Propofol
Propofol (2-6 di-isopropylphenol) is a phenolic derivative with effects on many receptors including:
- GABAA
Potentiates the effect of GABA, prolonging Cl- channel opening and hyperpolarising the cell. - Glycine
- Nicotinic ACh
- D2 receptors
| Property | Action |
|---|---|
| Class | Phenolic derivative |
| Uses | Induction of anaesthesia, sedation, TIVA |
| Presentation | White oil-in-water emulsion at a pH of 7-8.5 containing: - 10-20mg.ml-1 propofol - 10% Soybean oil (solubilising agent) - 1.2% Purified egg phosphatide (emulsifier) - 2.25% Glycerol (for tonicity) Bacteriostatic additives including: - Generics: Sodium metabisulfite - Diprivan: Disodium edetate (less allergenic) Risk of bacterial contamination limits shelf life. Energy content is 1.1kcal.ml-1 |
| pKa | 11 - almost all is unionised (and active) at physiologic pH |
| Route of Administration | IV only |
| Dosing | Induction: 1-2.5mg.kg-1 Maintenance: 4-12mg/kg/hr. Target plasma concentration of 4-8μg.ml-1 to maintain general anaesthesia |
| Distribution | 98% protein bound. Very high VD at 4L.kg-1. Rapid initial distribution: t1/2α (fast) 1-3 minutes, intermediate distribution t1/2α (slow) 30-70 minutes. t1/2ke0</sub> of 2.7 min. |
| Metabolism | Hepatic and extra-hepatic metabolism to inactive glucuronides and sulphates; t1/2β 2-12 hours. Clearance of 30-60ml.kg.min-1, unaffected by renal and hepatic disease. Context sensitive half-time peaks at 50 minutes following a 9 hour infusion. |
| Elimination | Tri-exponential. Renal elimination of inactive metabolites. |
| Resp | Respiratory depression, apnoea. Strong suppression of laryngeal reflexes. ↓ Response to hypoxia and hypercapnea. Bronchodilation. |
| CVS | ↓ Arterial and venous vasodilation (via stimulating NO release) causing ↓ SVR and ↓ VR, with ↓ BP. ↓ Inotropy via ↓ in SNS tone, ↓ MVO2. Depresses baroreceptor reflex. Pain on injection due to lipid emulsion. |
| CNS | Hypnosis. Rapid LoC (within 1 arm-brain circulation time). ↓ CMRO2, CBF, and ICP. Anticonvulsant. ↓ IOP. Paradoxical excitatory effects seen in ~10% - dystonic movements of subcortical origin. EEG demonstrates non-specific seizure-like activity. |
| MSK | Pain on injection into small veins |
| Renal | Green urine |
| GIT | Anti-emetic. ↓ Hepatic Blood Flow |
| Metabolic | Fat overload syndrome, lipaemia following prolonged infusion. Inhibits mitochondrial function. |
| Toxic Effects | Propofol infusion syndrome: Acidosis, bradycardia, and MODS following prolonged infusion (>24 hours), particularly with high doses (>4mg.kg-1.hr-1), in children, and potentially in the presence of mitochondrial defects. Believed due to inhibition of mitochondrial function. |
References
- Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.
- CICM July/September 2007 http://ceaccp.oxfordjournals.org/content/4/3/76.full.pdf http://www2.pedsanesthesia.org/meetings/2007winter/pdfs/Morgan-Friday1130-1150am.pdf