Summary of Local Anesthetic Mechanisms

Impulse blockade by local anesthetics may be summarized by the following chronology:

1. Solutions of local anesthetic are deposited near the nerve. Removal of free drug molecules
away from this locus is a function of tissue binding, removal by the circulation, and local
hydrolysis of aminoester anesthetics. The net result is penetration of the nerve sheath by the
remaining free drug molecules.

2. Local anesthetic molecules then permeate the nerve's axon membranes and reside there and in
the axoplasm. The speed and extent of these processes depend on a particular drug's pKa and
on the lipophilicity of its base and cation species.

3. Binding of local anesthetic to sites on voltage-gated Na channels prevents opening of the

channels by inhibiting the conformational changes that underlie channel activation. Local
anesthetics bind in the channel's pore and also occlude the path of Na+ ions.

4. During onset of and recovery from local anesthesia, impulse blockade is incomplete and
partially blocked flbers are further inhibited by repetitive stimulation, which produces an
additional, use-dependent binding to Na channels.

5. One local anesthetic binding site on the Na+ channel may be sufficient to account for the
drug's resting (tonic) and use-dependent (phasic) actions. Access to this site may potentially
involve multiple pathways, but for clinicai local anesthetics, the primary route is the
hydrophobic approach from within the axon membrane.

6. The clinically observed rates of onset and recovery from blockade are governed by the
relatively slow diffusion of local anesthetic molecules into and out of the whole nerve, not by
their much faster binding and dissociation from ion channels. A clinically effective block that
may last for hours can be accomplished with local anesthetic drugs that dissociate from
Na channels in a few seconds.

Infiltration A n e s t h e s i a

Any local anesthetic may be used for infiltration anesthesia. Onset of action is almost
immediate for all agents after intradermal or subcutaneous administration; however, the
duration of anesthesia varies (Table 30-4). Epinephrine will prolong the duration of
infiltration anesthesia by all local anesthetic drugs, although this effect is most pronounced
when epinephrine is added to lidocaine. The choice of a specific drug for infiltration
anesthesia largely depends on the desired duration of action

The dosage of local anesthetic required for adequate infiltration anesthesia depends on
the extent of the area to be anesthetized and the expected duration of the surgical
procedure. W h e n large surface areas have to be anesthetized, large volumes of dilute
anesthetic solutions should be used. These considerations are particularly important when
performing infiltration anesthesia in infants and smaller children. As an example, consider
a 4-kg infant receiving infiltration anesthesia with the maximum safe dose of lidocaine,
5 mg/kg. Dosing to 5 mg/kg , 4 kg permits 20 mg, which is 1 mL of a 2% solution or 4 mL
of a 0.5% solution. Lidocaine is effective for infiltration in concentrations as dilute as 0.3%
to 0.5%, so the more dilute solution can be used more safely to anesthetize a larger area.

Patients frequently experience pain immediately after subcutaneous injection of local

anesthetic solutions, in part because of the acidic nature of these solutions. For example,
neutralization of lidocaine solutions by the addition of sodium bicarbonate immediately
before injection reduces pain on skin infiltration and may improve onset (see earlier).
Table 3 0 4 - Infiltration Anesthesia
Plain Solution Epinephrine-Containing Solution
Drug
Concentration(%) Max Dose (mg) Duration (min) Max Dose (mg) Duration (min)
Short Duration
Procaine 1-2 500 20-30 600 30-45
Chloroprocaine 1-2 800 15-30 1000 30
Moderate Duration
Lidocairie 0,5-1 300 30-60 500 120
Mepivacaine 0,5-1 300 45-90 500 120
Prilocaine 0,5-1 350 30-90 550 120
Long Duration
Bupivacaine 0,25-0,5 175 120-240 200 180-240
Ropivacaine 0,2-0,5 200 120-240 250 180-240