Thiopentone

Thiopentone52'68-71 is the compound traditionally used for barbiturate anaesthesia in status epilepticus, at least in Europe. It is an effective antiepileptic drug, and may have additional cerebral-protective effects. In the doses used in status epilepticus it has an anaesthetic action, and all patients require intubation and most artificial ventilation. The most troublesome side effect is persisting hypotension and many patients require pressor therapy. Thiopentone has saturable pharmacokinetics, and a strong tendency to accumulate. Thus if large doses are given, blood levels may remain very high for protracted periods, and days may pass before consciousness is recovered after drug administration is discontinued. Blood level monitoring, both of the thiopentone and its active metabolite pentobarbitone, is therefore essential on prolonged therapy. Other toxic effects on prolonged therapy include pancreatitis and hepatic disturbance, and thiopentone may cause acute hypersensitivity. It should be administered cautiously in the elderly, and in those with cardiac, hepatic, or renal disease. Although it has been in use since the 1960s in status epilepticus, formal clinical trials of its safety and effectiveness in both adults and children are few. A full range of intensive care facilities is required during thiopentone infusions. Central venous pressure should be monitored, and blood pressure monitored via an arterial line. Pulmonary artery pressure monitoring is sometimes advisable, and EEG or cerebral function monitoring is essential if thiopentone infusions are prolonged. A concomitant dopamine infusion is frequently needed to maintain blood pressure. Thiopentone can react with polyvinyl infusion bags or giving sets. The continuous infusion should be made up in 0 9% sodium chloride (normal saline). The intravenous solution has a pH of 102-112, is incompatible with a large number of acidic or oxidising substances, and no drugs should be added. The aqueous solution is unstable if exposed to air.

The regimen commonly used is as follows: thiopentone is given as a 100-250 mg bolus over 20 seconds, with further 50 mg boluses every two to three minutes until seizures are controlled, with intubation and artificial ventilation. The intravenous infusion is then continued at the minimum dose

Box 6.5 Common reasons for the failure of emergency drug therapy to control seizures in status epilepticus

Inadequate emergency antiepileptic drug therapy (especially the administration of drugs at too low a dose)

Failure to initiate maintenance antiepileptic drug therapy (seizures will recur as the effect of emergency drug treatment wears off) Hypoxia, hypotension, cardiorespiratory failure, metabolic disturbance

Failure to identify the underlying cause

Failure to identify other medical complications (including hyperthermia, disseminated intravascular coagulation, hepatic failure)

Misdiagnosis (pseudostatus epilepticus is a common differential diagnosis that is often missed)

required to control clinical and electrographic seizure activity, usually between 3 and 5 mg/kg/h, and at thiopentone blood levels of about 40 mg/L. After 24 hours, the dose should be controlled by blood level monitoring. At this point, metabolism may be near saturation, and daily or twice daily blood level estimations should be made to ensure that levels do not rise excessively. The dose should be lowered if systolic blood pressure falls below 90 mm/Hg, or if vital functions are impaired. There is some evidence to suggest that barbiturate anaesthesia is more successful in those who have been loaded with phenobarbitone. Thiopentone should be continued for no less than 12 hours after seizure activity has ceased, and then slowly discontinued. The usual preparation is as a 25 g vial with 100 ml of diluent to produce a 25% solution.

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