348 and water may also have an impact on the final biochemical balance of all the other electrolytes in the dialysate Clinician choice of dialysate composition has largely been determined by observati[.]
348 and water may also have an impact on the final biochemical balance of all the other electrolytes in the dialysate Clinician choice of dialysate composition has largely been determined by observational data, rather than by study through clinical trials [17] In the batch dialysate system, a given dialysate volume of up to 100 L is prepared before the session and held in a sealed tank The dialysate circulates through the dialyzer and then returns to the reservoir Batch systems have advantages with respect to the control of volume balance and ultrafiltration Because of the reduced efficiency of the treatment with the progress of treatment time secondary to mixing of spent dialysate with fresh dialysate in the reservoir tank, and risk of bacterial contamination, single-pass systems have replaced batch systems in most dialysis programs One updated version of the batch system (Genius, Fresenius Medical Care, Bad Homburg, Germany) addresses issues of efficiency and may have advantages of operating with simplified technology [18] Historically, early hemodialysis sessions employed hypotonic dialysate sodium in the range of 120 mmol/L. Over several decades, with the advancement of dialysis equipment, dialysate sodium rose to higher levels, most commonly 140 mmol/L [19] Higher sodium concentrations in dialysate lead to increased thirst and fluid intake between dialysis sessions, complicating volume management, while lower sodium concentrations may increase the incidence of hypotensive episodes and muscle cramps during the dialysis session [20] Modern dialysis machines permit the operator to program variations in the sodium concentration of dialysate throughout the hemodialysis sessions This technique, known as “sodium modeling,” supposedly reduces intradialytic symptoms of hypotension and cramping; this has been reported in pediatric patients [21] Manufacturers offer numerous pre-programed “sodium profiles” on their hemodialysis machines from which the operator may choose There is considerable argument among dialysis providers as to whether sodium modeling is useful or whether it runs the risk of limiting appropriate F Schaefer and J M Symons sodium balance, putting the patient at risk for sodium excess and related issues of volume overload The dialysate potassium concentration is most commonly 2 mmol/L, chosen to induce a negative potassium balance in a patient with renal failure The dialysate can be adjusted to lower values in an effort to remove more potassium in patients with severe hyperkalemia Studies in adult patients suggest a greater risk when using lower dialysate potassium, likely due to the impact of sudden serum potassium changes on cardiac rhythm [22–24] For patients with lower serum potassium or those undergoing daily hemodialysis in the acute setting, dialysate potassium is often raised to 3 mmol/L to limit further losses The standard dialysate calcium concentration should be 1.25–1.5 mmol/L unless there is substantial hypo- or hypercalcemia Treatment of mineral bone disorder in patients on long-term hemodialysis with calcitriol and/or calcium containing phosphate binders can induce hypercalcemia [25] In these patients, dialysate calcium can be reduced to 0.75–1.25 mmol/L [26–28] In hypocalcemic patients, the dialysate calcium concentration may be increased to 1.75 mmol/L Dialysate magnesium concentrations range between 0.5 and 1 mmol/L to maintain normal serum magnesium concentrations [29, 30] Glucose should be near the physiological concentration Higher concentrations tend to cause insulin release and drive potassium into the cells, making it inaccessible for extraction The dialysis machine is able to provide variable dialysate bicarbonate concentrations because of individual variations of buffer requirements [31] Recognizing the deleterious impact of metabolic acidosis in patients with chronic kidney disease, guidelines from the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) suggested adjusting dialysis therapy to maintain serum bicarbonate levels at 22 mmol/L or greater [32] One may target slightly higher concentrations in patients with persistent metabolic acidosis, but caution is indicated at concentrations exceeding 35 mmol/L, as this can lead to decreased serum ionized calcium levels, which may lead to impaired vascular tone 20 Technical Aspects of Hemodialysis in Children and cardiac contractility [33] A rapid pH increase may be associated with the development of hypokalemia, probably with associated cardiac arrhythmia [34] Prior to delivery to the dialyzer, the dialysate is heated The temperature of dialysate entering the dialyzer is usually kept between 36 °C and 38 °C and can be adjusted individually The cardiovascular effects of dialysate temperature have been extensively studied in adults Lower dialysate temperatures decrease the incidence of dialysis- induced hypoxia and hypotension [35] Lower dialysate temperatures are also associated with a lower incidence of hypotensive episodes [36, 37] The production of an ultrapure dialysate, which is sterile and endotoxin-free, may limit inflammation associated with routine dialysate Ultrapure dialysate also allows one to perform “online” hemodiafiltration (see below), in which the generated sterile dialysate is also used as a substitution fluid Dialysis machines of the latest generation can filter the dialysate through a high- flux membrane, thereby further increasing microbiological purity and generating fluid for infusion in the setting of hemodiafiltration (see below) Dialysate Flow Rates To avoid saturation of dialysate during standard hemodialysis sessions, a common recommendation is to assure that dialysate flow rate is 1.5–2 times the blood flow rate Many dialysis machines have a minimum dialysate flow rate of 500 ml/ with the ability to increase flow step-wise to 800 ml/min These parameters would align with the recommendations in the setting of adult patients who may have vascular access that can generate blood flow rates between 300 and 400 ml/min Lower dialysate flow rates would limit waste but may also reduce efficiency if saturation of dialysate were to occur Some dialysis machines permit lower dialysate flow rates for extended hemodialysis as an alternative to continuous renal replacement therapy In this setting, the longer session length compensates for the lower efficiency that may occur with dialysate saturation 349 Ultrafiltration Control Changes in transmembrane pressure (TMP) yield variation in the ultrafiltration volume as blood passes through the dialyzer The rate of ultrafiltration depends on the TMP and the ultrafiltration coefficient (KUF) of the dialyzer Modern dialysis machines employ volumetric ultrafiltration control, in which automated systems adjust TMP to generate the desired ultrafiltration volume Ultrafiltration control systems for hemodialysis vary in their methods, using systems based on flow sensors, closed loops, or volumetric balancing The flow sensor system measures and compares dialysis inflow and outflow rates; the difference between these rates is the ultrafiltration rate The dialysis machine automatically adjusts the TMP to achieve the desired rate, based on the programmed ultrafiltration target In the closed-loop system, the dialysis fluid circulates in a closed circuit from which an ultrafiltration pump removes the desired fluid volume The system replaces circulating dialysate with fresh dialysate as needed The volumetric balancing system is based on matched pumps and balancing chambers separated by diaphragms that keep the dialysate inflow exactly equal to the dialysate outflow, creating a semiclosed loop The system generates the ultrafiltrate by an additional pump removing fluid from this loop An alternative to the volumetric methods of ultrafiltration control is gravimetric control, in which the device measures ultrafiltration rate by comparing the weights of bags filled with fresh dialysate and spent effluent Safety and Monitoring Systems Pressure Monitors Pressure monitors, built into the extracorporeal blood circuit, monitor the pressure of flowing blood both for safety and to assure smooth operation of the dialysis session Sudden changes exceeding the allowable pressure limits will trigger an alarm, stop the blood pump, and close the venous clamp Pressure monitoring in the blood 350 circuit allows detection of disconnections (sudden low pressure) and obstructions caused by tube kinking or blood clotting (sudden high pressure) Pressures in the extracorporeal circuit are measured in the arterial line preceding the blood pump, in the venous line before blood is returned to the patient, and, in some systems, in the line connecting the pump to the dialyzer The pressure between the vascular access and the blood pump is negative due to the resistances of the access device and tubing, causing the risk of air entry at the connection site The pressure downstream from the blood pump is always positive The arterial, venous, and dialysis fluid pressures are used to calculate the transmembrane pressure (TMP), which is the main determinant of fluid removal by ultrafiltration The maximum tolerance of pressure alarm limits should be set by the machine, and operator adjustments should be possible only within these limits The lower limit of the venous pressure should be above atmospheric pressure and close to the displayed value to enable early detection of disconnections of the venous blood line The minimal arterial pressure accepted by current dialysis machines is about −300 mmHg, but should be kept between −150 and −200 mmHg to limit endothelial trauma The venous return pressure should not exceed +200 mmHg However, the entire pressure gradient driving blood from the access into the arterial line depends on the negative arterial line pressure as well as on the pressure within the access Since the intraaccess pressure may vary from a few mmHg in central venous accesses to about 25 mmHg in arteriovenous fistulas and about 50 mmHg in arteriovenous grafts [38, 39], the same arterial line pressure produces different pressure gradients depending on the access On the other hand, using a 16-gauge needle at the same arterial pressure, blood flow would increase from 250 to 320 mL/ when switching from a central venous access to an arteriovenous graft [40] Air Trap An air trap is located in the arterial and the venous segments The air detector, located at the venous F Schaefer and J M Symons blood line, is necessary to prevent air embolism There are several methods used for air detection systems in hemodialysis; probably the most reliable is the ultrasonic method measuring changes of ultrasound transmittance caused by air bubbles or foam If foam or air is detected, the blood pump stops, and the blood tubing clamp immediately downstream of the air trap closes, preventing delivery of air to the patient Blood Leak Monitors Blood leakage into the dialysate after rupture of the filter membrane is detected by a blood leak detector located downstream of the dialyzer which measures the change in optical transmission by hemoglobin Conductivity Monitor In dialysis machines that employ single-pass dialysate delivery, as noted above, the proportioning system exactly measures the required amounts of A and B component concentrates, mixes with purified water, and generates the dialysate continuously during the hemodialysis session After thorough mixing, measurement of the electrical conductivity of the final dialysate plays an important role in detecting any aberrations from the desired concentrate composition If the conductivity is outside the desired range due to technical problems or running out of concentrate, an alarm sounds, and the system activates a bypass valve to prevent delivery of this inappropriate dialysate to the dialyzer To measure conductivity, metal electrodes in the flow of the dialysate apply a constant voltage, which generates an electrical current The presence of ions in the dialysate reduces resistance to current flow in a predictable manner; thus, dialysate conductivity serves as a method to monitor the dialysate for proper mixing Conductivity varies with temperature; for this reason, the device corrects readings to a standard temperature Given the risks to the patient of inappropriately mixed dialysate, the conductivity monitoring 20 Technical Aspects of Hemodialysis in Children 351 system requires frequent checking and preventive maintenance Electrical conductivity has become a surrogate for the concentration of Na+, especially for the measurement of online clearance or sodium modeling However, the use of solute conductivity as a surrogate of Na+ concentration is valid only within well-defined systems and prone to confounding effects; for example, the decrease of K+ concentration during dialysis will cause a parallel drop in effluent dialysate conductivity Non-invasive Blood Volume Monitoring In hemodialysis, fluid is removed by ultrafiltration from the intravascular space However, most of the fluid accumulated in the interdialytic period distributes in the extravascular space The fluid shift during the hemodialysis session between extra- and intravascular compartments (i.e., vascular refilling) is limited by physiologic factors such as the hydraulic conductivity of the microvascular wall [41] If the vascular refilling rate does not match the ultrafiltration rate, blood volume will drop, and a cascade of compensatory mechanisms will arise When a critically low blood volume is reached, symptomatic hypotension will occur [42] While it is somewhat chal- 100 RBV [%] 90 Curve symptomfree 85 95 Curve overload risk state Curve hypovolemic risk state 80 Fig 20.3 Schematic curve shapes of relative blood volume (RBV) measured by blood volume monitoring (BVM) Three major curve shapes can be distinguished lenging technically to measure accurately a patient’s absolute blood volume, technology exists to measure changes in the relative volume of blood that passes through the hemodialysis blood circuit Techniques include instantaneous hematocrit by optical density or density by sound velocity Proprietary algorithms in devices attached to the dialysis system can translate changes in blood density during ultrafiltration to a measurement of variation in blood volume from the start of the hemodialysis session The operator can monitor the change in relative blood volume as a marker of intravascular volume; observational studies have correlated higher rates of change in relative blood volume measured by these techniques with incidence of intradialytic symptoms and hypotension [43, 44] By contrast, little or no change in the slope of the relative blood volume monitor suggests constant refilling of the vascular compartment from the interstitial space, possibly indicating fluid excess within the patient (Fig. 20.3) [45] The existence of this technology, which some manufacturers integrate directly in their hemodialysis machines, raises questions as to whether online monitoring of relative blood volume may permit an automated feedback system to control ultrafiltration rate and reduce the risk of symptomatic hypotension related to overly aggressive fluid removal A study in adults did not demon- 30 60 90 120 150 180 time [min] 352 strate a clear improvement in intradialytic symptoms when an automated relative blood volume monitoring protocol was compared to standard patient monitoring with manual adjustment by dialysis staff [46] F Schaefer and J M Symons disinfection Bacterial adhesion and subsequent growth predominantly occur at rough surfaces or in stagnant water Ring loop systems are designed to prevent microbial proliferation in stagnant water Purified water is produced in excess by the water treatment module and pumped to the individual hemodialysis treatment stations The excess Dialysance and Online Monitoring water is recirculated to the water treatment device, where refiltration in the reverse osmosis module of Clearance permits reduction of the microbial load Although Ionic dialysance and patient’s plasma conductiv- reverse osmosis is effective in removing bacteria, ity can be calculated easily from online inlet and viruses, and pyrogens, small defects in the memoutlet dialysate conductivity measurements at brane may allow bacteria and pyrogens to penetwo different steps of dialysate conductivity [47, trate and contaminate the water produced Reverse 48] This technique forms the basis for online osmosis modules and ring loop systems must monitoring of clearance, serving as a proxy for therefore be disinfected regularly with chemicals urea clearance Several manufacturers include such as formaldehyde, peracetic acid, or other disonline conductivity measurements in latest- infectants or by high heat Stainless steel tubing generation dialysis machines Online urea kinet- should be preferred for the ring loop over plastic ics removes the need for blood sampling and since plastic surfaces are progressively roughened complex mathematical calculations in determin- by aging and disinfectants ing dialysis efficacy and provides immediate Bacterial growth in the resin bed of the water clearance information while dialysis is ongoing softener is restricted by regular regeneration with However, experience with online Kt/V is still lim- concentrated sodium chloride solution In case of ited, and validation studies are still lacking in excessive bacterial colonization, disinfection both adults and children [49] with formaldehyde solution, peracetic acid, or Ionic dialysis may have other potential uses others can be performed Water treatment devices The implementation of the conductivity kinetic are operated intermittently by automatic control model also permits monitoring to achieve a neu- systems during nights and at weekends to flush tral sodium balance at each HD session [50], an away adherent bacteria The limit for microbial improvement over previous approaches to sodium contamination has been set to a maximum of 200 kinetic modeling which required blood sampling colony-forming units (CFU) for purified water The conductivity kinetic modeling technique used to prepare the dialysis fluid and to 2000 may improve intradialytic cardiovascular stabil- CFU for effluent dialysate after the dialysis proity in adult hypotension-prone patients [51] cedure Substantial bacterial proliferation occurs Ionic dialysance can also be used to monitor the in the dialysis machine itself Bacterial adhesion blood flow through the vascular access [52] and subsequent proliferation is facilitated by numerous angles, valves, pumps, regions of low fluid flow rates, and temperatures around aintenance M 37 °C. Contamination of the dialysis fluid can only be limited by regular cleaning and disinfec isinfection and Sterilization D tion of the dialysis machine The cleaning process includes the removal of protein layers or Bacterial contamination inevitably occurs at vari- biofilms generated by slime-forming bacteria and ous sites of the dialysis system The degree of con- decalcification Disinfection can be performed by tamination with pathogenic organisms, bacterial thermic, chemical, or combined procedures proliferation, and subsequent endotoxin release Thermochemical disinfection with hot citric acid must be limited by technical measures and regular permits simultaneous decalcification 20 Technical Aspects of Hemodialysis in Children Descaling 353 responses There is speculation that suppressing inflammation may be useful in treating an Due to the inevitable deposition of calcium and inflammatory-malnutrition syndrome in dialysis magnesium salts in the dialysis machine over patients [57] Protein adsorption at membrane time, the dialysate system must be decalcified surfaces generates a biofilm that results in a prodaily, e.g., by rinsing with 20% citric or hydroxy- gressive loss of the diffusive and convective acetic acid capacity On the other hand, membrane-induced reactions such as complement activation are reduced by biofilm formation Complications and Troubleshooting The overall effects of the membrane type on treatment outcomes are controversial and may Dialyzer Reactions have been overestimated in the past This may be and Biocompatibility due to the complex biological effect profiles of individual membranes: A membrane which leads Dialyzer membranes and blood tubing materials to exorbitant activation of one molecular cascade interact with plasma proteins and blood cells may exert a much lower activation of other bioDue to its high surface area, the largest amount of molecules compared to another membrane these interactions occurs at the filter membrane The contact system of plasma can be activated Biocompatibility is the ability of a material to by negatively charged surfaces of dialysis memperform with an appropriate host response in a branes Activation leads to cleavage of kininogen specific application This response involves, by kallikrein and the release of bradykinin into among others, complement activation, monocyte the circulation, where it is normally inactivated and granulocyte activation, and endotoxin immediately by kininase I and angiotensin- transfer converting enzyme The negatively charged Minimizing the biological response during AN69 polyacrylonitrile membrane generates dialysis is important since there may be an impact small amounts of bradykinin in vitro [58] This on long-term patient morbidity and survival has led to severe clinical reactions in patients diaDialyzers with synthetic membranes induce a lyzed with AN69 membranes who are treated much lower activation of complement factors with ACE inhibitors [59] and angiotensin II than cellulose-based membranes [53] Dialyzer receptor antagonists [60] membranes activate the alternative complement Patient reactions to hemodialyzers are classipathway Plasma concentrations of activated fied as type A reactions, which occur soon after complement factors C3a and C5a increase during initiation of the hemodialysis session, and type B the first 15 min of hemodialysis This may lead to reactions, which are delayed Type A reactions many of the clinical reactions observed during are thought to be related to substances involved hemodialysis including anaphylactoid reactions, in dialyzer manufacture that may seep from the neutrophil trapping in the lung, and dialysis- dialyzer into the flowing blood and then enter the related hypoxemia [54, 55] patient A well-described example is ethylene Activation of circulating mononuclear cells by oxide, which is used in one method for dialyzer complement and bacterial endotoxins can induce sterilization Some patients may have anaphylacthe production of cytokines [56] Cytokine induc- toid reactions related to use of ACE inhibitors in tion during hemodialysis may cause fever and conjunction with dialyzer membranes made from chills, which are observed during hemodialysis polyacrylonitrile (PAN); this reaction has also with bacterially contaminated dialysate Synthetic been reported in CRRT with use of the AN-69 high-flux membranes have greater adsorptive membrane, one form of PAN membrane capacity for small molecular pyrogens than cel- Numerous case reports describe other circumlulosic membranes and may therefore lead to a stances associated with type A reactions Type A lower incidence of chronic inflammatory reactions may also be seen with bacterial con- ... compartment from the interstitial space, possibly indicating fluid excess within the patient (Fig. 20.3) [45] The existence of this technology, which some manufacturers integrate directly in their... semiclosed loop The system generates the ultrafiltrate by an additional pump removing fluid from this loop An alternative to the volumetric methods of ultrafiltration control is gravimetric control,... pressure alarm limits should be set by the machine, and operator adjustments should be possible only within these limits The lower limit of the venous pressure should be above atmospheric pressure and