Ketamine

Uses

1. Anesthesia: Induction and maintenance, particularly in trauma or unstable patients where preservation of spontaneous ventilation is desired.
2. Sedation: Utilized for procedural sedation.
3. Analgesia: Effective for acute and chronic pain management, including perioperative pain and conditions like Complex Regional Pain Syndrome (CRPS) and fibromyalgia.
4. Treatment-Resistant Depression (Off-label): Rapid-acting antidepressant for treatment-resistant depression.
5. Status Asthmaticus (Off-label): Bronchodilator effects in severe refractory asthma.
6. Acute Agitation: Rapid tranquilization of severely agitated patients in emergency settings.

Dosage and Administration

Anesthesia

• IV: 1-2 mg/kg over 1 minute for induction.
• IM: 4-10 mg/kg for induction.
• Maintenance: 0.5-1 mg/kg IV as needed.

Procedural Sedation

• IV: 0.5-1 mg/kg over 1 minute.
• IM: 4-5 mg/kg.

Analgesia

• IV (Sub-anesthetic dose): 0.1-0.5 mg/kg.
• IM: 0.5-1 mg/kg.
• Chronic Pain Infusions: 0.1-1.0 mg/kg/hr, often given over several hours or days.

Intranasal (Off-label)

• Analgesia: 0.2-0.75 mg/kg, used in some emergency settings for rapid pain relief.

Treatment-Resistant Depression

• IV: 0.5 mg/kg infused over 40 minutes, with dosing based on specific treatment protocols.

Dose Adjustment in Different Diseases

• Hepatic Impairment: Use with caution in severe liver disease; dose adjustments may be required.
• Renal Impairment: No major dose adjustments required, though prolonged use may pose risks of cystitis.
• Cardiovascular Disease: Lower doses may be necessary to mitigate the risk of hypertension and tachycardia.
• Psychiatric Disorders: Avoid in patients with severe psychotic conditions or schizophrenia.

Presentation/Form

• IV/IM Injection Solution: Available in 10 mg/mL, 50 mg/mL, and 100 mg/mL concentrations.

Pharmacokinetics

• Absorption: Rapid absorption following intramuscular or intranasal administration.
• Distribution: High lipid solubility allows for wide tissue distribution and rapid onset of action.
• Metabolism: Primarily metabolized in the liver by CYP3A4 and CYP2B6 enzymes.
• Elimination: Excreted mainly in urine as metabolites.
• Onset and Duration:
  • Onset (IV): 30 seconds.
  • Onset (IM): 3-5 minutes.
  • Duration: 5-10 minutes (IV), 12-25 minutes (IM).

Pharmacodynamics

• Mechanism of Action: Ketamine is a non-competitive NMDA receptor antagonist, acting at the phencyclidine (PCP) site to inhibit excitatory neurotransmission. It also interacts with opioid, monoaminergic, and cholinergic receptors, contributing to its analgesic, sedative, and antidepressant effects.
• Isomer Potency: The S(+) isomer of ketamine is twice as potent as the racemic mixture and may have fewer psychomimetic side effects.

Drug Interactions

• CNS Depressants (e.g., opioids, benzodiazepines): Potentiates CNS and respiratory depression.
• Sympathomimetics (e.g., epinephrine): Increased risk of hypertensive crises.
• Anticholinergics: Can worsen tachycardia and excessive secretions.
• SSRIs and MAO Inhibitors: Potential for serotonergic syndrome when combined.

Precautions and Special Considerations

• Pediatric Use: Widely used for pediatric sedation and anesthesia with low respiratory depression risk.
• Elderly: More prone to hypertension and emergence delirium; dose adjustments may be necessary.
• Pregnancy & Lactation: Crosses the placenta and may affect the fetus; use cautiously in pregnancy and breastfeeding.
• Dissociative Effects: Can be therapeutic (e.g., in PTSD treatment) but may also be distressing for some patients.
• Abuse Potential: Significant abuse potential due to psychoactive properties; careful monitoring required.
• Monitoring: Continuous cardiovascular and capnography monitoring during procedural sedation despite ketamine’s respiratory preservation.

Side Effects

• Common: Hypertension, tachycardia, hypersalivation, nausea, vomiting, hallucinations, emergence delirium.
• Serious: Respiratory depression (rare), increased intracranial pressure, laryngospasm (rare).
• Chronic Use: Can lead to ulcerative cystitis (particularly with recreational use) and cognitive effects like memory impairment and reduced attention span.

Recent Updates and Guidelines

• Depression Treatment: Increasing acceptance in treatment protocols for major depressive disorder, with ongoing studies exploring its efficacy and long-term safety.
• PTSD: Clinical trials investigating ketamine as a fast-acting intervention for severe PTSD symptoms.
• Emergence Delirium Mitigation: Strategies involving adjunct medications such as benzodiazepines to minimize dissociative and psychomimetic side effects.
• Pain Management Guidelines: Recommendations for sub-anesthetic dosing in perioperative and chronic pain settings are becoming more standardized.

References

1. Ketamine - NCBI StatPearls. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470357/
2. Stoelting’s Pharmacology and Physiology in Anesthetic Practice, 5th edition.
3. American Society of Anesthesiologists (ASA) Practice Guidelines.
4. Berman, R. M., et al. (2000). Antidepressant effects of ketamine in depressed patients. Biological Psychiatry, 47(4), 351-354.
5. Clinical trials on ketamine for depression and PTSD: National Institutes of Health (NIH).
6. World Health Organization (WHO) Guidelines on Pain Management.