2012B02 Compare and contrast propofol and sevoflurane for maintenance of anaesthesia with respect to kinetics, cardiovascular and central nervous system effects.

 

List:

·      Kinetics

·      CVS effects

·      CNS effects

 

Kinetics:

 

Propofol (PPF)

Sevoflurane (SF)

Implication

Decrement times

-1h 50% DT

-1h 90% DT

 

-8h 50% DT

-8h 90% DT

 

 

10 min

60 min

 

45 min

300 min

 

 

10 min

20 min

 

20 min

120 min

Similar after short infusion

PPF much slower after long infusion

Absorption

Straight into central compartment

Inhalational: diffusion across membrane down partial pressure gradient

PPF bolus -> more rapid ↑in Cp and Ce -> better if sudden stimulation

Distribution

Accumulation in many tissues

Highly lipid soluble (LS)

VD 4L/kg

98% PPB, esp albumin

Accumulation in many tissues

High fat-blood coefficient

VD unknown

Dissolved in blood cells, fat

Multicompartment modelling required

-3 for PPF (V1-2-3)

-5 for SF (vessel rich, lean, intermediate, vessel poor, fat)

Metabolism

Extensive>99%

Rapid (Cl 30-60mL/kg/min)

Phase 1: 2B6, 2C9, 3A4

Phase 2: glucuronidation or sulfation

Sites: liver + ? kidney ? lung

2-5% metabolism

Phase 1: CYP2E1 > other

Small contribution to offset

 

Metabolites

No active metabolites

Quinol -> green urine

Endogenous: fluorides and hexafluoroisopropanol

With CO2 absorber: compound A

No significant effects

Compound A does not reach toxic conc in humans

Excretion

0.3% PPF -> urine

Metabolites -> urine

95-98%

Lungs >>> skin

S: ↑offset if ↑VA, ↑FGF

P: offset can’t be sped up

Effect of liver failure

Minimal

Minimal

Both safe

Effect of renal failure

Minimal

Minimal

Both safe

Risk of accumulation

IV: indefinite accumulation possible

Inhaled: cannot exceed inspired partial pressure

 

 

CVS effects:

 

Propofol

Sevoflurane

Implication

Inotropy

↔/↓

SF may be preferable for patients with haemodynamic instability, sepsis.

Heart rate

↓ (blunted baro resp)

↔/↑
(↑↑in Guedel’s stage 2)

Cardiac output

↔/↓

SVR

↓↓

mAP

↓↓

PVR

↓↓

PPF ? preserves HPV in one lung ventilation

Coronary blood flow

SF ? safer if IHD

Ischaemic pre-conditioning

No

Y (activate ATP-sensitive K+ channel)

SF ? safer if IHD

↑ QTc

No

Yes

Not significant

 

CNS effects:

Parameter

Propofol

Sevoflurane

Implication

Amnesia

Ce50 ?1-2mcg/mL

0.25MAC

 

Hypnosis

Ce50 2-3mcg/mL

0.3 MAC

 

Immobility

Ce50 15mcg/mL

1 MAC (2%)

Adjuvants required for both, especially PPF

Immobility: standard deviation

 

5mcg/mL (30%)

↓ spinal cord effect

↓ diverse receptor targets

0.1MAC (10%)

 

Analgesia

No

No (antalgesic at low dose)

 

Anti-emetic

5-HT3 antagonist -> yes

5HT3 agonist -> proemetic

PPF TIVA if PHx PONV +++

EEG effects

↓frequency, ↑amplitude

BS if ↑↑[PPF]

Anticonvulsant

10% myoclonus

Same as for PPF.

Similar EEG signatures.

Both suitable for BIS or entropy monitoring.

CMRO2

Max ↓60% if isoelectric

Max ↑60% if isoelectric EEG

 

CBF

CMRO2

↑CBF above baseline at >1MAC

If normal ICP: SF -> luxury perfusion

If ↑ICP: PPF -> ↓ICP

CBF:CMRO2

↔Slope

↑slope

ICP

+/- ↑

 

 

 

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