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

578 successful application of spinal anesthesia. Although some of them
may be deleterious and require treatment, others can be beneficial for
the patient or can improve operating conditions. Most sympathetic
fibers leave the spinal cord between T1 and L2 (Chapter 8, Figure
8–1). Although local anesthetic is injected below these levels in the
lumbar portion of the dural sac, cephalad spread of the local anesthetic
occurs with all but the smallest volumes injected. This cephalad
spread is of considerable importance in the practice of spinal
anesthesia and potentially is under the control of numerous variables,
of which patient position and baricity (density of the drug relative to
the density of the CSF) are the most important (Greene, 1983). The
degree of sympathetic block is related to the height of sensory anesthesia;
often the level of sympathetic blockade is several spinal segments
higher, since the preganglionic sympathetic fibers are more
sensitive to low concentrations of local anesthetic. The effects of
sympathetic blockade involve both the actions (now partially unopposed)
of the parasympathetic nervous system and the response of
the unblocked portion of the sympathetic nervous system. Thus, as
the level of sympathetic block ascends, the actions of the parasympathetic
nervous system are increasingly dominant, and the compensatory
mechanisms of the unblocked sympathetic nervous system
are diminished. As most sympathetic nerve fibers leave the cord at
T1 or below, few additional effects of sympathetic blockade are seen
with cervical levels of spinal anesthesia. The consequences of sympathetic
blockade will vary among patients as a function of age,
physical conditioning, and disease state. Interestingly, sympathetic
blockade during spinal anesthesia appears to be minimal in healthy
children.
Clinically, the most important effects of sympathetic blockade
during spinal anesthesia are on the cardiovascular system. At
all but the lowest levels of spinal blockade, some vasodilation will
occur. Vasodilation is more marked on the venous than on the arterial
side of the circulation, resulting in blood pooling in the venous
capacitance vessels. This reduction in circulating blood volume is
well tolerated at low levels of spinal anesthesia in healthy patients.
With an increasing level of block, this effect becomes more
marked and venous return becomes gravity-dependent. If venous
return decreases too much, cardiac output and organ perfusion
decline precipitously. Venous return can be increased by a modest
(10-15 degree) head-down tilt or by elevating the legs. At high levels
of spinal blockade, the cardiac accelerator fibers, which exit
the spinal cord at T1-T4, will be blocked. This is detrimental in
patients dependent on elevated sympathetic tone to maintain cardiac
output (e.g., during congestive heart failure or hypovolemia),
and it also removes one of the compensatory mechanisms available
to maintain organ perfusion during vasodilation. Thus, as the
level of spinal block ascends, the rate of cardiovascular compromise
can accelerate if not carefully observed and treated. Sudden
asystole also can occur, presumably because of loss of sympathetic
innervation in the continued presence of parasympathetic activity
at the sinoatrial node (Caplan et al., 1988). In the usual clinical situation,
blood pressure serves as a surrogate marker for cardiac output
and organ perfusion. Treatment of hypotension usually is
warranted when the blood pressure decreases to ~30% of resting
values. Therapy is aimed at maintaining brain and cardiac perfusion
and oxygenation. To achieve these goals, administration of
oxygen, fluid infusion, manipulation of patient position, and the
administration of vasoactive drugs are all options. In practice,
SECTION II
NEUROPHARMACOLOGY
patients typically are administered a bolus (500-1000 mL) of fluid
prior to the administration of spinal anesthesia in an attempt to prevent
some of the deleterious effects of spinal blockade. Since the
usual cause of hypotension is decreased venous return, possibly
complicated by decreased heart rate, drugs with preferential venoconstrictive
and chronotropic properties are preferred. For this reason,
ephedrine, 5-10 mg intravenously, often is the drug of choice.
In addition to the use of ephedrine to treat deleterious effects of
sympathetic blockade, direct-acting α 1
adrenergic receptor agonists
such as phenylephrine (Chapter 12) can be administered either
by bolus or continuous infusion.
A beneficial effect of spinal anesthesia partially mediated by
the sympathetic nervous system is on the intestine. Sympathetic
fibers originating from T5-L1 inhibit peristalsis; thus, their blockade
produces a small, contracted intestine. This, together with a flaccid
abdominal musculature, produces excellent operating conditions
for some types of bowel surgery. The effects of spinal anesthesia on
the respiratory system mostly are mediated by effects on the skeletal
musculature. Paralysis of the intercostal muscles will reduce a
patient’s ability to cough and clear secretions, which may produce
dyspnea in patients with bronchitis or emphysema. Respiratory arrest
during spinal anesthesia is seldom due to paralysis of the phrenic
nerves or to toxic levels of local anesthetic in the CSF of the fourth
ventricle; it is much more likely to be due to medullary ischemia
secondary to hypotension.
Pharmacology of Spinal Anesthesia. Currently in the U.S., the
drugs most commonly used in spinal anesthesia are lidocaine, tetracaine,
and bupivacaine. Procaine occasionally is used for diagnostic
blocks when a short duration of action is desired. The choice of
local anesthetic is primarily determined by the desired duration of
anesthesia. General guidelines are to use lidocaine for short procedures,
bupivacaine for intermediate to long procedures, and tetracaine
for long procedures. As mentioned earlier, the factors
contributing to the distribution of local anesthetics in the CSF have
received much attention because of their importance in determining
the height of block. The most important pharmacological factors
include the amount, and possibly the volume, of drug injected and
its baricity. The speed of injection of the local anesthesia solution
also may affect the height of the block, just as the position of the
patient can influence the rate of distribution of the anesthetic agent
and the height of blockade achieved (described in the next section).
For a given preparation of local anesthetic, administration of
increasing amounts leads to a fairly predictable increase in the level
of block attained. For example, 100 mg of lidocaine, 20 mg of bupivacaine,
or 12 mg of tetracaine usually will result in a T4 sensory
block. More complete tables of these relationships can be found in
standard anesthesiology texts. Epinephrine often is added to spinal
anesthetics to increase the duration or intensity of block.
Epinephrine’s effect on duration of block is dependent on the technique
used to measure duration. A commonly used measure of block
duration is the length of time it takes for the block to recede by two
dermatomes from the maximum height of the block, while a second
is the duration of block at some specified level, typically L1. In
most studies, addition of 200 μg of epinephrine to tetracaine solutions
prolongs the duration of block by both measures. However,
addition of epinephrine to lidocaine or bupivacaine does not affect
the first measure of duration, but does prolong the block at lower