Sojourn liquid for inhalation vials, 250ml

Composition

Active ingredient: sevoflurane 100%

Pharmacological action

Pharmacotherapeutic group: means for inhalation Anesthesiicode ATX: N01AB08 Pharmacological properties

Pharmacodynamics

Sevoflurane provides rapid entry into and exit from anesthesia.

The depth of anesthesia can change rapidly depending on changes in the concentration of sevoflurane in the inhaled mixture. Induction of anesthesia with sevoflurane is accompanied by slightly pronounced arousal or minimal signs of irritation of the upper respiratory tract, does not cause excessive secretion in the tracheobronchial tree and stimulation of the central nervous system (CNS). Like other powerful agents for inhalation anesthesia, sevoflurane causes a dose-dependent suppression of respiratory function and a decrease in blood pressure (BP).

In studies in children, it was shown that the occurrence of cough was statistically less common with the use of mask introductory anesthesia with sevoflurane than with halothane. The threshold of arrhythmogenic effect of epinephrine with sevoflurane is the same as with isoflurane and higher than with halothane. The incidence of myocardial ischemia and myocardial infarction in patients with risk factors for these diseases is comparable with the use of sevoflurane and isoflurane.

The effect on blood circulation in the brain (intracranial pressure, cerebral blood flow, cerebral oxygen metabolism, cerebral perfusion pressure) is also comparable for sevoflurane and isoflurane. Sevoflurane has a minimal effect on intracranial pressure and does not reduce the reaction to CO2. Sevoflurane does not affect the concentration function of the kidneys even with prolonged anesthesia (up to about 9 hours).

The minimum alveolar concentration (MAC) is the concentration at which 50% of patients do not have a motor response to a single irritation (skin incision). The results of sevoflurane in different age groups are given in the section “Dosage and use”.

The oxygen content of sevoflurane is 2.05% in a 40-year-old adult.

The effectiveness of sevoflurane, like other halogenated drugs, decreases with age and with the addition of dinitrogen oxide.

Pharmacokinetics

Solubility

The low solubility of sevoflurane in the blood provides a rapid increase in alveolar concentration when administered under general anesthesia and a rapid decrease after stopping inhalation. The ratio of the alveolar concentration at the end of inspiration and the concentration in the inhaled mixture 30 minutes after inhalation of sevoflurane was 0.85. In the elimination phase, the ratio of alveolar concentrations after 5 minutes was 0.15.

Distribution and metabolism

Rapid elimination of sevoflurane from the lungs minimizes the drug’s metabolism. In humans, less than 5% of the absorbed dose of sevoflurane is metabolized by cytochrome P 450 (the CYP2E1 isoenzyme) to hexafluoroisopropanol, releasing inorganic fluoride and carbon dioxide (or one carbon dioxide). The resulting hexafluoroisopropanol is inactive, not genotoxic, quickly combines with glucuronic acid and is excreted from the body by the kidneys, the toxicity is comparable to that of sevoflurane. Other ways of sevoflurane metabolism have not been established. It is the only fluorinated volatile anaesthetic agent that is not metabolized to trifluoroacetic acid.

The concentration of fluoride ions depends on the duration of general anesthesia, the concentration of sevoflurane administered, and the composition of the anesthesia mixture.

Barbiturates do not cause sevoflurane defluorination.

Approximately 7% of adults in whom inorganic fluoride concentrations were measured in clinical trials exceeded 50 mmol / l; no clinically significant changes in renal function were found in any of these patients.

Indications

Introduction and maintenance general anesthesia in adults and children during surgical operations in the hospital and on an outpatient basis.

Use during pregnancy and lactation

Pregnancy In animal reproductive studies, sevoflurane in doses up to 1 MAC had no effect on reproductive function and no damaging effect on the fetus. Studies in pregnant women were not conducted. Sevoflurane can only be used during pregnancy if absolutely necessary. The results of animal studies of certain anesthetics/sedatives indicate their adverse effects on brain development at an early age. Studies in pregnant and young animals suggest that the use of anesthetics and sedatives that block NMDA receptors and / or enhance the effects of GABA, lasting more than 3 hours during the period of rapid brain growth or synaptogenesis, can lead to the destruction of neurons and oligodendrocytes in the developing brain and changes in the morphology of synapses and neurogenesis when using drugs of these groups. These studies included anaesthetics from various drug classes. The clinical significance of these preclinical data is still uncertain. This clinical study demonstrated the safety of sevoflurane for the mother and newborn when used for general anesthesia during cesarean section. The safety of sevoflurane during labor and during delivery through the natural birth canal has not been established. Sevoflurane, like other drugs for inhalation anesthesia, causes relaxation of the uterine musculature, as a result of which there is a potential risk of uterine bleeding. Sevoflurane should be used with caution in obstetric operations. Breast-feeding periodas there is no information on the elimination of sevoflurane in breast milk, women who are breast-feeding should refrain from breastfeeding during the use of the drug for 48 hours after its use.

Contraindications

• Hypersensitivity to sevoflurane or other halogenated drugs (for example, a history of hepatotoxicity associated with the use of these drugs, usually including increased activity of “liver” enzymes, fever, leukocytosis and/or eosinophilia).
• Confirmed or suspected genetic susceptibility to the development of malignant hyperthermia.
• Breast-feeding period.

With caution

• Kidney failure.
• Increased intracranial pressure.
• Neuromuscular diseases.
• Mitochondrial diseases.
• Coronary heart disease.
• Liver function disorders.
• Simultaneous use of drugs that can cause impaired liver function.
• Tendency to develop seizures.
• Use in obstetric operations.
• Tendency to prolong the QT interval and a history of pirouette-type tachycardia.
• Concomitant use with beta-sympathomimetics such as isoprenaline and with alpha – and beta-sympathomimetics such as epinephrine and norepinephrine due to the possible risk of ventricular arrhythmia.
• Simultaneous use with slow calcium channel blockers.

Side effects

From the central nervous system and peripheral nervous system:  agitation, drowsiness after coming out of general anesthesia, dizziness; in some cases, short-term convulsions were observed after using sevoflurane. Although consciousness usually recovers in a few minutes after sevoflurane is stopped, however, the state of intellectual capabilities within 2-3 days after anesthesia has not been studied. Within a few days after using sevoflurane (as well as other drugs for anesthesia), there may be slight changes in mood.

Respiratory system disorders:  dose-dependent respiratory depression, increased coughing, respiratory disorders (apnea after intubation, laryngospasm).

From the cardiovascular system:  dose-dependent cardiac depression, decreased or increased blood pressure, bradycardia, tachycardia.

From the digestive system:  nausea, vomiting, increased salivation; in some cases-transient violations of liver function indicators.

Allergic reactions:  in some cases-rash, urticaria, pruritus, bronchospasm, anaphylactic or anaphylactoid reactions.

From the side of laboratory parameters:  there may be a transient increase in glucose levels and the number of white blood cells.

Other services:  chills, fever.

In predisposed patients, powerful inhaled anesthesia agents, including sevoflurane, can cause a state of skeletal muscle hypermetabolism, which leads to an increase in their oxygen demand and the development of a clinical syndrome known as malignant hyperthermia. The first sign of this syndrome is hypercapnia, and clinical symptoms may include muscle rigidity, tachycardia, tachypnea, cyanosis, arrhythmias, and / or unstable blood pressure. Some of these non-specific symptoms may also occur with light anesthesia, acute hypoxia, hypercapnia, and hypovolemia. Renal failure may develop later (diuresis should be monitored and maintained if possible).

Most adverse reactions are mild or moderate and transient.

Interaction

Benzodiazepines and opioid analgesics are thought to reduce the effectiveness of sevoflurane.

The effectiveness of sevoflurane decreases with the simultaneous use of nitric oxide.

Sevoflurane has an effect on the intensity and duration of neuromuscular blockage caused by non-depolarizing muscle relaxants. When sevoflurane is administered as an adjunct to alfentanil/N2o anesthesia, the effects of pancuronium, vecuronium and atracurium are enhanced. When prescribing these muscle relaxants in combination with sevoflurane, their doses should be adjusted in the same way as in the case of use with isoflurane.The effect of sevoflurane on the effect of succinylcholine and the duration of action of depolarizing muscle relaxants has not been studied.

Since an increase in the effect of muscle relaxants is observed a few minutes after the start of sevoflurane inhalation, a decrease in the dose of muscle relaxants during introductory anesthesia may lead to a delay in tracheal intubation or inadequate muscle relaxation.

Among non-depolarizing drugs, the interaction of sevoflurane with vecuronium, pancuronium and atracurium was studied. Although there are no specific recommendations for their use, however, endotracheal intubation should not reduce the dose of non-depolarizing muscle relaxants; if anesthesia is maintained, the dose of non-depolarizing muscle relaxants should probably be lower than with anesthesiawith N2o / opioid analgesics. Additional doses of muscle relaxants are administered based on the response to nerve stimulation.

How to take, course of use and dosage

Premedication

Means for premedication should be selected by the anesthesiologist individually.

General anesthesia during surgical procedures

During general anesthesia, it is necessary to know the concentration of sevoflurane coming from the evaporator. For precise control of the supplied concentration of sevoflurane, specially calibrated evaporators should be used.

Introduction to general anesthesia

The dose is selected individually and titrated until the desired effect is achieved, taking into account the age and condition of the patient. Before inhaling sevoflurane, a fast-acting barbiturate or other drug for intravenous introductory general anesthesia may be administered. For general anesthesia, sevoflurane can be used in a mixture with oxygen or with oxygen and dinitrogen oxide. Prior to surgery, inhalation of sevoflurane at a concentration of up to 8% usually provides introduction to general anesthesia in less than 2 minutes in both adults and children.

Maintenance general anaesthetismthe required level of general anaesthesia can be maintained by inhaling sevoflurane at a concentration of 0.5-3% in combination with or without dinitrogen oxide.

MAC values for adults and children based on age

* full-Term newborns. MACS in premature newborns were not detected. ** 60% dinitrogen oxide / 40% O2 was used in children aged 1 to 3 years.

The MAC decreases with age. The average concentration of sevoflurane providing MAC in an 80-year-old patient is approximately 50% of that in a 20-year-old patient.

Getting out of general anesthesia

Patients usually recover quickly from general anesthesia with sevoflurane. In this regard, they may require postoperative analgesia earlier.

Overdose

In case of overdose, sevoflurane use should be discontinued, airway patency should be maintained, assisted or controlled ventilation with oxygen should be initiated, and adequate cardiovascular function should be maintained.

Special instructions

Use with caution when renal function is impaired, during neurosurgical interventions, if the patient has a threat of increased intracranial pressure (in combination with measures aimed at reducing intracranial pressure, such as hyperventilation).

Sevoflurane can only be used by doctors who have experience in general anesthesia. It is necessary to have at the ready equipment for restoration of airway patency, artificial ventilation, oxygen therapy and resuscitation.

The level of general anesthesia can change easily and quickly, so only specially calibrated vaporizers should be used to supply sevoflurane. With the deepening of general anesthesia, an increase in arterial hypotension and suppression of respiratory function are noted.

With maintenance anesthesia, an increase in the concentration of sevoflurane causes a dose-dependent decrease in blood pressure. An excessive drop in blood pressure may be associated with deep general anesthesia; in such cases, it can be increased by reducing the concentration of sevoflurane supplied.

As with all general anaesthetic agents, stable hemodynamics should be maintained in patients with CHD in order to avoid myocardial ischemia.

Patients coming out of general anesthesia should be carefully monitored before being transported to the department.

In the treatment of malignant hyperthermia, the withdrawal of drugs that caused its development, intravenous use of dantrolene sodium and maintenance symptomatic therapy are indicated.

Influence on the ability to drive motor vehicles and manage mechanisms

Patients should be advised that their ability to perform work that requires rapid response, such as driving a car or using potentially dangerous machinery, may be impaired for some time after anesthesia.

Storage conditions

Store at a temperature of 15 to 25 °C, in a tightly sealed bottle in an upright position in the original packaging until use. Transportation is allowed at temperatures from 15 to 30 °C. Keep out of reach of children.

The shelf

life for bottles with screw-on lids is 5 years. For vials with a special multi-component capping system – 3 years. Do not use after the expiration date indicated on the package.

Active ingredient

Sevoflurane

Conditions of release from pharmacies

By prescription

Dosage form

inhalation solution