Ketamine

Registered South African indications:

• Induction of anaesthesia
• Maintenance of general anaesthesia
• Management of minor surgical and diagnostic procedures (paediatrics)
• Repeated procedures that require intense analgesia (paediatrics)

Contraindications

South African recommendations

• Hypersensitivity to ketamine hydrochloride or to any of the inactive ingredients
• Conditions in which elevation of blood pressure would be a serious hazard
• Hypertension 
• History of cerebrovascular accident 
• Eclampsia
• Pre-eclampsia
• Severe coronary or myocardial disease
• Cerebral trauma
• Increased intra-ocular pressure 
• Penetrating wounds of the eye 
• Pregnancy
• Lactation
• Not for intrathecal use 

Recommendations in other jurisdictions

• Hypersensitivity to the active ingredient or to any of its excipients 
• Conditions in which elevation of blood pressure would be a serious hazard 
• Eclampsia 
• Pre-eclampsia 
• Severe coronary or myocardial disease 
• Cerebrovascular accident
• Cerebral trauma

Cautions

• Pregnancy (Recommendations in other jurisdictions)
• Breastfeeding (Recommendations in other jurisdictions)
• Hepatic impairment 
• Inexperienced clinician
• Rapid IV injection
• Mechanical stimulation of pharynx
• Procedures that cause visceral pain
• Chronic alcoholics
• Acute alcohol intoxication
• Preanaesthetic elevated cerebrospinal fluid pressure
• Globe injuries
• Raised intraoccular pressure
• Psychiatric history
• Intermittent prophyria
• History of seizures
• Hyperthyroidism
• Pulmonary infection
• Intracranial mass lesions
• Hydrocephalus
• Head injury
• Hypovolaemia
• Hypertension
• Tachyarrhythmias
• History of drug abuse
• Prolonged use

Forms avail. in SA and covered in this monograph: inj

Dosages below include:

• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

South African registered indications and dosages

Induction of anaesthesia
Maintenance of general anaesthesia
- In combination with oxygen and nitrous oxide

• IV: 1-2mg/kg, given over 60sec; Onset of anaesthesia: 30sec; Duration time: 5-10min
• IM: 5-10mg/kg; Onset of anaesthesia: 3-4min; Duration time: 12-25min

OR

• IV: Induction: Approx. 1mg/kg, as an infusion until induction is complete; Maintenance: 1-5mg/kg/hr, individualised to prevent nystagmus and response to surgical stimuli

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Administration should be preceded by atropine or another suitable antimuscarinic medicine

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Doses should be individualised

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An IV infusion solution (1mg/ml) is prepared by mixing 500mg of ketamine in 500ml of 5% glucose or 0.9% sodium chloride solution

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Upon termination of surgery, the ketamine infusion is discontinued

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Not for intrathecal use

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Indications and dosages registered in other jurisdictions

For anaesthesia in diagnostic and surgical procedures (short and longer procedures)
Induction of anaesthesia prior to the administration of other general anaesthetic agents
To supplement other anaesthetic agents
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
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

• IV: 2mg/kg body weight; Onset of anaesthesia: 30sec; Duration time: 5-10min
• IM: 10mg/kg body weight; Onset of anaesthesia: 3-4min; Duration time: 12-25min

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As with other general anaesthetic agents, the individual response to ketamine 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

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As a sole anaesthetic agent (IV infusion)

- General anaesthesia induction

• IV: 0.5-2mg/kg, as total induction dose

- Maintenance of anaesthesia

• IV (microdrip infusion): 10-45μg/kg/min (approx. 1-3mg/min)

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The use of ketamine 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

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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

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As a sole anaesthetic agent (Intermittent injection)

- Induction

• IV: 1-4.5mg/kg, given over 60sec; Average amount required for 5-10min surgical anaesthesia: 2mg/kg

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More rapid administration may result in respiratory depression and enhanced pressor response

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- In obstetrics (for vaginal delivery or in caesarean section)

• IV: 0.2-1.0mg/kg

As a sole anaesthetic agent (Intramuscular injection)

• IM: Initial: 6.5-13mg/kg; Minimum initial dose: 4mg/kg, has been used in diagnostic manoeuvres and procedures not involving intensely painful stimuli; 10mg/kg usually produces 12-25 min of surgical anaesthesia

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Dosage in obstetrics: Data are lacking for intramuscular injection and maintenance infusion of ketamine in the parturient population, and recommendations cannot be made

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- Maintenance of general anaesthesia

• IV/IM: 50% of full induction dose (as recommended above)

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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 ketamine by either the intravenous or intramuscular route

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The larger the total amount of ketamine 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

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As induction agent prior to the use of other general anaesthetics

• IV: Induction accomplished by a full IV dose of ketamine as defined above; When principal anaesthetic is slow acting: Repeat dose 5-8min following initial dose
• IM: Induction accomplished by a full IM dose of ketamine as defined above; When principal anaesthetic is rapid acting: Administration of the principal anaesthetic may be delayed up to 15min following the injection of ketamine

As supplement to anaesthetic agents

• IV/IM: Same range as above (the use of another anaesthetic agent may allow a reduction in the dose of ketamine)

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Ketamine is clinically compatible with the commonly used general and local anaesthetic agents when an adequate respiratory exchange is maintained. The dose of ketamine for use in conjunction with other anaesthetic agents is usually in the same range as the dosage stated above

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If skeletal muscle relaxation is desired, a muscle relaxant should be used and respiration should be supported

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Preoperative preparations:
Ketamine 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 ketamine-induced hypersalivation
Midazolam, diazepam, lorazepam, or flunitrazepam used as a premedicant or as an adjunct to ketamine, have been effective in reducing the incidence of emergence reactions

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Note: Eye movements may persist during ophthalmological procedures

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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 (5-10mg IV). A hypnotic dose of a thiobarbiturate (50-100mg IV) may be used to terminate severe emergence reactions. If any one of these agents is employed, the patient may experience a longer recovery period

Paed. forms avail. in SA and covered in this monograph: inj

Paed. dosages below include:

• South African Standard Treatment Guidelines indications and dosages
• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

South African Standard Treatment Guidelines indications and dosages

• Click here for the Pain Control (Standard Treatment Guidelines And Essential Medicines List For South Africa, Hospital Level, Paediatrics, 2023 Edition)
• Click here for the Anaesthetics (Standard Treatment Guidelines And Essential Medicines List For South Africa, Hospital Level, Paediatrics, 2023 Edition)

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South African registered indications and dosages

Management of minor surgical and diagnostic procedures
Repeated procedures that require intense analgesia
- Such as changing burn dressings

• IV: 1-2mg/kg, given over 60sec; Onset of anaesthesia: 30sec; Duration time: 5-10min
• IM: 5-10mg/kg; Onset of anaesthesia: 3-4min; Duration time: 12-25min

OR

• IV: Induction: Approx. 1mg/kg, as an infusion until induction is complete; Maintenance: 1-5mg/kg/hr, individualised to prevent nystagmus and response to surgical stimuli

---

Administration should be preceded by atropine or another suitable antimuscarinic medicine

---

Doses should be individualised

---

An IV infusion solution (1mg/ml) is prepared by mixing 500mg of ketamine in 500ml of 5% glucose or 0.9% sodium chloride solution

---

Upon termination of surgery, the ketamine infusion is discontinued

---

Not for intrathecal use

---

Indications and dosages registered in other jurisdictions

For anaesthesia in diagnostic and surgical procedures (short and longer procedures)
Induction of anaesthesia prior to the administration of other general anaesthetic agents
To supplement other anaesthetic agents
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
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

• See adult dosage

Pregnancy

South African recommendations

• Contraindicated
• Safety in pregnancy has not been established
• Ketamine crosses the placenta. Neonates exposed to ketamine during delivery have experienced respiratory depression and low Apgar scores requiring new-born resuscitation
• Marked increases in maternal blood pressure and uterine tone have been observed at intravenous doses greater than 2mg/kg

Recommendations in other jurisdictions

• Caution; not recommended
• 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 ≥1.5mg/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 2mg/kg
• Data are lacking for intramuscular injection and maintenance infusion of ketamine in the parturient population, and recommendations cannot be made

Breastfeeding

South African recommendations

• Contraindicated
• Safety in lactation has not been established

Recommendations in other jurisdictions

• Caution; not recommended
• The safe use of ketamine during lactation has not been established, and such use is not recommended
• Studies in animals have shown reproductive toxicity

Renal Impairment

• No dose adjustment recommended

Hepatic Impairment

• Caution; dose adjustment recommended
• 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

Elderly

• No dose adjustment recommended

Porphyria Information

• Possibly porphyrinogenic (PSP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Hallucinations
• Abnormal dreams
• Nightmares
• Confusion
• Agitation
• Abnormal behaviour
• Anxiety
• Delirium
• Flashbacks
• Dysphoria
• Insomnia
• Disorientation
• Nystagmus
• Hypertonia
• Tonic/clonic movements

Cardiovascular Disorders

• Increased blood pressure
• Tachycardia
• Bradycardia
• Arrhythmias
• Hypotension

Respiratory Disorders

• Tachypnoea
• Respiratory depression
• Laryngospasm
• Bronchospasm
• Apnoea

Gastrointestinal Disorders

• Nausea and vomiting
• Hypersalivation

Hepatobiliary Disorders

• Abnormal liver function tests
• Hepatic injury

Genitourinary Disorders

• Cystitis

Endocrine and Metabolic Disorders

• Anorexia

Skin and Subcutaneous Tissue Disorders

• Erythema
• Mobilliform rash
• Injection site rash
• Injection site pain

Immune, Blood and Lymphatic System Disorders

• Anaphylactic reactions

Sensory Disorders

• Diplopia
• Increased intraocular pressure

• Narcotics
• Barbiturates
• Diazepam
• Atracurium
• Tubocurarine
• Halogenated anaesthetics 
• Central nervous system depressants
• Thiopental
• Thyroxine
• Antihypertensives
• Theophylline
• CYP3A4 inhibitors
• CYP3A4 inducers

• Vital signs
• Monitor for emergence reactions

Specific cases may require

• Cardiac monitoring

Emergence reactions

• 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
• A benzodiazepine can be coadministered with ketamine to decrease the incidence of emergence delirium

Incompatibilities

• 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.

Ketamine appears to selectively interrupt association pathways of the brain before producing somesthetic sensory blockade. Numerous theories have been proposed to explain the effects of ketamine, including binding to N-methyl-D-aspartate (NMDA) receptors in the central nervous system, interactions with opiate receptors at central and spinal sites and interaction with norepinephrine, serotonin and muscarinic cholinergic receptors. Ketamine is also a potent bronchodilator and has sympathomimetic activity.

Injection (per ml) 10mg

• Ketamine-Fresenius (Bodene)
• Micro-Ketamine (Micro Healthcare)

Injection (per ml) 50mg

• Ketamine-Fresenius (Bodene)
• Micro-Ketamine (Micro Healthcare)

Injection (per ml) 100mg

• Ketamine-Fresenius (Bodene)
• Micro-Ketamine (Micro Healthcare)