Chapter 123. Local Anesthesia

Modern medicine can trace the use of local anesthetics back to the year 1884, when the Austrian Physician Karl Koller first used topical cocaine to assist with an ophthalmological operation.1 The following year, the premier Surgeon William Halstead first used injected cocaine to generate the intentional blockade of nerve transmission.2 Unfortunately for Halsted, his experiments with cocaine soon led to a concurrent dependency.3 The emerging illicit market for this compound soon prompted the search for a less toxic agent.3 Procaine, more commonly known by its trade name Novocain, was the first synthetic local anesthetic. It is a benzoic acid ester derivative developed by the German chemist Alfred Einhorn in 1904. Although it had less drawbacks than its cocaine predecessor, it was far from the ideal agent. Lidocaine was the first amide local anesthetic agent and was first produced in 1945. The market for more effective agents continued to blossom. Over the following decades, no less than 20 additional agents were developed for use as a local anesthetic agent, each possessing unique pharmacokinetic properties to tailor its utility to specific clinical applications. They are all synthetic derivatives of cocaine.

Parallel to this proliferation in pharmacologic development, the clinical utilization of these agents has become widespread throughout all medical specialties. The daily practice of Emergency Medicine presents multiple scenarios that necessitate their use. The Emergency Physician must maintain a familiarity with the local anesthetic agents available and their unique characteristics, have an expertise in their delivery, be knowledgeable of the potential side effects, and know how to avoid and treat adverse reactions to ensure the safest and most optimal pain relief.

At a cellular level, nerve cell function and signal conduction are dependent upon a resting negative intracellular electrical potential (approximately −70 mV) as compared to the surrounding extracellular environment. This polarity results from the abundance of sodium (Na+) cations found within the extracellular space. Membrane-based sodium–potassium (Na+/K+) pumps establish this sodium gradient. Adjacent voltage-gated sodium channels maintain the gradient by inhibiting the concentration mediated and electrically driven sodium influx that would invariably result. Upon the stimulation of an idle neuron, a small intracellular sodium influx ensues. This sodium influx results in a slight depolarization of the resting membrane potential. When a critical threshold of sodium influx is met, the voltage-gated sodium channels reflexively open. This results in a massive sodium ion influx and widespread membrane depolarization.4–6 Impulse transmission proceeds as this membrane depolarization is propagated down the entire length of the nerve fiber.7

Local anesthetic agents function by reversibly binding to membrane-based sodium channels, thereby inhibiting the initial sodium influx that results upon the stimulation of an idle neuron.4–9 If a significant number of these channels are blocked, the critical threshold of sodium influx required for the voltage-gated sodium channel opening cannot be met, widespread membrane depolarization cannot occur and nerve impulses will not be transmitted. Careful examination of neuronal cells reveals that the actual binding sites for local anesthetic agents are located on the internal surfaces of their cellular membranes. Therefore, in order to function, the local anesthetic agent must first diffuse across the bi-lipid cellular membrane as an uncharged lipophilic compound. Once intracellular, the local anesthetic agent is converted to its active cationic state, terminating signal transduction and subsequently producing tissue anesthesia.13

All local anesthetic agents generally share the same molecular framework. They contain a lipophilic aromatic group linked to an ionizable group, usually a tertiary amine, via an intermediate linkage.4,7 This intermediate linkage comes in two types, namely an amino-amide or an amino-ester bond. This property is used to classify the local anesthetics as either “amides” or “esters.” Beyond this basic dichotomy, further variations on this generalized structure generate the altered pharmacokinetics that impart the unique qualities to the individual local anesthetic agents.7

The potency of a given local anesthetic agent is directly proportional to its lipid solubility.9,10 More lipophilic agents tend to be more potent, as the more soluble agent will readily diffuse across the cellular membrane despite a lower concentration of the extraneuronal anesthetic. Therefore, a lower quantity of local anesthetic is needed to elicit the same endpoint response.11 However, variable potencies are rarely of significance to the Emergency Physician. The available preparations utilize concentrations of the local anesthetic specifically formulated to correct for this variable potency.

The primary determinant of a local anesthetic's onset of action is its pKa.12 The pKa is the pH at which a given drug exists in equal proportions as ionized and unionized molecules. The unionized molecules more readily cross the nerve cell membrane. A portion of the molecule becomes charged once inside the neuron. It is this ionized portion that binds most completely to receptor proteins within the sodium channels.4,10 Commercially available local anesthetic agents are weak bases with pKa's of 7.6 to 8.9.4 Agents with a lower pKa at physiologic pH (7.4) will have relatively more uncharged molecules free to cross the nerve cell membrane (i.e., faster onset) than agents with a higher pKa.6,10 Low tissue pH, such as seen in abscess cavities, results in so little local anesthetic in the uncharged form that the agent is ineffective.6 This phenomenon explains why local anesthetics function poorly in acidic environments (e.g., abscess cavities) as a greater percentage of the agent is secondarily converted to its ionized state within the extracellular environment. It also explains why the addition of a buffering agent such as sodium bicarbonate increases the pH of the injected local anesthetic solution, increasing the ratio of nonionized local anesthetic agent present, and enhancing the rapidity of anesthesia onset. Increasing the total quantity of local anesthetic injected, whether by manipulating its concentration or increasing the overall volume, will hasten the onset of activity by augmenting the diffusion gradient and more aggressively driving the local anesthetic agent intracellularly.7,8 Conversely, once successfully intracellular, local anesthetic agents with higher intrinsic pKa's generate more effective sodium channel blockade via their tendency to persist in an ionized and functionally active state.8,13 The rate at which a local anesthetic agent diffuses through surrounding non-neuronal tissues also appears to be an important variable.5,8

A local anesthetic agent's duration of activity is typically proportional to the overall degree of protein binding.6–8,10 Those that possess a higher affinity for the target receptor are less likely to be dislodged and thus exhibit a longer duration of action.7,10 All of the available local anesthetic agents produce a degree of localized vasodilation. This serves to increase regional blood flow, promote systemic absorption of extracellular fluid, and thusly decrease the total duration of activity.5,7,10 Therefore, counteracting this phenomenon by compounding a vasoconstrictor with the local anesthetic agent represents another practical way to increase the duration of action of a particular agent.4,14 This is accomplished clinically via the addition of small doses of epinephrine.

The two classes of local anesthetic agents undergo metabolism via different mechanisms.5,7,15–17 Esters are metabolized rapidly by plasma pseudocholinesterase to the major metabolite para-aminobenzoic acid or PABA.5,7,15 PABA is allergenic and likely responsible for the infrequent allergic reactions to ester agents.5,7,16 Patients with atypical pseudocholinesterase are at increased risk for systemic toxicity from ester anesthetic agents.16,17 Amide anesthetic agents are metabolized more slowly by the liver to a variety of metabolites that are unrelated to PABA. Patients with impaired liver function are at increased risk for systemic toxicity from amide anesthetic agents.16,17

Local anesthetic agents are used in the Emergency Department for local infiltration, regional nerve blockade (Chapter 126), peripheral nerve blockade, and topical application (Chapter 124). General principles concerning their use and local infiltration will be discussed in this chapter. A complete review of specific techniques and procedures are available elsewhere in this text.

Localized injected anesthesia, or infiltrative anesthesia, represents the most common use of local anesthetic agents within the Emergency Department. It is generally a safe procedure that is technically easy to perform and well tolerated by the patient. It can be readily used for the majority of surgical procedures that are routinely performed by the Emergency Physician. This includes wound repair, foreign body removal, cutaneous abscess drainage, intravascular catheter placement, and hematoma blocks to name a few.

The primary and most important contraindication to the use of a local anesthetic agent is a history of an allergic reaction. Less than 1% of all adverse reactions from local anesthetic agents are due to true IgE-mediated allergic phenomena.18 Ester agents are responsible for the majority of such cases, whereas allergic reactions to amide anesthetics are exceptionally rare.7,15,19–21 The physiology behind this finding is rooted in the divergent metabolism of the two classes of local anesthetic agents.

The ester-type local anesthetic agents are rapidly metabolized within the bloodstream by serum pseudocholinesterase, explaining their very short plasma half-lives. The secondary metabolites are derivatives of the organic compound PABA. They exhibit allergenic properties and are the agents responsible for the allergic response. This property makes ester-type local anesthetic agents (e.g., cocaine, procaine, and tetracaine) a less commonly used option in daily practice. Amide-type local anesthetic agents, however, are metabolized in the liver into nonallergenic byproducts via cytochrome P-450 mediated pathways. Allergic reactions to the amide-type local anesthetic agents are very rare but do occur. Methylparaben is a close analog of PABA and a preservative commonly used in multidose preparations of amide agents. It may account for the rare occurrence of an apparent allergic reaction to the amide class of local anesthetic agents.7,15,16,21–24

An agent from the opposite class may be chosen if a history of a prior allergic reaction to a particular agent is obtained from a patient requiring local anesthesia. There is no true cross reactivity between the esters and the amides.7 A preservative-free preparation should be chosen, however, to avoid possible reaction from this source.22 Solutions intended for single use or intravenous use tend to be free of preservatives. Intravenous formulations of lidocaine can be found in any standard Emergency Department “crash cart.”

The size of the anesthetic field required for a given procedure can further dictate the utility of infiltrative anesthesia. Larger fields, by default, will require the injection of larger quantities of local anesthetic solution. Do not exceed the maximum safe dose of a local anesthetic agent (Table 123-1). Consider an alternative anesthetic technique (e.g., regional nerve blockade, procedural sedation) if infiltrative anesthesia requires potentially toxic local anesthetic doses. An alternative is to dilute the local anesthetic solution in half using sterile normal saline. This diluted local anesthetic solution may not provide adequate anesthesia.

Certain procedures necessitate meticulous tissue reapproximation (e.g., facial lacerations). The injection of local anesthetic solution, especially in higher volumes, can distort the surrounding tissue and diminish the probability for an optimal outcome. Consider an alternative anesthetic technique in these situations.

Topical anesthetic agents are contraindicated on mucous membranes, the eye, denuded skin, or burned skin as they are rapidly absorbed through these tissues. Such absorption can produce severe systemic toxicity and death. Eye contact can produce corneal injury. Topical agents containing cocaine and epinephrine are contraindicated in regions of end artery flow because they can result in intense vasoconstriction.25

Infiltration of a wound with 1% diphenhydramine is clinically effective as an alternative agent in the rare circumstance that a patient has a true IgE-mediated allergy to the local anesthetic agents.26 Diphenhydramine is more painful to inject than the local anesthetic agents. It was less effective at attaining adequate anesthesia when compared to local anesthetic agents. Reserve the use of diphenhydramine for the rare instance of a patient with an actual local anesthetic allergy.26 Dilute the 5% parenteral formulation of diphenhydramine to 1% (add 1 mL of diphenhydramine to 4 mL of normal saline) to make a solution for local infiltration.

• Syringes, 1 mL to 20 mL sizes
• Needles, various sizes and lengths
• Local anesthetic solution, with and without epinephrine
• Alcohol swabs, povidone iodine, or chlorhexidine
• Gauze squares
• 8.4% sodium bicarbonate solution (1 meq/mL)
• Gloves
• Face mask with an eye shield or goggles
• 5% parenteral diphenhydramine solution

Universal precautions are of utmost importance in performing any procedure using a local anesthetic agent. It is vital to wear gloves when administering topical anesthetic agents to protect the fingers, to prevent absorption of the local anesthetic agent through the fingers of the healthcare worker, and to prevent introduction of bacteria into the wound. Wear a mask with a face shield or goggles to prevent accidental mucous membrane exposure if the injectable local anesthetic solution shoots out of the wound margins.

One of the most important determinants of pain response during administration of a local anesthetic agent is needle size. Use a 25 or 27 gauge needle for infiltration to minimize pain. A long needle allows for the infiltration of a larger region with a single needle pass and decreases the number of times tissues must be punctured. A 2.0 inch, 27 gauge needle is typically an optimal choice. The needle should not be inserted more than two-thirds of its length to prevent inadvertent breakage within the tissues.12 Another important factor is the rate of infiltration. A slow steady method minimizes the pain response.

Many Emergency Departments have a small local anesthesia tray or basket containing the necessary equipment for providing local anesthesia. Such a kit may include the following items. Needles in sizes from 18 to 30 gauge, 1 to 2 cm long and 4 cm long. Syringes ranging from 1 mL (tuberculin) through 10 mL. Cotton-tipped applicators for the application of topical agents. Local anesthetic agents such as 1% and 2% lidocaine, 0.25% and 0.5% mepivacaine and bupivacaine, and the same agents combined with 1:200,000 epinephrine. Sodium bicarbonate may be used for buffering the local anesthetic agent. Alcohol swabs, povidone iodine swabs or solution, or chlorhexidine are required for cleansing the skin. Nonsterile and sterile examination gloves are required for the infiltration of the local anesthetic agent and performing the procedure.

Discuss the procedure with the patient and/or their representative. The most common adverse reaction to a local anesthetic agent is a vasovagal reaction.12 This complication is more likely when patients are anesthetized while sitting in an upright position (e.g., dental procedures). The Emergency Physician must take precautions to alleviate secondary injury to the patient. Whenever possible, place the patient lying in a bed with side rails up to prevent injury no matter how minor the procedure. Friends and family members have been reported to syncopize upon witnessing injections. Therefore, they should either be asked to leave the room prior to starting or kept in a sitting position throughout the duration of the procedure. Sedation can minimize the response to treatment while maintaining stable vital signs and spontaneous respirations when the patient exhibits considerable anxiety. Refer to Chapter 129 regarding the details of procedural sedation.

Prepare the area prior to injecting local anesthetic solution. Clean the skin of any dirt and debris. Apply an alcohol swab, povidone iodine, or chlorhexidine to the skin over the injection site and the surrounding area and allow it to dry. Apply sterile drapes, if applicable, to delineate a sterile field.

Local Anesthetic Dosing

Infiltration anesthesia refers to the injection of a local anesthetic solution directly into the subcutaneous tissues about to be manipulated. The first step to be considered is the selection of the proper anesthetic. Barring a history of an allergic reaction to a given class of local anesthetic agents, the amide anesthetics lidocaine (Xylocaine) and bupivacaine (Marcaine) are the most common agents employed within the Emergency Department. The choice between these agents should be tailored to the individual patient and situation. Lidocaine exhibits a quicker onset of activity, whereas bupivacaine exhibits a longer duration of action (Table 123-1). Lidocaine possesses a wider margin of safety, with larger doses required to illicit a toxic response. In amide allergic patients, the ester agent procaine (Novocain) is a reasonable alternative.

It is important to keep in mind the maximal recommended doses for the chosen local anesthetic agent to avoid systemic toxicity (Table 123-1). The disadvantage of local infiltration is that a large amount of local anesthetic must be used for a small area. Extensive wounds may require toxic doses of local anesthetic agents. A lower concentration or the addition of epinephrine will allow a larger volume of local anesthetic to be used. Local infiltration may distort the wound edges and complicate the repair.

The maximal recommended dose of a local anesthetic agent is the same for local infiltration or regional nerve blockade. It is important to properly calculate the amount of local anesthetic agent administered to a patient. Local anesthetic solutions are supplied with the concentration denoted as a percentage (e.g., 1% lidocaine, 0.25% bupivacaine, 4% cocaine). This percentage must be converted to mg/mL. A 1% local anesthetic solution is prepared by dissolving 1 g of the local anesthetic agent in 100 mL of diluent. This results in a concentration of 10 mg/mL (1 g/100 mL = 1000 mg/100 mL = 10 mg/mL). A simple method to calculate the strength of a local anesthetic solution is to move the decimal point one place to the right to convert from a percentage to a concentration in mg/mL (e.g., 0.25% = 2.5 mg/mL, 2% = 20 mg/mL, 4% = 40 mg/mL). This value must be multiplied by the volume to be administered to determine the total amount (in mg) of local anesthetic agent administered. This value must be compared to the maximal allowable dose (Table 123-1) to ensure it is not a toxic dose.

Epinephrine Containing Agents

Epinephrine can be added to a local anesthetic solution to prolong its duration of action, to assist with hemostasis by local vasoconstriction, and to slow the absorption of the local anesthetic agent. This allows for larger quantities of local anesthetic solution to be injected without the concern for systemic toxicity. Local anesthetic agents are generally compounded with epinephrine in a 1:100,000 or 1:200,000 solution and usually come packaged as such by the manufacturer.

If a compounded solution is not available, one can be readily formulated. Begin by obtaining 1:1000 epinephrine that is usually administered to patients for severe allergic reactions or bronchospasm. This solution of 1:1000 contains 1 g of epinephrine per 1000 mL or 1 mg/mL of epinephrine. Diluting this solution by a factor of 100 will result in the desired 1:100,000 concentration. Place 0.1 mL of 1:1000 epinephrine into 10 mL of local anesthetic solution to make a dilution of 1:100,000 (or 0.010 mg/mL). Place 0.1 mL of 1:1000 epinephrine into 20 mL (or 0.05 mL in 10 mL) of local anesthetic solution to make a dilution of 1:200,000 (or 0.005 mg/mL).

Reducing the Pain of Infiltration

Local anesthetic agents are weak bases. They are packaged, however, as hydrochloride salts with a pH of 4 to 6 to increase their solubility and shelf life. This acid pH causes much of the pain associated with the injection of local anesthetic agents.4,6 Because epinephrine is unstable at a physiologic pH, commercial solutions containing epinephrine are generally formulated with similarly acidic pH values. Buffering lidocaine, mepivacaine, or bupivacaine with sodium bicarbonate has been shown to reduce the pain of injection significantly.25,27,28 Raising the pH of the local anesthetic agent increases the percentage of local anesthetic molecules in the nonionized diffusible state.27 This may allow nearly instantaneous penetration of the nerve cell membrane by the anesthetic molecules and block or reduce the pain of infiltration.27,29,30 Raising the pH also contributes to decreasing the pain of the injection. Buffering local anesthetic agents does not appear to affect the duration or degree of anesthesia. There does not appear to be an increase in the degree of anesthesia, the serum levels of the local anesthetic agent, or in toxicity of buffered anesthetic agents.

Caution must be exercised when buffering highly lipophilic and less soluble anesthetic agents, like bupivacaine, because precipitation can occur.4 To buffer a local anesthetic agent, use the prepackaged 50 mL ampules of 8.4% (1 meq/mL) sodium bicarbonate found in any “crash cart.” Add 1 mL of 8.4% (1 meq/mL) sodium bicarbonate to 10 mL of 1% lidocaine or 1% mepivacaine, with or without epinephrine, to achieve buffering.27 Add 0.05 to 0.10 mL of 8.4% (1 meq/mL) sodium bicarbonate to each 10 mL of 0.5% bupivacaine.28

The use of warm lidocaine [37°C (98.6°F) to 42°C (107.6°F)] decreases the pain of infiltration.31,32 The exact etiology of this is unknown. It is hypothesized that warm lidocaine does not stimulate cold receptors and it diffuses into tissues faster. Warm the local anesthetic agent by placing it in a blanket warmer or a water bath. The combination of both warming and buffering a compound results in an even less painful procedure.32,33

Other simple measures can help to limit the pain of the local anesthetic injection. Limit the infiltration of a local anesthetic solution to the subdermal space. This practice helps to limit the overall pain of injection, minimize the degree of tissue distortion, and protect the patient from the inadvertent injection into an intravascular space. When anesthetizing an open wound, make every attempt to infiltrate through the exposed wound edges rather than puncturing through the adjacent intact skin (Figure 123-1).34 This will provide a much less painful experience for the patient. Infiltrate grossly contaminated wounds percutaneously through clean and intact skin to decrease the risk of spreading the contamination and to decrease the risk of an infection related to the infiltration. Also limit the number of needle punctures through uninjured skin in contaminated wounds. The application of gentle pressure to the injection site prior to the injection, such as pressing a sterile cotton-tipped applicator against the skin, limits the pain associated with childhood vaccinations.35 Dentists have been using similar techniques for many years to perform dental blocks. The use of this technique in the Emergency Department is limited by the fact that infiltrations into previously inflamed tissue, and thus any kind of additional stimulation, may simply expose the patient to unwarranted additional pain. A slower rate of local anesthetic solution injection is associated with less pain.

Insert the needle into an open wound at its apex (Figure 123-2). Tunnel the needle its entire length down the wound margin. Inject the local anesthetic solution while slowly withdrawing the needle. Do not completely withdraw the needle from the skin. Redirect it along the opposing wound margin and repeat the technique. This can be performed down the entire length of the wound as necessary. Minimizing the number of skin punctures will help to minimize pain.

The pain upon injection of local anesthetic agents can be reduced by following a few simple suggestions. Warm and/or buffer the local anesthetic agent as discussed previously. Inject the local anesthetic agent slowly. Inject open wounds through the wound edges and not through intact skin. An exception to this is grossly contaminated wounds. Infiltrate subdermally to minimize pain and tissue distention. Insert and advance the needle to create a tract and inject as the needle is withdrawn to minimize tissue distention. Do not totally withdraw the needle after infiltration. Leave the tip of the needle within the skin and redirect the needle to prevent excessive skin punctures.

Combining Local Anesthetic Agents

Physicians have for some time combined various local anesthetic agents in an attempt to exploit the unique properties of each individual local anesthetic agent and achieve both a rapid onset of action and a prolonged duration of action.36,37 Lidocaine, with its rapid onset, can be safely mixed in a 1:1 ratio with longer acting bupivacaine or mepivacaine. Employing this mixture may be no more dangerous than sequentially administering equal doses of either parent compound. The value of such an approach is questionable. Enough concern still persists regarding the potential toxicity of this mixture to often preclude its use within the Emergency Department. The combined benefits might not be as relevant within the Emergency Department, as the majority of the studies referenced come from the anesthesia and surgical literature.

It is important to realize that the toxic effects in an overdose situation are additive, even if an amide and ester are combined.38,39 Mixing two local anesthetic agents can complicate the overall dosage calculations and enhance the potential for a toxic injection. It is also difficult to determine the maximum dose if two local anesthetic agents are mixed together. If the patient develops an allergic reaction, it will be impossible to determine which local anesthetic agent is the causative agent. The combination of local anesthetic agents can therefore not be currently recommended. Use lidocaine containing epinephrine to prolong the anesthetic effect rather than combining it with a second local anesthetic agent.

It has been known since the 1940s that injected antihistamines exhibit anesthetic properties. A 1956 study comparing the infiltration of diphenhydramine to procaine demonstrated equal anesthetic properties. Subsequent Emergency Medicine based studies have shown equal anesthetic results when comparing the injection of 1% solutions of either lidocaine or diphenhydramine, although the latter was associated with a more painful infiltration. A further study comparing 0.5% diphenhydramine to 1% lidocaine demonstrated a resolution in the disparity regarding the pain of injection, although at the expense of a decreased anesthetic effect.40 The overall duration of anesthesia produced by infiltrated diphenhydramine is shorter than that of lidocaine. A concern has arisen regarding the possible destruction of local tissue and subsequent skin necrosis associated with diphenhydramine infiltration. Multiple early experiences had reported this complication. However, an appropriate dilution prior to injection should eliminate this potential complication. Dilute 1 mL of standard parenteral 5% diphenhydramine solution with 4 mL of sterile normal saline to achieve a 1% solution that is suitable for injection.41,42 Diphenhydramine should be considered a viable alternative to the more commonly used local anesthetic agents when they are contraindicated.

It is important to wait long enough after the local anesthetic agent is administered to allow the onset of adequate anesthesia before the planned procedure is started. A period of 5 to 10 minutes is adequate for subcutaneous local infiltration. A period of 15 to 30 minutes may be required for peripheral nerve blocks. A simple examination of the area being anesthetized with fine touch and pinprick is important to insure adequate anesthesia prior to the procedure. It may be necessary to inject additional local anesthetic solution in areas of continued sensitivity, keeping in mind the total dose injected to avoid toxicity.

The Emergency Physician should observe the patient for a minimum of 15 minutes following the use of local anesthesia to insure no evidence of an adverse reaction. The length of time analgesia is maintained depends upon the agent used for the procedure (Table 123-1). The patient need not wait in the Emergency Department for normal sensation to return prior to discharge. They should be instructed to return to the Emergency Department if normal sensation has not returned within 12 to 24 hours.

Toxic reactions to local anesthetics agents are far more common than allergic sequelae.12,17,43 The propensity for toxicity is directly proportional to the potency of the drug.7,9,10 Table 123-1 lists the recommended maximal doses for commonly used local anesthetic agents. These are only estimates and in certain circumstances the toxic dose might be considerably less.7,20 Infiltration into highly vascular areas, inadvertent intravascular injection, or application to mucous membranes may cause toxicity at accepted standard doses.7

It is unlikely that toxic serum concentrations of local anesthetic agents will be reached in most clinical situations in the Emergency Department. For example, the maximum dose of 1% lidocaine without epinephrine in a 70 kg patient would be approximately 31.5 mL, a volume more than adequate for most wounds. It is important to be vigilant of the total dose administered, especially in patients with large or multiple lacerations in whom higher doses of local anesthetics may be required. A less concentrated form of the local anesthetic agent (e.g., 0.5% lidocaine as opposed to 1%) may be used when the maximum dose could be exceeded. General anesthesia in the Operating Room may be required to repair larger wounds.

The major manifestations of local anesthetic toxicity occur in the central nervous system (CNS) and the cardiovascular system.6,9,12,15 Initial signs and symptoms are of CNS excitation. This occurs as a result of the suppression of inhibitory cortical neurons that permits unopposed functioning of facilitatory pathways. Signs and symptoms include lightheadedness, dizziness, nystagmus, sensory disturbances (e.g., visual difficulties, tinnitus, perioral tingling, metallic taste in the mouth), restlessness, disorientation, and psychosis. Slurred speech, muscle twitching, and/or tremors may immediately precede seizures. There may also be augmentation of medullary and sympathetic activity with resultant tachypnea, hyperpnea, hypertension, and tachycardia. Generalized depression of the entire CNS can occur and is manifested as drowsiness, coma, and respiratory arrest.9,15

Management of CNS toxicity should begin with an assessment of the patient's airway, breathing, and circulation. Treatment is primarily supportive. Hypoxia and acidosis enhance CNS and myocardial absorption of local anesthetic agents and must be addressed aggressively. Hypocapnia raises the seizure threshold (to prevent convulsions) by inducing cerebral vasoconstriction and by decreasing the delivery of the local anesthetic agent to the CNS.7,44 An alert and cooperative patient may be instructed to hyperventilate if early signs of toxicity are present.6,20,45 Manage seizures with intravenous benzodiazepines as they raise the CNS threshold to local anesthesia-induced convulsions. The metabolism of local anesthetics is short enough that loading patients with long-acting antiseizure agents, such as phenytoin, is generally not required. The effect of phenytoin upon sodium channel conduction can potentiate the arrhythmogenic property of local anesthetics. Administer short-acting neuromuscular blocking agents, such as succinylcholine or vecuronium, until serum levels of the local anesthetic agent decline if the seizures fail to respond to benzodiazepines.7 Succinylcholine, however, is metabolized by pseudocholinesterase. This is the same plasma enzyme that metabolizes ester anesthetic agents. Therefore, avoid succinylcholine in ester-induced seizures.7,6,20

The cardiovascular system is relatively resistant to local anesthetic toxicity in comparison with the CNS.17,24 The cardiovascular system does not exhibit toxicity until much higher blood levels are reached.17,24 Cardiovascular toxicity results from the direct effects upon cardiac and vascular smooth muscle and the indirect effects upon autonomic tone. Complications are the result of negative inotropism, peripheral vasodilatation, and slowing of the myocardial conduction system.9,15 Arterial dilation combined with decreased cardiac contractility leads to progressive hypotension and eventual cardiovascular collapse. Additionally, the sodium and calcium channel blockade exhibited at more toxic doses of local anesthetic agents predisposes the patient to fatal arrhythmias. The end results are hypotension, bradycardia, prolonged electrocardiographic intervals, and cardiac arrest.9,10,15 Treatment is supportive with intravenous fluids, vasopressors, and inotropes as the mainstays of therapy. Avoid class IB antidysrhythmics due to their potential to accentuate cardiac sodium channel blockade. Vasopressors with positive inotropic effects, such as dopamine, will treat profound cardiovascular depression.7

Bupivacaine is more cardiotoxic than other local anesthetic agents. Treatment of bupivacaine cardiotoxicity has shown a potential benefit with the use of high dose intravenous insulin (2 IU/kg) in concert with supplemental intravenous glucose and intravenous potassium boluses.46 The infusion of a lipid emulsion (i.e., Intralipid) has been proposed for use in bupivacaine-associated cardiac arrests. Several recent case reports have substantiated the use of Intralipid. The actual mechanism of action is unclear, but proposals include the extraction of lipophilic anesthetics from their target tissues via the fatty emulsion and/or the direct antagonization of anesthetic mediated suppression of cardiac fatty acid metabolism.47

There is no accepted standard protocol for the administration of Intralipid. A proposed dosing regimen is described here. Of note, these rescue interventions should be attempted only in patients failing to respond to standard ongoing ACLS protocols. Administer an initial bolus of 1.5 mL/kg of a 20% Intralipid solution. This is the standard used for adult total parenteral nutrition (TPN). Repeat this dose up to two additional times over a 5 minute period for patients in refractive asystole. If the return of spontaneous circulation ensues, initiate a maintenance intravenous infusion of 0.25 mL/kg/min for 30 to 60 minutes. This allows the toxic effects of the local anesthetic agent to dissipate. The Intralipid infusion can be easily titrated to maintain a stable perfusing blood pressure. Of note, although often readily available, the drug propofol is compounded in a 10% lipid solution and therefore not applicable for similar use. The volume of propofol solution needed to reverse bupivacaine toxicity would require the administration of a toxic dose of propofol.48–50

Adding epinephrine to a local anesthetic agent increases both the amount of drug that can be administered and the duration of action.4,14 It also decreases bleeding into the surgical field. There are, however, significant drawbacks to the use of epinephrine. This includes increased pain of infiltration, increased wound inflammation, increased wound infection rates, uncomfortable side effects in susceptible patients (e.g., palpitations, tremors, syncope), and the potential for severe tissue ischemia if used in regions of end arterial circulation such as the digits, the tip of the nose, the pinna, or the penis.12 Emergency Medicine dogma cautions against the use of an epinephrine containing local anesthetic agent in these regions in order to avoid potential distal tissue infarction and necrosis. However, the clinical evidence supporting this concern is questionable, and the little that does exist is over 50 years old. A study of elective hand procedures demonstrated no adverse consequences following over 3000 digital injections of epinephrine containing local anesthetic solutions.51,52 Literature focused on the inadvertent infiltration of epinephrine into fingers via improperly used autoinjectors has failed to demonstrate a single significant case of tissue necrosis. The majority of these cases demonstrate a spontaneous return of perfusion with only conservative treatments (i.e., warm soaks and digital massage). Prolonged vasospasm and ischemia in these areas can be reversed with the subcutaneous infiltration of 1.0 mL of 1:1000 phentolamine (i.e., 1 mg) diluted with saline in a 1:1 mixture at the local anesthetic injection site.53–57 A less invasive alternative is to apply topical nitroglycerine paste to the affected area. Caution must be used when administering epinephrine to patients who are elderly, taking beta-blockers, or with a history of coronary artery disease, hypertension, hyperthyroidism, or pheochromocytoma.6,12 Inadvertent intravascular injection of epinephrine can have fatal consequences.58,59

The potential systemic complications unique to epinephrine are not often an issue. Using 1:100,000 preparations, one must infiltrate 30 mL of local anesthetic solution to attain a cumulative dose of 0.3 mg, a quantity commonly used subcutaneously in the practice of Emergency Medicine. Such a large volume is rarely encountered with infiltrative anesthesia. Consider an alternative anesthetic technique if such a large volume of local anesthetic solution containing epinephrine is required. Rare reports of patient mortality secondary to an inadvertent intravenous injection have been reported. Extreme care should be taken when using such preparations in any patient with suspected cardiovascular disease.

True allergic reactions are rare adverse events to the local anesthetic class of medications. Effective management of an allergic reaction depends upon its severity and may include the use of epinephrine, antihistamines, steroids, and vasopressors. A complete review of the management of allergic reactions and anaphylaxis can be found in standard Emergency Medicine textbooks.

Methemoglobinemia has been reported to occur following the use of both classes of local anesthetic agents. It is most commonly seen after the use of the topical agent benzocaine.60 The use of this medication is discussed elsewhere in this book. The Emergency Physician must be aware of this potential complication and intervene appropriately.

Injection of local anesthetic agents can cause complications in the area of the infiltration. These agents have not been shown to increase the incidence of wound infections. Do not inject local anesthetic agents into a joint prior to obtaining synovial fluid. They can result in false-negative culture results, false-negative crystal analysis, and false-positive (anesthetic crystals) crystal analysis. Needle punctures of arteries, nerves, and veins are usually a temporary inconvenience with no long-lasting consequences. Intraneural injection can result in temporary or permanent nerve injury. Never inject local anesthetic agents if the patient experiences paresthesias (indicating intraneural needle placement). Withdraw the needle 1 to 2 mm and allow the paresthesias to resolve before infiltrating with the local anesthetic solution. Never redirect the needle when more than the tip is subcutaneous to prevent needle breakage.

Local anesthetic agents have become an indispensible tool in the practice of Emergency Medicine. Emergency Physicians often rely on local anesthetic agents to relieve patient discomfort and provide wound care. Infiltrative anesthesia represents one of the most prevalent uses for these agents. It is relatively quick, easy to perform, well tolerated, and when performed correctly, has a large margin of safety. Complications can and do arise. The Emergency Physician must be ready to recognize the warning signs of local anesthetic toxicity and intervene appropriately. An expertise in the use of these agents plays an important role in the practice of the art of medicine. For hundreds of years physicians have sought to relive the pain and suffering of our patients. These agents allow us to come closer to attaining that goal.