Thiopentone is a positive allosteric modulator at GABAA receptors (at a separate site to benzodiazepines) in the CNS. Barbiturates cause:

  • Decreased rate of dissociation of GABA
    Increases the duration of channel opening, causing effective hyperpolarisation due to increased Cl- conductance.
    • Clinical effects differ from benzodiazepines as benzodiazepines increase frequency of opening, whilst barbiturates increase duration
  • Direct activation of the channel at higher doses
Property Thiopentone
Class Barbiturate
Uses Induction of anaesthesia, status epilepticus, control of ICP refractory to other measures
Presentation 500mg of yellow powder with NaCO3 for reconstitution as a 2.5% solution. Container uses nitrogen as a filler gas (to prevent HCO3-1 formation when CO2 combines with water during reconstitution, which ↓ pH and therefore water solubility). pH of 11 when reconstituted - bacteriostatic solution.
Isomerism Tautomer. pKa of 7.6, such that 60% is unionised at pH 7.4 (i.e. water solubility decreases once injected).
Route of Administration IV
Dosing Consider 75mg boluses, assessing haemodynamic and neuronal effects.
Distribution 65-85% protein bound. High lipid solubility and CBF gives a rapid, reliable onset. Rapid offset due to redistribution, with a fast t1/2α of 8 minutes. Prolonged elimination half life (11 hours) contributes to long CSHT. Increased unionised portion in acidosis. t1/2ke0 of 1.2 minutes.
Metabolism Capacity dependent CYP450 metabolism - saturates at high doses (long CSHT with infusion). Metabolised to (active) pentobarbital, which also increases the duration of its clinical effects.
Elimination Renal of metabolites, < 1% excreted unchanged
Resp Respiratory depression, bronchospasm, laryngospasm
CVS Vasodilation and venodilation (↓ MSFP), ↓ inotropy, with compensatory tachycardia (baroreceptor response preserved)
CNS Hypnosis and anaesthesia within 40 seconds of injection, with reliable loss of lash reflex. Anticonvulsant. Dose-dependent flattening of the EEG (β 🡒 α 🡒 θ 🡒 δ 🡒 burst suppression 🡒 isoelectric), causing progressive ↓ CMRO2 (55% of maximal during burst suppression), ↓ CBF, and ↓ ICP.

Resolution of induction dose in 5-10 minutes due to redistribution.
Endocrine ↓ RBF causing ↓ UO
GIT Hepatic enzyme induction
Immune Anaphylaxis ~1;20,000
Metabolic May precipitate acute porphyric crises and is contraindicated in these patients
Other Intraarterial injection causes precipitation as water solubility decreases at blood pH. Microembolisation and ischaemia result, which should be treated with intraarterial local anaesthesia, analgesia, anticoagulation, and sympathetic blockade of the limb.

Tissue necrosis on extravasation.


  1. Petkov V. Essential Pharmacology For The ANZCA Primary Examination. Vesselin Petkov. 2012.
  2. LITFL - Thiopentone
  3. Hill, SA. Pharmacokinetics of drug infusions. Continuing Education in Anaesthesia. 2004.
Last updated 2019-07-18

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