TPS500 mg/vial

Thiopental sodium is an ultra-short-acting barbiturate used, only by or under the direction of an anaesthesia specialist, for:

• Induction of general anaesthesia, followed by other anaesthetic agents for maintenance
• As the sole anaesthetic agent for brief (less than 15 minutes) surgical or diagnostic procedures
• Supplementation of regional anaesthesia
• Control of convulsive states, including status epilepticus not responding to other treatment, and convulsions occurring during anaesthesia or associated with local anaesthetic toxicity
• Reduction of elevated intracranial pressure, in a hospital/critical care setting

Contains TPS 500 mg/vial as the active ingredient, supplied as a powder for reconstitution into an injectable solution (commonly 2.5% w/v, i.e., 500 mg in 20 mL, once reconstituted), for intravenous use only.

Thiopental sodium is an ultra-short-acting barbiturate anaesthetic that has been used since the 1930s for the rapid induction of general anaesthesia, producing unconsciousness within about 30-40 seconds of an adequate intravenous dose. It works by enhancing (and, at higher concentrations, directly mimicking) the action of GABA, the brain's main inhibitory neurotransmitter, producing widespread depression of central nervous system activity. Thiopental produces hypnosis (unconsciousness) but not analgesia (pain relief), so it is generally combined with other agents for a complete anaesthetic plan. It must only be administered by, or under the direct supervision of, an anaesthesia specialist in a setting equipped to manage airway, breathing, and circulation, given its significant potential for causing severe respiratory depression and cardiovascular collapse, particularly if given too quickly or in an overly concentrated solution.

Therapeutic Class: General Anaesthetic (Ultra-Short-Acting Barbiturate)

Thiopental has a very rapid onset (unconsciousness within 30-40 seconds) due to its high lipid solubility, allowing rapid entry into the brain, but its effect is short-lived because it quickly redistributes out of the brain into other body tissues (including fat), rather than because it is rapidly eliminated from the body - repeated doses lead to progressive accumulation and prolonged recovery, since thiopental is actually metabolized relatively slowly by the liver. A total dose of 1 g generally should not be exceeded if prolonged recovery is to be avoided, and thiopental is not suitable for maintaining anaesthesia over an extended period, only for induction and very brief procedures.

• Given only by intravenous injection, by or under the direct supervision of a physician experienced in anaesthesia administration, in a setting equipped with resuscitation equipment and personnel able to manage the airway
• A small test dose should be given first and the patient observed for at least 60 seconds to assess sensitivity before full induction
• Injected slowly, titrated against patient response, to reduce the risk of respiratory depression and dangerously low blood pressure
• Avoid intra-arterial injection and extravasation, since thiopental's alkaline solution (pH about 10.6) can cause severe tissue damage if it enters an artery or leaks outside the vein
• Continuous monitoring of breathing, heart rate, and blood pressure is essential throughout administration and recovery

The following interactions are important, given thiopental's profound CNS-depressant effect:

• Opioid analgesics: potentiate thiopental's respiratory depressant effect.
• Alcohol, hypnotics, centrally acting muscle relaxants, anxiolytics, antipsychotics, and antihistamines: all enhance thiopental's sedative and respiratory depressant effects.
• MAOIs and lithium: patients on these medicines may need dose adjustment or temporary discontinuation before elective surgery involving thiopental, per the anaesthesia team's assessment.
• Antihypertensive and diabetes medicines: patients on these may need treatment adjustment before surgery, given thiopental's cardiovascular effects and the physiological stress of anaesthesia.

Common side effects

• Respiratory depression, including transient apnoea after induction
• Low blood pressure (hypotension)
• Tachycardia (fast heart rate)
• Shivering during recovery
• Sneezing, coughing during light anaesthesia

Serious side effects (require prompt medical attention)

• Severe respiratory depression or apnoea: patency of the airway must be protected at all times; assisted ventilation may be needed until spontaneous breathing resumes.
• Laryngospasm and bronchospasm: can occur with light thiopental anaesthesia at intubation, or from irritation of the airway; managed with skeletal muscle relaxants, positive pressure oxygen, or, in difficult cases, additional airway intervention.
• Myocardial depression and cardiac arrhythmias: particularly with higher doses or in patients with underlying cardiovascular disease; blood pressure can fall precipitously, especially in hypovolaemic patients.
• Anaphylactic and anaphylactoid reactions: urticaria, bronchospasm, vasodilation, and swelling - managed by conventional emergency treatment.
• Tissue necrosis if the injection is accidentally given intra-arterially or extravasates outside the vein, given the alkaline pH of the solution.
• Rare reports of immune haemolytic anaemia with renal failure and radial nerve palsy.

Pregnancy

Animal reproduction studies have not been conducted with thiopental, and it is not known whether it can cause fetal harm or affect reproductive capacity; thiopental should be given to a pregnant woman only if clearly needed, such as for anaesthesia required during pregnancy, under specialist supervision.

Breastfeeding

Thiopental readily crosses the placental barrier, and small amounts may appear in the milk of nursing mothers following administration of large doses; use during breastfeeding should be discussed with the treating anaesthesia and medical team.

• Must only be administered by an anaesthesia specialist in a setting with resuscitation equipment immediately available, given the significant risk of respiratory and cardiovascular depression.
• Use a test dose first to assess individual patient sensitivity before proceeding to the full induction dose.
• Avoid intra-arterial injection or extravasation, given the risk of severe tissue damage from the alkaline solution.
• Use with caution in patients with asthma, pharyngeal infection, hypotension, hypovolaemia, shock, severe anaemia, hyperkalaemia, severe cardiovascular disease, hepatic or renal dysfunction, myasthenia gravis, muscular dystrophy, adrenocortical insufficiency, raised intracranial pressure, or metabolic disorders.
• Avoid use for longer than approximately 48 hours in continuous infusion settings (such as for raised intracranial pressure), given the risk of delayed recovery of consciousness with prolonged use.
• A person competent in anaesthesia management should be in constant attendance from the time the injection is given until full recovery.

Overdose, typically from too rapid or repeated injection, can cause an alarming fall in blood pressure and shock, apnoea, laryngospasm, and other severe respiratory difficulties. Suspected overdose is a medical emergency requiring immediate management: discontinue the drug, secure a patent airway, and monitor and support oxygenation, ventilation, and circulation as needed, in a facility equipped for full resuscitation.

Store the unreconstituted powder at room temperature, protected from light, as directed on the specific product's label. Reconstituted solutions should be used according to the manufacturer's specified stability window; discard any unused portion.

• Children: Weight- and age-based induction dosing, with higher mg/kg doses generally required in younger infants; used only by anaesthesia specialists experienced in pediatric anaesthesia.
• Elderly and debilitated patients: More sensitive to thiopental's cardiovascular and respiratory depressant effects; smaller doses are advisable.
• Hepatic impairment: Low induction doses appear to be safe, but high doses can induce hepatic dysfunction and prolonged recovery can be anticipated given hepatic metabolism.
• Hypovolaemic or shocked patients: Especially susceptible to profound hypotension and cardiovascular collapse; used with extreme caution and reduced dosing.

Thiopental is used as a single injection or brief series of doses for induction of anaesthesia or a short procedure, not for maintaining anaesthesia over an extended period. When used for status epilepticus or raised intracranial pressure in a critical care setting, use beyond approximately 48 hours is generally avoided, given the risk of delayed recovery of consciousness.

The powder must be reconstituted with the diluent specified by the manufacturer (commonly sterile water for injection) to the desired concentration (commonly 2.5% w/v) immediately before use, following the specific product's instructions; use reconstituted solution promptly and discard any unused portion per the manufacturer's stability guidance.

Drug Class: Thiobarbiturate

Thiopental enhances the effect of GABA at GABA-A receptors in the brain, prolonging the opening of chloride channels and increasing inhibitory signalling throughout the central nervous system; at higher, anaesthetic concentrations, it can also directly activate these chloride channels even without GABA present. This produces rapid, profound central nervous system depression, resulting in loss of consciousness (hypnosis), though thiopental does not provide pain relief (analgesia) on its own.

Thiopental is used for induction of general anaesthesia in children of all ages, including neonates, with weight-based dosing that varies significantly by age (higher mg/kg doses in infants than in older children or adults); it must be administered only by an anaesthesia specialist experienced in pediatric anaesthesia, with full resuscitation capability available.