Natriumthiopental

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Vorlage:Distinguish Vorlage:Infobox drug Sodium thiopental, also known as Sodium Pentothal (a trademark of Abbott Laboratories, thiopental, thiopentone, or Trapanal (also a trademark), or Fatal-Plus in veterinary euthanasia contexts, is a rapid-onset short-acting barbiturate general anesthetic. It is the thiobarbiturate analog of pentobarbital, and an analog of thiobarbital. Sodium thiopental was a core medicine in the World Health Organization's List of Essential Medicines,[1] which is a list of minimum medical needs for a basic healthcare system, but was supplanted by propofol.[2] Despite this thiopental is still listed as an acceptable alternative to propofol, depending on local availability and cost of these agents.[2] It was previously the first of three drugs administered during most lethal injections in the United States, but the U.S. manufacturer Hospira stopped manufacturing the drug and the EU banned the export of the drug for this purpose.[3] Although thiopental abuse carries a dependency risk, its recreational use is rare.[4]

Uses

Anesthesia

Sodium thiopental is an ultra-short-acting barbiturate and has been used commonly in the induction phase of general anesthesia. Its use has been largely replaced with that of propofol, but retains popularity as an induction agent for rapid-sequence intubation and in obstetrics.Vorlage:Citation needed Following intravenous injection, the drug rapidly reaches the brain and causes unconsciousness within 30–45 seconds. At one minute, the drug attains a peak concentration of about 60% of the total dose in the brain. Thereafter, the drug distributes to the rest of the body, and in about 5–10 minutes the concentration is low enough in the brain that consciousness returns.Vorlage:Citation needed

A normal dose of sodium thiopental (usually 4–6 mg/kg) given to a pregnant woman for operative delivery (caesarian section) rapidly makes her unconscious, but the baby in her uterus remains conscious. However, larger or repeated doses can depress the baby.[5]

Sodium thiopental is not used to maintain anesthesia in surgical procedures because, in infusion, it displays zero-order elimination pharmacokinetics, leading to a long period before consciousness is regained. Instead, anesthesia is usually maintained with an inhaled anesthetic (gas) agent. Inhaled anesthetics are eliminated relatively quickly, so that stopping the inhaled anesthetic will allow rapid return of consciousness. Sodium thiopental would have to be given in large amounts to maintain an anesthetic plane, and because of its 11.5- to 26-hour half-life, consciousness would take a long time to return.Vorlage:Vague[6]

In veterinary medicine, sodium thiopental is used to induce anesthesia in animals. Since it is redistributed to fat, certain lean breeds of dogs such as sighthounds will have prolonged recoveries from sodium thiopental due to their lack of body fat and their lean body mass. Conversely, obese animals will have rapid recoveries, but it will be some timeVorlage:Vague before it is entirely removed (metabolized) from their bodies. Sodium thiopental is always administered intravenously, as it can be fairly irritating; severe tissue necrosis and sloughing can occur if it is injected incorrectly into the tissue around a vein.Vorlage:Citation needed

Sodium thiopental decreases the cardiac stroke volume, which results in a decrease in cardiac output. The decrease in cardiac output occurs in conjunction with a decrease in systemic vascular resistance, which results in hypotension. However, in comparison with propofol, the reflex tachycardia seen during states of hypotension is relatively spared (a bradycardia is common after administration of propofol) and therefore the observed fall in blood pressure is generally less severe.

Medically induced coma

In addition to anesthesia induction, sodium thiopental was historically used to induce medical comas.[7] It has now been superseded by drugs such as propofol because their effects wear off more quickly than thiopental. Patients with brain swelling, causing elevation of intracranial pressure, either secondary to trauma or following surgery, may benefit from this drug. Sodium thiopental, and the barbiturate class of drugs, decrease neuronal activity thereby decreasing cerebral metabolic rate of oxygen consumption (CMRO2), decrease intracranial vascular response to carbon dioxide (CO2), which in turn decreases intracranial pressure. Patients with refractory elevated intracranial pressure (RICH) due to traumatic brain injury (TBI) may have improved long term outcome when barbiturate coma is added to their neurointensive care treatment.[8][9][10][11] Reportedly, thiopental has been shown to be superior to pentobarbital in reducing intracranial pressure.[12] This phenomenon is also called a reverse steal effect.Vorlage:Citation needed

Status epilepticus

In refractory status epilepticus, thiopental may be used to terminate a seizure.

Euthanasia

Sodium thiopental is used intravenously for the purposes of euthanasia. In both Belgium and the Netherlands, where active euthanasia is allowed by law, the standard protocol recommends sodium thiopental as the ideal agent to induce coma, followed by pancuronium bromide to paralyze muscles and stop breathing.[13]

Intravenous administration is the most reliable and rapid way to accomplish euthanasia. Death is quick. A coma is first induced by intravenous administration of 20 mg/kg thiopental sodium (Nesdonal) in a small volume (10 ml physiological saline). Then, a triple dose of a non-depolarizing neuromuscular blocking drug is given, such as 20 mg pancuronium bromide (Pavulon) or 20 mg vecuronium bromide (Norcuron). The muscle relaxant should be given intravenously to ensure optimal availability but pancuronium bromide may be administered intramuscularly at an increased dosage level of 40 mg.[13]

Lethal injection

Vorlage:Further

Along with pancuronium bromide and potassium chloride, thiopental is used in 34 states of the United States to execute prisoners by lethal injection. A very large dose is given to ensure rapid loss of consciousness. Although death usually occurs within ten minutes of the beginning of the injection process, some have been known to take longer.[14] The use of sodium thiopental in execution protocols was challenged in court after a study in the medical journal The Lancet reported autopsies of executed inmates showed the level of thiopental in their bloodstream was insufficient to cause unconsciousness.

On December 8, 2009, Ohio became the first state to use a single dose of sodium thiopental for its capital execution, following the failed use of the standard three-drug cocktail during a recent execution, due to inability to locate suitable veins. Kenneth Biros was executed using the single-drug method.[15]

Washington became the second state in the U.S. to use the single-dose sodium thiopental injections for executions. On September 10, 2010, the execution of Cal Coburn Brown was the first in the state to use a single-dose, single-drug injection. His death was pronounced approximately one and a half minutes after the intravenous administration of five grams of the drug.[16]

After its use for the execution of Jeffrey Landrigan in the U.S., the UK introduced a ban on the export of sodium thiopental in December 2010,[17] after it was established that no European supplies to the U.S. were being used for any other purpose.[18] The restrictions were based on "the European Union Torture Regulation (including licensing of drugs used in execution by lethal injection)".[19] From 21 December 2011 the European Union extended trade restrictions to prevent the export of certain medicinal products for capital punishment, stating that "the Union disapproves of capital punishment in all circumstances and works towards its universal abolition".[20]

Truth serum

Vorlage:Details Thiopental (Pentothal) is still used in some places as a truth serum to weaken the resolve of a subject and make them more compliant to pressure.[21] The barbiturates as a class decrease higher cortical brain functioning, and also due to the loss of inhibition produced by barbiturates. Some psychiatristsVorlage:Who hypothesize that because lying is more complex than telling the truth, suppression of the higher cortical functions may lead to the uncovering of the truth. The drug tends to make subjects loquacious and cooperative with interrogators; however, the reliability of confessions made under thiopental is questionable.[22]

Psychiatry

Psychiatrists have used thiopental to desensitize patients with phobias[23] and to "facilitate the recall of painful repressed memories."[24] One psychiatrist who worked with thiopental is the Dutch Professor Vorlage:Ill, who used this procedure to help relieve trauma in surviving victims of the Holocaust.[25]

Mechanism of action

Sodium thiopental is a member of the barbiturate class of drugs, which are relatively non-selective compounds that bind to an entire superfamily of ligand-gated ion channels, of which the GABAA receptor channel is one of several representatives. This superfamily of ion channels includes the neuronal nAChR channel, the 5HT3R channel, the GlyR channel and others. Surprisingly, while GABAA receptor currents are increased by barbiturates (and other general anesthetics), ligand-gated ion channels that are predominantly permeable for cationic ions are blocked by these compounds. For example, neuronal nAChR channels are blocked by clinically relevant anesthetic concentrations of both sodium thiopental and pentobarbital.[26] Such findings implicate (non-GABA-ergic) ligand-gated ion channels, e.g. the neuronal nAChR channel, in mediating some of the (side) effects of barbiturates.[27] The GABAA receptor is an inhibitory channel that decreases neuronal activity, and barbiturates enhance the inhibitory action of the GABAA receptor.[28]

Controversies

Following a shortage that led a court to delay an execution in California, a company spokesman for Hospira, the sole American manufacturer of the drug, objected to the use of thiopental in lethal injection. "Hospira manufactures this product because it improves or saves lives, and the company markets it solely for use as indicated on the product labeling. The drug is not indicated for capital punishment and Hospira does not support its use in this procedure."[29] On January 21, 2011, the company announced that it would stop production of sodium thiopental from its plant in Italy because Italian authorities couldn't guarantee that exported quantities of the drug would not be used in executions. Italy was the only viable place where the company could produce sodium thiopental, leaving the United States without a supplier.[30]

Metabolism

Thiopental rapidly and easily crosses the blood brain barrier as it is a lipophilic molecule. As with all lipid-soluble anaesthetic drugs, the short duration of action of sodium thiopental is due almost entirely to its redistribution away from central circulation towards muscle and fat tissue, due to its very high fat:water partition coefficient (approximately 10), leading to sequestration in fat tissue. Once redistributed, the free fraction in the blood is metabolized in the liver. Sodium thiopental is mainly metabolized to pentobarbital,[31] 5-ethyl-5-(1'-methyl-3'-hydroxybutyl)-2-thiobarbituric acid, and 5-ethyl-5-(1'-methyl-3'-carboxypropyl)-2-thiobarbituric acid.[32]

Dosage

The usual dose range for induction of anesthesia using thiopental is from 3 to 6 mg/kg; however, there are many factors that can alter this. Premedication with sedatives such as benzodiazepines or clonidine will reduce requirements, as do specific disease states and other patient factors. Among patient factors are: age, sex, and lean body mass. Specific disease conditions that can alter the dose requirements of thiopentone and for that matter any other intravenous anaesthetic are: hypovolemia, burns, azotemia, liver failure, hypoproteinemia, etc.Vorlage:Citation needed

Side effects

As with nearly all anesthetic drugs, thiopental causes cardiovascular and respiratory depression resulting in hypotension, apnea, and airway obstruction. For these reasons, only suitably trained medical personnel should give thiopental in an environment suitably equipped to deal with these effects. Side effects include headache, agitated emergence, prolonged somnolence, and nausea. Intravenous administration of sodium thiopental is followed instantly by an odor and/or taste sensation, sometimes described as being similar to rotting onions, or to garlic. The hangover from the side effects may last up to 36 hours.

Although each molecule of thiopental contains one sulfur atom, it is not a sulfonamide, and does not show allergic reactions of sulfa/sulpha drugs.

Contraindications

Thiopental should be used with caution in cases of liver disease, Addison's disease, myxedema, severe heart disease, severe hypotension, a severe breathing disorder, or a family history of porphyria.[33][34]

Co-administration of pentoxifylline and thiopental causes death by acute pulmonary edema in rats. This pulmonary edema was not mediated by cardiac failure or by pulmonary hypertension but was due to increased pulmonary vascular permeability.[35]

History

Sodium thiopental was discovered in the early 1930s by Ernest H. Volwiler and Donalee L. Tabern, working for Abbott Laboratories. It was first used in human beings on March 8, 1934, by Dr. Ralph M. Waters[36] in an investigation of its properties, which were short-term anesthesia and surprisingly little analgesia.[37] Three months later,[38] Dr. John S. Lundy started a clinical trial of thiopental at the Mayo Clinic at the request of Abbott.[39] Abbott continued to make the drug until 2004, when it spun off its hospital-products division as Hospira.

Thiopental is famously associated with a number of anesthetic deaths in victims of the attack on Pearl Harbor. These deaths, relatively soon after the drug's introduction, were said to be due to excessive doses given to shocked trauma patients. However, recent evidence available through freedom of information legislation was reviewed in the British Journal of Anaesthesia,[40] which has suggested that this story was grossly exaggerated. Of the 344 wounded that were admitted to the Tripler Army Hospital, only 13 did not survive, and it is unlikely that thiopentone overdose was responsible for more than a few of these.

See also

References

Vorlage:Reflist

External links

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  1. ↑ WHO Model List of Essential Medicines 16th list, March 2009. World Health Organization, März 2009, abgerufen am 25. August 2017.
  2. ↑ a b WHO Model List of Essential Medicines 20th List (March 2017). (PDF) World Health Organization, März 2017, abgerufen am 25. August 2017.
  3. ↑ Death Penalty Opposition: EU Set to Ban Export of Drug Used in US Executions, Spiegel Online International. Abgerufen im 23 January 2014 
  4. ↑ , Kaye, Alan David,, Vadivelu, Nalini,, Urman, Richard D.,: Substance abuse: inpatient and outpatient management for every clinician. New York, ISBN 1-4939-1951-2 (worldcat.org).
  5. ↑ Christine A Gleason, Sandra E Juul: Avery's Diseases of the Newborn. Elsevier Health Sciences, 2011, ISBN 978-1-4557-2714-8, S. 169 (elsevierhealth.com [abgerufen am 13. August 2016]).Vorlage:Toter Link/!...nourl (Seite dauerhaft nicht mehr abrufbar, festgestellt im August 2018.)
  6. ↑ Morgan, DJ, Blackman, GL, Paull, JD, Wolf, LJ: Pharmacokinetics and plasma binding of thiopental. II: Studies at cesarean section. In: Anesthesiology. 54. Jahrgang, Nr. 6, 1981, S. 474–80, doi:10.1097/00000542-198106000-00006, PMID 7235275.
  7. ↑ Takeko Toyama: TRAUMA.ORG: Critical Care: Barbiturate Coma. In: trauma.org. Abgerufen am 18. August 2016.
  8. ↑ Almaas R, Saugstad OD, Pleasure D, et al (2000) Effect of barbiturates on hydroxyl radicals, lipid peroxidation, and hypoxic cell death in human NT2-N neurons. Anesthesiology 92:764-74
  9. ↑ Cole DJ, Cross LM, Drummond JC, et al (2001) Thiopentone and methohexital, but not pentobarbitone, reduce early focal cerebral ischemic injury in rats. Can J Anaesth 48:807-14
  10. ↑ Pérez-Bárcena J, Llompart-Pou JA, Homar J, et al (2008) Pentobarbital versus thiopental in the treatment of refractory intracranial hypertension in patients with traumatic brain injury: a randomized controlled trial. Crit Care. 12:R112.
  11. ↑ Shibuta S, Kosaka J, Mashimo T, et al (1998) Nitric oxide-induced cytotoxicity attenuation by thiopentone sodium but not pentobarbitone sodium in primary brain cultures. Br J Pharmacol. 124:804-10
  12. ↑ Pérez-Bárcena J, Barceló B, Homar J, JM Abadal, FJ Molina, A De La Peña, J Sahuquillo, J Ibáñez: [Comparison of the effectiveness of pentobarbital and thiopental in patients with refractory intracranial hypertension. Preliminary report of 20 patients]. In: Neurocirugia (Astur). 16. Jahrgang, Nr. 1, Februar 2005, S. 5–12; discussion 12–3, PMID 15756405 (spanisch, revistaneurocirugia.com (Memento des Originals vom 28. September 2007 im Internet Archive) [abgerufen am 18. Juli 2008]).
  13. ↑ a b Royal Dutch Society for the Advancement of Pharmacy: Administration and Compounding of Euthanasic Agents. The Hague, 1994, archiviert vom Original am 21. August 2008; abgerufen am 18. Juli 2008.
  14. ↑ Ohio executes inmate with 1-drug lethal injection. Abgerufen am 8. Dezember 2009 
  15. ↑ Edecio Martinez: Kenneth Biros Execution: Ohio Man First to Die Under 1-Drug Thiopental Sodium Method In: CBS News, 8 December 2009 
  16. ↑ Jennifer Sullivan: Killer on death row 16-1/2 years is executed In: The Seattle Times, 10 September 2010 
  17. ↑ Drug sold in UK to be used for execution in Georgia. In: bbc.co.uk. BBC News, 24. Januar 2011, abgerufen am 18. August 2016.
  18. ↑ Dominic Casciani: US lethal injection drug faces UK export restrictions. In: bbc.co.uk. BBC News, 29. November 2010, abgerufen am 18. August 2016.
  19. ↑ Controls on torture goods - Detailed guidance - GOV.UK. In: gov.uk. Abgerufen am 18. August 2016.
  20. ↑ EU Council Regulation (EU) No 1352/2011
  21. ↑ Truth serum used on 'serial child killers' In: Sydney Morning Herald, January 12, 2007 
  22. ↑ Anne Bannon, Stevens, Serita Deborah: The Howdunit Book of Poisons (Howdunit). Writers Digest Books, Cincinnati 2007, ISBN 1-58297-456-X.
  23. ↑ T. Pearlman: Behavioral desensitization of phobic anxiety using thiopental sodium. In: The American Journal of Psychiatry. 137. Jahrgang, Nr. 12. American Psychiatric Association, 1980, S. 1580–1582, doi:10.1176/ajp.137.12.1580, PMID 6108082 (psychiatryonline.org).
  24. ↑ Drugged Future? In: TIME, February 24, 1958 
  25. ↑ Stephen Snelders: The LSD Therapy Career of Jan Bastiaans, M.D. In: Newsletter of the Multidisciplinary Association for Psychedelic Studies. 8. Jahrgang, Nr. 1. Multidisciplinary Association for Psychedelic Studies, 1998, S. 18–20 (maps.org).
  26. ↑ M Weber, L Motin, S Gaul, F Beker, RH Fink, DJ Adams: Intravenous anesthetics inhibit nicotinic acetyl-choline receptor-mediated currents and Ca2+ transients in rat intracardiac ganglion neurons. In: British Journal of Pharmacology. 144. Jahrgang, Nr. 1, Januar 2005, S. 98–107, doi:10.1038/sj.bjp.0705942, PMID 15644873, PMC 1575970 (freier Volltext).
  27. ↑ NP Franks, WR Lieb: Which molecular targets are most relevant to general anaesthesia? In: Toxicology Letters. 100–101. Jahrgang, Nr. 1–2, 23. November 1998, S. 1–8, doi:10.1016/S0378-4274(98)00158-1, PMID 10049127.
  28. ↑ Anesthesia and Analgesia. University of Virginia School of Medicine, abgerufen am 5. August 2007.
  29. ↑ Jesse McKinley: Judges Question California's Motivation on Execution In: New York Times, 28 September 2010 
  30. ↑ U.S. Drug Maker Discontinues Key Death Penalty Drug, Fox News, 21 January 2011 
  31. ↑ Winters WD, Spector E, Wallach DP, Shideman FE: Metabolism of thiopental-S35 and thiopental-2-C14 by a rat liver mince and identification of pentobarbital as a major metabolite. In: J. Pharmacol. Exp. Ther. 114. Jahrgang, Nr. 3, Juli 1955, S. 343–57, PMID 13243246 (aspetjournals.org [abgerufen am 18. Juli 2008]).Vorlage:Toter Link/!...nourl (Seite nicht mehr abrufbar, festgestellt im Juni 2016.)
  32. ↑ Bory C, Chantin C, Boulieu R, J Cotte, JC Berthier, D Fraisse, MJ Bobenrieth: [Use of thiopental in man. Determination of this drug and its metabolites in plasma and urine by liquid phase chromatography and mass spectrometry]. In: Comptes Rendus de l'Académie des Sciences, Série III. 303. Jahrgang, Nr. 1, 1986, S. 7–12, PMID 3093002 (französisch).
  33. ↑ Pentothal (thiopental). eMedicineHealth, 12. April 2009;.
  34. ↑ M. F. M. James, R. J. Hift: Porphyrias. In: bja.oxfordjournals.org. 1. Juli 2000, abgerufen am 25. September 2013.
  35. ↑ Pereda J, Gómez-Cambronero L, Alberola A, G Fabregat, M Cerdá, J Escobar, L Sabater, J García-De-La-Asuneión, J Viña: Co-administration of pentoxifylline and thiopental causes death by acute pulmonary oedema in rats. In: Br. J. Pharmacol. 149. Jahrgang, Nr. 4, Oktober 2006, S. 450–5, doi:10.1038/sj.bjp.0706871, PMID 16953192, PMC 1978439 (freier Volltext).
  36. ↑ This Month in Anesthesia History: March. Anesthesia History Association, archiviert vom Original am 1. Mai 2011;.
  37. ↑ John E Steinhaus: The Investigator and His 'Uncompromising Scientific Honesty'. In: ASA Newsletter. 65. Jahrgang, Nr. 9. American Society of Anesthesiologists, September 2001, S. 7–9 (asahq.org (Memento des Originals vom 13. Mai 2011 im Internet Archive)).
  38. ↑ John S. Lundy: From this point in time: Some memories of my part in the history of anesthesia. In: Journal of the American Association of Nurse Anesthetists. 24. Jahrgang, Nr. 2. American Association of Nurse Anesthetists, 1966, S. 95–102 (aana.com (Memento des Originals vom 1. Mai 2011 im Internet Archive)).
  39. ↑ Virginia S. Thatcher: History of Anesthesia with Emphasis on the Nurse Specialist. J.B. Lippincott, 1953, ISBN 0-8240-6525-5, Chapter 7: Illegal or Legal? (aana.com (Memento des Originals vom 1. Mai 2011 im Internet Archive)).
  40. ↑ Bennetts FE: Thiopentone anaesthesia at Pearl Harbor. In: Br J Anaesth. 75. Jahrgang, Nr. 3, September 1995, S. 366–8, doi:10.1093/bja/75.3.366, PMID 7547061 (oxfordjournals.org [abgerufen am 18. Juli 2008]).
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