What is propofol used for? Influence on the gastrointestinal tract and kidneys. Pharmacological group of the substance Propofol

Gross formula

Pharmacological group of the substance Propofol

Nosological classification (ICD-10)

CAS code

Pharmacology

It has a nonspecific effect at the level of lipid membranes of CNS neurons. It does not have an initial exciting effect. Recovery from anesthesia is usually not accompanied by headache, postoperative nausea and vomiting. In most patients, general anesthesia occurs within 30-60 seconds. The duration of anesthesia, depending on the dose and concomitant drugs, ranges from 10 minutes to 1 hour. From anesthesia, the patient wakes up quickly and with a clear mind, the ability to open his eyes appears after 10 minutes.

It is well distributed and rapidly excreted, the clearance varies from 1.6 to 3.4 l / min in an adult weighing 70 kg. T 1/2 after IV infusion - from 277 to 403 minutes. The kinetics of propofol after an IV bolus infusion can be represented as a three-part model: a fast phase of distribution (T 1/2 - 2-4 min), β-phase elimination (T 1/2 - 30-60 min) and γ-phase elimination (T 1/2 - 200-300 min). During the γ-phase, the decrease in the concentration of the drug in the blood occurs slowly due to the prolonged redistribution from adipose tissue. Plasma protein binding - 97%. It is metabolized mainly by conjugation in the liver, as well as outside the liver. Inactive metabolites are excreted mainly by the kidneys (about 88%). Well overcomes histohematic barriers, incl. placental, BBB. In a small amount penetrates into breast milk. While maintaining anesthesia in the usual mode, there was no significant accumulation of propofol after surgical procedures lasting up to 5 hours.

The use of Propofol

Induction anesthesia, maintenance of general anesthesia; sedation of patients during mechanical ventilation, surgical and diagnostic procedures.

Contraindications

Hypersensitivity, children's age: up to 1 month - for induction of anesthesia and maintenance of anesthesia, up to 16 years - to provide a sedative effect during intensive care.

Application restrictions

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

Use during pregnancy and lactation

Propofol crosses the placental barrier and may have a depressing effect on the fetus. Contraindicated during pregnancy, as well as in high doses for anesthesia during delivery (except for termination of pregnancy).

Data from studies conducted in nursing mothers show that a small amount of propofol passes into breast milk. It is believed that this does not pose a danger to the infant if the mother starts breastfeeding a few hours after the introduction of propofol.

Side effects of Propofol

Decreased blood pressure, bradycardia (sometimes pronounced), short-term respiratory arrest, shortness of breath; rarely - convulsions, opisthotonus, pulmonary edema; during awakening - headache, nausea, vomiting, postoperative fever (rarely); local - pain at the injection site, rarely - phlebitis and vein thrombosis.

Interaction

Compatible with drugs for spinal and epidural anesthesia, with drugs used in premedication, with muscle relaxants and analgesics.

Overdose

Symptoms: depression of the cardiovascular and respiratory systems.

Treatment: symptomatic on the background of mechanical ventilation (oxygen), maintenance of hemodynamics (introduction of fluids and vasopressors).

Routes of administration

Propofol Precautions

In cases where there is a possibility of developing side effects associated with the activation of the vagus nerve, it is advisable to inject intravenous anesthesia with an anticholinergic before anesthesia. Should not be used in obstetric practice, because. propofol crosses the placental barrier and can cause neonatal depression (may be used in the first trimester during abortions).

The risk of pain along the vein can be significantly reduced by infusion through large diameter veins or by the simultaneous administration of a solution of lidocaine. The injection can only be done by specially trained personnel with the possibility of immediate use of mechanical ventilation, oxygen therapy, resuscitation in full.

Interactions with other active substances

Trade names

Propofol is a drug for non-inhalation anesthesia that has a short-term effect and causes a 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 triphasic. The first phase is characterized by the rapid distribution of the active substance (half-life is 2-4 minutes), the second phase is the rapid elimination of propofol (half-life is 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 rapidly excreted from the body (total clearance is 1.5-2 l/min). It is metabolized mainly 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 rate of infusion. Within recommended infusion rates, the pharmacokinetics of propofol is linear.

Indications for the use of the drug Propofol

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

The use of Propofol

Propofol is usually combined with the additional prescription of analgesics. Adults for induction anesthesia, regardless of whether premedication was performed or not, propofol is recommended to be titrated; adult patients in a satisfactory condition are injected 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 debilitated patients, a lower rate of administration (approximately 20 mg / 10 s). To maintain anesthesia, a constant 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, seeking to maintain 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. Elderly patients titrate propofol, taking into account the reaction of the patient.
When using propofol for induction 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 the age of 8 years, propofol 2.5 mg/kg is sufficient for induction anesthesia. For children under 8 years of age, propofol doses may be higher. To maintain anesthesia, children are given a constant infusion of propofol or repeated boluses; the introduction of propofol at a rate of 9-15 mg/kg per 1 hour allows you to maintain a sufficient depth of anesthesia. Propofol is not recommended as a sedative in children because its safety and efficacy in this age group have not been established; there are reports of the development of severe side effects (up to death), and these phenomena were most often observed in children with respiratory tract infections at doses exceeding the recommended ones.
Propofol can be used undiluted, as well as administered diluted at a concentration of 1:5 with 5% glucose solution.

Contraindications to the use of Propofol

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

Side effects of Propofol

During induction anesthesia, hypotension and short-term apnea may occur, rarely - epileptiform seizures, opisthotonus, pulmonary edema, pain at the injection site; during awakening, nausea, vomiting, headache, fever are possible. In rare cases, after the introduction of propofol, allergic reactions (erythema, bronchospasm, etc.), discoloration of urine, thrombosis and phlebitis may occur (especially with the introduction of propofol into small caliber veins).

Special instructions for the use of the drug Propofol

Anesthesia using propofol can only be performed by an experienced anesthetist, 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 a history of seizures, as well as in the appointment of propofol in patients with cardiovascular, respiratory, renal or hepatic diseases, debilitated or patients with severe dehydration.
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 appropriate to premedicate with an intravenous injection of an anticholinergic drug before induction anesthesia or while maintaining anesthesia.
If severe arterial hypotension occurs against the background of the administration of propofol, it may be necessary to administer fluids to correct the BCC and reduce the rate of propofol infusion.
For some time after anesthesia with the use of propofol, the ability to perform potentially hazardous activities (driving, working with complex mechanisms) decreases.
The introduction of propofol can be combined with spinal or epidural anesthesia.
The safety of propofol use in breastfeeding women 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 the equipment for its transfusion.

Propofol drug interactions

As a rule, the use of propofol requires the additional use of analgesics. Propofol is combined with drugs used for sedation, with muscle relaxants, inhalation anesthetics and analgesics; undesirable pharmacodynamic interactions are not noted. Before use, propofol should not be mixed with any parenteral preparations 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.

Propofol overdose, symptoms and treatment

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

List of pharmacies where you can buy Propofol:

• St. Petersburg

Propofol is a strong short-acting anesthetic that is administered intravenously. It is used for maintenance and as an induction anesthesia, as well as a sedative for mechanical ventilation during adult surgery. The drug is quite actively used in veterinary medicine. It is successfully used in many countries, and its generics are also sold.

Chemically, the drug cannot be attributed to barbiturates, in anesthesia it is able to replace pentothal, since the latter does not have such a quick and clean exit from anesthesia.

Propofol is a hypnotic that is not considered an analgesic, so it can be administered in combination with fentanyl to relieve pain. Among doctors, propofol is jokingly called "milk of amnesia", propofol got this name for its appearance and effect of amnesia.

Historical facts

Propofol was pioneered by Imperial Chemical Industries in the UK. In 1970, phenol derivatives were created for the first time, which led to the development of 2,6-diisoprofenol. The first test was made in 1977, and after that propofol was used as an anesthetic for induction of anesthesia. At first, the solvent of the drug was Cremophor (a special castor oil), but since there were frequent anaphylactic reactions to it, the drug was withdrawn from sale. It wasn't until 1985 that an emulsion containing a small percentage of soybean oil, sodium hydroxide, and other enzymes was developed. This emulsion preparation enters the pharmacological markets in 1986, and is called Diprivan. Due to its properties, Diprivan has been recognized by anesthesiologists all over the world; in Russia, this drug is not popular mainly because of its high cost in relation to its counterparts.

pharmachologic effect

Due to the fact that propofol is quite quickly soluble in fats, the drug instantly penetrates the brain, this is what causes its early action. During the delivery of the blood drug from the forearm to the brain, there is a complete shutdown of consciousness, this is approximately 90 seconds. Propofol binds to a greater extent to plasma proteins, to a lesser extent to plasma albumins. It is rapidly cleaved in the liver, forming inactive metabolites, which are excreted by the kidneys. Excreted unchanged in urine and feces. The pharmacokinetics of propofol is influenced by such factors as weight, gender, age, concomitant diseases.

Anesthesia with propofol

In medicine, continuous drip administration of propofol is used. It should be noted that the solution is an excellent nutrient medium for microflora, the ampoules are opened immediately before use, and anesthesia with propofol is applied immediately after the drug is drawn into the syringe.

Since propofol is not able to have an analgesic effect, it is used in conjunction with analgesics that block interoreception from reflexogenic zones. When anaesthetizing elderly patients, it is also recommended to use propofol with an analgesic, in this case, anesthesia occurs earlier using lower dosages.

The bolus administration of propofol consists in its rapid intravenous administration in an undiluted form of 2.0-2.5 mg / kg. In order to avoid disturbance of external respiration, the drug must be administered slowly, over 60-90 seconds. In the event that the drug is not enough, you can re-introduce propofol.

The surgical stage in this case occurs after 20-30 seconds from the start of the drug administration, at this stage anesthesia passes without obvious signs of arousal. Quite often, bradypnea or apnea develops. A single injection of the drug propofol causes short-term anesthesia for 6-9 minutes. This time is usually sufficient for surgical interventions in dentistry. The patient's recovery from anesthesia is calm, concomitant reactions are not observed, after 2-3 minutes the patient responds quite adequately.

For small children under 3 years of age, anesthesia with propofol is administered extremely slowly, until the first signs of anesthesia appear. Depending on the weight and age of the baby, the doctor chooses the dosage of the medicine. Interestingly, children 8 years of age require an exact dosage of 2.5 mg / kg, but in order to achieve the same effect in younger children, the drug may need more.

In order to maintain anesthesia in adults, the anesthetic is used as a bolus injection. An adult for long-term infusion requires, as a rule, 6-10 mg / kg of the drug. In some cases, the anesthesiologist may reduce the dose to 4 mg / kg, when administering anesthesia to patients, pensioners and other certain groups of people. Propofol is recommended for use in children under the age of 16 during examination, surgery, treatment, if it is necessary to achieve a sedative effect.

Contraindications

During pregnancy, regardless of the trimester and during breastfeeding, propofol is not recommended. This is due to the fact that the drug easily passes through the placental barrier and enters breast milk. Also, the drug is not used in obstetrics, it is forbidden to mix it with all injection solutions except for 5% glucose solution and lidocaine.

In case of lipid metabolism disorders, propofol or diprivan is used with caution so as not to cause complications. With caution, the drug is used for violations of the cardiovascular system, various diseases of the kidneys and liver, respiratory organs, in cases of weakness of the body, epilepsy. When conducting anesthesia with propofol in elderly or weakened by chronic diseases people, the dose of the drug is reduced.

Also, propofol is not used if the patient has a history of an allergic reaction to this drug.

Complications

This drug has recently become known to anesthesiologists. There are two complication factors in anesthesia with propofol:

• During and after anesthesia
• In the intensive care complex

There is a clearly expressed activity of the patient's movements, both at the entrance to anesthesia and at the exit from it. And also noticed intracranial hypertension, hallucinations, convulsions and other post-anesthetic disorders. Propofol most strongly reduces systolic blood pressure, in some cases it is possible to develop bradycardia, arrhythmia, atrial fibrillation, up to cardiac arrest. The drug depresses breathing and often leads to the development of apnea. Allergic reactions to propofol are extremely rare.

Diprivan

Propofol analogue. It is marketed as an emulsion and used in anesthesia. Since the active substance is propofol, the pharmacological actions of the drugs are similar. Diprivan is used during the introduction of the patient into anesthesia, and to maintain the induction of anesthesia. Diprivan provides an instant entry into anesthesia, as well as a fairly quick awakening. The drug is metabolized to a greater extent by the liver.

Diprivan is used:

• on induction into anesthesia
• during sedation of the patient during mechanical ventilation
• for sedation of short-term surgical interventions
• children under 16 years of age in intensive care sedation

Contraindications to the use of Diprivan

Diprivan has the following contraindications:

• pathology of the cardiovascular system (use with caution)
• dysfunction of the kidneys, liver
• during pregnancy (penetrates the placenta and depresses the organs of the fetus)
• not applicable in obstetrics
• when breastfeeding

Side effects

Side effects are in many ways similar to those that can be caused by any other anesthetic drugs. When administered under anesthesia, the drug rarely causes disturbances. In some cases, patients experience pain at the injection site of the anesthetic. During anesthesia, when Diprivan is used, blood pressure sometimes decreases, the pulse becomes less frequent, and a rush of blood is possible.

drug overdose

With an overdose of the drug Diprivan, there are violations in the cardiovascular system, respiratory organs. At the same time, the doctor begins to carry out artificial ventilation of the lungs with oxygen. In case of violations in the cardiovascular system, plasma substitutes are administered.

Special Instructions

Both drugs can only be used by specially trained personnel. While the drug is being administered, the patient's well-being is constantly monitored, and auxiliary equipment that can be used in emergency cases must be properly prepared. It is especially worth noting that during medical surgical procedures, spontaneous movements of the patient are possible, therefore, before undertaking manipulations, it is necessary to fix the patient well.

Thiopental sodium, hexenal

1 g in a vial is diluted in 10 ml of saline. solution (get 10% solution), then dilute another 4 times and get 2.5% solution.
After 3 years - 5-6 mg / kg, up to 3 years - 7-8 mg / kg i.v., but not more than 1 g in total, action 20 minutes. Intramuscularly injected 5% solution at the rate of 12-25 mg / kg, sleep after 7-8 minutes, duration 1 hour.

Propofol

Propofol (2,6-diisopropylphenol) consists of a phenolic ring to which two isopropyl groups are attached. Changing the length of the side chains of this alkylphenol affects the power, speed of induction and awakening.

Propofol is not water soluble, but a 1% aqueous solution (10 mg/mL) is used clinically as an emulsion containing soybean oil, glycerol and egg lecithin. An allergy to eggs is not an absolute contraindication to the use of propofol, because in most cases such an allergy is due to a reaction to the egg white (egg albumin), while lecithin is isolated from the yolk.

pharmacological properties.

Propofol is a fat-soluble, fast-acting drug for intravenous anesthesia. Anesthesia occurs within 30-60 seconds in most patients.

Protein binding - 98%.

The distribution of the drug can best be described using a three-chamber model: rapid distribution between blood and tissues (half-life 2-3 minutes), rapid disappearance from the blood during metabolism (half-life 30-60 minutes) and a slower final phase, during which propofol is excreted from poorly perfused tissues. The volume of distribution at constant infusion is 2-10 l/kg.

The rapid onset of the effect is due to the high lipophilicity of propofol and easy passage through the blood-brain barrier. Propofol is metabolized in the liver to inactive conjugates. Moderate cirrhosis does not affect the pharmacokinetics of propofol. Chronic renal failure does not affect the clearance of the drug, although its metabolites are excreted in the urine. Clearance 20-30 ml/min/kg.

Mechanism of action.

It is possible that the mechanism of action of propofol is due to the ability to facilitate the transmission of an inhibitory nerve impulse mediated by gamma-aminobutyric acid.

Indications for use.

Induction anesthesia and maintenance of general anesthesia.

Providing a sedative effect during intensive care (it is used both alone and in combination with other sedatives, for example, dormicum, which provides mutual reinforcement of the necessary and useful properties, reduction of disadvantages and a significant reduction in the cost of therapy).

Providing a sedative effect in surgical or diagnostic procedures combined with regional or local anesthesia (neuroaxial blocks in orthopedic and traumatological interventions, combinations of epidural, subarachnoid and combined spinal-epidural blocks with controlled sedation with propofol).

The use of a laryngeal mask (LM) during controlled sedation against the background of neuraxial blockade.

Contraindications.

Previously shown hypersensitivity to propofol or other components of the drug. Anesthesia in children under 3 years of age. Providing sedation in children under 16 years of age.

Effect on the body.

The cardiovascular system.

Propofol significantly reduces OPSS, myocardial contractility and preload, which leads to a significant decrease in blood pressure. It should be noted that stimulation of the sympathetic nervous system, due to laryngoscopy and tracheal intubation, usually quickly returns blood pressure to normal.

Arterial hypotension is exacerbated by the use of large doses of propofol, excessively rapid administration and the advanced age of the patient.

Propofol significantly inhibits the baroreceptor reflex. In the absence of diseases of the cardiovascular system and hypovolemia, changes in heart rate and CO are transient and insignificant. Ventricular dysfunction increases the risk of a significant decrease in CO as a result of a decrease in ventricular filling pressure and myocardial contractility.

Respiratory system.

Propofol causes profound respiratory depression: the induction dose usually causes apnea. Even lower doses of propofol, which allow for so-called "awake sedation", depress the respiratory response to hypoxia and hypercapnia. Deep inhibition of reflexes from the respiratory tract allows for tracheal intubation and the establishment of a laryngeal mask without muscle relaxation.

Central nervous system.

Propofol reduces cerebral blood flow and intracranial pressure. In intracranial hypertension without pressor support, propofol can cause an unacceptable decrease in cerebral perfusion pressure below a critical level (i.e.< 50 мм.рт.ст.).

Propofol eliminates vomiting and itching, which is a unique property for anesthetics. In some cases, propofol effectively eliminates seizures. Sometimes during induction there are muscle contractions, involuntary movements, hiccups. Propofol reduces intraocular pressure.

Method of application and dose.

Adults.

Introductory anesthesia.

The dose of propofol should be individualized according to the response of the patient and may be given by bolus injection or infusion. The usual starting dose for adults is 40 mg (4 ml) given as a slow intravenous bolus injection at 10 second intervals until clinical signs of anesthesia appear. The usual induction dose for healthy patients under 55 years of age is 1.5-2.5 mg/kg. The total dose can be reduced by slowing the rate of drug administration (20 to 50 mg/min). A dose of 1.0-1.5 mg/kg is usually sufficient for elderly patients. Lower doses, most commonly 20 mg (2 ml) at 10-second intervals, are recommended for patients with ASA grade 3 and 4 anesthesia risk.

Maintenance of general anesthesia.

Anesthesia can be maintained with propofol by continuous infusion or repeated bolus injections.

continuous infusion. The required infusion rate varies from 6 to 12 mg/kg/h in different patients. In elderly, debilitated and hypovolemic patients, as well as in patients with an ASA grade 3 and 4 anesthetic risk, the dose of propofol should be reduced to 4 mg/kg/h. For the onset of anesthesia (within approximately the first 10-20 minutes), some patients may require a slightly higher infusion rate (8-10 mg / kg / h).

Repeated bolus injections. The dose of repeated bolus injections is 25-50 mg (2.5-5.0 ml) depending on the patient's response.

Providing a sedative effect during intensive care.

Initially, bolus injections of 1.0-2.0 mg/kg should be used, followed by continuous infusion to maintain the desired level of sedation. Usually, an infusion rate of 0.3-4.0 mg/kg/h is sufficient. continuous administration of propofol should not exceed seven days.

Providing a sedative effect during surgical and diagnostic procedures.

Doses should be selected individually. A significant sedative effect is achieved by administering initially 0.5-1.0 mg/kg over 1-5 minutes and maintaining a constant infusion at a rate of 1.0-4.5 mg/kg/h. If more sedation is needed, bolus doses of 10-20 mg can be administered additionally. Lower doses of propofol are usually sufficient for patients with ASA grades 3 and 4 and older patients.

Propofol is not approved for use in children under 3 years of age because its safety has not been proven.

Introduction to general anesthesia.

The dose of propofol for children is calculated according to age and weight. The average dose for induction of anesthesia for children over 8 years of age is 2.5 mg / kg and is administered by slow intravenous injection until signs of anesthesia appear. Younger children may require higher doses of propofol per kilogram of body weight.

For propofol mononarcosis, the following formula can be used to calculate the induction dose: mg/kg = 5-0.125. age (years)

No data are available for children with ASA grades 3 and 4.

Maintenance of anesthesia.

Maintenance of anesthesia can be carried out by continuous infusion or bolus injections. Doses are selected individually, on average 9-15 mg / kg / h.

Traumatic operations: the first 10 minutes - 12-15 mg / kg / hour
the next 10 minutes - 6-8 mg / kg / hour
the next 10 minutes - 6 mg / kg / hour
then - 4 mg/kg/hour

Appendectomy: 9 mg/kg/hour for the first 30 minutes, then 6 mg/kg/hour.

Providing a sedative effect during intensive care, surgical and diagnostic procedures.

For these purposes, propofol is not used in children, since its safety and effectiveness in this case have not been proven.

Although a causal relationship has not been established, serious side effects have been reported in off-label use of propofol. Adverse reactions were most common in children with infectious diseases of the respiratory tract if the applied doses exceeded those recommended for adults.

Special precautions for handling the drug.

Propofol and any equipment needed to administer it must be strictly sterile because propofol contains no antimicrobial preservatives and the lipid emulsion supports the growth of bacteria and other microorganisms.

Any liquid solutions used concomitantly with propofol should be administered as close to the cannula as possible. Propofol should not be administered through a microbiological filter.

In accordance with the general recommendations regarding the use of lipid emulsions, the duration of the infusion of undiluted propofol should not exceed 12 hours at a time. Do not continue to use the remaining amount of propofol, and discard the equipment used for infusion administration at the end or no later than 12 hours after the start of the infusion. Repeat the infusion if necessary.

Introduction method.

Propofol is given intravenously only. To reduce pain upon injection, the initial dose of propofol may be mixed immediately before administration with lidocaine (10 mg/ml) for injection at a ratio of 1 part lidocaine to 20 parts propofol. For this purpose, other analgesics can also be used - fentanyl, alfentanil, meperidine, tramadol.

Propofol can be administered diluted or undiluted.

Appropriate equipment (drop counters, metered infusion and syringe pumps) should be used to maintain the required infusion rate and prevent accidental overdose.

Propofol can be diluted with 5% glucose for infusion. It should be diluted no more than 5 times (the minimum content of propofol is 2 mg / ml). Any diluted solutions must be used within 6 hours of preparation.

Special warnings and precautions for use.

Resuscitation facilities must be available in case of any complications.

Patients should be continuously monitored during propofol administration to detect possible hypotension, airway obstruction, hypoventilation, or insufficient oxygen supply early in the administration. Particular attention should be given to patients receiving propofol for sedation during non-ventilated surgical and diagnostic procedures.

Special precautions should be taken when administering propofol to patients with cardiac, respiratory, renal or hepatic insufficiency. Patients with hypovolemia and those whose general condition worsens represent another risk group.

Since propofol does not have the ability to reduce the tone of the vagus nerve, bradycardia and even asystole may occur. Anticholinergics should be administered before induction of anesthesia, especially if propofol is used in conjunction with other drugs,

which can cause bradycardia and in cases of predominance of the vagus nerve tone.

Special precautions should be taken in patients with high intracranial pressure and low mean arterial pressure, as there is a risk of a significant decrease in intracranial perfusion pressure.

Since propofol is a lipid emulsion, special precautions should be taken for patients with severe disorders of lipid metabolism, such as pathological hyperlipidemia. If propofol is prescribed to patients for whom excessive fat intake is a risk factor, blood lipid levels should be constantly monitored and, if necessary, the dose of the drug should be reduced. If the patient is receiving parenteral lipid emulsions in addition to propofol, the amount of lipid contained in propofol (0.1 g/ml) should be taken into account when calculating the total fat intake.

Propofol may cause convulsions in patients with epilepsy.

Propofol has no analgesic effect, so its administration should be combined with analgesics or regional anesthesia.

Interactions.

The use of propofol is well combined with spinal and epidural anesthesia, as well as with various drugs for premedication, muscle relaxants, inhalation anesthetics and analgesics. Some of the aforementioned drugs may lower blood pressure or depress respiration, thereby enhancing the effects of propofol. If opioid analgesics are administered for premedication, apnea may occur more frequently and last longer.

In patients receiving cyclosporine, the administration of lipid emulsions like propofol has in some cases resulted in leukoencephalopathy.

No pharmacological incompatibilities were noted. If propofol is used as an adjunct to local anesthesia, lower doses may be sufficient. Concomitant use of opioid analgesics may potentiate propofol-induced respiratory depression.

Pregnancy and lactation.

As a precaution, propofol is contraindicated during pregnancy. Propofol crosses the placental barrier and may have a depressing effect on the fetus. Propofol is contraindicated for anesthesia during delivery. Since safety in children has not been proven, propofol is contraindicated during lactation.

Side effects.

Propofol is generally well tolerated. The most commonly reported adverse effect is pain upon injection, which can be reduced by mixing the drug with lidocaine or injecting it into a larger vein. Thrombosis and phlebitis are rarely observed. In some cases, severe tissue reactions may occur after perivenous administration of the drug.

If propofol is administered together with lidocaine, the following adverse reactions caused by lidocaine may be observed: dizziness, vomiting, drowsiness, convulsions, bradycardia, cardiac disturbance, shock.

Anesthesia can cause hypotension and temporary apnea, which can be especially severe in patients with a general worsening condition. During the period of awakening, some patients experienced cases of headaches, nausea, and less often vomiting.

In some cases, hypersensitivity was noted, accompanied by anaphylactic symptoms: severe hypotension, bronchospasm, edema and facial erythema.

In connection with the long-term administration of propofol, there may be a change in the color of urine to green or reddish-brown, which is associated with the presence of quinol metabolites of propofol and is not dangerous.

Overdose.

Overdose can cause depression of the cardiovascular and respiratory systems. Respiratory depression should be treated with mechanical ventilation, and cardiac depression with vasopressors and plasma-substituting solutions.

Ketamine

intravenously 1-2 mg / kg 1-2.5% solution, the operation is allowed after 1-2 minutes, the action is 15-20 minutes. Intramuscularly - 8-10 mg / kg 5% solution, the operation is allowed after 5 minutes, 30

Neonates - 14 mg/kg i.m.

Ketamine for shock no more than 1 mg/kg i.v

Const infusion of ketamine - 10-20 mcg / kg / min = 1-2 mg / kg / hour 1% solution Only analgesic effect - 0.5-1 mg / kg i.m., begins to act after 15`When fentanyl is ineffective during surgery, add ketamine at a dose of 0.5 mg/kg i.v.

Sodium oxybutyrate

100 mg/kg for induction, 1/2 dose is injected slowly in a stream on glucose, the second 1/2 dose is administered drip for 10 minutes, then anesthesia occurs by the end of this 10th minute. With drip administration, GHB acts faster, induction of GHB with drip administration takes 10 minutes, with bolus - 20 minutes. Acts 45 minutes - 1 hour, removes potassium.

No. ml of 20% GHB per induction= (weight in kg)/2=100 mg/kg.

Midazolam

Composition and forms of release.

• One ampoule with 1 ml solution for intravenous, intramuscular and rectal administration contains:
• One 3 ml ampoule for intravenous, intramuscular and rectal administration contains:
• Midazolam hydrochloride 15 mg
• One 5 ml ampoule for intravenous, intramuscular and rectal administration contains:
• Midazolam hydrochloride 5 mg

Pharmachologic effect.

Dormicum's active ingredient, midazolam, belongs to the group of imidobenzodiazepines. The free base is a lipophilic substance, poorly soluble in water. The presence of a basic nitrogen atom in position 2 of the imidobenzodiazepine ring allows midazolam to form water-soluble salts with acids, which give stable and well-tolerated injection solutions. Midazolam becomes water soluble at pH<4.

The pharmacological action of midazolam is characterized by a rapid onset and, due to rapid biotransformation, a short duration. Due to its low toxicity, midazolam has a large therapeutic window.

Dormicum has a very fast sedative and pronounced hypnotic effect. It also has anxiolytic, anticonvulsant and muscle relaxant effects. Little effect on the structure of sleep. The effect is not typical.

After parenteral administration, a short anterograde amnesia occurs (the patient does not remember the events that occurred during the period of the most intense action of the active substance).

Pharmacokinetics.

Absorption after i / m administration.

Midazolam is absorbed from muscle tissue quickly and completely. The maximum plasma concentration is reached within 30 minutes. Bioavailability is over 90%.

Absorption after rectal administration.

Midazolam is rapidly absorbed. The maximum plasma concentration is reached within 30 minutes. Bioavailability is about 50%.

Distribution.

After intravenous administration, the midazolam plasma concentration curve is characterized by two distinct phases of distribution. The volume of distribution in the equilibrium state is 0.7-1.2 l / kg of body weight. The degree of binding to plasma proteins is 96-98%. The period of the initial distribution of T1 / 2alpha is 7.2 minutes.

In animal and human studies, midazolam has been shown to cross the placental barrier and into the fetal circulation. Small amounts are found in women's breast milk.

Metabolism.

Midazolam undergoes complete and rapid biotransformation. The main metabolite is a-hydroxymidazolam. In the liver, 40-50% of the dose is extracted. Many drugs have been found to inhibit the formation of this metabolite in vitro. For some of them, this has been confirmed in vivo (see Drug Interactions).

Withdrawal.

In healthy volunteers, the elimination half-life is 1.5-2.5 hours. Plasma clearance is in the range of 300-400 ml / min. If midazolam is administered by intravenous drip, the kinetics of its elimination does not differ from that after a jet injection. The half-life of the main metabolite, a-hydroxymidazolam, is shorter than the parent substance. It forms conjugates with glucuronic acid (inactivation). Metabolites are excreted through the kidneys.

Pharmacokinetics in special clinical situations.

In patients over 60 years of age, the half-life can increase up to 3 times, and in some patients in intensive care receiving midazolam intravenously for long-term sedation - up to 6 times. At a constant infusion rate, these patients have higher steady-state plasma concentrations of midazolam.

The half-life may also increase in patients with congestive heart failure and with reduced liver function.

In children from 3 to 10 years, the half-life is 1-1.5 hours.

In newborns, due to the immaturity of the liver, the half-life is increased and averages 6 hours (3-12 hours).

Indications.

Conscious sedation before diagnostic and therapeutic procedures performed under local anesthesia or without it (intravenous administration).

Premedication (in / m or rectally in children).

Introduction to anesthesia and maintenance of anesthesia. As a means for induction anesthesia for inhalation anesthesia or as a sedative component for combined anesthesia, including total intravenous anesthesia - TVA (intravenous bolus and drip).

Ataralgesia in combination with ketamine in children (intramuscularly).

Long-term sedation in intensive care (intravenous stream or drip).

Midazolam is used in combination with various methods of regional anesthesia by constant perfusion at a dose of 0.08-0.12 mg/kg/h.

In children, the use of midazolam for sedation in adeno- and tonsillectomy at a dose of 0.4-0.5 mg/kg, in combination with local anesthesia, due to anterograde amnesia, made it possible to practically remove psycho-emotional stress and the fear of visiting the doctor again.

Mode of application.

Midazolam is a strong sedative that requires slow administration and individual dose selection.

The dose should be titrated until the desired sedative effect is achieved, which corresponds to the clinical need, the physical condition and age of the patient, as well as the drug therapy received by him.

In patients over 60 years of age, debilitated or chronically ill, the dose should be selected carefully, taking into account the special factors inherent in each patient.

Intravenous sedation with the preservation of consciousness.

Dormicum should be administered intravenously slowly, at a rate of approximately 1 mg/30 sec. The effect occurs approximately 2 minutes after administration.

For adult patients, the initial dose is 2.5 mg 5-10 minutes before the start of the procedure. If necessary, enter subsequent doses of 1 mg. Usually a total dose not exceeding 5 mg is sufficient.

For patients over 60 years of age, debilitated or chronically ill, the initial dose is reduced to 1-1.5 mg and administered 5-10 minutes before the start of the procedure. If necessary, enter subsequent doses of 0.5-1 mg. Usually a total dose not exceeding 3.5 mg is sufficient.

Anesthesia.

Introductory anesthesia.

The desired level of anesthesia is achieved by gradual dose selection. The induction dose of dormicum is administered intravenously slowly, fractionally. Each repeated dose not exceeding 5 mg should be administered within 20-30 seconds, with intervals of 2 minutes between injections.

Adult patients who received premedication: 0.15-0.2 mg / kg, the total dose is not more than 15 mg.

Adult patients who have not received premedication: 0.3-0.35 mg / kg of body weight, the total dose is usually not more than 20 mg.

Maintenance of anesthesia.

Maintenance of the desired level of loss of consciousness can be achieved either by further divided administration, or by continuous intravenous infusion of dormicum, usually in combination with analgesics.

The dose for maintaining anesthesia is 0.03-0.1 mg/(kg5 h) if dormicum is used in combination with narcotic analgesics, and 0.03-0.3 mg/(kg5 h) if it is used in combination with ketamine .

Patients over 60 years of age, debilitated or chronically ill require smaller doses.

Children receiving ketamine for the purpose of anesthesia (ataralgesia) are recommended to administer a dose of 0.15 to 0.2 mg / kg intramuscularly.

Sufficiently deep sleep is usually achieved in 2-3 minutes.

Intravenous sedation in intensive care.

The desired sedative effect is achieved by gradual dose selection, followed by either continuous infusion or fractional jet administration of the drug.

An intravenous loading dose is administered fractionally, slowly. Each repeated dose of 1-2.5 mg is administered over 20-30 seconds, observing 2-minute intervals between injections.

The value of the intravenous loading dose can range from 0.03-0.3 mg/kg, and usually a total dose of not more than 15 mg is sufficient.

In patients with hypovolemia, vasoconstriction or hypothermia, the loading dose is reduced or not administered at all.

The maintenance dose may be 0.03-0.2 mg/(kg5 h).

If the patient's condition allows, the degree of sedation should be regularly assessed.

In patients with hypovolemia, vasoconstriction or hypothermia, the maintenance dose is reduced, sometimes up to 25% of the usual dose.

If dormicum is used simultaneously with strong analgesics, the latter should be administered before it, so that the dose of dormicum can be safely titrated at the height of sedation caused by the analgesic.

Special instructions for dosing.

Dormicum solution in ampoules can be diluted with 0.9% sodium chloride solution, 5% and 10% glucose solution, Ringer's solution and Hartman's solution in the ratio of 15 mg of midazolam per 100-1000 ml of infusion solution. These solutions remain physically and chemically stable for 24 hours at room temperature or 3 days at 5°C.

Contraindications.

Hypersensitivity to benzodiazepines, myasthenia.

Side effects.

Dormicum is well tolerated. Quite often there is a slight increase in blood pressure, slight changes in heart rate and respiration.

In rare cases, adverse reactions from the respiratory and cardiovascular systems were noted. They consisted of depression and respiratory arrest and / or cardiac arrest. Such life-threatening events are more likely in patients over 60 years of age and in the presence of pulmonary or cardiac insufficiency, especially if the injection is given too quickly or large doses are administered.

Nausea, vomiting, headache, hiccups, laryngospasm, shortness of breath, hallucinations, excessive sedation, drowsiness, ataxia were also noted. In some cases, amnesia after the use of dormicum was prolonged.

In rare cases, paradoxical reactions such as increased activity and aggressiveness, as well as involuntary movements (including tonic-clonic convulsions and muscle tremors) have occurred.

Local reactions from the veins may develop (pain on injection, thrombophlebitis).

Separate cases of generalized hypersensitivity in the form of skin rash, urticaria, angioedema, seizures in newborns, including premature babies, are described.

After prolonged intravenous use of dormicum, the development of drug dependence is possible, its sudden cancellation may be accompanied by withdrawal symptoms.

Precautionary measures.

Special precautions are needed when dormicum is administered parenterally to high-risk patients: over 60 years of age, with organic brain damage, debilitated and chronic, suffering from obstructive pulmonary diseases, chronic renal failure, impaired liver function and congestive heart failure. These high-risk patients require lower doses and constant monitoring for early detection of vital signs.

In rare cases, paradoxical reactions such as increased activity and aggressiveness, as well as involuntary movements (including tonic-clonic convulsions and muscle tremors) have been observed. If such symptoms appear, the patient's response to dormicum should be assessed before continuing its administration.

Dormicum for injection should be used only in the presence of resuscitation equipment, since its intravenous administration can inhibit myocardial contractility and cause respiratory arrest.

After parenteral administration of the drug, patients can be released from the hospital or clinic no earlier than 3 hours later and only with accompaniment. Patients should be warned not to drive vehicles for at least 12 hours prior to administration of dormicum.

Abrupt withdrawal of dormicum after prolonged intravenous use may be accompanied by withdrawal symptoms. Therefore, the dose is recommended to be reduced gradually.

Pregnancy, breastfeeding.

Like other medicines, dormicum should not be used during the first three months of pregnancy, unless considered absolutely necessary by the attending physician. Particular caution should be exercised in cases of the use of benzodiazepines in the first and second stages of labor, since high single doses can cause respiratory depression, hypotension, hypothermia and a violation of the sucking reflex in the newborn.

Midazolam passes into breast milk and should generally not be used in breastfeeding mothers.

drug interactions.

If dormicum is used with antipsychotics, hypnotics, sedatives, antidepressants, narcotic analgesics, anticonvulsants, anesthetics and sedative antihistamines, an increase in the inhibitory effect on the central nervous system may occur.

There is a potentially important interaction between midazolam and compounds that inhibit certain liver enzymes (especially cytochrome P450 ΙΙΙ A). Available data strongly suggest that these compounds influence the pharmacokinetics of midazolam and may prolong its sedative effect. Ketoconazole, itraconazole, erythromycin, diltiazem, verapamil, and cimetidine are now known to cause this reaction in vivo.

For this reason, patients receiving the above compounds (or others that inhibit cytochrome P450 ΙΙΙ A) should be closely monitored during the first few hours after midazolam administration. According to studies, ranitidine does not significantly affect the pharmacokinetics of intravenously administered midazolam.

Alcohol may increase the sedative effect of midazolam.

Overdose.

Symptoms of an overdose of dormicum are expressed mainly in an increase in its pharmacological effects: depression of the central nervous activity (from excessive sedation to coma), confusion, lethargy, muscle weakness or paradoxical arousal. In most cases, you only need to control vital functions.

An extremely high overdose can cause coma, areflexia, cardiopulmonary depression and apnea, which require the use of appropriate measures (artificial ventilation, cardiovascular support). Overdose phenomena can be stopped with a benzodiazepine antagonist - anexat (the active substance is flumazenil).

Special remarks.

Incompatibility.

Dormicum solution in ampoules cannot be diluted with 6% Macrodex solution in glucose solution. Do not mix dormicum with alkaline solutions, as midazolam precipitates with sodium bicarbonate.

Storage conditions.

Dormicum ampoules should not be frozen as they may burst. In addition, a precipitate may form, which dissolves on shaking at room temperature.

MAC of inhalation anesthetics