A Review of The Impact of Obstetric Anesthesia On Maternal and Neonatal Outcomes

Review Article
Deborah J. Culley, M.D., Editor
A Review of the Impact of Obstetric Anesthesia on

Maternal and Neonatal Outcomes
Grace Lim, M.D., M.S., Francesca L. Facco, M.D., M.S., Naveen Nathan, M.D.,
Jonathan H. Waters, M.D., Cynthia A. Wong, M.D., Holger K. Eltzschig, M.D., Ph.D.
Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/129/1/192/386686/20180700_0-00033.pdf by guest on 08 December 2020

ABSTRACT
Obstetric anesthesia has evolved over the course of its history to encompass comprehensive aspects of maternal care, rang-
ing from cesarean delivery anesthesia and labor analgesia to maternal resuscitation and patient safety. Anesthesiologists are
concerned with maternal and neonatal outcomes, and with preventing and managing complications that may present during
childbirth. The current review will focus on recent advances in obstetric anesthesia, including labor anesthesia and analgesia,
cesarean delivery anesthesia and analgesia, the effects of maternal anesthesia on breastfeeding and fever, and maternal safety.
The impact of these advances on maternal and neonatal outcomes is discussed. Past and future progress in this field will
continue to have significant implications on the health of women and children. (Anesthesiology 2018; 129:192-215)
O BSTETRIC anesthesiology has historically bridged

multiple disciplines including obstetrics, maternal-
fetal medicine, neonatology, general surgery, and anes-
social attitudes of patients who demanded it, persuaded by
public rhetoric from feminist advocates.2 In the early twen-
tieth century, “twilight sleep,” a combination of morphine
thesiology. Virginia Apgar, a surgeon turned obstetric and scopolamine, became common, but was ultimately
anesthesiologist, is best known for her namesake neonatal abandoned due to its depressant effects on the neonate. In
assessment scoring system. She is widely credited for early the mid-twentieth century, general anesthesia for cesarean
advances in neonatology. Her contributions exemplify how delivery gave rise to airway complications, including failed
obstetric anesthesiologists sought answers to scientific ques- tracheal intubations, maternal aspiration, and Mendelsohn
tions about anesthetic effects on the mother, fetus, and syndrome (aspiration pneumonitis).3 Anesthesiologists
neonate. Early investigations focused on the use of volatile began focusing their efforts on reducing anesthesia-related
agents for labor anesthesia, shifted to opioids and amnes-
adverse maternal and neonatal outcomes, including airway-
tics, and then to neuraxial techniques. Studies focused on
associated morbidity and mortality. As a result, neuraxial
the effects of these interventions on labor and the newborn.
labor anesthesia became increasingly used by the 1980s,
The “birth” of obstetric anesthesia began with the intro-
although it was simultaneously feared to be a risk factor for
duction of ether labor analgesia by obstetrician James Young
Simpson in 1847.1 While Simpson publicized this interven- cesarean delivery.4 Fortunately, most concerns were resolved
tion as effective and innovative, he expressed reservations by rigorous research, and by refining regional anesthesia
about its unknown effects on labor and the fetus. The medi- approaches.5 Advances that led to reductions in anesthesia-
cal community expressed concerns about safety and toxicity. related maternal morbidity and mortality included the use of
Women’s rights to request and receive labor pain relief was an epidural test dose, incremental epidural injection of local
controversial—religious mores of the nineteenth century anesthetic, elimination of bupivacaine 0.75% for epidural
viewed pain, including labor pain, as divine punishment, anesthesia, and lipid emulsion therapy for local anesthetic
and interference was considered sinful.2 Ultimately, the systemic toxicity. Past and ongoing research in obstetric
clinical use of ether and chloroform for labor analgesia was anesthesiology has contributed to a substantial reduction of
not driven by the scientific community, but by a shift in the anesthesia-related maternal mortality.5
This article is featured in “This Month in Anesthesiology,” page 1A.

Submitted for publication May 27, 2017. Accepted for publication January 22, 2018. From the Department of Anesthesiology (G.L., J.H.W.)
and Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Magee-Womens Research Institute and Foundation (F.L.F.),
University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Department of Anesthesiology, Northwestern University Feinberg School
of Medicine, Chicago, Illinois (N.N.); Department of Anesthesia, University of Iowa Carver College of Medicine, Iowa City, Iowa (C.A.W.); and
the Department of Anesthesiology, University of Texas Health Science Center, McGovern Medical School, Houston, Texas (H.K.E.).
Copyright © 2018, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. All Rights Reserved. Anesthesiology 2018; 129:192–215
Anesthesiology, V 129 • No 1 192 July 2018
Copyright © 2018, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
<zdoi;10.1097/ALN.0000000000002182>
EDUCATION
emphasis on the past decade. Continuing progress will have

important consequences to obstetric medicine, anesthesiol-
ogy, and perioperative patient care.
Labor Analgesia and Anesthesia

Methods of Labor Analgesia
Neuraxial Analgesia: Initiation and Maintenance. Labor
neuraxial analgesia is usually initiated by one of two meth-
ods: epidural or combined spinal-epidural analgesia (fig. 2).6
Combined spinal-epidural analgesia is often used for initi-
ation of analgesia in advanced labor because of rapid onset

of effective analgesia.7,8 Combined spinal-epidural analge-
sia has faster onset (2 to 5 min) than epidural analgesia
(15 to 20 min), greater uniformity in sensory blockade,
and improved sacral dermatome coverage.9 While some
studies report greater satisfaction and sense of control
associated with combined spinal-epidural analgesia, the
meta-analyses do not support this observation.9 Some
experts have argued that confirmation of correct epidural
catheter placement is delayed following initiation of com-
bined spinal-epidural analgesia; however, a 2016 study
suggests that may not be the case, and favors combined
spinal-epidural analgesia for earlier detection of failed epi-
dural analgesia.10 Other studies have shown that epidural
catheters sited as part of a combined spinal-epidural tech-
nique fail less often, both during labor and for intrapar-
tum cesarean delivery.11,12 A possible explanation for these
findings is confirmation of correct placement of the tip
of the epidural needle in the epidural space by virtue of
cerebrospinal fluid visualization through the spinal needle.
A 2014 meta-analysis did not find a definitive benefit of
combined spinal-epidural analgesia for catheter replace-
ment rates, supplemental epidural dosing, and epidural
vein cannulation; although the meta-analysis was limited
by significant between-study heterogeneity.13 A higher
risk of uterine tachysystole after combined spinal-epidural
Fig. 1. Subject areas of obstetric anesthesiology research analgesia than epidural analgesia has been reported and
advancements on maternal and neonatal outcomes over the may be attributable to the rapid decrease in circulating
last decade. Bubble size indicates relative publication vol-
catecholamines (which have a tocolytic effect) that accom-
ume of each topic. Topic list is not comprehensive.
panies rapid-onset of labor analgesia.8
A modification of the combined spinal-epidural tech-
Obstetric anesthesiologists have contributed to inter- nique is dural puncture epidural analgesia.14,15 In this
disciplinary initiatives advancing maternal safety (fig. 1). technique, the epidural space is identified and the dura is
Randomized control trials and impact studies improved punctured with a 25-gauge or smaller pencil-point spinal
understanding that neuraxial labor analgesia does not inde- needle, but no intrathecal medication is injected; an epidural
pendently influence the risk for cesarean delivery. Post- catheter is threaded in the routine manner. Dural punc-
partum pain management has improved, and multimodal ture epidural analgesia may be associated with improved
strategies have been enhanced such that analgesic efficacy sacral analgesia compared to epidural analgesia, with less
is maximized while maternal and fetal side effects are mini- pruritus, hypotension, supplemental epidural doses, and
mized. Anesthesia effects on lactation, maternal fever, neona- uterine tachysystole than combined spinal-epidural anal-
tal acid-base status, and cognitive development continue to gesia.14,15 A likely mechanism is the dural hole acts as a
be explored. Safer care systems emphasize low-dose neuraxial conduit to enhance epidural medication translocation into
anesthesia, hemorrhage preparedness and management, and the intrathecal space, allowing enhanced coverage of sacral
team crisis simulation. In this review, we focus on obstet- nerve roots while avoiding the side effects associated with
ric anesthesia advancements over the last two decades, with conventional combined spinal-epidural analgesia. Dural
Anesthesiology 2018; 129:192-215 193 Lim et al.
Obstetric Anesthesia Maternal-Infant Outcomes

Fig. 2. Epidural analgesia technique (A) versus combined spinal-epidural technique (B). In epidural analgesia, the epidural space
is located using an epidural needle, by a loss-of-resistance technique. A 19- to 20-gauge epidural catheter is threaded into the
space and used to dose medications. In combined spinal-epidural analgesia, the epidural space is located in the same fashion,
and prior to threading the epidural catheter, a small 25- to 27-gauge spinal needle is introduced through the epidural needle to
puncture the dura and to bolus a single dose of local anesthetic with or without opioid. The spinal needle is removed and a 19- to
20-gauge epidural catheter is threaded for subsequent dosing. Figure reprinted with permission from Eltzschig HK, Lieberman
ES, Camann WR: Regional anesthesia and analgesia for labor and delivery. N Engl J Med 2003; 348:319–32.6
puncture epidural analgesia may be a viable technique for hemodynamic effects and placental drug transfer.16
patients with a suspected difficult airway or failed epidural Dilute local anesthetics reduce the risk for motor block
labor analgesia, for whom confirmation of correct epidural which may contribute to instrumental delivery and post-
needle placement is critical, without incurring the side partum nerve palsies.17 Initiation of contemporary labor
effects of spinal medication dosing. epidural analgesia combines low-dose, long-acting amide
Modern labor analgesia favors initiation and main- local anesthetics, typically a bolus of 5 to 15 ml bupiva-
tenance of analgesia with low-dose local anesthesia and caine, 0.0625% to 0.125%, with a lipid soluble opioid,
opioid solutions to minimize risks of local anesthetic sys- typically fentanyl 50 to 100 µg or sufentanil 5 to 10 µg.18
temic toxicity (unintentional intravascular injection) or The drugs used to initiate combined spinal-epidural anal-
high- or total-spinal anesthesia (unintentional intrathe- gesia may vary based on the stage of labor. An opioid-only
cal injection). These low-dose strategies also minimize intrathecal dose (e.g., fentanyl 25 µg) is highly effective
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in treating pain associated with the first stage of labor, preferable to fixed-rate continuous epidural infusion
although it is accompanied by a high incidence of pru- because of lower total local anesthetic dose consumption,
ritus; a combination of intrathecal local anesthetic and lower incidence of motor blockade, and reduced need for
lipid soluble opioid (e.g., bupivacaine 1.25 to 2.5 mg anesthesia provider interventions.7 Settings for patient-
and fentanyl 15 µg) effectively treats somatic pain of the controlled epidural analgesia are variable, but generally
late first and second stages of labor.18 Epidural analge- include a background infusion of bupivacaine 0.05% to
sia is usually maintained with an infusion of bupivacaine 0.1% with fentanyl 1.5 to 3 µg/ml or sufentanil 0.2 to
0.05% to 0.1% with fentanyl 1.5 to 3 µg/ml or sufent- 0.33 µg/ml at 5 to 8 ml/h, a bolus of 5 to 10ml, and a lock-
anil 0.2 to 0.33 µg/ml at a rate of 8 to 15 ml/h into the out interval of 10 to 20 min.16
epidural space.18 Combining local anesthetic with lipid Programed intermittent epidural bolus has been recently
soluble opioid allows for profound visceral and somatic investigated for maintenance of labor epidural analgesia.

analgesia. The synergy between opioid and local anes- Rather than administering the maintenance dose as a con-
thetic medications allows dose-reduction of both drugs, tinuous infusion, with or without patient-controlled epi-
minimizing side-effects.19 dural analgesia, it is administered by the infusion pump
Continuous Epidural Infusion versus Programed Inter- programed to deliver boluses of epidural solution at regular
mittent Bolus. Prior to the advent of infusion pump intervals. The likely mechanism of improved analgesia is
technology, maintenance of labor analgesia occurred by greater medication spread in the epidural space; the epi-
manual intermittent boluses throughout labor. A major dural catheter is usually sited in a midlumbar epidural
disadvantage of this maintenance strategy was that analge- interspace, and satisfactory labor analgesia requires cover-
sia would eventually regress, leading to recurrence of pain, age of both low-thoracic and sacral dermatomes (fig. 3).
requiring another manual bolus; thus, analgesia was epi- One dosing strategy involves a solution of bupivacaine
sodic. With the advent of infusion pumps, continuous epi- 0.625% with fentanyl 2 µg/ml with an intermittent epi-
dural infusion techniques became popular. This technique dural bolus of 6-ml every 30 min, in addition to patient-
resulted in more stable analgesia and reduced supple- controlled epidural analgesia allowing a 5-ml bolus with
mental epidural dosing for breakthrough pain compared 10-min lockout.22 The programed intermittent epidural
to manual intermittent bolus strategies.7 As technology bolus technique allows maintenance of analgesia with less
improved, patient-administered bolusing (patient-con- local anesthetic without impairing maternal analgesia and
trolled epidural analgesia) was introduced. Evidence satisfaction, is associated with fewer supplemental epidural
from randomized trials support that analgesia is superior doses (less breakthrough pain), and has reduced risk for
when patient-controlled epidural analgesia is used with a motor block and instrumented delivery.22–25 In one trial,
background infusion compared to without a background motor block occurred more frequently (odds ratio 21.2,
infusion.7,20,21 Patient-controlled epidural analgesia is 95% CI, 4.9 to 129.3, P < 0.001) and earlier in women
Fig. 3. Maintenance of epidural analgesia by continuous epidural infusion versus programed intermittent epidural bolus. Differ-
ences in spread (blue pigment) of equivalent doses of local anesthetic over course of 1 h in (A) continuous epidural infusion and
in (B) programed intermittent epidural bolus are depicted.
randomized to receive continuous epidural infusion com- meta-analysis of five randomized trials found higher pain
pared with a programed intermittent epidural bolus to scores in women receiving remifentanil.36 However, one ran-
maintain analgesia. Instrumental delivery occurred more domized trial noted that while pain scores reductions were
frequently in the continuous epidural infusion group (20% greater with neuraxial analgesia, patient satisfaction scores
vs. 7%, P = 0.03).23 A meta-analysis of nine trials showed were not different.30 These findings support the repeated
lower local anesthetic dose and higher satisfaction scores observation that patient satisfaction for labor analgesia is
with programed intermittent epidural bolus.25 Higher not driven solely by reductions in pain intensity. In a 2014
local anesthetic doses may be associated with reduced pel- to 2015 survey, only 36% (95% CI, 26 to 46) of academic
vic floor muscle tone, reduced mobility, impaired Valsalva obstetric units in the United States used remifentanil for
maneuvers, and risk for instrumental delivery.26 Adminis- labor analgesia, with most doing so less than five times a
tration of local anesthetic by continuous infusion is inher- year.35

ently safer than bolus dosing. Bolus dosing by a human Compared to remifentanil, fentanyl patient-controlled
(anesthesia provider or patient) offers safety because the intravenous analgesia for labor analgesia has a lower rate of
presence of pain suggests that the catheter is not malposi- maternal sedation and respiratory depression; however, it
tioned in the subarachnoid space. A potential disadvantage has a higher rate of neonatal respiratory depression requir-
of programed intermittent epidural bolus is unintentional ing resuscitation at delivery.37 In one study, 59% of neonates
high neuroblockade that may accompany catheter migra- whose mothers used fentanyl compared with 25% for remi-
tion into the intrathecal space.27 fentanil patient-controlled intravenous analgesia required
Newer equipment now enables use of programed inter- resuscitation (odds ratio, 4.33; 95% CI, 1.75 to 10.76).37
mittent epidural bolus in clinical practice. The focus of Remifentanil may offer modest analgesic advantage over fen-
current research is identifying optimal settings for epidural tanyl (mean visual analog scale score, remifentanil: 46 mm vs.
bolus volume and interval, bolus infusion rate, and local fentanyl 60 mm, P < 0.01).32
anesthetic concentration.28 Nitrous Oxide. There is a renewed interest in the United States
Systemic Opioids for Labor Analgesia. Systemic opioids are in nitrous oxide for labor analgesia, although it has been
an alternative option for women for whom neuraxial anal- integrated into labor analgesia in other parts of the world
gesia may be contraindicated, cannot be achieved (techni- (e.g., Europe) for many years. Women who use nitrous oxide
cal failure to place an epidural catheter), or who prefer an report improved maternal satisfaction and coping compared
alternative method of labor analgesia. A common approach to no analgesia, although its analgesic efficacy is inferior to
involves fentanyl patient-controlled intravenous analgesia, neuraxial labor analgesia.38 These findings are not surprising,
typically 25 µg every 10 to 15 min, with an hourly lockout of given that maternal experience is known to be influenced by
100 µg.29 In the past decade, remifentanil patient-controlled factors such as a sense of control and ability to participate
intravenous analgesia has gained popularity due to its titrat- in decision-making, and is not exclusively influenced by the
ability and short latency (60 to 90 s). However, timing the provision of effective labor analgesia.39
self-administered bolus dose with the peak of uterine con- Nitrous oxide for labor analgesia has a long history of
tractions is difficult; the peak analgesic effect typically occurs safe maternal use, although rigorous study is lacking and
with the second contraction after the button is pushed, and questions remain regarding neonatal-childhood outcomes
contraction frequency may be irregular. Because remifent- and occupational risks of exposure.29 In experimental mod-
anil is rapidly metabolized by plasma esterases, it is appeal- els and in some clinical settings, nitrous oxide has been
ing for reduced fetal placental transfer, and for rapid fetal suggested to be neurotoxic and genotoxic, with potential
clearance of drug. Remifentanil patient-controlled intrave- adverse effects on the hematologic and immunologic sys-
nous analgesia provides reasonable analgesia and maternal tems.40–43 Several studies have reported no adverse neonatal
satisfaction, but maternal sedation, respiratory depression, events of this nature after maternal exposure to nitrous oxide
and apnea are well-described.30,31 In one trial, the risk for for labor, although these studies have been limited by flaws
maternal oxygen desaturation was significantly higher in in study design, conduct, analysis, and reporting.38 Nitrous
women receiving remifentanil compared to fentanyl.32 Mon- oxide is a potent greenhouse gas, although some experts con-
itoring of respiratory variables (respiratory rate, end-tidal tend that medical use of nitrous oxide has little environmen-
carbon dioxide, pulse oximetry, heart rate, and pulmonary tal impact.40 Occupational exposure (reproductive toxicity)
index) has low positive predictive values for surveillance of may be a concern if nitrous oxide delivery does not employ
maternal apnea.33 Therefore, remifentanil patient-controlled robust scavenging equipment.40
intravenous analgesia should be accompanied by continuous Nitrous oxide for labor analgesia and neuraxial analgesia
respiratory monitoring; we believe this monitoring is ide- result in similar degrees of maternal satisfaction. Its analgesic
ally achieved by 1:1 provider observation (nurse, midwife, or efficacy exhibits high inter-individual variability. However,
anesthesia provider).34,35 interest in increasing women’s choices for labor analgesia and
Remifentanil patient-controlled intravenous analgesia patient satisfaction in United States hospitals makes offering
is not superior to neuraxial labor analgesia techniques. A nitrous oxide during labor analgesia an attractive option.
EDUCATION
Pharmacogenomics and Pain Genetics. Scientific advance- Effect of Labor Analgesia on Labor Progress
ments in genetic medicine will likely allow development and Mode of Delivery
of personalized pain management strategies in the future, Labor Neuraxial Analgesia and Risk for Instrumental
but our current knowledge is still inadequate for precision Delivery. Epidural labor analgesia has been linked to
labor analgesia. For example, a single nucleotide polymor- increased risk for instrumental vaginal delivery, although
phism of the µ-opioid receptor gene (OPRM1, A118G) the nature of the relationship is controversial. Challenges
may be present in up to 30% of the obstetric population, to definitive investigations include obstetrician practice and
and is linked to altered responsiveness to neuraxial opi- the likelihood that instrumental delivery is attempted more
oids; the polymorphism increases binding and potency of often when effective neuraxial analgesia is present (table 1).
β-endorphins.44 These properties are linked to later request Understanding the relationship between neuraxial analgesia
for analgesia and lower neuraxial fentanyl and sufentanil and operative delivery is important because modern obstet-

dose requirements (ED50) in labor, compared to women rical skills in instrumental vaginal delivery is declining;18,50
with the wild-type alleles.44,45 In apparent contrast to these this trend may result in rising, indirect associations between
study results are the findings of a study from Asia; women labor neuraxial analgesia and increased rates of second stage
who were homozygous for the A118G polymorphism had cesarean deliveries.
increased opioid dose requirements after cesarean delivery, Meta-analyses of randomized trials comparing labor
and more breakthrough pain.46 A 2009 meta-analysis of neuraxial analgesia to systemic opioids found that the
studies of the effect of the OPRM1 A118G polymorphism mean duration of the first and second stages of labor were
on pain included studies from North America, Asia, and prolonged in neuraxial analgesia groups by 30 min and
Europe and found no effect of the polymorphism on opi- 15 min, respectively, and the rate of instrumental vagi-
oid dose requirement.47 nal delivery was increased in women receiving neuraxial
The influence of genetic polymorphisms on labor prog- analgesia (relative risk, 1.42; 95% CI, 1.28 to 1.57; 23
ress has been investigated. Terkawi et al. found that poly- trials, 7,935 women).51 However, many of the trials that
morphisms in the β2-adrenergic receptor gene were linked were included in the meta-analyses used epidural bupi-
to labor pain; however, these polymorphisms explained less vacaine concentrations of 0.25%. This concentration is
than 1% of the inter-subject variability.48 Similarly, catechol- considered high, by modern standards. Addressing this
O-methyltransferase and oxytocin gene receptor polymor- concern, the Comparative Obstetric Mobile Epidural
phisms were linked to slower transitions to active labor and Trial Study compared low-dose labor epidural techniques
slower latent phase of labor.49 While genetic factors will to a “traditional” or high-dose technique in a randomized
likely not entirely explain inter-individual differences in controlled design.52 The high-dose group received epi-
labor pain and labor progress, continuing advances in pain dural analgesia initiated with 10 ml bupivacaine 0.25%
genetics and pharmacogenetics may contribute to our future (25 mg), with subsequent boluses of 10-ml bupivacaine
ability to provide individualized therapies for labor pain and 0.25% (25 mg) on request (but no more than hourly).
analgesia. One low-dose group received epidural bupivacaine 0.1%
Table 1. Challenges to Definitive Investigations on Labor Neuraxial Analgesia Effect on Risk for Instrumental Delivery
Factor/Confounder Comment
Density of neuraxial block Dense analgesia may: (1) impair maternal expulsive efforts (motor block); (2) impede maternal coordina-
at second stage of labor tion of expulsive effort with uterine contraction (dense sensory block); (3) excessively relax pelvic floor
muscle tone and impair fetal head rotation
Obstetrician practice None of the trials are blinded, therefore, obstetricians who make the decision to perform an instrumental
vaginal delivery are not blinded to group allocation
Obstetricians may be more likely to perform instrumented delivery in a woman with effective second
stage analgesia
Trials on this topic have been performed in academic centers, where an obligation to teach instrumental
delivery exists
Practice type Randomized control trials from academic centers have shown an association between neuraxial analge-
sia and instrumental delivery
Impact studies (pre-post studies) carried out primarily at military medical centers or other nontraining
institutions have failed to find an association between neuraxial analgesia and instrumental delivery
Factors influencing degree Higher local anesthetic concentrations and higher higher total doses are linked to higher risk for instru-
of neuraxial block mental delivery; method of neuraxial analgesia maintenance (i.e., continuous infusion, programed
intermittent bolus) show variable results for rates of instrumental vaginal delivery, primarily driven by
differences in concentration and motor block
Method of neuraxial labor Comparisons of combined spinal-epidural and epidural techniques for outcome of instrumental delivery
analgesia initiation have had conflicting results
Table based on Wong CA: Epidural and spinal analgesia/Anesthesia for labor and vaginal delivery, Obstetric Anesthesia: Principles and Practice. Edited by
Chestnut DH, Mosby, 2014, pp 496.18
with fentanyl 2 μg/ml; analgesia was maintained with an neuraxial analgesia are more likely to be experiencing
infusion. The second low-dose group had combined spi- more painful labor.18 Factors associated with more pain-
nal-epidural initiation (spinal dose: bupivacaine 2.5 mg ful labor are themselves associated with an increased risk
and fentanyl 25 μg) and maintenance analgesia by inter- for cesarean delivery (e.g., fetal malrotation, fetal-pelvic
mittent injections of 0.1% bupivacaine with fentanyl. disproportion, dysfunctional labor).18 Early trials were
The investigators found that high-dose epidural analgesia limited by methodologic concerns, including mixed pop-
was associated with a reduced rate of normal spontane- ulations of nulliparous and parous women, use of differ-
ous vaginal delivery. These differences were explained by ent types of neuraxial analgesia, inconsistent density of
reduced instrumental vaginal delivery rates in the low- blockade, and high protocol violation and study group
dose groups.52 There was no difference in total dose of crossover rates.55–57 A study from Parkland Hospital in
local anesthetic between groups, likely due to method of Dallas, Texas (where the patient population is primar-

analgesia maintenance: the high-dose group had medica- ily indigent and labor is managed by the same group of
tion delivered by intermittent bolus, whereas the low-dose obstetricians and midwives) compared the cesarean deliv-
group had medication delivered by continuous infusion. ery rate in women receiving epidural analgesia to women
Specific analgesic technique and drug combination/dose receiving systemic meperidine analgesia.55 A per proto-
may be influential; a meta-analysis comparing combined col analysis suggested that the cesarean delivery rate was
spinal-epidural and epidural analgesia showed that instru- higher among women who used epidural analgesia (9% vs.
mental deliveries were lower in combined spinal-epidural 3.9%).55 However, the rate of crossover from meperidine
compared to “high-dose” epidural analgesia, but not com- to the epidural group was approximately 33%. After per-
pared to “low-dose” epidural analgesia.9 The true effect forming an intent-to-treat analysis, the cesarean delivery
and impact of labor epidural analgesia on risk for instru- rate was not different (6%) between groups.58 In a subse-
mental delivery remains poorly understood. quent study at the same hospital, there was no difference
More recently, an observational study of more than in cesarean delivery rates when intravenous patient-con-
600,000 deliveries in the Netherlands did not demonstrate trolled analgesia was used as a control. Use of this meth-
a change in instrumental delivery rates despite almost tri- odology resulted in better analgesia in the control group;
pling the labor neuraxial analgesia rate from 7.7 to 21.9% only 5 of 357 patients crossed over.59
over 10 yr.53 A meta-analysis of 28,443 patients showed A 2011 systematic review of 38 randomized trials did
no effect of increasing availability of labor neuraxial anal- not identify a link between labor epidural analgesia and
gesia on instrumental delivery rates.54 Concentration and risk for cesarean delivery.51 Impact studies (comparison
motor function may be important; a meta-analysis of 11 of the institution’s cesarean delivery rate before and after
randomized trials compared the instrumental delivery rate the introduction of a neuraxial labor analgesia service)
in high- versus low-concentration local anesthetic solu- have shown no association between labor neuraxial anal-
tion groups, and low-concentration strategies were linked gesia and cesarean delivery.54,60–62 Altogether, although
to reduced risk for assisted vaginal delivery and motor the debate persists, the evidence does not support that
block.17 Many studies have noted a relationship between neuraxial labor analgesia increases the risk for cesarean
total local anesthetic dose and motor blockade, but the delivery.7
association between motor blockade and instrumental “Early” labor epidural analgesia (i.e., epidural analgesia
delivery has been inconsistent.18 Although controversy per- performed during the latent phase of labor) was historically
sists, the available evidence suggests that functional labor believed to be a risk factor for cesarean delivery. Observa-
analgesia is associated with risk for instrumental delivery, tional trials suggested that women who requested neuraxial
possibly by virtue of analgesic density and motor impair- analgesia early in labor (commonly defined as cervical dila-
ment.18 Instrumental vaginal delivery may increase risk tion less than 4 cm) had a higher cesarean delivery rate.63
for lacerations and other perineal injuries, neonatal facial This translated into a common practice among obstetric
or cranial injuries, and pelvic organ prolapse. Given these practitioners in the 1990s, advising their patients to avoid
undesirable outcomes, the goal of modern labor epidural epidural analgesia in early labor.
analgesia favors minimizing motor blockade by initiating In contrast to observational trials, multiple random-
and maintaining analgesia using low-concentration local ized control trials comparing early to later initiation of
anesthetic solutions.7 Nevertheless, minimizing risk for labor neuraxial analgesia failed to find a link between
instrumental delivery while maximizing patient comfort early use and risk for cesarean delivery (table 2).64–70
requires skillful attention to individual patient needs and These trials compared early labor neuraxial analgesia and
clinical circumstances. systemic opioid analgesia; women randomized to receive
Mode of Delivery. Early observational studies identified early systemic opioid analgesia received neuraxial anal-
an association between neuraxial labor analgesia and gesia later in labor. The trials were well controlled; and
increased rates of cesarean delivery; however, the rela- crossover rates were not excessive. In two separate tri-
tionship is not surprising given that women requesting als, Chestnut et al. found early epidural analgesia among
EDUCATION
Table 2. Summary of Randomized, Controlled Trials Investigating Effect of Early Labor Epidural Analgesia on Mode of Delivery in
Nulliparous Women
Comparison Early Neuraxial Late Neuraxial

Study Year Groups Patient Population N Analgesia Analgesia
Chestnut65 1994 Early Epidural Spontaneous labor 172 17/172 (10%) 13/162 (8%)
Late Epidural 162
Chestnut66 1994 Early Epidural Receiving oxytocin 74 13/74 (18%) 14/75 (19%)
Late Epidural 75
Luxman67 1998 Early Epidural Spontaneous labor 30 2/30 (6.6%) 3/30 (10%)
Late Epidural 30
Wong64 2005 Early CSE Spontaneous labor 366 33/366 (18%) 75/362 (21%)

Late Epidural 362
Ohel68 2006 Early Epidural Spontaneous or 221 28/221 (13%) 25/228 (11%)
Late Epidural induced labor 228
Wang69 2009 Early Epidural Spontaneous labor 6394 1486/6394 (23%) 1456/6399 (23%)
Late Epidural 6399
Wong70 2009 Early Epidural Induction of labor 406 134/406 (33%) 126/400 (32%)
Late Epidural 400
All studies were powered for the primary outcome of cesarean delivery. “Early” neuraxial in most studies was defined as neuraxial analgesia initiated at less
than 4 cm cervical dilation, or at a cervical dilation of “at least” 1 cm.
CSE = combined spinal-epidural, N = number of subjects in the study.
nulliparous women was not associated with increased epidural analgesia and the duration of labor; however, studies
risk for cesarean delivery in both spontaneous and oxy- were of low quality and the CIs were wide.75
tocin-induced or oxytocin-augmented labor.65,66 These The reasons for the conflicting results are multifold.
findings were important because they supported the pro- Methodologically, trials differ in how they define the onset
vision of epidural analgesia during latent labor, whereas of labor. Epidural analgesia may delay cervical examina-
this practice was formerly thought to increase risk for tion due to effective analgesia (examinations establishing
cesarean delivery. Later, Wong et al. also found no dif- full cervical dilation are typically deferred until the partu-
ference in the rate of cesarean delivery among women rient complains of rectal pressure). Epidural analgesia has
who received combined spinal-epidural analgesia at less been linked to both increased and decreased uterine activ-
than 4 cm of cervical dilation compared with those who ity.8,76–78 Decreased uterine activity may be explained by
received early labor systemic opioid analgesia followed by coadministration of intravenous fluid, reducing circulating
epidural analgesia later in labor; onset and intensity of antidiuretic hormone, and reducing endogenous oxytocin
analgesia were superior in the combined spinal-epidural (both hormones are produced by the posterior pituitary
analgesia group.64 Ohel et al. found similar results; the gland).77 Increased uterine activity may be explained by
rates of cesarean delivery in women who received early a rapid reduction in circulating catecholamines associ-
compared with late epidural analgesia were similar (13% ated with initiation of analgesia;8,78 the withdrawal of β2-
vs. 11%, P = 0.77).68 adrenergic activity (tocolytic) may result in frequent and
Considering these findings, the data linking labor epi- more intense uterine contractions leading to uterine tachy-
dural analgesia to cesarean delivery may be better explained systole. Heterogeneous effects of epidural analgesia on uter-
by the observation that women with more painful labors, ine activity and first stage of labor may also be explained
especially early labor pain, are more likely to require cesarean by variability in neurophysiologic responses to labor, pain,
deliveries due to obstetrical factors such as fetal macroso- and analgesia.79
mia, malrotation, and dysfunctional labor.71–73 The practice Effective epidural analgesia is associated with a prolonged
of avoiding neuraxial labor analgesia in early labor for fear second stage of labor, with an estimated mean difference
that it will adversely affect the mode of delivery should be of 15 min, which is not clinically meaningful.74 However,
completely abandoned.7 the duration of the second stage of labor at the 95th per-
Progress of Labor. While some studies have demonstrated a centile may be prolonged up to 2 h in both nulliparous and
modest prolongation of the first stage of labor (mean approxi- parous women with epidural analgesia.80,81 The impact of
mately 30 min),74 others have shown neuraxial analgesia is prolonged second stage of labor on maternal and neonatal
associated with faster labor. Wong et al. and Ohel et al. found outcomes deserves scrutiny. Older studies have not shown
early labor neuraxial analgesia resulted in faster labor com- adverse maternal or neonatal outcomes associated with pro-
pared to treating early labor pain with systemic opioids and longed second stage of labor, provided that the fetal heart
initiating neuraxial analgesia later in labor.64,68 A 2017 meta- rate tracing remains reassuring and there is progressive fetal
analysis did not find a relationship between low-concentration descent.82–84 However, in a large multicenter observational
study, longer periods of active pushing were associated with to surgical anesthesia in the event of emergency cesarean
an increased relative risk for neonatal complications, such delivery. Disadvantages of neuraxial analgesia/anesthe-
as mechanical ventilation, sepsis, brachial plexus palsy, sia for external cephalic version include hypotension and
encephalopathy, and death, although the absolute risk was delayed hospital discharge, both of which may be dose-
low.85 Other studies have shown an increased risk of adverse dependent. Hypotension is typically easily treated, but
maternal outcomes (e.g., chorioamnionitis, high-degree lac- requires close monitoring. An economic analysis on the use
erations, atony, hemorrhage, fever) for every additional hour of neuraxial anesthesia for external cephalic version found
spent in the second stage of labor.86,87 Given the associa- it to be cost-effective, assuming an improved success rate
tion between prolonged second stage of labor and adverse of at least 11% from a baseline of 38%.95 This finding is
maternal and neonatal outcomes, the effect that neuraxial explained by the large differences in costs between vaginal
analgesia may have on labor duration remains an important delivery and cesarean delivery.

research question. Oral Intake in Labor. Aspiration pneumonitis or solid gas-
Neuraxial Anesthesia for External Cephalic Version. Exter- tric content asphyxiation was a leading cause of anesthesia-
nal cephalic version is a procedure wherein a breech fetus at related maternal mortality.3 The stomach shifts cephalad,
36 to 39 weeks gestation is manually rotated to the vertex displacing the lower-esophageal sphincter into the thorax.96
presentation, permitting a trial of labor and vaginal delivery. Lower esophageal sphincter pressure declines by 50% dur-
The procedure is an important strategy for prevention of pri- ing pregnancy.97 Reduced motilin produces slower intestinal
mary cesarean delivery (17% of primary cesarean deliveries transit times.98 While pregnancy does not increase gastric
are due to fetal malpresentation).88 Prevention of primary emptying time, endogenous or exogenous opioids prolong
cesarean delivery is an important public health concern gastric emptying times.99,100
given the high rates of cesarean delivery, maternal morbidi- To address aspiration-related maternal mortality in the
ties associated with cesarean delivery compared to vaginal middle part of the twentieth century, the following prac-
delivery, and increasing healthcare costs and maternal risk tices became the cornerstone of modern obstetric anesthesia
in subsequent pregnancies after primary cesarean delivery. practice: (1) widespread use of neuraxial anesthesia; (2) oral
Neuraxial anesthesia for attempted external cephalic version intake restrictions during labor; (3) preanesthetic antacid
is associated with a higher success rate.89 administration; (4) rapid-sequence induction for general
The findings of early studies of the role of neuraxial anes- anesthesia; (5) improvements in anesthesia training; and (6)
thesia in external cephalic version were equivocal.90,91 Some improvements in advanced airway devices. These practices
obstetricians are concerned that neuraxial analgesia will mask are reflected in current American Society of Anesthesiolo-
pain related to uterine rupture or placental abruption, rare gists recommendations.7 Because of these practices, maternal
but catastrophic complications of external cephalic version. mortality from aspiration has declined to extremely low lev-
A 2011 meta-analysis allays these concerns, showing no dif- els (estimated case fatality rate, 6.5 per million anesthetics in
ferences in the rates of placental abruption or uterine rupture the Unites States).5,101,102 Closed claims analysis shows a sig-
in neuraxial anesthesia versus control groups who received nificant reduction in malpractice claims from aspiration.103
no analgesia or systemic opioid analgesia.92 Risk for cesarean Because of the modern rarity of aspiration-related mortality,
delivery for nonreassuring fetal heart rate was also not differ- and with growing interest in limiting medical interventions
ent between neuraxial anesthesia and control groups. during low-risk labor, liberalizing oral intake during labor is
Meta-analyses of randomized control trials have identi- appealing.104 The World Health Organization advocates no
fied a 13 to 50% increase in the rate of successful external interference with a woman’s desire to eat and drink during
cephalic version with neuraxial anesthesia; most women low-risk labor.105 Liberalizing oral intake might have advan-
who have a successful external cephalic version have a suc- tages for patient satisfaction, and it seems intuitive that pro-
cessful vaginal delivery.89,92,93 The results of early meta-anal- viding energy during a demanding metabolic period might
yses suggested that the success rate may be dose-dependent: improve outcomes. Nil per os practices in pregnancy have
denser neuroblockade has a higher success rate.93 Surgical- been linked to a state of “accelerated starvation” due to shifts
level neuraxial anesthesia is postulated to enhance relax- to glycogenolytic and gluconeogenesis metabolic pathways.106
ation of abdominal wall musculature, assisting the manual Early studies shed light on outcomes with liberalized oral
efforts of the obstetrician. However, a 2017 study in which intake strategies in labor.107–109 In one study, women were
women were randomized to receive combined spinal-epi- randomized to a light meal or to water; epidural analgesia
dural analgesia with intrathecal fentanyl combined with with opioid-containing solutions was permitted.109 Women
varying doses of bupivacaine (2.5, 5, 7.5, and 10 mg) did in the light diet group had lower plasma β-hydroxybutyrate
not support a dose-response effect on external cephalic ver- and nonesterified fatty acids, indicating ketosis preven-
sion success rate (50, 52, 52 and 49%, respectively; P = tion. However, there were no differences in lactate, labor
0.99).94 There were no differences in obstetrician rating for duration, Apgar scores, and umbilical cord blood gases.
abdominal relaxation. An advantage of neuraxial anesthe- Light diet consumers were more likely to vomit, and vom-
sia for external cephalic version is the ability to convert ited higher volumes of particulate matter, during labor. In
EDUCATION
another study, rates of vomiting were similar between water with less stimulation upon surgical traction of the viscera, con-
and sports drinks, while reduced markers of ketoacidosis tributing to a lower rate of nausea, vomiting, and intraoperative
without increases in gastric volumes were found in sports supplemental analgesia compared to omission of intrathecal
drink consumers.107 A large trial found no differences in the fentanyl or sufentanil.114 Adding morphine (a water-soluble
rate of vaginal delivery, duration of labor, cesarean delivery, opioid) confers postoperative analgesia of up to 36 h.115 Epi-
or vomiting.108 nephrine (0.1 to 0.2 mg) is often added in clinical practice,
Meta-analyses in low-risk deliveries show no effect of food producing a 15% increase in block duration and improving
intake on mode of delivery and neonatal well-being, although the quality of intraoperative analgesia, while increasing block
pooled data were insufficient to address the risk for aspira- recovery time.116 Clonidine improves intraoperative analgesia
tion.110,111 There are two possible interpretations of these data. and reduces shivering and hyperalgesia, but is associated with
First, given the contemporary rarity of aspiration, maternal hypotension and sedation; its use in this setting is off-label.117

wishes should take priority, and oral intake guidelines liberal-
ized to allow maternal decision-making for light meals during Conversion of Epidural Analgesia to Surgical Anesthesia
low-risk labors. Alternatively, women seem to tolerate limited Epidural analgesia is converted to surgical anesthesia by
oral intake in labor without negative consequences, and con- administering high-concentration local anesthetic. Fifteen
sidering the large decrease in maternal mortality since nil per to 20 ml lidocaine, 2% with epinephrine 1:200,000 is com-
os strategies were implemented, there is no need to liberalize monly used. The addition of 8.4% sodium bicarbonate (1 ml
oral intake restrictions. Current American Society of Anes- for every 10 ml local anesthetic solution) alkalinizes the local
thesiologists guidelines allow clear liquid intake in uncompli- anesthetic solution, which hastens onset of action. Fifteen to
cated labor and complete avoidance of particulate and solid 20 ml 2-chloroprocaine, 3% may be used for urgent deliver-
food.7 Nil per os strategies for parturients undergoing elective ies because of its shorter latency. Successful conversion to
surgery (e.g., scheduled cesarean delivery or postpartum tubal epidural anesthesia is critical to avoid general anesthesia;
ligation) include fasting 2 h for clear liquids and 6 to 8 h for emergency general anesthesia is linked to poor outcomes
solid food, depending upon fat content.7 (postoperative pain and sedation, intraoperative awareness,
Considering the historical context in which nil per os strat- postpartum hemorrhage, and morbidity and mortality from
egies developed, along with ethical and logistical challenges aspiration or failed tracheal intubation). The ability to suc-
of conducting a trial addressing harm, we will likely continue cessfully convert epidural analgesia to anesthesia for intrapar-
seeing global and cultural discrepancies on oral intake during tum cesarean delivery has been proposed as a quality metric;
labor. Based on available data and history, our practice is to in the United Kingdom, the National Institute for Health
avoid solid food and particulate liquid ingestion in labor, par- and Care Excellence guidelines state that general anesthesia
ticularly if parenteral or neuraxial opioids were administered, should be used in less than 1% of all elective cesarean deliv-
to allow glucose-containing clear liquids as tolerated, and to eries and less than 5% of emergency cesarean deliveries.118
restrict oral intake in individuals after considering comorbidi- Several risk factors for failed conversion include delivery
ties that may increase the risk for cesarean delivery or aspira- urgency, supplemental analgesia during labor, initiation by
tion (e.g., obesity, diabetes mellitus, suspected difficult airway, epidural rather than combined spinal-epidural technique,
and nonreassuring fetal heart rate tracing). and anesthesia by generalist compared with obstetric anesthe-
siologists.11,12 In one study, generalist anesthesiologists had
Anesthesia for Cesarean Delivery significantly increased risk for failed conversion of epidural
Advances in Spinal Anesthesia for Cesarean Delivery analgesia to anesthesia for cesarean delivery (odds ratio 4.6,
Single-shot spinal anesthesia is the most common tech- 95% CI 1.8 to 11.5).11 Reasons for increased successful con-
nique for cesarean delivery due to its simplicity, quality version by obstetric anesthesiologists may include increased
of sensory blockade, and reliability. In contrast to epi- likelihood to manipulate the catheter, active management of
dural anesthesia, the total local anesthetic dose is lower; breakthrough labor pain, assessment of catheter functional-
there is no risk for local anesthetic systemic toxicity and ity and analgesic quality throughout labor, integration of
there is minimal fetal drug transfer.12,112 The effective dose information on labor and maternal-fetal status into analgesia
for hyperbaric bupivacaine in 95% of patients (ED95) is management, and enhanced team communication to antici-
13 mg when administered with intrathecal fentanyl and pate intrapartum cesarean delivery.11
morphine. Higher doses (e.g., 15 mg) are associated with
longer duration, but also with higher sensory blockade to Intraoperative Hypotension: The Ideal Vasopressor for
cervical dermatomes, and a higher incidence and degree of Cesarean Delivery
hypotension.113 Hypotension after spinal anesthesia is caused by a decrease
Adding a lipid-soluble opioid (e.g., fentanyl, sufentanil) to in systemic vascular resistance; cardiac output increases.119
local anesthesia enhances intraoperative anesthesia by reduc- The ideal vasopressor to maintain uterine perfusion has been
ing the total dose of local anesthetic, reducing hypotension, an area of intense research for several decades. Uteropla-
nausea, and vomiting.114 This enhanced anesthesia is associated cental blood flow lacks autoregulation, making it directly
dependent on uterine perfusion pressure and inversely pro- anesthesia hypotension in cesarean delivery, norepinephrine 8
portional to uterine vascular resistance. Pure α1-adrenergic µg was equivalent to phenylephrine 100 µg for the treatment
receptor agonists (phenylephrine) were expected to reduce of the first episode of hypotension.132 Considering the exis-
uterine blood flow and induce fetal acidosis, and ephedrine tence of a highly effective standard (phenylephrine infusion),
was found to be superior to α1-agonists in fetal animal stud- additional accumulation of evidence is necessary before nor-
ies. The first human trials comparing phenylephrine and epinephrine becomes a new standard.128
ephedrine were conducted in the late twentieth century.
Neonatal outcomes (umbilical artery pH, base excess) were Supplemental Oxygen
better in groups randomized to phenylephrine.120–122 No While supplemental oxygen is often routinely applied during
study found neonatal depression despite very large maternal cesarean delivery, evidence supporting improvement in mater-
doses of phenylephrine (in one study the 75th percentile dose nal and neonatal outcomes is lacking, and some suggest it may

was 2,130 µg).120–123 Consistently, the incidence of nausea cause harm by promoting free-radical generation and lipid
and vomiting is lower with phenylephrine infusion. While peroxidation.133,134 A trial of 80% versus 30% oxygen during
maternal bradycardia occurred with phenylephrine, patients cesarean delivery did not prevent wound infections or endo-
were asymptomatic and no adverse events were noted. metritis.135 A meta-analysis of 11 trials of supplemental oxygen
Ephedrine is associated with fetal acidosis due to placen- found no benefit for maternal desaturation and neonatal Apgar
tal transfer and direct fetal metabolism activation, but not scores.136 No convincing evidence of harm was identified,
from uterine blood flow perturbation.124 Experts conclude although higher maternal and neonatal markers of free-radicals
the efficacy and safety of phenylephrine make it superior for were measured when supplemental oxygen was administered;
systemic vascular resistance restoration after spinal anesthe- the clinical significance of these findings is not clear. Data are
sia.125,126 Prophylactic phenylephrine infusions (vs. intermit- lacking on the benefits or harms of supplemental oxygen in
tent boluses) are effective in preventing hypotension and women with comorbid conditions (e.g., preeclampsia, obesity,
require fewer anesthesia provider interventions.127 The cur- labor with nonreassuring fetal heart rate tracing) or in intra-
rent evidence supports prophylactic phenylephrine, titrated uterine resuscitation. Theoretically, these neonates may be at
to maintain blood pressure near baseline (the usual dose increased risk of harm with hyperoxia because of greater lipid
range is 25 to 100 µg/min).125–128 peroxidation from ischemia-reperfusion injury. The available
Notably, most research comparing vasopressor therapy for evidence suggests that routine supplemental oxygen for sched-
cesarean delivery has been in healthy women undergoing elec- uled, healthy cesarean deliveries with neuraxial anesthesia is not
tive cesarean delivery. Investigations for neonatal outcomes in beneficial,136 and its elimination may improve patient comfort.
maternal-fetal dyads with compromised placental function
(e.g., preeclampsia) have been lacking. In 2017, a randomized Postcesarean Delivery Pain and Analgesia
double-blind trial compared phenylephrine and ephedrine Pain after cesarean delivery is heterogeneous in expression
infusion strategies in women with preeclampsia presenting and intensity. The ability to predict the severity and chronic-
for cesarean delivery under spinal anesthesia.129 There were no ity of postcesarean delivery pain has the potential to person-
differences in umbilical arterial pH between groups. Similarly, alize anesthetic care by identifying the patients at highest risk
among women with preeclampsia with severe features who for severe pain and debilitation. Recent work has focused on
also had nonreassuring fetal status, a bolus dose of phenyleph- psychometric and psychophysical profiling. Expected post-
rine to treat spinal anesthesia-induced hypotension did not operative pain, baseline anxiety, and baseline fear of pain are
result in better fetal acid-base status compared with ephed- independent predictors for increased postoperative opioid
rine.130 It appears that for preeclamptic patients undergoing use, accounting for 40% of variance in postoperative pain
cesarean delivery, fetal outcomes are not influenced by choice and opioid used.137 Pan et al. validated a three-item ques-
of phenylephrine or ephedrine for prevention or treatment of tionnaire predicting pain after cesarean delivery;138 a follow-
spinal-anesthesia induced hypotension. up study applied the questionnaire to a tailored analgesia
Several investigators suggest norepinephrine has character- regimen targeted at women at high risk for severe postcesar-
istics of the “ideal” vasopressor to prevent and treat hypoten- ean delivery pain.139 This type of work is key to advancing
sion, but current evidence is limited.128 In one trial, patients individualized pain management strategies in obstetrics.
receiving norepinephrine had higher heart rate and cardiac Multimodal analgesia is the gold standard for postcesar-
output compared with phenylephrine.131 The incidence of ean delivery analgesia.140 A common strategy uses neuraxial
nausea and vomiting did not differ. Norepinephrine use was morphine, scheduled nonsteroidal antiinflammatory drugs
associated with lower umbilical artery and vein plasma cate- (NSAIDs) and acetaminophen, and limits systemic opioids
cholamine concentration and higher umbilical venous pH and to the treatment of breakthrough pain. Neuraxial morphine
oxygen content, potentially indicating higher uteroplacental is the most effective component of postcesarean delivery
oxygen delivery; the absolute differences were small (oxygen analgesia.141,142 It is easy to administer, inexpensive, and pro-
content phenylephrine, 11.8 ml/dl; oxygen content norepi- vides superior and prolonged analgesia for both static and
nephrine, 12.7 ml/dl; P = 0.047).131 In a study on postspinal dynamic pain.142 Its dynamic pain advantage is important
EDUCATION
for functional mobility in this population. Neuraxial mor- plane block is useful for treating incisional pain, but not visceral
phine-related side effects include pruritus, nausea, urinary pain. A transversus abdominis plane block may be helpful for
retention, and respiratory depression, although the risk for “rescue” analgesia for breakthrough pain after neuraxial mor-
the latter is significantly lower when morphine is admin- phine.154 Transversus abdominis plane block may be associ-
istered neuraxially than systemically.143,144 Side effects are ated with subclinical signs of local anesthetic systemic toxicity,
dose-dependent; high-dose intrathecal morphine (more than therefore, patients must be monitored closely after transversus
100 µg) has longer-lasting analgesia (4.5 h) compared with abdominis plane block.155 Considering the evidence, the addi-
low-dose morphine (50 to 100 μg), but is associated with tion of transversus abdominis plane block to the gold standard
a higher rate of pruritus and vomiting.145 Pain scores and (multimodal analgesia) is not routinely necessary for effective
supplemental systemic morphine consumption do not differ postcesarean delivery analgesia.
between the high- and low-doses. A quadratus lumborum block may have advantages over the

NSAIDs such as ketorolac, diclofenac, and ibuprofen are transversus abdominis plane block because of its more superficial
essential components of multimodal postcesarean delivery location (easier ultrasound visualization, theoretically improved
analgesia. Their use spares opioids by up to 50%, translating to safety). It involves deposition of local anesthetic into the fascial
a 30% reduction of opioid-related side effects such as vomit- plane located between the quadratus lumborum and erector
ing and sedation.146 The package insert for ketorolac states that spinae muscles; this space is continuous with the paravertebral
practitioners should “exercise caution when ketorolac is admin- space, thus enhancing medication spread to the include the sym-
istered to a nursing woman.”147 The excretion of ketorolac in pathetic chain. In two randomized trials, quadratus lumborum
breast milk is minimal and the American Academy of Pediatrics block combined with spinal anesthesia was found to be superior
lists ketorolac as, “usually compatible with breastfeeding.”147,148 to spinal anesthesia alone, and to transversus abdominis plane
Given the safety profile of ketorolac is unlikely to be differ- block with spinal anesthesia.156,157 A major limitation of these
ent from ibuprofen, an NSAID widely used in the postpartum trials was the absence of comparison to intrathecal morphine
period, we routinely use ketorolac in our practice if contraindi- (spinal anesthesia regimens did not have intrathecal morphine),
cations are not present. Contraindications to NSAIDs include therefore, no conclusions currently can be made about the supe-
renal disease (e.g., renal dysfunction in preeclampsia) and a his- riority of the block to current standard of care.
tory of Roux-en-Y gastric bypass surgery. Local anesthetic wound infiltration may be beneficial if
The use of acetaminophen also exhibits opioid-sparing cesarean delivery is performed under general anesthesia, but
effects by up to 20% and has an additive effect when admin- not under spinal anesthesia.158 Continuous wound infiltration
istered concomitantly with NSAIDs.149 Scheduling NSAIDs improves pain on movement and reduces opioid use, but high
and acetaminophen after cesarean delivery confers greater infusion rates required to achieve this benefit lead to wound
reductions in supplemental opioid use compared to pro re leakage, and low patient and practitioner acceptability.158
nata administration.150 Risk for surgical site infection is not increased, but these stud-
ies have not been powered for this outcome.159 Continuous
Peripheral Nerve Blocks for Postcesarean Delivery Analgesia wound infusion is less effective than parenteral morphine and
When other postcesarean delivery pain management modali- NSAIDs.158 Most trials have not included neuraxial morphine
ties are compared to neuraxial morphine, neuraxial morphine comparisons, so no definitive comments can be made about
consistently performs best for analgesic quality (fig. 4). Nev- superiority to neuraxial morphine. Similar to other nerve
ertheless, alternative modes of postcesarean delivery analgesia blocks, trials comparing ilioinguinal-iliohypogastric blocks
have been proposed. Peripheral nerve blocks for Pfannenstiel to intrathecal morphine have not shown a benefit, but these
and low-transverse incisional pain have been examined, includ- blocks may have a role in rescue analgesia.160–163 Overall, while
ing transversus abdominis plane, quadratus lumborum, and multimodal analgesia with neuraxial morphine, NSAIDs, and
ilioinguinal-iliohypogastric blocks, and continuous wound acetaminophen is the gold standard for postcesarean deliv-
infiltration. Transversus abdominis plane block is not supe- ery pain, supplemental analgesia using transversus abdomi-
rior to intrathecal morphine for postcesarean delivery analge- nis plane, quadratus lumborum, ilioinguinal-iliohypogastric
sia. In a comparison of intrathecal morphine combined with blocks, or wound infiltration may be useful in cases of break-
ropivacaine transversus abdominis plane block to intrathecal through pain, or when the gold standard multimodal analgesia
morphine combined with a sham block, there were no differ- cannot be delivered (e.g., cesarean delivery under general anes-
ences in pain with movement at 24 h, and no differences in thesia, contraindications to NSAID administration).
supplemental opioid dose.151 Two meta-analyses concluded
that transversus abdominis plane block is not superior to intra-
Obstetric Anesthesia Outcomes
thecal morphine, but transversus abdominis plane block may
be useful when neuraxial morphine is not part of the pain man- Effects of Labor Analgesia on the Fetus
agement strategy (e.g., cesarean delivery with general anesthe- Fetal bradycardia is occasionally observed after initiation of
sia, contraindications to neuraxial morphine).152,153 The likely neuraxial labor analgesia. One trial found the incidence of
explanation for these findings is that transversus abdominis fetal bradycardia was higher after combined spinal-epidural

Fig. 4. Postcesarean delivery pain management options and anatomical locations of peripheral nerve blocks. PCEA = patient-
controlled epidural analgesia.
than epidural analgesia (32% vs. 6%), although the study was bupivacaine was underpowered to determine whether a differ-
limited by nonstandardized spinal dosing and monitoring for ence in fetal bradycardia exists.164 Whether the observed fetal
only 15 min after injection.8 One trial found fetal bradycardia heart rate abnormalities are tied to worse neonatal outcomes
was higher after intrathecal sufentanil 7.5 µg only compared is unclear. The mechanism of analgesia-mediated bradycar-
with sufentanil 1.5 µg combined with epinephrine 2.5 µg and dia is thought to be rapid decrease in circulating epinephrine
bupivacaine 2.5 mg. Although the authors concluded that the concentration with the onset of neuraxial analgesia. Epineph-
rate of fetal bradycardia was directly related to the intrathe- rine is a tocolytic, and its acute withdrawal may contribute to
cal sufentanil dose, this conclusion requires further study; the uterine tachysystole, reducing placental perfusion time (only
low-dose sufentanil was administered in combination with occurs in uterine diastole). Reassuringly, studies have not
other drugs (i.e., more than one variable was manipulated found a difference between combined spinal-epidural and
among groups). Importantly, there were no differences in neo- epidural techniques and emergency cesarean delivery.78,165
natal outcomes (Apgar score, umbilical artery pH).78 A 2016 The usual measures of in utero fetal resuscitation (change in
meta-analysis of 17 randomized trials found that fetal heart maternal position, intravenous fluid bolus, discontinuation
rate abnormalities are more likely to occur with combined of exogenous oxytocin) are usually successful in restoring fetal
spinal-epidural techniques; however, a sensitivity analysis heart rate. Occasionally, administration of a tocolytic (nitro-
including only studies that used low-concentration epidural glycerin, terbutaline) is necessary.
EDUCATION
Breastfeeding and other inflammatory cytokines.172 Besides increased risk

Neuraxial analgesia’s effect on breastfeeding is controver- for neonatal sepsis evaluation and prophylactic treatment, it
sial. Most studies are observational and results are conflict- is not clear whether labor epidural-associated fever impacts
ing; some have identified a negative association, some found short- or long-term adverse infant outcomes. Research is now
no relationship, and some found a positive relationship.166 focusing on the implications of noninfectious inflammation
Studies lack control for multiple confounding variables (e.g., on neonatal outcomes. Future work should also emphasize
dosing and type of analgesia, intrapartum interventions, diagnostic means to differentiate labor epidural-associated
timing and method of breastfeeding measurements, social fever from fever caused by chorioamnionitis and funisitis
support, maternal return-to-work status) known to influ- (inflammation within the umbilical cord), as the latter are
ence breastfeeding success. Factors likely more important known to be linked to poor neonatal outcomes.
than labor epidural analgesia include early maternal-infant

bonding, skin-to-skin contact, and breastfeeding support.167 Infant and Childhood Neurocognitive Outcomes
A randomized trial found that epidural infusion solutions Some observational studies have linked intrapartum anes-
containing fentanyl concentrations as high as 2 μg/ml for thetic exposure to autism spectrum disorders; others have
maintenance of labor analgesia did not impact rates of suc- failed to demonstrate this relationship.177–179 The challenges
cessful breastfeeding at six weeks postpartum.168 in conducting and interpreting these studies lie in the multi-
Breastfeeding outcomes after general versus neuraxial ple confounders which independently impact risk for autism
anesthesia for cesarean delivery are also unclear. In one study, spectrum disorders (e.g., maternal conditions requiring anes-
women receiving general and neuraxial anesthesia for cesar- thetic exposure, social environments dictating the same).
ean delivery were similarly successful at breastfeeding in the An imperative exists to determine the effects of maternal
immediate postpartum period (96% regional vs. 89% gen- anesthetic exposure on fetal, neonatal, and childhood neuro-
eral); however, at 6 months, fewer women who received gen- cognitive outcomes,180 but currently there is little evidence
eral anesthesia were breastfeeding (39% vs. 71%).169 Results that these considerations should change anesthetic clinical
were similar from an observational trial in Turkey, where decision-making during labor and delivery.
women self-select either general or neuraxial anesthesia for
cesarean delivery.170 However, women who self-select gen- Depression
eral anesthesia likely differ in other factors known to affect Several studies suggest labor analgesia interventions may
breastfeeding success. Postoperative pain control is likely be associated with reduced postpartum depression risk.181,182
important; postoperative epidural analgesia is linked to suc- In 2014, Ding et al. found that epidural labor analgesia
cessful breastfeeding and infant weight gain.171 in Chinese women was associated with a reduced risk for
postpartum depression (odds ratio 0.31; 95% CI, 0.12 to
Fever and Neonatal Sepsis Workup 0.82).181 There were several methodologic limitations to the
Labor neuraxial analgesia is associated with intrapartum study. The cohort may not have been depression-free upon
fever of noninfectious inflammatory origin. Multiple studies enrollment and there was a high loss-to-follow-up rate in
support that labor epidural analgesia is linked to clinical fever the epidural analgesia group, possibly inflating the protective
(temperatures greater than 38.0o C).172 Study limitations effect of epidural analgesia.
include uncontrolled factors such as obstetric management, Nevertheless, an established relationship between pain
selection bias, crossover and dropout, and measurement and depression exists in the nonobstetric population,182 and
error.172 Concerningly, maternal fever in general (not given the dearth of data on this relationship in obstetrics,
restricted to epidural-associated fever) is associated with additional research is needed. The link between labor pain
poor neonatal outcomes, including assisted ventilation, low and postpartum depression may be biologic; activation of
1- and 5-min Apgar scores, seizures, and hypotonia.172 These neural networks in psychologic pain overlap with physical
outcomes occur more commonly in women who receive epi- pain neural networks.182 Pain catastrophizing is known to
dural analgesia and had a fever, but not among women who be linked to severity of the experienced physical pain.182
received epidural analgesia and remained afebrile.173 Other data suggest that analgesia may explain the protec-
Neonatal sepsis evaluation and maternal and neonatal tive relationship between the use of labor neuraxial anal-
antibiotic exposure is significantly increased among mother- gesia and postpartum depression symptoms, although the
infant dyads with labor epidural-associated fever.174–176 relative influence of labor analgesia on postpartum depres-
Current evidence supports that maternal fever related to sion may be less than other established risk factors such
labor epidural analgesia is noninfectious and inflammatory as baseline anxiety or depression, obesity, and genital tract
in origin, mediated by cytokines. Among women receiv- trauma during delivery.183 An observational study noted a
ing labor epidural analgesia, those with elevated IL-6 lev- protective interaction effect for depression among women
els on admission are more likely to develop fever.172 Other who planned and actually used labor epidural analgesia;
proposed theories include local anesthetic agonism of the women who planned to avoid labor epidural analgesia, but
TRPV-1 (“capsaicin”) receptor, triggering the release of IL-6 ultimately requested and used it, had higher risk for positive
postpartum depression screening, but this relationship was levels should be undertaken; levels less than200 mg/dl should
thought mediated by difficult labor rather than unmet prompt aggressive monitoring and treatment. The American
expectations.184 In view of the uncertainty in existing lit- Society of Anesthesiologists guidelines specify that fibrino-
erature, coupled with plausible psychologic and biologic gen levels should be treated early in obstetric hemorrhage.192
mechanisms explaining the relationship between labor pain Over-transfusion and under-resuscitation both carry risks.
and postpartum depression, additional research is clearly Efforts aimed at avoiding over-transfusion are likely in the
indicated to determine the true relationship between labor best interest of the parturient as restrictive transfusion strate-
pain, labor analgesia, and postpartum depression; if a link gies are linked to lower risks for infections, cardiac events,
is established, targeted approaches using preventative labor and death.193,194 However, this goal must be balanced with
analgesic therapies for vulnerable women may prove to be risk of under-resuscitation, because maternal death from
protective for postpartum depression. hemorrhage is often attributable to delayed recognition and

under-resuscitation.102
Anesthesiology Contributions to Maternal Professional society guidelines for obstetric blood man-
Safety agement differ from each other and from nonobstetric
Mortality due to Anesthesia guidelines.191 The American College of Obstetricians and
Anesthesia-related maternal mortality has decreased signifi- Gynecologists specifically recommends cell salvage for
cantly over the last half-century. Maternal mortality ratios women with rare antibodies and if banked blood is not avail-
due to anesthesia in the United States are currently estimated able, and for women who refuse allogeneic transfusion.195
at 1.0 per million live births—a 59% reduction from the Cell salvage may also limit allogeneic blood consumption
period of 1979 to 1990.5 Morbidity and mortality associ- and be cost-saving.196,197 Point-of-care testing has gained
ated with modern-day anesthesia care are often associated attention for its potential use in postpartum hemorrhage due
with complications of neuraxial anesthesia (e.g., high or to rapid results and detection of hyperfibrinolysis. Viscoelas-
total spinal anesthesia after failed epidural anesthesia and tic tests (thromboelastography) may be useful in assessing
unrecognized spinal catheters).5,102,185 Importantly, anesthe- clot strength and thrombin generation.198 However, in major
siologists continue to play a key role in the prevention of obstetric hemorrhage, laboratory testing performed better
non–anesthesia-related direct and indirect maternal deaths, at detecting large aberrations in coagulation values, which
such as those caused by hemorrhage, hemodynamic instabil- correlated better with estimated blood loss, than thrombo-
ity, critical illness, and sepsis.5,102 elastography.199 Point-of-care testing to guide component
transfusion in obstetric hemorrhage may mitigate alloge-
Postpartum Hemorrhage and Patient Blood Management neic transfusion, but whether laboratory-guided transfusion
Postpartum hemorrhage is a leading cause of maternal mor- improves maternal outcomes has not been well studied.
bidity, cardiac arrest, and mortality worldwide. It accounts The administration of antifibrinolytic agents (tranexamic
for approximately 12.5% of pregnancy-related deaths (1.8 acid) in obstetric hemorrhage has received recent attention.
deaths per 100,000 live births) in the United States.186 Most Its prophylactic use in planned cesarean deliveries leads to
cases of hemorrhage-related maternal mortality are prevent- clinically insignificant bleeding differences.200 Thrombo-
able.186 Protocolized approaches to postpartum hemorrhage embolic complication data in this population have been
have been developed, which have been shown to result in lacking. In 2017, results were published from the World
improved outcomes in many settings.187 The National Part- Maternal Antifibrinolytic Trial, which compared tranexamic
nership for Maternal Safety is a multidisciplinary work group acid versus placebo in 20,060 women with a clinical diag-
including anesthesiologists, maternal-fetal medicine special- nosis of postpartum hemorrhage;201 198 hospitals in 21
ists, obstetricians, nurses, and nurse-midwives. The group countries were included, primarily low-resource settings
has provided a consensus bundle on best practices for obstet- with high rates of maternal hemorrhage deaths. Women
ric hemorrhage.188 Despite the evidence showing improve- randomly received tranexamic acid 1 g or placebo. Death
ment in outcomes, there appears to be limited adoption of due to hemorrhage was significantly reduced in women who
these protocols; in 2014, only 67% of academic obstetric received tranexamic acid (1.5% vs. 1.9%; risk ratio, 0.81;
anesthesia units in the United States reported the use of a 95% CI, 0.65 to 1.00; P = 0.045). The need for laparotomy
postpartum hemorrhage protocol, with greater use in hos- to control bleeding was reduced (risk ratio 0.64; 95% CI,
pitals with delivery volumes more than 3,000 per year.189 0.49 to 0.85; P = 0.002). Importantly, maternal death was
Additional work to identify barriers to protocol adoption reduced by 31% if tranexamic acid was given within 3 h of
in low-volume centers will shed light on implementation birth. Tranexamic acid was beneficial regardless of cause of
strategies. hemorrhage (e.g., trauma, atony). The risk of hysterectomy
Maternal hematologic physiology differs from the non- and thromboembolic events were not different. The authors
pregnant state; severe obstetric hemorrhage is more likely to be concluded that tranexamic acid should be given as soon as
associated with early hypofibrinogenemia.190,191 In the setting possible in postpartum hemorrhage regardless of cause, or
of postpartum hemorrhage, early assessment of fibrinogen after any bleeding associated with hemodynamic instability.
EDUCATION
This conclusion is consistent with our own clinical practice. early warning criteria in figure 5 were met. Anesthesia pro-
Tranexamic acid is likely safe in obstetrics; whether the ben- viders are instrumental to early hemorrhage recognition,
efit of preventing death due to bleeding can be extrapolated treatment, and implementation of Maternal Early Warning
to well-resourced countries is unknown. Systems and should actively participate in establishing these
systems.
Early Warning Systems
The Modified Early Obstetric Warning System was first Oxytocin Protocols
described and recommended by the United Kingdom’s Active management of the third stage of labor reduces
Confidential Enquiries into Maternal and Child Health, a postpartum hemorrhage risk. Prophylactic uterotonic agents
national program that investigated all maternal deaths and (oxytocin) are given and controlled umbilical cord traction
other adverse outcomes.102 The group recognized that late for placenta delivery is performed. Studies published in the

recognition of maternal morbidity was contributing to poor past decade, primarily by anesthesiologists, have identified
outcomes and recommended a warning/screening system safe methods for oxytocin administration for active manage-
that included vital signs parameters (e.g., temperature, blood ment of the third stage of labor. The motivation to provide
pressure, respirations, neurologic response, and urine out- safe oxytocin doses stems from the uncommon but severe
put). A study published in 2011 validated these parameters side effects associated with oxytocin, including dose-depen-
and established threshold for elevated morbidity.202 The dent cardiac conduction abnormalities, coronary vasospasm,
parameters performed well as a screening tool, with a sen- and severe acute hyponatremia leading to seizures (oxytocin
sitivity of 89%, specificity of 79%, and negative predictive bears structural similarity to vasopressin).205 Furthermore,
value of 98%. In the United States, modifications were pro- high doses of oxytocin are not necessary to achieve clini-
posed by the National Partnership for Maternal Safety, based cal gains for active management of the third stage of labor.
on expert consensus from a multidisciplinary group of obste- A randomized trial compared oxytocin administration using
tricians, nurses, midwives, and anesthesiologists.203,204 The a “rule-of-threes” algorithm to “wide open” infusion of oxyto-
group recommend immediate action if any of the maternal cin (30 units in 500 ml normal saline). In the “rule-of-threes”
Fig. 5. Maternal Early Warning Criteria. The presence of any of these abnormal “triggers” should activate an immediate bedside
evaluation by a physician or qualified clinician who can accelerate care toward prompt diagnosis and treatment of the underlying
condition. Considerations for potential differential diagnoses are noted. Any nurse or clinician who is concerned about maternal
status should feel empowered to raise concerns up the chain of command to achieve an appropriate response. Mechanisms for
escalating notifications should be established. The triggers listed are not comprehensive for all possible obstetrical scenarios
and are not intended to replace clinical judgement. Adapted with permission from Mhyre JM, D’Oria R, Hameed AB, Lappen JR,
Holley SL, Hunter SK, Jones RL, King JC, D’Alton ME: The maternal early warning criteria: a proposal from the national partner-
ship for maternal safety. Obstet Gynecol 2014; 124:782–6.204
group, a 3-unit/3 ml oxytocin bolus was administered imme- maternal event, and venous thromboembolism.216–218 Bundles
diately after cesarean delivery, with optional repeat boluses are based on the best available evidence and are endorsed by
of 3-unit/3 ml oxytocin at 3 min and at 6 min after delivery. multiple professional groups including the American College of
This approach resulted in uterine tone at 3, 6, 9, and 12 min Obstetricians and Gynecologists, the American Society of Anes-
after delivery that was no less adequate than standard treat- thesiologists, the American College of Nurse-Midwives, and the
ment. The control group received significantly more oxyto- Association of Women’s Health, Obstetric, and Neonatal Nurses,
cin, while there were no differences in blood loss or need for among others. Each bundle is organized into five major areas:
additional uterotonic agents.206 readiness, recognition, response, reporting, and systems learning.
Oxytocin is often given as an infusion due to its short The resources are free and openly available to the public at www.
half-life of 1 to 5 min, thus a low-dose infusion protocol has safehealthcareforeverywoman.org (accessed March 9, 2018).
been studied. George et al. estimated that the oxytocin infu- Given the anesthesia provider’s expertise in resuscitation and

sion ED90 for satisfactory uterine tone in women undergoing systems-based response, we are ideal participants in multidisci-
elective cesarean delivery is 0.3 units/ min (18 units/h).207 plinary shared leadership strategies to implement these bundles.
Pre–post studies following the institutional introduction of
low-dose oxytocin infusion protocols have found reduced Conclusions
total dose of oxytocin with no impact on rates of postpartum Advances in obstetric anesthesiology over the last decade
hemorrhage, volume of estimated blood loss, or secondary have spanned multiple areas. Enhancements in neuraxial
uterotonic administration.208,209 labor analgesic techniques, postpartum neuraxial pain
Oxytocin receptor desensitization may explain the risk management modalities, and prevention of intraoperative
for postpartum hemorrhage from refractory atony in intra- hypotension during cesarean delivery have contributed to
partum cesarean delivery following oxytocin exposure dur- improvements in care. Still more progress is needed in many
ing labor.210,211 In vitro tests involving human myometrial areas, including questions about acute postpartum pain and
strips exposed to 2 h of oxytocin pretreatment versus control its potential influence on chronic pain, the influence of
demonstrated that the motility index (frequency × ampli- labor pain on perinatal depression, labor epidural-associated
tude) of strips not exposed to oxytocin were significantly fever, and the impact of labor analgesia on the duration of
greater than those pretreated with oxytocin.212,213 In vitro the second stage of labor and instrumental vaginal delivery.
testing has not identified whether “resting periods” are effec- Current and future scientific work on individual physiologic
tive in resensitizing myometrium. Therefore, giving more characteristics of pain, labor progress, and other aspects of
oxytocin in the setting of desensitization may not achieve the obstetric care may enhance clinicians’ ability to personal-
desired effect of increased uterine tone; in these cases, a dif- ize obstetric anesthesia therapies and interventions. Com-
ferent uterotonic agent that works by a different mechanism parative effectiveness studies on diagnostic and treatment
is indicated. In another study, the ED90 of oxytocin infu- modalities for pain during labor and the puerperium, the
sion for women with prior labor exposure to oxytocin was progress of labor, and obstetric hemorrhage, as well as the
44 units/h, much higher than the ED90 for women without effects of these modalities on patient-centered outcomes,
prior exposure to oxytocin.214 However, this higher dose is are necessary as our discipline advances further into the
associated with more side effects, including nausea, vomit- twenty-first century.
ing, and ST segment depression. Further in vivo and in vitro
investigations may elucidate the clinical significance of oxy- Research Support
tocin desensitization, and may inform oxytocin protocols for Supported by the Department of Anesthesiology and the De-
women exposed to oxytocin during labor. partment of Obstetrics and Gynecology, University of Pitts-
burgh School of Medicine, Pittsburgh, Pennsylvania; Depart-
Safety Bundles ment of Anesthesiology, University of Iowa Carver College of
The National Partnership for Maternal Safety’s goal is to Medicine and McGovern Medical School, Iowa City, Iowa; and
by the Department of Anesthesiology, Northwestern Univer-
reduce maternal morbidity and mortality in the United States. sity Feinberg School of Medicine, Chicago, Illinois. Dr. Lim is
The United States is the only country in the developed world supported by an award from the NIH/ORWH Building Inter-
that has had increasing rates of maternal mortality since 1990. disciplinary Research Careers in Women’s Health (BIRCWH),
The maternal mortality ratio in the United States was 12.4 per NIH K12HD043441 and by the NIH Ruth Kirschstein National
100,000 live births (95% CI, 11.1 to 13.9) in 1990; by 2013, it Service Award, NIH T32MG075770. Dr. Eltzschig is supported
by National Institutes of Health grant Nos. R01-DK097075,
increased to 18.5 (95% CI, 14.8 to 22.9).215 Maternal morbidity R01-HL098294, POI-HL114457, R01-DK082509, R01-HL109233,
and mortality are frequently preventable, and guidance on best R01-DK109574, R01-HL119837, and R01-HL133900. Dr. Facco
practices is instrumental in preventing maternal deaths.187 The is supported by National Institutes of Health grant No. R01-
National Partnership for Maternal Safety has developed safety HL120354.
“bundles” for maternal care in the areas of obstetric hemor-
rhage, hypertension in pregnancy, perinatal depression and anxi- Competing Interests
ety, reduction of primary cesarean birth, support after a severe The authors declare no competing interests.
EDUCATION
Correspondence 16. Wong CA: Advances in labor analgesia. Int J Womens Health
2010; 1:139–54
Address correspondence to Dr. Lim: Department of Anes-
17. Sultan P, Murphy C, Halpern S, Carvalho B: The effect of
thesiology, Magee-Womens Hospital of UPMC, 300 Halket low concentrations versus high concentrations of local anes-
Street, Suite 3510, Pittsburgh, Pennsylvania 15213. limkg2@ thetics for labour analgesia on obstetric and anesthetic out-
upmc.edu. Information on purchasing reprints may be comes: A meta-analysis. Can J Anaesth 2013; 60:840–54
found at www.anesthesiology.org or on the masthead page 18. Wong CA: Epidural and spinal analgesia/Anesthesia for labor
at the beginning of this issue. ANESTHESIOLOGY’s articles are and vaginal delivery, Obstetric Anesthesia: Principles and
made freely accessible to all readers, for personal use only, Practice. Edited by Chestnut DH, Mosby, 2014, pp 490
6 months from the cover date of the issue. 19. Ngan Kee WD, Khaw KS, Ng FF, Ng KK, So R, Lee A:

Synergistic interaction between fentanyl and bupivacaine
References given intrathecally for labor analgesia. ANESTHESIOLOGY 2014;
120:1126–36
1. Caton D: John Snow’s practice of obstetric anesthesia.
20. Bremerich DH, Waibel HJ, Mierdl S, Meininger D, Byhahn

ANESTHESIOLOGY 2000; 92:247–52
C, Zwissler BC, Ackermann HH: Comparison of continuous
2. Caton D: The influence of social values on obstetric anesthe- background infusion plus demand dose and demand-only
sia. AMA J Ethics 2015; 17:253–7 parturient-controlled epidural analgesia (PCEA) using ropi-
3. Mendelson CL: The aspiration of stomach contents into the vacaine combined with sufentanil for labor and delivery. Int
lungs during obstetric anesthesia. Am J Obstet Gynecol 1946; J Obstet Anesth 2005; 14:114–20
52:191–205 21. Missant C, Teunkenst A, Vandermeersch E, Van de Velde M:
4. Thorp JA, Hu DH, Albin RM, McNitt J, Meyer BA, Cohen GR, Patient-controlled epidural analgesia following combined
Yeast JD: The effect of intrapartum epidural analgesia on nul- spinal-epidural analgesia in labour: The effects of adding a
liparous labor: A randomized, controlled, prospective trial. continuous epidural infusion. Anaesth Intensive Care 2005;
Am J Obstet Gynecol 1993; 169:851–8 33:452–6
5. Hawkins JL, Chang J, Palmer SK, Gibbs CP, Callaghan WM: 22. Wong CA, McCarthy RJ, Hewlett B: The effect of manipu-
Anesthesia-related maternal mortality in the United States: lation of the programmed intermittent bolus time interval
1979-2002. Obstet Gynecol 2011; 117:69–74 and injection volume on total drug use for labor epidural
6. Eltzschig HK, Lieberman ES, Camann WR: Regional anesthe- analgesia: A randomized controlled trial. Anesth Analg 2011;
sia and analgesia for labor and delivery. N Engl J Med 2003; 112:904–11
348:319–32 23. Capogna G, Camorcia M, Stirparo S, Farcomeni A:

7. Practice Guidelines for Obstetric Anesthesia: An Updated Programmed intermittent epidural bolus versus continuous
Report by the American Society of Anesthesiologists Task epidural infusion for labor analgesia: The effects on mater-
Force on Obstetric Anesthesia and the Society for Obstetric nal motor function and labor outcome. A randomized dou-
Anesthesia and Perinatology. ANESTHESIOLOGY 2016; 124: ble-blind study in nulliparous women. Anesth Analg 2011;
270–300 113:826–31
8. Abrão KC, Francisco RP, Miyadahira S, Cicarelli DD, Zugaib 24. McKenzie CP, Cobb B, Riley ET, Carvalho B: Programmed
M: Elevation of uterine basal tone and fetal heart rate abnor- intermittent epidural boluses for maintenance of labor anal-
malities after labor analgesia: A randomized controlled trial. gesia: An impact study. Int J Obstet Anesth 2016; 26:32–8
Obstet Gynecol 2009; 113:41–7 25. George RB, Allen TK, Habib AS: Intermittent epidural bolus
9. Simmons SW, Taghizadeh N, Dennis AT, Hughes D, Cyna compared with continuous epidural infusions for labor anal-
AM: Combined spinal-epidural versus epidural analgesia in gesia: A systematic review and meta-analysis. Anesth Analg
labour. Cochrane Database Syst Rev 2012; 10:CD003401 2013; 116:133–44
10. Booth JM, Pan JC, Ross VH, Russell GB, Harris LC, Pan PH: 26. Thornton JG, Capogna G: Reducing likelihood of instrumen-
Combined spinal epidural technique for labor analgesia does tal delivery with epidural anaesthesia. Lancet 2001; 358:2
not delay recognition of epidural catheter failures: A single-
27. Betti F, Carvalho B, Riley ET: Intrathecal migration of an

center retrospective cohort survival analysis. ANESTHESIOLOGY
epidural catheter while using a programmed intermittent
2016; 125:516–24
epidural bolus technique for labor analgesia maintenance: A
11. Bauer ME, Kountanis JA, Tsen LC, Greenfield ML, Mhyre JM: case report. A A Case Rep 2017; 9:357–9
Risk factors for failed conversion of labor epidural analge-
28. Carvalho B, George RB, Cobb B, McKenzie C, Riley ET:

sia to cesarean delivery anesthesia: A systematic review and
Implementation of programmed intermittent epidural bolus
meta-analysis of observational trials. Int J Obstet Anesth
for the maintenance of labor analgesia. Anesth Analg 2016;
2012; 21:294–309
123:965–71
12. Riley ET, Cohen SE, Macario A, Desai JB, Ratner EF: Spinal
29. Markley JC, Rollins MD: Non-neuraxial labor analgesia:

versus epidural anesthesia for cesarean section: A compari-
son of time efficiency, costs, charges, and complications. Options. Clin Obstet Gynecol 2017; 60:350–64
Anesth Analg 1995; 80:709–12 30. Stocki D, Matot I, Einav S, Eventov-Friedman S, Ginosar Y,
13. Heesen M, Van de Velde M, Klöhr S, Lehberger J, Rossaint Weiniger CF: A randomized controlled trial of the efficacy
R, Straube S: Meta-analysis of the success of block follow- and respiratory effects of patient-controlled intravenous
ing combined spinal-epidural vs epidural analgesia during remifentanil analgesia and patient-controlled epidural anal-
labour. Anaesthesia 2014; 69:64–71 gesia in laboring women. Anesth Analg 2014; 118:589–97
14. Cappiello E, O’Rourke N, Segal S, Tsen LC: A randomized 31. Tveit TO, Halvorsen A, Seiler S, Rosland JH: Efficacy and side
trial of dural puncture epidural technique compared with effects of intravenous remifentanil patient-controlled analge-
the standard epidural technique for labor analgesia. Anesth sia used in a stepwise approach for labour: An observational
Analg 2008; 107:1646–51 study. Int J Obstet Anesth 2013; 22:19–25
15. Chau A, Bibbo C, Huang CC, Elterman KG, Cappiello EC, 32. Douma MR, Verwey RA, Kam-Endtz CE, van der Linden PD,
Robinson JN, Tsen LC: Dural puncture epidural technique Stienstra R: Obstetric analgesia: A comparison of patient-con-
improves labor analgesia quality with fewer side effects trolled meperidine, remifentanil, and fentanyl in labour. Br J
compared with epidural and combined spinal epidural Anaesth 2010; 104:209–15
techniques: A randomized clinical trial. Anesth Analg 2017; 33. Weiniger CF, Carvalho B, Stocki D, Einav S: Analysis of

124:560–9 physiological respiratory variable alarm alerts among
laboring women receiving remifentanil. Anesth Analg 2017; 53. Wassen MM, Hukkelhoven CW, Scheepers HC, Smits LJ,

124:1211–8 Nijhuis JG, Roumen FJ: Epidural analgesia and opera-
34. Saravanakumar K, Garstang JS, Hasan K: Intravenous patient- tive delivery: A ten-year population-based cohort study in
controlled analgesia for labour: A survey of UK practice. Int The Netherlands. Eur J Obstet Gynecol Reprod Biol 2014;
J Obstet Anesth 2007; 16:221–5 183:125–31
35. Aaronson J, Abramovitz S, Smiley R, Tangel V, Landau R: A 54. Segal S, Su M, Gilbert P: The effect of a rapid change in avail-
survey of intravenous remifentanil use for labor analgesia at ability of epidural analgesia on the cesarean delivery rate: A
academic medical centers in the United States. Anesth Analg meta-analysis. Am J Obstet Gynecol 2000; 183:974–8
2017; 124:1208–10 55. Ramin SM, Gambling DR, Lucas MJ, Sharma SK, Sidawi JE,
36. Liu ZQ, Chen XB, Li HB, Qiu MT, Duan T: A comparison of Leveno KJ: Randomized trial of epidural versus intravenous
remifentanil parturient-controlled intravenous analgesia with analgesia during labor. Obstet Gynecol 1995; 86:783–9
epidural analgesia: A meta-analysis of randomized controlled 56. Bofill JA, Vincent RD, Ross EL, Martin RW, Norman PF,

trials. Anesth Analg 2014; 118:598–603 Werhan CF, Morrison JC: Nulliparous active labor, epidural
37. Marwah R, Hassan S, Carvalho JC, Balki M: Remifentanil ver- analgesia, and cesarean delivery for dystocia. Am J Obstet

sus fentanyl for intravenous patient-controlled labour analge- Gynecol 1997; 177:1465–70
sia: An observational study. Can J Anaesth 2012; 59:246–54 57. Halpern SH, Leighton BL, Ohlsson A, Barrett JF, Rice A: Effect
38. Likis FE, Andrews JC, Collins MR, Lewis RM, Seroogy JJ, Starr of epidural vs parenteral opioid analgesia on the progress of
SA, Walden RR, McPheeters ML: Nitrous oxide for the man- labor: A meta-analysis. JAMA 1998; 280:2105–10
agement of labor pain: A systematic review. Anesth Analg 58. Sharma SK, Leveno KJ: Update: Epidural analgesia does not
2014; 118:153–67 increase cesarean births. Curr Anesthesiol Rep 2000; 2:18–24
39. Attanasio L, Kozhimannil KB, Jou J, McPherson ME, Camann 59. Sharma SK, Alexander JM, Messick G, Bloom SL, McIntire
W: Women’s experiences with neuraxial labor analgesia in DD, Wiley J, Leveno KJ: Cesarean delivery: A randomized trial
the Listening to Mothers II survey: A content analysis of of epidural analgesia versus intravenous meperidine analge-
open-ended responses. Anesth Analg 2015; 121:974–80 sia during labor in nulliparous women. ANESTHESIOLOGY 2002;
40. King TL, Wong CA: Nitrous oxide for labor pain: Is it a laugh- 96:546–51
ing matter? Anesth Analg 2014; 118:12–4 60. Yancey MK, Pierce B, Schweitzer D, Daniels D: Observations
41. Collado V, Nicolas E, Faulks D, Hennequin M: A review of the on labor epidural analgesia and operative delivery rates. Am
safety of 50% nitrous oxide/oxygen in conscious sedation. J Obstet Gynecol 1999; 180(2 Pt 1):353–9
Expert Opin Drug Saf 2007; 6:559–71 61. Fogel ST, Shyken JM, Leighton BL, Mormol JS, Smeltzer JS:
42. Rooks JP: Safety and risks of nitrous oxide labor analgesia: A Epidural labor analgesia and the incidence of cesarean deliv-
review. J Midwifery Womens Health 2011; 56:557–65 ery for dystocia. Anesth Analg 1998; 87:119–23
43. Sanders RD, Weimann J, Maze M: Biologic effects of nitrous 62. Gribble RK, Meier PR: Effect of epidural analgesia on the
oxide: A mechanistic and toxicologic review. ANESTHESIOLOGY primary cesarean rate. Obstet Gynecol 1991; 78:231–4
2008; 109:707–22 63. Seyb ST, Berka RJ, Socol ML, Dooley SL: Risk of cesarean
44. Landau R, Cahana A, Smiley RM, Antonarakis SE, Blouin JL: delivery with elective induction of labor at term in nullipa-
Genetic variability of mu-opioid receptor in an obstetric pop- rous women. Obstet Gynecol 1999; 94:600–7
ulation. ANESTHESIOLOGY 2004; 100:1030–3 64. Wong CA, Scavone BM, Peaceman AM, McCarthy RJ, Sullivan
45. Camorcia M, Capogna G, Stirparo S, Berritta C, Blouin JL, JT, Diaz NT, Yaghmour E, Marcus RJ, Sherwani SS, Sproviero
Landau R: Effect of μ-opioid receptor A118G polymorphism MT, Yilmaz M, Patel R, Robles C, Grouper S: The risk of cesar-
on the ED50 of epidural sufentanil for labor analgesia. Int J ean delivery with neuraxial analgesia given early versus late
Obstet Anesth 2012; 21:40–4 in labor. N Engl J Med 2005; 352:655–65
46. Sia AT, Lim Y, Lim EC, Goh RW, Law HY, Landau R, Teo
65. Chestnut DH, McGrath JM, Vincent RD Jr, Penning DH, Choi
YY, Tan EC: A118G single nucleotide polymorphism of WW, Bates JN, McFarlane C: Does early administration of
human mu-opioid receptor gene influences pain percep- epidural analgesia affect obstetric outcome in nulliparous
tion and patient-controlled intravenous morphine consump- women who are in spontaneous labor? ANESTHESIOLOGY 1994;
tion after intrathecal morphine for postcesarean analgesia. 80:1201–8
ANESTHESIOLOGY 2008; 109:520–6 66. Chestnut DH, Vincent RD Jr, McGrath JM, Choi WW, Bates
47. Walter C, Lötsch J: Meta-analysis of the relevance of the
JN: Does early administration of epidural analgesia affect
OPRM1 118A>G genetic variant for pain treatment. Pain obstetric outcome in nulliparous women who are receiving
2009; 146:270–5 intravenous oxytocin? ANESTHESIOLOGY 1994; 80:1193–200
48. Terkawi AS, Jackson WM, Hansoti S, Tabassum R, Flood P: 67. Luxman D, Wolman I, Groutz A, Cohen JR, Lottan M, Pauzner
Polymorphism in the ADRB2 gene explains a small por- D, David MP: The effect of early epidural block administra-
tion of intersubject variability in pain relative to cervical tion on the progression and outcome of labor. Int J Obstet
dilation in the first stage of labor. ANESTHESIOLOGY 2014; Anesth 1998; 7:161–4
121:140–8 68. Ohel G, Gonen R, Vaida S, Barak S, Gaitini L: Early versus
49. Terkawi AS, Jackson WM, Thiet MP, Hansoti S, Tabassum R, late initiation of epidural analgesia in labor: does it increase
Flood P: Oxytocin and catechol-O-methyltransferase recep- the risk of cesarean section? A randomized trial. Am J Obstet
tor genotype predict the length of the first stage of labor. Am Gynecol 2006; 194:600–5
J Obstet Gynecol 2012; 207:184.e1–8 69. Wang F, Shen X, Guo X, Peng Y, Gu X; Labor Analgesia

50. Goetzinger KR, Macones GA: Operative vaginal delivery:
Examining Group: Epidural analgesia in the latent phase of
Current trends in obstetrics. Womens Health (Lond) 2008; labor and the risk of cesarean delivery: A five-year random-
4:281–90 ized controlled trial. ANESTHESIOLOGY 2009; 111:871–80
51. Anim-Somuah M, Smyth RM, Jones L: Epidural versus non- 70. Wong CA, McCarthy RJ, Sullivan JT, Scavone BM, Gerber SE,
epidural or no analgesia in labour. Cochrane Database Syst Yaghmour EA: Early compared with late neuraxial analgesia
Rev 2011:CD000331 in nulliparous labor induction: A randomized controlled trial.
52. Comparative Obstetric Mobile Epidural Trial Study Group
Obstet Gynecol 2009; 113:1066–74
UK: Effect of low-dose mobile versus traditional epidural 71. Alexander JM, Sharma SK, McIntire DD, Wiley J, Leveno KJ:
techniques on mode of delivery: A randomised controlled Intensity of labor pain and cesarean delivery. Anesth Analg
trial. Lancet 2001; 358:19–23 2001; 92:1524–8
EDUCATION
72. Hess PE, Pratt SD, Soni AK, Sarna MC, Oriol NE: An associa- 88. American College of O, Gynecologists, Society for Maternal-
tion between severe labor pain and cesarean delivery. Anesth Fetal M: Obstetric care consensus no. 1: Safe prevention
Analg 2000; 90:881–6 of the primary cesarean delivery. Obstet Gynecol 2014;
73. Panni MK, Segal S: Local anesthetic requirements are greater 123:693–711
in dystocia than in normal labor. ANESTHESIOLOGY 2003; 89. Magro-Malosso ER, Saccone G, Di Tommaso M, Mele M,
98:957–63 Berghella V: Neuraxial analgesia to increase the success
74. Sharma SK, McIntire DD, Wiley J, Leveno KJ: Labor analgesia rate of external cephalic version: A systematic review and
and cesarean delivery: An individual patient meta-analysis of meta-analysis of randomized controlled trials. Am J Obstet
nulliparous women. ANESTHESIOLOGY 2004; 100:142–8; discus- Gynecol 2016; 215:276–86
sion 6A 90. Hofmeyr GJ: Interventions to help external cephalic version
75. Wang TT, Sun S, Huang SQ: Effects of epidural labor analge- for breech presentation at term. Cochrane Database Syst
sia with low concentrations of local anesthetics on obstetric Rev 2004:CD000184
outcomes: A systematic review and meta-analysis of random- 91. Cluver C, Hofmeyr GJ, Gyte GM, Sinclair M: Interventions
ized controlled trials. Anesth Analg 2017; 124:1571–80 for helping to turn term breech babies to head first pre-

76. Cheek TG, Samuels P, Miller F, Tobin M, Gutsche BB: Normal sentation when using external cephalic version. Cochrane
saline i.v. fluid load decreases uterine activity in active Database Syst Rev 2012; 1:CD000184
labour. Br J Anaesth 1996; 77:632–5 92. Sultan P, Carvalho B: Neuraxial blockade for external
77. Rahm VA, Hallgren A, Högberg H, Hurtig I, Odlind V: Plasma cephalic version: A systematic review. Int J Obstet Anesth
oxytocin levels in women during labor with or without epi- 2011; 20:299–306
dural analgesia: A prospective study. Acta Obstet Gynecol 93. Lavoie A, Guay J: Anesthetic dose neuraxial blockade
Scand 2002; 81:1033–9 increases the success rate of external fetal version: A meta-
78. Van de Velde M, Teunkens A, Hanssens M, Vandermeersch analysis. Can J Anaesth 2010; 57:408–14
E, Verhaeghe J: Intrathecal sufentanil and fetal heart rate 94. Chalifoux LA, Bauchat JR, Higgins N, Toledo P, Peralta FM,
abnormalities: A double-blind, double placebo-controlled Farrer J, Gerber SE, McCarthy RJ, Sullivan JT: Effect of intra-
trial comparing two forms of combined spinal epidural anal- thecal bupivacaine dose on the success of external cephalic
gesia with epidural analgesia in labor. Anesth Analg 2004; version for breech presentation: A prospective, random-
98:1153–9 ized, blinded clinical trial. ANESTHESIOLOGY 2017; 127:625–32
79. Pan PH, Eisenach JC: The pain of childbirth and its effect on 95. Carvalho B, Tan JM, Macario A, El-Sayed YY, Sultan P: Brief
the mother and the fetus, Chestnut’s Obstetric Anesthesia: report: A cost analysis of neuraxial anesthesia to facilitate
Principles and Practice, Fifth edition. Edited by Chestnut DH. external cephalic version for breech fetal presentation.
Philadelphia, PA, Elsevier Saunders, 2014, pp 421 Anesth Analg 2013; 117:155–9
80. Cheng YW, Shaffer BL, Nicholson JM, Caughey AB: Second 96. Van Thiel DH, Gavaler JS, Stremple J: Lower esophageal
stage of labor and epidural use: A larger effect than previ- sphincter pressure in women using sequential oral contra-
ously suggested. Obstet Gynecol 2014; 123:527–35 ceptives. Gastroenterology 1976; 71:232–4
81. Zhang J, Landy HJ, Branch DW, Burkman R, Haberman S, 97. Fisher RS, Roberts GS, Grabowski CJ, Cohen S: Altered
Gregory KD, Hatjis CG, Ramirez MM, Bailit JL, Gonzalez- lower esophageal sphincter function during early preg-
Quintero VH, Hibbard JU, Hoffman MK, Kominiarek M, nancy. Gastroenterology 1978; 74:1233–7
Learman LA, Van Veldhuisen P, Troendle J, Reddy UM; 98. Chiloiro M, Darconza G, Piccioli E, De Carne M, Clemente
Consortium on Safe Labor: Contemporary patterns of sponta- C, Riezzo G: Gastric emptying and orocecal transit time in
neous labor with normal neonatal outcomes. Obstet Gynecol pregnancy. J Gastroenterol 2001; 36:538–43
2010; 116:1281–7
99. Wong CA, Loffredi M, Ganchiff JN, Zhao J, Wang Z,
82. Derham RJ, Crowhurst J, Crowther C: The second stage of Avram MJ: Gastric emptying of water in term pregnancy.
labour: Durational dilemmas. Aust N Z J Obstet Gynaecol ANESTHESIOLOGY 2002; 96:1395–400
1991; 31:31–6
100. Porter JS, Bonello E, Reynolds F: The influence of epidural
83. Menticoglou SM, Manning F, Harman C, Morrison I: Perinatal
administration of fentanyl infusion on gastric emptying in
outcome in relation to second-stage duration. Am J Obstet
labour. Anaesthesia 1997; 52:1151–6
Gynecol 1995; 173(3 Pt 1):906–12
101. Lewis G: Saving mothers’ lives: The continuing benefits for
84. Saunders NS, Paterson CM, Wadsworth J: Neonatal and

maternal health from the United Kingdom (UK) Confidential
maternal morbidity in relation to the length of the second
Enquires into Maternal Deaths. Semin Perinatol 2012; 36:19–26
stage of labour. Br J Obstet Gynaecol 1992; 99:381–5
102. Cantwell R, Clutton-Brock T, Cooper G, Dawson A, Drife J,
85. Grobman WA, Bailit J, Lai Y, Reddy UM, Wapner RJ, Varner
Garrod D, Harper A, Hulbert D, Lucas S, McClure J, Millward-
MW, Caritis SN, Prasad M, Tita AT, Saade G, Sorokin Y, Rouse
Sadler H, Neilson J, Nelson-Piercy C, Norman J, O’Herlihy
DJ, Blackwell SC, Tolosa JE; Eunice Kennedy Shriver National
C, Oates M, Shakespeare J, de Swiet M, Williamson C,
Institute of Child Health and Human Development (NICHD)
Beale V, Knight M, Lennox C, Miller A, Parmar D, Rogers
Maternal-Fetal Medicine Units (MFMU) Network: Association
J, Springett A: Saving mothers’ lives: Reviewing maternal
of the duration of active pushing with obstetric outcomes.
deaths to make motherhood safer: 2006–2008. The Eighth
Obstet Gynecol 2016; 127:667–73
Report of the Confidential Enquiries into Maternal Deaths
86. Rouse DJ, Weiner SJ, Bloom SL, Varner MW, Spong CY,
in the United Kingdom. BJOG 2011; 118 Suppl 1:1–203
Ramin SM, Caritis SN, Peaceman AM, Sorokin Y, Sciscione A,
103. Davies JM, Posner KL, Lee LA, Cheney FW, Domino KB:
Carpenter MW, Mercer BM, Thorp JM Jr, Malone FD, Harper
Liability associated with obstetric anesthesia: A closed
M, Iams JD, Anderson GD; Eunice Kennedy Shriver National
claims analysis. ANESTHESIOLOGY 2009; 110:131–9
Institute of Child Health and Human Development Maternal-
Fetal Medicine Units Network: Second-stage labor duration 104. Sperling JD, Dahlke JD, Sibai BM: Restriction of oral intake
in nulliparous women: Relationship to maternal and perina- during labor: Whither are we bound? Am J Obstet Gynecol
tal outcomes. Am J Obstet Gynecol 2009; 201:357.e1–7 2016; 214:592–6
87. Le Ray C, Audibert F, Goffinet F, Fraser W: When to stop 105. Care in normal birth: a practical guide. Technical Working
pushing: Effects of duration of second-stage expulsion Group, World Health Organization, Birth, 1997, pp 121–3
efforts on maternal and neonatal outcomes in nulliparous 106. Metzger BE, Ravnikar V, Vileisis RA, Freinkel N: “Accelerated
women with epidural analgesia. Am J Obstet Gynecol 2009; starvation” and the skipped breakfast in late normal preg-
201:361.e1–7 nancy. Lancet 1982; 1:588–92
107. Kubli M, Scrutton MJ, Seed PT, O’Sullivan G: An evaluation 125. Macarthur A, Riley ET: Obstetric anesthesia controversies:
of isotonic “sport drinks” during labor. Anesth Analg 2002; Vasopressor choice for postspinal hypotension during
94:404–8 cesarean delivery. Int Anesthesiol Clin 2007; 45:115–32
108. O’Sullivan G, Liu B, Hart D, Seed P, Shennan A: Effect of food 126. Habib AS: A review of the impact of phenylephrine admin-
intake during labour on obstetric outcome: Randomised istration on maternal hemodynamics and maternal and
controlled trial. BMJ 2009; 338:b784 neonatal outcomes in women undergoing cesarean delivery
109. Scrutton MJ, Metcalfe GA, Lowy C, Seed PT, O’Sullivan G: under spinal anesthesia. Anesth Analg 2012; 114:377–90
Eating in labour. A randomised controlled trial assessing 127. Ngan Kee WD: The use of vasopressors during spinal anaes-
the risks and benefits. Anaesthesia 1999; 54:329–34 thesia for caesarean section. Curr Opin Anaesthesiol 2017;
110. Malin GL, Bugg GJ, Thornton J, Taylor MA, Grauwen N,
30:319–25
Devlieger R, Kardel KR, Kubli M, Tranmer JE, Jones NW: 128. Smiley RM: More perfect? Int J Obstet Anesth 2017; 29:1–4
Does oral carbohydrate supplementation improve labour 129. Higgins N, Fitzgerald PC, van Dyk D, Dyer RA, Rodriguez
outcome? A systematic review and individual patient data N, McCarthy RJ, Wong CA: The effect of prophylactic phen-
meta-analysis. BJOG 2016; 123:510–7 ylephrine and ephedrine infusions on umbilical artery

111. Singata M, Tranmer J, Gyte GM: Restricting oral fluid and blood pH in women with preeclampsia undergoing cesar-
food intake during labour. Cochrane Database Syst Rev ean delivery with spinal anesthesia: A randomized, double-
2013:CD003930 blind trial. Anesth Analg 2017 Sep 25 [Epub ahead of print]
112. Garry M, Davies S: Failure of regional blockade for caesar- 130. Dyer RA, Emmanuel A, Adams SC, Lombard CJ, Arcache MJ,
ean section. Int J Obstet Anesth 2002; 11:9–12 Vorster A, Wong CA, Higgins N, Reed AR, James MF, Joolay
113. Norris MC: Patient variables and the subarachnoid
Y, Schulein S, van Dyk D: A randomised comparison of
spread of hyperbaric bupivacaine in the term parturient. bolus phenylephrine and ephedrine for the management
ANESTHESIOLOGY 1990; 72:478–82 of spinal hypotension in patients with severe preeclampsia
and fetal compromise. Int J Obstet Anesth 2018; 33:23–31
114. Dahlgren G, Hultstrand C, Jakobsson J, Norman M, Eriksson
EW, Martin H: Intrathecal sufentanil, fentanyl, or placebo 131. Ngan Kee WD, Lee SW, Ng FF, Tan PE, Khaw KS: Randomized
added to bupivacaine for cesarean section. Anesth Analg double-blinded comparison of norepinephrine and phen-
1997; 85:1288–93 ylephrine for maintenance of blood pressure during spi-
nal anesthesia for cesarean delivery. ANESTHESIOLOGY 2015;
115. Palmer CM, Emerson S, Volgoropolous D, Alves D: Dose-
response relationship of intrathecal morphine for postc- 122:736–45
esarean analgesia. ANESTHESIOLOGY 1999; 90:437–44 132. Ngan Kee WD: A random-allocation graded dose-response
study of norepinephrine and phenylephrine for treating
116. Abouleish EI: Epinephrine improves the quality of spinal
hypotension during spinal anesthesia for cesarean delivery.
hyperbaric bupivacaine for cesarean section. Anesth Analg
ANESTHESIOLOGY 2017; 127:934–41
1987; 66:395–400
117. Lavand’homme PM, Roelants F, Waterloos H, Collet V, De 133. Khaw KS, Wang CC, Ngan Kee WD, Pang CP, Rogers MS:
Kock MF: An evaluation of the postoperative antihyperal- Effects of high inspired oxygen fraction during elective cae-
gesic and analgesic effects of intrathecal clonidine adminis- sarean section under spinal anaesthesia on maternal and
tered during elective cesarean delivery. Anesth Analg 2008; fetal oxygenation and lipid peroxidation. Br J Anaesth 2002;
107:948–55 88:18–23
118. Purva M, Russell I, Kinsella M: 8.8 Caesarean section anaes- 134. Solberg R, Andresen JH, Escrig R, Vento M, Saugstad OD:
thesia: Technique and failure rate, Raising the Standard: Resuscitation of hypoxic newborn piglets with oxygen
A Compendium of Audit Recipes for Continuous Quality induces a dose-dependent increase in markers of oxidation.
Improvement in Anaesthesia, 3rd edition. Edited by Colvin Pediatr Res 2007; 62:559–63
JR, Peden CJ. London, England, 2012, pp 220–221 135. Duggal N, Poddatoori V, Poddatorri V, Noroozkhani S,

119. Dyer RA, Reed AR, van Dyk D, Arcache MJ, Hodges O,
Siddik-Ahmad RI, Caughey AB: Perioperative oxygen sup-
Lombard CJ, Greenwood J, James MF: Hemodynamic plementation and surgical site infection after cesarean deliv-
effects of ephedrine, phenylephrine, and the coadministra- ery: A randomized trial. Obstet Gynecol 2013; 122:79–84
tion of phenylephrine with oxytocin during spinal anes- 136. Chatmongkolchart S, Prathep S: Supplemental oxygen for
thesia for elective cesarean delivery. ANESTHESIOLOGY 2009; caesarean section during regional anaesthesia. Cochrane
111:753–65 Database Syst Rev 2016; 3:CD006161
120. Hall PA, Bennett A, Wilkes MP, Lewis M: Spinal anaesthesia 137. Carvalho B, Zheng M, Harter S, Sultan P: A prospective

for caesarean section: Comparison of infusions of phenyl- cohort study evaluating the ability of anticipated pain,
ephrine and ephedrine. Br J Anaesth 1994; 73:471–4 perceived analgesic needs, and psychological traits to pre-
dict pain and analgesic usage following cesarean delivery.
121. LaPorta RF, Arthur GR, Datta S: Phenylephrine in treating
Anesthesiol Res Pract 2016; 2016:7948412
maternal hypotension due to spinal anaesthesia for caesar-
ean delivery: Effects on neonatal catecholamine concentra- 138. Pan PH, Tonidandel AM, Aschenbrenner CA, Houle TT,

tions, acid base status and Apgar scores. Acta Anaesthesiol Harris LC, Eisenach JC: Predicting acute pain after cesarean
Scand 1995; 39:901–5 delivery using three simple questions. ANESTHESIOLOGY 2013;
122. Lee A, Ngan Kee WD, Gin T: A quantitative, systematic
118:1170–9
review of randomized controlled trials of ephedrine versus 139. Booth JL, Harris LC, Eisenach JC, Pan PH: A randomized
phenylephrine for the management of hypotension during controlled trial comparing two multimodal analgesic tech-
spinal anesthesia for cesarean delivery. Anesth Analg 2002; niques in patients predicted to have severe pain after cesar-
94:920–6, table of contents ean delivery. Anesth Analg 2016; 122:1114–9
123. Ngan Kee WD, Khaw KS, Ng FF: Comparison of phenyl- 140. Sutton CD, Carvalho B: Optimal pain management after

ephrine infusion regimens for maintaining maternal blood cesarean delivery. Anesthesiol Clin 2017; 35:107–24
pressure during spinal anaesthesia for Caesarean section. 141. Cohen SE, Subak LL, Brose WG, Halpern J: Analgesia after
Br J Anaesth 2004; 92:469–74 cesarean delivery: Patient evaluations and costs of five opi-
124. Ngan Kee WD, Khaw KS, Tan PE, Ng FF, Karmakar MK: oid techniques. Reg Anesth 1991; 16:141–9
Placental transfer and fetal metabolic effects of phenyleph- 142. Lim Y, Jha S, Sia AT, Rawal N: Morphine for post-caesar-
rine and ephedrine during spinal anesthesia for cesarean ean section analgesia: Intrathecal, epidural or intravenous?
delivery. ANESTHESIOLOGY 2009; 111:506–12 Singapore Med J 2005; 46:392–6
EDUCATION
143. Carvalho B: Respiratory depression after neuraxial opioids ilioinguinal-iliohypogastric block with intrathecal mor-
in the obstetric setting. Anesth Analg 2008; 107:956–61 phine for postoperative cesarean delivery analgesia.
144. Pöpping DM, Elia N, Marret E, Wenk M, Tramèr MR: Opioids ScientificWorldJournal 2012; 2012:107316
added to local anesthetics for single-shot intrathecal anes- 161. Coffman JC, Fiorini K, Small RH: Ilioinguinal-iliohypogastric
thesia in patients undergoing minor surgery: A meta-analy- block used to rescue ineffective transversus abdominis
sis of randomized trials. Pain 2012; 153:784–93 plane block after cesarean delivery. Int J Obstet Anesth
145. Sultan P, Halpern SH, Pushpanathan E, Patel S, Carvalho B: 2015; 24:394–5
The effect of intrathecal morphine dose on outcomes after 162. Kim ES, Kim HK, Baik JS, Ji YT: Continuous ilioinguinal-
elective cesarean delivery: A meta-analysis. Anesth Analg iliohypogastric nerve block for groin pain in a breast-
2016; 123:154–64 feeding patient after cesarean delivery. Korean J Pain 2016;
146. Marret E, Kurdi O, Zufferey P, Bonnet F: Effects of nonste- 29:193–6
roidal antiinflammatory drugs on patient-controlled anal- 163. Naghshineh E, Shiari S, Jabalameli M: Preventive effect of
gesia morphine side effects: Meta-analysis of randomized ilioinguinal nerve block on postoperative pain after cesar-
controlled trials. ANESTHESIOLOGY 2005; 102:1249–60 ean section. Adv Biomed Res 2015; 4:229

147. TORADOL(R), ketorolac tromethamine [package insert].
164. Hattler J, Klimek M, Rossaint R, Heesen M: The effect of
Nutley, New Jersey: Roche Laboratories; 2013. Reference combined spinal-epidural versus epidural analgesia in
ID: 3281582. 1–27 laboring women on nonreassuring fetal heart rate tracings:
148. American Academy of Pediatrics Committee on D: Transfer Systematic review and meta-analysis. Anesth Analg 2016;
of drugs and other chemicals into human milk. Pediatrics 123:955–64
2001; 108:776–89 165. Mardirosoff C, Dumont L, Boulvain M, Tramèr MR: Fetal

149. Ong CK, Seymour RA, Lirk P, Merry AF: Combining
bradycardia due to intrathecal opioids for labour analgesia:
paracetamol (acetaminophen) with nonsteroidal antiinflam- A systematic review. BJOG 2002; 109:274–81
matory drugs: A qualitative systematic review of analgesic 166. French CA, Cong X, Chung KS: Labor epidural analgesia
efficacy for acute postoperative pain. Anesth Analg 2010; and breastfeeding: A systematic review. J Hum Lact 2016;
110:1170–9 32:507–20
150. Valentine AR, Carvalho B, Lazo TA, Riley ET: Scheduled
167. Chang ZM, Heaman MI: Epidural analgesia during labor

acetaminophen with as-needed opioids compared to as- and delivery: Effects on the initiation and continuation of
needed acetaminophen plus opioids for post-cesarean pain effective breastfeeding. J Hum Lact 2005; 21:305–14; quiz
management. Int J Obstet Anesth 2015; 24:210–6 315–9, 326
151. Costello JF, Moore AR, Wieczorek PM, Macarthur AJ, Balki 168. Lee AI, McCarthy RJ, Toledo P, Jones MJ, White N, Wong CA:
M, Carvalho JC: The transversus abdominis plane block, Epidural labor analgesia-fentanyl dose and breastfeeding
when used as part of a multimodal regimen inclusive of success: A randomized clinical trial. ANESTHESIOLOGY 2017;
intrathecal morphine, does not improve analgesia after 127:614–24
cesarean delivery. Reg Anesth Pain Med 2009; 34:586–9 169. Lie B, Juul J: Effect of epidural vs. general anesthesia on
152. Abdallah FW, Halpern SH, Margarido CB: Transversus
breastfeeding. Acta Obstet Gynecol Scand 1988; 67:207–9
abdominis plane block for postoperative analgesia after 170. Kutlucan L, Seker İS, Demiraran Y, Ersoy Ö, Karagöz İ,

Caesarean delivery performed under spinal anaesthesia? Sezen G, Köse SA: Effects of different anesthesia protocols
A systematic review and meta-analysis. Br J Anaesth 2012; on lactation in the postpartum period. J Turk Ger Gynecol
109:679–87 Assoc 2014; 15:233–8
153. Mishriky BM, George RB, Habib AS: Transversus abdom- 171. Hirose M, Hara Y, Hosokawa T, Tanaka Y: The effect of post-
inis plane block for analgesia after Cesarean delivery: A operative analgesia with continuous epidural bupivacaine
systematic review and meta-analysis. Can J Anaesth 2012; after cesarean section on the amount of breast feeding and
59:766–78 infant weight gain. Anesth Analg 1996; 82:1166–9
154. Mirza F, Carvalho B: Transversus abdominis plane blocks 172. Arendt KW, Segal BS: The association between epidural labor
for rescue analgesia following Cesarean delivery: A case analgesia and maternal fever. Clin Perinatol 2013; 40:385–98
series. Can J Anaesth 2013; 60:299–303 173. Petrova A, Demissie K, Rhoads GG, Smulian JC, Marcella
155. Griffiths JD, Le NV, Grant S, Bjorksten A, Hebbard P, Royse S, Ananth CV: Association of maternal fever during labor
C: Symptomatic local anaesthetic toxicity and plasma with neonatal and infant morbidity and mortality. Obstet
ropivacaine concentrations after transversus abdominis Gynecol 2001; 98:20–7
plane block for Caesarean section. Br J Anaesth 2013; 174. Kaul B, Vallejo M, Ramanathan S, Mandell G: Epidural labor
110:996–1000 analgesia and neonatal sepsis evaluation rate: A quality
156. Blanco R, Ansari T, Girgis E: Quadratus lumborum block for improvement study. Anesth Analg 2001; 93:986–90
postoperative pain after caesarean section: A randomised 175. Lieberman E, Lang JM, Frigoletto F Jr, Richardson DK,

controlled trial. Eur J Anaesthesiol 2015; 32:812–8 Ringer SA, Cohen A: Epidural analgesia, intrapartum fever,
157. Blanco R, Ansari T, Riad W, Shetty N: Quadratus lumbo- and neonatal sepsis evaluation. Pediatrics 1997; 99:415–9
rum block versus transversus abdominis plane block for 176. Mayer DC, Chescheir NC, Spielman FJ: Increased intrapar-
postoperative pain after cesarean delivery: A randomized tum antibiotic administration associated with epidural anal-
controlled trial. Reg Anesth Pain Med 2016; 41:757–62 gesia in labor. Am J Perinatol 1997; 14:83–6
158. Bamigboye AA, Hofmeyr GJ: Local anaesthetic wound infil- 177. Bilder D, Pinborough-Zimmerman J, Miller J, McMahon W:
tration and abdominal nerves block during caesarean sec- Prenatal, perinatal, and neonatal factors associated with
tion for postoperative pain relief. Cochrane Database Syst autism spectrum disorders. Pediatrics 2009; 123:1293–300
Rev 2009:CD006954 178. Flick RP, Lee K, Hofer RE, Beinborn CW, Hambel EM,

159. Tharwat AA, Yehia AH, Wahba KA, Ali AE: Efficacy and
Klein MK, Gunn PW, Wilder RT, Katusic SK, Schroeder DR,
safety of post-cesarean section incisional infiltration with Warner DO, Sprung J: Neuraxial labor analgesia for vaginal
lidocaine and epinephrine versus lidocaine alone in reduc- delivery and its effects on childhood learning disabilities.
ing postoperative pain: A randomized controlled double- Anesth Analg 2011; 112:1424–31
blinded clinical trial. J Turk Ger Gynecol Assoc 2016; 17:1–5 179. Hattori R, Desimaru M, Nagayama I, Inoue K: Autistic and
160. Vallejo MC, Steen TL, Cobb BT, Phelps AL, Pomerantz
developmental disorders after general anaesthetic delivery.
JM, Orebaugh SL, Chelly JE: Efficacy of the bilateral Lancet 1991; 337:1357–8
180. American Society of Anesthesiologists: ASA Response to

196. Albright CM, Rouse DJ, Werner EF: Cost savings of red cell
the FDA Med Watch Warning. Available at: https://www. salvage during cesarean delivery. Obstet Gynecol 2014;
asahq.org/advocacy/fda-and-washington-alerts/washing- 124:690–6
ton-alerts/2016/12/asa-response-to-the-fda-med-watch. 197. Waters JH, Lee JS, Karafa MT: A mathematical model of

Accessed March 13, 2018 cell salvage compared and combined with normovolemic
181. Ding T, Wang DX, Qu Y, Chen Q, Zhu SN: Epidural labor hemodilution. Transfusion 2004; 44:1412–6
analgesia is associated with a decreased risk of postpartum 198. Butwick A, Ting V, Ralls LA, Harter S, Riley E: The associa-
depression: a prospective cohort study. Anesth Analg 2014; tion between thromboelastographic parameters and total
119:383–92 estimated blood loss in patients undergoing elective cesar-
182. Wisner KL, Stika CS, Clark CT: Double duty: Does epidural ean delivery. Anesth Analg 2011; 112:1041–7
labor analgesia reduce both pain and postpartum depres- 199. Karlsson O, Jeppsson A, Hellgren M: Major obstetric haem-
sion? Anesth Analg 2014; 119:219–21 orrhage: Monitoring with thromboelastography, laboratory
183. Lim G, Farrell LM, Facco FL, Gold MS, Wasan AD: Labor analyses or both? Int J Obstet Anesth 2014; 23:10–7
analgesia as a predictor for reduced postpartum depression 200. Novikova N, Hofmeyr GJ, Cluver C: Tranexamic acid for pre-

scores: A retrospective observational study. Anesth Analg venting postpartum haemorrhage. Cochrane Database Syst
2017 Dec 11 [Epub ahead of print] Rev 2015:CD007872
184. Orbach-Zinger S, Landau R, Harousch AB, Ovad O, Caspi 201. Collaborators TWT: Effect of early tranexamic acid admin-
L, Kornilov E, Ioscovich A, Bracco D, Davis A, Fireman S, istration on mortality, hysterectomy, and other morbidities
Hoshen M, Eidelman LA: The relationship between wom- in women with post-partum haemorrhage (WOMAN): An
en’s intention to request a labor epidural analgesia, actually international, randomised, double-blind, placebo-controlled
delivering with labor epidural analgesia, and postpartum trial. Lancet 2017; 389:2105–16
depression at 6 weeks: A prospective observational study.
202. Singh S, McGlennan A, England A, Simons R: A validation
Anesth Analg 2017 Sep 19 [Epub ahead of print]
study of the CEMACH recommended modified early obstet-
185. D’Angelo R, Smiley RM, Riley ET, Segal S: Serious complica- ric warning system (MEOWS). Anaesthesia 2012; 67:12–8
tions related to obstetric anesthesia: The serious complica-
tion repository project of the Society for Obstetric Anesthesia 203. Maternal Early Warning Criteria, National Partnership for

and Perinatology. ANESTHESIOLOGY 2014; 120:1505–12 Maternal Safety, 2017
186. De La Rosa K, Mhyre J, Anderson FW: Maternal mortal-
204. Mhyre JM, DʼOria R, Hameed AB, Lappen JR, Holley SL,
ity from hemorrhage in Michigan 1998–2011 [8]. Obstet Hunter SK, Jones RL, King JC, DʼAlton ME: The mater-
Gynecol 2016; 127 Suppl 1:3S nal early warning criteria: a proposal from the national
partnership for maternal safety. Obstet Gynecol 2014;
187. Main EK, Cape V, Abreo A, Vasher J, Woods A, Carpenter 124:782–6
A, Gould JB: Reduction of severe maternal morbidity from
hemorrhage using a state perinatal quality collaborative. 205. Jonsson M, Hanson U, Lidell C, Nordén-Lindeberg S: ST

Am J Obstet Gynecol 2017; 216:298.e1–298.e11 depression at caesarean section and the relation to oxytocin
dose. A randomised controlled trial. BJOG 2010; 117:76–83
188. Main EK, Goffman D, Scavone BM, Low LK, Bingham D,
Fontaine PL, Gorlin JB, Lagrew DC, Levy BS; National 206. Kovacheva VP, Soens MA, Tsen LC: A randomized, double-
Parternship for Maternal Safety; Council for Patient Safety blinded trial of a “rule of threes” algorithm versus continu-
in Women’s Health Care: National Partnership for Maternal ous infusion of oxytocin during elective cesarean delivery.
Safety: Consensus bundle on obstetric hemorrhage. Anesth ANESTHESIOLOGY 2015; 123:92–100
Analg 2015; 121:142–8 207. George RB, McKeen D, Chaplin AC, McLeod L: Up-down

189. Kacmar RM, Mhyre JM, Scavone BM, Fuller AJ, Toledo P: determination of the ED(90) of oxytocin infusions for the
The use of postpartum hemorrhage protocols in United prevention of postpartum uterine atony in parturients under-
States academic obstetric anesthesia units. Anesth Analg going Cesarean delivery. Can J Anaesth 2010; 57:578–82
2014; 119:906–10 208. Dagraca J, Malladi V, Nunes K, Scavone B: Outcomes after
190. Charbit B, Mandelbrot L, Samain E, Baron G, Haddaoui B, institution of a new oxytocin infusion protocol during the
Keita H, Sibony O, Mahieu-Caputo D, Hurtaud-Roux MF, third stage of labor and immediate postpartum period. Int J
Huisse MG, Denninger MH, de Prost D; PPH Study Group: Obstet Anesth 2013; 22:194–9
The decrease of fibrinogen is an early predictor of the 209. Lee AI, Wong CA, Healy L, Toledo P: Impact of a third stage
severity of postpartum hemorrhage. J Thromb Haemost of labor oxytocin protocol on cesarean delivery outcomes.
2007; 5:266–73 Int J Obstet Anesth 2014; 23:18–22
191. Shaylor R, Weiniger CF, Austin N, Tzabazis A, Shander A, 210. Grotegut CA, Paglia MJ, Johnson LN, Thames B, James

Goodnough LT, Butwick AJ: National and international AH: Oxytocin exposure during labor among women with
guidelines for patient blood management in obstetrics: A postpartum hemorrhage secondary to uterine atony. Am J
qualitative review. Anesth Analg 2017; 124:216–32 Obstet Gynecol 2011; 204:56.e1–6
192. American Society of Anesthesiologists Task Force on
211. Phaneuf S, Rodríguez Liñares B, TambyRaja RL, MacKenzie
Perioperative Blood M: Practice guidelines for perioperative IZ, López Bernal A: Loss of myometrial oxytocin receptors
blood management: An updated report by the American during oxytocin-induced and oxytocin-augmented labour.
Society of Anesthesiologists Task Force on Perioperative J Reprod Fertil 2000; 120:91–7
Blood Management. ANESTHESIOLOGY 2015; 122:241–75 212. Balki M, Ramachandran N, Lee S, Talati C: The recovery
193. Salpeter SR, Buckley JS, Chatterjee S: Impact of more
time of myometrial responsiveness after oxytocin-induced
restrictive blood transfusion strategies on clinical out- desensitization in human myometrium in vitro. Anesth
comes: A meta-analysis and systematic review. Am J Med Analg 2016; 122:1508–15
2014; 127:124–131.e3 213. Balki M, Erik-Soussi M, Kingdom J, Carvalho JC: Oxytocin pre-
194. Shaz BH, Hillyer CD, Waters JH: Patient blood management: treatment attenuates oxytocin-induced contractions in human
Key for accountable care organizations. JAMA Surg 2013; myometrium in vitro. ANESTHESIOLOGY 2013; 119:552–61
148:491–2 214. Lavoie A, McCarthy RJ, Wong CA: The ED90 of prophylac-
195. American College of Obstetricians Gynecologists: ACOG
tic oxytocin infusion after delivery of the placenta during
Practice Bulletin: Clinical Management Guidelines for cesarean delivery in laboring compared with nonlaboring
Obstetrician-Gynecologists Number 76, October 2006: women: an up-down sequential allocation dose-response
Postpartum hemorrhage. Obstet Gynecol 2006; 108:1039–47 study. Anesth Analg 2015; 121:159–64
EDUCATION
215. Kassebaum NJ, Bertozzi-Villa A, Coggeshall MS, Shackelford V, Nash D, Nejjari C, Nelson RG, Neupane SP, Newton CR,
KA, Steiner C, Heuton KR, Gonzalez-Medina D, Barber R, Ng M, Nieuwenhuijsen MJ, Nisar MI, Nolte S, Norheim OF,
Huynh C, Dicker D, Templin T, Wolock TM, Ozgoren AA, Nyakarahuka L, Oh IH, Ohkubo T, Olusanya BO, Omer SB,
Abd-Allah F, Abera SF, Abubakar I, Achoki T, Adelekan Opio JN, Orisakwe OE, Pandian JD, Papachristou C, Park
A, Ademi Z, Adou AK, Adsuar JC, Agardh EE, Akena D, JH, Caicedo AJ, Patten SB, Paul VK, Pavlin BI, Pearce N,
Alasfoor D, Alemu ZA, Alfonso-Cristancho R, Alhabib S, Ali Pereira DM, Pesudovs K, Petzold M, Poenaru D, Polanczyk
R, Al Kahbouri MJ, Alla F, Allen PJ, AlMazroa MA, Alsharif GV, Polinder S, Pope D, Pourmalek F, Qato D, Quistberg
U, Alvarez E, Alvis-Guzmán N, Amankwaa AA, Amare DA, Rafay A, Rahimi K, Rahimi-Movaghar V, ur Rahman S,
AT, Amini H, Ammar W, Antonio CA, Anwari P, Arnlöv J, Raju M, Rana SM, Refaat A, Ronfani L, Roy N, Pimienta TG,
Arsenijevic VS, Artaman A, Asad MM, Asghar RJ, Assadi Sahraian MA, Salomon JA, Sampson U, Santos IS, Sawhney
R, Atkins LS, Badawi A, Balakrishnan K, Basu A, Basu S, M, Sayinzoga F, Schneider IJ, Schumacher A, Schwebel DC,
Beardsley J, Bedi N, Bekele T, Bell ML, Bernabe E, Beyene Seedat S, Sepanlou SG, Servan-Mori EE, Shakh-Nazarova M,
TJ, Bhutta Z, Bin Abdulhak A, Blore JD, Basara BB, Bose D, Sheikhbahaei S, Shibuya K, Shin HH, Shiue I, Sigfusdottir
Breitborde N, Cárdenas R, Castañeda-Orjuela CA, Castro RE, ID, Silberberg DH, Silva AP, Singh JA, Skirbekk V, Sliwa K,
Catalá-López F, Cavlin A, Chang JC, Che X, Christophi CA, Soshnikov SS, Sposato LA, Sreeramareddy CT, Stroumpoulis

Chugh SS, Cirillo M, Colquhoun SM, Cooper LT, Cooper C, K, Sturua L, Sykes BL, Tabb KM, Talongwa RT, Tan F,
da Costa Leite I, Dandona L, Dandona R, Davis A, Dayama Teixeira CM, Tenkorang EY, Terkawi AS, Thorne-Lyman AL,
A, Degenhardt L, De Leo D, del Pozo-Cruz B, Deribe K, Tirschwell DL, Towbin JA, Tran BX, Tsilimbaris M, Uchendu
Dessalegn M, deVeber GA, Dharmaratne SD, Dilmen U, Ding US, Ukwaja KN, Undurraga EA, Uzun SB, Vallely AJ, van
EL, Dorrington RE, Driscoll TR, Ermakov SP, Esteghamati Gool CH, Vasankari TJ, Vavilala MS, Venketasubramanian N,
A, Faraon EJ, Farzadfar F, Felicio MM, Fereshtehnejad Villalpando S, Violante FS, Vlassov VV, Vos T, Waller S, Wang
SM, de Lima GM, Forouzanfar MH, França EB, Gaffikin H, Wang L, Wang X, Wang Y, Weichenthal S, Weiderpass E,
L, Gambashidze K, Gankpé FG, Garcia AC, Geleijnse JM, Weintraub RG, Westerman R, Wilkinson JD, Woldeyohannes
Gibney KB, Giroud M, Glaser EL, Goginashvili K, Gona P, SM, Wong JQ, Wordofa MA, Xu G, Yang YC, Yano Y, Yentur
González-Castell D, Goto A, Gouda HN, Gugnani HC, Gupta GK, Yip P, Yonemoto N, Yoon SJ, Younis MZ, Yu C, Jin KY,
R, Gupta R, Hafezi-Nejad N, Hamadeh RR, Hammami M, El Sayed Zaki M, Zhao Y, Zheng Y, Zhou M, Zhu J, Zou
Hankey GJ, Harb HL, Havmoeller R, Hay SI, Pi IB, Hoek XN, Lopez AD, Naghavi M, Murray CJ, Lozano R: Global,
HW, Hosgood HD, Hoy DG, Husseini A, Idrisov BT, Innos regional, and national levels and causes of maternal mortal-
K, Inoue M, Jacobsen KH, Jahangir E, Jee SH, Jensen PN, Jha ity during 1990-2013: A systematic analysis for the Global
V, Jiang G, Jonas JB, Juel K, Kabagambe EK, Kan H, Karam Burden of Disease Study 2013. Lancet 2014; 384:980–1004
NE, Karch A, Karema CK, Kaul A, Kawakami N, Kazanjan
216. DʼAlton ME, Friedman AM, Smiley RM, Montgomery DM,
K, Kazi DS, Kemp AH, Kengne AP, Kereselidze M, Khader
Paidas MJ, DʼOria R, Frost JL, Hameed AB, Karsnitz D,
YS, Khalifa SE, Khan EA, Khang YH, Knibbs L, Kokubo Y,
Levy BS, Clark SL: National Partnership for Maternal Safety:
Kosen S, Defo BK, Kulkarni C, Kulkarni VS, Kumar GA,
Consensus bundle on venous thromboembolism. Obstet
Kumar K, Kumar RB, Kwan G, Lai T, Lalloo R, Lam H,
Gynecol 2016; 128:688–98
Lansingh VC, Larsson A, Lee JT, Leigh J, Leinsalu M, Leung
R, Li X, Li Y, Li Y, Liang J, Liang X, Lim SS, Lin HH, Lipshultz 217. Kendig S, Keats JP, Hoffman MC, Kay LB, Miller ES, Moore
SE, Liu S, Liu Y, Lloyd BK, London SJ, Lotufo PA, Ma J, Simas TA, Frieder A, Hackley B, Indman P, Raines C,
Ma S, Machado VM, Mainoo NK, Majdan M, Mapoma CC, Semenuk K, Wisner KL, Lemieux LA: Consensus bundle on
Marcenes W, Marzan MB, Mason-Jones AJ, Mehndiratta MM, maternal mental health: Perinatal depression and anxiety.
Mejia-Rodriguez F, Memish ZA, Mendoza W, Miller TR, Mills Obstet Gynecol 2017; 129:422–30
EJ, Mokdad AH, Mola GL, Monasta L, de la Cruz Monis J, 218. Rosenbaum T, Mhyre JM: The anesthesiologist’s role in the
Hernandez JC, Moore AR, Moradi-Lakeh M, Mori R, Mueller national partnership for maternal safety’s hemorrhage bun-
UO, Mukaigawara M, Naheed A, Naidoo KS, Nand D, Nangia dle: A review article. Clin Obstet Gynecol 2017; 60:384–93

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Review Article

Deborah J. Culley, M.D., Editor

A Review of the Impact of Obstetric Anesthesia on

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O BSTETRIC anesthesiology has historically bridged

This article is featured in “This Month in Anesthesiology,” page 1A.

Anesthesiology, V 129 • No 1 192 July 2018

emphasis on the past decade. Continuing progress will have

Labor Analgesia and Anesthesia

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Anesthesiology 2018; 129:192-215 193 Lim et al.

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Anesthesiology 2018; 129:192-215 194 Lim et al.

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Comparison Early Neuraxial Late Neuraxial

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Anesthesiology 2018; 129:192-215 199 Lim et al.

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Breastfeeding and other inflammatory cytokines.172 Besides increased risk

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Anesthesiology 2018; 129:192-215 205 Lim et al.

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180. American Society of Anesthesiologists: ASA Response to

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