RU2300395C2 - Method for applying isolated small intestine loop as artificial biological kidney - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method involves exposing and excising small intestine loop in length not exceeding 1/3 of the whole its length. Both isolated loop ends are brought out over the frontal abdominal wall surface. Dialysis is carried out through the isolated intestine loop. Dialyzing solution is forced into the central loop end. The dialyzing solution flows from peripheral loop end into reservoir containing dialyzing solution. Perfusion time is equal to 2-6 h in the specific case. Dialyzing composition is packaged in portions to be dissolved in 5, 10 or 20 l of water. A dialysis procedure being over, both fistulas are connected to each other with tube-plug. The isolated loop is fed with food additives having their composition close to chymus during pauses between sessions.

EFFECT: excluded patient dependence on patient care institution; accessibility to wide circle of patients at terminal hepatic insufficiency stage.

5 cl, 1 dwg

Description

The invention relates to medicine and, in particular, to the treatment of acute and chronic renal failure.

According to medical statistics in the Russian Federation, about 150 thousand patients need treatment for the terminal stage of renal failure, and about 5 million in the world.

Known RF patent No. 2020970 "ARTIFICIAL KIDNEY" describing an artificial kidney device containing connective communications, a hemodialyzer, divided by a semipermeable membrane into a section for blood intended for connection to the patient's circulatory system, and a section for dialysis fluid having an inlet connected to a dialysis source fluid, and having an outlet for used dialysis fluid and blood ultrafiltrate. The difference is that for the treatment of chronic renal failure in unsteady conditions through discrete dialysis sessions (procedures) of a total weekly duration of not more than 24 hours, the kidney contains a means for collecting and measuring the amount of consumed dialysis fluid and ultrafiltrate and a membrane that provides urine throughput at least 40 ml / min and, with respect to ultrafiltration, at least 8 ml / h / mmHg The disadvantages of the prototype are the need for sterility, the lack of individual selection for the patient, the concentration of sodium in the dialysis fluid and limited functionality.

Also known is RF patent No. 22575724 "ARTIFICIAL KIDNEY", which eliminates some of the disadvantages of the previous invention and provides an individual selection for the patient the concentration of sodium in the dialysis fluid and the expansion of the functionality of the device. An artificial kidney contains a reference voltage source, a comparison unit, a character analysis unit, a module selection unit, an analog-to-digital converter, an element NOT, a clock pulse generator, elements of the first and second groups ZI, a sodium concentration sensor (in the patient’s blood), an arterial discharge syringe - venous shunt, first and second connectors, blood circuit, hemodialyzer, blood section, semipermeable membrane, dialysis fluid section, output line, spent dialysis fluid collection means and ultrafilter ATA, weighing device, movable support, arterial-venous shunt, inlet line, flow meter, dialysis components reservoir, clamp, sterile connecting device. The reservoir of dialysis components contains the first, second and third containers, dispensers of the first and second groups, controlled valves of the first and second groups and the mixing unit.

Also known is RF patent No. 2032426 "DEVICE FOR HEMODIALYSIS", the purpose of which is to increase the biocompatibility of the device by adjusting the pH and redox potential of the dialysis solution within the physiological norm without changing the ionic strength of the solution. A disadvantage of the above devices and methods is the fact that hemodialysis is a treatment when the patient’s blood is pumped through an artificial kidney apparatus, first of all, this method requires sterility and threatens the patient with very serious complications in a large percentage of cases. Secondly, a very expensive method (cost from 20 to 40 thousand US dollars per year per patient).

In Russia, hemodialysis using an artificial kidney is available only to less than 5% of those who need it. These are mainly patients living in the largest cities of Russia, and the remaining patients die. Patients living at the expense of an artificial kidney are constantly attached to a medical institution. Three hemodialysis per week for 5-6 hours makes their life unbearably difficult.

Despite numerous complications when using an artificial kidney: sepsis, septic endocarditis with damage to the heart valves, hemolysis, thrombosis of arteriovenous fistula with possible thromboembolism in the pulmonary artery, fistula aneurysms, congestion of the right half of the heart due to continuous discharge of arterial blood into a vein, loss of fibrin, numerous bone damage, etc., yet hemodialysis remains the most effective way to replace the lost kidney function of the existing ones. Under his protection, you can wait for the donor kidney. However, a transplanted kidney may not take root, and if it does take root, the constant intake of immunosuppressants will lead to a decrease in the body's resistance to infection and the patient may die from a banal pneumonia. So, donor kidney transplantation until the complete resolution of tissue incompatibility is not a panacea in the treatment of patients with end-stage renal failure.

There is also peritoneal dialysis. He, like hemodialysis, is carried out in strictly sterile conditions. Failure to comply with this rule can lead to such a formidable complication as peritonitis, which in the age of antibiotics in 20-25% of cases ends fatally. It is less effective and requires longer dialysis (for 8-9 hours 3-4 times a week). This method is more often used in children and young people, in whom, due to the small diameter of the vessels of the limbs, it is impossible to create an arteriovenous fistula to connect to an artificial kidney.

The methods described above for purifying blood from nitrogenous slag sometimes tie patients to specialized medical institutions for life and make their travel abroad impossible.

For more than 60 years, a method has been known to cleanse the body of nitrogenous slag by washing the small intestines with a dialysis fluid (intestinal dialysis). Among the known solutions, mention should be made of the patent KR 9602848, which describes the compositions for conducting intestinal dialysis, and the patent EG 22643, which describes the device of catheters for intestinal dialysis. A double-lumen probe is inserted through the mouth or nose into the stomach, and then under the control of an x-ray it is displaced into the small intestines. Using one channel of the probe moderately inflate the spray can. It enhances intestinal motility, and the probe moves further, and when its end is 40 cm from the pylorus, they begin to inject dialyzing hypertonic solution in an amount of up to 15 liters into the jejunum. The solution introduced in this way is excreted from the body along with chyme and feces naturally. Washing of the intestine in this way 3-4 times a week in the morning on an empty stomach in the intensity of excretion of urea and creatinine from the body, according to some authors, is only slightly inferior to peritoneal dialysis. The described method is very painful and not applicable in young children and in weakened elderly patients suffering from cardiovascular diseases. With this method, the villi of the small intestines are not washed off sufficiently from mucus and chyme, which reduces the effectiveness of the method.

The introduction of a large amount of dialysis fluid into the intestines, especially in hypersthenics, leads to an increase in pressure in the abdominal cavity and, as a result, to a significant increase in the diaphragm and a decrease in the internal volume of the chest. This leads to respiratory failure and a displacement of the heart upward with an excess of the pulmonary artery and ascending aorta.

This method of intestinal dialysis, like hemodialysis, attaches the patient to the hospital for the rest of his life. He cannot go away from home for more than 1-2 days, for example, to a summer house or to another city to visit relatives. His life becomes monotonous, painful and boring. Young people are particularly affected.

However, the described method for purifying the body’s liquid medium from nitrogenous slags, unlike hemodialysis and peritoneal dialysis, does not require sterility. And if we could save patients from overfilling the intestines with a huge amount of fluid and conduct a session in a medical institution under the control of X-rays, and even save the patient from ejecting from the body 4 times a week a significant part of nutrients and intestinal enzymes, then intestinal dialysis would create competition as hemodialysis, and peritenial dialysis.

Comparing the pros and cons of all types of dialysis, we came to the conclusion that it is not necessary to flush all the intestines with an analysis solution, but only its limited length, isolated from the main part of the intestines. And this means using as a biological model of an artificial kidney the method of formation of intestinal fistulas according to Tiri-Well described in all physiology textbooks, proposed for studying the secretory function of small intestines of dogs.

It remains only to calculate the optimal length of the small intestine, which, without risking the patient’s health, can be turned off from digestion and used for a new purpose - to clean the body’s fluid from nitrogenous slags and other metabolic poisons by washing the intestinal mucosa with dialysis solutions already known in chemical composition: acetate, bicarbonate, etc. It is known that in an adult, the length of the small intestine is 6.5-7 meters, which is 4.3 times the length of the tep (see N.K. Lysenkov, V.I. Bushkovich, M.G. Suspension. Textbook of normal anatomy - M .: Medgiz, 1958, p.337).

According to Fragnnhait (1925), the human body fully compensates for the removal of the small intestine to 1/3 of its length. When removing more than 1/3 of the length, a pronounced tendency to diarrhea is observed and the patient is unable to restore his original weight.

In this regard, it is proposed to use less than 1/3 of the length of the small intestine to create an artificial biological kidney.

The essence of the method is as follows.

First, the patient is surgically removed and cut off a piece of small intestine 1 (drawing) with a length of less than 1/3 of the length of all small intestines.

Both ends are brought to the anterior abdominal wall, and the free edges of the intestines are sutured to the skin, forming Tiri-Well fistulas, and the patency of the interrupted intestine is restored using a manual or mechanical suture 2. After reliable fusion of the intestinal mucosa with the skin, dialysis sessions isolated from digestion begin segment of the small intestine, for which through both fistulas into the intestine to a depth of 4-5 cm soft, for example silicone cannulas 3 and 4 are inserted, at the ends of which there are inflatable cuffs. The opposite ends of the cannula are connected to the rubber tubes 5 and 9, one of which 5 passes through a pump 6, for example, of a roller type and the free end of which is immersed in a dialysis fluid heated to 38-39 ° C and poured into a container 7, and the end of the second tube 9 lowered into the same container. The injection of fluid into the central end of the intestine is carried out in different modes (laminar, turbulent, pulsating, reciprocating, vibrating, etc.), while the fluid is returned through a tube 9 to a container 7, and the patient himself prepares the solution for intestinal dialysis dissolving a powder or concentrated solution of a special composition in non-sterile, but preferably boiled tap, well or spring water, previously tested for its concentration: Na +, Ca ++, Mg ++, Cl ^- , at the place of residence. The modes and time of intestinal dialysis is initially prescribed by the doctor who oversees the patient. An example of a specific application of the method of intestinal dialysis and a device for its implementation in an experiment on a dog.

Experience of 03.03.2005 (experimental laboratory of the District Military Clinical Hospital No. 1586, Podolsk) Operation: Removing both kidneys and removing the ends of the jejunum loop on the abdominal wall. This is the preparatory stage before intestinal dialysis.

The experimental animal is a purebred dog, female, weighing 16.4 kg. Primedikapiya - item./k. 1 ml of atropine, 2 ml of droperidol. Thiopental intravenous anesthesia - 1 ml of 2.5% solution per 1 kg of animal weight.

Operation. Median laparotomy. Both kidneys were intracapsularly removed. Retreating 20 cm from the ligament of Treitz, the jejunum is cut off. The second intersection of the intestine is 60 cm to the periphery. The intestinal patency was restored by stitching it with a universal stapler (USA - 19) with a double-row stitching seam with the formation of an external cuff.

Both ends of the excised intestinal loop were brought out to the anterior abdominal wall on the left and formed two fistulas in the left iliac region (Tiri-Vell fistula). The wound was sutured in layers.

Before surgery, blood urea is 5.2 mmol / l, creatinine is 0.11 mmol / l.

After 2.5 days (03.03.2005), the condition of the dog deteriorated sharply - it lies. Body weight - 15.8 kg. Blood urea - 39.0 mmol / L, creatinine - 0.96 mmol / L. Severe azotemia. The dog was taken to the operating room. She was carried in her arms and fixed on the operating table. Through elastic fistulas, soft elastic cannulas were inserted into both ends of the intestine to a depth of 3-4 cm, they were fixed there with inflatable cuffs and they began to pump warm (38-39 ° С) dialysis fluid with a roller pump into the central end of the intestine at a speed of 500 ml per minute. In this case, the fluid flowed from the peripheral end of the intestine back into a plastic canister with a capacity of 20 liters.

Washing the loop of the jejunum lasted 4.5 hours. During this time, 135 liters of dialysis fluid passed through it. With each hour of intestinal dialysis, the dog's condition improved. She became more active, and it became impossible to keep her without sedatives tied to the table, which served as the reason for the cessation of dialysis. By this time, blood urea decreased from 39 to 23 mmol / L, and creatinine from 0.96 to 0.36 mmol / L.

The dog independently reached its cage in the vivarium. Result on the face.

If we take into account that the liquid medium of the body is distributed evenly in the intracellular, intercellular and intravascular space and makes up 50% of the weight of the dog, then in this particular case it is 9.6 liters. So, in the whole body of the dog, before the dialysis session, 374 mmol of urea (9.6 L × 39 mmol / L = 374 mmol) accumulated, and creatinine 9.21 mmol (9.6 L × 0.96 mmol / L = 9.21 mmol). In the perfusate (20 L), at the end of dialysis, urea was found at a concentration of 9.3 mmol / L, which means that 186 mmol of urea was present in the entire perfusate. Thus, due to intestinal dialysis within 4.5 hours, it was possible to remove 49.7% of urea from the entire body of the dog.

Creatinine in perfusate was detected at a concentration of 0.08 mmol / L, and 1.6 mmol accumulated in the whole dialysis solution. This means that after 4.5 hours of dialysis, about 17% of creatinine was removed from the dog’s liquid medium.

After a session of intestinal dialysis, body weight decreased to 15.2 kg. This means that 600 ml of fluid was removed from the dog’s body, which was achieved by introducing glucose into the dialysis solution.

In this experiment, every 1.5 hours, blood tests were performed for protein, hemoglobin, hematocrit, potassium, calcium, sodium and magnesium. All these indicators were without significant dynamics.

The following intestinal dialysis sessions in this dog were conducted on March 7, 2005, March 10, 2005, March 12, 2005, and identical results were obtained.

In order not to lose intestinal juice, constantly secreted from the peripheral end of the isolated intestine, and therefore protein, both fistulas after a dialysis session were connected with a plastic tube. Now the produced intestinal juice was circulating in a circle, and so that the intestine disconnected from the digestion process did not atrophy from inactivity, after each dialysis session egg white was introduced into its central end, whipped on a glucose solution.

On March 10, intestinal dialysis was performed for 6 hours. In this case, it was possible to remove 70.8% of urea from the body, which, in terms of the efficiency of blood purification from nitrogenous slags, is comparable to modern hemodialysis using an artificial kidney.

On March 10, after another dialysis, a rubber tourniquet was applied to the dog’s left forepaw and tightened to vein compression. He was left until the next dialysis session as an experimental model of prolonged tissue compression. March 12, the dog was taken for perfusion. The front paw is sharply swollen and the dog does not step on it. At the time of insertion of the cannula into the ends of the isolated intestine, the dog suddenly shook and the pulse on the femoral artery disappeared. The animal began to agonize, but the heart was still beating. A nurse, seeing a tourniquet on her paw, quickly took it off, thinking that it was she who had left him after taking the blood the previous time, and then repented. It became clear that the hypoxic poison accumulated in the forepaw rushed into the general bloodstream and caused fatal poisoning of the animal, especially since the dog had no kidneys. 0.2 ml of norepinephrine and 0.2 ml of corglucon were injected intravenously. A very frequent threadlike pulse appeared on the thigh. Urgent dialysis was started. After 15-20 minutes, the pulse on the thigh was already satisfactory filling. The dog came to life and reacted vividly to everything that was happening. Dialysis was performed for 5 hours and 51.6% of urea and 32.9% of creatinine were excreted. During this time, the edema noticeably subsided and the dog reached the vivarium under its own power.

Recent experience has shown that intestinal dialysis is effective not only in the complete absence of kidney function, but also in the syndrome of prolonged compression of tissues with severe venous congestion.

Due to the lack of funds to pay for the required number of employees for conducting chronic dog experiments, the experiment was terminated. In this regard, the next dialysis was not performed on March 14 and the dog died on March 15, having lived without kidneys only due to intestinal dialysis for 12 days. There is no doubt that this dog would live as long as it had intestinal dialysis. In two control experiments, the kidneys of 2 dogs were removed and the ends of the isolated intestines were removed to the anterior abdominal wall, but dialysis was not performed. Dogs died within 3 and 3.5 days after removal of the kidneys from uremia.

The results obtained in the experiment allow us to recommend the proposed method for use in clinical practice. Surgeons in conventional city hospitals can do the preliminary operation for patients with chronic renal failure, and after the maturation of the fistulas, which will take 20-30 days, you can begin intestinal dialysis, but already in the nephrology department.

Having picked up the perfusion regimen for the patient and having taught him to do dialysis on his own, you can let the patient go home, putting him on the dispensary record.

Technical result: this method of using an isolated loop of the small intestine as an artificial biological kidney allows intestinal dialysis to be effective not only in the complete absence of kidney function, but also in the syndrome of prolonged compression of tissues with severe venous stasis.

The method allows to exclude the patient’s dependence on attachment to a medical institution and is available for a wide range of patients requiring treatment of end-stage renal failure.

Claims (5)

1. The method of intestinal dialysis, characterized in that they isolate and cut off a loop of the small intestine with a length not exceeding 1/3 of the entire length of the small intestine, both ends of the loop of the intestine isolated from digestion are brought to the front abdominal wall, after which dialysis is carried out through an isolated loop of the intestine, in this case, the dialysis solution is pumped into the central end of the isolated loop, which flows from its peripheral end into the container with the dialysis solution. 2. The method according to claim 1, characterized in that the perfusion time is from 2 to 6 hours 3. The method according to claim 1, characterized in that the dialysis composition is packaged in dry or liquid form based on its dissolution in 5, 10 and 20 liters of water. 4. The method according to claim 1, characterized in that after the dialysis session, both fistulas are connected by a tube-plug. 5. The method according to claim 1, characterized in that in the intervals between dialysis sessions produce "feeding" an isolated loop of food additives, the composition is close to the chyme.