- Induction of anaesthesia (3-7mg/kg)
- One arm-brain circulation time occurs in 20s, although greater depth of anaesthesia occurs in 4-5 arm-brain circulation times
- Duration of action 15mins
- Last-line management of refractory raised ICP in traumatic brain injury
- If sufficient plasma dose is achieved by infusion it produces an isoelectric EEG and confirms maximal reduction of CMRO2 (55%)
- Treatment of status epilepticus
- Can be used rectally (i.e. via the GI tract) at a dose of 1g/22kg and an onset time of 15mins
Thiopental
Thiopental
- Thiopental is the thiobarbiturate analogue of the oxybarbiturate pentobarbital
- Thiopental is formulated in a rubber topped bottle as a pale yellow powder containing:
- The sodium salt of thiopental 500mg
- 6% anhydrous Na2CO3 [sodium carbonate] by weight
- Nitrogen in place of air
- These measures are designed to improve solubility as:
- When mixed with water, the Na2CO3 forms NaHCO3 + Na+ + OH-
- This results in a strongly alkaline solution of pH 10.5
- This favours the water-soluble enol form of thiopentone
- The carbon dioxide in air reacts with water to release bicarbonate and hydrogen ions
- This would make the solution less alkaline and favour the water-insoluble keto form
- Use of nitrogen in place of air prevents this occurring
- The resultant solution is a racemic mixture of 2.5% thiopental with a pKa of 7.6
- It is a straw-coloured, clear liquid with a faint garlic smell
- It ss bacteriostatic due to the alkaline pH
Absorption
- Rapid onset due to high lipid solubility and Ke0 of 55s (vs. 2.9mins for propofol)
- Can be used rectally (i.e. via the GI tract)
Distribution
- 80% protein bound although only 60% unionised at pH 7.4 (due to pKa 7.6) - this means only 12% of drug is immediately available
- Therefore significantly less drug is required to induce GA in patients who are acidotic (more unionised) or have reduced protein binding (e.g. critical illness, NSAID use)
- Volume of distribution 2.2L/kg
- Rapidly distributed into tissues means there is rapid emergence from a single bolus
Metabolism
- Hepatic oxidation to:
- Mostly inactive metabolites
- Pentobarbital, which is active
- When given via infusion its metabolism may become zero-order (saturation kinetics) due to saturation of liver enzymes
- As such its effects will be prolonged and recovery will be delayed; therefore not used for maintenance of anaesthesia
Excretion
- Clearance 3.5ml/kg/min
- Half life of 6-15hours
Respiratory
- Dose-dependent respiratory depression (via reductions in VT and minute volume)
- A greater degree of laryngo-/broncho-spasm than propofol as airway reflexes aren't depressed
- Is not a bronchodilator
Cardiovascular
- Negative inotropy and reduced SVR cause a dose-dependent, up to 20% drop in CO
- Associated hypotension, secondary to venodilatation and peripheral pooling
- There is a compensatory tachycardia mediated by the baroreceptor reflex
- The effects are more pronounced if hypovolaemic, acidotic or have reduced protein binding e.g. sepsis
Neurological
- Smooth, rapid induction of anaesthesia
- Reduced CBF, ICP, and CMRO2
- Antanalgesic in low doses
- Reduced IOP
- Anticonvulsant properties
Renal
- Reduces renal plasma flow and therefore urine output due to:
- Increased ADH release
- Reduced cardiac output
Intra-articular injection
- If injected arterially, the tautomeric equilibrium swings to the keto-form, which precipitates into thiopental crystals
- These wedge in small vessels and cause ischaemia and pain
- Doesn't occur IV due to dilution with more venous blood
- Treatment is with analgesia, IV papaverine/procaine, sympathetic block and anticoagulation
Other
- Anaphylaxis in 1 in 20,000 patients
- Is an CYP450 enzyme inducer
- Can precipitate acute porphyric crisis and is absolutely contraindicated in porphyria
- Peri-vascular injection is very painful and may cause serious tissue necrosis if large doses extravasate
- Will precipitate out if mixed with acidic solutions or oxidising agents, in particular aminosteroid NMBA, lidocaine and morphine