RU2219929C1 - Method for treating patients for persisting vegetative state - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: method involves recording electroencephalogram. Hypersynchronized electroencephalogram being found, narcotic treatment is administered with opioid analgesic preparations and α₂-adrenoantagonist agents to reach stable monotonous strip on electroencephalogram and trunk activeness arrest. Then multiple mode stimulation is applied. The stable monotonous strip on electroencephalogram being found, multiple mode stimulation is carried out on the benzodiazipines application background. The benzodiazipines are administered at a dose not exceeding therapeutic efficiency of midasolam at a dose of 0.15 mg/kg. EFFECT: enhanced effectiveness of treatment. 5 cl, 8 dwg

Description

 The invention relates to medicine, namely to neuroresuscitation, neurosurgery and neurology, and can be used to treat patients with a persistent vegetative state (PVA).

 There is a method of treating patients with PVA of non-traumatic genesis (posthypoxic encephalopathy) by administering large doses of barbiturates (therapeutic anesthesia) in combination with hyperbaric oxygenation (HBO) (Negovsky V.A., Gurvich A.M., Zolotokrylova E.S. Post-resuscitation disease . - M.: Medicine, 1987, p. 418-421). The disadvantage of this method is the inability to conduct electrophysiological control. Large doses of barbiturates inhibit the bioelectric activity of the brain, and the HBO technique makes it difficult to record EEG technically.

 There is also a method of treating PVA, proposed Yudelson Ya. B. (Ya.B. Yudelson, Yu.V. Yuryeva. Vegetative state. - Smolensk: SGMA, 2002. - P. 25), aimed at enhancing the afferent flow by activating the multimodal sensory systems of the brain (polymodal stimulation). The disadvantage of this method is the lack of exposure to the generator of pathologically enhanced excitation (GPUV).

 Closest to the claimed is a method of treating patients with PVA (due to traumatic brain disease (TBHM)) under the supervision of an EEG (Borshchagovsky M. L., Gavrilov S. S., Balashov A. N., Fradkova G. V. A comprehensive assessment of the condition and differentiated therapy of neuroresuscitation patients with traumatic brain injury: Methodological recommendations. - L., 1990. - P. 11-16), adopted as a prototype. Depending on the clinic and EEG, the authors distinguish three types of patients with TBHM, two of which are patients corresponding to the diagnosis of PVA according to the clinical and EEG data. 1st — normoreactive irritative type — characterized by hypersynchronized EEG with the manifestation of hyperergic centrogenic reactions that require correction during treatment. For the purpose of correction, therapeutic anesthesia is used with the use of barbiturates and Na hydroxybutyrate. The 2nd — hyporeactive type — is characterized by a monotonous flat EEG, and intensive therapy in this case is represented by generally accepted methods for stabilizing the stem circulation (“3G” - therapy, improving blood rheological properties, metabolic cerebroprotection with Na hydroxybutyrate, etc.) and replacement therapy .

The disadvantages of the prototype:
- The problem of treating PVA is considered only in patients with TBHM and only taking into account the dynamics of TBHM. Although the concept of PVA is more ambiguous, and according to the definition of the American Academy of Neurology adopted in 1989, it is considered as a clinical state of a complete lack of self-awareness and the environment, accompanied by sleep-wake cycles with the full or partially preserved function of the hypothalamus and brain stem, and it is a definite ( "persistent", i.e. transient) state of the brain is a variant of a patient's exit from a coma of a very different etiology, both traumatic and non-traumatic genesis.

 - Neurophysiological aspects of the formation of stable pathological systems are not taken into account (G. Kryzhanovsky. General pathophysiology of the nervous system. Guide. - M .: Medicine, 1997. - 352 p.).

 - The principles of the recommended intensive care are absolutely fair, but they do not contain a systemic nature and a targeted effect on the formed (forming) GPUV and most likely can be characterized as symptomatic therapy.

 - The use of Na oxybutyrate excludes dynamic EEG monitoring of the functional state of the brain (FSM), taking into account the peculiarities of the effect of this drug on the bioelectric activity of the brain (suppresses).

 - The possibility of changing the EEG and, therefore, the FSM in the treatment process (i.e., the staged process) is not considered. A registered EEG is evaluated as a strictly pathogonal sign of a certain type of TBHM.

 - The temporal, clinical, neurological and electrophysiological criteria for assessing the effectiveness of the therapy and its timely correction are not specified, although it indicates possible complications and prognosis based on the type of TBHM, based on statistics.

 - The recommended treatment does not lay the foundation for early rehabilitation in case of positive dynamics.

 The invention is aimed at creating a method of treating patients with PVA under electrophysiological control, which allows, depending on the EEG pattern, to select the optimal treatment tactics: from deep diprivation (therapeutic anesthesia) to polymodal stimulation (activation of visual, auditory, olfactory, tactile, etc. sensory analytic systems), moreover, with hypersynchronized EEG, therapeutic anesthesia is performed to suppress pathologically enhanced trunk activity (GPUV), and with a stable monotonous flat EEG, a polymodal is performed new stimulation against the background of sedation with benzodiazepine drugs.

 The invention consists in the following. In patients with PVA, EEG is recorded. If the EEG is hypersynchronized and is characterized by stem flashes of slow waves or continuous distant synchronization, theta-delta activity, then the complex of therapeutic measures includes therapeutic anesthesia for stopping the GPUV until the stem activity disappears and a stable monotonous flat EEG appears. Therapeutic anesthesia is carried out according to generally accepted methods using drugs that have a combined effect on the opioid and adrenergic antinociceptive systems, which allows dynamic EEG control. The depth of anesthesia depends on the EEG pattern (the disappearance of hypersynchronization and other signs of stem cell irritation). The duration of therapeutic anesthesia is very variable - from several hours to several days - and depends on the degree of stability of the GPUV. After the appearance of a stable monotonous flat EEG and a persistent disappearance of stem activity within the "diagnostic window", the treatment tactics are changed and multimodal stimulation is performed. In the initial monotonous flat EEG, primary polymodal stimulation is performed against sedation with benzodiazepines, under the influence of which positive EEG rearrangements are detected and the positive effect of polymodal stimulation is fixed, weakening the effect of hcpv on the physiological bioelectric activity of the brain.

The inventive method differs from the prototype in that:
- the choice of a method for treating patients with PVA is based on the principles of pathogenetic therapy and takes into account the neurophysiological aspects of pathology in accordance with the concept of academician G. Kryzhanovsky. and is aimed at suppressing the GPUV;
- a dynamic EEG control is included in the monitoring complex for patients with PVA, which allows you to quickly respond to changes in FSM and timely adjust treatment tactics;
- therapeutic anesthesia is carried out according to a technique that allows you to register EEG;
- complex treatment includes polymodal stimulation, which, with positive dynamics, is considered as a method of early rehabilitation;
- multimodal stimulation is carried out under EEG control against the background of small doses of benzodiazepines, which helps to identify, maintain and consolidate the positive changes in the EEG.

 - therapeutic measures have a clear focus on restoring the neuropsychic activity of the brain in patients with PVA, regardless of the etiology, and are focused on maintaining the electrophysiological activity of the brain at a level as close to normal as possible.

The method is as follows. EEG is recorded in a patient with PVA and therapeutic anesthesia and / or multimodal stimulation are performed against the background of EEG registration, depending on the pattern of recorded EEG. If there is a pattern of hypersynchronized EEG, therapeutic fentanyl-clonid anesthesia is included in the complex treatment. The method of therapeutic anesthesia with the use of an α ₂ -adrenoagonist and narcotic analgesics allows you to record EEG and maintain the electrophysiological activity of the brain at the level closest to normal, and the depth of anesthesia is determined by the minimum doses of drugs (determined by titration), at which stem activity disappears. The average doses of fentanyl and clonidine are 0.8-1.2 and 0.3-0.6 μg / kg / h, respectively. The duration of therapeutic anesthesia continues until a stable monotonous EEG is obtained and the stem activity disappears with EEG control against the background of a "diagnostic window". After receiving a stable monotonous EEG, therapeutic measures - polymodal stimulation (photo stimulation, listening to audio recordings, active communication with relatives, massage, exercise therapy, etc. - activation of sensory channels of perception), in which the appearance of stem flashes on the EEG, more often alpha theta range - the excessive activating effect of nonspecific median structures is removed. A particularly positive moment against this background is the appearance of short-term discharge (paroxysmal) waves - the cortex ceases to be in a state of protective inhibition. Positive dynamics is further determined by restoring the bioelectric activity of the brain in the form of increasing the amplitude of biopotentials, the appearance of faster (alpha-beta) forms of activity and the further organization of EEG (rhythms appear on the EEG, and not just activity). The presence of an initially monotonous flat EEG is an indication for primary polymodal stimulation in the presence of benzodiazepines. The introduction of benzodiazepines in doses not exceeding the therapeutic effect of midazolam at a dosage of 0.15 mg / kg allows weakening the effect of hcpv and supporting positive EEG rearrangements if they occur.

 A method of treating patients with PVA was developed and passed clinical trials in the Department of Anesthesiology and Intensive Care of the Russian National Pedagogical Institute named after prof. A.L. Polenova in the treatment of 18 patients. In 12 patients whose EEG parameters were maintained in the optimal “corridor” by neutralizing GPUV with therapeutic anesthesia followed by multimodal stimulation, a distinct positive dynamics was observed. And in 6 patients who underwent primary polymodal stimulation against the background of the administration of midazolam at a dose of 0.1 to 0.15 mg / kg of midazolam, a positive dynamics was also observed.

 We give examples - extracts from medical records.

 Example 1. Patient S., 5 years old, a medical history of 1379-96, was in the RNHI them. A. L. Polenova from 10/10/96 to 01/23/97 with a diagnosis of PVA. Posthypoxic encephalopathy. Condition after asphyxiation.

 From the anamnesis: September 26, 1996 fell from a cliff and was covered with sand. After 7-10 minutes, it was dug out of sand. Spontaneous breathing was absent. 15 minutes after mouth-to-mouth resuscitation and closed heart massage, spontaneous breathing appeared and the child was taken to the Kirov Central Hospital.

 Upon admission to the PHI, the condition is very serious, subcompensated by vital functions. Neurologically: the level of consciousness is a persistent vegetative state (the gaze does not fix, it does not complete tasks, the sleep and wake cycle are preserved, the pupils are narrow, D = S, the reaction to light is preserved, the oculocephalic reflexes are preserved, periodically-floating movements of the eyeballs, the face is symmetrical, trismus facial muscles, the tongue behind the midline, the pharyngeal reflex is high, does not swallow on its own, probe nutrition.Tetraparesis with a marked increase in muscle tone in the flexors of the arms and extensors of the legs, at any time Dragee (sound, tactile, pain) reacts with hypertonicity to opistotonus. Diencephalic crises are observed periodically, accompanied by hypertonicity of the flexors of the arms and extensors of the legs, hyperthermia, isothermia, increased A / D, heart rate, BH, hyperemia and sebum of the face and skin. tachypus up to 26 per min.

 A comprehensive examination of cerebral CG was carried out - a moderately expressed dropsy from 10/15/96 an optometrist - the pupils are narrow, the reaction to light is preserved, the fundus without gross changes. On radiographs of the lungs - congestion in the basal parts of both lungs.

 EEG from 10.15.96 - hypersynchronized EEG - slow-wave activity unmodulated, without zonal differences, low-amplitude activity of the theta-delta range is recorded. Against this background, flashes of high-amplitude delta waves arise; there is no reaction to photostimulation. EEG data indicate gross diffuse changes involving the stem structures of the diencephalic-mesencephalic level (Fig. 1).

 For 20 days, therapeutic anesthesia was performed under EEG control. Intravenous drip was introduced a mixture of a solution of fentanyl 0.005% - 6.0 + solution of clonidine 0.01% - 1.0 + solution of sodium chloride 0.9% - 500.0. Clinically observed regression of diencephalic crises.

 On the EEG from 10.24.96 - a stable monotonous flat EEG - low-amplitude activity of the theta range with elements of beta activity is noted. The presence of stem flashes is not registered (figure 2).

 The complex treatment included polymodal stimulation (photostimulation, listening to audio recordings, emotional communication with relatives, massage, exercise therapy).

 On the EEG from 11/14/96, positive dynamics are revealed in the form of the absence of slow waves and the appearance of chaotic groups of alpha vibrations. A particularly positive point is the occurrence of bilaterally synchronous outbreaks of paroxysmal activity (figure 3).

 From the moment of admission to the intensive care unit A.L. Polenova underwent intensive therapy, which included conventional management of patients with PVA, aimed at improving brain metabolism, maintaining adequate brain perfusion, neurotransmitter therapy and antibacterial therapy. In clinical and neurological dynamics, the boy’s condition gradually improved.

 On the EEG from 12/04/96 a clear positive dynamics is an increase in the amplitude values of biopotentials, the appearance of rhythm polymorphism and their organization (Fig. 4).

 By December 20, the boy’s condition was compensated, speech production appeared, memory returned, began to actively make contact, began to walk independently. In neurological status during discharge, bilateral pyramidal symptoms persist with a predominance in the left hand. Discharged at the place of residence with a recommendation to conduct further rehabilitation treatment in the children's rehabilitation center.

 Example 2. Patient Ch., 31 years old, medical history 1082-02, is located in the Russian National Research Institute of Chemical Medicine. A. L. Polenova from 05.17.02 to the present with a diagnosis of PVA, posthypoxic encephalopathy.

 From the anamnesis: intraoperative cardiac arrest 02.04.2002

 When transferred to RNHI them. A.L. Polenov's condition of the patient is severe, compensated by vital functions. Neurological status is represented by PVA. Lies with his eyes open, his eyes fix, he watches his eyes with objects. An emotional reaction is noted when communicating with relatives. When applying pain stimuli, it tries to localize the pain. Pupils D = S, live photoreactions, eyeball movements in full. The face is symmetrical, paresis of the facial muscles was not detected. Tongue along the midline, pharyngeal reflex preserved. Muscle tone is very high, especially in the hands. Tetraparesis. Mixed tone increase, mainly in flexors. Severe symptoms of oral automatism (Marinescu-Rodovici, proboscis). Tendon and periosteal reflexes with slight asymmetry D <S, Babinsky's symptom is bilateral, with an expanded reflexogenic zone (positive Oppenheim, Chedok, Schaeffer). Abdominal reflexes are extremely low, quickly exhausted. Hemodynamics is stable. Spontaneous breathing through the tracheostomy cannula. Somatically revealed infectious foci - tracheobronchitis, pyelonephritis. Periodically, diencephalic crises were observed, accompanied by hyperthermia with isothermia, diabetes insipidus, hyperemia and greasiness of the face and skin.

 When examining on MRI from 05/13/02: Median formations are not displaced. The lateral ventricles are moderately dilated. Subarachnoid spaces are not expanded. Focal changes in the substance of the brain are not identified. The pituitary gland is not enlarged. Stem structures without features.

 PET from 05/30/02: A series of tomograms (15 sections) in the study of glucose metabolism revealed a diffuse metabolic lesion of the cerebral cortex with a predominance in the apical regions without significant interhemispheric asymmetry. A relatively safe level of glucose metabolism is observed in the cerebellum and brain stem, as well as in the anterior subcortical nuclei. A diffuse decrease in glucose consumption in the frontal lobes is from 23 to 11% in different departments, in the parietal lobes - from 20 to 10%, in the temporal lobes - 11% (relative to the cerebellum). Mild hypometabolism is observed in the poles and adjacent parts of the cortex of the occipital lobes, as well as in the visual tubercles, especially in the left. Conclusion: moderate posthypoxic metabolic lesion of the cerebral cortex (metabolic rate decreased by 23-10%) and the phenomenon of deafferentation in the optic tubercles.

 - EEG from 05/18/02: The alpha rhythm is represented by single, sometimes groups of elements. The recording is polymorphic from beta to theta waves, while maintaining the correct zonal distribution of rhythms. The response to photostimulation is weak, practically absent. EEG data indicate diffuse moderately pronounced changes (figure 5).

 Produced in / in the introduction of benzodiazepines (dormicum).

 - With the introduction of 2.5 mg of dormicum on the EEG, restructuring of the rhythms began in the form of the disappearance of slower forms and the appearance of an ordered beta rhythm with elements of the alpha rhythm. With a total introduction of 5 mg, further normalization of the EEG in the form of the appearance of the correct alpha rhythm (Fig.6). At 7.5 mg of dormicum, the nature of the EEG is the same, but a significant clinical effect is a decrease in spasticity. At 10 mg - EEG and the clinical effect is the same. With the introduction of 0.25 mg of anexate, the gradual disappearance of the alpha rhythm with a predominance of beta activity. At 0.5 mg of an anoxate, EEG is similar to the initial one. Recommended sedation of the patient in a dose of dormicum 7.5 mg (0.12 mg / kg) during multimodal stimulation.

 The complex treatment includes polymodal stimulation (photostimulation, listening to audio recordings, emotional communication with relatives, massage, exercise therapy).

 On the EEG from 05.23.02 - fast activity, mainly of the beta range, is recorded with the appearance of alpha activity during rhythmic photostimulation. Single flashes were recorded in the background and more frequent during rhythmic photostimulation - theta waves. EEG data indicate diffuse moderately pronounced changes (the nature of the changes against the background of iv administration of 2.5 mg of dormicum), irrigation of diencephalic structures (Fig. 7).

 From the moment of admission to the intensive care unit A.L. Polenova underwent intensive therapy, which included the generally accepted management of patients with PVA, aimed at improving brain metabolism, maintaining adequate brain perfusion, and neurotransmitter therapy. Also, therapy was carried out aimed at the destruction of GPUV (multimodal stimulation against a background of 7.5 I / O dormicum, etc.), acupuncture, therapeutic massage, physiotherapy exercises, physiotherapy and antibacterial therapy. Received a full balanced enteral therapy. The tracheostomy is removed, the tracheostomy course has healed. Against the background of the therapy, a significant positive dynamics in EEG and positive dynamics in neurological status were noted. The patient is conscious, contact, performs tasks, speaks separate words. It responds adequately to the inspection. Emotional lability persists. Pupils D = S, live photoreactions. The face is symmetrical. Tetraparesis with increased tone in the mixed type, the tone in the right hand is maximized. Symptom of Babinsky bilateral. Symptoms of oral automatism persist (Marinescu-Rodovici, proboscis). Hemodynamics is stable. Spontaneous breathing, adequate.

 On the EEG from 06/10/02 - activity of the alpha and beta ranges, alternating with theta waves, is recorded. Positive dynamics is noted in the form of the disappearance of stem irritation and, most importantly, the appearance of a rhythm (mainly alpha rhythm) more stable on the left, although the organization of the rhythm is also on the right (Fig. 8).

 Using the proposed method allows the treatment of patients with PVA under EEG control and, depending on the pattern of recorded EEG, timely correct adverse changes in the electrophysiological activity of the brain and maintain it at the optimal physiological level by suppressing the pathological activity of stem structures with therapeutic anesthesia and / or conducting polymodal stimulation on the background small doses of benzodiazepines.

 The method allows to create favorable conditions for the normalization of the bioelectric activity of the brain, the restoration of physiological regulatory functions of the brain, the weakening and destruction of GPUV, and in general to restore neuropsychic activity and improve treatment outcomes of patients with PVA.

Claims (5)

1. A method of treating patients with a persistent vegetative state, including registration of an electroencephalogram (EEG), characterized in that they correct the functional state of the brain by changing its bioelectrical activity, and against the background of EEG registration, therapeutic anesthesia is performed with opioid analgesics and α ₂ -adrenoagonists followed by polymodal stimulation or carry out polymodal stimulation on the background of the introduction of benzodiazepines. 2. The method according to claim 1, characterized in that in the pattern of a hypersynchronized EEG, therapeutic anesthesia is performed. 3. The method according to claim 2, characterized in that therapeutic anesthesia is performed until a stable monotonous flat EEG appears and the stem activity ceases. 4. The method according to PP.2 and 3, characterized in that when the pattern is stable, monotonous flat EEG and the absence of stem activity, polymodal stimulation is performed. 5. The method according to claim 1, characterized in that with the initially monotonous flat EEG, polymodal stimulation is carried out against the background of the administration of benzodiazepines in doses not exceeding the therapeutic effect of midazolam in a dosage of 0.15 mg / kg.

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