++
The choice of local anesthetic is based on potency of the agent, onset
and duration of anesthesia, and side effects of the drug. Two distinct
groups of local anesthetics are used in spinal anesthesia, esters and
amides, which are characterized by the bond that connects the aromatic
portion and the intermediate chain. Esters contain an ester link between the
aromatic portion and the intermediate chain, and examples include procaine,
chloroprocaine, and tetracaine. Amides contain an amide link between the
aromatic portion and the intermediate chain, and examples include
bupivacaine, ropivacaine, etidocaine, lidocaine, mepivacaine, and
prilocaine. Although metabolism is important for determining activity of
local anesthetics, lipid solubility, protein binding, and
pKa also influence activity.39
++
Lipid solubility relates to the potency of local anesthetics. Low lipid
solubility indicates that higher concentrations of local anesthesia must be
given to obtain nerve blockade. Conversely, high lipid solubility produces anesthesia at
low concentrations. Protein binding affects the duration of action of a
local anesthetic. Higher protein binding results in longer duration of
action. The pKa of a local anesthetic is the pH at which
ionized and nonionized forms are present equally in solution, which is
important because the nonionized form allows the local anesthetic to diffuse
across the lipophilic nerve sheath and reach the sodium channels in the
nerve membrane. The onset of action relates to the amount of local
anesthetic available in the base form. Most local anesthetics follow the
rule that the lower the pKa, the faster the onset of
action and vice versa. Please refer to Chapter 6 (Clinical Pharmacology of
Local Anesthetics) for more discussion of this topic.
+++
Pharmacokinetics of Local Anesthetics in the Subarachnoid Space
++
Pharmacokinetics of local anesthetics includes uptake and elimination
of the drug. Four factors play a role in the uptake of local anesthetics
from the subarachnoid space into neuronal tissue, (1) concentration of local
anesthetic in CSF, (2) surface area of nerve tissue exposed to CSF,
(3) lipid content of nerve tissue, and (4) blood flow to nerve
tissue.40,41
++
The uptake of local anesthetic is greatest at the site of highest
concentration in the CSF and is decreased above and below this site. As
discussed previously, uptake and spread of local anesthetics after spinal
injection are determined by multiple factors including dose, volume, and
baricity of local anesthetic and patient positioning.
++
Both the nerve roots and the spinal cord take up local anesthetics after
injection into the subarachnoid space. The more surface area of the nerve
root exposed, the greater the uptake of local anesthetic.42–45
The spinal cord has two mechanisms for uptake of local
anesthetics. The first mechanism is by diffusion from the CSF to the pia
mater and into the spinal cord, which is a slow process. Only the most
superficial portion of the spinal cord is affected by diffusion of local
anesthetics. The second method of local anesthetic uptake is by extension
into the spaces of Virchow–Robin, which are the areas of pia mater that
surround the blood vessels that penetrate the central nervous system. The
spaces of Virchow–Robin connect with the perineuronal clefts that surround
nerve cell bodies in the spinal cord and penetrate through to the deeper
areas of the spinal cord. Figure 13–6 is a representation of the
periarterial Virchow–Robin spaces around the spinal cord.
++
++
++
Lipid content determines uptake of local anesthetics. Heavily myelinated
tissues in the subarachnoid space contain higher concentrations of local
anesthetics after injection. The higher the degree of myelination, the
higher the concentration of local anesthetic, as there is a high lipid
content in myelin. If an area of nerve root does not contain myelin, an
increased risk of nerve damage occurs in that area.46
++
Blood flow determines the rate of removal of local anesthetics from spinal
cord tissue. The faster the blood flow in the spinal cord, the more rapid
the anesthetic is washed away. This may partly explain why the concentration
of local anesthetics is greater in the posterior spinal cord than in the
anterior spinal cord, even though the anterior cord is more readily accessed
by the Virchow–Robin spaces. After a spinal anesthetic is administered,
blood flow may be increased or decreased to the spinal cord, depending on
the particular local anesthetic administered, eg, tetracaine increases cord
flow but lidocaine and bupivacaine decrease it, which affects elimination of
the local anesthetic.47–49
++
Elimination of local anesthetic from the subarachnoid space is by vascular
absorption in the epidural space and the subarachnoid space. Local
anesthetics travel across the dura in both directions. In the epidural
space, vascular absorption can occur, just as in the subarachnoid space.
Vascular supply to the spinal cord consists of vessels located on the spinal
cord and in the pia mater. Because vascular perfusion to the spinal cord
varies , the rate of elimination of local anesthetics
varies.40
++
The distribution and decrease in concentration of local anesthetics is
based on the area of highest concentration, which can be independent of the
injection site. Many factors affect the distribution of local anesthetics in
the subarachnoid space. Table 13–2 lists some of these
factors.50
++
++
The three most important factors for determining spread of local
anesthesia in the subarachnoid space are baricity of the local anesthetic
solution, position of the patient during and just after injection, and dose
of the anesthetic injected.
++
Baricity plays an important role in determining the spread of local
anesthetic in the spinal space and is equal to the density of the local
anesthetic divided by the density of the CSF at 37°C.51–58
Local anesthetics can be hyperbaric, hypobaric, or isobaric when
compared to CSF, and baricity is the main determinant of how the local
anesthetic is distributed when injected into the CSF. Table 13–3
compares the density, specific gravity, and baricity of different substances
and local anesthetics.50,51,53,59,60
++
++
Hypobaric solutions are less dense than CSF and tend to rise against
gravity. Isobaric solutions are as dense as CSF and tend to remain at the
level at which they are injected. Hyperbaric solutions are more dense than
CSF and tend to follow gravity after injection.
++
Hypobaric solutions have a baricity of less than 1.0 relative to CSF and are
usually made by adding distilled sterile water to the local anesthetic.
Tetracaine, dibucaine, and bupivacaine have all been used as hypobaric
solutions in spinal anesthesia. Patient positioning is important after
injection of a hypobaric spinal anesthetic because it is the first few
minutes that determine the spread of anesthesia. If the patient is in
Trendelenburg position after injection, the anesthetic will spread in the
caudal direction and if the patient is in reverse Trendelenburg position,
the anesthetic will spread cephalad after injection. If a procedure were to
be performed in the perineal or anal area in the prone, jackknife position,
a hypobaric spinal anesthetic would be an excellent choice to avoid
the need for waiting for the anesthetic to “set in” and
repositioning the patient after injection.
++
++
The baricity of isobaric solutions is equal to 1.0. Tetracaine and
bupivacaine have both been used with success for isobaric spinal anesthesia,
and patient positioning does not affect spread of the local anesthetic,
unlike the case with hyperbaric or hypobaric solutions. Injection can be
made in any position, and then the patient can be placed into the position
necessary for surgery. Gravity dose not play a role in the spread of
isobaric solutions, unlike with hypo- or hyperbaric local anesthetics.
++
Hyperbaric solutions in spinal anesthesia have baricity greater than 1.0. A
local anesthetic solution can be made hyperbaric by adding dextrose or
glucose. Bupivacaine, lidocaine and tetracaine have all been used as
hyperbaric solutions in spinal anesthesia. Patient positioning affects the
spread of the anesthetic. A patient in Trendelenburg position would have the
anesthetic travel in a cephalad direction and vice versa.
++
Dose and volume both play a role in the spread of local anesthetics after
spinal injection, although dose has been shown to be more important than
volume.61 Concentration of local anesthetic before
injection has no bearing on distribution because after injection, due to the
mixing of the CSF and local anesthetic, there is a new concentration.
+++
Effects of the Volume of the Lumbar Cistern on Block Height
++
CSF is produced in the brain at 0.35 mL/min and fills the subarachnoid
space. This clear, colorless fluid has an approximate volume of
150 mL in adults, half of which is in the cranium and half in the spinal canal. However,
CSF volume varies considerably, and decreased CSF volume can result from
obesity, pregnancy, or any other cause of increased abdominal
pressure.62 This is partly due to compression of the
intervertebral foramen, which displaces the CSF.
++
++
Multiple factors affect the distribution of local anesthesia after
spinal blockade,50 one being CSF volume. Carpenter showed
that lumbosacral CSF volume correlated with peak sensory block height and
duration of surgical anesthesia.63
The density of CSF is related to peak sensory block level, and lumbosacral CSF volume
correlates to peak sensory block level, and onset and duration of motor
block.64 However, due to the wide variability in CSF
volume the ability to predict the level of the spinal blockade after local
anesthetic injection is very poor, even if body mass index (BMI) is
calculated and used.
++
Cocaine was the first spinal anesthetic used, and procaine and
tetracaine soon followed. Spinal anesthesia with lidocaine,
bupivacaine, tetracaine, mepivacaine, and ropivacaine have
also been introduced in clinical use over the last several decades.
Some of the more common local anesthetics used for spinal anesthesia will be
discussed in this portion of the chapter. In addition, there is a growing interest in medications that produce
anesthesia and analgesia while limiting side effects. A variety of
medications, including vasoconstrictors, opioids,
α2-adrenergic agonists, and acetylcholinesterase
inhibitors, have been added to spinal medications to enhance analgesia
while reducing the motor blocade with local anesthetics.
++
Lidocaine was first used as a spinal anesthetic in 1945, and it had been
one of the most widely used spinal anesthetics since. Onset of anesthesia
occurs in 3 to 5 min with a duration of anesthesia that lasts for 1 to 1.5
h. Lidocaine spinal anesthesia can be used for short to intermediate
length operating room cases. One drawback of lidocaine has been the association with
transient neurologic symptoms (TNS), which present as low back pain and
lower extremity dysesthesias with radiation to the buttocks, thighs, and
lower limbs after recovery from spinal anesthesia. TNS occurs in about
14% of patients receiving lidocaine spinal anesthesia.65–67
Because of the risk of TNS associated with lidocaine, other
intermediate-acting local anesthetics with lower risk of TNS are being used instead of lidocaine in many practices.
++
++
Bupivacaine is a viable alternative to lidocaine for spinal anesthesia
and has been used frequently with very little incidence of TNS.68–70
Onset of anesthesia occurs in 5 to 8 min with a duration of
anesthesia that lasts from 90 to 150 min; thus it is appropriate for
intermediate to long operating room cases. For outpatient spinal anesthesia,
small doses of bupivacaine are recommended to avoid prolonged discharge time
due to offset of block. Bupivacaine has almost replaced lidocaine as the most
commonly used spinal local anesthetic in the United States. Bupivacaine is
often packaged as 0.75% in 8.25% dextrose. Other forms of spinal
bupivacaine include 0.5% with or without dextrose and 0.75% without
dextrose.
++
Tetracaine has an onset of anesthesia within 3 to 5 min and a duration of
70 to 180 min, and like bupivacaine, is used for cases that are
intermediate to longer duration. The 1% solution is often mixed
with 10% glucose in equal parts to form a hyperbaric spinal anesthetic
that is used for perineal and abdominal surgery. With tetracaine, TNS occurs
at a lower rate than with lidocaine spinal anesthesia. The addition of
phenylephrine however, may play a role in the development of TNS.71–73
++
Mepivacaine is similar to lidocaine and has been used since the 1960s
for spinal anesthesia. The incidence of TNS reported after mepivacaine
spinal anesthesia varies widely, with rates from 0% to 30%.74–76 Ropivacaine was introduced in 1996. For applications in spinal
anesthesia, ropivacaine has been found to be less potent than spinal
bupivacaine. Ropivacaine has significantly less risk of TNS than spinal
lidocaine. Studies comparing ropivacaine to bupivacaine in spinal anesthesia
are in progress.77–79
++
Table 13–4 shows some of the local anesthetics used for spinal
anesthesia and dosage duration, and concentration for different levels of
spinal blockade.79–88
++
+++
Additives to Local Anesthesia
++
Vasoconstrictors are often added to local anesthetics, and both
epinephrine and phenylephrine have been studied. Anesthesia is intensified
and prolonged with smaller doses of local anesthetics when epinephrine or
phenylephrine is added. Tissue vasoconstriction is produced, thus limiting
the systemic reabsorption of the local anesthetic and prolonging the
duration of action by keeping the local anesthetic in contact with the nerve
fibers. However, ischemic complications can occur after the use of vasoconstrictors
in spinal anesthesia. In some studies, epinephrine was implicated as the
cause of cauda equina syndrome because of anterior spinal artery ischemia.
Regardless, most studies did not demonstrate an association between the use of
vasoconstrictors for spinal anesthesia and the incidence of cauda
equina.89,90 Phenylephrine has been shown to increase the risk of TNS.73,91
++
Epinephrine is thought to work by decreasing local anesthetic uptake
and thus prolonging the spinal blockade of local anesthetics. However,
vasoconstrictors can cause ischemia, and there is a theoretical concern of spinal cord
ischemia when epinephrine is added to spinal anesthetics. Animal models have
not shown any decrease in spinal cord blood flow or increase in spinal cord
ischemia when epinephrine is given for spinal blockade, even though some
neurologic complications associated with the addition of epinephrine
exist.47,49,92,93
++
++
Epinephrine comes packaged as 1 mg in 1 mL, which is a 1:1000 solution.
The dosage of epinephrine added to local anesthetics is 0.1 to 0.5 mg,
meaning 0.1 mL to 0.5 mL is added to the local anesthetic solution. Adding
0.1 mL of epinephrine to 10 mL of local anesthetic yields a 1:100,000
concentration of epinephrine. Adding 0.1 mL of epinephrine to 20 mL of local
anesthetic yields a 1:200,000 concentration, and so on (0.1 mL in 30 mL =
1:300,000). Calculation of epinephrine concentration does not need to be
complex if this simple formula is remembered.
++
Epinephrine prolongs the duration of spinal anesthesia.94–96
In the past, it was thought that epinephrine had no effect on
hyperbaric spinal bupivacaine using two-segment regression to test neural
blockade.97 However, a recent study showed that
epinephrine prolongs the duration of hyperbaric spinal bupivacaine when
pinprick, transcutaneous electrical nerve stimulation (TENS) equivalent to
surgical stimulation (at umbilicus, pubis, knee, and ankle), and tolerance
of a pneumatic thigh tourniquet were used to determine neural
blockade.98 Currently there is controversy regarding
prolongation of spinal bupivacaine neural blockade when epinephrine is
added.99–102 The same controversy exists about the
prolongation of spinal lidocaine with epinephrine.103–107
All three types of opioid receptors are found in the dorsal horn of the
spinal cord and serve as the target for intrathecal opioid injection.
Receptors are located on spinal cord neurons and terminals of afferents
originating in the dorsal root ganglion. Fentanyl, sufentanil, meperidine,
and morphine have all been used intrathecally. Side effects that may be seen
include pruritus, nausea and vomiting, and respiratory
depression.108–112
++
Alpha2-adrenergic agonists can be added to spinal
injections of local anesthetics in order to enhance pain relief and prolong
sensory block and motor block. Enhanced postoperative analgesia has been
demonstrated in cesarean deliveries, fixation of femoral fractures, and knee
arthroscopies when clonidine was added to the local anesthetic solution.
Clonidine prolongs the sensory and motor blockade of a local anesthetic
after spinal injection.113–115 Sensory blockade is
thought to be mediated by both presynaptic and postsynaptic mechanisms.
Clonidine induces hyperpolarization at the ventral horn of the spinal cord
and facilitates the action of the local anesthetic, thus prolonging motor
blockade when used as an additive. However, when used alone in intrathecal
injections, clonidine does not cause motor block or
weakness.116 Side effects can occur with the use of spinal
clonidine, and include hypotension, bradycardia, and sedation. Currently,
neuraxial clonidine is approved by the Food and Drug Administration (FDA)
for intractable neuropathic pain.117,118
++
Acetylcholinesterase inhibitors prevent the breakdown of acetylcholine and
produce analgesia when injected intrathecally. The antinociceptive effects
are due to increased acetylcholine and generation of nitric oxide. It has
been shown in a rat model that diabetic neuropathy can be alleviated after
intrathecal neostigmine injection.119 Side effects of
intrathecal neostigmine include nausea and vomiting, bradycardia requiring
atropine, anxiety, agitation, restlessness, and lower extremity
weakness.120–122 Although spinal neostigmine provides
extended pain control, the side effects that occur do not allow its
widespread use.