Components:
Method of action:
Treatment option:
Medically reviewed by Fedorchenko Olga Valeryevna, PharmD. Last updated on 26.06.2023
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Ketamin is indicated in children and in adults.
Ketamin is recommended:
As an anaesthetic agent for diagnostic and surgical procedures. When used by intravenous or intramuscular injection, Ketamin is best suited for short procedures. With additional doses, or by intravenous infusion, Ketamin can be used for longer procedures. If skeletal muscle relaxation is desired, a muscle relaxant should be used and respiration should be supported.
For the induction of anaesthesia prior to the administration of other general anaesthetic agents. To supplement other anaesthetic agents.
Specific areas of application or types of procedures:
When the intramuscular route of administration is preferred.
Debridement, painful dressings, and skin grafting in burned patients, as well as other superficial surgical procedures.
Neurodiagnostic procedures such as pneumoencephalograms, ventriculograms, myelograms, and lumbar punctures.
Diagnostic and operative procedures of the eye, ear, nose, and mouth, including dental extractions.
Note: Eye movements may persist during ophthalmological procedures.
Anaesthesia in poor-risk patients with depression of vital functions or where depression of vital functions must be avoided, if at all possible.
Orthopaedic procedures such as closed reductions, manipulations, femoral pinning, amputations, and biopsies.
Sigmoidoscopy and minor surgery of the anus and rectum, circumcision and pilonidal sinus.
Cardiac catheterization procedures.
Caesarean section; as an induction agent in the absence of elevated blood pressure.
Anaesthesia in the asthmatic patient, either to minimise the risks of an attack of bronchospasm developing, or in the presence of bronchospasm where anaesthesia cannot be delayed.
Ketamin injection is indicated as the sole anesthetic agent for diagnostic and surgical procedures that do not require skeletal muscle relaxation. Ketamin is best suited for short procedures but it can be used, with additional doses, for longer procedures.
Ketamin injection is indicated for the induction of anesthesia prior to the administration of other general anesthetic agents.
Ketamin injection is indicated to supplement low-potency agents, such as nitrous oxide.
Specific areas of application are described in the CLINICAL PHARMACOLOGY Section.
For intravenous infusion, intravenous injection or intramuscular injection.
NOTE: All doses are given in terms of Ketamin base
Adults, elderly (over 65 years) and children:
For surgery in elderly patients Ketamin has been shown to be suitable either alone or supplemented with other anaesthetic agents.
Preoperative preparations
Ketamin has been safely used alone when the stomach was not empty. However, since the need for supplemental agents and muscle relaxants cannot be predicted, when preparing for elective surgery it is advisable that nothing be given by mouth for at least six hours prior to anaesthesia.
Premedication with an anticholinergic agent (e.g. atropine, hyoscine or glycopyrolate) or another drying agent should be given at an appropriate interval prior to induction to reduce Ketamin- induced hypersalivation.
Midazolam, diazepam, lorazepam, or flunitrazepam used as a premedicant or as an adjunct to Ketamin, have been effective in reducing the incidence of emergence reactions.
Onset and duration
As with other general anaesthetic agents, the individual response to Ketamin is somewhat varied depending on the dose, route of administration, age of patient, and concomitant use of other agents, so that dosage recommendation cannot be absolutely fixed. The dose should be titrated against the patient's requirements.
Because of rapid induction following intravenous injection, the patient should be in a supported position during administration. An intravenous dose of 2 mg/kg of bodyweight usually produces surgical anaesthesia within 30 seconds after injection and the anaesthetic effect usually lasts 5 to10 minutes. An intramuscular dose of 10 mg/kg of bodyweight usually produces surgical anaesthesia within 3 to 4 minutes following injection and the anaesthetic effect usually lasts 12 to 25 minutes. Return to consciousness is gradual.
A. Ketamin as the sole anaesthetic agent
Intravenous Infusion
The use of Ketamin by continuous infusion enables the dose to be titrated more closely, thereby reducing the amount of drug administered compared with intermittent administration. This results in a shorter recovery time and better stability of vital signs.
A solution containing 1 mg/ml of Ketamin in dextrose 5% or sodium chloride 0.9% is suitable for administration by infusion.
General Anaesthesia Induction
An infusion corresponding to 0.5 - 2 mg/kg as total induction dose.
Maintenance of anaesthesia
Anaesthesia may be maintained using a microdrip infusion of 10 - 45 microgram/kg/min (approximately 1 - 3 mg/min).
The rate of infusion will depend on the patient's reaction and response to anaesthesia. The dosage required may be reduced when a long acting neuromuscular blocking agent is used.
Intermittent Injection
Induction
Intravenous Route
The initial dose of Ketamin administered intravenously may range from 1 mg/kg to 4.5 mg/kg (in terms of Ketamin base). The average amount required to produce 5 to 10 minutes of surgical anaesthesia has been 2.0 mg/kg. It is recommended that intravenous administration be accomplished slowly (over a period of 60 seconds). More rapid administration may result in respiratory depression and enhanced pressor response.
Dosage in Obstetrics
Intramuscular Route
The initial dose of Ketamin administered intramuscularly may range from 6.5 mg/kg to 13 mg/kg (in terms of Ketamin base). A low initial intramuscular dose of 4 mg/kg has been used in diagnostic manoeuvres and procedures not involving intensely painful stimuli. A dose of 10 mg/kg will usually produce 12 to 25 minutes of surgical anaesthesia.
Dosage in Hepatic Insufficiency:
<)Dosage in Obstetrics
Data are lacking for intramuscular injection and maintenance infusion of Ketamin in the parturient population, and recommendations cannot be made.
Maintenance of general anaesthesia
Lightening of anaesthesia may be indicated by nystagmus, movements in response to stimulation, and vocalization. Anaesthesia is maintained by the administration of additional doses of Ketamin by either the intravenous or intramuscular route.
Each additional dose is from ½ to the full induction dose recommended above for the route selected for maintenance, regardless of the route used for induction.
The larger the total amount of Ketamin administered, the longer will be the time to complete recovery.
Purposeless and tonic-clonic movements of extremities may occur during the course of anaesthesia. These movements do not imply a light plane and are not indicative of the need for additional doses of the anaesthetic.
B. Ketamin as induction agent prior to the use of other general anaesthetics
Induction is accomplished by a full intravenous or intramuscular dose of Ketamin as defined above. If Ketamin has been administered intravenously and the principal anaesthetic is slow- acting, a second dose of Ketamin may be required 5 to 8 minutes following the initial dose. If Ketamin has been administered intramuscularly and the principal anaesthetic is rapid-acting, administration of the principal anaesthetic may be delayed up to 15 minutes following the injection of Ketamin.
C. Ketamin as supplement to anaesthetic agents
Ketamin is clinically compatible with the commonly used general and local anaesthetic agents when an adequate respiratory exchange is maintained. The dose of Ketamin for use in conjunction with other anaesthetic agents is usually in the same range as the dosage stated above; however, the use of another anaesthetic agent may allow a reduction in the dose of Ketamin.
D. Management of patients in recovery
Following the procedure the patient should be observed but left undisturbed. This does not preclude the monitoring of vital signs. If, during the recovery, the patient shows any indication of emergence delirium, consideration may be given to the use of diazepam (5 to 10 mg I.V. in an adult). A hypnotic dose of a thiobarbiturate (50 to 100 mg I.V.) may be used to terminate severe emergence reactions. If any one of these agents is employed, the patient may experience a longer recovery period.
Note: Barbiturates and Ketamin, being chemically incompatible because of precipitate formation, should not be injected from the same syringe.
If the Ketamin dose is augmented with diazepam, the two drugs must be given separately. Do not mix ketamine hydrochloride and diazepam in syringe or infusion flask. For additional information on the use of diazepam, refer to the WARNINGS and DOSAGE AND ADMINISTRATION Sections of the diazepam insert.
Preoperative Preparations
- While vomiting has been reported following ketamine hydrochloride administration, some airway protection may be afforded because of active laryngeal-pharyngeal reflexes. However, since aspiration may occur with Ketamin and since protective reflexes may also be diminished by supplementary anesthetics and muscle relaxants, the possibility of aspiration must be considered. Ketamin is recommended for use in the patient whose stomach is not empty when, in the judgment of the practitioner, the benefits of the drug outweigh the possible risks.
- Atropine, scopolamine, or another drying agent should be given at an appropriate interval prior to induction.
Onset And Duration
Because of rapid induction following the initial intravenous injection, the patient should be in a supported position during administration.
The onset of action of Ketamin is rapid; an intravenous dose of 2 mg/kg (1 mg/lb) of body weight usually produces surgical anesthesia within 30 seconds after injection, with the anesthetic effect usually lasting five to ten minutes. If a longer effect is desired, additional increments can be administered intravenously or intramuscularly to maintain anesthesia without producing significant cumulative effects.
Intramuscular doses, in a range of 9 to 13 mg/kg (4 to 6 mg/lb) usually produce surgical anesthesia within 3 to 4 minutes following injection, with the anesthetic effect usually lasting 12 to 25 minutes.
Dosage
As with other general anesthetic agents, the individual response to Ketamin is somewhat varied depending on the dose, route of administration, and age of patient, so that dosage recommendation cannot be absolutely fixed. The drug should be titrated against the patient's requirements.
Induction
Intravenous Route
The initial dose of Ketamin administered intravenously may range from 1 mg/kg to 4.5 mg/kg (0.5 to 2 mg/lb). The average amount required to produce five to ten minutes of surgical anesthesia has been 2 mg/kg (1 mg/lb).
Alternatively, in adult patients an induction dose of 1 mg to 2 mg/kg intravenous ketamine at a rate of 0.5 mg/kg/min may be used for induction of anesthesia. In addition, diazepam in 2 mg to 5 mg doses, administered in a separate syringe over 60 seconds, may be used. In most cases, 15 mg of intravenous diazepam or less will suffice. The incidence of psychological manifestations during emergence, particularly dream-like observations and emergence delirium, may be reduced by this induction dosage program.
Note: The 100 mg/mL concentration of ketamine hydrochloride should not be injected intravenously without proper dilution. It is recommended the drug be diluted with an equal volume of either Sterile Water for injection, USP, Normal Saline, or 5% Dextrose in Water.
Rate of Administration
It is recommended that Ketamin be administered slowly (over a period of 60 seconds). More rapid administration may result in respiratory depression and enhanced pressor response.
Intramuscular Route
The initial dose of Ketamin administered intramuscularly may range from 6.5 to 13 mg/kg (3 to 6 mg/lb). A dose of 10 mg/kg (5 mg/lb) will usually produce 12 to 25 minutes of surgical anesthesia.
Maintenance Of Anesthesia
The maintenance dose should be adjusted according to the patient's anesthetic needs and whether an additional anesthetic agent is employed.
Increments of one-half to the full induction dose may be repeated as needed for maintenance of anesthesia. However, it should be noted that purposeless and tonic-clonic movements of extremities may occur during the course of anesthesia. These movements do not imply a light plane and are not indicative of the need for additional doses of the anesthetic.
It should be recognized that the larger the total dose of Ketamin administered, the longer will be the time to complete recovery.
Adult patients induced with Ketamin augmented with intravenous diazepam may be maintained on Ketamin given by slow microdrip infusion technique at a dose of 0.1 to 0.5 mg/minute, augmented with diazepam 2 to 5 mg administered intravenously as needed. In many cases 20 mg or less of intravenous diazepam total for combined induction and maintenance will suffice. However, slightly more diazepam may be required depending on the nature and duration of the operation, physical status of the patient, and other factors. The incidence of psychological manifestations during emergence, particularly dream-like observations and emergence delirium, may be reduced by this maintenance dosage program.
Dilution
To prepare a dilute solution containing 1 mg of ketamine per mL, aseptically transfer 10 mL from a 50 mg per mL vial or 5 mL from a 100 mg per mL vial to 500 mL of 5% Dextrose Injection, USP or Sodium Chloride (0.9%) Injection, USP (Normal Saline) and mix well. The resultant solution will contain 1 mg of ketamine per mL.
The fluid requirements of the patient and duration of anesthesia must be considered when selecting the appropriate dilution of Ketamin injection. If fluid restriction is required, Ketamin injection can be added to a 250 mL infusion as described above to provide a Ketamin concentration of 2 mg/mL. Ketamin injection 10 mg/mL vials are not recommended for dilution.
Supplementary Agents
Ketamin is clinically compatible with the commonly used general and local anesthetic agents when an adequate respiratory exchange is maintained.
The regimen of a reduced dose of Ketamin supplemented with diazepam can be used to produce balanced anesthesia by combination with other agents such as nitrous oxide and oxygen.
Ketamin is contra-indicated in persons in whom an elevation of blood pressure would constitute a serious hazard.
Ketamin should not be used in patients with eclampsia or pre-eclampsia, severe coronary or myocardial disease, cerebrovascular accident or cerebral trauma.
Ketamin is contraindicated in those in whom a significant elevation of blood pressure would constitute a serious hazard and in those who have shown hypersensitivity to the drug.
To be used only in hospitals by or under the supervision of experienced medically qualified anaesthetists except under emergency conditions.
As with any general anaesthetic agent, resuscitative equipment should be available and ready for use.
Respiratory depression may occur with overdosage of Ketamin, in which case supportive ventilation should be employed. Mechanical support of respiration is preferred to the administration of analeptics.
The intravenous dose should be administered over a period of 60 seconds. More rapid administration may result in transient respiratory depression or apnoea and enhanced pressor response.
Because pharyngeal and laryngeal reflexes usually remain active, mechanical stimulation of the pharynx should be avoided unless muscle relaxants, with proper attention to respiration, are used.
Although aspiration of contrast medium has been reported during Ketamin anaesthesia under experimental conditions (Taylor, P A and Towey, R M, Brit. Med. J. 1971, 2: 688), in clinical practice aspiration is seldom a problem.
In surgical procedures involving visceral pain pathways, Ketamin should be supplemented with an agent which obtunds visceral pain.
When Ketamin is used on an outpatient basis, the patient should not be released until recovery from anaesthesia is complete and then should be accompanied by a responsible adult.
Ketamin should be used with caution in patients with the following conditions:
- Use with caution in the chronic alcoholic and the acutely alcohol-intoxicated patient.
- Ketamin is metabolised in the liver and hepatic clearance is required for termination of clinical effects. A prolonged duration of action may occur in patients with cirrhosis or other types of liver impairment. Dose reductions should be considered in these patients. Abnormal liver function tests associated with Ketamin use have been reported, particularly with extended use (>3 days) or drug abuse.
- Since an increase in cerebrospinal fluid (CSF) pressure has been reported during Ketamin anaesthesia, Ketamin should be used with special caution in patients with preanaesthetic elevated cerebrospinal fluid pressure.
- Use with caution in patients with globe injuries and increased intraocular pressure (e.g. glaucoma) because the pressure may increase significantly after a single dose of Ketamin.
- Use with caution in patients with neurotic traits or psychiatric illness (e.g. schizophrenia and acute psychosis)
- Use in caution in patients with acute intermittent porphyria.
- Use in caution in patients with seizures.
- Use in caution in patients with hyperthyroidism or patients receiving thyroid replacement (increased risk of hypertension and tachycardia)
- Use in caution in patients with pulmonary or upper respiratory infection (Ketamin sensitises the gag reflex, potentially causing laryngospasm)
- Use in caution in patients with intracranial mass lesions, a presence of head injury, or hydrocephalus.
Emergence Reaction
The psychological manifestations vary in severity between pleasant dream-like states, vivid imagery, hallucinations, nightmares and emergence delirium (often consisting of dissociative or floating sensations). In some cases these states have been accompanied by confusion, excitement, and irrational behaviour which a few patients recall as an unpleasant experience..
Emergence delirium phenomena may occur during the recovery period. The incidence of these reactions may be reduced if verbal and tactile stimulation of the patient is minimised during the recovery period. This does not preclude the monitoring of vital signs.
Cardiovascular
Because of the substantial increase in myocardial oxygen consumption, Ketamin should be used in caution in patients with hypovolemia, dehydration or cardiac disease, especially coronary artery disease (e.g. congestive heart failure, myocardial ischemia and myocardial infarction). In addition Ketamin should be used with caution in patients with mild-to-moderate hypertension and tachyarrhythmias.
Cardiac function should be continually monitored during the procedure in patients found to have hypertension or cardiac decompensation.
Elevation of blood pressure begins shortly after the injection of Ketamin, reaches a maximum within a few minutes and usually returns to preanaesthetic values within 15 minutes after injection. The median peak rise of blood pressure in clinical studies has ranged from 20 to 25 percent of preanaesthetic values. Depending on the condition of the patient, this elevation of blood pressure may be considered a beneficial effect, or in others, an adverse reaction.
Long-Term Use
Cases of cystitis including haemorrhagic cystitis have been reported in patients being given Ketamin on a long term basis. This adverse reaction develops in patients receiving long term Ketamin treatment after a time ranging from 1 month to several years. Ketamin is not indicated nor recommended for long term use. Hepatotoxicity has also been reported in patients with extended use (> 3 days).
Drug Abuse and Dependence
Ketamin has been reported as being a drug of abuse. Reports suggest that Ketamin produces a variety of symptoms including, but not limited to, flashbacks, hallucinations, dysphoria, anxiety, insomnia, or disorientation. Cases of cystitis including haemorrhagic cystitis and cases of hepatotoxicity have also been reported. If used on a daily basis for a few weeks, dependence and tolerance may develop, particularly in individuals with a history of drug abuse and dependence. Therefore the use of Ketamin should be closely supervised and it should be prescribed and administered with caution.
WARNINGS
Cardiac function should be continually monitored during the procedure in patients found to have hypertension or cardiac decompensation.
Postoperative confusional states may occur during the recovery period. (See Special Note.)
Respiratory depression may occur with overdosage or too rapid a rate of administration of Ketamin, in which case supportive ventilation should be employed. Mechanical support of respiration is preferred to administration of analeptics.
PRECAUTIONS
General
Ketamin injection should be used by or under the direction of physicians experienced in administering general anesthetics and in maintenance of an airway and in the control of respiration.
Because pharyngeal and laryngeal reflexes are usually active, Ketamin should not be used alone in surgery or diagnostic procedures of the pharynx, larynx, or bronchial tree. Mechanical stimulation of the pharynx should be avoided, whenever possible, if Ketamin is used alone. Muscle relaxants, with proper attention to respiration, may be required in both of these instances.
Resuscitative equipment should be ready for use.
The incidence of emergence reactions may be reduced if verbal and tactile stimulation of the patient is minimized during the recovery period. This does not preclude the monitoring of vital signs (see Special Note).
The intravenous dose should be administered over a period of 60 seconds. More rapid administration may result in respiratory depression or apnea and enhanced pressor response.
In surgical procedures involving visceral pain pathways, Ketamin should be supplemented with an agent which obtunds visceral pain.
Use with caution in the chronic alcoholic and the acutely alcohol-intoxicated patient.
An increase in cerebrospinal fluid pressure has been reported following administration of Ketamin. Use with extreme caution in patients with preanesthetic elevated cerebrospinal fluid pressure.
Usage In Pregnancy
Since the safe use in pregnancy, including obstetrics (either vaginal or abdominal delivery), has not been established, such use is not recommended (see Animal Pharmacology And Toxicology, Reproduction).
Geriatric Use
Clinical studies of Ketamin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Pediatric Use
Safety and effectiveness in pediatric patients below the age of 16 have not been established.
Patients should be cautioned that driving a car, operating hazardous machinery or engaging in hazardous activities should not be undertaken for 24 hours or more after anaesthesia.
This medicine can impair cognitive function and can affect a patient's ability to drive safely. This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988. When prescribing this medicine, patients should be told:
- The medicine is likely to affect your ability to drive
- Do not drive until you know how the medicine affects you
- It is an offence to drive while under the influence of this medicine
- However, you would not be committing an offence (called 'statutory defence') if:
o The medicine has been prescribed to treat a medical or dental problem and
o You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and
o It was not affecting your ability to drive safely
The following Adverse Events have been reported:
| MedDRA System Organ Class | Frequency†| Undesirable Effects |
| Immune system disorders | Rare | Anaphylactic reaction* |
| Metabolism and nutrition disorders | Uncommon | Anorexia |
| Psychiatric disorders | Common | Hallucination, Abnormal dreams, Nightmare, Confusion, Agitation, Abnormal behaviour |
| Uncommon | Anxiety | |
| Rare | Delirium* Flashback*, Dysphoria*, Insomnia, Disorientation* | |
| Nervous system disorders | Common | Nystagmus, Hypertonia, Tonic clonic movements |
| Eye disorders | Common | Diplopia |
| Not Known | Intraocular pressure increased | |
| Cardiac disorders | Common | Blood pressure increased, Heart rate increased |
| Uncommon | Bradycardia, Arrhythmia | |
| Vascular disorders | Uncommon | Hypotension |
| Respiratory, thoracic and Mediastinal disorders | Common | Respiratory rate increased |
| Uncommon | Respiratory depression, Laryngospasm | |
| Rare | Obstructive airway disorder*, Apnoea* | |
| Gastrointestinal disorders | Common | Nausea, Vomiting |
| Rare | Salivary hypersecretion* | |
| Hepatobiliary disorders | Not known | Liver function test abnormal, Drug-induced liver injury** |
| Skin and subcutaneous tissue disorders | Common | Erythema, Rash morbilliform |
| Renal and urinary disorders | Rare | Cystitis*, Haemorrhagic cystitis* |
| General disorders and administration site conditions | Uncommon | Injection site pain, Injection site rash |
†Common (>1/100 to <1/10); Uncommon (>1/1,000 to <1/100); Rare (>1/10,000 to <1/1,000); Not known (frequency cannot be estimated from the available data)
* AE frequency estimated from post-marketing safety database
** Extended period use (> 3 days) or drug abuse
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
Cardiovascular: Blood pressure and pulse rate are frequently elevated following administration of Ketamin alone. However, hypotension and bradycardia have been observed. Arrhythmia has also occurred.
Respiration: Although respiration is frequently stimulated, severe depression of respiration or apnea may occur following rapid intravenous administration of high doses of Ketamin. Laryngospasms and other forms of airway obstruction have occurred during ketamine hydrochloride anesthesia.
Eye: Diplopia and nystagmus have been noted following Ketamin administration. It also may cause a slight elevation in intraocular pressure measurement.
Genitourinary: Severe irritative and inflammatory urinary tract and bladder symptoms including cystitis have been reported in individuals with history of chronic ketamine use or abuse.
Psychological: (See Special Note.)
Neurological: In some patients, enhanced skeletal muscle tone may be manifested by tonic and clonic movements sometimes resembling seizures (see DOSAGE AND ADMINISTRATION Section).
Gastrointestinal: Anorexia, nausea and vomiting have been observed; however, this is not usually severe and allows the great majority of patients to take liquids by mouth shortly after regaining consciousness (see DOSAGE AND ADMINISTRATION Section).
General: Anaphylaxis. Local pain and exanthema at the injection site have infrequently been reported. Transient erythema and/or morbilliform rash have also been reported.
For medical advice about adverse reactions contact your medical professional. To report SUSPECTED ADVERSE REACTIONS, contact JHP at 1-866-923-2547 or MEDWATCH at 1-800-FDA-1088 (1- 800-332-1088) or http://www.fda.gov/medwatch/.
Drug Abuse And Dependence
Ketamine has been reported being used as a drug of abuse.
Reports suggest that ketamine produces a variety of symptoms including, but not limited to anxiety, dysphoria, disorientation, insomnia, flashbacks, hallucinations, and psychotic episodes.
Ketamine dependence and tolerance are possible following prolonged administration. A withdrawal syndrome with psychotic features has been described following discontinuation of long-term ketamine use. Therefore, ketamine should be prescribed and administered with caution.
Respiratory depression can result from an overdosage of Ketamin hydrochloride. Supportive ventilation should be employed. Mechanical support of respiration that will maintain adequate blood oxygen saturation and carbon dioxide elimination is preferred to administration of analeptics.
Ketamin has a wide margin of safety; several instances of unintentional administration of overdoses of Ketamin (up to 10 times that usually required) have been followed by prolonged but complete recovery.
Respiratory depression may occur with overdosage or too rapid a rate of administration of Ketamin, in which case supportive ventilation should be employed. Mechanical support of respiration is preferred to administration of analeptics.
Pharmacotherapeutic group: Other general anesthetics.
ATC Code: N01A X03
Ketamin is a rapidly acting general anaesthetic for intravenous or intramuscular use with a distinct pharmacological action. Ketamin hydrochloride produces dissociative anaesthesia characterised by catalepsy, amnesia, and marked analgesia which may persist into the recovery period. Pharyngeal-laryngeal reflexes remain normal and skeletal muscle tone may be normal or can be enhanced to varying degrees. Mild cardiac and respiratory stimulation and occasionally respiratory depression occur.
Mechanism of Action:
Ketamin induces sedation, immobility, amnesia and marked analgesia. The anaesthetic state produced by Ketamin has been termed “dissociative anaesthesia†in that it appears to selectively interrupt association pathways of the brain before producing somesthetic sensory blockade. It may selectively depress the thalamoneocortical system before significantly obtunding the more ancient cerebral centres and pathways (reticular-activating and limbic systems). Numerous theories have been proposed to explain the effects of Ketamin, including binding to N-methyl-D-aspartate (NMDA) receptors in the CNS, interactions with opiate receptors at central and spinal sites and interaction with norepinephrine, serotonin and muscarinic cholinergic receptors. The activity on NMDA receptors may be responsible for the analgesic as well as psychiatric (psychosis) effects of Ketamin. Ketamin has sympathomimetic activity resulting in tachycardia, hypertension, increased myocardial and cerebral oxygen consumption, increased cerebral blood flow and increased intracranial and intraocular pressure. Ketamin is also a potent bronchodilator. Clinical effects observed following Ketamin administration include increased blood pressure, increased muscle tone (may resemble catatonia), opening of eyes (usually accompanied by nystagmus) and increased myocardial oxygen consumption.
Absorption
Ketamin is rapidly absorbed following intra-muscular administration.
Distribution
Ketamin is rapidly distributed into perfused tissues including brain and placenta. Animal studies have shown Ketamin to be highly concentrated in body fat, liver and lung.
In humans at an intravenous bolus dose of 2.5 mg/kg, the distribution phase of Ketamin lasts about 45 minutes, with a half-life of 10 to 15 minutes, which is associated with the duration of the anaesthetic effect (about 20 minutes). Plasma Ketamin concentrations are about 1.8 to 2.0 μg/mL at 5 minutes after an intravenous bolus injection of 2 mg/kg dose, and about 1.7 to 2.2 μg/mL at 15 minutes after an intramuscular injection of 6 mg/kg dose in adults and children.
In parturients receiving an intramuscular dose of 250 mg (approximately 4.2 mg/kg), placental transfer rate of Ketamin from maternal artery to umbilical vein was 47% at the time of delivery (1.72 versus 0.75 µ g/mL). Average delivery time for these parturients was 12 minutes from the time of Ketamin injection to vaginal delivery of a newborn.
Biotransformation
Biotransformation takes place in liver. Termination of anaesthetic is partly by redistribution from brain to other tissues and partly by metabolism. CYP3A4 enzyme is the primary enzyme responsible for Ketamin N-demethylation to norKetamin in human liver microsomes; with CYP2B6 and CYP2C9 enzymes as minor contributors.
Elimination
Elimination half-life is approximately 2-3 hours, and excretion renal, mostly as conjugated metabolites.
Animal research has shown that Ketamin can induce NMDA antagonist-induced neuronal cell death in juvenile animals (apoptosis) when administered in high doses, for prolonged periods, or both. In some cases this led to abnormalities in behaviour, learning and memory. The relevance of this finding to human use is unknown.
Ketamin is chemically incompatible with barbiturates and diazepam because of precipitate formation. Therefore, these should not be mixed in the same syringe or infusion fluid.
For single use only. Discard any unused product.
