Hemofiltration

Hemofiltration is based on the use of a highly permeable membrane in a hemofilter, which is connected to an artery and vein using modified hemodialysis lines. The arteriovenous pressure gradient makes it possible to move blood along the extracorporeal circuit without using a pump. Slow continuous ultrafiltration and fluid reinfusion are the main methods of maintaining fluid balance in patients in intensive care units. Continuous arteriovenous hemofiltration is based only on convection. Blood purification is achieved through ultrafiltration and replacement of fluid lost during filtration, in contrast to diffusion used in "classical" hemodialysis. Since the 1980s, this technique has been regularly used in intensive care units for patients whose critical condition did not allow the use of other types of RRT. It is important to note that its use allowed clinics not equipped with hemodialysis equipment and devices to perform RRT in patients with acute renal failure. The unconditional advantage of continuous arteriovenous hemofiltration is the absence of a negative impact on the circulatory system and the ability to adequately control the fluid balance. In addition, it is possible to conduct intensive treatment for patients with oligoanuria, including infusion-transfusion and drug therapy, parenteral and enteral nutrition. However, certain limitations have been identified in this method in patients with multiple organ failure syndrome. The maximum efficiency that can be achieved with its help reaches 14-18 liters of ultrafiltrate per day. Consequently, the daily clearance of urea cannot exceed 18 liters. Considering that most patients with multiple organ failure syndrome have a pronounced state of hypercatabolism, this clearance of urea leads to insufficient control of its level and, naturally, to inadequate treatment.

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Mechanism of action

During blood perfusion through a hemofilter, a wide range of freely circulating toxicants and their metabolites (molecular weight up to prealbumin) are removed with the filtrate. The filtrate is comparable in composition to primary urine formed in the kidneys. The amount of toxicants removed depends on the volume of fluid replaced in the vascular bed. The intensity of detoxification is proportional to the filtration rate and the coefficient of metabolite sieving through a given semipermeable membrane. The volume of fluid replacement and the duration of the procedure are determined depending on the clinical and biological parameters of the patient.

Unhindered passage of osmotically active substances through the membrane in the liquid flow maintains the initial osmolarity of the blood and the BCC. Isoosmolar dehydration is the basis for the prevention of intracellular hyperhydration and cerebral edema (disturbed balance syndrome).

An important disadvantage of the access is the unstable blood flow rate in the extracorporeal circuit, caused by a decrease in the arteriovenous gradient during hypotension, often observed in patients in intensive care units, or thrombosis of the circulating circuit and filter. These complications are often observed with continuous arteriovenous hemofiltration, since its high speed leads to a significant increase in the hematocrit level, blood viscosity and hyperproteinemia in the blood volume inside the filter itself, which thromboses when the blood flow slows down in the extracorporeal circuit. These disadvantages of the method are often the reason for stopping treatment that is extremely necessary for the patient, thereby reducing its effectiveness as a whole. All this served as a reason for a significant limitation of the use of arteriovenous hemofiltration in intensive care units and for the development of new technical means and methods of continuous replacement RRT.

Due to the introduction of new-generation double-lumen catheters and perfusion modules into clinical practice, venovenous hemofiltration and venovenous hemodiafiltration have become widespread and are considered the "gold standard" of dialysis therapy in intensive care units. In these types of treatment, a perfusion module is used to provide blood flow along the extracorporeal circuit. The effectiveness of the method is significantly increased by using convection, ultrafiltration and diffusion. Blood flow not exceeding 200 ml/min, with a similar speed of dialysate supplied countercurrent to the direction of blood flow, allows maintaining urea clearance during the procedure at high values (up to 100 ml/min).

Continuous venovenous hemodiafiltration, compared with "classical" hemodialysis, provides complete hemodynamic stability, unlimited control over fluid balance, allows for adequate nutritional support, makes it possible to control the concentration of dissolved substances, and correct or prevent the development of electrolyte imbalance. The results of a randomized controlled trial published in 2000 by Claudio Ronco showed that increasing the volume of hemofiltration with continuous therapy methods can improve the survival of patients with acute renal failure and sepsis. The potential benefit of increasing the volume of ultrafiltration is associated with the positive effect of continuous RRT on humoral mediators of sepsis, which are adsorbed on the filter membrane or directly removed by convection. This study proved the validity of increasing the "dose" of hemofiltration in patients with acute renal failure and sepsis.

Thus, this technique today serves as an effective form of artificial support for kidney function and has “extrarenal” indications for blood purification in complex intensive therapy of multiple organ failure and sepsis.

The use of synthetic, biocompatible, highly permeable membranes allows, through convection, to achieve an increase in the clearance of substances with an average molecular weight, primarily cytokines, many of which are soluble in water. Due to this, it is possible to reduce their concentration in the bloodstream using extracorporeal blood purification techniques. Since many pro- and anti-inflammatory mediators are classified as substances with an "average" molecular weight, research is constantly being conducted to study the effectiveness of convective methods (hemofiltration and hemodiafiltration) in their elimination. The results of experimental and clinical studies of recent years indicate that modern methods of extracorporeal detoxification can eliminate only a limited number of "medium" molecules, such as cytokines, complement components, etc. Of course, the convective mechanism of mass transfer is much more effective in this regard than the diffusion one, but usually when performing constant procedures in patients with acute renal failure, a "renal dose" of hemofiltration rate of up to 2 l/h is used. This dose is sufficient to implement adequate RRT and a minimal, clinically insignificant ability to eliminate inflammatory mediators. On the other hand, it has been proven that the adsorption of inflammatory mediators on the hemofilter membrane is quite significant, especially in the early stages of extracorporeal blood purification (the first 2-3 hours from the beginning of the procedure). Adsorption of circulating cytokines and complement components on the porous membrane of the filter allows for a temporary decrease in their concentration in the plasma, which is of significant biological and clinical significance. Unfortunately, hemofilter membranes are not designed for sorption, and as the pores become saturated, their effectiveness in removing cytokines quickly decreases.

Thus, the "renal dose" of hemofiltration (up to 2 l/h) is sufficient to replace renal function in the treatment of acute renal failure, but is insufficient to change the level of inflammatory mediators in multiple organ failure syndrome and sepsis. Therefore, continuous hemofiltration is not used in sepsis, except in cases of its combination with severe renal dysfunction.

High volume hemofiltration

According to research data, the advantages of using high-volume venovenous hemofiltration are obvious in patients with multiple organ failure and sepsis. Clinical studies have shown the effectiveness of using high-volume venovenous hemofiltration with a decrease in mortality among patients with sepsis and an improvement in hemodynamic parameters against the background of a decrease in the need for vasopressors and adrenomimetics. According to research data, increasing the hemofiltration dose above the usual "renal dose" has a positive effect on the survival of patients with multiple organ failure syndrome.

The ultrafiltration rate with this method reaches 6 l/h or more, and the daily volume is 60-80 l. High-volume venovenous hemofiltration is used only during the daytime (6-8 hours), and the technique is called pulsating. This is due to the need for a high blood flow rate, accurate calculation of the ultrafiltration volume, and an increased need for replacement solutions.

Reasons for the positive effect of high-volume venovenous hemofiltration in the complex therapy of sepsis:

• Shortening the proinflammatory phase of sepsis by filtering the unbound portion of cytokines, thereby reducing associated damage to organs and tissues.
• Decreased concentration and elimination of blood components responsible for the state of shock in humans (endothelin-1, responsible for the development of early pulmonary hypertension in sepsis; endocannabinoids responsible for vasoplegia; myocardial depressant factor involved in the pathogenesis of acute heart failure in sepsis).
• Reduction of plasma concentration of factor PAM (plasminogen activating inhibitor), reduction of diffuse intravascular coagulopathy. It is known that the level of factor PAI-I in sepsis correlates with high values on the APACHE II scale and a significant mortality rate.
• Reducing the manifestations of immunoparalysis after sepsis and reducing the risk of developing secondary infection.
• Suppression of apoptosis of macrophages and neutrophils.

Thus, high-volume veno-venous hemofiltration is a method of extracorporeal detoxification that allows for a significant reduction in the plasma concentration of most inflammation mediators, providing the ability to "manage" the systemic inflammatory response. However, filters and membranes used for hemofiltration in the treatment of acute renal failure with their pore size and sieving coefficients are unlikely to be of significant importance for extracorporeal therapy of sepsis.