What are the guidelines for using ketamine (Ketamine hydrochloride) for medical treatment?

From the Guidelines

Ketamine hydrochloride should be used with caution and only in a controlled medical setting, due to its potential for significant side effects, including increased blood pressure, heart rate, hallucinations, and dissociation, as well as its potential for abuse.

Guidelines for Use

Ketamine is a dissociative anesthetic medication primarily used for:

• Anesthesia induction: typical dosing ranges from 1-4.5 mg/kg IV or 4-10 mg/kg IM, with onset within 30 seconds for IV administration and 3-4 minutes for IM 1.
• Procedural sedation: lower doses of 0.5-1 mg/kg IV or 2-4 mg/kg IM are common 1.
• Treatment-resistant depression: sub-anesthetic doses are used, typically 0.5 mg/kg IV infused over 40 minutes, often administered in a series of 6 treatments over 2-3 weeks 1.

Important Considerations

• Ketamine must be administered in a controlled medical setting with continuous monitoring of vital signs 1.
• Patients should be NPO (nothing by mouth) for 6 hours before administration and must have a responsible adult to accompany them home afterward 1.
• Ketamine is contraindicated in patients with severe hypertension, aneurysmal vascular disease, increased intracranial pressure, and those with a history of psychosis 1.
• Ketamine has potential for abuse and should be used cautiously in patients with substance use disorders 1.

Recent Recommendations

• The 2022 U.S. Department of Veterans Affairs and U.S. Department of Defense clinical practice guideline recommends ketamine as an adjunctive treatment for short-term reduction in suicidal ideation in patients with suicidal ideation and major depressive disorder (MDD) 1.
• Esketamine, a derivative of ketamine, is also approved for the treatment of depressive symptoms in adults with MDD and acute suicidal ideation or behavior, but its effectiveness in preventing suicide or reducing suicidal ideation or behavior has not been established 1.

From the FDA Drug Label

Ketamine hydrochloride injection should be administered by or under the direction of physicians experienced in the administration of general anesthetics, maintenance of a patent airway, and oxygenation and ventilation. The ketamine hydrochloride injection dosage must be individualized and titrated to the desired clinical effect. If a longer duration of effect is desired, additional increments can be administered intravenously or intramuscularly to maintain anesthesia. However, a higher total dose will result in a longer time to complete recovery Induction of Anesthesia Intravenous Route: The initial dose of ketamine hydrochloride injection administered intravenously may range from 1 mg/kg to 4.5 mg/kg. The average amount required to produce 5 to 10 minutes of surgical anesthesia within 30 seconds following injection is 2 mg/kg. Administer ketamine hydrochloride injection slowly (i.e., over a period of 60 seconds). Rapid administration may result in respiratory depression and enhanced vasopressor response. The induction dose may be administered as an intravenous infusion at a rate of 0.5 mg/kg/min. Intramuscular Route: The initial dose of ketamine hydrochloride injection administered intramuscularly may range from 6.5 to 13 mg/kg. A dose of 9 to 13 mg/kg usually produces surgical anesthesia within 3 to 4 minutes following injection, with the anesthetic effect usually lasting 12 to 25 minutes.

The guidelines for using ketamine (Ketamine hydrochloride) for medical treatment are as follows:

• Administration: Ketamine hydrochloride injection should be administered by or under the direction of physicians experienced in the administration of general anesthetics.
• Dosage: The dosage must be individualized and titrated to the desired clinical effect.
• Induction of Anesthesia:
  • Intravenous Route: 1 mg/kg to 4.5 mg/kg.
  • Intramuscular Route: 6.5 to 13 mg/kg.
• Key Considerations:
  • Administer slowly over a period of 60 seconds.
  • Rapid administration may result in respiratory depression and enhanced vasopressor response.
  • Higher total dose will result in a longer time to complete recovery.
  • Continuously monitor vital signs and have emergency airway equipment immediately available 2, 2.
• Supplementation: Ketamine hydrochloride injection can be administered to supplement other general and local anesthetic agents 2.

From the Research

Guidelines for Using Ketamine for Medical Treatment

The use of ketamine for medical treatment, particularly for chronic pain and treatment-resistant depression, has been studied in various research papers 3, 4, 5, 6, 7.

• Dosing and Administration: Ketamine is most commonly administered in the dose of 0.5 mg/kg, but some patients may respond to doses as low as 0.1 mg/kg, and others may require up to 0.75 mg/kg 5. The ketamine dose is conventionally administered across 40 minutes; however, safety and efficacy have been demonstrated in sessions ranging between 2 and 100 minutes in duration 5.
• Route of Administration: The intravenous route is the most commonly employed, but safety and efficacy have been described with other routes of administration, including oral, sublingual, transmucosal, intranasal, intramuscular, and subcutaneous routes 5.
• Side Effects and Monitoring: The side effects of ketamine include psychedelic symptoms, nausea/vomiting, somnolence, cardiovascular stimulation, and hepatoxicity 3. Close monitoring of patients receiving ketamine is mandatory, particularly aimed at CNS, haemodynamic, renal, and hepatic symptoms as well as abuse 3.
• Cardiovascular Safety: The increase in systolic and diastolic blood pressure is dose-dependent and begins shortly after administration, peaking at around 30 to 50 minutes, and resolving at approximately 2 to 4 hours after the dose administration 4. Blood pressure should be assessed prior to dosing with ketamine, and hypertensive individuals should receive effective lifestyle/pharmacologic management prior to treatment 4.
• Treatment Duration and Frequency: Patients may receive a single session of treatment or a course of treatment during the acute phase, and treatment may rarely be continued for weeks to years to extend and maintain treatment gains in refractory cases 5. The ideal frequency is perhaps best individualized, wherein ketamine is dosed a little before the effect of the previous session is expected to wear off 5.