Local Anesthetics

Brian Levy

Jonathan Sherbino

Introduction

Local anesthetics are commonly used in the emergency department (ED) for laceration repair and regional analgesia.
Inca Indians first used cocaine, derived from Erythroxylon coca bushes found in the Andes during cranial trephination.
Small nerve fibers are more sensitive to local anesthetics, while myelinated fibers are blocked before nonmyelinated fibers.

Biochemistry

Generic structure of local anesthetic agents.
- Aromatic ring (lipophilic) – intermediate chain – hydrophilic tail.
Anesthetic properties determined by:
- pKa – amount of local anesthetic that penetrates through the tissues.
- Partition coefficient – intrinsic lipid solubility.
- Degree of protein binding.
- Type of intermediate chain determines two basic types: the “esters” and the “amides.”
  - Amino-esters:
    - “Esters” include cocaine, procaine, tetracaine, and chloroprocaine.
    - Esters are hydrolyzed by plasma pseudocholinesterase.
  - Amino-amides:
    - “Amides” include lidocaine, mepivacaine, prilocaine, bupivacaine, and etidocaine.
    - Easy memory trick: amides have the letter “i” occurring twice in the generic name.

Anatomy of Nerves

Structure of peripheral nerves.
- Bundles of individual nerve fibers or fasciculi are encased in a longitudinal array of collagen fibers known as the endoneurium.
- Buried within the endoneurium are the actual nerve fibers comprised of an axon or multiple axons, which may or may not be myelinated.
Neuron resides within the fasciculi encased in the endoneurium
- In general, neurons contain dendrite(s), which act as signal collectors that monitor the environment, receive signals from other neurons and feed information to the neuron body.

Physiology

Neural impulses are conducted by the axon, which conducts signals from the cell body to a synapse.
In unmyelinated nerve fibers, conduction moves as a “ripple” along the entire surface of the axon.
Myelin sheath insulates the axon, speeding impulse conduction.
- Impulses skip from node to node along these myelinated axons, depolarizing the entire intervening axon segments all at once (salutatory conduction).
Neural transmission is made possible by specialized voltage-gated sodium channels, which contain a pore allowing selective ion movement.

Mechanism of Action of Local Anesthetics

Effect of pKa

Upon tissue infiltration, the lipid-soluble nonionized portion of anesthetic diffuses through the tissue, ultimately across the lipid bilayer axonal membrane.
Nerve tissue is lipophilic (up to and including the axons’ myelinated sheathes, which are simply fat).
- The higher the proportion of nonionic molecules, the greater the degree to which the anesthetic can penetrate the tissue.
- Only the nonionized portion of the anesthetic solution can penetrate nerve tissue through the axon.
Clinical effect of given dosage also impacted by pH of the tissue into which the anesthetic is infused:
- When the pH of the solution or tissue containing the anesthetic is greater than the drug’s pK_a, then a greater proportion of the anesthetic molecules in solution will be in nonionized form. Hence, the lower the pK_a, the faster the onset of anesthesia.
- Nonionized form is more lipophilic, therefore enhancing neural tissue penetration and speeding onset of action.
- Inflamed tissue and abscesses tend to have low pH, which unfavorably impacts local anesthetic penetration.
Once within the axoplasm, a portion of the drug re-ionizes, and this ionic portion is thought to enter the sodium channels where it slows the movement of sodium ions, thereby preventing the formation/flow of action potentials.

Effect of Intrinsic Lipid Solubility

Lipid solubility is typically expressed as “partition coefficient.”
- Partition coefficient compares solubility of agent in a nonpolar solvent with solubility in a polar solvent such as water.
- The greater the partition coefficient, the greater the potency, and more rapid the onset.

Effect of Protein Binding

Duration of blockade determined by intrinsic protein binding of agent.
- Higher protein binding causes tighter bonding to sodium channel receptors and greater duration of blockade.

Effect of Vasoconstrictors (e.g., Epinephrine)

Benefits of adding vasoconstrictors include the following:
- Slows systemic absorption, allowing increased maximum dosages without increased risk of systemic toxicity.
- By slowing systemic absorption via local decrease of blood flow, duration of action lengthens.
- Vasoconstrictors reduce local blood flow, promoting hemostasis and improve visualization of field.
- Epinephrine typically added in concentrations of 1:100,000 or 1:200,000.
  - Epinephrine does not prolong action of bupivacaine.
  - Traditional texts continue to recommend against use of epinephrine in areas of body perfused only by end arterioles:
    - More recent literature review (regarding digital infiltration) refutes this long-standing “prohibition” as “medical mythology.”

Effect of Nerve Anatomy

When local anesthetics infiltrate a peripheral nerve, they diffuse from the outer surface “mantle” of the nerve toward the inner fibers “core.”
- In general, the mantle fibers innervate more proximal structures anatomically, and core fibers innervate more distal structures.
- Expect faster onset of nerve block more proximally than distal blocking action.

Local Anesthetic Agents

See Table 11.1.

Short-Duration Agents

Procaine:
- Largely replaced by lidocaine due to high incidence of hypersensitivity reactions.
Chloroprocaine:
- Most frequent use has been in short-duration epidural anesthesia.
- Believed to be the least toxic local anesthetic to the central nervous system (CNS) and cardiovascular system.
  - Prior controversy suggesting neurological deficits after large inadvertent subarachnoid injection.
    - Traced to bisulfite preservative no longer contained in current formulations.
    - Lumbar spasms reported with preparations of chloroprocaine that contained EDTA, which is no longer part of current formulations.

Table 11.1: Local anesthetics

Name generic (trade)	Class	Concentration (%)	Maximum dose (with epinephrine)	Onset	Duration (min)
Short acting
Procaine (Novocaine)	Ester	1–2	7 mg/kg (9 mg/kg)	10–15	20–30 (30–45)
Chloroprocaine (Nesacaine)	Ester	1–2		6–12	15–30 (30)
Moderate acting
Lidocaine (Xylocaine)	Amide	1–2	4–5 mg/kg (7 mg/kg)	5–15	30–60 (120)
Mepivacaine	Amide	0.5–1	4–5 mg/kg (7 mg/kg)	5–15	45–90 (120)
Prilocaine (Citanest)	Amide	0.5–1	8 mg/kg	15–25	30–90 (120)
Long acting
Bupivacaine (Marcaine)	Amide	0.25–0.5	2 mg/kg (3 mg/kg)	15–30	120–240 (180–240)
Ropivacaine (Naropin)	Amide	0.2–0.5	1–15	120–240	(180–240)
Topical tetracaine^a (Pontocaine)	Ester	3–10			30–60
^aTopical tetracaine has a fast onset of action and duration. Used primarily for rapid ophthalmic and pharyngeal anesthesia.

Moderate-Duration Agents

Lidocaine:
- Most multipurpose and versatile of local anesthetics.
  - Fast onset and relatively short duration make it ubiquitous agent for lacerations, foreign body removal, abscess drainage, lumbar punctures, catheter insertions, and so forth.
- Variety of concentrations are available from 0.5%–4%, however, 2% is particularly useful when minimal volume is desirable (e.g., fingers).
- Now restricted for intrathecal use due to concern that even small doses can induce “transient neurologic symptoms” (TNS), which involves onset of pain in the lower extremities from a few hours to 24 hours after apparently uncomplicated administration of spinal anesthesia.
Mepivacaine:
- Lower relative incidence of TNS than lidocaine.
- Alkalinization with bicarbonate, as with lidocaine, may speed its onset of action.
  
  Only gold members can continue reading. Log In or Register to continue
  Share this:
  Click to share on Twitter (Opens in new window)
  Click to share on Facebook (Opens in new window)
  Related
  
  Related posts:
  
  Monitoring During Procedural Sedation Adverse Events and Complications of Procedural Sedation Chest Pain Back Pain Pediatric Pain Management Renal and Biliary Colic
  
  Stay updated, free articles. Join our Telegram channel