Hemofiltration

Hemofiltration is based on the use of a high-permeability membrane in a hemofilter, which is connected to the artery and vein with the help of modified hemodialysis lines. The gradient of arteriovenous pressure creates the possibility of blood circulation through the extracorporeal circuit without the use of a pump. Slow continuation of ultrafiltration and reinfusion of fluid, are the main ways to maintain fluid balance in patients in intensive care units. Permanent arteriovenous hemofiltration is based only on convection. Purification of blood is achieved through ultrafiltration and replacement of fluid lost during filtration, in contrast to the diffusion used in "classical" hemodialysis. Since the 80s of the last century in patients whose critical condition did not allow the use of other types of PTA, this technique has been regularly used in intensive care units. It is important to note that its use made it possible for clinics not equipped with hemodialysis equipment and equipment to perform PTA in patients with acute renal insufficiency. Unconditional advantage of constant arteriovenous hemofiltration is the absence of negative influence on the circulatory system and the possibility of adequate control of the fluid balance. In addition, the ability to conduct patients with oligoanuria intensive treatment, including infusion-transfusion and drug therapy, parenteral and enteral nutrition. But in patients with the syndrome of multiple organ dysfunction, certain limitations were revealed in this method. The maximum efficiency, which can be achieved with its help, reaches 14-18 l of ultrafiltrate per day. Therefore, the daily clearance of urea can not exceed 18 liters. Given that the majority of patients with multiple organ dysfunction syndrome have a marked hypercatabolic state, this urea clearance leads to insufficient control of its level and, of course, to inadequate treatment.

[1], [2], [3], [4]

Mechanism of action

When blood is perfused through a hemofiltration with filtrate, a wide range of freely circulating toxicants and their metabolites (molecular weight to prealbumin) is removed. The filtrate is comparable in composition to the primary urine formed in the kidneys. The amount of toxicants to be removed depends on the volume of the liquid replaced in the vascular bed. The intensity of detoxification is proportional to the filtration rate and the coefficient of sifting metabolites through this 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 through the membrane in the liquid flow of osmotically active substances preserves the initial osmolarity of the blood and BCC. Isoosmolar dehydration underlies the prevention of intracellular hyperhydration and cerebral edema (syndrome of disturbed balance).

An important drawback of access is the unstable blood flow velocity in the extracorporeal circuit, caused by a decrease in the arteriovenous gradient in hypotension, often observed in patients in intensive care units, or thrombosis of the circulating circuit and filter. These complications are often observed with constant arteriovenous hemofiltration, since its high rate leads to a significant increase in the level of hematocrit, blood viscosity and hyperproteinemia in the blood volume inside the filter itself, which is thrombosed when the blood flow is slowed through the extracorporeal circuit. These shortcomings of the method often cause the cessation of the patient's extremely necessary treatment, thereby reducing its overall effectiveness. All this served as an occasion for a significant limitation of the use of arteriovenous hemofiltration in intensive care units and the development of new technical means and methods of permanent substitution PTA.

Thanks to the introduction of new-generation double-lumen catheters and perfusion modules into clinical practice, veno-venous haemofiltration and veno-venous hemodiafiltration, which are considered the "gold standard" of dialysis therapy in intensive care units, have become widespread. With these treatments, a perfusion module is used to provide blood flow through the extracorporeal circuit. Due to the use of convection, ultrafiltration and diffusion, the efficiency of the method is significantly increased. Blood flow, not exceeding 200 ml / min, with a similar dialysate rate, countercurrent to the direction of the blood flow, allows maintaining urea clearance during the procedure at high values (up to 100 ml / min).

The constant veno-venous hemodiafiltration in comparison with the "classical" hemodialysis ensures the gallbladder stability of hemodynamics, unlimited control of the fluid balance, allows for adequate nutritional support, enables to control the concentration of dissolved substances, correct or prevent the development of electrolyte imbalance. The results of a randomized controlled trial published in 2000 by Claudio Ronco showed that an increase in the volume of hemofiltration with permanent therapy can improve the survival of patients with acute renal failure and sepsis. The potential benefit from increasing the volume of ultrafiltration is associated with the positive effect of a constant PTA on the humoral mediators of sepsis, which are adsorbed on the filter membrane or are directly eliminated by the convection process. 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 of kidney function and has "non-adrenal" indications for blood purification in complex intensive therapy for multiple organ failure and sepsis.

The use of synthetic, biocompatible, highly permeable membranes allows, due to convection, to achieve a growth in the clearance of substances with an average molecular weight, especially 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 "average" molecular weight, studies are constantly being conducted that study the effectiveness of convective methods (haemofiltration and hemodiafiltration) in their elimination. The results of experimental and clinical studies of recent years show that with the help of modern methods of extracorporeal detoxification, only a limited number of "medium" molecules such as cytokines, complement components, etc., can be eliminated. Of course, the convective mechanism of mass transfer is much more effective in this respect than the diffusion , however, usually when performing permanent procedures in patients with acute renal failure, a "renal dose" of the hemofiltration rate to 2 l / h is used. This dose is sufficient for the implementation of adequate PTA and minimal, clinically insignificant ability to eliminate inflammatory mediators. On the other hand, it has been proven that the adsorption of inflammatory mediators on the membrane of hemofilters is very significant, especially in the early stages of extracorporeal cleansing of blood (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 makes it possible to temporarily lower their concentration in the plasma, which has a significant biological and clinical significance. Unfortunately, the hemofilters membranes are not intended for sorption and, as the pores are saturated, their effectiveness in the removal of cytokines is rapidly reduced.

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 it is not sufficient to change the level of inflammatory mediators in the syndrome of multiple organ failure and sepsis. Therefore, permanent hemofiltration for sepsis is not used, except in cases of its combination with severe kidney dysfunction.

High-volume haemofiltration

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

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

The causes of the positive effect of high-volume venous-venous hemofiltration in the complex therapy of sepsis:

• The shortening of the proinflammatory phase of sepsis by filtering the unbound portion of the cytokines, thereby reducing the concomitant lesions of organs and tissues.
• Reduction in concentration and elimination of blood components responsible for the shock state in humans (endothelin-1, responsible for the development of early pulmonary hypertension in sepsis, endocannabinoids responsible for vasoplegia, myocardium-depressive factor involved in the pathogenesis of acute heart failure in sepsis).
• Reduction of the concentration in the plasma of the PAM factor (inhibitor of plasminogen activation), reduction of diffuse intravascular coagulopathy. It is known that the level of PAI-I in sepsis correlates with high values on the APACHE II scale and a significant level of mortality.
• Decreased manifestations of immunoparality after sepsis and reduced risk of secondary infection.
• Suppression of apoptosis of macrophages and neutrophils.

Thus, high-volume veno-venous hemofiltration is a method of extracorporeal detoxification that allows to significantly reduce the concentration in the plasma of the majority of inflammatory mediators, providing the possibility of "controlling" the systemic inflammatory response. However, the filters and membranes used for hemofiltration in the treatment of acute renal failure with their pore size and sieving factors are unlikely to be significant for extracorporal therapy of sepsis.