P1: PCX Printer: Yet To Come
9780521704632c08 CUFX213A/Peck 9780521618168 December 28, 2007 10:38
8 General anaesthetic agentsIntra-arterial injection
As 2.5% thiopental at pH 10.5 is injected into arterial blood with a pH of 7.4 the
tautomeric equilibrium swings away from the enol towards the keto form resulting
in a less water-soluble solution. This in turn leads to the precipitation of thiopental
crystalls which become wedged into small blood vessels leading to ischaemia and
pain. Thiopental does not precipitate when injected intravenously as it is continually
diluted by more venous blood. Treatment should begin immediately and may include
intra-arterial injection of papaverine or procaine, analgesia, sympathetic block of the
limb and anticoagulation.
Peri-vascular injection is painful and may cause serious tissue necrosis if large
doses extravasate.Methohexitone
Methohexitone is a methylated oxybarbiturate and is no longer available in the UK.Presentation
Methohexitone was produced as the sodium salt with sodium carbonate (6% by
weight) which was readily soluble in water forming an alkaline solution (pH 11.0).
Ithad a pKa = 7.9 so that 75% of unbound drug was unionized at pH 7.4. However,
60% of an administered dose was protein bound. There are four optically active
isomers but the preparation used clinically was a racemic mixture ofα-dandα-l
methohexitone.Uses
Methohexitone was used as a 1% solution at 1–2 mg.kg−^1 for the induction of anaes-
thesia where excitatory phenomena were of little concern (notably for electrocon-
vulsive therapy).Effects
Methohexitone has a similar pharmacological profile to thiopental, producing rapid
loss of consciousness, rapid emergence due to distribution and exerts similar effects
on the cardiovascular and hepatic systems. It may also precipitate a porphyric
crisis.Differences from thiopental
Methohexitone sometimes caused an excitatory phase before loss of conscious-
ness, with muscle twitching, increased tone and hiccup. It occasionally precipitated
convulsions in those with a history of epilepsy and its use in this setting was con-
troversial. Recovery was more rapid after methohexitone due to a higher hepatic
clearance. When injected intra-arterially or subcutaneously there were fewer vascu-
lar complications and there was less tissue damage. This was probably due to the