Instruction for use: Sevoflurane

Latin name:Sevofluranum (genus. Sevoflurani)

Chemical name

1,1,1,3,3,3-Hexafluoro-2- (fluoromethoxy) propane

Gross formula

C₄H₃F₇O

Pharmacological group of substance Sevoflurane:

Anesthetic means

The nosological classification (ICD-10)

Z100 * CLASS XXII Surgical practice: Abdominal surgery; adenomectomy; Amputation; Coronary angioplasty; Angioplasty of the carotid arteries; Antiseptic skin treatment for wounds; Antiseptic Hand; Appendectomy; atherectomy; Balloon coronary angioplasty; Vaginal hysterectomy; The coronary bypass; Interventions in the vagina and cervix; Interventions on the bladder; Intervention in the mouth; Restoration and reconstructive surgery; Hand hygiene of medical personnel; Gynecologic surgery; Gynecological intervention; Gynecological surgery; Hypovolemic shock during operations; Disinfection of purulent wounds; Disinfection of wounds edges; Diagnostic intervention; Diagnostic procedures; Cervical Diathermocoagulation; Long-surgery; Replacing the fistula catheters; Infection in orthopedic surgery; Artificial heart valve; cystectomy; Short-term outpatient surgery; Short-term operation; Short surgical procedures; Krikotireotomiya; Blood loss during surgery; Bleeding during surgery and in the postoperative period; Kuldotsentez; laser photocoagulation; laser coagulation; retinal laser coagulation; Laparoscopy; Laparoscopy in Gynecology; CSF fistula; Small gynecological operations; Small surgical procedures; Mastectomy and subsequent plastic; mediastinotomy; Microsurgical operations on the ear; Mukogingivalnye operation; suturing; Minor surgery; neurosurgical operation; Immobilization of the eyeball in ophthalmic surgery; testectomy; pancreatectomy; Perikardektomiya; The period of rehabilitation after surgery; The period of convalescence after surgery; Percutaneous transluminal coronary angioplasty; Pleural thoracentesis; Pneumonia postoperative and posttraumatic; Preparation for surgical procedures; Preparation for surgery; Preparation of the surgeon's hands before surgery; Preparation of the colon for surgical procedures; Postoperative aspiration pneumonia in neurosurgical and thoracic surgery; Postoperative nausea; Postoperative bleeding; postoperative granuloma; postoperative shock; The early postoperative period; myocardial revascularization; Radiectomy; gastric Resection; bowel resection; uterine Resection; liver Resection; enterectomy; Resection of part of the stomach; Reocclusion of the operated vessel; Bonding tissues during surgical procedures; Removal of sutures; Condition after eye surgery; Condition after surgery; Condition after surgery in the nasal cavity; Condition after gastrectomy; Status after resection of the small intestine; Condition after tonsillectomy; Condition after removal of the duodenum; Condition after phlebectomy; Vascular surgery; Splenectomy; Sterilization of surgical instruments; Sterilization of surgical instruments; sternotomy; Dental surgery; Dental intervention in periodontal tissues; strumectomy; Tonsillectomy; Thoracic surgery; Thoracic surgery; total gastrectomy; Transdermal intravascular coronary angioplasty; Transurethral resection; Turbinektomiya; Removal of a tooth; cataract surgery; Removal of cysts; tonsillectomy; Removal of fibroids; Removing the mobile primary teeth; Removing polyps; Removing broken tooth; Removal of the uterus body; Removal of sutures; Fistula likvoroprovodyaschih ways; Frontoetmoidogaymorotomiya; Surgical infection; Surgical treatment of chronic limb ulcers; Surgery; The surgery in the anal area; The surgery on the colon; Surgical practice; The surgical procedure; Surgical interventions; Surgery on the gastrointestinal tract; Surgical procedures on the urinary tract; Surgical procedures on the urinary system; Surgical intervention of the genitourinary system; Surgical procedures on the heart; Surgical manipulation; surgery; Surgery on the veins; Surgical intervention; Vascular surgery; Surgical treatment of thrombosis; Surgery; cholecystectomy; Partial gastric resection; hysterectomy; Percutaneous transluminal coronary angioplasty; Percutaneous transluminal angioplasty; Coronary artery bypass; tooth Extirpation; Extirpation of milk teeth; pulpectomy; pulsative cardiopulmonary bypass; tooth Extraction; teeth Extraction; cataract extraction; Electrocoagulation; endourological intervention; episiotomy; Etmoidotomiya; Complications after tooth extraction

Z100.0 * Anesthesiology and premedication: Abdominal surgery; Adenomectomy; Amputation; Angioplasty of the coronary arteries; Carotid artery angioplasty; Antiseptic treatment of skin in wounds; Antiseptic treatment of hands; Appendectomy; Atheroctomy; Balloon coronary angioplasty; Vaginal hysterectomy; Venous bypass; Interventions on the vagina and cervix; Interventions on the bladder; Interference in the oral cavity; Reconstructive-reconstructive operations; Hand hygiene of medical personnel; Gynecological Surgery; Gynecological interventions; Gynecological operations; Hypovolemic shock during surgery; Disinfection of purulent wounds; Disinfection of the edges of wounds; Diagnostic Interventions; Diagnostic procedures; Diathermocoagulation of the cervix; Long-term surgeries; Replacement of fistulous catheters; Infection in orthopedic surgical interventions; Artificial heart valve; Kistectomy; Short-term outpatient surgery; Short-term operations; Short-term surgical procedures; Cryotyreotomy; Blood loss during surgical interventions; Bleeding during surgery and in the postoperative period; Kuldotsentez; Laser coagulation; Laserocoagulation; Laser retinopathy of the retina; Laparoscopy; Laparoscopy in gynecology; Likvornaya fistula; Small gynecological operations; Small surgical interventions; Mastectomy and subsequent plastic surgery; Mediastinotomy; Microsurgical operations on the ear; Mukinging operations; Suturing; Minor surgery; Neurosurgical operation; Eclipse of the eyeball in ophthalmic surgery Orchiectomy; Pancreatectomy; Pericardectomy; The rehabilitation period after surgical operations; Reconvalence after surgical intervention; Percutaneous transluminal coronary angioplasty; Pleural Thoracocentesis; Pneumonia postoperative and post traumatic; Preparing for surgical procedures; Preparing for a surgical operation; Preparation of the surgeon's arms before surgery; Preparation of the colon for surgical interventions; Postoperative aspiration pneumonia in neurosurgical and thoracic operations; Postoperative nausea; Postoperative hemorrhage; Postoperative granuloma; Postoperative shock; Early postoperative period; Myocardial revascularization; Resection of the apex of the tooth root; Resection of the stomach; Bowel resection; Resection of the uterus; Liver resection; Small bowel resection; Resection of a part of the stomach; Reocclusion of the operated vessel; Gluing of tissues during surgical interventions; Suture removal; Condition after eye surgery; Condition after surgery; Condition after surgery in the nasal cavity;Condition after gastrectomy; Condition after resection of the small intestine; Condition after tonsillectomy; Condition after removal of duodenum; Condition after phlebectomy; Vascular Surgery; Splenectomy; Sterilization of surgical instrument; Sterilization of surgical instruments; Sternotomy; Dental surgery; Dental intervention on periodontal tissues; Strumectomy; Tonsillectomy; Thoracic surgery; Total gastrectomy; Transdermal intravascular coronary angioplasty; Transurethral resection; Turbinectomy; Removal of a tooth; Cataract removal; Removing Cysts; Removal of tonsils; Removal of myoma; Removal of mobile milk teeth; Removal of polyps; Removal of a broken tooth; Removal of the uterus; Removal of seams; Urethrotomy; Fistula of the luminal ducts; Frontoetmoidohaimorotomy; Surgical infection; Surgical treatment of chronic ulcers of extremities; Surgery; Surgery in the anus; Surgery on the large intestine; Surgical practice; Surgical procedure; Surgical interventions; Surgical interventions on the digestive tract; Surgical interventions on the urinary tract;Surgical interventions on the urinary system; Surgical interventions on the genitourinary system; Surgical intervention on the heart; Surgical procedures; Surgical operations; Surgical operations on veins; Surgical intervention; Vascular; Cholecystectomy; Partial resection of the stomach; Extraperitoneal hysterectomy; Percutaneous transluminal coronary angioplasty; Percutaneous transluminal angioplasty; Coronary artery bypass grafting; Extirpation of the tooth; Extirpation of infant teeth; Extirpation of pulp; Extracorporeal circulation; Extraction of the tooth; Extraction of teeth; Extraction of cataracts; Electrocoagulation; Endourological interventions; Episiotomy; Ethmoidotomy; Complications after tooth extraction

CAS code

28523-86-6

Characteristics of the substance Sevoflurane

Means for inhalation anesthesia.

Pharmacology

Pharmacological action - anesthesia inhalation.

Pharmacodynamics

Sevoflurane provides a quick introduction to anesthesia and rapid exit from it. The depth of anesthesia can vary rapidly depending on the change in the concentration of sevoflurane in the inspired 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 CNS. Like other powerful agents for inhalation anesthesia, sevoflurane causes a dose-dependent suppression of respiratory function and a decrease in blood pressure. 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 incidence of myocardial ischemia and myocardial infarction in patients with risk factors for these diseases is comparable with the use of sevoflurane and isoflurane.

Influence on blood circulation in the brain (ICP, cerebral blood flow, cerebral oxygen metabolism, cerebral perfusion pressure) is also comparable in sevoflurane and isoflurane. Sevoflurane has minimal effect on ICP and does not reduce the response 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 motor reaction in response to the standard skin irritation (incision of the skin). MAK for sevoflurane decreases with increasing patient's age, and also with the introduction of dinitrogen oxide (nitrous oxide). 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 inactive, non-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.

Application of the substance Sevoflurane

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 hepatic enzyme activity, fever, leukocytosis and / or eosinophilia); confirmed or suspected genetic susceptibility to the development of malignant hyperthermia; the period of lactation.

Restrictions on the use

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; the tendency to lengthen the QT interval and tachycardia of the "pirouette" type in the anamnesis; simultaneous use with beta-sympathomimetics, such as isoprenaline, and with alpha and beta sympathomimetics, such as epinephrine and norepinephrine, because of the possible risk of developing ventricular arrhythmia; simultaneous application with CCB.

Application in pregnancy and lactation

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

Since there is no information on breeding sevoflurane with breast milk, breastfeeding women should refrain from breastfeeding during the period of drug use and within 48 hours after 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 uterus musculature, as a result of which there is a potential risk of uterine bleeding. With midwifery operations, sevoflurane should be used with caution.

The action category for fetus by FDA is B.

Side effects of the substance Sevoflurane

Like all powerful agents for inhalation anesthesia, sevoflurane can cause a dose-dependent inhibition 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 inhalation anesthetics, other drugs administered intraoperatively or in the postoperative period, as well as with the patient's response to surgery.

The most frequent adverse reactions were as follows: in adults, decreased blood pressure, nausea, vomiting; in elderly patients - a bradycardia, depression of a BP, a nausea; in patients of childhood - agitation, cough, nausea.

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

From the side of the immune system: unknown - anaphylactic reactions, 1 pseudo-anaphylactic reaction, hypersensitivity.

From the side of metabolism and nutrition: unknown - hyperkalemia; infrequently hypercreatininaemia.

Violation of the psyche: very often - agitation.

From the nervous system: often - drowsiness, dizziness, headache; infrequently - confusion of consciousness; unknown - convulsions, dystonia, increased ICP.

From the CVS: very often - bradycardia, lowering blood pressure; very often - tachycardia, increased blood pressure; infrequent arrhythmia, ventricular extrasystole, supraventricular extrasystole, complete AV blockade, bigemia, T wave inversion, atrial fibrillation, atrial arrhythmia, AV blockade of the second degree, ST segment reduction, bleeding, syncope; unknown - cardiac arrest (<0.01%), ventricular fibrillation, QT interval prolongation associated with ventricular pirouette tachycardia.

On the part of the respiratory system: very often - cough; often - breathing disorders, laryngospasm, airway obstruction, respiratory arrest; infrequently - apnea, bronchospasm, hypoxia; unknown - shortness of breath1, wheezing, 1 respiratory depression, pulmonary edema.

On the part of the digestive system: very often - vomiting, nausea; often - increased salivation.

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

From the skin and subcutaneous tissues: unknown - contact dermatitis1, itching, rash1, edema of the face1, urticaria.

From the musculoskeletal system and connective tissue: unknown - rigidity of muscles.

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

General disorders and disorders at the injection site: often - chills, fever, hypothermia; unknown - a feeling of discomfort in the chest area1, malignant hyperthermia (see "Precautions").

Changes in laboratory parameters: frequent - transient violations of liver function, changes in blood glucose concentration, transient increase in fluoride concentrations2, 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.

^{1 The effect can be associated with hypersensitivity reactions, especially in cases of prolonged occupational exposure to inhaled anesthetics.}

^{During and after general anesthesia, sevoflurane may show a transient increase in the serum concentration of inorganic fluoride 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.}

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 a reported use of drugs capable of causing such abnormalities. Most of the reported reactions were transient and resolved on their own.

CNS

Convulsions: according to post-marketing surveillance, seiz- flurane has been reported 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 it, upon withdrawal from anesthesia and in the postoperative period - for up to 1 day after anesthesia.

Hypersensitivity

Reported cases of hypersensitivity (including cases of contact dermatitis, rash, dyspnea, wheezing, chest discomfort, facial edema, anaphylactic reactions); in particular, such cases were noted against a background of prolonged professional contact with inhalation anesthetics, including. sevoflurane.

Hypermetabolism of muscles

In sensitive patients, powerful inhalation anesthetics, incl. 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.

Interaction

The safety and efficacy of sevoflurane is confirmed with simultaneous use with various drugs, which are often used in surgical practice, incl. to influence the function of the central and autonomic nervous system, muscle relaxants, antimicrobial agents, including aminoglycosides, hormones and synthetic substitutes, drugs and blood cardiovascular agents, 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 arrhythmias. 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 CCB, in particular dihydropyridine derivatives. Caution should be exercised when using CCB concomitantly with inhalational anesthetics because of the risk of increasing the negative inotropic effect.

Concomitant use of suxamethonium and volatile anesthetics in children in rare cases, caused an increase in the level of potassium in the blood serum, which led to the emergence of cardiac arrhythmias and death in the postoperative period. It was shown that other fluorinated volatile compounds for inhalation anesthesia displace the drug from the connection with blood and tissue proteins in vitro. The ability of sevoflurane to dislodge drugs from the connection with serum and tissue proteins has not been studied. However, clinical studies of adverse effects with the use of sevoflurane in patients taking drugs with a high ability to bind to plasma proteins and low Vd (eg, phenytoin) were 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

The deterioration of AV 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 decrease in heart rate, blood pressure and respiratory rate.

Inductors of isoenzyme CYP2E1

Drugs and other substances capable of inducing the induction of the cytochrome P450 isoenzyme CYP2E1 (for example, isoniazid, ethanol) can cause increased sevoflurane metabolism and a significant increase in the concentration of fluoride in the blood plasma. Simultaneous use of sevoflurane and isoniazid can enhance the hepatotoxic effect 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 the 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 action 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: first, with intubation of the trachea, do not reduce the dose of nondepolarizing muscle relaxants; Secondly, 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 in / in an anesthetic, for example propofol, lower concentrations of sevoflurane may be required.

Preparations of St. John's wort perfumed

Patients who have been taking preparations containing St. John's wort for a long time have experienced severe hypotension and delayed withdrawal from anesthesia with halogenated inhalation anesthetics.

Overdose

Symptoms: include respiratory depression and circulatory insufficiency.

Treatment: In case of suspected overdose, discontinue sevoflurane administration and initiate supportive measures (to ensure patency of the patient's airway, to start assisted or controlled lung ventilation with clean oxygen along with measures to ensure stable cardiovascular activity).

Routes of administration

Inhalation.

Precautions for the substance Sevoflurane

General recommendations

Sevoflurane can be used only by specialists trained in general anesthesia, in departments equipped with everything necessary to ensure airway patency, ventilation, oxygen therapy and resuscitation.

The use of sevoflurane can lead 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 ECG, blood pressure, oxygen saturation, and partial pressure of carbon dioxide (CO2) at the end of the exhalation.

During anesthesia, increasing the concentration of sevoflurane leads to the development of a dose-dependent decrease in blood pressure. Because sevoflurane is insoluble in the blood, these hemodynamic changes may occur earlier than with the use of other inhalation anesthetics. Deep anesthesia can be associated with a significant decrease 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, due to 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 should be used to supply sevoflurane. The dosage of sevoflurane 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.

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

LS for general anesthesia, including sevoflurane, should be used with caution in patients with mitochondrial diseases.

An increase in the concentration of sevoflurane to maintain general anesthesia causes a dose-dependent 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, as well as other means for general anesthesia, in patients with ischemic 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 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 dried CO2 sorbents

When sevoflurane is used in anesthetic apparatus containing over-dried CO2 sorbents (especially those containing potassium hydroxide), rare cases of excessive overheating and / or spontaneous smoke and / or inflammation of anesthesia apparatus are described. When the reservoirs with CO 2 sorbent are overheated, an unusual delay in the increase or an unexpected decrease in the inhaled concentration of sevoflurane may be observed. The exothermic reaction of the decomposition of sevoflurane with the formation of degradation products occurring during the interaction of sevoflurane with a CO2 sorbent is enhanced if the sorbent dries up; for example, during a long passage of dry gas through a reservoir with CO2 sorbent. The 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 machines 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 CO2 sorbent is over-dried, then it should be replaced before applying sevoflurane. When drying CO2 sorbent, 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 must be regularly changed regardless of the 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 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 serum CPK activity and, in some cases, a change in the urine composition indicative of 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. 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 in this group of patients has not been fully established, and should be used with caution in patients with renal insufficiency.

Materials of controlled studies with a low rate of gas mixture flow are limited, however, clinical and experimental data indicate the possibility of kidney damage, presumably due to component A (one of the decay products of sevoflurane). According to these data, the use of sevoflurane for more than 2 MAX × hours at a feed rate of a gas mixture of less than 2 liters / minute 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 MAC × hours, at a feed rate of 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 in 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 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 using sevoflurane against a background of liver disorders or in patients who receive drugs that knowingly cause liver dysfunction. In patients undergoing other after use of inhaled anesthetics liver injury, jaundice, fever of unknown origin or eosinophilia, it is recommended to avoid the use of sevoflurane, if there exists the possibility of using a general anesthetic drugs for in / or administration of regional anesthesia.

Malignant hyperthermia

In susceptible people powerful tools for inhalation anesthesia, including sevoflurane, can cause a state of hypermetabolism of skeletal muscle, which leads to an increase in their oxygen demand and the development of the clinical syndrome known as malignant hyperthermia. The first sign of this syndrome is hypercapnia. Muscular stiffness, tachycardia, rapid breathing, cyanosis, arrhythmia and / or unstable blood pressure can also be observed. Some of these nonspecific symptoms may also occur with mild anesthesia, acute hypoxia, hypercapnia, and hypovolemia.

In clinical trials, one case of malignant hyperthermia was reported. In addition, cases of development of malignant hyperthermia (including fatal) were reported in post-marketing observations. Treatment of malignant hyperthermia involves the cancellation of PM that caused its development (e.g. sevoflurane) on / in the introduction and maintenance intensive dantrolene symptomatic therapy, including maintenance of normal body temperature, respiration and circulation functions, control of water and 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 an increase in ICP, sevoflurane should be used with caution in combination with measures aimed at reducing ICP, 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 impaired liver function, as well as in 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 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 using sevoflurane against a background of liver disorders or in patients who receive drugs that knowingly cause liver dysfunction. In patients undergoing other after use of inhaled anesthetics liver injury, jaundice, fever of unknown origin or eosinophilia, it is recommended to avoid the use of sevoflurane, if there exists the possibility of using a general anesthetic drugs for in / or administration of regional anesthesia.

Malignant hyperthermia

In susceptible people powerful tools for inhalation anesthesia, including sevoflurane, can cause a state of hypermetabolism of skeletal muscle, which leads to an increase in their oxygen demand and the development of the clinical syndrome known as malignant hyperthermia. The first sign of this syndrome is hypercapnia. Muscular stiffness, tachycardia, rapid breathing, cyanosis, arrhythmia and / or unstable blood pressure can also be observed. Some of these nonspecific symptoms may also occur with mild anesthesia, acute hypoxia, hypercapnia, and hypovolemia.

In clinical trials, one case of malignant hyperthermia was reported. In addition, cases of development of malignant hyperthermia (including fatal) were reported in post-marketing observations. Treatment of malignant hyperthermia involves the cancellation of PM that caused its development (e.g. sevoflurane) on / in the introduction and maintenance intensive dantrolene symptomatic therapy, including maintenance of normal body temperature, respiration and circulation functions, control of water and 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 an increase in ICP, sevoflurane should be used with caution in combination with measures aimed at reducing ICP, 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 received sevoflurane for the induction of anesthesia observed dystonic movements that disappeared 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 the induction of general anesthesia with sevoflurane.

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 a study performed with the interruption 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.

Influence on ability to drive vehicles and other mechanisms. 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 deteriorate. The possibility of resuming employment by these activities is determined by the anesthesiologist.