[21] Its distinguishing features as an anesthestic are preserved breathing and airway reflexes, stimulated heart function with increased blood pressure, and moderate bronchodilation.

[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.

[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.

These effects did not persist beyond one week, although a higher dropout rate in some studies means that the benefit duration remains unclear.

[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.

Ketamine, generally, stimulates breathing; however, in the first 2–3 minutes of a high-dose rapid intravenous injection, it may cause a transient respiratory depression.

[citation needed] The symptoms of psychosis such as going into a hole, disappearing, feeling as if melting, experiencing colors, and hallucinations are described by 6–10% of people.

Dizziness, blurred vision, dry mouth, hypertension, nausea, increased or decreased body temperature, or feeling flushed are the common (>10%) non-psychiatric side effects.

[74] Urinary toxicity occurs primarily in people who use large amounts of ketamine routinely, with 20–30% of frequent users having bladder complaints.

The second line treatments are epithelium-protective agents such as oral pentosan polysulfate or intravesical (intra-bladder) instillation of hyaluronic acid.

[76] Chronic ketamine abuse has also been associated with biliary colic,[80] cachexia, gastrointestinal diseases, hepatobiliary disorder, and acute kidney injury.

[81] Most people who were able to remember their dreams during ketamine anesthesia report near-death experiences (NDEs) when the broadest possible definition of an NDE is used.

Some daily users reported withdrawal symptoms, primarily anxiety, shaking, sweating, and palpitations, following the attempts to stop.

Clonidine reduces the increase of salivation, heart rate, and blood pressure during ketamine anesthesia and decreases the incidence of nightmares.

[20][91] Blocking of the NMDA receptor results in analgesia by preventing central sensitization in dorsal horn neurons; in other words, ketamine's actions interfere with pain transmission in the spinal cord.

[11] However, multiple other NMDA receptor antagonists, including memantine, lanicemine, rislenemdaz, rapastinel, and 4-chlorokynurenine, have thus far failed to demonstrate significant effectiveness for depression.

[122][118][109][123] Ketamine has been found to increase dopaminergic neurotransmission in the brain, but instead of being due to dopamine reuptake inhibition, this may be via indirect/downstream mechanisms, namely through antagonism of the NMDA receptor.

Early research by the Philip Seeman group found ketamine to be a D2 partial agonist with a potency similar to that of its NMDA receptor antagonism.

[20] The typical intravenous antidepressant dosage of ketamine used to treat depression is low and results in maximal plasma concentrations of 70 to 200 ng/mL (0.29–0.84 μM).

[137] Ketamine may be quantitated in blood or plasma to confirm a diagnosis of poisoning in hospitalized people, provide evidence in an impaired driving arrest, or assist in a medicolegal death investigation.

Blood or plasma ketamine concentrations are usually in a range of 0.5–5.0 mg/L in persons receiving the drug therapeutically (during general anesthesia), 1–2 mg/L in those arrested for impaired driving, and 3–20 mg/L in victims of acute fatal overdosage.

[31] These investigations demonstrated ketamine's short duration of action and reduced behavioral toxicity made it a favorable choice over phencyclidine (PCP) as an anesthetic.

Hearing about this problem and the "disconnected" appearance of treated people, Mrs. Edward F. Domino,[142] the wife of one of the pharmacologists working on ketamine, suggested "dissociative anesthesia".

[7] At sub-anesthetic doses, ketamine produces a dissociative state, characterised by a sense of detachment from one's physical body and the external world that is known as depersonalization and derealization.

[156] At sufficiently high doses, users may experience what is called the "K-hole", a state of dissociation with visual and auditory hallucination.

[157] John C. Lilly, Marcia Moore, D. M. Turner, and David Woodard (among others) have written extensively about their own entheogenic and psychonautic experiences with ketamine.

[159] In 2006, the Russian edition of Adam Parfrey's Apocalypse Culture was banned and destroyed by authorities owing to its inclusion of an essay by Woodard about the entheogenic use of, and psychonautic experiences with, ketamine.

[169] In veterinary anesthesia, ketamine is often used for its anesthetic and analgesic effects on cats,[170] dogs,[171] rabbits, rats, and other small animals.

[174] Veterinarians often use ketamine with sedative drugs to produce balanced anesthesia and analgesia, and as a constant-rate infusion to help prevent pain wind-up.