Nerve impulse transmission occurs when voltage-gated sodium channels on the neuronal membrane open, allowing a massive influx of sodium. This causes membrane depolarization and propagation of the impulse. Local anesthetics block nerve impulse transmission in the peripheral and central nervous system without causing central nervous system depression or altered mental status. The block generally occurs in a stepwise sequence depending on the concentration and volume of the local anesthetic, with autonomic impulses blocked first, then sensory impulses, and finally, motor impulses.

Local anesthetics work to anesthetize skin, subcutaneous tissue, and peripheral nerves for invasive or surgical procedures. The duration of action of local anesthetics can range from 30 minutes to 12 hours or more. The range depends on the location of the block (high blood supply equals shorter duration), the local anesthetic used, and its preparation (liposomal preparations create extended-release drugs).

Commonly used local anesthetics in clinical practice include the following:

Amino Amides

• Mepivacaine
• Lidocaine
• Etidocaine
• Bupivacaine
• Levobupivacaine
• Ropivacaine

Amino Esters

• Procaine
• Cocaine
• Chloroprocaine
• Tetracaine
• Benzocaine

Recently the FDA approved liposomal bupivacaine for postoperative analgesia. Hopefully, this will decrease the reliance on opiates in the post-surgical period.

Many reports indicate that lidocaine may also act as a tinnitus suppressing agent. The drug requires intravenous injection, but the risk of systemic toxicity has been a significant concern.[1][2][3][4]

Local anesthetics block voltage-gated sodium channels, which prevents sodium influx into the cell and blocks impulse transmission. Local anesthetics are also class I antiarrhythmic drugs due to the blockade of cardiac sodium channels, with lidocaine being the class IB prototype. They selectively block channels that are frequently depolarizing (tachyarrhythmias) and slow transmission.

Two subclasses of local anesthetics categorize according to the location where metabolism occurs. The amino-amides such as bupivacaine, ropivacaine, and lidocaine, are hydrolyzed in the liver, whereas plasma cholinesterases metabolize the amino-esters such as procaine, chloroprocaine, and tetracaine. 

Amino amides are stable in solution, whereas the amino esters are unstable. Allergic or hypersensitivity reactions are more likely to occur with amino esters than amino amides.

Local anesthetics work in the nonionic form. In the presence of a low pH, the ionized form is dominant, and this can delay the onset of action; this also explains why local anesthetics are not effective in sites of inflammation, where an acidic environment is common. Thus, many clinicians add sodium bicarbonate to overcome the acidity and increase the efficacy of the local anesthetic.

Epinephrine is often added to a local anesthetic solution, which allows the clinician to use a lower dose of the anesthetic and improve safety. Further, epinephrine acts as a vasoconstrictor and delays absorption of the anesthetic into the peripheral arteriole, thus increasing the duration of action. The addition of epinephrine can also improve hemostasis by inducing vasoconstriction in the surgical field.

However, the dose of epinephrine used should not be more than 1:100,000. In certain patients, the drug can cause arrhythmias, especially in patients receiving halothane. Epinephrine can also compromise flap viability. Finally, the patient should not use epinephrine on the nose, ear, or penis.

Local anesthetics can be applied topically and subcutaneously to anesthetize local tissues. They can also be administered around peripheral nerves and in the neuraxial space to anesthetize larger nerves or dermatomal distributions. Lidocaine is also administered intravenously to provide surgical anesthesia for an extremity, such as Bier block, or as a cardiac antiarrhythmic.[5][6]

Local anesthetics have a significant risk of systemic toxicity when administered intravascularly. Symptoms usually manifest in the central nervous system first (metallic taste, auditory changes, circumoral numbness, blurred vision, agitation, seizures), followed by cardiovascular effects (hypotension, decreased cardiac contractility, dysrhythmias, complete heart block, cardiovascular collapse). Bupivacaine is particularly cardiotoxic, and there have been reports of cardiovascular collapse in the absence of antecedent neurologic symptoms. Cardiopulmonary bypass or extracorporeal membrane oxygenation is still useful in refractory cases.[7][8][9][8]

Hypersensitivity

Allergic or hypersensitivity reactions to local anesthetics are rare. In most cases, the hypersensitive response is not to the anesthetic itself but the preservative solution. The risk of an allergic reaction is higher with the ester group than with the amides. The cause of the hypersensitivity reaction appears to be para-aminobenzoic acid, which is a breakdown product generated by the actions of the enzyme, pseudocholinesterase. Para-aminobenzoic acid is considered extremely antigenic and rapidly sensitizes lymphocytes.

More commonly, reactions to a local anesthetic arise from apprehension, anxiety, and phobia about needles. These feelings may result in a vasovagal response, a panic attack, or a syncopal episode.

If a patient develops a hypersensitive reaction to one anesthetic in the ester group, he or she will generally also be sensitive to all other anesthetics in the same class. Thus, it is better to use an amino group anesthetic in such scenarios.

Allergies have been reported for each class of local anesthetics, but crossover sensitivity does not occur. Ester local anesthetics are metabolized to a para-aminobenzoic acid-like compound, and anaphylaxis has been reported. Amide local anesthetics sometimes contain the preservative methylparaben, which has also been reported to cause severe allergic reactions. It is essential to know which class of local anesthetic caused the reaction and avoid that class in the future. Patients with depressed hepatic function may have a prolonged duration of action or a higher risk of toxicity with amides. Patients with a cholinesterase deficiency may have prolonged effects of esters.