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 metabisulphate
- 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 hypercapnoea. 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 Hyponosis. Rapid LoC (within 1 arm-brain circulation time). ↓ CMRO2, CBF, and ICP. Anticonvulsant. ↓ IOP. Parodoxical 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

  1. Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.
  2. 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
Last updated 2017-09-22

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