Muscle relaxants are medications that relax the human striated muscles. Muscle relaxants are drugs that reduce the tone of skeletal muscles, thereby reducing a person’s motor activity, up to complete immobilization. Until a certain time, they were widely used exclusively in anesthesiological practice to relieve muscle tone during operations. Today, the scope of use of muscle relaxants in medicine and aesthetic cosmetology has expanded significantly.
Types of muscle relaxants
Based on the mechanism of action, there are two main types of muscle relaxants:
Central muscle relaxants are drugs that inhibit the central structures of muscle tone. These chemicals have a direct effect on the parts of the central nervous system, brain and spinal cord that are involved in the regulation of muscle tone. Peripheral muscle relaxants are agents that penetrate into direct neuromuscular transmission. These medications relax voluntary muscles by blocking the signal from the motor nerve to the muscle.
Proserinum
Subcutaneously and intravenously.
Adults are usually prescribed 0.5 mg (1 ml of solution) under the skin 1-2 times a day.
In the treatment of myasthenia gravis, Prozerin can be prescribed in combination with aldosterone antagonists. Treatment of myasthenia gravis is long-term. With the development of myasthenic crisis in adults, 0.5 - 1 ml of solution is administered intravenously (with 0.9% sodium chloride solution), then subcutaneously in regular doses at short intervals. To enhance the effect of Prozerin, additional ephedrine is sometimes injected under the skin - 1 ml of a 5% solution. For other diseases, the duration of treatment is 25-30 days; if necessary, the course of treatment is repeated after a 3-4 week break.
To stimulate labor, 0.5 mg (1 ml of solution) can be injected under the skin 1-2 times at intervals of 1 hour; simultaneously with the first injection, 1 mg (1 ml of 0.1% solution) of atropine can be injected once under the skin.
To stop the effect of muscle relaxants, atropine sulfate is first administered intravenously at a dose of 0.5-0.7 mg (0.5-0.7 ml of a 0.1% solution), wait for an increase in heart rate and after 1.5-2 minutes it is administered intravenously 1. 5 mg (3 ml solution) Proserin. If the effect of this dose turned out to be insufficient, the same dose is re-administered (if bradycardia appears, an additional injection of atropine is given). A total of 5-6 mg (10-12 ml of solution) of Prozerin can be administered over 20-30 minutes. During the procedure, ensure adequate ventilation.
Children are prescribed 0.05 mg (0.1 ml of solution) under the skin for 1 year of life, but not more than 0.75 ml of 0.05% solution per injection. Typically, children are prescribed Proserin once a day, but if necessary, the daily dose of the drug can be divided into 2-3 doses. Side effect
Hypersalivation; spastic contraction and increased intestinal motility; nausea; vomit; flatulence; diarrhea; headache; dizziness; weakness; loss of consciousness; drowsiness; miosis; visual impairment; arrhythmias; brady- or tachycardia; atrioventricular block; nodal rhythm; nonspecific changes in the electrocardiogram; heart failure; decreased blood pressure; dyspnea; respiratory depression to the point of stopping; bronchospasm; tremor; spasms and twitching of skeletal muscles, including fasciculations of the tongue muscles, convulsions; dysarthria; arthralgia; increased urination; profuse sweating; allergic reactions (facial redness, rash, itching, anaphylaxis).
To relieve side effects, reduce the dose or stop using the drug; if necessary, administer atropine (1 ml of 0.1% solution), methocinium iodide or other anticholinergic drugs.
Principle of action and scope of application of muscle relaxants
Based on their chemical structure, centrally acting muscle relaxants can be divided as follows:
- Glycerol derivatives - Meprotan, Isoprotan, Prenderol and others.
- Benzimidazole derivatives – Flexin and so on.
- A group of mixed muscle relaxants - Mydocalm, Baclofen, Fenaglycodol and others.
Central muscle relaxants block polysynaptic reflexes by inhibiting the activity of interneurons of the spinal cord, while they have virtually no effect on monosynaptic reflex actions. Along with the central relaxing effect, muscle relaxants are also endowed with other types of effects, due to which they are widely used in medical practice:
- in neurology for diseases accompanied by increased muscle tone;
- for diseases with impaired motor activity of patients;
- in surgery to relax the abdominal muscles;
- for complex hardware diagnostics of certain diseases;
- during electroconvulsive therapy;
- in anesthesiology without stopping natural breathing;
- for the prevention of post-traumatic complications and so on.
Peripheral muscle relaxants are divided into:
- Non-depolarizing - Arduan, Tubocurarine chloride, Mellictin, Pipecuronium, Diplacin and others.
- Depolarizing - Ditilin and so on.
- Mixed muscle relaxants - Dixonium and many others.
All of them have an effect on the cholinergic receptors of skeletal muscles, so they are used for local relaxation of muscle tissue, as well as reducing pain and muscle spasms. They gently relieve muscle tone during microsurgical interventions and reposition of bone fragments, and facilitate tracheal intubation. Muscle relaxants with a peripheral mechanism of action create conditions for immobilization during straightening of dislocations and in drug therapy for sprains, during endoscopic manipulations and artificial hypothermia.
Summary. We analyzed the causes and timing of hospital mortality in acute oral poisoning with karbofos. It has been established that in the toxicogenic stage of intoxication, mortality is mainly caused by exotoxic shock, coma with cerebral edema and central respiratory paralysis, and in the somatogenic stage - by infectious complications, mainly pulmonary. After the first day of intoxication, more than 90% of deaths develop against the background of severe neuromyopathy, which is not the direct cause of death, but contributes to serious impairment of vital functions. The use of relaxing doses of antidepolarizing muscle relaxants in the complex treatment of karbofos poisoning significantly reduces the severity of toxic neuromyopathy, which is manifested by a more rapid restoration of muscle strength, a decrease in the frequency and duration of peripheral respiratory paralysis, a decrease in the average length of bed time and mortality. Keywords:
acute poisoning, treatment, karbofos, organophosphate insecticides, neuromyopathy, peripheral respiratory paralysis, muscle relaxants.
INTRODUCTION
Acute poisonings with organophosphate insecticides (OPIs) remain one of the pressing problems of clinical toxicology, despite the fact that their number has noticeably decreased in recent decades. Their significance is determined by the severity of intoxication and high mortality. So, according to E.A. Luzhnikov’s hospital mortality rate for these poisonings is 20–24% [7]. In case of severe poisoning, even with the use of modern treatment methods (efferent detoxification, complex antidote and pathogenetic therapy), it can reach 30 - 50 or more [7].
One of the obligate manifestations of severe FOI poisoning is toxic neuromyopathy (NMP), which clinically in the early stages of intoxication (days 1 - 2) is manifested by widespread spontaneous and provoked myofibrillations, choreotic hyperkinesis and muscle rigidity (phase I), later replaced by progressive weakness , paresis and paralysis of skeletal muscles (phase II) [6,14,18]. The most significant neuromuscular disorders are paresis or paralysis of the respiratory muscles (RPM) - peripheral respiratory paralysis [1,5,12]. It is distinguished from early, central paralysis by its gradual development through the stage of tachypnea, late periods (from the end of the first to 7-10 days) of occurrence, against the background of preserved consciousness and diffuse NMP, as well as a duration usually ranging from several to 14 days (and in in some cases - up to 1.5 - 2 months), requiring equally long-term artificial ventilation [8,19]. Prognostically unfavorable for the development of PDM are such early symptoms as the patient’s inability at the end of the first - beginning of the second day to keep his head elevated above the pillow for more than 10 seconds, to sit up in bed without using his hands, and a significant decrease in carpal dynamometry indicators [6].
With all the diversity of opinions about the causes of neuromuscular disorders caused by FOI, the prevailing idea is that the leading ones are cholinomimetic effects with the development of a persistent depolarization block [9,10,17]. Its long-term existence leads to significant (even necrosis) damage to the neuromuscular plate [3,4,16,18].
The main means that can eliminate a neuromuscular block are considered to be cholinesterase reactivators (ChE), and the use of these drugs is justified even when a noticeable restoration of enzyme activity does not occur based on other mechanisms of their action (binding of poison, protection of cholinergic synapses, etc.) [2,18]. Unfortunately, in contrast to the experimental results, the results of the clinical use of ChE reactivators are much more modest - in severe intoxications, they only somewhat alleviate neuromuscular disorders.
It is also important to eliminate potassium deficiency, which is characteristic of severe FOI intoxications; however, intensive use of its drugs, although it reduces the incidence of neuromuscular disorders, does not prevent PDM [11].
The lack of reliable means of influencing neuromuscular disorders served as the basis for studying the possibility of using antidepolarizing (competitive) muscle relaxants in complex therapy, which are capable, judging by the mechanism of their action, of preventing excessive cholinomimetic effects on the neuromuscular junction [13].
The purpose of our study was, on the one hand, to study the effect of NMP on the outcomes of FOI intoxication, and on the other hand, the feasibility of using antidepolarizing muscle relaxants as a means of treating toxic neuromyopathy in severe karbofos poisoning.
MATERIALS AND METHODS
At the first stage, a retrospective analysis of medical records and autopsy reports of 87 patients who died as a result of severe forms of acute oral poisoning with karbofos was carried out to establish the timing and causes of deaths.
The second stage of the clinical study included the results of examination and treatment of 45 patients aged from 21 to 68 years (32 men, 13 women) who were treated in the intensive care unit of the military field therapy clinic of the Military Medical Academy and the Interregional Center for the Treatment of Poisons Research Institute SP named after I.I. Dzhanelidze regarding acute poisoning with severe and extremely severe karbofos. Patients with severe concomitant somatic pathology were excluded from the study.
Upon admission, patients were divided into two groups: the first (comparison) - (20) received standard therapy, the second (25) in addition to standard therapy, used antidepolarizing muscle relaxants. In the first three patients, d-tubocurarine (tubarin) was used; however, later, given its ability to cause ganglion block and histamine release, arduan (pipecuronium), which does not have these disadvantages, was used. The drugs were administered in low (relaxing) doses (tubarin - 0.1 mg/kg, ardouane - 0.01 - 0.015 mg/kg), which did not cause respiratory arrest. The appropriate dose was dissolved in 250 - 500 ml of physiological solution, and the infusion was carried out intravenously. The indications for the use of muscle relaxants were widespread spontaneous and provoked myofibrillations in severe forms of poisoning. The drugs were administered until the provoked fibrillations stopped; if they relapsed, the injection was repeated in the same or half dose. On the first day, 2 injections were usually carried out, on the second day they were limited (in the presence of myofibrillations) to a single infusion.
Patients in these groups did not differ significantly in gender, age, severity of condition, volume and timing of medical care at the prehospital stage.
In both groups, standard treatment was carried out - tube gastric lavage, enterosorption, administration of antidotes (anticholinergics and cholinesterase reactivators), hemosorption, infusion therapy using glucose-saline solutions, plasma substitutes, high doses of potassium, etc., as well as other pathogenetic and symptomatic activities according to indications.
The dynamics of clinical parameters were recorded, as well as the presence of PDM in patients, the duration of mechanical ventilation during PDM, the increase in carpal dynamometry indicators, blood plasma ChE activity, main biochemical parameters, the average bed-day of those recovered, course doses of antidotes, and the number of deaths.
The diagnosis of poisoning was verified by a chemical-toxicological study of biological media (gas chromatography method).
Statistical processing of data was carried out using Student's T test.
RESULTS AND ITS DISCUSSION.
When analyzing the timing of hospital mortality in those poisoned with karbofos, it was found that in the toxicogenic stage of intoxication (the first 48 hours), an unfavorable outcome was recorded in 39.1%, while in the somatogenic stage this figure was 60.9%. Analysis of the causes of deaths allows us to say that in the toxicogenic phase it was mainly caused by exotoxic shock, coma with cerebral edema and central respiratory paralysis, and in the somatogenic phase, infectious complications, mainly pulmonary, came first (Table 1) . At the same time, it should be noted that the vast majority (more than 90%) of deaths later than the first day of intoxication developed against the background of severe neuromyopathy, which was not the direct cause of death (due to mechanical ventilation), but contributed to serious impairment of vital functions.
The results obtained when using relaxing doses of competitive muscle relaxants in the complex therapy of karbofos poisoning allow us to give a positive assessment of these drugs. Thus, in the group receiving Arduan (Table 2), two deaths were observed (as a result of coma and exotoxic shock), while in the second there were 7 such outcomes (3 in the toxicogenic and 4 in the somatogenic stage; p
Below is a clinical illustration indicating the advisability of further studying the effectiveness of competitive muscle relaxants in FOI poisoning.
Patient V., 27 years old, drank 150 ml of a concentrated solution of karbofos with suicidal intent. Discovered by relatives approximately 7 - 8 hours after taking the poison. The emergency doctor assessed the patient's condition as terminal: deep coma, hoarse, rare breathing, areflexia, pinpoint pupils, diffuse cyanosis, pulse and blood pressure in the peripheral arteries are not determined, widespread spontaneous myofibrillations, vomit and feces with a strong odor of karbofos. The trachea was intubated, a large amount of mucus and gastric contents with the smell of poison were removed from it. Mechanical ventilation was started, intravenous administration of 30.0 ml of 0.1% atropine solution, 450 mg of dipyroxime, 400.0 ml of rheopolyglucin, 100 ml of 0.5% dopmin, 60 mg of dexazone and 250 mg of hydrocortisone, and gastric tube lavage was performed.
Upon admission to the clinic (9 hours after taking the poison), the condition was extremely serious. Coma with loss of pain sensitivity, corneal reflexes are sharply weakened, tendon reflexes, and cough are not evoked. Pupils 3 mm, without photoreaction. There are no pathological reflexes or meningeal symptoms. Muscle tremors, diffuse spontaneous myofibrillations. Skin marbling, hyperhidrosis, acrocyanosis. Pulse 120 per minute, rhythmic, blood pressure 80 - 90/50 mm. Hg Art. The boundaries of the heart are not changed, the sounds are dull. He is on a ventilator. A significant amount of dry rales are heard over the lungs. The abdomen is soft, the liver and spleen are not enlarged. The ECG shows sinus tachycardia, signs of hypokalemia. Serum ChE activity is 6.3 µmol/s*l (normal 45 + 5 µmol/s*l). Diagnosis: acute oral poisoning with extremely severe karbofos, encephalopathy of mixed origin, cerebral edema, central respiratory paralysis, prehospital aspiration, bronchospastic syndrome, DN - stage III, mechanical ventilation; exotoxic shock stage II, toxic neuromyopathy, stage I, gastrointestinal syndrome.
The clinic continued mechanical ventilation, repeated tube gastric lavage, sanitation bronchoscopy, enterosorption, started infusion therapy, including glucose-saline solutions, plasma substitutes, glucocorticoids, antidotes (atropine for the first day in the hospital 80 mg, dipyroxime 900 mg), camemium chloride (15 g.), piracetam, heparin, antibiotics, etc.; after hemodynamic stabilization, a hemosorption operation was performed (SKN-2K sorbent, perfusion rate 120 - 150 ml/min, volume - 60 l). After hemosorption, the depth of the coma decreased somewhat, reflexes quickened, the patient was transferred to mechanical ventilation in the SIMV mode, but diffuse myofibrillations remained. The patient was administered 2 mg of Arduan, after which twitching of the skeletal muscles and chest rigidity disappeared. After 2 hours, consciousness and adequate spontaneous breathing were restored (26 min.). Carpal dynamometry: right - 12, left - 10 kg. 3 hours after the administration of Ardoin, spontaneous myofibrillations appeared again. 2 mg of Arduan was reintroduced. Myofibrillations have been eliminated. However, soon the patient's shortness of breath increased (up to 40 per minute), cyanosis appeared, which was the basis for resuming mechanical ventilation. Mechanical breathing lasted about three hours, then independent adequate ventilation was restored.
By the end of the second day the patient was extubated. Antidote therapy with atropine and measures to prevent infectious complications were continued. Muscle strength increased quickly. On the 3rd day, he holds his head for 15 - 20 seconds; on the 5th day he sits up in bed independently, stands up, hand dynamometry: right - 27, left - 26 kg. The further course of the disease was determined by asthenic syndrome, symptoms of tracheobronchitis and myocardial dystrophy. He was discharged on the 16th day in satisfactory condition. In total, 325 mg of atropine and 2.4 g of dipyroxime were used during the treatment.
The peculiarity of this observation is that intoxication caused by a multiple lethal dose of poison, complicated by aspiration during late provision of medical care, initially proceeded as extremely severe, accompanied by the development of coma, central respiratory paralysis, exotoxic shock, but later, under the influence of complex therapy, including, along with traditional measures, prolonged administration of Ardoin, peripheral respiratory paralysis was short-term, the symptoms of NMP quickly regressed and the poisoning did not lead to the development of pneumonia, typical for such forms of intoxication.
The mitigation of the manifestations of NMP under the influence of competitive muscle relaxants speaks in favor of the point of view according to which it is the cholinomimetic effect of organophosphorus compounds that causes the development of not only the first, but also contributes to the formation of the second phase of neuromuscular disorders. In our opinion, prolonged administration of the drug is especially important, since competitive muscle relaxants act for a short time. The prospects for studying the problem are connected, in our opinion, with the further accumulation of factual material, development of optimal dosages and regimens of use, early introduction of these drugs, starting from the prehospital stage (by specialized toxicological ambulance teams), as well as with the study of other pharmacological agents (magnesium preparations, calcium, actoprotectors, etc.) capable of influencing the state of neuromuscular conduction and the function of skeletal muscles in case of poisoning with organophosphorus compounds.
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Possible effects of muscle relaxants
Having a significant effect on the central nervous system, muscle relaxants can cause the following consequences for human health and well-being:
- lethargy and apathy;
- drowsiness;
- dizziness;
- nausea and vomiting;
- headache;
- arterial hypotension;
- muscle microdamage;
- convulsions and so on.
Long-term use of muscle relaxants leads to addiction and drug dependence on them. This group of medications is not recommended for use by persons whose occupation is associated with concentration and high reaction, as well as by children and adolescents.
Muscle relaxants should be used only as prescribed by a doctor, with great caution in the presence of contraindications and intolerance to certain components, as well as in chronic and severe diseases. Assessing the effectiveness of these drugs, interactions with other drugs and adjusting their doses should also be carried out by a qualified medical specialist.
Proper administration of muscle relaxants reduces the risk of possible consequences for the human body. Due to the frequent complications of these drugs, short-acting muscle relaxant drugs are predominantly used in clinical practice.
Rocuronium
Rocuronium bromide is administered intravenously either as a bolus injection or as a continuous infusion (see “Compatibility when mixed with other medicinal products”).
As with the use of other muscle relaxants, rocuronium bromide should only be administered by or under the supervision of experienced clinicians who are familiar with the effects of muscle relaxants.
The dose of rocuronium bromide, as in the case of other muscle relaxants, must be selected individually for each patient. When selecting the dose, the method of anesthesia and the expected duration of the operation, the method of sedation and the expected duration of mechanical ventilation, possible interactions with other co-prescribed drugs, and the general condition of the patient should be taken into account.
To assess the degree of neuromuscular block and restoration of neuromuscular conduction, it is recommended to use appropriate neuromuscular monitoring methods.
Inhalational anesthetics enhance the neuromuscular block caused by rocuronium bromide. This enhancement, however, becomes clinically significant only when, during general anesthesia, the concentration of volatile substances in tissues reaches a level sufficient for such an interaction. Therefore, dose adjustment of rocuronium bromide should be done by administering lower maintenance doses at longer intervals or by using lower infusion rates of rocuronium bromide during long (more than 1 hour) procedures performed under inhalation anesthesia (see Interactions with Other Drugs). drugs and other forms of interactions").
Risk of medical errors:
Accidental administration of neuromuscular blocking drugs may result in serious adverse reactions, including death.
In adult patients, the following doses may be recommended as a general guideline for endotracheal intubation and to provide muscle relaxation during operations of varying durations and for use in the intensive care unit.
During surgical interventions
Endotracheal intubation
The standard dose of rocuronium bromide for endotracheal intubation during routine anesthesia is 0.6 mg/kg, after which adequate conditions for tracheal intubation develop in approximately 60 seconds in most patients.
When performing rapid sequential induction of anesthesia to facilitate tracheal intubation, the recommended dose is 1.0 mg/kg rocuronium bromide. In this case, adequate conditions for tracheal intubation develop within 60 seconds in almost all patients.
When using a dose of 0.6 mg/kg rocuronium bromide for rapid sequential induction of anesthesia, it is recommended to intubate the patient's trachea 90 seconds after administration of the drug.
Information regarding the use of rocuronium bromide during rapid sequence induction of anesthesia in patients undergoing cesarean section is listed in the section "Use in Pregnancy and Lactation."
High doses
The choice of a higher dose must be justified for each individual patient. It was noted that the introduction of initial doses of up to 2 mg/kg of rocuronium bromide during surgical operations occurred without side effects from the cardiovascular system. The use of these doses of rocuronium bromide reduces the time of onset of its action and increases the duration of action (see section "Pharmacodynamics").
Maintenance doses
The recommended maintenance dose is 0.15 mg/kg rocuronium bromide; in case of long-term inhalation anesthesia it should be reduced to 0.075-0.1 mg/kg. Maintenance doses are best administered when the amplitude of muscle contractions has recovered to 25% of the control level or when 2-3 responses appear during TOF monitoring.
Continuous infusion
If rocuronium bromide is administered by continuous infusion, it is recommended to start with a loading dose of 0.6 mg/kg rocuronium bromide and begin the infusion when neuromuscular conduction begins to recover. The infusion rate should be adjusted to maintain skeletal muscle contractile responses at 10% of control levels or to maintain 1-2 responses when monitored in TOF mode. In adults, with intravenous general anesthesia, the infusion rate required to maintain the neuromuscular block at this level is 0.3-0.6 mg/kg/h, and with inhalation anesthesia 0.3-0.4 mg/kg/ h. Continuous monitoring of neuromuscular conduction is recommended as the required infusion rate may vary depending on the individual patient and different anesthetic techniques.
Children
For children from 1 month of age, the recommended dose for intubation during normal anesthesia (0.6 mg/kg rocuronium bromide) and maintenance dose (0.15 mg/kg rocuronium bromide) are the same as for adults.
For pediatric continuous infusion, the infusion rate is the same as for adults (0.3-0.6 mg/kg/h), except for children (2-11 years) who may require higher infusion rates. The initial infusion rate for children is the same as for adults (0.3-0.6 mg/kg/h). Already during the procedure, the speed should be adjusted in order to maintain the amplitude of muscle contractions at a level of 10% of the control amplitude or the presence of 1-2 responses when monitoring in the four-discharge stimulation mode (TOF). There is currently insufficient data on the use of rocuronium bromide in newborns (0-1 months).
Experience with the use of rocuronium bromide during rapid sequence induction of anesthesia in children is limited. Therefore, rocuronium bromide is not recommended to facilitate tracheal intubation during rapid sequence induction of anesthesia in children.
Elderly patients and patients with liver and/or biliary tract diseases and/or renal failure
The standard intubation dose for elderly patients and patients with diseases of the liver and/or biliary tract, and/or in the presence of renal failure, during normal anesthesia is 0.6 mg/kg rocuronium bromide. When performing a rapid sequence induction procedure in patients with an expected prolonged duration of action of the muscle relaxant, a dose of 0.6 mg/kg rocuronium bromide is recommended.
Regardless of the administration technique, the recommended maintenance dose for these patients is 0.075-0.1 mg/kg rocuronium bromide; the recommended infusion rate is 0.3-0.4 mg/kg/h (See also “Continuous infusion”).
Overweight and obese patients
When using the drug in patients with overweight or obesity (these are considered patients whose body mass index is more than 30), the dose of rocuronium bromide should be reduced, calculating them based on body mass index values that are normal for a given age and gender.
Use in the intensive care unit
Tracheal intubation
Doses are similar to those for surgical interventions.
Maintenance doses
It is recommended to start with a dose of 0.6 mg/kg rocuronium bromide, followed by a transition to a continuous infusion of the drug when neuromuscular conduction is restored to 10% of the initial level or 1-2 responses are received when stimulated in TOF mode. Doses of rocuronium bromide should be adjusted individually depending on the effect.
The recommended initial infusion rate to maintain neuromuscular block at 80-90% (1-2 responses with TOF stimulation) in adult patients is 0.3-0.6 mg/kg/h during the first hour of administration, after Therefore, over the course of 6-12 hours, it is necessary to reduce the infusion rate, in accordance with the individual reaction of the patient. After this, individual dosage requirements remain relatively constant.
Controlled clinical studies have shown significant interindividual variability in hourly infusion rate with a mean of 0.2-0.5 mg/kg/h depending on the cause and extent of organ dysfunction(s), concomitant drug treatment and individual patient characteristics. . Continuous monitoring of neuromuscular conduction is strongly recommended to ensure optimal control of each patient. Administration of the drug for up to 7 days has been studied.
Special patient groups
Rocuronium bromide is not recommended for use to facilitate mechanical ventilation in the intensive care unit in children and elderly patients due to the lack of data on the safety and effectiveness of the drug in these groups of patients.