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Section IICoredrugs in anaesthetic practice(pregnancy, myocardial infarction, renal failure, post-operatively and in infancy) the
free fraction of drug is reduced.
The degree of protein binding will affect the degree of placental transfer. Bupiva-
caine is more highly bound than lidocaine, so less crosses the placenta. If the foetus
becomes acidotic there will be an increase in the ionized fraction and local anaes-
thetic will accumulate in the foetus (ion trapping). Ester local anaesthetics do not
cross the placenta in significant amounts due to their rapid metabolism.Metabolism and elimination
Esters are hydrolyzed rapidly by plasma cholinesterases and other esterases to inac-
tive compounds. Para-aminobenzoate is one of the main metabolites and has been
associated with hypersensitivity reactions especially in the atopic patient. This rapid
hydrolysis results in a short elimination half-life. Cocaine is the exception, undergo-
ing hepatic hydrolysis to water-soluble metabolites that are excreted in the urine.
Amides undergo hepatic metabolism by amidases. Amidase metabolism is much
slower than plasma hydrolysis and so amides are more prone to accumulation when
administered by continuous infusion. Reduced hepatic blood flow or hepatic dys-
function can decrease amide metabolism.Toxic doses
Raised systemic blood levels of local anaesthetic lead initially to the central ner-
vous system and then to cardiovascular toxicity. However, the absorption of local
anaesthetic varies widely depending on the site of administration and presence of
vasoconstrictors. Therefore, the concept of a toxic dose without regard to the site of
administration is meaningless. The toxic plasma levels are given in Table10.2.Intravenous regional anaesthesia
Bupivacaine has been used for intravenous regional techniques, but following a num-
ber of deaths attributed to cardiac toxicity it is no longer used in this way. Prilocaine
(0.5%) is commonly used in this setting although lidocaine may also be used.Lidocaine
Lidocaine is an amide local anaesthetic that is also used to control ventricular tach-
yarrhythmias. It has class Ib anti-arrhythmic actions (see Chapter 14 ).Preparations
Lidocaine is formulated as the hydrochloride and is presented as a colourless solution
(0.5–2%) with or without adrenaline (1 in 80–200 000); a 2% gel; a 5% ointment; a spray
delivering 10 mg.dose−^1 and a 4% solution for topical use on mucous membranes.Kinetics
Lidocaine is 70% protein bound toα 1 -acid glycoprotein. It is extensively metabo-
lized in the liver by dealkylation to monoethylglycine-xylidide and acetaldehyde.