1. Clinical Overview
Ketamine is a rapid-acting, non-barbiturate, phencyclidine derivative dissociative anesthetic agent. It is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, producing a trance-like state characterized by profound analgesia, amnesia, and dissociation from the environment while maintaining protective airway reflexes, spontaneous respirations, and cardiovascular stability. In the Indian context, it is a critical agent for procedural sedation, anesthesia in resource-limited settings, and is increasingly used for treatment-resistant depression and chronic pain syndromes.
| Onset | Duration | Bioavailability |
|---|---|---|
| Intravenous: 30-60 seconds; Intramuscular: 3-5 minutes; Intranasal: 5-10 minutes. | Intravenous: 5-10 minutes (anesthetic effect); Analgesic effect can last 30-60 minutes post-administration. | Intravenous: 100%; Intramuscular: ~93%; Intranasal: ~45-50%; Oral: ~16-20% (due to significant first-pass metabolism). |
2. Mechanism of Action
Ketamine's primary mechanism is non-competitive antagonism of the N-methyl-D-aspartate (NMDA) receptor, an ionotropic glutamate receptor. By binding to the phencyclidine site within the receptor's ion channel, it blocks glutamate-mediated excitatory neurotransmission. This leads to functional and electrophysiological dissociation between the thalamocortical and limbic systems, producing a cataleptic state where the patient appears awake but is disconnected from sensory input (dissociative anesthesia). Its antidepressant action is linked to rapid increase in synaptic plasticity and glutamate surge, leading to increased BDNF and mTOR signaling, effectively 'resetting' maladaptive neural circuits.
3. Indications & Uses
- Induction and maintenance of general anesthesia (especially in hemodynamically unstable patients, asthma, sepsis).
- Procedural sedation and analgesia (e.g., wound dressing, orthopedic manipulations, dental procedures in uncooperative patients).
- Analgesia for refractory acute pain (e.g., trauma, burns, sickle cell crisis in emergency departments).
4. Dosage & Administration
Adult Dosage: IV Induction: 1-2 mg/kg (slowly over 60 seconds). IV Maintenance: 0.5-1 mg/kg as needed. IM: 4-10 mg/kg. Procedural Sedation: 0.5-1 mg/kg IV or 2-4 mg/kg IM. Analgesia: 0.1-0.5 mg/kg IV/IM. For TRD (off-label): 0.5 mg/kg IV infused over 40 minutes, typically administered 2-3 times per week for 2-4 weeks.
Administration: For IV use: Dilute to 1-2 mg/mL (e.g., 100mg in 50-100mL of Normal Saline or 5% Dextrose). Administer as a slow IV push over 60 seconds or as a controlled infusion. For IM use: Administer deep into a large muscle mass. Pre-treatment with an anticholinergic (e.g., Glycopyrrolate 0.2 mg IV) can reduce hypersalivation. A benzodiazepine (e.g., Midazolam 0.02-0.05 mg/kg IV) given 3-5 minutes prior can reduce emergence reactions.
5. Side Effects
Common side effects may include:
- Cardiovascular: Hypertension, tachycardia.
- Neurological: Dizziness, diplopia, nystagmus, confusion, vivid dreams.
- Psychiatric: Emergence reactions (agitation, delirium, hallucinations, dysphoria) upon recovery.
- Gastrointestinal: Nausea, vomiting, increased salivation.
- Local: Pain at injection site (IM).
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Theophylline / Aminophylline | Increased risk of seizures. | Major |
| CNS Depressants (e.g., Alcohol, Benzodiazepines, Opioids, Barbiturates) | Additive CNS and respiratory depression. | Major |
| Halothane | Potentiates ketamine's cardiovascular effects (hypertension, tachycardia) and prolongs its half-life. | Moderate |
| Thyroid Hormones | Increased risk of hypertension and tachycardia. | Moderate |
| Antihypertensives | Ketamine may counteract their hypotensive effect. | Moderate |
| CYP3A4 Inhibitors (e.g., Clarithromycin, Ketoconazole, Ritonavir) | Increased ketamine plasma levels, prolonged effect. | Moderate |
| CYP3A4 Inducers (e.g., Rifampicin, Carbamazepine, Phenytoin) | Decreased ketamine plasma levels, reduced efficacy. | Moderate |
7. Patient Counselling
- DO inform your doctor about all medications, supplements, and history of substance abuse, mental illness, or heart problems.
- DO arrange for someone to drive you home and stay with you for 24 hours after the procedure.
- DO report any history of bad reactions to anesthetics.
- DON'T consume alcohol for at least 24 hours before and after receiving ketamine.
- DON'T drive, operate machinery, or sign legal documents for at least 24 hours post-administration.
- DON'T take any new medicines without consulting your doctor after ketamine treatment.
8. Toxicology & Storage
Overdose: Manifestations include profound CNS depression leading to coma, respiratory arrest, hypotonia, seizures, hypertensive crisis, tachycardia, and cardiac arrest. Emergence reactions can be severe and prolonged.
Storage: Store at controlled room temperature (15°-25°C). Protect from light. The solution is colorless to slightly yellowish; discard if discolored or contains particulate matter. As a Schedule X drug, it must be stored in a locked cupboard/box with proper inventory records (as per Rule 65 of Drugs and Cosmetics Rules). Keep out of reach of children and unauthorized persons.