Anesthesia for Cesarean Delivery by zfz19897

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									                        Anesthesia for Cesarean Delivery

                                Lawrence C. Tsen, MD
               Director of Anesthesia, Center for Reproductive Medicine
                            Brigham and Women’s Hospital
              Associate Professor in Anaesthesia, Harvard Medical School


Despair thy charm;
And let the angel whom thou still hast serv’d
Tell thee Macduff was from his mother’s womb
Untimely ripp’d.
Shakespeare, MacBeth Act V:Scene 8

History and Introduction:

The origin of the procedure termed cesarean section predates the Roman Emperor Julius
Cesar (100BC), whose namesake is often invoked, but who was most likely not born in
this manner. Jacques Guillimeanu, in his book of midwifery in 1589, was the first person
of record to use the word “cesarean” in connection with “section”, however, as their Latin
equivalents (caesaru and seco) both imply cutting, cesarean “birth” or “delivery” may be
the most appropriate description. Cesarean delivery is generally defined as a laparotomy
(opening of the abdominal cavity through an anterior incision) plus a hysterotomy (an
incision into the uterus) to remove a fetus.

The high mortality rate associated with the procedure, mostly from hemorrhage and
infection, continued into the 19th century and dissuaded most obstetricians from this mode
of delivery. With improvements in both obstetric surgical and anesthetic techniques, the
safety and incidence of the procedure increased; over the past two decades, with the
advent of fetal heart rate and tocodynameter monitoring, a reduction in breech and
forceps-assisted deliveries, and a changing social and mediocolegal environment,
cesarean deliveries now account for 25-30% of deliveries nationally and internationally.1
Anesthesia-related maternal mortality, although declining during the last few decades,
still accounts for 3-12% of maternal deaths with the majority associated with intubation,
ventilation, and oxygenation failures during the provision or attempted provision of
general anesthesia.

Prevention of Cesarean Delivery:

Anesthesiologists, and the techniques employed for obstetric anesthesia and analgesia,
can play a role in the prevention of cesarean delivery. While the association between
regional analgesia and the progress and outcome of labor is often the first relationship
cited, the research and results generated have a number of confounders, are controversial
and deserve a completely separate discussion. A significant impact on reducing cesarean
deliveries, however, can be made by providing adequate analgesia for forceps/vacuum
deliveries, utilizing nitroglycerin in cases of fetal entrapment (50 µg IV, waiting 40-50


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seconds prior to delivery attempt), promoting the use of labor neuraxial techniques for
multiple gestation births, and most dramatically, by encouraging the use of central
neuraxial techniques for external cephalic version.

External Cephalic Version:

Occurring in approximately 3-5% of term pregnancies, breech fetal presentations can
significantly alter obstetric and anesthetic management. External cephalic version (ECV)
is a method by which manual external pressure is applied to the maternal abdomen to
change the position of a fetus from a breech to cephalic presentation. The use of ECV
has been associated with decreases in the fetal and maternal morbidity and costs
associated with a breech or operative delivery. Despite these advantages, ECVs represent
an underutilized option, in part due to limited success rates; these success rates can be
improved significantly by three variables that anesthesiologists can influence: the timing
of anesthetic interventions, the co-administration of tocolytics, and the anesthetic
techniques employed.

Timing:

ECVs are usually performed around the 36th week of gestation to balance fetal
moveability versus viability should an immediate cesarean delivery be necessary. As
ECVs become increasingly difficult in later gestation due to the growth of the fetus and a
decreasing ratio of amniotic fluid volume to fetal size, the importance of timing becomes
apparent.

Neuraxial analgesia is frequently requested for an ECV reattempt only after prior
attempts have failed. The timing of this reattempt, often scheduled for a week or two
later, could independently be responsible for lower success rates; the available literature
appears to corroborate this hypothesis. When ECVs were reattempted with the addition of
epidural anesthesia 1 to 3 weeks after the initial attempt, (i.e. at the 38th or 39th gestational
week), lower success rates i.e. 39.7% (27/68) 2 and 56% (9/16) 3 have been observed. By
contrast, when ECVs were reattempted with the addition of epidural analgesia
immediately following an initial attempt at the 37th gestational week, success rates have
been very high (89%).4 Encouraging an immediate ECV reattempt with the addition of a
central neuraxial blockade is of value.

Tocolytic Use:

Beta Agonists

While the effect of uterine tocolytics, such as the beta-agonists terbutaline, salbutamol
and ritodrine, on the success of ECV remains controversial, the current ECV practice
bulletin published by the American College of Obstetricians and Gynecologists (ACOG)5
and a recent review of randomized and quasi-randomized trials of ECV support their
use.6 As an example, Fernandez et al.7 demonstrated a doubling of the success rate (52%
vs. 27%) with the use of a tocolytic agent versus a placebo. Of interest, ECV reattempts


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with anesthesia are often conducted without these potentially beneficial adjuvants.3,4 The
use of these tocolytic agents, even in the presence of neuraxial techniques, should be
supported.

Nitroglycerin

The recent use of nitroglycerin as a uterine relaxant has allowed for its consideration and
demonstration as a successful adjuvant during ECV.8 In a recent study,4 uterine relaxation
with terbutaline was augmented with nitroglycerin for ECV attempts conducted under
neuraxial blockade; 6 of 8 patients who received nitroglycerin in this setting had
successful ECV attempts. No adverse effects were observed due to the nitroglycerin.
While the independent effect of nitroglycerin for uterine tocolysis in the setting of ECV
deserves further investigation, as an adjuvant that anesthesiologists are familiar with, it
appears to improve ECV success.

Tocolytics with Neuraxial Anesthesia Techniques

The success of ECVs performed with tocolytics appears to be improved with the use of
regional anesthesia. With all patients receiving tocolytics, Schorr et al.,9 randomized
patients to undergo attempted external version with or without an epidural (2% lidocaine
with 1:200,000 epinephrine to a T6 sensory level). In 69 demographically and
obstetrically similar parturients, the overall success rate of external version was higher in
the epidural group (69% vs. 32%), with more successful versions occurring on the first
attempt. There were no cases of fetal distress or abruptio placentae in either group.
Abdominal delivery was ultimately noted in 79% of the control group versus 34% in the
epidural group.

There are no completed reports comparing the success of ECV attempts with the
independent use of a tocolytic agent versus an epidural or spinal anesthestic.

Technique:

Central neuraxial analgesic and anesthetic techniques most likely improve ECV success
by relaxing the abdominal wall muscles, improving patient comfort during the ECV
attempt, and allowing the obstetrician to provide a more concerted attempt. The relative
safety and benefit of performing ECV attempts and reattempts with anesthetic techniques,
in terms of fetal outcome, limited need for emergent operative deliveries, and cost-benefit
analyses has been favorably recorded in studies utilizing these techniques to date.7

Epidural Technique

The evidence cited above demonstrates the value of epidural anesthesia techniques for
primary and repeat ECV attempts.




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Spinal Technique

The use of the spinal technique has been reported for ECV attempts and recently for
reattempts. With primary attempts, analgesic doses were utilized with contrasting results.
Dugoff et al.10 noted no improvement with the intrathecal administration of bupivacaine
2.5 mg with sufentanil 10 µg (44% and 42%), whereas Birnbach et al.11 noted a
significant improvement (80% vs. 33%) with the use of sufentanil 10 µg alone. Reasons
for these contrasting outcomes may ultimately reflect differences in obstetric practice,
such as how much force is applied and/or how much maternal discomfort is tolerated for
a given level of analgesia or anesthesia. As a consequence, whether ECV version success
can be predictably produced with analgesic doses using spinal techniques or whether the
results of such studies can be extrapolated to other practices will require further
investigation.

This being said, the findings of Birnbach11 validate the potential value of spinal
techniques in both primary and reattempted ECVs. In a small retrospective analysis of
spinal anesthesia (lidocaine 45 mg with fentanyl 10 µg) a high success rate (83%) was
noted with the use of spinal anesthesia in the setting of previously failed ECV attempts.4

Combined Spinal Technique

Whether utilized for primary or failed ECV attempts, a combined spinal epidural
technique with a short duration intrathecal local anesthetic may represent an optimal
technique. The short anesthetic duration would allow for a timely discharge in the event
of a successful version and should success or failure mandate a trial of labor or an
operative delivery, particularly in the setting of an emergent cesarean delivery, the
epidural catheter would allow additional analgesia or anesthesia to be administered
potentially without the need for general anesthesia.

ECVs done under neuraxial anesthesia can potentially increase maternal safety, reduce
morbidity, decrease cesarean sections, and produce cost savings. Central neuraxial
anesthetic techniques have been associated with increased success rates of primary and
previously failed ECVs. Immediately reattempting ECVs with the addition of these
techniques (or performing primary attempts with these techniques), providing uterine
tocolysis including nitroglycerin, and using catheter-based neuraxial techniques are
considerations that add value and success to ECV attempts.

Anesthesia for Cesarean Delivery:

The Practical Guidelines for Obstetrical Anesthesia12 from the ASA Task Force on
Obstetrical Anesthesia observe that cesarean delivery can be successfully managed with
all conduction techniques (spinal, epidural, CSE). The report also notes that general
anesthesia may be associated with increased maternal mortality/morbidity as well as
lower neonatal Apgar scores; these differences, however, in maternal and fetal outcomes
following general vs. regional anesthesia may be related in part to an observation bias.


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Thus, the use of any technique should consider specific case-by-case assessments of
clinical, laboratory, anesthetic, and obstetric issues.

Is regional anesthesia the preferred technique?

Complications related to anesthesia represent the sixth leading cause of peripartum
maternal mortality in the United States and abroad,13 with the risk of a maternal death
being 16.7 times greater with general versus regional anesthesia. 14 Almost all deaths
associated with general anesthesia are related to problems with intubation and ventilation,
which can be explained in part by the airway changes that occur over the course of
pregnancy and labor. As such, a risk/benefit analysis for the use of general anesthesia
should be strongly considered prior to its use. In an acknowledgment of the risks
associated with general anesthesia, the American College of Obstetricians and
Gynecologists (ACOG) has accepted that “cesarean deliveries for a non-reassuring fetal
heart rate pattern do not necessarily preclude the use of regional anesthesia.”15

Anesthesiologists, however, should be comfortable with their skills and treatment
algorithms for the administration of general anesthesia to the parturient, as even when the
philosophy and practice of a group aggressively favors regional anesthetic use, the need
for general anesthesia arises. In a review of anesthetic techniques utilized for all cesarean
sections at the Brigham & Women’s hospital from 1990-1995, the use of general
anesthesia was between 3.5-7.2% per year.16 A perceived lack of time or
contraindications to regional anesthesia were responsible for 70-90% of the general
anesthesia cases/year, an additional 6-24% were due to failed regional techniques, and the
remaining cases were due to patient refusal. In parturients at high risk for cesarean
delivery, and especially in those who have critically increased airway risks or
contraindications to neuraxial techniques, advance planning and communication with
patients and obstetric colleagues can potentially limit the use of general anesthesia. The
early placement and confirmation of an epidural catheter allows for its rapid extension for
surgical anesthesia, even if not utilized for labor analgesia.

Should newer local anesthetics be used?

Potentially reduced recovery times and toxicity profiles have fostered a growing interest
in the newer local anesthetics, ropivacaine and levobupivacaine. However, when
compared with racemic bupivacaine, distinct advantages of the newer and more
expensive solutions remain clinically unclear.

Although the safety of ropivacaine for elective cesarean deliveries has been established, 17
the conclusion that ropivacaine is less cardiotoxic than bupivacaine is based in part on an
assumption of equipotency. However, ropivacaine has been consistently noted to be 40%
less potent than bupivacaine when compared epidurally for labor analgesia,18 as well as
intrathecally for surgical anesthesia.19 Because ropivacaine and bupivacaine toxicity may
not be enhanced in pregnancy,20 cardiac toxicity should only occur when an
unintentionally large intravascular dose of either drug is administered. Proper epidural
administration of either drug, including attention to incremental dosing practices, total


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dose guidelines, and toxicity symptoms, should not result in toxic blood levels. In
addition, although more rapid motor recovery following cesarean delivery has been
reported with epidural ropivacaine (versus racemic bupivacaine at an equivalent
concentration), this again may be due to the differences in potency.21

Whereas ropivacaine represents a new chemical entity, levo (L) bupivacaine represents a
single enantiomer of the racemic bupivacaine currently in use. Although a margin of
safety has been demonstrated in terms of CNS and cardiac toxicity in animal studies,22
further study is needed to determine the magnitude of the difference. Clinical
investigations appear to demonstrate that levobupivacaine offers similar blocking
characteristics and complication profiles. Bader et al.,23 using 30 mL epidural L-
bupivacaine 0.5% vs. racemic bupivacaine 0.5% for elective cesarean deliveries, noted no
differences in the block onset or resolution, nor any significant differences in signal
averaged EKG’s, complications, or maternal and/or fetal plasma pharmacokinetics. The
equivocal advantage and the increased cost of L-bupivacaine has already appeared to
determine its overall use.

At this time, there appears to be no compelling advantage heralding the use of newer
local anesthetics for cesarean delivery. The safety of the lower concentrations (0.5%) of
bupivacaine currently in epidural use for cesarean deliveries, the availability and more
common use of other epidural local anesthetics (chloroprocaine and lidocaine), and the
greater attention to safe practices, such as incremental dosing, will most likely limit the
use of ropivacaine and L-bupivacaine.

Should lower doses of bupivacaine be used?

In an attempt to obtain faster motor recovery and discharge times, increase maternal
satisfaction and potentially lower costs, the amount of local anesthetics has been reduced
through dose reductions and/or the use of adjuvant medications. One method of overall
dose reduction is the use of spinal versus epidural anesthesia. Riley et al.24 in a
retrospective study, demonstrated the advantage of spinal versus epidural anesthesia for
elective cesarean deliveries in terms of time management, costs, charges, and
complications (defined as failed blocks, intravascular injections, inadvertent dural
punctures, PDPH). A second method of dose reduction is the use of lower total amounts
of bupivacaine. In addition to the reduction in the concentration of epidural bupivicaine
(from 0.75% to 0.5%) used for cesarean delivery, a reduction in the total dose of spinal
bupivacaine has been proposed (Table 1).

Table 1: Doses of Spinal Bupivacaine for Cesarean Delivery

Hyperbaric Bupivacaine Dose        Motor Recovery to T10                      Notes
                                   (minutes)
15 mg25                            162.1 ± 33.8                               7/12 c-level
12 mg26                            140 ± 16.5                                 3/16 c-level
7.5-8.0 mg + 25 mg epidurally27    146 ± 43.9                                 CSE
6.6 mg + 3.3µg sufenta 28          110 ± 27 isobaric; 92 ± 24 hyperbaric      CSE


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c-level: Cervical Vertebral Level; CSE: Combined Spinal Epidural Technique

Although these data suggest that very low doses of spinal bupivacaine can be utilized for
cesarean delivery, dosing within this range should consider the employment of a CSE
technique, as supplementation can be provided through the epidural catheter. Although
the epidural catheter of a CSE is often “untested” (despite some clinicians utilizing a
small test dose of lidocaine 1.5% with epinephrine upon placement), most studies
indicate that the catheter is reliable should supplementation be necessary. Norris et al. 29,
in a patient database review noted lower failures rates (4% and 6%, respectively) with
CSE (n=183) versus epidural (n=133) catheters initially placed for labor and later utilized
for surgery. Albright et al. 30 in a clinical series noted a significantly lower overall failure
rate for CSE, versus epidural or spinal anesthesia alone, and Davies et al.31 prospectively
observed lower anxiety and pain scores and higher maternal satisfaction with a CSE
versus an epidural for cesarean delivery. Taken together, these reports suggest that CSE
techniques are as reliable, and offer greater flexibility, than other central neuraxial
alternatives for cesarean delivery.

Can hypotension be prevented?

The use of central neuraxial techniques for cesarean delivery has grown in large measure
due to the overall maternal and fetal safety profiles. Maternal hypotension, however,
frequently follows such techniques and when severe and sustained can lead to impairment
of the uterine and intervillous blood flow, and result in fetal hypoxia, acidosis, and
neonatal depression.32 Three interventions, including left uterine displacement,33
intravascular volume expansion,34,35 and vasopressor prophylaxis and treatment,36 have
attempted to reduce the incidence of hypotension with variable success. Although the use
of smaller spinal doses of local anesthetic is an intriguing hypothesis for controlling
hypotension, when comparisons are made, recognition must be given to the potential
effects of fluid types and volumes and the vasopressors used; studies that more robustly
assess individual variables will need to be conducted (Table 2).

Table 2: Spinal Bupivacaine Dose and the Incidence of Hypotension in Patients
Undergoing Cesarean Delivery.

Study      Bupivacaine          Hypotension       Fluids                  Vasopressors
Tsen et    12 mg                70%               LR 1000 mL              10 mg ephedrine
al.26                                             preload;                prophylaxis
Sarvela et 9 mg                 58%               LR 1000 mL              15 mg ephedrine
al.37                                             preload; LR 500         prophylaxis
                                                  mL post-spinal;

Vercauter     6.6 mg + 3.3µg 33%                  LR 1000 mL              5 mg ephedrine
en et al.28   sufenta                             preload; 6% starch      prophylaxis
                                                  500 mL preload;
LR: Lactated Ringers



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Are there valuable adjuvant medications?

Adjuvant medications are utilized to express their own benefits and reduce the dose and
side effects of local anesthetics. For cesarean delivery, a prolongation of post-operative
analgesia and a reduction in motor blockade are pharmacologic goals. Aside from
epinephrine and narcotics, neostigmine and clonidine are two agents undergoing clinical
investigation.

Interest in neostigmine followed animal studies demonstrating increased analgesia
duration and a reduced incidence of hypotension when added intrathecally.38 When
evaluated for elective cesarean delivery, the addition of neostigmine in spinal doses up to
100 µg significantly reduced post-operative pain with no effect on fetal heart rate tracings
or Apgar scores,39 and equivocal alterations on the incidence of bradycardia and
hypotension. 40 Unfortunately, a high incidence of side effects, including prolonged
motor blockade, nausea, and vomiting, has been observed with spinal doses as little as
6.25 µg,41 and will most likely limit the clinical utility of this medication.

Currently only a limited number of clinical studies exist which examine the use of
clonidine for labor and post-cesarean analgesia. 42 With doses varying from 15-50 µg and
50-120 µg in spinal and epidural techniques respectively, clondine has demonstrated the
ability to prolong analgesia and decrease shivering; however, mild hypotension and
sedation have been witnessed as not infrequent side effects. 43 Currently clonidine has
only one specific neuraxial indication (intractable cancer pain), and a “black box” FDA
warning that “epidural clonidine is not recommended for obstetrical, postpartum, and
perioperative pain management”. The FDA warning mentions the unacceptability of
hemodynamic instability risks. With a cost of approximately $50 for a 10 mL vial of
clonidine, additional studies will need to more fully examine the clinical utility and cost
benefit of this medication.

Preservative free morphine sulfate is perhaps the most popular adjuvant due to a post-
cesarean analgesia duration of 17-27 hours. Palmer et al. studied the dose response to the
intrathecal44 and epidural45 use of morphine following cesarean delivery. Intrathecally,
by comparing 0.0, 0.025, 0.05, 0.1, 0.2, 0.3, 0.4, and 0.5 mg doses, a dose of 0.1mg was
found to produce analgesia comparable to doses as high as 0.5mg. Given free access to
additional analgesics via PCA, parturients were noted to self-administer low but constant
amounts in all dose ranges above 0.075 mg morphine. In addition, although the
incidence of pruritus appeared dose related, this relationship was not found with nausea
and vomiting. When given in the epidural space, a comparison of 1.25, 2.5, 3.75, and 5
mg doses observed that the quality of post-cesarean analgesia did not improve beyond
3.75 mg. In comparison to the intrathecal study, neither nausea and vomiting nor pruritus
(beyond 1.25 mg) appeared dose related.

Is there a perfect cocktail?

An infinite number of medication combinations exist. However, based on the most
recent evidence, there appears to be advantages in utilizing the following combinations


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(Table 3). Smaller doses of spinal bupivacaine may be used if the expected cesarean
delivery duration is short, or a CSE is administered. In the epidural space, lidocaine 2%
offers a rapid onset, dense block; both of these factors are enhanced with the use of 8.4%
bicarbonate 1mL per 10 mL of Lidocaine.

Table 3: Suggested Spinal and Epidural Medications for Cesarean Delivery

Medication              Spinal                                             Epidural
Local Anesthetic        Bupivacaine 9-12 mg, (depending on technique)      Lidocaine
                                                                           2% +
                                                                           bicarbonate
Fentanyl                15-35 µg46                                         50-100 µg
Morphine                0.1 mg                                             3.75 mg

Post-operative bliss:

Pain, pruritis, nausea/vomiting, and postoperative shivering are four issues which
complicate postoperative recovery. Pain is optimally handled with prophylaxis:
neuraxial morphine administered intra-operatively provides very good analgesia of long
duration. Should breakthrough pain occur, analgesia can be augmented with a non-
steroidal agent; Wilder-Smith et al. observed that the combination of a narcotic and a
NSAID was more effective for the provision of postoperative cesarean delivery analgesia
and the prevention of pain sensitization, than the two drugs given individually.47 Torodol
has been listed as being compatible with breast-feeding by the American Academy of
Pediatrics, and has been demonstrated to be effective for post-cesarean delivery
analgesia.48

Although pruritus following neuraxial blockade has a number of postulated mechanisms
and treatments,49 a direct antagonist or partial antagonist, such as nalbuphine 4 mg IV,
appears to have a greater effect than some other modalities.50 Nausea and emesis
following cesarean delivery can be difficult to treat; recently cyclizine 50 mg IV has been
observed to be superior to dexamethasone 8mg IV following intrathecal morphine for
cesarean delivery.51 Finally, postoperative shivering can have a number of causes and
treatments. Intravenous meperidine 25 mg, clonidine 150 µg, doxapram 100 mg,
ketanserin 10 mg, or alfentanil 250 µg have all been demonstrated to be effective,
although meperidine appears to be the most consistently effective.5253

Conclusion:

The rapidly changing field of obstetrical anesthesia has placed more emphasis on certain
techniques and dosing regimens. By reflecting on and adopting many of these advances,
fewer parturients undergoing cesarean delivery will hopefully comment:

This was the most unkindest cut of all.
Shakespeare, Julius Caesar, Act III, v 2



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