LOCAL ANESTHETICS Flashcards
1
Q
What was the first local anesthetic introduced into clinical practice? What was its
clinical use?
A
- The first local anesthetic introduced into clinical practice was cocaine. Cocaine’s
use has been limited by its systemic toxicity, its irritant properties when placed
topically or near nerves, and its substantial potential for physical and
psychological dependence. (130)
2
Q
- What is the basic structure of local anesthetics?
A
○ Local anesthetics consist of a lipophilic end and a hydrophilic end connected by
a hydrocarbon chain.
○ The lipophilic end is an aromatic ring, and the hydrophilic end is a tertiary amine and proton acceptor.
○ The bond that links the hydrocarbon
chain to the lipophilic end of the structure is either an ester (—CO—) or an amide
(—HNC—). The local anesthetic is thus classified as either an ester or an amide local
anesthetic. (131, Figure 11-2)
3
Q
- Why are local anesthetics marketed as hydrochloride salts?
A
- Local anesthetics are bases that are poorly water-soluble. For this reason they
are marketed as hydrochloride salts. The resulting solution is generally slightly
acidic with a pH of about 6
4
Q
- What are two differences between ester and amide local anesthetics that make
classifying local anesthetics important?
A
- The metabolism and possibly the potential to produce allergic reactions differ
between ester and amide local anesthetics, making this classification of local
anesthetics important.
5
Q
- Name four ester local anesthetics.
A
- The ester local anesthetics include procaine, chloroprocaine, cocaine, and
tetracaine
6
Q
- Name seven amide local anesthetics.
A
- The amide local anesthetics include lidocaine, mepivacaine, bupivacaine,
levobupivacaine, etidocaine, prilocaine, and ropivacaine.
7
Q
- What is an easy way to remember whether a local anesthetic is an ester or an amine?
A
- As a general rule, ester local anesthetics will have only one “i” in their generic name,
while the amides will have two.
8
Q
- What is the mechanism of action of local anesthetics?
A
- Local anesthetics act by producing a conduction blockade of neural impulses in the
affected nerve. This is accomplished through the prevention of the passage of
sodium ions through ion-selective sodium channels in the nerve membranes.
The inability of sodium ions to pass through their ion selective channels results
in slowing of the rate of depolarization. As a result, the threshold potential is not
reached and an action potential is not propagated.
9
Q
- Where is the major site of local anesthetic effect?
A
- Local anesthetics are thought to exert their predominant action on the nerve
by binding to a specific receptor on the sodium ion channel. The location of
the binding site appears to be within the inner vestibule of the sodium
channel
10
Q
- How is the effect of a local anesthetic on the nerve terminated?
A
- The conduction blockade produced by a local anesthetic is normally completely
reversible(i.e., reversal of the blockadeis spontaneous, predictable, and complete
11
Q
- How is the resting membrane potential and the threshold potential altered in nerves
that have been infiltrated by local anesthetic?
A
- Neither the resting membrane potential nor the threshold potential is appreciably
altered by local anesthetics.
12
Q
- What is the temporal progression of the interruption of the transmission of
neural impulses between the autonomic nervous system, motor system, and sensory
system after the infiltration of a mixed nerve with local anesthetic?
A
- The temporal progression of the interruption of the transmission of impulses is
autonomic, sensory, and then motor nerve blockade. This yields a temporal
progression of autonomic nervous system blockade, then sensory nervous system
blockade, followed by skeletal muscle paralysis. (1
13
Q
- What is frequency-dependent blockade? How does frequency-dependent blockade
relate to the activity of local anesthetics?
A
- According to the modulated receptor model, sodium ion channels alternate between
several conformational states, and local anesthetics bind to these different
conformational states with different affinities. During excitation, the sodium channel
moves from a resting-closed state to an activated-open state, with passage of sodium
ions and consequent depolarization. After depolarization, the channel assumes an
inactivated-closed conformational state. Local anesthetics bind to the activated and
inactivated states more readily than the resting state, attenuating conformational
change. Drug dissociation from the inactivated conformational state is slower than
from the resting state. Thus, repeated depolarization produces more effective
anesthetic binding. The electrophysiologic consequence of this effect is progressive
enhancement of conduction blockade with repetitive stimulation, an effect referred
to as use-dependent or frequency-dependent block. For this reason, selective
conduction blockade of nerve fibers by local anesthetics may in part be related to
the characteristic frequency of activity of the nerve.
14
Q
- What three characteristics are nerve fibers classified by? What are the three main
nerve fiber types?
A
- Fiber diameter, the presence or absence of myelin, and function are the three
characteristics by which nerve fibers are classified. A, B, and C are the three main
types of nerve fibers.
15
Q
- Which types of nerve fibers are myelinated? What is the function of myelin and how
does it affect the action of local anesthetics?
A
- The A and B nerve fiber types are myelinated. Myelin is composed of plasma
membranes of specialized Schwann cells that wrap around the axon during axonal
growth. Myelin functions to insulate the axolemma, or nerve cell membrane, from
the surrounding conducting media. It also forces the depolarizing current to
flow through periodic interruptions in the myelin sheath called the nodes of
Ranvier. The sodium channels that are instrumental in nerve pulse propagation
and conduction are concentrated at these nodes of Ranvier. Myelin increases the
speed of nerve conduction and makes the nerve membrane more susceptible to
local anesthetic-induced conduction blockade.
16
Q
- How many consecutive nodes of Ranvier must be blocked for the effective blockade
of the nerve impulse by local anesthetic?
A
- In general, three consecutive nodes of Ranvier must be exposed to adequate
concentrations of local anesthetic for the effective blockade of nerve impulses to
occur.
17
Q
- Which two nerve fiber types primarily function to conduct sharp and dull pain
impulses? Which of these two nerve fibers is more readily blocked by local
anesthetic?
A
- The nerve fiber type A-d, which is myelinated, conducts sharp or fast/first pain
impulses. The nerve fiber type C, which is unmyelinated, conducts dull burning pain
impulses. The large diameter type A-d fiber appears to be more sensitive to
blockade than the smaller diameter type C fiber. This lends support to the theory
that myelination of nerves has a greater influence than nerve fiber diameter on the
conduction blockade produced by local anesthetics. In clinical practice, however,
the relatively high concentrations of local anesthetic that are generally achieved
will overcome this difference
18
Q
- Which two nerve fiber types primarily function to conduct impulses that result in
large motor and small motor activity?
A
- The nerve fiber types A-a and A-b, which are both myelinated, conduct motor nerve
impulses. The nerve fiber type A-a conducts large motor nerve impulses, and
the nerve fiber type A-b conducts small motor nerve impulses.
19
Q
- What is meant by differential block? Name an anesthetic that has had limited use
because of its poor sensory selectivity.
A
- Differential block refers to the relative block of sensory versus motor function. For
equivalent analgesia or anesthesia, etidocaine tends to produce more profound
motor block than most commonly used local anesthetics, making it an unfavorable
choice, particularly for use in labor or postoperative pain management
20
Q
- How do local anesthetics diffuse through nerve fibers when deposited around a
nerve? Which nerve fibers are blocked first as a result?
A
- Local anesthetics diffuse along a concentration gradient from the outer surface,
or mantle, of the nerve toward the center, or core, of the nerve. As a result, the
nerve fibers located in the mantle of the nerve are blocked before those in
the core of the nerve.
21
Q
- How are the nerve fibers arranged from the mantle to the core in a peripheral nerve
with respect to the innervation of proximal and distal structures? How does this
correlate with the temporal progression of local anesthetic-induced blockade of
proximal and distal structures?
A
- In a peripheral nerve, the nerve fibers in the mantle generally innervate more
proximal anatomic structures. The distal anatomic structures are more frequently
innervated by nerve fibers near the core of the nerve. This physiologic
orientation of nerve fibers in a peripheral nerve explains the observed initial
proximal analgesia with subsequent progressive distal spread as local anesthetics
diffuse to reach more central core nerve fibers.
22
Q
- What very fundamental difference exists between the local anesthetics and most
systemically administered drugs?
A
- In contrast to most systemically administered drugs, the local anesthetics are
deposited at the target site, and systemic absorption and circulation serve to
attenuate or curtail their effect rather than distribute them to their site of action. (
23
Q
- Is the pKa of local anesthetics more than or less than 7.4?
A
- The pKa of most local anesthetics is greater than 7.4 (benzocaine is a notable
exception with a pKa of approximately 3.5). This means that the pH at which the
cationic form and nonionized form will be equivalent is greater than 7.4 for almost
all of the clinically used anesthetics.
24
Q
- At physiologic pH, does most local anesthetic exist in the ionized or nonionized
form? What form must the local anesthetic be in to cross nerve cell membranes?
A
- Most local anesthetic molecules exist in the ionized, hydrophilic form at physiologic
pH. However, local anesthetics must be in the nonionized, lipid-soluble form to
cross the lipophilic nerve cell membranes.
25
Q
- Does local tissue acidosis create an environment for higher or lower quality local
anesthesia? Why?
A
- Local tissue acidosis is associated with a lower quality anesthesia. This is presumed
to be due to an increase in the ionized fraction of the drug in an acidotic
environment, with less of the neutral form available to penetrate the cell membrane.
26
Q
- What is the primary determinant of local anesthetic potency?
A
- The primary determinant of the potency of a local anesthetic is its lipid
solubility.
27
Q
- After a local anesthetic has been absorbed from the tissues, what are the primary
determinants of local anesthetic peak plasma concentrations?
A
- The rate of systemic uptake and the rate of clearance of the drug are the two
primary determinants of peak plasma concentrations of a local anesthetic after
its absorption from tissue sites
28
Q
- How are ester local anesthetics cleared?
A
- Ester local anesthetics are cleared by hydrolysis by pseudocholinesterase enzymes
in the plasma. (
29
Q
- How are the amide local anesthetics metabolized?
A
- Amide local anesthetics undergo degradation in the liver by hepatic microsomal
enzymes.
30
Q
- How does the addition of epinephrine or phenylephrine to a local anesthetic
solution prepared for injection affect its potential for systemic toxicity?
A
- Less than 5% of the injected dose of local anesthetic undergoes renal excretion
unchanged. The low water solubility of local anesthetics limits their renal
excretion. (1
31
Q
- What are two organs that influence the potential for local anesthetic systemic toxicity?
A
- The lungs and the liver both influence the potential for local anesthetic
systemic toxicity. The extent to which the lungs extract local anesthetics from
the circulation—so-called first-pass pulmonary extraction—influences systemic
toxicity by preventing the rapid accumulation of local anesthetics in the plasma.
The liver also influences local anesthetic systemic toxicity, especially for the
amide local anesthetics that depend upon the liver for metabolism.
32
Q
- What accounts for chloroprocaine’s relatively low systemic toxicity?
A
- The relatively rapid hydrolysis by plasma cholinesterase makes chloroprocaine less
likely to produce sustained plasma concentrations. (
33
Q
- Patients with atypical plasma cholinesterase are at an increased risk for what
complication with regard to local anesthetics?
A
- Patients with atypical plasma cholinesterase enzyme may be at increased risk
for developing excessive plasma concentrations of ester local anesthetics. Ester
local anesthetics rely on plasma hydrolysis for their metabolism, which may
be limited or absent in these patients. (
34
Q
- What disease states may influence the rate of clearance of lidocaine from the plasma?
A
- Lidocaine, an amide local anesthetic, is cleared by hepatic metabolism. The
clearance of lidocaine from the plasma parallels hepatic blood flow. Liver disease
or decreases in hepatic blood flow as can occur with congestive heart failure or
general anesthesia can decrease the rate of metabolism of lidocaine.
35
Q
- How extensive is renal excretion of the parent local anesthetic compound?
A
- The low water solubility of the local anesthetics usually limits renal excretion of the
parent compound to less than 5% of the administered dose.
36
Q
- How does the addition of epinephrine or phenylephrine to a local anesthetic
solution prepared for injection affect its systemic absorption?
A
- The addition of epinephrine or phenylephrine to a local anesthetic solution produces
a local tissue vasoconstriction. This results in a slowing of the rate of systemic
absorption of the local anesthetic. (136. The addition of epinephrine or phenylephrine to a local anesthetic solution produces
a local tissue vasoconstriction. This results in a slowing of the rate of systemic
absorption of the local anesthetic. (1
37
Q
- How does the addition of epinephrine or phenylephrine to a local anesthetic
solution prepared for injection affect its duration of action?
A
- The addition of epinephrine or phenylephrine to a local anesthetic solution produces
local tissue vasoconstriction. This results in a prolonged duration of action of the
local anesthetic by keeping the anesthetic in contact with the nerve fibers for a
longer period of time
38
Q
- How does the addition of epinephrine or phenylephrine to a local anesthetic
solution prepared for injection affect its potential for systemic toxicity?
A
- The addition of epinephrine or phenylephrine to a local anesthetic solution causes
a slower rate of systemic absorption and a prolonged duration of action.
This increases the likelihood that the rate of metabolism will match the rate of
absorption, resulting in a decrease in the possibility of systemic toxicity.
Inclusion of epinephrine may also decrease the potential for toxicity by serving as
a marker for misplaced intravascular injection, whereby the elevation of heart
rate can serve as a warning of such misplacement, alerting the clinician
to halt injection and thus prevent the administration of additional
anesthetic
39
Q
- How does the addition of epinephrine or phenylephrine to a local anesthetic
solution prepared for injection affect the rate of onset of anesthesia?
A
- The addition of epinephrine or phenylephrine to a local anesthetic solution has little
effect on the rate of onset of anesthesia.
40
Q
- How does the addition of epinephrine or phenylephrine to a local anesthetic
solution prepared for injection affect local bleeding?
A
- The addition of epinephrine or phenylephrine to a local anesthetic solution
decreases bleeding in the area infiltrated due to its vasoconstrictive properties.
41
Q
- What are some potential negative effects of the addition of epinephrine to a local
anesthetic solution prepared for injection?
A
- The systemic absorption of epinephrine from the local anesthetic solution may
contribute to cardiac dysrhythmias or accentuate hypertension in vulnerable
patients. (136)
42
Q
- Name some situations in which the addition of epinephrine to a local anesthetic
solution prepared for injection may not be recommended.
A
- The addition of epinephrine to a local anesthetic solution may not be recommended
in patients with unstable angina, cardiac dysrhythmias, uncontrolled hypertension,
or uteroplacental insufficiency. The addition of epinephrine to a local anesthetic
solution is not recommended for intravenous anesthesia or for peripheral nerve
block anesthesia in areas that may lack collateral blood flow, such as the digits
(though the soundness of this latter proscription has been recently questioned).
43
Q
- What are some potential negative side effects associated with the administration of
local anesthetics?
A
- Potential negative side effects associated with the administration of local
anesthetics include systemic toxicity, neurotoxicity, and allergic reactions.
44
Q
- What is the most common cause of local anesthetic systemic toxicity?
A
- Local anesthetic systemic toxicity occurs as a result of excessive plasma
concentrations of a local anesthetic drug. The most common cause of local
anesthetic systemic toxicity is accidental intravascular injection of local
anesthetic solution during the performance of a nerve block.
45
Q
- What are the factors that influence the magnitude of the systemic absorption of
local anesthetic from the tissue injection site?
A
- The magnitude of the systemic absorption of local anesthetic from the tissue
injection site is influenced by the pharmacologic profile of the local anesthetic, the
total dose injected, the vascularity of the injection site, and the inclusion of a
vasoconstrictor in the local anesthetic solution
46
Q
- From highest to lowest, what is the relative order of peak plasma concentrations of
local anesthetic associated with the following regional anesthetic procedures:
brachial plexus, caudal, intercostal, epidural, sciatic/femoral?
A
- The relative order from highest to lowest of peak plasma concentrations of local
anesthetic associated with regional anesthesia is intercostal nerve block, caudal
block, epidural, brachial plexus, and sciatic/femoral.
47
Q
- Which two organ systems are most likely to be affected by excessive plasma
concentrations of local anesthetic?
A
- The central nervous system and cardiovascular system are most likely to be affected
by excessive plasma concentrations of local anesthetic.
48
Q
- What are the initial and subsequent manifestations of central nervous system
toxicity due to increasingly excessive plasma concentrations of local anesthetic?
A
- The initial manifestations of central nervous system toxicity due to excessive
plasma concentrations of local anesthetic include circumoral numbness, facial
tingling, restlessness, vertigo, tinnitus, and slurred speech. With progressively
increasing concentrations of local anesthetic in the plasma, symptoms may progress
to manifestations of central nervous system excitation, such as facial and extremity
muscular twitching and tremors. Finally, tonic-clonic seizures, apnea, and death
can follow. However, deviations from this classic progression are common
49
Q
- What is a possible pathophysiologic mechanism for seizures that result from
excessive plasma concentrations of local anesthetic?
A
- Local anesthetic drugs in excessive plasma concentrations sufficient to cause
seizures are believed to initially depress inhibitory pathways in the cerebral
cortex. This allows for the unopposed action of excitatory pathways in the central
nervous system, which manifests as seizures. As the concentration of local
anesthetic in the plasma increases, there is subsequent inhibition of both excitatory
and inhibitory pathways in the brain. Ultimately this leads to generalized global
central nervous system depression.
50
Q
- What are some potential adverse effects of local anesthetic-induced seizures?
A
- Potential adverse effects of local anesthetic-induced seizures are arterial
hypoxemia, metabolic acidosis, and pulmonary aspiration of gastric contents.
The mainstay of treatment of local anesthetic-induced seizures, as with all seizures,
is aimed toward supporting the patient while attempting to abort the seizure
with anticonvulsant drugs. Supplemental oxygen should be administered.
The patient’s airway may need to be secured with a cuffed endotracheal tube if there
is a need to facilitate adequate ventilation and delivery of oxygen to the lungs,
and to protect the airway from the aspiration of gastric contents.
51
Q
- How should local anesthetic-induced seizures be treated?
A
- Anticonvulsant drugs that can be used to stop local anesthetic-induced seizures
include diazepam and propofol. Diazepam is the preferred agent, though propofol
is generally more readily accessible for immediate administration. However,
propofol should be used cautiously in small doses as seizures may portend
cardiovascular toxicity that might be augmented by propofol’s cardiovascular
depression.
52
Q
- What is the indication for and disadvantage of the administration of neuromuscular
blocking drugs for the treatment of seizures?
A
- Anticonvulsant drugs that can be used to stop local anesthetic-induced seizures
include diazepam and propofol. Diazepam is the preferred agent, though propofol
is generally more readily accessible for immediate administration. However,
propofol should be used cautiously in small doses as seizures may portend
cardiovascular toxicity that might be augmented by propofol’s cardiovascular
depression.
53
Q
- Is the cardiovascular system more or less susceptible to local anesthetic toxicity
than the central nervous system?
A
- The cardiovascular system is generally less susceptible to local anesthetic toxicity
than the central nervous system. That is, the dose of local anesthetic required to
produce central nervous system toxicity is less than the dose of local anesthetic
required to result in cardiotoxicity.
54
Q
- What are two mechanisms by which local anesthetics produce hypotension?
A
- Two mechanisms by whichlocal anesthetics produce hypotensioninclude the relaxation
of peripheral vascular smooth muscle and direct myocardial depression.
55
Q
- What is the mechanism by which local anesthetics exert their cardiotoxic effects?
How is this manifested on the electrocardiogram?
A
- Local anesthetics exert their cardiotoxic effects primarily through the blockade of
sodium ion channels in the myocardium. This blockade results in an increase in the
conduction time throughout the heart, manifested as a prolongation of the P-R
interval and widening of the QRS complex. Local anesthetics also produce a dose-
dependent negative inotropic effect. Clinically, these may result in a decreased
cardiac output. With extremely elevated serum levels of local anesthetic,
bradycardia and sinus arrest can result.
56
Q
- How is the relative cardiotoxicity between local anesthetic agents compared?
What is the relative cardiotoxicity between lidocaine, bupivacaine, and
ropivacaine?
A
- The relative cardiotoxicity of local anesthetic agents is made through a comparison
of the dose (or serum concentration) required to produce cardiovascular collapse
relative to central nervous system toxicity. Through the evaluation of these ratios,
it has been determined that bupivacaine is roughly twice as cardiotoxic as
lidocaine and that levobupivacaine and ropivacaine are intermediate.
57
Q
- How does bupivacaine differ from lidocaine with respect to their cardiotoxic effects,
and what underlying electrophysiologic differences exist between lidocaine and
bupivacaine that might contribute to their differing clinical toxicities?
A
- The maximum recommended concentration of bupivacaine to be administered
for epidural anesthesia in obstetrics is 0.5%. This recommendation emerged as a
result of numerous fatal cardiotoxic reactions that occurred with the
administration of 0.75% bupivacaine in this patient population.
58
Q
- What is the maximum recommended concentration of bupivacaine to be
administered for obstetric epidural anesthesia? Why?
A
- The maximum recommended concentration of bupivacaine to be administered
for epidural anesthesia in obstetrics is 0.5%. This recommendation emerged as a
result of numerous fatal cardiotoxic reactions that occurred with the
administration of 0.75% bupivacaine in this patient population.
59
Q
- What relatively simple and apparently effective therapy for treatment of systemic
local anesthetic toxicity has been recently introduced into clinical practice?
What appears to be its predominant mechanism of action?
A
- Recently, a series of systematic experimentation and clinical events have identified a
practical and apparently effective therapy for systemic anesthetic toxicity. Following
experiments in rats and dogs, which demonstrated that administration of a lipid
emulsion could attenuate bupivacaine cardiotoxicity, numerous clinical cases
were reported in which intravenous lipid appears to have been effective in reversing local anesthetic systemic toxicity. The mechanism by which lipid is effective is
incompletely understood, but its predominant action is most likely related to its
ability to extract bupivacaine (or other lipophilic drugs) from aqueous plasma or
tissue targets, thus reducing their effective concentration (“lipid sink”).
60
Q
- The administration of which local anesthetics have been associated with
methemoglobinemia? What is the mechanism by which this occurs? How can it be
treated?
A
- The administration of prilocaine has been associated with methemoglobinemia in a
dose-dependent manner, with significant toxicity generally occurring with doses
exceeding 600 mg. Methemoglobinemia results from the accumulation of ortho-
toluidine, a metabolite of prilocaine. Ortho-toluidine is an oxidizing compound
that oxidizes hemoglobin to methemoglobin, creating methemoglobinemia.
Methemoglobinemia that occurs through the administration of prilocaine is
spontaneously reversible. Alternatively, methylene blue may be administered
intravenously to treat this condition. Methemoglobinemia can also be a
significant clinical problem with benzocaine topically administered on mucosal
surfaces
61
Q
- What is the nature of the neurotoxicity that has been reported in association with
the use of chloroprocaine? What is the mechanism by which this occurs?
A
- The administration of chloroprocaine has been associated with prolonged motor
and sensory deficits when administered at recommended doses for epidural
anesthesia that appeared to have been inadvertently administered into the
subarachnoid space. Early studies suggested that this effect might have
occurred due to a combination of the low pH of the anesthetic solution (pH
approximately 3.0)and the antioxidant sodium bisulfite, which resulted in the
liberation of sulfur dioxide. However, this mechanism has been challenged by more
recent studies, which implicate the high doses of chloroprocaine, per se.
62
Q
- What is TNS?
A
- Transient neurologic symptoms (TNS) is a syndrome of pain/dysesthesia in the
lower back, posterior thighs, or buttocks that generally occurs within 24 hours of
recovery from a spinal anesthetic. Full recovery from the symptoms most often
occurs within 3 days. Importantly, TNS is not associated with sensory loss, motor
weakness, or bowel or bladder dysfunction. Risk factors for TNS following spinal
anesthesia include the use of lidocaine, lithotomy position during surgery, and
outpatient status. Indeed, when these three risk factors are combined, the incidence
rate has been found to be 24%. Similar to lithotomy, positioning for knee
arthroscopy appears to dramatically increase risk.
63
Q
- What is the mechanism by which local anesthetics have resulted in cauda
equina syndrome?
A
- Cauda equina syndrome represents the clinical manifestation of injury to the nerve
roots caudal to the conus. Symptoms may include perineal sensory loss, bowel and
bladder dysfunction, and lower extremity motor weakness. In the past, a cluster
of cases was reported in association with the use of lidocaine administered through
microbore spinal catheters (also referred to as small-bore and defined as smaller
than 27 gauge). It is believed that pooling of local anesthetic in the most
dependent portion of the subarachnoid space led to high concentrations of local
anesthetic around the nerve roots of the cauda equina and subsequent irreversible
neurotoxicity. Small-bore catheters for continuous spinal anesthesia are no longer
marketed in the United States. However, risk remains because similar neurotoxic
injury can occur with repetitive doses of any local anesthetic even if administered
through a large-bore (e.g., epidural) catheter. In fact, this mechanism of neurotoxic
injury has also been reported with repeat needle injection after a failed
single-injection spinal anesthesia.
64
Q
- What changes have been recommended with respect to the dose of lidocaine
used for spinal anesthesia?
A
- Recent experience suggests that lidocaine has greater potential for direct
neurotoxicity than traditionally appreciated. In addition to the aforementioned
cases of cauda equina syndrome with small-bore catheters, lidocaine appears to be
capable of inducing injury when administered at the high end of the manufacturer’s
specified dose range for spinal anesthesia (100 mg). Accordingly, it has been
suggested that if this drug is used for spinal anesthesia, the dose should be limited to
75 mg, and the concentration of the anesthetic solution should not exceed 2.5%.
However, lidocaine with epinephrine remains an appropriate and popular choice for
epidural anesthesia and peripheral blocks. (
65
Q
- What changes in practice have occurred with respect to the relative use of
lidocaine for spinal anesthesia?
A
- The occurrence of major (cauda equina syndrome) and minor (TNS) sequelae
occuring with lidocaine has resulted in near abandonment of this agent
for spinal anesthesia.
66
Q
- What is the allergenic potential of local anesthetics? What are the potential
causes of an allergic reaction associated with administration of local
anesthetics?
A
- Less than 1% of all adverse reactions to local anesthetics are believed to be true
allergic reactions. When an allergic reaction to a local anesthetic is suspected to
have occurred, full documentation should be made in the chart regarding the dose
and route of local anesthetic administered and the reaction that occurred. There are
three potential causes of an allergic reaction to administered local anesthetic. In
addition to the anesthetic itself, a reaction might result from exposure to one of its
metabolites. For example, it has been traditionally taught that ester local anesthetics
have a proclivity to induce allergic reactions due to one of its breakdown products,
para-aminobenzoic acid, making esters more likely than amides to cause allergic
reactions, though some have questioned the validity of this assertion. Allergic
reactions may also occur to another component of the anesthetic solution (e.g., the
preservative methylparaben, used in some commercial preparations of both amides
and esters, appears to have significant antigenic potential).
67
Q
- Does cross-sensitivity exist between the classes of local anesthetics?
A
- Cross-sensitivity has not been found to exist between the classes of local
anesthetics. A patient found to be allergic to ester local anesthetics would not be
expected to be allergic to amide local anesthetics.
68
Q
- What is the principal use of tetracaine in current clinical practice?
A
- Tetracaine is primarily used as a spinal anesthetic in current clinical practice,
where its long duration of action, particularly if used with a vasoconstrictor, can at
times be a useful attribute.
69
Q
- What other local anesthetics might be used in place of lidocaine for short-duration
or outpatient surgery?
A
- Of the available local anesthetics, two have received considerable attention as
alternatives to lidocaine for short-duration spinal anesthesia: prilocaine and
chloroprocaine. However, while prilocaine has an acceptable profile for short-
duration anesthesia, it is not available in the United States in a formulation that
would be appropriate to administer intrathecally. Consequently, chloroprocaine
appears to be the favored contender for lidocaine’s replacement. The rationale for
using chloroprocaine for deliberate intrathecal administration largely rests on the
relative dose (i.e., the dose required for spinal anesthesia is an order of magnitude
less than those previously associated with injuries occuring with inadvertent
intrathecal injection of anesthetic intended for the epidural space). Chloroprocaine
rarely, if ever, results in TNS, and it has a duration of action as a spinal anesthetic
that is even shorter than lidocaine, making it extremely well suited for short-
duration outpatient spinal anesthesia. Although the issue of bisulfite toxicity has
not been adequately resolved, chloroprocaine administered intrathecally should be
bisulfite-free, and the dose should not exceed 60 mg.
70
Q
- What is an enantiomer?
A
- Isomers are different compounds that have the same molecular formula. Subsets of
isomers that have atoms connected by the same sequence of bonds but that have
different spatial orientations are called stereoisomers. Enantiomers are a particular
class of stereoisomers that exist as mirror images. The term chiral is derived from the
Greek cheir for “hand,” because the forms can be considered nonsuperimposable
mirror images. Enantiomers have identical physical properties except for the
direction of the rotation of the plane of polarized light. This property is used to
classify the enantiomer as dextrorotatory (þ) if the rotation is to the right or
clockwise and as levorotatory (–) if it is to the left or counterclockwise. A racemic
mixture is a mixture of equal parts of enantiomers and is optically inactive because
the rotation caused by the molecules of one isomer is cancelled by the opposite
rotation of its enantiomer. Chiral compounds can also be classified on the basis of
absolute configuration, generally designated as R (rectus) or S (sinister).
Enantiomers may differ with respect to specific biologic activity.
71
Q
- What two marketed local anesthetics are chiral compounds?
A
- Ropivacaine and levobupivacaine differ from other local anesthetics because
they are chiral compounds rather than racemic mixtures. Both are S() enantiomers,and were marketed in response to the cardiotoxic effects of bupivacaine because they
appear to cause modestly less myocardial depression and are modestly
less arrhythmogenic than bupivacaine
72
Q
- What is eutectic mixture of local anesthetics (EMLA)?
A
- EMLA is a topical anesthetic cream that consists of lidocaine 2.5% and 2.5%
prilocaine. This mixture has a lower melting point than either component, and it
exists as an oil at room temperature that is capable of overcoming the barrier of the
skin. EMLA cream is particularly useful in children for relieving pain associated
with venipuncture or placement of an intravenous catheter, although it may take up
to an hour before adequate topical anesthesia is produced.
