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Perfusion Program Foundations of Perfusion Technology & Techniques What we will cover: Unit 9 - Different types of ultrafiltrators Operational characteristics of ultrafilters Impact of hemoconcentrators on circulating concentrations of drugs and ions Use of the hemoconcentrator before, during, a...

Perfusion Program Foundations of Perfusion Technology & Techniques What we will cover: Unit 9 - Different types of ultrafiltrators Operational characteristics of ultrafilters Impact of hemoconcentrators on circulating concentrations of drugs and ions Use of the hemoconcentrator before, during, and after CPB Hemoconcentration, Ultrafiltration, and Application • Patients undergoing CPB often develop fluid overload and electrolyte imbalances • Exposure to foreign surfaces of the extracorporeal circuit and surgical trauma can itself promote capillary permeability and shifting of fluid to the extravascular space • Ultrafiltration and dialysis can help attenuate these changes and are therefore important adjuncts to CPB and related extracorporeal technologies. Hemoconcentration, Ultrafiltration, and Application • Ultrafiltration and dialysis are both utilized to manage blood volume, hemoglobin, protein, and certain electrolyte concentrations • In addition, several studies suggest that ultrafiltration and dialysis may reduce mediators that initiate a systemic inflammatory response syndrome (SIRS) • (Definition): Ultrafiltration is the movement of water across a membrane as the result of a hydrostatic pressure gradient or transmembrane pressure (TMP) • No dialysate on the opposite side of the membrane is required Hemoconcentration, Ultrafiltration, and Application • As water diffuses, it creates a solute concentration gradient across the membrane. • These solutes then diffuse across the membrane, equalizing the concentrations in a process of solute removal called convection. • The fluid removed during ultrafiltration is called ultrafiltrate or plasma water. Hemoconcentration, Ultrafiltration, and Application • Dialysis refers to a process in which the blood is separated from a crystalloid solution or dialysate by a semipermeable membrane • A solute concentration gradient exists between the blood and the dialysate, resulting in solute transport by diffusion from a higher to a lower concentration. • Ultrafiltration may be employed during dialysis by altering the TMP. Hemoconcentration, Ultrafiltration, and Application A Brief History. . . • In 1854, Thomas Graham, a Scottish chemist, presented a paper entitled “Osmotic Force” • described the process of separating substances using a semipermeable membrane • He later demonstrated that treated parchment paper could be used to separate larger molecules or colloids from crystalloids • He was also the first to describe the direct relation between solute molecular weight and solute diffusion rate • In 1913, John Jacob Abel’s interest in deriving usable solutes from animal blood led to the first reported dialysis procedure • Abel used a collodion membrane and, because blood was circulated outside the animal, it was necessary for Abel to find a way to keep the blood from clotting when exposed to foreign surfaces. • Abel solved this problem by creating hirudin, an anticoagulant derived from crushed leech heads (found in saliva of leeches) • First clinical dialysis procedure was performed by George Haas in 1924 • Between 1924 and 1928 he dialyzed six patients, but unfortunately had no survivals. • However, Haas made significant progress in the field of hemodialysis in 1927 by the addition of a blood pump and use of a newly discovered anticoagulant, heparin. Hemoconcentration, Ultrafiltration, and Application Brief History continued… (less brief) • After World War II, Willem Kolff, at the University of Groningen in the Netherlands, built an artificial kidney employing the regenerated cellulose membrane, cellophane • This device was a rotating drum barrel made of slats, with open spaces between the slats. • The membrane material used was a relatively new material originally developed for food packaging • The cellophane sausage casing was wound around the drum. • The drum was rotated by an electric motor and submerged in a tank filled with dialysate solution. • The blood was drawn from the patient into the cellophane casing by gravity (Fig. 4.1). • Between 1943 and 1944, Kolff dialyzed a total of 15 patients; however, only one survived. • In 1945, he dialyzed a comatose patient in acute renal failure for 1 week. • Her renal function returned and she eventually recovered to be released from the hospital FIGURE 4.1. Rotating drum kidney designed by Willem Kolff in the 1940s Hemoconcentration, Ultrafiltration, and Application Flat Plate Dialyzer • Development of the flat or parallel plate dialyzer began in 1947 by Leonard Skeggs and Jack Leonards • Sheets of membrane material were sandwiched between two rubber pads and incorporated multiple membrane layers to reduce the blood volume and increase the membrane surface area. • By the early 1950s, Kiil reported results with a flat plate dialyzer in which blood was made to flow between two sheets of cellophane supported by solid mats with grooves for the circulation of dialysate. Hemoconcentration, Ultrafiltration, and Application Hollow Fiber Dialyzer • In 1956, Richard Stewart began the development of the hollow fiber dialyzer design • It was made from a modified cellulose material, cellulose diacetate, and provided a high-efficacy solute transport while maintaining a low priming volume and a low resistance to blood flow • The membrane material, extruded in hollow fibers, was cut and bundled together, then potted in polyurethane on each end and encased in a polycarbonate shell • Blood flowed through the hollow fiber and the dialysate flowed around the hollow fibers • Where have we seen this structure before????? • This model became commercially available in 1970 and is the type of dialyzer and ultrafiltrator most widely used currently. Hemoconcentration, Ultrafiltration, and Application Ultrafiltration (aka: Hemoconcentration) • Ultrafiltration is achieved through the filtration of water across a semipermeable membrane using the energy derived from a hydrostatic pressure gradient • When water crosses the membrane, it creates a solute concentration gradient between the blood and the ultrafiltrate side of the membrane, which has no solutes • The dissolved solutes, which have a higher concentration in the blood, follow the concentration gradient and are transferred from the blood to the ultrafiltrate, the so-called solute drag or convection • This process of removing plasma water or ultrafiltrate from the blood utilizes a microporous membrane material commonly manufactured in a hollow fiber configuration. Hemoconcentration, Ultrafiltration, and Application Ultrafiltration (aka: Hemoconcentration) – tell me more. . . • A semipermeable membrane implies that certain substances will penetrate the membrane while others will not • This relates to microscopic holes in the membrane, which only allow water and small molecular weight solutes to pass. • If one side of the tank is filled with blood and a pressure is exerted on that compartment, water from the blood will move across the membrane into the other compartment • Because of their higher concentration in the blood compartment, the solutes with small molecular weight will move to the water side of the compartment until there is an equal concentration on both sides • This results in a concentration of blood cells and large molecules on one side of the membrane and water and small molecules on the other side (Fig. 4.2) Hemoconcentration, Ultrafiltration, and Application TransMembrane Pressure (TMP) • During ultrafiltration, the blood passes through a bundle of hollow fibers made from a microporous membrane. • The hollow fibers are between 180 and 200 μm in diameter and the pores of the microporous membrane are between 5 and 10 nm • Thousands of hollow fibers are configured in a bundle and encased in a polycarbonate shell • As blood flows through the hollow fibers of an ultrafiltrator, also called a hemoconcentrator, it creates a positive pressure within the hollow fibers • This pressure differential between the blood side and the atmospheric pressure on the ultrafiltrate side of the membrane drives water across the membrane = TMP • In many ways the process mimics glomerular filtration Hemoconcentration, Ultrafiltration, and Application TransMembrane Pressure (TMP) • The pressure gradient between the blood path and the ultrafiltrate compartment is called the transmembrane pressure. • The TMP can be expressed by the formula: • TMP = (Pin + Pout)/2 + V • where Pin = Blood inlet pressure, Pout = Blood outlet pressure, and V = Negative pressure applied to the effluent side of the hemoconcentrator (cannister for effluent drainage connected to wall suction). • To avoid membrane rupture, the TMP must not exceed the manufacturer's recommended pressures of 500 to 600 mm Hg. • The rate of fluid removal depends on the membrane permeability, blood flow, TMP, and hematocrit Hemoconcentration, Ultrafiltration, and Application Question: What would be the comparison for Transmembrane Pressure (TMP)? Answer: Blood Pressure!!! • Just like an increase in TMP will increase the rate of effluent removal, increase BP will cause an increased rate of fluid removal across the glomerulus (measured by GFR (glomerular filtration rate) in lab tests. Hemoconcentration, Ultrafiltration, and Application • Because the process of ultrafiltration removes plasma water and diffusible solutes in equal concentration to the plasma water, the overall concentration of the diffusible solutes are not affected. • Read that again – VERY IMPORTANT TO UNDERSTAND • Although dependent on the membrane material and pore size, typically, solutes greater than 65,000 Da (Dalton) are not removed by ultrafiltration. • Cellular elements, plasma proteins, and protein-bound solutes will not be removed and will therefore be concentrated Hemoconcentration, Ultrafiltration, and Application Sieving Coefficient • The ability of a solute to be filtered through the ultrafiltrator membrane depends on the molecular weight of the solute compared with the membrane pore size, the proportion of the solute that is protein bound, and the surface charge of the solute • The sieving coefficient is the ratio of ultrafiltrate solute concentration to plasma solute concentration and ranges from 0 to 1.0 • A sieving coefficient of 1.0 indicates that the ultrafiltrate solute concentration and the plasma solute concentration are equal and that the solute passes freely across the membrane • A sieving coefficient of 0 indicates that none of the solute passes through the membrane • Small molecular weight solutes that are not protein bound are easily removed by ultrafiltration and have a sieving coefficient of 1.0 • In the case of partially protein-bound small molecular weight solutes, the ultrafiltrate solute concentration will be equal to the non–protein-bound solute concentration. Hemoconcentration, Ultrafiltration, and Application Ultrafiltration in Bypass • The use of ultrafiltration during CPB was first reported in 1979 by Darup et al. • In the early 1980s, several other investigators reported utilizing ultrafiltration in the extracorporeal circuit and found that removing plasma water during CPB resulted in improvement in a number of aspects of patient care • During CPB, excess crystalloid may accumulate in the venous reservoir through cardioplegia and surgical irrigation from cardiotomy suction. • Patients undergoing CPB for heart surgery may have increased blood volumes due to congestive heart failure and/or renal failure • Ultrafiltration may remove excess fluid • the amount of fluid removed is limited by the minimal level allowed in the venous reservoir of the extracorporeal circuit • Once the minimum reservoir volume has been achieved, further increases in hematocrit and plasma protein levels may only be accomplished by the addition of homologous red blood cells or albumin • After the addition of the red cells or albumin, ultrafiltration may continue until the volume equal to the added red cells or albumin is removed Hemoconcentration, Ultrafiltration, and Application Ultrafiltration in Bypass (cont) • Ultrafiltration can concentrate the blood without the removal of plasma proteins, can be utilized during CPB when there is excess reservoir volume, and is particularly useful when the patient is resistant to diuretics • Studies have shown that patients who undergo ultrafiltration demonstrate increased protein and red blood cell concentrations and decreased lung waters, reduced fluid balance, and reduced tissue edema. • It has also been found to improve perioperative hemostasis and reduce postoperative ventilatory support. Hemoconcentration, Ultrafiltration, and Application Let’s put it in place • The hemoconcentrator or ultrafiltrator is configured in parallel to the extracorporeal circuit. • Blood may be propelled through a pump, but for simplicity, it is generally configured in the extracorporeal circuit as a passive shunt from a point of higher pressure (post-pump) to lower pressure (reservoir). • A flowmeter may be used for more precise measurements and is highly recommended in pediatric patients. • When using a centrifugal pump, the flow probe should be distal to the ultrafiltrator shunt to determine the actual blood flow to the patient and not the combined blood flow to the patient and ultrafiltrator. Hemoconcentration, Ultrafiltration, and Application Z-Buf (Zero-Balance Ultrafiltration) • primary purpose of ultrafiltration during CPB is to remove excess water and to concentrate the cellular elements and proteins in the blood. • Electrolytes and other solutes are also removed but in equal concentration to the patient's plasma water. • patient's plasma concentration of diffusible solutes remains unchanged • Subsequent investigations testing for various substances in the ultrafiltrate found measurable levels of cytokines • Because most cytokine and complement levels reach their peak during rewarming, Journois et al. (Gravlee text) hypothesized that continuous ultrafiltration during this period would further attenuate the inflammatory response • To allow continuous ultrafiltration during the rewarming phase of CPB, the authors replaced the ultrafiltrate with a balanced electrolyte solution (Ex. Our priming solutions – Normosol, Plasmalyte) Hemoconcentration, Ultrafiltration, and Application More about ZBUF. . . • A form of Z-BUF has also been used by perfusionists to correct hyperkalemia • Potassium loads during cardiopulmonary bypass originate from potassiumbased cardioplegia and homologous red blood cells and may exceed the patient's ability to clear excess potassium through normal glomerular filtration • As the patient's blood volume is reduced by ultrafiltration, the potassium level is not affected because the ultrafiltrate potassium levels will always be in equal concentration to the plasma. • When ultrafiltration is continuous, the potassium levels can be lowered by replacing the volume with a solution low in potassium. • Z-BUF has also been used to correct severe electrolyte and acid–base disturbances in adults undergoing cardiac surgery. • Electrolyte and acid–base corrections can be accomplished rapidly, and because the clinician can select the concentration of diffusible solutes in the replacement fluid, they can more accurately predict treatment effects Hemoconcentration, Ultrafiltration, and Application Hemoconcentration, Ultrafiltration, and Application MODIFIED ULTRAFILTRATION (MUF) • Ultrafiltration during CPB is limited by the blood reservoir level. • For pediatric patients, it is a challenge post-CPB to concentrate the residual circuit blood down to a volume that can be readily transfused into a small intravascular space. • In 1991, Naik et al. described a procedure in pediatric patients in which, following termination of CPB, the residual contents of the extracorporeal circuits were ultrafiltrated and transfused while the patients were still cannulated and attached to the extracorporeal circuit. • They called this procedure modified ultrafiltration or MUF. • In MUF, nearly all of the circuit contents are concentrated and transferred to the patient without the risk of hypervolemia, while the circuit remains primed with crystalloid solution. • One disadvantage of MUF is that it requires the patient to remain cannulated for 10 to 20 minutes after CPB termination, and, to maintain the integrity of the extracorporeal circuit, protamine may not be administered during MUF. Hemoconcentration, Ultrafiltration, and Application More details about Ultrafiltration. . . • Removal of Direct Thrombin Inhibitors • Heparin-induced thrombocytopenia (HIT) is a lifethreatening complication of heparin administration that occurs in up to 5% of patients exposed to heparin, regardless of the dose, schedule, or route of administration • HIT is an increasingly common clinical finding in patients presenting for cardiac surgery utilizing CPB. • Bivalrudin, a reversible direct thrombin inhibitor, is a molecular anticoagulant with short half-life and the potential to remove 45% to 65% of the drug using MUF (or UF for adults) Hemoconcentration, Ultrafiltration, and Application KEY Points • CPB presents challenges to the management of hemodilution, electrolyte levels, as well as fluid shifts because of the capillary leak associated with the systemic inflammatory response. • Ultrafiltration can reduce hemodilution by removing excess body water, and can also be utilized to concentrate the residual CPB circuit blood as in MUF. • Z-BUF functions like hemofiltration by removing plasma water but, as opposed to ultrafiltration, the amount of water removed is in excess of what is necessary to reverse hemodilution. • • As additional water is removed, it is replaced with a balanced electrolyte solution. • • Z-BUF can be used to correct certain electrolyte imbalances. • Use of Z-BUF with MUF has demonstrated improved post-CPB outcomes and reduced levels of inflammatory mediators. • The conventional dialysis circuit is simplified for use in the extracorporeal circuit. • • Dialysis can be used to manage patient volume and electrolyte imbalances, similar to Z-BUF or hemofiltration. • • Ultrafiltration appears to more efficiently remove middle-molecule uremic solutes than dialysis. Hemoconcentration, Ultrafiltration, and Application Hemoconcentration, Ultrafiltration, and Application Hemoconcentration, Ultrafiltration, and Application