PROPOFOL

  • Know Propofol well – important ED drug. Know PK, PD, dosages and toxicities.
Structure/Class
  1. 2,6 diisopropyl phenol is the chemical name for Propofol
Pharmacodynamics
  1. Thought to act by potentiating the chloride current through GABA-A channels
  2. Organ system effects are as follows:
    • CVS
      • Propofol causes the MOST PROFOUND decrease in systemic blood pressure when compared with other induction agents. This is due to profound arteriolar and venodilation, leading to a marked reduction in preload and afterload. Also, there is a strong inhibition of the normal baroreceptor response, so there is only a small increase in HR. *Use carefully in the elderly/already hypovolemic patient*
    • CNS
      • Propofol is a hypnotic with no analgesic properties.
      • It decreases cerebral metabolic rate and cerebral blood flow, therefore reducing ICP and intra-ocular pressure. However, be aware that the reduction in MAP and cerebral blood flow in combination may cause a critical reduction in cerebral perfusion pressure.
    • Respiratory
      • Propofol is a potent respiratory depressant.
      • Decreases both RR and TV (but decreases TV more)
      • It blunts the respiratory center’s response to hypoxia/hypercapnia
      • It blunts upper airway reflexes more so than thiopental (good for instrumenting airway/LMA)
    • Others
      • Propofol related infusion syndrome (PRIS). Characterized by tachycardia and metabolic acidosis. Seen in long term sedation/high doses.
      • Good anti-emetic properties
      • Pain on injection (use lignocaine/larger vein)
Absorption/administration
  1. IV only
Distribution
  1. Very lipid soluble
  2. Highly protein bound – 97%
  3. Vd is high – 2 to 10L/kg
Metabolism
  1. Rapidly metabolized in the liver to inactive products, and then excreted in the urine.
    • Note that plasma clearance is high and exceeds hepatic blood flow – there is probably extra-hepatic metabolism as well (the lung is thought to account for 30% of metabolism)
  2. However, note that the termination of the drug effect after a single bolus dose is mainly due to redistribution of the drug from the CNS to other less well-perfused areas.
    • Distribution T ½ ~2-4 minutes, awakening occurs in 8-10 minutes
    • Elimination T ½ is 4-23 hours.
Excretion
  1. Urinary
Indications
  1. Procedural sedation in ED
  2. Induction agent prior to intubation
  3. Maintenance of sedation in ED/ICU (ventilated patients)
Contraindications
  1. Absolute contraindications are known hypersensitivity or egg allergy
Special precautions
  1. Elderly
  2. Already hypovolemic
  3. Additional CNS depression with other drugs (BZD/Opioids/ODs)
Interactions
Adverse events
  1. Hypotension
  2. Transient apnoea
  3. Inability to protect airway
  4. Anaphylaxis/NV/Headache (very rare)
Dosing/administration
  1. Induction – 1 to 2.5mg/kg (80-200mg in the average person).
  2. Children need larger doses and pre-medicated patients need lower doses.
Toxicology
Withdrawal syndrome
Special notes