RU2464976C1 - Method of treating patients in vegetative condition - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to intensive therapy and neurology, and deals with treatment of patients in vegetative condition. For this purpose micro-catheter is placed in carotid pool to the level of cavernous part of the most damaged hemisphere of brain or in vertebral-basilar pool to V4 segment in case of presence of signs of post-dislocation affection of brain stem in patients with consequence of craniocerebral injury, as well as in case of diffuse reduction of metabolism by over 60% in patients with consequence of hypoxic affection of brain. Then during 7 days continuous infusion of medications is carried out: successively introduced are neoton 14-20 mg/kg/day, nimotop 0.1-0.2 mg/kg/day, ceraxon 85-100 mg/kg/day, and daily dose is divided for two introductions. Simultaneously infusion of heparin 10000-12000 un/ per day is carried out.

EFFECT: method ensures efficient treatment due to creation of high concentration of medications in area of brain affection in patients with different etiology of vegetative condition.

2 ex

Description

The invention relates to medicine, namely to intensive care of patients with a neurological profile, and can be used in the treatment of patients in a vegetative state.

To date, unified approaches to drug therapy of patients in a vegetative state have not been developed. The lack of a single point of view on the appropriateness of prescribing various neurotransmitter drugs in patients in the vegetative state is due to the fact that the primary damage to the central nervous system leading to the vegetative state is diverse, as well as disruption of the body in the vegetative state (B. Jennett. The vegetative state. Cambridge University Press, 228 p., 2002).

There is a method of treating patients in a vegetative state (RF patent No. 2219929): when a hypersynchronized electroencephalogram is detected, therapeutic anesthesia with opioid analgesics in combination with an α2-adrenoagonist clonidine is performed until a stable monotonic flat electroencephalogram appears, after which polymodal stimulation is performed; when an initially monotonous flat electroencephalogram is detected, polymodal stimulation is carried out against the background of the introduction of benzodiazepines. The disadvantages of the method are: the possibility of treating a limited group of patients with the above-described changes in the electroencephalogram, the possible pronounced sedative effect of benzodiazepines, up to respiratory depression.

Closest to the claimed is a method of treating patients in a vegetative state (Belsky D.V., Belkin A.A., Schegolev A.V., Kondratyev A.N., Kondratyeva E.A. PK-Merz with vegetative status and "small consciousness ”// Prescription: a scientific and practical journal for pharmacists and doctors, Minsk, 2008, No. 5, p.66-70), adopted as a prototype. The method is as follows: PK-Merz (amantadine sulfate) is prescribed: in the first three days from 08:00 to 20:00 intravenously, 2 bottles of 500 ml (200 mg each). From the fourth day, the patient is transferred to the PC-Merz intake orally (100 mg tablets, from 08:00 to 20:00, administration through a probe is possible), on the fourth and tenth days, 2 tablets 2 times a day. Daily dose of 400 mg. 11th-28th day - 1 tablet 2 times a day. Daily dose 200 mg.

However, the prototype is not effective enough, because:

- the drug is administered intravenously and then orally, therefore, by the time it enters the brain, its concentration is significantly reduced,

- the drug used is mainly effective in patients with the consequences of a traumatic brain injury having neuromediator-dopamine insufficiency.

The invention is aimed at creating a method of treating patients in a vegetative state, providing an increase in the concentration of drugs delivered to the brain in patients with various etiologies of the vegetative state.

The specified technical result in the implementation of the invention is achieved by the fact that in the known method of treating patients in a vegetative state by administering a neurotransmitter drug, the peculiarity is that in the carotid pool to the level of the cavernous region of the most affected hemisphere of the brain or in the vertebral-basilar pool to the V4 segment, if signs of post-dislocation damage to the brain stem in patients with a consequence of traumatic brain injury, as well as with a diffuse decrease in metabolism more than 60% in patients with a consequence of hypoxic brain damage establish a microcatheter, then neoton 14-20 mg / kg / day, nimotope 0.1-0.2 mg / kg / day, ceraxon 85-100 mg are continuously administered continuously for seven days / kg / day, and the daily dose is divided into two injections, heparin is simultaneously infused with 10000-12000 units. per day.

Intraarterial administration significantly improves the effectiveness of the drug, since a large circle of blood circulation is passed, which allows you to create the highest concentration of the drug in certain areas of the brain.

The method is as follows. The patient undergoes a full range of examinations, including neuroimaging techniques: CT or MRI, EEG, as well as PET with F-deoxy glucose labeled. A comprehensive assessment of neurological symptoms, CT scans, MRI scans, as well as the severity of metabolic decline according to PET data allows you to choose the vascular pool in which the catheter will be installed. A catheter is inserted into the carotid pool of the most affected cerebral hemisphere. In the presence of signs of post-dislocation damage to the brain stem in patients with a traumatic brain injury, as well as with a diffuse decrease in metabolism of more than 60% in patients with a consequence of hypoxic brain damage, a catheter is placed in a vertebral-basilar pool.

Selective catheterization is performed with a Prowler Plus Select microcatheter for prolonged infusion. An introducer AVANTI + 5F is placed in the right femoral artery. The Envoy 5F transducer is brought into the selected pool — the carotid or vertebral artery — through the conductor. The Prowler Plus Select microcatheter is inserted into the pool of the internal carotid artery to the level of the cavernous region or into the pool of the vertebral artery to the V4 segment. A continuous infusion of drugs is carried out for seven days: neoton is administered sequentially 14-20 mg / kg / day, nimotope 0.1-0.2 mg / kg / day, ceraxon 85-100 mg / kg / day, and the daily dose is divided into two injections, heparin is simultaneously infused 10000-12000 units. per day. On the seventh day, the arterial catheter is removed, the level of glucose metabolism in the brain (PET) is monitored, and the neurological status is assessed over time.

The method was developed and passed clinical trials on the basis of the resuscitation department of FGU RNHI im. A.L. Polenova in the treatment of 27 patients in a vegetative state. At the same time, positive results were obtained in the form of an increase in the degree of glucose metabolism according to PET data and restoration of consciousness in five patients.

We give examples - extracts from medical records.

Example 1

Patient B., 30 years old, and / b No. 301-2010.

The patient was admitted on January 28, 2010 at the RNHI im. A.L. Polenova with a diagnosis of acute carbon monoxide poisoning in the smoke of a severe fire from 12/05/2009, thermochemical damage to the respiratory tract 3 degrees, acute cerebral insufficiency of mixed (toxic, posthypoxic) genesis with the exit to the vegetative state. Concomitant diagnosis: type 1 diabetes mellitus, subcompensation.

From the anamnesis it is known that the patient suffered from a fire. She was admitted to the Janelidze Research Institute 20 hours after an injury with a diagnosis of carbon monoxide poisoning, thermochemical damage to the respiratory tract of grade 3, acute cerebral insufficiency of mixed origin, coma 3, type 1 diabetes mellitus, decompensation.

Upon admission to the Janelidze Research Institute, the condition is extremely serious, on a Glasgow coma scale - 4 points, acute respiratory failure - mechanical ventilation, decompensation of diabetes mellitus - ketoacidosis. SKT dated December 7, 2009 - signs of cerebellar edema, increasing hydrocephalus, pansinusitis.

The coma period was about 14 days, in the future - exit to a vegetative state.

Upon admission to the Federal State Pharmacological Institute, the RNHI is in a stable state, spontaneous breathing, the tracheostomy course has healed, and hemodynamics is stable. He is awake, his gaze practically does not fix, at the request, his gaze does not translate, he does not follow bright objects. He does not perform simple tasks, therefore, against the background of steady wakefulness, there are no signs of self-awareness and the environment - the patient corresponds to the vegetative state. The pupils are equal, with a good reaction to light, the corneal reflexes are preserved, symmetrical, the face is symmetrical, trismus. Swallows a small amount of liquid. Food in the main volume through the probe. Primitive limbic reactions in the form of crying, increasing tone on the mother’s voice. Muscle tone is increased in the flexors of the arms and extensors of the legs up to 2 points on the Ashvoda tone scale, tendon and periosteal reflexes are increased, are caused from dilated reflexogenic zones, Achilles reflexes are increased up to the clonus, Babinsky symptom on both sides.

The survey complex was carried out:

MRI (3 Tesla) with tractography 02/11/2010: a picture of the toxic-hypoxic lesion of the parieto-occipital areas, basal nuclei, mainly the right hemisphere of the brain, cerebellum.

EEG (upon admission): gross diffuse changes in the bioelectrical activity of the brain, which correspond to the residual activity of the cortex outside the influence of the stem structures, during photostimulation - without rearrangements, with the introduction of benzodiazepines, pronounced rearrangements of the pattern with the appearance of fast waves, distinct, prognostically significant rearrangements are absent.

PET with fluorodeoxyglucose 02/10/2010: diffuse glucose hypometabolism in the cerebral cortex, most pronounced in the convexital cortex of the posterior junction of the temporal, parietal, occipital lobes of the right cerebral hemisphere.

Based on data from studies indicating a predominant lesion of the right hemisphere of the brain, a vascular pool for catheter placement was selected. According to the claimed method 02/26/2010 in x-ray was performed superselective catheterization of the right internal carotid artery for prolonged arterial infusion. For seven days, an extended intra-arterial infusion of neurotransmitter drugs was carried out: neotone 15 mg / kg / day, nimotope 0.1 mg / kg / day, ceraxon 90 mg / kg / day, the daily dose was divided into two injections, heparin was introduced in parallel with 10,000 units . per day. The patient tolerated the infusion well.

PET repeated (after intra-arterial infusion 03/10/10 g .: the emerging positive dynamics of diffuse disorders of energy metabolism.

When monitoring EEG 14 days after intra-arterial infusion: a clear response to photostimulation.

Within a month after the intra-arterial infusion, there was a positive trend: it fixes the gaze, translates it at the request, does not pronounce the words, but tries to move its lips, removes the eyeballs to the right and left, eye slits OD≤OS, pupils OD≥OS, live photoreactions, smoothed right nasolabial fold, swallows, stereotyped chewing automatisms, positive proboscis and palmar-chin reflexes, does not perform tasks. Thus, a clear positive dynamics was achieved in neurological symptoms in the form of increased contact with the patient, exit from the vegetative state - the appearance of signs of consciousness corresponding to the state of small consciousness.

Example 2

Patient Ch., 46 years old, and / b 2104-2010.

Diagnosis: acute brain injury, severe brain contusion with compression of the right hemisphere of the brain with an acute subdural hematoma. Traumatic subdural hemorrhage. Transverse fracture of the pyramid of the left temporal bone, linear fracture of the occipital bone on the left. Vegetative state.

Anamnesis of the disease: injured on June 14, 2010, on June 14, 2010 according to emergency indications an operation was performed: DKPT of the skull in the right temporoparietal region, removal of acute subdural hematoma. The patient was in the Department of Anesthesiology and Resuscitation of VMA from June 16, 2010 to 26.07 .2010 g.

Upon admission to the FGU RNHI: awake, does not fix the gaze, does not perform tasks, the level of consciousness meets the international criteria for the diagnosis of a vegetative state. Tetraplegia, pseudobulbar disorders.

Brain MRI from 07/06/2010: signs of post-traumatic contusion foci in the subconvexital sections of the frontal and temporal lobes, diffuse focal concussion-ischemic areas in the basal nuclei, in the area of the corpus callosum, in the legs of the brain and in the area of the warolian bridge, lysing subdural hematoma along the convexital and interhemispheric surface of the brain.

EEG data indicate a dysfunction of the stem structures, mainly the oral part of the trunk: diencephalic (thalamic) and some predominance of synchronizing mesencephalic structures. Decreased neurodynamics of the cortex, including post-dislocation genesis, in the posterior parts of both hemispheres.

Given the presence of post-dislocation lesions of the brain stem: brain legs, varolium bridge, a vertebral-basilar pool was chosen for intra-arterial infusion. According to the claimed method, a catheter was installed in the right vertebral artery, intra-arterial infusion was carried out for seven days: successively neoton 20 mg / kg / day, nimotope 0.1 mg / kg / day, ceraxon 95 mg / kg / day, the daily dose was divided for two injections, heparin was simultaneously administered 12000 units. per day. 19 days after arterial infusion, a restoration of consciousness was noted (clearly fixes the gaze, performing simple tasks - shows the tongue, shakes hands). Considering the fact that no neurological status was observed in the previous neurotransmitter therapy using intravenous, tablet forms, it was the intra-arterial infusion of neurotransmitter drugs that significantly accelerated and strengthened the sanogenetic mechanisms that help restore consciousness in this patient.

Claims (1)

A method of treating patients in a vegetative state by administering a neurotransmitter drug, characterized in that in the carotid pool to the level of the cavernous region of the most affected hemisphere of the brain or in the vertebral-basilar pool to the V4 segment in the presence of signs of post-dislocation damage to the brain stem in patients with a consequence of craniocerebral trauma, as well as with a diffuse decrease in metabolism of more than 60% in patients with a consequence of hypoxic brain damage, establish a microcatheter, then for For 7 days, a continuous infusion of drugs is carried out: neotone is administered sequentially 14-20 mg / kg / day, nimotope 0.1-0.2 mg / kg / day, ceraxon 85-100 mg / kg / day, and the daily dose is divided for two injections, heparin is simultaneously infused with 10000-12000 units. per day.