Ketamine Propharm

/ Propharm

As with other general anesthetic agents, the individual response to ketamine 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.
For full details see prescribing information.

* As the sole anaesthetic agent for diagnostic and surgical procedures. When used by intravenous or intramuscular injection, Ketamine is best suited for short procedures. With additional doses, or by intravenous infusion, Ketamine can be used for longer procedures.
* 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.

* Hypersensitivity to the active substance or to any of the excipients
* Patients at risk of serious harm from increased blood pressure
* Should not be used in patients with eclampsia or pre-eclampsia, severe coronary or myocardial disease, cerebrovascular accident or cerebral trauma.

* 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 ketamine, 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.
* In surgical procedures involving visceral pain pathways, ketamine should be
supplemented with an agent which obtunds visceral pain.
* When ketamine 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.
Ketamine should be used with caution in patients with the following conditions:
* Chronic alcoholic and the acutely alcohol-intoxicated patient.
* Ketamine 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 ketamine 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 ketamine anaesthesia, this medicine should be used with special caution in patients with preanaesthetic elevated cerebrospinal fluid pressure.
* Globe injuries and increased intraocular pressure
(e.g., glaucoma) because the pressure may increase significantly after a single dose of ketamine.
* Neurotic traits or psychiatric illness (e.g. schizophrenia and acute psychosis).
* Acute intermittent porphyria
* Seizures
* Patients with hyperthyroidism or patients receiving thyroid replacement (increased risk of hypertension and tachycardia).
* Pulmonary or upper respiratory infection
* 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, ketamine 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, ketamine 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 ketamine, 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
Ketamine is not indicated nor recommended for long-term use.
Cases of cystitis, including haemorrhagic cystitis, acute kidney injury,
hydronephrosis, and ureteral disorders have been reported in patients being given ketamine on a long term basis, especially in the setting of ketamine abuse. (These adverse reactions develop in patients receiving long-term ketamine treatment after a time ranging from 1 month to several years).
Hepatotoxicity such as mixed liver injury, cholestatic liver injury and biliary dilation has also been reported in patients with extended use (> 3 days).
Drug Abuse and Dependence
Ketamine has been reported as being a drug of abuse. Reports suggest that ketamine produces a variety of symptoms including, but not limited to, flashbacks, hallucinations, dysphoria, anxiety, insomnia, or disorientation.
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 ketamine should be closely supervised and it should be prescribed and administered with caution.

Common: Hallucination, Abnormal dreams, Nightmare, Confusion, Agitation,
Abnormal behavior, Nystagmus, Hypertonia, Tonic-clonic movements, Diplopia, Blood pressure increased, Heart rate increased, Respiratory rate increased, Erythema, Rash morbilliform.
For full details see prescribing information.

Barbiturates and/or narcotics prolonged recovery time may occur if used concurrently with ketamine. Ketamine is chemically incompatible with barbiturates and diazepam because of precipitate formation. Therefore, these should not be mixed in the same syringe or infusion fluid.
Diazepam is known to increase the half-life of ketamine and prolongs its
pharmacodynamic effects. Dose adjustments may therefore be needed.
Atracurium and tubocurarine: The neuromuscular blocking effects of atracurium and tubocurarine may be potentiated when administered with ketamine, leading to respiratory depression and possible apnoea.
Halogenated anaesthetics: The use of halogenated anaesthetics concomitantly with ketamine can lengthen the elimination half-life of ketamine and delay recovery from anaesthesia. Concurrent use of ketamine (especially in high doses or when rapidly administered) with halogenated anaesthetics can increase the risk of developing bradycardia, hypotension or decreased cardiac output.
CNS depressants: The use of ketamine with other central nervous system (CNS) depressants (e.g. ethanol, phenothiazines, sedating H1 – blockers or skeletal muscle relaxants) can potentiate CNS depression and/or increase risk of developing respiratory depression.
Reduced doses of ketamine may be required with concurrent administration of other anxiolytics, sedatives and hypnotics.
Thiopental: Ketamine has been reported to antagonise the hypnotic effect of thiopental.
Thyroid hormones: Patients taking thyroid hormones have an increased risk of developing hypertension and tachycardia when given ketamine.
Antihypertensive agents: Concomitant use of antihypertensive agents and ketamine increases the risk of developing hypotension.
Ergometrine: Concomitant use with ergometrine may lead to an increase in blood pressure.
Sympathomimetics (directly or indirectly acting) and vasopressin may enhance the sympathomimetic effects of ketamine.
Theophylline or aminophylline: When ketamine and theophylline or aminophylline are given concurrently, a clinically significant reduction in the seizure threshold may be observed.
CYP3A4 Inhibitors: Drugs that inhibit CYP3A4 enzyme activity generally decrease hepatic clearance, and increased plasma concentration of ketamine. Coadministration of ketamine with drugs that inhibit CYP3A4 enzyme may require a decrease in ketamine dosage to achieve the desired clinical outcome.
CYP3A4 Inducers: Drugs that induce CYP3A4 enzyme activity generally increase hepatic clearance, resulting in decreased plasma concentration of ketamine. Coadministration of ketamine with drugs that induce CYP3A4 enzyme may require an increase in ketamine dosage to achieve the desired clinical outcome.

Pregnancy: Ketamine crosses the placenta. This should be borne in mind during operative obstetric procedures in pregnancy. No controlled clinical studies in pregnancy have been conducted. The use in pregnancy has not been established, and such use is not recommended, with the exception of administration during surgery for abdominal delivery or vaginal delivery. Some neonates exposed to ketamine at maternal intravenous doses ≥ 1.5 mg/kg during delivery have experienced respiratory depression and low Apgar scores requiring newborn resuscitation.
Marked increases in maternal blood pressure and uterine tone have been observed at intravenous doses greater than 2 mg/kg.
Data are lacking for intramuscular injection and maintenance infusion of ketamine in the parturient population, and recommendations cannot be made.
Lactation: The safe use of ketamine during lactation has not been established, and such use is not recommended.

Respiratory depression can result from an overdosage of ketamine 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.
Ketamine has a wide margin of safety; several instances of unintentional
administration of overdoses of ketamine (up to 10 times that usually required) have been followed by prolonged but complete recovery.

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