Thiopentone

Chemical

Barbiturate

Use

  1. Induction anaesthesia → Gold standard RSI
  2. Status epilepticus
  3. Cerebral protection

Presentation

Pale yellow powder

  • 500mg thiopental sodium
  • 6% anhydrous Na2CO3
  • N2 (instead of air as H+ of CO2 → ↑acidity & makes less H2O soluble)
  • Reconstituted with H2O
  • Alkaline pH = bacteriostatic pH 10.8
  • Incompatible with acidic drugs

Dose

3 – 7mg/kg

Route

IV

  • Extravasation = tissue necrosis
  • Intra-arterial injection = thrombosis & arterial constriction

Onset

Fast ~15 sec

1 arm-brain-circulation

DoA (duration)

15 min

MoA (mechanism)

  • Binds GABAA Receptors
  • ↓dissociation of GABA from receptors
  • Prolongs Cl– channel opening = hyperpolarises cell
  • Hyperpolarisation → ↑inhibition of post synaptic n.

PD

Neuro

  • Dose dependent ↓CMRO2
  • O2/flow coupling → ∴ ↓ CBF
  • ↓CBF → ∴ ↓ ICP & ↓IOP
  • No analgesia
  • Anticonvulsant

EEG

  • Dose dependent suppression
  • β → α → σ → δ → burst suppression → ‘silent’

CVS

  • – ve inotropy
  • ↓HR
  • ↓CO & MAP
  • ↓cardiac MRO2
  • ↓SVR (VD)
  • ↓PVR (& ↓ preL)

1° effect = ↓symp outflow from CNS

Resp

  • Potent respiratory depression
  • Apnoea on induction
  • Depressed laryngeal reflex
  • ↓response ↑PaCO2
  • May cause bronchoconstriction

GI

  • ↓motility
  • ↓splanchnic BF
  • ↑heme production = precipitate porphyria

Renal

  • ↓RBF
  • ↓GFR & ↑ADH

PK

A

Well absorbed PO & PR

D

85% PPB

Albumin (acidic drug)

VD 2L/kg

High lipid solubility

60% UNIONISED pH 7.4

M

Extensively metabolised by Liver 

-> ring desulfuration to the active metabolite Pentobarbital

-> Thiopental & Pentobarbital then subject to oxydation and hydroxylation to carboxylic acids and alcohols (pharmacologically inert)

Low hepatic ER ∴ elimination depends on Hepatic Enzyme Activity not hepatic BF

When infused metabolism displays ZERO ORDER K (saturation of hepatic enzyme)

15% metabolised per hr

E

Metabolites in urine (0.3% excreted unchanged)

t ½ B 3 – 23hrs

Adverse Effects

  • Severe anaphylaxis in 1/200,000
  • Porphyric crisis
    • Stimulates mitochondrial enzyme which accelerates heme production
    • Overproduction of porphyrins
    • Abdominal pain, peripheral neuropathy, hypertension, ↑HR, fatality

GOLD STANDARD RSI

  • More lipid soluble
  • Higher dose (5 – 7mg/kg vs 2 – 3mg/kg)

→ You can give a higher dose of PPF but have no BP

→ Both ‘work’ in 1 arm brain time, but much deeper in 30 sec with Thio

  • ∴ Gold standard for RSI