Local Anesthetics

Mitzi L. Williams

Donald R. Green

The use of local anesthetics in foot and ankle surgery is a topic of great importance. Not only does local anesthesia interrupt transmission of the autonomic, sensory, and motor neural impulses, but the usage of local agents also decreases a patient’s requirement for both inhaled anesthesia and intravenous medications. This can only assist patients with an expedited return to physiologic function and further pain control. When placed in proximity to nerve membranes, a reversible blockade is produced (1). Subsequently, recovery from the effects of local anesthetics has been described as spontaneous with rare nerve fiber damage. With an understanding of anatomy, anesthetic agents, and technique, local anesthesia benefits patients in both a surgical and clinical setting.

HISTORY

In 1860, the first local anesthetic agent, cocaine, was extracted from the leaves of the Erythroxylon coca bush. This potent agent was found to produce topical anesthesia with numerous side effects. Sigmund Freud and Karl Koller were the first to use cocaine as an anesthetic in ophthalmologic procedures in 1884 (2). Consequently, the need for safer and more effective local agents arose when cocaine was found to produce psychological dependence and irritation. Cocaine was also noted to cause hypertension and vasoconstriction. Procaine, the first synthetic local anesthetic, was introduced by Einhorn in 1904 (2). This ester when metabolized was later found to produce a metabolite, para-aminobenzoic acid, which functioned as an allergen. Tetracaine likewise produced similar allergic reactions and influenced researchers to develop synthetic agents less likely to produce allergic responses. Lofgren, in 1943, developed an amide called lidocaine. The amide derivatives of diethylaminoacetic acid were born. Amides were found to produce reversible regional anesthesia with low allergy potential.

ANATOMY: NERVE CLASSIFICATION

Nerve fibers have been divided into A fibers, B fibers, and C fibers. These nerve fibers associated with the mammalian nerve were categorized according to their diameters, conduction velocity, and other physiologic characteristics. Myelination, for example, is an important finding. Conduction velocity is highest in myelinated fibers and can be up to 50 times faster than unmyelinated fibers.

A fibers are both large and myelinated. These traits allow for rapid conduction of motor and sensory impulses. Unfortunately, A fibers are the most vulnerable to injury. Mechanical pressure and lack of oxygen from extended use of a tourniquet would place A fibers at risk of damage.

Myelinated B fibers have a slower conduction velocity due to their smaller diameter. B fibers are also found to provide some autonomic functions, which make them unique. The slowest pain and autonomic impulses are produced by C fibers. This slow signal transmission is attributed to their unmyelinated nature and small diameter (Table 6.1).

These nerve fibers are important when discussing the function of local anesthesia. In the peripheral nervous system, pain fibers are of small diameter. A delta fibers are targeted as they are thinly myelinated and unmyelinated fibers that signal sharp, short-lived pain. Contrary to this, C fibers transmit chronic burning pain. Local agents easily inhibit these signals produced by small diameter nerves. Both types of pain-conducting fibers, C and A delta, are blocked by similar concentrations of local anesthetics despite the different diameters (Table 6.2).

SPINOTHALAMIC TRACT

There are many pathways involved with signaling transmission of pain. The spinothalamic tract is the system composed of small diameter nerve fibers relaying sharp pain, temperature, crude touch, and noxious stimuli. This tract originates from the peripheral skin and concludes in the dorsal horn on the contralateral side of the thalamus. On examination, a brain stem lesion or spinal cord lesion resulting in pain perception deficits is noted on the contralateral side. On the other hand, a spinal cord lesion produces ipsilateral touch and proprioception deficits.

LOCAL ANESTHESIA: MECHANISM

OF ACTION

The pathophysiology of propagating electrical impulses can be divided into three phases. These phases consist of a negative resting potential (-70 mV), depolarization (+35 mV), and return of negative resting potential (2). First, the nerve is found to be in a state of negative resting potential where an abundance of sodium ions are found outside of the nerve cell membrane. To generate an impulse, the cell must reach threshold and further be depolarized with the help of the sodium/potassium adenosine triphosphate (ATP) pump.

Sodium enters the cell membrane and generates a transmembrane electric potential. Threshold is then reached when rapid influx of sodium ions ensues. This rapid influx activates sodium channels and increases sodium ion permeability. The cell is now found to have a more positive resting potential of -55 mV. The rapid influx of sodium continues while potassium exits the cell. When depolarized, a signal is transmitted. This state is brief prior to the return of the negative resting potential.

Finally, the nerve cell membrane becomes impermeable to sodium ions. Potassium ions move into the cell, and the negative resting potential is reinstated. It is this process as well as the sodium/potassium ATP pump that local anesthetics act upon.

Local anesthetics function by inhibiting depolarization of the nerve membrane. Local anesthetics hence interfere with both sodium and potassium currents and prevent signal transmission. Consequently, an action potential is never produced since threshold is never obtained. The majority of local agents retard sodium influx into cells preventing depolarization. Still, these agents also block potassium currents, which continue to reduce the cell membranes ability to create an action potential. As the local anesthetic wears off, the signaling transmission process is restored and depolarization of the nerve cell membrane will be uninhibited.

TABLE 6.1 Nerve Characteristics

Nerve Fiber	Characteristics
A	Largest, myelinated
B	Moderate size, myelinated
C	Small, unmyelinated

It is important to also understand the mechanism that allows local anesthesia to enter the cell and work properly. Local anesthetics are weak bases manufactured in the form of a hydrochloride salt. This form allows for the local agent to be water soluble. At physiologic pH, the protonated and unprotonated forms of the local anesthetic molecule exist in equilibrium. Still, only the unprotonated or unionized form will diffuse readily across the nerve cell membrane. The lower pH inside the cell protonates the local anesthetic molecule and prevents its escape. This is a process called ion trapping (2,3).

The protonated molecule is trapped and bound to its binding site inside the cell. Clinically, this is important when treating various types of infections. Wound infections create a state of acidosis, which decreases the pH outside of the cell. In this condition, the majority of local anesthetic molecules are protonated outside of cell and cannot diffuse inside the cell to produce anesthesia. This acidity reduces effectiveness and action of all local anesthetics. The administration of local anesthesia proximal to a site of infection would be more advantageous.

STRUCTURE

Two broad groups exist for classifying local anesthetic agents. The basis for classification depends on the local anesthetic’s structure. Local anesthetics consist of a lipophilic unsaturated benzene ring, hydrophilic tertiary amine, and proton acceptor. These constructs are separated by a hydrocarbon chain. This hydrocarbon chain is linked to the lipophilic portion by either an ester (-CO-) or amide (-HNC-) bond (2,3). Esters and amides vary in spite of metabolism and allergy potential (Table 6.3).

TABLE 6.2 Nerve Classification

Nerve Fiber		Function
A
	α	Proprioception, somatic motor
	β	Touch, pressure
	γ	Muscle tone
	δ	Sharp pain, temperature, touch
B		Preganglionic autonomic nervous system
C		Dull pain reflex response, temperature, touch
		Postganglionic sympathetics

TABLE 6.3 Maximum Doses

Local Anesthetic	mg/mL	Maximum mg	Maximum mL
1% Lidocaine plain	10 mg/mL	300 mg	30 mL
2% Lidocaine plain	20 mg/mL	300 mg	15 mL
1% Lidocaine with epinephrine	10 mg/mL	500 mg	50 mL
2% Lidocaine with epinephrine	20 mg/mL	500 mg	25 mL
1% Carbocaine	10 mg/mL	300 mg	30 mL
2% Carbocaine	20 mg/mL	300 mg	15 mL
0.5% Marcaine plain	5 mg/mL	175 mg	35 mL
0.5% Marcaine with epinephrine	5 mg/mL	225 mg	45 mL

Esters, such as procaine (C₁₃H₂₀N₂O₂), undergo hydrolysis by plasma esterases in the blood. The incidence of an allergic reaction is rare yet a greater potential for an allergic response exists for this group. Procaine has a half-life of 40 to 80 seconds and is excreted via the renal system. Procaine has the advantage of constricting blood vessels as does cocaine. Still, procaine does not produce the euphoric and addictive qualities of cocaine.

Hypoallergenic alternatives such as lidocaine are used more frequently today. Amides, in general are metabolized by the liver and most commonly excreted by the renal system. Lidocaine (C₁₄H₂₂N₂O) is fast acting and has a half-life of 1.5 to 2 hours. Bupivacaine (C₁₈H₂₈N₂O), on the other hand, is longer acting with a half-life of 3.5 hours in adults and 8.1 hours in neonates. Amides are not risk free as they can lead to toxicity. Care should be taken with patients who have hepatic impairment or congestive heart failure. Most adverse drug reactions result from improper administration technique resulting in systemic exposure (Tables 6.4 and 6.5).

EPINEPHRINE: FOOT AND ANKLE SURGERY

Although some literature recommends against epinephrine containing local anesthetics in digital surgery, this warning appears to be based on anecdotal evidence versus research. Surveys and studies have documented that epinephrine is safe to use with local anesthetics when administered cautiously (4,6). Likewise, the use of epinephrine allows for surgery without a tourniquet. The duration of epinephrine is not longlived. When administered, epinephrine lasts from 20 minutes to 1 hour (7). Circulation is not completely occluded to the involved digits (8,9).

TABLE 6.4 Dose per Kilogram

Local Anesthetic	Dose
Lidocaine	4 mg/kg
Lidocaine with epinephrine	7 mg/kg
Carbocaine	4 mg/kg

TABLE 6.5 Comparative Pharmacology

Classification	Onset	Duration after Infiltration (min)	Maximum Single Dose for Infiltration (mg)
Procaine	Rapid	45-60	500
Chloroprocaine	Rapid	30-45	600
Tetracaine	Slow	60-180	100
Lidocaine	Rapid	60-120	300
Mepivacaine	Slow	90-180	300
Prilocaine	Slow	60-120	400
Bupivacaine	Slow	240-480	175
Ropivacaine	Slow	240-480	200

Epinephrine shortens the onset of anesthesia, prolongs the effect, and produces vasoconstriction (10). Vasoconstriction not only decreases bleeding but also slows the rate of absorption of anesthetic. This allows more time to metabolize the anesthetic and further prolongs its action. Therefore, larger doses of local anesthesia with epinephrine can be used as compared with anesthesia without epinephrine. Epinephrine in concentrations of 1:100,000 and 1:200,000, works well and safely for surgery. The most common side effect is transient tachycardia after inadvertent intravascular injection.

At higher doses and with 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. The maximum dose should be decreased in patients with heart disease to 0.2 mg or 20 mL of a 1:100,000 solution (New York Heart Association). Epinephrine is contraindicated in patients with pheochromocytoma, hyperthyroidism, severe hypertension, or severe peripheral vascular disease. Relative contraindications include pregnancy and psychological instability (11).

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