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

levels. In different clinical situations, one or the other measure of
anesthesia duration may be more relevant, and this must be kept in
mind when deciding whether to add epinephrine to spinal local
anesthetics. The mechanism of action of vasoconstrictors in prolonging
spinal anesthesia is uncertain. It has been hypothesized that
these agents decrease spinal cord blood flow, decreasing clearance
of local anesthetic from the CSF, but this has not been convincingly
demonstrated. Epinephrine and other α-adrenergic agonists have
been shown to decrease nociceptive transmission in the spinal cord,
and studies in genetically modified mice suggest that α 2A
adrenergic
receptors play a principal role in this response (Stone et al., 1997).
Such actions may contribute to the beneficial effects of epinephrine,
clonidine, and dexmedetomidine when these agents are added
to spinal local anesthetics.
Drug Baricity and Patient Position. The baricity of the local anesthetic
injected will determine the direction of migration within the
dural sac. Hyperbaric solutions will tend to settle in the dependent
portions of the sac, while hypobaric solutions will tend to migrate in
the opposite direction. Isobaric solutions usually will stay in the
vicinity where they were injected, diffusing slowly in all directions.
Consideration of the patient position during and after the performance
of the block and the choice of a local anesthetic of the appropriate
baricity is crucial for a successful block during some surgical
procedures. Lidocaine and bupivacaine are marketed in both isobaric
and hyperbaric preparations, and if desired, can be diluted with sterile,
preservative-free water to make them hypobaric.
Complications of Spinal Anesthesia. Persistent neurological
deficits following spinal anesthesia are extremely rare. Thorough
evaluation of a suspected deficit should be performed in collaboration
with a neurologist. Neurological sequelae can be both immediate
and late. Possible causes include introduction of foreign
substances (such as disinfectants or talc) into the subarachnoid
space, infection, hematoma, or direct mechanical trauma. Aside
from drainage of an abscess or hematoma, treatment usually is
ineffective; thus, avoidance and careful attention to detail while
performing spinal anesthesia are necessary.
High concentrations of local anesthetic can cause irreversible
block. After administration, local anesthetic solutions are
diluted rapidly, quickly reaching nontoxic concentrations.
However, there are several reports of transient or longer-lasting
neurological deficits following lidocaine spinal anesthesia, particularly
with 5% lidocaine (i.e., 180 mmol) in 7.5% glucose (Zaric
and Pace, 2009). Spinal anesthesia sometimes is regarded as contraindicated
in patients with pre-existing disease of the spinal cord.
No experimental evidence exists to support this hypothesis.
Nonetheless, it is prudent to avoid spinal anesthesia in patients with
progressive diseases of the spinal cord. However, spinal anesthesia
may be very useful in patients with fixed, chronic spinal cord
injury.
A more common sequela following any lumbar puncture,
including spinal anesthesia, is a postural headache with classic
features. The incidence of headache decreases with increasing age of
the patient and decreasing needle diameter. Headache following lumbar
puncture must be thoroughly evaluated to exclude serious complications
such as meningitis. Treatment usually is conservative, with
bed rest and analgesics. If this approach fails, an epidural blood
patch with the injection of autologous blood can be performed; this
procedure usually is successful in alleviating postdural puncture
headaches, although a second blood patch may be necessary. If two
epidural blood patches are ineffective in relieving the headache, the
diagnosis of postdural puncture headache should be reconsidered.
Intravenous caffeine (500 mg as the benzoate salt administered over
4 hours) also has been advocated for the treatment of postdural puncture
headache; however, the efficacy of caffeine is less than that of
a blood patch, and relief usually is transient.
Evaluation of Spinal Anesthesia. Spinal anesthesia is a safe and
effective technique, especially during surgery involving the lower
abdomen, the lower extremities, and the perineum. It often is combined
with intravenous medication to provide sedation and amnesia.
The physiological perturbations associated with low spinal anesthesia
often have less potential harm than those associated with general
anesthesia. The same does not apply for high spinal anesthesia. The
sympathetic blockade that accompanies levels of spinal anesthesia
adequate for mid- or upper-abdominal surgery, coupled with the difficulty
in achieving visceral analgesia, is such that equally satisfactory
and safer operating conditions can be realized by combining the
spinal anesthetic with a “light” general anesthetic or by the administration
of a general anesthetic and a neuromuscular blocking agent.
Epidural Anesthesia
Epidural anesthesia is administered by injecting local anesthetic into
the epidural space—the space bounded by the ligamentum flavum
posteriorly, the spinal periosteum laterally, and the dura anteriorly.
Epidural anesthesia can be performed in the sacral hiatus (caudal
anesthesia) or in the lumbar, thoracic, or cervical regions of the
spine. Its current popularity arises from the development of catheters
that can be placed into the epidural space, allowing either continuous
infusions or repeated bolus administration of local anesthetics.
The primary site of action of epidurally administered local anesthetics
is on the spinal nerve roots. However, epidurally administered
local anesthetics also may act on the spinal cord and on the paravertebral
nerves.
The selection of drugs available for epidural anesthesia is
similar to that for major nerve blocks. As for spinal anesthesia, the
choice of drugs to be used during epidural anesthesia is dictated primarily
by the duration of anesthesia desired. However, when an
epidural catheter is placed, short-acting drugs can be administered
repeatedly, providing more control over the duration of block.
Bupivacaine, 0.5-0.75%, is used when a long duration of surgical
block is desired. Due to enhanced cardiotoxicity in pregnant
patients, the 0.75% solution is not approved for obstetrical use.
Lower concentrations—0.25%, 0.125%, or 0.0625%—of bupivacaine,
often with 2 μg/mL of fentanyl added, frequently are used to
provide analgesia during labor. They also are useful preparations for
providing postoperative analgesia in certain clinical situations.
Lidocaine 2% is the most frequently used intermediate-acting
epidural local anesthetic. Chloroprocaine, 2% or 3%, provides rapid
onset and a very short duration of anesthetic action. However, its use
in epidural anesthesia has been clouded by controversy regarding its
potential ability to cause neurological complications if the drug is
accidentally injected into the subarachnoid space (discussed earlier).
The duration of action of epidurally administered local anesthetics
frequently is prolonged, and systemic toxicity decreased, by addition
of epinephrine. Addition of epinephrine also makes inadvertent
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CHAPTER 20
LOCAL ANESTHETICS