Pharmacology
Anaesthesia
Which of the following is NOT a typical effect of thiopental sodium:
Answer:
Thiopental causes decreased tidal volume and respiratory rate with resultant respiratory depression and transient apnoea. Thiopental reduces systolic, diastolic and mean arterial blood pressure through vasodilation and a reduction in preload and afterload. Thiopental often causes an increase in heart rate at induction. Thiopental causes a reduced cerebral metabolism with a consequent reduction in cerebral blood flow and intracranial pressure.Thiopental Sodium
Pharmacology / Anaesthesia
Last Updated: 4th April 2019
Thiopental sodium, a barbiturate, was the most commonly used intravenous induction agent until the introduction of propofol. It is still commonly used in the UK and is the preferred drug for rapid sequence induction of anaesthesia. Induction is generally smooth and rapid but dose-related cardiovascular and respiratory depression can occur. Recovery after a single dose is rapid due to redistribution, however, metabolism is slow and sedative effects can persist for 24 hours. Repeated doses have a cumulative effect and recovery is much slower.
Administration
The induction dose of thiopental for a healthy young adult is 4 - 5 mg/kg body weight. Thiopental is prepared as a 2.5 % solution. The recommended induction dose should be given over a period of about 20 s. If the thiopental is injected more rapidly the onset of anaesthesia is quicker and the cardiovascular and respiratory depression greater.
A reduced dose may be required in:
- Conditions associated with low plasma protein such as malnutrition, chronic renal failure and cirrhosis
- The elderly
- Hypothyroidism
An increased dose may be required in:
- Children
- Chronic alcohol abuse
- Long term treatment with drugs that induce the cytochrome P450 enzyme system in the liver
Pharmacokinetics
After a single induction dose of 4 mg/kg body weight, there is a rapid rise in the plasma level of thiopental. The plasma level peaks at around 90 to 100 s and then decreases rapidly due to redistribution. 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. Loss of consciousness occurs in about 30 s (one arm-brain circulation time) and return of consciousness occurs within 10 min.
Thiopental is metabolised only very slowly and metabolism plays no part in the return of consciousness. 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. The distribution half life is 2 - 8 min and elimination half life is about 10 h.
Pharmacodynamics
- Central nervous system
- Loss of consciousness and anaesthesia
- Reduced cerebral metabolism with a consequent reduction in cerebral blood flow and intracranial pressure
- Anticonvulsant effects (may be used in refractory status epilepticus)
- Reduced intraocular pressure
- Cardiovascular system
- Reduced systolic, diastolic and mean blood pressure (due to vasodilation and a decrease in preload and afterload); fall in BP is less than with propofol but can be significant in patients who have cardiac disease or are hypovolaemic
- Heart rate may increase slightly at induction
- Respiratory system
- Reduced respiratory rate and tidal volume with respiratory depression and transient apnoea
- Sensitised laryngeal and pharyngeal reflexes (may result in laryngospasm in response to surgical stimulation, presence of secretions, or the insertion of oral airway or laryngeal mask airway at too light a plane of anaesthesia)
- Decreased ventilatory response to hypoxia (can precipitate bronchospasm in susceptible patients)
Cautions
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 absolutely contraindicated in these patients.
Side Effects
- Extravasation of thiopental during injection can lead to tissue damage. Accidental intra-arterial injection causes vasospasm and may lead to thrombosis and tissue necrosis.
- Involuntary muscle movements on induction
- Cough and laryngospasm
- Arrhythmias
- Hypotension
- Headache
- Hypersensitivity reactions
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
