Show the model answerAttempt it first — that is what makes it stick
What earns the marks10 marks
| (a) Four components with proportions | 1 mark. Naming them is not enough — 1%, 10%, 1.2%, 2.25%, and the preservative |
|---|---|
| (b) Organised in three headings | 3 marks. Physicochemical, pharmacokinetic, pharmacodynamic. Points not organised this way are the ones candidates overlook |
| (b) Specific to propofol | No mark if the ideal property named does not actually belong to propofol. Name its superiority over the other available agents |
| (c) Mechanism, not the effect | 6 marks. The commonest single failure: BP down, CO down, SVR down, with no explanation of why |
| (c) The bradycardia | Specifically recorded as forgotten. Reflex tachycardia is rare; bradycardia and even asystole occur |
| (c) Risk factors | Explicitly said to add marks. Dose, speed, age, volume status, concurrent opioid |
1 mark
The contents of an ampoule of 1% propofol
Four components and a preservative, each with a proportion and a reason.
| Component | Proportion | What it is for |
|---|---|---|
| Propofol | 1% — 10 mg/mL | The drug. 2,6-diisopropylphenol, insoluble in water, which is why everything else is here |
| Soybean oil | 10% | The lipid phase of the oil-in-water emulsion, in which the propofol is dissolved |
| Purified egg phospholipid | 1.2% | Emulsifier — egg yolk lecithin, which stabilises the oil droplets in the aqueous phase |
| Glycerol | 2.25% | Tonicity-adjusting agent, making the emulsion isotonic |
| Sodium hydroxide | To pH ≈ 7 | pH adjustment |
| Preservative — EDTA, or sodium metabisulfite, or benzyl alcohol | Formulation-dependent | Antimicrobial. The emulsion is an excellent bacterial growth medium; this was added after that was recognised |
Commonly lost: Most candidates named the contents but did not give the correct proportions, and most forgot the preservative. Four numbers and one extra component secure the whole mark.
3 marks
Features of propofol as an ideal induction agent
Answer under three headings. The instruction was to name what makes propofol superior to the other available agents, not to recite the generic ideal-agent list.
| Category | Property of propofol | Why it is superior to the alternatives |
|---|---|---|
| Physicochemical | ||
| Ready-to-use formulation | Supplied as a stable emulsion; no reconstitution | Thiopentone must be reconstituted and keeps for days, not months |
| pKa 11 | Almost entirely unionised at pH 7.4 | Its available fraction does not move with the patient's acid–base state, unlike thiopentone's |
| Neutral pH | pH about 7 | Safe intra-arterially, where thiopentone at pH 10.5 precipitates and causes distal ischaemia |
| Pharmacokinetic | ||
| Very high clearance | 1.5–2.2 L/min, which exceeds hepatic blood flow | Extrahepatic metabolism exists — mainly renal — so no dose adjustment is needed in hepatic disease |
| Short context-sensitive half-time | Under 40 minutes even after 8 hours of infusion | The property that makes total intravenous anaesthesia possible; thiopentone's rises without plateau |
| Rapid onset and offset | One arm–brain circulation; 5–10 minutes after 2–2.5 mg/kg | Ketamine does not achieve onset in one arm–brain circulation |
| Metabolites of little or no activity | Conjugated to inactive glucuronides | Thiopentone's metabolites include pentobarbitone, a long-acting barbiturate |
| Pharmacodynamic | ||
| Airway reflexes obtunded | A supraglottic airway can be placed without a relaxant | No other induction agent does this as reliably; thiopentone may provoke laryngospasm |
| Antiemetic | At sub-hypnotic concentrations | Ketamine and etomidate both increase nausea and vomiting |
| Anticonvulsant | Dose-dependent | Useful, though the excitatory movements have to be distinguished from seizures |
| No adrenal or endocrine effect | None | Etomidate suppresses 11β-hydroxylase for up to 72 hours after one dose |
Commonly lost: No mark is awarded if the ideal property named does not belong to propofol. Listing the generic sixteen-point ideal-agent list without saying which ones propofol actually meets answers a different question — and the fourth section of the April 2023 paper is where that list is what was wanted.
6 marks — the section that decided the question
The cardiovascular effects of propofol
Every effect gets its mechanism. The question was decided here, and it was decided on whether the mechanism was given.
| Effect | Magnitude | Mechanism |
|---|---|---|
| Fall in systemic vascular resistance | 15–25% | The dominant effect, and two mechanisms act together: inhibition of central sympathetic vasoconstrictor outflow, and a direct action on vascular smooth muscle through reduced intracellular calcium availability and stimulation of nitric oxide release |
| Venodilatation and reduced preload | Contributes to the fall in output | Increased venous capacitance reduces venous return. This is the limb most readily corrected by fluid loading, which is why fluid given as tolerated blunts the response |
| Reduced myocardial contractility | Present, secondary in magnitude | Direct negative inotropy from reduced transsarcolemmal calcium influx. Real, but smaller than the vascular effect at clinical doses |
| Fall in mean arterial pressure | 10–40% | The product of the three above. The wide range reflects how strongly it depends on dose, speed of injection, volume status and age |
| Heart rate unchanged or falling; bradycardia and asystole reported | About −10% | Propofol resets and blunts the baroreceptor reflex, so the reflex tachycardia that should defend the pressure does not appear. There is also a vagotonic effect. This is the finding that distinguishes propofol from thiopentone, which does produce a compensatory tachycardia |
| Reduced myocardial oxygen consumption and coronary blood flow | Both fall, roughly in parallel | Reduced afterload and contractility lower demand; coronary flow follows metabolic demand down. The balance is usually maintained, but not in a patient whose coronary perfusion pressure was already marginal |
Commonly lost: Most candidates mentioned the cardiovascular effects only, without describing the mechanism, and forgot the bradycardia or even asystole. Both were explicitly recorded. Writing “blood pressure falls” where the answer needed “blood pressure falls because systemic vascular resistance falls, and the baroreflex that should compensate is blunted” is the difference between the two halves of this cohort.
The teaching behind this section — propofol’s cardiovascular effects