Thiopental Injection BP

Thiopental Sodium BP 500mg

Freeze-dried powder for solution for injection in a vial.

1. Thiopental is used for the induction of general anaesthesia and is also used as an adjunct to provide hypnosis during balanced anaesthesia with other anaesthetic agents, including analgesics and muscle relaxants.

2. Thiopental is also used as an adjunct for control of convulsive disorders of various aetiology, including those caused by local anaesthetics.

3. Thiopental has now been used to reduce the intracranial pressure in patients with increased intracranial pressure, if controlled ventilation is provided.

Intravenous injection.

Thiopental Injection BP is administered intravenously normally as a 2.5% w/v (500mg in 20ml) solution. On occasions it may be administered as a 5% w/v solution (500mg in 10ml).

The intravenous injection preparation should be used after reconstitution of the sterile powder with Water for Injections, usually to produce a 2.5% w/v solution and this should be discarded after seven hours.

Use in anaesthesia

Normal dosage for the induction of anaesthesia is 100mg to 150mg injected over 10 to 15 seconds. If necessary a repeat dose of 100mg to 150mg may be given after one minute. No fixed dosage recommendations for the intravenous injection can be given, since the dosage will need to be carefully adjusted according to the patient's response. Factors such as age, sex, and weight of the patient should be taken into consideration. Thiopental sodium reaches effective concentrations in the brain within 30 seconds and anaesthesia is normally produced within one minute of an intravenous dose.

Adult

100mg to 150mg intravenously over 10 to 15 seconds, normally as a 2.5% w/v solution.

A repeat dose of 100mg to 150mg may be given after one minute.

The intravenous injection should be given slowly and the amounts given titrated against the patient's response to minimise the risk of respiratory depression or the possibility of overdosage. The average dose for an adult of 70kg is roughly 200mg to 300mg (8mls to 12mls of a 2.5% w/v solution) with a maximum of 500mg.

Children

2 to 7mg/kg bodyweight, intravenously over 10 to 15 seconds, normally as a 2.5% w/v solution. A repeat dose of 2 to 7mg/kg may be given after one minute. The dose is 2 to 7mg/kg based on the patient's response. The dose for children should not exceed 7mg/kg.

Elderly

Smaller adult doses are advisable.

Use in convulsive states

75mg to 125mg (3mls to 5mls of a 2.5% w/v solution) should be given as soon as possible after the convulsion begins. Further doses may be required to control convulsions following the use of a local anaesthetic. Other regimens, such as the use of intravenous or rectal diazepam, may be used to control convulsive states.

Use in neurological patients with raised intracranial pressure

Intermittent bolus injections of 1.5 to 3mg/kg of bodyweight may be given to reduce elevations of intracranial pressure if controlled ventilation is provided.

Thiopental is contraindicated in respiratory obstruction, acute asthma, severe shock and dystrophia myotonica. Administration of any barbiturate is contraindicated in porphyria.

Care should also be exercised with severe cardiovascular diseases, severe respiratory diseases and hypertension of various aetiology.

Patients with hypersensitivity reactions to barbiturates.

Special care is needed in administering thiopental to patients with the following conditions:- hypovolaemia, severe haemorrhage, burns, dehydration, severe anaemia, cardiovascular disease, status asthmaticus, severe liver disease, myasthenia gravis and muscular dystrophies, adrenocortical insufficiency (even when controlled by cortisone), cachexia and severe toxaemia, raised intracranial pressure, raised blood urea, raised plasma potassium, metabolic disorders e.g. thyrotoxicosis, myxoedema, diabetes.

Thiopental may precipitate acute circulatory failure in patients with cardiovascular disease, particularly constrictive pericarditis.

Thiopental can cause respiratory depression and a reduction in cardiac output.

Headache is also reported with the use of barbiturate anaesthetics.

Reduced doses are recommended in shock, dehydration, severe anaemia, hyperkalaemia, toxaemia, myxoedema or other metabolic disorders. Thiopental sodium is metabolised primarily by the liver so doses should be reduced in patients with hepatic impairment. Reduced doses are also indicated in the elderly and in patients who have been premedicated with narcotic analgesics.

Thiopental has been shown to interact with sulphafurazole. Reduced initial doses may be required to achieve adequate anaesthesia, but repeat doses may also be necessary to maintain anaesthesia.

Increased doses may be necessary in patients who have either an habituation or addiction to alcohol or drugs of abuse. Under these circumstances it is recommended that supplementary analgesic agents are used.

Accidental intra-arterial injection of thiopental causes severe arterial spasm and an intense burning pain around the injection site. In the case of accidental intra-arterial injection of thiopental the needle should be left in-situ so that an injection of an antispasmodic, such as papaverine or prilocaine hydrochloride may be given. Anticoagulant therapy may also be started to reduce the risk of thrombosis.

Thiopental injection should be used with caution in patients with adrenocortical insufficiency or with raised intracranial pressure.

Thiopental has been shown to interact with sulphafurazole.

It should be noted that thiopental will interact with beta-blockers and calcium antagonists causing a fall in blood pressure.

The sedative properties of antipsychotics and anxiolytics may be potentiated by thiopental.

Thiopental readily crosses the placental barrier and also appears in breast milk. Therefore, breast-feeding should be temporarily suspended or breast milk expressed before the induction of anaesthesia. It has been shown that thiopental can be used without adverse effects during pregnancy although the total dose should not exceed 250mg. However, when considering use of thiopental the clinician should only use the drug when the expected benefits outweigh any potential risks.

Post-operative vertigo, disorientation and sedation may be prolonged and out-patients given thiopental should therefore be advised not to drive or use machinery, especially within the first 24 to 36 hours.

Laryngeal spasm may occur, together with coughing or sneezing, during the induction procedure. For this reason it is not advised to use thiopental alone for peroral endoscopy.

Extravasation causes local tissue necrosis and severe pain. This can be relieved by application of an ice pack and local injection of hydrocortisone. The 5% w/v solution is hypertonic and may cause pain on injection and thrombophlebitis.

Allergic reactions, skin reactions and hypersensitivity have been rarely reported.

Bronchospasm, respiratory depression and myocardial depression or cardiac arrhythmias may occur.

Overdosage produces acute respiratory depression, hypotension, circulatory failure and apnoea. Treatment must be artificial ventilation, lowering of the patient's head and infusion of plasma volume expanders.

Thiopental is a short-acting substituted barbiturate that is more lipid soluble than other groups of barbiturates. The drug reversibly depresses the activity of all excitable tissues. The CNS is particularly sensitive and normally a general anaesthesia can be achieved with thiopental without significant effects on peripheral tissues.

Thiopental acts through the CNS with particular activity in the mesencephalic reticular activating system. The barbiturates exert different effects on synaptic transmission, mostly those dependent on GABA. Autonomic ganglia of the peripheral nervous system are also depressed.

Following intravenous administration, unconsciousness occurs within 30 seconds and will be continued for 20 to 30 minutes after a single dose. Rapid uptake occurs to most vascular areas of the brain followed by redistribution into other tissues.

Thiopental is strongly bound to plasma protein, which impairs excretion through the kidney. The metabolites are usually inactive and are then excreted. Thiopental, therefore, whilst having a short duration of action, may have a long elimination phase.

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the Summary of Product Characteristics.

None

Solutions of thiopental injection have a pH of 10 to 11 and are strongly alkaline in order to maintain stability. Solutions are incompatible with acid, acidic salts and solutions such as pethidine, morphine and promethazine.

48 months.

Do not store above 25ºC. Store reconstituted solution between 2°C to 8ºC in an upright position and use within 7 hours. Use once following reconstitution and discard any residue.

20ml Type III clear glass vials with 20mm bromylbutyl caoutchouc siliconised rubber closures.

Pack size: 25 vials per pack.

Not applicable.

Link Pharmaceuticals Limited, Bishops Weald House, Albion Way, Horsham, West Sussex RH12 1AH, UK

PL 12406/0014

5 April 1999

January 2003

POM