RU2572019C1 - Method of treating sepsis in treating abdominal organs complicated by hepatic failure - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method involves a selective sorption of endotoxin through a vascular access, and an infusion therapy with administering an antibiotic. The absorption is preceded by an infusion of 10% albumin into a portal vein in an amount of 100 ml. The infusion is followed by the selective sorption of gram-negative flora endotoxins through the portal vein 30-45 minutes after the albumin infusion is completed. The gram-negative flora active antibiotic is infused into the portal vein during the whole period of the sorption; after the procedure is completed, a hepatoprotector is administered into the portal vein.

EFFECT: method enables achieving higher survival rate in this category of patients, providing earlier and more complete reduction of activity of the systemic inflammatory response, and causes the faster stabilisation of haemodynamics and reduction of multiple organ failure symptoms.

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Description

The invention relates to medicine and can be used in intensive care units for the complex treatment of sepsis in patients with diseases of the abdominal organs induced by gram-negative flora, complicated by the development of liver failure.

As you know, inflammatory diseases of a number of abdominal organs (acute destructive pancreatitis, appendicitis, purulent cholangitis, etc.) are often complicated by the development of peritonitis and sepsis. The etiological factor of this process in the vast majority of cases is gram-negative flora, whose endotoxin is an etiotropic factor in the development of endogenous toxicosis syndrome, which plays a leading role in sepsis. Endotoxin is a lipopolysaccharide that is part of the bacterial wall and is released during the lysis of a bacterial cell. Normally, the elimination of endotoxin entering the portal vein is carried out by a system of fixed macrophages of the liver, however, with the development of peritonitis and sepsis, especially complicated by multiple organ failure, the detoxification function of the liver often suffers, which provokes the development of a vicious cycle of pathogenesis with the progression of a systemic inflammatory reaction and further degeneration of the liver functions.

A known method of detoxification in patients with peritonitis (RF Patent No. 24111046, IPC A61M 1/34, publ. 2008), including prolonged venous hemofiltration with the simultaneous introduction of the Hyperhaes solution through the subclavian vein or abdominal aorta.

The disadvantage of this method is the non-specific nature of therapy, which does not allow for direct exposure to the etiotropic factor for the development of peritonitis.

The closest is a method of treating sepsis in diseases of the abdominal cavity or retroperitoneal space, including selective sorption of endotoxin via vascular access, infusion therapy with the introduction of an antibiotic, and hemofiltration (RF Patent No. 2500434, IPC A61M 1/34, publ. 2012). The procedure is carried out through the central vein, i.e. affect the level of endotoxin in the systemic circulation.

The disadvantage of this method is that sorption of that part of the pathogen that has not been eliminated by the system of fixed macrophages of the liver is performed, which means that this method does not allow you to adjust the level of endotoxin entering the liver through the portal vein system. The ongoing complex of manipulations does not have the effect of protection of the detoxification function of the liver, and the infusion of antibacterial drugs is carried out into the systemic circulation, which does not allow creating the maximum concentration of the antibiotic in the zone of maximum pathogen activity.

The objective of the invention is to eliminate these drawbacks, increase the effectiveness of detoxification by selective sorption of endotoxin before blood enters the capillaries of the liver, inclusion in the infusion program of substances with non-specific toxin-binding activity and high osmolarity. In addition, it is planned to create a method that will enhance the effectiveness of detoxification by changing the point of introduction of antibacterial drugs (directly into the portal vein blood), which will improve the delivery of the antibiotic to the site of maximum pathogen activity.

To do this, in the method of treating sepsis in inflammatory diseases of the abdominal organs complicated by liver failure, including selective sorption of endotoxin via vascular access, infusion therapy with the introduction of an antibiotic, it is proposed to infuse 10% albumin solution into the portal vein in a volume of 100 ml prior to sorption. Then carry out selective sorption of endotoxins of gram-negative flora also through the portal vein 30-45 minutes after the end of the albumin infusion, while infusion therapy with an antibiotic active against gram-negative flora is carried out in the portal vein during the entire time of the sorption, and immediately after the procedure hepatoprotector is injected into the portal vein.

The introduction of an antibiotic into the portal vein blood allows you to create its maximum concentration in the area of inflammation and to carry out the lysis of microorganisms. The use of selective sorption of endotoxin with blood sampling at the same point allows eliminating endotoxin immediately, preventing it from entering the liver or significantly reducing its concentration, which allows support for impaired hepatic function. This effect is potentiated by the use of hepatoprotectors as part of the technique. The use of albumin solution in the infusion method is based on its non-specific ability to bind various kinds of toxins, and also allows to achieve redistribution of fluid between the third space and the vascular bed in favor of the latter.

The method is as follows.

During the treatment of sepsis with diseases of the abdominal organs with signs of liver failure, intraoperative catheterization of the portal vein is performed intraoperatively during planned rehabilitation of the abdominal cavity.

After that, prior to the extracorporeal selective sorption of endotoxin, a human albumin solution of 10% - 100 ml is infused to improve the lymphatic drainage function of the portal vein system. Vascular access - dialysis catheter in the portal vein.

The sorption procedure begins 30-45 minutes after the end of the infusion of the albumin solution.

Perform selective sorption of endotoxin of gram-negative bacteria. Vascular access - a three-lumen catheter in the portal vein of the patient; perfusion at a rate of 80-120 ml / min is carried out through a specific sorbent containing immobilized polymyxin-B, capable of selectively sorbing endotoxin. The duration of the procedure is 2 hours. Heparinization - 5 thousand units of heparin bolus at the beginning of the procedure. During the procedure, a broad spectrum of antibiotics is infused (protected B-lactams, cephalosporins of 3-4 generations), active against gram-negative flora (taking into account the determination of the sensitivity of specific strains).

At the end of the procedure, hepatoprotective solutions are infused, for example, Heptral or Hepa-Merz, etc., into the blood of the portal vein.

To determine the need for a second procedure, the endotoxin activity in the blood of the inferior vena cava is measured by the EAA method, followed by an assessment of the dynamics of the ratio.

Monitoring the level of endotoxin in the blood one day after the end of the procedure; if the trend is negative, repeat the procedure.

Monitoring of liver function indicators at the end of the procedure and one day after it.

Example 1

Patient G., 38 years old, was admitted to the department of surgical hemocorrection and detoxification of MONICA with a diagnosis of Acute destructive pancreatitis. Abscess of the stuffing bag. Spilled purulent peritonitis. Multiple organ failure. A patient with a clinic of bacterial sepsis, septic shock in blood cultures revealed Ps. Aeruginosa (2 × 10 * 8 CFU / ml), sensitive to cefoperazone, sulperazone.

With programmed laparotomy, portal vein catheterization was performed. The activity of endotoxin according to EAA was 0.69. According to general clinical examination methods, the patient had a progressive increase in markers of acute liver failure. Prior to the extracorporeal detoxification session, a 10% - 100 ml human albumin solution was infused through a three-lumen dialysis catheter installed in the patient's portal vein. The selective sorption of endotoxin was started 30 minutes after the end of the infusion of albumin solution. Vascular access - a three-lumen catheter in the portal vein of the patient; perfusion at a rate of 120 ml / min. The duration of the procedure is 2 hours. Heparinization - 5 thousand units of heparin bolus at the beginning of the procedure.

During the procedure, 2 g of Cefoperazone-Sulbactam antibacterial drug was infused. At the end of the procedure, heptral solution was infused with 10 ml of blood into the portal vein blood.

Monitoring of liver function indicators at the end of the procedure and one day after it. At the end of the first procedure, the activity of endotoxin in the blood was 0.47. However, a day later, a negative trend in the activity of endotoxin was noted with its increase to 0.63. A second session of extracorporeal detoxification was carried out according to the above method. At the end of the procedure, the activity of endotoxin significantly decreased - to 0.36.

The patient showed pronounced positive dynamics of liver function indices, stabilization of hemodynamics, and improvement of indicators according to the APACNE2 and SOFA scales. Achieved stabilization of the patient. An analysis of endotoxin activity, carried out a day after the second procedure, showed the absence of an increase in its level. In the further state of the patient, positive dynamics were observed, the patient was discharged from the hospital on the 36th day.

Example 2

Patient P., 27 years old, was admitted to the department of surgical hemocorrection and detoxification of MONICA with a diagnosis of Acute gangrenous appendicitis. Spilled purulent peritonitis. Multiple organ failure. In a patient with a clinic of bacterial sepsis, septic shock in blood cultures, E. coli (1 × 10 * 9 CFU / ml), sensitive to sulferezone, was detected. With programmed laparotomy, portal vein catheterization was performed. The endotoxin activity according to EAA in the blood of the patient was 0.71. According to general clinical examination methods, the patient also noted an increase in the concentration of markers of acute liver failure. It was decided to conduct extracorporeal detoxification.

Prior to selective sorption, a three-lumen dialysis catheter installed in the portal vein of the patient was infused with 10% - 100 ml human albumin solution. The selective sorption of endotoxin was started 40 minutes after the end of the infusion of the albumin solution. Vascular access - a three-lumen catheter in the portal vein of the patient; perfusion at a rate of 110 ml / min. The duration of the procedure is 2 hours. Heparinization - 5 thousand units of heparin bolus at the beginning of the procedure. During the procedure, an infusion of the antibacterial drug Sulperazone in an amount of 2 g is performed. At the end of the procedure, an infusion of the Gepa-Merts r. 10 g was made into the blood of the portal vein.

At the end of the first procedure, the activity of endotoxin in the blood was 0.39. A day after the procedure, a negative trend in the activity of endotoxin was not registered. Marked positive dynamics of indicators of hepatic function, stabilization of hemodynamics, improvement of indicators on ARACNE2 and SOFA scales. Subsequently, a positive dynamics was observed in the patient's condition, was discharged from the hospital on the 29th day.

The proposed technique was applied on the basis of the MONICA surgical hemocorrection and detoxification department. In total, it was used in the treatment of 12 patients. For comparative analysis, we used the analysis of data from a group of patients with peritonitis caused by gram-negative flora who did not undergo extracorporeal detoxification. All patients in the comparison group showed signs of hepatocellular insufficiency. When applying the proposed methodology, out of 12 patients 3 died, the average duration of hospitalization was 42 days. In the comparison group of 32 patients, 14 died; the average length of hospitalization is 64 days.

Thus, the above technique allows to achieve a higher survival rate of patients with sepsis in diseases of the abdominal organs, for example, severe peritonitis, complicated by liver failure. The effect is achieved by reducing the degree of endotoxinemia directly in the focus of the pathological process and reducing its effect on the target organs (first of all, the system of fixed macrophages of the liver). This mechanism allows for an earlier and more complete decrease in the activity of the systemic inflammatory response, and also leads to a more rapid stabilization of hemodynamics and a reduction in the symptoms of multiple organ failure. The method is tested on the basis of the Department of surgical hemocorrection and detoxification GBUZ MO MONIKI them. M.F. Vladimirsky, the results of its use are satisfactory, the safety of use allows us to recommend the technique for widespread use.

Claims (1)

A method for the treatment of sepsis in inflammatory diseases of the abdominal organs complicated by liver failure, including selective sorption of endotoxin via vascular access, infusion therapy with the introduction of an antibiotic, characterized in that before the sorption, 10% albumin solution is infused into the portal vein in a volume of 100 ml, and then carry out selective sorption of endotoxins of gram-negative flora also through the portal vein 30-45 minutes after the end of the albumin infusion, while infusion therapy with an antibiotic active against gram-negative flora is carried out in the portal vein during the entire time of sorption, and immediately after completion of the procedure, hepatoprotector is introduced into the portal vein.