Functional and Structural Components of a Peripheral Nerve

The functional nerve unit includes the nerve axon and its surrounding Schwann cell sheath. The Schwann cell (Fig. 29-1) may surround several unmyelinated axons or a single myelinated nerve fiber and form a myelin sheath. Junctions between sheaths along the axon called nodes of Ranvier contain sodium channels necessary for depolarization. As myelin sheath thickness increases from autonomic to sensory to motor fibers, the nodes of Ranvier are spaced farther apart. The most important structure affecting transmission of nerve impulses is the axon membrane (Fig. 29-2). The membrane consists of a double layer of phospholipids into which are embedded protein molecules that serve as channels containing pores for the movement of ions in and out of the cell. Most pores have a filter, or gate, that controls ion-specific movement and a sensory mechanism that opens or closes the gate. Bundles of nerve fibers (Fig. 29-3) are embedded in the endoneurium, which is made of collagen fibrils, and they are surrounded by a cellular layer, the perineurium. The perineurium functions as a diffusion barrier and maintains the composition of extracellular fluid around the nerve fibers. Surrounding the entire structure is the outer layer of a peripheral nerve, the epineurium, which is composed of areolar connective tissue.

The Nerve Impulse and Transmission

The inside of a nerve fiber, or axoplasm, is negative (−70 mV) at rest in comparison to the outside. This resting potential is the net result of the differences in ionic concentration on each side of the axonal membrane and the forces that tend to maintain that difference. Specifically, there is a surplus of sodium extracellularly and potassium intracellularly. The sodium channel is closed, thereby preventing these ions from moving along their concentration gradient (out → in). Although potassium can leave the cell to follow its concentration gradient (in → out), the need to maintain electrical neutrality inside the cell prevents it from completely doing so. Potassium is in equilibrium between the concentration gradient and the electrochemical gradient, thus creating the negative resting potential.

The sodium channel opens when a nerve is stimulated. Sodium ions enter slowly at first until a critical threshold is reached. They then enter the cell rapidly, along the electrochemical and concentration gradients, and cause depolarization. The influx of sodium is halted when the membrane potential reaches +20 mV, but potassium continues to move out of the cell and repolarizes it until the resting potential is reached. When the excitation process has been completed and the nerve cell is electrically quiet, the relative excess of sodium inside the cell and potassium outside the cell is readjusted by the adenosine triphosphate-dependent sodium-potassium pump.

Depolarization of a portion of the nerve causes a current to flow along the adjacent nerve fiber. This current makes the membrane potential less negative and actuates the sensor to open the next sodium channel. The action potential cycle is repeated, thereby propagating the impulse. Nerve conduction is essentially unidirectional because the sodium channel is not only closed but inactivated as well and delayed closure of specific potassium channels prevents the critical threshold from being reached in the segment just depolarized. An impulse spreads continuously down the axon in unmyelinated nerve fibers. In myelinated fibers, current flows from node to node and depolarizes intervening segments at once. This saltatory conduction causes a faster rate of impulse transmission in myelinated fibers.

The Active Form

Anesthetic solutions contain uncharged and charged forms. The concentration of the uncharged form increases in more alkaline milieus. Only this uncharged lipid-soluble form can cross tissue and membrane barriers. Once the uncharged drug is through a barrier, it reequilibrates into uncharged and charged forms in a proportion dependent on the prevailing pH. Because local anesthetics are more effective in alkaline solutions, it was originally thought that the uncharged form was responsible for conduction blockade. Alkaline solutions are currently believed to be more effective because of increased penetration through tissue barriers. The cationic charged form is responsible for the actual neuronal blockade.

The Physiologic and Cellular Basis for Neuronal Blockade

Prevention of sodium influx across the nerve membrane forms the physiologic basis for conduction blockade. Local anesthetics slow sodium influx, thereby decreasing the rate of rise and amplitude of depolarization. If sufficient anesthetic is present and the firing threshold is not reached, the action potential is not formed. With no action potential, no impulse is transmitted and conduction is blocked, which results in local anesthesia.

How anesthetic agents prevent sodium influx is still not completely understood. It is believed that the cationic charged form blocks the action potential from inside the membrane; the agent enters the sodium channel from the axoplasmic side and binds to a receptor.4,5 This “specific receptor” theory is well accepted and is considered the predominant mechanism in preventing influx of sodium. However, this theory cannot account for the action of benzocaine and other neutral compounds or the uncharged base forms of the common local anesthetics.

In summary (Fig. 29-4), when a local anesthetic (other than benzocaine) surrounds the perineurium, it equilibrates into its uncharged and charged forms based on tissue pH and pK_a. In a more alkaline environment, a greater proportion of the uncharged form is present. The uncharged lipid-soluble form penetrates tissue, nerve sheath, and nerve membrane to gain access to the axoplasm and reequilibrates into both charged and uncharged forms. The charged form enters the sodium channel, decreases movement of sodium into the cell, and halts nerve transmission. The uncharged base is also involved in sodium channel blockade, but the exact nature of this mechanism is unknown.

Onset of Action

The pK_a of an anesthetic is the primary physiochemical factor that determines its onset of action. Increased tissue penetration and a shortened onset of action are found in drugs with a lower pK_a because more of the lipid-soluble uncharged form is present (Tables 29-2 and 29-3). Although in isolated nerve fibers the onset of action directly parallels pK_a, other physiochemical factors also influence drug activity. For example, prilocaine and lidocaine have the same pK_a, but lidocaine’s onset is faster because of its enhanced ability to penetrate through nonnerve tissue.

The site of administration also influences the onset of action. Onset times are prolonged as the amount of interspersed tissue or the size of the nerve sheath increases because of the greater distance that the agent must travel to reach its receptor. The pattern of onset for large nerves is determined by the structural arrangement of its fibers. Peripheral (mantle) fibers are blocked before core fibers. Because mantle fibers innervate more proximal regions, nerve blockade proceeds in a proximal to distal progression.

Adding sodium bicarbonate to raise the pH of the anesthetic solution (a technique that decreases pain on injection) yields a higher concentration of the uncharged lipid-soluble form and decreases onset time. Increasing the total dose by using a higher concentration of the same volume or a greater volume of the same concentration also shortens onset time. For most procedures performed in the ED, the time of onset of most agents is short enough that manipulation to achieve shorter times is unnecessary.

Potency

The lipid solubility of an anesthetic is a primary physicochemical factor determining potency. The drug’s partition coefficient, not the concentration of the lipid-soluble form determined by the pK_a or pH, confers its lipid solubility. Because the nerve membrane is lipid, lipophilic anesthetics pass more easily into the cell and few molecules are needed to block conduction (see Tables 29-2 and 29-3).

The degree of vasodilation produced by the anesthetic also affects potency because vasodilation promotes vascular absorption, thereby reducing the amount of locally available drug. Lidocaine is more lipid soluble than prilocaine or mepivacaine, but it produces more vasodilation. Although lidocaine is twice as potent as prilocaine or mepivacaine in vitro, it is equipotent in vivo. Though not a primary reason for its use, epinephrine, by producing vasoconstriction and making more molecules available to the nerve, increases the depth of anesthesia. Drugs more readily absorbed by fat have reduced potency. Increased concentration also increases potency. Choosing an anesthetic for its potency is not usually necessary for any given site because the commercially available concentration of an agent may be manipulated to make most drugs equianesthetic. For example, lidocaine, being one fourth as potent as bupivacaine, is usually used at four times the concentration (1% to 2% versus 0.25% to 0.5%, respectively). For different sites and techniques, different concentrations and volumes of a given agent are needed to produce adequate blockade.

Duration

The degree of protein binding of an anesthetic primarily determines its duration of action. Agents that bind more tightly to the protein receptor remain in the sodium channel longer (see Tables 29-2 and 29-3). Like potency, the duration of action is reduced by the vasodilation produced by local anesthetics. Prilocaine, which is less protein bound than lidocaine, has a longer duration of action because of its lesser degree of vasodilation. The duration of action also varies with the mode of administration. It is shorter when agents are applied topically.

The duration of action may be prolonged by several methods. Increasing the dose, usually by increasing the concentration, prolongs the duration to limits imposed by toxic effects. Raising the pH of the anesthetic solution has also been shown to prolong duration.6,7 The most practical way to increase duration is to use solutions that contain epinephrine.⁸ Epinephrine causes vasoconstriction, decreases systemic absorption, and allows more drug to reach the nerve. The effect of epinephrine varies according to the agent. Anesthetics that intrinsically produce more vasodilation (e.g., procaine, lidocaine, mepivacaine) benefit more from epinephrine’s vasoconstrictive action. The long-acting, highly lipid-soluble agents (e.g., bupivacaine, etidocaine) are less affected because they are substantially taken up by extradural fat and released slowly. In fact, lidocaine with epinephrine may be effective for as long as bupivacaine without epinephrine. Generally, most ED procedures can be accomplished quickly before the anesthesia wears off regardless of which drug is selected. Choose agents with a long duration of action when the procedure is lengthy or if postoperative analgesia is desired.

Agents and Uses

Effective anesthesia of the intact mucous membranes (not intact skin) of the nose, mouth, throat, tracheobronchial tree, esophagus, and genitourinary tract may be provided by several anesthetics (Box 29-1). Tetracaine, lidocaine, and cocaine are the most effective commonly used agents (Table 29-4 and Box 29-1). Benzocaine (14% to 20%) is commonly used for intraoral or pharyngeal anesthesia (Fig. 29-5). The anesthesia produced is superficial and does not relieve pain that originates from submucosal structures. The onset of action may be slow, which limits its usefulness in urgent situations (such as passing a nasogastric tube). Agents applied topically can be absorbed systemically, and concentrated topical agents can cause toxicity.

Tetracaine solution is an effective and potent topical agent with a relatively long duration of action. It is used in concentrations from 0.25% to 1% with a recommended maximum adult dose of 50 mg. In overdose, it has the disadvantage of severe cardiovascular toxicity without any preceding central nervous system (CNS) stimulatory phase.

Lidocaine is also an effective topical agent that is marketed in a variety of forms (solutions, jellies, and ointments) and concentrations (2% to 10%). The 10% form is most effective, and minimal topical anesthesia is achieved with less potent concentrations. Lidocaine is commonly used as the 2% viscous solution prescribed for inflamed or irritated mucous membranes of the mouth and pharynx. Patient misuse of viscous lidocaine, by repeated self-administration, can lead to serious toxicity. Topical lidocaine provides an adequate duration for most procedures, with the maximum safe dose being 250 to 300 mg.

Cocaine is an effective, but potentially toxic topical agent that is applied to the mucous membranes of the upper respiratory tract. Although it is an ester, hepatic metabolism occurs, as does hydrolysis by plasma pseudocholinesterase. Absorption is enhanced in the presence of inflammation. Cocaine is the only anesthetic that produces vasoconstriction at clinically useful concentrations, hence its popularity for treating epistaxis. This major advantage is offset by its susceptibility to abuse and toxic potential. The toxic effects are due to direction stimulation of the CNS and blockade of norepinephrine reuptake in the peripheral nervous system. Cocaine should not be administered to patients who are sensitive to exogenous catecholamines or who are taking monoamine oxidase (MAO) inhibitor antidepressants. Clinical manifestations of toxicity include CNS excitement, seizures, and hyperthermia. Central and peripheral effects of hypertension, tachycardia, and ventricular arrhythmias may also be seen. Acute myocardial infarction has been reported after topical application.⁹ Cocaine is commonly used as a 4% solution with a maximum safe dose of 200 mg (2 to 3 mg/kg). A 10% solution is available, but this concentration adds little to the topical effect while enhancing the potential for toxicity. Coronary vasoconstriction may occur with doses as low as 2 mg/kg applied to the nasal mucosa. Although the clinical effect of this vasoconstriction is usually benign and without electrocardiographic changes, topical cocaine should be used cautiously in patients with known or suspected coronary artery disease. Dyclonine offers advantages over other topical anesthetic agents. It is a ketone derivative without an ester or amide linkage and may be used in patients who are allergic to the common anesthetics. Extensive experience with the topical preparation has shown it to be effective and safe.¹⁰ Dyclonine is marketed in 0.5% and 1% solutions, often in sore throat preparations, with a maximum adult recommended dose of 300 mg.

Benzocaine is an ester that is marketed in its neutral form in 14% to 20% preparations (Cetacaine, Americaine, Hurricaine) (see Fig. 29-5). Its low water solubility prevents significant penetration of the mucous membranes, thus reducing systemic toxicity if applied to intact mucosa. However, it is not a potent anesthetic and has a brief duration of action. It is more allergenic than other topical agents. Benzocaine is usually dispensed in an admixture with other therapeutic ingredients and is clinically effective only at relatively high (>14%) concentrations. Benzocaine is available as a nonprescription gel and liquid (6.3% to 20% Anbesol, for example) and is used for a variety of maladies, including ear pain, mouth pain, and teething. It is commonly used by dentists to produce mucosal anesthesia before intraoral nerve blocks (see Chapter 30). Adriani and Zepernick¹⁰ recommended this agent for lubricating catheters, airways, endotracheal tubes, and laryngoscopes and reported only one adverse reaction (methemoglobinemia) in their experience with approximately 150,000 patients. Methemoglobinemia occurs rarely after mucosal absorption of benzocaine used repeatedly for teething infants and after standard doses of benzocaine sprays used in endoscopic procedures.¹¹

An excellent topical preparation is a combination of lidocaine, prilocaine, and tetracaine, especially useful for dental mucosa anesthesia (see Fig. 30-3). Topical gel mixtures of 2.5% lidocaine and 2.5% prilocaine (eutectic mixture of local anesthetics [EMLA]) are commonly used on intact skin but have also been used on mucous membranes. EMLA is more effective than 20% benzocaine when applied to the oral mucosa before needle injection for dental anesthesia. One study demonstrated that pain was reduced more quickly with EMLA than with benzocaine when applied to the buccal mucosa.¹²

As with infiltrated anesthesia, toxic reactions to topically applied anesthetics correlate with the peak blood levels achieved and not necessarily with the dose administered. Systemic absorption of a topical agent is more rapid, with a higher level being achieved than with the same dose given by infiltration (Fig. 29-6). The total dose of a topical anesthetic should be considerably less than that used for infiltration at a given site. Fractionating the total dose into three portions administered over a period of several minutes effectively reduces peak blood levels. Inadvertent suppression of the gag reflex, combined with difficulty swallowing, may lead to aspiration, an important potential adverse reaction to topical anesthesia of the nose, mouth, and pharynx. Infections from drug solutions in multidose vials for topical anesthesia of the larynx and trachea have not been substantiated.

Technique and Precautions

A commonly used “magic mouthwash” for the topical treatment of painful gingivostomatitis in children is often prescribed by emergency clinicians and pediatricians. There has been little scientific study of the preparation and it is not available commercially, but it has been used safely for decades. It consists of equal parts viscous lidocaine (2%), Maalox as a binder, and diphenhydramine elixir. Corticosteroids or nystatin is often added when the mixture is used to treat chemotherapy-induced mucositis.¹³ However, a recent review found no evidence that magic mouthwash is effective in treating this condition.¹⁴ The creamy mixture is swished around the mouth and expectorated or painted on specific lesions with a cotton swab. Packing an area with a cotton ball soaked with this mixture is one option. Repeated doses or swallowing of the elixir can produce systemic toxicity, so careful instruction should be given to limit use of the solution to every few hours. This combination would be theoretically less toxic than simply using topical lidocaine.

Emergency clinicians often prescribe 2% viscous lidocaine (20 mg/mL) for patients with pharyngitis, stomatitis, dental pain, or other inflammatory or irritative lesions in the oropharynx. Although this intervention is widely used and generally safe, the common misconception that topical anesthesia is totally innocuous may result in poor patient instructions and serious consequences. Topical lidocaine is helpful for painful mouth lesions but is of little practical value for acute pharyngitis, for which systemic analgesics are usually a better option. Seizures and death from topical lidocaine have been reported when excessive repeated doses have been administered.15,16 Toxic blood levels may occur because the anesthetic effect of viscous lidocaine lasts for only 30 to 60 minutes and patients with recurrent pain may either ignore or be ignorant of the safe dosing interval of 3 hours and medicate themselves more frequently. Patients tend to increase each dose to obtain greater relief, and inflammation may increase systemic absorption. In addition, painful oral lesions may last for several days.

Children are at higher risk for the rare toxicity of oral lidocaine. When compared with adults, children may exhibit increased lidocaine absorption, decreased clearance, and a longer half-life.¹⁷ Continued medication use allows lidocaine and its major metabolites monoethylglycinexylidide (MEGX) and glycinexylidide (GX) to accumulate. Both MEGX and GX are produced from the hepatic metabolism of lidocaine and are excreted in urine. They possess anesthetic and antiarrhythmic activity and have the potential for CNS toxicity. Although these metabolites are less potent than lidocaine, their elimination half-lives are considerably longer. Several investigators regard MEGX and GX to be the cause of CNS toxicity with prolonged topical use of lidocaine.¹⁶ The length of time that viscous lidocaine is retained in the mouth and whether the excess is expectorated or swallowed also affect the blood level produced. Expectorating the medication after swishing it in the mouth produces much lower blood levels than when it is swallowed. It seems logical that the most hazardous mode of administration would be to retain the solution in the mouth “until absorbed.”

Clearly explain the proper way to use viscous lidocaine and inform patients not to dose themselves ad libitum. Note that a 2% solution contains 20 mg/mL, or 100 mg per standard teaspoon (5 mL). The recommended maximum adult dose is 300 mg (15 mL of a 2% solution) no more frequently than every 3 hours. When possible, instruct the patient to decrease the dose by using direct cotton swab application. When gargled or swished in the mouth, limit application time to 1 to 2 minutes, and instruct the patient to expectorate excess solution. Limit use to 2 or 3 days, especially if swallowing the solution is necessary to obtain relief. Prescribe lower doses for patients at risk for decreased clearance (see “Systemic Toxic Reactions” later in this chapter). Doses for children are prescribed at 3 mg/kg. Because infants cannot expectorate well, do not use viscous lidocaine for minor oral irritation and teething. Recommend that no food be eaten for 1 hour after application because anesthesia of the oropharynx can interfere with swallowing and cause aspiration. Special note should be made of the over-the-counter availability of benzocaine, commonly used for toothaches and teething. A gel or liquid (Anbesol) is available in 6.3% to 20% formulations. When used repeatedly in the oral cavity on irritated tissue, systemic toxicity, including methemoglobinemia, may occur.

Lidocaine 4% solution can be atomized with a standard nebulizer device commonly used for delivering asthma medications and inhaled by the patient before insertion of a nasogastric tube. This method effectively anesthetizes the nasopharyngeal and oropharyngeal tissues, thereby easing the pain with tube insertion.18,19

Agents and Uses

The stratum corneum provides a cutaneous barrier that prevents the commonly marketed aqueous solutions (acid salts) from producing anesthesia, but saturated solutions of the bases of local anesthetics are effective on intact skin. When applied topically to abraded skin, most anesthetic agents result in peak blood levels similar to those resulting from infiltration in 6 to 10 minutes.

Technique

Complications

General adverse reactions to anesthetic agents are discussed in the “Complications” section later in this chapter.

Tetracaine base is quite safe, with a low blood concentration after proper use. In one study, cutaneous erythema developed at the site of application in approximately 25% of patients.²⁴ This vasodilatory effect may actually be an advantage when starting IV lines or performing venipuncture. EMLA is also quite safe. Although it has a high rate of local skin reactions, they are mild and transient, with disappearance 1 to 2 hours after removal of the cream. Despite the reported successful use of EMLA cream on skin ulcers, Hansson and associates²⁵ and Powell and coworkers³⁸ described an increase in bacterial growth, infection, and inflammation when used in experimental wounds. Methemoglobinemia resulting from the metabolites of prilocaine may occur with EMLA.²³ The risk for clinically significant methemoglobinemia seems remote when EMLA is used properly. It is contraindicated in any infant younger than 3 months and in infants between 3 and 12 months of age who are currently taking methemoglobinemia-inducing drugs (nitrites, sulfonamides, antimalarials, phenobarbital, and acetaminophen). The risk for adverse effects is increased in patients with anemia, respiratory or cardiovascular disease, and deficiencies in glucose-6-phosphate dehydrogenase or methemoglobin reductase. Prolonged inhalation of ethyl chloride spray may produce general anesthesia, coma, or cardiorespiratory arrest. Ethyl chloride is also flammable, thus precluding its use with electrocautery.

Topically applied anesthetics are often covered with an occlusive dressing to contain the medication. Covering the medication with an occlusive dressing may dramatically increase drug absorption and the amount of metabolites. Oni and associates demonstrated that 4% lidocaine cream applied to volunteers with an occlusive dressing resulted in three times the level of serum lidocaine and double the level of MEGX when the same dose was applied to volunteers without occlusion.³⁹ Use caution when occluding topical anesthetics over intact skin because markedly elevated serum level of drug may be reached.

Background

In 1980, Pryor and colleagues⁴⁰ reported their experience with a topical anesthetic solution (tetracaine-adrenaline-cocaine [TAC]) for wound repair. The original formula, used in most subsequent studies, consists of a solution of 0.5% tetracaine, 1 : 2,000 epinephrine (adrenaline), and 11.8% cocaine. Traditionally, anesthesia is produced by firmly applying a solution-saturated gauze pad or cotton ball directly to the laceration for 10 minutes. The resulting loss of cutaneous sensation is centered about the area of application. Gel formulations of topical wound anesthesia (TWA) with alternative mixtures of agents promise to improve the ease and safety of topical anesthetic solutions for wound repair in the ED. Advantages of TWA include painless application, no distortion of wound margins, good hemostasis, and good patient and parental acceptance in the pediatric age group.

Indications and Contraindications

Use of TWA is generally restricted to young children with wounds less than 5 cm in length in whom the delay in application of an anesthetic is acceptable and proper application can be ensured (Fig. 29-7). TWA containing vasoconstricting agents is not generally used in structures without a collateral blood supply (e.g., digits, tip of the nose, pinna of the ear, penis), although there is no evidence that this is unsafe. When some wound preparation is desired before anesthesia, remove large debris and clotted blood to allow the appropriate application of TWA and then finish wound preparation once the wound is properly anesthetized.

TWA appears to be less effective on the trunk and extremities than on the face and scalp and less effective than lidocaine infiltration in these areas. The 10- to 20-minute onset time may be unacceptable in a busy ED.⁴¹ Two other often mentioned drawbacks may be more theoretical than real. Vasoconstrictor-induced higher infection rates (see “Complications” later in this chapter) have not been clearly demonstrated. The argument that the necessary 10-minute application period is time-consuming and takes valuable nursing time is partially offset by using the child’s caretaker or adhesive paper tape alone to hold the solution in place. It is not necessary for anyone to “hold” the medicine in place when gel is used.

Some EDs still stock topical anesthetic gels that contain cocaine. Cocaine use is complex because of cost and federal regulations requiring storage in a locked cabinet and maintenance of separate written records of its use. In view of the evidence that mixtures without cocaine are efficacious, avoid the potential complications related to cocaine, and do not have the potential for abuse that cocaine does, the practicality of cocaine-containing TWA has been questioned.⁴²

Agents and Effectiveness

Technique and Dosage

Because the topical mixtures noted earlier (especially TAC) are not innocuous anesthetics, pay close attention to the technique of application and the recommended maximum dose. There is no uniformly accepted application technique, composition of components, or concentration of components.

Generally, apply topical solutions such as TWA to the wound in a gravity-dependent position and carefully fill the wound cavity. After 3 minutes, place a single 2- × 2-cm gauze pad or cotton ball saturated with TWA on the wound. Tape or hold the pad firmly in place for 15 to 20 minutes. The person holding the gauze should wear latex examination gloves to minimize the risk for cutaneous absorption of the solution. The average dose of TWA mixture for most wounds is 2 mL.

Gaufberg and coauthors⁵⁷ described “sequential layer application” (SLA) of topical lidocaine with epinephrine (TLE) to deeper wounds that might not typically be amenable to the use of TWA. Cotton soaked with TLE was applied to the wound surface and 2 mm of surrounding skin for 10 to 15 minutes and then removed. A second similarly soaked piece of cotton was packed deeper into the wound for 10 to 15 minutes. Deep wounds were treated with a third piece of TLE-soaked cotton placed deeper into the wound. Anesthesia was presumed when 3 mm or more of pallor was seen on all wound margins. The group receiving lidocaine by SLA was compared with a group receiving infiltrated 2% buffered lidocaine with epinephrine. Both groups experienced a similar degree of anesthesia during suturing. Mean time to anesthesia with SLA was 29 minutes versus 5 minutes for the infiltration group. Despite the longer time in the SLA group, the authors argued that the additional time is worthwhile because the painful injection, risk for hollow-bore needle injury, and tissue distortion with infiltration were eliminated. If time permits, the SLA technique may be useful for wounds that would have otherwise required infiltrated anesthesia.

Hegenbarth and associates⁴³ estimated the maximum safe dose of full-strength TAC to be 0.09 mL/kg based on the known maximal safe dose of infiltrated tetracaine, the mucosal application of cocaine, and an estimate of absorption of solution onto the applicator. The key to safety is to avoid TAC on mucosal surfaces or areas in which sniffing or swallowing may accidentally occur. Topical mucosal anesthesia is discussed elsewhere in this chapter.

Prepare an epinephrine-cocaine gel by adding 0.15 g of methylcellulose to 1.5 mL of epinephrine-cocaine solution. Stir the mixture thoroughly for a minute or two until a gel consistency is obtained. After sterile preparation, place the wound in a gravity-dependent position and apply the gel with a cotton-tipped swab to coat the entire wound cavity and margins. Allow the wound to stand for 15 to 20 minutes and thoroughly wash the wound cavity to remove the gel. In Bonadio and Wagner’s study,⁴⁹ the average dose used was 0.35 mL of gel containing only 40 mg of cocaine. Again, other agents are equally efficacious and safer; select these over cocaine-containing mixtures whenever possible.

Complications

Most adverse events associated with TWA occur with mixtures that contain cocaine. Lidocaine toxicity is a well-recognized adverse event when higher doses are used (see “Systemic Toxic Reactions” later in this chapter), but lidocaine toxicity has not been reported with TWA mixtures.

Mucosal application may rarely lead to significant systemic toxicity; fatalities have been reported after application. Even after nonmucosal TAC use, cocaine levels appear in the blood and cocaine metabolites appear in the urine in the majority of patients,58,59 but tetracaine does not. Gel formulations of TAC tend to stay in the wound and thus reduce the risk of solution runoff onto mucosal surfaces. There is no need to use a gauze pad to apply the medication in a gel formulation or to hold it in place. Because the entire applied dose will stay in the wound, a lower dose can be used. Gel also provides more uniform application to tissues, which improves the anesthetic effect. In tissues containing end-arteries, ischemia caused by vasoconstrictors may occur. Avoid TAC on the digits, the tip of the nose, the penis, and the pinna of the ear. Use TAC with caution on patients with coronary artery disease, uncontrolled hypertension, seizures, or peripheral vascular disease. Patients with decreased plasma cholinesterase levels are theoretically at increased risk for systemic toxic effects, but this potential risk is of little clinical concern.

• For a wound with excessive bleeding, use lidocaine with epinephrine and sodium bicarbonate.

• For an apprehensive patient, use lidocaine with sodium bicarbonate.

• For anticipated prolonged postprocedure pain, use bupivacaine.

Buffering

Raising the pH of an anesthetic by adding sodium bicarbonate decreases pain dramatically, whereas lowering the pH by adding epinephrine increases pain. Buffering is probably the best way to reduce the pain of local anesthetic injections, and its routine use is highly recommend. It is probable that pH is not the sole factor in producing pain because the pain produced by various agents does not correlate strictly with the pH. Sodium bicarbonate probably works by increasing the ratio of nonionized to ionized molecules, which either renders the pain receptors less sensitive or causes more rapid diffusion of solution into the nerve and a shorter time to the onset of anesthesia.

To alkalinize lidocaine, add 1 mL of sodium bicarbonate (8.4%, 1 mmol/mL) to every 10 mL of anesthetic solution. As the pH of the solution is raised, the anesthetic becomes unstable and has a decreased shelf life. It was initially recommended that buffered lidocaine be prepared just before use to avoid precipitation and degradation, but buffered lidocaine retains its effectiveness for 1 week and refrigeration may further increase its shelf life.61,62 Bicarbonate may be combined with plain lidocaine for both infiltrative anesthesia^63,64 and digital nerve blocks.⁶⁵ In one volunteer study, sodium bicarbonate was effectively combined with lidocaine and epinephrine.⁶²

Sodium bicarbonate can be added to bupivacaine, but the solution tends to precipitate as the pH rises. The clinical effect of such precipitation is unclear, but if it occurs, it is probably prudent to use another solution prepared with less buffer. Precipitation varies directly with the concentration of bupivacaine and the time since mixture.⁶⁶ Cheney and coworkers⁶⁷ showed that 0.05 mL of 8.4% sodium bicarbonate (measured in a tuberculin syringe) could be mixed with 10 mL of 0.5% bupivacaine without precipitation. The goal of using bupivacaine is to prolong the duration of anesthesia; this effect can also be accomplished somewhat by using buffered lidocaine (plain or with epinephrine).

In view of the amount of published literature demonstrating that adding sodium bicarbonate to lidocaine before infiltrative anesthesia reduces the pain of injection without adverse effects, lidocaine should almost always be buffered when infiltrated in the ED; there is no practical reason to avoid the addition of bicarbonate.

Temperature Manipulation

Warming an anesthetic to body temperature (37°C to 42°C) reduces the pain of infiltration,68,69 but warming may not reduce injection pain as much as buffering with sodium bicarbonate does. Bartfield and colleagues⁷⁰ found that lidocaine warmed to 38.9°C was more painful than room-temperature buffered lidocaine during intradermal injection. Brogan and associates,⁷¹ using lidocaine warmed to 37°C, found the warmed lidocaine and room-temperature buffered lidocaine to be equivalent during wound infiltration. Neither study found a synergistic effect with combined warming and buffering. Martin and coworkers⁷² found that warmed (37°C) lidocaine was no less painful than buffered lidocaine. Anesthetic solutions can be warmed in a baby food warmer with thermostat temperature control or in an IV solution warmer. Warming is not believed to adversely affect the shelf life of the local anesthetic.

Locally cooling the area to be infiltrated may provide additional pain relief. Leff and colleagues⁷³ demonstrated that patients receiving local infiltrative anesthesia for repair of an inguinal hernia had less pain when the incision area was cooled before infiltration. Patients were randomized to two groups and had a 1000-mL bag of saline placed over the inguinal area for 5 minutes. One group used saline bags at room temperature; the other group used saline bags cooled to 4°C. A significant decrease in pain perception was found in the group in which the inguinal area was cooled before lidocaine infiltration. Cooling of wounds in the ED before infiltration has not been studied.

Injection

The pain from injection of local anesthetics is primarily a result of skin puncture (which can be minimized with small-gauge needles) and subcutaneous injection. Although patients fear the needle, there is little perceived pain merely from the needle’s presence in subcutaneous tissue. Place the injection in subdermal tissue to minimize needle puncture pain and the tissue distention that occurs with intradermal placement. Place the needle “up to the hub” and inject while withdrawing along the just-created subdermal tunnel to minimize tissue distention. After an initial injection, instead of totally withdrawing the needle from the tissue, redirect it along another path to lessen the number of skin punctures. Slowly inject the smallest volume necessary to reduce pain.

Because the patient barely feels a needle placed subcutaneously and skin puncture is often quite painful, make all wound injections through the wound edge and not through the skin (Fig. 29-9).^74,75 Spread of infection beyond the wound margin has not been demonstrated clinically with this technique. Some clinicians choose to inject the anesthetic through intact skin in patients with a grossly contaminated wound. Bierman⁷⁶ described a technique of patient distraction by applying light pressure to alternate sides of the wound with one’s fingers and repeated ambiguous questioning about feeling the light pressure rather than the ongoing wound injection. Ask school-aged children to count backward or to say the “ABCs” to distract them during injection. Inject 1% lidocaine through intact skin with the needle bevel facing upward because this is less painful than injecting with the needle bevel facing downward.⁷⁷

To prevent a systemic toxic reaction, avoid giving an intravascular injection. For infiltration anesthesia with a small-gauge needle, however, aspiration is usually unnecessary unless the injection is deeper than the subcutaneous area or the area to be injected contains many large vessels.

Indications

Intrapleural anesthesia introduces a local anesthetic into the pleural space (i.e., between the parietal and visceral pleura) through an epidural catheter. The anesthetic can be introduced through a previously placed chest tube. The technique can provide relief for several conditions, primarily postthoracotomy pain, postcholecystectomy pain, and most importantly for emergency clinicians, posttraumatic chest pain (e.g., rib fractures, pneumothorax, hemothorax). This procedure is not only useful for pain relief but also facilitates turning, coughing, and deep breathing. Several studies have demonstrated improved respiratory mechanics when intrapleural anesthesia is used.85,86 Though not unanimous, most studies show that intrapleural anesthesia is effective in providing analgesia.^87,88 Concern has been raised that intrapleural anesthesia may create a level of anesthesia below the umbilicus and make posttraumatic abdominal examinations unreliable. Until this issue is clarified, it seems prudent to rule out intraabdominal injury before intrapleural anesthesia is used.⁸⁹

Technique

If a chest tube is in place, it is preferable to inject anesthetic into the pleural space through the chest tube. Clamp the tube for 10 to 15 minutes to allow the anesthetic to diffuse. When the tube cannot be taken off suction or if no tube is present, inject the local anesthetic percutaneously.⁹⁰ With the patient in the lateral position (with the affected side up), place a 16-gauge Tuohy needle 8 to 10 cm from the posterior midline in the eighth intercostal space. Angle the needle 30 to 40 degrees with respect to the skin and aim medially, with the bevel up and directed just above the rib. After perforating the posterior intercostal membrane (felt as a distinct resistance), remove the stylet and attach a well-wetted, air-filled glass syringe to the Tuohy needle. Advance the needle until it enters the pleural space, which is denoted by the plunger being drawn down the syringe as a result of the negative pressure created during inspiration. Remove the syringe and introduce an epidural catheter 5 to 6 cm into the pleural space. Remove the Tuohy needle, obtain a chest radiograph to confirm proper position, and secure the catheter.

The most commonly used anesthetic and dose is 20 mL (0.3 mL/kg) of 0.5% bupivacaine. A dose repeated every 8 hours is safe and effective.⁹¹ Alternatively, infuse 0.25% bupivacaine at 0.1 to 0.2 mL/kg/hr after a bolus has been administered.⁸⁵ The solution presumably diffuses from the pleural space “back” through the parietal pleura and the intercostal muscle to reach the intercostal spaces, where it blocks the intercostal nerves. The level of anesthesia can extend from T2 to T12 and involve the skin, chest, abdominal wall, and potentially the viscera if the visceral afferent fibers are blocked at the sympathetic chain in the paravertebral gutter.

Though not yet a consistently proven or a completely standardized technique, intrapleural anesthesia offers promise for patients and is a valuable procedure for the emergency clinician to master.

Wound Healing

Local anesthetics produce cytotoxic effects on cell structure and function in a dose- and time-related manner. These effects, at doses well below those used clinically, involve fibroblasts more than nervous tissue. Local anesthetics impair mitochondrial function and fibroblast proliferation and hasten apoptosis in vitro; the clinical relevance of these effects to the ED use of local anesthetics is likely to be minimal.92,93 Collagen synthesis is inhibited by lidocaine and bupivacaine.⁹⁴ Morris and Tracey⁹⁵ found that lidocaine in increasing concentrations progressively reduces the tensile strength of wounds. Epinephrine added to 1% and 2% concentrations of lidocaine further reduced tensile strength, but when epinephrine was added to distilled water or to 0.5% lidocaine, it had little effect. Several conclusions may be clinically relevant. Although it may delay the onset of anesthesia, 0.5% lidocaine solution, without epinephrine, may be best for maintaining wound strength.

Eriksson and associates⁹⁶ found that lidocaine reduces the inflammatory response in wounds by decreasing the number of white cells and their metabolic activity. Although an inflammatory response may be beneficial in a contaminated wound, it can be detrimental in a sterile wound because of tissue toxicity created by the release of superoxide anions, lysosomal enzymes, thromboxanes, leukotrienes, and interleukins. The clinical relevance of this is unknown. None of the concerns mentioned earlier should prohibit the use of standard anesthetics or epinephrine when their use is otherwise indicated.

Wound Infection

Though not generally appreciated, it has long been known that local anesthetics possess antimicrobial activity in vitro. Lidocaine and procaine demonstrate concentration-dependent inhibition of culture growth of most gram-negative organisms.97–99 Gram-positive isolates are also significantly affected by lidocaine and, to a lesser extent, by procaine. Lidocaine inhibits the growth of common nosocomial pathogens, including Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, and several strains of methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci.⁹⁹ Administering anesthetics before obtaining material for culture, including injecting a joint before arthrocentesis, may give false-negative culture results. To avoid this problem, if possible inject the skin at the injection site and along the needle tract but not into the actual joint space until after a synovial fluid specimen has been obtained for culture. Berg and coworkers¹⁰⁰ demonstrated that lidocaine administered before tissue biopsy of chronic wounds did not affect the culture results when the exposure time before culture was less than 2 hours. This effect is also significant when anesthetic ointments are applied before culture. EMLA cream applied before culture demonstrates powerful antimicrobial properties.¹⁰⁰ Furthermore, it has been shown that adding sodium bicarbonate to lidocaine greatly enhances its inhibitory effect on bacteria.¹⁰¹ Although local anesthetics can interfere with culture testing, several studies have shown that local anesthetics, by themselves, do not appear to alter the incidence of wound infection.^102,103

Epinephrine appears to exert a deleterious effect on host defenses, at least in animal models. Studies of infiltrated and topically applied epinephrine solutions in contaminated animal wounds show an increased potential for infection.102,103 Epinephrine-induced vasoconstriction may contribute to tissue hypoxia, retard the killing of S. aureus by leukocytes, and reduce leukocyte migration into the tissue.¹⁰⁴ Most clinical studies using topical anesthetics with vasoconstrictor properties (e.g., TAC mixtures) do not demonstrate a significant rise in infection rates.^40,43,44,49 The concerns mentioned earlier should not prohibit the use of epinephrine for wound preparation when its use is otherwise appropriate.

Use of Epinephrine with Local Anesthetics

Epinephrine in conjunction with local anesthetics prolongs the duration of anesthesia and produces a temporary hemostatic effect, but its inclusion in digital block solutions has traditionally been discouraged because of the belief that it can lead to ischemia and necrosis. Areas of special concern include the digits, penis, tip of the nose, and earlobe. Although tissue ischemia and sloughing have been reported with concentrations of 1 : 20,000, current practice involves concentrations in the range of 1 : 100,000 to 1 : 200,000 and the use of submaximal doses. Several authors suggest that epinephrine-containing solutions can be safely injected into the fingers without adverse sequelae.106–109

A study of more that 3000 cases of elective injection of low-dose epinephrine (≤1 : 100,000) into the hand and fingers failed to identify a single case of digital tissue loss, and phentolamine was not required to reverse vasoconstriction.¹⁰⁶ Of 1111 procedures reported by Chowdhry and coauthors¹¹⁰ involving digital blocks with 1% lidocaine plus epinephrine (1 : 100,000) at a dose ranging between 0.5 and 10 mL (average, 4.3 mL), no patient in the epinephrine group exhibited digital ischemia or experienced nerve injuries or unusually delayed wound healing. Current data support the use of epinephrine, when correctly applied, for the performance of digital blocks of the fingers and toes.

The use of phentolamine (Regitine), which produces postsynaptic α-adrenergic blockade, is recommended for clinically significant vasoconstrictor-induced tissue ischemia. This medication is usually given by local infiltration, in the area where epinephrine has been injected, at a dose of 0.5 to 5.0 mg diluted 1 : 1 with saline. If local infiltration is ineffective because of tension within a tissue compartment or if the area of vasoconstriction is large, give phentolamine by the intraarterial route.¹¹¹

High Blood Levels

Systemic toxic reactions result from high blood levels of local anesthetic. Several factors are important in producing high blood levels, including the site and mode of administration, rate, dose and concentration, addition of epinephrine, specific drug, clearance, maximum safe dosage, and inadvertent intravascular injection.

Host Factors

Four factors tend to lower the body’s systemic tolerance to local anesthetic agents: hypoxia, acid-base status, protein binding, and concomitant drug use.

Recognition of CNS Toxicity

The earliest manifestation of systemic toxicity is CNS stimulation resulting from blockade of inhibitory synapses. CNS depression follows and is produced by direct depression of the medulla, although hypoxia may play a role. The signs and symptoms are dose related. Potential signs and symptoms of CNS toxicity, in progressing order, are numbness of the tongue, light-headedness, tinnitus, visual disturbances, muscle twitching, convulsions, coma, and apnea. Drowsiness, commonly seen with lower doses of lidocaine, is not associated with bupivacaine or etidocaine. Tetracaine may produce apnea or cardiovascular toxicity without CNS manifestations.

Recognition of Cardiovascular Toxicity

Moderate blood concentrations of local anesthetics produce slight increases in cardiac output, heart rate, and arterial pressure because of the effects of direct peripheral vasodilation and CNS stimulation. At concentrations generally well above CNS toxicity levels, local anesthetics cause direct myocardial depression, hypotension, and bradycardia, perhaps leading to cardiovascular collapse. These agents also slow electrical conduction and lead to reentry phenomena and various supraventricular and potentially lethal ventricular dysrhythmias, especially with bupivacaine and etidocaine.

Prevention of Toxicity

Knowledge of factors contributing to toxicity guides preventive measures. Avoid esters in patients with an atypical form or a quantitative deficiency of pseudocholinesterase. Use amides with caution in patients with severe liver disease or congestive heart failure. Pay attention to maximum safe dosages based on the site, technique, use of epinephrine, and patient status. Add epinephrine when possible to decrease the rate of drug absorption at vascular sites. Reduce the drug concentration by saline dilution to increase the volume for administration when a large area must be infiltrated. Frequently aspirate in areas of high vascularity, even though a negative aspiration may not prevent IV administration.¹²⁰ Slow infiltration is advised for safety and is also associated with less pain.

Treatment of Systemic Toxicity

Local anesthetics should not be administered without the ability to recognize and treat a toxic reaction, including having all necessary equipment and drugs readily available and being knowledgeable in their use. Despite taking all possible precautions, toxic reactions still occur, and close observation of the patient allows early detection and treatment.

Providing proper oxygenation and ventilation at the earliest sign of a reaction is the cornerstone of treatment. Encourage patients who are alert to moderately hyperventilate to lower the pressure of carbon dioxide (Pco₂) and raise the seizure threshold. Intubation with high-flow oxygen and hyperventilation is performed for patients who cannot adequately ventilate. Initiate IV access and monitor vital signs and cardiac rhythm closely.

Seizures are generally self-limited but are treated if they persist or prevent adequate ventilation. Because respiratory depression secondary to toxicity may follow, low-dose lorazepam or an ultrashort-acting barbiturate (thiopental or sodium methohexital) is preferred. Intubate the patient to ensure an effective airway and prevent further lactic acidosis if the seizures persist. If toxicity is caused by an ester, especially if there is an associated pseudocholinesterase problem, succinylcholine will compete with the anesthetic for the pseudocholinesterase and may increase the toxicity of both compounds.

Treat hypotension and bradycardia with fluids, leg elevation, α- and β-agonists (epinephrine, ephedrine, or dopamine), or atropine as the need dictates. Although lidocaine (with diazepam pretreatment) has been shown to be effective for bupivacaine-induced ventricular dysrhythmias, strong theoretical and experimental evidence indicates that bretylium is more effective.121,122 However, until bretylium becomes available again, amiodarone is a reasonable alternative. High doses of atropine and epinephrine can be successful in correcting pulseless idioventricular rhythm. Cardiopulmonary resuscitation is instituted when necessary.

Intravenous Lipid Emulsion

Animal studies, case reports/small series, and personal opinion have advocated the use of 20% lipid emulsion intravenously as a remarkable antidote to resuscitate bupivacaine- and mepivacaine-related cardiac arrest, a situation that is usually fatal (see http://lipidrescue.com). Rosenblatt and associates¹²³ described the IV injection of 100 mL of 20% Intralipid (Baxter formulation used for hyperalimentation) followed by an infusion (0.5 mL/kg/min over a 2-hour period) and related this intervention to successful resuscitation in a scenario that appeared hopeless. Picard¹²⁴ considers lipid emulsion a “crucial antidote” that should be available when local anesthetics are used for peripheral nerve blocks. It is unclear whether this intervention will prove useful for local anesthetic–related cardiac arrest, but the initial data are encouraging. Lipid emulsion therapy in otherwise hopeless situations of cardiac arrest secondary to local anesthetic overdose is supported (Box 29-3). It appears prudent and intuitive to initiate this antidote before cardiac arrest when significant local anesthetic toxicity is identified.

Allergenic Agents

True allergic reactions are rare and account for only 1% to 2% of all adverse reactions, but they are important to recognize because of their serious potential. Ester solutions (procaine, tetracaine) that produce the metabolite paraaminobenzoic acid (PABA) account for the majority of these reactions. Amide solutions (lidocaine, bupivacaine) are rarely involved, and usually the preservative methylparaben (MPB), which is structurally similar to PABA, is responsible. Although pure esters and pure amides do not cross-react, amides may appear to do so if multidose vials containing MPB are used. Patients may manifest an allergic response on first contact with a local anesthetic because of previous sensitization to these agents. MPB is found in creams, ointments, and various cosmetics, and PABA is an ingredient in many sunscreen preparations. Patients who are latex sensitive may have an allergic reaction incorrectly attributed to the local anesthetic.

Cell-mediated delayed reactions manifested as dermatitis are rare; it is immediate hypersensitivity that most concerns the emergency clinician. A spectrum of signs and symptoms may occur, from rhinitis and mild urticaria to bronchospasm, upper airway edema, or anaphylactic shock. Onset may be immediate and occur even during administration of the agent. Treat anaphylaxis in the usual manner.

The more frequent problem facing emergency clinicians is a patient who claims to have a past history of allergy to local anesthetics. Most patients assume that any adverse reaction to a local anesthetic procedure is an allergy. Because allergy is rarely the cause, a careful history and a review of previous records, if available, are crucial in evaluating these patients. Procaine, trade name Novocaine, was commonly used in dentistry, and many patients who experienced many types of reactions in the dentist’s office, rarely true allergy, state they are allergic to Novocaine. Procaine is no longer used in dental practice, but procaine is the local anesthetic in intramuscular penicillin preparations (procaine penicillin G).

Attempts to uncover the actual cause of the past reaction and the specific agent involved are often fruitless. Ask about the exact signs and symptoms, technique of administration, amount of drug used, and how the patient was treated. If an allergic reaction cannot be ruled out and the drug previously used is known, use an agent from the other class (whether amide or ester). Lidocaine from a dental cartridge does not contain MPB, and if this were the allergenic source, an ester agent could be used. However, if lidocaine from a multidose vial is implicated, do not use an ester because MPB may cross-react with PABA. In this case it may be safer to use an amide without MPB or to choose an alternative (see later). In most cases the allergen is an ester, and the patient can safely be given an amide without MPB. Single-dose ampules of 1% lidocaine without MPB, readily obtainable from a resuscitation cart, can be used for this purpose.

Uncertainty often exists regarding the specific agent involved, and the clinician must choose an alternative approach to local anesthesia. If the wounds are extensive and the risk is acceptable, procedural sedation (see Chapter 33) or general anesthesia may be used. Conversely, if minimal pain is expected and the procedure is short (e.g., one or two sutures or staples in the scalp), no anesthesia may be required. These methods may be useful, but the degree of anesthesia produced is frequently not sufficient. Antihistamines injected into a wound have been used successfully for many years and represent a good alternative. Local anesthetic efficacy is found in varying degrees with all antihistamines. Ketamine anesthesia may be a useful alternative in some situations and is commonly used in children.

Diphenhydramine and Benzyl Alcohol

Several studies have demonstrated that 1% diphenhydramine (Benadryl) is as effective as 1% lidocaine for infiltrative anesthesia.125–127 As long as diphenhydramine is not used at concentrations greater than 1%, potential problems of skin necrosis or significant sedation are rare. Dilute the standard 5% parenteral form to a 1% concentration for subcutaneous injection (1 mL of drug to 4 mL of saline). The duration of action of diphenhydramine is shorter than that of lidocaine but appears to be adequate for most procedures. The injection pain of diphenhydramine exceeds that of lidocaine but can be diminished by reducing the concentration to 0.5%. At this lower concentration, the effectiveness of this agent on facial wounds is lost.¹²⁸ The addition of epinephrine to 0.5% diphenhydramine results in a more painful solution with a shorter duration of action than a standard buffered lidocaine with epinephrine solution.¹²⁹ Benzyl alcohol (0.9%) with epinephrine (1 : 100,000) compares favorably with diphenhydramine as an effective local anesthetic. This appears to be a useful alternative to diphenhydramine when lidocaine cannot be used but is of shorter duration than diphenhydramine.^130–132

Skin Testing

Skin testing and progressive subcutaneous challenge doses deserve special mention because they appear to be logical and well-studied approaches. However, intradermal skin testing with local anesthetics is controversial and often of no practical benefit in the ED. False-positive results are frequently produced by local release of histamine in response to needle trauma, tissue distention, or preservatives in the solution.¹³³ In addition, a high incidence of false-negative results can occur. It is questionable whether these low-molecular-weight drugs or their allergenic metabolites are ever capable of eliciting positive responses.¹³⁴ Other disadvantages of skin testing include its time-consuming nature and potential hazard when even minute traces of an allergen may precipitate a serious reaction. Subcutaneous challenge testing in graduating doses has been advocated and may well eliminate many false responses, but it does not eliminate the problems of time and hazard. Swanson,¹³⁵ recognizing that allergy to pure lidocaine is extremely rare, recommended 0.1 mL as a single intradermal skin test. Although his approach eliminates the time disadvantage, intradermal placement can still produce false responses. It would seem more reasonable to give this test dose subcutaneously while exercising due caution in the unlikely event that a patient exhibits a serious reaction.

Summary of Anesthetic “Allergy” Management

Generally speaking, the optimal approach to a patient with a presumed anesthetic allergy is to determine the specific anesthetic agent associated with a presumed allergic reaction and then use a preservative-free agent from the other class (see earlier discussion). If the agent is unknown, use an antihistamine or give 0.1 mL of preservative-free lidocaine as a subcutaneous test dose and proceed with the full dose if no reaction occurs within 30 minutes. Given the studies mentioned earlier, prudent choices would seem to be diphenhydramine (Benadryl) or benzyl alcohol. Epinephrine (1 : 100,000) can be added to both these drugs to prolong the duration of action. Ketamine anesthesia is also an alternative.

Catecholamine Reactions

Anxiety and vasoconstrictor (epinephrine) reactions are discussed together because each produces similar manifestations caused by elevated catecholamine levels. These relatively common disorders are difficult to distinguish from each other and are not generally serious.

Excess catecholamine levels produce tachycardia, palpitations, hypertension, apprehension, tremulousness, diaphoresis, tachypnea, pallor, and on occasion, anginal chest pain. Thus, catecholamine excess may resemble the CNS stimulation phase of local anesthetic toxicity.

Catecholamine reactions are not usually caused solely by exogenous epinephrine because if it is used in its optimal concentration (1 : 200,000), the maximum safe dose (0.25 mg) is rarely exceeded. However, many patients produce significant endogenous catecholamines because of anxiety about the anesthetic approach or upcoming procedure. In this case, even the addition of small amounts of epinephrine could trigger a catecholamine reaction. Therefore, patient preparation includes proper explanation and reassurance to decrease anxiety. Exercise caution with patients who have hyperthyroidism, hypertension, or atherosclerotic cardiovascular disease, although these conditions do not contraindicate the judicious use of epinephrine-containing anesthetics. Do not give epinephrine-containing anesthetics to patients taking MAO inhibitors.

Treatment of a catecholamine reaction includes stopping further drug administration, observing the patient closely, and administering α- or β-antagonists or benzodiazepine agents, if necessary, to combat severe reactions.