Thiopental

Uses and Administration

Thiopental is a short-acting barbiturate anaesthetic. It is given intravenously, usually for the induction of general anaesthesia ( Refer to ), but may be used as the sole anaesthetic to maintain anaesthesia for short procedures with minimal painful stimuli. It is also used in anaesthesia as a supplement to other anaesthetics and as a hypnotic in balanced anaesthesia. Thiopental sodium may also be used intravenously in the control of refractory tonic-clonic status epilepticus and in neurosurgical patients to reduce increased intracranial pressure. It has also been given rectally for basal anaesthesia or basal narcosis.

Thiopental does not usually produce excitation and induction of anaesthesia is usually smooth. It has poor muscle relaxant properties and a muscle relaxant must be given before intubation is attempted. Thiopental also has poor analgesic properties and small doses may even lower the pain threshold. Recovery from moderate doses usually occurs within 10 to 30 minutes, but the patient may remain sleepy or confused for several hours. Large doses, repeated smaller doses, or continuous use may markedly delay recovery.

In anaesthesia, the dosage of thiopental varies greatly according to the state of the patient and the nature of other drugs being used concurrently (see under Precautions Refer to and Interactions Refer to for further details). Thiopental is usually given intravenously as the sodium salt as a 2.5% solution but a 5% solution is occasionally used. UK licensed product information states that a typical dose for inducing anaesthesia is 100 to 150 mg injected over 10 to 15 seconds, repeated after 30 to 60 seconds according to response. It also recommends that the total dosage used should not exceed 500 mg; in pregnant patients the total maximum dose is 250 mg. In some other countries, it has been recommended that induction begin with a test dose of 25 to 75 mg; thereafter, a dose of 50 to 75 mg may be given at intervals of 20 to 40 seconds according to response. Once anaesthesia has been established, additional doses of 25 to 50 mg may be given as necessary. When thiopental is used as the sole anaesthetic, anaesthesia can be maintained by repeat doses as needed or by continuous intravenous infusion of a 0.2 or 0.4% solution.

To reduce elevations of intracranial pressure in neurological patients, thiopental sodium is licensed for use as intermittent bolus injections of 1.5 to 3 mg/kg if adequate ventilation is provided (but see also Cerebrovascular Disorders, Refer to ). Higher doses have been tried.

For suggested doses in refractory tonic-clonic status epilepticus, see Status Epilepticus, Refer to .

For dosage in children and theelderly, see also Refer to and Refer to , respectively.

(last reviewed 2013-12-09; last modified 2011-09-23)

References.

(last reviewed 2013-12-09; last modified 2005-06-22)

References

1. Russo H, Bressolle F. Pharmacodynamics and pharmacokinetics of thiopental.Clin Pharmacokinet. 1998; 35: 95–134. PubMed

Administration in children

For the induction of anaesthesia in children, UK licensed product information recommends that thiopental sodium is given by slow intravenous injection (over 10 to 15 seconds) in a dose of 2 to 7 mg/kg; the dose may be repeated after 1 minute. Intravenous injections are normally given as a 2.5% solution.

In the treatment of prolonged status epilepticus (see Refer to ), the BNFC recommends an initial dose of up to 2 mg/kg in neonates or up to 4 mg/kg in children aged 1 month to 17 years, given as a slow intravenous injection; for all patients, this should then be followed by a continuous intravenous infusion of up to 8 mg/kg per hour, adjusted according to response.

(last reviewed 2013-12-09; last modified 2016-12-22)

Administration in the elderly

It is usually recommended that the dosage of barbiturate anaesthetics is reduced in the elderly. A study1 in elderly patients showed that although reducing the rate of intravenous injection reduced the speed of induction, the dosage required was also reduced. Giving thiopental sodium 2.5% solution at a rate of 125 mg/minute induced anaesthesia in a mean of 90.8 seconds and required a mean dose of 2.8 mg/kg. Corresponding values for a rate of 500 mg/minute were 40.8 seconds and 5 mg/kg, respectively.

(last reviewed 2013-12-09; last modified 2011-09-16)

References

1. Berthoud MC, et al.. Comparison of infusion rates of three i.v. anaesthetic agents for induction in elderly patients.Br J Anaesth. 1993; 70: 423–7. PubMed

Anaesthesia

Some of the adverse effects of the neuromuscular blocker suxamethonium may be reduced when thiopental is used as part of the anaesthetic regimen. For a suggestion that thiopental may help to counteract the rise in intra-ocular pressure associated with the use of suxamethonium for intubation, see under Anaesthesia, Refer to .

(last reviewed 2013-12-09; last modified 2004-08-04)

Cerebrovascular disorders

Barbiturates have been considered as suitable anaesthetics for use in patients with or at risk of raised intracranial pressure. Barbiturate-induced coma (commonly with pentobarbital or thiopental) has been used, both therapeutically and prophylactically, to protect the brain from ischaemia resulting from neurological insults including head injury, stroke, Reye's syndrome, and hepatic encephalopathy.1-3 Rationale includes the ability of barbiturates to reduce intracranial pressure and to reduce metabolic demands of cerebral tissues. Although thiopental protected patients against the neuropsychiatric complications of cardiopulmonary bypass,4 the Brain Resuscitation Clinical Trial I Study Group5 found no cerebral benefit from thiopental in comatose survivors of cardiac arrest. Nor did others6 observe any benefit from thiopental-induced coma in infants with severe birth asphyxia. A review in 1989 considered that there was no convincing evidence of improvement in neurological outcome to justify the risks of the procedure in conditions causing global ischaemia, although use of barbiturates without necessarily inducing coma might have a limited role in reduction of raised intracranial pressure refractory to other therapy. Use of barbiturates in the setting of regional cerebral ischaemia, including use during cardiopulmonary bypass to prevent focal neurological complications, remained controversial.1A systematic review7 came to similar conclusions, pointing out that although the barbiturates may reduce intracranial pressure their hypotensive effects are likely to offset any beneficial action on cerebral perfusion, perhaps accounting for the lack of evidence for any clinical benefit. In addition, there have been individual case reports of effects on blood-potassium associated with thiopental-induced coma (see Effects on Electrolytes, under Adverse Effects and Treatment, Refer to ).

For a discussion of the treatment of raised intracranial pressure, including a mention of the use of barbiturates, see Refer to .

(last reviewed 2013-12-09; last modified 2011-09-16)

References

1. Rogers MC, Kirsch JR. Current concepts in brain resuscitation.JAMA. 1989; 261: 3143–7. PubMed

2. Lyons MK, Meyer FB. Cerebrospinal fluid physiology and the management of increased intracranial pressure.Mayo Clin Proc. 1990; 65: 684–707. PubMed

3. Woster PS, LeBlanc KL. Management of elevated intracranial pressure.Clin Pharm. 1990; 9: 762–72. PubMed

4. Nussmeier NA, et al.. Neuropsychiatric complications after cardiopulmonary bypass: cerebral protection by a barbiturate.Anesthesiology. 1986; 64: 165–70. PubMed

5. Abramson NS, et al.. Randomized clinical study of thiopental loading in comatose survivors of cardiac arrest.N Engl J Med. 1986; 314: 397–403. PubMed

6. Eyre JA, Wilkinson AR. Thiopentone induced coma after severe birth asphyxia.Arch Dis Child. 1986; 61: 1084–9. PubMed

7. Roberts I, Sydenham E. Barbiturates for acute traumatic brain injury. Available in The Cochrane Database of Systematic Reviews; Issue 3. Chichester: John Wiley; 1999 (accessed 16/06/05). PubMed

Status epilepticus

General anaesthesia may be used to control refractory tonic-clonic status epilepticus ( Refer to ). A short-acting barbiturate such as thiopental is usually used.

Doses of thiopental sodium in the treatment of status epilepticus appear to vary widely and may be defined by local clinical protocols. Licensed product information and the BNF recommend a dose of 75 to 125 mg intravenously as a 2.5% solution. Other regimens advocate an initial loading dose followed by further intermittent doses or a continuous infusion. European guidelines for the management of status epilepticus in adults suggest thiopental is started with a bolus of 3 to 5 mg/kg, then further boluses of 1 to 2 mg/kg every 2 to 3 minutes until seizures are controlled, followed by continuous intravenous infusion at a rate of 3 to 7 mg/kg per hour, titrated against EEG burst suppression, which should be maintained for at least 24 hours.1 Recovery may be prolonged.2

For the dose of thiopental in children, see Administration in Children, Refer to .

(last reviewed 2013-12-09; last modified 2014-01-07)

References

1. Meierkord H, et al.. European Federation of Neurological Societies. EFNS guideline on the management of status epilepticus in adults.Eur J Neurol. 2010; 17: 348–55. PubMed

2. Parviainen I, et al.. High-dose thiopental in the treatment of refractory status epilepticus in intensive care unit.Neurology. 2002; 59: 1249–51. PubMed

Precautions

Barbiturate anaesthetics are contra-indicated in severe shock, dystrophia myotonica, and when there is dyspnoea or respiratory obstruction such as in acute severe asthma or when maintenance of an airway cannot be guaranteed.

Barbiturate anaesthetics should be used with caution in patients with dehydration, hypovolaemia, severe haemorrhage, burns, severe anaemia, hyperkalaemia, toxaemia, myasthenia gravis, myxoedema and other metabolic disorders, or severe renal disease. Caution is also required in those with cardiovascular disease, adrenocortical insufficiency, cachexia, or increased intracranial pressure or blood urea. Reduced doses are required in the elderly and in severe hepatic disease.

See also Precautions for General Anaesthetics, Refer to .

(last reviewed 2013-12-09; last modified 2011-09-23)

Breast feeding

No adverse effects have been seen in breast-fed infants whose mothers received thiopental, and the last available guidance from the American Academy of Pediatrics1 considered that it was therefore usually compatible with breast feeding.

In two groups of 8 women undergoing induction with thiopental, the milk-to-plasma ratio was less than 1 in both groups and it was considered that the effects of thiopental on breast-fed infants would be negligible.2

(last reviewed 2013-12-09; last modified 2011-09-23)

References

1. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk.ibid.Pediatrics. 2001; 108: 776–89. PubMed online

2. Andersen LW, et al.. Concentrations of thiopentone in mature breast milk and colostrum following an induction dose.Acta Anaesthesiol Scand. 1987; 31: 30–2. PubMed

Porphyria

The Drug Database for Acute Porphyria, compiled by the Norwegian Porphyria Centre (NAPOS) and the Porphyria Centre Sweden, classifies thiopental as porphyrinogenic; it should be prescribed only for compelling reasons and precautions should be taken in all patients.1

(last reviewed 2013-12-09; last modified 2011-10-13)

References

1. The Drug Database for Acute Porphyria. Available at: Link (accessed 05/10/11)

Adverse Effects, Treatment and Precautions

Adverse Effects and Treatment

As for Phenobarbital, Refer to .

Excitatory phenomena such as coughing, hiccuping, sneezing, and muscle twitching or jerking may occur with any of the barbiturate anaesthetics, particularly during induction, but they occur more frequently with methohexital than with thiopental. Symptoms of laryngeal spasm or bronchospasm including cough and sneezing may also occur during induction. The intravenous injection of concentrated solutions of thiopental sodium such as 5% may result in thrombophlebitis. Extravasation of barbiturate anaesthetics may cause tissue necrosis. Intra-arterial injection causes severe arterial spasm with burning pain and may cause prolonged blanching of the forearm and hand and gangrene of digits. Hypersensitivity reactions have been rarely reported. Barbiturate anaesthetics can cause respiratory depression. They depress cardiac output and often cause an initial fall in blood pressure, and overdosage may result in circulatory failure. Arrhythmias may occur. Excessive doses are associated with hypothermia and profound cerebral impairment. Postoperative vomiting is infrequent but shivering may occur and there may be persistent drowsiness, confusion, and amnesia. Other relatively common postoperative effects include anorexia, malaise, fatigue, and dizziness; delirium has been seen in elderly patients. Headache has also been reported.

See also under Adverse Effects of General Anaesthetics, Refer to .

(last reviewed 2013-12-09; last modified 2011-09-23)

Effects on electrolytes

Although barbiturate-induced coma with intravenous thiopental is used in the management of raised intracranial pressure, it has been associated with reports of hypokalaemia and severe rebound hyperkalaemia.1-3 Frequent monitoring of serum-potassium concentrations during the first 24 hours after stopping thiopental infusion,1and tapering the dose,2 have been recommended by some.

(last reviewed 2013-12-09; last modified 2011-09-23)

References

1. Bouchard PM, et al.. Thiopental-associated dyskalemia in severe head trauma.J Trauma. 2008; 64: 838–42. PubMed

2. Neil MJE, Dale MC. Hypokalaemia with severe rebound hyperkalaemia after therapeutic barbiturate coma.Anesth Analg. 2009; 108: 1867–8. PubMed

3. Jung JY, et al.. Sequential occurrence of life-threatening hypokalemia and rebound hyperkalemia associated with barbiturate coma therapy.Clin Nephrol. 2009; 71: 333–7. PubMed

Hypersensitivity

Anaphylactic reactions to thiopental have been reported1,2 although such reactions are rare. There has also been a report of haemolytic anaemia and renal failure with the development of an anti-thiopental antibody in a patient who had undergone general anaesthesia induced by thiopental.3

(last reviewed 2013-12-09; last modified 2011-09-16)

References

1. Westacott P, et al.. Anaphylactic reaction to thiopentone: a case report.Can Anaesth Soc J. 1984; 31: 434–8. PubMed

2. Moneret-Vautrin DA, et al.. Simultaneous anaphylaxis to thiopentone and a neuromuscular blocker: a study of two cases.Br J Anaesth. 1990; 64: 743–5. PubMed

3. Habibi B, et al.. Thiopental-related immune hemolytic anemia and renal failure: specific involvement of red-cell antigen I.ibid.N Engl J Med. 1985; 312: 353–5. PubMed

Intra-arterial injection

Accidental intra-arterial injection of thiopental sodium produces severe arterial spasm with intense burning pain. Anaesthesia, paresis, paralysis, and gangrene may occur. Therapy has concentrated on dilution of injected thiopental, prevention and treatment of arterial spasm, prophylaxis of thrombosis, thrombectomy and other measures to sustain good blood flow. There has been a report1 of the successful use of urokinase intra-arterially in the management of one patient accidentally given thiopental intra-arterially.

(last reviewed 2013-12-09; last modified 2004-03-22)

References

1. Vangerven M, et al.. A new therapeutic approach to accidental intra-arterial injection of thiopentone.Br J Anaesth. 1989; 62: 98–100. PubMed

Interactions

Producing anaesthesia with the usual dose of barbiturate anaesthetics in patients accustomed to taking alcohol or other CNS depressants may be difficult; additional anaesthetics may be necessary. Patients being treated with phenothiazine antipsychotics may develop increased hypotension. Some phenothiazines, especially promethazine, may also increase the incidence of excitatory phenomena produced by barbiturate anaesthetics; cyclizine may possibly have a similar effect. Opioid analgesics can potentiate the respiratory depressant effect of barbiturate anaesthetics and the dose of the anaesthetic may need to be reduced. Use with nitrous oxide greatly reduces the dose of barbiturate anaesthetics required for anaesthesia. Reduced doses of thiopental may be required in patients receiving sulfafurazole.

See also Interactions of General Anaesthetics, Refer to .

(last reviewed 2013-12-09; last modified 2011-09-23)

Antidepressants

Potentiation of barbiturate anaesthesia may be expected in patients receiving tricyclic antidepressants or MAOIs (see Anaesthesia under Precautions of Amitriptyline, Refer to and for Phenelzine, Refer to , respectively).

(last reviewed 2013-12-09; last modified 2008-08-19)

Antipsychotics

For mention of the effect of droperidol on thiopental see Gastrointestinal Drugs, Refer to .

(last reviewed 2013-12-09; last modified 2008-08-19)

Aspirin

Pretreatment with aspirin, a highly protein-bound drug, has been shown to potentiate thiopental anaesthesia.1

(last reviewed 2013-12-09; last modified 2001-08-17)

References

1. Dundee JW, et al.. Aspirin and probenecid pretreatment influences the potency of thiopentone and the onset of action of midazolam.Eur J Anaesthesiol. 1986; 3: 247–51. PubMed

Gastrointestinal drugs

Metoclopramideprofoundly reduced the dose of thiopental required to produce hypnosis in female patients; droperidolhad a similar effect.1

(last reviewed 2013-12-09; last modified 2004-04-26)

References

1. Mehta D, et al.. Metoclopramide decreases thiopental hypnotic requirement.Anesth Analg. 1993; 77: 784–7. PubMed

Probenecid

Pretreatment with probenecid, a highly protein-bound drug, potentiates thiopental anaesthesia.1

(last reviewed 2013-12-09; last modified 2010-07-09)

References

1. Dundee JW, et al.. Aspirin and probenecid pretreatment influences the potency of thiopentone and the onset of action of midazolam.Eur J Anaesthesiol. 1986; 3: 247–51. PubMed

Pharmacokinetics

Thiopental is highly lipid soluble and when it is given intravenously as the sodium salt, concentrations sufficient to produce unconsciousness occur in the brain within 30 seconds. Onset of action occurs within 8 to 10 minutes when thiopental sodium is given rectally but absorption may be unpredictable if a suspension rather than a solution is used. Recovery from anaesthesia is also rapid due to redistribution to other tissues, particularly fat. About 80% of thiopental may be bound to plasma proteins, although reports show a wide range of figures. Thiopental is metabolised almost entirely in the liver, but as it is only released slowly from lipid stores this occurs at a very slow rate.

It is mostly metabolised to inactive metabolites but a small amount is desulfurated to pentobarbital . Repeated or continuous use can lead to accumulation of thiopental in fatty tissue and this can result in prolonged anaesthesia and respiratory and cardiovascular depression. Elimination of thiopental after bolus injection can be described by a triexponential curve. The terminal elimination half-life has been reported to be 10 to 12 hours in adults and about 6 hours in children. However, values of 26 to 28 hours have been reported in obese patients and pregnant patients at term. Thiopental readily diffuses across the placenta and is distributed into breast milk.

(last reviewed 2013-12-09; last modified 2011-09-16)

References.

(last reviewed 2013-12-09; last modified 2011-09-23)

References

1. Gaspari F, et al.. Elimination kinetics of thiopentone in mothers and their newborn infants.Eur J Clin Pharmacol. 1985; 28: 321–5. PubMed

2. Swerdlow BN, Holley FO. Intravenous anaesthetic agents: pharmacokinetic-pharmacodynamic relationships.Clin Pharmacokinet. 1987; 12: 79–110. PubMed

3. Esener Z, et al.. Thiopentone and etomidate concentrations in maternal and umbilical plasma, and in colostrum.Br J Anaesth. 1992; 69: 586–8. PubMed

4. Gedney JA, Ghosh S. Pharmacokinetics of analgesics, sedatives and anaesthetic agents during cardiopulmonary bypass.Br J Anaesth. 1995; 75: 344–51. PubMed

5. Norman E, et al.. Placental transfer and pharmacokinetics of thiopentone in newborn infants.Arch Dis Child Fetal Neonatal Ed. 2010; 95: 277–F282. PubMed

Preparations: Single-Ingredient

The following preparations list represents a compilation of all available salt forms or related substances for this drug product.

The symbol ¤ denotes a preparation which is discontinued or no longer actively marketed.

ARGENTINA: Bensulf; Hipnopento¤; Pentothal¤; Thipenthal;AUSTRALIA: Intraval Sodium¤; Pentothal;BELGIUM: Nesdonal¤; Pentothal¤;BRAZIL: Thionembutal¤; Thiopentax;CANADA: Pentothal¤;CHILE: Penthotal¤;DENMARK: Pentocur; Pentothal¤;FINLAND: Pentocur; Pentothal¤;FRANCE: Nesdonal¤; Pentothal¤;GERMANY: Trapanal;GREECE: Pentothal¤;HONG KONG: Intraval Sodium¤; Pentothal¤;HUNGARY: Trapanal¤;INDIA: Anesthal; Intraval Sodium;INDONESIA: Pentothal;IRELAND: Intraval Sodium¤;ISRAEL: Pentothal¤;ITALY: Farmotal; Pentothal;MALAYSIA: Pentotex;MEXICO: Inductal¤; Pensodital; Pentarim; Pentothal; Sodipental¤;NETHERLANDS: Nesdonal¤; Pentothal;NORWAY: Pentocur; Pentothal¤;NEW ZEALAND: Intraval¤; Pentothal¤;PHILIPPINES: Pentazol; Penthal; Pentobrim; Pentothal; Thiosol;SOUTH AFRICA: Intraval Sodium¤; Sandothal¤;SINGAPORE: Pentothal¤;SPAIN: Pentothal¤; Tiobarbital;SWEDEN: Pentocur; Pentothal¤;SWITZERLAND: Pentothal¤;THAILAND: Anesthal; Intraval Sodium¤; Pentothal¤; Thiopen;TURKEY: Ekipental; Pental; Pentothal¤;UNITED KINGDOM: Intraval Sodium¤;UNITED STATES: Pentothal¤;VENEZUELA: Pentax; Pentothal¤;

Preparations: Pharmacopoeial

The following preparations list represents a compilation of all available salt forms or related substances for this drug product.

BP 2019: Thiopental Injection;USP 42: Thiopental Sodium for Injection;

Therapeutic Use

• General Anaesthetics

Last Updated 1/21/20