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  1. Pharmacology

    1. Propofol (2,6-diisopropylphenol) is a sedative-hypnotic-anesthetic agent in a class of alkyl phenol compounds. It is an oil at room temperature, highly lipid-soluble, and administered as an emulsion. It is also an antioxidant, anticonvulsant, and anti-inflammatory agent, reduces intracranial pressure, and has bronchodilator properties. The proposed site of action of propofol is at the GABA(A) receptor, where it activates the chloride channel. There may also be some action at the glutamate and glycine receptor sites. Propofol is considered an antagonist at the N- methyl-D-aspartate (NMDA) receptor. It is also an inhibitor of cytochrome P-450 enzymes.

    2. Intravenous injection of a therapeutic dose of propofol induces hypnosis within approximately 40 seconds.

    3. It is highly protein bound (97-99%), with a volume of distribution of approximately 60 L/kg after a continuous 10-day infusion. Propofol has a high clearance rate estimated at 1.6-3.4 L/min in 70-kg adults. This clearance rate exceeds hepatic blood flow and suggests extrahepatic metabolism.

    4. Propofol is metabolized rapidly in the liver by conjugation to glucuronide and sulfate intermediates that are water-soluble and inactive. This occurs predominantly via oxidation by cytochrome P-450 (CYP) enzyme 2B6. Cytochrome P-450 isoforms 2A6, 2C9, 2C19, 2D6, 2E1, 3A4, and 1A2 are also involved in the metabolism of propofol to a lesser extent. There is minimal enterohepatic circulation, and less than 1% is excreted unchanged.

  2. Indications

    1. Induction and maintenance of general anesthesia in adults and children aged 3 years and older. Can be used for maintenance in children aged 2 months and older.

    2. Monitored sedation in adults during procedures.

    3. Monitored sedation in intubated, mechanically ventilated adult patients.

    4. Propofol has also been used as an adjunct anesthetic agent in the management of refractory withdrawal syndromes associated with alcohol or other sedative-hypnotics (eg, GHB and barbiturates) and in the treatment of status epilepticus. (These are not FDA-approved indications.)

  3. Contraindications

    1. Hypersensitivity to propofol or any of its components. Contraindicated in patients with allergies to eggs, egg products, soybeans, and soy products. The labeling on the Europe-manufactured product (Fresenius Propoven 1%) includes peanut hypersensitivity as a contraindication owing to concerns regarding potential peanut oil and soybean oil cross-reactivity.

    2. Formulations vary and may contain benzyl alcohol, sodium benzoate, disodium edetate, or sodium metabisulfite. Consult individual product labeling for specific excipient information.

  4. Adverse effects

    1. Pain at the injection site can occur (use larger veins or premedicate with lidocaine).

    2. Anaphylaxis, apnea, hypotension, bradycardia, supraventricular tachydysrhythmias, conduction disturbances, cough, bronchospasm, rash, pruritus, and hyperlipidemia may occur.

    3. Anesthetic doses require respiratory support. Avoid rapid bolus doses because of the higher risk for hypotension, bradycardia, apnea, and airway obstruction.

    4. Anesthetic doses may be associated with myoclonus, posturing, and seizure-like movement phenomena (jerking, thrashing). Seizures have been noted when patients were weaned from propofol.

    5. Propofol infusion syndrome is a serious and life-threatening condition characterized by severe metabolic acidosis, hyperkalemia, lipemia, renal failure, rhabdomyolysis, hepatomegaly, cardiac arrhythmias, and myocardial failure. Risk factors include patients with decreased oxygen delivery to tissues, serious neurological injury, sepsis, high dosages of vasoconstrictors, steroids, inotropes, ...

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