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CHAPTER 26 Local Anesthetics 465

soluble than tetracaine, bupivacaine, and ropivacaine. The latter blocked before the smaller unmyelinated C fibers involved in pain
agents are more potent and have longer durations of local anes- transmission (Table 26–3).
thetic action. These long-acting local anesthetics also bind more Another important factor underlying differential block
extensively to proteins and can be displaced from these binding derives from the state- and use-dependent mechanism of action
sites by other protein-bound drugs. In the case of optically active of local anesthetics. Blockade by these drugs is more marked
agents (eg, bupivacaine), the R(+) isomer can usually be shown to at higher frequencies of depolarization. Sensory (pain) fibers
be slightly more potent than the S(–) isomer (levobupivacaine). have a high firing rate and relatively long action potential dura-
tion. Motor fibers fire at a slower rate and have a shorter action
C. Neuronal Factors Affecting Block potential duration. As type A delta and C fibers participate in
1. Differential block—Since local anesthetics are capable of high-frequency pain transmission, this characteristic may favor
blocking all nerves, their actions are not limited to the desired blockade of these fibers earlier and with lower concentrations of
loss of sensation from sites of noxious (painful) stimuli. With local anesthetics. The potential impact of such effects mandates
central neuraxial techniques (spinal or epidural), motor paraly- cautious interpretation of non-physiologic experiments evaluat-
sis may impair respiratory activity, and autonomic nerve block- ing intrinsic susceptibility of nerves to conduction block by local
ade may promote hypotension. Further, while motor paralysis anesthetics.
may be desirable during surgery, it may be a disadvantage in 3. Anatomic arrangement—In addition to the effect of
other settings. For example, motor weakness occurring as a intrinsic vulnerability to local anesthetic block, the anatomic
consequence of epidural anesthesia during obstetrical labor organization of the peripheral nerve bundle may impact the
may limit the ability of the patient to bear down (ie, “push”) onset and susceptibility of its components. As one would predict
during delivery. Similarly, when used for postoperative anal- based on the necessity of having proximal sensory fibers join the
gesia, weakness may hamper ability to ambulate without nerve trunk last, the core will contain sensory fibers innervating
assistance and pose a risk of falling, while residual autonomic the most distal sites. Anesthetic placed outside the nerve bundle
blockade may interfere with bladder function, resulting in uri- will thus reach and anesthetize the proximal fibers located at the
nary retention and the need for bladder catheterization. These outer portion of the bundle first, and sensory block will occur in
issues are particularly problematic in the setting of ambulatory sequence from proximal to distal.
(same-day) surgery, which represents an ever-increasing per-
centage of surgical caseloads.
2. Intrinsic susceptibility of nerve fibers—Nerve fibers differ ■ CLINICAL PHARMACOLOGY OF
significantly in their susceptibility to local anesthetic blockade. It LOCAL ANESTHETICS
has been traditionally taught, and still often cited, that local anes-
thetics preferentially block smaller diameter fibers first because Local anesthetics can provide highly effective analgesia in well-
the distance over which such fibers can passively propagate an defined regions of the body. The usual routes of administration
electrical impulse is shorter. However, a variable proportion of include topical application (eg, nasal mucosa, wound [incision
large fibers are blocked prior to the disappearance of the small site] margins), injection in the vicinity of peripheral nerve end-
fiber component of the compound action potential. Most notably, ings (perineural infiltration) and major nerve trunks (blocks), and
myelinated nerves tend to be blocked before unmyelinated nerves injection into the epidural or subarachnoid spaces surrounding
of the same diameter. For example, preganglionic B fibers are the spinal cord (Figure 26–4).

TABLE 26–3 Relative size and susceptibility of different types of nerve fibers to local anesthetics.

Conduction
Fiber Type Function Diameter (lm) Myelination Velocity (m/s) Sensitivity to Block
Type A
Alpha Proprioception, motor 12–20 Heavy 70–120 +
Beta Touch, pressure 5–12 Heavy 30–70 ++
Gamma Muscle spindles 3–6 Heavy 15–30 ++
Delta Pain, temperature 2–5 Heavy 5–25 +++
Type B Preganglionic autonomic <3 Light 3–15 ++++
Type C
Dorsal root Pain 0.4–1.2 None 0.5–2.3 ++++
Sympathetic Postganglionic 0.3–1.3 None 0.7–2.3 ++++