2018A Question 07
Justify the dose of propofol you would expect to use to induce anaesthesia in the following scenarios, using pharmacokinetic and pharmacodynamic principles:
- 4 year old child weighing 15kg (25%)
- 75 year old man weighing 70kg (25%)
- 40 year old weighing 70kg with severe hypovolaemic shock (50%)
Examiner Report
63% of candidates achieved a pass in this question.
To pass this question required documenting appropriate dosing regimens and justifying them using pharmacological principles. The induction dose of propofol is primarily dependent on the volume of the intravascular compartment, cardiac output and the brain sensitivity to the drug. Most candidates described appropriate doses and explained the altered volumes of distribution in each scenario. The effect of cardiac output on the apparent volume of distribution was poorly understood with most discussions being exclusively devoted to the effect on the duration of onset of action. Pharmacodynamic concerns particularly with regards to adverse cardiovascular effects were generally well noted. Pleasingly most candidates noted that propofol should be used with great caution in the shocked patient and a markedly reduced dose is indicated.
Many candidates provided a generic list of pharmacokinetic and pharmacodynamic data for propofol which did not attract marks. A common misconception made was that alterations in clearance and metabolism affect induction doses. They do not. Many candidates asserted that an elderly patient would have a significantly reduced cardiac output. This is not the case in an elderly patient without co-morbidities. Several candidates erroneously suggested that cardiac output in a patient with severe hypovolaemic shock would be increased. Better answers addressed scenario (c) well and noted that the shocked patient has a markedly reduced intravascular compartment volume and cardiac output with preservation of normal CBF - consequently a larger proportion of their contracted blood volume is directed to a brain which has increased sensitivity to anaesthetic agents. Again, better candidates described how they would ameliorate the adverse pharmacodynamic effects of propofol in this scenario.
Model Answer
Structure:
- Introduction
- 4, 15kg
- 75M, 70kg
- 40, 70kg, hypovolaemic shock
Introduction
| Factor | Details |
|---|---|
Propofol (PPF) |
- Rapid onset IV anaesthetic - Positive allosteric modulator at GABA-A in brain > spinal cord - Aims: Ensure hypnosis, amnesia, immobility, +/- depression of airway reflexes - Induction side effects: ↓ cardiac output (CO), ↓ SVR, ↓ MAP, ↓ organ perfusion, apnoea |
| Why IV induction? | - ↑ Rate of rise in effect site concentration (Ce) → ↑ Rate of onset - ↓ Time in Guedel’s stage 2 → ↓ Vomiting/aspiration, laryngospasm |
| IV induction kinetics | - ≠ Steady state kinetics - Path: Peripheral veins → Central blood volume (great vessels, heart, lungs) → Effect site - Factors increasing peak Ce: - ↑ Dose → ↑ Ce - ↑ Speed of injection → ↓ Dilution by venous return → ↑ Ce - ↓ Total blood volume (TBV 70mL/kg) hence central blood volume→ ↓ Dilution - ↓ Cardiac output (CO) (normally 5L/min 70mL/kg) → ↓ Dilution by venous return - ↑ %CO to brain (normally 750mL.min-1, 50mL.min-1/100g, 15% CO) → ↑ Dose to brain |
| Effect of pre-medication | - Pre-med synergism → ↓ PPF required - With ?0.025mg.kg-1 midazolam: 30% ↓ PPF requirement for hypnosis - With 1μg/kg fentanyl: 20% ↓ PPF dose for hypnosis, 50% ↓ PPF dose for immobility - Hence ↓ risk of side effects |
4, 15kg
| Factor | Details |
|---|---|
| Dose | - 3-5mg.kg-1 IV induction - 2-3mg.kg-1 between inhalational induction and airway securement |
| PK | - ↑ CO/kg ~100-140mL.kg-1.min-1 cf. 70mL.kg-1.min-1, ↑↑ when anxious - ↑ TBV ~80mL/kg cf. 70mL/kg → ↑ CBV - ↑ %CO to brain, approx. +50% – 75mL.min-1/100g |
| PD | - ↑ Resistance to anaesthetics - Age: Youth →↑ MAC, ↑ PPF Ce50 (peak at 6 months) - Anxiety: ↑ CNS and SNS activity |
| Risk analysis | - ↑ Risk of laryngospasm if underdosed - Sensitive laryngeal reflexes - ↓ Risk CVS toxicity if overdose - Responsive vessels - Effective autoregulation - Rapid baroreceptor response |
75M, 70kg
| Factor | Details |
|---|---|
| Dose | - 1-1.25mg.kg-1 = 70-90mg |
| PK | - Changes ∝ sarcopaenia; attenuated if fit - CO: Variable ↓ - TBV, CBV: Variable ↓ |
| PD | - ↓ MAC with age: 6% per decade after 40 (hence ↓ PPF Ce50) - ↓ Laryngeal reflexes |
| Risk analysis | - ↓ Risk of laryngospasm if underdosed - ↓ Laryngeal reflexes - ↑ Risk CVS toxicity if overdosed - Atherosclerosis → ↓ Autoregulation - Poor baroreceptor response |
40, 70kg, Hypovolaemic Shock
| Factor | Details |
|---|---|
| Dose | - Healthy: 2-2.5mg.kg-1 - Shock: 10% i.e. 0.2-0.25mg.kg-1 = 20mg - Resuscitated: 50% i.e. 1-1.25mg.kg-1 = 70-90mg |
| PK | - Changes ∝ blood loss - ↓ CO (due to ↓ preload, attenuated by ↑ SNS) - ↓ TBV, ↓ CBV (≥20% blood vol loss → Shock) - ↔ CBF (due to SNS-mediated vasoconstriction sparing vital organs) - ↑↑ %CO to brain (e.g. 30% cf. 15%) |
| PD | - ↓ MAC (hence ↓ PPF Ce50) - MAP≤50 - Acidosis |
| Risk analysis | - ↓ Risk laryngospasm - ↑↑ Risk CVS toxicity if overdosed |