RU2527348C1 - Method for integrated treatment of necrotising enterocolitis in newborns and infants - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: antibacterial, infusion, syndromic, immunosupportive therapies and surgical management are conducted taking into account infant's severity and a process stage. The presence of an intrauterine infection is additionally detected. The presence and manifestation of purulent-septic values are determined. including procalcitonin, C-reactive protein, Calph-Caliph leucocytic intoxication index and immunoglobulin A. If observing at least one intrauterine infection and an increase of purulent-septic values in more than 1.5 times than a norm, a lymphotropic therapy is prescribed once a day for 7-10 days in the form of a single subcutaneous injection of a broad-spectrum antibacterial preparation into a right inguinal region 1 cm above an inguinal ligament, and two intravenous introductions of the other antibiotic.

EFFECT: invention enables reducing drug load on the patients, reducing risk of developing complications and neonatal and infant death.

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Description

The present invention relates to medicine, namely to therapy, and can be used in the complex treatment of newborns and young infants with uncomplicated and complicated course of necrotic enterocolitis (NEC).,

Necrotic enterocolitis is a serious multi-organ disease of newborns and young infants, which is often complicated by perforation, peritonitis and peritoneal shock. According to literature data, NEC occurs with a frequency of 2.1-4% of newborns entering the intensive care unit. Mortality with NEC is 40-80%, and in patients with severe forms of the course and concomitant pathology it reaches - 100% of cases, so the development of new methods for diagnosing and treating this disease is an urgent task.

There is a method of conservative treatment of patients with uncomplicated NEC, which includes the appointment of antibiotic therapy (Karavaeva SA. Abstract of a doctoral dissertation. Surgical treatment of necrotic enterocolitis, St. Petersburg, 2002, S. 19-20).

The antibiotics of choice for the first antibacterial course are semisynthetic penicillins and aminoglycosides (ampicillin and gentamicin). In addition, drugs that affect the anaerobic flora - metrogil, metronidazole, clindamycin - are necessarily prescribed. In the absence of clinical improvement, antibiotics are changed, prescribing drugs with a wider spectrum of action (cephalosporin and fortum aminoglycoside, netromycin) in age doses. To maintain and stimulate the immune system, drugs containing Ig M (pentoglobin) at a dose of 300-500 mg / kg are used, in some cases hemoplasmotransfusion (at a rate of 10 ml / kg). For the prevention of leuko- and neutropenia, folic acid is prescribed (0.5 mg / day). To increase the efficiency of the phagocytic activity of neutrophils, pentoxyl (up to 0.12 g / day) is used. An important component in the treatment is biological products - probiotics and eubiotics (lactobacterin, bifidum-bacterin, linex).

A known method for the comprehensive pre- and postoperative treatment of complicated forms of NEC, including decompression of the stomach with a nasogastric tube, complete parenteral nutrition from 3-5 to 15 days or more, prescribing broad-spectrum antibiotics, metronidazole, diflucan, immuno-replacement therapy (pentaglobin, immunoglobulin, imunofan, viferon), selective decontamination of the intestine, probiotics; infusion and syndromic drug therapy aimed at eliminating disorders of homeostasis and hemodynamics; restoration of intestinal motility, vitamins, enzymes; enteral nutrition with adapted split mixtures (alfare, alprem, etc.) (Arapova A.V., Olkhova E.B., Shchitinin V.E. Ulcerative necrotic enterocolitis in newborns // Pediatric Surgery. No. 1, 2003, p.11 -fifteen).

As a prototype of the invention, a well-known method for the complex treatment of NEC in newborns and infants, including the appointment of antibiotic therapy, taking into account the severity of the condition of the child and the stage of the process, infusion, syndromic and immuno-replacement therapy, surgical treatment and postoperative management of the patient (Karpova I.Yu. Necrotic enterocolitis in newborns: clinic, diagnosis and treatment // Modern technologies in medicine. No. 2, 2012, S.138-142).

Comprehensive pre- and postoperative treatment of uncomplicated and complicated course of NEC involves: full parenteral nutrition 3-5 days or more, depending on the severity of the child's condition and the restoration of passage through the intestines; decompression of the stomach by a nasogastric tube; infusion and syndromic therapy to stabilize the hemostatic system and hemodynamic parameters; the use of broad-spectrum antibiotics (cephalosporins of the third generation) in combination with aminoglycosides (amikacin) and metronidazole; immuno-substitution therapy (pentaglobin, immunoglobulin, viferon); selective intestinal decontamination, pre- and probiotics bacteriophages, Inulin, Florin forte, Bifiform); intake of vitamins and enzymes to restore intestinal motility; the use of biogenic drugs to improve metabolic processes and accelerate tissue regeneration (solcoseryl intravenously, jet).

However, the known method of complex treatment does not fully enhance the therapeutic effect of antibacterial drugs, because the traditional scheme of antibacterial and anti-inflammatory therapy used does not provide adequate relief of the purulent-inflammatory process. This is due to the growth of antibiotic-resistant pyogenic flora and a violation of the immunobiological reactivity of the body.

The objective of the invention is to create a method of complex treatment of NEC in newborns and infants, which allows to reduce the number of postoperative complications and mortality due to direct rehabilitation of the lymphatic channel and stimulation of the patient's own defenses, as well as improve the condition of patients.

The problem is solved in that in the known method for the complex treatment of necrotic enterocolitis in newborns and infants, including antibacterial, infusion, syndromic, immunosuppression, surgical treatment, taking into account the severity of the condition of the child and the stage of the process, additionally determine the presence of intrauterine infection, the presence and severity of purulent-septic parameters: procalcitonin, C-reactive protein, leukocyte intoxication index Kalf-Kalif and immunoglo uline A, and in the presence of at least one intrauterine infection and an increase in procalcitonin, C-reactive protein, leukocyte intoxication index of Kalf-Kalif and immunoglobulin A 1.5 times higher than normal, lymphotropic therapy is prescribed once a day for 7-10 days in the form of a single subcutaneous injection of a broad-spectrum antibacterial drug into the right inguinal region 1 cm above the pupartic ligament and two intravenous administration of another antibacterial drug.

A known method of lymphotropic therapy, which is a method of introducing drugs into the lymphatic system.

During the treatment of certain diseases, sometimes to achieve the maximum positive effect, it is required to introduce the drug into the zone of lymph nodes and blood vessels. The high therapeutic effect of lymphotropic therapy is due to the presence of relationships between tissues / organs and the lymphatic system. This makes it possible to deliver the drug directly to the affected organ. In addition, with this method, the optimal concentration of the drug in the outbreak remains during the day, which reduces the frequency of drug administration (for example, with antibacterial therapy), which in turn reduces the course and daily dosage. It should also be noted that the drug, administered lymphotropically, has no toxic effects on the kidneys, intestines, liver, since only a tiny fraction of the drug enters the bloodstream. When carrying out lymphotropic therapy, injections are carried out in areas with a maximum representation of the lymph nodes and blood vessels that are associated with a particular organ. So, there is a known method of indirect endolymphatic antibiotic therapy (Dzhumbaev S.U., Buyanov V.M., Danilov K.Yu. et al. Experimental and clinical justification of lymphotropic antibiotic therapy in surgery // Clinical Surgery. - 1987. - No. 1. - C .14-17), iliac lymphography - for indirect antibiotic therapy for destructive forms of acute appendicitis (NP Drachevsky. Treatment of gangrenous and perforated appendicitis: Author. Diss. Candidate of Medical Sciences - St. Petersburg. 1991. 19 p .; Drachevsky N.P., Kurygin A.A. et al. Indirect lymphotropic antibiotic therapy SRI destructive appendicitis // Bulletin of surgery -. 1993. - T.150, №5 6. - S.118-122). With peritonitis and in gynecological practice, the procedure is performed alternately on both sides (Zubarev PN, Sinenchenko GI. Use of endolymphatic administration of antibiotics in the complex treatment of patients with postoperative abdominal infiltrates // Clinical Surgery. - 1990. - No. 1. - S.42-43).

However, lymphotropic therapy is not used in newborns and infants, especially in the group of children with critically low body weight (up to 1 kg), taking into account a very serious condition, mechanical ventilation (mechanical ventilation) and being in the incubator to maintain a stable temperature regime, and also due to the lack of objective criteria for the possibility of lymphotropic therapy.

New in the proposed method is the determination of objective indications for lymphotropic therapy in newborns and young infants with NEC. The criteria for inclusion in the complex treatment of lymphotropic therapy are: the presence of at least one intrauterine infection (IUI), an increase in the content of procalcitonin, C-reactive protein, immunoglobulin A (IgA), the value of the leukocyte intoxication index (LII) is 1.5 times higher than normal. The proposed criteria fully and objectively reflect the severity of the purulent-septic state of the patient.

New signs - criteria of purulent-septic indicators, the severity of which allows to strengthen the complex treatment of NEC in newborns and young infants, by justifying the use of lymphotropic therapy, can reduce fatal outcomes, reduce the number of postoperative complications due to more rational and effective treatment tactics. Lymphotropic therapy allows not only to bring antibacterial drugs directly to the site of inflammation, but also helps to create long-acting high concentrations of them in the blood and other body tissues, provides stimulation of the body's own defenses, which helps to improve the condition of patients, reduces the risk of complications and reduce mortality. Thanks to this approach, it becomes possible to abandon a large drug load on the child's body and from a number of intravenous antibiotics without the risk of complications. The proposed method is informative and simple to apply in practical health care.

Distinctive features showed in the inventive combination of new properties that are not explicitly derived from the prior art in this field and are not obvious to a specialist. No identical set of features was found in the analyzed literature.

Based on the foregoing, this technical solution should be considered relevant to the conditions of patentability: "novelty", "inventive step", "industrial applicability".

To confirm the technical effect, clinical trials were conducted at the Department of Pediatric Surgery on the basis of the City Children's Clinical Hospital No. 1 GBUZ NO, 80 patients with necrotic enterocolitis aged 1 to 12 days were observed. There were 46 boys (57.5%), 34 girls (42.5%). Upon admission, the condition of the newborns was regarded as severe, corresponding to the NEC II-III degree. 58 newborns were conservatively treated. Given the severity of the condition, 22 patients were operated on. In the postoperative period, in 11 (50%) cases, a fatal outcome occurred.

In newborns with NEC stage I A, B - II A, B, when admitted to the clinical picture, they noted: CNS depression syndrome, hyper excitability, respiratory rhythm and cardiac activity disturbance, unstable body temperature, mixed acidosis, excicosis, sluggish sucking, regurgitation with bile, weight loss, soreness and bloating, frequent, poor stools with mucus and greens (sometimes with blood), sluggish peristalsis, and stool retention. An X-ray examination revealed paresis of the stomach, uneven gas filling of the gastrointestinal tract, a local increase in the thickness of the intestinal wall due to edema and inflammation, the phenomenon of a “static” loop, and the phenomenon of dynamic intestinal obstruction.

The proposed method was used in 18 newborns at different stages of the postoperative period (from 1 to 3-5 days after surgery).

The most significant purulent-septic parameters were chosen as criteria for the appointment of lymphotropic therapy: intrauterine infection (IUI), procalcitonin, C-reactive protein, Kalf-Kalif leukocyte intoxication index (LII), immunoglobulin A (Ig A), the excess of which is 1, 5 and above the norm proves the necessity of prescribing lymphotropic therapy. Indications for lymphotropic therapy were complications after surgery in the form of sluggish peritonitis with intestinal paresis (n = 5) and the emerging postoperative infiltrates in the abdominal cavity (n = 3).

Table number 1 Criteria for the appointment of lymphotropic therapy in the treatment of NEC in infants Indicators Quantitative values of indicators 1. Intrauterine infection (IUI) 1 infection or more 2. Procalcitonin " from 10 ng / ml 3. C - reactive protein 8 mg / l and higher 4. LII 2 and above 5. Ig A 1.0 g / l and higher

During treatment, clinical, laboratory and instrumental monitoring of the condition of patients was carried out, followed by a comparative analysis with the data of patients who did not receive lymphotropic administration of antibiotics.

The results obtained prove that when conducting complex treatment according to the proposed method, the condition of the patients improved more dynamically. In the clinical picture, the phenomena of peritonitis and the size of the infiltrate decreased, the general condition improved.

The proposed method is as follows.

In a newborn or infant, the severity of the condition, the stage of the process, and complex therapy are prescribed. Prescribe antibacterial therapy, taking into account the severity of the condition of the child and the stage of the process, infusion, syndromic and immunosubstitution therapy, surgical treatment and postoperative management of the patient. Usually, 2 antibiotics are prescribed by intravenous administration, for example: cefobide (100 mg / kg) 3 times a day and amikacin 15 mg / kg) 2 times a day for 7-10 days. In the absence of the effect of the selected treatment and / or worsening of the patient’s condition, additional studies are carried out and the presence of intrauterine infection, the presence and severity of purulent-septic parameters: procalcitonin, C-reactive protein, leukocyte intoxication index Kalf-Kalif and immunoglobulin A. In the presence of at least one intrauterine infection and an increase in indicators 1.5 times higher than normal and higher, lymphotropic therapy is prescribed in the form of a single subcutaneous injection of a broad spec antibacterial drug pa action once daily in the right inguinal region 1 cm above the crural arch during 7 days and two intravenous administration of antibiotic. Thus, one intravenous administration of an antibiotic is replaced by lymphotropic. A single dose of the drug is drawn into the syringe and with the help of an insulin needle (provides the most delicate injection) in the right inguinal region 1 cm above the pupartic ligament at an angle of 60 to the skin surface, the drug is injected subcutaneously, for 7-10 days, then purulent-septic is monitored indicators in dynamics. The second antibiotic is administered as usual.

An example of a specific performance is given in the form of an extract from a medical history.

Patient X., 13 days. Child from 3 pregnancies, 1 birth. The course of pregnancy is unknown, the mother is 22 years old. Birth weight 2300 g, prematurity 36 weeks. Apgar score 6 points. Taking into account the degree of prematurity and severity of the condition for further observation and treatment, the child was transferred to the nursing department of premature children of hospital No. 27.

The hospital noted a serious condition. On the 2nd day, the boy was transferred to mechanical ventilation. The food was absorbed from the 2nd to 11th day of life. The treatment was prescribed: antibiotic therapy (cefotoxime 60 mg 2 times a day in combination with metronidazole, iv), 10% glucose solution, vitamins C, B. Hemostatic therapy (decinone, calcium gluconate, FFP No. 2).

On the 12th day of life, the child’s condition worsened, general anxiety appeared, and stagnant discharge began to move along the nasogastric tube. The abdomen is moderately swollen in all departments, soft, painful with deep palpation. Auscultation did not listen to peristalsis.

At the age of 13 days, from the hospital No. 27, the child was resuscitated by the intensive care unit to the intensive care unit of the Children's City Clinical Hospital No. 1 with a diagnosis of Suspected necrotic enterocolitis.

When viewed in a hospital, the condition is very serious. Body temperature 36.6 ° C. The skin is pale pink, clean, dry, moderate cyanosis of the nasolabial triangle, acrocyanosis. Neurological symptoms were noted: lethargy, muscular dystonia, areflexia. In the lungs, breathing is shallow, carried out in all departments, moist rales are heard. Saturation up to 99%. Heart sounds are rhythmic, muffled, noises are not heard. BH 46 per minute, heart rate 140 per minute. A / D 65/38 mmHg Art. The abdomen is swollen, moderately tense in all departments, painful, peritoneal symptoms are dubious. The liver + 3 cm from the edge of the costal arch, the spleen is not palpable. Peristalsis is not heard. There is no discharge from the gastric tube. A stool with a streak of blood.

In an emergency, the child underwent a panoramic radiography of the abdominal cavity, on which extended intestinal loops, a thickening of the intestinal wall, and uneven pneumatization of the intestine were found.

In the general analysis of white blood cells up to 10.7 × 10 ⁹ / l with a shift of the formula to the left (stab neutrophils 30%). The presence of young forms (myelocytes - 8%, metamyelocytes - 5%). C-reactive protein up to 210 μmol / L. Anisocytosis, poikilocytosis. In the analysis of urine, traces of protein up to 0.03 g / l, leukocytes 10-15 in half vision, the presence of fungi of the genus Candid.

Using PCR diagnostics confirmed intrauterine infection (chlamydia, ureoplasmosis).

In the intensive care unit, preoperative therapy was prescribed, which includes complete parenteral nutrition, an infusion program, antibacterial therapy (cefobide, amikacin in combination with metronidazole). Syndrome treatment (etamzilate, vikasol, infucol, 10% glucose solution, potassium chloride, FFP, reamberin, red blood cell mass, acesol, immunoglobulin, infezol).

When analyzing the quantitative characteristics of the proposed purulent-septic parameters, it was noted: procalcitonin - 10 ng / ml, C-reactive protein - 13 mg / l, LII - 3, Ig A - 1.5 g / l, which indicated the need for use lymphotropic therapy.

The main point of antibacterial treatment was the replacement of one intravenous administration of cefotaxime solution with subcutaneous lymphotropic administration, which was performed as follows: a single dose of cefotaxime (10 mg) diluted in 2 ml of 0.25 was administered subcutaneously into the right inguinal region 1 cm above the pupar ligament % solution of novocaine. The course of lymphotropic therapy was carried out for 7 days.

As a result of the treatment, a significant clinical and laboratory effect was obtained, which is expressed in improving the patient's condition and positive stabilization of purulent-septic parameters: procalcitonin - 5.5 ng / ml, C-reactive protein - 8 mg / l, LII - 2, Ig A - 0.6 g / l

Indices of electrolyte metabolism: potassium 4.1 ± 0.3 mmol / l, sodium 145 ± 1.0 mmol / l, calcium 2.3 ± 0.6 mmol / l.

Data on non-protein nitrogenous components: creatinine 75.9 ± 1.0 mmol / L, urea 5.0 ± 0.8 mmol / L, urea nitrogen 4.6 ± 1.7 mmol / L, residual nitrogen 13.0 ± 2, 5 mmol / l.

Blood protein level: total protein 64.0 ± 0.3 μcatal / l, albumin 38.0 ± 0.4 μcatal / l.

A study of the enzymatic activity and pigment exchange of blood serum revealed: alanine aminotransferase 1.5 ± 0.3 μcatal / l, aspartate aminotransferase 0.85 ± 0.5 μcatal / l, lactate dehydrogenase 358.8 ± 0.7 U / l, total bilirubin 75, 1 ± 1.6 μmol / L, direct bilirubin 57.1 ± 1.0 μmol / L.

On day 18, feeding with the adapted mixture began. In control tests of blood and urine - without pathology

In satisfactory condition on the 25th day the child was discharged home.

Claims (1)

A method for the complex treatment of necrotic enterocolitis in newborns and young infants, including antibacterial, infusion, syndromic, immuno-replacement therapy, surgical treatment, taking into account the severity of the child’s condition and stage of the process, characterized in that it further determines the presence of intrauterine infection, determines the presence and severity of purulent septic parameters: procalcitonin, C-reactive protein, leukocyte intoxication index Kalf-Kalif and immunoglobulin A, and with After at least one intrauterine infection and an increase in purulent-septic parameters more than 1.5 times higher than normal, lymphotropic therapy is prescribed once a day for 7-10 days in the form of a single subcutaneous injection of a broad-spectrum antibacterial drug in the right inguinal region by 1 see above the pupartic ligament and two intravenous administration of another antibiotic.