"Propofol is the workhorse of modern induction: a rapid, clean hypnotic that wakes the patient clear-headed and free of nausea — but one that vasodilates, apnoeises and, in high-dose infusions, can turn lethal. Its virtues and its dangers both flow from the same lipophilic phenol."
Tanya's notes, triangulated with Miller's Anesthesia; Morgan & Mikhail's Clinical Anesthesiology; Stoelting's Pharmacology & Physiology in Anesthetic Practice.An IV sedative-hypnotic phenol in a lipid emulsion
Propofol is 2,6-di-isopropylphenol — a highly lipid-soluble IV sedative-hypnotic supplied as a slightly viscous, milky-white oil-in-water emulsion (1% and 2% preparations). Being insoluble in water, it is carried in a lipid vehicle:
| Component | Typical amount | Role |
|---|---|---|
| Soybean oil | 10% | Lipid vehicle — dissolves propofol |
| Egg lecithin (phosphatide) | 1.2% | Emulsifier — stabilises the oil-in-water mixture |
| Glycerol | 2.25% | Maintains tonicity (isotonic) |
| Preservative (e.g. EDTA) | — | Bacteriostatic — the emulsion supports microbial growth |
The lipid emulsion is an excellent culture medium. Use strict asepsis, discard opened vials/syringes promptly (within hours). It is stable at room temperature and not light-sensitive.
Fospropofol
A water-soluble prodrug cleaved by alkaline phosphatase → propofol + phosphate + formaldehyde. It has a slower onset/offset and characteristically causes perineal (peri-anal) paraesthesia/burning and pruritus (attributed to the phosphate metabolite).
Fast on, fast off — with important extrahepatic clearance
Onset
Time to peak effect ~90–100 s — one arm–brain circulation. Onset is by rapid uptake into the vessel-rich brain.
Offset by redistribution
Initial distribution half-life 2–8 min; effect terminates by redistribution to muscle/fat. Elimination half-life 4–7 h; context-sensitive half-time stays short (~40 min even after 8 h infusion) — hence its suitability for TIVA.
Metabolism
Hepatic conjugation + oxidation → 1,4-di-isopropylquinol; glucuronidation gives propofol-1-glucuronide and quinol-4-glucuronide — all inactive. Excreted renally.
Special populations
| Group | Change | Dose |
|---|---|---|
| Elderly | Smaller central compartment, ↓ cardiac output, ↓ clearance, ↑ sensitivity | Reduce |
| Children | Larger central compartment, ↑ clearance | Increase (mg/kg) |
| Hepatic disease | Extrahepatic clearance compensates | No significant change |
A GABA-A agonist, and much more
Propofol potentiates the inhibitory GABA-A receptor (↑ chloride conductance) producing hypnosis and sedation. Additional CNS actions from the notes:
| Action | Consequence |
|---|---|
| GABA-A agonism | Hypnosis & sedation |
| NMDA inhibition | Contributes to anaesthesia |
| ↑ Dopamine in nucleus accumbens | Reward/abuse potential |
| ↓ Serotonin in area postrema | Antiemetic effect |
| ↓ CMRO₂, ↓ CBF, ↓ ICP & ↓ CPP | Neuroprotective (limits excitotoxic/ischaemic injury); concentration-dependent ↓ in BIS |
| ↓ IOP | Useful for ophthalmic/airway instrumentation |
| Paradox at high concentration | Can provoke excitatory movements / grand-mal-type seizures |
A potent respiratory depressant
- Apnoea on induction — accentuated and prolonged when combined with opioids.
- ↓ Tidal volume, ↑ respiratory rate → an unpredictable change in minute ventilation.
- Acts on carotid-body chemoreceptors and depresses the ventilatory response to hypoxia (and to hypercapnia).
- Bronchodilation in COPD; attenuates vagally/methacholine-induced bronchoconstriction.
- Potentiates hypoxic pulmonary vasoconstriction (HPV).
The vasodilator that drops the pressure
- Heart rate is largely unchanged — it resets/inhibits the baroreflex, blunting the reflex tachycardia. The actual HR change depends on the degree of hypotension, the patient's ability to compensate and co-administered drugs.
- Suppresses atrial tachycardias; no direct effect on SA/AV node.
- Cardioprotection is dose-dependent (antioxidant effect); myocardial O₂ supply–demand generally preserved.
Give slowly and reduce the dose in the elderly, hypovolaemic or cardiovascularly compromised — a standard bolus can cause marked hypotension and apnoea.
The distinguishing extras
- Does not enhance neuromuscular-blocker action; does not trigger malignant hyperthermia.
- No effect on ACTH stimulation, fibrinolytic, haematologic or hepatic function.
- Enhances macrophage activity but is associated with a tendency to infection (largely a formulation/asepsis issue).
- Anti-tumorigenic signals: inhibits VEGF, ↑ NK-cell activity, ↑ cancer-cell apoptosis.
From induction to the antiemetic mini-dose
| Indication | Dose |
|---|---|
| Induction of anaesthesia | 1–2.5 mg/kg IV |
| Maintenance (TIVA) | 50–150 µg/kg/min |
| Sedation | 25–75 µg/kg/min (not for long-term sedation in paediatric patients) |
| Antiemetic effect | ~10 mg IV |
| Antipruritic effect | 10–15 mg IV |
From pain on injection to a lethal infusion syndrome
| Effect | Note / management |
|---|---|
| Pain on injection | Due to the irritant phenol — use a larger vein, avoid the dorsum of the hand, or add lidocaine to the propofol |
| Hypotension | Vasodilation ± myocardial depression |
| Apnoea | Especially with opioids |
| Myoclonus | Excitatory movement |
| Thrombophlebitis | Rare |
| Allergic reaction | Uncommon |
Associated with high-dose (>4 mg/kg/h) prolonged (>48 h) infusions — potentially fatal. Features: acute refractory bradycardia → asystole, plus metabolic acidosis (base deficit >10 mmol/L), rhabdomyolysis, hyperlipidaemia and an enlarged/fatty liver.
Risk factors: poor oxygen delivery, sepsis, brain injury, large dose, and inborn fatty-acid-oxidation disorders. Management: stop propofol, supportive care ± dialysis/ECMO.
Chiefly with midazolam, opioids and neuraxial block
- Midazolam ↓ propofol's metabolic clearance and alters haemodynamics; conversely propofol raises midazolam concentrations (mutual potentiation).
- Alfentanil raises propofol concentration (↓ its clearance).
- An epidural blocking ~20 segments can reduce the propofol dose requirement by ~30% (partly via ↓ hepatic/renal blood flow).
High-yield one-liners
Q: Emulsion constituents?
10% soybean oil, 1.2% egg lecithin (emulsifier), 2.25% glycerol (tonicity) ± EDTA (bacteriostatic).
Q: Why no dose change in liver disease?
Clearance exceeds hepatic blood flow → significant extrahepatic (lung/kidney) metabolism.
Q: PRIS threshold & hallmark?
>4 mg/kg/h for >48 h; refractory bradycardia + metabolic acidosis + rhabdomyolysis.
Q: Antiemetic dose?
~10 mg IV (↓ serotonin in the area postrema).
Q: Fospropofol's signature side effect?
Perineal paraesthesia and pruritus (phosphate metabolite).
References
- Dr. Tanya. Induction Agents — handwritten viva notes (primary source for this node).
- Gropper MA, Cohen NH, Eriksson LI, et al. (eds). Miller's Anesthesia. 9th ed. Elsevier; 2020.
- Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail's Clinical Anesthesiology. 7th ed. McGraw-Hill; 2022.
- Flood P, Rathmell JP, Urman RD. Stoelting's Pharmacology & Physiology in Anesthetic Practice. 6th ed. Wolters Kluwer; 2022.