Thiopentone sodium It is an ultrashort acting thiobarbiturate, highly soluble in water yielding a very alkaline solution, which must be prepared freshly before injection. Extravasation of the solution or inadvertent intraarterial injection produces intense pain; necrosis and gangrene can occur.
Thiopental,5-ethyl-5-(1-methylbutyl)2-thiobarbituric acid, is synthesized by the alkylation of ethylmalonic ester with 2-bromopentane in the presence of sodium ethoxide. The product ethyl-(1-methylbutyl)malonic ester undergoes heterocyclization with thiourea, using sodium ethoxide as a base.
Thiopental is an extremely short-lasting barbiturate that makes anesthesia pleasant and smooth for the patient. When using the usual therapeutic doses, coming back into consciousness happens 15 min after administration.
Injected intravenous (3-5 mg/kg) as a 2.5% solution, thiopentone sodium produces unconsciousness in 15-20 sec. Its undissociated form has high lipid solubility; therefore it enters brain almost instantaneously. Initial distribution depends on organ blood flow-brain gets large amounts. However, as other less vascular tissues (muscle, fat) gradually take up the drug, blood concentration falls and it back diffuses from the brain: consciousness is regained in 6-10 min (half life of distribution phase is 3 min).
On repeated injection, the extracerebral sites are gradually filled up, so that lower doses produce anaesthesia which lasts longer. Its ultimate disposal occurs mainly by hepatic metabolism (elimination half life is 8-12 hr), but this is irrelevant for termination of action of a single dose. Residual CNS depression may persist for > 12 hr. The patient should not be allowed to leave the hospital without an attendant before this time.
Thiopentone is a poor analgesic. Painful procedures should not be carried out under its influence unless an opioid or N,O has been given; otherwise, the patient may struggle, shout and show reflex changes in blood pressure and respiration.
It is a weak muscle relaxant; does not irritate air passages. Respiratory depression with inducing doses of thiopentone is generally marked; transient apnoea can occur. The blood pressure falls immediately after injection, mainly due to vasodilatation, but recovers rapidly. However, cardiovascular col- lapse may occur if hypovolemia, shock or sepsis are present. Cardiac contractility is reduced, but reflex tachycardia occurs. However, thiopentone does not sensitize the heart to Adr, arrhythmias are rare.
Cerebral blood flow is reduced, both due to fall in blood pressure as well as constriction of cerebral vessels. However, cerebral oxygenation does not suffer, because there is greater decrease in cerebral metabolic rate and oxygen, consumption, while cerebral perfusion is maintained. Thiopentone was a commonly used inducing agent, but has now been largely replaced by propofol.
Laryngospasm occurs generally when respiratory secretions or other irritants are present in the airways, or when intubation is attempted while anaesthesia is light. This can be prevented by atropine premedication and administration of succinylcholine immediately after thiopentone. Succinylcholine and thiopentone react chemically should not be mixed in the same syringe.
Shivering and delirium may occur during recovery. Pain in the postoperative period is likely to induce restlessness; adequate analgesia should be provided. Postanaesthetic nausea and vomiting are uncommon. Thiopentone can precipitate acute intermittent porphyria in susceptible individuals, and is contraindicated in such subjects.
