2008B02 Describe the pharmacokinetic principles of total intravenous anaesthesia using propofol.

 

List:

·     Principles: aim, delivery, monitoring

·     Compartment modelling

·     Induction

·     Maintenance

·     Offset

 

Principles:

Aim

·  Achieve target rapidly and with minimal overshoot

·  Maintain target with minimal variability

Delivery

·  Manual: e.g. Bristol technique

·  TCI: Marsh (Cpt), Schnider (Cet)

Monitoring

·  EEG monitoring

·  Vital signs

·  No means of measuring [propofol] at the bed-side

Summary

·  Loading dose followed by infusion

·  Infusion rate decreases as compartment equilibration occurs

·  Over-pressuring of central compartment accelerates rate of rise in effect site

Graph (TCI)

 

Compartment modelling:

Diagramme

Limitations

·  Fundamental oversimplification of body composition

·  Inability to measure Ce for propofol

·  Inaccuracy at induction

·  Inaccurate estimates of lean weight

·  Kinetic variability: e.g. blood volume

·  Dynamic variability: e.g. receptor polymorphism

·  Processor maximum rate 1200mL/h

 

Induction:

TCI induction kinetics

·  Poorly modelled

·  Loading dose = Cpt x VDC

·  At 70kg, VDC 0.45L/kg, Cpt 4mcg/mL, dose = 126mg

·  Infusion rate (Q) max 1200mL/h in most machines

Alternative induction kinetics

Time to LOC ∝ peak Cp / time to peak Cp

 

(A) Peak Cp ∝

·  Dose size

·  Speed of injection

·  1/Cardiac output

·  1/Central blood volume (Central blood volume ∝ total blood volume)

·  Speed and extent of recirculatory second peak (important if bolus is slow)

(B) Time to peak Cp ∝

·  Cardiac output (note contradictory effects of cardiac output)

·  1/Distance from injection site to heart

 

Maintenance:

 

·  Q ∝ distribution x metabolism

Early

·  Early: high Q e.g. 100mL/h (distribution +++ metabolism ++)

Later

·  Later: slow Q e.g. 50mL/h (metabolism ++ distribution +)

Steady state

·  Steady state: CSS (mg/mL) = infusion rate (mg/min) / clearance (mL/min)

 

Offset:

Distribution phase

·  Cpt ∝ 1/(distribution x metabolism); rapid ↓Cpt

Terminal elimination phase

·  Cpt ∝ redistribution/metabolism; slower ↓Cpt

Modelling

·  Multi-exponential decay curve (C = Ae-at + Be-bt + Ge-gt)

Emergence

·  Estimated to occur at ~1mcg/mL

·  Highly variable