eMedicine - Local Anesthesia and Regional Nerve Block Anesthesia : Article by Robyn Gmyrek

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Local Anesthesia and Regional Nerve Block Anesthesia

Article Last Updated: Feb 7, 2007

Local anesthetics provide a reversible regional loss of sensation. Local anesthetics reduce pain, thereby facilitating surgical procedures. Delivery techniques broaden the clinical applicability of local anesthetics. These techniques include topical anesthesia, infiltrative anesthesia, ring blocks, and peripheral nerve blocks.

Local anesthetics are safer than general or systemic anesthetics; therefore, they are used whenever possible. In addition, they are relatively easy to administer and readily available. Local anesthetics have been undergoing development for centuries, and, as this article illustrates, research continues to provide surgeons with pharmacologic variety and to provide patients with anesthetic agents that have superior safety and efficacy profiles.

Although the medical world cannot cure every disease, the control of pain to ensure patient comfort should be a goal. In 1860, cocaine, the oldest anesthetic, was extracted from the leaves of the Erythroxylon coca bush. In 1884, Sigmund Freud and Karl Koller were the first to use it as an anesthetic agent during ophthalmologic procedures.

Procaine, a synthetic alternative to cocaine, was not developed until 1904. Procaine is an ester of para-aminobenzoic acid (PABA). As procaine is metabolized, PABA, a known allergen, is released as a metabolic product. The potential for severe allergic reactions limits the use of procaine and other ester-type anesthetic agents. Tetracaine, another ester-type anesthetic, was introduced in 1930. Tetracaine is more potent than procaine, it causes similar allergic reactions.

In 1943, an alternative class of anesthetics was discovered when Lofgren developed lidocaine. This agent is an amide derivative of diethylaminoacetic acid, not PABA; therefore, it has the benefit of a low allergic potential. Since then, multiple amide-type anesthetics have been introduced into clinical use. Slight chemical alterations to the compounds have imparted beneficial characteristics, including increased duration and potency, to each. These compounds offer the surgeon more choices, and anesthetics can be appropriately matched to different procedures.

Reviewing the physiology of nerve conduction is important before any discussion of local anesthetics. Nerves transmit sensation as a result of the propagation of electrical impulses; this propagation is accomplished by alternating the ion gradient across the nerve cell wall, or axolemma.

In the normal resting state, the nerve has a negative membrane potential of -70 mV. This resting potential is determined by the concentration gradients of 2 major ions, Na⁺ and K⁺, and the relative membrane permeability to these ions (also known as leak currents). The concentration gradients are maintained by the sodium/potassium ATP pump (in an energy-dependent process) that transports sodium ions out of the cell and potassium ions into the cell. This active transport creates a concentration gradient that favors the extracellular diffusion of potassium ions. In addition, because the nerve membrane is permeable to potassium ions and impermeable to sodium ions, 95% of the ionic leak in excitable cells is caused by K⁺ ions in the form of an outward flux, accounting for the negative resting potential. The recently identified 2-pore domain potassium (K2P) channels are believed to be responsible for leak K⁺ currents.

When a nerve is stimulated, depolarization of the nerve occurs, and impulse propagation progresses. Initially, sodium ions gradually enter the cell through the nerve cell membrane. The entry of sodium ions causes the transmembrane electric potential to increase from the resting potential. Once the potential reaches a threshold level of approximately -55 mV, a rapid influx of sodium ions ensues. Sodium channels in the membrane become activated, and sodium ion permeability increases; the nerve membrane is depolarized to a level of +35 mV or more.

Once membrane depolarization is complete, the membrane becomes impermeable to sodium ions again, and the conductance of potassium ions into the cell increases. The process restores the excess of intracellular potassium and extracellular sodium and reinstates the negative resting membrane potential. Alterations in the nerve cell membrane potential are termed the action potential. Leak currents are present through all the phases of the action potential, including setting of the resting membrane potential and repolarization.

Local anesthetics inhibit depolarization of the nerve membrane by interfering with both Na⁺ and K⁺ currents. The action potential is not propagated because the threshold level is never attained.

Although the exact mechanism by which local anesthetics retard the influx of sodium ions into the cell is unknown, 2 theories have been proposed. The membrane expansion theory postulates that the local anesthetic is absorbed into the cell membrane, expanding the membrane and leading to narrowing of the sodium channels. This hypothesis has largely given way to the specific receptor theory. This theory proposes that the local anesthetic diffuses across the cell membrane and binds to a specific receptor at the opening of the voltage-gated sodium channel. The local anesthetic affinity to the voltage-gated Na⁺ channel increases markedly with the excitation rate of the neuron. This binding leads to alterations in the structure or function of the channel and inhibits sodium ion movement. Blockade of leak K⁺ currents by local anesthetics is now also believed to contribute to conduction block by reducing the ability of the channels to set the membrane potential.

On the basis of their diameter, nerve fibers are categorized into 3 types. Type A fibers are the largest and are responsible for conducting pressure and motor sensations. Type B fibers are myelinated and moderate in size. Type C fibers, which transmit pain and temperature sensations, are small and unmyelinated. As a result, anesthetics block type C fibers more easily than they do type A fibers. Therefore, patients who have blocked pain sensation still feel pressure and have mobility because of the unblocked type A fibers.

All local anesthetics have a similar chemical structure, which consists of 3 components: an aromatic portion, an intermediate chain, and an amine group (see Image 3). The aromatic portion, usually composed of a benzene ring, is lipophilic, whereas the amine portion of the anesthetic is responsible for its hydrophilic properties. The degree of lipid solubility of each anesthetic is an important property because its lipid solubility enables its diffusion through the highly lipophilic nerve membrane. The extent of an anesthetic's lipophilicity is directly related to its potency.

Local anesthetics are weak bases that require the addition of hydrochloride salt to be water soluble and therefore injectable. Salt equilibrates between an ionized form and a nonionized form in aqueous solution. Equilibration is crucial because, although the ionized form is injectable, the nonionized base has the lipophilic properties responsible for its diffusion into the nerve cell membrane. The duration of action of an anesthetic or the period during which it remains effective is determined by its protein-binding activity, because the anesthetic receptors along the nerve cell membrane are proteins.

The intermediate chain, which connects the aromatic and amine portions, is composed of either an ester or an amide linkage (see Image 3). This intermediate chain can be used in classifying local anesthetics.

Local anesthetics are classified into 2 groups: the ester group and the amide group. The classification is based on the chemical structure of the intermediate chain. This structural difference affects the pathway by which local anesthetics are metabolized and the allergic potential.

Ester anesthetics are listed in the Table. They are metabolized by hydrolysis, which depends on the plasma enzyme pseudocholinesterase. Some patients have a rare genetic defect in the structure of this enzyme and may be unable to metabolize ester-type anesthetics; this inability increases the possibility of their having toxic reactions and elevated levels of anesthetics in the blood. In addition, 1 of the metabolic products generated by hydrolysis is PABA, which inhibits the action of sulfonamides and is a known allergen. In patients with a known allergy to an ester anesthetic, the use of all other ester-type anesthetic agents should be avoided.

Amide-type local anesthetics (see Table) are metabolized by microsomal enzymes located in the liver. The specific microsomal enzyme responsible for the elimination of lidocaine is cytochrome P-450 3A4. Therefore, amide-type anesthetics should be used with care in patients with severe liver disease and patients taking medications that interfere with the metabolism of the anesthetic, and the patients should be carefully monitored for signs of toxicity.

Cytochrome P-4503A4 is present in the small bowel and the liver. Commonly used medications known to inhibit cytochrome P-4503A4 are listed below (adapted from Klein and Kassarjdian). Specific potent inhibitors of cytochrome P-4503A4 that have been associated with clinically relevant interactions include itraconazole, ketoconazole (azole antifungals), erythromycin, clarithromycin, cyclosporin (macrolides), amprenavir, indinavir, nelfinavir, ritonavir (HIV protease inhibitors), diltiazem, mibefradil (calcium channel blockers), and nefazodone. Grapefruit juice is also a potent inhibitor of P-4503A4 but appears to affect only the enteric enzyme, which does not play a role in the metabolism of local anesthetics.

If the enzyme is inhibited because of the concurrent use of medications, it is unavailable to metabolize the anesthetic and potentially toxic levels of the anesthetic can occur. In addition, beta-blockers may decrease blood flow to the liver; therefore, they may also decrease the metabolism of amide-type anesthetics and may cause serum levels of the anesthetic to increase.

Infiltrative anesthesia is the most commonly used local anesthetic technique. The anesthetic agent is infiltrated directly into the surgical site by means of either intradermal injection or subcutaneous injection. Lidocaine, in a 1% concentration, is most commonly used for this type of infiltration. However, when increased procedure times are expected, anesthetics with a longer duration of action sometimes are substituted.

Intradermal injection has the advantages of a rapid onset of action after injection and an increased duration of anesthesia compared with those of deeper anesthetic placement. However, intradermal injection significantly distorts the tissues, and it is more painful than subcutaneous injection. If the subcutaneous injection of an anesthetic is planned, intradermally inject a wheal of the anesthetic prior to performing the deeper injection. Subcutaneous infiltration should not begin until the plunger of the syringe is pulled back and material is aspirated to ensure that intravascular injection does not occur. This technique is not reliable when a 30-gauge needle is used. If a vessel is penetrated, some authors suggest constant movement of the needle tip during infiltration to prevent excessive intravascular injection.

The infiltration of the anesthetic commonly distorts the landmarks of the site; therefore, the surgical area to be anesthetized must be identified and marked prior to injection. The skin should be held taut, and the tip of the needle inserted, if possible, into a follicular opening. This maneuver reportedly decreases the pain associated with skin perforation.

The anesthetic should be infiltrated in a deep dermal location. Accentuation of the follicles or a peau d'orange appearance may be apparent if the anesthetic is injected into the upper dermis. The superficial placement of fluid is associated with greater patient discomfort. The anesthetic diffuses through the dermis with the infiltration; fortunately, this effect limits the number of needle penetrations needed to anesthetize a particular site. If additional needle sticks are needed, they should be placed in an already anesthetized area.

Ring Block or Field Block

A specific type of infiltration anesthesia is the ring block or field block. To perform a ring block, the anesthetic agent is circumferentially injected around the surgical site without injecting the area to be excised (see Image 4). This infiltration prevents the nerve impulses from entering the area. A ring block is useful when the distortion of a surgical site due to the infiltration of anesthesia is not desired. In addition, ring blocks are useful when direct injection into the surgical field is not desired (ie, to avoid rupture in cyst excision, to avoid potential seeding of malignant cells). Ring blocks allow a decreased volume of anesthetic to be used to anesthetize a larger area.

When ring blocks are used, the anesthetic should be injected into both the superficial and deep planes to be maximally effective. Scalp blocks and ear blocks are specific examples of the ring-block technique.

Branches of several peripheral nerves innervate the scalp. The supratrochlear and supraorbital nerves, which are branches of the ophthalmic division of the trigeminal nerve, innervate the frontal part of the scalp. Branches from the zygomaticotemporal nerve, auriculotemporal nerve, and lesser occipital nerve innervate the lateral part of the scalp. Branches of the greater and lesser occipital nerve, which originate from the cervical plexus, innervate the posterior part of the scalp (see Image 5).

A scalp block may be performed by injecting small wheals of local anesthetic approximately 2 inches apart to complete a ring, which begins at the mid forehead and continues through the level of the superior auricular sulcus toward the occiput and back to the mid forehead. These injections are followed by further injections of the anesthetic at the level of subcutaneous tissue and then subfascially below the galea, again to complete a ring (see Image 6).

Approximately 20-30 mL of anesthetic may be needed to complete the block. The addition of epinephrine is safe in this area, and it may help reduce bleeding and decrease absorption of the anesthetic. The injections should be carefully administered to avoid the temporal arteries, which are in the vicinity of the injection site. If these arteries are lacerated, a hematoma may form. If the artery is perforated, pressure should be applied for 20 minutes.

Four nerve branches supply the sensory innervation of the ear. The anterior half of the ear is supplied by the auriculotemporal nerve, which is a branch of the mandibular portion of the trigeminal nerve. The posterior half of the ear is innervated by 2 nerve branches derived from the cervical plexus: the great auricular nerve and the lesser occipital nerve. The auditory branch of the vagus nerve innervates the concha and external auditory canal (see Image 7).

A ring block around the circumference inhibits cutaneous sensation to the entire ear, except the concha and the external auditory canal. The needle is inserted into the skin at the junction where the earlobe attaches to the head. The anesthetic should be infiltrated while the needle is advanced to the subcutaneous plane. Infiltration is continued toward the tragus. The needle may be pulled back and then redirected posteriorly; infiltration may continue along the inferior posterior auricular sulcus. The infiltration process is continued along the preauricular sulcus and then the superior posterior auricular sulcus to complete the ring (see Image 8).

Caution should be exercised to avoid puncturing the temporal artery. If perforation occurs, pressure should be applied for 20-30 minutes. If anesthesia of the concha is required, it must be achieved by locally infiltrating the area. A combination of anesthetic and epinephrine can be used; however, necrosis can occur in patients with arteriolar insufficiency.

Regional Block

Peripheral nerve blocks are achieved by injecting anesthetic solution around a nerve root to produce anesthesia in the distribution of that nerve. The blocks are particularly advantageous when infiltration anesthesia may cause unacceptable distortion of the surgical site or require an amount of anesthetic that exceeds the maximum recommended dose. Regional blocks allow a smaller amount of anesthetic to be used, thereby reducing the risk of systemic toxicity. Regional blocks also allow anesthesia of larger surface areas with less distortion of the surgical site.

Regional blocks require complete knowledge of the anatomy; therefore, they may be technically challenging to perform. Compared with local infiltration, peripheral nerve blocks have a higher risk of nerve laceration and intravascular injection. The elicitation of paresthesia to ensure proximity to the nerve is not warranted nor is it recommended. In fact, if paresthesias are elicited prior to injection, the needle should be pulled back slowly until paresthesias no longer are appreciated.

Amide-type anesthetics most often are used for regional blocks. Higher concentrations, usually 2% lidocaine, are advantageous in producing a larger concentration gradient, which promotes diffusion into the nerve. Vasoconstrictors are not recommended because they have the potential to increase vascular insufficiency. Furthermore, because the anesthetic solution is not placed directly into the surgical site, the vasoconstrictive benefits would be minimal at the surgical site even if a peripheral nerve block is performed with an anesthetic solution containing epinephrine.

Several factors must be considered when a nerve block is performed. First and most important is the anatomy of the area to be treated. The surgeon must always know the anatomic landmarks and the location of the nerve to be blocked, keeping in mind individual variation. The local anesthetic should be placed in a subcutaneous location because most nerves are subdermal. In a regional block, a 30-gauge needle is most often used to deliver the anesthetic. Aspiration through a small-bore needle is somewhat unreliable for ensuring that the intravascular space has not been entered. Therefore, a 25-gauge needle is recommended for regional blocks; aspiration should always be performed before the anesthetic is injected. The length of the needle is determined by the estimated distance from the injection site to the nerve root targeted for the block.

The supraorbital and supratrochlear nerves innervate the frontal part of scalp and forehead. Both nerves are branches of the first division or ophthalmic branch of the trigeminal nerve.

The supraorbital nerve exits the skull through the supraorbital foramen that lies in the midpupillary line, which is approximately 2.5 cm lateral to the facial midline along the supraorbital ridge. The supratrochlear nerve exits the skull along the upper medial corner of the orbit in the supratrochlear notch, which is approximately 1.5 cm medial to the supraorbital foramen (see Image 9).

Supraorbital and supratrochlear nerve blocks can be performed from either the area of the supraorbital foramen or the area of the supratrochlear notch. If performed from the supraorbital foramen, the area should be located, and a skin wheal raised at the site. The needle is inserted through the anesthetized area and advanced to the bone. Approximately 1-3 mL of anesthetic solution is placed outside the foramen at the level of the inferior frontalis muscle. The foramen should not be entered; if the patient complains of paresthesias, the injection should be aborted. The needle is slowly withdrawn 1-2 mm, until the patient no longer feels the paresthesias, before the injection is continued.

The supratrochlear nerve may be reached by advancing the needle 1.5 cm medial to the junction of the supraorbital ridge and the root of the nose. As before, 1-3 mL of anesthetic fluid is injected (see Image 10).

If the block is performed from the area of the supratrochlear nerve, a wheal should be placed over the root of the nose at the junction of the nasal root and supraorbital ridge. The skin is infiltrated along the length of the entire eyebrow. When this block is used, patients should be warned about the possibility of swelling in the upper and/or lower eyelids. For this type of block, 2-4 mL of anesthetic solution per side is usually sufficient, and no more than 6 mL should be injected into either side. As with any injection, the risk of ecchymosis or hematoma formation exists.

The infraorbital nerve innervates the lower eyelid, medial aspect of the cheek, upper lip, and lateral portion of the nose. It is a branch of the second division or maxillary branch of the trigeminal nerve. The infraorbital nerve exits the skull through the infraorbital foramen, which is 1 cm inferior to the infraorbital ridge and approximately 2.5 cm lateral to the facial midline in the midpupillary line (see Image 11). After exiting the infraorbital foramen, the infraorbital nerve divides into 4 branches: the inferior palpebral, internal nasal, external nasal, and superior labial branches.

An infraorbital block may be performed in 2 ways: via direct cutaneous injection or via intraoral injection. The infraorbital foramen should be palpated, and approximately 2 mL of anesthetic is injected near, but not into, the canal to surround the nerve. Some authors suggest injecting the anesthetic in 0.5-mL depots, rather than 1 bolus, while changing the position of the needle around the nerve.

If the block is to be preformed via the intraoral approach, the application of a topical anesthetic to the mucosa before injection may increase patient comfort. The infraorbital foramen should be palpated with the middle finger of one hand while the thumb and index finger of the same hand are used to raise the lip. During palpation of the foramen, the needle is inserted into the superior labial sulcus at the apex of the canine fossa (see Image 1). Approximately 2 mL of anesthetic solution is injected in the vicinity of the infraorbital foramen.

Warn patients that swelling of the lower eyelid and ecchymosis may occur with the infraorbital block. In addition, if anesthetic solution is injected into the orbit, excessive pain, diplopia, exophthalmos, and blindness can occur. The likelihood of the reactions is increased if the needle is placed superior to the infraorbital rim or into the infraorbital foramen.

The mental nerve innervates the lower lip and chin (see Image 12). It is a branch of the third division or mandibular portion of the trigeminal nerve. The mental nerve exits the skull through the mental foramen, which is located approximately 2.5 cm from the midline of the face in the midpupillary line.

Either a cutaneous or intraoral approach can be used to block the mental nerve (see Image 2). To block the nerve cutaneously, the foramen should be palpated, and a wheal of anesthesia placed. Then, the needle should be reinserted and advanced to the vicinity of the mental foramen but not into it. Approximately 1-3 mL of anesthetic should be injected into the area. Alternatively, when an intraoral approach is used, the foramen should be palpated with the middle finger of one hand and the lip lifted by the thumb and index finger of the same hand. The needle should be inserted at the inferior labial sulcus at the apex of the first bicuspid and 1-3 mL of anesthetic injected.

The digits are innervated by 4 digital nerves: 2 superior or dorsal nerve branches and 2 inferior or ventral nerve branches (see Image 13). On the dorsal surface of the fingers, the digital nerves are branches of the radial and ulnar nerves. On the ventral or palmar surface of the fingers, the digital nerves are branches of the median and ulnar nerves. The digital nerves that supply the toes are branches of the peroneal nerve on the dorsal surface, whereas the tibial nerve innervates the ventral or plantar surface of the toes.

The 2 types of proximal digital blocks are dorsal (traditional ring block) and palmar (single transthecal and subcutaneous palmar techniques). The different techniques used to perform proximal blocks have similar efficacy. However, palmar techniques are inadequate for anesthetizing the thumb and the dorsal aspect of the third digit's proximal phalanx because of incomplete anesthesia.

The traditional ring block consists of 2 dorsal punctures on either side of the digit. The needle is inserted into the dorsolateral aspect of the digit, and approximately 1 mL of anesthetic is injected just under the dermis. This single injection port allows the anesthetic to infiltrate to both the dorsal and ventral digital nerves. The needle is then withdrawn, and the procedure is repeated in the opposite side of the digit (see Image 14). The fluid diffuses to the area of the nerves. Waiting for several minutes for the anesthesia to become effective is best. The surgical site always should be tested before beginning the procedure.

Transthecal anesthesia uses the flexor tendon sheath for infusion of anesthesia. It involves a single injection of 2-3 mL of 1 or 2% epinephrine-free lidocaine through the flexor tendons at the base of the digit.

Subcutaneous anesthesia also uses a single injection on the palmar side but consists of placing 2-3 mL of 1 or 2% epinephrine-free lidocaine in the subcutaneous tissue at the level of the first digital crease.

The use of epinephrine is not recommended in performing a digital block. Epinephrine use is contraindicated in patients with edematous digits and in patients with vasospastic disease. The use of a tourniquet may be a helpful alternative to increase the duration of the digital block and to aid in hemostasis. A tourniquet may be created by using a variety of materials; several authors recommend a Penrose drain for this purpose. The drain may be placed at the base of the digit and secured with a straight hemostat. The tourniquet should be placed tightly enough to prevent arterial flow. If it is not tight enough, only the veins are compressed. With continued arterial flow, the finger becomes engorged. The tourniquet is left in place for as short a time as possible; less than 10 minutes is recommended.

Although 1% or 2% lidocaine is most often used for this type of block, mepivacaine can be used because it is not a vasodilator. In addition, the injection of large volumes of anesthetic to this area of limited distensibility should be avoided. Vascular compromise and ischemia are reported with the use of large volumes (usually >8 mL) of anesthesia.

Topical anesthesia refers to the modification of pain sensation or the loss of sensation caused by an agent that is applied topically to the skin. Topical anesthesia includes the administration of cryoanesthetics and the application of local anesthetic compounds, which must penetrate the epidermis to have a physiologic effect. Because the stratum corneum is an effective barrier, the delivery of anesthetics can be challenging. Recent advances in laser technology and the subsequent increase in the use of laser treatments have fueled the need for improved topical anesthetic agents and the development of such agents.

Cryoanesthesia refers to the external application of cold to the skin to produce numbness. Ice, refrigerant sprays, and liquid nitrogen have been used for this purpose. Ice applied directly to the site for 30-60 seconds provides superficial short-duration anesthesia that may be acceptable for quick, shave biopsy. This application is particularly useful in children or adults who have a fear of needles.

Refrigerant sprays, such as ethyl chloride and dichlorotetrafluoroethane, are useful for anesthetizing superficial lesions prior to their removal. These sprays are particularly helpful for anesthetizing tumors related to molluscum prior to their curettage and cysts or furuncles prior to their incision and drainage. After a frost is produced on the skin, a 10- to 12-second period of anesthesia occurs before the skin temperature and sensation return to normal. As a result of this limited time frame, an assistant often has to spray the area while the surgeon performs the procedure.

Tetracaine is a long-acting ester anesthetic that can be combined with epinephrine (adrenaline) and cocaine or with epinephrine and lidocaine to form mixtures known as TAC and LET, respectively. TAC and LET are topical anesthetics used widely to anesthetize lacerations before repair. They do not induce anesthesia in intact skin; therefore, their usefulness is limited.

Tetracaine is also available in the form of a 4% gel, amethocaine (Ametop), which is not yet approved by the US Food and Drug Administration (FDA). Data from clinical trials in children have demonstrated that topical 4% amethocaine is a safe and effective topical local anesthetic when used on patients undergoing venipuncture, intravenous cannulation, and other minor cutaneous procedures. The onset of action of amethocaine is 30-45 minutes, and the duration of action is 4-6 hours. Amethocaine seems to be equivalent to lidocaine-prilocaine in providing clinically acceptable anesthesia.

Topical lidocaine is available in a 2% or 5% concentration in a viscous or jelly formulation. These preparations are most effective when they are applied to mucosal surfaces. Lidocaine is also available as a 4% gel microemulsion (Tropicaine) or in a liposomal vehicle as a 4% or a 5% cream (LMX 4% and LMX 5%, respectively). These preparations facilitate the diffusion through the stratum corneum, providing rapid-onset anesthesia and a longer duration of action. Several studies have shown that the efficacy of these lidocaine preparations is equivalent to that of EMLA.

The recommended application time for Tropicaine and LMX is 30 minutes, and occlusion is not required. The maximum area of application should not exceed 100 cm² in children and 600 cm² in children weighing greater than 10 kg and in adults. Lidocaine iontophoresis, which delivers lidocaine into the skin under the influence of an electric current, has been shown to provide adequate anesthesia for venous cannulation and shave biopsies.

EMLA cream (Astra USA, Westborough, Mass) is a eutectic mixture of 2.5% lidocaine and 2.5% prilocaine in an oil-in-water emulsion. This topical anesthetic cream provides adequate anesthesia for superficial curettage, dermabrasion, several laser procedures, epilation, and cryosurgery. However, EMLA does not seem to be helpful in reducing the pain associated with topical photodynamic treatment of actinic keratoses. EMLA is the most widely used topical agent and has proven efficacy based on results from several clinical trials. EMLA cream must be applied directly to the surgical site and placed under occlusion for 1-3 hours. The anesthetic effects of EMLA may persist for as long as 2 hours.

EMLA cream, although safe, is reported to cause systemic toxicity in children. In fact, both CNS manifestations and methemoglobinemia are reported with the use of EMLA cream. Clinicians should closely adhere to the dosing guidelines listed in the Physicians' Desk Reference. They are as follows:

Currently, EMLA is also marketed as a patch and as a sterile cream, which is used mainly for the analgesia of leg ulcers prior to debridement.

The S-Caine Peel is a 1:1 eutectic mixture of lidocaine 7% base and tetracaine 7% base in a cream vehicle that dries to form a flexible membrane that can be easily removed. The S-Caine Peel has been shown to provide adequate anesthesia for different types of laser therapies, including laser treatment of leg veins and tattoo removal. The application time is 30-60 minutes.

Although local anesthetics are relatively safe when administered properly, they have the potential to cause both regional and systemic reactions.

Local Effects

Local effects are usually a result of the injection technique. These effects include pain, ecchymosis, hematoma formation, infection, and nerve laceration. Pain is always felt when a local anesthetic is injected; however, associated discomfort can be minimized by using good technique. Several factors, including needle puncture of the skin, tissue irritation resulting from the anesthetic, and distention of tissues caused by infiltration, are responsible for the discomfort associated with the use of local anesthetics.

Pediatric patients and patients who are extremely anxious may benefit from pretreatment of the injection area with a topical anesthetic. Pretreatment eliminates the initial pain that occurs when the needle perforates the skin. Small-diameter needles also decrease the pain associated with injection. Fortunately, for most dermatologic procedures, a 30-gauge needle can be used to infiltrate tissue.

Tissue irritation caused by local anesthetics is related to the acidity of the infiltrated solution; therefore, increasing the pH of the mixture can decrease associated discomfort. The addition of epinephrine to an anesthetic solution decreases the pH of the solution, making it more acidic (pH 3.5-4.5) and leading to a more painful injection. The solution can be neutralized by the addition of sodium bicarbonate 8.4% to minimize discomfort. For example, sodium bicarbonate 8.4% can be added to lidocaine with epinephrine in a 1:10 ratio to achieve a solution pH similar to that of tissue fluid (pH 7.3-7.4).

Discomfort associated with distension of the tissues during the injection of local anesthetics is caused by the rate of injection and the volume of fluid injected. To limit the pain, the anesthetic should be slowly administered to allow the stretch receptors time to accommodate the new volume of fluid (Auletta, 1991). In addition, the volume of solution injected should be the smallest volume needed to achieve a loss of sensation at the surgical site.

The formation of ecchymosis or a local hematoma is a result of the perforation of cutaneous blood vessels. These complications are encountered more commonly in areas of high vascularity, including the mucous membranes, head, and genitalia. Ecchymosis and hematoma are even more pronounced when the patient has a bleeding diathesis or when the patient has been taking aspirin or other anticoagulants. If ecchymosis occurs, the patient should simply be reassured. If hematoma formation occurs, the patient should be evaluated. The hematoma may require drainage with an 18-gauge needle, followed by the application of a pressure dressing.

Infection is an additional local complication of anesthetic use that usually occurs when proper sterile technique is not used. Cleansing the skin surface with alcohol is adequate in otherwise clean or noninfected areas. If signs of infection are noted, treatment includes appropriate culture studies and antimicrobial therapy. If abscess formation occurs, drainage may also be required.

Nerve laceration, although rare, may occur during the infiltration of a local anesthetic. This complication more commonly occurs during the placement of regional blocks than the placement of other blocks. Clinical indications of nerve laceration include paresthesias, shooting or sharp stinging sensations, and excessive pain during needle insertion. Paresthesias of the infraorbital nerve are characterized by sharp or shooting sensations involving the upper lip, nasal ala, and upper teeth.

If the needle is suspected to have entered or lacerated a nerve, it should be withdrawn slowly and deliberately by 1-2 mm, until the paresthesias are no longer present. The needle should never be advanced further, moved laterally, or inserted into the foramen, because these maneuvers further increase the risk of nerve laceration. Although dysesthesias may remain for an extended duration, in most patients, the nerve regenerates and sensation normalizes over time.

Tendon injury is an inherent aspect of transthecal digital anesthesia since the needle is pushed through the tendon. This may cause persistent discomfort lasting 1-2 days post surgery. Tendon sheath infection and late occurrence of trigger finger have also been reported.

Cutaneous adverse effects that have been reported with the most commonly used topical anesthetic EMLA include itching, burning, pain, pallor, erythema, edema, and purpura. Irritant dermatitis, allergic contact dermatitis, and contact urticaria have also been reported, but these are very unusual.

Amethocaine may induce an urticarial reaction at the site of application, and the risk of such a reaction seems to be significantly higher when amethocaine is used over the antecubital fossa and in younger children.

Systemic Effects

Systemic effects usually occur when blood concentrations of local anesthetic increase to toxic levels. Effects are most often encountered after the unintentional intravenous injection or administration of an excessive dose of an anesthetic. Adding a vasoconstrictor (eg, epinephrine) can reduce the systemic absorption of an anesthetic. When using topical anesthetics, strict adherence to the maximal dose or area recommended is advised; additionally, great caution must be exercised when using topical anesthetics on mucosal surfaces because of the much greater absorption.

Importantly, remember that (1) the metabolism of ester anesthetics is decreased in patients with deficient pseudocholinesterase activity and (2) the metabolism of amide anesthetics in patients who are taking medications that inhibit the cytochrome P-450 system is decreased. In addition, the potency of an anesthetic is directly correlated with the potential for toxicity. Allergic reactions, although systemic, are not related to serum levels of the anesthetic, but rather, they are considered idiosyncratic and can occur at any dose.

Maximal safe doses of lidocaine for local anesthesia have been determined. For adults, a maximum of 4.5 mg of lidocaine per kilogram of body weight can be administered, whereas as much as 7 mg/kg can be used if the lidocaine solution has 1:100,000 epinephrine added as a vasoconstrictor. For children, lower maximal doses are recommended; only 1.5-2.5 mg/kg of plain lidocaine and 3-4 mg/kg of lidocaine with epinephrine should be used.

Systemic toxicity resulting from excessive blood levels of anesthetics is clinically manifested as adverse reactions in the CNS and cardiovascular system. The CNS is affected in a predictable and dose-dependent fashion. As serum levels of lidocaine increase, effects on the CNS become more severe.

Any physician who uses local anesthetics must be aware of the signs and symptoms of systemic toxicity. At serum lidocaine levels in the range of 1-5 mcg/mL, patients may complain of tinnitus, lightheadedness, circumoral numbness, diplopia, or a metallic taste in the mouth. In addition, they may complain of nausea and/or vomiting, or they may become more talkative. As serum levels increase to 5-8 mcg/mL, nystagmus, slurred speech, localized muscle twitching, or fine tremors may be noticed. Patients also have been noted to have hallucinations at these levels. If blood lidocaine levels reach 8-12 mcg/mL, focal seizure activity occurs; this can progress to generalized tonic-clonic seizures. Respiratory depression occurs at extremely high blood levels (20-25 mcg/mL) and can progress to coma.

If signs of CNS toxicity are noted, steps must be taken to reduce hypoxia and acidosis, because these states increase the toxicity of local anesthetics. The patient's airway should be maintained, and supplemental oxygen provided. If blood levels of carbon dioxide increase, protein binding of lidocaine decreases and results in higher levels of free lidocaine in the blood. Increased respiration and respiratory alkalosis increase the seizure threshold and decrease the uptake of the local anesthetic into the CNS. If convulsions occur, the patient's airway should be maintained, and supplemental oxygen administered. If seizure activity is sustained, 5-10 mg of diazepam should be administered slowly (1-2 mg/min) until the seizures cease.

Compared with the CNS, the cardiovascular system is less susceptible to the effects of local anesthetics. Most adverse effects of the cardiovascular system that occur with the administration of local anesthetics are a result of the addition of epinephrine rather than direct effects of the anesthetic. However, high blood levels of local anesthetics directly reduce cardiac contractility. In addition to the direct vasodilatory effects of most local anesthetics, the decrease in cardiac function can cause hypotension. Atrioventricular blocks, bradycardia, and ventricular arrhythmias also are reported; these are more common in patients with known conduction disturbances and requiring antiarrhythmic medications.

The treatment of conduction disturbances should be appropriately tailored to the type of reaction. The treatment of hypotension requires the physician to initiate advanced cardiac life support protocols, that is, he or she should ensure that the patient has a patent airway, provide supplemental oxygen, and elevate the patient's legs. If necessary, intravenous fluid should be administered, and the use of vasopressor agents such as ephedrine should be considered. Ephedrine can be intravenously administered in 5-mL incremental doses to a total of 15-30 mg, until a blood pressure response is noted.

Lidocaine and the FDA-approved topical anesthetics EMLA and LMX are pregnancy category B medications.

Allergic reactions

Allergic reactions to local anesthetics are extremely rare, especially with amide local anesthetics, and account for less than 1% of the reactions caused by local anesthetics. Reactions can be type 1 (ie, anaphylactic) or type 4 (ie, delayed-type hypersensitivity) reactions. These reactions are not dose related, but, rather, they are idiosyncratic. Skin prick and intradermal test results are negative in the vast majority of patients, but some authors recommend testing with the most commonly used amide local anesthetic (lidocaine).

Type 1 reactions are usually caused by ester-type anesthetics. The ester group of local anesthetics have a much greater allergenic potential than that of the amide group. Pseudocholinesterases, which produce the highly allergenic metabolic product PABA, break down ester-type anesthetics. Cross-reactivity exists among ester anesthetics; therefore, the use of all anesthetics in this structural group should be avoided in a patient with an established sensitivity to one ester-type anesthetic.

No cross-reactivity appears to exist between ester and amide anesthetics; however, cross-reactivity in anaphylactic reactions has not been investigated thoroughly. In addition, reactions to preservatives, specifically methylparaben and sodium metabisulfate (found in multiple-dose vials of amide anesthetics), may cause adverse reactions in a patient who is allergic to an ester-type anesthetic. Preservative-free single-dose vials of lidocaine are available for use if an amide anesthetic is to be used in a patient with a true hypersensitivity reaction to ester-type anesthetics.

Clinical signs of type I reactions include pruritus, urticaria, facial swelling, wheezing, dyspnea, cyanosis, laryngeal edema, nausea, vomiting, and abdominal cramping. Epinephrine with a concentration of 1:1000 should be subcutaneously administered at a dose of 0.3-0.5 mL. This dose can be repeated every 20-30 minutes to a maximum of 3 doses. If anaphylaxis ensues, a 5-mL dose of epinephrine 1:10,000 should be administered intravenously.

Type IV (ie, delayed-type hypersensitivity) reactions account for 80% of allergic reactions to local anesthetics. They are more common with the use of topical anesthetics and may occur with anesthetics of the amide and ester subtypes. Clinical manifestations are similar to those of allergic contact dermatitis and include erythema, plaques, and pruritus. Patients with a history of type IV reactions are not at an increased risk of type I reactions due to amide-type anesthetics. Contact dermatitis caused by topical anesthetics should be treated with topical steroid preparations.

Alternative agents for use as anesthetics in patients with a known allergy to both ester- and amide-type local anesthetics include isotonic sodium chloride solution and injectable antihistamines. An intradermal injection of 0.9% sodium chloride solution can provide temporary anesthesia suitable for shave or punch biopsy. Physical pressure on the nerve endings resulting from the volume injected is postulated to be responsible for the anesthetic effect. Nonbacteriostatic sodium chloride solution should be used if the patient has an allergy to the methylparaben preservative in the local anesthetic. A bacteriostatic solution, which contains benzyl alcohol, has known anesthetic properties and can be used for limited procedures such as punch biopsy.

Injectable antihistamines, such as diphenhydramine, have been administered to patients who are allergic to local anesthetics. The mechanism of anesthetic action is unknown. Injectable diphenhydramine is effective, but it has a short duration of activity, it is sedating, and its injection is painful. In addition, tissue necrosis is reported after the local injection of 5% diphenhydramine. If used for injection, diphenhydramine should be diluted to 1% by mixing 1 vial of 50-mg diphenhydramine with 4 mL of a bacteriostatic sodium chloride solution.

Reactions to local anesthetic additives

With the exception of cocaine, local anesthetics directly cause relaxation of the vascular smooth muscle, which leads to vasodilation. This effect increases bleeding at the surgical site. Vasoconstrictors, such as epinephrine, are often added to anesthetic solutions to counteract this effect. The vasoconstrictor effect of epinephrine is maximal at 7-15 minutes, and this effect is clinically evident as blanching of the skin. This blanching also is useful in determining the area that is anesthetized.

Vasoconstriction not only decreases bleeding but also slows the rate of systemic absorption of the anesthetic, which allows the body more time to metabolize the anesthetic and prolongs anesthesia. Therefore, larger volumes of anesthetic can be injected when epinephrine is added to a solution. A premixed solution of lidocaine with epinephrine in a concentration of 1:100,000 (1 mg/100 mL) is available. Concentrations greater than this are associated with a higher rate of adverse effects, including an increased risk of tissue necrosis as a result of prolonged ischemia.

Systemic effects of epinephrine can occur with a dose as little as 2 mL of an anesthetic solution containing epinephrine in a concentration of 1:100,000. The most common clinical manifestation is transient tachycardia. At higher doses and with an inadvertent intravascular injection, palpitations, diaphoresis, angina, tremors, nervousness, and hypertension can occur. The maximum dose of epinephrine is 1 mg or 100 mL of a 1:100,000 solution. In patients with a history of heart disease, especially unstable angina and arrhythmias, the maximum dose should be decreased to 0.2 mg or 20 mL of a 1:100,000 solution (recommendation of the NY Heart Association).

Epinephrine is contraindicated in patients with pheochromocytoma, hyperthyroidism, severe hypertension, or severe peripheral vascular occlusive disease. Relative contraindications include pregnancy and psychological instability; epinephrine can induce an acute psychotic episode in predisposed patients.

The FDA designates epinephrine as a pregnancy category B medication (ie, usually safe but benefits must outweigh the risks). No known adverse effects on the fetus are reported; however, during the first trimester, vasoconstriction may cause fetoplacental ischemia and affect organogenesis. In the last trimester, epinephrine can induce premature labor if placental ischemia occurs. If possible, surgery should be performed without epinephrine, or it should be postponed until after delivery.

Epinephrine must be used with caution in patients taking propranolol because life-threatening reactions have been reported; these include hypertension, myocardial infarction, and stroke. Epinephrine stimulates alpha-receptors to cause vasoconstriction and increase vascular resistance. Beta-receptors balance this effect by causing vasodilation (beta2-receptors) and an increased heart rate (beta1-receptors). Like other nonselective beta-blockers, propranolol antagonizes both beta1-receptors and beta2-receptors. Therefore, in the presence of propranolol, the effects of epinephrine on alpha-receptors are unbalanced, and the result is pure alpha stimulation, which leads to severe hypertension and reflex bradycardia.

Although propranolol is the only nonselective beta-blocker reported to have this effect, probably all nonselective beta-blockers have the potential to cause severe hypertension and reflex bradycardia in the presence of epinephrine. A significant risk does not appear to be associated with the use of epinephrine and cardioselective beta-blockers. Although the use of epinephrine in patients who are taking nonselective beta-blockers is not contraindicated, it should be avoided if possible. Apparently, the effect may be dose related, and caution should be exercised because individual variability is reported.

In addition to nonselective beta-blockers, monoamine oxidase inhibitors, tricyclic antidepressants, butyrophenones, and phenothiazines can cause hypotension or hypertension in patients who are taking epinephrine.

Pain resulting from the infiltration of a local anesthetic can be reduced by using a solution with a pH close to physiologic range (ie, pH 7.3-7.4). The pH of plain lidocaine is 6.3-6.4. When epinephrine is added to lidocaine, the pH decreases to 3.5-4.5. The pH of the solution must be acidic to prevent the degradation of epinephrine.

To reduce the pain of an injection of lidocaine and epinephrine, 1 mL of sodium bicarbonate 8.4% is added to 10 mL of the anesthetic solution to neutralize the solution. Buffered solutions should be discarded after 1 week because the effectiveness of epinephrine decreases by almost 25% during this time.

Hyaluronidase is a bovine-derived enzyme that hydrolyzes hyaluronic acid in the connective tissue and facilitates the diffusion of the anesthetic. Although it can increase the spread of anesthesia, hyaluronidase also decreases the duration of action of the anesthetics because it increases absorption. As expected, this increased absorption leads to the potential for a greater incidence of toxic reactions that correspond to elevated blood levels. To decrease distortion of the surgical site, the addition of hyaluronidase is useful for nerve blocks and procedures around the orbit.

Hyaluronidase is marketed in ampules. One ampule is equivalent to 150 United States Pharmacopeia (USP) units per milliliter. The usual dilution is 150 U in 30 mL of anesthetic. A patient can have an allergy to hyaluronidase. Hyaluronidase is a foreign protein, and its use is contraindicated in patients with a known allergy to bee stings. In addition, hyaluronidase contains the preservative thimerosal, which is a known allergen. To evaluate the potential for an allergic reaction before infiltration, a test dose should be injected intradermally. If urticaria is observed at the site of the test injection, the use of hyaluronidase is contraindicated.

In 1987, Jeffery Klein, a dermatologist, first created the technique of tumescent anesthesia in liposuction procedures. Tumescent anesthesia is based on the use of dilute solutions of lidocaine (0.05-0.1%) in large volumes to provide superior anesthesia. Epinephrine (1:1,000,000) is added for hemostasis, and the solution is buffered with sodium bicarbonate to decrease injection discomfort. Concentrations as high as 55 mg/kg have been used safely with the tumescent technique.

The use of such high total doses of anesthetic without systemic toxicity is understood. The absorption kinetics of lidocaine change when high-volume, low-concentration solutions are used. Decreased concentrations of lidocaine also result in slower plasma absorption with decreased peak plasma levels. The development of this anesthetic delivery system has revolutionized the surgical technique of liposuction.

Local anesthetics are vital to cutaneous surgery. They are effective, inexpensive, easily accessible, and relatively safe. Any surgeon using these agents should be aware of the proper technique for their use and the potential adverse effects. The ongoing investigation of new agents with alternate delivery systems and the improved safety profiles continually enhance our ability to develop innovative surgical techniques.