DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

• those with a long (400-450 minutes) duration of action, such as
bupivacaine, ropivacaine, and tetracaine
Block duration of the intermediate-acting local anesthetics
such as lidocaine can be prolonged by the addition of epinephrine
(5 μg/mL). The degree of block prolongation in peripheral nerves
following the addition of epinephrine appears to be related to the
intrinsic vasodilatory properties of the local anesthetic and thus is
most pronounced with lidocaine.
The types of nerve fibers that are blocked when a local anesthetic
is injected about a mixed peripheral nerve depend on the concentration
of drug used, nerve-fiber size, internodal distance, and
frequency and pattern of nerve-impulse transmission (see above, sections
on Frequency and Voltage-Dependence and Differential
Sensitivity). Anatomical factors are similarly important. A mixed
peripheral nerve or nerve trunk consists of individual nerves surrounded
by an investing epineurium. The vascular supply usually is
centrally located. When a local anesthetic is deposited about a peripheral
nerve, it diffuses from the outer surface toward the core along a
concentration gradient (DeJong, 1994; Winnie et al., 1977).
Consequently, nerves in the outer mantle of the mixed nerve are
blocked first. These fibers usually are distributed to more proximal
anatomical structures than are those situated near the core of the
mixed nerve and often are motor. If the volume and concentration of
local anesthetic solution deposited about the nerve are adequate, the
local anesthetic eventually will diffuse inward in amounts adequate
to block even the most centrally located fibers. Lesser amounts of
drug will block only nerves in the mantle and the smaller and more
sensitive central fibers. Furthermore, since removal of local anesthetics
occurs primarily in the core of a mixed nerve or nerve trunk, where
the vascular supply is located, the duration of blockade of centrally
located nerves is shorter than that of more peripherally situated fibers.
The choice of local anesthetic and the amount and concentration
administered are determined by the nerves and the types of
fibers to be blocked, the required duration of anesthesia, and the size
and health of the patient. For blocks of 2-4 hours, lidocaine (1-1.5%)
can be used in the amounts recommended earlier (see “Infiltration
Anesthesia”). Mepivacaine (up to 7 mg/kg of a 1-2% solution) provides
anesthesia that lasts about as long as that from lidocaine.
Bupivacaine (2-3 mg/kg of a 0.25-0.375% solution) can be used
when a longer duration of action is required. Addition of 5 μg/mL
epinephrine slows systemic absorption and therefore prolongs duration
and lowers the plasma concentration of the intermediate-acting
local anesthetics.
Peak plasma concentrations of local anesthetics depend on
the amount injected, the physical characteristics of the local anesthetic,
whether epinephrine is used, the rate of blood flow to the site
of injection, and the surface area exposed to local anesthetic. This is
of particular importance in the safe application of nerve block anesthesia,
since the potential for systemic reactions is related to peak
free serum concentrations. For example, peak concentrations of lidocaine
in blood following injection of 400 mg without epinephrine
for intercostal nerve blocks average 7 μg/mL; the same amount of
lidocaine used for block of the brachial plexus results in peak concentrations
in blood of ~3 μg/mL (Covino and Vassallo, 1976).
Therefore, the amount of local anesthetic that can be injected must
be adjusted according to the anatomical site of the nerve(s) to be
blocked to minimize untoward effects. Addition of epinephrine can
decrease peak plasma concentrations by 20-30%. Multiple nerve
blocks (e.g., intercostal block) or blocks performed in vascular
regions require reduction in the amount of anesthetic that can be
given safely, because the surface area for absorption or the rate of
absorption is increased.
Intravenous Regional Anesthesia (Bier’s Block)
This technique relies on using the vasculature to bring the local
anesthetic solution to the nerve trunks and endings. In this technique,
an extremity is exsanguinated with an Esmarch (elastic)
bandage, and a proximally located tourniquet is inflated to 100-
150 mm Hg above the systolic blood pressure. The Esmarch bandage
is removed, and the local anesthetic is injected into a
previously cannulated vein. Typically, complete anesthesia of the
limb ensues within 5-10 minutes. Pain from the tourniquet and
the potential for ischemic nerve injury limits tourniquet inflation to
2 hours or less. However, the tourniquet should remain inflated for
at least 15-30 minutes to prevent toxic amounts of local anesthetic
from entering the circulation following deflation. Lidocaine, 40-
50 mL (0.5 mL/kg in children) of a 0.5% solution without epinephrine
is the drug of choice for this technique. For intravenous
regional anesthesia in adults using a 0.5% solution without epinephrine,
the dose administered should not exceed 4 mg/kg. A few
clinicians prefer prilocaine (0.5%) over lidocaine because of its
higher therapeutic index. The attractiveness of this technique lies
in its simplicity. Its primary disadvantages are that it can be used
only for a few anatomical regions, sensation (pain) returns quickly
after tourniquet deflation, and premature release or failure of the
tourniquet can produce toxic levels of local anesthetic (e.g., 50 mL
of 0.5% lidocaine contains 250 mg of lidocaine). For the last reason
and because its longer durations of action offer no advantage,
the more cardiotoxic local anesthetic, bupivacaine, is not recommended
for this technique. Intravenous regional anesthesia is used
most often for surgery of the forearm and hand, but can be adapted
for the foot and distal leg.
Spinal Anesthesia
Spinal anesthesia follows the injection of local anesthetic into the
cerebrospinal fluid (CSF) in the lumbar space. For a number of reasons,
including the ability to produce anesthesia of a considerable
fraction of the body with a dose of local anesthetic that produces
negligible plasma levels, spinal anesthesia remains one of the most
popular forms of anesthesia. In most adults, the spinal cord terminates
above the second lumbar vertebra; between that point and the
termination of the thecal sac in the sacrum, the lumbar and sacral
roots are bathed in CSF. Thus, in this region there is a relatively large
volume of CSF within which to inject drug, thereby minimizing the
potential for direct nerve trauma.
A brief discussion of the physiological effects of spinal anesthesia
relating to the pharmacology of the local anesthetics used is
presented here. See more specialized texts (e.g., Cousins et al., 2008)
for additional details.
Physiological Effects of Spinal Anesthesia. Most of the physiological
side effects of spinal anesthesia are a consequence of the sympathetic
blockade produced by local anesthetic block of the
sympathetic fibers in the spinal nerve roots. A thorough understanding
of these physiological effects is necessary for the safe and
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CHAPTER 20
LOCAL ANESTHETICS