Propofol contraindications for use. MAC of inhalational anesthetics. Indications and contraindications for use

Instructions for use of the drug for specialists

PROPOFOL® (PROPOFOL®)

Trade name

Propofol®

International nonproprietary name

Propofol

Dosage form

Emulsion for intravenous administration

20 ml emulsion contains

active substances - propofol 200 mg,

excipients:

soybean oil, egg phosphatides, glycerin, sodium hydroxide, water for injection.

Description

Almost white homogeneous emulsion

Pharmacotherapeutic group

Other anesthetics

ATS code NO1AX10

Pharmacological properties

Pharmacokinetics

Propofol is 97% bound to plasma proteins. Half-life after intravenous infusion ranged from 277 to 403 minutes. The kinetics of propofol after intravenous bolus injection can be presented as a three-phase model: fast phase distribution (half-life 2-4 minutes), B-phase elimination (half-life 30-60 minutes) and Y-phase elimination (half-life 200-300 minutes). During the Y-phase, the decrease in drug concentration in the blood occurs slowly due to slow redistribution from deep areas of adipose tissue. In a clinical setting, this phase does not affect the time of awakening. Propofol is metabolized primarily by conjugation in the liver with a clearance of about 2 l/min, but metabolism also occurs outside the liver. Inactive metabolites are excreted mostly by the kidneys (about 88%).

When anesthesia was maintained as usual, no significant accumulation of propofol was observed after surgical procedures lasting up to 6 hours.

Pharmacodynamics

A product for non-inhalation general anesthesia, which has a rapid (after 30-60 s) and short-term effect. Does not have an initial stimulating effect.

Reduces total peripheral vascular resistance, blood pressure, minute volume of blood, intracranial and intraocular pressure.
The development of sleep is due to a nonspecific effect on the ion channels of neuron membranes in the central nervous system. Strengthens GABAergic processes in the brain.
Recovery from anesthesia is usually not accompanied by headache, postoperative nausea or vomiting.

In most patients, general anesthesia occurs within 30-60 seconds. The duration of anesthesia, depending on the dose and accompanying medications, ranges from 10 minutes to 1 hour.

Indications for use

Induction of anesthesia, maintenance of general anesthesia

Sedation of patients undergoing artificial respiration during intensive care

Sedation during surgery or diagnostic procedures with regional or local anesthesia.

Directions for use and doses

Propofol® is prescribed only intravenously. It is not recommended to use Propofol® in the form of bolus injections. Shake slightly before use. Any remaining solutions should be thrown away.

All actions with Propofol and the equipment necessary for its administration must be carried out under conditions of strict sterility, since Propofol® does not contain any antimicrobial preservatives and, like any fat emulsion, supports the growth of bacteria and other microorganisms. Propofol® is drawn into a sterile syringe under sterile conditions immediately after opening the vial, and then immediately administered. Propofol® is not administered through a microbiological filter.

Each vial should be carefully inspected before injection for any abnormalities. If any changes are detected, the drug cannot be used. Shake slightly before use. Unused remains of the drug should be destroyed.

Appropriate equipment must be used to ensure the required infusion rate. Drop counters, measured infusion or syringe pumps are quite suitable for this purpose. Using a conventional infusion set does not reliably prevent accidental overdose. When determining the maximum volume of propofol in the burette, the danger of uncontrolled infusion must be taken into account.

The dose of Propofol® is individually selected by an experienced anesthesiologist depending on the patient’s body weight, sensitivity to propofol and other concomitant medications. It is recommended to adjust the dose of Propofol depending on the patient's response until clinical signs onset of anesthesia.

For induction of anesthesia, regardless of the presence or absence of premedication, adults (with average body weight, in satisfactory general condition) - intravenously, by “titrating” 40 mg every 10 s until the appearance of clinical signs of anesthesia.

For most patients under the age of 55 years and patients of ASA classes I and II (American Society of Anesthesiologists), the dose is 1.5-2.5 mg/kg; over 55 years of age and patients of ASA classes III and IV, lower doses are 1-1.5 mg/kg ( approximately 20 mg every 10 s until induction of general anesthesia).

For children over 8 years of age, IV slowly until clinical signs of sleep onset appear. The dose is selected according to age and/or body weight. The average dose is 2.5 mg/kg; for children under 8 years of age, doses may be higher. Children at risk of anesthesia classes III and IV ASA - in smaller doses.

To maintain anesthesia, use either an intravenous drip or a repeated bolus. When performing a continuous infusion, the rate of administration is determined individually. Typically, a rate of 4-12 mg/kg/h will ensure adequate anesthesia is maintained. With repeated bolus injections, depending on clinical picture anesthesia, prescribed in doses of 25-50 mg.
For children, to ensure adequate general anesthesia, administer at a rate of 9-15 mg/kg/h or through repeated bolus doses required to maintain the required depth of anesthesia.

To ensure a sedative effect during intensive care in patients on mechanical ventilation, it is administered intravenously. The infusion rate is set individually, taking into account the desired depth of sedation. As a rule, an infusion rate of 0.3-4 mg/kg/h ensures a satisfactory hypnotic effect. Continuous administration should not exceed 7 days.

The duration of continuous infusion of undiluted propofol should not exceed 12 hours.

Administration after preliminary dilution: mix 1 part of propofol and 5 parts of a 5% dextrose solution for intravenous infusion in polyvinyl chloride bags or glass bottles. Concentration active substance in a diluted solution should not be less than 2 mg/ml. When breeding in polyvinyl chloride bags, it is recommended to fill the bag completely; The diluted solution should be prepared by removing the infusion solution and replacing it with an equivalent volume of propofol. The solution is prepared under vaseptic conditions immediately before use. The mixture remains stable for 6 hours at a temperature of 2-25 degrees C.

Side effects

When injected into anesthesia, a decrease in pressure and temporary stop breathing, which can be severe, especially in patients with general deterioration. Less commonly, epileptoform movements, convulsions and opisthotonus were observed, sometimes several hours or days after drug administration. Cases of pulmonary edema have also been reported. Sometimes upon awakening consciousness deteriorates again short time. In some cases there were allergic reactions associated with sanitary symptoms such as severe hypotension, bronchospasm, edema or erythema of the face. During the use of propofol, bradycardia and, in some cases, cardiac arrest occurred.

heart (asystopia). Very in rare cases When propofol was used for sedation during intensive care at doses above 4 mg/kg/hour, rhabdomyolysis, metabolic acidosis, hyperkalemia, or heart failure, sometimes fatal, have been observed. Very rarely, pancreatitis has developed after the administration of propofol, but a cause-and-effect relationship has not been clearly confirmed. Postoperative chills, fever, cold sensations and euphoria were also noted. In the background long-term use Propofol may cause green or reddish-brown urine discoloration, which is caused by the quinol metabolites of propofol and is not dangerous. Changes in sexual behavior may occur, as with the use of other anesthetics. After repeated administration of propofol, mild thrombopenia was observed.

Often there is pain at the injection site, which can be reduced by injecting the drug into one of the large veins in the forearm or in the cubital fossa. Phlebitis and venous thrombosis are rarely observed. In some cases, severe tissue reactions occurred after paravenous administration of propofol.

Contraindications

Increased sensitivity to any of the components of the drug

Induction of anesthesia and maintenance of anesthesia in children under 3 years of age

Adolescence under 16 years of age (to ensure sedation during artificial ventilation lungs).

Use with caution in elderly or debilitated patients, children, patients with impaired cardiac, renal or hepatic function, and in patients with hypovolemia.

Drug interactions

It should be taken into account that the use of propofol together with premedications, inhalation drugs or analgesics can increase anesthesia, as well as adverse reactions from cardiovascular system If opioids are used for premedication, respiratory arrest may occur more frequently and last longer.

The concentration of propofol in the blood may temporarily increase after administration of fentanyl. There is no need to adjust the maintenance dose.

In patients receiving cyclosporine, leukoencephalopathy has been observed in some cases when lipid-containing emulsions like Propofol® were administered.

When using Propofol® as an adjunct to local anesthetics, lower doses of propofol may be sufficient. Concomitant administration of opioids may worsen propofol-induced respiratory depression.

Special instructions

Propofol (for anesthesia and sedation) should only be used in hospitals or clinics and, due to the need to maintain ventilation and adequate arterial oxygenation, resuscitation equipment should be in close proximity.

When administering Propofol®, the condition of patients should be constantly monitored in order to determine whether early stage possible decrease in blood pressure, obstruction respiratory tract, hypoventilation or insufficient oxygen supply. It is necessary to pay special attention patients receiving Propofol® for sedation during surgical or diagnostic procedures without the use of artificial ventilation.

The safety and effectiveness of propofol for sedation in children under 16 years of age have not been demonstrated.

Although there is no evidence of a cause-and-effect relationship, serious adverse events (including deaths) have been reported during unlicensed use of the drug when patients under 16 years of age are sedated. These side effects include, in particular, the development of metabolic acidosis, hyperlipidemia, necrosis skeletal muscles and/or heart failure. These side effects were most often observed in children with respiratory tract infections receiving the drug for sedation in the intensive care unit at doses exceeding the recommended limits for adults.

Also, very rare cases of metabolic acidosis, rhabdomyolysis, hyperkalemia and/or rapidly progressing heart failure (sometimes fatal) have been reported in adult patients receiving the drug for more than 58 hours at doses exceeding 5 mg/kg/h. This is more than maximum dose at 4 mg/kg/h, currently recommended for sedation during intensive care. Heart failure in such cases is usually not relieved by inotropic therapy.

Prescribers are advised, whenever possible, not to exceed a dose of 4 mg/kg/h, which is usually sufficient for sedation of mechanically ventilated patients during intensive care (for treatment durations greater than 1 day). Providers should be alert to the development of such adverse effects and should reduce the dose or switch to a different sedative at the first appearance of symptoms.

Propofol does not have vagolytic activity, and its use was accompanied by cases of bradycardia, sometimes deep, as well as asystole. The possibility of intravenous administration of an anticholinergic agent should be considered before induction of anesthesia or during maintenance of anesthesia, especially when propofol is used in conjunction with other drugs that can cause bradycardia, and also in cases where vagal tone is likely to predominate.

Propofol® contains egg lecithin as an emulsifier. As a result of dissolution, lysolecithin is formed, a compound that has hemolytic properties in vitro. In clinical settings, even complete dissolution, the risk of hemolysis remains low if recommended dosages are followed. In the presence of pathologies (liver and/or renal failure) with low albumin concentrations, this risk increases, and therefore the corresponding indicators should be regularly checked.

Must be observed special caution when administering Propofol® to patients with high intracranial pressure And low rate mean arterial pressure due to the risk of a significant decrease in intracerebral perfusion pressure.

Since Propofol® is a lipid emulsion, appropriate precautions must be taken when administering the drug to patients with severe disorders of lipid metabolism, such as, for example, pathological hyperlipidemia. When prescribing Propofol® to patients at particular risk of excess fat, blood lipid concentrations should be monitored and, if necessary, the dose reduced. If the patient, in addition to Propofol®, receives other parenteral lipid emulsions, when calculating total fat intake, the amount of fat contained in Propofol® (0.1 g/ml) should be taken into account.

Lipid concentrations should be monitored in all patients receiving sedation for more than 3 days.

In patients suffering from epilepsy, Propofol may cause seizures. Before administering anesthesia to patients with epilepsy, it is necessary to ensure that the patient has been given the necessary antiepileptic drugs. It is not recommended to use Propofol during electric shock treatment.

Propofol's own analgesic effect is insufficient. To ensure sufficient pain relief, it is recommended to use analgesics.

Before transferring the patient to a regular department, you should ensure that he is fully awakened from general anesthesia. It should be noted that the effects of general anesthesia may adversely affect the patient's ability to perceive instructions that are given to him after the operation.

Propofol® and any equipment necessary for its administration are intended for each patient individually. According to general recommendations for the use of fat emulsions, the duration of infusions of undiluted propofol should not exceed 12 hours at a time. The remaining Propofol® and infusion set should be discarded after the end of the infusions or no later than 12 hours after the start of the infusions. If necessary, the infusion can be re-administered.

Upon discharge from hospital, the patient should be escorted home. The patient should be advised to abstain from alcohol consumption.

Pregnancy and lactation

Pregnancy

Propofol crosses the placental barrier and may have a depressant effect on the fetus. For this reason, Propofol is contraindicated during pregnancy, as well as in high doses for anesthesia in nature, with the exception of termination of pregnancy.

Lactation

Should stop breast-feeding.

Features of the influence on the ability to drive a car and operate machinery

Care must be taken when driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

An overdose can cause depression of the cardiovascular and respiratory systems.

Treatment: For depression respiratory system Artificial oxygen ventilation is recommended, and if the cardiovascular system is depressed, the patient’s position should be changed so that his head is higher and his legs lower. If necessary, you can use vasopressor and plasma replacement agents or electrolyte solutions such as Ringer's solution.

Release forms and packaging

20 emulsions for intravenous administration in ampoules and 5 ampoules with instructions for use in a cardboard box.

Storage conditions

At a temperature from +2ºС to +25ºС in a place protected from light. Do not freeze. Keep out of the reach of children!

Shelf life

After opening the bottle, the drug should be used immediately.

Do not use after expiration date!

Pharmacy release form

By prescription

Manufacturer

Xi"an Lipont Pharmaceutical Co., Ltd

C -708 Chuangye Building, Keji 1st Road, Xi"an Hi-tech Zone,China

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Propofol is a non-inhalation anesthetic agent that has a short-term effect and causes the rapid onset of drug-induced sleep (within about 30 seconds after administration). Recovery of consciousness usually occurs quickly. The mechanism of action of propofol has not been fully elucidated.
The pharmacokinetics of propofol after bolus administration is three-phase. The first phase is characterized by rapid distribution of the active substance (half-life is 2-4 minutes), the second phase is characterized by rapid elimination of propofol (half-life - 30-60 minutes); This is followed by a longer, final phase, which is characterized by the redistribution of propofol from poorly perfused tissues into the blood. Propofol is well distributed and quickly eliminated from the body (total clearance is 1.5-2 l/min). Metabolized primarily in the liver, inactive metabolites are excreted in the urine. In cases where propofol is used to maintain anesthesia, its concentration in the blood reaches a stable level corresponding to the infusion rate. Within the recommended infusion rates, the pharmacokinetics of propofol is linear.

Indications for use of the drug Propofol

Introductory IV anesthesia; maintaining anesthesia; to achieve a sedative effect in patients undergoing mechanical ventilation.

Use of the drug Propofol

Propofol is usually combined with additional analgesics. For adults, for induction anesthesia, regardless of whether premedication was performed or not, propofol is recommended to be titrated; adult patients in satisfactory condition administered intravenously at a rate of approximately 40 mg/10 s until clinical signs of anesthesia appear. For most adult patients under the age of 55 years, the average dose of propofol is 2-2.5 mg/kg. For elderly patients, as a rule, a lower dose is required, for weakened patients - a higher dose. low speed administration (approximately 20 mg/10 s). To maintain anesthesia, a continuous infusion of propofol is carried out (usually at a rate of 4-12 mg/kg per 1 hour) or it is repeatedly administered as a bolus in doses of 25-50 mg, achieving the maintenance of the required depth of anesthesia. To ensure a sedative effect during intensive care and during mechanical ventilation, propofol is administered intravenously at a rate of 0.3-4 mg/kg per 1 hour until a satisfactory clinical effect is achieved. In elderly patients, propofol is titrated based on the patient's response.
When using propofol for induction of anesthesia in children, it is administered slowly until clinical signs of anesthesia appear. The dose is adjusted according to age or body weight. For most children over 8 years of age, 2.5 mg/kg propofol is sufficient for induction of anesthesia. For children under 8 years of age, propofol doses may be higher. To maintain anesthesia, children receive a continuous infusion of propofol or re-inject it as a bolus; administration of propofol at a rate of 9-15 mg/kg per hour allows maintaining a sufficient depth of anesthesia. Propofol is not recommended for use as a sedative in children, since the safety and effectiveness of its use in this area age group not installed; There are reports of the development of severe side effects(up to fatal outcome), and these phenomena were most often observed in children with respiratory tract infections when doses higher than recommended were administered.
Propofol can be used undiluted or administered diluted in a concentration of 1:5 with 5% glucose solution.

Contraindications to the use of the drug Propofol

Hypersensitivity to propofol, age up to 3 years, pregnancy.

Side effects of the drug Propofol

During induction anesthesia, hypotension and short-term apnea may occur, rarely - epileptiform seizures, opisthotonus, pulmonary edema, pain at the injection site; During the awakening period, nausea, vomiting, headache, and fever are possible. In rare cases, after the administration of propofol, allergic reactions (erythema, bronchospasm, etc.), changes in the color of urine, thrombosis and phlebitis may be observed (especially when propofol is administered into small-caliber veins).

Special instructions for the use of the drug Propofol

Anesthesia using propofol can only be performed by an experienced anesthesiologist, with equipment for resuscitation and constant monitoring of the functions of the cardiovascular and respiratory systems.
Propofol should be used with extreme caution in patients with epilepsy and seizures history, as well as when prescribing propofol to patients with cardiovascular, respiratory, renal or hepatic diseases, weakened or patients with severe dehydration of the body.
Propofol does not have a sufficient vagolytic effect; its use may be accompanied by severe bradycardia or the development of asystole. If it is necessary to use propofol simultaneously with other drugs that have a negative chronotropic effect, it seems advisable to carry out premedication with intravenous administration of an anticholinergic drug before induction of anesthesia or while maintaining anesthesia.
When severe symptoms occur during the administration of propofol arterial hypotension It may be necessary to administer fluids to correct blood volume and reduce the rate of propofol infusion.
For some time after anesthesia with propofol, the ability to perform potentially dangerous species activities (transport management, working with complex mechanisms).
The administration of propofol can be combined with spinal or epidural anesthesia.
The safety of propofol in women during breastfeeding has not been established.
The duration of propofol administration should not exceed 12 hours. At the end of the infusion or after 12 hours, it is necessary to replace the propofol solution and equipment for its transfusion.

Drug interactions Propofol

Typically, the use of propofol requires additional use analgesics. Propofol is combined with medicines used for premedication, with muscle relaxants, inhalational anesthetics and analgesics; There are no undesirable pharmacodynamic interactions observed. Before use, propofol should not be mixed with any drugs for parenteral administration or infusion media, with the exception of 5% glucose solution in containers made of polyvinyl chloride or glass, as well as lidocaine for injection in plastic syringes.

Overdose of Propofol, symptoms and treatment

May be accompanied by respiratory and cardiac depression; monitoring recommended external respiration and cardiac activity, if necessary - mechanical ventilation, oxygen therapy, the use of plasma expanders and pressor agents.

List of pharmacies where you can buy Propofol:

Saint Petersburg

Propofol is a non-inhalation anesthetic agent that has a short-term effect and causes rapid onset of drug-induced sleep (within about 30 s after administration). Recovery of consciousness usually occurs quickly. The mechanism of action of propofol has not been fully elucidated.

The pharmacokinetics of propofol after bolus administration is three-phase. The first phase is characterized by rapid distribution of the active substance (half-life is 2-4 minutes), the second phase is characterized by rapid elimination of propofol (half-life 30-60 minutes); This is followed by a longer, final phase, which is characterized by the redistribution of propofol from poorly perfused tissues into the blood. Propofol is well distributed and quickly eliminated from the body (total clearance is 1.52 l/min). Metabolized primarily in the liver, inactive metabolites are excreted in the urine. In cases where propofol is used to maintain anesthesia, its concentration in the blood reaches a stable level corresponding to the infusion rate. Within the recommended infusion rates, the pharmacokinetics of propofol is linear.

Indications

Introductory IV anesthesia; maintaining anesthesia; to achieve a sedative effect in patients undergoing mechanical ventilation.

Application

When using propofol for induction of anesthesia in children, it is administered slowly until clinical signs of anesthesia appear. The dose is adjusted according to age or body weight. For most children over 8 years of age, 2.5 mg/kg propofol is sufficient for induction of anesthesia. For children under 8 years of age, propofol doses may be higher. To maintain anesthesia, children receive a continuous infusion of propofol or re-inject it as a bolus; administration of propofol at a rate of 915 mg/kg per hour allows maintaining a sufficient depth of anesthesia. Propofol is not recommended for use as a sedative in children, since the safety and effectiveness of its use in this age group have not been established; There are reports of severe side effects (including death), and these phenomena were most often observed in children with respiratory tract infections when doses higher than recommended were administered.

Propofol can be used undiluted or administered diluted in a concentration of 1:5 with 5% glucose solution.

Contraindications

Hypersensitivity to propofol, age up to 3 years, pregnancy.

Side effects

During induction anesthesia, hypotension and short-term apnea may occur, rarely epileptiform seizures, opisthotonus, pulmonary edema, pain at the injection site; during the period of awakening, nausea, vomiting, headache, fever. In rare cases, after the administration of propofol, allergic reactions (erythema, bronchospasm, etc.), changes in the color of urine, thrombosis and phlebitis may be observed (especially when propofol is administered into small-caliber veins).

Special instructions

Propofol should be used with extreme caution in patients with epilepsy and a history of seizures, as well as when prescribing propofol to patients with cardiovascular, respiratory, renal or hepatic diseases, weakened people or patients with severe dehydration of the body.

Propofol does not have a sufficient vagolytic effect; its use may be accompanied by severe bradycardia or the development of asystole. If it is necessary to use propofol simultaneously with other drugs that have a negative chronotropic effect, it seems advisable to carry out premedication with intravenous administration of an anticholinergic drug before induction of anesthesia or while maintaining anesthesia.

If severe arterial hypotension occurs during the administration of propofol, it may be necessary to administer fluids to correct the volume of blood volume and reduce the rate of propofol infusion.

For some time after anesthesia with the use of propofol, the ability to perform potentially dangerous activities (driving vehicles, working with complex mechanisms) decreases.

The administration of propofol can be combined with spinal or epidural anesthesia.

The safety of propofol in women during breastfeeding has not been established.

The duration of propofol administration should not exceed 12 hours. At the end of the infusion or after 12 hours, it is necessary to replace the propofol solution and equipment for its transfusion.

Interactions

As a rule, the use of propofol requires the additional use of analgesics. Propofol is combined with drugs used for premedication, muscle relaxants, inhalational anesthetics and analgesics; There are no undesirable pharmacodynamic interactions observed. Before use, propofol should not be mixed with any drugs for parenteral administration or infusion media, with the exception of 5% glucose solution in polyvinyl chloride or glass containers, as well as lidocaine for injection in plastic syringes.

Overdose

May be accompanied by respiratory and cardiac depression; Monitoring of external respiration and cardiac activity is recommended, if necessary mechanical ventilation, oxygen therapy, use of plasma expanders and pressor agents.

Formula: C12H18O, chemical name: 2,6-bis-(1-Methylethyl)phenol.
Pharmacological group: neurotropic drugs/ anesthetics.
Pharmacological action: sedative, anesthetic.

Pharmacological properties

Propofol has an effect at the level of lipid membranes of central neurons nervous system nonspecific action. Propofol does not have an initial stimulating effect. Typically, recovery from anesthesia is not accompanied by postoperative nausea and vomiting or headache. In most patients, general anesthesia occurs within 30–60 seconds. The duration of anesthesia depends on the dose and concomitant medications and ranges from 10 minutes to 1 hour. The patient awakens from anesthesia with a clear consciousness and quickly, after 10 minutes, it becomes possible to open his eyes.

Propofol is well distributed in the body and is quickly eliminated, clearance is 1.6–3.4 l/min in an adult patient weighing 70 kg. The half-life of propofol when administered intravenously is 277 - 403 minutes. In the form of a three-part model, the kinetics of propofol when administered intravenously can be represented as a bolus: rapid distribution phase (with a half-life of 2–4 minutes), β-phase elimination (with a half-life of 30–60 minutes) and γ-phase elimination (with a half-life of 200–60 minutes). 300 minutes). In the γ-phase, the decrease in the content of propofol in the blood occurs slowly due to prolonged redistribution from adipose tissue. Propofol is 97% bound to plasma proteins. Propofol is mainly metabolized in the liver by conjugation. Approximately 88% of inactive metabolites are excreted by the kidneys. Propofol passes well through tissue barriers (including both placental and blood-brain barriers), and is excreted in small quantities into breast milk. When maintaining anesthesia as usual after surgical procedures lasting up to 5 hours, no significant accumulation of propofol was observed.

Indications

Maintenance of general anesthesia, induction of anesthesia, sedation of patients during artificial ventilation, diagnostic and surgical procedures.

Method of administration of propofol and dose

Propofol is administered intravenously. Induction of anesthesia: adults - 40 mg every 10 seconds (until clinical signs of anesthesia appear), children over 8 years old - 2.5 mg/kg. Maintenance of anesthesia: use either repeated boluses or continuous infusion. The dose is set individually, adequate anesthesia is achieved when administered at a rate of 4–12 mg/kg/h, for children - 9–15 mg/kg/h. For sedation during intensive care in patients who are on mechanical ventilation, 0.3–4 mg/kg/h is administered intravenously.

When there is a danger of adverse reactions, which are associated with activation vagus nerve, then it is advisable to administer an anticholinergic intravenously before induction of anesthesia. Do not use propofol in obstetric practice, since the drug penetrates the placental barrier and can lead to neonatal depression (it is possible to use propofol in the 1st trimester of pregnancy during operations to terminate it). Possibility of appearance pain along the vein can be significantly reduced when the drug is administered into large-diameter veins or when sharing lidocaine solution. Propofol injection should be performed only by specially trained personnel with the possibility of immediate use of artificial ventilation, oxygen therapy, and the full scope of resuscitation measures.

Contraindications for use

Hypersensitivity, age: up to 16 years - to provide a sedative effect during intensive care, up to 1 month - to maintain anesthesia and induction of anesthesia.

Restrictions on use

Epilepsy, lipid metabolism disorders, hypovolemia, anemia, severe decompensated diseases of the respiratory system, circulatory system, liver and kidneys, in weakened and elderly patients, lactation, pregnancy.

Use during pregnancy and breastfeeding

Propofol penetrates the placental barrier and can have a depressing effect on the fetus. Therefore, propofol is contraindicated during pregnancy (except for termination of pregnancy), as well as for anesthesia during delivery in high doses. Propofol is excreted in small quantities into breast milk. It is believed that this does not pose a danger to the baby only if the mother begins breastfeeding a few hours after using propofol.

Side effects of propofol

Low blood pressure, bradycardia, shortness of breath, short-term cessation of breathing, rarely - opisthotonus, convulsions, pulmonary edema; upon awakening - nausea, headache, vomiting, postoperative fever; local reactions- pain at the injection site, rarely - vein thrombosis and phlebitis.

Interaction of propofol with other substances

Propofol is compatible with drugs for epidural and spinal anesthesia, With medicines, which are used for premedication, with analgesics and muscle relaxants.

Overdose

An overdose of propofol causes depression of the respiratory and cardiovascular systems. Required: symptomatic therapy against the background of artificial ventilation, maintenance of hemodynamics (administration of vasopressors and fluids).

1 ml of emulsion contains: active substance: propofol 10 mg;

excipients: soybean oil 100 mg, glycerol 22.5 mg; phospholipids egg yolk 12.0 mg; oleic acid (for pH correction) 0.4 - 0.8 mg; sodium hydroxide (for pH correction) 0.05 - 0.11 mg; water for injections up to 1 ml.

Description

White homogeneous emulsion.

Pharmacological action

Propofol (2,6-diisopropylphenol) is a short-acting general anesthetic with fast start actions. Depending on the rate of administration, the onset of anesthesia takes 30-40 seconds. The duration of action after administration of a bolus dose, depending on metabolism and elimination, is 4-6 minutes.

Clinical efficacy and safety

When Propofol Fresenius is used as recommended, there is no clinically significant accumulation of propofol after multiple injections or infusions. Patients quickly regain consciousness.

When Propofol Fresenius is used to induce anesthesia, bradycardia and a decrease in blood pressure may be observed, which is likely due to a vagotonic effect and inhibition of sympathetic activity. Hemodynamic parameters usually normalize during anesthesia.

Children and teenagers

Limited studies on the duration of anesthesia in children indicate that safety and effectiveness remain unchanged for anesthesia lasting up to 4 hours. Literature data on the use of propofol in children for long-term anesthesia also demonstrate safety and effectiveness.

Pharmacokinetics

Propofol Fresenius is 97% bound to plasma proteins. Drug kinetics following intravenous bolus injection can be represented by a three-part model: rapid distribution phase (half-life 2-4 minutes), P-phase (half-life 30-60 minutes) and y-phase (half-life 200-300 minutes). ). During the γ-phase, the decrease in drug concentration in the blood occurs slowly due to slow redistribution from poorly perfused, probably fatty tissues. In a clinical setting, this phase does not affect the time of awakening. Propofol Fresenius is metabolized primarily by conjugation in the liver with a clearance of about 2 l/min, but metabolism also occurs outside the liver. Clearance in children is higher than in adults. The half-life after intravenous infusion ranged from 277 to 403 minutes. Inactive metabolites are excreted mostly by the kidneys (about 88%). When general anesthesia was maintained as usual, no significant accumulation of Propofol Fresenius was observed after surgical procedures lasting at least 5 hours. Within the recommended infusion rates, pharmacokinetics are linear.

Indications for use

For induction of anesthesia and its maintenance in adults and children over 1 month;

To provide a sedative effect in adults and children over 16 years of age receiving intensive care and undergoing mechanical ventilation;

In order to provide a sedative effect in conscious adults during surgical and diagnostic procedures.

Contraindications

Hypersensitivity to any of the components of the drug, pregnancy, childhood up to 1 month. For sedation of patients under 16 years of age during intensive care.

Allergy to soy or peanuts.

In the presence of cardiac, circulatory or respiratory failure it should be compensated before the administration of Propofol Fresenius.

In patients with severe heart failure and other severe heart diseases, unless extreme caution and intensive monitoring of the patient is provided.

Particular caution should be exercised in patients with high intracranial pressure and low mean blood pressure who have increased risk significant drop in intracranial perfusion pressure.

Pregnancy and lactation

Propofol Fresenius penetrates the placental barrier and can have a depressing effect on the fetus. For this reason, the drug is contraindicated during pregnancy, as well as in high doses for general anesthesia during childbirth, with the exception of operations to terminate pregnancy.

Studies conducted in lactating women have shown that propofol is excreted in small amounts in breast milk. Therefore, nursing mothers should stop breastfeeding for 24 hours after administration of propofol, and also express and discard breast milk.

Directions for use and doses

Only intravenously. When administering Propofol Fresenius, the physician should have at his disposal the equipment usually used during general anesthesia, including means of monitoring the functioning of the cardiovascular system (ECG, pulse, oximetry) and resuscitation equipment.

The dose of Propofol Fresenius is selected individually depending on the patient’s response to premedication. As a rule, when using the drug, additional administration of analgesic drugs is required.

General anesthesia in adults Induction of anesthesia

To induce general anesthesia, Propofol Fresenius is administered in small doses (approximately 20-40 mg every 10 seconds) until clinical signs of anesthesia appear. Usual dose for adults under the age of 55 years is 1.5-2.5 mg/kg body weight. During continuous infusion, 0.3-4.0 mg/kg body weight/hour is administered. It is not recommended to exceed the infusion rate of 4.0 mg/kg body weight/hour.

At older ages, the required dose generally decreases. In patients in American Society of Anesthesiologists (ASA) classes III and IV, induction of anesthesia develops more slowly, requiring slower administration of Propofol Fresenius: approximately 2 ml (20 mg) every 10 seconds.

Maintenance of anesthesia

When using Propofol Fresenius, maintenance of anesthesia is achieved either by continuous infusion or by repeated bolus injections.

To maintain anesthesia by continuous infusion, the dose and rate of administration are selected individually, usually 4-12 mg/kg body weight/hour of propofol is administered. For minor operations, such as minimally invasive procedures, a lower maintenance dose of approximately 4 mg/kg body weight/hour may be sufficient.

A reduction in the dose of Propofol Fresenius to 4 mg/kg body weight/hour is also recommended for elderly patients, patients with hypovolemia and patients with grade III-IV severity of the condition according to the ASA classification.

To maintain anesthesia through repeated bolus injections, Propofol Fresenius should be administered in a dose of 25 to 50 mg, which corresponds to 2.5 to 5 ml of the drug.

In elderly patients, rapid bolus administration is not indicated due to the possibility of cardiopulmonary depression.

General anesthesia in children older than 1 month

Due to the lack of experience with the use of Propofol, Fresenius should not be used in children under 1 month of age.

Induction of anesthesia

When used for induction purposes, it is recommended to titrate the dose until clinical signs of the onset of general anesthesia appear. The dose should be adjusted based on the patient's age and/or weight. When inducing general anesthesia in children over 8 years of age, approximately Propofol Fresenius 2.5 mg/kg body weight is usually required. It is necessary to administer the drug slowly in repeated fractional doses until clinical signs of general anesthesia appear. Younger children may require more high dose. The initial dose of Propofol Fresenius should be 3 mg/kg body weight, and if necessary, an additional dose of 1 mg/kg body weight can be administered.

Due to lack of experience clinical application for small children from groups high risk(III - IV degree of severity of the condition according to the ASA classification) lower doses are recommended.

Maintenance of anesthesia

To maintain anesthesia in children by continuous infusion, the recommended doses of Propofol Fresenius are 9-15 mg/kg body weight per hour. Children under 3 years of age may require a higher dose within the recommended dosage limit than older children. The dose should be selected individually and special attention should be paid to the adequacy of pain relief. Maximum duration application should not exceed approximately 60 minutes, with the exception of specific situations requiring more long-term use, for example malignant hyperthermia, when inhalational anesthetics cannot be used.

The use of Propofol Fresenius as a sedative during intensive therapy in adults

The dose is selected depending on the required depth of sedation. When maintaining general anesthesia through continuous infusion, a dose of Propofol Fresenius is used from 0.3 to 4.0 mg/kg body weight per hour. Administration rates higher than 4.0 mg/kg body weight per hour are not recommended. When administering fat emulsions to a patient, it must be taken into account that 1 ml of Propofol Fresenius contains 0.1 g of fat.

Propofol Fresenius should not be used as a sedative in children under 16 years of age.

Elderly patients, patients with heart, respiratory, kidney or liver diseases, as well as patients with hypovolemia and epilepsy, Propofol Fresenius should be administered at a reduced rate.

Methods of administration

Infusion of Propofol Fresenius in undiluted form is allowed. Dilution of Propofol Fresenius is recommended only with 5% glucose solution for intravenous administration or 0.9% sodium chloride solution for intravenous administration in glass bottles.

Shake before administration!

Use only homogeneous emulsion from an intact container.

Before use, the rubber membrane of the container or the neck of the ampoule is sprayed with an alcohol aerosol or wiped with a swab soaked in alcohol.

Since Propofol Fresenius is a fat emulsion that does not contain preservatives and does not have antimicrobial activity, the drug can serve favorable environment For rapid growth microorganisms. When opening a bottle or ampoule containing Propofol Fresenius, it is necessary to strictly observe the rules of asepsis. Administration of the drug must be started without delay.

During the entire period of administration of Propofol Fresenius, the rules of aseptic handling of the drug and the parenteral infusion system must be observed. When co-infusing Propofol Fresenius with other drugs and solutions in the same system, it is recommended that the latter be administered closer to the cannula. Propofol Fresenius must not be administered through a microbiological filter. Propofol Fresenius and other infusion systems containing propofol are intended for single injection or infusion into only one patient individually.

Infusion of undiluted Propofol Fresenius

When infusing undiluted Propofol Fresenius, it is recommended to always use devices to control the volume of the drug administered, such as a drop counter, syringe pumps or volumetric infusion pumps.

When administering fat emulsions, including Propofol Fresenius, it is recommended to use the same infusion system for no more than 12 hours. After 12 hours of use, the system containing Propofol Fresenius or the container with the drug should be replaced.

Infusion of diluted Propofol Fresenius

To administer diluted Propofol Fresenius, it is possible to use various options systems for intravenous infusions. However, the use of standard systems does not guarantee against accidental uncontrolled administration of large volumes of diluted Propofol Fresenius. The IV system should include devices to monitor the volume of drug administered, such as a drop counter, burette, or volumetric infusion pump. When determining the maximum dilution of the burette, the risk of introducing large doses propofol. The recommended dilution of Propofol Fresenius is 1 part propofol and 4 parts 5% glucose solution for intravenous administration or 0.9% sodium chloride solution for intravenous administration (the content of the active substance in the diluted solution should not be less than 2 mg/ml). The dilution is prepared under aseptic conditions immediately before administration of the drug; the infusion should be completed no later than 6 hours after preparing the dilution. Propofol Fresenius should not be diluted with other solutions for infusion or injection. Co-administration of a 5% glucose solution, 0.9% sodium chloride solution with Propofol Fresenius is allowed through a tee with a valve in close proximity to the injection site.

To reduce pain at the injection site of Propofol Fresenius, it is permissible to mix it immediately before administration with a preservative-free 1% solution of lidocaine hydrochloride for injection (20 parts of Propofol Fresenius + 1 part of 1% solution of lidocaine hydrochloride for injection).

Muscle relaxant drugs such as atracurium besilate and mivacurium chloride can be administered at the injection site of Propofol Fresenius only after jet rinsing.

Propofol Fresenius should not be used after the expiration date.

Administration of Propofol Fresenius emulsion should begin immediately after opening the ampoule or vial.

The system for administering undiluted Propofol Fresenius must be replaced at the end of the 12-hour period after opening the ampoule or vial. Dilutions of Propofol Fresenius with 5% glucose solution for intravenous administration or 0.9% sodium chloride solution for intravenous administration must be prepared under aseptic conditions immediately before infusion, their administration must be completed within 6 hours after preparation of the dilution.

Any remaining contents of ampoules or vials after use must be destroyed.

Side effect

When introduced into general anesthesia Low blood pressure and temporary respiratory arrest may develop and may be severe, especially in patients with general deterioration. Less commonly, epileptoform movements, convulsions and opisthotonus were observed, sometimes several hours or days after drug administration. Cases of pulmonary edema have also been reported. Sometimes upon awakening, consciousness deteriorates again for a short time. In some cases, allergic reactions have been observed in the presence anaphylactic symptoms such as severe hypotension, bronchospasm, facial edema or erythema. Bradycardia, arrhythmia and, in some cases, cardiac arrest (asystole) have occurred during the use of Propofol Fresenius. In very rare cases, when using Propofol Fresenius for sedation during intensive care at doses above 4 mg/kg/h, rhabdomyolysis, metabolic acidosis, hyperkalemia or heart failure have been observed. Very rarely, pancreatitis developed after the administration of Propofol Fresenius; but the cause-and-effect relationship has not been clearly confirmed. Postoperative chills, fever, cold sensation, and euphoria were also noted. Against the background of long-term use of Propofol, Fresenius may be observed

green or reddish-brown coloration of urine caused by quinol metabolites of propofol and not dangerous. There may be changes in sexual behavior, as with the use of other anesthetics. After repeated administration of Propofol Fresenius, mild thrombocytopenia was observed. During the period of awakening - nausea, vomiting, dizziness, headache, cough.

Propofol Fresenius is usually well tolerated. There is often pain at the injection site, which can be relieved by mixing the drug with lidocaine or by injecting the drug into one of the large veins in the forearm or in the cubital fossa. Phlebitis and venous thrombosis are rarely observed. In isolated cases, severe tissue reactions have occurred following intravenous administration of Propofol Fresenius.

Below are unwanted effects, which are classified as the following:

Very frequent (>1:10)

Frequent (from >1:100 to<1:10)

Infrequent (from > 1:1 LLC to< 1:100)

Rare (from > 1:10000 to<1:1000)

Very rare (<1:10000)

Unknown (cannot be estimated from available data)

Within each group, undesirable effects are presented in descending order of their importance.

Immune disorders

Rare: anaphylactic reactions, including Quincke's edema, bronchospasm, erythema and arterial hypotension.

Very rare: allergic reactions to soybean oil.

Metabolic disorders

Frequent: hypertriglyceridemia.

Mental disorders

Rare: euphoria and increased sexual function during the recovery period. Neurological disorders

Frequent: spontaneous movements and myoclonus during induction of anesthesia, minimal agitation.

Rare: headache, dizziness, chills and cold sensations during the recovery period. Epileptiform movements, including convulsions and opisthotonos.

Very rare: late epileptiform seizures, developing over several hours or days. Risk of seizures in patients with epilepsy after administration of propofol. Cases of lack of consciousness after surgery.

Cardiac changes/vascular disorders

Frequent: during induction of anesthesia, hypotension, bradycardia, tachycardia, hot flashes.

Uncommon: severe hypotension. It may be necessary to reduce the rate of administration of Propofol Fresenius and/or replace the fluid, if necessary, vasoconstrictors. The possibility of a sharp decrease in blood pressure in patients with impaired coronary or cerebral blood flow or in patients with hypovolemia should be taken into account.

Increasing bradycardia (up to asystole) during general anesthesia. Intravenous administration of anticholinergic drugs is possible during induction of general anesthesia or during maintenance anesthesia.

Rare: arrhythmia during the recovery period. Thrombosis and phlebitis at the injection site.

Changes in the respiratory system, chest and mediastinum

Frequent: upon induction of anesthesia, hyperventilation, transient apnea, cough, hiccups.

Uncommon: cough during maintenance anesthesia.

Rare: cough during the recovery period. "

Very rare: pulmonary edema.

Gastrointestinal disorders

Rare: nausea and vomiting during recovery.

Very rare: Cases of pancreatitis have been described after administration of propofol, although a cause-and-effect relationship has not been established.

Changes in the skin and subcutaneous tissues

Very rare: severe tissue changes after accidental paravenous injection. Changes in the kidneys and urinary tract

Rare: change in urine color after prolonged use of propofol.

General and local reactions

Very common: pain at the injection site at the beginning of administration.

Pain at the site of propofol injection can be minimized by simultaneous administration of lidocaine or its infusion into a larger forearm vein or cubital fossa. When coadministered with lidocaine, it is rare (>1:10,000 to<1:1000) наблюдались следующие нежелательные эффекты: головокружение, рвота, сонливость, судороги, брадикардия, сердечная аритмии и шок.

Rare: postoperative fever.

Very rare: isolated cases of severe undesirable effects in the form of a complex of symptoms have been described: rhabdomyolysis, metabolic acidosis, hyperkalemia and heart failure, sometimes with death. In most cases, these symptoms were observed in intensive care units in patients receiving doses greater than 4 mg/kg/h.

Overdose

Symptoms:

Depression of the cardiovascular and respiratory systems.

If respiratory depression occurs, artificial ventilation with oxygen is recommended, and if the cardiovascular system is depressed, the patient's position should be changed so that his head is in an elevated position. If necessary, you can use vasopressor agents, plasma replacement agents or electrolyte solutions such as Ringer's solutions, and symptomatic therapy.

Interaction with other drugs

Propofol Fresenius can be used in conjunction with other drugs usually used for premedication, inhalation anesthesia, muscle relaxants or local anesthetics. Cases of pharmacological incompatibility have not yet been reported. A reduction in the dose of the drug is required if general anesthesia is accompanied by local anesthesia.

The use of benzodiazepines, parasympatholytics or inhalational anesthetics in conjunction with Propofol Fresenius prolongs the anesthetic effect and reduces the respiratory rate.

After joint premedication with opiates, the frequency and duration of apnea may increase. During the administration of suxamethonium or neostigmine, bradycardia and cardiac arrest may occur.

Propofol Fresenius in combination with these drugs that have a hypotensive effect and affect breathing may enhance these phenomena.

It should be taken into account that the use of Propofol Fresenius against the background of premedication simultaneously with inhalation or other analgesics may potentiate anesthesia and side effects from the cardiovascular system. The combined use of drugs that depress the central nervous system, for example, alcohol, general anesthetics or narcotic analgesics, leads to a pronounced manifestation of their sedative effect. If the administration of Propofol Fresenius is combined with parenterally administered drugs in the central nervous system, severe respiratory and cardiac depression is possible.

After administration of fentanyl, the blood level of Propofol Fresenius temporarily increases. There is evidence that the administration of fat emulsions, such as Propofol Fresenius, to patients receiving cyclosporine causes leukoencephalopathy.

Features of application

Propofol Fresenius does not reduce the tone of the vagus nerve, and its use in some cases is accompanied by bradycardia (sometimes pronounced), as well as asystole. Before induction or during maintenance of general anesthesia with Propofol Fresenius, the possibility of intravenous anticholinergic administration should be considered, especially in cases of suspected increased vagal tone or when Propofol Fresenius is used in conjunction with other drugs that can cause bradycardia.

To relieve pain at the injection site when inducing general anesthesia with Propofol Fresenius, lidocaine can be administered before administering the drug emulsion. When using lidocaine, it should be taken into account that it should not be used in patients with hereditary porphyria.

Propofol Fresenius should only be used by physicians trained in anesthesiology or intensive care.

The effectiveness and safety of Propofol Fresenius for (background) relaxation in children under 16 years of age has not been studied. Serious side effects, including death, have been reported when the drug is used unlicensed for (background) relaxation in children under 16 years of age, although a causal relationship has not been established. In particular, cases of metabolic acidosis, hyperlipidemia, rhabdomyolysis and/or heart failure have been reported. These effects were most often observed in children with respiratory tract infections receiving doses of the drug in intensive care units that exceeded adult doses. Similarly, rare cases of metabolic acidosis, rhabdomyolysis, hyperkalemia, and/or rapidly progressive heart failure (in some cases fatal) have been reported in adults treated for longer than 48 hours at rates greater than 5 mg/kg/hour. This rate exceeds the maximum rate of 4 mg/kg/hour recommended for use of the drug for the purpose of relaxation of patients in intensive care units. Heart failure in such cases is usually not responsive to maintenance therapy with inotropes.

Once again, we remind doctors, if possible, not to exceed the dosage of 4 mg/kg/hour, which is usually sufficient for relaxation of patients on mechanical ventilation in intensive care units (for treatment durations of more than 1 day). Physicians should be alert for these side effects and reduce the dose or switch to other sedatives at the first sign of their occurrence.

In some cases, after using Propofol Fresenius, a period of postoperative unconsciousness of the patient was observed, accompanied by increased muscle tone. Although consciousness returned spontaneously, patients who are unconscious require careful monitoring.

Propofol Fresenius contains soybean oil, which in rare cases can cause severe allergic reactions.

Before discharging the patient from the clinic, you should ensure that he has fully recovered from general anesthesia.

During the entire infusion period, the principles of asepsis should be observed both in relation to the drug Propofol Fresenius and in relation to the infusion equipment. Parallel administration of other substances through the infusion system for Propofol Fresenius should be carried out as close to the cannula as possible. The drug should not be administered through an antibacterial filter.

Propofol Fresenius and all infusion equipment for its administration can only be used once and only for one patient.

The rate of administration of Propofol Fresenius should be reduced in patients with congenital dementia, patients with epilepsy, with impaired function of the heart, lungs, liver and kidneys, and with hypovolemic conditions.

Special precautions should be taken in patients with impaired fat metabolism, as well as in other conditions that require caution when infusing a fat emulsion, since 1 ml of Propofol Fresenius contains 0.1 g of fat.

If it is necessary to administer an increased dose of the drug to overweight patients, the increased risk of hemodynamic disturbances and adverse effects on the cardiovascular system should be taken into account.

After 3 days of using Propofol Fresenius in the intensive care unit, lipid levels should be checked. After 3 days of using Propofol Fresenius in the intensive care unit, lipid levels should be checked.

Due to the increased dose of the drug required for patients with severe obesity, the risk of changes in hemodynamics and effects on the cardiovascular system should be taken into account.

The use of Propofol Fresenius as a sedative in adults can only be carried out by doctors with special training in anesthesiology and intensive care.

Propofol Fresenius should not be administered by personnel performing diagnostic or surgical procedures.

Although a cause-and-effect relationship has not been established, the use of Propofol Fresenius in children as a sedative has caused serious complications, in some cases even death. Such cases were most often observed during unauthorized use in children with respiratory tract infections, and the dose exceeded the recommended dose for adults.

Epilepsy

Patients with epilepsy should receive antiepileptic therapy before induction of anesthesia. Although propofol has been shown to be effective against status epilepticus in a number of studies, the use of propofol in patients with epilepsy may increase the risk of seizures. Propofol Fresenius is not recommended for use during electroconvulsive therapy.

Driving a car and working with machinery

After the administration of Propofol Fresenius, the patient should remain under medical supervision for an appropriate period of time. The patient should be informed that he should not drive vehicles or machinery, should avoid drinking alcohol and working in potentially hazardous conditions. The patient can be sent home only with an accompanying person.