RU2174838C2 - Method for treating severe manifestations of bronchial obstructive syndrome in children - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: method involves intravenously administering nitroglycerin as microjets at a dose of 1 mcg/kg/min as 2-4 days long course. EFFECT: improved breathing function of lungs; reduced pulmonary hypertension; improved bronchial dilation; accelerated alleviation of perivascular and peribronchial edema state. 4 tbl

Description

 The invention relates to medicine, namely to pediatrics.

 According to modern literature, most authors: Rachinsky S.V., Tatochenko V.K., Artamonov R.G. (Respiratory diseases in children: a guide for doctors. - M. Medicine. -1987-p. 186-194, "Obstructive bronchitis in children." M. 1996-p. 103-147), Gavalov S.M. ("Bronchoobstructive syndrome in children" Novosibirsk. 1992), Tsybulkin E.K. ("Threatening conditions in children" S.P. 1994-pp. 74-78), Salonen RO (Acta Farmacol. Toxicol. 57 Suppi. 3: 1-38; 1985), Wilkie R., M. Bryan, 1987, Denjean A et al. (J. Pediatr. 6, pp. 974-979, 1992) and others. The main types in the treatment of bronchial obstructive syndrome (BOS) in young children offer different types of bronchodilators acting on various pathogenetic links of the pathological process. Their arsenal is huge and includes xanthine drugs, beta-2-adrenergic agonists, anticholinergics. However, the role of bronchospasm increases in children with repeated episodes of biofeedback. As a rule, the age of these children is older than 1.5 - 2 years.

 Violation of respiratory functions in young children is primarily associated with the development of peribronchial edema (Tatochenko V.K., Artamonov R.G., 1987, 1996, Respiratory diseases in children: a guide for doctors.- M.: Medicine- 1987-p. 186-194; "Obstructive bronchitis in children." M.1996 -p. 103-147; Gavalov S. M. "Bronchial obstructive syndrome in children" - Novosibirsk. 1992).

 Hence, according to our data, the effectiveness of bronchospasmolytic therapy in infants is low, although there is conflicting information in this literature in modern literature.

 The main drug in the treatment of biofeedback is aminophylline, which in many clinics for severe biofeedback is used according to the dosage schemes proposed by the staff of the Department of Clinical Pharmacology of the Smolensk Medical Institute (L. Strachunsky et al. 1993, Pediatrics-N 2. -1993. -S. 67-70).

 Along with positive properties, the drug has many negative properties, which makes its use often impossible in pediatric practice. The therapeutic dose of aminophylline is close to toxic, which causes its side and toxic effects: dyspeptic disorders, anxiety, agitation, muscle tremor, tachycardia, convulsive syndrome. The drug increases the myocardial oxygen demand (Gusel V.A., Markova I.V. "Pediatrician's Guide to Clinical Pharmacology", 1990- pp. 177-180; Vidal 1997-p. 704). Tatochenko V.K., Artamonov R.G. ["Obstructive bronchitis in children" M. 1996, pp. 104-147] suggest the use of glucocorticoids in doses of 6-8 mg / kg in a short course for the treatment of severe obstructive bronchitis (OB).

 In practical work, at the same time, as a rule, more than 10 drugs are used to treat severe OB, which is undoubtedly unacceptable from both an economic and pharmacological point of view.

 We conducted studies of central and peripheral hemodynamics, respiratory disorders, oxygen status, autonomic nervous system, in 80 young children with OB.

In our studies, we used impedance pneumography with the SpaceLabs apparatus with registration of the respiratory rate (BH), the ratio of the tidal volume to the surface of the body (DO / m ² ), the ratio of the minute volume of respiration to the surface of the body (MOD / m ² ), and the ratio of inspiratory time to expiratory time (T _exp / T _exp ), the ratio of expiratory time to the respiratory cycle (T _exp / RR); echocardiography (ECHO-KG) using the LOGIQ-500 apparatus with registration of heart rate (HR), cardiac index (SI), shock index (UI), left ventricular expulsion fraction (PI), mean pressure in the pulmonary artery (С _p. DLA), pulse oximetry with registration of oxygen saturation by the apparatus "BCl";cardiointervalography; central venous pressure by Waldman's apparatus; blood pressure using a Hewlett Packard 78352C monitor; acid-base state (KHS) by the apparatus "Radiometr" ABL-50 with the study of pH, partial tension of carbon dioxide (pCO ₂ ), oxygen (pO ₂ ), base deficiency (BE). The following changes have been identified.

 1) Pulmonary hypertension, significantly increasing with the severity of the disease.

 2) A significant predominance of the hyperdynamic regime of central hemodynamics. The level of compensation of the cardiovascular system also changed with the severity of the disease. In severe OB, a sub- and decompensated type of hemodynamics.

 3) Hyperventilation syndrome (according to impedance pneumography).

 4) The initial sympathic-hypersympathicotonia, increasing with the severity of the disease, with a predominance of asympatheticotonic reactivity in severe patients.

 5) Marked disturbances in peripheral blood flow, high tissue oxygen demand (tissue hypoxia) with increased compensatory lung function. Metabolic subcompensated acidosis with accumulation when the state of carbon dioxide is aggravated (hypercarbemia).

 All patients had a combination of respiratory and cardiovascular disorders.

 The technical result of the proposed method for the treatment of severe OB is to increase the effectiveness of therapeutic measures, reduce the number of drugs used, which improves the quality and effectiveness of therapeutic measures, reduces the time of treatment for OB in young children. The above is achieved by intravenous, microjet administration of nitroglycerin at a dose of 2-6 μg / kg / min, followed by a decrease in dose to 1 μg / kg / min, course 2-4 days.

 The selected drug in the treatment of severe biofeedback in young children was used in 15 children.

 According to the literature (Gusel V.A., Markova I.V. ("Pediatrician's Guide to Clinical Pharmacology" 1990- pp. 115-116), Vidal, 1997, pp. 393-394, Drummond V., Lock J., 1989 (In the book "Clinical Pharmacology of Newborns" by Markov I.V., Shabalov N.P., L. Sotis, 1993)) nitroglycerin is a distinct vasodilator that reduces the intracellular activity of calcium ions in vascular smooth muscle cells. In small doses, a venous vasodilating effect predominates.

 The drug reduces pre- and afterload on the heart, increases cardiac output, myocardial contractility, reduces the size of the heart and blood volume in the vessels of the lungs. All this facilitates the work of the heart, reduces the need for myocardium in oxygen, improves metabolism in the heart muscle. Direct myotropic action is also noted.

 Nitroglycerin is mainly used in adults with left ventricular heart failure, myocardial infarction. We did not find information about using it to treat severe OB in the literature available to us.

 In recent literature, materials on the use of nitric oxide have been intensively covered in recent years. The latter is increasingly being used as a vasodilator in the treatment of pulmonary hypertension in adults. It is believed that the effect of nitroglycerin is associated with the release of nitric oxide in the lumen of the vessel. But today no one uses nitroglycerin as a bronchodilator (A.P. Zilber, “Respiratory Medicine.” -Petrozavodsk., Pp. 418-422).

 All of the above allows us to recommend the use of nitroglycerin in order to stop respiratory failure in combination with hemodynamic, circulatory disorders, which is observed in children with severe OB.

 In addition, the bronchodilator effect of nitroglycerin was revealed, which was most likely caused by a decrease in peribronchial edema and the passage of fluid to the vascular sector. The diuretic effect of nitroglycerin contributed to the elimination of fluid.

 Method and route of administration: intravenously, microjet, continuously.

 Dose: 2 mcg / kg / min.

 The most admissible dose: 6 mkg / kg / min.

 Gradual withdrawal of the drug during the day, with a transition to a dose of 1 μg / kg / min.

 Average duration of administration: 3 to 4 days.

 If necessary, switch to oral administration of nitrosorbite in a dose of 0.05 - 0.1 mg / kg.

 We use 1%, 0.1% nitroglycerin solution, dilute it to 20 ml, 0.9% sodium chloride solution or 5% glucose solution.

 We load the syringe into the infusomat and inject the prepared solution at a given speed (usually 1-2 ml / h).

 Side effects of nitroglycerin, described in detail in various publications, we have not observed. This is due to low doses of the drug and its pharmacokinetic features (rapid destruction).

 Some sources (Herling IM (Am. Heart J.108: 141-149.1984)) report that nitroglycerin is able to bind to the polyvinyl chloride from which the intravenous infusion systems are made, so glass syringes or polyethylene systems should be used (Khan MG, 1988, In P. Marino's book "Intensive Care" -1998-p. 241-244).

 A comparative characteristic of the KShchS, ECHO-KG, pneumography, pulse oximetry data obtained before administration of the drug, 12 hours and 3 days after the administration of nitroglycerin, is given in table. 1.

 Reliably revealed a decrease compared with the norm of the oxygen tension in the blood taken from the pulp of the finger (capillary blood) before the administration of nitroglycerin and its increase after administration of the drug. In other indicators of the coronary artery disease there are no significant changes in dynamics, which reflects various mechanisms of compensation and maintenance of tissue homeostasis.

 Initial arterial hypertension and normalization of blood pressure after the administration of nitroglycerin were found.

 An ECHO-KG study reveals a hyperdynamic hemocirculation regimen. The degree of hyperdynamia significantly decreases after the appointment of the drug. Myocardial contractility increases, heart rate decreases, pulmonary artery pressure significantly decreases. The data obtained by pneumography, allow us to characterize the initial ventilation mode as a hyperventilation syndrome, which reflects the compensatory functions of the respiratory system, aimed at maintaining oxygen balance. This is achieved due to a reliable increase in respiration rate, an increase in the minute volume of respiration (in many patients there is a decrease in tidal volume, which leads to a large spread of data and the absence of changes in the dynamics).

 When prescribing nitroglycerin, already 12 hours after administration, the severity of hyperventilation syndrome decreases due to a reduction in BH, which undoubtedly translates pulmonary ventilation into a more economical mode of functioning. Relatively increases the ratio of inspiratory time to expiratory time (Vd / Vyd), decreases the dynamics of the ratio of expiratory time to the respiratory cycle (Vyd / R-R).

 Pulse oximetry revealed an initially reduced saturation of oxygen in capillary blood, reflecting tissue hypoxia, associated mainly with impaired hemodynamics, the state of microcirculation. When prescribing nitroglycerin, a significant increase in saturation, oxygen tension in capillary blood is observed, which characterizes the improvement of tissue perfusion.

 In the table. Figure 2 presents a comparative description of the indicators of CSF, ECHO-KG, pneumography, pulse oximetry in patients receiving and not receiving nitroglycerin in the subacute period (when exiting obstructive syndrome).

 Indicators of KShchS, central hemodynamics, pressure in the pulmonary artery system did not significantly differ in the groups.

 However, a pneumographic study showed a statistically significant difference in the severity of the hyperventilation syndrome.

 In children receiving nitroglycerin, the severity of hyperventilation syndrome decreased, which was characterized by a decrease in BH, respiratory and minute respiratory volume relative to the body surface. The duration of stay in the intensive care unit and intensive care unit is significantly reduced.

 The use of nitroglycerin allows you to abandon the use of aminophylline, cardiotonics, because when it is used, a bronchodilator effect is achieved, stabilization of hemomicrocirculatory disorders, oxygen supply to tissues is improved, which makes it possible to reduce the number of drugs, reduces the length of stay of patients in the intensive care unit with severe OB.

Example. Busygin Artem 6 months., Was in the intensive care unit of Ivanovo Design Bureau with a diagnosis of
"Adenovirus infection. Obstructive bronchitis. DN Z. NK 2A. Perinatal encephalopathy, late recovery period, motor impairment syndrome."

 Upon receipt, the condition is serious. The severity is due to the phenomena of pulmonary heart failure, obstructive respiratory failure. Excited. The skin is pale, clean, of sufficient moisture. Central cyanosis. Swelling of the eyelids. Hyperemia of the pharynx. Cough dry, frequent. A percussion sound with a boxy tint. Dyspnea of an expiratory character.

 Dry, wheezing wheezing as you exhale. Tachycardia not corresponding to hyperthermia. Heart sounds are muffled. Heart rate 180 in 1 min. Liver + 3 cm. Spleen + 1 cm. Urinates enough.

 The child is prescribed nitroglycerin at a dose of 2 μg / kg / min. Data on the initial state, laboratory and instrumental methods of research are presented in table. 3 and 4.

 According to KShchS at admission there was a respiratory alkalosis. There was a high oxygen content in the arterial and significantly reduced in capillary and venous blood. There was a high tissue demand for oxygen. With the introduction of nitroglycerin, the blood flow, cardiac activity, and respiratory system improved, which was reflected in the ACS: normalized pH of capillary blood, tension and oxygen saturation.

 With cardiointervalography, the initial hypersympathicotonia was observed with asymptaticotonic reactivity. With the introduction of nitroglycerin, the degree of sympathicotonia decreases, autonomic reactivity becomes hypersympathicotonic.

 With ECHO-KG - in dynamics, after the administration of nitroglycerin, the severity of hyperdynamia decreases, heart rate, SI decrease, and SI increases. Pulmonary artery pressure decreases. The sizes of the right ventricle are reduced, which indicates an improvement in its contractility, a decrease in the load on the right heart.

 With pneumography, the ratio of inspiratory time to expiratory time increases, which indicates an improvement in bronchial patency; the severity of hyperventilation syndrome decreases (BH, MOD) are reduced. Increased blood oxygen saturation.

 Despite a decrease, compared with the norm of CVP, with standard infusion therapy, the administration of nitroglycerin does not further aggravate hypovolemia, but rather, under conditions of hypoxic, energy-dynamic damage to the myocardium, the drug helps both reduce preload and directly improve blood supply to cardiomyocytes.

 Thus, according to our research, in the treatment of severe forms of OB in young children with nitroglycerin at a dose of 2-6 μg / kg / min, administered intravenously, by micro-jet infusion, with a gradual decrease in dose to 1 μg / kg / min, course 2-4 days, a beneficial effect on hemodynamics, ventilation-perfusion relationships; in addition, the bronchodilator effect of the drug in children was revealed, which makes it possible to use the drug in this category of patients.

 The use of the drug allows for pathogenetically substantiated treatment of biofeedback in young children with a minimum number of drugs, which, combined with a reduction in treatment time in the intensive care unit and intensive care, gives an undoubted economic effect.

Claims (1)

 A method of treating severe bronchial obstructive syndrome in young children, including drug therapy, characterized in that intravenous, microjet administration of nitroglycerin is used at a dose of 2 to 6 μg / kg / min, followed by a dose reduction to 1 μg / kg / min, course 2 to 4 of the day.

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