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 Sodium sodium is contra-indicated in respiratory obstruction, acute asthma, severe shock and dystrophia myotonica. Administration of any barbiturate is contra-indicated 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.
Solutions of Thiopental Sodium sodium 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.
Summary of the safety profile
Laryngeal spasm may occur, together with coughing or sneezing, during the induction procedure. For this reason it is not advised to use Thiopental Sodium sodium alone for peroral endoscopy.
A fall in blood pressure is often seen when Thiopental Sodium sodium is first given.
Although frequencies established in controlled clinical trials are not available for Thiopental Sodium sodium, the following are known to be relatively common in patients post general anaesthesia: drowsiness; nausea, with or without vomiting; decreased appetite; malaise; fatigue; dizziness; headache; and delirium in elderly patients.
Excessive doses are associated with hypothermia and profound cerebral impairment.
Tabulated summary of adverse reactions
Adverse reactions from literature searches, the KKI database and spontaneous reports with Thiopental Sodium sodium are listed in the table below.
Within the system organ class, the adverse reactions are listed by frequency using the following convention: very common (>1/10); common (>1/100 to <1/10); uncommon (>1/1,000 to <1/100); rare (>1/10,000 to <1/1,000); very rare (<1/10,000) and not known (cannot be estimated from the available data).
| System Organ Class | Adverse reaction | Frequency |
| Immune system disorder | Hypersensitivity, anaphylactic and anaphylactoid reactions | Not known |
| Metabolism and nutrition disorders | Decreased appetite, hypokalaemia, hyperkalaemia | Not known |
| Psychiatric disorders | Delirium, confusional state | Not known |
| Nervous system disorders | Cerebral impairment, amnesia, dizziness, somnolence, headache | Not known |
| Cardiac disorders | Myocardial depression, arrhythmia | Not known |
| Vascular disorders | Hypotension, circulatory collapse | Not known |
| Respiratory, thoracic and mediastinal disorders | Bronchospasm, respiratory depression, laryngospasm, cough, sneezing, apnoea | Not known |
| Gastrointestinal disorders | Nausea, vomiting | Not known |
| Skin and subcutaneous tissue disorders | Skin reaction | Not known |
| General disorders and administration site conditions | Malaise, fatigue, chills, extravasation, hypothermia | Not known |
| Investigations | Cardiac output decreased, blood pressure decreased | Not known |
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard
There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the Summary of Product Characteristics.
1. Thiopental Sodium sodium 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 Sodium sodium is also used as an adjunct for control of convulsive disorders of various aetiology, including those caused by local anaesthetics.
3. Thiopental Sodium sodium has now been used to reduce the intracranial pressure in patients with increased intracranial pressure, if controlled ventilation is provided.
Pharmacotherapeutic Group: Anesthetics, General; Barbiturates, Plain
ATC code: N01AF03
Thiopental Sodium sodium 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 Sodium sodium without significant effects on peripheral tissues.
Thiopental Sodium sodium 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 Sodium sodium is strongly bound to plasma protein, which impairs excretion through the kidney. The metabolites are usually inactive and are then excreted. Thiopental Sodium sodium, therefore, whilst having a short duration of action, may have a long elimination phase.
Thiopental Sodium sodium causes respiratory depression and a reduction in cardiac output and may precipitate acute circulatory failure in patients with cardiovascular disease, particularly constrictive pericarditis.
When particular caution is required
Special care is needed in administering Thiopental Sodium sodium to patients with the following conditions:- hypovolaemia, severe haemorrhage, burns, cardiovascular disease, status asthmaticus, myasthenia gravis, adrenocortical insufficiency (even when controlled by cortisone), cachexia, raised intracranial pressure and raised blood urea.
Dose reduction required
Reduced doses are recommended in shock, dehydration, severe anaemia, hyperkalaemia, toxaemia, metabolic disorders e.g. thyrotoxicosis, myxoedema and diabetes.
Use in hepatic and renal disease
Thiopental Sodium sodium is metabolised primarily by the liver so doses should be reduced in patients with hepatic impairment. Barbiturate anaesthetics should be used with caution in severe renal disease. Reduced doses are also indicated in the elderly and in patients who have been premedicated with narcotic analgesics.
) and in underlying disease
Thiopental Sodium sodium 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.
Patients taking long-term medications such as aspirin, oral anticoagulants, oestrogens, MAOIs and lithium may need to adjust the dose or stop therapy prior to elective surgery. Patients with diabetes or hypertension may need to adjust their therapy before anaesthesia.
Increased doses
Increased doses may be necessary in patients who have either a habituation or addiction to alcohol or drugs of abuse. Under these circumstances it is recommended that supplementary analgesic agents are used.
Extravasation
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.
Accidental intra-arterial injection
Accidental intra-arterial injection of Thiopental Sodium sodium causes severe arterial spasm and an intense burning pain around the injection site. In the case of accidental intra-arterial injection of Thiopental Sodium 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.
Use in neurological patients with raised intracranial pressure
Thiopental Sodium has been associated with reports of severe or refractory hypokalaemia during infusion; severe rebound hyperkalaemia may occur after cessation of Thiopental Sodium infusion. The potential for rebound hyperkalaemia should be taken into account when stopping Thiopental Sodium therapy.
This medicinal product contains 53.5mg sodium per vial. To be taken into consideration by patients on a controlled sodium diet.
Post-operative vertigo, disorientation and sedation may be prolonged and out-patients given Thiopental Sodium sodium should therefore be advised not to drive or use machinery, especially within the first 24 to 36 hours.
Intravenous injection.
Thiopental Sodium Sodium 500mg Injection 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 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.
Solutions for administration are prepared by adding Water for Injection and shaking to dissolve the contents of the vial. The following guide may be followed:
|
500mg vial | 2.5% Solution 25mg per ml Add 20ml | 5% Solution 50mg per ml Add 10ml |
Solutions must be used within 7 hours or preparation, or discarded. Do not use if the solution is discoloured.
