Plastic surgery





The clinically useful local anesthetics are either amino amides or amino esters. These agents are effective when applied topically, injected subcutaneously, or injected in the area of major peripheral nerves.


Local anesthetics cause a blockade in nerve condition. The local anesthetic diffuses passively through the neuronal cell membrane in the nonionic state, becomes charged, and blocks the sodium channel within the neuron. With sodium conductance inhibited, threshold potential is not reached and an action potential is not generated.


The molecular structure of local anesthetic agents consists of an aromatic moiety at one end, an amine moiety at the other end, and an intermediate chain between. The latter contains either an amide or an ester linkage, allowing local anesthetics to be classified as either amides or esters. Commonly used esters are procaine (Novocain), chloroprocaine, tetracaine, and cocaine. Commonly used amides are lidocaine, mepivacaine, prilocaine, bupivacaine (Marcaine), and etidocaine. Differences in the metabolism of local anesthetics, their stability in solution, and differences in allergenicity are all related to the presence of an ester or amide linkage.


Esters undergo hydrolysis in the plasma by pseudocholinesterase, whereas the amides are metabolized in the liver. The rate of metabolism of local anesthetics is related to the number of additional carbon atoms on the aromatic or amine side of the molecule.

Stability in Solution

Esters are unstable in solution. Amides are stable in solution.


Esters are also more likely to cause allergenic reactions than amides. A true allergic reaction to lidocaine is extremely rare, although many patients will state, incorrectly, that they have such an allergy.

Potency and Toxicity

Potency and toxicity are determined by the structure of the aromatic and the amine group.


The profile of a particular local anesthetic agent is related to its lipid solubility, protein binding, acid strength (pKa), and vasodilator activity.


Anesthetic potency is determined primarily by the degree of lipid solubility. The local anesthetic molecule must penetrate the nerve cell membrane to have an effect. In vitro, hydrophobicity alone determines the potency of a given local anesthetic. In clinical settings, however, other factors, such as vasodilatory activity and the tissue redistribution properties of the different local anesthetics, influence potency to some extent.

Onset of Action. The onset of action is primarily a result of the pKa, but the dose and the concentration are also factors. In vitro studies confirm the relationship between pKa of a local anesthetic compound and the onset of anesthesia. Lidocaine has a pKa of 7.4 and a more rapid onset of action than tetracaine, which has a pKa of 8.6.

Duration of Action. In the clinical arena, the duration of local anesthesia is principally influenced by the vasodilator effects of the individual drugs. With the exception of cocaine, all local anesthetics cause some degree of vasodilation. The greater the degree of vasodilation, the greater the amount of the drug that is absorbed by the vascular system, leaving less drug to act on the nerve cell. Therefore, the degree of vasodilation is inversely related to the duration of action. See the section “Addition of Epinephrine.”

Duration and Potency Summary. In summary, agents with low potency and short duration are procaine (Novocain) and chloroprocaine; agents with moderate potency and duration are lidocaine (Xylocaine), mepivacaine, and prilocaine; agents with a high potency and a long duration are tetracaine, bupivacaine (Marcaine), and etidocaine.

Effect of Total Dose

Other factors determine a local anesthetic agent’s activity in the clinical setting. Total dose is probably the single most important factor in determining satisfactory local anesthesia. Also, as mentioned earlier in the section “Onset of Action,” the greater the dose, other factors being equal, the faster the onset of action.

Addition of Epinephrine

The addition of vasoconstrictors is another factor determining the performance of the local anesthetic. Epinephrine markedly prolongs the duration of action of all local anesthetics when used for local infiltration or peripheral nerve blocks. By decreasing the rate of vascular absorption, vasoconstrictors cause a higher concentration of local anesthetic molecules to be available to act on the nerve cell membrane.

Epinephrine is frequently used in combination with local anesthetics at concentrations of 1:100,000 or 1:200,000. In fact, epinephrine is probably equally effective at much lower doses (1:1,000,000) and might decrease the danger of an intravascular injection.

Location of Injection

The anatomy of the site of injection also has a role in determining the activity of a local anesthetic. Intradermal injection allows for the most rapid onset of action but the shortest duration of these agents, whereas brachial plexus block injections yield some of the longest durations and slowest onsets of action seen with local anesthetics. Although intradermal injection provides the most rapid onset, it is more painful than subcutaneous injection.


There are two general types of peripheral nerve blockade: major and minor. Blocks of individual nerves, such as radial nerve block, are referred to as minor, and blocks of two or more nerves or a plexus of nerves are called major nerve blocks. A wide variety of local anesthetics can be used for minor nerve blocks. The drug is usually selected based on the duration of anesthesia that is required. The duration of action of minor nerve blockade is prolonged by the addition of epinephrine to the local anesthetic solution.

A commonly used major nerve block is the brachial plexus (or axillary) block (see Chapter 71). Although the onset of action for minor nerve blocks is generally rapid for all the local anesthetics, there are differences in onset between the various anesthetic agents when major nerve blocks are performed. Epinephrine, in general, will prolong the duration of brachial plexus blockade. The longer acting local anesthetics do not demonstrate as much prolongation of action with epinephrine as do the shorter acting agents. Tables 12.1 and 12.2 show the maximal dose, onset, and duration of action of the commonly used local anesthetics for minor and major nerve blocks.


Topical anesthesia is increasingly important in pediatric intravenous insertion and is used by some surgeons to lessen the discomfort of injectables such as Restylane and Botox. These topical agents will provide dermal anesthesia if applied far enough in advance but do nothing to lessen the burning associated with subcutaneous injection.

Eutectic mixture of local anesthetics (EMLA) is a combination of 25 mg lidocaine and 50 mg prilocaine per gram of EMLA. L-M-X4 contains 4% lidocaine per gram. These formulations decrease pain secondary to intravenous insertion and also provide adequate analgesia for split-thickness skin graft harvesting. L-M-X4 may have a slightly faster onset but both preparations are best applied between 30 and 60 minutes prior to the procedure and are best covered with an occlusive dressing such as Tegaderm or OpSite.

Several other topical local anesthesia preparations are available that provide brief periods of anesthesia when they are applied to mucous membranes or abraded skin. The most common local anesthetic agents used topically are lidocaine, dibucaine, tetracaine, and benzocaine.


The most common method of achieving local anesthesia for minor office procedures is infiltration anesthesia, in which the agent is injected into the operative site without selectively blocking a specific nerve. Any local anesthetic can be used for infiltration except cocaine. Injection may be intradermal, subcutaneous, or both. Again, the duration of action will vary and the addition of epinephrine will prolong the duration of analgesia. Dilute anesthetic solutions are recommended for large areas to avoid toxicity. Infiltration of local anesthetic causes a painful, burning sensation. Injection into the dermis is the most painful and provides the fastest onset of action. Addition of sodium bicarbonate decreases the pain associated with infiltration. Table 12.3 shows the maximal dose and duration of local anesthetics when used for infiltration anesthesia. When maximal doses are employed, the onset is very rapid regardless of which agent is selected.


To avoid toxicity, local anesthetics must be administered within a safe dose range and in the correct anatomic location. During local anesthesia, when toxic reactions occur, they are almost always the result of inadvertent intravascular injection or the administration of an excessively large dose. Many patients report an “allergy” to local anesthesia that was probably actually symptoms related to an intravascular injection and probably related to the epinephrine rather than the local anesthetic. Every effort should be made to avoid intravascular injection. The syringe should always be aspirated before the local anesthetic is injected, regardless of the anatomic site of injection. Repeat aspirations should be made after injecting 2 to 3 mL of local anesthetic. If blood is seen in the syringe, the needle must be repositioned. An intravascular injection of an epinephrine-containing solution may produce a dangerously hypertensive response.

As mentioned earlier, the addition of epinephrine to the anesthetic solution delays absorption and results in lower anesthetic blood levels, as well as a longer duration of action. Epinephrine is especially useful when local anesthetic is being injected into highly vascular areas such as the face. It was previously believed that epinephrine should be omitted from anesthetic solutions injected in proximity to end arteries (e.g., fingers, toes, and penis) because of the danger of ischemic necrosis. Recent studies cast doubt on this dictum.

The toxicity of local anesthetic agents affects the central nervous system (CNS) and the cardiovascular system (CVS). CNS toxicity occurs at a lower dose range than does CVS toxicity. Whereas CNS toxicity is more common, CVS toxicity is more dangerous and more challenging to treat.

Local anesthetics freely cross the blood–brain barrier. The initial result of toxic levels of local anesthetics is depression of cortical inhibitory pathways, which allows excitatory pathway activity to be unopposed. When even higher blood levels are reached, generalized CNS depression occurs. Early signs of CNS toxicity include light-headedness, restlessness, tinnitus and other auditory or visual disturbances, slurred speech, tremors, metallic taste in the mouth, and numbness of the lips or tongue. If more local anesthesia is given, grand mal seizures may result. At even higher blood levels, loss of consciousness, apnea, and cardiovascular collapse are seen. If a large dose of local anesthetic is anticipated, pretreatment with a benzodiazepine may prevent toxicity. Diazepam doubles the seizure threshold for lidocaine.

CVS toxicity is the result of direct myocardial depression by the local anesthetic. A depressant effect on vascular smooth muscle, as well as on the conducting system, is seen. This effect is rarely observed in the clinical setting. Cardiac stimulation is the more common result of toxic levels of local anesthetics and is the result of an increase in CNS activity. CVS toxicity may present itself as a drop in blood pressure, an increase or decrease in heart rate, ventricular fibrillation, or cardiac arrest.

The inadvertent intravenous injection of bupivacaine (Marcaine) or etidocaine can result in severe cardiovascular compromise and collapse, frequently refractory to attempts at resuscitation. This is because of the high degree of tissue binding of these two local anesthetics. Consequently, bupivacaine (Marcaine) should probably not be used when an intravascular injection is likely. For example, it should probably not be used for subcutaneous injection prior to a facelift where large volumes of solution are injected in a vascular area. Also, the pregnant patient is more sensitive to CVS toxicity of bupivacaine (Marcaine) than is the nonpregnant patient.


Experience with the “tumescent technique” of local anesthesia infiltration casts doubt on previous “facts” regarding maximal local anesthetic dose. This technique involves the infiltration of large volumes of a dilute solution of lidocaine (0.1% or 0.05%) and epinephrine (1:500,000 to 1:1,000,000) into the subcutaneous adipose tissue prior to liposuction procedures. Studies demonstrate that doses up to 35 mg/kg lidocaine (five times the manufacturer’s recommended dose) can be given safely. Serial serum lidocaine levels drawn postoperatively appear to verify the safety of this technique, which has been extended to other procedures such as abdominoplasty (see Chapter 53). The safety of this technique probably depends on the anatomy of the site of injection and the dilute nature of the solution injected. The face is not the same as the body. Although the exact dose of lidocaine that can be used safely in the face has not been clarified, it is clear that doses such as 35 mg/kg, which are safe in the subcutaneous tissues of the trunk, are far too large for the face. Until a safe maximum dose is defined, surgeons are advised to use no more than the 7 mg/kg recommended by the manufacturer.


The first step in the treatment of a patient who is convulsing as a consequence of local anesthetic toxicity is hyperventilation with an Ambu bag and face mask using 100% oxygen. Hypercarbia can worsen CNS toxicity. If the patient has a full stomach, an endotracheal tube should be placed as soon as possible to prevent aspiration. Hyperventilation may terminate the seizure, but if it does not, diazepam, 0.1 mg/kg, or thiopental, 2 mg/kg, intravenously is usually effective.

In the patient who is hypotensive as a result of local anesthetic toxicity, the treatment is intravenous fluids, peripheral vasoconstrictors (e.g., phenylephrine), and Trendelenburg positioning. An inotropic agent (e.g., dopamine) may also be required. The patient in whom arrhythmias develop as a consequence of toxicity may be refractory to therapy. If the arrhythmia is causing the cardiac output to be significantly compromised, or if cardiac arrest occurs, a prolonged period of resuscitation may be necessary, as these conditions are known to resolve over time as redistribution of the local anesthetic occurs.


Cocaine is unique in that it has both local anesthetic and vasoconstrictive action. It has considerable potential for abuse and addiction. Over the past several decades, the illegal use of cocaine has become epidemic. Cocaine is a crystalline, water-soluble powder (pKa 8.6) that is readily absorbed through mucous membranes. It undergoes hydrolysis by plasma pseudocholinesterase. A small percentage of cocaine is metabolized in the liver.

As with the other local anesthetics, the mechanism of action of cocaine involves inhibition of conduction in nerve fibers by blockade of sodium channels, which, in turn, prevents an action potential from being generated. Cocaine is the only local anesthetic that is a potent sympathomimetic. It blocks reuptake of norepinephrine and epinephrine, both in the CNS and systemically. Cocaine has multiple effects on the CNS, resulting in intense behavioral stimulation, euphoria, and arousal. The seizure threshold is initially raised, but is lowered with increasing dose, and seizures can result. The adrenergic effects of cocaine are responsible for the increased heart rate, hypertension, mydriasis, tremors, and perspiration seen with an overdose.

Traditionally, the most common clinical use of cocaine in plastic surgery is as a topical anesthetic and vasoconstrictor in rhinoplasty. It is no longer often used as other agents are safer and cheaper and have less potential for abuse. The addition of epinephrine to the topical cocaine may enhance vasoconstriction but is not safe. The combination can cause dangerous arrhythmias. It is not even clear that adding epinephrine to topical cocaine enhances the operating conditions. Studies have not demonstrated a consistent benefit from adding epinephrine to either 10% cocaine or to lower concentrations of topical cocaine.

General anesthesia and topical cocaine are frequently used together, and there are multiple studies and case reports describing the complexity of drug interactions that occur. These reports offer conflicting views of the effect that cocaine has on anesthetic requirements as well as the effect of the combination of cocaine and varying anesthetics on their arrhythmogenic potential. Studies on the combination of cocaine and general anesthetics suggest that anxious or unpremeditated patients are more prone to arrhythmias and that cocaine should not be applied before induction or soon after induction, before the achievement of a deep level of anesthesia. In those patients in whom topical cocaine was used after induction, and after a deep level of anesthesia was achieved, there were no arrhythmias. Therefore, a patient’s endogenous catecholamines are involved in these complex drug interactions.

There is also widespread agreement that ketamine significantly enhances the arrhythmogenicity of cocaine. Additionally, patients receiving monoamine oxidase (MAO) inhibitors are especially at risk for dangerous interactions with cocaine. Topical cocaine should be avoided unless the patient has been taken off the MAO inhibitor 2 weeks before the surgical procedure. Because of its sympathomimetic effects, cocaine also should be avoided in hypertensive patients. Unfortunately, individual response to cocaine varies. In some patients, ventricular fibrillation and cardiac arrest can occur as a result of a dose as small as 0.4 mg/kg.

The safe maximum dose for nasally administered 4% cocaine solution is 1.5 mg/kg. Each drop of 4% cocaine solution has approximately 3 mg cocaine. Given the above disadvantages of cocaine, however, there may no longer be a good indication for its use.

Suggested Readings

1.  Covino BG. Pharmacology of local anesthetic agents. Ration Drug Ther. 1987;21:1.

2.  De Jong RH, Heavner JE. Diazepam prevents local anesthetic seizures. Anesthesiology. 1971;34:523.

3.  Fleming JA, Byck R, Barash PG. Pharmacology and therapeutic applications of cocaine. Anesthesiology. 1990;73:518.

4.  Hallen B, Uppfeldt M. Does lidocaine-prilocaine cream permit pain free insertion of IV catheters in children? Anesthesiology. 1982;57:340.

5.  Kelton PL Jr. Local anesthetics, cocaine, and CPR. Sel Read Plast Surg. 1992;7(5):1.

6.  Klein JA. Tumescent technique for regional anesthesia permits lidocaine doses of 35 mg/kg for liposuction. J Dermatol Surg Oncol. 1990;16:248.

7.  Koehntop DE, Liao J-C, Van Bergen FH. Effects of pharmacologic alterations of adrenergic mechanisms by cocaine, tropolone, aminophylline, and ketamine on epinephrine-induced arrhythmias during halothane-nitrous oxide anesthesia. Anesthesiology. 1977;46:83.

8.  Lynch C. Depression of myocardial contractility in vitro by bupivacaine, etidocaine, and lidocaine. Anesth Analg. 1986;65:551.

9.  Ohlsen L, Englesson S, Evers H. An anaesthetic lidocaine/prilocaine cream (EMLA) for epicutaneous application tested for cutting split skin grafts. Scand J Plast Reconstr Surg. 1985;19:201.

10.  Strichartz GR, Covino BG. Local anesthetics. In: Miller RD, ed. Anesthesia. 3rd ed. New York, NY: Churchill Livingstone; 1990:437.

11.  Swerdlow M, Jones R. The duration of action of bupivacaine, prilocaine and lignocaine. Br J Anaesth. 1970;42:335.