Drugs List

Therapeutic Indications

Uses

Induction of general anaesthesia

Adjunctive treatment to produce hypnosis during balanced anaesthesia with other anaesthetic agents, (including analgesics and muscle relaxants)

Adjunctive treatment to control convulsive disorders of various aetiology, including those caused by local anaesthetics.

Reduction of intracranial pressure in patients with raised intracranial pressure under controlled ventilation.

Administration

For slow intravenous injection after reconstitution.

For intravenous administration only.
Extravasation causes local tissue necrosis and severe pain.
Accidental intra-arterial injection causes severe arterial spasm and a severe burning pain at the injection site. If this occurs, the injection needle should be left in -situ so that an antispasmodic can be administered. Anticoagulant therapy may also be required to minimise the risk of thrombosis.

Reconstitution

Thiopental injection is usually administered as a 2.5% w/v solution containing 500mg in 20ml. It may also be administered as a 5% w/v solution containing 500mg in 10ml.

The sterile powder should be reconstituted with Water for Injections.

Reconstituted solution should be stored between 2 - 8 degrees C in an upright position and discarded 7 hours after preparation. The solution is for single use only and any residue should be discarded.

Incompatibilities

Thiopental sodium solutions have a pH of 10 to 11 and are strongly alkaline in order to maintain stability.

Solutions are not compatible with acid, acidic salts and solutions such as pethidine, morphine and promethazine.

Contraindications

Respiratory obstruction
Acute asthmatic attack
Myotonic dystrophy
Porphyria
Circulatory failure

Precautions and Warnings

Procedures should always be performed in a properly equipped and staffed area. Equipment and drugs required for monitoring and resuscitation should be available immediately.

Thiopental sodium should be used with care in patients with any of the following:
Cardiovascular disease, especially constrictive pericarditis (thiopental may cause acute circulatory failure)
Severe respiratory diseases
Hypertension of various aetiology
Hypovolaemia
Severe haemorrhage
Burns
Dehydration
Severe anaemia
Status asthmaticus
Myasthenia gravis
Muscular dystrophies
Adrenocortical insufficiency (even when controlled with cortisone)
Cachexia
Septicaemia
Raised intracranial pressure
Raised blood urea
Raised plasma potassium
Metabolic disorders such as thyrotoxicosis, myxoedema and diabetes mellitus
Severe renal impairment

Reduced doses are recommended in patients with any of the following:
Shock
Dehydration
Severe anaemia
Hyperkalaemia
Septicaemia
Myxoedema
Metabolic disorders
Hepatic impairment - see Dosage; Hepatic Impairment

Dosage should also be reduced in elderly or debilitated patients and those who received premedication with narcotic analgesics.

Increased doses may be required in patients with an alcohol or drug habit/addiction. Supplementary analgesics are recommended in these patients.

Pregnancy - see Pregnancy section
Breastfeeding - see Lactation section

Awakening from a moderate dose of thiopental anaesthetic is rapid because the drug rapidly distributes into other tissues, notably fat. Subsequent metabolism is slow. Patients should be advised not to drive or operate machinery following thiopental administration, especially during the first 24 - 36 hours. Post-operative vertigo, disorientation and sedation may be prolonged following the procedure.
Repeated doses have a cumulative effect, especially in neonates when recovery may be delayed.

Thiopental has been associated with reports of severe or refractory hypokalaemia during infusion; severe rebound hyperkalaemia may occur after cessation of thiopental infusion.
The potential for rebound hyperkalaemia should be taken into account when stopping thiopental therapy.

Pregnancy and Lactation

Pregnancy

Thiopental has been used without adverse effects during pregnancy. The manufacturer advise that doses should not exceed 250mg.
Injectable anaesthetics reach their maximum concentrations immediately, then quickly fall due to distribution and metabolism. Thiopental rapidly crosses the placenta, achieving concentrations almost equal to those in the mother's circulation. After use in labour, the longer the time from anaesthetic administration to delivery, the lower the concentrations expected in the newborn. With low doses (up to 5mg/kg) during labour, no significant foetal impairment is expected, but with higher doses neonatal respiratory depression may occur. Newborns should be observed for depressed respiration.
One study showed poorer APGAR scores, Neurologic and Adaptive Capacity scores, and slower initiation of breastfeeding after anaesthesia with thiopental when compared to epidural anaesthesia.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password at https://www.toxbase.org/

Crosses placenta? - Yes

Effects on foetus if used during labour - At higher doses neonatal respiratory depression may occur. Observe newborn for depressed respiration. No significant foetal impairment is expected with low doses.

Lactation

Thiopental is secreted in breast milk in small amounts. It is recommended that breastfeeding should be temporarily suspended following the procedure. The available data suggest that breastfeeding may be safely resumed as soon as the mother has recovered and is able to nurse the infant. Although the half-life is prolonged in infants, a toxic effect is not anticipated. One study showed poorer APGAR scores, Neurologic and Adaptive Capacity scores, and slower initiation of breastfeeding after anaesthesia with thiopental when compared to epidural anaesthesia during labour.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Drug excreted in breast milk? - Yes in small quantities

Side Effects

Laryngeal spasm Cough Sneezing Pain on injection Thrombophlebitis Allergic reaction Hypersensitivity reactions Skin reactions Bronchospasm Respiratory depression Decreased cardiac output Myocardial depression Cardiac arrhythmias Headache Rash Vomiting Shivering Drowsiness Confusion Amnesia Anorexia Malaise Fatigue Dizziness Delirium Hypotension Hyperkalaemia Hypokalaemia

Presentation

Powder for solution for injection containing 500mg thiopental sodium per vial

Drugs List

Therapeutic Indications

Uses

Induction of general anaesthesia

Adjunctive treatment to produce hypnosis during balanced anaesthesia with other anaesthetic agents, (including analgesics and muscle relaxants)

Adjunctive treatment to control convulsive disorders of various aetiology, including those caused by local anaesthetics.

Reduction of intracranial pressure in patients with raised intracranial pressure under controlled ventilation.

Dosage

No fixed dosage recommendations can be given as the dosage has to be adjusted according to the patient's response. Factors such as age, sex and bodyweight should be taken into account.

Effective concentrations of thiopental sodium are reached in the brain within 30 seconds and anaesthesia is normally produced within one minute of the injection.

The injection should be administered slowly and titrated against the patient's response to reduce the risk of respiratory depression and overdose.

Adults

Elderly

Children

Neonates

Patients with Renal Impairment

Patients with Hepatic Impairment

Additional Dosage Information

Administration

For slow intravenous injection after reconstitution.

For intravenous administration only.
Extravasation causes local tissue necrosis and severe pain.
Accidental intra-arterial injection causes severe arterial spasm and a severe burning pain at the injection site. If this occurs, the injection needle should be left in -situ so that an antispasmodic can be administered. Anticoagulant therapy may also be required to minimise the risk of thrombosis.

Reconstitution

Thiopental injection is usually administered as a 2.5% w/v solution containing 500mg in 20ml. It may also be administered as a 5% w/v solution containing 500mg in 10ml.

The sterile powder should be reconstituted with Water for Injections.

Reconstituted solution should be stored between 2 - 8 degrees C in an upright position and discarded 7 hours after preparation. The solution is for single use only and any residue should be discarded.

Incompatibilities

Thiopental sodium solutions have a pH of 10 to 11 and are strongly alkaline in order to maintain stability.

Solutions are not compatible with acid, acidic salts and solutions such as pethidine, morphine and promethazine.

Contraindications

Respiratory obstruction
Acute asthmatic attack
Myotonic dystrophy
Porphyria
Circulatory failure

Precautions and Warnings

Procedures should always be performed in a properly equipped and staffed area. Equipment and drugs required for monitoring and resuscitation should be available immediately.

Thiopental sodium should be used with care in patients with any of the following:
Cardiovascular disease, especially constrictive pericarditis (thiopental may cause acute circulatory failure)
Severe respiratory diseases
Hypertension of various aetiology
Hypovolaemia
Severe haemorrhage
Burns
Dehydration
Severe anaemia
Status asthmaticus
Myasthenia gravis
Muscular dystrophies
Adrenocortical insufficiency (even when controlled with cortisone)
Cachexia
Septicaemia
Raised intracranial pressure
Raised blood urea
Raised plasma potassium
Metabolic disorders such as thyrotoxicosis, myxoedema and diabetes mellitus
Severe renal impairment

Reduced doses are recommended in patients with any of the following:
Shock
Dehydration
Severe anaemia
Hyperkalaemia
Septicaemia
Myxoedema
Metabolic disorders
Hepatic impairment - see Dosage; Hepatic Impairment

Dosage should also be reduced in elderly or debilitated patients and those who received premedication with narcotic analgesics.

Increased doses may be required in patients with an alcohol or drug habit/addiction. Supplementary analgesics are recommended in these patients.

Pregnancy - see Pregnancy section
Breastfeeding - see Lactation section

Awakening from a moderate dose of thiopental anaesthetic is rapid because the drug rapidly distributes into other tissues, notably fat. Subsequent metabolism is slow. Patients should be advised not to drive or operate machinery following thiopental administration, especially during the first 24 - 36 hours. Post-operative vertigo, disorientation and sedation may be prolonged following the procedure.
Repeated doses have a cumulative effect, especially in neonates when recovery may be delayed.

Thiopental has been associated with reports of severe or refractory hypokalaemia during infusion; severe rebound hyperkalaemia may occur after cessation of thiopental infusion.
The potential for rebound hyperkalaemia should be taken into account when stopping thiopental therapy.

Pregnancy and Lactation

Pregnancy

Thiopental has been used without adverse effects during pregnancy. The manufacturer advise that doses should not exceed 250mg.
Injectable anaesthetics reach their maximum concentrations immediately, then quickly fall due to distribution and metabolism. Thiopental rapidly crosses the placenta, achieving concentrations almost equal to those in the mother's circulation. After use in labour, the longer the time from anaesthetic administration to delivery, the lower the concentrations expected in the newborn. With low doses (up to 5mg/kg) during labour, no significant foetal impairment is expected, but with higher doses neonatal respiratory depression may occur. Newborns should be observed for depressed respiration.
One study showed poorer APGAR scores, Neurologic and Adaptive Capacity scores, and slower initiation of breastfeeding after anaesthesia with thiopental when compared to epidural anaesthesia.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password at https://www.toxbase.org/

Crosses placenta? - Yes

Effects on foetus if used during labour - At higher doses neonatal respiratory depression may occur. Observe newborn for depressed respiration. No significant foetal impairment is expected with low doses.

Lactation

Thiopental is secreted in breast milk in small amounts. It is recommended that breastfeeding should be temporarily suspended following the procedure. The available data suggest that breastfeeding may be safely resumed as soon as the mother has recovered and is able to nurse the infant. Although the half-life is prolonged in infants, a toxic effect is not anticipated. One study showed poorer APGAR scores, Neurologic and Adaptive Capacity scores, and slower initiation of breastfeeding after anaesthesia with thiopental when compared to epidural anaesthesia during labour.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Drug excreted in breast milk? - Yes in small quantities

Effects on Ability to Drive and Operate Machinery

Patients should be advised not to drive or operate machinery following thiopental administration, especially during the first 24 - 36 hours. Post-operative vertigo, disorientation and sedation may be prolonged following the procedure.

Counselling

Advise patients that they should not to drive or operate machinery following thiopental administration, especially during the first 24 - 36 hours.

Side Effects

Laryngeal spasm Cough Sneezing Pain on injection Thrombophlebitis Allergic reaction Hypersensitivity reactions Skin reactions Bronchospasm Respiratory depression Decreased cardiac output Myocardial depression Cardiac arrhythmias Headache Rash Vomiting Shivering Drowsiness Confusion Amnesia Anorexia Malaise Fatigue Dizziness Delirium Hypotension Hyperkalaemia Hypokalaemia

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Shelf Life and Storage

Powder
Do not store above 25 degrees C

Reconstituted solution
Store between 2 - 8 degrees C in an upright position.
Use within 7 hours of preparation.
For single use only and any residue should be discarded.

Further Information

Last Full Review Date: December 2011

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition.
ed. Schaefer, Peters & Miller; Elsevier Academic Press, London, 2007

Martindale The Extra Pharmacopeia 35th Edition 2007

Summary of Product Characteristics: Thiopental Injection. Archimedes Pharma UK ltd. Revised March 2014.

Drugs in Lactation Database, LactMed, THIOPENTAL record, Revised 3rd February 2009
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Accessed 5th December 2011

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 04 September 2017