Propofol
CLASS
- IV hypnotic agent
MECHANISM OF ACTION
- potentiates the inhibitory transmitters glycine & GABA which enhance spinal inhibition.
PHARMACEUTICS
- white
- oil-in-water emulsion
- 1% or 2%
- soybean oil
- purified egg phosphatide
- sodium hydroxide
- lecithin
DOSE
- onset: 30-60 seconds
- induction Bolus – 1.5 – 2.0mg/kg -> maintenance 4 – 12mg/kg/hr
- children: induction dose : increase dose by 50% -> maintenance: increase by 25 to 50%
- plasma concentrations: sedation: 0.5 – 1.5 mcg/mL, hypnosis: 2 – 6 mcg/mL
INDICATIONS
- Induction + maintenance of General Anaesthesia
- Sedation
- Status epilepticus
- N+V treatment in chemotherapy
ADVERSE EVENTS
- hypotension
- negative inotropy
- bradycardia
- propofol infusion syndrome -> see below
- apnoea
- pain on injection
- hypertriglyceridemia
PHARMACOKINETICS
- Absorption – IV
- Distribution – 97% protein bound, Vd large
- Metabolism – hepatic
- Elimination – urine, t1/2 = 10-70 min
PROS AND CONS
Advantages in ICU
- characteristically white emulsion mixture (decreased risk of drug errors with multiple infusion in ICU)
- rapid onset
- rapid offset (short context-sensitive half time) -> good for waking up quickly and neurologically +/- extubation
- used for toleration of ventilation, procedures, sedation for transport
- causes bronchodilation
- anti-emetic
- safe in porphyria
- safe in MH patients
- maintenance of cerebral metabolism and blood flow (unlike volatile agents that have been occasionally used in ICU for sedation +/- bronchodilation)
- decrease in ICP
- anticonvulsant (good agent in cerebral oedema and seizures)
- no active metabolites (unlike midazolam and morphine)
- cheap (compared to dexmedetomidine)
Disadvantages in ICU
- painful in injection
- no provision of analgesia (unlike clonidine or dexmetidtomidine, need to infuse opioid for analgesia)
- causes vasodilation and negative inotropy -> hypotension (may not be tolerated in patient with severe cardiovascular compromise ie. severe sepsis with multiorgan failure, midazolam and opioid more sensible in this context)
- can cause apnoea and decreased response to PaCO2 and PaO2 -> have to provide controlled ventilation if using boluses.
- decrease renal blood flow and GFR from hypotension
- metabolised by liver (unlike remifentanil which has organ independent metabolism and inactivation)
- doses of >4mg/kg/hr for >48 hours associated with propofol infusion syndrome -> severe metabolic acidosis, bradycardia, multiorgan failure and treatment resistant cardiac arrest (described mainly in children)
- expensive (compared to midazolam and morphine)
- may support bacterial growth if infused over long period of time (>8 hours) although does now have EDTA and sodium metabisulphide which are anti-bacterial agents in its formulation
Critical Care
Compendium
Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.
After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.
He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE. He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.
His one great achievement is being the father of three amazing children.
On Twitter, he is @precordialthump.
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