RU2033190C1 - Method for extracorporal regeneration of plasma after plasmapheresis - Google Patents

Abstract

FIELD: medicine, particularly, intensive therapy. SUBSTANCE: this method prescribes adding sodium hypochlorite solution having concentration of 1200 mg% with 10:1 volume ratio to plasma prepared by method of plasmapheresis, standing whole during 4 to 16 h and measuring exposure time during dynamic monitoring changes in effective concentration of albumin. EFFECT: disclosed method allows reinfusing patient's plasma and reducing demand for donor protein preparations.

Description

 The invention relates to medicine, in particular to intensive care and resuscitation, and relates to the treatment of surgical patients suffering from purulent-inflammatory pathology of the abdominal organs and accompanied by high intoxication.

 Purulent-inflammatory diseases of the abdominal organs, accompanied by a high degree of intoxication (diffuse peritonitis, pancreatic necrosis, severe jaundice with hepatic-renal failure, abdominal sepsis) are characterized by the accumulation of toxic xenobiotics in the blood, increased levels of metabolites (bilirubin, urea, nitrogen, creatine, creatine transaminases, "medium" molecules, etc.), hypo- and dysproteinemia, a decrease in the transport function of albumin, pronounced water and electrolyte disorders, ki lotno-base imbalance, which leads to severe multiorgan failure.

 Several methods of treating severe endointoxication are known, but each of them has a number of significant drawbacks.

 In recent years, the technique of indirect electrochemical oxidation of blood with sodium hypochlorite solutions for the treatment of exo- and endotoxicoses has become widespread.

 Sodium hypochlorite, obtained by electrolysis of physiological saline in electrochemical plants EDO-3M, EDO-4M, is a compound with a small molecular weight and small structural dimensions, which is a carrier of "active" oxygen. In the presence of organic substances, sodium hypochlorite carries out the reaction of their hydroxylation, that is, it models the function of the natural biocatalyst of cytochrome P-450.

 In the body, sodium hypochlorite releases “active” oxygen, oxidizing toxic and ballast substances such as bilirubin, urea, creatinine, ammonia, cholesterol, uric acid, aniline, acetone, acetoacetate, transaminases and others. Oxidizing the lipid layer of cell membranes, it has a powerful bactericidal effect. Sodium hypochlorite is able to destroy some drugs, for example barbiturates, tranquilizers, alcohols, glucose, some antibiotics and others.

 Currently, sodium hypochlorite is used as a tool for local (external) use in the treatment of purulent wounds. In low concentrations, it is used for intravenous administration with an antimicrobial purpose, for the treatment of exo- and endotoxicoses, and for removing patients from a diabetic coma.

 However, intravascular administration of sodium hypochlorite solution has several disadvantages.

 Firstly, a solution of low concentration (not more than 600 mg.) Is used, which leads to a decrease in the oxidizing ability of the solution, it is not possible to obtain a sufficient detoxifying effect. The use of solutions of a higher concentration is impossible due to the pronounced damaging effect on the formed elements of the blood.

 Secondly, for intravenous infusion, catheterization of the central vein is required to avoid damage to the intima of the peripheral vessels.

 Thirdly, with the intravenous administration of a solution of sodium hypochlorite, the metabolism of those drugs that form the basis of drug treatment uncontrollably changes.

 And finally, this method of using the solution often causes a hypoglycemic state, leads to increased bleeding due to damage to fibrinogen.

 A highly effective method of treating toxicosis is plasmapheresis, performed after surgical debridement of the main focus of infection and preliminary correction of water-electrolyte and protein solutions. The method consists in the multiple removal of the patient's blood plasma containing toxic components of toxicosis, using separating, filtering, centrifuging devices, manually.

 The disadvantage of therapeutic plasmapheresis is the need for a full replacement of plasmoter with protein preparations, freshly frozen plasma, and albumin. Thus, this method provides for plasma exchange and is essentially an exchange transfusion of plasma, which makes this method extremely expensive and dangerous due to the risk of immune reactions.

 A plasma detoxification method has been developed with the aim of reinfusion to patients by plasma absorption method. The method consists in perfusion of blood plasma obtained after plasmapheresis through a hemosorption column. Changes in the biochemical composition of plasma after plasma sorption are characterized by a moderately pronounced decrease in the content of toxic metabolites: urea by 12.7% creatinine by 24.6% of average molecules by 32.8% of B2 microglobulin by 36.7%. Clinical effectiveness of plasma absorption is observed with perfusion of at least 1 8 volumes of circulating plasma.

 Possessing a detoxifying ability, the method has a number of significant drawbacks. The main one is a significant, up to 40% loss of plasma proteins on the surface of the hemosorbent. The increase in the transport capacity of albumin, unfortunately, is almost completely offset by the loss of this most important protein on activated carbons of any brand.

 Plasma sorption performed for obstructive jaundice using sorption columns with SKN brand coal with a capacity of 400 ml leads to an increase in the transport capacity of albumin by an average of 12% according to the fluorescence express method), with a decrease in the total amount of albumin by 8-15% To increase the sorption effect, one has to resort to replacing the hemosorption column, since the desorption effect develops within 40 minutes from the start of the procedure, and this leads to further loss of protein.

 Thus, the method of plasmapheresis followed by plasmasorption is technically difficult, and taking into account the cost of hemosorbents, it is an extremely expensive method of treating toxicosis. The plasma obtained after it is characterized by a low albumin content, which does not completely abandon the use of donor protein preparations. In connection with the above reasons, the plasma absorption method is not widely used in practical medicine.

 The essence of the proposal is the extracorporeal regeneration of blood plasma obtained after plasmapheresis by indirect electrochemical oxidation with a high concentration of sodium hypochlorite solution, which allows complete detoxification, preserves the plasma protein composition, and avoids contact with blood cells. Thus, in an effective and cheap way to obtain blood plasma suitable for reinfusion to a patient.

 For the first time, a new mechanism of the therapeutic effect of a solution of sodium hypochlorite with its extracorporeal combination with blood plasma was discovered, which allows to restore the transport function of albumin in patients undergoing treatment for purulent-inflammatory pathology of the abdominal organs with a 2-3 degree of endotoxemia.

 The method is as follows.

 Patients undergo surgical debridement of the main focus of infection. Treatment plasmapheresis is carried out in a volume of 1200-1600 ml of plasma extraction. Plasma under aseptic conditions is collected in sterile vials and combined with a solution of sodium hypochlorite in a volume ratio of plasma a solution of sodium hypochlorite 10: 1. Use a concentration of sodium hypochlorite solution equal to 1200 mg%. The resulting compound is exposed for at least 4 hours. The time required in each case for plasma detoxification, varies depending on the initial level of toxicosis and usually does not exceed 16 hours. The duration of exposure is determined by dynamically controlling the increase in the transport capacity of albumin .

This method does not require specific temperature conditions, but long-term (over 8 hours) exposure of the compound is desired to hold it in a domestic refrigerator at a temperature of 4-6 ° ^C.

 This concentration of sodium hypochlorite solution was determined as the best according to the results of numerous preliminary laboratory studies conducted under constant dynamic control of changes in the transport function of albumin and biochemical parameters.

 A pronounced detoxifying effect was established, which manifests itself in a significant reduction in the level of toxic metabolites: bilirubin by 54-70% urea by 60% creatinine by 60-80%, almost complete inactivation of transaminases. At the same time, there is a significant increase in the transport capacity of albumin.

 Changes in the transport ability of albumin are determined by the dynamics of the effective concentration of albumin (ECA) and the specific binding ability of albumin (USCA). An effective albumin concentration is understood to mean the amount of free albumin binding centers not occupied by any substances. Normal values of ECA coincide with the interval of normal values of the total concentration of albumin in the blood serum and are 40-55 g / l. The specific binding ability of albumin is understood to mean the ratio of ECA to the total concentration of albumin, normally UCCA 1.0, and significantly decreases with toxicosis of various etiologies.

 ECA is determined by fluorescence express method on the apparatus "Probe 2", "Probe 3", the values of the CSSA are calculated mathematically.

 Sodium hypochlorite oxidizes both the free components of toxicosis and those fixed on albumin receptors. Releases them and, thus, restores the transport ability of albumin, which is effectively used to transfer the substances necessary for the body, drugs, newly formed toxins to the organs of natural detoxification.

 When using this method of blood plasma regeneration, the effective concentration of albumin increases by 90-120% and its specific binding ability reaches 0.93-0.98. Moreover, these positive changes are more pronounced in patients suffering from extreme high intoxication. The total amount of protein is reduced only by 8-12% due to the fraction of large molecular cryoglobulins that precipitate during prolonged (more than 12 hours) exposure under hypothermia in a domestic refrigerator.

 Sodium hypochlorite in biological fluids has a short decay period. When stabilizing the maximum obtained ECA parameters (which determines the duration of exposure), sodium hypochlorite in plasma is not determined. Thus, there is only the effect of plasmadilution with saline.

 The result is a regenerated blood plasma, which can be used for reinfusion to the patient during programmed plasmapheresis sessions.

 PRI me R 1. Patient B. 47 years old, was admitted to the intensive care unit of the City Clinical Hospital N 67 08.11.1991, with a diagnosis of blunt trauma to the abdomen, separation of the gall bladder, diffuse gall peritonitis. Condition after laparotomy, cholecystectomy from 11/08/1991, rehabilitation and drainage of the abdominal cavity. Suffers from chronic alcoholism.

On admission the patient's condition is very severe: Yellowness skin, weakness, body temperature 38.5 ^{° C,} pulse 120-130 min, BP 100/60 mm Hg. Art. CVP 0 cm water column In the blood test, moderate leukocytosis 12.6x10 ⁹ / l, stab shift to 30% lymphopenia, ESR 27 mm / h, leukocyte index CALPH CALIFA 3.7.

 Biochemical indicators from 11/08/1991

 Total protein 76 g / l, albumin 35 g / l, globulins 41 g / l, urea 26 mmol / l, creatinine 365 mmol / l, total bilirubin 306 μmol / l: direct 220, indirect 186, potassium 6.1 mmol / l, calcium 2.1 mmol / l, ALT 1.7 mmol / hl, AST 1.0 mmol / hl. The effective concentration of albumin (ECA) is 18 g / l. The specific binding ability of albumin USCA) 0.51. During the observation revealed a sharply reduced rate of urine output to 200 ml per day. Based on clinical and laboratory data, hepatic-renal failure syndrome, endotoxemia of the 2nd to 3rd degree were established. Intensive infusion therapy and drug treatment were carried out, including transfusion of glucose-salt solutions, plasma substitutes, freshly frozen plasma. In therapy, enzyme inhibitors, penicillin antibiotics, aminoglycosides were used. However, the patient’s condition without improvement, by 9.11.1991, there were signs of encephalopathy, anuria.

 After stabilization of the main hemodynamic parameters: blood pressure 120/75 mm RT. Art. Heart rate 96 per minute. CVP + 7 cm of water. Art. performed therapeutic plasmapheresis according to a manual technique. Plasma exfusion was 1200 ml. Plasma sorption through the hemosorbent SUGS was performed using the Unirol apparatus for 40 min with a perfusion rate of 100 ml / h.

 Plasma biochemical parameters after plasma absorption: total protein 64 g / l, albumin 26 g / l, globulins 38 g / l, urea 23 mmol / l, creatinine 347 mmol / l, total bilirubin 120 μmol / l: direct 94, indirect 36 ; potassium 4.8 mmol / l, calcium 1.6 mmol / l, ALT 0.6 mmol / hl, AST 0.3 mmol / hl, ECA 20 g / l, USCA 0.31.

 Thus, the detoxifying effect of plasma adsorption was characterized by the following changes: a decrease in urea level by 11.6% creatinine by 5.03% total bilirubin by 60.8, direct bilirubin by 57.3% indirect bilirubin by 80.7, ALT by 64.7 % AST by 70% However, not a single indicator has reached the norm. Moreover, the total amount of protein decreased by 15.8% albumin by 25.7%. Therefore, despite the fact that ECA increased by 11.1%, the specific binding ability of albumin decreased from 051 to 0.31. In this regard, the detoxifying effect was assessed as unsatisfactory and plasma loss was compensated by donor blood products.

PRI me R 2. Patient T. 64 years old, was admitted to the intensive care unit GKB N 23 11.11.1992 with a diagnosis of perforation of the colon, spilled fecal peritonitis. Condition after laparostomy, imposition of a double-barreled anus from 11/11/1992, Acute hepatic-renal failure. Endotoxicosis 3 tbsp. Upon admission, the patient's condition is extremely serious. Artificial ventilation is carried out. The skin is pale jaundice, body temperature 36.1 ^about C, pulse 146 per min, rare ventricular extrasystole, blood pressure 95/60 mm Hg CVP + 2 cm aq. In the blood test, leukocytosis is 16.7 x 10 ⁹ / l, stab shift to 27% lymphopenia, ESR 34 mm / h, leukocyte index Kalf Kalifa 4.1. Metabolic acidosis: pH 6.8, BE 7, pCO ₂ 33, PO ₂ 84, hematocrit blood concentration 53%
Biochemical indicators from 11/11/1992, total protein 77 g / l, albumin 32 g / l, globulins 46 g / l, urea 23 mmol / l, creatinine 245 mmol / l, total bilirubin 118 μmol / l: direct 40, indirect 78; potassium 5.8 mmol / l, calcium 2.0 mmol / l, ECA 13 g / l, USCA 0.41.

Intensive infusion therapy and drug treatment were carried out. 12.11.1992, the patient was transferred to independent breathing. However, a pronounced toxic encephalopathy and a sharp decrease in the rate of diuresis were revealed, which indicated the insufficiency of the treatment being carried out and the increase in intoxication. Correction of the volemia and the main hemodynamic parameters was carried out. November 12, 1992, therapeutic plasmapheresis was performed on a PF 0.5 apparatus with a plasma extraction volume of 1800 ml. Plasma is collected in sterile vials without a blood preservative and connected to a solution of sodium hypochlorite at a concentration of 1200 mg% in a volume ratio of plasma a sodium hypochlorite solution of 10: 1. The compound was placed in a household refrigerator and exposed at 4 ° ^C. Every 2 hours, the effective concentration of albumin determined, the maximum value of this index was identified for 11-12 hours exposure. By this time, ECA approached the initial total albumin and its further increase was not observed. A biochemical study of plasma was performed.

 Biochemical changes in blood plasma after its electrochemical indirect oxidation with sodium hypochlorite solution (all data are given taking into account the dilution coefficient). Total protein 74 g / l, albumin 31 g / l, globulins 43 g / l, urea 6.5 mmol / l, creatinine 126 mmol / l, total bilirubin 20 μmol / l: direct 7, indirect 13; ECA 29 g / l, USCA 0.93.

 Thus, the detoxifying effect of indirect electrochemical detoxification was characterized by the following changes: a decrease in urea by 71.7% 0 creatinine by 52.8% total bilirubin by 85.4% direct bilirubin by 92.6% indirect 64% Total protein decreased by 4 % albumin by 3.2% At the same time, the transport function of albumin (ECA) increased by 123% (more than 2 times), which resulted in an increase in the specific binding ability of albumin (USCA) to almost the norm. All indicators of biochemically determined metabolites reached normal values, the detoxifying effect of the method was regarded as satisfactory. The plasma regenerated by this method was reinfused during the next plasmapheresis session, which did not require the use of donor protein preparations.

PRI me R 3. Patient A. 23 years old, was admitted to the intensive care unit GKB N 04/23/03/92, with a diagnosis of acute gangrenous perforated appendicitis, diffuse peritonitis. 04/23/1992, performed an appedectomy, laparostomy, sanitation of the abdominal cavity. From the anamnesis it is known that the patient is sick for 3 days, did not seek medical help, was treated independently. On admission the patient's condition is very severe: pale skin, with signs of microcirculation disorder, body temperature 37.9 ^{° C,} pulse 124-130 min, rhythmic, BP 105/60 mm Hg CVP + 4 cm of water. Art. In the blood test, expressed leukocytosis up to 21 x 10 ⁹ / l, stab shift to 31% lymphopenia, ESR 46 mm / h, leukocyte index Kalf Kalifa 5.3. Metabolic acidosis: pH 7.0, BE 6, hematocrit blood concentration 54% With auscultation of the lungs, weakened breathing over the right half of the chest. A survey radiograph of the organs of the chest cavity was performed. On the basis of physical and radiographic data, right-sided drain pneumonia was diagnosed. Given the underlying pathology, this case was regarded as abdominal sepsis, septic pneumonia. Subsequently, the diagnosis was confirmed by the results of blood culture inoculation. Intensive infusion, antibacterial and respiratory therapy was carried out. However, the patient's condition remained very serious, with a tendency to worsen. When control x-rays of the chest cavity revealed a tendency to abscess formation. The patient high fever up to 39 ^° C progressively worsens performance in biochemical blood studies.

 Biochemical parameters as of April 28, 1992. Total protein, 72 g / l, albumin 30 g / l, globulins 42 g / l, urea 26.4 mmol / l, creatinine 312 mmol / l, total bilirubin 20.2 μmol / l : direct 7.6, indirect 12.6; AST 3.2 mmol / hl, ALT 1.6 mmol / hl, ECA 14 g / l, USCA 0.46.

 Taking into account the data of the clinic and laboratory tests, it was decided to carry out plasmapheresis treatment followed by extracorporeal indirect electrochemical plasma detoxification with sodium hypochlorite solution.

On April 28, 1992, plasmapheresis was performed on a PC 6 apparatus with a plasma extraction volume of 1600 ml. The plasma was collected into sterile bottles without gemokonservanta and is connected with a sodium hypochlorite concentration of 1200 mg% in volumetric ratio of plasma sodium hypochlorite solution 10: 1, after which the compound exhibited in hypothermia conditions at a temperature of 4 ° ^C. After 16 hours, the maximum increase was noted ECA indicators and USSA.

 Biochemical changes in plasma after its extracorporeal indirect electrochemical oxidation with sodium hypochlorite solution.

 Total protein 70 g / l, albumin 28 g / l, globulins 42 g / l, urea 3.8 mmol / l, creatinine 102 mmol / l, total bilirubin 6.3 μmol / l: direct 4.2, indirect 2, 1; AST is not determined, ALT is not determined, ECA 27 g / l, CSSA 0.97.

 In this case, the effect of indirect electrochemical detoxification was characterized by the following changes: a decrease in urea level by 75.4% creatinine by 67.6, complete inactivation of transaminases, a noticeable decrease in the level of bilirubin, which in the outcome did not exceed the norm. The effective concentration of albumin, and hence its transport function, increased by 92.8%, which is confirmed by the specific binding ability of albumin, which is almost equal to unity. Plasma was a sign of regenerated and its reinfusion to the patient was carried out.

 23 observations were made of the use of the claimed method for extracorporeal plasma plasma regeneration of surgical patients suffering from severe purulent-inflammatory pathology of the abdominal organs: diffuse purulent peritonitis, pancreatic necrosis, obstructive jaundice, abdominal sepsis. In each case, endotoxyses of 2-3 tbsp. Were diagnosed. multiple organ failure syndrome, the traditional treatment had no effect, which was an indication for the claimed method of treatment.

 Thus, the method is cheap and effective, allows you to regenerate the plasma of patients, minimize the need for donor protein preparations and reduce the risk of possible immune reactions.

Claims (1)

 METHOD FOR EXTRACORPORAL REGENERATION OF PLASMA AFTER PLASMAFERESIS, including plasma detoxification under the control of effective albumin concentration and biochemical parameters, characterized in that a solution of sodium hypochlorite with a concentration of 1200 mg · in a volume ratio of 10 1 is added to the plasma, after which it is kept for at least 4 hours to the maximum possible increase effective albumin concentration.