Local Anesthetics (also see Chapter
14
)
Bupivacaine
Bupivacaine is an amide local anesthetic commonly used for spinal
and epidural anesthesia and analgesia in obstetric practice. Its long duration of
action, differential sensory to motor block,[139]
and relative lack of tachyphylaxis make it a popular choice.
The placental transfer of bupivacaine, as with other amide local
anesthetics, is governed by two factors: the degree of ionization at physiologic
pH and the extent of protein binding. Bupivacaine has a pKa
of 8.05 (highly ionized at physiologic pH) and is 95% protein bound; thus, it has
limited transfer to the placenta when compared with other local anesthetics. The
UV/M ratio (the ratio at delivery of the concentration of local anesthetic in blood
or plasma from the umbilical vein to the concentration of local anesthetic in maternal
blood) for bupivacaine ranges from 0.31 to 0.44 and is much lower than that for lidocaine.
[140]
Safety concerns were raised after reports
of several deaths related to the cardiovascular or cardiac toxicity of bupivacaine.
[141]
[142]
After
these reports, the FDA prohibited the use of a 0.75% epidural solution in obstetric
practice. Changes in clinical practice have also lessened the risk of inadvertent
intravascular local anesthetic injections with the increasing use of multiorifice
catheters (which allow greater accuracy of aspiration of heme when the catheters
have been placed intravascularly) and the practice of incremental dosing. Bupivacaine
consists of two stereoisomers, S-
and R+
, and is marketed as
a racemic mixture of these isomers. When separated, the R component was found to
contribute to bupivacaine's unwanted toxicity.[143]
[144]
This finding led researchers to develop the
use of S isomers for clinical practice, which resulted in the introduction of ropivacaine
(the S isomer of the propyl homolog of bupivacaine) and levobupivacaine (the S isomer
of bupivacaine).
Lidocaine
Lidocaine has been used for many years in obstetric anesthesia.
It has a quick onset of action with an intermediate duration of action. UV/M ratios
reported in the literature are approximately 0.4 to 0.6.[145]
Even though lidocaine is very popular for use as an epidural local anesthetic for
operative delivery (2% with epinephrine), it is not popular for labor analgesia because
of motor block. Although early reports suggested that lidocaine compromises neonatal
neurobehavioral function,[146]
numerous follow-up
studies have not substantiated this association.[147]
Controversy has developed regarding the use of 5% hyperbaric lidocaine for spinal
anesthesia because of reports of transient neurologic symptoms. In 1994, the FDA
issued a letter concerning 5% hyperbaric lidocaine in which physicians were urged
to dilute the lidocaine with saline or CSF before injection. These precautions were
subsequently incorporated into the package insert for this drug. More recent data,
however, indicate that the 2.5% and 2% solutions may still cause transient radicular
irritation.[148]
As a result and despite many years
of use without clinical evidence of neurotoxicity, many anesthesiologists have abandoned
the use of spinal 5% hyperbaric lidocaine.
2-Chloroprocaine
2-Chloroprocaine is an ester local anesthetic with a rapid onset
time and short-lived duration of action. Its rapid metabolism by ester hydrolysis
(t1/2
= 45 seconds) makes it a safe agent for use in obstetrics because
almost no drug crosses the placenta.[149]
As a
result of this property and its speed of onset, its primary role in obstetric anesthesia
is for establishment of epidural anesthesia for emergency cesarean section when an
epidural catheter is already in place. In addition to its short duration of action,
a potential disadvantage of chloroprocaine is that it may interfere with the action
of epidurally administered opioids.[150]
This interaction
with opioids may be due to antagonism at the μ- and κ-opioid receptors.
[151]
Furthermore, it has been reported that chloroprocaine
may also interfere with the action of subsequently administered epidural bupivacaine.
[152]
Previous preparations of 2-chloroprocaine
were considered to be neurotoxic because of reports of arachnoiditis after unintentional
subarachnoid injection of this anesthetic.[153]
Subsequent reports incriminated the low pH of the anesthetic along with the preservatives
used for stabilization.[154]
Replacement of metabisulfite
and methylparaben has eliminated the risk of neurotoxicity. However, caution is
advised because despite the availability of preservative-free preparations marketed
as MPF (methylparaben free), formulations containing preservatives are still commercially
available.[155]
Levobupivacaine
Based on data that the cardiotoxicity of bupivacaine was more
pronounced with the R+
enantiomer, the S-
enantiomer (levobupivacaine)
was developed for clinical use. Levobupivacaine is a long-acting local anesthetic
with a clinical profile similar to that of bupivacaine. Both animal and human volunteer
studies have demonstrated a safety profile greater than that of racemic bupivacaine.
The lethal dose of levobupivacaine was 1.3- to 1.6-fold higher than that of racemic
bupivacaine in most animal studies, thereby providing supportive evidence for the
greater safety of levobupivacaine should accidental intravascular injection occur.
[156]
Like racemic bupivacaine, levobupivacaine
crosses the placenta. The UV/M ratio for levobupivacaine was noted to be 0.3 in
women undergoing elective cesarean section after the administration of 30 mL of 0.5%
levobupivacaine by means of an epidural.[157]
Studies
have demonstrated that levobupivacaine compares favorably with bupivacaine for epidural
anesthesia for cesarean section.[157]
Assessment
of sensory block with 0.5% bupivacaine and 0.5% levobupivacaine demonstrated no difference
in adequacy of the block or time taken to reach a surgically adequate block. Similarly,
other authors have recently reported that they found no difference with regard to
onset or duration of sensory block when patients received either 0.5% levobupivacaine
or 0.5% bupivacaine for cesarean section. In addition, the onset and fade-out of
sensory and motor blockade, the quality of anesthesia, and muscle relaxation were
comparable between the two groups.[158]
Levobupivacaine
has also been used to provide epidural analgesia for labor. A recent multicenter
study comparing levobupivacaine and bupivacaine reported that these drugs have equivalent
analgesic efficacy. In addition, motor blockade was similar between the groups.
[159]
As with other local anesthetics, recent evidence
suggests that fentanyl significantly reduces levobupivacaine requirements for epidural
analgesia in labor.[160]
Ropivacaine
Ropivacaine is a homolog of mepivacaine and bupivacaine. It was
the first S-
(levo) isomer of a local anesthetic to be marketed. Ropivacaine
is less soluble than bupivacaine; therefore, it may be less potent. Although clinical
evidence suggests that the two drugs might be similar in potency,[161]
minimum local anesthetic concentration (MLAC) studies have found that the analgesic
potency of ropivacaine was 0.60 (0.47 to 0.75) relative to bupivacaine. Claims for
reduced toxicity and motor block must be considered with differences in analgesic
potency kept in mind.[162]
