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%)

 

List:

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

·      4y0

·      75yo 70kg

·      40yo shock

 

Intro:

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:

o ↑Dose -> ↑Ce

o ↑Speed of injection -> ↓dilution by venous return -> ↑Ce

o ↓Total blood volume (TBV 70mL/kg) hence central blood volume-> ↓dilution

o ↓Cardiac output (CO) (normally 5L/min 70mL/kg) -> ↓dilution by venous return

o ↑%CO to brain (normally 750mL/min, 50mL/min/100g, 15% CO) -> ↑dose to brain

Effect of pre-medication

·   Pre-med synergism -> ↓PPF required

·   With ?0.025mg/kg midazolam: 30% ↓PPF requirement for hypnosis

·   With 1mcg/kg fentanyl: 20% ↓PPF dose for hypnosis, 50% ↓PPF dose for immobility

·   Hence ↓ risk of side effects

 

4yo 15kg:

Dose

·   3-5mg/kg IV induction

·   2-3mg/kg between inhalational induction and airway securement

PK

·   ↑ CO/kg ~100-140mL/kg/min cf. 70mL/kg/min, ↑↑ when anxious

·   ↑ TBV ~80mL/kg cf. 70mL/kg -> ↑CBV

·   ↑ %CO to brain, approx. +50% – 75mL/min/100g

PD

·   ↑Resistance to anaesthetics

o Age: youth ->↑MAC, ↑PPF Ce50 (peak at 6 months)

o Anxiety: ↑CNS and SNS activity

Risk analysis

·   ↑Risk of laryngospasm if underdosed

o Sensitive laryngeal reflexes

·   ↓Risk CVS toxicity if overdose

o Responsive vessels

o Effective autoregulation

o Rapid baroreceptor response

 

75yo 70kg:

Dose

·   1-1.25mg/kg = 70-90mg

PK

·   Changes sarcopaenia; attenuated if fit

o CO: variable ↓

o 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

 

40yo 70kg hypovolaemic shock:

Dose

·   Healthy: 2-2.5mg/kg

·   Shock: 10% i.e. 0.2-0.25mg/kg = 20mg

·   Resuscitated: 50% i.e. 1-1.25mg/kg = 70-90mg

(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, ↓CBV (≥20% blood vol loss -> shock)

o ↔ CBF (due to SNS-mediated vasoconstriction sparing vital organs)

o ↑↑ %CO to brain (e.g. 30% cf. 15%)

PD

·   ↓MAC (hence ↓PPF Ce50)

o mAP<50

o Acidosis

Risk analysis

·   ↓Risk laryngospasm

·   ↑↑Risk CVS toxicity if overdosed

 

 

 

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