1 What role do local anesthetics play in the practice of anesthesiology?

As local anesthetics reversibly block nerve conduction, they are used to provide regional anesthesia for surgery and postoperative analgesia for painful surgical procedures. Local anesthetics given intravenously attenuate the pressor response to tracheal intubation, decrease coughing during intubation and extubation, and are antiarrhythmic.

2 How are local anesthetics classified?

Aminoesters: Esters are local anesthetics the intermediate chain of which forms an ester link between the aromatic and amine groups. Commonly used ester local anesthetics include procaine, chloroprocaine, cocaine, and tetracaine (Figure 14-1).

Aminoamides: Amides are local anesthetics with an amide link between the aromatic and amine groups. Commonly used amide anesthetics include lidocaine, prilocaine, mepivacaine, bupivacaine, levobupivacaine, ropivacaine, and etidocaine.

Figure 14-1 Structure of esters and amides.

3 How are local anesthetics metabolized?

Esters undergo hydrolysis by pseudocholinesterases found principally in plasma. Amides undergo enzymatic biotransformation primarily in the liver. The lungs may also extract lidocaine, bupivacaine, and prilocaine from circulation. Chloroprocaine is least likely to produce sustained elevation in blood levels because of very rapid hydrolysis in the blood. Risk of toxicity to esters is increased in patients with atypical pseudocholinesterase and severe liver disease and in neonates. Liver disease or decreases in liver blood flow as may occur in patients with congestive heart failure or during general anesthesia can decrease the metabolism of aminoamides.

4 How are impulses conducted in nerve cells?

Transmission of impulses depends on the electrical gradient across the nerve membrane, which in turn depends on the movement of sodium (Na·) and potassium (K·) ions. Application of a stimulus of sufficient intensity leads to a change in membrane potential (from −90 mV to −60 mV), subsequent depolarization of the nerve, and propagation of the impulse. Depolarization is caused by inflow of Na ions from the extracellular to the intracellular space. Repolarization is caused by outflow of K· ions from the intracellular to the extracellular space. The Na-K· pump restores equilibrium in the nerve membrane after completion of the action potential.

5 What is the mechanism of action of local anesthetics?

The cascade of events (Figure 14-2) follows:

Diffusion of the unionized (base) form across the nerve sheath and membrane

Reequilibration between the base and cationic forms in the axoplasm

Binding of the cation to a receptor site inside of the Na channel, resulting in its blockade and consequent inhibition of Na conductance

Figure 14-2 Mechanism of action of local anesthetics.

6 Your patient states that he was told he is allergic to Novocain, which he received for a tooth extraction. Should you avoid using local anesthetics in this patient?

Probably not. Allergy to local anesthetics is rare despite frequent use of local anesthetics. Less than 1% of adverse reaction to local anesthetics is true allergy. Most reactions labelled as allergy are probably one of the following: vasovagal response, systemic toxicity, or systemic effects of epinephrine. True allergy would be suggested by history of rash, bronchospasm, laryngeal edema, hypotension, elevation of serum tryptase, and positive intradermal testing.

Esters produce metabolites related to p-aminobenzoic acid and are more likely to produce allergic reactions than are amide local anesthetics. Allergic reactions following use of local anesthetics may also be caused by methylparaben or other preservatives in commercial preparations of local anesthetics. There is no cross-sensitivity between classes of local anesthetics. Therefore patients known to be allergic to ester local anesthetics could receive amide local anesthetics. Caution is still warranted in case the patient is allergic to the preservative that may be common to both classes of drugs.

7 What determines local anesthetic potency?

The higher the solubility, the greater the potency (Table 14-1). This relationship is more clearly seen in isolated nerve than in clinical situations when factors such as vasodilation and tissue redistribution response to various local anesthetics influence the duration of local anesthetic effect. For example, high lipid solubility of etidocaine results in profound nerve blockade in isolated nerve. Yet, in clinical epidural use etidocaine is considerably sequestered in epidural fat, leaving a reduced amount of etidocaine available for neural blockade.

8 What factors influence the duration of action of local anesthetics?

The greater the protein binding, the longer the duration of action. The duration of action is also influenced by peripheral vascular effects of the local anesthetics. For example, lidocaine, prilocaine, and mepivacaine provide anesthesia of similar duration in an isolated nerve. However, lidocaine is a more potent vasodilator, increasing absorption and metabolism of the drug, thus resulting in a shorter clinical blockade than that produced by prilocaine or mepivacaine.

9 What determines local anesthetic onset time?