Because anesthetics eliminate pain, and because pain can be a warning sign of complications, patients recovering from anesthesia must be protected from inadvertent harm until the anesthetic wears off. Caution the patient against activities that might result in unintentional harm.
Time Course of Local Anesthesia
Ideally, local anesthesia would begin promptly and would persist no longer (or shorter) than needed. Unfortunately, although onset of anesthesia is usually rapid (Tables 21.2 and 21.3), duration of anesthesia is often less than ideal. In some cases, anesthesia persists longer than needed. In others, repeated administration is required to maintain anesthesia of sufficient duration.
TABLE 21.2
Topical Local Anesthetics: Trade Names, Indications, and Time Course of Action
| Indications | Time Course of Action* | |||||
| Chemical Class | Generic Name | Trade Name | Skin | Mucous Membranes | Peak Effect (min) | Duration (min) |
| Amides | Dibucaine | Nupercainal | ✓ | <5 | 15-45 | |
| Lidocaine† | Xylocaine, Lidoderm, others | ✓ | ✓ | 2-5 | 15-45 | |
| Esters | Benzocaine | Many names | ✓ | ✓ | <5 | 15-45 |
| Cocaine | Generic only | ✓ | ✓ | 1-5 | 30-60 | |
| Tetracaine† | None‡ | ✓ | ✓ | 3-8 | 30-60 | |
| Others | Dyclonine | Sucrets (spray) | ✓ | <10 | <60 | |
| Pramoxine | Tronolane, others | ✓ | 3-5 | — | ||
TABLE 21.3
Injectable Local Anesthetics: Trade Names and Time Course of Action
| Time Course of Action* | ||||
| Chemical Class | Generic Name | Trade Name | Onset (min) | Duration (hr) |
| Amides | Lidocaine† | Xylocaine | <2 | 0.5-1 |
| Bupivacaine | Marcaine | 5 | 2-4 | |
| Mepivacaine | Carbocaine | 3-5 | 0.75-1.5 | |
| Prilocaine | Citanest | <2 | ≥1 | |
| Ropivacaine | Naropin | 10-30‡ | 0.5-6‡ | |
| Esters§ | Chloroprocaine | Nesacaine | 6-12 | 0.5 |
| Tetracaine† | Pontocaine | ≤15 | 2-3 | |
Onset of local anesthesia is determined largely by the molecular properties of the anesthetic. Before anesthesia can occur, the anesthetic must diffuse from its site of administration to its sites of action within the axon membrane. Anesthesia is delayed until this movement has occurred. The ability of an anesthetic to penetrate the axon membrane is determined by three properties: molecular size, lipid solubility, and degree of ionization at tissue pH. Anesthetics of small size, high lipid solubility, and low ionization cross the axon membrane rapidly. In contrast, anesthetics of large size, low lipid solubility, and high ionization cross slowly. Obviously, anesthetics that penetrate the axon most rapidly have the fastest onset.
Termination of local anesthesia occurs as molecules of anesthetic diffuse out of neurons and are carried away in the blood. The same factors that determine onset of anesthesia (molecular size, lipid solubility, degree of ionization) also help determine duration. In addition, regional blood flow is an important determinant of how long anesthesia will last. In areas where blood flow is high, anesthetic is carried away quickly, and effects terminate with relative haste. In regions where blood flow is low, anesthesia is more prolonged.
Use With Vasoconstrictors
Local anesthetics are frequently administered in combination with a vasoconstrictor, usually epinephrine. The vasoconstrictor decreases local blood flow and thereby delays systemic absorption of the anesthetic. Delaying absorption has two benefits: It prolongs anesthesia and reduces the risk for toxicity. Because absorption is slowed, less anesthetic is used and a more favorable balance is established between the rate of entry of anesthetic into circulation and the rate of its conversion into inactive metabolites.
It should be noted that absorption of the vasoconstrictor itself can result in systemic toxicity (e.g., palpitations, tachycardia, nervousness, hypertension). If adrenergic stimulation from absorption of epinephrine is excessive, symptoms can be controlled with alpha- and beta-adrenergic antagonists.
Pharmacokinetics
Absorption and Distribution
Although administered for local effects, local anesthetics do get absorbed into the blood and become distributed to all parts of the body. The rate of absorption is determined largely by blood flow to the site of administration.
Metabolism
The process by which a local anesthetic is metabolized depends on the class—ester or amide—to which it belongs. Ester-type local anesthetics are metabolized in the blood by enzymes known as esterases. In contrast, amide-type anesthetics are metabolized by enzymes in the liver. For both types of anesthetic, metabolism results in inactivation.
The balance between rate of absorption and rate of metabolism is clinically significant. If a local anesthetic is absorbed more slowly than it is metabolized, its level in blood will remain low, and systemic reactions will be minimal. Conversely, if absorption outpaces metabolism, plasma drug levels will rise, and the risk for systemic toxicity will increase.
Adverse Effects
Adverse effects can occur locally or distant from the site of administration. Local effects are less common.
Central Nervous System
When absorbed in sufficient amounts, local anesthetics cause central nervous system (CNS) excitation followed by depression. During the excitation phase, seizures may occur. If needed, excessive excitation can be managed with an intravenous benzodiazepine (diazepam or midazolam). Depressant effects range from drowsiness to unconsciousness to coma. Death can occur secondary to depression of respiration. If respiratory depression is prominent, mechanical ventilation with oxygen is indicated.
Cardiovascular System
When absorbed in sufficient amounts, local anesthetics can affect the heart and blood vessels. In the heart, these drugs suppress excitability in the myocardium and conducting system and thereby can cause bradycardia, heart block, reduced contractile force, and even cardiac arrest. In blood vessels, anesthetics relax vascular smooth muscle; the resultant vasodilation can cause hypotension.
Allergic Reactions
An array of hypersensitivity reactions, ranging from allergic dermatitis to anaphylaxis, can be triggered by local anesthetics. These reactions, which are relatively uncommon, are much more likely with the ester-type anesthetics (e.g., chloroprocaine) than with the amides. Patients allergic to one ester-type anesthetic are likely to be allergic to all other ester-type agents. Fortunately, cross-hypersensitivity between the esters and amides has not been observed. Therefore the amides can be used when allergies contraindicate use of ester-type anesthetics. Because they are unlikely to cause hypersensitivity reactions, the amide-type anesthetics have largely replaced the ester-type agents when administration by injection is required.
Methemoglobinemia
Topical benzocaine can cause methemoglobinemia, a blood disorder in which hemoglobin is modified such that it cannot release oxygen to tissues. If enough hemoglobin is converted to methemoglobin, death can result. Methemoglobinemia has been associated with benzocaine liquids, sprays, and gels. Most cases were in children younger than 2 years treated with benzocaine gel for teething pain. Because of this risk, topical benzocaine should not be used in children younger than 2 years without the advice of a health care professional, and should be used with caution in older children and adults when applied to mucous membranes of the mouth.
Properties of Individual Local Anesthetics
Chloroprocaine
Chloroprocaine [Nesacaine] is the prototype of the ester-type local anesthetics. The drug is not effective topically and must be given by injection. Administration in combination with epinephrine delays absorption. Although chloroprocaine is readily absorbed, systemic toxicity is rare because plasma esterases rapidly convert the drug to inactive, nontoxic products. Being an ester-type anesthetic, procaine poses a greater risk for allergic reactions than do the amide-type anesthetics. Individuals allergic to chloroprocaine should be considered allergic to all other ester-type anesthetics, but not to the amides.
Lidocaine
Lidocaine, introduced in 1948, is the prototype of the amide-type agents. One of today’s most widely used local anesthetics, lidocaine can be administered topically and by injection. Anesthesia with lidocaine is more rapid, more intense, and more prolonged than an equal dose of procaine. Effects can be extended by coadministration of epinephrine. Allergic reactions are rare, and individuals allergic to ester-type anesthetics are not cross-allergic to lidocaine. If plasma levels of lidocaine climb too high, CNS and cardiovascular toxicity can result. Inactivation is by hepatic metabolism.
In addition to its use in local anesthesia, lidocaine is employed to treat dysrhythmias (see Unit XXII on drugs for acute care). Control of dysrhythmias results from suppression of cardiac excitability secondary to blockade of cardiac sodium channels.
Cocaine
Cocaine was our first local anesthetic. It is an ester-type anesthetic. In addition to causing local anesthesia, cocaine has pronounced effects on the sympathetic and central nervous systems. These sympathetic and CNS effects are due largely to blocking the reuptake of norepinephrine by adrenergic neurons.
Anesthetic Use
Cocaine is an excellent local anesthetic. Administered topically, the drug is employed for anesthesia of the ear, nose, and throat. Anesthesia develops rapidly and persists for about 1 hour. Unlike other local anesthetics, cocaine causes intense vasoconstriction (by blocking norepinephrine uptake at sympathetic nerve terminals on blood vessels). Accordingly, the drug should not be given in combination with epinephrine or any other vasoconstrictor. Despite its ability to constrict blood vessels, cocaine is readily absorbed after application to mucous membranes. Significant effects on the brain and heart can result. The drug is inactivated by plasma esterases and liver enzymes.
CNS Effects
Cocaine produces generalized CNS stimulation. Moderate doses cause euphoria, talkativeness, reduced fatigue, and increased sociability and alertness. Excessive doses can cause seizures. Excitation is followed by CNS depression. Respiratory arrest and death can result.
Although cocaine does not seem to cause substantial physical dependence, psychological dependence can be profound. The drug is subject to widespread abuse and is classified under Schedule II of the Controlled Substances Act. Cocaine abuse is discussed in Chapter 33.
Cardiovascular Effects
Cocaine stimulates the heart and causes vasoconstriction. These effects result from (1) central stimulation of the sympathetic nervous system and (2) blockade of norepinephrine uptake in the periphery. Stimulation of the heart can produce tachycardia and potentially fatal dysrhythmias. Vasoconstriction can cause hypertension. Cocaine presents an especially serious risk to individuals with cardiovascular disease (e.g., hypertension, dysrhythmias, angina pectoris).
Other Local Anesthetics
In addition to the drugs discussed previously, several other local anesthetics are available. These agents differ with respect to indications, route of administration, mode of elimination, duration of action, and toxicity.
The local anesthetics can be grouped according to route of administration: topical versus injection. (Very few agents are administered by both routes, primarily because the drugs that are suitable for topical application are usually too toxic for parenteral use.) Table 21.2 lists the topically administered local anesthetics along with trade names and time course of action. Table 21.3 presents equivalent information for the injectable agents.
Clinical Use of Local Anesthetics
Local anesthetics may be administered topically (for surface anesthesia) and by injection (for infiltration anesthesia, nerve block anesthesia, intravenous regional anesthesia, epidural anesthesia, and spinal anesthesia). The uses and hazards of these anesthesia techniques are discussed next.
Topical Administration
Surface anesthesia is accomplished by applying the anesthetic directly to the skin or a mucous membrane. The agents employed most commonly are lidocaine, tetracaine, and cocaine.
Therapeutic Uses
Local anesthetics are applied to the skin to relieve pain, itching, and soreness of various causes, including infection, thermal burns, sunburn, diaper rash, wounds, bruises, abrasions, plant poisoning, and insect bites. Application may also be made to mucous membranes of the nose, mouth, pharynx, larynx, trachea, bronchi, vagina, and urethra. In addition, local anesthetics may be used to relieve discomfort associated with hemorrhoids, anal fissures, and pruritus ani.
Systemic Toxicity
Topical anesthetics applied to the skin can be absorbed in amounts sufficient to produce serious or even life-threatening effects. Cardiac toxicity can result in bradycardia, heart block, or cardiac arrest. CNS toxicity can result in seizures, respiratory depression, and coma. Obviously, the risk for toxicity increases with the amount absorbed, which is determined primarily by (1) the amount applied, (2) skin condition, and (3) skin temperature. Accordingly, to minimize the amount absorbed, and thereby minimize risk, patients should do the following:
Administration by Injection
Injection of local anesthetics carries significant risk and requires special skills. Injections are usually performed by an anesthesiologist. Because severe systemic reactions may occur, equipment for resuscitation should be immediately available. Also, an intravenous line should be in place to permit rapid treatment of toxicity. Inadvertent injection into an artery or vein can cause severe toxicity. To ensure the needle is not in a blood vessel, it should be aspirated before injection. After administration, the patient should be monitored for cardiovascular status, respiratory function, and state of consciousness. To reduce the risk for toxicity, local anesthetics should be administered in the lowest effective dose.
Infiltration Anesthesia
Infiltration anesthesia is achieved by injecting a local anesthetic directly into the immediate area of surgery or manipulation. Anesthesia can be prolonged by combining the anesthetic with epinephrine. The agents employed most frequently for infiltration anesthesia are lidocaine and bupivacaine.
Nerve Block Anesthesia
Nerve block anesthesia is achieved by injecting a local anesthetic into or near nerves that supply the surgical field, but at a site distant from the field itself. This technique has the advantage of producing anesthesia with doses that are smaller than those needed for infiltration anesthesia. Drug selection is based on required duration of anesthesia. For shorter procedures, lidocaine or mepivacaine might be used. For longer procedures, bupivacaine would be appropriate.
