• a thiobarbiturate


  1. Induction of anaesthesia
  2. Treatment of status epilepticus
  3. Neuroprotection


  • IV or PR
  • RSI: 3-7 mg/kg IV can give in divided doses and lasts 5-15 min
  • PR: 1 g per 22 kg of bodyweight –> acts within 15 min
  • Elevated ICP 1-2 mg/kg IV as required
  • For thiopentone coma dosing, please see below
  • Ensure to give a good flush pre and post-thiopentone, don’t lose that important cannula or lumen.


  • Is a hypnotic and anticonvulsant
  • Barbiturates work predominantly at the GABAA receptors at the alpha and beta sites (as opposed to the alpha and gamma sites like benzodiazepines)
  • Prolong GABA receptor opening duration (benzodiazepines increase the frequency), and cause direct activation of the channel at higher doses
  • Primarily act at synapses by depressing post-synaptic sensitivity to neurotransmitters and impairs pre-synaptic neurotransmitter release.
    • Multisynaptic pathways are depressed preferentially, such as the RAS
  • Membrane stabilising effects thought to be similar to local anaesthetics – enter the cell unionised, then become ionised and decrease Na+ and K+ conductance
  • In high concentrations – depresses enzymes responsible for glucose oxidation which form ATP and depress Ca2+ dependent channels
  • Also inhibits Ca2+ dependent neurotransmitter release and enhances Cl conductance in the absence of GABA


  • hygroscopic yellow powder
  • thiopentone sodium (weak acid)
  • stored under an atmosphere of nitrogen and contains 6% sodium carbonate
    • This is to improve the solubility of thiopentone where:
      • Sodium carbonate creates a strongly alkaline solution when combined with water and,
      • If the vial was stored in air, CO2 would form a less alkaline solution
  • reconstituted with sterile water
  • produces a 2.5% solution
  • Of note, barbiturates are not readily soluble in water at neutral pH, their solubility depends on transformation from the keto to the enol form which occurs more readily in an alkaline solution –> Tautomerism
  • Is a racemic mixture
  • Not removed by dialysis


  • Absorption
    • Acts in one arm-brain circulation time and lasts 5-15 mins after bolus – accumulates with repeated administration
    • Rectal administration: 1 g/22 kg of bodyweight acts in 15mins
  • Distribution
    • Vd ~2 L/kg
    • ~80% protein bound in the plasma, predominantly albumin
    • pKa of 7.6 with 60% unionised at pH 7.4 –> where only 12% free drug is immediately available
    • Distribution half-life: T1/2 (alpha) fast: 8 min // T1/2 (alpha) slow: 60 min
    • Rapid onset due to:
      • High blood flow to the brain
      • Lipophilicity
      • Low % ionised
  • Metabolism
    • Hepatic
    • Saturable pathway –> first order –> Zero order kinetics
    • Liver oxidation (CYP450) –> pentobarbital (active metabolite)
  • Elimination
    • Predominantly in the urine, 0.5% unchanged
    • Clearance is 2.7-4.1 mL/kg/min
    • Elimination half-life:
      • T 1/2 (beta): 11 hours
    • Long CSHT


  • CNS:
    • Hypnosis
    • Decrease in cerebral metabolic rate of oxygen (CMRO2)
    • Decrease in cerebral blood flow (CBF)
    • Decrease in intracranial pressure (ICP)
    • Decrease in intraocular pressure
    • Anticonvulsant
    • Antanalgesic in small doses
    • EEG (Alpha –> delta –> burst suppression –> isoelectric)
  • CVS
    • Venous vasodilation > arterial vasodilation
    • Direct negative inotropic effect
    • Compensatory tachycardia (due to preserved baroreceptor reflex)
  • RESP
    • Respiratory depression
    • Intact upper airway reflexes
    • Bronchospasm (due to histamine release)
    • Decreased ventilatory response to hypoxia and hypercarbia
  • GIT
    • Decreased hepatic blood flow
    • Induction of hepatic enzymes
    • Depression of intestinal activity
  • GUT
    • Deceased urine output (decreased CO –> decreased RBF // increased ADH release)
    • Anaphylaxis
    • Tissue necrosis in extravasation
    • Accidental arterial injection –> microembolisation / ischaemia
    • More precipitate acute porphyria
    • Immunosuppressive at high doses


  • Severe anaphylaxis 1:20 000 incidence
  • Extravasation leads to tissue necrosis
  • Prolonged infusion:
    • Hypokalaemia / hyponatraemia / increased infection risk
  • Sudden cessation can lead to rebound critical hyperkalaemia after prolonged infusion


  • Absolute
    • Allergy to barbiturates
    • Porphyria
    • Constrictive pericarditis
    • Status asthmaticus
    • Severe respiratory compromise
  • Relative
    • Severe cardiac dysfunction / shock
    • Hepatic dysfunction
    • Renal dysfunction
    • Myxoedema
    • Addison’s disease
    • Severe anaemia
    • Myasthenia gravis


  • Used for neuroprotection, e.g. several elevated intracranial pressure, and status epilepticus
  • An example of an infusion guideline used at Institution 1 is:
    • Loading dose of 5-20 mg/kg over 1 hour
    • Then commence infusion at 3-4 mg/kg/hr
  • Hypokalaemia is known to develop with prolonged infusion, aim to not replace if possible (due to concerns for rebound hyperkalaemia), replace if arrhythmias, ECG changes, or if K+ drops below 2 mmol/L
  • Titrate infusion dose as guided by BIS or cEEG burst suppression
  • Thiopentone is immunosuppressive at high doses and often sepsis is the reason to cease the infusion
  • A high dose prolonged infusion may cause vasopressin-resistant diabetes insipidus requiring bursts of DDAVP (4 microgs IV intermittently)


  • Look… the evidence isn’t great.
  • Currently still recommended for elevated ICP refractory to standard medical and surgical treatment by the Brain Trauma Foundation with IIb level of evidence
  • Oh’s 8th Edition of the Intensive Care Manual gives a throwaway line of “Barbituates are not recommended on current evidence” and then lists the BTF guidelines as its reference
  • The most important aspect when considering any large sedative bolus is to ensure haemodynamic stability!




CCC 700 6

Critical Care


ICU Advanced Trainee BMedSci [UoN], BMed [UoN], MMed(CritCare) [USyd] from a broadacre farm who found himself in a quaternary metropolitan ICU. Always trying to make medical education more interesting and appropriately targeted; pre-hospital and retrieval curious; passionate about equitable access to healthcare; looking forward to a future life in regional Australia. Student of LITFL.

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.

| INTENSIVE | RAGE | Resuscitology | SMACC

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