Ultrafiltration and Dialysis | Thoracic Key

Ultrafiltration and Dialysis | Thoracic Key
June 7, 2016 0 Comments

Sufferers present process cardiopulmonary bypass (CPB) typically develop fluid overload and electrolyte imbalances (1,2,3). As well as, publicity to international surfaces of the extracorporeal circuit and surgical trauma can itself promote capillary permeability and shifting of fluid to the extravascular house (1,2,3). Ultrafiltration and dialysis may also help attenuate these adjustments and are due to this fact necessary adjuncts to CPB and associated extracorporeal applied sciences. Ultrafiltration and dialysis are each utilized to handle blood quantity, hemoglobin, protein, and sure electrolyte concentrations (2,4). As well as, a number of research recommend that ultrafiltration and dialysis could cut back mediators that provoke a systemic inflammatory response syndrome (SIRS) (5,6,7).

Ultrafiltration is the motion of water throughout a membrane as the results of a hydrostatic strain gradient or transmembrane strain (TMP) (8). No dialysate on the other facet of the membrane is required. As water diffuses, it creates a solute focus gradient throughout the membrane. These solutes then diffuse throughout the membrane, equalizing the concentrations in a strategy of solute removing known as convection. The fluid eliminated throughout ultrafiltration is named ultrafiltrate or plasma water.

Dialysis refers to a course of wherein the blood is separated from a crystalloid resolution or dialysate by a semipermeable membrane (9). A solute focus gradient exists between the blood and the dialysate, leading to solute transport by diffusion from the next to a decrease focus. Ultrafiltration could also be employed throughout dialysis by altering the TMP (10).

The aim of this chapter is to explain the idea of ultrafiltration and dialysis and clarify their varied makes use of and advantages within the extracorporeal circuit throughout CPB.


In 1854, Thomas Graham, a Scottish chemist, offered a paper entitled “Osmotic Drive,” which described the method of separating substances utilizing a semipermeable membrane (11). He later demonstrated that handled parchment paper may very well be used to separate bigger molecules or colloids from crystalloids. He was additionally the primary to explain the direct relation between solute molecular weight and solute diffusion price. After Graham’s paper was revealed, different investigators continued to review varied membrane supplies that is likely to be used to separate colloids from crystalloids. In 1855, Adolf Fick described using collodion, a cellulose-trinitrate by-product, as a diffusive membrane (12).

In 1913, John Jacob Abel’s curiosity in deriving usable solutes from animal blood led to the primary reported dialysis process (13). Abel used a collodion membrane and, as a result of blood was circulated exterior the animal, it was mandatory for Abel to discover a strategy to hold the blood from clotting when uncovered to international surfaces. Abel solved this downside by creating hirudin, an anticoagulant derived from crushed leech heads.

The primary medical dialysis process was carried out by George Haas in 1924 (9). Between 1924 and 1928 he dialyzed six sufferers, however sadly had no survivals. Nevertheless, Haas made vital progress within the subject of hemodialysis in 1927 by the addition of a blood pump and use of a newly found anticoagulant, heparin.

All through the Thirties, many investigators developed and studied varied semipermeable membrane supplies, together with cellophane and chemically modified cellulose (14,15). After World Conflict II, Willem Kolff, on the College of Groningen within the Netherlands, constructed a man-made kidney using the regenerated cellulose membrane, cellophane. This system was a rotating drum barrel product of slats, with open areas between the slats. The membrane materials used was a comparatively new materials initially developed for meals packaging. The cellophane sausage casing was wound across the drum. The drum was rotated by an electrical motor and submerged in a tank full of dialysate resolution. The blood was drawn from the affected person into the cellophane casing by gravity (Fig. 4.1). Between 1943 and 1944, Kolff dialyzed a complete of 15 sufferers; nevertheless, just one survived. In 1945, he dialyzed a comatose affected person in acute renal failure for 1 week. Her renal perform returned and she or he ultimately recovered to be launched from the hospital (16). Kolff’s guide, “New Methods of Treating Uremia” (17) grew to become the primary handbook for treating sufferers on hemodialysis, and following World Conflict II he collaborated with colleagues at Brigham Hospital to make vital enhancements to his authentic system, which grew to become generally known as the Kolff-Brigham kidney. Between 1954 and 1962, he shipped his dialysis machines to 22 facilities worldwide. This dialysis machine
was copied by others and by the mid-Forties there have been many dialysis applications all through the world. In 1950, Kolff collaborated with Drs. Victor Vertes and Bruno Watschinger to enhance a beforehand described coil-type dialyzer wherein cellulose acetate tubing was wrapped round a plastic core. He developed the primary ready-to-use disposable synthetic kidney by putting the gadgets in polyethylene luggage for sterilization (18).

FIGURE 4.1. Rotating drum kidney designed by Willen Kolff within the Forties.

The event of the flat or parallel plate dialyzer started in 1947 by Leonard Skeggs and Jack Leonards (19). On this design, sheets of membrane materials had been sandwiched between two rubber pads and included a number of membrane layers to cut back the blood quantity and improve the membrane floor space. By the early Fifties, Kiil reported outcomes with a flat plate dialyzer wherein blood was made to movement between two sheets of cellophane supported by strong mats with grooves for the circulation of dialysate.(20) In 1956, Richard Stewart started the event of the hole fiber dialyzer design (21). It was constructed from a modified cellulose materials, cellulose diacetate, and supplied a high-efficacy solute transport whereas sustaining a low priming quantity and a low resistance to blood movement. The membrane materials, extruded in hole fibers, was minimize and bundled collectively, then potted in polyurethane on every finish and encased in a polycarbonate shell. Blood flowed by way of the hole fiber and the dialysate flowed across the hole fibers. This mannequin grew to become commercially obtainable in 1970 and is the kind of dialyzer and ultrafiltrator most generally used at the moment.


Ultrafiltration is achieved by way of the filtration of water throughout a semipermeable membrane utilizing the power derived from a hydrostatic strain gradient (11). When water crosses the membrane, it creates a solute focus gradient between the blood and the ultrafiltrate facet of the membrane, which has no solutes. The dissolved solutes, which have the next focus within the blood, comply with the focus gradient and are transferred from the blood to the ultrafiltrate, the so-called solute drag or convection. This strategy of eradicating plasma water or ultrafiltrate from the blood makes use of a microporous membrane materials generally manufactured in a hole fiber configuration.

Mechanism of Motion

Take into account a tank separated by a semipermeable membrane. A semipermeable membrane implies that sure substances will penetrate the membrane whereas others is not going to. This pertains to microscopic holes within the membrane, which solely permit water and small molecular weight solutes to cross. If one facet of the tank is full of blood and a strain is exerted on that compartment, water from the blood will transfer throughout the membrane into the opposite compartment. Due to their increased focus within the blood compartment, the solutes with small molecular weight will transfer to the water facet of the compartment till there’s an equal focus on each side. This leads to a focus of blood cells and enormous molecules on one facet of the membrane and water and small molecules on the opposite facet (Fig. 4.2).

Throughout ultrafiltration, the blood passes by way of a bundle of hole fibers constructed from a microporous membrane. The hole fibers are between 180 and 200 µm in diameter and the pores of the microporous membrane are between 5 and 10 nm (22,23). Hundreds of hole fibers are configured in a bundle and encased in a polycarbonate shell (Fig. 4.3). As blood flows by way of the hole fibers of an ultrafiltrator, additionally known as a hemoconcentrator, it creates a constructive strain throughout the hole fibers. This strain differential between the blood facet and the atmospheric strain on the ultrafiltrate facet of the membrane drives water throughout the membrane. As within the tank analogy, water is shifted from the blood path to the ultrafiltrate compartment; a solute focus gradient is generated between the blood and the ultrafiltrate. By convection, solutes smaller than the membrane pore measurement transfer with the water to equalize the solute focus gradient. In some ways the method mimics glomerular filtration (Desk 4.1).

The strain gradient between the blood path and the ultrafiltrate compartment is named the transmembrane strain. The TMP may be expressed by the system

TMP = (Pin + Pout)/2 + V

the place Pin = Blood inlet strain, Pout = Blood outlet strain, and V = Destructive strain utilized to the effluent facet of the hemoconcentrator.

To keep away from membrane rupture, the TMP should not exceed the producer’s beneficial pressures of 500 to 600 mm Hg. The speed of fluid removing relies on the membrane permeability, blood movement, TMP, and hematocrit (22). The membrane permeability is said to the pore measurement, membrane materials, and membrane thickness, and is described by the ultrafiltration coefficient (OkUF) (22,24,25). The OkUF relates the speed of water removing to the TMP for a specific system at a relentless
blood movement. Typical charges are between 2 and 50 mL/hr/mm Hg. Because the OkUF items indicate, improve within the TMP will increase the speed of water removing. The OkUF can also be depending on the blood movement by way of the ultrafiltrator, with increased blood movement leading to the next OkUF (Fig. 4.4). Simply as decrease hematocrit ranges and decrease plasma protein concentrations will improve glomerular filtration price, they will even improve the ultrafiltration price.

FIGURE 4.2. Convection. A: Blood compartment is pressurized and water from the blood strikes throughout the membrane. B: Ends in blood on one facet of the membrane and water on the opposite facet, which creates a solute focus gradient between the 2 elements. C: Small molecular weight solutes diffuse throughout the membrane to equalize the focus gradient.

FIGURE 4.3. Hole fiber hemoconcentrator.

TABLE 4.1. Dialyzer-nephron comparability



Blood influx tubing

Afferent arteriole

Hole fibers


Dialyzer assortment compartment

Bowman capsule

Drainage tubing

Amassing tubule

Blood outflow tubing

Efferent arteriole

As a result of the method of ultrafiltration removes plasma water and diffusible solutes in equal focus to the plasma water, the general focus of the diffusible solutes usually are not affected. Though depending on the membrane materials and pore measurement, usually, solutes better than 65,000 Da usually are not eliminated by ultrafiltration. Mobile components, plasma proteins,
and protein-bound solutes is not going to be eliminated and can due to this fact be concentrated (26).

FIGURE 4.4. Transmembrane strain (TMP) versus ultrafiltration price (OkUF) for a typical hemoconcentrator. To maximise OkUF, each the blood movement (Q) and the TMP should be adjusted.

Sieving Coefficient

The power of a solute to be filtered by way of the ultrafiltrator membrane relies on the molecular weight of the solute in contrast with the membrane pore measurement, the proportion of the solute that’s protein certain, and the floor cost of the solute (27). The sieving coefficient is the ratio of ultrafiltrate solute focus to plasma solute focus and ranges from 0 to 1.0. A sieving coefficient of 1.0 signifies that the ultrafiltrate solute focus and the plasma solute focus are equal and that the solute passes freely throughout the membrane. A sieving coefficient of 0 signifies that not one of the solute passes by way of the membrane. Small molecular weight solutes that aren’t protein certain are simply eliminated by ultrafiltration and have a sieving coefficient of 1.0. Within the case of partially protein-bound small molecular weight solutes, the ultrafiltrate solute focus can be equal to the non-protein-bound solute focus.

Indications and Outcomes

Using ultrafiltration throughout CPB was first reported in 1979 by Darup et al. (4). Within the early Nineteen Eighties, a number of different investigators reported using ultrafiltration within the extracorporeal circuit and located that eradicating plasma water throughout CPB resulted in enchancment in various features of affected person care (28,29,30,31,32).

Sufferers present process CPB are topic to vital hemodilution, primarily because of the extracorporeal circuit prime of 1 to 2 L of crystalloid resolution, with homologous blood merchandise and plasma proteins hardly ever added to the extracorporeal circuit prime to attenuate financial institution blood utilization (33). Throughout CPB, extra crystalloid could accumulate within the venous reservoir by way of cardioplegia and surgical irrigation from cardiotomy suction. Sufferers present process CPB for coronary heart surgical procedure could have elevated blood volumes attributable to congestive coronary heart failure and/or renal failure (34). Ultrafiltration could take away extra fluid; nevertheless, the quantity of fluid eliminated is proscribed by the minimal degree allowed within the venous reservoir of the extracorporeal circuit. As soon as the minimal reservoir quantity has been achieved, additional will increase in hematocrit and plasma protein ranges could solely be completed by the addition of homologous crimson blood cells or albumin. After the addition of the crimson cells or albumin, ultrafiltration could proceed till the amount equal to the added crimson cells or albumin is eliminated (Fig. 4.5).

The extracorporeal circuit additionally exposes the affected person’s blood to international surfaces which will set off SIRS and, particularly, improve capillary permeability (35). Subsequently, as CPB is initiated, the affected person is topic to a dilutional decline in hemoglobin and serum protein concentrations and get in touch with activated inflammatory capillary leak, resulting in fluid motion to the interstitial house, tissue edema, and decreased end-organ perfusion.

Ultrafiltration can focus the blood with out the removing of plasma proteins, may be utilized throughout CPB when there’s extra reservoir quantity, and is especially helpful when the affected person is proof against diuretics (28,29). Research have proven that sufferers who endure ultrafiltration display elevated protein and crimson blood cell concentrations (28,36) and decreased lung waters (29), decreased fluid steadiness (29), and decreased tissue edema (37,38,39). It has additionally been discovered to enhance perioperative hemostasis and cut back postoperative ventilatory help (4).

Technical Purposes

The hemoconcentrator or ultrafiltrator is configured in parallel to the extracorporeal circuit. Blood could also be propelled by way of a pump (28,40), however for simplicity, it’s typically configured within the extracorporeal circuit as a passive shunt from some extent of upper strain to decrease strain. Within the pumpless configuration, the influx to the ultrafiltrator originates from a port or connection off the high-pressure arterial line (distal to the arterial pump) and the outflow of the ultrafiltrator returns to a decrease strain port or connection situated both on the venous line or the venous reservoir (Fig. 4.6). With out the pump, the movement by way of the ultrafiltrator depends on the strain differential between the influx and outflow of the ultrafiltrator. This may be simply approximated within the grownup affected person by utilizing the ideas of movement and resistance. Throughout CPB, the perfusionist screens line strain distal to the arterial pump, which ranges between 150 and 250 mm Hg, and depends on blood-flow price and resistance. The resistance to movement is set by arterial cannula measurement, design, and placement, in addition to the affected person’s arterial blood strain. If the ultrafiltrator shunt, which is parallel to the primary circuit, is opened and the pump movement and different resistance-related variables stay the identical, blood movement to the affected person by way of the arterial cannula will decline and the road strain will drop attributable to diminished resistance to blood movement. If the arterial pump movement is elevated
to the purpose the place line strain returns to baseline, then, theoretically, movement to the affected person must also return to baseline. The distinction between previous pump movement and new pump movement is the movement shunted to the hemoconcentrator (Fig. 4.7). A clamp on the ultrafiltrator blood outflow line will cut back shunting, but it surely is not going to improve strain contained in the hole fibers nor will it improve TMP or ultrafiltration price. It can, the truth is, cut back ultrafiltration price as a result of blood movement by way of the ultrafiltrator has been decreased. A flowmeter could also be used for extra exact measurements and is extremely beneficial
in pediatric sufferers (41). When utilizing a centrifugal pump, the movement probe must be distal to the ultrafiltrator shunt to find out the precise blood movement to the affected person and never the mixed blood movement to the affected person and ultrafiltrator.

FIGURE 4.5. Ultrafiltration can maximize the impact of homologous crimson blood cell administration. PRBC, packed crimson blood cells; Hct, hematocrit.

FIGURE 4.6. The hemoconcentrator is configured as a passive shunt parallel to the cardiopulmonary bypass (CPB) circuit.

FIGURE 4.7. Instance of blood movement by way of a hemoconcentrator setup as a passive shunt from the arterial line that shunts blood away from the affected person. This shunt varies and relies on the arterial line strain. A: Hemoconcentrator shunt is closed. The pump blood movement is 5 L/min, which is delivered to the affected person by way of the arterial line requiring a line strain of 150 mm Hg. B: Hemoconcentrator shunt is opened. If the pump movement stays at 5 L/min the road strain will drop; nevertheless, the distribution of blood movement by way of the hemoconcentrator and to the affected person is unknown. C: If the pump movement is elevated such that the road strain returns to baseline, then it may be assumed that the blood movement to the affected person has returned to five L/min and that the blood movement by way of the hemoconcentrator is the distinction between the previous pump movement and the brand new pump movement (on this case 0.25 L/min).

Tubing from the effluent facet of the ultrafiltrator is connected to a set canister and, on condition that ultrafiltrators used for CPB have comparatively excessive ultrafiltration charges (additionally termed excessive flux), ample charges of fluid removing are achieved by establishing a hydrostatic strain gradient by altering the peak between the ultrafiltrator and the canister. The hydrostatic gradient can differ between 60 and 90 cm, leading to an efficient hydrostatic strain of roughly 45 to 65 mm Hg. The TMP could also be augmented by making use of a vacuum supply to the effluent facet of the ultrafiltrator.

The method of ultrafiltration could probably result in hypovolemia, with elevated osmolarity within the intravascular quantity inflicting interstitial fluid to slowly shift into the vascular house (30). A affected person supported on CPB can tolerate the next price of ultrafiltration with out turning into hemodynamically unstable as a result of the cardiac output is managed by the bypass pump and doesn’t depend upon the intravascular quantity.


The first function of ultrafiltration throughout CPB is to take away extra water and to pay attention the mobile components and proteins within the blood. Electrolytes and different solutes are additionally eliminated however in equal focus to the affected person’s plasma water. Subsequently, the affected person’s plasma focus of diffusible solutes stays unchanged. As talked about beforehand, investigators learning ultrafiltration throughout and instantly after CPB discovered enhancements in affected person hemodynamics, cardiac contractility, and oxygenation. Initially these advantages had been attributed to water removing; nevertheless, subsequent investigations testing for varied substances within the ultrafiltrate discovered measurable ranges of cytokines (42,43,44,45,46). As a result of most cytokine and complement ranges attain their peak throughout rewarming, Journois et al. (47) hypothesized that steady ultrafiltration throughout this era would additional attenuate the inflammatory response. To permit steady ultrafiltration in the course of the rewarming part of CPB, the authors changed the ultrafiltrate with a balanced electrolyte resolution. They matched the ultrafiltration price with the infusion price by loading the ultrafiltration effluent line and the electrolyte resolution infusion tubing right into a single curler pump. The effluent and infusion tubing had been loaded in reverse instructions in order that the ultrafiltration price was equal to the infusion price and the affected person remained isovolemic. When evaluating sufferers who acquired Z-BUF throughout rewarming to a management group that didn’t obtain ultrafiltration throughout CPB, an enchancment was famous in postoperative alveolar-arterial oxygen gradient that considerably correlated with the amount of ultrafiltrate eliminated within the Z-BUF group. The remedy group additionally had much less blood loss and a decrease physique temperature within the intensive care, additional supporting the idea that the irritation course of had been attenuated. Z-BUF is just like hemofiltration utilized in dialysis items, whereby plasma water is ultrafiltrated at a excessive price with the amount eliminated changed with a balanced electrolyte resolution (48,49).

A type of Z-BUF has additionally been utilized by perfusionists to appropriate hyperkalemia (49,50). Potassium hundreds throughout cardiopulmonary bypass originate from potassium-based cardioplegia and homologous crimson blood cells and should exceed the affected person’s potential to clear extra potassium by way of regular glomerular filtration (51,52,53). Because the affected person’s blood quantity is decreased by ultrafiltration, the potassium degree shouldn’t be affected as a result of the ultrafiltrate potassium ranges will at all times be in equal focus to the plasma. When ultrafiltration is steady, the potassium ranges may be lowered by changing the amount with an answer low in potassium.

Z-BUF has additionally been used to appropriate extreme electrolyte and acid-base disturbances in adults present process cardiac surgical procedure.
Electrolyte and acid-base corrections may be completed quickly, and since the clinician can choose the focus of diffusible solutes within the alternative fluid, they’ll extra precisely predict remedy results (54,55).

Circuitry and Administration of Z-BUF

In Z-BUF, the hemoconcentrator is positioned within the CPB circuit and plasma water is eliminated just like ultrafiltration. Nevertheless, in Z-BUF, the amount of plasma water eliminated is changed by an equal quantity of a balanced electrolyte resolution.

When the aim of Z-BUF is to take away inflammatory mediators, the alternative fluid may be commercially manufactured options corresponding to Hartman resolution, lactated Ringers, Plasma-Lyte-A, or Normosol. These alternative options include acetate or lactate, each of which endure conversion to bicarbonate within the liver and muscle and supply the mandatory buffer to offset the bicarbonate loss throughout Z-BUF. Bicarbonate-containing options are themselves unstable and might type precipitates when combined with options containing calcium or magnesium. When utilizing Z-BUF to cut back potassium ranges, the beforehand talked about alternative options don’t effectively dilute potassium ranges as a result of all of them include greater than 4 mEq/L of potassium. It’s a problem to seek out an simply obtainable, cost-effective, balanced electrolyte resolution low in potassium, and due to this fact 0.9% sodium chloride is usually used. As a result of 0.9% sodium chloride doesn’t include bicarbonate, it should be changed within the type of sodium bicarbonate. If Z-BUF with 0.9% sodium chloride is utilized in extra, the affected person can develop hypernatremia because of the excessive sodium content material of 0.9% sodium chloride (154 mEq/L). If 20 mEq of sodium bicarbonate is added to every liter of 0.9% sodium chloride to switch the misplaced bicarbonate, every liter will include 174 mEq of sodium. Within the occasion that these options are given, the clinician should make sure to monitor sodium ranges to keep away from hypernatremia. As well as, as a result of many sufferers are on preoperative diuretics, they current to the working room with low sodium ranges. If the sodium ranges are normalized rapidly (>2 mEq/L/hr), sufferers could also be in danger for central pontine myelinolysis, which is characterised by focal demyelination within the pons and extrapontine areas of the mind (56). Z-BUF with 0.9% sodium chloride additionally depletes magnesium and calcium and might elevate chloride, leading to hyperchloremic metabolic acidosis (57

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