General Anesthetics
Inhalational and intravenous general anesthetics, their molecular targets, and the components of the anesthetic state.
## Components of General Anesthesia
General anesthesia comprises four components: unconsciousness (hypnosis), analgesia, amnesia, and muscle relaxation (immobility). No single agent optimally provides all four, so balanced anesthesia uses combinations of IV induction agents, inhalational maintenance agents, opioids, and neuromuscular blockers.
## Inhalational Anesthetics
Modern volatile agents include sevoflurane, desflurane, and isoflurane. Nitrous oxide is a gaseous supplement. Potency is measured by MAC (minimum alveolar concentration) -- the concentration at which 50% of patients do not move in response to surgical incision.
| Agent | MAC (%) | Blood:Gas Partition | Notes |
|-------|---------|-------------------|-------|
| Sevoflurane | 2.0 | 0.65 | Smooth induction; preferred for pediatric mask induction |
| Desflurane | 6.0 | 0.42 | Very rapid recovery; airway irritant (not for mask induction) |
| Isoflurane | 1.2 | 1.4 | Moderate speed; coronary vasodilator |
| Nitrous oxide | 104 | 0.47 | Analgesic supplement; too weak for sole maintenance |
Lower blood:gas partition coefficient means faster onset and recovery. All volatile agents cause dose-dependent respiratory depression, hypotension, and reduce cerebral metabolic rate. Malignant hyperthermia (triggered by volatile agents + succinylcholine) is treated with IV dantrolene.
## Intravenous Anesthetics
- **Propofol** -- GABA-A positive modulator; rapid onset and recovery; dose-dependent hypotension; used for induction and TIVA (total intravenous anesthesia)
- **Etomidate** -- minimal cardiovascular depression; used in hemodynamically unstable patients; inhibits 11-beta-hydroxylase (adrenal suppression with prolonged use)
- **Ketamine** -- NMDA antagonist; produces dissociative anesthesia with analgesia; maintains airway reflexes and blood pressure; emergence delirium is a limitation
- **Midazolam** -- benzodiazepine for anxiolysis and amnesia; not a primary anesthetic but a useful adjunct
- **Dexmedetomidine** -- alpha-2 agonist; sedation without respiratory depression; used for procedural sedation and ICU
## Molecular Mechanisms
Most general anesthetics enhance GABA-A receptor function (propofol, volatile agents, barbiturates) or block NMDA receptors (ketamine, nitrous oxide). The precise mechanism of consciousness loss remains incompletely understood but involves disruption of thalamocortical connectivity.
## Key Takeaways
- Balanced anesthesia combines agents to achieve hypnosis, analgesia, amnesia, and relaxation
- MAC quantifies inhalational anesthetic potency; lower blood:gas solubility means faster kinetics
- Propofol and sevoflurane dominate modern practice for induction and maintenance, respectively
- Malignant hyperthermia is a pharmacogenetic emergency requiring immediate dantrolene