Pharmacology
Anesthesia
General, regional, local — controlled, reversible loss of sensation or consciousness
Anesthesia is the controlled, reversible suppression of sensation, awareness, or both. General anesthesia produces unconsciousness, amnesia, immobility, and analgesia, typically through a combination of an induction agent (propofol), a volatile maintenance agent (sevoflurane), an opioid, and a neuromuscular blocker. Regional anesthesia (spinals, epidurals, peripheral nerve blocks) interrupts conduction in larger nerve trunks. Local anesthesia targets a small field. The mechanisms span GABA-A potentiation, NMDA antagonism, sodium channel block, and opioid receptor activation — all reversible within minutes to hours.
- Induction agentPropofol 1-2.5 mg/kg IV (most common)
- Volatile MACSevoflurane ~2.0%, isoflurane ~1.2%
- Spinal anesthesia onset5-10 minutes; duration 1-3 hours
- Awareness incidence~1 in 1000-2000 cases
- Mortality (healthy patient)~1 in 200,000
- Malignant hyperthermia triggerVolatile agents + succinylcholine
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Why anesthesia matters
- Surgery. Modern surgery is impossible without reliable, reversible anesthesia — every operating room is built around it.
- Obstetrics. Epidural labor analgesia and spinal anesthesia for cesarean delivery have transformed maternal experience and safety.
- Critical care. ICU sedation strategies (propofol, dexmedetomidine, fentanyl) directly affect ventilator-free days and delirium rates.
- Pain medicine. Regional and neuraxial blocks reduce opioid requirements and chronic post-surgical pain.
- Pediatrics. Pediatric anesthesia balances rapid uptake (high MAC, smaller FRC) against neurodevelopmental concerns of repeated exposure.
- Trauma. Rapid sequence induction with appropriate hemodynamic support is the cornerstone of emergency airway management.
- Pharmacology training. Anesthetics illustrate dose-response, pharmacokinetics, and receptor pharmacology more clearly than almost any other drug class.
Common misconceptions
- "General anesthesia is just deep sleep." It is a coordinated suppression of consciousness, memory, movement, and pain — physiologically distinct from sleep on EEG.
- "Local anesthetics are inherently safe." Lidocaine and bupivacaine cause seizures and cardiac arrest at high blood levels; doses must be weight-based.
- "Spinals always cause headaches." Post-dural puncture headache rates are under 1% with modern pencil-point needles; technique matters enormously.
- "Patients can't feel surgery if they're paralyzed." Neuromuscular blockade does not provide unconsciousness — awareness during paralysis is the worst-case scenario.
- "Epinephrine in local anesthetic is dangerous." 1:200,000 epinephrine prolongs block, reduces toxicity, and is safe outside end-arterial fields.
- "Anesthesia and analgesia are the same thing." A patient can be unconscious yet inadequately analgesed, with sympathetic stress responses driving morbidity.
Frequently asked questions
How does general anesthesia work?
General anesthetics target multiple pathways. Propofol, etomidate, barbiturates, and volatile agents potentiate GABA-A receptors, hyperpolarizing neurons. Ketamine antagonizes NMDA receptors, producing dissociative anesthesia. Volatile agents also activate two-pore potassium channels and inhibit certain glutamate receptors. The combination produces unconsciousness, amnesia, analgesia, and immobility — no single drug delivers all four optimally, hence balanced anesthesia.
What is MAC?
Minimum Alveolar Concentration is the inhaled anesthetic concentration at which 50% of patients fail to move in response to surgical incision. It is the standard potency metric for volatile agents. Sevoflurane MAC is ~2.0%, isoflurane ~1.2%, desflurane ~6.0%. MAC decreases with age, opioids, hypothermia, and pregnancy; it increases with chronic alcohol use and youth. Surgical depth is typically maintained at 1.0-1.5 MAC.
How do spinal and epidural anesthesia differ?
Spinal anesthesia injects a small dose of local anesthetic directly into CSF; onset is rapid (5-10 minutes) and the block dense but limited in duration. Epidural anesthesia places drug in the epidural space outside the dura; onset is slower (15-20 minutes), the catheter allows continuous infusion, and the block is more titratable. Spinals are preferred for cesarean section and short orthopedic procedures; epidurals dominate labor analgesia and major abdominal surgery.
What does succinylcholine do?
Succinylcholine is a depolarizing neuromuscular blocker that mimics acetylcholine at the motor endplate, causing fasciculations followed by sustained depolarization and paralysis. Onset is 30-60 seconds with duration 5-10 minutes — uniquely fast for rapid-sequence intubation. Risks include hyperkalemia (especially in burns, denervation, prolonged immobility), bradycardia, and triggering malignant hyperthermia in susceptible patients.
What is malignant hyperthermia?
An autosomal dominant disorder of the ryanodine receptor (RYR1) that causes uncontrolled calcium release from sarcoplasmic reticulum when triggered by volatile anesthetics or succinylcholine. Presentation: tachycardia, rising end-tidal CO₂, hyperthermia (late), muscle rigidity, hyperkalemia, rhabdomyolysis. Untreated mortality approaches 70%; treatment is dantrolene (which blocks the ryanodine receptor) plus aggressive cooling and supportive care. Mortality with prompt treatment is under 5%.
How is awareness under anesthesia detected?
Awareness during general anesthesia occurs in roughly 1 in 1000-2000 cases and is more common in cardiac surgery, trauma, and cesarean section under GA. Processed EEG monitors (BIS, entropy) target a depth index between 40-60 to reduce risk. Etomidate-based and ketamine-based inductions raise awareness risk. Patients with awareness may develop PTSD; structured postoperative interviews (Brice questionnaire) help detect cases for support and follow-up.
Why are local anesthetics potentially toxic?
At high blood levels, lidocaine, bupivacaine, and ropivacaine block sodium channels in the brain and heart. Early CNS signs (perioral numbness, tinnitus, agitation) precede seizures and respiratory arrest. Cardiac toxicity follows — bupivacaine in particular can cause refractory ventricular fibrillation. Treatment is supportive plus IV lipid emulsion (Intralipid 20%), which acts as a "lipid sink" extracting drug from cardiac tissue. Maximum doses must be calculated by weight before injection.