Propofol

Quick Answer

Propofol (2,6-diisopropylphenol) is the most commonly used intravenous anaesthetic agent for induction and maintenance of general anaesthesia and sedation in ICU. Structure: Simple phenol derivative with two isopropyl groups; highly lipophilic (logP 3.8), formulated as 1% oil-in-water emulsion (soybean oil 10%, egg lecithin 1.2%, glycerol 2.25%, water—similar to intralipid, provides 1.1 kcal/mL). Mechanism: Potentiates GABA-A receptor function (increases channel opening frequency, not duration); also inhibits NMDA receptors and modulates sodium channels; produces hypnosis, amnesia, anti-emetic effect. Pharmacokinetics: Rapid onset (arm-brain circulation time, 30-45 seconds), rapid redistribution (initial distribution half-life 2-4 minutes, elimination half-life 30-60 minutes), large volume of distribution (2-10 L/kg, tissue distribution), high hepatic clearance (1.5-2 L/min, exceeds hepatic blood flow—extrahepatic metabolism likely), context-sensitive half-time 20-45 minutes after 1-4 hour infusion. Metabolism: Hepatic glucuronidation and hydroxylation (conjugated to inactive metabolites), extrahepatic metabolism in lungs and kidneys, no active metabolites. Dosing: Induction 1.5-2.5 mg/kg IV (reduce in elderly, cardiac disease, hypovolaemia), maintenance infusion 100-200 μg/kg/min (6-12 mg/kg/hour) or TCI target 4-6 μg/mL, sedation ICU 5-50 μg/kg/min. Advantages: Rapid onset/offset (clear headed recovery), anti-emetic (dopamine antagonism in CTZ), bronchodilation (smooth muscle relaxation), reduces ICP and CMRO2 (neuroanaesthesia), amnestic properties. Side effects: Cardiovascular depression (vasodilation > myocardial depression, dose-dependent hypotension, especially in elderly, hypovolaemic, cardiac patients), respiratory depression (apnoea, reduced tidal volume, bronchodilation), pain on injection (lipid emulsion irritant, prevent with lignocaine 0.5 mg/kg IV pre-injection or larger vein, cooling propofol), propofol infusion syndrome (PRIS—metabolic acidosis, cardiac failure, rhabdomyolysis, renal failure, hyperlipidaemia, hepatomegaly; rare, associated with high doses >4 mg/kg/hour for >48 hours in critically ill, especially children), allergy (rare, due to egg/soybean—avoid if true allergy to these foods), bacterial growth in emulsion (strict asepsis, use within 12 hours of opening, dedicated line). TIVA/TCI: Target controlled infusion using Marsh or Schnider pharmacokinetic models; Schnider model includes age, weight, height, lean body mass; Marsh uses weight only; effect-site targeting (ke0 0.26 min-1 Marsh, 0.456 min-1 Schnider). [1-10]