RU2090189C1 - Agent for treatment of infectious toxicosis of infants - Google Patents

Abstract

FIELD: medicine, in particular, pediatrics. SUBSTANCE: used as a medicine for treatment of infectious toxicosis is kaviton in amount of 1 mg/kg per day intravenous, by drops with a speed 6 drop per min. EFFECT: prevention of development of vital complications, reduced invalidity. 2 tbl

Description

 The invention relates to medicine, namely to pediatrics, intensive care.

 Studies on patent and medical literature have revealed a number of drugs for the correction of violations of the rheological properties of blood in general: hemodez, albumin, reopoliglyukin, mannitol, heparin, antiplatelet agents and antihistamines (Golovin G.V. et al. Correlation of rheological properties of blood in transfusiology / G.V. Golovin, I.V. Dutkevich, A.G. Shapkin and others // Bulletin of surgery named after Grekov, 1986, N 11, pp. 129-133; Karabanov G.N. Inchenko K.S. The deformability of red blood cells in the clinical aspect // Herald of surgery, 1986, N12, -s. 99-103; Neinov G .N. Changes in the permeability of the wall of blood capillaries and their correction in purulent-septic diseases in children. // Pediatrics, 1987, N 8, pp. 61-64; Papayan A.V. Tsybulkin E.K. Acute toxicosis in early childhood L. Medicine, 1984).

 In recent years, cavinton has been widely used to correct vascular disorders in various adult diseases. In particular, the research of Burtseva E.M. Atamanyuk E.D. // Endovascular (catheter) therapy. M. 1979, p. 116-117; E.M. Burtsev, L.A. Usov, E.D. Atamanuk, L.G. Miller // Journal of Neuropathology and Psychiatry. 1983, N 1, p. 59-66, long-term catheter endovascular therapy with cavinton of ischemic stroke is used. The authors argue that the maximum effect of Cavinton therapy is achieved in the first three days of illness.

It is known that under the influence of cavinton, blood supply to the brain improves due to inhibition of platelet aggregation and adhesion, improved erythrocyte deformability (Burtsev E.M. Turgitov A.I. On the therapeutic effect of cavinton in chronic cerebrovascular insufficiency // Journal of Neuropathology and Psychiatry, 1985, N 1, pp. 53-56; Shilyaev R.R. et al. The use of cavinton and piracetam in intensive care of complicated forms of pneumonia in children / R.R. Shilyaev, V.V. Chemodanov, S.V. Shibaev, etc. / / Russian National Congress "Man and Medicine", 1st: Abstract. M. 1992, N 473). In addition, according to Gabrielyan E.S. (The role of leukocytes in hematovasal regulation of blood circulation // Bull. Experimental biology and medicine, 1989, N 6, pp. 660-662), Cavinton is an inhibitor of phosphodiesterases. [one]
The aim of the invention is to prevent the development of vital complications, disability and reduce the length of stay of children with infectious toxicosis in the intensive care unit. The goal is achieved by using cavinton as a means of correcting rheological disorders.

 The theoretical rationale for this method is as follows.

 With infectious toxicosis in young children, many parameters that determine the homeostasis of the body are subject to significant changes. Moreover, the leukocyte cell is especially sensitive to changes in the conditions of the internal environment. So it is believed that blood neutrophils are completely replaced every 10 hours, and all the shifts that have been outlined during this period will be recorded by cells that have returned to the bloodstream (Mayansky A.N. Pathogenetic aspects of neutrophil-dependent reactions // Patol. Physiology and expert therapy. , 1989, issue 6, pp. 66-72).

 With infectious toxicosis, leukocyte cells thus change their structural and functional parameters, which in essence are functionally disadvantageous for ensuring blood rheology and microcirculation, worsening the course of the pathological process in the first 3 days.

 On the first day, a decrease in the deforming ability of cells is noted, moreover, neutrophil is a more rigid cell than a lymphocyte, but on the second day the plasticity of lymphocyte cells decreases to their minimum level.

 From the first day, toxic stimuli activate the production of lymphokines by lymphocytes with a maximum on day 2, having a significant effect on the rheological and anti-inflammatory properties of neutrophils.

 From day 3, the effect of leukocytes on the terminal blood flow weakens and structural changes begin to prevail in them, allowing cells to participate more actively in acute inflammation reactions. The following days, leukocyte cells perform their specific functions.

 Given the fact that with toxicosis there are significant violations of the structural and functional parameters of leukocytes, especially in the first 3 days of an extreme condition, it is important to establish the optimal drug that helps to eliminate rheological disorders of both neutrophils and lymphocytes.

 As a means of correcting rheological disorders of leukocytes, Cavinton is proposed, which is able to improve cell plasticity, eliminate the state of hyperagesivity, reduce activation and the associated processes of accumulation of lipid peroxidation products in cells.

 Methodologically, the study was carried out as follows: children with infectious toxicosis were prescribed cavinton at a rate of 1 mg / kg and were injected intravenously at a 5% glucose solution at a rate of 6-8 drops per minute. At the same time, patients did not receive other reactive drugs: reopoliglukin, hemodesis, chimes, pentoxifylline in a planned manner. Clinical and laboratory examination, including the study of indicators of deformability, adhesion, migration, damage to neutrophils and lymphocytes, assessment of capillaroscopic changes was carried out before administration and 30 minutes after the end of drug administration.

 In most patients with infectious toxicosis, in the treatment of which a solution of cavinton was used, the condition was regarded as serious before administration of the drug. On the part of the central nervous system, symptoms of cerebral disturbances were noted in the form of excitement, followed by lethargy, severe motor anxiety, and a monotonous cry. Changes in peripheral blood circulation were manifested by a persistent decrease in the local temperature of the limbs, pallor, gray skin color in 1/3 of cases, and pale color with a cellular violet pattern in 2/3 of cases. 1/3 of the children developed intestinal paresis. Signs of heart failure were clinically determined: tachycardia (162.9 ± 10.2 beats per minute), muffled heart sounds, liver displacement up to 5 cm below the edge of the costal arch.

 Respiratory disorders were manifested by increased respiration (56.7 ± 5.5 breaths per minute), mixed dyspnea, grunting breathing, perioral cyanosis, and the participation of auxiliary muscles in the act of breathing. Patients were characterized by a polymorphism of physical data (scattered dry and wet rales, mosaic of percussion changes).

After completion of the introduction of cavinton, the condition of the patients improved and was regarded as close to moderate. Children were conscious, active. Signs of peripheral circulatory disturbances decreased: the skin had a pale or pale pink color, the limbs became warm to the touch. There were no symptoms of intestinal paresis. Under the influence of cavinton, the heart rate decreased by 10% compared with the initial data, with auscultation, clear heart tones were determined. Respiratory rate decreased by 20.5%
During laboratory monitoring (Table 1), it was revealed that under the influence of cavinton, the deforming ability of neutrophil cells increased from 0.69 ± 0.03 srvc. units up to 0.86 ± 0.02 conventional units (p <0.001). Lymphocyte deformability index behaved similarly, increasing from 0.71 ± 0.03 srvc. before drug administration, up to 0.86 ± 0.02 conventional units (p <0.001).

 Under the influence of cavinton, there was a tendency to decrease the adhesion of lymphocytes by 18.8% and 15.9% for neutrophils, which is a positive result, since it reduces the state of hyperagesicity of cells, returning cells to an adequate functional state. At the same time, it seems that cavinton has a stimulating effect on lymphocytes, since after its use, an increase in the production of lymphokines (MIF) by these cells was noted, causing a decrease in the leukocyte migration index to 67.1 ± 4.4% (p <0.05) .

 This property of cavinton can be regarded as functionally beneficial, since a decrease in the migration ability of neutrophils reduces the possibility of PMNL exit from the channel and tissue damage (Mehta S. et al. Neutrophil function ishemic heart disease / S. Mehta, J. Dinerman, P. Mehta et al. // Circulation, 199, vol, 79, N 3, p. 549-556).

 Under the influence of cavinton (Table 2), a tendency to a decrease in the neutrophil damage index was noted, the intracellular landscape changed: against the background of a decrease in the number of cells with a vacuolated nucleus and karyorexis, an increase in cells with pseudopodia and karyolysis was noted. The indicator of lymphocyte damage did not change, remaining above the control values (p <0.05), while after the treatment, intracellular changes, primarily cytoplasmic vacuoles, disappeared.

 So, Cavinton therapy leads to the stabilization of cells, which causes a clear clinical effect that occurs against the background of normalization of peripheral blood flow.

 In children with infectious toxicosis, starting from the second day, against the background of Cavinton therapy, a distinct positive dynamics of the capillaroscopic pattern was noted, in particular, the diameter of microvessels approached the parameters of healthy children, the number of functioning capillaries increased and only a few of them had a convoluted shape. The blood flow velocity in microvessels and its homogeneity were restored (only single cell aggregates were determined). The overall capillaroscopic background was clear with a satisfactorily visualized subpapillary network. The improvement in microcirculatory characteristics correlated with a decrease in the clinical signs of damage to the central nervous system, respiratory and cardiovascular systems. The duration of the period of developed clinical manifestations of toxicosis in children of this group averaged 2.5 days.

 The tactics of treatment with Cavinton consists of its intravenous drip at a dose of 1 mg / kg / day during the first 3 days of the period of developed clinical manifestations of infectious toxicosis.

 Clinical example.

 Patient Semyon B. 9 months. A child from 1 pregnancy, proceeding against the background of gestosis of the I and II half, the threat of interruption, polyhydramnios. Childbirth in 38 weeks. Birth weight 3,200 g, length 51 cm.

 Holds his head from 2 months. sits from 7 months. first teeth 8 months

 In the first year of life at the age of 3 months. the child suffered acute bronchitis. Since birth, at the neuropathologist's follow-up, regarding perinatal encephalopathy.

The real disease in the child began with the symptoms of acute respiratory viral infections in the form of a respiratory syndrome (runny nose, dry cough). In the future, the condition of the child worsened. There was a persistent rise in body temperature to 38.8 ^o C, vomiting up to 10 times a day, refusal of food and water, lethargy. The doctor has diagnosed infectious toxicosis.

 When viewed in the intensive care unit on the second day of infectious toxicosis, the child's condition is regarded as serious. The child is conscious, expressed psychomotor agitation, rushing around in the crib, monotonous cry. The skin is clean, pale with a pronounced purple cellular pattern, hyperesthesia of the skin. The limbs are cold to the touch. Cyanosis of the nasolabial triangle. Stiff neck.

 Breathing groaning frequency of 70 in 1 min. With percussion, shortening in the lower parts of both lungs. Auscultation in the lower parts of the breath is weakened, a lot of finely bubbly moist rales is heard. Pulse 200 beats per minute. Heart sounds are deaf. The stomach is moderately swollen, tense. The liver protrudes 5 cm from under the edge of the costal arch, the spleen 2 cm.

 Traditional therapy in the form of neurovegetative blockade (pipolfen), vascular preparations (aminophylline, nicotinic acid), infusion therapy (polarizing mixture) allowed to achieve only some stabilization of the state.

A laboratory examination revealed a significant deterioration in the structural and functional properties of leukocytes. So, the coefficient of deformability of neutrophils was 0.61 srvc. lymphocytes 0.56 conventional units the rate of spontaneous neutrophil adhesion increased to 59.3% of lymphocytes to 88.6%; the leukocyte migration index was 80%. With capillaroscopy of the nail bed, the subpapillary network is not visible, the background is cloudy, the capillaries are convoluted. Spasm of arterioles and venules is expressed. The number of functioning capillaries is 3-4 per 1 mm ² . The blood flow is slow, intermittent. 4 to 10 arteriovenular anastamoses.

 Thus, the active involvement of leukocyte cells in the pathological process, contributing, on the one hand, to seizure of arterioles and their collapse, on the other hand, their high adhesive ability and migration activity, leads to the formation of microthrombi in the venules, damage to the endothelium, and the active release of plasma from the blood channel and with it activated leukocyte cells that cause tissue damage. The traditional means used do not have a leukocyte-stabilizing effect and thus do not contribute to the elimination of rheological disorders that determine the severity of peripheral blood flow disorders.

 The inclusion of Cavinton at a dose of 1 mg / kg by intravenous drip into the treatment plan made it possible to achieve the following: the condition of the child after the end of administration was regarded as serious. The child is awake, asleep. The skin is pale, limbs are warm. Rhythmic breathing at a frequency of 54 per minute. Heart sounds are muffled. Pulse 160 beats per minute. The abdomen is soft, not swollen. Liver +5 cm, spleen +2 cm.

The deformability coefficient of neutrophils increased to 0.89 conventional units. lymphocytes 0.84 conv. units The spontaneous neutrophil adhesion rate 48.1% lymphocytes 51.3% The leukocyte migration rate decreased to 74.5%
During capillaroscopy, a moderate turbidity of the background, normalization of the tone of the capillaries, the number of functioning capillaries increased to 7 8 per 1 mm ² , arteriovenular anastomoses 1 by 10, the nature of the blood flow was defined as coarse-grained, slowed down.

 The subsequent use of cavinton in the treatment plan allowed the child to be transferred to the somatic department for 4 days of infectious toxicosis in satisfactory condition for further treatment of the underlying disease (pneumonia).

 Thus, the claimed tool allows you to conduct a targeted therapeutic effect on neutrophils and lymphocytes, improves the rheological parameters of cells, reduces the degree of microcirculatory disorders, prevents tissue damage PMNL, emerging from the bloodstream, which can improve outcomes, prevent the development of vital complications and reduce the length of patient’s stay with infectious toxicosis in the intensive care unit.

Claims (1)

 The use of cavinton as a tool for the treatment of infectious toxicosis in young children.

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