What are the effects of ketamine (Ketamine hydrochloride)?

From the Guidelines

Ketamine is a dissociative anesthetic medication that should be used with caution due to its potential side effects, and its administration should be limited to medical professionals in a controlled environment. Ketamine has multiple medical uses, including anesthesia, pain management, and treatment for depression. It's typically administered at doses of 0.5-2 mg/kg for anesthesia induction, 0.1-0.5 mg/kg for pain management, and 0.5 mg/kg for depression treatment, with routes including intravenous, intramuscular, intranasal, and oral 1.

Mechanism of Action and Effects

Ketamine works primarily by blocking NMDA receptors in the brain, which affects glutamate neurotransmission and leads to its dissociative effects. Common immediate effects include dissociation (feeling detached from reality), analgesia (pain relief), sedation, and potential psychedelic experiences including visual distortions and altered perception of time.

Side Effects and Risks

Side effects can include increased heart rate and blood pressure, nausea, dizziness, and psychological reactions like anxiety or confusion. Long-term or recreational use carries risks of bladder problems (ketamine cystitis), cognitive impairment, and psychological dependence 1.

Administration and Monitoring

Ketamine should only be used under medical supervision as it's a controlled substance with potential for misuse. For therapeutic applications, patients should be monitored during administration, avoid driving or operating machinery for 24 hours after treatment, and be aware that effects typically last 1-2 hours with residual effects possibly continuing for several hours afterward. The use of ketamine for endoscopic sedation has been studied predominantly in the pediatric setting, and it has been found to be safe and effective when used in combination with midazolam 1.

Special Considerations

In adults, ketamine has been useful as an adjunct to standard sedation for difficult-to-sedate patients, but its use has been limited due to concerns over emergence reactions 1. Ketamine produces a dose-dependent increase in heart rate, blood pressure, and cardiac output, mediated through stimulation of the sympathetic nervous system, and its use should be avoided in patients with ischemic heart disease, cerebrovascular disease, or hypertension 1.

Key Recommendations

• Ketamine should be used with caution and only in a medical setting.
• Patients should be monitored closely during administration and for several hours after treatment.
• The use of ketamine should be limited to medical professionals with experience in its administration and management of potential side effects.
• Patients should be aware of the potential risks and side effects of ketamine, including bladder problems, cognitive impairment, and psychological dependence.

From the FDA Drug Label

The administration of anesthetic and sedation drugs, such as ketamine hydrochloride, that either block NMDA receptors or potentiate the activity of GABA during the period of rapid brain growth or synaptogenesis, results in widespread neuronal and oligodendrocyte cell loss in the developing brain and alterations in synaptic morphology and neurogenesis. Ketamine hydrochloride, a racemic mixture of ketamine, is a non-selective, non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, an ionotropic glutamate receptor. Abuse is the intentional, non-therapeutic use of a drug, even once, for its psychological or physiological effects. Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. Physical dependence has been reported with prolonged use of ketamine. Withdrawal symptoms have been reported after the discontinuation of frequently used (more than weekly), large doses of ketamine for long periods of time. Tolerance has been reported with prolonged use of ketamine. Changes in heart rate and blood pressure, respiratory depression, and apnea may occur with overdosage or by a rapid rate of administration of ketamine hydrochloride.

Ketamine Effects:

• Neurotoxicity: Ketamine may cause neuronal and oligodendrocyte cell loss in the developing brain.
• Abuse and Dependence: Ketamine has the potential for abuse and dependence, particularly in individuals with a history of drug abuse or dependence.
• Mechanism of Action: Ketamine is a non-selective, non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor.
• Overdosage: Changes in heart rate and blood pressure, respiratory depression, and apnea may occur with overdosage or rapid administration.
• Tolerance and Withdrawal: Tolerance and withdrawal symptoms have been reported with prolonged use of ketamine.

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From the Research

Overview of Ketamine

• Ketamine is a drug with a variety of clinical implications, including use in anesthesia, analgesia, and treatment of mental health disorders 4.
• It has been shown to be effective in treating depression, bipolar affective disorders, alcohol and heroin addiction, asthma, and epilepsy 4.
• Ketamine functions as a noncompetitive antagonist targeting the N-methyl-D-aspartate (NMDA) receptor, with a complex mechanism of action 4.

Therapeutic Effects

• Subanaesthetic doses of ketamine have been demonstrated to have rapid and sustained antidepressant effects 5.
• Ketamine has been shown to have therapeutic effects for a range of psychiatric conditions, including depression, bipolar disorder, and suicidal ideation 5.
• Systematic reviews and meta-analyses provide support for robust, rapid, and transient antidepressant and anti-suicidal effects of ketamine 5.

Procedural Sedation and Analgesia

• Ketamine has been used in combination with midazolam for procedural sedation and analgesia in adult emergency department patients, with effective results and minimal adverse effects 6.
• A systematic review and network meta-analysis found that ketamine-propofol provided better patient satisfaction and shorter recovery times compared to midazolam-opioids 7.
• Ketamine has been compared to propofol/fentanyl for brief orthopedic procedural sedation in a pediatric emergency department, with propofol/fentanyl showing shorter recovery times and comparable effectiveness in reducing procedural distress 8.

Safety and Adverse Effects

• Ketamine is generally regarded as safe, with low doses and short-term use typically not leading to significant adverse effects 4.
• However, ketamine can cause respiratory compromise, emesis, and myoclonia, although these effects are usually transient and do not result in a change in the patient's disposition 6.
• A systematic review and network meta-analysis found that respiratory adverse events were less frequent with ketamine compared to midazolam-opioids, but gastrointestinal and neurological adverse events were more common with certain ketamine combinations 7.