Pablo Monedero, Ismael González, Jesús Olivas

Abstract

A considerable number of plastic surgery procedures are done under local anesthesia with or without sedation; hence knowledge of their mechanism of action, dosages, and potential complications is of utmost relevance. Local anesthetics (LAs) block nerve conduction by binding to a modulated receptor located on the interior of the sodium channel, which prevents the increase in membrane permeability to sodium ions that would normally lead to a nerve impulse. The more potent and longer-acting LAs are more lipid soluble and show increased protein binding and less systemic absorption, but at the expense of having a higher potential for systemic toxicity. Even though systemic toxicity from LAs is an uncommon occurrence, when it occurs it should be managed promptly and effectively with supportive measures and intravenous (IV) administration of 20% lipid emulsion. LAs are used for field or regional blocks. Regional blocks supply anesthesia to a large territory with a comparatively small quantity of LA, avoiding the complications of general anesthesia and the systemic toxicity of large volumes of LA. Regional blocks in the face and limbs can be performed easily and effectively for a number of different procedures, such as wound closure, skin cancer excision and flap reconstruction, and nerve entrapment syndromes. This chapter describes the main aspects of the physiology of LAs and their use in the clinical setting, along with a technical description of the main blocks used in plastic surgery.

Keywords: local anesthetics, maximum dose, regional block, sedation, toxicity

The first local anesthetic (LA), cocaine, was isolated from leaves of the coca plant in 1860. The medicinal use of coca was first investigated and described by Freud in 1884. Koller, an Austrian ophthalmologist, introduced the use of cocaine as a topical anesthetic for ophthalmologic procedures, and subsequently the clinical application of cocaine became widespread. The development of organic chemistry enabled the synthesis of procaine, another ester LA, analogue of cocaine, in 1905. In the 1940s lidocaine, the first amide LA, was introduced with fewer undesirable effects and deeper anesthesia than procaine. Bupivacaine was synthesized in 1957 with a longer duration of action. Levobupivacaine and ropivacaine were later introduced to reduce cardiac toxicity.

Nerve fibers show differences in susceptibility to LA blockade based on size, myelination, and length of fiber exposed to LA. In addition, a differential pattern of sensory block after application of LA to a peripheral nerve is observed. Temperature sensation is lost first, followed by sharp pain, and finally light touch. The quality of nerve blockade is determined not only by the potency of the individual LA but also by its concentration and volume. The latter is important because a sufficient length of axon must be blocked in order to prevent regeneration of the impulse in the adjacent node of Ranvier.

The onset of action of LAs depends on the route of administration and dosage (e.g., concentration). In peripheral nerve blocks (PNBs) where LA is injected in the vicinity of the target nerve(s), the amount of drug that reaches such nerve(s) will depend on diffusion of the drug and the proximity of injection. For a given route of administration, increasing the concentration can accelerate onset.

The duration of action of LAs is determined primarily by their protein binding. LAs with a high affinity for protein remain bound to the nerve membrane for longer periods of time. In other words, the higher the affinity for Na⁺ channels binding, the longer the duration of the LA. Furthermore, duration of action is also influenced by the rate of vascular uptake of LA from the injection site.

All currently available LAs consist of a lipophilic phenyl ring and a hydrophobic tertiary amine. In general, with increasing length of the carbon backbone of the tertiary amine, LAs exhibit greater lipid solubility, protein binding, potency, and duration of action. Based on the type of chemical bond, amide or ester, linking the phenyl ring with the tertiary amine, LAs are classified as amino-amides (articaine, bupivacaine, lidocaine, prilocaine, ropivacaine) or amino-esters (cocaine, chloroprocaine, procaine, tetracaine). Amide and ester LAs differ in their chemical stability, metabolism, and allergic potential. Amides are extremely stable, whereas esters are relatively unstable, particularly in neutral or alkaline solution. Amide compounds undergo enzymatic degradation in the liver, whereas ester compounds are hydrolyzed by plasmatic esterase enzymes. The metabolites of esters include p-aminobenzoic acid (PABA), which can occasionally induce allergic reactions. Allergies to amides are very rare.

Based on their chiral form, LAs are classified as single enantiomers or racemic mixtures. Enantiomers consist of two stereoisomers (left/sinister/S or right/dexter/R) that are mirror images of each other with respect to a specific chiral center. A racemic mixture contains equal amounts of the two enantiomers. The two forms possess different pharmacological properties that are of clinical importance. All currently available LAs are racemic mixtures, with the exception of lidocaine (achiral), levobupivacaine (S), and ropivacaine (S). Levobupivacaine’s potency and efficacy are comparable to those of bupivacaine, but it has significantly less cardiac and central nervous system (CNS) toxicity, likely due to reduced affinity for subtypes of Na⁺ channels expressed in brain and cardiac tissues.

Systemic toxicity manifests primarily in the cardiovascular and central nervous systems. The signs and symptoms of LA toxicity range from mild symptoms (ringing in the ears, metallic taste, tingling of the lips, and agitation) to severe neurologic (seizures) and cardiovascular signs (hypertension, hypotension, tachycardia, bradycardia, ventricular arrhythmias, and cardiac arrest).

The effect of LAs on the cardiovascular system is dual: by directly affecting cardiac myocytes and peripheral vascular smooth muscle cells, and indirectly by their action on the autonomic nervous system. The more potent, lipophilic LAs, such as bupivacaine, tetracaine, and etidocaine, are more cardiotoxic than the less lipophilic agents, such as procaine, prilocaine, and lidocaine

LAs readily cross the blood–brain barrier and generalized CNS toxicity may occur from systemic absorption or direct vascular injection. LAs’ potential for generalized CNS toxicity approximately parallels their action potential blocking potency. Signs of generalized CNS toxicity are dose dependent, with low doses producing CNS depression, and higher doses resulting in CNS excitation and seizures. Increasing doses of LAs produce light-headedness, tinnitus, and tongue numbness, before the appearance of seizures, unconsciousness, and ultimately respiratory arrest and cardiovascular depression with heart arrest.

Treatment of LA systemic toxicity consists of IV administration of 20% lipid emulsion (1.5 mL/kg bolus, followed by 0.25 mL/kg/min infusion), together with supportive airway and hemodynamic management. Calcium channel blockers and β-blockers should be avoided; vasopressin is not recommended and initial doses of epinephrine should be small (10–100 µg IV). If there is no clinical improvement after 30 minutes, the bolus dose of lipid emulsion 1.5 mL/kg should be repeated and the continuous infusion increased to 0.5 mL/kg/min.

Most adverse reactions to LAs are nonallergic and include psychomotor responses related to anxiety, sympathetic stimulation from pain or epinephrine, or toxic effects attributable to heightened sensitivity to known properties of the drug. However, two different types of allergic reactions have been described: allergic contact dermatitis and urticaria–anaphylaxis. Allergic contact dermatitis (type IV hypersensitivity) produces delayed swelling at the site of injection within 72 hours. Urticaria, anaphylaxis, and immediate allergic reactions (type I hypersensitivity), which typically begin within 1 hour of drug administration, are described in only a handful of case reports. Patients with suspected allergic reactions to LAs should be evaluated because most can tolerate other LA agents. An approach to safely precluding these reactions includes skin testing and controlled drug challenge.

Peripheral nerve injury is rare with PNBs. Related symptoms are transient, lasting days to months. Major complications resulting in permanent (> 6 months) nerve damage range between 0.015 and 0.09%. Most nerve injuries are believed to occur secondary to intraneural injection, which can be minimized if injection is halted and the needle withdrawn if undue resistance to injection is encountered or if the patient feels sharp pain or paresthesias. Additional risk factors for nerve injury include preexisting nerve pathology (including diabetes) and the use of standard longer-beveled needles. Symptoms of nerve injury are primarily sensory (pain, tingling, or paresthesia), though they may include a combination of motor and sensory deficits depending on the nerve involved and the severity of injury. Most symptoms resolve within 6 months; if symptoms are either severe or persistent, the patient should be referred to a neurologist.

Although many drugs have been added to LAs with the aim of decreasing onset time, increasing duration, increasing block density, or decreasing toxicity, they are not universally used because their side effects are felt to outweigh their benefits. The limited available evidence regarding potential adjuvants includes epinephrine, sodium bicarbonate, fentanyl, dexamethasone, and α2-agonists. Epinephrine is the most common vasoconstrictor added to PNBs, typically at a concentration of 1:200,000 to 1:400,000. It is used both to indicate rapid vascular uptake (e.g., during inadvertent intravascular injection an increase in heart rate of ≥ 20 bpm and/or an increase in systolic blood pressure ≥ 15 mm Hg after a dose of 15 µg of epinephrine should raise a suspicion of intravascular injection) and to decrease the LA’s absorption, which may in turn reduce potential toxicity (in vascular areas) and prolong duration of the block. Side effects of epinephrine include tachycardia and a potential for ischemia to nerves and other tissues due to vasoconstriction. Consequently, in patients at risk of cardiac ischemia or those with possibly decreased perineural blood flow (e.g., postchemotherapy, diabetes, or vascular disease), it is reasonable to use lower concentrations (1:400,000). Sodium bicarbonate is used to reduce onset time of the LA effect. The quicker onset is most evident in LAs with commercially added epinephrine—which are formulated at a lower pH—but is often not of clinical significance. The addition of fentanyl or morphine to PNBs does not provide a clear clinical benefit. The addition of dexamethasone to LAs in PNBs was associated with longer duration of action in several trials. The addition of clonidine to LA for PNB prolongs the duration of sensory and motor blockade, albeit at the expense of a higher risk of hypotension, bradycardia, and sedation.

Benzodiazepines (BDZs) enhance the effect of the neurotransmitter γ-aminobutyric acid (GABA) at the GABA_A receptor, resulting in sedative, hypnotic, anxiolytic, anticonvulsant, and muscle relaxant properties. Used as systemic adjuvants to PNB, BDZs reduce anxiety and improve patient cooperation. According to their half-life, BDZs are categorized as short (midazolam, tetrazepam, or triazolam), intermediate (alprazolam, chlordiazepoxide, lorazepam, or lormetazepam), or long-acting (bromazepam, clonazepam, clorazepate, diazepam, or flunitrazepam).

BDZs are safe and effective for short-term use, although cognitive impairment and paradoxical effects, such as agitation, panic, aggression, or behavioral disinhibition occasionally occur. Low doses of short or intermediate BDZs are best titrated to optimize sedative effects.

BDZ overdose produces CNS depression with impaired balance, ataxia, and slurred speech. Severe symptoms include coma and respiratory depression. Supportive care is the mainstay of treatment of BDZ overdose. There is an antidote, flumazenil, which can be used to reverse excessive sedation of BDZs.

Regional nerve blocks provide anesthesia to a relatively large territory with small volumes of LA, thus avoiding potential complications of general anesthesia and the systemic toxicity associated with the administration of large volumes of LA. In addition, nerve blocks minimize patient discomfort, allowing a number of different procedures, such as local flaps in the face and limbs, debridement and suture of complex wounds, injection of botulinum toxin and limb surgery, with fast recovery. Herein we will describe the anatomy of cutaneous innervation of the face, scalp, ear, hand and wrist, and ankle and foot, followed by the technique of blocking the main nerves supplying these areas.