Last updated: 09/13/2023
- Thiopental is a short-acting intravenous barbiturate with rapid-onset sedation, hypnosis, and smooth emergence, but a long context-sensitive half-time.1
- For induction of anesthesia, thiopental has largely been replaced by propofol when available, but thiopental remains listed as the alternative to propofol in the World Health Organization’s list of essential medications.2
- Although thiopental’s legitimate medical use is established, the drug's negative history involving euthanasia in capital punishment and use as a truth serum ultimately led to its withdrawal by some governments as well as manufacturers in the United States.3
Introduction and Brief History
- Thiopental was developed in the 1930s and became widely used as an induction agent due to its rapid onset of sedation, short duration of action, and hypnosis.
- Even after its competitor, propofol, became available in the 1990s and largely replaced this agent, it was still widely utilized clinically in geriatric, neurologic, cardiovascular, and obstetric patients.
- As overall demand for this medication decreased, profits from manufacturing also diminished. At the same time, alternative uses of the drug included capital punishment, narcoanalysis in psychiatry, and as a truth serum which created a negative perception of thiopental. Ultimately, these factors led the main manufacturer, Hospira, to discontinue the production of thiopental in 2011.3
- Thiopental remains widely available in many low- and middle-income countries and is frequently used for anesthetic induction.
- Trade names include pentothal, penthiobarbital sodium, thiomebumal, thiopental Na, thiopental sodium, and thiopentone.4
Mechanism of Action and Pharmacokinetics
- The mechanism of action of thiopental is not fully elucidated, but the molecule binds to the gamma-aminobutyric acid (GABA)-A receptor, increasing the time at which the chloride ionopore is open. This increases the activity of GABA and exerts inhibitory effects on the central nervous system (CNS), primarily at the cerebral cortex and reticular formation.5,6
- The rapid onset of action of thiopental is secondary to its rapid distribution into the effect site.
- The rapid awakening following an induction dose is secondary to rapid redistribution from the central to peripheral compartment.
- Thiopental is predominantly metabolized in the liver and eliminated via the kidneys.
- The elimination half-life of thiopental is 3-26 hours.
- Thiopental has a long context-sensitive half time. Repeated doses lead to prolonged anesthesia as the drug accumulates in the fatty tissues and acts as a reservoir.
Effects on Organ Systems1
Central Nervous System
- Thiopental decreases cerebral metabolic oxygen requirement (CMRO2) and cerebral blood flow (CBF), thereby decreasing intracranial pressures. The decrease in CMRO2 (up to 50% normal) is greater than the decrease in CBF.
- Thiopental is thought to possess “neuroprotective” properties and can be used for cerebral protection during incomplete brain ischemia (e.g., carotid endarterectomy, temporary occlusion of cerebral arteries, etc.). However, there is no benefit in the setting of global cerebral ischemia (e.g., cardiac arrest).
- Thiopental causes dose-dependent electroencephalogram (EEG) changes and “burst suppression” with larger doses. Thiopental has potent anticonvulsant activity.
- Thiopental decreases cardiac output by decreasing systemic vascular resistance and venous return. It also causes direct myocardial suppression. Decreased doses should be used in the setting of hypovolemia.
- Thiopental causes dose-dependent respiratory depression by depressing the medullary respiratory center and decreasing the ventilatory response to hypoxia and hypercarbia.
- Thiopental does not depress airway reflexes as much as propofol and events such as laryngospasm or bronchospasm can occur in lightly anesthetized patients.
- Thiopental has been used intravenously in clinical anesthesia for induction, reduction of intracranial pressure, and as an anticonvulsant based on its favorable pharmacologic profile.1
Dose and Dosing Considerations
- Intravenous dosage4:
- Adult induction dose: rapid induction (3-4 mg/kg) divided into 2 to 4 doses
- Pediatric dose: induction, (neonate) 3-4 mg/kg; (1-6 months) 5-8 mg/kg IV; (1-15 y) 5-6 mg/kg
- Decreased doses should be used in patients with severe renal dysfunction and in the elderly.4
- Table 2 reviews key pharmacokinetics and pharmacodynamics of thiopental.
- Administration of thiopental can contribute to respiratory depression, laryngospasm, vasodilation, and decreases in blood pressure. Thiopental is a known vesicant that can cause tissue injury, pain, and necrosis with extravasation.4
- Thiopental administration in an unmonitored setting or at supratherapeutic doses can cause coma and death induced by respiratory depression and cardiovascular collapse.4
- Potential contraindications to the administration of thiopental include thiopental hypersensitivity, absence of suitable veins for intravenous administration given the high consequence of extravasation, and acute intermittent porphyria or variegate porphyria (South African)4 hypersensitivity to thiopental.
- Hospira, the main manufacturer of thiopental in the United States, discontinued the production of the drug in 2011 as the result of ongoing criticism due to its use in capital punishment euthanasia in the United States.7
- The American Society of Anesthesiologists issued a statement in 2011 regarding the clinical void created when the drug was made unavailable.8 There were also many articles in the popular press regarding failed or painful executions that resulted from the shortage of thiopental in the years that followed its withdrawal from the market. See the links below in Other Resources section for more information on this topic.
- Abola R, Geralemou S, Szafran M, et al. Intravenous Anesthetics. In: Barash PG, Cullen BF, Stoelting RK, et al., eds. Clinical Anesthesia 8th ed. Lippincott Williams & Wilkins; 2017.
- World Health Organization Model List of Essential Medicines – 23rd List, 2023. Geneva: World Health Organization; 2021. Link
- Orkaby A, Desai SP. The death of sodium pentothal: The rise and fall of an anesthetic turned lethal. J Hist Med Allied Sci. 2021;76(3):294-318. PubMed
- Thiopental sodium. Micromedex Solutions. Greenwood Village, CO: Truven Health Analytics. Updated July 3, 2023. Accessed July 10, 2023. Link.
- National Center for Biotechnology Information. PubChem Compound Summary for CID 3000715, Thiopental. Accessed July 16, 2023. Link
- Thiopental. Uses, interactions, mechanism of action | DrugBank Online. June 13, 2005. Accessed July 16, 2023. Link
- Steenhuysen J. Update 1-US company to stop making drug used in executions. Reuters. January 22, 2011. Accessed September 4, 2023. Link
- ASA statement on sodium thiopental’s removal from the market. American Society of Anesthesiologists. January 21, 2011. Accessed July 16, 2023. Link
- Belluck P. What’s in a lethal injection “cocktail”? The New York Times. April 9, 2011. Accessed July 16, 2023. Link
- Caldwell N, Chang A, Myers J. Gasping for air: Autopsies reveal troubling effects of lethal injection. NPR. September 21, 2020. Accessed July 16, 2023. Link
- Lopez G. How a shortage of lethal injection drugs put the death penalty before the Supreme Court. Vox. March 27, 2015. Accessed July 16, 2023. Link
- Stern JE. The cruel and unusual execution of Clayton Lockett. The Atlantic. May 14, 2015. Accessed July 12, 2023. Link
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