IV Anesthetic Agents

• GABA-A receptors (most common target) — primary inhibitory neurotransmitter. Activation ↑ chloride conductance → hyperpolarization.
• Propofol & barbiturates ↓ rate of GABA dissociation → ↑ duration of channel opening.
• Benzodiazepines facilitate GABA binding → ↑ frequency of channel opening.
• NMDA receptors — glutamate-gated excitatory channels. Ketamine is a non-competitive antagonist.
• α2 receptors — Dexmedetomidine is a selective α2 agonist → inhibits NE release at locus coeruleus (sedation) and dorsal horn (analgesia).

Adjust DOWN for elderly, hypovolemic, and frail patients (reduced volume of distribution, slower redistribution).

• 2,6-diisopropylphenol in egg lecithin emulsion (egg yolk → relevant to egg allergy, which is usually egg white). Soybean oil → relevant to soy allergy.
• Bacteria grow readily → strict sterile technique; label with 12-hour expiration.
• Induction: 1.5–2.5 mg/kg. Infusion: 100–200 mcg/kg/min (hypnosis), 25–75 mcg/kg/min (sedation).
• ↑ doses in children (larger Vd, higher clearance). ↓ doses in elderly.
• ↓ CMRO₂, CBF, ICP. Cerebral vasoconstrictor (counterintuitive).
• Anticonvulsant.
• ↓ SVR (arterial AND venous) + direct myocardial depressant.
• Pain on injection in 32–67% — mitigate with lidocaine 20–40 mg in the syringe or large-vein injection.
• Antiemetic at sub-hypnotic doses (10–20 mg).
• PRIS (Propofol Infusion Syndrome): > 4 mg/kg/h for prolonged periods → severe metabolic acidosis, rhabdomyolysis, cardiac and renal failure, hypertriglyceridemia. High mortality, especially in children. Supportive treatment.

• Imidazole; GABA-A modulator.
• 0.2–0.3 mg/kg IV. Minimal hemodynamic effect → workhorse for unstable patients.
• Side effects:
• Myoclonus on induction (cortical disinhibition, not seizure)
• Pain on injection (propylene glycol carrier)
• PONV (high incidence)
• Adrenal suppression via 11β-hydroxylase inhibition — even a single dose can suppress cortisol for ~24 h. Outcomes data mixed; consider risk-benefit in septic shock.
• No analgesia.
• ↓ CBF, ↓ CMRO₂; preserves CPP.

• Phencyclidine derivative; non-competitive NMDA antagonist. Dissociative anesthesia.
• IV induction: 1–2 mg/kg. IM: 4–6 mg/kg (useful when no IV in pediatrics or behavioral emergency).
• Analgesic infusion: 0.1–0.5 mg/kg/h (modern multimodal analgesia).
• ↑ HR, ↑ BP via central sympathetic stimulation (caution in CAD, uncontrolled HTN). In catecholamine-depleted patients, direct myocardial depression dominates → ↓ BP.
• Preserves airway reflexes & respiratory drive.
• Bronchodilator — first-line for severe asthma.
• ↑ secretions (consider glycopyrrolate).
• Emergence reactions / hallucinations — mitigate with benzodiazepine or low-dose propofol.
• Historical concern about ↑ ICP — modern data more permissive in TBI.

• Mechanism: ↑ frequency of GABA-mediated chloride channel openings.
• Effects: anxiolysis, anterograde amnesia, sedation, anticonvulsant, muscle relaxation (centrally mediated).
• Midazolam is the workhorse: water-soluble, rapid onset (1–3 min IV), short duration (30–60 min after a single dose).
• Premedication doses: Adult 1–2 mg IV. Pediatric PO 0.5 mg/kg (max 20 mg).
• Synergistic respiratory depression with opioids.
• Paradoxical agitation in elderly and children.
• Reversal: flumazenil 0.2 mg IV q1 min (max 1 mg). Avoid in chronic benzo users — precipitates seizures.

• Highly selective α2 agonist (1620:1 vs clonidine 220:1).
• Provides sedation, analgesia, sympatholysis with preserved respiratory drive — ideal for awake fiberoptic intubation, MAC sedation, ICU sedation.
• Load: 1 mcg/kg over 10 min (often skipped in elderly / cardiac). Infusion: 0.2–0.7 mcg/kg/h.
• Bradycardia and hypotension are common; transient hypertension can occur with bolus loading.
• ↓ opioid and volatile requirements.
• ↓ emergence delirium (especially pediatric).

• Historical but tested: ultra-short-acting barbiturate, potent GABA potentiator.
• Thiopental 3–6 mg/kg IV induction; long context-sensitive half-time → no longer used clinically (largely unavailable).
• Cerebral protection (↓ CMRO₂); used in some neuro applications.
• Contraindications: acute intermittent porphyria (precipitates attack).
• Pain on injection, venous irritation, severe tissue necrosis if extravasated.
• Methohexital still used for ECT (lowers seizure threshold less than other agents).