RU2695355C1 - Method for correction of cognitive disorders in resuscitation patients with septic encephalopathy - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: invention refers to medicine, namely to therapy, and concerns correction of cognitive disorders in resuscitation patients with septic encephalopathy. For this purpose, in addition to the etiopathogenetic therapy of sepsis, 20 ml of cytoflavin dissolved in 200 ml of physiologic saline is introduced. Introduction is performed intravenously drop-by-drop 2 times day for 10 days.EFFECT: method provides effective correction of cognitive disorders in the given group of patients ensured by optimization of neuronal intracellular metabolism and increased resistance of membranes of nerve and glial cells to ischemia accompanying septic encephalopathy.1 cl, 3 ex

Description

The invention relates to medicine (resuscitation and intensive care), and in particular to a method for the correction of cognitive impairment in resuscitation patients of adult and / or childhood with septic encephalopathy in the complex conduct of the etiopathogenetic treatment of sepsis and medical treatment of cognitive disorders.

It is known to use the drug cytoflavin in ophthalmology for the prevention and treatment of postoperative patients, RU No. 2464000 C1, A61F 9/008, A61K 38/04, A61K 38/05, 10/20/2012; RU No. 2462280 C1, A61N 1/20, A61K 31/194, A61K 31/455, 09/27/2012; RU No. 2310424 C1, A61F 9/00, A61N 1/32, A61K 31/194, A61K 31/525, 11/20/2007.

A known method of treating patients with abusal headache, including detoxification therapy with a course of 10 days according to the scheme: daily morning and evening, the patient is injected intravenously with cytoflavin at a dose of 10 ml, diluted in 200 ml of 0.9% NaCl solution during alternative pain relief, prophylactic and behavioral therapy, RU No. 2547565 C1, A61K 31/708, A61K 31/194, 04/10/2015.

There is a method of treating influenza and other flu-like diseases complicated by pneumonia, providing for the appointment of antibiotic therapy and the introduction of the drug interleukin-1, followed by intravenous drip of the drug cytoflavin once a day for four days, RU No. 2518277 C2, A61K 31/194, A61K 31 / 455, A61K 31/525, 06/10/2014.

A known method of treating patients with severe acute poisoning, including the introduction of the drug cytoflavin as part of general therapy, RU No. 2429826 C1, A61K 31/341, A61K 31/194, A61K 31/455, A61K 31/525, 09/27/2011; RU No. 2419448 C1, A61K 36/57, A61K 31/00, 05.27.2011.

It is known to use the drug cytoflavin for cancer patients, RU No. 2526828 CI, A61K 31/194, A61K 31/7084, A61K 31/525, 08/27/2014; RU No. 2479324 C2, A61M 21/00, A61K 31/194, A61K 35/14, 04/20/2013; RU No. 2463045 C1, A61K 31/194, A61K 31/455, A61K 31/525, A61K 31/166, 10/10/2012.

The use of the drug cytoflavin in gynecology is known as drug therapy in the treatment of inflammatory diseases, RU No. 2499594 C1, A61K 31/194, A61P 15/00, 11/27/2013; RU No. 2445058 C1, A61G 10/02, A61K 31/167, A61K 31/194, A61K 31/405, 03.20.2012; RU No. 2436603 C1, A61K 31/194, 12.20.2011; RU No. 2391104 C1, A61K 31/525, A61K 31/522, A61K 31/375, A61K 31/355, 06/10/2010; RU No. 2348399 C1, A61K 31/02, A61K 31/525, A61K 31/455, 03/10/2009.

It is known to use the drug cytoflavin in dermatology for the treatment of oral or intravenous drip, RU No. 2573986 C1, A61K 31/194, A61K 31/455, A61K 31/525, A61N 1/32, 01/27/2016; RU No. 2444353 C2, A61K 31/194, A61K 31/196, A61K 31/43, A61K 31/455, 03/10/2012; RU No. 2436574 C2, A61K 31/194, A61K 31/455, A61K 31/522, A61K 31/525, 12.20.2011; RU No. 2430721 C1, A61K 31/075, A61K 31/194, A61K 31/455, A61K 31/525, A61K 31/573, 10/10/2011.

In the analysis of known methods, the administration of the drug cytoflavin to patients with septic encephalopathy for the correction of developed cognitive impairment was not found.

A known method for the correction of cognitive dysfunctions and autonomic-sensory polyneuropathy in patients with vibrational disease, including drug therapy and the introduction of intravenous drip of cytoflavin for 10 days, RU No. 2461373 C1, A61K 31/194, A61K 31/455, A61K 31/525, A61K 31/166, А61Р 25/00, 09/20/2012.

This technical solution is made as the closest analogue of the present invention.

The closest analogue method performs the correction of cognitive dysfunctions and autonomic-sensory polyneuropathy in patients with vibrational disease by prescribing spa treatment and drug therapy. As drug therapy, cytoflavin is administered intravenously at the rate of 20 ml per 200 ml of a 5% glucose solution, daily for 10 days.

The closest analogue method improves the quality of rehabilitation measures in case of vibrational disease by correcting cognitive-mnestic disorders of higher cortical functions.

The present invention is based on the solution of a problem that allows the correction of developed cognitive impairment in resuscitation patients with septic encephalopathy, to increase the effectiveness of the intensive care.

The technical result of the present invention consists in the treatment of cognitive impairment simultaneously with the etiopathogenetic drug therapy of sepsis by optimizing neuronal intracellular metabolism and mechanisms of neurotransmission, increasing the resistance of nerve and glial cell membranes to ischemia against septic encephalopathy, and increasing the effectiveness of etiopathogenetic intensive therapy of sepsis under optimal conditions the introduction of cytoflavin.

According to the invention, this problem is solved due to the fact that the method of correction of cognitive impairment in resuscitation patients with septic encephalopathy includes drug therapy and the introduction of intravenous drip of cytoflavin for 10 days.

Correction of cognitive impairment is carried out simultaneously with etiopathogenetic drug therapy of sepsis by the introduction of an intravenous drop of 20 ml of cytoflavin at a dilution of 200 ml of 0.9% sodium chloride solution 2 times a day due to the optimization of neuronal intracellular metabolism and neurotransmission mechanisms, increasing the resistance of the membranes of nerve and glial cells to ischemia with septic encephalopathy.

In addition, the correction of cognitive impairment is carried out by pediatric resuscitation patients with septic encephalopathy against the background of etiopathogenetic drug therapy of sepsis, excluding the age group of newborns.

The applicant has not identified sources containing information about technical solutions identical to the present invention, which allows us to conclude that it meets the criterion of "novelty."

Due to the implementation of the distinguishing features of the invention (in conjunction with the features indicated in the restrictive part of the formula), important new properties of the object are achieved.

Conducting drug therapy of cognitive disorders simultaneously with the etiopathogenetic drug therapy of sepsis allows the correction of developed cognitive disorders in resuscitation patients with septic encephalopathy.

The use of cytoflavin in the optimal mode of administration increases the effectiveness of the intensive care.

The applicant is not aware of any publications that would contain information on the influence of the distinguishing features of the invention on the achieved technical result. In this regard, according to the applicant, it can be concluded that the claimed technical solution meets the criterion of "inventive step".

The present invention is carried out as follows.

A method for the correction of cognitive disorders is carried out in resuscitation patients of adult and / or childhood with septic encephalopathy.

Correction of cognitive disorders is carried out simultaneously with the etiopathogenetic drug therapy of sepsis.

Combination therapy includes the introduction of an intravenous drip of 20.0 ml of cytoflavin per day, 10.0 ml of cytoflavin per dilution of 200 ml of 0.9% sodium chloride solution 2 times a day.

Correction of cognitive disorders on the background of etiopathogenetic drug therapy of sepsis is carried out by optimizing neuronal intracellular metabolism and neurotransmission mechanisms, increasing the resistance of nerve and glial cell membranes to ischemia against the background of septic encephalopathy.

With sepsis, the central nervous system always suffers, its dysfunction is expressed as minimal cognitive impairment, hyper- or hypoactive delirium, coma, which corresponds to the classification of septic encephalopathy.

Patients with a detected infection site (meningitis, pneumonia, urinary tract infection, abdominal infection after surgery, etc.) and the general reaction of the body to the infection site in the form of a systemic inflammatory response, according to laboratory markers, including procalcitonin level more than 2 ng / ml, in combination with organ dysfunction (respiratory, cardiovascular, cerebral, excretory, digestive systems, etc.), a diagnosis of sepsis is made.

Organ dysfunction and its severity, as well as the number of functional systems of the body involved in the pathological process during sepsis, are the basis for assessing the severity of the condition of resuscitation patients using special scales (for example, the SOFA, APACHE II, PELOD scales in pediatric practice, etc.) .

Patients of adult and / or childhood who are diagnosed with sepsis on the basis of a combination of clinical, laboratory and instrumental generally accepted diagnostic criteria are shown medication for cognitive disorders as a consequence of cerebral organ dysfunction - septic encephalopathy.

With septic encephalopathy, cytoflavin therapy is indicated according to the proposed scheme, taking into account the effect of cytoflavin.

The effect of cytoflavin is a cytoprotective neuronal mechanism and promotes the activation of aerobic glycolysis and stimulation of the synthesis of gamma-aminobutyric acid in neurons.

Correction of cognitive impairment with the introduction of cytoflavin on the background of etiopathogenetic drug therapy of sepsis

carried out by optimizing neuronal intracellular metabolism and mechanisms of neurotransmission, increasing the resistance of the membranes of nerve and glial cells to ischemia against the background of septic encephalopathy.

It is these mechanisms that correct cognitive impairment due to the development of septic encephalopathy, and the result of which they are.

The implementation of the method is confirmed by Examples 1, 2, 3.

Example 1

Patient R., 2 years 4 months old, was taken to the regional children's hospital from the interdistrict hospital with the diagnosis: “Acute right-sided total community-acquired pneumonia. DN III Art. Sepsis. Infectious-toxic shock "in a state of drug-induced depression of consciousness and breathing (micro-jet infusion of thiopental Na at a dose of 3.0 mg / kg / h), prolonged orotracheal intubation, mechanical ventilation.

Hemodynamic parameters with inotropic and vasopressor support - microjet infusion of adrenaline 0.1% at a dose of 0.20 μg / kg / min, there is a tendency to hypotension (BP 86/28 (41)). A micro-jet infusion of Solu-cortef is carried out at a dose of 15 mg / kg / min.

An anamnesis of the disease is 7 days. She was urgently hospitalized to the inter-district hospital from home with a sharp deterioration 1 day ago.

Upon admission to the inter-district hospital, the level of C-reactive protein is 528.1 mg / l. Procalcitonin test (quantitative method) - 51.39 ng / ml. Diagnosed with sepsis.

Upon admission to the children's regional hospital, the condition is regarded as extremely serious; the severity of the condition is caused by multiple organ failure syndrome (SPON): cerebral insufficiency, mixed respiratory failure, circulatory failure, impaired water-electrolyte balance, metabolic disturbances, phenomena of endogenous intoxication against the background of the focus of infection - total right-sided pneumonia.

Given the history, clinical data (the condition is extremely serious, due to SPON), laboratory examination data (laboratory signs of a pronounced systemic inflammatory response (SVR): leukocytosis with a shift in the leukocyte formula, hyperlactatemia, high levels of C-reactive protein and procalcitonin), decompensated disturbances in water -electrolyte balance, data from instrumental research methods (radiological signs of total right-sided pneumonia), the clinical diagnosis is made: community-acquired avostoronnyaya pneumonia. Sepsis from 03/23/2018. SPON. DN III Art. NK III Art.

The patient underwent etiopathogenetic therapy of sepsis in the following volume:

- supportive and corrective infusion therapy in volume up to physiological needs;

- respiratory support under the control of the gas composition of the blood and the acid-base state of the blood (CBS);

- neurovegetative stabilization - micro-jet infusion of sodium thiopental at a dose of 3.0 mg / kg / h;

- inotropic and vasopressor support: microjet infusion of dopamine 4% at a dose of 10.0 μg / kg / min, microjet infusion of norepinephrine 0.2% at a dose of 0.40 μg / kg / min;

- antibacterial therapy - cefotaxime at a dose of 300 mg every 6 hours (100 mg / kg / day), amikacin at a dose of 15 mg / kg every 24 hours (continuation of therapy started in the area in agreement with the on-call pediatrician);

- immunomodulating, antiviral therapy - Viferon-1 suppositories of 150 thousand units every 12 hours No. 14;

- antifungal therapy - diflucan in a prophylactic dose of 3 mg / kg every 24 hours;

- symptomatic antipyretic therapy (paracetamol 1%, cefecon-D suppository);

- enteral administration of boiled water of 10.0 ml every 4 hours in order to assess the tolerance of the gastrointestinal tract;

- observation by a pediatrician;

- examination of an ophthalmologist, ENT doctor;

- monitor observation and laboratory control;

- maintaining an individual microclimate and protective mode.

Against the background of therapy by the 3rd day, the patient without negative dynamics. Markers of a systemic inflammatory response (CRP 72-78 mg / L, procalcitonin test-10 ng / ml) were noted to decrease, and the dosage for inotropic and vasopressor support was reduced.

Compensated for CBS and gas composition of the blood. Ionogram indicators within the reference values. Enteral nutrition assimilates, fever subfebrile. Ventilation in SIMV mode.

From the 5th day, negative dynamics according to laboratory and clinical data are noted, right-sided exudative pleurisy, right-sided pneumothorax were diagnosed, pleural puncture was performed, 133.0 ml of serous-yellow discharge was evacuated; the girl has febrile fever up to 38.9 ° C, promedol 50.0 μg / kg 1 hour is included in the structure of the neurovegetative blockade.

On the 8th day, there is an increase in C-reactive protein to 168.6 mg / l; procalcitonin test - 0.5 ng / ml.

The antibacterial therapy has been changed, otherwise the pathogenetic and symptomatic therapy continues in the same volume.

After 2 weeks from admission to the intensive care unit, the child’s condition remains severe, without negative dynamics, signs of right-sided pneumonia, signs of polysegmental pneumonia on the left remain: against the background of an uneven decrease in pneumatization of the right lung due to infiltration, small rounded areas of enlightenment in the medial sections of the right lung are determined.

Markers of a systemic inflammatory response are markedly reduced: C-reactive protein levels to 52.1 mg / l, PCT to 0.5 ng / ml. Clinically, there is a decrease in oxygen dependence, there remains a need for inotropic drugs with a decrease in dynamics, avoiding vasopressors, gastrointestinal dysfunction is preserved without an increase in dynamics.

On the 18th day, neurovegetative stabilization was canceled, sodium thiopental and promedol were disabled. The level of respiratory support is VIVL in SIMV mode. Hemodynamic parameters are stable outside inotropic support. The level of C-reactive protein is 1.6 mg / L.

Therapy was started in the form of an infusion of a solution of cytoflavin 10.0 ml 2 times a day in a dilution of 200.0 ml of 0.9% sodium chloride solution for 10 days.

On the 19th day, the level of consciousness is a stupor, taking into account the previous drug sedation in the structure of the neurovegetative blockade.

By the evening of 19 days the child is extubated, respiratory support moistened with air-oxygen mixture through an oxygen mask.

From the 20th day of treatment in the intensive care unit, the girl spontaneously opens her eyes, there is a slight tremor in the upper limbs, chaotic movements, most of the day lies with her eyes closed. EEG monitoring for 48 min revealed the registration of severe disorganization and a slowdown in the main rhythm.

Increased indices of slow-wave and high-frequency activities. Data for the presence of true epileptiform activity was not detected.

Neurological status on the 6th day from the start of neurometabolic therapy with cytoflavin, the 23rd day of treatment in the intensive care unit: the consciousness is clear, it follows objects, pupils D = S, eyeball movements are not limited. Facial expression is symmetrical. Tongue in the midline.

Muscle tone is increased in the left arm and lower extremities. On examination, tremor in the left hand. Deep tendon reflexes D = S, high with the expansion of reflexogenic zones. Symptom of Babinsky on the left.

On the 24th day, the girl eats with appetite, drinks with pleasure, picks up toys, sleeps well at night.

On the 27th day of hospitalization, she was transferred to the pulmonology department in a moderate state, antimicrobial therapy (meronem, sultasin) continues, neurological status after the course of therapy with cytoflavin with positive dynamics: the girl speaks separate words, most of the time is in position sitting. It stands at the support with support.

Pathological stop signs are not determined.

I gained 2 kg in weight.

She was discharged from the hospital under the supervision of a pediatrician and a neurologist at the place of residence in a satisfactory condition, walks with support, speech production in a sufficient amount by age.

Example 2

Patient S., 77 years old, was admitted to the clinic on an emergency basis in a state of deep stunning in April 2014, is not available for productive contact.

According to relatives, 2 days ago there was a chill, an increase in body t to 38.5 ° C, against the background of hyperthermia, it became inaccessible to contact. Before fever, I walked on my own with a wand, serviced myself.

From the anamnesis: transferred stroke in the pool of the posterior cerebral artery on 08. 2013 of a cardioembolic nature; 15 years suffering from coronary heart disease, angina pectoris II FC, a constant form of AF. CHF IIa. Type II diabetes, subcompensation. Obesity I Art. Diabetic nephropathy. Chr. Pyelonephritis. COPD, moderate course, without exacerbation.

The examination revealed clinical and laboratory signs of exacerbation of XP. pyelonephritis with a decrease in the rate of urine output of less than 0.5 ml / h, in the general analysis of urine, white blood cells cover all fields of view, unchanged red blood cells - 10-15 in s / sp., altered red blood cells - 4-6 in s / sp, protein - 0 , 18 g / l; bacteriuria; radiological signs of bilateral lower lobar pneumonia.

On the day of hospitalization, in the biochemical analysis of blood, the level of C-reactive protein is 514.5 mg / l, transaminases are normal, total bilirubin is 17.6 mmol / l, creatinine is 60.0 mmol / l, urea is 11.20 mmol / l; in the clinical analysis of blood leukocytosis 28.6⋅10 ⁹ / l without shift of the formula to the left, lymphopenia, ESR 61 mm / h.

Transferred to the intensive care unit for further treatment. Procalcitonin test (PCT) by semi-quantitative method> 10 ng / ml.

The combination of the results of clinical, laboratory and instrumental examination methods made it possible to diagnose sepsis.

The etiopathogenetic therapy of sepsis was carried out in accordance with the clinical recommendations approved by the Ministry of Health of the Russian Federation, including antibacterial (amoxiclav, lindacin, clacid), infusion, detoxification, and antiplatelet therapy in combination with the introduction of 10.0 ml of cytoflavin diluted with 200.0 ml of a 0.9% solution sodium chloride intravenously twice a day for 10 days.

On the third day from hospitalization and the start of the etiopathogenetic treatment of sepsis in combination with the introduction of cytoflavin, the patient became available for contact, opens his eyes, performs commands, on the 4th day there was a monosyllabic speech production, the level of CRP on the 4th day decreased to 154.1 mg / l

From the 5th day, the patient lies open eyes during the day, sleeps at night, the circadian rhythm of sleep-wakefulness is preserved. Eats and drinks through the mouth. Answers questions, oriented in himself, place and time.

Since 6 days, physical rehabilitation methods have been connected: massage, exercise therapy, verticalization of the patient in bed. At the end of the 10-day course of cytoflavin administration, the patient is neurologically in a clear mind, contacted, oriented, speech production is slightly reduced. Assessment of cognitive function using the Mini-Kog test: tasks were completed correctly, no gross cognitive impairment was detected.

Antibacterial, infusion, detoxification therapy continued for 3 weeks. Before discharge from the hospital, C-reactive protein is 31.5 mg / L. The patient was discharged after 1 month from hospitalization in a compensated state under the supervision of a physician and neurologist at the place of residence on a planned cardiac, antihypertensive, anticoagulant therapy with recommendations to continue treatment with cytoflavin in tablet form, 2 tablets. 2 times a day.

Example 3

Patient B., 34 years old, with a gestational age of 28 weeks, was admitted to a multidisciplinary hospital in an emergency in consciousness, with nausea, vomiting, abdominal pain, body temperature of 39.0 ° C.

From the anamnesis it is known that 4 hours before the worsening condition she ate shauvermu.

In the emergency room, there was an instability of hemodynamic parameters with a decrease in adsystole, diastole, average to 90/60 mm Hg, confusion, acrocyanosis, impaired microcirculation in the distal extremities, a symptom of a "white" capillary spot> 3 s. In a clinical blood test, leukocytosis is 26.8⋅10 ⁹ / L with a shift of the formula to the left, ESR 45 mm / h.

The result of the performed procalcitonin test: 247 ng / ml. A patient with a diagnosis of septic shock was urgently transferred to the intensive care unit, infusion therapy was started, vasoactive therapy with norepinephrine microjet 0.2 μg / kg / min, antimicrobial therapy with broad-spectrum antibiotics.

After 1 h, the patient's condition worsened, an increase in the dose of vasopressors was required to maintain an average blood pressure of 65 mm Hg, neurologically - stupor, the fetal heartbeat was not heard. The uterus is atonic. The consultation, consisting of obstetrician-gynecologists, resuscitation anesthetists, surgeons, decided on emergency surgical intervention-termination of pregnancy for medical reasons.

The patient was operated on on an emergency basis (uterine extirpation was performed), after 24 hours she was withdrawn from septic shock, later the clinical picture was presented by multiple organ failure (acute cardiovascular, respiratory, cerebral, hepatic, renal, intestinal, hemostasiological disorders in the form of DIC) syndrome).

In the treatment of this patient, all modern intensive care methods and technologies were used that are applicable to the etiopathogenetic therapy of sepsis, including plasmapheresis, low-flow venous-venous ultrahemofiltration, hemodialysis.

The patient did not receive intravenous cytoflavin therapy during the treatment of sepsis.

After 3 weeks from diagnosis and the beginning of intensive therapy, the patient was withdrawn from the neurovegetative blockade (midazolam + fentanyl), weaned from respiratory support.

The tracheostomy cannula is removed on the 41st day from the tracheostomy in the intensive care unit, the muscle tone is sufficient, it breathes independently for a day, SpO2 96-97% without oxygen insufflation, the level of neurological deficit: conscious, disoriented in place and time, does not remember events preceding the development of septic shock, cannot perform the Mini-Kog test, does not remember the names of mothers, relatives, speech production is reduced.

After 2 days, a slight improvement in neurological status was noted in the dynamics: I remembered the names of the children, my spouse, I was self-oriented, did not ask about pregnancy. Performing a Mini-Kog test is difficult.

The presented clinical observations in Example 1 and Example 2 illustrate the effectiveness of drug correction of cognitive impairment in a child and adult patient with verified sepsis and septic encephalopathy using cytoflavin, which is included in the intensive care regimen along with the etiopathogenetic treatment of sepsis.

Example 3 demonstrates the development of gross cognitive impairment against the background of septic shock, sepsis with multiple organ failure, including septic encephalopathy, in a young woman without neurological deficit before the development of the disease.

In our opinion, the inclusion of cytoflavin in the intensive care regimen at a time when the patient was withdrawn from septic shock and received etiopathogenetic complex therapy of sepsis would be appropriate for optimizing neuronal intracellular metabolism and mechanisms of neurotransmission, increasing the resistance of nerve and glial cell membranes to ischemia on background tissue hypoperfusion in a septic patient.

In the proposed invention, the “Method for the correction of cognitive impairment in resuscitation patients with septic encephalopathy” includes the introduction of intravenous cytoflavin, which is widely used in drug therapy of various diseases, and the practical use of the proposed method determines, according to the applicant, that his criterion is “industrial applicability”.

The proposed method allows you to:

- carry out the correction of developed cognitive disorders in resuscitation patients with septic encephalopathy;

- increase the effectiveness of intensive care.

Claims (2)

1. A method for the correction of cognitive impairment in resuscitation patients with septic encephalopathy, which consists in the fact that when implementing the method, in addition to the etiopathogenetic drug therapy of sepsis, 20 ml of cytoflavin diluted in 200 ml of saline are administered intravenously 2 times a day for 10 days. 2. The method according to p. 1, characterized in that the correction of cognitive impairment in resuscitation patients of childhood with septic encephalopathy, excluding the age group of newborns