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[19] Ketamine is an
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[20]
At anesthetic doses, ketamine induces a state of dissociative anesthesia, a
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[21] Its distinguishing features as an anesthestic are preserved breathing and airway reflexes, stimulated heart function with increased
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[21] At lower, sub-anesthetic doses, it is a promising agent for treatment of
pain and
treatment-resistant depression.
[22] As with many antidepressants, the results of a single administration wane with time.
[23]
Ketamine is used as a recreational drug for its
hallucinogenic and
dissociative effects.
[24] When used recreationally, it is found both in crystalline powder and liquid form, and is often referred to by users as "Special K" or simply "K". The long-term effects of repeated use are largely unknown and are an area of active investigation.
[25][26][27] Liver and urinary toxicity have been reported among regular users of high doses of ketamine for recreational purposes.
[28]
Ketamine was first synthesized in 1962, derived from
phencyclidine in pursuit of a safer anesthetic with fewer hallucinogenic effects.
[29][30] It was approved for use in the United States in 1970.
[19] It has been regularly used in
veterinary medicine and was extensively used for
surgical anesthesia in the
Vietnam War.
[31] It is on the
World Health Organization's List of Essential Medicines.
[32] It is available as a
generic medication.
[33]
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The use of ketamine in anesthesia reflects its characteristics. It is a drug of choice for short-term procedures when
muscle relaxation is not required.
[34] The effect of ketamine on the
respiratory and
circulatory systems is different from that of other anesthetics. It suppresses breathing much less than most other available anesthetics.
[35] When used at anesthetic doses, ketamine usually stimulates rather than depresses the circulatory system.
[36] Protective airway reflexes are preserved,
[37] and it is sometimes possible to administer ketamine anesthesia without protective measures to the airways.
[34] Psychotomimetic effects limit the acceptance of ketamine; however,
lamotrigine[38] and
nimodipine[39] decrease psychotomimetic effects and can also be counteracted by
benzodiazepines or
propofol administration.
[40] Ketofol is a combination of ketamine and
propofol.
Ketamine is frequently used in severely injured people and appears to be safe in this group.
[41] It has been widely used for emergency surgery in field conditions in war zones,
[42] for example, during the
Vietnam War.
[43] A 2011
clinical practice guideline supports the use of ketamine as a
sedative in
emergency medicine, including during physically painful procedures.
[21] It is the drug of choice for people in
traumatic shock who are at risk of
hypotension.
[44] Ketamine is unlikely to lower blood pressure, which is dangerous for people with severe head injury;
[45] in fact, it can raise blood pressure, often making it useful in treating such injuries.
[46][47]
Ketamine is an option in children as the sole anesthetic for minor procedures or as an induction agent followed by
neuromuscular blocker and
tracheal intubation.
[42] In particular, children with
cyanotic heart disease and
neuromuscular disorders are good candidates for ketamine anesthesia.
[40][48]
Due to the bronchodilating properties of ketamine, it can be used for anesthesia in people with
asthma,
chronic obstructive airway disease, and with severe reactive airway disease including active
bronchospasm.
[42][40][49]
Ketamine infusions are used for acute pain treatment in emergency departments and in the perioperative period for individuals with refractory pain. The doses are lower than those used for anesthesia, usually referred to as sub-anesthetic doses. Adjunctive to
morphine or on its own, ketamine reduces morphine use, pain level, nausea, and vomiting after surgery. Ketamine is likely to be most beneficial for surgical patients when severe post-operative pain is expected, and for opioid-tolerant patients.
[50][51]
Ketamine is especially useful in the pre-hospital setting due to its effectiveness and low risk of respiratory depression.
[52] Ketamine has similar efficacy to opioids in a hospital emergency department setting for the management of acute pain and the control of procedural pain.
[53] It may also prevent
opioid-induced hyperalgesia[54][55] and
postanesthetic shivering.
[56]
For chronic pain, ketamine is used as an intravenous analgesic, mainly if the pain is
neuropathic.
[30] It has the added benefit of counteracting
spinal sensitization or
wind-up phenomena experienced with
chronic pain.
[57] In multiple clinical trials, ketamine infusions delivered short-term pain relief in neuropathic pain diagnoses, pain after a traumatic spine injury,
fibromyalgia, and
complex regional pain syndrome (CRPS).
[30] However, the 2018 consensus guidelines on chronic pain concluded that, overall, there is only weak evidence in favor of ketamine use in spinal injury pain, moderate evidence in favor of ketamine for CRPS, and weak or no evidence for ketamine in mixed neuropathic pain, fibromyalgia, and
cancer pain. In particular, only for CRPS, there is evidence of medium to longer-term pain relief.
[30]
Ketamine is a rapid-acting
antidepressant,
[19] but its effect is transient.
[58] Intravenous ketamine infusion in
treatment-resistant depression may result in improved mood within 4 hours reaching the peak at 24 hours.
[22][25] A single dose of intravenous ketamine has been shown to result in a response rate greater than 60% as early as 4.5 hours after the dose (with a sustained effect after 24 hours) and greater than 40% after 7 days.
[59] Although only a few pilot studies have sought to determine the optimal dose, increasing evidence suggests that 0.5 mg/kg dose injected over 40 minutes gives an optimal outcome.
[60] The antidepressant effect of ketamine is diminished at 7 days, and most people relapse within 10 days. However, for a significant minority, the improvement may last 30 days or more.
[25][26][59][61]
One of the main challenges with ketamine treatment can be the length of time that the antidepressant effects last after finishing a course of treatment. A possible option may be maintenance therapy with ketamine, which usually runs twice a week to once in two weeks.
[25][26][27] Ketamine may decrease
suicidal thoughts for up to three days after the injection.
[62]
An
enantiomer of ketamine –
esketamine commercially sold as
Spravato – was approved as an antidepressant by the
European Medicines Agency in 2019.
[63] Esketamine was approved as a nasal spray for
treatment-resistant depression in the United States
[64] and elsewhere in 2019 (see
Esketamine and Depression). The Canadian Network for Mood and Anxiety Treatments (CANMAT) recommends esketamine as a third-line treatment for depression.
[26]
A
Cochrane review of
randomized controlled trials in adults with unipolar
major depressive disorder,
[19] found that when compared with placebo, people treated with either ketamine or esketamine experienced reduction or remission of symptoms lasting 1 to 7 days.
[65] There were 18.7% (4.1 to 40.4%) more people reporting some benefit and 9.6% (0.2 to 39.4%) more who achieved remission within 24 hours of ketamine treatment. Among people receiving esketamine, 2.1% (2.5 to 24.4%) encountered some relief at 24 hours, and 10.3% (4.5 to 18.2%) had few or no symptoms. These effects did not persist beyond one week, although a higher dropout rate in some studies means that the benefit duration remains unclear.
[65]
Ketamine may partially improve depressive symptoms
[19] among people with
bipolar depression at 24 hours after treatment, but not three or more days.
[66] Potentially, ten more people with bipolar depression per 1000 may experience brief improvement, but not the cessation of symptoms, one day following treatment. These estimates are based on limited available research.
[66]
In February 2022, the US
Food and Drug Administration issued an alert to healthcare professionals concerning
compounded nasal spray products containing ketamine intended to treat depression.
[67]
Ketamine is used to treat
status epilepticus[68] that has not responded to standard treatments, but only case studies and no randomized controlled trials support its use.
[69][70]
Ketamine has been suggested as a possible therapy for children with severe acute asthma who do not respond to standard treatment.
[71] This is due to its
bronchodilator effects.
[71] A 2012 Cochrane review found there were minimal adverse effects reported, but the limited studies showed no significant benefit.
[71]
Some major
contraindications for ketamine are:
[30][50]
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