antimicrobial locking solution significantly reduced the risk of a catheterrelated infection (relative risk [RR] 0.32; 95% confidence interval [CI] 0.100.42).83 A comparison of UFH 1,000 U/mL to the combination solution of 4% sodium citrate with gentamicin 320 µg/mL as a catheterlock solution significantly reduced the incidence of catheterrelated bloodstream infections.84 The value of catheterlocking solutions for treatment and prevention of catheterrelated infections is increasingly becoming evident, but the possibility of antibiotic resistance with the wide use of antibiotics in catheter locks remains a concern. Gentamicin resistance to coagulasenegative Staphylococcus was reported in a retrospective study using routine postHD administration of gentamicin (4 mg/mL) combined with UFH (5,000 U/mL) as a catheterlock solution. Over the 4year study, there were 80 CRBSIs with 21 episodes (26%) of gentamicin resistance identified. The increase in gentamicin resistance led to a discontinuation of the gentamicinheparin catheterlock solutions.85 PERITONEAL DIALYSIS Although the concept of peritoneal lavage has been described as far back as the 1700s, it wasn’t until the 1920s that PD was first employed as an acute treatment for uremia. It was used infrequently during subsequent years until the concept of PD as a chronic therapy for ESRD was proposed in the 1960s. Over the ensuing years, the number of patients receiving PD increased slowly until the early 1980s. At that time, several innovations in PD delivery systems were introduced, such as improved catheters and dialysate bags. These innovations led to improved outcomes, decreased morbidity, Downloaded 2024923 10:41 P Your IP is 141.217.20.120 mortality, and a corresponding increase in the use of PD as a viable alternative to HD for the treatment of ESRD. However, the worldwide use of PD 19 /has Chapter 64: Hemodialysis and Peritoneal Dialysis, Kevin M. Sowinski; Mariann D. Churchwell Page 43 declined over the past decade. Some patients, such as those with more hemodynamic instability ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility (eg, hypotension) or significant residual renal function (RRF), and perhaps patients who desire to maintain a significant degree of selfcare may be better suited to PD than to HD. Table 642 shows the advantages and disadvantages of PD. PERITONEAL DIALYSIS Wayne State University Although the concept of peritoneal lavage has been described as far back as the 1700s, it wasn’t until the 1920s that PD was first Access employed Providedas by:an acute treatment for uremia. It was used infrequently during subsequent years until the concept of PD as a chronic therapy for ESRD was proposed in the 1960s. Over the ensuing years, the number of patients receiving PD increased slowly until the early 1980s. At that time, several innovations in PD delivery systems were introduced, such as improved catheters and dialysate bags. These innovations led to improved outcomes, decreased morbidity, mortality, and a corresponding increase in the use of PD as a viable alternative to HD for the treatment of ESRD. However, the worldwide use of PD has declined over the past decade. Some patients, such as those with more hemodynamic instability (eg, hypotension) or significant residual renal function (RRF), and perhaps patients who desire to maintain a significant degree of selfcare may be better suited to PD than to HD. Table 642 shows the advantages and disadvantages of PD. Principles of Peritoneal Dialysis The three basic components of HD—namely, a bloodfilled compartment separated from a dialysatefilled compartment by a semipermeable membrane—are also present in PD.4 In PD, the dialysatefilled compartment is the peritoneal cavity, into which dialysate is instilled via a peritoneal catheter that traverses the abdominal wall. The contiguous peritoneal membrane surrounds the peritoneal cavity. The cavity, which normally contains about 100 mL of lipidrich lubricating fluid, can expand to a capacity of several liters. The peritoneal membrane that lines the cavity functions as the semipermeable membrane, across which diffusion and ultrafiltration occur. The peritoneal dialyzing membrane is comprised of a monocellular layer of peritoneal mesothelial cells, the basement membrane, and underlying connective and interstitial tissue. The peritoneal membrane has a total area that approximates body surface area (approximately 12 m2). Blood vessels supplying and draining the abdominal viscera, musculature, and mesentery constitute the bloodfilled compartment. Unlike HD, the crucial components of PD cannot be manipulated to maximize solute and fluid removal. Because the blood is not in intimate contact with the dialysis membrane as it is in HD, metabolic waste products must travel a considerable distance to the dialysatefilled compartment. In addition, unlike HD, there is no easy method to regulate blood flow to the surface of the peritoneal membrane, nor is there a countercurrent flow of blood and dialysate to increase diffusion and ultrafiltration via changes in hydrostatic pressure. Similarly, there is no easy means available to manipulate the peritoneal membrane. Thus, to enhance PD clearance involve alterations in dialysate volume, dwell

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