Description

Ketamine

Ketamine is a medication mainly used for starting and maintaining anesthesia. It induces a trance-like state while providing pain relief, sedation, and memory loss. Other uses include sedation in intensive care and treatment of pain and depression. Heart function, breathing, and airway reflexes generally remain functional. Effects typically begin within five minutes when given by injection, and last up to approximately 25 minutes.

Common side effects include agitation, confusion, or hallucinations as the medication wears off. Elevated blood pressure and muscle tremors are relatively common. Spasms of the larynx may rarely occur. Ketamine is an NMDA receptor antagonist, but it may also have other actions.

Ketamine was discovered in 1962, first tested in humans in 1964, and approved for use in the United States in 1970. It was extensively used for surgical anesthesia in the Vietnam War due to its safety. It is on the World Health Organization’s List of Essential Medicines, the safest and most effective medicines needed in a health system. It is available as a generic medication. The wholesale price in the developing world is between US$0.84 and US$3.22 per vial. Ketamine is also used as a recreational drug for its hallucinogenic and dissociative effects

Medical uses

Anesthesia

Uses as an anesthetic:

  • Anesthesia in children, as the sole anesthetic for minor procedures or as an induction agent followed by muscle relaxant and tracheal intubation
  • Asthmatics or people with chronic obstructive airway disease
  • As a sedative for physically painful procedures in emergency departments
  • Emergency surgery in field conditions in war zones
  • To supplement spinal or epidural anesthesia/analgesia using low doses
  • To prevent opioid-induced hyperalgesia

Since it suppresses breathing much less than most other available anesthetics, ketamine is used in medicine as an anesthetic; however, due to the hallucinations it may cause, it is not typically used as a primary anesthetic, although it is the anesthetic of choice when reliable ventilation equipment is not available.

Ketamine is frequently used in severely injured people and appears to be safe in this group. A 2011 clinical practice guideline supports the use of ketamine as a dissociative sedative in emergency medicine. It is the drug of choice for people in traumatic shock who are at risk of hypotension. Low blood pressure is harmful in people with severe head injury and ketamine is least likely to cause low blood pressure, often even able to prevent it.

The effect of ketamine on the respiratory and circulatory systems is different from that of other anesthetics. When used at anesthetic doses, it will usually stimulate rather than depress the circulatory system. It is sometimes possible to perform ketamine anesthesia without protective measures to the airways. Ketamine is considered relatively safe because protective airway reflexes are preserved.

It has been successfully used to prevent postanesthetic shivering.

Asthma

Ketamine is used as a bronchodilator in the treatment of severe asthma. However, evidence of clinical benefit is limited.

Seizures

Ketamine is sometimes used in the treatment of status epilepticus that has failed to adequately respond to standard treatments.

Pain management

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. If given intrathecally, its adverse cognitive effects are largely avoided at analgesic doses.

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.

Depression

Ketamine has been found to be a rapid-acting antidepressant in depression. It also may be effective in decreasing suicidal ideation, although based on lower quality evidence. The 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 may persist for up to several weeks 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, ketamine has been described 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 for use as an antidepressant, but its enantiomer, esketamine, was developed as a nasal spray for treatment-resistant depression and was approved for this indication in the United States in March 2019. The effectiveness of esketamine is limited however, with significant effectiveness for treatment-resistant depression seen in only two of five clinical trials. Although there is evidence to support the effectiveness of ketamine and esketamine in treating depression, there is a lack of consensus on dosing and the effects and safety 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 and esketamine for depression