Ketamine 5. Ketamine - instructions, indications, composition, method of application. General induction anesthesia

For induction and basic anesthesia, for short-term surgical interventions requiring and not requiring muscle relaxation, for painful instrumental and diagnostic manipulations, for transporting patients, for treating burn surfaces.

Release form of the drug Ketamine

solution for intravenous and intramuscular injection 5%; ampoule 2 ml with ampoule knife, cardboard pack 10;
solution for intravenous and intramuscular injection 5%; ampoule 10 ml with ampoule knife, cardboard pack 10;
solution for intravenous and intramuscular administration 50 mg/ml; ampoule 2 ml with ampoule knife, blister pack 5, cardboard box (box) 100;
solution for intravenous and intramuscular administration 50 mg/ml; ampoule 2 ml with ampoule knife, blister pack 5, carton pack 1;
solution for intravenous and intramuscular administration 50 mg/ml; vial (bottle) 5 ml, blister pack 5, carton pack 1;
solution for intravenous and intramuscular administration 50 mg/ml; bottle (bottle) 5 ml, blister pack 5, cardboard box (box) 30;
solution for intravenous and intramuscular administration 50 mg/ml; ampoule 2 ml with ampoule knife, blister pack 5, cardboard box (box) 20;
solution for intravenous and intramuscular administration 50 mg/ml; ampoule 2 ml with ampoule knife, blister pack 5, cardboard pack 2;
solution for intravenous and intramuscular administration 50 mg/ml; ampoule 2 ml with ampoule knife, blister pack 5, cardboard box (box) 50;
solution for intravenous and intramuscular administration 50 mg/ml; ampoule 5 ml with ampoule knife, blister pack 5, carton pack 1;
solution for intravenous and intramuscular administration 50 mg/ml; ampoule 5 ml with ampoule knife, blister pack 5, cardboard box (box) 100;
solution for intravenous and intramuscular administration 50 mg/ml; ampoule 5 ml with ampoule knife, blister pack 5, cardboard pack 2;
solution for intravenous and intramuscular administration 50 mg/ml; 5 ml ampoule with ampoule knife, blister pack 5, cardboard box (box) 20;
solution for intravenous and intramuscular administration 50 mg/ml; vial (bottle) 5 ml, blister pack 5, cardboard box (box) 50;
solution for intravenous and intramuscular administration 50 mg/ml; ampoule 2 ml with ampoule knife, cardboard pack 5;
solution for intravenous and intramuscular administration 50 mg/ml; ampoule 5 ml with ampoule knife, blister pack 5, cardboard box (box) 50;

Compound
1 ampoule with 2 ml solution for injection contains ketamine 100 mg; in a carton box 10 pcs.

Pharmacodynamics of the drug Ketamine

Means for non-inhalation anesthesia. With a single intravenous injection of ketamine, the narcotic effect occurs 30-60 seconds after administration and lasts 5-10 minutes (up to 15 minutes). With the / m administration of ketamine at a dose of 4-8 mg / kg, the effect occurs after 2-4 minutes (up to 6-8 minutes) and lasts an average of 12-25 minutes (up to 30-40 minutes). Ketamine causes a pronounced analgesic effect (up to 2 hours), but insufficient muscle relaxation. With the introduction of ketamine, pharyngeal, laryngeal and cough reflexes, independent adequate pulmonary ventilation are preserved. Metabolized in the liver.

Pharmacokinetics of Ketamine

Ketamine is a lipophilic compound and, therefore, is rapidly distributed to organs well supplied with blood, incl. in the brain, and then redistributed to tissues with reduced perfusion. Metabolized in the liver. T1 / 2 is 2-3 hours. It is excreted by the kidneys mainly in the form of conjugated metabolites.

Use of Ketamine during pregnancy

Ketamine crosses the placental barrier. The safety of ketamine use during pregnancy has not been established. Use in this category of patients is not recommended.

Contraindications to the use of the drug Ketamine

Cerebral circulation disorders, arterial hypertension, angina pectoris and heart failure in the decompensation phase, preeclampsia and eclampsia, epilepsy in childhood.

Side effects of Ketamine

From the side of the cardiovascular system: increased blood pressure, tachycardia.

From the digestive system: hypersalivation.

From the side of the central nervous system: psychomotor agitation and hallucinations in the period of recovery from anesthesia.

From the respiratory system: shortness of breath, respiratory depression.

Local reactions: extremely rarely, pain and hyperemia along the vein is possible at the injection site.

Dosage and administration of Ketamine

Depending on the indications, the age of the patient, the clinical situation, drugs used for premedication, a single dose for intravenous administration is 0.5-4.5 mg/kg, for intramuscular administration - 4-13 mg/kg.

Interactions of the drug Ketamine with other drugs

Ketamine potentiates the action of drugs for inhalation anesthesia. Enhances the effect of tubocurarine, but does not change the effect of pancuronium and succinylcholine.

Ketamine is chemically incompatible with barbiturates due to the formation of a precipitate.

Special instructions for taking Ketamine

Use with caution in patients with kidney disease. In operations on the larynx and pharynx, ketamine is used in combination with muscle relaxants.

Influence on the ability to drive vehicles and control mechanisms

After using ketamine for at least 24 hours, patients should refrain from driving vehicles and other potentially hazardous activities.

Storage conditions for Ketamine

List A .: In a place protected from light.

Shelf life of Ketamine

Belonging of the drug Ketamine to the ATX-classification:

N Nervous system

N01 Anesthetics

N01A General anesthetics

N01AX Other drugs for general anesthesia

Ketamine: instructions for use and reviews

Latin name: Ketamine

ATX Code: N01AX03

Active substance: ketamine (Ketamine)

Manufacturer: Moscow Endocrine Plant (Russia)

Description and photo update: 27.08.2019

Registration number:

Trade name of the drug: Ketamine

International (non-proprietary) name: ketamine

Dosage form: solution for intravenous and intramuscular administration

Compound: 1 ml solution contains:
Active substance: ketamine hydrochloride equivalent to 50 mg of ketamine - 57.6 mg.
Excipients: benzethonium chloride, sodium chloride, water for injection.

Description: clear, colorless or slightly colored liquid.

Pharmacotherapeutic group: means for non-inhalation general anesthesia.

ATX code:

Pharmacological properties
Pharmacodynamics. The drug causes an analgesic effect with incomplete depression of consciousness and the preservation of spontaneous breathing, pharyngeal, laryngeal and cough reflexes (the dose of the drug that causes apnea is 8 times higher than the hypnotic dose). The surgical stage of general anesthesia does not develop with the use of ketamine (the visceral analgesic activity of ketamine is insufficient, which should be taken into account during abdominal operations).
Causes a specific set of symptoms: somatic analgesia, a condition resembling neuroleptanalgesia, increases blood pressure, myocardial contractility, minute blood volume (MOC) and myocardial oxygen demand, relaxes the smooth muscles of the bronchi. Practically does not reduce the tone of skeletal muscles, can cause involuntary muscle twitches.
In adults, the minimum dose that causes a hypnotic effect with a single intravenous injection is 0.5 mg / kg of body weight (depression of consciousness lasts one and a half minutes). At a dose of 1 mg / kg of the drug, it depresses consciousness for 6 minutes, at a dose of 1.5 mg / kg - for 9 minutes, at a dose of 2 mg / kg - for 10-15 minutes. With intramuscular injection of 4-8 mg / kg, the effect occurs after 2-4 minutes (6-8 minutes) and lasts an average of 12-25 minutes (up to 30-40 minutes).
In children with intramuscular injection, general anesthesia occurs after 2-6 minutes, with intravenous administration - after 15-60 seconds, the duration of action is 15-30 and 5-15 minutes, respectively.
During the period of recovery of consciousness, drowsiness is noted, against the background of which reactions often occur in the form of hallucinations, delirium, vivid figurative dreams. After awakening, patients may remain disoriented, sometimes for 6-8 hours. The frequency and severity of these reactions, as well as the cardiostimulating effect, decrease when ketamine is combined with antipsychotic drugs (neuroleptics) and anxiolytic drugs (tranquilizers) - droperidol, diazepam.
The analgesic effect of ketamine in somatic pain is manifested when prescribing subnarcotic doses. The maximum analgesic effect occurs 10 minutes after injection into the vein and lasts for 2-3 hours, with intramuscular injection, the effect is longer.
Pharmacokinetics. Ketamine, being a lipophilic compound, easily penetrates the histohematogenous barriers, including the blood-brain barrier. Communication with plasma proteins - 12%. The volume of distribution is 1.8-2 l / kg, the half-life is 2.3 hours. Ketamine is metabolized by demethylation; the main part of the metabolic products is excreted within 2 hours with urine, a small amount of metabolites can remain in the body for several days. Cumulation with repeated administration is not observed.

Indications for use
Introductory and basic general anesthesia (especially in patients with low blood pressure or if it is necessary to maintain spontaneous breathing, or when performing artificial ventilation of the lungs with respiratory mixtures that do not contain dinitrogen oxide (nitrous oxide).
Emergency surgical interventions (including at the stages of evacuation, in particular, in patients with traumatic shock and blood loss).
Various surgical operations with multicomponent intravenous anesthesia.
Painful diagnostic procedures (endoscopy, cardiac catheterization), minor surgical procedures for burns, dressings, etc. procedures.

Contraindications
Hypersensitivity to the drug, arterial hypertension (and other conditions in which an increase in blood pressure is contraindicated), angina pectoris or myocardial infarction (including in the last 6 months), severe renal failure, cerebrovascular accident (incl. history), pre-eclampsia, eclampsia, epilepsy and other convulsive conditions, alcoholism, pregnancy and lactation.
Contraindications to ketamine anesthesia in children are any diseases accompanied by convulsive activity.

Carefully- decompensated chronic heart failure, operations on the larynx and pharynx.

Dosage and administration
Ketamine is administered intravenously (simultaneously by stream or fractional and drip) or intramuscularly.
Adults the drug is administered intravenously, at the rate of 2-3 mg / kg, intramuscularly - 4-8 mg / kg of body weight. To maintain anesthesia, the drug is administered at 0.5-1 mg / kg intravenously or 3 mg / kg intramuscularly or intravenously by drip, at a rate of 2 mg / kg / h (using an infusator or by dripping a 0.1% solution of ketamine (in 5 % dextrose solution (glucose) or 0.9% sodium chloride solution) at a rate of 20-50 drops / min.
In children the drug is used for induction anesthesia for various types of combined anesthesia (injected intramuscularly once at a rate of 4-5 mg / kg in the form of a 5% solution after appropriate premedication). For basic anesthesia, ketamine is administered intramuscularly (5% solution) or intravenously (1% solution in a jet or 0.1% solution drip at a rate of 50-60 drops / min); when administered intramuscularly, the dose depends on the body weight and age of the children: newborns and infants - 8-12 mg / kg, children from 1 to 6 years old - 6-10 mg / kg, 7-14 years old - 4-8 mg / kg . Intravenously administered at a dose of 2-3 mg/kg. Anesthesia is maintained by repeated injections of ketamine (3-5 mg/kg intramuscularly or 0.5-1 mg/kg intravenously by bolus or drip injection of a 0.1% solution of the drug at a rate of 30-60 drops/min).
To enhance the action of ketamine, it is usually used in combination with antipsychotic drugs (droperidol) and analgesics (fentanyl, promedol, etc.), while the dose of ketamine should be reduced.

Side effect
From the nervous system: depression of the respiratory center, muscle rigidity, involuntary muscle activity (for prevention, diazepam should first be administered); during the period of recovery from general anesthesia - psychomotor agitation, hallucinations, prolonged disorientation, psychosis.
From the respiratory system: shortness of breath, obstruction of the upper respiratory tract due to spasm of the masticatory muscles and retraction of the tongue, increased bronchial secretion and salivation.
From the side of the cardiovascular system: increased blood pressure, tachycardia.
From the digestive system: hypersalivation, nausea.
Local reactions: soreness and hyperemia along the vein at the injection site.

Overdose
With the introduction of ketamine in high doses intravenously (3 mg / kg), respiratory depression may be observed in some cases. In these cases, artificial ventilation is indicated. With the appearance of hallucinations, it is advisable to use antipsychotics (haloperidol), with convulsive syndrome - diazepam. If necessary, carry out symptomatic therapy.

Interaction with other drugs
Ketamine enhances the effects of drugs for general anesthesia, narcotic analgesics, antipsychotics (neuroleptics), anxiolytics (tranquilizers), and other drugs that depress the central nervous system.
Before using ketamine, it is necessary to cancel lincomycin, lithium preparations (for 1-2 days), monoamine oxidase inhibitors (for 15 days). Do not mix in the same syringe with barbiturates (pharmaceutically incompatible - sedimentation).
Droperidol and benzodiazepines, incl. sibazon, reduce the risk of psychomimetic and motor activity, as well as the occurrence of tachycardia and arterial hypertension.
It is not recommended to prescribe with sympathomimetics and drugs that have a stimulating effect on the cardiovascular system (increased hypertensive and arrhythmogenic effects, increased myocardial oxygen demand).
The cardiostimulating effect of ketamine is weakened when combined with antipsychotic drugs, anxiolytics.
Ketamine enhances the muscle relaxant effect of tubocurarine and dithylin, does not change - pancuronium and suxamethonium.
During general anesthesia in patients taking iodine-containing drugs and thyroid hormones, there is a high probability of increased blood pressure and tachycardia (eliminated by beta-blockers).

special instructions
Ketamine is used only in a hospital or emergency room.
To prevent increased secretion of the mucous membranes and salivary glands, atropine or methocinium iodide should be included in the composition of premedication, and the main dose of the drug should be slowly administered (not exceeding 3 mg / kg). During ketamine anesthesia, carry out inhalation with a mixture of oxygen and air in a ratio of 1:2.
When using ketamine, you should monitor the function of breathing, especially the patency of the upper respiratory tract (possible spasm of the chewing muscles and retraction of the tongue).
Caution should be exercised during operations on the larynx and pharynx (muscle relaxants are used).
Diazepam is administered intramuscularly or intravenously to prevent muscle rigidity and involuntary twitches during premedication.
To prevent the development of psychomimetic action, droperidol, diazepam should be included in the composition of sedatives.

Release form
Solution for intravenous and intramuscular administration 50 mg/ml. 2 ml and 5 ml in ampoules or 5 ml in vials. 5 ampoules or vials in a blister pack.
1, 2 blister packs (5 ampoules each) with instructions for use in a cardboard pack; 20, 50 or 100 blisters, respectively, with 10, 25 and 50 instructions for use in a cardboard box or cardboard box (for a hospital).
1 blister pack (5 bottles) and instructions for use in a cardboard pack; 30-50 blister packs (5 bottles each) with instructions for use (according to the number of packs) in a cardboard box or cardboard box (for a hospital).

Storage conditions
In a place protected from light and out of the reach of children. List II of the List of Narcotic Drugs, Psychotropic Substances and Their Precursors Subject to Control in the Russian Federation.

Best before date
2 years. Do not use after the expiry date stated on the package.

Terms of dispensing from pharmacies
Apply in a hospital setting.

Manufacturer:
Federal State Unitary Enterprise "Moscow Endocrine Plant"
Moscow, 109052, st. Novokhokhlovskaya, 25.

active substance: ketamine;

1 ml of solution contains ketamine hydrochloride 57.6 mg (in terms of ketamine 50 mg);

Excipients: benzethonium chloride, sodium chloride, water for injection.

Dosage form. Injection.

Basic physical and chemical properties: clear colorless or slightly colored liquid.

Pharmacotherapeutic group. Means for general anesthesia. ATX code N01A X03.

Pharmacological properties

Pharmacodynamics.

Ketamine is an anesthetic with a pronounced analgesic effect. The drug causes the so-called dissociative anesthesia, which is described as a functional dissociation between the thalamo-neocortical and limbic systems. The analgesic effect of the drug is already manifested at a subdissociative dose and lasts longer than anesthesia. Sedative and hypnotic actions are less pronounced. In the region of the spinal cord and peripheral nerves, the drug exhibits a local anesthetic effect.

When using ketamine, muscle tone remains unchanged or may increase. Therefore, protective reflexes, as a rule, are not disturbed. The seizure threshold does not decrease. Spontaneous breathing may increase intracranial pressure, which can be avoided with controlled breathing.

Because ketamine causes sympathicotonia, blood pressure and heart rate may increase; along with an increase in coronary blood flow in the myocardium, the need for oxygen increases. Ketamine has a negative inotropic effect and an antiarrhythmic effect (direct cardiac effect).

Due to the antagonistic action, peripheral vascular resistance does not change.

After the use of Ketamine, marked hyperventilation is observed without significant deviations in the parameters of blood gases. Ketamine relaxes the bronchial muscles.

Pharmacokinetics.

Ketamine is fat soluble. The maximum plasma concentration is observed 20 (5-30) minutes after the first dose intravenously.

With intramuscular injection, the bioavailability of the drug is 93%. Approximately 47% of ketamine binds to blood proteins. The first phase of the drug's action (alpha phase) lasts approximately 45 minutes, T 1/2 = 10–15 minutes. Clinically, the first phase is manifested by the anesthetic effect of the drug. Ketamine is rapidly distributed to tissues that have a good blood supply (such as the brain). The concentration of ketamine in tissues corresponds to a two-phase open model. The cessation of the anesthetic effect occurs due to redistribution from the central nervous system to peripheral tissues, in which the blood supply is less, and biotransformation in the liver into active metabolites. Among the metabolites of ketamine is one that causes a hypnotic effect. The half-life of the second phase (beta phase) is approximately 2.5 hours. 90% of metabolites are removed by the kidneys. Ketamine crosses the placenta.

clinical characteristics.

Indications

Use as an anesthetic (monotherapy) during non-durable (short-term) diagnostic procedures and surgical interventions in children and in some special cases in adults: induction and maintenance of anesthesia.

For general anesthesia in combination with other drugs (especially benzodiazepine), the drug should be prescribed at a lower dose.

Special indications for the use of ketamine (alone or in combination with another drug):

• painful procedures (change of dressing in a patient with burns);
• neurodiagnostic procedures (pneumoencephalography, ventriculography, myelography);
• endoscopy;
• some procedures in ophthalmology;
• diagnostic and surgical interventions in the neck or oral cavity; in the treatment of teeth;
• otolaryngological interventions;
• gynecological extraperitoneal interventions;
• interventions in obstetrics, anesthesia for caesarean section;
• interventions in orthopedics and traumatology;
• carrying out anesthesia for patients in a state of shock and with hypotension, due to the peculiarities of the action of ketamine on the heart and blood circulation;
• conducting anesthesia for patients who prefer intramuscular administration of the drug (for example, children).

Contraindications

• Hypersensitivity to the active substance or to other components of the drug.
• Eclampsia, preeclampsia.
• Ketamine is contraindicated in patients in whom an increase in blood pressure may pose a serious threat to life; patients with traumatic brain injury, intracranial hemorrhage, stroke, severe cardiovascular disease, cerebrovascular accident.

Interaction with other drugs and other types of interactions.

The concomitant use of barbiturates and/or other anesthetics with ketamine prolongs the time to awaken from anesthesia.

Co-administration with diazepam may prolong the half-life of ketamine and increase its pharmacodynamic effects, so they should not be mixed in the same administration system.

Ketamine in combination with atracurium and tubocurarine may increase neuromuscular blockade, including respiratory depression and apnea.

The use of halogenated anesthetics concomitantly with ketamine may prolong the half-life of ketamine and increase the time to awaken from anesthesia. Co-administration of ketamine (especially at high doses or when administered rapidly) with halogenated anesthetics increases the risk of bradycardia, hypotension, or reduced cardiac output.

The use of ketamine with other drugs that reduce the activity of the central nervous system (for example, ethanol, phenothiazines, antihistamines or muscle relaxants) may increase CNS depression and / or increase the risk of respiratory failure. There may be a need to reduce the dose of the drug while using hypnotics, sedatives and tranquilizers. Ketamine has been reported to antagonize the hypnotic effect of thiopental.

In patients receiving thyroid hormone therapy, the risk of high blood pressure and tachycardia increases with the use of Ketamine.

The simultaneous use of antihypertensive drugs and ketamine increases the risk of hypotension.

When combined with aminophylline (theophylline), the seizure threshold may decrease. There is evidence of unforeseen extensor muscle spasms that occurred during the simultaneous use of these drugs.

Drugs that inhibit CYP3A4 reduce hepatic clearance and increase plasma concentrations of CYP3A4 substrates such as ketamine. Concomitant use of ketamine and CYP3A4 inhibitors requires a dose reduction of ketamine to achieve optimal clinical effect.

CYP3A4 stimulating drugs increase hepatic clearance and decrease plasma levels of CYP3A4 substrates such as ketamine. Concomitant use of ketamine and CYP3A4 stimulants requires an increase in the dose of ketamine to achieve optimal clinical effect.

Sympathomimetics (direct or indirect action) and vasopressin may enhance the sympathomimetic effects of ketamine. Simultaneous use with ergometrine can lead to an increase in blood pressure.

Application features

Can be combined with any type of local anesthesia.

The drug should be prescribed by a specialist - an anesthesiologist.

As with other general anesthetics, resuscitation tools and equipment must be prepared when using ketamine.

Since the use of the drug may cause respiratory depression, it is necessary to have a device for artificial ventilation of the lungs. The use of the device should be combined with the use of analeptics.

Intravenous Ketamine should be administered slowly (over 1 minute). Rapid administration of the drug can lead to respiratory depression or stop and a sharp increase in blood pressure.

Since pharyngeal reflexes are usually preserved during Ketamine therapy, mechanical irritation of the pharynx should be avoided. When intervening in the larynx, pharynx or trachea, a combination of Ketamine with muscle relaxants and careful control of breathing is necessary.

In surgical interventions involving visceral pain pathways, it may be necessary to administer other analgesics.

When using Ketamine on an outpatient basis, the patient can be released only after full recovery of consciousness and accompanied by an adult.

Ketamine should be used with extreme caution in the following conditions:

• chronic alcoholism and acute alcohol intoxication.

Ketamine is metabolized in the liver, and its complete release through the liver leads to the cessation of clinical effects. An extension of the duration of action may occur in patients with cirrhosis of the liver or other types of liver failure. Therefore, the dose of ketamine should be reduced in these patients. There were also reports of abnormal liver function tests associated with long-term use of the drug, in particular, these deviations were observed in patients who took the drug for more than 3 days, or in people with drug dependence;

• increased pressure in the spinal canal;
• penetrating eye injury and / or increased intraocular pressure (eg, glaucoma), since pressure can increase significantly even after a single use of ketamine;
• a history of seizures, mental illness (eg schizophrenia, acute psychosis);
• acute intermittent porphyria;
• hyperthyroidism or thyroid replacement therapy (increased risk of increased blood pressure and heart rate);
• infectious diseases of the upper respiratory tract and lungs (since ketamine increases the sensitivity of the pharyngeal reflex, which in turn can lead to laryngospasm);
• brain tumors, head trauma or hydrocephalus.

Reactions that can be observed after the patient comes out of anesthesia.

Psychological disorders can range from mild to more severe, such as dream-like fantasy experiences, vivid visions, hallucinations, nightmares, postanesthetic delirium (often manifested by dissociative sensations and a feeling of free flight), in some cases these conditions are accompanied by confusion, psychomotor agitation, irrational behavior. The above manifestations were observed only in a few patients.

During the period of recovery from anesthesia, acute delirium may occur. This reaction can be prevented by administering benzodiazepines or by reducing verbal, tactile, and visual stimuli. But this does not exclude monitoring of vital parameters.

Because Ketamine increases myocardial oxygen consumption, it should be used with caution in patients with hypovolemia, dehydration, or cardiac disease, especially coronary heart disease (eg, congestive heart failure, ischemia, and myocardial infarction). Ketamine is also used with caution in patients with mild to moderate hypertension and tachyarrhythmias.

For patients with arterial hypertension or heart failure, monitoring of cardiac function during anesthesia is necessary. Premedication with diazepam reduces the hypertensive response. The maximum increase in blood pressure (20-25%) is observed a few minutes after intravenous administration of the drug, but after 15 minutes, blood pressure returns to its original values. Depending on the patient's condition, an increase in blood pressure can be considered as a positive effect or as an adverse reaction. The cardiac stimulating effect of ketamine can be prevented by prior intravenous administration of diazepam at a dose of 0.2-0.25 mg/kg of body weight.

Ketamine is not recommended for long term use. There are reports of cases of cystitis, including hemorrhagic cystitis, in patients treated with Ketamine for a long period (from 1 month to several years).

With prolonged use, hepatotoxicity (more than 3 days) may develop.

Cases of abuse of ketamine have also been reported. There is evidence that ketamine contributes to the occurrence of such manifestations: dysphoria, hallucinations, the “reverse frame” symptom, feelings of fear and anxiety, insomnia or disorientation, as well as cases of cystitis or hemorrhagic cystitis. The use of ketamine on a daily basis for several weeks can be addictive, especially in individuals who have or have had a drug addiction. Therefore, the drug should be used in the above conditions and diseases under the close supervision of the medical staff and with caution.

This medicinal product contains less than 1 mmol/dose sodium (23 mg)/dose sodium, i.e. practically free of sodium.

Use during pregnancy or lactation.

Ketamine crosses the placenta. This should be taken into account in the case of operative obstetric procedures during pregnancy, with the exception of the administration of the drug during a caesarean section or vaginal delivery. The safety of use during pregnancy and lactation has not been established, and such use is not recommended.

Ketamine enters the neonate when ≥ 1.5 mg/kg IV is given to the pregnant woman during labour, which may cause respiratory failure and a low Apgar score in the neonate.

With the introduction of a pregnant woman intravenously ≥ 2 mg / kg during childbirth, blood pressure and uterine tone increase.

The ability to influence the reaction rate when driving vehicles or operating other mechanisms.

Patients should be warned not to drive or operate machinery or engage in any other hazardous activity for at least 24 hours after anesthesia.

Ketamine may impair cognitive function, which may affect the ability to drive a vehicle.

Dosage and administration

Apply intramuscularly, intravenously or intravenously drip.

The individual response to Ketamine, as well as to other systemic anesthetics, depends on the dose, route of administration and age of the patient. Therefore, the selection of the dose of the drug should be carried out individually.

When used in combination, the dose of Ketamine should be reduced.

The following doses are used for adults, elderly patients (over 65 years) and children.

Intravenous administration. Enter slowly over 1 minute.

An initial dose of 0.7-2 mg/kg body weight that provides surgical anesthesia for 5-10 minutes approximately 30 seconds after administration (in patients at high risk, elderly patients or patients who are in shock, a dose of 0 is recommended .5 mg/kg body weight).

Intramuscular administration. An initial dose of 4-8 mg/kg body weight, which provides surgical anesthesia for 12-25 minutes a few minutes after administration.

Intravenous drip. Add 500 mg of Ketamine to 500 ml of 0.9% sodium chloride solution or 5% glucose solution.

Initial dose: 80-100 drops per minute.

Maintenance dose: 20-60 drops per minute (2-6 mg/kg body weight per hour).

The adult dose is 2-6 mg/kg body weight per hour.

Maintenance anesthesia. If necessary, half of the initial dose or the initial dose can be re-administered intramuscularly or intravenously.

The appearance of nystagmus, a motor reaction to irritation indicate a lack of anesthesia, so in this case it may be necessary to administer a second dose. However, involuntary movements of the limbs can occur regardless of the depth of anesthesia!

Children.

The drug is used in pediatric practice.

Overdose

The therapeutic index of Ketamine is wide. With the introduction of large doses or with rapid intravenous administration, respiratory failure may occur. In this case, before the restoration of adequate spontaneous breathing, it is necessary to carry out artificial ventilation of the lungs and, if necessary, administer analeptics.

Adverse reactions

From the immune system.

Rare: anaphylactic reactions.

Metabolic disease.

Uncommon: anorexia.

Mental disorders.

Often: hallucinations, abnormal or nightmare dreams, confusion, psychomotor agitation, inappropriate behavior.

Infrequently: a feeling of anxiety.

Rare: delirium, flashback, dysphoria, insomnia, confusion.

From the side of the nervous system.

Often: nystagmus, increased skeletal muscle tone and tonic-clonic convulsions.

From the organs of vision.

Often: diplopia.

Unknown frequency: increased intraocular pressure.

Cardiac disorders.

Often: increased blood pressure and heart rate.

Uncommon: bradycardia, arrhythmia.

vascular disorders.

Uncommon: hypotension.

From the respiratory system.

Often: increased respiratory rate.

Uncommon: respiratory depression, laryngospasm.

Rare: airway obstruction or respiratory arrest.

From the hepatobiliary system.

Unknown frequency: changes in laboratory parameters of liver function, drug-induced liver damage.

From the gastrointestinal tract.

Often: nausea, vomiting.

Rarely: salivation.

From the skin and subcutaneous tissues.

Often: urticaria, erythema and / or morbilliform rash.

From the side of the kidneys and urination.

Rare: cystitis, hemorrhagic cystitis.

General disorders and reactions at the injection site.

Infrequently: reactions at the injection site, including pain and / or rash at the injection site.

Best before date

Do not use the drug after the expiration date indicated on the package.

Storage conditions

Store in original packaging at a temperature not exceeding 25 ºС.

Keep out of the reach of children.

Incompatibility.

Barbiturates must not be administered in the same syringe with Ketamine due to chemical incompatibility. If it is necessary to simultaneously use Ketamine with diazepam, the drugs should be administered separately, not mixed in the same syringe or infusion.

Do not use solvents that are not listed in the "Method of application and dosage" section.

Package.

2 ml in an ampoule; 10 ampoules in a pack; 5 ampoules in a blister, 2 blisters in a pack.

10 ml in a vial; 5 bottles in a pack; 5 bottles in a blister, 1 blister in a pack.

Manufacturer

PJSC Farmak.

Location of the manufacturer and its address of the place of business.

Ukraine, 04080, Kyiv, st. Frunze, 74.

INN: Ketamine

Manufacturer: Farmak PAO

Anatomical-therapeutic-chemical classification: Ketamine

Registration number in the Republic of Kazakhstan: No. RK-LS-5 No. 003486

Registration period: 31.03.2016 - 31.03.2021

Instruction

Tradename

International non-proprietary name

Dosage form

Solution for injection 50 mg/ml

Compound

1 ml of the drug contains

active substance- ketamine hydrochloride 57.6 mg (in terms of ketamine 50 mg),

Excipients: benzethonium chloride, sodium chloride, water for injection.

Description

Clear colorless or slightly colored liquid

Pharmacotherapeutic group

Anesthetics. General anesthetics. Other general anesthetics. Ketamine

ATX code N01AX03

Pharmacological properties

Pharmacokinetics

Ketamine is rapidly distributed to well-vascularized tissues, including the brain and placenta. Animal studies have shown that ketamine is highly concentrated in adipose tissue, the liver, and the lungs. The cessation of the anesthetic effect occurs partly due to redistribution from the central nervous system to peripheral tissues, partly through biotransformation in the liver into active metabolites. The half-life is approximately 2-3 hours. Excreted by the kidneys, mostly in the form of conjugated metabolites.

Pharmacodynamics

Ketamine is a fast-acting general anesthetic for intravenous and intramuscular use with a pronounced pharmacological action. The drug causes the so-called dissociative anesthesia, characterized by catalepsy, amnesia and severe pain relief, which may persist during the period of recovery from anesthesia. When using Ketamine, pharyngeal-laryngeal reflexes remain normal; skeletal muscle tone may be normal or increased to varying degrees.

There is a slight stimulation of the cardiac and respiratory systems, and sometimes respiratory depression occurs.

Ketamine causes sedative and hypnotic effects, amnesia and severe analgesia. The state of anesthesia that Ketamine causes is called "dissociative anesthesia" due to the fact that it selectively interrupts associative connections in the brain before blocking proprioceptive deep sensitivity. It can selectively depress the thalamo-neocortical system before significantly blunting the centers and connections of the brain (by activating the reticular formation and the limbic system). Numerous theories attempt to explain the effect of Ketamine, including binding to N-methyl-D-aspartate (NMDA) receptors in the central nervous system, interactions with opiate receptors, and interactions with norepinephrine, serotonin, and muscarinic cholinergic receptors. NMDA receptor activity may be responsible for the analgesic as well as psychiatric effects of Ketamine. Ketamine has sympathomimetic activity, which leads to tachycardia, hypertension, increased oxygen consumption by the myocardium and brain, increased cerebral circulation and increased intracranial and intraocular pressure. Ketamine is also a powerful bronchodilator. Clinical effects that have been observed after administration of Ketamine include: increased blood pressure, increased muscle tone (may resemble catatonia), eye opening (usually accompanied by nystagmus), and increased myocardial oxygen consumption.

Indications for use

As an anesthetic in diagnostic and surgical procedures. Intravenous and intramuscular injections are best for short procedures. With the introduction of additional doses or by administration as an intravenous infusion, Ketamine can be used for longer procedures. If muscle relaxation is needed, a muscle relaxant should be used and breathing support should be provided.

For the induction of anesthesia before the introduction of other general anesthetics.

Special indications for the use of ketamine or types of procedures:

Carrying out anesthesia for patients in whom preference is given to intramuscular administration of the drug;

Wound dressing, painful procedures (dressing changes) and skin grafting in patients with burns, as well as other superficial surgical procedures;

Neurodiagnostic procedures such as pneumoencephalography, ventriculography, myelography, lumbar punctures;

Diagnostic and surgical interventions in the areas of the eyes, ears, nose and mouth, including tooth extraction (note: eye movements may be preserved during an ophthalmic procedure);

Anesthesia for patients with a significant risk of deterioration or the need to avoid deterioration of vital functions;

Orthopedic procedures (closed reposition, manipulations, placement of a pin in the thigh, amputation, biopsy);

Sigmoidoscopy and minor surgical procedures on the anus, rectum, circumcision and pilonidal sinus;

Cardiac catheterization procedures;

Introduction to anesthesia for caesarean section in the absence of high blood pressure;

During anesthesia in patients with asthma to minimize the risk of developing bronchospasm or in the presence of bronchospasm, if anesthesia cannot be delayed.

Dosage and administration

Ketamine is administered intravenously (stream or drip) or intramuscularly.

Note: All doses are given in terms of the active substance ketamine.

The following doses apply to adults, elderly patients (over 65 years of age) and children. For surgical interventions in elderly patients, Ketamine can be used as monotherapy or in combination with other anesthetics.

Preoperative preparation

In emergency cases, it is allowed to use Ketamine as the only anesthetic not on an empty stomach. However, since it is impossible to predict the need for other drugs and muscle relaxants, in preparation for elective surgery, it is advisable not to eat and drink 6 hours before anesthesia.

Premedication with anticholinergics (eg, atropine, hyoscine, etc.) should be given at intervals prior to Ketamine administration to reduce ketamine-induced salivation.

Midazolam, diazepam, lorazepam, or flunitrazepam, when used for premedication or as an adjunct to ketamine, reduce the incidence of adverse reactions.

Start of anesthesia and duration

Individual response to Ketamine may vary with dose, route of administration, and age of the patient, as well as the concomitant use of other agents. Therefore, dose selection should be carried out individually. Ketamine is a fast-acting drug, so the patient must be in the optimal position for the procedure.

An intravenous dose of 2 mg/kg body weight provides surgical anesthesia 30 seconds after injection for a duration of 5-10 minutes. An intramuscular dose of 10 mg/kg body weight provides surgical anesthesia 3-4 minutes after an injection lasting 12-25 minutes.

Ketamine as sole anesthetic

IV infusion

The use of Ketamine by continuous administration allows you to choose a more accurate dose compared to intermittent administration. This results in a shorter recovery time from anesthesia.

It is carried out at the rate of 1 mg / ml of Ketamine, diluted in 0.9% sodium chloride solution or 5% dextrose.

General induction anesthesia

Administer as an infusion at a dose of 0.5-2 mg/kg.

Maintenance of anesthesia

Anesthesia can be maintained using an infusion pump at a rate of 10-45 mcg/kg/min (approximately 1-3 mg/min).

The rate of infusion depends on the patient's response to anesthesia. The dose may be reduced if a long-acting muscle relaxant is used.

Intermittent administration

Intravenous administration

The initial dose of intravenous Ketamine can range from 1 mg/kg to 4.5 mg/kg (based on the active substance ketamine). The average dose required to provide surgical anesthesia lasting 5-10 minutes is 2.0 mg/kg. Slow intravenous administration (over 60 seconds) is recommended. Faster administration may lead to respiratory depression and increased blood pressure.

Intramuscular administration

The initial dose of Ketamine for intramuscular administration ranges from 6.5 mg / kg to 13 mg / kg (based on the active substance ketamine). A low initial intramuscular dose (4 mg/kg) is used for diagnostic manipulations and procedures that are not associated with severe pain. A dose of 10 mg/kg usually provides anesthesia within 12-25 minutes.

Dosing in hepatic impairment

The need to reduce the dose should be considered in patients with cirrhosis of the liver or other types of liver failure (see section "Special Instructions").

Maintenance of general anesthesia

Nystagmus, motor reactions to irritation and voice indicate weakening of anesthesia. To maintain anesthesia, additional doses of Ketamine are administered intravenously or intramuscularly.

Each additional dose should be from half to the full original dose of administration, regardless of the route of administration.

However, involuntary limb movements can occur regardless of the depth of anesthesia!

Ketamine as an inducing agent before using other general anesthetics

Induction is achieved by intravenous or intramuscular injection of a full dose of Ketamine. If Ketamine was administered intravenously and the primary anesthetic is a delayed release, a second dose of Ketamine should be given 5 to 8 minutes after the initial dose. If Ketamine was administered intramuscularly and the main anesthetic is fast acting, the main anesthetic should be administered 15 minutes after the Ketamine injection.

Ketamine as an adjunct to anesthetics

Ketamine is clinically compatible with commonly used general and local anesthetics with proper respiratory support. The dose of Ketamine for use in combination with other anesthetics is usually in the same range, however, the use of another anesthetic may allow a reduction in the dose of Ketamine.

Follow-up of patients during the recovery period

After the procedure, the patient should be observed, but not disturbed. This does not exclude monitoring of vital signs. If delirium occurs, diazepam (5 to 10 mg IV in adults) may be used. A hypnotic dose of thiobarbiturate (50 to 100 mg IV) may be used to reduce severe reactions on recovery. When using these drugs, the recovery time after anesthesia may increase.

Side effects

Undesirable effects according to the frequency of occurrence are classified into the following categories: very often (> 1/10); often (>1/100,<1/10); нечасто (>1/1000, <1/100), редко (>1/10000, <1/1000), очень редко (<1/10000, включая единичные случаи).

From the side of the immune system

Rarely : anaphylactic reactions.

Metabolic disorders

Infrequently : anorexia.

Mental disorders

Often : hallucinations, abnormal or nightmare dreams, confusion, psychomotor agitation, inappropriate behavior.

Infrequently: a feeling of fear, anxiety.

Rare: delirium, flashback, dysphoria, insomnia, confusion.

From the side of the nervous system

Often : nystagmus, increased skeletal muscle tone and tonic-clonic convulsions.

From the organs of vision

Often : diplopia.

Not known: increased intraocular pressure.

Cardiac disorders

Often : increased blood pressure and heart rate.

Uncommon: bradycardia, arrhythmia.

Vascular disorders

Infrequently : hypotension.

From the respiratory system

Often : increase in respiratory rate.

Uncommon: respiratory depression, laryngospasm.

Rare: airway obstruction or respiratory arrest.

From the hepatobiliary system

unknown : changes in laboratory parameters of liver function.

From the gastrointestinal tract

Often : nausea, vomiting.

Rarely: salivation.

From the sideskin and subcutaneous tissue

Often: erythema and/or morbilliform rash.

Not known: urticaria.

From the sidekidney and urinary

Rarely : cystitis, hemorrhagic cystitis.

General disorders and reactions at the injection site

Infrequently : reactions at the injection site, including pain and / or rashes at the injection site.

Contraindications

hypersensitivity to the active substance or to other components of the drug

eclampsia, preeclampsia

ketamine is contraindicated in patients in whom an increase in blood pressure can pose a serious threat to life; patients with traumatic brain injury, intracranial hemorrhage, stroke, severe cardiovascular disease, cerebrovascular accident.

Drug Interactions

The concomitant use of barbiturates and/or other anesthetics with Ketamine causes a prolongation of the awakening time after anesthesia.

Ketamine in combination with atracurium and tubocurarine may increase neuromuscular blockade, including respiratory depression and apnea.

The use of halogenated anesthetics concomitantly with Ketamine may lengthen the half-life of Ketamine and increase the time to awaken from anesthesia. Concomitant use of ketamine (especially at high doses or when administered rapidly) with halogenated anesthetics may increase the risk of developing bradycardia, hypotension, or reduced cardiac output.

The use of Ketamine with other drugs that reduce the activity of the central nervous system (for example, ethanol, phenothiazines, antihistamines or muscle relaxants) may increase CNS depression and / or increase the risk of respiratory failure. It may be necessary to reduce the dose of the drug while using hypnotics, sedatives and tranquilizers. Ketamine has been reported to antagonize the hypnotic effect of thiopental.

In patients receiving thyroid hormone therapy, the risk of high blood pressure and tachycardia increases with the use of Ketamine.

The simultaneous use of antihypertensive drugs and Ketamine increases the risk of hypotension.

When combined with aminophylline (theophylline), the seizure threshold may decrease. There is evidence of unpredictable extensor muscle spasms associated with concomitant use of these medicinal products.

special instructions

Can be combined with any type of local anesthesia.

The drug should be prescribed by a specialist - an anesthesiologist.

As with other general anesthetics, when using Ketamine, it is necessary to prepare tools and equipment for resuscitation.

Since the use of the drug may cause respiratory depression, it is necessary to have a device for artificial ventilation of the lungs. The use of the device should be combined with the use of analeptics.

Intravenous Ketamine must be administered slowly (over 1 minute). Rapid administration of the drug can lead to respiratory depression or stop and a sharp increase in blood pressure.

Since pharyngeal reflexes are usually preserved during Ketamine therapy, mechanical irritation of the pharynx should be avoided. When intervening in the larynx, pharynx or trachea, a combination of Ketamine with muscle relaxants and careful control of breathing is necessary.

In surgical interventions involving the visceral pathways of pain sensitivity, it may be necessary to administer other analgesics.

When using Ketamine on an outpatient basis, the patient can be released only after full recovery of consciousness and accompanied by an adult.

Ketamine should be used with extreme caution in the following conditions:

chronic alcoholism and acute alcohol intoxication;

Ketamine is metabolized in the liver and its complete release through the liver leads to the cessation of clinical effects. Prolongation of action may occur in patients with cirrhosis of the liver or other types of liver failure. Therefore, the dose of Ketamine should be reduced in such patients. There have also been reports of abnormal liver function tests associated with long-term use of the drug, in particular, these abnormalities were observed in patients who used the drug for more than 3 days or in people with drug dependence.

with increased pressure in the spinal canal;

in patients with penetrating eye injury and / or increased intraocular pressure (eg, glaucoma), because the pressure can increase significantly even after a single use of Ketamine;

patients with neurotic disorders or mental illness (for example: schizophrenia, acute psychosis);

patients with acute intermittent porphyria;

patients with epileptic seizures;

patients with hyperthyroidism or patients receiving thyroid replacement therapy (increased risk of increased blood pressure and heart rate);

patients with infectious diseases of the upper respiratory tract or lungs (since Ketamine increases the sensitivity of the pharyngeal reflex, which in turn can cause laryngospasm).

patients with intracranial masses, head trauma or hydrocephalus.

Reactions and features that can be observed after the patient comes out of anesthesia.

Psychiatric disorders can range from very mild to more severe, such as dream-like fantasy experiences, vivid visions, hallucinations, nightmares, postanesthesia delirium (which is often manifested by dissociative sensations and a feeling of free flight), in some cases these states are accompanied by confusion, psychomotor agitation, irrational behavior. The above manifestations were observed only in some patients.

During the period of recovery from anesthesia, acute delirium may occur. This reaction can be prevented by administering benzodiazepines or by reducing verbal, tactile, and visual stimuli. However, this does not exclude monitoring of vital parameters.

Because Ketamine increases myocardial oxygen consumption, it should be used with caution in patients with hypovolemia, dehydration, or cardiac disease, especially coronary heart disease (eg, congestive heart failure, ischemia, and myocardial infarction). Ketamine is also used with caution in patients with mild to moderate hypertension and tachyarrhythmias.

Patients with arterial hypertension or heart failure require constant monitoring of cardiac function during anesthesia. Premedication with diazepam reduces the hypertensive response. The maximum increase in blood pressure (20-25%) is observed a few minutes after intravenous administration of the drug, but after 15 minutes, blood pressure returns to its initial values. Depending on the condition of the patient, an increase in blood pressure may be considered as a positive effect, or in other cases, as an adverse reaction.

There are reports of reported cases of cystitis, including hemorrhagic cystitis, in patients who received Ketamine for a long period (from 1 month to several years). Ketamine is not prescribed or recommended for long term use.

Cases of abuse of ketamine have also been reported. There is evidence that ketamine contributes to the onset of manifestations: dysphoria, hallucinations, the symptom of "reverse frame", feelings of fear and anxiety, insomnia or disorientation, as well as cases of cystitis or hemorrhagic cystitis. The use of Ketamine daily for several weeks can be addictive, especially in individuals who have or have had a history of drug dependence. Therefore, it is necessary to use the drug under the close supervision of the medical staff and with caution in the aforementioned conditions and diseases.

Incompatibility.

Due to chemical incompatibility, barbiturates should not be administered in the same syringe with Ketamine.

If it is necessary to simultaneously use Ketamine with diazepam, the drugs should be administered separately and should not be mixed in the same syringe or infusion.

Do not use solvents not listed in the section "Method of administration and dosage".

Application in pediatrics

The drug is used in pediatric practice.

Use during pregnancy and lactation

Ketamine crosses the placenta. This should be taken into account during operative obstetric procedures during pregnancy. With the exception of the administration of the drug during caesarean section or vaginal delivery, safe use during pregnancy and lactation has not been established, and such use is not recommended.

Features of the effect of the drug onability to drive vehicles and potentially dangerous mechanisms

Patients should be warned not to drive or operate machinery or engage in any other hazardous activities for at least 24 hours after anesthesia.

Ketamine may impair cognitive function, which may affect the ability to drive a vehicle.

Overdose

When using Ketamine, respiratory depression is possible, so a ventilator is required. Preference is given to mechanical support of breathing instead of the introduction of analeptics.

Ketamine has a large safety factor; several cases of unintentional overdose of Ketamine (exceeding the required dose up to 10 times) were accompanied by a long, but complete exit from anesthesia.

Release form and packaging

2 ml glass ampoules of the 1st hydrolytic class with a ring or a break point.

10 ml in transparent glass vials for injection, sealed with combined caps (with an aluminum cap with a rubber gasket and a plastic liner) or with a rubber stopper for injection vials and an aluminum cap combined with a plastic cap.

Self-adhesive labels are attached to ampoules and vials.

10 ampoules, together with instructions for medical use in the state and Russian languages, are placed in a cardboard box with corrugated inserts.

5 bottles, together with instructions for medical use in the state and Russian languages, are placed in a cardboard box with an insert.

Or 5 ampoules or 5 vials are put into a blister pack made of polymeric material. 1 blister pack (with vials) or 2 blister packs (with ampoules) together with instructions for medical use in the state and Russian languages ​​are placed in a cardboard pack.