PROPOFOL
Clinical safety rating: safe
Animal studies have demonstrated safety
Propofol enhances the activity of gamma-aminobutyric acid (GABA) at GABA-A receptors, leading to increased chloride conductance, neuronal hyperpolarization, and anesthetic effects. It also inhibits N-methyl-D-aspartate (NMDA) receptors and modulates calcium influx via L-type calcium channels.
| Metabolism | Primarily hepatic via conjugation to glucuronide and sulfate; also metabolized by CYP2B6 and CYP2C9. Metabolites are renally excreted. |
| Excretion | Renal: <1% unchanged; hepatic metabolism to inactive glucuronide and sulfate conjugates, excreted renally (≈88%) and fecally (≈1-2%). |
| Half-life | Terminal elimination half-life: 4-7 hours (after prolonged infusion, context-sensitive half-life increases up to 60 minutes after 8-hour infusion). |
| Protein binding | 95-99% bound primarily to albumin (≈48%) and alpha-1-acid glycoprotein (≈50%), with minor binding to lipoproteins. |
| Volume of Distribution | Initial Vd: 0.2-0.4 L/kg (central compartment); steady-state Vd: 2-10 L/kg (extensive tissue distribution). |
| Bioavailability | IV: 100%; enteral: negligible due to first-pass metabolism; oral bioavailability <1%. |
| Onset of Action | IV bolus: 30-45 seconds (one arm-brain circulation time). |
| Duration of Action | IV bolus: 5-10 minutes for hypnosis (single dose), rapid redistribution; prolonged infusion: recovery within 10-15 minutes after short infusion, context-sensitive half-life relevant for longer infusions. |
Induction: 2-2.5 mg/kg IV bolus. Maintenance: 25-75 mcg/kg/min IV infusion. For sedation: 25-100 mcg/kg/min IV.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for GFR >10 mL/min. For GFR <10 mL/min, use with caution due to propylene glycol accumulation, monitor for metabolic acidosis. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 50%. Child-Pugh C: Avoid use or reduce by 75% due to prolonged clearance and risk of hypotension. |
| Pediatric use | Induction: 2.5-3.5 mg/kg IV over 30 sec. Maintenance: 125-300 mcg/kg/min for age <3 years; 100-200 mcg/kg/min for age 3-12 years. For sedation: 25-100 mcg/kg/min. |
| Geriatric use | Reduce induction dose to 1-1.5 mg/kg IV; decrease infusion rate by 20-50% due to reduced clearance and increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CNS depressants may enhance sedative effects Can cause profound respiratory depression and hypotension.
| Breastfeeding | Propofol is excreted into breast milk in very low concentrations, with an estimated M/P ratio of 1.2-1.5. The relative infant dose is <0.1% of weight-adjusted maternal dose. Consider discarding milk for 24 hours after administration due to potential sedative effects on the infant. |
| Teratogenic Risk | First trimester: Propofol is not associated with major congenital malformations based on limited human data, but animal studies show developmental toxicity at high doses. Second trimester: No clear evidence of fetal harm. Third trimester: Use may cause neonatal respiratory depression, hypotonia, and neurobehavioral effects; risk of fetal bradycardia and hypoxia. Propofol crosses the placenta rapidly. |
■ FDA Black Box Warning
No FDA black box warnings.
| Common Effects | Respiratory depression |
| Serious Effects |
["Hypersensitivity to propofol or any component of the formulation (including egg lecithin, soybean oil, or disodium edetate)","Patients with severe lipid metabolism disorders (e.g., pancreatitis with hypertriglyceridemia)","Not for use in general anesthesia in obstetrics (crosses placenta; may cause neonatal depression)","Relative: hypovolemia, hemodynamic instability, increased intracranial pressure (use with caution)"]
| Precautions | ["Hypotension and bradycardia: may require fluid resuscitation or vasopressors","Respiratory depression and apnea: must have airway management equipment available","Propofol infusion syndrome (PRIS): rare but fatal with high doses >4 mg/kg/hr for >48 hours; characterized by metabolic acidosis, rhabdomyolysis, hyperkalemia, and cardiac failure","Risk of pancreatitis: monitor lipase if symptoms develop","Abrupt discontinuation may cause withdrawal symptoms after prolonged use","Not recommended for use in patients with propofol allergy or egg/soybean oil hypersensitivity (formulation contains egg lecithin and soybean oil)"] |
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| Fetal Monitoring | Continuous maternal ECG, blood pressure, oxygen saturation, and capnography. Fetal heart rate monitoring during third trimester or when fetus is viable. Assess neonatal Apgar scores and respiratory status after delivery if used near term. |
| Fertility Effects | Propofol has been associated with decreased sperm motility and viability in animal studies at high doses. Human data are limited; no conclusive evidence of impaired fertility at clinical doses. |