Pharm-12B02 Compare and contrast propofol and sevoflurane ...

Pharm-12B02 Compare and contrast propofol and sevoflurane for maintenance of anaesthesia with respect to kinetics, cardiovascular and central nervous system effects. 22%

Background Propofol (2,6-diisopropylphenol) is an intravenous anaesthetic agent Sevoflurane (fluoromethyl hexafluoroisopropyl ether) is a volatile anaesthetic agent Both are commonly used in the induction and maintenance of general anaesthesia

Pharmacokinetics Absorption Propofol intravenous Sevoflurane inhaled ! rate of uptake highly dependent on inhaled concentration, alveolar ventilation, co-administered agents, etc In general, propofol is able to more quickly and reliably alter effect site concentration than sevoflurane ! more quickly alter depth of anaesthesia

Distribution Both propofol and sevoflurane have large volumes of distribution Propofol has high protein affinity (98% bound) During maintenance of anaesthesia ! peripheral compartments (muscle, fat) slowly become saturated both propofol and sevoflurane kinetics require multi-compartmental modelling Context sensitive half time increases with duration of anaesthesia for both propofol and sevoflurane. Overall, the offset of action of propofol is similar to sevoflurane.

Metabolism Propofol is metabolised at both hepatic and extra-hepatic sites (likely lungs) to inactive glucuronides and sulfates ? it has large clearance (30 mL/kg/min). Sevoflurane is metabolised by the liver (CYP2E1) ! hexafluoroisopropanol + fluoride + CO2. Only a small fraction is metabolised (~5%).

Hepatic and liver diseases have no significant clinical effect on propofol and sevoflurane metabolism.

Excretion

Both propofol and sevoflurane metabolites are excreted via kidneys.

Sevoflurane excretion is highly dependent on alveolar ventilation and composition of alveolar gas.

Cardiovascular effects

Contractility Heart rate

Stroke volume Cardiac output SVR MAP Coronary blood flow Ischaemic preconditioning QTc

Propofol Reduced Reduced (blunts reflex HR) Can cause asystole Reduced Reduced Reduced (via NO release) Reduced Reduced No Minimal change

Sevoflurane Maintained Maintained

Slightly reduced Maintained Reduced (via Ca2+ channel block) Reduced Increases Yes Increased

CNS effects

Maintenance dose Cerebral vascular resistance Cerebral blood flow ICP Cerebral metabolic O2 demand Analgesic properties EEG changes

Examiner's comments

Propofol Plasma conc 1.5 ~ 5 ?g/mL

Unchanged ~ increased Reduced Reduced Reduced Nil 10% manifest excitatory effects with dystonic movements Nil epileptiform activity on EEG High dose = burst suppression May be used to treat status epilepticus

Sevoflurane MACawake = 0.6% MAC 1.8% Reduced Increased Increased (not suitable for neurosx) Reduced (luxury perfusion) Nil Nil association with epileptiform activity High dose = burst suppression

22 % of candidates passed this question.

There are three parts to the question. Candidates who did not address all areas rarely passed.

Note that the question specifically refers to maintenance rather than onset on anaesthesia. A comparison of the drugs was required; separate essays lost marks. It is important to show understanding of what figures mean, rather than just quoting lists of numbers.

Vague statements such as, "Propofol is metabolised in the liver", did not attract marks. When using abbreviations, standard ones such as CNS do not require explanation. Non standard ones such as DD do.

In terms of pharmacokinetics: Both drugs can be described using a three compartment model. When calculating offset of effect, redistribution of propofol is less important in an infusion than with a bolus dose. Propofol offset was often said to be faster than sevoflurane. It actually varies with the duration of anaesthesia. When attempting to turn over cases in the operating theatre, a half life of 40 minutes is not considered short. It should be remembered that it is the metabolites of the drugs, rather than the drugs themselves which are cleared renally.

Many candidates believed that there is a negative feedback loop between end tidal concentration and minute volume in a spontaneously breathing patient. This is only true when using an in-circuit vaporiser.

Other frequent mistakes were:

? To compare sevoflurane with desflurane rather than propofol ? To assume the blood gas coefficient equates to lipid solubility. ? To mis-state the metabolites of sevoflurane, or to assume that Compound A is

produced in the body. ? To oversimplify the effect of sevoflurane on cerebral blood flow and ICP.

 ................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download