4. Local Anaesthetics: Influences on Onset and Duration

the axoplasmic part of the sodium channel is blocked by the ionized part of the local anaesthetic molecule, but a charged moiety will not traverse the lipid and connective tissue membranes. It is only when existing in the uncharged form that the drug can gain access to the axoplasm.

the addition of bicarbonate will raise the pH of the weakly acidic solution nearer the pKa The addition of 1.0 ml NaHCO3 8.4% to 10.0 ml of lidocaine 2% will raise its pH from 6.5 to 7.2 More drug will exist in the non-ionized form, and so penetration will be more rapid. NaHCO3 significantly reduces the latency of lidocaine, although its effect on bupivacaine is less impressive, with some studies reporting only a 2–3-minute improvement

After infiltration of the drug, it is believed that the increased amount of CO2 moves into the axoplasm, where it increases the levels of the weak carbonic acid.

Dexamethasone: the addition of this glucocorticoid to local anaesthetics for plexus and peripheral nerve anaesthesia is a popular current technique, and there are a number of systematic reviews to confirm that doses up to 8 mg can almost double the duration of some blocks. so it is as likely that the effect seen may simply be the consequence of systemic absorption.

Clonidine: this does appear to have a direct action on peripheral nerves, mediated via the hyperpolarization of cation channels, and is effective in increasing the duration of neuraxial blocks, at least partly by spinal α2-agonism.

: this is a partial μ-agonist which may also block voltage-gated Na+ channels and thereby exert a local anaesthetic effect. It also acts on κ- and δ-opioid receptors. It can in some reports almost double the duration of plexus blocks, and studies suggest that the effect is not due to systemic absorption.

Adrenaline (epinephrine): the addition of adrenaline is of very modest benefit, and when added to local anaesthetic for peripheral nerve block

depending on operative urgency. Typical regimens include levobupivacaine 0.5%  20 ml, lidocaine 2%  20 ml, and levobupivacaine 0.5%  10 ml plus lidocaine 2%  10 ml. It is common to add adrenaline 100 μg (5 μgml−1 is 1 in 200,000), and many anaesthetists add an opioid such as fentanyl or diamorphine. Some also alkalinize the solutions by adding sodium bicarbonate 8.4%, 1.0 ml per 10 ml

Local anaesthetics have been shown to interact with some of these proteins to modify the physiological response.

protein binding influences the duration of action of a compound, and lipid solubility is a prime determinant of intrinsic anaesthetic potency. Lidocaine has low lipid solubility, whereas that of bupivacaine is high.

Liposomes are one alternative formulation. A liposome is formed when amphipathic lipid molecules (i.e. ones which have both hydrophobic and hydrophilic properties) encounter an aqueous medium, and become so orientated as to form a phospholipid bilayer which is similar to a cell membrane Their release varies according to the characteristics of the particular liposome