Pharmacology for Anaesthesia and Intensive Care

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Section IICoredrugs in anaesthetic practice

Table 8.2.Lipid solubility and protein binding of a few barbiturates.

Type Lipid solubility Protein binding (%)

Thiopental Thio +++++ 80

Pentobarbitone Oxy +++ 40

Phenobarbitone Oxy + 10

readily in alkaline solutions (Figure8.4). In general, thiobarbiturates are very lipid-

soluble, highly protein bound and completely metabolized in the liver. In contrast,

the oxybarbiturates are less lipid-soluble, less protein bound, and some are excreted

almost entirely unchanged in the urine (Table8.2).

Thiopental

Thiopental is the sulphur analogue of the oxybarbiturate pentobarbitone.

Presentation

Thiopental is formulated as the sodium salt and presented as a pale yellow powder.

The vial containes sodium carbonate (Na 2 CO 3 ,6%byweight) and nitrogen in place

of air. These two measures are designed to improve solubility of the solution by the

following mechanisms:

1. Sodium carbonate reacts with water in the following manner
   Na 2 CO 3 +H 2 O→NaHCO 3 +Na++OH−
   The result is a strongly alkaline solution (pH 10.5) favouring the water-soluble
   enol form which is more desirable as a preparation.


2. Air contains small amounts of carbon dioxide. Were this to be present and react
   with water it would tend to release bicarbonate and hydrogen ions which in turn
   would result in a less alkaline solution. As a result thiopental would be in a less
   favourable solution in terms of water solubility. Nitrogen is used in place of air to
   prevent this occuring.
   The 2.5% solution is stable for many days and should be bacteriostatic due to its
   alkaline pH.

Uses

Apart from induction of anaesthesia (3–7 mg.kg−^1 intravenously) thiopental is occa-

sionally used in status epilepticus. At sufficient plasma concentrations (most easily

maintained by continuous infusion) thiopental produces an isoelectric EEG, con-

firming maximal reduction of cerebral oxygen requirements. Inotropic support may

be required to maintain adequate cerebral perfusion at these doses. It has previously

been used rectally, although it has a slow onset via this route.