RU2423140C1 - Method of treating surgical endotoxicosis - Google Patents

Abstract

FIELD: medicine. ^ SUBSTANCE: invention relates to medicine, namely to surgery, and can be applied for treatment of surgical endotoxicosis, complicated with intestinal insufficiency. For this purpose applied is solution of mixture of powder sublimates of juice, water extract of plant tops and water extract of marc of young table beet. Mixture of powder sublimates is dissolved in quantity 40 g of dry substance per 1 l of neutral anolyte ANK with concentration 0.01-0.02% to obtain standard solution 1-2% by pectin. Obtained solution is introduced enterally drop-by-drop through capillary probe with 5 days course. Solution introduction insures enterosorption, nutritive support, stimulation of intestine motor functions. ^ EFFECT: application in solution of powder sublimates not only marc and juice, but plant tops of table beet insures improved amino-acid composition as well as improved solubility of powder product, which makes it possible to introduce solution through capillary probe, without causing its clogging. ^ 2 tbl, 2 ex

Description

The invention relates to medicine, namely to surgery, and can be used to treat surgical endotoxemia complicated by intestinal failure.

In surgical endotoxemia and intestinal failure, stress immunodeficiency develops, which is associated with complex translocation of the intestinal microflora due to impaired barrier function of the intestinal wall, intestinal auto-toxicity, suppression of the immune and stress-limiting systems, stimulation of the stress-implementing system of the body, which worsens the prognosis of treatment of this pathology. Enterosorption binds toxic intestinal contents, and when pectin-containing preparations are used, intestinal motility is stimulated and intestinal contents are removed naturally. Thus, the toxic load on the organs and systems of the body, including on immunity.

The method of enterosorption, used to detoxify the body, with three to four single doses of enterosorbent for several days allows you to achieve an effect equal to the hemosorption procedure. The method is non-invasive, has no complications associated with extracorporeal detoxification, and is more physiological. Currently, a number of enterosorbents are used to treat the pathology of the digestive system, including 1% aqueous solution of pectin ("Clinical use of the drug Enterosgel in patients with pathology of the digestive system." New approaches to therapy. Guidelines for doctors. Edited by Prof. I.V. Maev, Yu.N. Shevchenko, Assoc. A.B. Petukhova, M., 2000, S.5-8). Particularly noteworthy are highly dispersed hydrophilic powder sorbents because of their relatively large sorbent surface and good fluidity in the solution for administration into the intestine through a nasointestinal probe.

Naso-intestinal intubation has several disadvantages: difficulty swallowing, the possibility of regurgitation of the gastric contents into the respiratory tract, the formation of pressure sores along the probe, and the morbidity of execution.

The prototype of the invention is a method of treating "surgical" endotoxemia, in particular peritonitis. To do this, use the powdered product of table beets prepared from freeze-dried raw materials (production of NPF Biorhythm, Russian Federation, Moscow). From the first day after the operation, a homogenized aqueous suspension of the product is administered via a Janet syringe at the rate of 20 g of dry matter per 300 ml of drinking water at 18-22 ° C into the nasointestinal probe, after intraoperative washing of the small intestine. The introduction is carried out 3 times a day, a course of 3-5 days. The method, due to the properties of sublimate of beet, provides simultaneous enterosorption, stimulation of intestinal motility and nutritional support (RF Patent No. 2245159, IPC A61K 35/78, A61P 41/00. Method for the treatment of surgical endotoxemia. B. S. Briskin, D.A. .Demidov, TPGazina / MGMSU. Published on January 27, 2005, Bull. No. 3).

The disadvantages of the prototype are: the presence of a precipitate of insoluble particles of beet meal, the instability of the aqueous suspension and the solution according to the concentration of pectin and pH of the reducing medium, which complicates the dissociation of protopectins to replenish the utilized pectins and limits the enterostimulating, antiseptic and nutritive properties of the injected drug. The presence of an insoluble fraction during probe introduction into the intestine leads to a loss of up to 1/5 of the powder, which is excreted unchanged with the stool and makes it impossible to introduce the reconstituted product into probes whose diameter is less than 0.5 cm due to their periodic occlusion.

The objective of the invention is to increase the effectiveness of the treatment of surgical endotoxemia.

The technical result consists in optimizing enterosorption, additional duodenogastrosorption, nutritional support, stimulation of motility of the small intestine to stop the state of immunodeficiency and immunomodulation of cellular and humoral immunity in the early postoperative period.

This is achieved due to the fact that a solution of a mixture of powdered sublimates of juice, an aqueous extract of tops and an aqueous extract of oilcake of young table beet in an amount of 40 g of dry matter per 1 liter of ANK neutral anolyte for 5 days is injected dropwise through a capillary probe.

To prepare a powder product, tops and root crops of young table beets with vegetation of 6-7 leaves are used according to OST 10 300-2002. Powder products are produced separately from tops, pulp and juice according to TU 9199-013-00353158-97, product certificate No. 77.72.10.916.P.05042.

Optimum preservation of the composition and properties of the raw materials, high hygroscopicity and sorption activity, the physical form of the finely divided powder are provided by technologies using sublimation (RF patent No. 2136182 and No. 2154969).

A feature of the technology is that the water extracts from the tops and pulp are sublimated together with the juice, which makes it possible to obtain a completely soluble homogeneous product when it is restored to its native state.

The choice of component ratio was carried out by computer simulation according to biomedical requirements, which identified three component formulations, of which formulation 1 was optimal in terms of the ratio of active substances (table No. 1).

Table number 1 Compounds obtained by computer simulation of water-soluble powder preparations of beetroot Name one 2 3 Moisture content, % four four four Total protein, g 9.78 9.39 10.17 Fats, g 1.92 1.87 1.98 Carbohydrates, g 35.81 37.95 32.95 Dietary fiber, g
Cellulose 14.15 13,99 14.28 Lignin 5.81 6.88 4.74 Hemicellulose 6.90 7.90 6.15 Starch 1,63 1.71 1.55 Pectin substances 3.63 4.21 3.04 Vitamins mg /%
Vitamin C 25.28 24.58 25.97 B-carotene 20.27 19.08 21.46 IN 1 3.02 2.85 3.21 IN 2 0.84 0.79 0.9 PP 0.76 0.74 0.81 Minerals, mg / 100 g
Sodium 400 376 423 Potassium 2572 2426 2730 Calcium 161 152 171 Magnesium 431 405 456 Phosphorus 391 368 414 Iron 34.5 32,5 36.5 Energy value, kcal 200 206 190

Sorption activity is determined by: a large sorbing surface due to the physical form of a finely dispersed powder, hydrophilicity due to sublimation; the presence of lignin, pectins and protopectins.

Stabilized pectins, forming a hydrophilic gel, stimulate intestinal motility, including with paresis. Nutritional capabilities are determined by the nutritional value of carbohydrates, amino acids, provitamins and vitamins, trace elements of the beetroot preparation.

The obtained samples are superior in value to the drug used in the prototype method - table No. 2.

Table number 2 Analysis of a sample of a dry preparation of beet prototype Name of indicator Beetroot pattern Mass fraction of carbohydrates,% 67.9 Mass fraction of fiber,% 6.3 Mass fraction of lignin,% 6.8 Mass fraction of pectins,% 0.7-1.0 Amino acids, wt% ** Lysine * 0.30 Histidine * 0.25 Arginine * 0.35 Aspartoginic Acid 0.65 Threonine * 0.24 Serine 0.31 Glutamic acid ** 2.79 Proline 0.34 Glycine 0.25 Alanya 0.47 Cystine 0,07 Valine 0.33 Methionine * 0.09 Isoleucine 0.25 Leucine 0.32 Tyrosine 0.21 Phenylalanine * 0.19 Iodine,% 0.36 Betaine,% 0.469 * irreplaceable

The formulation of the new PSP is better in amino acid composition due to the enrichment of root crops with tops.

The new drug has complete water solubility due to the fact that its preparation uses water extraction of beet tops and beet pulp. At the same time, completely water-soluble preparations can be introduced into capillary probes with an external diameter of 2.8-3.2 mm, which are inserted into the intestine through an endoscope and do not have the disadvantages of typical probes for nasointestinal intubation.

When restored, it does not give a precipitate, which allows it to be introduced dropwise through a capillary probe with an external diameter of 2.8-3.2 mm.

These probes are installed endoscopically, which is less traumatic compared to conventional nasointestinal intubation, does not entail complications associated with it. These probes are easier to carry by patients because of their small diameter, and it is impossible to inject reconstituted prototype powder through them because of the presence of insoluble sediment particles in it, which cause clogging of these probes.

To restore the dry product in an amicrobial antiseptic neutral medium, a neutral anolyte ANK with a concentration of 0.01-0.02% was used, in accordance with the instructions and the technological map of the apparatus (STEL-10N-120-01 installation, modification 40-03, manufactured by AOOT NPO Screen ”, Moscow, RF). According to GOST 12.1.007, the ANC belongs to the 4th class of low-hazard substances, when introduced into the stomach and applied to the skin, it is low toxic, when administered parenterally it does not exert a local irritating effect on the skin and mucous membranes at a concentration of 0.01 - 0.02%. In a higher concentration, ANC has a locally irritating effect, in a lower concentration it loses antiseptic properties.

40 g of powder is diluted per 1 liter of ANK neutral anolyte, to obtain a standard solution of 1-2% for pectin.

On average, the positive balance of a single injection of the solution on the 1st day was 600 ± 50 ml, on the 2nd day 800 ± 50 ml, on the 3rd and 900 ± 50 ml, on the 4th-5th day, the solution was not isolated; Ultrasound and X-ray examination restored intestinal peristalsis, the probes were removed and natural nutrition began. Thus, the course of treatment is at least 5 days, i.e. to a complete positive balance of absorption of the solution by the small intestine, the disappearance of signs of intoxication and restoration of intestinal motility.

The presence of a retrograde discharge of a solution of a pectin-containing preparation through the stomach is an additional positive aspect of treatment, since in this case, passive washing of the duodenum and stomach occurs, i.e. duodenogastrosorption with the removal of toxic contents in the nasogastric tube.

A single drip of a daily dose of a solution leads to large losses due to discharge through a nasogastric tube due to intestinal failure. Therefore, the daily dose was administered in 2 divided doses, i.e. every 12 hours.

The method is as follows: intestinal contents are intraoperatively removed by retrograde pumping through a nasogastric tube, then a nasointestinal capillary tube is inserted through an adjacent nasal passage to the beginning of the jejunum, it is fixed with a plaster to the nose and auricle, its patency is checked by injecting saline solution, and if necessary, the site is monitored probe standing radiologically.

From the first day of the postoperative period, drip introduction into the intestine of a solution in the ratio of 40 g of powder per 1 liter of ANK neutral anolyte with a concentration of 0.01-0.02% through an intravenous infusion system, under the control of a nasogastric tube for 5 days, begins.

In the clinic (in the surgical department of the Hospital of the Central Union of the Russian Federation), the proposed method was used in the treatment of 42 patients with diffuse peritonitis of various etiologies in the toxic and terminal stages with concomitant enteric insufficiency of varying severity. All patients were examined clinically, laboratory, instrumental. After surgery, patients were treated in the intensive care unit. From the first day in combination with conventional intensive care, he applied the proposed method of treatment.

The results of treatment were evaluated by the dynamics of severity of the condition using the SAPS scale (Le Gall G.R., 1984), leukocyte intoxication index (LII), substances of medium molecular weight (SCMM) in blood plasma, resolution rate of intestinal paresis, mortality and immunity dynamics.

Baseline data and indicators of immunity were compared with those after application of SRP. The initial level of plasma cortisol with peritonitis was 488.5 ± 50.6 mg / ml with a norm of 354 ± 41.0 mg / ml. Hypercortisolemia was accompanied by a decrease in the activity of SERS II to 1.4 ± 0.1, with a norm of 2.0 ± 0.16 and inhibition of the activity of protective stress-limiting receptors to 0.8 ± 0.04, with a norm of 1.4 ± 0.11 . As a result, the balance of stress-realizing and stress-limiting mechanisms shifted towards damage (cortisol / SERS III) to 611.2 ± 50.0, with a norm of 252.8 ± 15.0. In the immune status, a decrease in T-lymphocytes (DM 3+) to 52.0 ± 5.0%, with a norm of 61.8 ± 4.8%, due to a decrease in the number of T-helpers (DM 4+) to 32.0 ± 3.0% with a norm of 45.0 ± 4.3%. The immunoregulatory index (IRI = SD 4 + / SD 8+) decreased by 2 times compared with the norm (1.7 ± 0.1, with a norm of 3.4 ± 0.3). Dysimmunoglobulinemia was observed in the form of a decrease in the level of IgA to 1.1 ± 0.2 g / l at a rate of 2.43 ± 0.2 g / l, IgG to 10.1 ± 1.2 g / l at a rate of 12.0 ± 1 , 0 g / l. Inhibition of phagocytosis activity and intensity was noted, PHI = 51.0 ± 5.0% with a norm of 79.0 ± 6.0%, AF = 4.2 ± 0.3 with a norm of 9.5 ± 1.0.

After treatment with PSP, a decrease in the level of plasma cortisol to 380.0 ± 30.0 mg / ml was observed versus 488.5 ± 50.6 mg / ml before treatment, the normalization of the activity of type II HSC was 1.9 ± 0.1 against 1, 4 ± 0.1 before treatment (p <0.05), as well as an increase in the activity of stress-protective reception (SERS III) to 1.3 ± 0.1 against 0.8 ± 0.04 (p <0.01) before treatment. As a result, the balance of stress-realizing and stress-limiting mechanisms has changed in the direction of decreasing the activity of immune-damaging stress-realizing and stimulating stress-limiting factors (cortisol / GKR III) to 292.0 ± 20.0 against 611.2 ± 50.0 to treatment (p <0.01).

The immune status after treatment with PSP was characterized by an increase in the number of T-lymphocytes (DM 3+) to 58.0 ± 6.0% versus 52.0 ± 5.0% before treatment, as well as an increase in the number of T-helpers (DM 4+) up to 42.0 ± 4.0% versus 32.0 ± 3.0% before treatment. The number of T-suppressors (DM 8+) decreased to 1.3 ± 1.2% compared to 19.3 ± 3.0% before treatment.

As a result of treatment, IRI increased 2 times (up to 3.3 ± 0.4 p <0.01). The phagocytic activity of neutrophils increased - PHI = 76.0 ± 8.0% against 51.0 ± 5.0% before treatment and the intensity of phagocytosis - PS = 8.8 ± 0.9 against 4.2 ± 0.3 before treatment ( p <0.01).

The immunity B-link was characterized by an increase in IgA level to 2.0 ± 0.3 g / l against 1.1 ± 0.2 g / l before treatment (p <0.05) and IgG level to 12.0 ± 1.6 g / l against 10.1 ± 1.2 g / l before treatment (p <0.05).

Clinical example No. 1. Patient M., 54 years old, medical history No. 251, was admitted to the surgical department of the Hospital of the Central Union of the Russian Federation on March 27, 2008 with a direct diagnosis: acute cholecystitis, peritonitis, a day after the onset of the disease. At admission: general condition is serious, pulse 120 in 1 minute, A.D. 105 and 70 mmHg. column, shortness of breath, acrocyanosis, the stomach is tense, does not participate in breathing, Shchetkin’s symptom is positive in all departments, pathology was not found on the chest x-ray, chest pneumatosis in the overview of the abdominal cavity, multiple small intestinal arches, no free gas in the abdominal cavity . After preoperative preparation, it is urgently operated. Operation No. 114 - Laparotomy, cholecystectomy, sanitation and drainage of the abdominal cavity, nasogastric and endoscopic nasointestinal intubation. On the operation: in the abdominal cavity up to 800 ml of fibrinous-purulent effusion, plaque of fibrin on the parietal and visceral peritoneum in all parts of the abdominal cavity, gangrene of the gallbladder, paresis of the small intestine. The abdominal cavity is washed with a solution of chlorhexidine, drained, drained from four points. Postoperative diagnosis: acute gangrenous cholecystitis, diffuse fibrinous-purulent peritonitis, paresis of the small intestine. Through a nasogastric tube, retrograde 2.0 L of stagnant contents was evacuated.

For postoperative treatment, the patient was transferred to the intensive care unit. At the initial examination: the severity of the condition according to SAPS 8.0, LII 8.5, VSMM 600. From the first day after the operation, a solution of a mixture of powder sublimates of juice, an aqueous extract of tops and an aqueous extract of cake of young table beet in an amount of 40 was administered entrally dropwise through a capillary probe. g of dry matter per 1 liter of neutral ANolyte ANK concentration of 0.01% for 5 days.

The positive total balance of infusion into the small intestine on day 1 is 1100 ml, on day 2, 1500 ml, on day 3, 1800 ml, on day 4-5, 2000 ml.

According to the nasogastric tube, on the 1st-2nd day a discharge of beetroot with an admixture of bile and stagnation, on the 3rd day only an infusion solution. There are no complications from the side of the surgical wound. Diuresis 1.5-2.3 l / day. From 2 days a liquid beetroot stool appeared. On the 3rd day there is no discharge from the abdominal cavity, drainage from the abdominal cavity has been removed, activation has begun.

On the 5th day, intestinal paresis resolved, nasogastric and nasointestinal capillary probes were removed. General condition according to SAPS 2.0, LII 4.5, VSMM 300. The patient was transferred to 3 surgical departments, nutrition was started, table 1 was surgical. On the 7th day, he was transferred to ordinary food - 15 table. On day 8, the surgical wound healed by first intention, skin sutures were removed. With dynamic ultrasound on 3-5-7 days there are no complications from the abdominal cavity. On the 9th day in a satisfactory condition, the patient was discharged under the supervision of a polyclinic surgeon.

Clinical example No. 2. Patient F., 38 years old, medical history No. 96, was admitted to the surgical department of the Hospital of the Central Union of the Russian Federation on 28.01.09 with a diagnosis of acute appendicitis, peritonitis widespread 30 hours after the onset of the disease. On admission: the general condition is severe, the pulse is 116 beats in 1 min., BP 100/70 mm Hg, the abdomen is swollen, tense, does not participate in breathing, Shchetkin’s symptom is determined throughout the abdomen. Produced No. 26 Laparotomy, appendectomy, sanitation and drainage of the abdominal cavity, nasogastric and endoscopic nasointestinal intubation. The gangrenous altered appendix was removed, in the abdominal cavity up to 1 liter of turbid with the smell of purulent exudate in all departments, swollen, paretic intestinal loops with fibrin. The abdominal cavity is sanitized by washing with an aqueous solution of chlorhexidine and saline and draining. Performed nasogastric intubation, retrogradely evacuated up to 2 liters of stagnant intestinal contents. The operation is completed by ligature laparostomy for reorganization of the abdominal cavity. An endoscopically placed capillary nasointestinal probe at the beginning of the jejunum. The severity of the condition according to the SAPS scale is 7.8, LII - 9.6, VSMM 500. On the first day of the postoperative period, a solution of a mixture of powder sublimates of juice, an aqueous extract of tops and an aqueous extract of oilcake of young table beet in an amount of 40 g was injected dropwise through a capillary probe. dry matter per 1 liter of neutral anolyte ANK concentration of 0.02% for 5 days.

The positive total balance of infusion into the small intestine on the 1st day of 900 ml, on the 2nd day of 1200 ml, on the 3rd day of 1800 ml, on the 4th-5th day of 2000 ml. According to the nasogastric tube, on day 1-2, an infusion solution mixed with bile and stagnation, on day 3, only an infusion solution. Diuresis 1.6-2.2 l / day. There are no complications from the side of the surgical wound. On the 2nd day, a liquid beetroot-colored stool appeared, intestinal noises appeared, gases began to escape. Activation of the patient has begun.

The state of the abdominal cavity, with program reorganization, has improved, there is no exudate in it, loops of the small intestine are peristaltic, the abdominal wall is sewn tightly. With ultrasound on 3-4-5 days there are no complications. On the 4th day there is no discharge from the abdominal cavity, drainage from the abdominal cavity is removed. On the 5th day, the nasogastric and nasointestinal probes were removed, nutrition began - table 1 was surgical. The general state of moderate severity - on the SAPS scale - 5.2, LII - 4.4, SCMM 300. On day 6 he was transferred to the surgical department. The wound healed by first intention, skin sutures were removed on the 9th day, nutrition began - table 15. He was discharged on the 11th day in satisfactory condition under the supervision of a polyclinic surgeon.

Claims (1)

A method of treating surgical endotoxemia by means of enterosorption, nutritional support and stimulation of intestinal motility with a powdered beetroot product made from freeze-dried raw materials, characterized in that a solution of a mixture of powdered sublimates of juice, an aqueous extract of tops and an aqueous extract of pulp of a young canteen is administered dropwise via a capillary probe beets in the amount of 40 g of dry matter per 1 liter of neutral ANolyte ANK concentration of 0.01-0.02% to obtain a standard solution of 1-2% for pectin, to Ursa 5 days.