2018A07 Justify the dose of propofol you would expect to use to induce anaesthesia in the following scenarios,
using pharmacokinetic and pharmacodynamic principles:
a) 4 year old child weighing 15kg (25%)
b) 75 year old man weighing 70kg (25%)
c) 40 year old weighing 70kg with severe hypovolaemic shock (50%)

· Intro – propofol, why IV induction, IV kinetics, pre-med

· 4y0

· 75yo 70kg

· 40yo shock

Propofol

· Rapid onset IV anaesthetic

· Effects via GABA-A in brain > spinal cord

Dosing

· Aims: unconsciousness, airway reflex suppression

· If too much: -> CVS toxicity (↓SVR, ↓cardiac function, ↓mAP, ↓organ perfusion)

· If not enough: -> airway complications (laryngospasm, aspiration), awareness

Determinants

Factors affecting propofol requirement:

Administration:

· ↑Speed of injection -> ↓dilution by venous return

Kinetic:

· N.B. induction kinetics ≠ steady state kinetics

· ↓Cardiac output -> ↑dilution (normally 70mL/kg/min)

· ↓Central blood volume -> ↓dilution (∝ total blood volume, normally 70mL/kg)

· ↑% Cardiac output to brain (normally 58mL/min/100g, 15% CO)

Dynamics: (i.e. Cp50 for unconsciousness)

· Patient: ↓Cp50 with age (↓MAC 6% per year, peak at 6mo)

· Pathology: ↓Cp50 with severe illness (↓mAP, ↓O2, ↑CO2, ↓pH, ↓temp)

· Adjuvants: midazolam 0.025mg/kg -> ↓30%; 1mcg/kg fentanyl -> ↓20%
(synergism -> ↓propofol -> ↓toxicity)

Dose	· 3-5mg/kg IV induction (say 75mg!)
PK	· ↑CO/kg ~100-140mL/kg/min cf. 70mL/kg/min, ↑↑ when anxious · ↑TBV ~80mL/kg cf. 70mL/kg -> ↑CBV · ↑%CO to brain, approx. +30% – 75mL/min/100g
PD	· ↑Resistance to anaesthetics o Age: youth ->↑MAC, ↑Cp50 o Anxiety: ↑CNS and SNS activity
Risk analysis	· ↑Risk of airway complications o Sensitive laryngeal reflexes · ↓Risk CVS toxicity o Responsive vessels o Effective autoregulation o Rapid baroreceptor response

Dose	· 1-1.5mg/kg (say 75mg!)*
PK	· Changes ∝ sarcopaenia; attenuated if fit o CO: variable ↓ o TBV: variable ↓
PD	· ↓MAC with age · ↓Laryngeal reflexes
Risk analysis	· ↓Risk of airway complications o ↓Laryngeal reflexes · ↑Risk of CVS toxicity o ↓Autoregulation o ↓Baroreceptor response o Atherosclerosis

*I’d probably give 100mg IRL, but it’s so neat that the scenarios arrive at the same figure :)

Dose	· Healthy: 2-2.5mg/kg · Shock: 10% i.e. 0.2-0.25mg/kg (say 20mg) · Resuscitated: 50% i.e. 1-1.25mg/kg (say 75mg!) (see Pharmacology and Physiology for Anaesthetists, Hemmings and Egan, 2nd Edition)
PK	· Changes ∝ blood loss o ↓ CO (due to ↓preload, attenuated by ↑SNS) o ↓ TBV (by definition) o ↑%CO to brain (due to cerebral autoregulation + peripheral vasoconstriction)
PD	· ↓MAC, ↓Cp50 o mAP<50 o Acidosis
Risk analysis	· ↓Risk of airway complications · ↑↑Risk of CVS toxicity