Mechanism of Action and the Concept of Dissociative Anesthesia
Chemically, ketamine is an arylcyclohexylamine, a phencyclidine derivative. Its primary target in the brain is the NMDA receptor. The drug acts as a non-competitive antagonist, blocking the excitatory effects of glutamate on central nervous system structures.
Ketamine induces dissociative anesthesia, a state of functional disconnection where certain brain regions are depressed while others remain active. Unlike other intravenous anesthetics (propofol, etomidate, sodium thiopental), ketamine produces marked analgesia. Consciousness is only partially lost, accompanied by a mild hypnotic effect and amnesia. The classical stage of surgical anesthesia is not achieved.
Effects on Vital Functions and Hemodynamics
Ketamine is a drug of choice in emergency settings due to its safety profile regarding vital functions:
- Respiration and reflexes: Spontaneous breathing is fully preserved (apnea does not occur with slow injection). Muscle tone does not drop, and protective reflexes (laryngeal, pharyngeal, cough) remain active.
- Cardiovascular system: It is the only intravenous anesthetic that exerts a stimulating effect on the cardiovascular system. It causes tachycardia (increased heart rate), elevated cardiac output, and increased blood pressure (hypertension).
The mechanism of this cardiostimulation involves activation of sympathetic tone and inhibition of neuronal norepinephrine reuptake. Peak hemodynamic effects are observed at 2–4 minutes, with a return toward baseline occurring within 10–20 minutes.
Pharmacokinetics and Indications
The drug is highly lipophilic, ensuring rapid penetration across the blood-brain barrier (BBB).
Indications:
- Induction of anesthesia.
- General anesthesia.
- Stand-alone analgesia for short, painful procedures (e.g., burn debridement and dressing changes).
Onset and Duration:
- Intravenous administration: rapid onset (within 30–60 seconds), duration of anesthesia is 5–10 minutes.
- Intramuscular administration: onset within 2–6 minutes, duration is 15–30 minutes.
Adverse Effects and Their Management
The primary limitation restricting ketamine's routine use is its specific effect on the central nervous system during emergence from anesthesia. Patients frequently develop delirium characterized by:
- Psychomotor agitation.
- Vivid, often unpleasant or frightening dreams.
- Visual hallucinations.
The high risk of postoperative psychoses necessitates pharmacological prophylaxis. Benzodiazepines (such as diazepam) are traditionally administered to mitigate these side effects.
Formulations and Dosing
Ketamini hydrochloridum is formulated as a 5% solution:
- In 2, 5, and 10 mL ampoules.
- In 20 mL vials.
Dosing Regimen:
- Intravenous: 2–3 mg/kg (administered as a single IV push).
- Intramuscular: 4–8 mg/kg.