Hemodialysis Technique
what is dialysis
Hemodialysis Technique--- As discussed in the previous chapter, the clearance of a solute is dependent on the Qb, Qd, and membrane efficiency. The dialyzer membranes have different pore sizes that are variably distributed, larger pores being fewer than smaller pores. Small solutes like urea can be transported through all pore sizes whereas the larger molecules such as vitamin B12 or beta-2-microglobulin can only pass through the larger pores. Thus the clearance of the larger solutes, unlike urea, is more influenced by the membrane and less by Qb and Qd.
1.1 Blood Flow Rate
what is dialysis
what is dialysis
Because clearance is calculated using Qb, it would be understandable to mistakenlyassume that the relationship between urea clearance and Qb is linear. However, al though urea clearance increases steadily as Qb is increased from zero, at faster flow rates, the dialyzer is unable to continue to transport urea with the same efficiency and the urea concentration at the dialyzer outlet increases. In other words, the urea removed as a percentage of urea inflow into the dialyzer decreases and (as clearance is Qb multiplied by the fractional decline in urea) the clearance curve plateaus
1.2 Dialysate Flow Rate
what is dialysis
what is dialysis
An increase in Qd generally increases the urea clearance. This effect is negligible, however, as long as Qd is 150−250 ml/min faster than Qb. With high-efficiency dialyzers, there is little (<10%) increase in urea clearance if Qd is increased from 500 ml/min to 800 ml/min, provided that Qb remains 350 ml/min.
1.3 Dialyzer Efficiency and Mass Transfer Area Coefficient (KoA)
what is dialysis
what is dialysis
Dialyzer efficiency is measured in terms of clearance at a given Qb and Qd. Usually, these values are measured for urea and other solutes at a Qb of 200 ml/min and a Qd of 500 ml/min. Another measure of dialyzer efficiency is solvent removal in terms of the ultrafiltration coefficient (K uf ). However, dialyzer efficiency is more accurately measured as the mass transfer coefficient (KoA). The KoA of a solute is defined as the maximum (theoretical) ability of a membrane to allow the transfer of a solute through its pores when Qb and Qd are unlimited. Thus, KoA is the clearance of a solute when dialysate and blood flow are not the limiting factors. The higher the value of KoA, the more permeable the membrane for that solute. Thus, the higher KoA of a dialyzer for a solute, the more that solute would be cleared, and this value is proportional to the surface area and porosity of a membrane. However, if the surface area becomes too large, the relationship will not remain linear (this will be further discussed later).
1.4 Different Hemodialysis Techniques
1.4.1. Different Hemodialysis Techniques
what is dialysis
diffusion is the predominant method of solute clearance. There is a very small
amount of hydrostatic UF to remove the excess fluid volume gained between dialysis sessions, contributing a small solute clearance by convection.
amount of hydrostatic UF to remove the excess fluid volume gained between dialysis sessions, contributing a small solute clearance by convection.
1.4.2. Hemofiltration
what is dialysis
The technique of hemofiltration (HF) uses a large quantity of hydrostatic UF. Plasma ultrafiltrate is replaced with plasma-like electrolyte solution. Solute removal is Hemofiltration The technique of hemofiltration (HF) uses a large quantity of hydrostatic UF. Plasma ultrafiltrate is replaced with plasma-like electrolyte solution. Solute removal is
The technique of hemofiltration (HF) uses a large quantity of hydrostatic UF. Plasma ultrafiltrate is replaced with plasma-like electrolyte solution. Solute removal is Hemofiltration The technique of hemofiltration (HF) uses a large quantity of hydrostatic UF. Plasma ultrafiltrate is replaced with plasma-like electrolyte solution. Solute removal is
1.4.3. Hemodiafiltration
what is dialysis
what is dialysis
In order to improve solute clearance, hemofiltration (convective transport) may be combined with diffusive transport by allowing dialysate to flow on the ultrafil-
trate side. Intermittent use of this technique is called hemodiafiltration (HDF) , while continuous use (commonly used in acute renal failure) is called continuous arteriovenous hemodiafiltration (CAVHD) or continuous venovenous hemodiafiltration (CVVHD), depending on the location of the catheter(s)
1.4.4. Slow Low Efficiency Dialysis (SLED)
what is dialysis
what is dialysis
Slower removal of solutes is better tolerated than rapid removal. Thus, in an acutel yill patient, sometimes the slow removal is achieved by reducing the dialysate flow to 300 ml/min or lower with blood flow not exceeding 200 ml/min, and the treatment time is prolonged to 8–24 h. This technique, slow low efficiency dialysis (SLED), is better tolerated with less hemodynamic instability.
1.4.5. Ultrafiltration
what is dialysis
what is dialysis
If volume removal alone is needed, it can be achieved by intermittent UF (IUF) or
slow and continuous UF (SCUF), without replacement of ultrafiltrate.
1.5 Hemodialysis Setup
what is dialysis
what is dialysis
Hemodialysis apparatus can be divided in two major components Blood circuit
Dialysate circuit
1.5.1.Blood Circuit
The blood circuit comprises:
1-Tubing set with ports,
2- drip chambers, and an access device
3- Blood pump
4 -Hemodialyzer
3- Blood pump
4 -Hemodialyzer
1.5.1.1 Tubing Set
Blood is drawn from the patient into the blood tubing, either through a central venous catheter or through a needle inserted into the patient’s vascular access (fistula or graft). Blood tubing can be divided into two major segments. The segment that carries blood from the patient to the hemodialyzer is traditionally called the “arterial segment,” while the segment that carries blood from the dialyzer back to the patient is called the “venous segment.” Usually, each of these segments has a drip chamber into which blood flows and any air rises to the top. Blood drains from the drip chamber into the blood tube, continuing its course toward the dialyzer from the arterial and to the patient from the venous drip chamber. Pressure in these segments is monitored (arterial pressure monitor 1 in arterial drip chamber located before the blood pump and venous pressure monitor in the venous drip chamber), and if it goes beyond the set ranges, the alarm sounds and the blood pump stops. The venous drip chamber also has a level and air detector. If the blood level drops below the detector
level because of too much air, an air alarm sounds, the pump stops, and the tubing segment below the drip chamber is clamped to prevent any air being introduced into the patient. Some systems have an additional arterial pressure monitor between the blood pump and the dialyzer (arterial pressure monitor 2) that enables the reading of pressure between the pump and the dialyzer. The pressure in the arterial segment before the pump (monitor 1) is negative and after the pump (monitor 2) is positive, reflecting the resistance caused by the dialyzer. Pressure in the venous segment is positive, reflecting the resistance caused by the vascular access. The drop in pressure between post pump pressure and venous pressure represents the effect of ultrafiltration. For the calculation of transmembrane pressure (TMP), either the average of the two pressures (if post pump arterial pressure is measured) or the venous pressure is
used. The TMP is the pressure on the blood side of the dialyzer membrane minus the pressure on the dialysate side. The blood tubing is usually sterilized using ethyleneoxide (Eto), thus, the blood tubing needs to be thoroughly rinsed prior to connecting the tubing to the patient
used. The TMP is the pressure on the blood side of the dialyzer membrane minus the pressure on the dialysate side. The blood tubing is usually sterilized using ethyleneoxide (Eto), thus, the blood tubing needs to be thoroughly rinsed prior to connecting the tubing to the patient
1.5.1.2 Blood Pump
what is dialysis
what is dialysis
The most common type of blood pump is the roller design. Rotating rollers compress the pump segment of the tubing and sweep the blood forward. The speed of rotation determines Qb. The usual Qbs range from 200 to 500 ml/min in adults (median rate about 350 ml/min). If the pump is set at a certain rate but access is unable to provide blood at that rate, the pressure in the arterial chamber 1 drops below the set range and the alarm stops dialysis. Similarly, any excessive resistance to blood being returned to the patient increases pressure in the venous drip chamber and the system will stop if the set range is exceeded. There are two access-related reasons for insufficient blood flow—that the arterial segment is not receiving the desired blood flow or that the venous side cannot return the flow back to the patient. The former means that
the pump is causing too much negative pressure. This pressure limit is usually set at −200 mmHg, with any drop below this limit sounding the alarm. Problems with the return of blood cause the pressure in the venous drip chamber to increase and a pressure greater than 200 mmHg is usually considered unsafe.
The blood pump is a “demand driven” pump; thus, the blood pump rotation (flow
rate) is set at a fixed rate and the pump “demands” blood at this rate. The design of the pump is inflexible, leading to frequent alarm interruptions. The other commonproblem with the blood pump is the trauma the rollers cause to the pump segment of the blood tubing (spalling), limiting the tubing’s useful life [1]. The pump segment tubing material is silicone rubber and the rest of the blood tubing is usually made of polyvinyl chloride. The diameter of the pump tubing segment determines the “stroke volume” of blood per sweep. This requires that the rollers completely occlude the tubing segment, incomplete occlusion would reduce the stroke volume and Qb. At a very high pump speed, often the arterial pressure becomes too negative and tubing may partially collapse, again reducing the stroke volume and Qb. To get the reliable Qb, the pump needs to be frequently checked and calibrated.
the pump is causing too much negative pressure. This pressure limit is usually set at −200 mmHg, with any drop below this limit sounding the alarm. Problems with the return of blood cause the pressure in the venous drip chamber to increase and a pressure greater than 200 mmHg is usually considered unsafe.
The blood pump is a “demand driven” pump; thus, the blood pump rotation (flow
rate) is set at a fixed rate and the pump “demands” blood at this rate. The design of the pump is inflexible, leading to frequent alarm interruptions. The other commonproblem with the blood pump is the trauma the rollers cause to the pump segment of the blood tubing (spalling), limiting the tubing’s useful life [1]. The pump segment tubing material is silicone rubber and the rest of the blood tubing is usually made of polyvinyl chloride. The diameter of the pump tubing segment determines the “stroke volume” of blood per sweep. This requires that the rollers completely occlude the tubing segment, incomplete occlusion would reduce the stroke volume and Qb. At a very high pump speed, often the arterial pressure becomes too negative and tubing may partially collapse, again reducing the stroke volume and Qb. To get the reliable Qb, the pump needs to be frequently checked and calibrated.
1.5.1.3 Hemodialyzer
what is dialysis
what is dialysis
The dialyzer is the site of the movement of molecules (dialysis process) and is
the critical part of the dialysis apparatus. It contains a semipermeable membrane, through one side of which flows blood and the other side dialysate. This membrane consists of either thousands of capillary fibers (hollow fiber dialyzers) or of a sheet that is arranged in parallel plates (parallel plate dialyzers). The hollow fiber design is the version used most frequently The major components of this are: Blood ports—carry blood into (arterial port) and out of (venous port) the dialyzer Headers—from the blood port, the blood enters the arterial header space and dialyzed blood enters the venous header space (before entering the venous blood port)
Potting material—the hollow capillary fibers are anchored to the dialyzer casing
with a potting material, separating the blood from the dialysate compartment
Space between header and fibers—this critical space is where clotting most often occurs
with a potting material, separating the blood from the dialysate compartment
Space between header and fibers—this critical space is where clotting most often occurs
Capillary fibers—about 10,000 capillary fibers made of permeable material are
contained within the dialyzer casing. The blood flows inside the fibers and the
dialysate flows on the outside
contained within the dialyzer casing. The blood flows inside the fibers and the
dialysate flows on the outside
Dialysate ports—there are two ports on the side of the casing, one for dialysate
inflow and one for the outflow
inflow and one for the outflow
Space between ports and potting material—this space is critical because dialysate flow (and thus clearance) in this space is relatively poor
Dialyzer Characteristics
Selection of a dialyzer is based on material and performance characteristics:
Membrane: The material that constitutes the membrane can be divided into four
broad groups:
Membrane: The material that constitutes the membrane can be divided into four
broad groups:
(i) Cellulose membrane:
Early material derived from plant polysaccharide was called cellophane. Later, other forms of cellulosic materials (based on the manufacturing process) were used; these included cuprophan (cuprammonium cellulose), saponified cellulose ester, and regenerated cellulose. The cellulosic membranes were widely used and are less expensive than the other membrane materials but cause more immunoactivation. Their use in the USA over recent years has declined because of being less bio-compatible.
(ii) Substituted cellulose membrane:
The cellulose membranes described above
contain free hydroxyl groups that are thought to activate complements when
exposed to blood. In an attempt to reduce this, free hydroxyl groups have been
bonded to materials like acetate to form substituted cellulose membranes such
as cellulose acetate, diacetate, and triacetate. These are thought to be more bio-
compatible.
contain free hydroxyl groups that are thought to activate complements when
exposed to blood. In an attempt to reduce this, free hydroxyl groups have been
bonded to materials like acetate to form substituted cellulose membranes such
as cellulose acetate, diacetate, and triacetate. These are thought to be more bio-
compatible.
(iii) Mixed cellulosic–synthetic membrane:
During the manufacturing process, a tertiary amine compound is added to the cellulose thus the membrane surface becomes more biocompatible. These membranes are called Hemophan (Cellosyn).
(iv) Synthetic membrane:
Several synthetic membranes are currently in use. These differ from cellulosic membrane in several aspects. The synthetic membranes are generally more biocompatible, have higher hydraulic permeability, and are more expensive. Some of these membranes also adsorb plasma proteins, immunoglobulins, and complements. Common synthetic membranes materials include polysulfone (PS), polyacrylonitrile (PAN), polycarbonate, polymethylmethacrylate (PMMA), and polyamide. Biocompatibility of the membrane: The dialyzer membranes cause activation of blood cells, complement blood cells, and complement cascade. This is thought to occur mostly by free hydroxyl moieties present on the surface of cellulosic membranes. The activated cells produce cytokines and lead to various clinical sequelae and dialytic reactions. Antioxidants are also produced during dialysis and new dialyzers are being produced in which the membrane is coated with antioxidant materials such as vitamin E. The use of these dialyzers has been reported to be associated with less production of oxidants. The biocompatibility is attributed to the membrane material, with cellulosic membranes being the least biocompatible, synthetic membranes the most biocompatible, and others in between. The potting materials as well as the middle layer (the layer between the two skins of the membrane) can also cause bio-incompatibility.
• Dialyzer performance:
Dialyzer performance is judged by solute clearance and
UF characteristics:
(i) Solute clearance:
The solute removal characteristic of a dialyzer is one of the key measures of its performance. It is reported in terms of clearance of solutes such as urea, creatinine, phosphate (PO 4 ), uric acid, beta-2-microglobulin, and vitamin B 12 . Clearance depends on the thickness and surface area of the membrane and on the density, characteristics, and size of the pores. Urea clearance is the most commonly used measure, since it is used in the calculation of the dose of dialysis. The clearance data provided by the manufacturer usually comes from in vitro experiments using water and is always higher than the blood clearance obtained in vivo. Therefore, the manufacturer’s in vitro data must not be used to determine the dialysis prescription using urea kinetics. Generally, creatinine clearance is 70–95% of urea clearance. PO 4 and uric acid clearances are not always reported but can be useful in treating markedly elevated PO 4 or uric acid levels (e.g., those encountered with tumor lysis syndrome and acute renal failure). However, PO 4 is an intracellular ion and, using a dialyzer with a high PO 4 clearance, the plasma value can fall quickly without a major impact on total body removal of this ion. Vitamin B 12 (with a molecular weight of 1355) has lower clearance and helps in defining the permeability of the dialyzer for larger (middle) molecules. Recently, beta-2-microglobulin clearance has also been used as a method of assessing membrane characteristics, particularly the flux of the membrane.
(ii) UF characteristic:
(ii) UF characteristic:
The UF characteristic of a dialyzer is measured as the K uf , the
volume of plasma water removed per hour per mmHg of TMP, and is reported
in terms of the ultrafiltration rate (ml/h/mmHg). Thus, the UF rate (UFR) can be
accurately calculated for each treatment from the K uf of the dialyzer and TMP
during the procedure.
volume of plasma water removed per hour per mmHg of TMP, and is reported
in terms of the ultrafiltration rate (ml/h/mmHg). Thus, the UF rate (UFR) can be
accurately calculated for each treatment from the K uf of the dialyzer and TMP
during the procedure.
Example
A dialyzer with a K uf of 4 ml/h/mmHg is used for a treatment. The prepump arterial pressure is −100, the post-pump arterial pressure is not measured, the venous pressure is 100 mmHg, and the patient needs to lose 2.7 kg during a 3-h run. What should be the dialysate pressure to achieve the above UF goal
if no UF modeling is used? TMP = P b –P d and UFR = TMP × K uf ; UFR = 2, 700 ml/3 h, or 900 ml/h where P b is the pressure on the blood side and P d is the pressure on the
dialysate side of the membrane 900 ml/h = TMP × 4 ml/h/mmHg; or TMP = 900 ml/h ÷ 4 ml/h or 225 mmHg 225 mmHg = P b –P d , or 225 = 100−P d ; or P d = −125 mmHg, or the dialysate side would have to supplement the blood side pressure by having a negative pressure
If a dialyzer with a K uf of 15 is used and rest of the variables remain
unchanged, the 100 mmHg venous pressure would cause more UF than
desired, in this case, the P d would be positive to slow down the UFR by
countering the P b
TMP = 60 and P d = 40(P b remains 100).
if no UF modeling is used? TMP = P b –P d and UFR = TMP × K uf ; UFR = 2, 700 ml/3 h, or 900 ml/h where P b is the pressure on the blood side and P d is the pressure on the
dialysate side of the membrane 900 ml/h = TMP × 4 ml/h/mmHg; or TMP = 900 ml/h ÷ 4 ml/h or 225 mmHg 225 mmHg = P b –P d , or 225 = 100−P d ; or P d = −125 mmHg, or the dialysate side would have to supplement the blood side pressure by having a negative pressure
If a dialyzer with a K uf of 15 is used and rest of the variables remain
unchanged, the 100 mmHg venous pressure would cause more UF than
desired, in this case, the P d would be positive to slow down the UFR by
countering the P b
TMP = 60 and P d = 40(P b remains 100).
From the above example, it is clear that dialyzers with a high K uf can cause excessive UF and need fine balancing of pressure from the dialysate side in order to prevent over ultrafiltration. Thus the dialyzers with a K uf of >8 ml/h/mmHg should only be used with machines with volumetric control ability. In dialyzers with a very high K uf (such as 100 ml/h/mmHg), a large pressure drop occurs along the length of the capillary fiber and often a back-leak of dialysate occurs or even a small leak in the membrane can cause infusion of dialysate from the venous end of the fibers into the blood. For this reason, very porous dialyzers may be safe only with ultrapure dialysate. Surface area and porosity of the membrane: Dialyzer clearance is dependent on the porosity of the dialyzer and the total surface area of the dialyzer membrane. The surface area of most dialyzer membranes ranges from 0.8 to 2.1 m 2 . For the less biocompatible membranes such as cuprophan, the larger the surface area, the more
potential there is for immunoactivation (see below). Priming volume: Priming volume is the volume of the blood compartment of the dialyzer and is therefore equal to the volume of blood that will fill this compartment. For dialyzers used with adults, this volume ranges from 50 to 150 ml.
Membrane thickness: Usually, thin membranes are more permeable than thicker membranes. However, thinner membranes cannot withstand as high a TMP as
thicker membranes. In addition to dialyzer performance characteristics, the dialyzer sterilization technique may be of importance. The most common method of sterilization is with Eto. Removal of Eto prior to use of the dialyzer is very important because some patients experience a severe anaphylactic reaction to small amounts of Eto, which is difficult to remove from the potting material without thorough rinsing. In Eto-sensitive patients, only dialyzers sterilized by alternative methods (e.g., gamma radiation or
steam autoclaving) should be used. Because of the risk of severe reaction to Eto,
this method is becoming less commonly used and gamma radiation and steam sterilization are becoming more popular.
potential there is for immunoactivation (see below). Priming volume: Priming volume is the volume of the blood compartment of the dialyzer and is therefore equal to the volume of blood that will fill this compartment. For dialyzers used with adults, this volume ranges from 50 to 150 ml.
Membrane thickness: Usually, thin membranes are more permeable than thicker membranes. However, thinner membranes cannot withstand as high a TMP as
thicker membranes. In addition to dialyzer performance characteristics, the dialyzer sterilization technique may be of importance. The most common method of sterilization is with Eto. Removal of Eto prior to use of the dialyzer is very important because some patients experience a severe anaphylactic reaction to small amounts of Eto, which is difficult to remove from the potting material without thorough rinsing. In Eto-sensitive patients, only dialyzers sterilized by alternative methods (e.g., gamma radiation or
steam autoclaving) should be used. Because of the risk of severe reaction to Eto,
this method is becoming less commonly used and gamma radiation and steam sterilization are becoming more popular.
High-Efficiency High-Flux Dialyzers
Dialyzers that are more efficient and contain high flux membranes have become
very popular during the last two decades. It is worthwhile to clarify the various
membrane characteristics because confusion regarding the definitions and terminology is prevalent. Flux: The term flux defines the ability to ultrafilter plasma water, or the K uf of a membrane. Thus, a membrane with K uf of <10 ml/h/mmHg is called a low-flux membrane and a membrane with >20 ml/h/mmHg is called a highflux membrane. Efficiency: Efficiency denotes the solute removal by diffusion based on the KoA of urea; membranes with a KoA urea of <500 ml/min are called low efficiency membranes and those with >600 ml/min are called high-efficiency membranes. Generally, the high-flux dialyzers also have high-efficiency membranes and vice versa. However, theoretically, the two could be very different Mass transfer area coefficient (KoA): As discussed in Chapter 1, the KoA is the clearance of a solute at infinite Qb and Qd, usually expressed in terms of urea clearance or KoA urea . This theoretical value can be calculated from clearance and blood and dialysate flows: KoA = (Qb × Qd)/(Qb − Qd) × ln[(1 − Ks/Qb) ÷ (1 − Ks/Qd)], where Ks = the dialyzer clearance of a solute such as urea. Thus, the KoA value is more affected by clearance than Qb or Qd.
very popular during the last two decades. It is worthwhile to clarify the various
membrane characteristics because confusion regarding the definitions and terminology is prevalent. Flux: The term flux defines the ability to ultrafilter plasma water, or the K uf of a membrane. Thus, a membrane with K uf of <10 ml/h/mmHg is called a low-flux membrane and a membrane with >20 ml/h/mmHg is called a highflux membrane. Efficiency: Efficiency denotes the solute removal by diffusion based on the KoA of urea; membranes with a KoA urea of <500 ml/min are called low efficiency membranes and those with >600 ml/min are called high-efficiency membranes. Generally, the high-flux dialyzers also have high-efficiency membranes and vice versa. However, theoretically, the two could be very different Mass transfer area coefficient (KoA): As discussed in Chapter 1, the KoA is the clearance of a solute at infinite Qb and Qd, usually expressed in terms of urea clearance or KoA urea . This theoretical value can be calculated from clearance and blood and dialysate flows: KoA = (Qb × Qd)/(Qb − Qd) × ln[(1 − Ks/Qb) ÷ (1 − Ks/Qd)], where Ks = the dialyzer clearance of a solute such as urea. Thus, the KoA value is more affected by clearance than Qb or Qd.
Traditionally, dialyzers have always been reprocessed and reused—mainly for convenience and to save time. With the popularity of the more expensive high-efficiency dialyzers, cost saving has become the major factor for reuse. However, recently, the interest has shifted from reuse to no reuse, because of the concern about the process and its effect on the treatment and patient. Although there is no clear evidence of reuse having any adverse effect on patients or treatment, some reports even have cited the possible benefit of reuse. With no reuse, the cost of dialysis supplies increases, and the impact on the environment by increasing the amount of contaminated waste is of major concern.
The reuse technique involves rinsing with clean water and/or cleaning agents
such as sodium hypochlorite (bleach), hydrogen peroxide, or peracetic acid. Af-
ter thorough cleaning, the dialyzer is sterilized; formaldehyde is the most common agent used but glutaraldehyde has also been used for this purpose, and there has been interest in using heat. Before the dialyzer is used again, several safety checks are mandatory:
Dialyzers are tested chemically to ensure that no sterilizing agent remains.
Membrane patency is checked by the use of a pressure test. Dialyzer efficacy is tested to ensure that enough membrane surface is still avail able for dialysis. This is done by measuring the fiber bundle volume (FBV). If the FBV is >80–85% of the baseline value, the dialyzer is deemed to have an adequate number of patent fibers. Any dialyzer with a lower value should be discarded.
The reuse technique involves rinsing with clean water and/or cleaning agents
such as sodium hypochlorite (bleach), hydrogen peroxide, or peracetic acid. Af-
ter thorough cleaning, the dialyzer is sterilized; formaldehyde is the most common agent used but glutaraldehyde has also been used for this purpose, and there has been interest in using heat. Before the dialyzer is used again, several safety checks are mandatory:
Dialyzers are tested chemically to ensure that no sterilizing agent remains.
Membrane patency is checked by the use of a pressure test. Dialyzer efficacy is tested to ensure that enough membrane surface is still avail able for dialysis. This is done by measuring the fiber bundle volume (FBV). If the FBV is >80–85% of the baseline value, the dialyzer is deemed to have an adequate number of patent fibers. Any dialyzer with a lower value should be discarded.
1.5.2 Dialysate Circuit
The major components of the dialysate circuit
1-Dialysate
2-Dialysate delivery system
1.5.2.1 Dialysate
These days, bicarbonate dialysates are almost exclusively used for dialysis. Concentrated dialysate that is proportioned by mixing with treated water in the machines is the most common form. However, mixing of concentrated NaHCO 3 and CaCl 2 leads to the precipitation of CaCO 3 .
CaCl 2 + NaHCO 3 → Ca(HCO 3 ) 2 + NaCl → CaCO 3 + H 2 O + CO 2
CaCl 2 + NaHCO 3 → Ca(HCO 3 ) 2 + NaCl → CaCO 3 + H 2 O + CO 2
The precipitation is avoided by separating the concentrated NaHCO 3
(B-concentrate) from the rest of the constituents of the dialysate (A-concentrate). To further reduce the risk of CaCO 3 formation, an acid is added to the A-concentrate,this keeps the pH of the final dialysate below 7.4 after the proportioning and mixing of the A- and B-concentrates. The lower pH drives the equation to the left, resulting in more soluble calcium chloride and calcium bicarbonate instead of less soluble calcium carbonate formation. Based on the acidifying agent, two types of A-concentrates are available:
Acetate-containing acid concentrate (acetate dialysate): The acid concentrate
contains acetic acid, usually 4 mEq/l (in liquid concentrate) or 8 mEq/l (in powdered concentrate, Granuflo R Fresenius) in the final dialysate.
Citrate-containing acid concentrate (citrate dialysate): The predominant acid is
citric acid, usually 2.4 mEq/l, with 0.3. mEq/l acetic acid (Citrasate R , Advanced
Renal Technologies). The composition of the rest of the constituents is identical in the two forms of dialysate. Clinical effects: The presence of citric acid has been reported to have some beneficial effects, mostly related to its anticoagulant properties During the recent years, there have been concerns about acetate causing activation of cells and inflammatory markers. There is a lot of interest in further reducing or removing acetate from the dialysate.
Liquid versus dry concentrate: Both acetate- and citrate-containing concentrates
are available in either dry form or liquid form. The dry concentrate is dissolved
in appropriate volume of treated water before connecting it the machine. Exam-
ples of dry forms are Granuflo R (8 mEq/l acetate) by Fresenius, and DRYalysate R (2.4 mEq/l citrate) by Advanced Renal Technologies. Examples of liquid formulations are Naturalyte R and Citrasate R , by Fresenius and Advanced Renal Technologies, respectively.
Acetate-containing acid concentrate (acetate dialysate): The acid concentrate
contains acetic acid, usually 4 mEq/l (in liquid concentrate) or 8 mEq/l (in powdered concentrate, Granuflo R Fresenius) in the final dialysate.
Citrate-containing acid concentrate (citrate dialysate): The predominant acid is
citric acid, usually 2.4 mEq/l, with 0.3. mEq/l acetic acid (Citrasate R , Advanced
Renal Technologies). The composition of the rest of the constituents is identical in the two forms of dialysate. Clinical effects: The presence of citric acid has been reported to have some beneficial effects, mostly related to its anticoagulant properties During the recent years, there have been concerns about acetate causing activation of cells and inflammatory markers. There is a lot of interest in further reducing or removing acetate from the dialysate.
Liquid versus dry concentrate: Both acetate- and citrate-containing concentrates
are available in either dry form or liquid form. The dry concentrate is dissolved
in appropriate volume of treated water before connecting it the machine. Exam-
ples of dry forms are Granuflo R (8 mEq/l acetate) by Fresenius, and DRYalysate R (2.4 mEq/l citrate) by Advanced Renal Technologies. Examples of liquid formulations are Naturalyte R and Citrasate R , by Fresenius and Advanced Renal Technologies, respectively.
The clinical effects of the two currently used acid concentrates
Type of dialysate Disadvantages Advantages
Acetate-containing
bicarbonate dialysate Intradialytic compli-
cations,
Activation of cells
Activation of inflam-
matory proteins
bicarbonate dialysate Intradialytic compli-
cations,
Activation of cells
Activation of inflam-
matory proteins
Citrate-containing
bicarbonate dialysate Decrease in Ca and
Mg Reduced clotting:
• Increase in the
dose of dialysis
• Heparin-free
acute/chronic
dialysis
• Reduced heparin
chronic dialysis
• Increase in reuse
of dialyzer
bicarbonate dialysate Decrease in Ca and
Mg Reduced clotting:
• Increase in the
dose of dialysis
• Heparin-free
acute/chronic
dialysis
• Reduced heparin
chronic dialysis
• Increase in reuse
of dialyzer
Bicarbonate concentrate: Bicarbonate is available in powder form. The powder is either mixed manually with appropriate volume of water prior to connecting to the machine, or the powder comes filled in a cartridge and is attached to the machine. With the cartridge form, the water is delivered to the cartridge and the concentrated solution is used directly from the cartridge by the machine.
Lactate-containing dialysate: In a small number of home dialysis patients using
frequent and slower rate dialysis, the NxStage machine uses a dialysate that contains lactate in place of bicarbonate as a basic anion. Thus, currently used dialysates contain bicarbonate as the predominant basic anion (used for the vast majority of patients) or lactate (used for only a small number of patients).
Lactate-containing dialysate: In a small number of home dialysis patients using
frequent and slower rate dialysis, the NxStage machine uses a dialysate that contains lactate in place of bicarbonate as a basic anion. Thus, currently used dialysates contain bicarbonate as the predominant basic anion (used for the vast majority of patients) or lactate (used for only a small number of patients).
1.5.2.2 Dialysate Delivery System
The dialysate delivery system blends and provides dialysate to the dialyzer, monitors dialysate quality, and controls and monitors UF from the patient. It can be divided into four
major components:
Water preparation system: Treated (purified) water is delivered to the machine, where it is heated to an appropriate temperature (34–39 ◦ C) by a heater and deaerated (usually by subjecting the heated water to a negative pressure, using a pump). Water is then delivered to the proportioning system.
Proportioning system: There are different types of proportioning systems based
on whether dialysate, water, or both are metered. Simply stated, the proportioning system takes appropriate volumes (based on how concentrated the concentrate is) of parts A and B of the concentrate and mixes them with the appropriate volume of (in the appropriate ratio) treated water to form the final A and B dialysates, the final mixing of the two diluted parts A and B makes the final dialysate; the composition is shown in Table 2.2. The final dialysate is then checked for proper mixing (proportioning) by measuring the conductance of electricity through the final dialysate. The rate of flow of an electric current through any solution is proportional to the concentration of electrolytes present in the solution, thus, distilled water is a very poor conductor of electricity, and the salt solution is a good conductor. Thus, from the rate of electrical conductance, the concentration of salt in the solution can be verified. Roughly, the conductance is about 1/10th of the sodium concentration, thus
a dialysate of 135 mEq/l sodium concentration should have a conductivity value
of 13.5 ms/s. If the conductivity of the dialysate is in the acceptable range, the
dialysate is allowed to proceed to the dialyzer. If the conductivity is out of range,
the dialysate is diverted to the bypass loop. The temperature of the dialysate is also monitored prior to its passage through the dialyzer, if the temperature is out of range, the dialysate is diverted to bypass. It is important to have separate and independent sensors monitoring and controlling the proportioning units.
on whether dialysate, water, or both are metered. Simply stated, the proportioning system takes appropriate volumes (based on how concentrated the concentrate is) of parts A and B of the concentrate and mixes them with the appropriate volume of (in the appropriate ratio) treated water to form the final A and B dialysates, the final mixing of the two diluted parts A and B makes the final dialysate; the composition is shown in Table 2.2. The final dialysate is then checked for proper mixing (proportioning) by measuring the conductance of electricity through the final dialysate. The rate of flow of an electric current through any solution is proportional to the concentration of electrolytes present in the solution, thus, distilled water is a very poor conductor of electricity, and the salt solution is a good conductor. Thus, from the rate of electrical conductance, the concentration of salt in the solution can be verified. Roughly, the conductance is about 1/10th of the sodium concentration, thus
a dialysate of 135 mEq/l sodium concentration should have a conductivity value
of 13.5 ms/s. If the conductivity of the dialysate is in the acceptable range, the
dialysate is allowed to proceed to the dialyzer. If the conductivity is out of range,
the dialysate is diverted to the bypass loop. The temperature of the dialysate is also monitored prior to its passage through the dialyzer, if the temperature is out of range, the dialysate is diverted to bypass. It is important to have separate and independent sensors monitoring and controlling the proportioning units.
Volumetric-controlled machines: These machines have two integral parts to
ensure accurate ultrafiltration,
(1) the balancing chamber
(2) the UF controller
1. Balancing chamber:
The risk of over-ultrafiltration because of the use of per- meable dialyzers required the development of a machine that could accurately track the ultrafiltration and control the rate. This was achieved by ensuring that dialysate inflow into and outflow out of the dialyzer were same. The “balancing” of the two flows is most commonly achieved by allowing the inflow and outflow into a rigid chamber and keeping the two volumes separated by a diaphragm that deflects an equal distance from the middle. This balancing chamber concept works by inflowing a fixed volume into the chamber, and the fixed deflection of
the diaphragm pushes an equal volume out of the chamber. The interplay of the
four sets of one-way valves ensures that an equal volume of dialysate goes into
and comes out of the dialyzer. Two sets of these balancing chambers acting in
alternate cycles achieve a more continuous flow of the dialysate.
the diaphragm pushes an equal volume out of the chamber. The interplay of the
four sets of one-way valves ensures that an equal volume of dialysate goes into
and comes out of the dialyzer. Two sets of these balancing chambers acting in
alternate cycles achieve a more continuous flow of the dialysate.
2. UF controller:
A separate line branches out of the dialysate outflow line, the flow in this line is controlled by a UF pump. The pump in turn is controlled by a central computer unit that gets information from the dialyzer inlet and outlet pressures for both blood and dialysate; the unit also gets information about the required rate and net volume of UF fed into the machine prior to the treatment. This computer unit then controls the UF rate by controlling the UF pump. Monitors and detectors: For safety, several monitors and detectors are used in the
dialysate delivery system:
(i) Conductivity monitor: As discussed earlier, the appropriate mixing of concentrate with water is monitored by conductivity. Because this monitor essentially checks the electrolyte concentrations in the final dialysate, any malfunction that is accompanied by abnormal proportioning can be potentially fatal for the patient. Any deviation from the narrow set range leads to the sounding of an alarm and the interruption of dialysis.
(ii) Temperature monitor: Patients need to be dialyzed with dialysate at 36–42 ◦ C. Dialysis at <36 ◦ C is associated with the patient feeling cold and uncomfortable, and a dialysate temperature of >42 ◦ C is associated with severe hemolysis and cardiopulmonary arrest. The dialysate temperature is monitored and a thermostat controls the water heater. Any increase in temperature beyond the set range triggers an alarm and dialysis is stopped (usual safe range set between 35–39 C).
(iii) Blood leak detector: Blood leak sensors are placed on the dialysate outflow line. These are usually flow-through photo-optical or blue frequency spectrum sensors.
(iv) pH sensors: Some machines have a pH electrode as part of the proportioning system. These are generally used to prevent any mistake in connecting the appropriate concentrates to the machine (e.g., B concentrate not being connected).
(v) Arterial and venous pressure monitors: Both arterial and venous drip chambers are connected to a pressure sensor through a filter. The pressure ranges are set in the safe range to monitor the blood delivery to and from the system. The prepump arterial pressure would usually be a negative number representing the demand by the pump. Generally, the safe lower limit of the arterial pressure is no lower than −100 mmHg. The venous pressure is generally kept below 200 mmHg.
(vi) Air detector: An air detector is located on the venous drip chamber. If too much air collects, an alarm sounds, the pump stops, and a blood line below the drip chamber is clamped to prevent an accidental infusion of air.
(ii) Temperature monitor: Patients need to be dialyzed with dialysate at 36–42 ◦ C. Dialysis at <36 ◦ C is associated with the patient feeling cold and uncomfortable, and a dialysate temperature of >42 ◦ C is associated with severe hemolysis and cardiopulmonary arrest. The dialysate temperature is monitored and a thermostat controls the water heater. Any increase in temperature beyond the set range triggers an alarm and dialysis is stopped (usual safe range set between 35–39 C).
(iii) Blood leak detector: Blood leak sensors are placed on the dialysate outflow line. These are usually flow-through photo-optical or blue frequency spectrum sensors.
(iv) pH sensors: Some machines have a pH electrode as part of the proportioning system. These are generally used to prevent any mistake in connecting the appropriate concentrates to the machine (e.g., B concentrate not being connected).
(v) Arterial and venous pressure monitors: Both arterial and venous drip chambers are connected to a pressure sensor through a filter. The pressure ranges are set in the safe range to monitor the blood delivery to and from the system. The prepump arterial pressure would usually be a negative number representing the demand by the pump. Generally, the safe lower limit of the arterial pressure is no lower than −100 mmHg. The venous pressure is generally kept below 200 mmHg.
(vi) Air detector: An air detector is located on the venous drip chamber. If too much air collects, an alarm sounds, the pump stops, and a blood line below the drip chamber is clamped to prevent an accidental infusion of air.
1.5.2.3 Dialysis Water
Drinking water contains chemical, microbiological, and other contaminants. A
healthy adult drinks about 10–12 l of water per week, this water goes across a selective barrier of the gastrointestinal tract, and excess chemicals are removed by the healthy kidney. In contrast, during dialysis, a dialysis patient is exposed to more than 350 l of water weekly, the water passes through the nonselective dialyzer membrane, and there is no kidney to maintain the normal balance of chemicals. More over, the highly permeable high-flux membrane used today increases the risk of ontaminants passing through the membrane and into the blood gives the commonly present contaminants and medical syndrome caused by these in dialysis patients. Some common contaminants have been shown to be injurious to patients. Contaminants include aluminum (causing bone and brain problems and anemia), copper (causing hemolytic anemia and febrile reactions), and chloramine (causing hemolytic anemia). If the large quantities of salt and electrolytes that are normally present in the water are allowed to remain, higher concentrations of these occur in the final dialysate. The Association for the Advancement of Medical Instrumentation (AAMI) has recommended minimum standards for the water used in dialysis Thus, the water for dialysis must be purified of these contaminants prior to its use by the proportioning system of the dialysis machine.
healthy adult drinks about 10–12 l of water per week, this water goes across a selective barrier of the gastrointestinal tract, and excess chemicals are removed by the healthy kidney. In contrast, during dialysis, a dialysis patient is exposed to more than 350 l of water weekly, the water passes through the nonselective dialyzer membrane, and there is no kidney to maintain the normal balance of chemicals. More over, the highly permeable high-flux membrane used today increases the risk of ontaminants passing through the membrane and into the blood gives the commonly present contaminants and medical syndrome caused by these in dialysis patients. Some common contaminants have been shown to be injurious to patients. Contaminants include aluminum (causing bone and brain problems and anemia), copper (causing hemolytic anemia and febrile reactions), and chloramine (causing hemolytic anemia). If the large quantities of salt and electrolytes that are normally present in the water are allowed to remain, higher concentrations of these occur in the final dialysate. The Association for the Advancement of Medical Instrumentation (AAMI) has recommended minimum standards for the water used in dialysis Thus, the water for dialysis must be purified of these contaminants prior to its use by the proportioning system of the dialysis machine.
1.5.2.4 Water Treatment System
Two major types of water purification systems are in common use: (1) reverse os- mosis (R/O) and (2) deionizer (D/I). However, to protect and prolong the lives of R/O membrane or the D/I resins, water goes through several steps of “pretreatment”. Pretreatment system: The first component of the pretreatment system is a sediment filter that removes sediments such as silt, rust, and clay as water percolates through the filter. Next, there is a water softener that is filled with resin charged with NaCl; as water passes around these resin beads, the Ca and Mg in the water are exchanged with NaCl, thus, water coming out has less Ca and Mg. The softner is periodically recharged by flushing it with brine. The water next is passed through a set of activated charcoal columns. Some organic contaminants and especially the chlo-rine and chloramines are adsorbed on the charcoal surface and removed from the water. This is important because chloramines can damage the R/O membranes and are not effectively removed by the D/I. Exhaustion of the charcoal column has led to several significant incidences of chloramine toxicity. It is, therefore, required that treated water is checked for chloramines at least three times a day to ensure proper functioning of the charcoal columns. Sets of several gradually decreasing sizes of filters (from 5 to 2 μm) are placed to remove smaller particles. The pretreated water
is then passed through the final water treatment system, either R/O or D/I.
Reverse osmosis system (R/O): Membranes with very small holes are arranged
in a cartridge either in the form of a parallel plate or capillary fibers. The holes
are so small that they only allow water molecules to pass through, retaining any-
thing larger, including sodium and urea. The pretreated water is forced through these holes by a pump that generates enough pressure to squeeze water molecules against higher osmolar pressure, thus, the name, reverse osmosis. The membrane separates the pure water or permeate from the “rejected” water, the pure water is allowed to circulate through the dialysis unit to be used for the dialysate proportioning; the rejected water is drained out. The R/O membranes are made from either cellulosic or synthetic materials. Cellulosic membranes are prone to be damaged by bacteria, whereas the synthetic membranes (polyamide, polysulfones, etc.) are more vulnerable to chemicals such as chloramines and chlorine. The efficacy of the membrane is continuously monitored by measuring the resistance to electrical current through the product (permeate) and feed water. A membrane that rejects >85% of conductant water is considered to be functioning well, if this rejection rate goes below 85%, the membrane needs to be changed. The rejection ratio = (1− [conductivity permeate/conductivity feed water]) ×100. Deionization (D/I): Removal of inorganic ions by exchanging the inorganic ions with H + and OH − ions is the process of D/I. The most common type is a mixed-bed D/I that consists of resins fixed with H + (cation)
and other resins coated with OH − ions (anion). As water with dissolved inorganic ions percolates first through the cation exchange resin, the dissolved cations (Na, Ca, Mg, etc.) are exchanged for H + . Water then passes through the anion exchange resins and anions (Cl, Fl, NO 3 , etc.) are exchanged with OH − , H + , and OH − , then forming pure water that, after going through submicron filters and often ultraviolet light, is permitted to loop around the unit. The product water coming out of D/I is monitored by checking the resistivity, which should be greater than 1 mΩ /cm to be
acceptable. Most of the major catastrophies afflicting groups of patients have been caused by improperly treated water delivering contaminants to the blood. Thus, it is mandatory to use an effective water treatment system and to continuously monitor the quality of the water. Moreover, the increased use of highly permeable high-flux dialyzers increases the potential for the transfer of contaminants into the blood, thus, the water needs to be further purified. Some units use a tight membrane filter (dialyzer); the dialysate passes across this first dialyzer prior to its delivery to the patient dialyzer. This “ultrapure” dialysate further protects the patient.
Two major types of water purification systems are in common use: (1) reverse os- mosis (R/O) and (2) deionizer (D/I). However, to protect and prolong the lives of R/O membrane or the D/I resins, water goes through several steps of “pretreatment”. Pretreatment system: The first component of the pretreatment system is a sediment filter that removes sediments such as silt, rust, and clay as water percolates through the filter. Next, there is a water softener that is filled with resin charged with NaCl; as water passes around these resin beads, the Ca and Mg in the water are exchanged with NaCl, thus, water coming out has less Ca and Mg. The softner is periodically recharged by flushing it with brine. The water next is passed through a set of activated charcoal columns. Some organic contaminants and especially the chlo-rine and chloramines are adsorbed on the charcoal surface and removed from the water. This is important because chloramines can damage the R/O membranes and are not effectively removed by the D/I. Exhaustion of the charcoal column has led to several significant incidences of chloramine toxicity. It is, therefore, required that treated water is checked for chloramines at least three times a day to ensure proper functioning of the charcoal columns. Sets of several gradually decreasing sizes of filters (from 5 to 2 μm) are placed to remove smaller particles. The pretreated water
is then passed through the final water treatment system, either R/O or D/I.
Reverse osmosis system (R/O): Membranes with very small holes are arranged
in a cartridge either in the form of a parallel plate or capillary fibers. The holes
are so small that they only allow water molecules to pass through, retaining any-
thing larger, including sodium and urea. The pretreated water is forced through these holes by a pump that generates enough pressure to squeeze water molecules against higher osmolar pressure, thus, the name, reverse osmosis. The membrane separates the pure water or permeate from the “rejected” water, the pure water is allowed to circulate through the dialysis unit to be used for the dialysate proportioning; the rejected water is drained out. The R/O membranes are made from either cellulosic or synthetic materials. Cellulosic membranes are prone to be damaged by bacteria, whereas the synthetic membranes (polyamide, polysulfones, etc.) are more vulnerable to chemicals such as chloramines and chlorine. The efficacy of the membrane is continuously monitored by measuring the resistance to electrical current through the product (permeate) and feed water. A membrane that rejects >85% of conductant water is considered to be functioning well, if this rejection rate goes below 85%, the membrane needs to be changed. The rejection ratio = (1− [conductivity permeate/conductivity feed water]) ×100. Deionization (D/I): Removal of inorganic ions by exchanging the inorganic ions with H + and OH − ions is the process of D/I. The most common type is a mixed-bed D/I that consists of resins fixed with H + (cation)
and other resins coated with OH − ions (anion). As water with dissolved inorganic ions percolates first through the cation exchange resin, the dissolved cations (Na, Ca, Mg, etc.) are exchanged for H + . Water then passes through the anion exchange resins and anions (Cl, Fl, NO 3 , etc.) are exchanged with OH − , H + , and OH − , then forming pure water that, after going through submicron filters and often ultraviolet light, is permitted to loop around the unit. The product water coming out of D/I is monitored by checking the resistivity, which should be greater than 1 mΩ /cm to be
acceptable. Most of the major catastrophies afflicting groups of patients have been caused by improperly treated water delivering contaminants to the blood. Thus, it is mandatory to use an effective water treatment system and to continuously monitor the quality of the water. Moreover, the increased use of highly permeable high-flux dialyzers increases the potential for the transfer of contaminants into the blood, thus, the water needs to be further purified. Some units use a tight membrane filter (dialyzer); the dialysate passes across this first dialyzer prior to its delivery to the patient dialyzer. This “ultrapure” dialysate further protects the patient.
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