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%)
Standard deviation (immobility)	5mcg/mL (30%) ↓ spinal cord effect ↓ diverse receptor targets	0.1MAC (10%)	For achieving immobility: -Adjuvants helpful for sevoflurane -Adjuvants essential for propofol
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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