RU2239450C1 - Method for treatment of pneumonia in newborns - Google Patents

Abstract

FIELD: medicine, pediatrics, neonatalogy, immunology.

SUBSTANCE: invention can be used for treatment of pneumonia in newborns. For this aim method involves applying recombinant interleukin-2, roncoleukin, for carrying out the topical immunomodulating therapy of bronchopulmonary zone in combination with antibacterial, infusion and post-syndrome therapy. This preparation is administrated by divided, jet, endotrachial route in the dose 0.1 mg in volume 1 ml, 1-5 times with interval for 2-3 days. Method provides reducing the level of anti-inflammatory cytokines in the inflammation focus allowing to exclude or to diminish bronchopulmonary diseases in newborns in further.

EFFECT: improved method for treatment.

2 cl, 1 tbl, 3 ex

Description

The present invention relates to medicine, namely to pediatrics, neonatology and immunology.

Pneumonia occupy an important place in the structure of neonatal morbidity and mortality, require intensive care, and can lead to chronic diseases of the bronchopulmonary system (Tabolin V.A. et al., 1998; Bocharova I.I. et al., 2001; Degtyareva M.V. ., 2001; Gillian E., et al., 1993).

The traditional treatment of pneumonia includes antibiotic therapy in accordance with the expected microflora, as well as indications for mechanical ventilation and infusion therapy. Newborns with pneumonia need expensive therapy and subsequent long-term rehabilitation, which, unfortunately, does not exclude the chronicity of the process and even complete disability of the child (Shabalov N.P., 1988; Antonov A.G., 1997; Volodin N.N., 1998) .

In the pathogenesis of pneumonia in newborns (congenital, postnatal), a significant role is played by the presence of local dysfunctional disorders of the immune system (Buck C. et al., 1994; Buron E. et al., 1999; Groneck P. et al., 2000; Schaller- bals et al., 2002).

In neonatal practice in the complex treatment of pneumonia, immunoglobulins for intravenous administration (IVIG) have found widespread use, the use of which allows the creation of effective concentrations of functionally active antibodies in the blood as soon as possible. The daily dose is 400 mg / kg, the route of administration is intravenous administration using an infusion pump or drip, the rate of administration is 1 ml / kg / h for the first 15 minutes, then 3-4 ml / kg / h (Degtyareva M.V. Modern possibilities of immunocorrecting therapy of severe infectious-inflammatory and immunopathological conditions in newborns. A practical guide for doctors, M., 2001). This method is accepted by us as a prototype.

Based on the fact that, according to many researchers, the local mucosal immune system is largely autonomous (Buck C. et al., 1994; Viscardi RM, et al., 2002), we examined local immunity in infants with pneumonia against the background of the use of systemic immunopreparations according to the recommended schemes. It was shown that, despite the pronounced effects of systemic immunity, the dynamics of local changes were not always adequate. In addition, the local use of immunomodulatory drugs can reduce the dose of the latter and avoid some, sometimes undesirable systemic effects.

Based on this, there is a need to develop a method of targeted local immunomodulating therapy.

The objective of the present invention is to increase the effectiveness of treatment by adequate local immunomodulating therapy of newborns with the reasonable use of pathogenetically significant immunomodulators.

The essence of the invention is complex therapy, including antibacterial, infusion, and syndromic therapy and local immunomodulating therapy by fractional jet endotracheal administration of recombinant interleukin-2 - Roncoleukin in a dose of 0.1 mg in a volume of 1 ml with an interval of 2-3 days.

The method is as follows: along with the use of antibacterial, infusion, and syndromic therapy, after lavage of the tracheobronchial tree through the endotracheal tube, fractionally, first into the right bronchus, then 0.5 ml of Roncoleukin in a total dose of 0.1 mg is injected several times into the left bronchus (1-5) times with an interval of 2-3 days. The method was tested on newborn children with severe pneumonia, who are on respiratory support.

This method of endotracheal administration (fractional, jet) was chosen after studying the biological activity of recombinant IL-2 with other drug delivery options. So, when trying to obtain aerosols for inhalation using mechanical inhalers and nebulizers (ultrasonic and pump), it was found that when dissolving a single dose (0.1 mg) in volumes of 1 to 10 ml, it foams sharply, both with the addition of albumin and without that. It was found that the biological activity of IL-2 decreases exponentially and after 5 minutes it reaches only 15-20% of the original. Thus, the only possible method is an inkjet, with distribution on both bronchi.

In the neonatal intensive care units of the perinatal center and emergency hospital in Krasnodar in 2001-2003. a comparative study of the effectiveness of the proposed method of therapy compared with the traditional (prototype). For this, two equal (21 children) groups of newborn children with pneumonia were formed by random sampling. All patients received antibiotic therapy, infusion and syndromic drug therapy as basic therapy, taking into account the acid-base state, the value of venous and peripheral hematocrit, hemoglobin, electrolyte composition and biochemical parameters of blood serum.

The first group of children received IVIG, the second (main) - Roncoleukin in the above way.

Children with pneumonia who were on traditional therapy usually developed leukopenia with lymphopenia by 5-7 days, a significant decrease (compared with healthy newborns) of the bactericidal activity of neutrophilic leukocytes, the absolute and relative concentration of CD4 +, with a slight increase in CD16 + CD56 +, CD25 + and HLA DR +. In the main group, the lymphopenic phase of pneumonia was slightly expressed, there was a sharp increase in the concentration of lymphocytes having receptors for IL-2 and HLA DR +, as well as NK cells, accompanied by stimulation of the absorbent and bactericidal phases of phagocytosis. By 18 days, most patients of the main group had a clinical recovery with a tendency to normalize the studied immunity parameters.

In the main group, a fatal outcome was registered in 1 child, in the comparison group - in 3. A shortening of the central vein catheterization period was revealed: in the control group, the presence of a subclavian catheter for conducting infusion therapy was mandatory for 12.3 ± 3.4 days, and in the main group, this period was shortened to 6.7 ± 2.3 days. The duration of treatment of pneumonia in the main group was 17.1 ± 0.3 days, in the comparison group - 21.4 ± 0.5 days (p <0.001). The duration of antibiotic therapy decreased from 21.1 ± 1.5 days in the control group to 15.5 ± 0.8 days in the main group.

Example 1: Patient S., a boy, age 2 days, was admitted to the neonatal intensive care unit with a diagnosis of meconium aspiration, aspiration pneumonia. The child was on mechanical ventilation from the first day of life, the condition of the child was severe. The patient was given complex therapy: antibacterial - claforan at a dose of 100 mg / kg for 12 days, netromycin at a dose of 7.5 mg / kg for 10 days, infusion therapy with solutions of 10% glucose and 0.9% NaCl, as well as local Roncoleukin therapy, which was injected endotracheally fractionally into the right and left bronchi jet in a total dose of 0.1 mg in a volume of 1 ml in an amount of 1 time. A day later, the child was removed from the ventilator and transferred to independent breathing. The child was given one course of antibiotic therapy. The condition of the child has improved, the skin is pink, muscle tone and physical activity are satisfactory, breastfeeding. In the lungs, puerile breathing, heart sounds are rhythmic. In the general analysis of blood at discharge: erythrocytes 5.0 × 10 ⁹ / L, Hb - 160 g / L, platelets - 310 × 10 ⁹ / L, leukocytes 10.2 × 10 ⁹ / L, stab neutrophils - 4%, segmented neurophiles - 26%, lymphocytes 53%, monocytes 12%, eosinophils 3%, basophils 2%. The child was discharged home on the 14th day of therapy in a satisfactory condition.

Example 2: Patient A. Boy, age 1 day. A child from II pregnancy, the first pregnancy ended in a miscarriage at 15 weeks, the real one proceeded in the first half without features, in the second half - the threat of interruption, the mother has chronic pyelonephritis. Childbirth I at 35 weeks, birth weight 2720 g. The condition at birth is severe, due to respiratory failure, neurological symptoms. Intensive care measures were taken in the delivery room. The child was transferred to the intensive care unit, where he was diagnosed with Congenital pneumonia. DN III degree. Perinatal damage to the brain, hypoxic-ischemic genesis, acute period in the form of inhibition syndrome. Prematurity 35 weeks. The condition of the child from birth is serious. Upon admission to the intensive care unit, the child was sluggish, dynamic, expressed muscle hypotension, hyporeflexia, cyanosis and apnea attacks. The skin is pale with a grayish tint, foamy discharge from the mouth. Percussion over the lungs was a shortening of the tone in the lower sections, auscultation - an abundance of small-bubbling and crepitating wheezing, heart rate of 166 beats per minute, muffling of heart sounds. Body temperature 36.7 ° C. PaCO ₂ 60 mmHg, PaO ₂ 44 mmHg, pH 7.14. In the general blood test: erythrocytes - 5.0 × 10 ⁹ / L, Нb - 150 g / L, platelets - 290 × 10 ⁹ / L, leukocytes 17.2 × 10 ⁹ / L, metamyelocytes - 4%, stab neutrophils - 9%, segmented neutrophils - 47%, lymphocytes - 25%, monocytes - 11%, eosinophils - 3%, basophils - 1%.

The child was transferred to mechanical ventilation. On chest x-ray - bilateral pneumonia. During rehabilitation from a tracheobronchial tree, a viscous purulent sputum was obtained. From the first day antibacterial therapy was prescribed - claforan 100 mg / kg and netromycin 10 mg / kg, infusion therapy - glucose 10%, acidosis correction - sodium bicarbonate 2%. Feeding probe.

From 2 days of life, Roncoleukin was connected to the treatment, which was administered fractionally jet, first into the right, then into the left bronchi in a total dose of 0.1 mg in a volume of 1 ml in an amount of 5 times with an interval of 2 days. During the period of this therapy, pronounced positive dynamics were observed during the course of the disease. On the 10th day of therapy, the child was transferred to spontaneous breathing, the feeding volume was brought up to 320 ml / day, the food was absorbed, did not vomit, muscle tone and motor activity increased. The skin is pink, auscultation over the lungs harsh breathing, single crepitating wheezing, heart sounds are muffled. In the general analysis of blood: erythrocytes - 4.5 × 10 ⁹ / L, Нb - 120 g / L, platelets - 280 × 10 ⁹ / L, leukocytes - 11.2 × 10 ⁹ / L, metamyelocytes - 2%, stab neutrophils - 3%, segmented neutrophils - 25%, lymphocytes - 55%, monocytes - 12%, eosinophils - 3%. For further treatment and nursing, the child was transferred to the second stage of nursing in the department of pathology of newborn children. The child was discharged home on the 24th day of therapy.

Example 3: Child M. A girl, 2 days old, was in the neonatal intensive care unit with a diagnosis of Congenital pneumonia. A child from 1 pregnancy, proceeding against the background of the threat of interruption, the mother is infected with chlamydia. Delivery on time, anhydrous period of 9 hours. The condition of the baby at birth is severe (breathlessness of NPV more than 60 in 1 minute, wheezing, stridor, cyanosis attacks) and continued to progressively worsen. On the radiograph, diffuse bloating of the lungs, small focal infiltrates against the background of reticulo-small-sized lesions of the interstitial tissue were noted. The treatment included - oxygen therapy (mechanical ventilation from 2 days), antibiotic therapy (fortum 100 mg / kg - for 12 days, amikacin 7.5 mg / kg - 7 days, at the end of the course of amikacin, summamed 10 mg / kg is connected - 3 days), infusion therapy (glucose 10%), correction of electrolyte disturbances (NaCl 0.9%, KCl 7.5%), correction of acidosis (sodium bicarbonate 2%). From 2 days, Roncoleukin was connected to the complex treatment, which was administered fractionally jet endotracheally in a total dose of 0.1 mg in a volume of 1 ml in an amount of 2 times with an interval of 3 days. By the end of 5 days, the child was transferred to independent breathing. Only one course of antibacterial therapy was given to the child. The child's condition improved, which was confirmed by clinical and laboratory data, and on the 14th day of therapy was discharged home in satisfactory condition.

The table shows data reflecting the main parameters of the state of the immune system in newborns with pneumonia under treatment using the traditional and proposed method of therapy.

The technical result of the method is that the proposed method of complex pathogenetically targeted local immunomodulatory therapy with Roncoleukin improves the quality of treatment and prognosis in newborns with pneumonia, reduces the duration of antibiotic therapy, reduces the cost of treatment, reduces mortality, length of hospital stay and, as a result, has economic and social significance.

Claims (2)

1. A method of treating pneumonia in newborns, including the use of traditional therapy and immunotherapy, characterized in that they carry out local immunomodulating therapy of the bronchopulmonary zone by fractional jet endotracheal administration of recombinant interleukin 2 - Roncoleukin. 2. The method according to claim 1, characterized in that Roncoleukin is administered in a dose of 0.1 mg in a volume of 1 ml in an amount of 1-5 times with an interval of 2-3 days.