2020B15 Discuss factors that determine the time to awakening after cessation of a propofol target infusion (TCI).

List:

· Emergence modelling

· Uptake

· Elimination

· Threshold

Emergence modelling:

Determinants

1. Uptake (into all compartments)

2. Elimination (from effect site via central compartment)

3. Threshold (median effect site concentration for emergence – i.e. Ce₅₀)

Kinetic model

	Perfusion	Capacity
V₁	+++	+ (~4L)
V₂	++	++ (~30L)
V₃	+	+++ (~200L)

Washout curve

Half lives:

· t_1/2_α fast: 2 mins

· t_1/2α slow: 20-50 mins

· t_1/2β: 5-12 hours

Decrement times

· Fast offset after short infusion

· Slow offset after long infusion

1. Uptake (factors increasing it)

Infusion	· ↑Duration · ↑Infusion rate / target concentration
Patient	· ↑Cardiac output -> ↑tissue blood flow (child, pregnant, obese, septic) · ↑Compartment volumes -> ↑capacity (lean tissue, fat)
Algorithm	· Marsh > Schnider · Male > female · ∝ weight, height, youth
Logistics	· Factors impeding titration: o Neuromuscular blockade o Absence of processed EEG

2. Elimination (factors slowing it)

Short case

Offset during distribution phase:

· ↓Distribution to V₂, V₃

o ↓Cardiac output (old age, heart failure, hypovolaemia)

o ↓Compartment volumes (cachexia)

Long case

Offset during terminal elimination phase: (note bivalent factors!)

· ↑Redistribution from V₂, V₃

o ↑Cardiac output

o ↑Compartment volumes

· ↓Metabolism (↓mAP -> ↓hepatic blood flow; liver disease if severe)

· ↓Excretion (<1%)

3. Threshold (factors lowering it)

Pharmacology

· Synergistic: opioids, benzo

· Additive: sevoflurane, N₂O

Physiology

· Old age

· Pregnancy (↓30%)

· Night time (↓10%)

Pathology

· ↓↓PaO₂

· ↑↑PaCO₂

· ↓↓mAP

· ↓↓pH

· ↓↓Temp

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