RU2067454C1 - Method of hemodynamic correction in newborns after hypoxia - Google Patents

Abstract

FIELD: medicine, pediatrics. SUBSTANCE: method involves the intravenous administration of preparation cytomack at dose 0.5-1.0 ml 0.25% solution per 1 kg child body mass, every day for the first postnatal life days. EFFECT: improved myocardium contractility, simplified treatment, elimination of toxic effect.

Description

 The invention relates to medicine, namely to pediatrics, and can be used in practical neonatology to correct hemodynamics in newborns undergoing hypoxia.

 Currently, the high proportion of children born from abnormal pregnancy and childbirth and undergoing perinatal hypoxia. Oxygen starvation of tissues causes a change in metabolism in the body of the fetus and newborn, the result of which is a violation of the energy supply of the cell, in particular, in the myocardium. A decrease in energy production in myocardial cells is accompanied by a decrease in cardiac contractility. In addition, the heart of a newborn who has undergone hypoxia, which is under conditions of postpartum restructuring of hemodynamics and pulmonary hypertension, works with increased functional load. These factors cause a violation of cardiac activity, as a result of which various pathological types of hemodynamics arise. Hemodynamic disorders in these children in the first days after birth are mostly mild and do not threaten the life of the child. They fit the classification of acute heart failure in newborns in stage I, less often in stage II A, but significantly affect the processes of postpartum adaptation of newborns to extrauterine life. (Neonatologist Handbook / Edited by V.A. Tabolin, N.P. Shabalov, L. Medicine, 1984, p. 170-181). This heart failure is secondary in nature and is associated with a high sensitivity of the newborn’s myocardium to metabolic disorders and is due to hypoxia, metabolic acidosis, and electrolyte disturbances. Complicated postpartum adaptation of the cardiovascular system in these newborns lengthens the time of nursing in the maternity hospital, which ultimately leads to a rise in the cost of treatment and maintenance of the child. Therefore, the urgent task is to develop methods for the correction of impaired hemodynamics that underwent hypoxia of the newborn in the first days of life.

 Currently, correction of impaired hemodynamics in newborns is carried out by acting on three main pathogenesis links: strengthening myocardial contractile function, leading to an increase in cardiac output; a decrease in the volume of circulating plasma and, as a result, a decrease in the functional load on the myocardium; a decrease in vascular peripheral tone, accompanied by a decrease in venous inflow to the right ventricle and a functional load on the heart.

 A decrease in the volume of circulating plasma is achieved by the use of diuretics, which in newborns, due to the unstable regulation of the water-electrolyte balance, can lead to serious changes in water-salt metabolism, thereby negatively affecting the general condition of the child.

 The use of drugs that change the tone of the vascular wall in newborns is also limited due to the fact that vascular drugs used in neonatology, changing the tone of peripheral vessels, cause a sharp redistribution of blood in various parts of the body, which can adversely affect regional hemodynamics, in particular, the heart and brain , taking into account the already existing posthypoxic changes in intracranial hemoliquorodynamics in these children. These methods of hemodynamic correction are mainly used in newborns who have signs of acute heart failure II-B III degree. (Neonatologist's Handbook / Edited by V.A. Tabolin, N.P. Shabalov. L. Medicine, 1984, p. 171).

 A good way to correct hemodynamics in the first days of life is to use drugs that enhance myocardial contractile function. This is achieved in two main ways: the use of cardiac glycosides and the use of drugs that improve energy and metabolism directly in the cells of the heart muscle.

 Closest to the proposed method and chosen by the authors for the prototype is a known method for the correction of hemodynamics in newborns undergoing hypoxia, including the use of cardiac glycosides in two stages. At the first stage, the dose of saturation of cardiac glycosides is calculated in the range of 50-70 μg per 1 kilogram of the child's body weight (by digoxin). This dose is given in two days, 1/2 dose immediately, and then 2 times in 1/4 dose after 8-12 hours. At the second stage, the maintenance dose is calculated. It is equal to 1 / 6-1 / 7 of the dose of saturation. A maintenance dose is administered daily in the following days. By this method, cardiac glycosides are injected intravenously slowly into the peripheral veins of a child (I.V. Markova, N.P. Shabalov. Clinical pharmacology of newborns. L. Medicine, 1984, p. 104).

 However, the use of cardiac glycosides in newborns who have undergone hypoxia and have pathological changes in the blood plasma acidosis, hypoglycemia, dielectrolyte changes, meets significant difficulties. In particular, in conditions of hypoxia, the boundaries of the effective therapeutic dose of action of cardiac glycosides change. As a result, significant difficulties arise in selecting an individual saturation dose, which in one case will not cause a therapeutic effect, in another it leads to an overdose and the appearance of symptoms of acute poisoning with cardiac glycosides, with even greater hemodynamic impairment. In addition, cardiac glycoside therapy according to the generally accepted technique is cumbersome. This method requires painstaking work with the patient in the selection of an individual therapeutic dose, continuous monitoring of the functioning of the heart. All this limits the widespread use of cardiac glycosides in newborns under conditions of hypoxia, and this technique is mainly used in the treatment of acute heart failure in patients with congenital heart defects.

 The aim of the invention is to simplify the method of treatment, improve the contractility of the myocardium, eliminate the possible toxic effect of the drug and eliminate the need for cumbersome methods of monitoring the effectiveness of the treatment.

 This goal is achieved by the fact that in the known method of correcting hemodynamics in newborns who have undergone hypoxia, by using pharmacological agents as a pharmacological agent, cytomac is administered intravenously in a dose of 0.5-1.0 ml of 0.25% solution per 1 kilogram of body weight daily, during the first days of life after birth.

 A comparative analysis of the proposed solution with the prototype showed that the proposed method differs from the known use of the drug cytomac in a dose of 0.5-1.0 ml of 0.25% solution daily during the first days after birth, which meets the criterion of "novelty."

 Comparison with other technical solutions showed that cytomac (cytochrome-c) heme-containing protein, which plays an enzymatic role in the processes of tissue respiration at its final stage of oxygen interaction with the tissue substrate, which leads to the synthesis of most of the cell energy. With parenteral administration of cytochrome-c, the penetration of oxygen deep into the cells (in particular, into the mitochondria) improves (Markova I.V. Shabalov N.P. Clinical pharmacology of newborns. L. Medicine, 1984, pp. 66-67). The purpose of the drug is indicated for hypoxic conditions of any degree.

 Currently, there is a method of reducing posthypoxic brain damage in newborns of the first days of life. To this end, cytochrome c is administered intravenously, slowly slowly, at a dose of 4.0 ml of a 0.25% solution in glucose solution. (Shabalov N.P. Yaroslavsky V.K. Khodov D.A. Lyubimenko V.A. Asphyxia of newborns. L. Medicine, 1990, p. 170-171).

 However, in neonatology, in order to improve myocardial contractility, the use of the cytomac drug is not known, and the optimal doses of this drug have not been established, which allows us to conclude that the criterion of "inventive step" is present.

A study of the effect of the cytomac preparation on hemodynamics was carried out using an Uzkar-3 ultrasonic echocardiograph in M-mode. Registration of echocardiograms was carried out before intravenous administration of cytomac and every hour after administration for the next four hours. The calculated cytomac volume was injected slowly intravenously into the saphenous veins of the child’s head or limbs. On the echocardiogram, the systolic and diastolic size of the left ventricle was measured. Diastolic and systolic volumes of the left ventricle were calculated according to the most common formula Teicholz (1976). As indicators characterizing the state of central hemodynamics, the stroke volume of the left ventricle (UO) and the minute volume of blood circulation (MO) were emitted. Myocardial contractile function was evaluated by the following parameters: ejection fraction (PI), percentage of shortening of the diameter of the left ventricle from diastole to systole (Δ%), speed of circular myocardial shortening (V _CF ). Ultrasonic location of the newborn’s heart structures, calculation of central hemodynamics parameters and myocardial contractility indices was carried out according to the generally accepted methodology in pediatrics (V. Safronov et al. Echocardiographic research method in pediatrics. Gorky, 1978, p. 10-17). Statistical processing of the obtained data was carried out by the method of variation statistics.

 Using the described method, 30 full-term newborns were examined during the first week of life. The mothers of these children experienced a complicated pregnancy in the form of toxicosis, nephropathy, vegetative-vascular dystonia, hypertension, anemia. A complicated course of childbirth was most often observed in the form of weak labor, childbirth, rapid or rapid childbirth, early discharge of amniotic fluid. All newborns had clinical signs of perinatal hypoxia of varying severity. In particular, on the part of the cardiovascular system in the first days after birth, they had a syndrome of impaired postpartum adaptation of hemodynamics, which was manifested by muffled heart tones, a tendency to tachy or bradycardia, pallor or cyanosis of the skin, perioral and acrocyanosis, and subcutaneous fat pastorality layer. The described clinical syndrome manifested itself in most newborns during physical exertion (feeding, doctor examination, swaddling, manipulations with newborns), in some children and at rest. Echocardiographic examination in them showed the presence of one of the pathological types of hemodynamic disturbances of the hypokinetic variant, which was characterized by reduced myocardial contractility and heart rate compared with the age norm of UO, MO.

 In order to work out the optimal dose of the drug, all studies were divided into 3 groups. The 1st group included 20 newborns who received cytomac at a dose of 0.5-1.0 ml per 1 kilogram of body weight of the child. The second group consisted of 5 children, to whom cytomac was administered at a dose of less than 0.5 ml per 1 kilogram of body weight. In the third group, newborns (5) received the drug at a dose of more than 1.0 ml per 1 kilogram of body weight. The average body weight and the basic initial hemodynamic parameters in all the studied groups of newborns were approximately equal.

As a result of a hemodynamic study in newborns of the 1st group, it was found that within the first hour after intravenous administration of cytomac, statistically significantly increased UO, MO, and increased myocardial contractility (PI, DD% V _CF ) (Table 1). This hemodynamic effect was maximally pronounced up to 2 hours, then it decreased slightly, remaining at approximately the same level during the entire observation period. Clinical observation of children from this group showed a decrease, and in some cases, the disappearance of symptoms of impaired hemodynamics (pinking of the skin, a decrease in crocianosis, perioral cyanosis, normalization of heart rate).

 In infants of the second group, after intravenous administration of cytomac at a dose of less than 0.5 ml per 1 kilogram of body weight, no changes in hemodynamics were noted on echocardiograms. Myocardial contractility indices also did not differ from the initial ones (Table 2). Clinically, these newborns showed no change in the symptoms of impaired hemodynamics.

 The indicators of central hemodynamics and myocardial contractility in children of the third group after intravenous administration of cytomac at a dose of more than 1.0 ml per 1 kilogram of body weight tended to increase, but these changes were short-lived and by the second hour of UO, MO returned to the initial level. The same pattern was observed with respect to the indices of myocardial contractility (Table 3). During a clinical examination, some of the children in this group experienced a decrease in the intensity of some pathological symptoms of impaired hemodynamics, and some of these children did not find such changes.

 Evaluation of the results obtained by studying the reaction of hemodynamics to the intravenous administration of cytomak allows us to conclude that it is advisable to use it as a drug that increases myocardial contractility in newborns undergoing hypoxia. In order to correct impaired postpartum adaptation of hemodynamics in these children, it is rational to use cytomac at a dose of 0.5-1.0 ml per 1 kilogram of the child’s body weight. The pronounced therapeutic effect after intravenous administration of cytomac in the specified dose persists for more than four hours.

 The method is as follows: a newborn child is weighed and, taking into account his weight, the doctor calculates the optimal dose of cytomac based on the recommended (0.5-1, ml per 1 kilogram of the child’s body weight). Then, the obtained volume of the drug solution is diluted in glucose solution and injected intravenously slowly using a syringe or microinjector of the Lineomat type into the saphenous veins of the head or limbs of the baby during the first days of life after birth.

Examples of specific performance of this method in the form of extracts from medical records:
Example 1

 Boy L. was born from I pregnancy, I childbirth. During pregnancy, the mother had neurocirculatory dystonia of the hypertonic type. Delivery on time. During childbirth, labor weakness developed. After birth, a newborn has a twofold cord entanglement around the neck. The child was born with a weight of 3350 g, body length 52 cm, with an Apgar score of 4-6 points, in a state of asphyxiation of the II degree.

 On the first day of life, the condition is clinically assessed as moderate. There was a decrease in motor activity, physiological reflexes of the newborn, and muscle tone. The skin was pink with a cyanotic hue, acrocyanosis. Pueril breath, up to 48 in 1 minute. Borders of the heart within the age norm. Heart sounds were muffled, rhythmic, heart rate 136 in 1 minute. The liver was palpated 2.0 cm from the edge of the costal arch.

 On the third day of life, the condition of the child remained moderate. The positive dynamics, mainly from the side of the central nervous system, was insignificant and was expressed as an improvement in some physiological reflexes of newborns. Clinical manifestations of impaired hemodynamics were noted in the form of acro- and perioral cyanosis, muffling of heart sounds. Echocardiography in the child was recorded hypokinetic variant of hemodynamics with reduced rates of UO, MO and myocardial contractility. In order to correct hemodynamics, the newborn was prescribed intravenous administration of a 0.25% cytomac solution in a volume of 3.0 ml (which amounted to 0.89 ml per 1 kilogram of the child’s body weight). 1 hour after cytomac administration, an increase in the main hemodynamic and myocardial contractility indices of the myocardium by 66 and MO by 36.0% was recorded on the echocardiogram. During the next 5 hours of observation, the central hemodynamics and myocardial contractility remained at approximately the same level. Clinical observation of the child showed a decrease in acro- and perioral cyanosis, pink skin color, a slight decrease in heart rate. Auscultatory heart tones became more distinct.

 In the following days, with the use of cytomac, the child's condition progressively improved. The pathological symptoms of the cardiovascular system disappeared. There was a significant positive trend in neurological status. On the 8th day, the child was discharged home in a satisfactory condition, while the physiological reflexes of the newborn were satisfactorily caused in him, his muscle tone improved, and his weight gain was 150 grams.

 Example 2

 Boy Z. was born from II pregnancy, I childbirth. Real pregnancy in the mother proceeded without complications. Delivery on time. Premature detachment of an abnormally located placenta during childbirth caused acute fetal hypoxia, as a result of which a cesarean section was performed. The child was removed with a tight cord around the neck and trunk, in a state of asphyxia of the III degree and an Apgar score of 2-5 points. Spontaneous breathing appeared 5 minutes after resuscitation.

 In the first day of life, the condition was serious. There was a slight painful cry, a significant suppression of the physiological reflexes of the newborn, muscle tone. The skin is pale, perioral and acrocyanosis. Pueryl respiration in the lungs up to 58-60 in 1 minute. The boundaries of the heart were determined within the age norm. Heart sounds were muffled, rhythmic, tachycardia up to 160-170 in 1 minute. The liver protruded from the costal arch by 2.0 cm. The pastility of the lower abdomen was determined.

 On the third day of life, an echocardiographic study showed a hypokinetic version of hemodynamics. Clinically, from the side of the cardiovascular system, symptoms of pallor of the skin with the phenomena of acro- and perioral cyanosis persisted. In this regard, the newborn was prescribed intravenous administration of cytomac in a volume of 2.0 ml (which amounted to 0.54 ml per 1 kilogram of body weight).

 1 hour after the introduction of cytomac, the main hemodynamic parameters increased: UO by 36.6% MO increased myocardial contractility by 35.0%. This hemodynamic effect lasted more than 4 hours of observation. As a result of hemodynamic correction, a positive clinical effect was observed in the form of a decrease in the intensity of symptoms of the cardiovascular system. The skin became pink, the manifestations of acro- and perioral cyanosis decreased, the number of breaths and heart contractions decreased. An improvement in general condition was observed by the next day. The child became more active, some physiological reflexes improved, and it became better to suck. In the following days of nursing in the maternity hospital during treatment with cytomac, the child showed a positive dynamics of the general condition, the disappearance of pathological symptoms from the cardiovascular system and on the 6th day he was transferred to the second stage of treatment in a moderate state.

 Comparison of the proposed method with the prototype revealed the following positive effect (table 4).

Claims (1)

 A method for correcting hemodynamics in newborns undergoing hypoxia by pharmacological effects on the myocardium, characterized in that as a pharmacological agent, cytomac is administered intravenously at a dose of 0.5 to 1.0 ml of a 0.25% solution per 1 kg of body weight daily for first days of life after birth.

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