Propofol

What is Propofol? ¹²

• Sedative agent for induction and maintenance of anesthesia.
• Rapid redistribution allows brief, deep sedation (e.g., joint reductions, cardioversions, ECT).

Mechanism of Action & Pharmacokinetics ¹²

• Exact mechanism is not fully understood, likely potentiates GABA receptors.
• Highly protein-bound and lipophilic, metabolized in the liver via conjugation, and excreted through the renal system.
• Half-life:
  • Redistribution: 2 - 8 minutes.
  • Elimination: 4 - 7 hours.

Pharmacodynamics ¹²

Cardiovascular

• Decreases arterial blood pressure by reducing systemic vascular resistance through arterial and venous vasodilation.
• Reduces preload, afterload, and cardiac output.
• Inhibits the baroreceptor response, preventing the compensatory increase in heart rate typically seen with hypotension.

Respiratory

• Depresses respiratory drive, leading to dose-dependent apnea
• Inhibits hypoxia-mediated drive to breathe and reduces the ventilatory response to elevated CO2.
• Suppresses upper airway reflexes, facilitating tracheal intubation and LMA placement.
• Decreases tidal volume while increasing respiratory rate, with minimal impact on minute ventilation.

Central Nervous System

• Decreases cerebral metabolic rate (CMR), cerebral blood flow (CBF), intracranial pressure (ICP), and intraocular pressure (IOP).
• Exhibits anticonvulsant properties and can be used in the treatment of refractory seizures.
• May result in a critical decrease in cerebral perfusion pressure (CPP) in patients with raised ICP, particularly if mean arterial pressure (MAP) drops significantly.

Indications ¹²

Anesthetic Indications

• Induction and maintenance of general anesthesia (TIVA technique).
• Sedation during procedures (e.g., mechanical ventilation, intubation).

Other Indications

• Treatment of refractory seizures.
• Treatment of refractory postoperative nausea and vomiting.

Dosage ²

• Induction Dose: 1.5 - 2.5 mg/kg IV; reduced to 1 - 2 mg/kg in patients premedicated with opioids or benzodiazepines. Children may require higher induction doses (up to ~4 mg/kg).
• Maintenance Dose: 20 - 200 µg/kg/min IV infusion. See TIVA.
• Half-life: Redistribution: 2 - 8 minutes; Elimination: 4 - 7 hours.

Complications ¹²

• Pain on injection, often mitigated by co-administration of lidocaine.
• Hypotension, particularly in patients with reduced cardiovascular reserve or fixed cardiac output.
• Propofol infusion syndrome (rare but serious)
• QT prolongation (rare).

References