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 state of 'dissociative anesthesia' characterized by profound analgesia, amnesia, and sedation while maintaining protective airway reflexes, spontaneous respiration, and cardiovascular stability. In the Indian context, it is a critical drug for anesthesia in resource-limited settings and is increasingly used for treatment-resistant depression and chronic pain management.
| Onset | Duration | Bioavailability |
|---|---|---|
| Intravenous: 30-60 seconds; Intramuscular: 3-5 minutes; Intranasal: 5-15 minutes. | Intravenous: 5-10 minutes (anesthetic effect); Analgesic effect: 30-60 minutes; Psychotomimetic effects: 1-2 hours. | Intravenous: 100%; Intramuscular: ~93%; Intranasal: ~45-50%; Oral: ~16-20% (due to extensive 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. This blockade inhibits excitatory neurotransmission, leading to functional and electrophysiological dissociation between the thalamocortical and limbic systems, resulting in a trance-like state of 'dissociative anesthesia'. It also interacts with opioid receptors (mu and kappa), monoaminergic receptors, muscarinic receptors, and voltage-gated sodium channels, contributing to its analgesic and psychotomimetic effects.
3. Indications & Uses
- Induction and maintenance of general anesthesia, particularly in high-risk patients (hypovolemic shock, asthma)
- Procedural sedation and analgesia in emergency departments and minor surgical procedures
- Analgesia for refractory severe acute pain (e.g., trauma, burns, post-operative)
- Treatment-resistant major depressive disorder (off-label but established in clinical practice)
4. Dosage & Administration
Adult Dosage: **Induction of Anesthesia:** IV: 1-2 mg/kg (approx. 50-100 mg for 50kg adult) over 60 seconds. IM: 4-6 mg/kg. **Procedural Sedation/Analgesia:** IV: 0.2-0.5 mg/kg bolus, may repeat. Infusion: 0.1-0.5 mg/kg/hr. IM: 2-4 mg/kg. **Treatment-Resistant Depression (IV):** 0.5 mg/kg infused over 40 minutes, typically twice weekly for 2-4 weeks.
Administration: **Route:** IV (preferred), IM, intranasal, oral (for depression, compounded). **IV Administration:** Dilute to 1-2 mg/mL (e.g., 50mg in 25-50mL of Normal Saline or 5% Dextrose). Administer over 60 seconds for induction, over 40 minutes for depression protocol. **IM:** Inject deep into a large muscle mass. **Premedication:** An anticholinergic (e.g., atropine 0.01-0.02 mg/kg) is often given to reduce hypersalivation. A benzodiazepine (e.g., midazolam) may be given to attenuate emergence reactions.
5. Side Effects
Common side effects may include:
- Cardiovascular: Hypertension, tachycardia, increased cardiac output
- Neurological: Dizziness, diplopia, nystagmus, vivid dreams, dysphoria
- Psychiatric: Emergence reactions (agitation, confusion, hallucinations, delirium) during recovery
- Gastrointestinal: Nausea, vomiting, increased salivation
- Local: Pain at injection site (IM)
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Theophylline / Aminophylline | Increased risk of seizures; pharmacodynamic interaction lowering seizure threshold. | Major |
| CNS Depressants (e.g., Benzodiazepines, Opioids, Alcohol, Propofol) | Additive CNS and respiratory depression. Benzodiazepines reduce emergence reactions. | Moderate |
| Sympathomimetics (e.g., Epinephrine, Dopamine) | Additive hypertensive and tachycardic effects. | Moderate |
| Thyroid Hormones (e.g., Levothyroxine) | Increased risk of hypertension and tachycardia. | Moderate |
| CYP3A4 Inhibitors (e.g., Clarithromycin, Ketoconazole, Ritonavir) | Increased ketamine plasma levels, prolonged effect and toxicity risk. | Moderate |
| CYP3A4 Inducers (e.g., Rifampicin, Carbamazepine, Phenytoin) | Decreased ketamine plasma levels, reduced efficacy. | Moderate |
| Neuromuscular Blocking Agents (e.g., Succinylcholine) | Ketamine may potentiate neuromuscular blockade. Risk of prolonged apnea. | Moderate |
| Halothane | Increased risk of bradycardia and hypotension. | Moderate |
7. Patient Counselling
- **DO** inform your doctor about all medications, supplements, and history of substance abuse, mental illness, or heart/liver/kidney disease.
- **DO** fast as instructed (usually 6-8 hours for solids, 2 hours for clear liquids) before a planned procedure.
- **DO** arrange for someone to drive you home and stay with you for 24 hours after receiving ketamine.
- **DON'T** drive, operate machinery, sign legal documents, or make important decisions for at least 24 hours.
- **DON'T** consume alcohol or other sedatives for at least 24 hours after administration.
8. Toxicology & Storage
Overdose: **Manifestations:** Profound prolonged dissociative state, respiratory depression or arrest, severe hypertension or hypotension (late stage), tachycardia, arrhythmias, increased ICP, seizures, coma, and death. Psychiatric symptoms can be severe and prolonged.
Storage: **Store at controlled room temperature, 20°C to 25°C (68°F to 77°F).** Protect from light. Keep in the original container. **Important:** As a Schedule X drug, it must be stored in a locked cupboard/chest under the direct supervision of a qualified person (e.g., pharmacist, anesthetist). Maintain a separate, dedicated register for its purchase and dispensing as per Indian law. Do not freeze. Discard any unused portion of the vial after single use to prevent contamination. For compounded oral formulations, follow specific storage instructions provided by the compounding pharmacy.