RU2570399C1 - Method of treating severe acute psychopharmaceutical poisoning in children - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention describes a method of treating severe acute psychopharmaceutical poisoning in children by conducting a combined therapy: taking infusion detoxification measures including administration of starting colloidal solution in order to recover the volemic status, and conducting a medicinal treatment of progressive dysfunctions in a child's body; for the first hours of the combined therapy, immediately after the administration of starting colloidal solution, before the medicinal treatment, providing the stable volemic status, Reamberin 10 ml/kg of body weight a day at 5 ml a minute, a medication mixture consisting of 5% glucose and Riboxinum 20 mg/kg of patient's body weight are administered one by one during 3 to 5 days.

EFFECT: method is characterised by the high clinical effectiveness; enables correcting the functional insufficiency of the main body systems within a short time, achieving the reliable stabilisation of primary homeostasis parameters and preventing the progression of life-threatening complications, such as toxic encephalopathy and cardiopathy, reducing an asthenisation level; the length of treatment and staying in hospital are also considerably reduced.

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Description

The invention relates to medicine, namely to methods for treating severe forms of acute poisoning with psychopharmacological agents in children, and can be used in toxicology, pediatrics and resuscitation.

The widespread use of psychopharmacological agents in modern practical medicine creates the conditions for the occurrence of acute poisoning as a result of their improper use, accidental use, for self-medication and suicidal attempts (E. Luzhnikov, Clinical Toxicology: textbook / E.A. Luzhnikov, G.N. Sukhodolova: - 4th ed., Revised and enlarged. - M .: Medical Information Agency LLC, 2008. - 576 pp., Ill .; Ostapenko Yu.N. The current state of acute morbidity of chemical etiology in the Russian Federation / Yu.N. Ostapenko, N .N. Litvinov, R.S. Khonelidze [et al.] // Toxicol.Vest. - 2004.-№3. - P. 2-6 .;).

According to the annual reports of the Children's Toxicological Center of Moscow over the past ten years, among the leading poisonings, drugs that affect the central nervous system are the leading ones. According to the International Coder of Diseases of the 10th revision, this is group T.42 (anticonvulsants, sedatives, hypnotics, benzodiazepines) and group T.43 (antidepressants, antipsychotics), they account for 30 to 37% of cases.

Currently, the problem of improving the treatment of severe forms of acute poisoning with psychopharmacological agents in childhood and finding ways to solve it is relevant.

First of all, this is due to certain anatomical and physiological characteristics of the child's body, especially in early childhood. Well-known is the fact of the functional immaturity of the central nervous and cardiovascular systems of the child, as a result of which there is a rapid development of various threatening pathological conditions: cerebral edema, hypovolemic states, dyselectrolyte and metabolic disorders. (A.V. Mazurin, I.M. Vorontsov, Propaedeutics of childhood diseases, M., Medicine, 1986, p.432; L.O. Badalyan. Pediatric neurology, third edition, M., Medicine, 1984 , p. 576; Emergencies in children, W. Steiniger, K.E. Mulendal, translated from German, Medtrust, 1996, p. 512).

Considering the characteristics of the child’s body, the high frequency of poisoning with psychopharmacological agents in children, the low adaptability of traditional treatment regimens for severe forms of acute poisoning with psychopharmacological agents, the development of new algorithms for conducting infusion-detoxification therapy, which allows quickly correcting emerging systemic disorders and achieving effective cellular energy protection of vital systems, is extremely relevant.

There is a method of treating severe forms of acute poisoning with psychopharmacological agents in children by conducting complex therapeutic measures, including infusion and detoxification measures and pharmacotherapy aimed at correcting developing functional disorders in the child’s body (Kuznetsov D.I. The use of forced diuresis in acute exogenous poisoning in children in conditions of resuscitation, Materials of the conference of inventors and rationalizers. 1981, pp. 29-32; Sukhodolova G.N. Features of acute poisoning of lek rstvami children, lectures for practitioners. The Russian National Congress "Man and Medicine", Moscow, 1998, pp. 59-65). The patient is cleansed of the gastrointestinal tract (gastric lavage through a tube followed by the introduction of activated charcoal into the stomach, cleansing enemas or laxatives) and increased urine output. In severe forms of the disease, forced diuresis is carried out in the form of intravenous administration of glucose-salt solutions: 0.9% sodium chloride solution, Ringer's solution and other electrolyte solutions, as well as 5 and 10% glucose solutions at the rate of 8-10 ml / kg of weight per hour . For the prevention of metabolic disorders and the prevention of energy deficiency in cells, pharmacological agents include riboxin, ATP and cocarboxylase in the complex of ongoing therapy.

The disadvantage of this method is the weak neuroprotective effect and insufficiently effective correction of dysmetabolic disorders. As a result, the length of hospital stay of patients and the cost of treatment are increased.

The disadvantages of this method include the risk of serious side effects with the introduction of high doses of drugs such as ATP (development of arterial hypotension) and KKB (allergic reactions), which can complicate the course of the underlying disease.

There is also a method of treating severe forms of acute poisoning with psychopharmacological agents in children (Acute poisoning with tranquilizers of the benzodiazepine series in children, Khabush M.T., Sukhodolova G.N., in the book Emergency Clinical Toxicology (a guide for doctors) Edited by E. Luzhnikov. , M., Medical practice. - M., 2007, pp. 442-447), in which the pharmacological antidote anxate is additionally included in the treatment regimen, which provides a therapeutic effect due to pharmacological antagonism.

However, the use of anexate as part of therapy allows you to stop the syndrome of impaired consciousness, but not completely eliminate it. A limitation for its use is that anexate competitively blocks only benzodiazepine receptors and, therefore, can only be used in cases of poisoning with psychopharmacological agents of the benzodiazepine series.

In order to increase the effectiveness of the treatment of acute poisoning with psychopharmacological agents as part of the medical complex in children, shaky lavage is used as a detoxification method (Use of intestinal lavage for the treatment of children with phenazepam poisoning. G.N.Sukhodolova, L.A. Kovalenko, D.M. Dolginov, Materials of the city scientific-practical conference, Volume 214. M., N.V. Sklifosovsky Research Institute of Emergency Medicine, 2010, pp. 22-24), which allows to achieve a more complete cleansing of the intestine, reduce the flow of toxic substances into the systemic circulation , which leads to a shortening of the toxicogenic period of acute poisoning.

However, this method does not have a pathogenetic orientation, it was developed for the treatment of children of an older age group and is not used in the treatment of young children.

As the closest analogue, a method has been adopted for treating severe forms of acute poisoning with psychopharmacological agents in children, including infusion-detoxification measures and the simultaneous use of pharmaceutical drugs with metabolic effects: riboxin, ATP, cocarbaxylase (E. Luzhnikov, Clinical toxicology: textbook / E.A. G.N.Sukhodolova: - 4th ed., Revised and supplemented. - M .: Medical Information Agency LLC, 2008. - 576 pp., Ill.).

However, in this case, patients have incomplete compensation of the formed metabolic disorders in the myocardium, which creates the conditions for the formation of functional insufficiency of the cardiovascular system (toxic cardiopathy), as well as in this group of patients, despite the therapy, the manifestations of asthenic syndrome caused by the manifestations of toxic encephalopathy. The terms of treatment of patients in a known manner is 5 days or more.

The objective of the invention is to provide a method for the treatment of severe forms of acute poisoning with psychopharmacological agents in children, ensuring the rapid clinical regression of symptoms of exogenous intoxication and effective correction of metabolic disorders, to prevent the development of functional insufficiency of the main body systems and reduce treatment time.

The essence of the invention lies in the fact that in a method of treating severe forms of acute poisoning with psychopharmacological agents in children by conducting complex therapy: infusion-detoxification measures, including the introduction of a starting colloidal solution aimed at restoring the volemic status, and pharmacotherapy of developing functional disorders in the child’s body, the first hours from the start of complex therapy immediately after the introduction of the starting colloidal solution before the pharmaco Therapies against the background of a stable volemic status carry out the sequential administration of Reamberin into the child’s body at a rate of 10 ml / kg weight per day at a rate of 5 ml per minute, and then a drug mixture consisting of 5% glucose and riboxin solution at a rate of 20 mg / kg weight body of the patient with a course of 3 to 5 days.

Using the invention allows to obtain the following technical result.

The proposed method has high clinical efficacy.

It allows you to quickly correct the functional insufficiency of the basic systems of the body, achieve reliable stabilization of the leading parameters of homeostasis and prevent the development of life-threatening complications, such as toxic encephalopathy and cardiopathy, and reduce the degree of asthenization in patients.

Due to this, the treatment and hospital stay of patients are significantly reduced.

The use of Reamberin in the infusion therapy according to the algorithm proposed by the authors influences the pathogenetic mechanisms of acute chemical illness, taking into account the characteristics of the central nervous and cardiovascular systems of the child’s body and leads to the rapid elimination of emerging functional disorders and stabilization of oxygen balance to a level of pO _{2 of} 90.63 ± 2.81 mm Hg, saturation -96.09 ± 0.80%, normalize CBS and eliminate tissue hypoxia: restore BE and lactate to proper values; normalize the functional state of the central nervous system, which is manifested in a complete recovery of consciousness in patients by the third day of the disease and a decrease in the manifestations of asthenic syndrome; significantly reduce dysmetabolic disorders and thereby improve the functional state of the myocardium.

The technical result is achieved due to the new technology developed by the authors, which provides for the inclusion in the treatment complex of the drug Reamberin - a balanced isotonic infusion solution based on succinic acid - N-methylammonium sodium succinate (reamberin), a combination of properties, mutual complement and synergism with the combined use of drugs as part of infusion therapy.

The developed complex has a high metabolic activity, provides effective regulation of the oxygen balance of the child’s body, as a result of which the oxygen balance is improved, adequate tissue respiration is achieved, due to reliable cellular energy protection, the energy balance of vital systems: the cardiovascular and central nervous systems is improved, with further recovery normal functional activity of the child's body.

Reamberin is a drug with a detoxifying effect for parenteral use. It has antihypoxic and antioxidant effects, restores the energy potential of cells. The drug activates the enzymatic processes of the Krebs cycle and promotes the utilization of fatty acids and glucose by cells, normalizes the acid-base balance and the gas composition of the blood. It has a moderate diuretic effect. The advantage of reamberin is the balance of the electrolyte composition.

In developing the invention, the authors were guided by the following provisions.

The pathogenesis of acute chemical disease is complex and multifactorial. The main manifestation of poisoning by psychopharmacological agents is toxic damage to the nervous system as a result of a specific toxic effect with a violation of the level of consciousness. At the same time, mechanisms devoid of “chemical” specificity are simultaneously included in the systemic response, such as hypoxia, metabolic disturbances, and others, which are the main reason for the formation of irreversible damage in various functional systems of the body and manifest themselves clinically in the syndrome complex of homeostasis insolvency (A.V. Alekhnovich, VB Ivanov, KK Ilyashenko, Compensor mechanisms and adaptive processes in acute poisoning with psychotropic drugs, M., 2010, p. 300; EA Luzhnikov, GN Sukhodol ova, Clinical Toxicology, Textbook, fourth edition revised and supplemented, M., Medical Information Agency LLC, 2008, p. 576).

The authors set the task: to optimize the intensive care algorithm for severe forms of acute poisoning with psychopharmacological agents in children, taking into account the characteristics of the child’s body, aimed at correcting tissue metabolism disorders, primarily associated with hypoxia, which is the key to achieving a clinical effect.

The authors pay special attention to the timeliness and speed of restoration of the adequate functioning of the central nervous system in children with severe forms of acute poisoning by psychopharmacological agents, since it is one of the main regulatory centers in maintaining stable homeostasis.

The authors developed the following algorithm for conducting complex therapy: immediately after the introduction of the starting colloidal solution, pharmacotherapy, against the background of a stable volemic status, is followed by the sequential administration of Reamberin into the child’s body at a rate of 10 ml / kg weight per day at a rate of 5 ml per minute, and then drug a mixture consisting of a 5% solution of glucose and riboxin at the rate of 20 mg / kg body weight of the patient with a course of 3 to 5 days.

The sequential administration of these drugs according to the scheme developed by the authors allows us to quickly achieve reliable stabilization of the leading parameters of homeostasis and avoid the development of complications such as toxic encephalopathy and cardiopathy, and reduce the degree of asthenization in patients.

The authors established a previously unknown therapeutic effect manifested in the complex use of Reamberin for the treatment of acute poisoning with severe psychopharmacological agents in children: the rapid restoration of the functional activity of the central nervous system by stimulating the production of GABA, the synthesis of which is significantly slowed down in children with this disease, which occurs due to administration against the background of a stable volemic status of the drug reambirin, which in combination with the drug introduced immediately after its infusion and riboxin and glucose provides a cardioprotective effect due to the acceleration of ATP synthesis in cardiomyocytes.

This is manifested in a reduction in the duration of neuropsychiatric disorders from 17.70 ± 1.63 hours to 12.40 ± 1.51 hours. In turn, an improvement in the functional state of the central nervous system allows maintaining an adequate state of hemodynamics and respiratory function, which ensures normal oxygen delivery to tissues and, due to the inclusion of self-regulation processes, the processes of cellular metabolism are improved.

The method is as follows.

Treatment of children with severe forms of acute poisoning with psychopharmacological agents is carried out in children's hospitals, it can also be carried out on the basis of the Department of Toxicology with intensive care units or the intensive care unit.

After studying the anamnesis, clinical and necessary laboratory and instrumental data, adequate complex therapy is selected depending on the severity of the patient and the available syndrome complex of the clinical manifestations of the disease.

The patient undergoes gastric lavage using a probe, after which an adsorbent is introduced into the stomach - activated carbon at the rate of 1 g / kg body weight in children weighing no more than 20 kg and 0.5-1 g / kg of body weight in children weighing over 20 kg Bowel cleansing is performed using a cleansing or siphon enema.

Then start infusion therapy. To ensure venous access, puncture and catheterization of one of the main veins is performed. Basic infusion therapy includes crystalloid solutions: electrolytes - isotonic sodium chloride solution, ringer solution; polyelectrolyte solutions - stereofundin and others, as well as sugars - most often 5 and 10% glucose solutions. Using these solutions, which are used according to therapeutic schemes, provide the physiological need for water and electrolytes, as well as the correction of water-electrolyte disturbances and acid-base imbalance.

According to indications, in order to stimulate diuresis, a lasix diuretic is additionally prescribed.

To restore the volemic status (intravascular volume), colloidal solutions are used: hydroxyethylated starches, dextrans, albumin, etc.

In the first hours from the start of complex therapy, immediately after the introduction of the starting colloidal solution, before pharmacotherapy, against the background of a stable volemic status, Reamberin is sequentially introduced into the body of the child at the rate of 10 ml / kg weight per day at a rate of 5 ml per minute, and then the drug mixture , consisting of a 5% solution of glucose and riboxin at the rate of 20 mg / kg body weight of the patient with a course of 3 to 5 days.

Further, infusion therapy includes pharmacological preparations, the action of which is aimed at normalizing metabolic and antioxidant processes - ATP, KKB and vitamin E; as well as drugs that improve the relogic and coagulation properties of blood - trental, chimes, heparin.

In clinical conditions, the method is used to treat severe forms of acute poisoning with psychopharmacological agents (PPS) in 40 patients. The age of patients ranged from 1 to 5 years (25 patients) and from 11 to 15 years (15 patients). In all patients, the diagnosis of poisoning was confirmed by a chemical toxicological study. The comparison group consisted of 40 patients who received standard infusion therapy.

Examination of the victims included the following standard research methods: general blood test, biochemical blood test, gas and acid-base balance of the blood, ECG.

Evaluation of the results was carried out upon admission on the 1st and 3rd day of illness according to the regression of clinical symptoms and laboratory and instrumental data.

Table 1 presents data on the length of stay of patients in the intensive care unit and in the hospital, as well as the time of regression of the main clinical manifestations: the time to recover consciousness in patients who received the proposed treatment in the observation group, and patients who received basic therapy.

Table 1 Indicator Comparison Group (n = 40) Observation Group (n = 40) Duration of neurological disorders (hours) 17.70 ± 1.63 12.40 ± 1.51 Duration of stay in intensive care unit (hours) 55.13 ± 4.21 36.05 ± 3.51 * Duration of hospital stay (days) 5.51 ± 0.15 3.33 ± 0.27 * Note: * - a significant difference in the indicator compared with the observation group (p <0.05 by student).

In patients treated by the proposed method, the duration of neurological disorders is lower than in patients in the comparison group. They also noted a reduction in the length of stay in the intensive care unit by 1.5 times and a length of stay in the hospital by 1.6 times.

Table 2 presents the dynamics of some indicators characterizing the functional state of the body.

table 2 Clinical sign Comparison Group (n = 40) Observation Group (n = 40) Exodus 1 day 3 days Exodus 1 day 3 days Clear mind abs. 0 28 40 0 24 32 % - 70 one hundred - 60 80 * Decreased activity abs. 40 34 eighteen 40 34 26 % one hundred 85 45 one hundred 85 65 * Muscle hypotension abs. 33 17 8 thirty 23 fifteen % 82 42 twenty 75 57 37 Metabolic disorders in the myocardium abs. 38 16 40 - twenty % 95 - 37 one hundred - fifty* Note: * - p <0.05 when compared with the observation group, according to Fisher’s exact probability criteria.

The value of the proposed method for the treatment of severe forms of acute poisoning with psychopharmacological agents in children is to achieve a faster clinical regression of symptoms of exogenous intoxication and effective correction of metabolic disorders, which can improve the functional state of the child's body and reduce the length of stay of patients in the intensive care unit and the length of hospitalization.

Example 1. Patient S., 1 year 5 months (medical history No. 15254), was admitted to the Department of Toxicology 12/18/2010. From the anamnesis it is known that 3 hours before admission, a child due to an oversight of his parents could eat up to 15 tablets (phenazepam, amitriptyline). After which the child showed a change in activity, the boy woke up with difficulty when trying to wake him, did not stand on his feet. The ambulance team delivered the child to the hospital.

Upon admission, the patient is in serious condition. The level of consciousness is a coma of 7 points on the Glasgow scale. Sharp muscle hypotension. To pain stimuli - a chaotic motor reaction. The pupils are narrow, the reaction to light is reduced. Marked pallor of the skin with a violation of microcirculation in the form of cyanosis of the nasolabial triangle, acrocyanosis and marbled skin pattern. Breathing is independent, superficial. Heart rate: 118 beats per minute, HELL: 85/43 mmHg Heart sounds are deaf, rhythmic. There was a decrease in the rate of urine output and intestinal motility.

In the study of KShchS: pH - 7.48; pCO ₂ - 37.9 mmHg; pO ₂ - 83.7 mmHg; Saturation - 97%; lactate - 1.7 mmol / l; HCO ₃ - 26.1 mmol / l; BE - 1.4 mmol / l.

On the ECG, there were signs of metabolic disturbances in the myocardium, sinus tachycardia and incomplete blockade of the right bundle branch block.

In a chemical-toxicological study, amitriptyline and benzodiazepine derivatives were found in the patient's urine qualitatively.

Diagnosis: acute poisoning by psychopharmacological agents in a severe form.

Upon admission to the intensive care unit of the Department of Toxicology, a nasogastric tube is installed for the child, central venous access is provided by puncture and catheterization of the femoral vein according to the Seldinger method, and complex infusion, detoxification therapy has been started. 13 grams of activated carbon were introduced into the stomach.

To restore the volemic status, a colloidal solution of Reftan was used.

After its introduction, stabilization of the volemic status was noted: blood pressure at the level of 95/55 mm Hg and a decrease in microcirculatory disorders.

After this, against the background of stabilization of the volemic status, Reamberin was included in the infusion therapy, which was administered at a rate of 5 ml per minute at the rate of 10 ml / kg of weight per day, and at the end of its introduction, an infusion mixture consisting of a solution of 5% glucose with riboxin 20 mg / kg body weight of the patient in a course of 3 days.

Further, pharmacological preparations are included in the infusion therapy, the action of which is aimed at normalizing metabolic and antioxidant processes - ATP, KKB and vitamin E; as well as drugs that improve the rheological and coagulation properties of blood - trental.

After 6 hours, the patient showed a decrease in the depth of depression of consciousness to a level of deep stupor on the Glasgow scale of 10 points, and after 12 hours from the start of therapy, a complete recovery of consciousness. Hemodynamic parameters are normal, there are no microcirculatory disorders. According to KSHS: pH 7.38; pCO ₂ 37 mmHg; pO ₂ 87 mmHg; saturation 98%; BE - 1.4 mmol / l; HCO ₃ 23 mmol / l; lactate 0.6 mmol / l. When conducting an ECG on the third day of the disease, metabolic disorders in the myocardium were not determined. On the fourth day from the moment of admission, the boy was discharged home in satisfactory condition under the outpatient supervision of a pediatrician.

Example 2. Patient R., 14 years 2 months (medical history No. 12141), was admitted to the Department of Toxicology 02/28/2011. From the anamnesis it is known that 12 hours before admission, a child with a suicidal purpose took an unknown amount of phenazepam. After which there was a change in activity and behavior, there was an unsteady gait and slurred speech. The ambulance team delivered the child to the hospital.

Upon admission, the patient is in serious condition. Level of consciousness - stunning 13 points on the Glasgow scale. Episodes of psychomotor agitation are replaced by drowsiness. Poorly oriented in time and space. Sharp muscle hypotension, dysartyria and severe ataxia. The pupils are dilated, the response to light is reduced. Pallor of the skin is noted. Breathing is independent. Heart rate of 106 beats per minute, blood pressure 110/60 mm Hg Heart sounds are muffled, rhythmic.

In the study of KShchS: pH 7.43; pCO ₂ 38.9 mmHg; pO ₂ 67.4 mmHg; carbonation 94.5%; lactate 1.5 mmol / l; HCO ₃ 24.1 mmol / l; BE - 0.4 mmol / l.

On the ECG, there were signs of metabolic disturbances in the myocardium, sinus tachycardia, and increased electrical activity of the myocardium.

During a chemical toxicological study, phenazepam was qualitatively detected in the patient's urine.

Diagnosis: acute poisoning by psychopharmacological agents (phenazepam) in severe form.

Upon admission to the intensive care unit of the Department of Toxicology, a nasogastric tube is installed for the child, central venous access is provided by puncture and catheterization of the femoral vein according to the Seldinger method, and complex infusion, detoxification therapy has been started. 20 grams of activated charcoal are introduced into the stomach.

To restore the volemic status, a colloidal solution of Reftan was used, after the introduction of which stabilization of blood pressure was noted at the level of 95/55 mm Hg and a decrease in microcirculatory disorders.

After this, against the background of stabilization of the volemic status, Reamberin was included in the infusion therapy, which was administered at a rate of 5 ml per minute at the rate of 10 ml / kg of weight per day, and at the end of its introduction, an infusion mixture consisting of a solution of 5% glucose with riboxin 20 mg / kg body weight of the patient in a course of 3 days.

Further, pharmacological preparations are included in the infusion therapy, the action of which is aimed at normalizing metabolic and antioxidant processes - ATP, KKB and vitamin E; as well as a drug that improves the rheological and coagulation properties of blood - trental.

After 5 hours, a regression of neuropsychiatric symptoms was noted. The girl began to adequately respond to the examination and answer questions. No episodes of psychomotor agitation were observed. 7 hours after administration, stabilization of blood pressure was noted at the level of 95/55 mm Hg and a decrease in microcirculatory disorders.

The child is in clear consciousness, but ataxia and mild dysarthria persisted. Muscle tone is satisfactory. Hemodynamic parameters are normal, there are no microcirculatory disorders. According to KShchS pH 7.38; pCO ₂ 41 mmHg; pO ₂ 84.1 mmHg; saturation 97%; BE - 0.2 mmol / l; HCO ₃ 24.2 mmol / l; lactate 1.0 mmol / l. When conducting an ECG on the third day of the disease, metabolic disorders in the myocardium were not determined. On the third day from the moment of receipt, the girl was discharged home in satisfactory condition under the outpatient supervision of a pediatrician.

Claims (1)

A method of treating severe forms of acute poisoning with psychopharmacological agents in children by conducting complex therapy: infusion and detoxification measures, including the introduction of a starting colloidal solution aimed at restoring the volemic status, and pharmacotherapy of developing functional disorders in the child’s body, characterized in that in the first hours from the beginning of complex therapy immediately after the introduction of the starting colloidal solution before pharmacotherapy against a background of stable In order to obtain full volemic status, Reamberin is sequentially introduced into the child’s body at the rate of 10 ml / kg of weight per day at a rate of 5 ml per minute, and then a drug mixture consisting of 5% glucose and riboxin solution at the rate of 20 mg / kg of the patient’s body weight from 3 to 5 days.