Sevofluran-Vial (Sevoflurane-Vial)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceSevofluraneSevoflurane
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    • Dosage form: & nbspFfluid for inhalation.
    Composition:

    Active substance: sevoflurane - 100%.

    Description:

    Transparent, colorless, easily mobile liquid.

    Pharmacotherapeutic group:inhalation anesthetic
    ATX: & nbsp

    N.01.A.B   Halogenated hydrocarbons

    N.01.A.B.08   Sevoflurane

    Pharmacodynamics:

    Sevoflurane provides a quick introduction to anesthesia and rapid exit from it. The depth of anesthesia can change rapidly depending on the change in the concentration of sevoflurane in the inhaled mixture.

    The induction of anesthesia with sevoflurane is accompanied by a slightly pronounced excitation 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. 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 frequent with the use of masked introductory anesthesia with sevoflurane than with halothane.

    The threshold of arrhythmogenic effect of epinephrine with the use of sevoflurane is the same as with isoflurane and higher than with halothane.

    The occurrence of myocardial ischemia and myocardial infarction in patients with the risk factors of these diseases is comparable with the use of sevoflurane and isoflurane.

    Influence on blood circulation in the brain (intracranial pressure, cerebral blood flow, cerebral oxygen metabolism, cerebral perfusion pressure) is also comparable in sevoflurane and isoflurane. Sevoflurane has a minimal effect on intracranial pressure and does not reduce the reaction to CO2.

    Sevoflurane affects 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 reaction in response to a standard stimulus (incision of the skin). MAK for sevoflurane decreases with increasing age of the patient, and also with the introduction of dinitrogen oxide (nitrous oxide) (see Table 1). MAQ of sevoflurane in oxygen is 2.05% for a 40-year-old adult.

    Pharmacokinetics:

    Solubility

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

    Distribution and Metabolism

    The rapid removal of sevoflurane from the lungs minimizes the metabolism of the drug. In humans less than 5% of the absorbed dose of sevoflurane is metabolized by cytochrome P450 (isoenzyme CYP2E1) into hexafluoroisopropanol with the release of inorganic fluorine and carbon dioxide (or one carbon dioxide). The resulting hexafluoroisopropanol is not active, not genotoxic, rapidly combines with glucuronic acid and is excreted from the body by the kidneys, the toxicity is comparable to the toxicity of sevoflurane. Other ways of metabolism of sevoflurane are not established. It is the only fluorinated volatile agent for anesthesia, 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 mixture for anesthesia.

    Barbiturates do not cause defluorination of sevoflurane.

    Approximately 7% of adults who had in clinical studies measured concentrations of inorganic fluoride, they exceeded 50 μmol / l; clinically significant changes in kidney function in none of these patients have not been identified.

    Indications:

    Sevoflurane is indicated as an inhalant for the administration and / or maintenance of general anesthesia for surgical intervention in inpatient and outpatient settings in adults and children.

    Contraindications:

    - Hypersensitivity to sevoflurane or other halogenated drugs (eg history of associated 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;

    - the period of breastfeeding.

    Carefully:

    - Renal failure;

    - increased intracranial pressure;

    - neuromuscular diseases;

    - mitochondrial diseases;

    - cardiac ischemia;

    - impaired liver function;

    - simultaneous use of drugs that can cause damage to liver function;

    - tendency to develop seizures;

    - application in obstetrical operations;

    - tendency to lengthen the interval QT and tachycardia of the "pirouette" type in the anamnesis;

    - simultaneous use with β-sympathomimetics, such as isoprenaline, and with α- and β-sympathomimetics, such as epinephrine and norepinephrine, because of the possible risk of ventricular arrhythmia;

    - simultaneous application with blockers of "slow calcium channels".

    Pregnancy and lactation:

    Pregnancy

    In reproductive studies in animals sevoflurane in doses up to 1 MAK did not affect the reproductive function and damaging effects on the fetus. Studies in pregnant women have not been conducted. Sevoflurane can be used in pregnancy only if the potential benefit to the mother justifies the possible risk to the fetus.

    Since there is no information on the excretion of sevoflurane with breast milk, women breastfeeding,should refrain from breastfeeding during the use of the drug and within 48 hours after its use.

    Childbirth

    The clinical study demonstrated the safety of sevoflurane for the mother and newborn when used for general anesthesia in cesarean section. The safety of sevoflurane during labor and delivery is not established through the natural birth canal. Sevoflurane, like other drugs for inhalation anesthesia, causes relaxation of the musculature of the uterus, as a result of which there is a potential risk of uterine bleeding.

    In obstetrical operations sevoflurane should be used with caution.

    Dosing and Administration:

    Inhalation.

    Premedication

    Means for premedication should be selected by an anesthesiologist individually.

    General anesthesia during surgical interventions

    During general anesthesia, it is necessary to know the concentration of sevoflurane coming from the evaporator. To maintain the accuracy of the drug concentration, specially designed evaporators calibrated for sevoflurane should be used.

    Table 1.MAK sevoflurane depending on the patient's age

    Age of the patient (years)

    Sevoflurane (%) in oxygen

    Sevoflurane (%) in 65% N2O / 35% O2

    0-1 month *

    3,3

    No data

    1- <6 months

    3,0

    No data

    6 months - <3 years

    2,8

    2,0**

    3-12

    2,5

    No data

    25

    2,6

    1,4

    40

    2,1

    1,1

    60

    1,7

    0,9

    80

    1,4

    0,7

    * Post-war newborns. MAC in preterm neonates is not defined

    ** in patients aged one to three years 60%N2O / 40% O2

    Introduction to general anesthesia

    It is possible to use short-acting barbiturates or other drugs for intravenous anesthesia with subsequent inhalation administration of sevoflurane. The dose of sevoflurane is selected individually and titrated until the desired effect is achieved, taking into account the age and condition of the patient.

    For administration to general anesthesia sevoflurane can be used in a mixture with oxygen or with oxygen and dinitrogen oxide. Before surgery, inhalation of sevoflurane at a concentration of up to 8% usually provides an introduction to general anesthesia in less than 2 minutes in both adults and children.

    Maintaining general anesthesia

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

    Use in elderly patients

    With age, the MAC decreases.The average concentration of sevoflurane providing the MAK of a patient aged 80 years is approximately 50% of that of a patient aged 20 years.

    Exit from general anesthesia

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

    Side effects:

    Like all powerful drugs for inhalation anesthesia, sevoflurane can cause dose-dependent suppression of heart and respiratory function. Most adverse reactions are mild or moderate and transient. Often after surgery and general anesthesia, nausea, vomiting and delirium are noted, which may be associated with inhalational anesthetics, other drugs prescribed intraoperatively or in the postoperative period, as well as with the patient's response to surgical intervention.

    The most frequent adverse reactions were:

    - in adult patients: lowering blood pressure, nausea, vomiting;

    - in elderly patients: bradycardia, decreased arterial pressure, nausea;

    - in patients of childhood: agitation, cough, nausea and vomiting.

    Undesirable reactions, possibly associated with the use of sevoflurane, are reflected with the distribution according to organ systems and the incidence of: Often (≥1/10), often (≥1/100 - <1/10), infrequently (≥1/1000 - <1/100), unknown (the frequency is unknown).

    Immune system disorders: unknown - anaphylactic reactions **, pseudo-anaphylactic reactions, hypersensitivity.

    Disorders from the metabolism and nutrition: unknown - hyperkalemia; infrequently - hypercreatininaemia.

    Mental disturbance: Often - agitation.

    Disturbances from the nervous system: often - drowsiness, dizziness, headache; infrequently - confusion of consciousness; unknown - cramps, dystonia, increased intracranial pressure.

    Disorders from the cardiovascular system: very often - bradycardia, lowering blood pressure; often - tachycardia, increased blood pressure; infrequent arrhythmia, ventricular extrasystole, supraventricular extrasystole, complete atrioventricular block, bigemia, inversion of the T wave, atrial fibrillation, atrial arrhythmia, atrioventricular blockade of the second degree, ST segment reduction, bleeding,syncopal states; unknown - heart failure (<0.01%), ventricular fibrillation, lengthening the interval QT, associated with ventricular tachycardia type "pirouette".

    Respiratory system disorders: very often - cough; often - breathing disorders, laryngospasm, airway obstruction, respiratory arrest; infrequently - apnea, bronchospasm, hypoxia; unknown - shortness of breath **, wheezing **, respiratory depression, pulmonary edema.

    Disturbances from the digestive system: Often - vomiting; nausea; often - increased salivation.

    Disturbances from the liver and bile ducts: unknown - hepatitis, hepatic insufficiency, liver necrosis, pancreatitis, jaundice.

    Disturbance of the skin and subcutaneous tissues: unknown - contact dermatitis **, pruritus, rash **, face edema **, urticaria.

    Disturbances from musculoskeletal and connective tissue: unknown - rigidity of muscles.

    Violation of the kidneys and urinary tractth: unknown - tubular interstitial nephritis, acute renal failure; infrequent - urinary retention, glucosuria.

    General disorders and disorders at the site of administration: often - chills, fever, hypothermia; unknown - a feeling of discomfort in the chest, malignant hyperthermia (see section "Special instructions").

    Changes in laboratory indicators: often - transient violations of liver function, changes in blood glucose concentration, transient increase in fluoride concentrations *, increased activity of ACT in the blood; infrequently, an increase in ALT activity in the blood, an increase in LDH activity in the blood, a change in the number of leukocytes.

    * - during and after general anesthesia with sevoflurane there may be a transient increase in the serum concentration of inorganic fluorides in the blood plasma. Usually, their concentration reaches a maximum within 2 hours after discontinuing sevoflurane administration and returns to the preoperative value within 48 hours. In clinical studies, an increase in the concentration of fluorides did not lead to impaired renal function.

    ** - the effect can be associated with hypersensitivity reactions, especially in cases of prolonged professional contact with inhalation anesthetics.

    Liver and bile ducts

    In the postoperative period, cases of hepatitis or liver dysfunction (of mild, moderate and severe course, with or without jaundice) were noted.However, histologically, none of the cases of hepatitis was confirmed by histological examination. In most cases, patients with a history had already had liver function abnormalities, or there was evidence of the use of drugs that could cause such disorders. Most of the reported reactions were transient and resolved on their own.

    The central nervous system (CNS)

    Convulsions: according to the post-marketing observation, seiz- flurane was used in cases of seizures. Most cases have been reported in children and adult patients of a young age, without cases of a history of seizures. In several cases, concomitant therapy has not been reported; At least 1 case of seizures is confirmed by EEG. In most cases, single episodes of seizures have been reported that were resolved on their own or after appropriate therapy; nevertheless, cases of multiple seizures were also noted. Seizures arose during induction with sevoflurane, or soon after, during withdrawal from anesthesia and in the postoperative period - for up to 1 day after anesthesia.

    Hypersensitivity

    Hypersensitivity cases have been reported (including cases of contact dermatitis, rash, dyspnoea, wheezing, feelings of discomfort in the chest, facial swelling, anaphylactic reactions); in particular, similar cases were noted against a background of prolonged professional contact with inhalation anesthetics, including sevoflurane.

    Hypermetabolism of muscles

    In sensitive patients, powerful inhalation anesthetics, including sevoflurane, can provoke the development of hypermetabolic state of skeletal muscles, which leads to an increase in the need for oxygen and manifests itself as a clinical syndrome of malignant hyperthermia.

    Overdose:

    Symptoms of sevoflurane overdose include respiratory depression and circulatory insufficiency.

    If suspected overdose, discontinue the administration of sevoflurane and start supporting activities: to ensure patency of the patient's airways, to initiate ancillary or controlled ventilation of the lungs with clean oxygen along with measures to ensure stable cardiovascular activity.

    Interaction:

    The safety and efficacy of sevoflurane is confirmed with simultaneous application to various medications that are often used in surgical practice, including those affecting the function of the central and autonomic nervous system, muscle relaxants, antimicrobial agents, including aminoglycosides, hormones and their synthetic analogs, blood preparations and cardiovascular drugs, including epinephrine.

    Beta-sympathomimetics, such as isoprenaline, and alpha and beta sympathomimetics, such as epinephrine and norepinephrine, should be used with caution when combined with sevoflurane because of the possible risk of ventricular arrhythmia.

    Non-selective MAO inhibitors: there is a danger of developing a hypertensive crisis during the operation. It is recommended to stop treatment with indiscriminate MAO inhibitors 2 weeks before the operation.

    The use of sevoflurane can cause a marked decrease in blood pressure in patients receiving "slow calcium channel" blockers, in particular dihydropyridine derivatives.

    Caution should be exercised when using blockers of "slow calcium channels" concomitantly with inhalational anesthetics because of the risk of increasing the negative inotropic effect.

    Simultaneous use of suxamethonium and inhalational anesthetics in children in rare cases caused an increase in the serum potassium level, which led to cardiac arrhythmia and death in the postoperative period.

    It has been shown that other fluorinated volatile compounds for inhalation anesthesia displace drugs from the connection with blood and tissue proteins in vitro.

    The ability of sevoflurane to displace medicinal products from the connection with serum and tissue proteins has not been studied. However, in clinical studies of undesirable effects in the appointment of sevoflurane to patients taking drugs with high binding capacity with plasma proteins and a low volume of distribution (for example, phenytoin), was not observed.

    Sympathomimetics of indirect action

    There is a risk of developing a hypertensive crisis with the joint use of sevoflurane and sympathomimetics of indirect action (amphetamines, ephedrine).

    Beta-blockers

    Sevoflurane can enhance the negative inotropic, chronotropic and dromotropic action of beta-blockers (by blocking the cardiovascular compensatory mechanisms).

    Verapamil

    Deterioration of atrioventricular conduction was observed with the combined use of verapamil and sevoflurane.

    Barbiturates, benzodiazepines, narcotic analgesics

    Sevoflurane can be used with barbiturates, as well as with benzodiazepines and narcotic analgesics. Benzodiazepines and narcotic analgesics presumably reduce the MAC of sevoflurane.

    The simultaneous use of opioids, such as alfentanil and sufentanil, in combination with sevoflurane, can lead to a reduction in the heart rate, blood pressure and respiratory rate.

    Inductors of isoenzyme CYP2E1

    Medicinal preparations and other substances capable of inducing isoenzyme induction CYP2E1 cytochrome P450 (e.g., isoniazid, ethanol), may cause increased metabolism of sevoflurane and a significant increase in the concentration of fluoride in the blood plasma. The simultaneous use of sevoflurane and isoniazid can increase hepatotoxicaction of isoniazid.

    Dinitrogen oxide

    MAK of sevoflurane decreases with simultaneous application of dinitrogen oxide. The equivalent of MAK is reduced by approximately 50% in adults and approximately 25% in children.

    Muscle relaxants

    Sevoflurane has an effect on the intensity and duration of neuromuscular blockade caused by nondepolarizing muscle relaxants. With the introduction of sevoflurane as an adjunct to the general anesthesia with alfentanil-dinitrogen oxide, it enhances the effect of pancuronium bromide, vecuronium bromide and atracurium bezylate. With the appointment of these muscle relaxants in combination with sevoflurane their doses should be adjusted in the same way as with isoflurane. The effect of sevoflurane on the effect of suxamethonium and the duration of action of depolarizing muscle relaxants has not been studied.

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

    Among non-depolarizing muscle relaxants, the interaction with vecuronium bromide, pancuronium bromide and atracurium bezylate was studied.In the absence of specific recommendations for their use, the following rules should be adhered to: (1) when intubation of the trachea should not reduce the dose of nondepolarizing muscle relaxants; (2) while maintaining general anesthesia, doses of nondepolarizing muscle relaxants should probably be lower than with dinitrogen anesthesia with an oxide / narcotic analgesic. Additional doses of muscle relaxants are administered taking into account the response to nerve stimulation.

    In the case of an initial anesthetic with an intravenous anesthetic, for example propofol, lower concentrations of sevoflurane may be required.

    Preparations of St. John's Wort

    Patients who have been taking drugs for a long time containing St. John's Wort have been observed to have severe hypotension and delayed withdrawal from anesthesia with halogenated inhalation anesthetics.

    Special instructions:

    General recommendations

    Sevofluran-Vial can be used only by specialists trained in general anesthesia, in departments equipped with everything necessary to ensure airway patency, artificial respiration, oxygen therapy and resuscitation.

    The use of sevoflurane can cause to respiratory depression; this effect can be enhanced by the premedication of narcotic analgesics or the use of other drugs that can cause respiratory depression. It is necessary to monitor and maintain the respiratory function of the patient.

    All patients undergoing anesthesia with sevoflurane should be monitored, including monitoring the electrocardiogram (ECG), blood pressure (BP), oxygen saturation, and partial pressure of carbon dioxide (CO2) at the end of exhalation.

    During anesthesia, increasing the concentration of sevoflurane leads to the development of a dose-dependent decrease in blood pressure. Because the sevoflurane insoluble in the blood, indicated hemodynamic changes may occur earlier than with the use of other inhalation anesthetics. Deep anesthesia can be associated with a significant reduction in blood pressure and respiratory depression; to correct these phenomena it is recommended to reduce the concentration of sevoflurane in the gas mixture.

    It is necessary to pay special attention to the selection of a dose of sevoflurane in patients with hypovolemia, hypotension or other hemodynamic disorders, developed, for example, as a result of concomitant treatment.

    The concentration of the drug coming from the evaporator must be accurately known. Since inhalation anesthetics differ in their physical properties, only specially calibrated evaporators for the preparation Sevoflurane-Vial should be used to administer Sevoflurane-Vial. Dosage of the drug during general anesthesia should be selected individually depending on the patient's response. With deepening of general anesthesia, there may be an increase in arterial hypotension and respiratory depression.

    Individual reports were received on the lengthening of the interval QT, very rarely associated with tachycardia such as "pirouette" (in some cases, lethal). Sevoflurane-Vial should be used with caution in patients exposed to these complications. Separate reports were received on cases of ventricular arrhythmia in patients of childhood with Pompe disease.

    Preparations for general anesthesia, including the preparation Sevofluran-Vial, should be apply with caution to patients with mitochondrial diseases.

    Increasing the concentration of sevoflurane to maintain general anesthesia causes a dose-related decrease in blood pressure.Excessive reduction in blood pressure can be associated with profound general anesthesia; in such cases it can be increased by decreasing the concentration of the sevoflurane fed.

    When using Sevoflurane-Vial, as well as other means for general anesthesia, in patients with coronary heart disease it is necessary to maintain stable hemodynamics in order to avoid myocardial ischemia.

    After exiting anesthesia, patients need additional monitoring prior to transfer to the profile department.

    Since sevoflurane has a quick way out of anesthesia, there may be a need for early relief of postoperative pain. Despite the fact that recovery of consciousness during sevoflurane anesthesia usually occurs within a few minutes, the effect of the drug on the intellectual function within 2-3 days after anesthesia has not been studied. As with other anesthetics, there may be slight changes in mood, which can persist for several days after anesthesia. A quick exit from anesthesia in children can be accompanied by agitation and a decrease in communicative abilities (in about 25% of cases).

    Replacement of over-dried sorbents CO2

    When using the preparation Sevofluran-Vial in apparatus for anesthesia, containing over-dried sorbents CO2 (especially those containing potassium hydroxide), rare cases of excessive overheating and / or spontaneous smoke and / or inflammation of anesthesia apparatus are described. When the tanks with CO sorbent are overheated2 there may be an unusual delay in the increase or an unexpected decrease in the inhaled Sevoflurane-Vial concentration, despite the existing evaporator settings. Exothermic reaction of decomposition of sevoflurane with the formation of products of this decomposition, which occurs when sevoflurane interacts with the sorbent CO2, increases if the sorbent dries up; for example, with the long passage of dry gas through a reservoir with sorbent CO2. Formation of decomposition products of sevoflurane (methanol, formaldehyde, carbon monoxide, and components A, B, C and D) was observed in the respiratory circuit of experimental anesthesia apparatus with over-dried sorbents, when the concentration of sevoflurane reached a maximum (8%) for 2 or more hours.Concentrations of formaldehyde, formed in such conditions, reached values ​​that can cause mild irritation of the respiratory tract. The clinical evaluation of the effects of the decomposition products of sevoflurane on the organism under extreme conditions has not been carried out.

    If the anesthetist suspects that the sorbent CO2 it must be replaced before using sevoflurane. When the sorbent CO is dried2 the color of the indicator does not always change. Consequently, the absence of color changes in the indicator can not be considered a confirmation of adequate hydration. Sorbents CO2 It is necessary to change regularly irrespective of color of the indicator.

    Hyperkalemia in the perioperative period

    The use of funds for inhalation anesthesia in children caused in rare cases an increase in the concentration of potassium in the serum, which led to the development of cardiac arrhythmias and death in the postoperative period. The risk is higher in patients with latent and clinically manifested neuromuscular diseases, especially in patients with Duchenne's myodystrophy. In most cases, there was a connection between the development of these complications and the simultaneous use of suxamethonium.In these patients there was also a significant increase in the activity of creatine phosphokinase in the serum and, in some cases, changes in the composition of urine, indicating myoglobinuria. Despite some resemblance to manifestations of malignant hyperthermia, none of these cases showed muscle stiffness or symptoms associated with increased metabolism in the muscles. It should immediately begin activities to stop hyperkalemia and stable arrhythmia and conduct a survey to identify a latent neuromuscular disease.

    Impaired renal function

    The safety of Sevoflurane-Vial in this group of patients has not been established, it should be used with caution in patients with renal insufficiency.

    Materials of controlled studies with a low rate of gas mixture supply are limited, however, clinical and experimental data indicate the possibility of kidney damage, presumably due to component A. According to these data, the use of sevoflurane for more than 2 MAX x hours at a gas mixture flow rate of less than 2 l / min may be associated with the development of proteinuria and glucosuria.The exposure level of component A, at which clinical nephrotoxicity is possible, is not established; nevertheless, it is necessary to take into account all the factors leading to an increase in the exposure of component A in humans, in particular the duration of exposure, the speed of the gas mixture and the concentration of sevoflurane. In the course of anesthesia, the concentration of the inhaled sevoflurane should be titrated and the rate of delivery of the gas mixture monitored to reduce the exposure of component A to a minimum. For this purpose, the exposure of sevoflurane should not exceed 2 MAK x hours, at feed rates from 1 to <2 l / min. The feed rate of the gas mixture <1 l / min is not recommended.

    Clinical experience with sevoflurane in patients with renal insufficiency (creatinine clearance> 1.5 mg / dL) is limited; thus, the safety of the drug in these patients is not established.

    Impaired liver function

    Post-marketing observations recorded very rare cases of violations of the liver function (from mild to severe) or hepatitis (with jaundice or without it) in the postoperative period.

    Sevoflurane should be used with caution in patients with impaired liver function, as well as with the joint use of drugs that can cause a violation of liver function.

    There is evidence that the use of halogenated anesthetics in history, especially during the previous 3 months, may increase the risk of developing liver damage. There are reports that exposure to halogenated hydrocarbons in history may increase the risk of liver damage.

    There have been reports of rare cases of mild, moderate or severe postoperative liver or hepatitis dysfunction (with or without jaundice). It is advisable to use caution when applying sevoflurane against a background of liver disorders or in patients who receive treatment with drugs known to cause liver dysfunction. In patients who have suffered liver damage, jaundice, fever of unknown origin or eosinophilia after using other inhalation anesthetics, it is recommended that sevoflurane should be avoided if general anesthesia is available with intravenous or regional anesthesia.

    Malignant hyperthermia

    In susceptible people, powerful means for inhalation anesthesia, 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. Muscular stiffness, tachycardia, rapid breathing, cyanosis, arrhythmias and / or unstable blood pressure can also be observed. Some of these nonspecific symptoms may also occur with mild anesthesia, acute hypoxia, hyperapnea and hypovolemia.

    In clinical trials, one case of malignant hyperthermia was reported. In addition, cases of malignant hyperthermia (including fatal) were reported in post-marketing observations.

    Treatment of malignant hyperthermia involves the withdrawal of drugs that caused its development (for example, sevoflurane), intravenous dantrolene (detailed information on the use of dantrolene is given in its instructions for use) and supports intensive symptomatic therapy, including normal body temperature, respiratory and circulatory functions, control water-electrolyte and acid-base balance.Later, kidney failure may develop, so you should monitor and, if possible, maintain diuresis.

    Neurosurgical interventions

    If the patient is at risk of increasing intracranial pressure, Sevoflurane-Vial should be used with caution in combination with measures aimed at reducing intracranial pressure, such as hyperventilation.

    Convulsions

    There are reports of rare cases of seizures associated with the use of sevoflurane.

    The use of sevoflurane was associated with seizures in children and young adults, as well as in elderly people without predisposing risk factors. A careful examination of patients with a risk of seizures before using sevoflurane is necessary. In children, the depth of anesthesia should be limited. When selecting a dose of sevoflurane in patients at risk of seizures, it is necessary to conduct an EEG to optimize the dosage of sevoflurane.

    Use in children

    Cases of seizures are known against sevoflurane. Many of these cases occurred in children (starting from the age of two months) and adolescents; most of them had no risk factors for seizures.

    Sevoflurane should be used with caution in patients with a tendency to develop seizures.

    Children who were prescribed sevoflurane for the induction of anesthesia, dystonic movements observed disappearing independently without requiring treatment. The causal relationship with sevoflurane is not confirmed.

    Children with Down's syndrome have an increased risk of bradycardia and hypotension during and after sevoflurane induction.

    Anesthesia in Obstetrics

    Caution should be exercised when using sevoflurane in obstetric practice. Sevoflurane has a relaxing effect on the uterus, which may increase the risk of uterine bleeding, as evidenced by the study performed with the termination of pregnancy. The available data confirm the safety of the use of sevoflurane for the mother and child in the course of the planned cesarean section. The safety of sevoflurane during delivery through the natural birth canal has not been studied.

    Effect on the ability to drive transp. cf. and fur:

    Although after ceasing the supply of sevoflurane, consciousness is usually restored after a few minutes, its effect on cognitive function was not studied within 2-3 days after general anesthesia.Within a few days after applying sevoflurane, as well as other means for general anesthesia, there may be slight changes in mood. Patients should be informed that, after general anesthesia, the ability to perform various tasks requiring rapidity of psychomotor reactions, such as driving a vehicle or working with a technique that requires special attention, may be impaired. The possibility of resuming employment by these activities is determined by the anesthesiologist.

    Form release / dosage:

    Liquid for inhalation.

    Packaging:

    To 100 ml or 250 ml in a bottle of brown transparent glass sealed with a screwed aluminum cover with the control of the first opening, with a plastic gasket, a label is affixed to each bottle.

    Each bottle together with instructions for use is placed in a cardboard pack.

    30 packs of cardboard are placed in a cardboard box (for hospitals).

    Storage conditions:

    In the dark place at a temperature of no higher than 25 ° C.

    Keep out of the reach of children.

    Shelf life:

    3 years.

    Do not use after the expiration date.

    Terms of leave from pharmacies:For hospitals
    Registration number:LP-003706
    Date of registration:28.06.2016
    Expiration Date:28.06.2021
    The owner of the registration certificate:VIAL, LLC VIAL, LLC Russia
    Manufacturer: & nbsp
    Representation: & nbspVIAL, LLCVIAL, LLC
    Information update date: & nbsp15.08.2016
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