Thiopental: An Overview

Question 1

What is the chemical structure of thiopental?

Answer 1

sodium 5-ethyl-5-(1-methylbutyl)-2-thiobarbiturate.

Question 2

What does thiopental look like?

Answer 2

It is a yellowish powder. It is stored in ampoules in an atmosphere of nitrogen to prevent oxidation. The ampoules also contain 6 % anhydrous sodium carbonate to increase solubility in water.

Question 3

How many mg are in a vial of thiopental and how is it drawn up?

Answer 3

500mg, drawn up into 20ml distilled water to make 25mg/ml solution (2.5%).

Question 4

What is the pH of thiopental solution?

Answer 4

10.5

Question 5

Which fluid would cause precipitation of thiopental?

Answer 5

Ringer’s lactate (Hartmanns). NB no other drugs should be drawn up with it as these can also cause precipitation.

Question 6

In which two ways is the barbiturate ring altered in thiopental?

Answer 6

A sulphur atom is substituted for the oxygen at position two of the barbiturate ring, resulting in a rapid onset and shorter duration of action.

A methyl butyl group is substituted at position five of the barbiturate ring. This increases the potency of the drug.

Question 7

What makes a 1% solution?

Answer 7

1g in 100ml (or 10mg/ml)

Question 8

You have estimated that your patient needs 300 mg of thiopental to induce anaesthesia. How many millilitres of a 2.5 % solution of thiopental would you inject to give 300 mg?

Answer 8

12ml

Question 9

What is the induction dose of thiopental for a healthy young adult?

Answer 9

4-5 mg/kg body weight.

Question 10

What is the pKa of thiopental?

Answer 10

7.6 which means that about 50-60 % of the drug is non-ionized at a body pH of 7.4.

As pH decreases (acidaemia), the proportion of non-ionized drug increases.

Question 11

How does redistribution of thiopental occur in the body?

Answer 11

Redistribution occurs quickly to the vessel rich group (e.g. liver, kidney, brain) of tissues and then to muscle and fat.

The level in the muscles peaks at around 20 min and in the fat at around 45 min.

Question 12

Metabolism of thiopental is very slow and not related to return of consciousness (this is due to redistribution in fat). How does metabolism occur?

Answer 12

Metabolism of thiopental occurs in the liver. It is mainly broken down into inactive carboxylic acid analogues which are excreted by the kidneys. A small fraction of thiopental undergoes desulphuration to pentobarbital which is a long acting hypnotic. Inhibition of hepatic microsomal enzyme activity may prevent the main metabolic pathway from taking place and increase the amount that is desulphurated.

Question 13

What is the implication of slow metabolism of thiopental?

Answer 13

Only 10 to 15 % of the dose of thiopental is metabolized per hour. Therefore up to about 30 % of the injected dose of thiopental may still remain in the body after 24 h. If it is necessary to give further doses of thiopental within the first two days, a smaller dose is required.

Question 14

What is the volume of distribution of thiopental?

Answer 14

The volume of distribution is 1.2–2.0 L/kg body weight.

Question 15

What are the distribution and elimination half lives of thiopental?

Answer 15

Its distribution half life is 2-8 min; elimination half life about 10 h.

Question 16

What are four factors affecting the pharmacokinetics of thiopental?

Answer 16

1. Protein binding
2. Age
3. Enzyme induction
4. Chronic alcohol abuse

Question 17

Explain how protein binding affects the pharmacokinetics of thiopental.

Answer 17

About 75-85 % of an injected dose of thiopental is bound to plasma protein, mainly albumin. Conditions associated with low plasma proteins such as malnutrition, chronic renal failure and cirrhosis of the liver result in more of the injected thiopental being unbound and a reduced dose would normally be required.

Other drugs which are bound to serum albumin could also increase the fraction of unbound thiopental, and the dose would have to be reduced.

Question 18

Explain how age affects the pharmacokinetics of thiopental.

Answer 18

The volume of distribution is less in the elderly and a smaller dose is required.

Metabolism and elimination of thiopental is impaired in the elderly and recovery may be delayed.

Children need a larger dose to induce anaesthesia and the effects tend to wear off sooner.

Question 19

Explain how enzyme induction affects the pharmacokinetics of thiopental.

Answer 19

Long term treatment with drugs that induce the cytochrome P450 enzyme system in the liver (e.g. phenytoin or other barbiturates such as phenobarbitone) results in a reduced effect of thiopental.

Enzyme induction results in quicker breakdown of the thiopental but this has only a minor effect. There is probably a degree of tolerance at the cellular level in patients on long term barbiturates which would account for the larger doses of thiopental needed.

Question 20

Explain how chronic alcohol abuse affects the pharmacokinetics of thiopental.

Answer 20

These patients are less sensitive to thiopental and a larger dose may be required. This is probably due to the development of tolerance at a cellular level.

Question 21

Thiopental is rapidly excreted unchanged by the kidneys T/F

Answer 21

False. Thiopental is broken down in the liver to pentobarbital and to other inactive, water soluble metabolites which are then excreted by the kidneys.

Question 22

Thiopental is rapidly metabolised T/F

Answer 22

False. The metabolism of thiopental is slow, only 10-15 % of the dose of thiopental is metabolized per hour.

Question 23

Thiopental is un-ionized at physiological pH T/F

Answer 23

False

Question 24

A smaller dose than normal of thiopental would be required to induce anaesthesia in a 40 year old patient with a history of chronic renal failure T/F

Answer 24

True. Chronic renal failure is generally associated with low serum albumin. As thiopental is bound to serum albumin, more free drug may be available. Patients with chronic renal failure may also have high blood pressure and may have a larger fall in the blood pressure with a normal dose of thiopental.

Question 25

In which patients is thiopental absolutely contraindicated?

Answer 25

Barbiturates induce hepatic enzymes. The enzyme gamma aminolevulinic acid synthetase, which produces porphyrins, can be induced and in susceptible patients an attack of acute intermittent porphyria can occur. Thiopental is therefore absolutely contraindicated in these patients.

Question 26

Which endocrine condition would cause a patient to need a reduced dose of thiopental?

Answer 26

Patients who are hypothyroid are very sensitive to the actions of thiopentone. A smaller dose is needed and it will act for much longer.

Question 27

What can happen if thiopental is injected intra-arterially?

Answer 27

Accidental intra-arterial injection causes vasospasm and may lead to thrombosis and tissue necrosis. The patient will complain of severe pain if the injection is intra-arterial. Extravasation of thiopental during injection can also lead to tissue damage.

Question 28

How would you manage an intra-arterial injection of thiopental?

Answer 28

1. Stop the injection
2. Leave the cannula in the artery
3. Call for help
4. Inject a vasodilator (e.g. papaverine 20–40 mg dissolved in 20 ml normal saline)
5. Consider a stellate ganglion or a brachial plexus block. This may reduce the spasm of the artery
6. Give heparin IV and start oral anti-coagulants after the operation
7. Explain to the patient what happened
8. Follow your hospital’s protocol for a critical incident

Question 29

A 5 % solution of thiopental is preferred because the volume you need to inject is smaller T/F

Answer 29

False. A 5 % solution would cause greater tissue damage on extravasation or intra-arterial injection. This risk is greater than any benefit due to a lesser volume of drug being injected.

Question 30

In a patient who needs a second anaesthetic 6 h after the first, the same dose of thiopental would be needed to induce anaesthesia T/F

Answer 30

False. Thiopental is metabolized very slowly and a substantial amount would still be in the body fat stores after 6 h, therefore a smaller dose would be needed to induce anaesthesia.

Question 31

Thiopental is the induction agent of choice in a patient who has day case surgery T/F

Answer 31

False. The slow metabolism also results in prolonged drowsiness and a feeling of a ‘hangover’, so thiopental is not the induction agent of choice for day case surgery. Propofol is preferred.

Question 32

Thiopental allows early insertion of a laryngeal mask airway T/F

Answer 32

False. Thiopental does not depress laryngeal reflexes and early insertion of a laryngeal mask airway (or even an oropharyngeal airway) can induce laryngospasm.

Question 33

Thiopental can cause hypotension and respiratory depression T/F

Answer 33

True