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.
Adult: **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.
Note: **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.
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.
Pregnancy: **Category D (Indian FDA/US FDA).** May cause fetal harm. Crosses the placenta. Use only if clearly needed, such as for emergency surgery in a pregnant woman. Avoid in early pregnancy unless absolutely necessary.
Driving: **DO NOT drive or operate machinery for at least 24 hours after administration.** Ketamine impairs judgment, thinking, motor skills, and reaction time. Effects may linger subtly.
| 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 |