Sevoflurane - instructions for use, dose, side effects, contraindications

Active substanceSevofluraneSevoflurane

Similar drugsTo uncover

Sevoran®

solution d / inhal.

Abbott Laboratories SA Spain

Sevoflurane

solution d / inhal.

Baxter Healthcare Corporation Puerto Rico

Sevofluran-Vial

liquid d / inhal.

VIAL, LLC Russia

Dosage form: & nbspinhalation fluid

Composition:

sevoflurane 100%

Description:clear colorless liquid

Pharmacotherapeutic group:inhalation anesthetic

ATX: & nbsp

N.01.A.B Halogenated hydrocarbons

N.01.A.B.08 Sevoflurane

Pharmacodynamics:

Sevoflurane is a halogenated methyl isopropyl ether, which, when inhaled, causes a rapid induction of general anesthesia and a rapid exit from it. Sevoflurane causes dose-dependent, reversible loss of consciousness and pain sensitivity, suppression of voluntary motor activity, decreased autonomic reflexes, and sedation of the respiratory and cardiovascular systems. Sevoflurane has a low blood / gas partition coefficient (0.65), which leads to a rapid exit from general anesthesia.

The minimum alveolar concentration (MAC) is the concentration at which 50% of patients do not have a motor reaction in response to a standard stimulation (skin incision). MAK for sevoflurane decreases with increasing age of the patient, and also with the introduction of dinitrogen oxide (nitrous oxide) (see Table 1).

Cardiovascular effects: sevoflurane can cause a concentration-dependent decrease in blood pressure. Sevoflurane causes sensitization of the myocardium to the arrhythmogenic effect of exogenous epinephrine (epinephrine). Sensitization is similar to that caused by isoflurane.

Pharmacokinetics:

Sevoflurane has a low solubility in the blood and tissues, which leads to a rapid achievement of alveolar concentration sufficient to provide anesthesia, and subsequent rapid elimination until the termination of general anesthesia.

Sevoflurane is metabolized by cytochrome P450 2E1 to hexafluoroisopropanol (HPIP) with the release of inorganic fluoride and CO2. The resulting GFIP is rapidly conjugated with glucuronic acid and excreted in the urine. Other ways of metabolism of sevoflurane have not been identified. Only about 5% of the dose of sevoflurane undergoes metabolism, which is due to preferential and rapid elimination through the lungs.

Cytochrome P450 2E1 is the main isoform involved in the metabolism of sevoflurane, which can be induced by chronic exposure to isoniazid and ethanol.This is similar to the metabolism of isoflurane and enflurane, but differs from the metabolism of methoxyflurane, which is metabolized by various cytochrome P450 isoforms. Barbiturates do not have the ability to induce sevoflurane metabolism.

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:

if there are contraindications to general anesthesia;
with known or suspected hypersensitivity to sevoflurane or other halogenated anesthetics (eg, history of liver function abnormalities, fever or leukocytosis of an unknown genesis after anesthesia by one of these drugs);
patients with confirmed hepatitis in history because of the use of halogenated inhalation anesthetics or with moderate to severe or severe impairment of hepatic function in anamnesis, with jaundice, fever and eosinophilia after sevoflurane anesthesia;
patients with known or suspected hereditary predisposition to malignant hyperthermia.

Pregnancy and lactation:

Pregnancy

In reproductive studies conducted in rats and rabbits at doses up to 1 MAK, it was found that sevoflurane, used without the CCl adsorbent, does not cause reproductive harm and does not have a damaging effect on the fetus. Controlled clinical studies of the use of sevoflurane during pregnancy have not been conducted; consequently, in pregnant women sevoflurane It should be used only if the benefits of general anesthesia clearly outweigh the possible risks to the fetus.

Childbirth and delivery

In a clinical study, the safety of the drug Sevoflurane was demonstrated with the use of the drug in mothers and infants as part of general anesthesia with a planned cesarean section. Safety of the medicinal product Sevoflurane with delivery through the natural birth canal has not been proven. Due to its pharmacological properties, sevoflurane has a relaxing effect on the myometrium. According to the clinical study, with the interruption of pregnancy, there was an increase in uterine bleeding.

Breastfeeding period

Since it is not known whether sevoflurane with breast milk, caution should be exercised when prescribing sevoflurane to mothers breastfeeding.

Reproduction

In reproductive studies conducted in rats and rabbits at doses up to 1 MAK, it was found that sevoflurane does not cause a violation of the reproductive function.

Dosing and Administration:

Inhalation.

Surgical stage of general anesthesia

To maintain the accuracy of the drug concentration, specially designed evaporators calibrated for sevoflurane should be used.

Table 1. MAQ of sevoflurane depending on the patient's age

Age of the patient (years)	Sevoflurane (%) in oxygen	Sevoflurane (%) in 65% N20 / 35% 02
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	M
60	1,7	0,9
80	1,4	0,7

* MAC in preterm infants is not defined

** 60% N20 / 40% used in patients aged one to three years 02 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.

Induction of general anesthesia with sevoflurane alone can be achieved by inhaling 0.5-1.0% sevoflurane in oxygen (Og) in combination with or without dinitrogen oxide; the required depth of general anesthesia is achieved by increasing the concentration of sevoflurane in increments of 0.5-1.0%; the maximum concentration of sevoflurane in adults and children is 8%. Inhaled concentrations of sevoflurane up to 5% in adults and up to 7% in children usually provide a surgical stage of general anesthesia in less than two minutes.

Maintaining general anesthesia

Maintenance of general anesthesia during surgical interventions can be ensured by using 0.5-3% concentration of sevoflurane in oxygen while using 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.

Carefully

Sevoflurane should be administered only by persons trained in the proper conduct of general anesthesia. Equipment to maintain free airway patency,artificial lung ventilation, enrichment with oxygen and cardiovascular resuscitation should be ready for immediate use. Continuous monitoring of all patients receiving sevoflurane anesthesia should be carried out, including ECG monitoring, blood pressure, oxygen saturation and carbon dioxide (CCH) at the end of the exhalation.

General Patient Monitoring

The concentration of sevoflurane supplied by the evaporator must be accurately known. Since inhalation anesthetics differ in their physical properties, evaporators specially calibrated for sevoflurane should be used.

The use of general anesthesia should be individualized and take into account the patient's response. As the anesthesia deepens, hypotension and respiratory depression increase.

As the concentration of sevoflurane increases and, as a consequence, the general anesthesia deepens, the blood pressure decreases and respiratory activity is suppressed. Due to the insolubility of sevoflurane in the blood, hemodynamic changes may occur more quickly than with the use of other inhalation anesthetics.Excessive reduction in blood pressure or respiratory depression may depend on the depth of general anesthesia, and they can be eliminated by decreasing the inhaled concentration of sevoflurane. A thorough assessment should be made of the outcome of general anesthesia before the patient is transferred from the postoperative ward to the department.

Particular attention should be given to the selection of doses for patients with hypovolemia, hypotension or other disorders of hemodynamics, for example, due to concomitant therapy.

Care should be taken when using the drug for anesthesia in obstetrics due to the relaxing effect of sevoflurane on the myometrium and increased uterine bleeding.

Patients who have undergone repeated exposure to halogenated anesthetics in a relatively short period of time may have an increased risk of liver damage.

As with all anesthetics, in patients with coronary artery disease, maintaining stable hemodynamics in order to prevent myocardial ischemia is of great importance.

Malignant hyperthermia

In predisposed individuals, strong inhalation anesthetics can provoke a conditionhypermetabolism of skeletal muscles, which leads to high oxygen consumption and the development of a clinical syndrome known as malignant hyperthermia. It was reported that rare cases of malignant hyperthermia develop with the use of sevoflurane. Clinical syndrome manifests hypercapnia and may include muscle rigidity, tachycardia, tachypnea, cyanosis, arrhythmia and / or unstable blood pressure. Some of these non-specific signs may also occur during mild anesthesia, acute hypoxia, hypercapnia, and hypovolemia. The death of malignant hyperthermia caused by sevoflurane was reported.

Treatment of malignant hyperthermia includes the abolition of a provoking agent (eg, sevoflurane), intravenous dantrolene sodium administration, and the appointment of maintenance therapy. Later, kidney failure may develop; should be monitored and, if possible, supported by urination.

Sevoflurane should not be used in persons with a known or suspected predisposition to develop malignant hyperthermia.

In rare cases, the use of funds for inhalation anesthesia in children was accompanied by an increase in serum potassium levels, which led to cardiac arrhythmias and death in the postoperative period.

The most susceptible to the development of hyperkalemia patients with latent or obvious neuromuscular diseases, especially Duchenne's myodystrophy. There was also reported a cardiac arrest with hyperkalemia in a child with Duchenne's myodystrophy after anesthesia with sevoflurane. In most, but not all of these cases, there was a connection with the concomitant use of succinylcholine. In these patients, there was also a significant increase in the level of creatine kinase in the serum, and in some cases changes in the urine, corresponding to myoglobinuria. Despite the similarity of these manifestations with malignant hyperthermia, none of the patients showed signs or symptoms of muscle rigidity or hypermetabolic status.

Early and aggressive treatment of hyperkalemia and resistant arrhythmias is recommended, as well as a follow-up examination to detect a latent neuromuscular disease.

Single reports were received on the lengthening of the QT interval, which is very rarely associated with the development of ventricular pirouette tachycardia. Caution should be exercised in appointing sevoflurane to patients with this predisposition.

Children suffering from Pompe disease have single cases of ventricular arrhythmia.

Caution should be exercised when using general anesthesia, including sevoflurane, in patients with mitochondrial dysfunction.

In children who received sevoflurane for induction anesthesia, dystonic movements were observed. The relationship of this phenomenon with sevoflurane is not confirmed.

The withdrawal from general anesthesia with sevoflurane usually occurs quickly, so patients may need anesthesia in the early postoperative period.

Cases of mild, moderate or severe postoperative liver or hepatitis with or without jaundice, including liver necrosis and hepatic insufficiency, have been reported.

It is advisable to use caution when using sevoflurane in patients with existing impaired liver function or receiving drugs that knowingly cause liver dysfunction.In patients who have a history of liver damage, jaundice, fever of unknown origin or eosinophilia after an inhalation anesthesia by any drug other than sevoflurane, you should refrain from using sevoflurane if there is a possibility of intravenous or regional anesthesia.

Replacement of over-dried scavengers

Upon the contact of sevoflurane with the scavenger CGH, an exothermic reaction occurs. If the absorber is over-dried, for example, after an extended period of dry gas passage through the absorber tank, the exothermic reaction is enhanced. We describe rare cases of excessive heating, smoke and / or self-ignition of the anesthesia apparatus when sevoflurane is used together with the dried CO2 absorber. An unexpected increase in delay or an unexpected decrease in the respirable concentration of sevoflurane, compared with the values set for the evaporator, may be due to overheating of the reservoir with COo absorber.

When sevoflurane is contacted with alkaline absorbers of CO? under certain conditions, the degradation of sevoflurane may occur.

Degradation and formation of degradation products (methanol, formaldehyde, carbon monoxide, and substances A, B, C, D and E) increases with the use of dried CCH scavengers (especially absorbers containing potassium hydroxide), with an increase in the absorber temperature and at elevated concentrations of sevoflurane.

Sevoflurane can not be used with over-dried CBN scavengers

CO2 absorbers containing potassium hydroxide are not recommended for joint

application with sevoflurane.

If the attending physician suspects that the scavenger is overdried, then it should be replaced before applying sevoflurane. The color indicator of most COL scavengers does not necessarily change color when they dry out. In this connection, the absence of noticeable changes in the color of the indicator can not serve as a reliable indicator of sufficient moisture absorber. CO2 absorbers must be regularly changed

in accordance with the requirements of instructions for the use of anesthesia equipment, regardless of the color of the indicator.

Use of the drug in patients with impaired renal function

Clinical experience with sevoflurane in patients with renal insufficiency (serum creatinine> 1.5 mg / dl) is limited,and the safety of sevoflurane in this

category of patients not established. In patients with renal insufficiency sevoflurane should be used with caution. In the postoperative period, kidney function should be monitored regularly.

Kidney damage

Although the data of controlled clinical trials on the use of sevoflurane in low-flow anesthesia are limited, the available facts from experimental studies and human studies suggest a potential possibility of kidney damage due to exposure to substance A. Studies conducted on animals and humans show that sevoflurane, used more than 2 MAC hours at a fresh gas flow rate of less than 2 L / min may be associated with proteinuria and glucosuria.

The level of substance A, at which clinical manifestations of nephrotoxicity could be expected, is not established. It is necessary to take into account all the factors leading to the effects of A in humans, especially the duration of exposure, the fresh gas flow rate and the concentration of sevoflurane.

The concentration of inhaled sevoflurane and the fresh gas feed rate should be selected in such a way as to minimize the effect of Substance A.Effects of sevoflurane should not exceed 2 MAC hours at fresh gas feed rates from 1 to 2 liters / minute. The feed rate of fresh gas <1 l / min is not recommended. Neurosurgery

In patients at risk of increased intracranial pressure (ICP) sevoflurane should be used with caution and in combination with measures aimed at reducing ICP, such as hyperventilation.

Convulsions

Reported rare cases of seizures with the use of sevoflurane.

The use of sevoflurane was accompanied by convulsions, which were observed in patients of childhood, adults of young and older age, who had or did not have predisposing risk factors. Apparently, the epileptiform effect is dose-dependent and intensifies with increasing depth of anesthesia. The decision to use sevoflurane in patients at risk for seizures should be based on an assessment of the benefit-risk ratio. In children, the depth of anesthesia should be limited. Monitoring of the functional activity of the brain (electroencephalography) allows to optimize the dose of sevoflurane and helps to avoid the development of convulsive activity in predisposed patients.

Use in children

The use of sevoflurane can be accompanied by cramps. Mostly they were found in children (over 2 months) and in adolescence, most of whom had no predisposing risk factors. The decision to use sevoflurane in patients at risk for seizures should be based on an assessment of the benefit-risk ratio.

A quick exit from anesthesia in children can cause a short-term agitation, which can lead to difficulties in contact with staff (approximately 25% of cases of general anesthesia in children).

Induction and maintenance of general anesthesia in patients aged 1 to 18 years have been studied in controlled clinical trials. Sevoflurane It has no sharp odor and can be used for masking induction in children. The concentration of sevoflurane required to maintain general anesthesia depends on the age. In children when used in combination with dinitrogen oxide, MAK-equivalent dose of sevoflurane should be reduced. The MAK of sevoflurane in preterm infants was not evaluated.

Children with Down's syndrome reported significantly more frequent and severe bradycardia with induction anesthesia with sevoflurane.

Use in patients with hypovolemia, arterial hypotension, hemodynamic disorders

Sevoflurane has a dose-dependent cardiodepressive effect and causes a dose-dependent reduction in systemic vascular resistance.

Side effects:

Like all other active inhalation anesthetics, sevoflurane can cause a dose-dependent depression of respiration and cardiac activity. Most other adverse events are mild and transient. In the postoperative period, nausea and vomiting were observed, which are common complications of surgical intervention and general anesthesia, which can be caused by the use of inhalation anesthetics, other agents administered during and after surgery, and the patient's response to a surgical operation.

The most frequent adverse reactions were:

- in adults: lowering blood pressure, nausea, vomiting;

- in the elderly: bradycardia, lowering blood pressure and nausea;

- in children: agitation, coughing, vomiting and nausea.

Unwanted reactions, occurring more often than in isolated cases,are listed according to the following gradation: very frequent (> 1/10), frequent (> 1/100 - <1/10), infrequent (> 1/1000 - <1/100), rare (> 1/10000 - < 1/1000), very rare (<1/10000) are reactions recorded in clinical studies. The frequency is unknown, it is applicable to undesirable reactions recorded in the post-marketing period.

System-Organ Class	Frequency	Unwanted reaction
Infringements from	Infrequent	Leukocytosis
blood and lymphatic	Frequency	T rhombocytopenia
systems	unknown
Infringements from	Frequency	Anaphylactic reaction¹
immune system	unknown	Anaphylactoid reaction¹Gipsensitivity Edema of the eyelids
Disorders of the psyche	Very Frequent	Agitation
	Infrequent	Confused Consciousness
Infringements from	Very Frequent	Drowsiness
nervous system		Headache Headache
	Frequent	Agitation⁶
	Infrequent	Confused Consciousness
	Frequency	Convulsions²’¹⁵
	unknown	Dystonic movements Increased intracranial pressure Increased blood pressure Nervousness Insomnia
Infringements from	Frequency	Conjunctivitis
organ of vision	unknown
Infringements from	Very Frequent	Bradycardia
hearts	Frequent	Tachycardia

Adverse reactions recorded in clinical trials and post-marketing period

System-Organ Class	Frequency	Unwanted reaction
	Infrequent	Complete atrioventricular blockade Cardiac arrhythmia (including ventricular arrhythmias) Atrial fibrillation Extrasystoles (ventricular, supraventricular, associated with bigemia)
	Frequency	Heart failure⁴
	unknown	Ventricular fibrillation Ventricular tachycardia of the "pirouette" type Ventricular tachycardia Extended QT interval electrocardiograms Atrioventricular blockade of the second degree Fainting Arrhythmia of the atria ST electrocardiograms Inversion of the T wave of the electrocardiogram
Infringements from	Very Frequent	Arterial hypotension
vessels	Frequent	Arterial hypertension
Infringements from	Very Frequent	Cough
respiratory system,	Frequent	Disturbance of breathing
organs of the chest and		Inhibition of respiration
the mediastinum		Laryngospasm Obstruction of the respiratory tract
	Infrequent	Apnea Asthma Hypoxia

and

System-Organ Class	Frequency	Unwanted reaction
	Frequency unknown	Bronchospasm Dispnoe¹ Wheezing¹Breathing delay G and ventilation Stridor Г ипервентиляция Pharyngitis Hiccups Increased sputum separation
Infringements from gastrointestinal tract	Very Frequent	Vomiting Nausea
	Frequent	Increased salivation
	Frequency unknown	Pancreatitis Distortion of taste Dry mouth
Disorders from the metabolism and nutrition	Frequency unknown	Hyperglycemia Hyperglycemia G and hypophosphataemia
Disturbances from musculoskeletal and connective tissue	Frequency unknown	Muscle Rigidity Rhabdomyolysis
Disorders from the liver and bile ducts	Frequent	Increase in activity of aspartate aminotransferase
	Infrequent	Increased activity of alanine aminotransferase Increase in lactate dehydrogenase activity

System-Organ Class	Frequency	Unwanted reaction
	Frequency	Hepatitis'
	unknown	Liver failure¹'² Liver Necrosis¹² Jaundice Increased activity of alkaline phosphatase Hyperbilirubinemia
Infringements from	Infrequent	Increase in creatinine content in
kidney and urinary		blood
ways		Glucosuria Urinary retention
	Frequency	Tubulointerstitial nephritis
	unknown	Renal insufficiency Increase in blood urea nitrogen in blood Albuminuria Oliguria Abnormal urine output
Infringements from	Frequency	Contact dermatitis¹
skin and subcutaneous tissue	unknown	Itching Rash¹Edema of the face Urticaria
General disorders and	Frequent	Chills / shivering
violations in place		Fever
introduction of		Hypothermia
	Frequency	Discomfort in the chest¹
	unknown	Malignant hyperthermia¹ Edema Asthenia
Laboratory and	Frequent	Inconsistency with the level of glucose
instrumental		blood

System-Organ Class	Frequency	Unwanted reaction
data		Inadequacy of liver function⁵ Inconsistency in the norm of the number of leukocytes Increase in the concentration of phosphorus in the blood¹
	Infrequent	Increase in the concentration of creatinine
		in serum
Injuries, intoxications and	Frequent	Hypothermia
complications of manipulation

1 - this section describes the undesirable reaction; ² - see "With caution";

² - see the subsection "Undesirable reactions when used in children";

3 - there are very rare reports of cardiac arrest with the use of sevoflurane in the postgrade period;

4 - cases of transient changes in liver function parameters were observed with the use of sevoflurane and similar medications;

5 - when the drug is used in children, the incidence of this undesirable reaction is classified as "very frequent."

Description of individual adverse reactions

A temporary increase in the concentration of inorganic fluorides in the serum can occur during and after anesthesia with sevoflurane. Concentrations of inorganic fluorides peak usually within two hours after the end of anesthesia with sevoflurane and return to the concentrations noted in the preoperative period within 48 hours. In clinical studies, elevated fluoride concentrations were not associated with impaired renal function.

There are rare reports of hepatitis in the postoperative period. In addition, during the post-marketing period, there were rare reports of hepatic insufficiency and liver necrosis associated with the use of potent volatile anesthetics, including sevoflurane. However, the actual occurrence and the relationship of sevoflurane with these phenomena can not be reliably established (see the section "With caution").

There are rare reports of hypersensitivity reactions (manifested contact dermatitis, rash, shortness of breath, wheezing, chest discomfort, facial edema, eyelid edema, erythema, urticaria, pruritus, bronchospasm, anaphylactic or anaphylactoid reactions), headache, and increased activity of liver enzymes in persons whose professional activities are associated with long-term contact with inhalation anesthetics, including sevoflurane.

In susceptible individuals volatile potent inhalation anesthetics can cause a hypermetabolic state of skeletal muscle, leading to high oxygen demand and the clinical syndrome known as malignant hyperthermia (see. Section "Precautions").

Undesirable reactions when used in children

Post-marketing reports indicate that the use of sevoflurane was accompanied by convulsions. Mostly they were found in patients of childhood and adolescence, in the history of the majority of which there were no cramps.In several reported cases, concomitant drug therapy was not used, and at least one case was confirmed by electroencephalography (EEG). Although in many cases there were single convulsions that were resolved spontaneously or after treatment, cases of repeatedly recurrent seizures were also reported. Seizures arose during or soon after the induction of anesthesia with sevoflurane, during the withdrawal from anesthesia, and during the postoperative recovery until the day after general anesthesia. It is necessary to conduct a clinical evaluation with the use of sevoflurane in patients at risk of seizures (see the section "With caution").

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:

It was shown that sevoflurane is safe and effective when used simultaneously with a wide range of drugs often used in surgical practice, such as drugs acting on the central and autonomic nervous system, muscle relaxants, antibacterial drugs, including aminoglycosides, hormones and synthetic substitutes, blood derivatives and drugs that affect on the cardiovascular system, including epinephrine.

Dinitrogen oxide

Like other halogenated inhalation anesthetics, the MAO of sevoflurane decreases when combined with dinitrogen oxide. The MAK-equivalent dose of sevoflurane is reduced by approximately 50% in adults and by 25% in children (see "Dosage and Administration").

Drugs that cause neuromuscular blockade

As with other inhalation anesthetics sevoflurane intensifies both the intensity and duration of the neuromuscular blockade caused by nondepolarizing muscle relaxants, such as pancuronium, vecuronium, and atracurium. When used as an adjunct for alfentanil-LgO anesthesia, sevoflurane strengthens the neuromuscular block induced by pancuronium, vecuronium, or atrakurium. The dosage of these drugs should be adjusted when prescribed in combination with sevoflurane. The effect of sevoflurane on the duration of the depolarizing blockade of neuromuscular transmission induced by succinylcholine has not been studied. Sefotofuran potentiation of the effects of muscle relaxants requires a balance of the muscle with the partial pressure created by sevoflurane.

Reducing the dose of neuromuscular blockers during the initial anesthesia may lead to a later onset of conditions suitable for endotracheal intubation, or to improper muscle relaxation due to increased neuromuscular blockers, and is observed a few minutes after the initiation of sevoflurane administration.

Among the nondepolarizing muscle relaxants, the interactions between vecuronium, pancuronium and atracurium have been studied. In the absence of specific guidelines: (1) with endotracheal intubation, the dose of nondepolarizing muscle relaxants is not reduced; and, (2) during the narcosis maintenance period, a lower dose of nondepolarizing muscle relaxants may be required compared to the dose required during anesthesia with IgE / narcotic analgesics.With the introduction of additional doses of muscle relaxants should be guided by the response to stimulation of the nerves. Benzodiazepines and opioids

Benzodiazepines and opioids can reduce the MAQ of sevoflurane by the same principle as other inhalation anesthetics. When introduced sevoflurane is compatible with benzodiazepines and opioids, often used in surgical practice.

In the joint use of sevoflurane and such opioids as fentanyl, alfentanil and sufentanil, possibly a synergistic decrease in the heart rate, a decrease in blood pressure and respiratory rate.

Beta-blockers

Sevoflurane can enhance the negative inotropic, chronotropic and dromotropic effects of beta-blockers due to blockade of compensatory mechanisms of the cardiovascular system.

Adrenaline / epinephrine

Sevoflurane, like isoflurane, sensitizes the myocardium to the arrhythmogenic effect of exogenously administered epinephrine. Doses of epinephrine above 5 μg / kg body weight, administered under the mucosa, can cause a variety of ventricular arrhythmias.

Inductors CYP2E1

Drugs and substances that increase the activity of the cytochrome P450 isoenzyme CYP2E1, for example, isoniazid or alcohol, can enhance the metabolism of sevoflurane and lead to a significant increase in the concentration of fluoride in the plasma. The combined use of sevoflurane and isoniazid can potentiate the hepatotoxic effects of isoniazid.

Sympathomimetics of indirect action

There is a risk of developing a hypertensive crisis with the simultaneous use of sevoflurane and drugs that have an indirect sympathomimetic effect (amphetamines, ephedrine).

Verapamil

With the simultaneous use of verapamil and sevoflurane, there was a violation of atrioventricular conduction.

St. John's wort perforated

Cases of severe hypotension and delayed withdrawal from general anesthesia by halogenated inhalation anesthetics have been described in patients treated with St. John's wort for a long time.

Intravenous anesthetics

The appointment of sevoflurane is compatible with the use of barbiturates, propofol and other commonly used intravenous anesthetics. After using intravenous anesthesia, a decrease in the concentration of sevoflurane may be required.

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

Patients should be advised that work requiring quick response, such as driving a vehicle or controlling machinery, may be

disrupted for some time after general anesthesia. The possibility of resuming employment by these activities is determined by the anesthesiologist.

Form release / dosage:Liquid for inhalation.

Packaging:

For 250 ml in aluminum bottles, covered from the inside with epoxy phenol resin. The vials are closed with a plastic screw cap with an internal polytetrafluoroethylene liner.

6 bottles together with the instructions for use are placed in a cardboard box.

Storage conditions:

At a temperature of no higher than 30 ° C in an upright position.

To avoid leakage of the drug, store tightly closed screw cap. Close with a screw cap immediately after use.

Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:For hospitals

Registration number:LP-001662

Date of registration:19.04.2012

The owner of the registration certificate:Baxter Healthcare CorporationBaxter Healthcare Corporation Puerto Rico

Manufacturer: & nbsp

BAXTER HEALTHCARE Corp. USA

Representation: & nbspBaxter Baxter USA

Information update date: & nbsp15.09.2015

Illustrated instructions

Instructions

Sevoflurane (Sevoflurane)