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 so-called dissociative anesthesia, which is described as functional dissociation between the thalamo-neocortical and limbic systems. The analgesic effect of the drug appears already at a subdissociative dose and lasts longer than anesthesia. Sedative and hypnotic effects are less pronounced. In area 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 impaired. The seizure threshold does not decrease. During spontaneous breathing, it may increase intracranial pressure, which can be avoided with controlled breathing.
Because ketamine causes sympathicotonia, blood pressure and heart rate may increase; simultaneously with an increase in coronary blood flow in the myocardium, the need for oxygen increases. Ketamine has a negative inotropic effect and antiarrhythmic effect(direct cardiac effect).
Due to its antagonistic action, peripheral vascular resistance does not change.
After using Ketamine, pronounced hyperventilation is observed without significant deviations in blood gas parameters. Ketamine relaxes the muscles of the bronchi.
Pharmacokinetics.
Ketamine is fat soluble. The maximum concentration in blood plasma is observed 20 (5–30) minutes after intravenous administration of the first dose.
When administered intramuscularly, the bioavailability of the drug is 93%. Approximately 47% of ketamine is bound 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 into tissues that have a good blood supply (for example, 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 there is less blood supply, and biotransformation in the liver into active metabolites. Among the metabolites of ketamine there 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) for non-durable (short-term) diagnostic procedures and surgical interventions in children and in some special cases in adults: induction of anesthesia and its maintenance.
For general anesthesia in combination with other drugs (especially benzodiazepines) medicine prescribe in a lower dose.
Special indications for the use of ketamine (alone or in combination with another drug):
- painful procedures(changing a bandage for a patient with burns);
- neurodiagnostic procedures (pneumoencephalography, ventriculography, myelography);
- endoscopy;
- some procedures in ophthalmology;
- diagnostic and surgical interventions in the neck area or oral cavity; in dental treatment;
- otolaryngological interventions;
- gynecological extraperitoneal interventions;
- interventions in obstetrics, induction of anesthesia for surgery caesarean section;
- interventions in orthopedics and traumatology;
- administering anesthesia to patients in a state of shock and with hypotension, due to the peculiarities of the action of ketamine on the heart and circulation;
- administering anesthesia to 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 with increased blood pressure may pose a serious threat to life; patients with traumatic brain injury, intracranial hemorrhage, stroke, severe cardiovascular diseases, disorders cerebral circulation.
Interaction with other drugs and other types of interactions.
Concomitant use of barbiturates and/or other anesthetic agents with Ketamine prolongs the time to awakening after anesthesia.
Concomitant use with diazepam may prolong the half-life of ketamine and increase its pharmacodynamic effects, so they should not be mixed in the same system when administered.
Ketamine in combination with atracurium and tubocurarine may potentiate the blockade of neuromuscular transmission, including respiratory depression and apnea.
Use of halogenated anesthetics concomitantly with ketamine may prolong the half-life of ketamine and increase the time to awakening from anesthesia. Concomitant use Ketamine (especially in high doses or when administered rapidly) with halogenated anesthetics increases the risk of bradycardia, hypotension, or decreased 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 enhance CNS depression and/or increase the risk of developing respiratory failure. There may be a need to reduce the dose of the drug when using hypnotics, sedatives and tranquilizers simultaneously. Ketamine has been reported to antagonize the hypnotic effects of thiopental.
In patients receiving thyroid hormone therapy, the risk of increased blood pressure and tachycardia when using Ketamine is increased.
Concomitant 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 unexpected extensor muscle cramps that occurred while taking these medications simultaneously.
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.
Drugs that stimulate CYP3A4 increase hepatic clearance and reduce plasma concentrations of CYP3A4 substrates such as ketamine. Concomitant use of ketamine and CYP3A4 stimulants requires an increased dose of ketamine to achieve optimal clinical effect.
Sympathomimetics (direct or indirect) and vasopressin may enhance the sympathomimetic effects of ketamine. Concomitant use with ergometrine may lead to an increase in blood pressure.
Features of application
Can be combined with any type of local anesthesia.
The drug must be prescribed by a specialist - an anesthesiologist.
As with other general anesthesia agents, resuscitation tools and equipment must be prepared when using ketamine.
Since respiratory depression is possible when using the drug, 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 may cause respiratory depression or arrest and sharp increase blood pressure.
Since pharyngeal reflexes are usually preserved during Ketamine therapy, mechanical irritation of the pharynx should be avoided. When intervening on the larynx, pharynx or trachea, a combination of Ketamine with muscle relaxants and careful monitoring of breathing is necessary.
At surgical interventions with the involvement of visceral pain pathways, it may be necessary to administer other analgesics.
When using Ketamine in outpatient setting the patient can be released only after full recovery 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 complete release through the liver results in cessation of clinical effects. Prolongation of action may occur in patients with cirrhosis or other types of liver failure. Therefore, the dose of ketamine should be reduced in such patients. Abnormal liver function tests have also been reported normal indicators which were associated with long-term use of the drug, in particular, these deviations were observed in patients taking the drug for more than 3 days, or in persons with drug addiction;
- increased pressure in the spinal canal;
- penetrating eye trauma and/or increased intraocular pressure(for example, glaucoma), since blood 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 replacement therapy drugs thyroid gland(increases the risk of increased blood pressure and heart rate);
- infectious diseases of the upper respiratory tract and lungs (as 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 recovers from anesthesia.
Psychological disorders can range from mild to more severe, such as fantastical experiences, similar topics, which appear in a dream, vivid visions, hallucinations, nightmares, post-anesthesia delirium (often manifested by dissociative sensations and a feeling of free flight), in some cases these conditions are accompanied by confusion, psychomotor agitation, and irrational behavior. The above manifestations were observed in only a few patients.
During recovery from anesthesia, acute delirium may occur. This reaction can be prevented by administering benzodiazepines or reducing verbal, tactile and visual stimulation. But this does not exclude monitoring vital parameters.
Because Ketamine increases myocardial oxygen consumption, it should be used with caution in patients with hypovolemia, dehydration, or cardiac disease, especially coronary disease heart (eg, congestive heart failure, ischemic conditions and myocardial infarction). Ketamine should also be used with caution in patients with arterial hypertension light and moderate degree and for tachyarrhythmias.
For patients with 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 the blood pressure returns to its original values. Depending on the patient's condition, an increase in blood pressure may be considered a positive effect or a adverse reaction. The cardiac stimulatory effect of ketamine can be prevented by prior intravenous administration of diazepam at a dose of 0.2–0.25 mg/kg body weight.
Ketamine is not recommended for use during long period. There are reports of cases of cystitis, including hemorrhagic cystitis, in patients receiving Ketamine for long term(from 1 month to several years).
With prolonged use, hepatotoxicity may develop (more than 3 days).
Ketamine abuse has also been reported. There is evidence that ketamine contributes to the following symptoms: dysphoria, hallucinations, flashback symptoms, feelings of fear and anxiety, insomnia or confusion, and cases of cystitis or hemorrhagic cystitis. Using ketamine on a daily basis over several weeks can cause addiction, especially in individuals who have or have had a drug addiction. Therefore, the drug should be used for the above-mentioned conditions and diseases under the close supervision of medical staff and with caution.
This medicinal product contains less than 1 mmol/dose sodium (23 mg)/dose sodium, which is essentially sodium-free.
Use during pregnancy or breastfeeding.
Ketamine crosses the placenta. This should be noted in the case of surgical obstetric procedures during pregnancy, with the exception of drug administration during cesarean section or vaginal delivery. birth canal. Safety of use during pregnancy and lactation has not been established and such use is not recommended.
Ketamine enters the newborn's body when ≥ 1.5 mg/kg is administered intravenously to the pregnant woman during labor, which may cause respiratory failure and low Apgar scores in the newborn.
When ≥ 2 mg/kg is administered intravenously to a pregnant woman during labor, blood pressure and uterine tone increase.
The ability to influence the reaction rate when driving vehicles or other mechanisms.
Patients should be warned that driving a car or operating other machinery or engaging in any other dangerous species activities are prohibited for at least 24 hours after anesthesia.
Ketamine may worsen cognitive function, which may affect your ability to control the vehicle.
Directions for use and doses
Apply intramuscularly, intravenously or intravenously.
Individual reaction to Ketamine, as well as to other anesthetics systemic action, 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 of age) and children.
Intravenous administration. It should be administered slowly over 1 minute.
The initial dose is 0.7–2 mg/kg body weight, which provides surgical anesthesia for 5–10 minutes approximately 30 seconds after administration (patients with high risk, elderly patients or patients who are in a state of shock, a dose of 0.5 mg/kg body weight is recommended).
Intramuscular administration. The initial dose is 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 dose for an adult is 2–6 mg/kg body weight per hour.
Maintenance anesthesia. If necessary, half the initial dose or the initial dose can be repeated intramuscularly or intravenously.
The appearance of nystagmus and a motor reaction to irritation indicate insufficient anesthesia, so in this case it may be necessary to administer a repeat dose. However, involuntary movements of the limbs can appear regardless of the depth of anesthesia!
Children.
The drug is used in pediatric practice.
Overdose
The therapeutic index of Ketamine is wide. When administering large doses or with rapid intravenous administration, there may be respiratory failure. In this case, until adequate spontaneous breathing is restored, it is necessary to carry out artificial ventilation lungs and, if necessary, administer analeptics.
Adverse reactions
From the immune system.
Rarely: anaphylactic reactions.
Metabolic disease.
Uncommon: anorexia.
Mental disorders.
Common: hallucinations, abnormal or nightmares, confusion, psychomotor agitation, inappropriate behavior.
Uncommon: feeling of anxiety.
Rarely: delirium, reverse frame symptom, dysphoria, insomnia, disorientation.
From the nervous system.
Common: nystagmus, increased tone skeletal muscles and tonic-clonic seizures.
From the organs of vision.
Common: diplopia.
Unknown frequency: increased intraocular pressure.
Cardiac disorders.
Common: increased blood pressure and heart rate.
Uncommon: bradycardia, arrhythmia.
Vascular disorders.
Uncommon: hypotension.
From the outside respiratory systems s.
Common: 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.
Common: nausea, vomiting.
Rarely: drooling.
From the skin and subcutaneous tissues.
Common: urticaria, erythema and/or morbilliform rash.
From the kidneys and urination.
Rarely: cystitis, hemorrhagic cystitis.
General disorders and reactions at the injection site.
Uncommon: administration site reactions, 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 are prohibited from being administered in the same syringe together with Ketamine due to chemical incompatibility. If simultaneous use of Ketamine with diazepam is necessary, the drugs should be administered separately and not mixed in the same syringe or infusion.
Do not use solvents not listed in the “Method of administration and dosage” section.
Package.
2 ml per ampoule; 10 ampoules per pack; 5 ampoules in a blister, 2 blisters in a pack.
10 ml in a bottle; 5 bottles per pack; 5 bottles in a blister, 1 blister in a pack.
Manufacturer
PJSC Farmak.
The location of the manufacturer and its address of place of business.
Ukraine, 04080, Kyiv, st. Frunze, 74.
INN: Ketamine
Manufacturer: Farmak PJSC
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
Instructions
Tradename
International nonproprietary 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 into well-vascularized tissues, including the brain and placenta. Animal studies have shown that ketamine is highly concentrated in adipose tissue, liver and 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. It is 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 pronounced pharmacological action. The drug causes so-called dissociative anesthesia, characterized by catalepsy, amnesia and severe anesthesia, which can persist during recovery from anesthesia. When using Ketamine, pharyngolaryngeal reflexes remain normal; Skeletal muscle tone may be normal or varying degrees rise.
There is slight stimulation of the cardiac and respiratory systems, and sometimes respiratory depression occurs.
Ketamine causes sedative and hypnotic effects, amnesia and pronounced analgesia. The state of anesthesia that Ketamine produces is called “dissociative anesthesia” due to the fact that it selectively interrupts associative connections in the brain before blocking proprioceptive deep sensation. It can selectively inhibit the thalamo-neocortical system before significantly blunting the centers and connections of the brain (activating the reticular formation and limbic system). Numerous theories attempt to explain the effects of Ketamine, including binding to N-methyl-D-aspartate (NMDA) receptors in the central nervous system, interaction with opiate receptors and interaction 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 myocardial and cerebral oxygen consumption, increased cerebral circulation and increased intracranial and intraocular pressure. Ketamine is also a potent bronchodilator. Clinical effects that have been observed following Ketamine administration include: increased blood pressure, increased tone muscles (may resemble catatonia), eye opening (usually accompanied by nystagmus) and increased myocardial oxygen consumption.
Indications for use
As an anesthetic during diagnostic and surgical procedures. Intravenous and intramuscular injections best suited for short procedures. When given in additional doses or given as an intravenous infusion, Ketamine can be used for longer procedures. If muscle relaxation is necessary, use a muscle relaxant and provide breathing support.
For induction of anesthesia before administration of other general anesthetics.
Specific indications for ketamine or types of procedures:
Conducting anesthesia for patients who prefer intramuscular administration of the drug;
Treatment of wounds, 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 eyes, ears, nose and mouth, including tooth extraction (note: eye movements may persist during an ophthalmic procedure);
Anesthesia for patients with a significant risk of deterioration or the need to avoid deterioration of life important functions;
Orthopedic procedures (closed reduction, manipulation, pin placement in the femur, 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 bronchospasm or in the presence of bronchospasm, if anesthesia cannot be delayed.
Directions for use and doses
Ketamine is administered intravenously (stream or drip) or intramuscularly.
Note: All doses are indicated in terms of the active substance ketamine.
The doses below 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 in case of emergency It is allowed to use Ketamine as the only anesthetic not on an empty stomach. However, since the need to use other drugs and muscle relaxants cannot be predicted, when preparing for elective surgery It is advisable not to take food or liquid 6 hours before anesthesia.
Premedication with anticholinergic drugs (for example, atropine, hyoscine, etc.) should be carried out at a certain interval before Ketamine administration in order to reduce ketamine-induced increased salivation.
Midazolam, diazepam, lorazepam or flunitrazepam, when used for premedication or as an adjunct to Ketamine, reduce the incidence of adverse reactions.
Onset of anesthesia and duration
Individual response to Ketamine may vary depending on the dose, route of administration and age of the patient, as well as 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 lasting 5-10 minutes. An intramuscular dose of 10 mg/kg body weight provides surgical anesthesia 3-4 minutes after injection lasting 12-25 minutes.
Ketamine as the sole anesthetic
Intravenous infusion
The use of Ketamine through continuous administration allows for a more accurate dose to be selected compared to intermittent administration. This causes more a short time recovery from anesthesia.
It is carried out at the rate of 1 mg/ml 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 Ketamine when administered intravenously 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 recommended intravenous administration(within 60 seconds). More rapid administration may result in respiratory depression and increased blood pressure.
Intramuscular administration
Initial dose of Ketamine for intramuscular injection ranges from 6.5 mg/kg to 13 mg/kg (based on the active ingredient ketamine). A low initial intramuscular dose (4 mg/kg) is used for diagnostic procedures and procedures not associated with strong painful sensations. A dose of 10 mg/kg typically provides anesthesia within 12-25 minutes.
Dosing for liver failure
The need to reduce the dose should be considered in patients with cirrhosis or other types of liver failure (see section "Special Instructions").
Maintaining general anesthesia
Nystagmus, motor responses to stimulation and voice indicate weakening of anesthesia. To maintain anesthesia, additional doses of Ketamine are administered intravenously or intramuscularly.
Each additional dose should be one-half to the full original dose administered, regardless of route of administration.
However, involuntary movements of the limbs can occur regardless of the depth of anesthesia!
Ketamine as an inducing agent before the use of other general anesthetics
Induction is achieved by intravenous or intramuscular administration of a full dose of Ketamine. If Ketamine is administered intravenously and the primary anesthetic is delayed-acting, a repeat dose of Ketamine should be administered 5-8 minutes after the initial dose. If Ketamine was administered intramuscularly and the main anesthetic fast action, the administration of the main anesthetic should be carried out 15 minutes after the Ketamine injection.
Ketamine as an adjunct to anesthetics
Ketamine is clinically compatible with commonly used generic and local anesthetics with proper respiratory support. The dose of Ketamine for use in combination with other anesthetics is generally in the same range, however the use of a different anesthetic may allow a lower dose of Ketamine.
Monitoring 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) can be used. A hypnotic dose of thiobarbiturate (50 to 100 mg IV) may be used to reduce severe reactions during recovery. When using these drugs, recovery time from anesthesia may be longer.
Side effects
Adverse 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 immune system
Rarely : anaphylactic reactions.
Metabolic disorders
Infrequently : anorexia.
Mental disorders
Often : hallucinations, abnormal or nightmares, confusion, psychomotor agitation, inappropriate behavior.
Uncommon: feeling of fear, anxiety.
Rarely: delirium, reverse frame symptom, dysphoria, insomnia, disorientation.
From the nervous system
Often : nystagmus, increased skeletal muscle tone and tonic-clonic convulsions.
From the organs of vision
Often : diplopia.
Unknown: 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 breathing 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: drooling.
From the outsideskin and subcutaneous tissues
Often: erythema and/or morbilliform rash.
Unknown: urticaria.
From the outsidekidneys and urination
Rarely : 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.
Contraindications
hypersensitivity to the active substance or to other components of the drug
eclampsia, preeclampsia
ketamine is contraindicated in patients in whom elevated blood pressure may pose a serious threat to life; patients with traumatic brain injury, intracranial hemorrhage, stroke, severe cardiovascular diseases, and cerebrovascular accidents.
Drug interactions
Concomitant use of barbiturates and/or other anesthesia with Ketamine causes prolongation of the time to awakening after anesthesia.
Ketamine in combination with atracurium and tubocurarine may potentiate the blockade of neuromuscular transmission, including respiratory depression and apnea.
Use of halogenated anesthetics concomitantly with Ketamine may prolong the half-life of Ketamine and increase the time to awakening from anesthesia. Concomitant use of Ketamine (especially at high doses or when administered rapidly) with halogenated anesthetics may increase the risk of bradycardia, hypotension, or decreased 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 enhance CNS depression and/or increase the risk of developing respiratory failure. It may be necessary to reduce the dose of the drug with the simultaneous use of sleeping pills, sedatives and tranquilizers. Ketamine has been reported to antagonize the hypnotic effects of thiopental.
In patients receiving thyroid hormone therapy, the risk of increased blood pressure and tachycardia when using Ketamine is increased.
Concomitant 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 cramps that were accompanied by the simultaneous use of these drugs.
special instructions
Can be combined with any type of local anesthesia.
The drug must be prescribed by a specialist - an anesthesiologist.
As with other general anesthesia agents, resuscitation tools and equipment must be prepared when using Ketamine.
Since respiratory depression is possible when using the drug, 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 arrest 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 on the larynx, pharynx or trachea, a combination of Ketamine with muscle relaxants and careful monitoring of breathing is necessary.
During surgical interventions involving the 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 restoration 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 complete release through the liver results in cessation of clinical effects. Prolongation of action may occur in patients with liver cirrhosis or other types of liver failure. Therefore, the dose of Ketamine should be reduced in such patients. Abnormalities in liver function tests have also been reported that have been associated with long-term use of the drug, particularly in patients who have used the drug for more than 3 days or in individuals with drug dependence.
with increased pressure in the spinal canal;
in patients with penetrating ocular trauma and/or increased intraocular pressure (eg, glaucoma), because the pressure may increase significantly even after a single use of Ketamine;
patients with neurotic disorders or mental illnesses (for example: schizophrenia, acute psychosis);
patients with acute intermittent porphyria;
patients with epileptic seizures;
patients with hyperthyroidism or patients receiving thyroid replacement therapy (increases the risk of increased blood pressure and heart rate);
patients with infectious diseases of the upper respiratory tract or lungs (as Ketamine increases the sensitivity of the pharyngeal reflex, which in turn can cause laryngospasm).
patients with intracranial space-occupying lesions, head trauma or hydrocephalus.
Reactions and features that may be observed after the patient recovers from anesthesia.
Psychiatric disorders can range from mild to more severe, such as fantastical experiences such as those imagined in dreams, vivid visions, hallucinations, nightmares, post-anesthetic delirium (which often manifested as dissociative sensations and a feeling of free flight), in some cases these states are accompanied by confusion, psychomotor agitation and irrational behavior. The above manifestations were observed only in some patients.
During recovery from anesthesia, acute delirium may occur. This reaction can be prevented by administering benzodiazepines or reducing verbal, tactile and visual stimulation. 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 those with coronary artery disease (eg, congestive heart failure, ischemic conditions, and myocardial infarction). Ketamine should also be used with caution in patients with mild to moderate hypertension and tachyarrhythmias.
Patients with 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 the blood pressure returns to initial values. Depending on the patient's condition, an increase in blood pressure may be considered a positive effect, or in other cases, an adverse reaction.
There are reported cases of cystitis, including hemorrhagic cystitis, in patients who received Ketamine for an extended period (1 month to several years). Ketamine is not prescribed or recommended for long-term use.
Ketamine abuse has also been reported. There is evidence that ketamine contributes to symptoms such as dysphoria, hallucinations, flashback symptoms, fear and anxiety, insomnia or confusion, and cases of cystitis or hemorrhagic cystitis. Using Ketamine daily for several weeks may cause addiction, especially in individuals who have or have a history of drug addiction. Therefore, the drug must be used under close medical supervision and with caution in the above-mentioned conditions and diseases.
Incompatibility.
Due to chemical incompatibility, barbiturates cannot be administered in the same syringe with Ketamine.
If simultaneous use of Ketamine with diazepam is necessary, the drugs should be administered separately and should not be mixed in the same syringe or infusion.
Do not use solvents not specified in the section "Method of administration and dosage."
Use in pediatrics
The drug is used in pediatric practice.
Use during pregnancy and lactation
Ketamine crosses the placenta. This should be paid attention to during surgical obstetric procedures during pregnancy. With the exception of administration during cesarean section or vaginal delivery, safe use during pregnancy and lactation has not been established and such use is not recommended.
Features of the drug's effect onability to drive vehicles and potentially dangerous machinery
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 your ability to drive.
Overdose
When using Ketamine, respiratory depression is possible, so a ventilator is necessary. Preference is given to mechanical respiratory support instead of the administration of analeptics.
Ketamine has a great safety factor; several cases of unintentional overdose of Ketamine (up to 10 times the required dose) were accompanied by a long but complete recovery from anesthesia.
Release form and packaging
2 ml in glass ampoules of hydrolytic class 1 with a ring or break point.
10 ml in clear glass bottles for injection, sealed with combination caps (with an aluminum cap with a rubber gasket and a plastic liner) or with a rubber stopper for injection bottles and an aluminum cap combined with a plastic cap.
Self-adhesive labels are placed on ampoules and vials.
10 ampoules, together with instructions for medical use in the state and Russian languages, are placed in a cardboard pack with corrugated inserts.
5 bottles each, along with instructions for medical use in the state and Russian languages, are placed in a cardboard pack with an insert.
Or 5 ampoules or 5 bottles are placed in a blister pack made of polymer material. 1 blister pack (with bottles) or 2 blister packs (with ampoules) together with instructions for medical use in the state and Russian languages are placed in a cardboard pack.
Ketamine (hydrochloride form) (ketamine)
Composition and release form of the drug
5 ml - bottles (5) - cardboard packs.
pharmachologic effect
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 intramuscular administration of ketamine at a dose of 4-8 mg/kg, the effect occurs within 2-4 minutes (up to 6-8 minutes) and lasts on average 12-25 minutes (up to 30-40 minutes). Ketamine causes a pronounced analgesic effect (up to 2 hours), but insufficient muscle relaxation. When ketamine is administered, the pharyngeal, laryngeal and cough reflexes and independent adequate pulmonary ventilation are preserved. Metabolized in the liver.
Pharmacokinetics
Ketamine is a lipophilic compound and therefore is quickly distributed to organs well supplied with blood, incl. into 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.
Indications
For introductory and basic anesthesia, for short-term surgical interventions that require and do not require muscle relaxation, for painful instrumental and diagnostic manipulations, for transporting patients, and treating burn surfaces.
Contraindications
Cerebrovascular accidents, arterial hypertension, angina pectoris and failure in the decompensation phase, preeclampsia and eclampsia, epilepsy in childhood.
Dosage
Depending on the indications, age of the patient, 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.
Side effects
From the cardiovascular system: increased blood pressure, tachycardia.
From the digestive system: hypersalivation.
From the side of the central nervous system: psychomotor agitation and hallucinations during recovery from anesthesia.
From the respiratory system: shortness of breath, respiratory depression.
Local reactions: extremely rarely, pain and hyperemia along the vein are possible at the injection site.
Drug interactions
Ketamine potentiates the effect of inhalational anesthetics. 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 precipitates.
special instructions
Use with caution in patients with kidney disease. For operations on the larynx and pharynx, ketamine is used in combination with
The substance, called Ketamine, was first synthesized in 1962 by American researcher Calvin Stevens. The scientist worked at Parke-Davis, trying to find a formula for a safe anesthetic that could become an alternative to phencyclidine, which had a number of dangerous side effects (the drug caused hallucinations, could provoke an epileptic seizure, and was also neurotoxic).
Three years later, Ketamine, then known under the working name CI-581 (clinical investigation 581), was tested in practice for the first time. After its first clinical use, the drug was used by American military personnel who served in Vietnam in the late 1960s. In 1970, when Ketamine was approved for widespread use in the United States, the drug became the first non-inhalational anesthetic with minimal effects on circulation and respiration when administered. Subsequently, the drug began to be actively used in psychiatry.
The use of Ketamine has declined significantly due to deaths occurring in the United States and Europe between 1987 and 2000. The deceased used the drug in a dosage that significantly exceeded the recommended one, due to some side effects of the drug. The fact is that “Ketamine” had by that time gained dubious popularity as a drug after the publication of the books “Journey to a Bright World” by Marcia Moore and Howard Alltounian, and “The Scientist” by John Lilly. Today, the drug is used primarily in veterinary medicine and as an anesthetic in military medicine (in developing countries).
In the USSR, the first studies related to the use of Ketamine in the treatment of alcoholism and drug addiction began in the mid-1980s by Evgeny Krupitsky. The work, which lasted about two decades, was stopped due to tightening Russian legislation. Since the early 1990s, against the backdrop of the emergence of so-called psychedelic literature in our country, Ketamine has become increasingly used as a narcotic drug.
According to the Federal Law of January 8, 1998 No. 3-FZ “On Narcotic Drugs and Psychotropic Substances,” the drug was included in the list of psychotropic drugs. Five years later, when the Federal Drug Control Service was created and a number of amendments were made to the law, the use of Ketamine in veterinary medicine in Russia sharply decreased.
Now the use of this drug for medical purposes is strictly regulated, and fines have been introduced for violating the rules. Ketamine can only be used by appropriately licensed institutions, including veterinary institutions. They must store the medicine in a safe equipped with a double alarm.
In the past, domestic veterinarians widely used Ketamine as an anesthetic. The forced refusal of most specialists from the drug, which has proven itself to be one of the most effective and at the same time mild anesthetics, provoked many protests from animal rights activists, pet lovers and owners, as well as veterinarians themselves. However, government agencies have not listened to their arguments over the past ten years.
Composition and release form
The active ingredient of the drug is the NMDA antagonist ketamine (in the form of hydrochloride). The drug is produced in the form of a solution intended for intravenous and intramuscular administration.
Ketamine is available in 5 ml bottles. 1 ml of solution contains 250 mg of active substance. The bottle is packed in a cardboard box.
pharmachologic effect
Ketamine is a non-inhalational anesthetic drug. In some cases, the drug is used as an analgesic (mainly in emergency medicine and in patients who cannot be prescribed opioid analgesics and barbiturates), as well as for the treatment of bronchospasm.
Being a non-competitive direct-acting antagonist of NMDA receptors (by blocking the receptor ion channel), Ketamine is capable of exerting an inhibitory effect on the function of neurons in the associative zone of the cerebral cortex and thalamus, which is responsible for switching sensory impulses from the reticular activating system to the cerebral cortex.
At the same time, Ketamine has a stimulating effect on parts of the limbic system involved in awareness of sensations, including the hippocampus. As a result, the patient develops functional disorganization of nonspecific connections in the midbrain and thalamus (dissociative anesthesia). Clinically, this is expressed as follows: the patient appears awake, he is able, in particular, to swallow and open his eyes, but loses the ability to analyze sensory stimuli and respond adequately to them.
Research has previously confirmed that Ketamine has the ability to bind to opioid receptors in the brain and dorsal horn of the spinal cord. It is assumed that this explains the analyzing effect of the drug.
The greater level of activity of Ketamine in relation to the cortex than the thalamus may be due to the uneven distribution of NMDA receptors in the central nervous system.
Pharmacokinetics
After a single intravenous injection of Ketamine, the narcotic effect usually occurs within 30-60 seconds and lasts for 5-10 minutes (sometimes up to 15 minutes).
When using the drug intramuscularly at a dosage of 4-8 mg/kg, Ketamine begins to act in 2-4 minutes (up to 6-8 minutes). The effect lasts 12-25 minutes (sometimes up to 40 minutes).
The pronounced analgesic effect of Ketamine can last for up to two hours. After administration of the drug, the patient retains pharyngeal, laryngeal and cough reflexes, and the level of spontaneous pulmonary ventilation remains adequate.
After administration, Ketamine, being part of the group of lipophilic compounds, is quickly distributed to organs well supplied with blood, including the brain. Then the agent begins to be redistributed into tissues with a reduced level of perfusion.
The drug is metabolized in the liver. The half-life of the drug is usually two to three hours. Ketamine leaves the patient’s body primarily through the kidneys in the form of conjugated metabolites.
Indications
In modern medicine, the drug “Ketamine” is used:
- for introductory and basic anesthesia during short-term surgical interventions, regardless of whether muscle relaxation is required;
- during painful instrumental and diagnostic procedures;
- when transporting patients;
- when treating burn surfaces.
Dosage regimen
"Ketamine" is prescribed by the attending physician on an individual basis, taking into account the indications, the patient's age, the clinical situation and the drugs used for premedication.
When administered intravenously, a single dosage is usually 0.5-4.5 mg/kg; for injection into the muscle, a formula of 4-13 mg/kg is usually used.
Side effects
Patients prescribed Ketamine may experience various types of undesirable effects. The most common ones are:
- from the cardiovascular system: increased blood pressure, tachycardia;
- from the digestive system: salivation (hypersalivation);
- from the central nervous system: psychomotor agitation and hallucinations (when recovering from anesthesia);
- from the respiratory system: shortness of breath, respiratory depression;
In extremely rare cases, local reactions may occur - pain at the injection site and hyperemia along the vein.
Contraindications for use
The drug "Ketamine" is not used if the patient is diagnosed with:
- cerebrovascular accidents;
- arterial hypertension;
- angina pectoris and heart failure (in the decompensation phase);
- preeclampsia and eclampsia;
- epilepsy in childhood.
special instructions
Considering the ability of Ketamine to penetrate the placental barrier, and studies on the effectiveness and safety of the drug in pregnant women have not yet been conducted, the use of the drug in patients of this category is not recommended.
1 ml of 5% solution contains 50 mg of active ingredient ketamine hydrochloride .
Release form
Ketamine is available in ampoules of 2 and 10 ml. Each cardboard pack contains 10 ampoules.
pharmachologic effect
What is Ketamine? This is a drug that, when administered intramuscularly or intravenously, can have narcotic (anesthetic) and analgesic effects. Pharmacological group – "Anesthetics" . The active substance has a short-term effect, and in narcotic doses allows you to maintain adequate independent breathing. The drug has dissociative general anesthesia, which is explained by its inhibitory effect on the subcortical formations of the thalamus and the associative zone.
Mechanism of action of Ketamine based on selective suppression of neuronal transmission in the structure of the cerebral cortex, as in thalamus , and in associative zones. At the same time, there is stimulation limbic system And hippocampus . As a result, functional separation of nonspecific connections develops in the structure of the thalamus and midbrain, incoming nociceptive afferent stimuli to the higher brain centers from the spinal cord are blocked, and impulse transmission to the medulla oblongata (reticular formation) is inhibited. It is believed that the analgesic and hypnotic effects of Ketamine are associated with the influence of the active substance on various types of receptors. The effects of the drug are not associated with blocking sodium channels in the nervous system and effects on GABA receptors. Wikipedia contains information on the history of Ketamine synthesis.
Pharmacodynamics and pharmacokinetics
Ketamine is a lipophilic compound that can be distributed quite quickly, first in well-supplied organs, and then in tissues with reduced perfusion. Metabolized in the hepatic system. It is excreted through the kidneys in the form of conjugated substances-metabolites.
Indications for use
Ketamine what is it? The medication is used both for mononarcosis (1 component) and for combined anesthesia, mainly in people with low blood pressure, or when it is necessary to maintain spontaneous breathing in the patient. Most often, Ketamine is used during evacuation during massive and traumatic shock, during short-term cardiac surgery, and in emergency surgery. Ketamine is prescribed for:
- cardiac catheterization ;
- endoscopic manipulations;
- dressings in otorhinolaryngology, ophthalmology and dentistry.
The medication can be used in obstetric practice.
Contraindications
- eclampsia in severe forms of circulatory decompensation;
- pronounced .
If necessary, use muscle relaxants During operations on the larynx, Ketamine is prescribed with caution. Mixing with barbiturate solutions is unacceptable due to the risk of precipitation.
Side effects
The medication has a general effect on the human body. When the solution is administered, a rise in blood pressure by 20-30%, an increase in heart rate, an increase in minute blood volume, and a decrease in peripheral vascular resistance are recorded. Application of Sibazon ( ) helps reduce the stimulatory effect of Ketamine on cardiac function. In most cases, the active component does not inhibit the reflexes of the upper respiratory tract and does not cause bronchospasm, laryngospasm, vomiting or nausea. Respiratory depression recorded with rapid intravenous infusion of solution. and Metacin can reduce salivation. When the medication is administered, hypertonicity and involuntary movements may be recorded (it can be stopped with the administration of tranquilizers). There may be redness of the skin along the vein at the injection site; upon awakening from anesthesia - prolonged disorientation And psychomotor agitation .
Instructions for use of Ketamine (Method and dosage)
The solution is administered intravenously (fractionally/in a stream) or intramuscularly. Adults are administered intravenously 2-3 mg, intramuscularly - 4-8 mg per 1 kg of weight. Repeated administration of Ketamine allows prolongation of anesthesia (rate 2 mg/kg/hour). This method of administration is possible in the presence of infusion pumps or is achieved by drip administration of a 1% Ketamine solution in sodium chloride solution or isotonic solution (30-60 drops per minute).
In pediatric practice, the solution is used for combined anesthesia. The calculation is made according to the following scheme: 4-5 mg/kg in the form of a 5% solution. Mandatory premedication is required.
The drug can be used in conjunction with analgesics ( , depidolor, etc.) and antipsychotics (for example, Droperidol), however, this requires a dose reduction.
Overdose
Registered respiratory depression , which requires timely artificial ventilation .
Interaction
Ketamine is chemically incompatible with barbiturates (a precipitate is formed). The medication is capable of potentiating the effect of all drugs used for inhalation anesthesia . The drug enhances the effect of tubocurarine, but does not affect the effectiveness of succinylcholine and pancuronium.
Terms of sale
Sold only for hospitals and medical institutions, not intended for free sale.
Storage conditions
Best before date
special instructions
In case of pathology of the renal system, use with caution. During surgical interventions on the pharynx and larynx, the administration of muscle relaxants is mandatory. During the day after the administration of Ketamine, you should not drive a vehicle due to slow reaction and decreased attention.
Analogs
Level 4 ATX code matches:- Ketanest;
- Ketalar .
During pregnancy and lactation
The active component passes through the placental barrier. At the moment, the safety of Ketamine has not been established. Not recommended for pregnant women and .
