Pharmacology
Anaesthesia
Regarding propofol, which of the following statements is INCORRECT:
Answer:
Elderly patients have a reduced volume of distribution and slower clearance of the drug. They are therefore more sensitive to the effects of propofol and the drug wears off more slowly. They need less of the drug, which should be injected slowly, monitoring its effect on the patient. The opposite is true in children, who need larger doses of propofol. This is particularly so in children under three years of age. Propofol is not recommended for induction of anaesthesia in children under one month of age or for maintenance of anaesthesia in children under three years old.Propofol
Pharmacology / Anaesthesia
Last Updated: 21st June 2020
Propofol is a short-acting drug with a rapid onset, and a rapid recovery with less hangover effect than the other intravenous anaesthetics. It can produce hypotension and respiratory depression to a greater extent than other intravenous anaesthetic agents.
Uses
Propofol is the most widely used intravenous anaesthetic in the UK. It can be used for induction or maintenance of anaesthesia in adults and children, but it is not generally used in neonates. It can also be used for sedation during procedures and sedation for adults in intensive care. Propofol reduces airway and pharyngeal reflexes, therefore it is the ideal drug to use with the laryngeal mask airway (LMA).
Administration
The induction dose in an unpremedicated young adult is 2 – 2.5 mg/kg body weight. Premedication with opioid or benzodiazepine markedly reduces the dose of propofol needed to induce anaesthesia. Elderly patients need a smaller dose whereas children need a larger dose.
After induction with propofol, anaesthesia can be maintained in one of two ways; using a volatile inhalational agent or using an infusion of propofol.
Pharmacokinetics
When a single induction dose of 2 mg/kg is injected, there is a rapid rise in the blood levels of propofol and loss of consciousness occurs within 20 - 40 s. Clinically this will be manifest by loss of verbal contact with the patient. Blood levels peak around 90 - 100 s. Blood levels then rapidly decline due to the redistribution and elimination of the propofol. The distribution half life of propofol is 2 to 8 min; elimination half life can be up to 6 h. Return of consciousness occurs within 10 min.
Propofol is very rapidly cleared from the blood and has a clearance rate of 1.5 to 2.2 L/min. It is rapidly metabolised in the liver. There are two metabolic pathways involved – conjugation to glucuronide and hydroxylation to quinol which is subsequently glucuronidated. Clearance of propofol from the plasma is greater than would be expected if it were only metabolised in the liver, therefore there are probably extra-hepatic sites of its metabolism. Less than 1% of a dose is excreted unchanged by the kidneys.
Pharmacodynamics
- Central nervous system
- Sedation, loss of consciousness and anaesthesia
- Antiemetic effects
- Reduced cerebral metabolism and blood flow with consequent reduction in intracranial pressure and cerebral perfusion pressure
- Reduced intraocular pressure
- Cardiovascular system
- Reduced systolic, diastolic and mean blood pressure (due to vasodilation and a reduction in pre- and afterload)
- Slightly negative inotropic effect
- Heart rate remains mostly unchanged
- Respiratory system
- Decreased tidal volume and respiratory rate producing respiratory depression
- Decreased ventilatory response to carbon dioxide
- Reduced upper airway reflexes
Cautions
In hypotensive states, the blood flow to fat and muscle is reduced thus the volume of distribution is reduced and patients will be more sensitive to the effects of propofol. Propofol itself can produce hypotension and great caution must be exercised in giving propofol to hypotensive patients. If a patient is in a state of shock, it is advisable not to use propofol for induction of anaesthesia.
Side Effects
Possible side effects include:
- Hypotension
- Bradycardia
- Tachycardia
- Arrhythmias
- Pruritus and/or rash
- Nausea and/or vomiting
- Pain on injection
- Excitation phenomena such as involuntary movements
- Headache
- Transient apnoea
- Propofol infusion syndrome (prolonged infusion of propofol doses exceeding 4 mg/kg/hour may result in potentially fatal effects, including metabolic acidosis, arrhythmias, cardiac failure, rhabdomyolysis, hyperlipidaemia, hyperkalaemia, hepatomegaly, and renal failure)
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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 |
