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