RU2422162C1 - Method of hepatic failure treatment - Google Patents

Abstract

FIELD: medicine. ^ SUBSTANCE: invention relates to medicine, namely, to efferent therapy, and can be applied in treatment of patients with hepatic failure after performed cardio-surgical operation. For this purpose realised is veno-venous hemofiltration with application of standard bicarbonate solution. If clinical and laboratory signs of hepatic failure increase following sessions of hemofiltration are carried out during 5-8 hours with application of dialytic solution based on standard bicarbonate solution with 2% content of albumen. After session of hemofiltration with such solution, laboratory control of basic functional hepatic indices is performed. In case of necessity additional sessions with application of dialytic solution which contains 2% albumen are carried out. ^ EFFECT: method makes it possible to increase efficiency of small-flow veno-venous hemofiltration due to increase of clearance of endotoxins, associated with blood plasma proteins. ^ 2 cl, 2 ex

Description

The invention relates to medicine, in particular to anesthesiology and resuscitation, and can be used in the treatment of liver failure, for example, in patients after cardiac surgery.

Despite some successes in modern intensive care, the mortality of patients with acute liver failure, or acute decompensation of chronic liver failure, remains unacceptably high and does not decrease below 60%, even in specialized hepatological centers. According to the World Health Organization, among causes of death, liver failure consistently ranks sixth. The cause of high mortality is complications that join as the underlying disease progresses and lead to the development of multiple organ failure in the terminal stage of chronic diffuse liver disease. Decompensation of chronic liver diseases is often associated with multiple organ dysfunction, including hemodynamic instability, the development of renal and cerebral dysfunction, which leads to a high risk of death. Critical conditions associated with severe hypoxia of the internal organs are complicated by their damage to various degrees. The loss of the function of detoxification systems (kidneys and liver) entails the progression of endotoxemia, the development of histotoxic hypoxia and the aggravation of gas exchange disorders in all organs and systems, including the detoxification organs themselves. Thus, a “vicious circle” is formed, which determines an extremely high mortality rate in acute renal and hepatic-renal failure. You can change the results of treatment only by preventing and eliminating the hypoxic effect on organs and systems, including detoxification organs.

The creation and use of artificial liver function support systems is the main idea of modern intensive care for patients with liver failure, which has reduced mortality from 85 to 60%.

A known method of sorption detoxification, based on perfusion of blood through coal or synthetic sorbents (Collection of articles, 2009. - Issue 13. - T.1. - S.308-311). During sorption detoxification of blood or plasma, the sorbent effectively removes metabolites of medium and large molecular weight, hydrophobic, fat-soluble and protein-bound toxic complexes. The disadvantages of the method are the lack of selectivity in the excretion of metabolites - a variety of substances penetrate and are fixed on its surface through the transport pores: enzymes, vitamins, hormones - therefore, detoxification is usually accompanied by a violation of homeostasis. In the process of sorption, the blood cells, mainly leukocytes and platelets, to a lesser extent erythrocytes and lymphocytes, the number of which accordingly decreases at the exit from the sorbent column by 40-70% and 18-25%, is also injured. In patients after operations under cardiopulmonary bypass and cytopenia, including thrombocytopenia, anemia and forced drug hypocoagulation, the use of sorption is extremely dangerous and not always effective.

Known methods of plasmapheresis, consisting in gravitational or filtration removal (apheresis) from the bloodstream of a certain amount of plasma after preliminary separation of blood into the liquid part and the shaped elements, with the return to the vascular bed of the latter (MONIKI. Discrete exchange plasmapheresis. Http://monikiweb.ru/ SPNec / diskretn.htm. - C.1-6). The condition for plasmapheresis is the correction of volemic disorders associated with plasma loss, replenishment of the volume of circulating blood. The disadvantage of this method is the high frequency of adverse reactions (5% of cases) caused by hypocalcemia due to the introduction of a citrate solution into the blood, cooling of the blood and injected solutions in the extracorporeal system, changes in fluid balance (hypo- and hypervolemia) and electrolyte content. An overdose of anticoagulants can cause hemorrhages, and an insufficient dose can cause thrombosis. One of the contraindications to plasmapheresis is considered to be a decompensated state of the cardiovascular system, acute cerebrovascular accident, hypertensive crisis, neuropsychiatric disorders - these are the basic components of postoperative multiple organ failure in cardiac surgery.

Closest to the claimed method is the albumin dialysis method or a molecular adsorbing recirculating system — an extracorporeal detoxification method that combines the effectiveness of the sorbent, which is albumin, and the biocompatibility of modern dialysis membranes (Tretyakov B.V. “MARS” system for the return of molecular adsorption - albumin mediated hemodiafiltration method / B.V. Tretyakov, S.N. Petrov // http: //www/mks.ru/library/conf/biomedpribor/2008/sec.08-13.html, p.1-6)

In contrast to hemodialysis and hemosorption, this system implements the principle of indirect detoxification through a special highly permeable membrane. Blood perfusion is carried out inside the capillaries of the dialyzer, while donor albumin acts as the dialysate from the outside. According to the concentration gradient, toxic substances diffuse through a semipermeable membrane from the blood into the external albumin circuit, which receives toxins. Due to the limited permeability (up to 50 kDa), only substances with small and medium molecular weight pass through the membrane, which avoids the loss of endogenous functional molecules. Subsequently, due to recirculation through a conventional dialyzer, sorbent and anion exchange resin, the binding capacity of the toxin-rich donor albumin is regenerated. A key point of MARS technology is the transfer through an modified highly permeable dialysis membrane of toxins having an affinity for blood albumin to an acceptor. The acceptor is human donor albumin circulating in a closed loop. Water-soluble low molecular weight substances are removed by a concentration gradient, as in dialysis.

Unlike hemodialysis, which has only two circuits - the patient’s blood and dialysis fluid, the MARS procedure has three circuits: patient’s blood, dialysis fluid and albumin circuit. Through the intermediate albumin circuit, an indirect, i.e. outside direct contact with blood, the removal of both water-soluble and protein-bound toxins. The main disadvantage of this method is the high cost of both equipment and consumables and, as a consequence, the low cost-effectiveness of such procedures in non-specialized centers that are not involved in liver transplantation.

The technical result of the invention is to increase the efficiency of low-flow venous-venous hemodiafiltration in liver failure by eliminating the need for additional equipment and supplies.

A method is proposed for treating patients with liver failure after cardiac surgery, including veno-venous hemodiafiltration using a standard bicarbonate dialysis solution.

The difference is that with an increase in clinical and laboratory signs of liver failure, subsequent hemofiltration is carried out for 5-8 hours using a dialysis solution based on a standard bicarbonate solution with 2% albumin.

The difference is also that after each dialysis session with a solution with 2% albumin, laboratory monitoring of the main functional liver parameters is carried out and, if necessary, reuse of the dialysis solution with 2% albumin is carried out.

Hemodiafiltration with a dialysis solution containing 2% albumin significantly increases the clearance of endotoxins associated with blood plasma proteins and allows you to abort or clinically reduce the degree of manifestation of liver failure in patients with multiple organ failure after cardiac surgery.

The essence of the proposed method lies in the fact that in patients with multiple organ failure after cardiac surgery, low-flow venous-venous hemodiafiltration is the method of choice of basic intensive care. The specificity of interventions and pathologies prevents the effective use of sorption or afferent detoxification techniques. With an increase in clinical and laboratory signs of liver failure during hemodiafiltration, a 5-8-hour session is conducted on a dialysis solution with 2% albumin. To do this, 20% albumin is added to the standard bicarbonate dialysis solution until a 2% solution is created. Hemodiafiltration is carried out with the same blood flow rate of 150-200 ml / min with calculated heparinization (units / kg) in a 50% post-dilution mode with a substitute and dialysis solution flow of at least 35-45 ml / kg / h, with the required ultrafiltration rate for each patient . At the end of the dialysis session with a 2% albumin solution for 12-24 hours, laboratory monitoring of the main functional liver parameters is carried out and with continued hemofiltration, the albumin dialysis solution can be reused.

Example 1

Patient T., 66 years old, case history No. 902, was admitted to the intensive care unit 02/13/2009 with a diagnosis of Coronary heart disease, angina pectoris 4th functional class, post-infarction coronary cardiosclerosis, mitral valve insufficiency, 2nd functional class, NK2B, permanent form atrial fibrillation. Surgery under cardiopulmonary bypass: coronary artery bypass grafting, mitral valve repair, radiofrequency ablation, intraoperative myocardial infarction, cardiogenic shock, intra-aortic balloon counterpulsation. The postoperative period was complicated by bleeding, which required resternotomy with additional hemostasis and massive, up to 8 doses of erythrocyte mass, blood transfusion. By 24 hours of the postoperative period, the patient has a detailed picture of multiple organ failure with a predominance of heart weakness (low-output syndrome), acute lung injury syndrome (ARDS), acute renal failure (oligoanuria less than 0.5 ml / kg / h with stimulation of 10 mg / kg lasix), about which hemodiafiltration was started on a Prismaflex apparatus (Gambro, Sweden) in a 50% post-dilution mode with a Prismasol-2 solution at a blood flow rate of 180 ml / min, ultrafiltration of 100 ml / h, a dialysate flow and substitute 40 ml / kg / h . With a gradual stabilization of basic functions by the third day of the postoperative period, the patient was dominated by a clinic of developing liver failure - the ictericity of the sclera and skin integument increased, the value of bilirubin increased to 200 g / l mainly due to the direct fraction; with high transaminases - ACT 176 ME, ACT 142 ME; γ-glutamyltranspeptidase (GGTP) up to 90.7 ME, alkaline phosphatase 5.1 μkat / L and a decrease in coagulation indices. An eight-hour session was conducted with the inclusion in the hemodiafiltration circuit of a 2% albumin dialysis solution with a dialysis stream of 1 l / h. At the end of albumin dialysis, bilirubin decreased by 30% to 147 g / l while maintaining high transaminases — ACT 132, ALT 118, GGTP 74.5 ME; The alkaline phosphatase is 3.9 μkat / l; therefore, after 20 hours, a second session was performed with 2% albumin for 6 hours. At the end of the session, the bilirubin values slightly exceeded the normal ones - 50.6 g / l (indirect fraction 35.5 g / l ), and the values of tranaminases were at the upper limit of the norm - ACT 45.8, ALT 39.1 ME. After 19 days, the patient was transferred to the cardiac surgery department in the absence of signs of liver failure requiring conservative therapy.

Example 2

Patient A., 53 years old, case history No. 1136, was admitted to the intensive care unit 02/13/2009 with a diagnosis of Bioprosthesis dysfunction in the mitral position, tricuspid valve insufficiency, 2nd functional class, NK2B-3, pulmonary edema, bilateral hydrothorax, urolithiasis , CRF 0-1. Emergency surgery: mitral valve replacement, annuloplasty of the tricuspid valve. Due to the problems of repeated access, the duration of cardiopulmonary bypass exceeded 210 minutes. In the postoperative period, by 12 h, against the background of a pronounced systemic inflammatory response, anuria, RDSV, dyshidria, for which hemodiafiltration on the Prismaflex apparatus was started in a 50% post-dilution mode with a fixed flow rate of Prismasol-2 substitute 40 ml / kg, 1 l of dialysate / h with a starting ultrafiltration of 50 ml / h, blood flow velocity of 185 ml / min (min 150, max 200) with dosed bolus heparinization at an ACT level of 180 ± 20 s. During the first postoperative days, the patient's clinical and biochemical indicators of liver failure increased - the appearance of ictricity of sclera and skin integument; total bilirubin from 74.4 ± 12.9 to 232.5 ± 28.2 g / l (with the prevalence of the indirect fraction); ACT from 86.5 ± 20 to 181.5 ± 35.5 ME; ALT from 51.3 + 15.5 to 155 ± 45 ME; alkaline phosphatase (ALP) from 2.7 + 1.9 μkat / L to 3.65 + 1.1; γ-glutamyltranspeptidase (GGTP) from 57.2 ± 16.4 to 61.8 + 15.8 ME with a decrease in total protein from 56.5 ± 9.9 to 42 ± 10.5 g / l (albumin less than 50%) , which served as an indication to the beginning of dialysis with a 2% solution of albumin. The duration of the procedure is 10 hours with a dialysate flow of 1 l / h. At the end of the procedure (with ongoing hemodiafiltration), a decrease in total bilirubin to baseline was obtained - 82 ± 12 g / l with almost normal transaminases - ACT 46.5 + 10.5 ME; ALT 37 ± 12.5 ME; ALP 2.55 ± 1.15; GGTP 53.3 ± 10.9 (total protein 61 ± 9.3 g / l, albumin 62 ± 8%). On further observation, 2-3 days after the end of hemodiafiltration, bilirubin (96.7 ± 16.3 g / l) and transaminases (ACT 58.9 ± 9.1 ME, ALT 48.4 + 11.5) increased, but their increase was not persistent, and with standard conservative therapy, the patient was transferred to the cardiac surgery department on the 20th day.

Claims (2)

1. A method for the treatment of liver failure after cardiac surgery, including veno-venous hemofiltration sessions using a standard bicarbonate solution, characterized in that, with an increase in clinical and laboratory signs of liver failure, subsequent hemofiltration is carried out for 5-8 hours using a dialysis solution based on standard bicarbonate solution with 2% albumin. 2. The method according to claim 1, characterized in that after a hemofiltration session with a dialysis solution containing 2% albumin, laboratory monitoring of the main functional liver parameters is carried out and, if necessary, repeated sessions are performed using a dialysis solution containing 2% albumin.