Group: parenteral anaesthetic agentInjection: 50 mg (hydrochloride)/ml in 10-ml ampoule
Ketamine is a phencyclidine derivative. In anaesthetic doses it produces a trance like state known as “dissociative anaesthesia”.
Anaesthesia persists for up to 15 minutes after a single intravenous injection and is characterized by profound analgesia. Ketamine may be used as the sole agent for diagnostic and minor surgical interventions. It is less likely than other anaesthetic agents to induce vomiting. Since it does not induce hypotension the patient does not have to remain supine and its sympathomimetic effects are of particular value in patients who are shocked, severely dehydrated or severely anaemic.
Because pharyngeal and laryngeal reflexes are only slightly impaired, the airway may be less at risk than is the case with other general anaesthetic techniques. It is of particular value in children and poor-risk patients, and also in asthmatic patients, because it rarely induces bronchospasm.
Ketamine produces no muscular relaxation. It tends to raise heart rate and intracranial and intraocular pressure. In hypertensive patients it may raise blood pressure unduly. Hallucinations can occur during recovery (although rarely in children), but they are avoided if ketamine is used solely as an induction agent and followed by a conventional inhalational anaesthetic. Their incidence may also be greatly reduced by administration of diazepam both as a premedication and after the procedure.
Subanaesthetic concentrations of ketamine may be used to provide analgesia for painful procedures of short duration such as the dressing of burns, radiotherapeutic procedures, marrow sampling and minor orthopaedic procedures.
Ketamine may be used for induction of anaesthesia prior to administration of inhalational anaesthetics, or for both induction and maintenance of anaesthesia for short-lasting diagnostic and surgical interventions, including dental procedures that do not require skeletal muscle relaxation. It is of particular value for children requiring frequent repeated anaesthetics.
Its use in conjunction with a muscle relaxant and controlled ventilation for more prolonged anaesthesia should be considered only by specialist anaesthetists because experience is required in assessing the depth of anaesthesia. Emergence from the anaesthetic state is heralded, in these circumstances, by tachycardia, a rise in blood pressure, nystagmus and attempts at swallowing.
Ketamine may be used for postoperative pain management. Low doses of ketamine may reduce morphine use, nausea, and vomiting after surgery. Ketamine has similar efficacy to opioids in a hospital emergency department setting for management of acute pain and for control of procedural pain.
It may also be used as an intravenous analgesic with opiates to manage otherwise intractable pain, particularly if this pain is neuropathic. It has the added benefit of counteracting spinal sensitization or wind-up phenomena experienced with chronic pain. At these doses, the psychotropic side effects are less apparent and well managed with benzodiazepines.
Ketamine is an analgesic that is most effective when used alongside a low-dose opioid; because, while it does have analgesic effects by itself, the doses required for adequate pain relief when it is used as the sole analgesic agent are considerably higher and far more likely to produce disorienting side effects. A review article in 2013 concluded, “despite limitations in the breadth and depth of data available, there is evidence that ketamine may be a viable option for treatment-refractory cancer pain”.
Low-dose ketamine is sometimes used in the treatment of complex regional pain syndrome (CRPS). A 2013 systematic review found only low-quality evidence to support the use of ketamine for CRPS.
Some evidence has found ketamine to be a rapid-acting antidepressant in depression, for instance in major depressive disorder, treatment-resistant depression, and bipolar depression. It also may be effective in rapidly alleviating suicidal ideation, although based on lower quality evidence. The rapid-onset antidepressant effects of ketamine were first shown in small studies in 2000 and 2006. They have since been demonstrated and characterized in subsequent studies.
A single low, sub-anesthetic dose of ketamine given via intravenous infusion may produce antidepressant effects within four hours in people with depression. These antidepressant effects persist for at least a week following a single infusion. This is in contrast to conventional antidepressants like selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), which generally require at least several weeks for their benefits to occur and become maximal.
Moreover, based on the available preliminary evidence, the magnitude of the antidepressant effects of ketamine appears to be more than double that of conventional antidepressants. On the basis of these findings, a 2017 review described ketamine as the single most important advance in the treatment of depression in over 50 years. It has sparked interest in NMDA receptor antagonists for depression, and has shifted the direction of antidepressant research and development.
Ketamine has not been approved or marketed for use as an antidepressant. In addition, while as of 2017 there was evidence to support the effectiveness of ketamine in treating depression, there was a lack of consensus on optimal dosing and the effects of long-term therapy.
Ketamine can produce euphoria and dissociative hallucinogen effects at higher doses, and thus has an abuse potential. Moreover, ketamine has been associated with cognitive deficits, urotoxicity, hepatotoxicity, and other complications in some individuals with long-term use. These undesirable effects may serve to limit the use of ketamine for depression. Dozens of “ketamine clinics” have opened across the United States, where intravenous ketamine is used off-label to treat depressed people. Esketamine, the more active S(+) enantiomer of racemic ketamine, is under development by Johnson & Johnson as a nasal spray for daily administration.
Dosage and administration
Administration of ketamine should always be preceded by premedication with atropine to reduce salivary secretions.
Premedication with diazepam reduces the subsequent requirement for ketamine and the incidence of emergence reactions but in this case there is a need for endotracheal intubation.
Dosage requirements vary with age, the physical condition of the patient and rate of administration.
As a general guide the following regimens are recommended:
1-2 mg/kg by slow intravenous injection over a period of 60 seconds. More rapid administration may result in respiratory depression or apnoea and an enhanced pressor response. A dose of 2 mg/kg produces surgical anaesthesia within 1-2 minutes which may be expected to last 5 to 10 minutes.
6-8 mg/kg by deep intramuscular injection. This dose produces surgical anaesthesia within 3-5 minutes and may be expected to last up to 25 minutes.
Induction and maintenance
Following induction, as above, serial doses of 50% of the original intravenous dose or 25% of the intramuscular dose are administered as required. The need for supplementary doses is established largely by movement in response to surgical stimuli.
Anaesthesia may also be maintained by slow microdrip infusion of ketamine at a rate of 1-2 mg/minute, augmented with diazepam 2-5 mg administered intravenously, as required, from a separate syringe to a maximum of 20 mg.
Tonic and clonic movements resembling seizures occur in some patients. These are not indicative of a light plane of anaesthesia or of a need for additional doses of the anaesthetic.
As an analgesic:
500 micrograms/kg i.m. or i.v. followed, if necessary, by a dose of 250 micrograms/kg.
Return to consciousness is gradual. Emergence reactions with delirium may occur during the recovery period. Their incidence is reduced if unnecessary disturbance of the patient is avoided during recovery (although vital signs may be monitored) and they are unlikely to occur if diazepam is administered preoperatively and supplemented, if necessary, by a further 5-10 mg i.v. at the end of the procedure. Hypnotic doses of thiopental (50-100 mg i.v.) may be required to suppress overt reactions but this will considerably prolong the recovery period.
• Hypersensitivity to ketamine.
• Moderate to severe hypertension, congestive cardiac failure, or a history of cerebrovascular accident.
• Acute or chronic alcohol intoxication.
• Cerebral trauma, intracerebral mass or haemorrhage or other causes of raised intracranial pressure.
• Eye injury and increased intraocular pressure.
• Psychiatric disorders such as schizophrenia and acute psychoses.
Ketamine should, whenever possible, be used under the supervision of an experienced specialist anaesthetist who is confident of intubating the patient should this become necessary. Equipment for resuscitation and endotracheal intubation should be immediately available and ready for use.
Pulse and blood pressure should be closely monitored, particularly in patients with hypertension, congestive cardiac failure or thyrotoxicosis. Mechanical stimulation of the pharynx should be avoided unless muscle relaxants are used.
Supplementary analgesia is often required in surgical procedures involving visceral pain pathways. Morphine may be used but the addition of nitrous oxide will often suffice.
During recovery, patients must remain undisturbed and under observation. Outpatients must be discharged in the care of a responsible adult and advised not to drive or operate machinery for at least 24 hours.
Use in pregnancy
Ketamine is contraindicated in pregnancy before term, since it has oxytocic activity. It is also contraindicated in patients with eclampsia or pre-eclampsia. It may be used for assisted vaginal delivery by an experienced anaesthetist, but the dosage has to be adjusted within wide limits to individual circumstances. It is better suited for use during caesarean section; ketamine results in less fetal and neonatal depression than do other anaesthetics and the short exposure required has not been associated with emergence reactions when diazepam is used concomitantly.
The emergence reactions experienced during recovery are sometimes accompanied by irrational behaviour. These effects rarely persist for more than a few hours but recurrences can occur at any time within 24 hours of exposure.
Transient elevation of pulse rate and blood pressure is common, and dysrhythmias have occurred. Conversely, hypotension and bradycardia are occasionally reported.
Infrequent reactions include:
• Anorexia, nausea and vomiting
• local pain and exanthema at the injection site
• transient generalized erythema and morbilliform rashes
• transient postoperative diplopia, nystagmus and elevated intraocular pressure
• laryngospasm and other forms of airway obstruction.
Barbiturates and diazepam are chemically incompatible with ketamine. They should never be administered from the same syringe or via the same infusion set.
Ether, halothane and other cerebral depressants may considerably prolong the effect of ketamine and delay recovery.
Transient respiratory depression may necessitate mechanical support of ventilation.
Ketamine injection should be protected from light.