Sedative · Induction agent
Propofol (Diprivan)
Also called Diprivan
Indications
- Sedation of intubated, mechanically ventilated adults
- Induction and maintenance of general anesthesia
- Procedural sedation (monitored anesthesia care)
- Refractory status epilepticus as a continuous infusion (off-label)
- Raised ICP, to lower cerebral metabolism and blood volume (off-label)
Dosing
Propofol drip card and mL/h converterStart: 5 mcg/kg/min (0.3 mg/kg/h)
| Where | Dose |
|---|---|
| Airway and RSI | Propofol: 1–2 mg/kg (lower in shock); drops BP |
| Airway and RSI | Propofol bolus: 10–20 mg IV, then infusion |
Mechanism of action
Propofol is a positive allosteric modulator of the GABA-A receptor. It binds transmembrane pockets between subunits, at both the β–α interfaces used by etomidate and the α–β and γ–β interfaces used by barbiturates, away from the benzodiazepine site, so flumazenil does not reverse it. It prolongs chloride channel opening when GABA binds and, at high concentrations, opens the channel directly, hyperpolarizing neurons in the cortex, thalamus and reticular activating system. It has no analgesic effect at sedative doses.
Pharmacology
- CNS: dose-related sedation to unconsciousness; lowers cerebral O₂ use, blood flow and ICP; anticonvulsant, though myoclonus can occur at induction
- Cardiovascular: vasodilation and some myocardial depression; induction doses often drop BP 25–40%, more with hypovolemia or age, and the blunted baroreflex keeps heart rate from rising
- Respiratory: depresses ventilation and the CO₂ and hypoxic responses; apnea after induction doses; suppresses airway reflexes
- Other: antiemetic and antipruritic at low doses; does not trigger malignant hyperthermia
Pharmacokinetics
| Onset | 30–60 s IV; hypnosis usually within 40 s (label) |
|---|---|
| Duration | 5–10 min after a bolus, ended by redistribution |
| Context-sensitive half-time | Under 40 min after infusions up to 8 h (Hughes 1992) |
| Half-life | Terminal 2–14 h after short use; 1–3 days after a 10-day infusion (label), though waking stays fast |
| Distribution | Very lipophilic; Vd at steady state approaches 60 L/kg after a 10-day infusion (label) |
| Protein binding | 98–99% |
| Metabolism | Liver glucuronidation (about 70%, UGT1A9) and CYP2B6 hydroxylation, then conjugation; the kidneys do up to a third; metabolites inactive |
| Clearance | 23–50 mL/kg/min (label), more than liver blood flow |
| Elimination | Urine as conjugates (88% over 5 days); under 0.3% unchanged |
| Organ failure | Little change in chronic cirrhosis or chronic kidney failure (label) |
Chemistry
- 2,6-diisopropylphenol, an achiral alkylphenol unrelated to barbiturates or benzodiazepines
- Almost insoluble in water, so it comes as a 1% (10 mg/mL) emulsion of 10% soybean oil, 2.25% glycerol and 1.2% egg lecithin, pH 7–8.5
- pKa 11: un-ionized at body pH and very lipid-soluble, so brain uptake is fast
- The emulsion supports bacterial growth, which EDTA or other preservatives only slow: finish an opened vial or filled syringe, and change the tubing, within 12 h (current labels)
- Supplies 1.1 kcal/mL as fat; count it in nutrition
Adverse effects and cautions
In the one-pagers
- Sedation, Pain and Delirium ScalesPADIS Guideline Key Points: Propofol or dexmedetomidine over benzodiazepines (2018). 2025: dexmedetomidine over propofol in ventilated adults if light sedation or less delirium is the priority. Dexmedetomidine is not for deep sedation; consider another agent if bradycardia risk is high.
- ICU Nutrition and RefeedingHow much: week 1 vs later: Count hidden calories: propofol 1.1 kcal/mL, clevidipine 2 kcal/mL (labels), D5W 170 kcal/L, CRRT citrate
- Airway and RSIRSI drugs: Propofol: 2–2.5 mg/kg; 1–1.5 if frail: About 40 s: Hypotension, apnea
- Asthma and COPD ExacerbationsIntubating severe asthma: Rapid sequence: ketamine 1–2 mg/kg (bronchodilates, less hypotension) or propofol, with rocuronium 1–1.2 mg/kg or succinylcholine
- Preventing ICU InfectionsCLABSI: insertion and line care: Tubing: continuous sets 96 h to 7 days; blood or lipids within 24 h; propofol 12 h (label)
- Right Heart Failure and Pulmonary HypertensionIntubation and home prostacyclin: Etomidate or reduced-dose ketamine; avoid propofol boluses; keep apnea short.
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In the algorithms
Other sedative drugs
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Sources
- FDA label: Diprivan (2025)
- Sahinovic 2018 (propofol review)
- Hughes 1992
- Chiara 2013 (GABA-A sites)
For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow the order, the label and your institution's protocols.