Local Anesthetics

Introduction

As the number of plastic surgical procedures performed under local anesthesia continues to grow, a thorough understanding of local anesthetic techniques has become essential. Furthermore, emergency care of lacerations, avulsions and other acute injuries also necessitates an adequate grasp of local anesthesia. It is important to obtain informed consent prior to using local anesthesia. Discussion of the risks and benefits of the surgery alone is not sufficient. Anesthetic-related issues such as adverse reactions, systemic toxicity, nerve damage, hematoma and pain both during and after the injection should be addressed.

Mechanism of Action

Local anesthetics exert their effect by temporarily blocking nerve conduction. This is achieved by interference with influx of sodium ions through the sodium channel. This leads to a slowing of the rate of membrane depolarization, a lowering of the threshold potential, and the inhibition of propagation of the action potential down the length of the axon. The smallest unmyelinated sensory nerves (C fibers) are affected first. The motor nerves are usually larger and myelinated, and are unaffected or only mildly affected by the actions of local anesthetics at the doses commonly used.

Pharmacodynamics

Local anesthetics can be classified based on their molecular structure as either amides or esters (Table 7.1). The amides, such as lidocaine, are metabolized in the liver by microsomal enzymes and excreted in the urine. The esters, such as cocaine, are quickly metabolized by plasma pseudocholinesterase into PABA and excreted in the urine.

Table 7.1. Commonly used local anesthetic agents and their duration of action

Anesthetic Agent Class Duration of Action

Lidocaine (Xylocaine) Amide 1.5-2 hours

-Lidocaine with epinephrine up to 3 hours Bupivicaine (Marcaine) Amide 3-6 hours

-Bupivicaine with epinephrine up to 10 hours Mepivicaine (Carbocaine) Amide 2.5-3 hours Cocaine (Cocaine) Ester 0.5-3 hours Tetracaine (Pontocaine) Ester 1-3 hours

Local anesthetics are acidic, in the pH range of 5-7 . Their pH further decreases with the addition of epinephrine to the anesthetic solution. Once they enter the tissue, the body’s bicarbonate buffer system converts the acidic solution to a more basic form. This is the active, uncharged form of the drug that can diffuse through the plasma membrane of the neurons. Bupivicaine, with its higher pKa, has a slower onset of action than lidocaine, which has a lower pKa. Acidic tissue, such as a hypoxic or infected wound, increases the fraction of ionized drug, thus delaying the onset and decreasing the efficacy of local anesthetics.

The Addition of Epinephrine

A vasoconstricting agent such as epinephrine, is often added to local anesthetic solutions. This provides the following benefits:

• Decreases the rate of systemic absorption
• Reduces the risk of systemic side effects
• Prolongs the duration of action of the anesthetic
• Improved hemostasis due to its vasoconstrictive effects

Premixed solutions containing epinephrine are acidified even further than plain local anesthetics. This increased acidity delays the onset of action and is more painful on injection. There is no utility in using greater than 1:100,000 epinephrine solutions. No additional vasoconstrictive benefit is offered, whereas the risk of toxicity increases in a dose-dependent manner. Adequate hemostasis relies greatly on allowing adequate time for the vasoconstrictive effects to occur. This usually takes 7-10 minutes.

Contraindications to the use of epinephrine-containing solutions include patients with unstable angina, cardiac dysrhythmias, severe uncontrolled hypertension, or pregnant patients with placental insufficiency. Relative contraindications include hyperthyroidism and concurrent use of MAOI or tricyclic antidepressants. When contraindicated, phenylephrine (1:20,000) can be substituted, however it is not as effective as epinephrine.

The Addition of Bicarbonate

Sodium bicarbonate can be added to local anesthetics in order to alkalinize the solution. This neutralization of the low pH creates a solution that is less irritating to the tissues and less painful on administration. The limiting factor in the addition of bicarbonate is the tendency for the lipid soluble agents, such as bupivicaine, to precipitate at the more neutral pH values. Therefore, bicarbonate can be added to lidocaine but should generally not be used with bupivicaine.

Lidocaine

Lidocaine is the most widely used local anesthetic. It is prepared as a 1% (10 mg/ ml) or 2% (20 mg/ml) solution with or without epinephrine. Its duration of action is about 1.5 hours without epinephrine, and this is doubled to 3 hours with the addition of epinephrine to the solution (1:100,000). Lidocaine can also be used as a dilute solution (0.2%–0.5%) for certain procedures such as a rhytidectomy. This solution is adequately anesthetizing and vasoconstrictive. A commonly used dilute solution, the modified Klein solution, can be prepared as follows: 20 ml of 2% lidocaine, 5 ml of sodium bicarbonate, and 1 ml of 1:1,000 epinephrine all mixed in 500 ml of lactated Ringer’s solution. The maximum safe dose for plain lidocaine is reported as 3-4 mg/kg. With the addition of epinephrine, this increases to 7 mg/kg.

Recent literature, however, refutes this figure, providing evidence for a much higher maximal safe dose-up to 35 mg/kg when combined with epinephrine.

Bupivicaine

Bupivicaine is widely used in plastic surgery because of its long duration of action. It is effective for 3-6 hours, significantly longer than lidocaine. The addition of epinephrine can increase this duration to 10 hours. It comes as a 0.25% or 0.5% solution, with or without epinephrine. It is somewhat more painful than lidocaine on administration. It should not be used for large volume infiltration because of its high toxicity profile. It can, however, be combined with lidocaine for lengthy facial procedures such as a rhytidectomy. This combination has a rapid onset of action due to the lidocaine, and a long duration of action due to the bupivicaine. The maximum safe dose of bupivicaine is 2.5 mg/kg, and this increases to 3 mg/kg with the addition of epinephrine.

Mepivicaine

Mepivicaine is similar to lidocaine except for its slightly longer duration of action. Its anesthetic effects can last up to 3 hours. It is prepared as a 0.5% or 1% mixture. It is much less commonly used than lidocaine due to its higher cost and lesser availability. It also has a slightly increased risk of toxicity compared to that of lidocaine.

Eutectic Mixture of Local Anesthetics (EMLA)

EMLA is typically a cream composed of 2.5% lidocaine and 2.5% prilocaine. It provides dense topical anesthesia 45-60 min after application. It must be covered with an occlusive dressing for this period in order for the cream to be effective. Within 2 hours, the maximal depth of penetration is reached. EMLA cream is not widely used because of the long latency until onset of action and the need for the occlusive dressing. It is effective in children who will not tolerate a needle stick, as long as it is applied sufficiently in advance.

Cocaine

Cocaine is used primarily as a topical agent for septo-rhinoplasty procedures. It comes in 4% or 10% solutions. As opposed to other local anesthetics, cocaine produces significant local vasoconstriction without the addition of epinephrine. Its onset is extremely rapid (1-2 minutes), but it takes an additional 5 minutes for its vasoconstrictive effects to begin. Its duration of action is up to 3 hours. Cocaine can be highly toxic by sensitizing the heart to circulating catecholamines. This can lead to tachycardia, hypertension, coronary vasospasm and dysrhythmias. Its CNS effects are stimulatory before leading to confusion, dysphoria and seizures. The maximum safe dose is about 3 mg/kg.

Tetracaine

Tetracaine, similar to cocaine, is used as a topical agent in nasal surgery. It can also be combined with EMLA as a topical agent for anesthesia for closed nasal reduction. It comes as a 0.05% to 4% solution. It has a rapid onset and is effective for 1-3 hours. Tetracaine is several times more potent than cocaine. It is extremely toxic due to its slow rate of metabolism, and the maximum safe dose is 1 mg/kg.

Toxicity

The risk for adverse reactions with local anesthetics is low, but it is important to be familiar with the signs and symptoms of toxicity. Some sites on the body are at greater risk for toxicity due to their robust blood supply. The face and scalp are rich in vascularity, and the systemic absorption of the drug from these sites is higher. In addition, patients with pseudocholinesterase deficiency, myasthenia gravis and those taking cholinesterase inhibitors are at a higher risk for overdose. Certain local anesthetics pose a higher risk of toxicity due to their lipid solubility. For example, bupivicaine is more lipid soluble than lidocaine and has a higher risk of toxicity.

The cardiovascular and CNS are the two systems most commonly affected by local anesthetic toxicity. CNS manifestations occur before cardiac signs, and the early signs and symptoms include restlessness, headache, disorientation, dizziness, blurred vision, tinnitus, slurred speech, nystagmus and twitching. Late signs of toxicity include generalized seizures, apnea and death. Treatment of seizures is by administration of a benzodiazepine such as diazepam or midazolam. Cardiovascular manifestations appear after those in the CNS and include myocardial depression, hypotension or shock, and dysrhythmias such as prolonged P-R interval and widening of the QRS complex. Of the commonly used local anesthetics, bupivicaine is the most cardiotoxic due to its strong affinity for the cardiac calcium channels.

Allergic Reactions

Allergies to local anesthetics are extremely rare, and account for less than one percent of adverse drug reactions during anesthesia. Reactions can range from a subtle rash to a full-blown anaphylactic response. The amides, such as lidocaine, rarely cause allergic reactions. The esters, however, such as cocaine, are metabolized by plasma pseudocholinesterase into PABA, and allergic reactions to these anesthetics are more common. If an allergic reaction does occur following administration of a local anesthetic, the culprit is usually one of the preservatives or additives in the solution rather than the anesthetic agent itself.

Pearls and Pitfalls

It has become increasingly clear that the maximum safe dose of lidocaine is much higher than previously thought. The traditional value of 7 mg/kg as the maximal dose of lidocaine with epinephrine is probably much too low. Recent literature supports a value closer to 35 mg/kg. Furthermore, the common use of dilute solutions of lidocaine with epinephrine has demonstrated that concentrations above 1% are not required. In the vast majority of cases, dilute solutions of lidocaine will provide adequate anesthesia, and the addition of epinephrine will greatly increase the maximal dose that can be safely used, while decreasing blood loss. One should wait at least 7-10 minutes for the vasoconstrictive effects of the epinephrine to take effect.

Suggested Reading

1. Ahlstrom KK, Frodel JL. Local anesthetics for facial plastic procedures. Otolaryng Clin N Am 2002; 35(1):29.
2. Baker IIIrd JD, Blackmon Jr BB. Local anesthesia. Clin Plast Surg 1985; 12(1):25.
3. Klein JA. Tumescent technique for regional anesthesia permits lidocaine doses of 35 mg/kg for liposuction. J Dermatol Surg Oncol 1990; 16(3):248.
4. Zilinsky I, Bar-Meir E, Zaslansky R et al. Ten commandments for minimal pain during administration of local anesthetics. J Drugs Dermatol 2005; 4(2):212.