Nvpo Nvio Cesareas

Best Practice & Research Clinical Anaesthesiology xxx (xxxx) xxx
Contents lists available at ScienceDirect
Best Practice & Research Clinical

Anaesthesiology
journal homepage: www.elsevier.com/locate/bean
The optimum management of nausea and

vomiting during and after cesarean delivery
Hon Sen Tan, MD, MMed, Research Fellow,
Ashraf S. Habib, MB BCh, MSc, MHSc, FRCA, Professor of
Anesthesiology, Obstetrics and Gynecology *
Department of Anesthesiology, Division of Women's Anesthesia, Duke University Medical Center, Box 3094,
Durham, NC, 27710, USA
Keywords:
Intraoperative and postoperative nausea and vomiting (IONV and
neuraxial anesthesia
PONV) afflict up to 80% of parturients undergoing cesarean de-
intrathecal opioids
nausea livery with neuraxial anesthesia. Preventing nausea and emesis is a
vomiting top priority for women undergoing cesarean delivery and is
cesarean delivery included in the quality of recovery measures and enhanced re-
covery after cesarean delivery protocols.
The majority of known perioperative emetic triggers can be avoi-
ded or mitigated by optimizing anesthetic and surgical manage-
ment. IONV may arise from spinal anesthesia-induced
hypotension, intraoperative pain, and medications such as utero-
tonics and antibiotics. Furthermore, uterine exteriorization and
peritoneal irrigation increase IONV risk. Conversely, preventing
PONV mainly focuses on optimizing analgesia through an opioid-
sparing, multimodal strategy. In addition, combination prophy-
lactic antiemetic therapy should be instituted in this high-risk
population to further reduce the risk of IONV and PONV.
© 2020 Elsevier Ltd. All rights reserved.
* Corresponding author. Department of Anesthesiology, Duke University Medical Center, Box 3094, Durham, NC, 27710, USA.
E-mail address: ashraf.habib@duke.edu (A.S. Habib).
https://doi.org/10.1016/j.bpa.2020.04.012
1521-6896/© 2020 Elsevier Ltd. All rights reserved.
Please cite this article as: Tan HS, Habib AS, The optimum management of nausea and vomiting during
and after cesarean delivery, Best Practice & Research Clinical Anaesthesiology, https://doi.org/10.1016/
j.bpa.2020.04.012
2 H.S. Tan, A.S. Habib / Best Practice & Research Clinical Anaesthesiology xxx (xxxx) xxx
Introduction
Cesarean delivery is one of the most common surgical procedures performed, comprising 7% of
surgeries worldwide [1]. Intraoperative nausea and vomiting (IONV) and postoperative nausea and
vomiting (PONV) affect up to 80% of women undergoing cesarean delivery under neuraxial anesthesia
[2,3]. This places a large parturient population at the risk of emetic-related adverse outcomes.
Avoidance of IONV/PONV is one of the top concerns of parturients undergoing cesarean delivery [4],
and is included in patient satisfaction surveys, quality of recovery assessments, and enhanced recovery
after cesarean delivery protocols [5,6]. In this article, we will summarize risk factors, as well as in-
terventions to optimize the prophylaxis and treatment of IONV and PONV.
Minimizing risk factors associated with intraoperative nausea and vomiting
Emetogenic triggers of IONV during cesarean delivery include anesthetic factors, such as spinal
anesthesia-induced hypotension and the administration of opioids, uterotonics, and antibiotics, in
addition to surgical factors such as visceral stimulation, exteriorization of the uterus, and peritoneal
irrigation. As these are modifiable risk factors, IONV risk can potentially be reduced by optimizing
anesthetic and surgical approaches.
Intraoperative hypotension
Intraoperative hypotension occurs in up to 75% of women receiving spinal anesthesia for cesarean
delivery [7], resulting in brain stem ischemia and the consequent activation of the vomiting center [2].
Furthermore, hypotension-induced reduction in splanchnic blood flow releases emetogenic factors
from the gastrointestinal tract, such as serotonin [8]. The avoidance of maternal hypotension signifi-
cantly reduces IONV.
As peripheral arteriolar dilatation is the main etiological factor for hypotension, vasopressors are
the mainstay modality for the management of hypotension, while other strategies such as fluid loading
or lower limb compression have limited efficacy [9]. Phenylephrine is currently considered the first-
line agent for the management of spinal-induced hypotension, as it is associated with less IONV and
improved neonatal acid-base status compared to ephedrine [10]. Alternatives to phenylephrine include
norepinephrine and metaraminol, as their mild b-adrenergic effects may avoid bradycardia and
concomitant reduction in cardiac output associated with phenylephrine use [10].
The ideal method of phenylephrine administration, dosing, and target systolic blood pressure (SBP)
values have been the subject of considerable research. Consensus guidelines recommend commencing
prophylactic phenylephrine infusion immediately after placing the spinal anesthetic, beginning with
25e50 mg min1 and titrating to SBP target >90% of baseline [10]. This recommendation is based on
studies showing (1) prophylactic phenylephrine infusion started immediately after spinal anesthetic
significantly reduced hypotension and IONV compared to reactive treatment with phenylephrine
boluses after hypotension had developed [11,12]; (2) an infusion rate of 25e50 mg min1 maintained
SBP >80% with less physician interventions and reactive hypertension compared to 75e100 mg min1
[13]; and (3) an infusion targeting SBP ¼ 100% of baseline resulted in less IONV compared to 90% or 80%
of baseline (4%, 16%, and 40%, respectively) [14].
Fluid loading strategies have limited efficacy in preventing spinal-induced hypotension, but crys-
talloid coload administered in conjunction with prophylactic phenylephrine infusion reduced hypo-
tension and phenylephrine requirements compared to administering fluids at a maintenance rate [15].
Colloids (preload or coload) or crystalloids (coload) have some limited efficacy in preventing hypo-
tension [9], with colloid preloading or coloading being superior to crystalloid coloading [9]. However,
the higher efficacy of colloids should be weighed against increased cost, anaphylaxis risk, and long
intravascular retention time [2]. In contrast, crystalloid preloading is ineffective in preventing hypo-
tension [16], and is not recommended.
Left uterine displacement is routinely used to reduce inferior vena cava compression; however, a
minimum angle of 15 is required to reduce hypotension and phenylephrine requirements [17].
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Intraoperative pain
Intraoperative pain is transmitted through Ad- and C-fibers, but local anesthetics preferentially
block the former while sparing C-fibers carrying visceral pain that can induce IONV [18]. Neuraxial
lipophilic opioids such as fentanyl and sufentanil improve block quality and reduce IONV [2,19e21]. In
particular, intrathecal fentanyl reduces intraoperative analgesic supplementation by 82%, along with a
59% reduction in IONV risk [22]. For intrathecal administration, fentanyl 10e15 mg [21,23] or sufentanil
2.5e5 mg [19] improves block quality without significant adverse effects, while doses of fentanyl >25 mg
and sufentanil >5 mg increase pruritus [24e26]. For epidural administration, fentanyl 50 mg [27] or
sufentanil 20e30 mg [28] are recommended; fentanyl >50 mg exhibits a ceiling effect for analgesia [27],
while sufentanil >30 mg increases the risk of IONV and pruritus [29]. Because of its slower onset of
action, neuraxial morphine contributes mainly to PONV, and will be discussed later.
Uterotonic agents and antibiotics
Of uterotonic agents in current practice, ergonovine is the most emetogenic due to its interaction
with dopaminergic, serotonergic and a-adrenergic receptors [30]. Oxytocin or carbetocin may also
induce IONV secondary to their hypotensive effects [31,32], which can be reduced by administering the
minimally effective dose through slow infusion [32]. Carboprost stimulates the gastrointestinal tract
and increases IONV, though not to the extent of other uterotonic agents [2]. Finally, commonly used
antibiotics such as cefazolin have been associated with IONV [2], and the slow administration of those
agents is recommended to reduce this risk.
Surgical stimuli
Uterine exteriorization significantly increases IONV by two-fold [33,34], while intra-abdominal

saline irrigation increases IONV risk by 70% and PONV by 92% compared to controls, without signifi-
cant change in blood loss, return of gastrointestinal function, or infectious complications [35]. These
maneuvers are highly emetogenic because of the stimulation of visceral pain C-fibers [18] and vagal
fibers innervating the uterus and abdominal viscera [36]. Hence, appropriate surgical technique plays
an important role in reducing IONV, with uterine exteriorization, peritoneal irrigation, and excessive
visceral manipulation avoided where possible.
Minimizing risk factors associated with postoperative nausea and vomiting
Pain and opioid use
PONV is mainly triggered by the emetogenic effects of opioids and severe pain [37]. The goal of
adequate postoperative analgesia while minimizing opioid use is best addressed with a multimodal
opioid-sparing strategy [38,39]. The use of neuraxial morphine is becoming an analgesic mainstay for
cesarean delivery, with an optimum dose of 100 mg for intrathecal administration [40,41] and 3e4 mg
for epidural use [42]. Higher neuraxial morphine doses minimally prolong analgesic duration with no
reduction in the need for rescue analgesia or pain scores, while increasing the incidence of PONV and
pruritus [42e44].
Compared to an opioid-based analgesic regimen, multimodal strategies improve analgesia and
decrease opioid utilization [38,39]. For instance, acetaminophen provides an opioid-sparing effect of
20% [45] with minimal adverse effects [46], and should be routinely used for 2e3 days after cesarean
delivery. Similarly, nonsteroidal anti-inflammatory drugs (NSAIDs) have a 30%e50% opioid-sparing
effect, and are associated with a reduction in PONV [38,47]. The combination of acetaminophen and
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NSAIDs is synergistic [48] and both agents should be administered together whenever possible [49].
Furthermore, NSAIDs and acetaminophen should be administered on a scheduled basis rather than on
demand, because the former strategy is associated with improved analgesia, decreased rescue opioid
requirement, and reduction in PONV [50]. In addition, plain acetaminophen should be used as it im-
proves analgesia and reduces opioid consumption compared to acetaminophen-opioid combined
tablets [51].
Transversus abdominis plane (TAP) blocks have been shown to reduce opioid consumption, pain
scores, and PONV in parturients who do not receive intrathecal morphine, such as those undergoing
general anesthesia [52]. However, in parturients who receive intrathecal morphine, TAP blocks confer
only a small reduction in dynamic pain scores during the early postoperative period [52]. In contrast,
intrathecal morphine improves pain scores, opioid consumption, and time to rescue analgesic, but
increases the risk of PONV compared to TAP blocks [52]. Similarly, initial data on quadratus lumborum
(QL) blocks have demonstrated potential in reducing postcesarean delivery pain and opioid re-
quirements compared to placebo, but there is insufficient evidence that QL blocks improve analgesia or
reduce PONV in patients receiving neuraxial morphine [53]. Additional research is needed before
routine truncal blocks can be recommended.
Vestibular stimulation
Vestibular stimulation-induced PONV can be triggered by sudden changes in body position [37]. It is
mediated by histamine H1 and muscarinic cholinergic pathways, hence antihistamines and anticho-
linergics may be of benefit [37,54].
Hydration
As a result of preoperative fasting, parturients typically present for surgery with a fluid deficit. In
the nonobstetric population, preoperative volume expansion may mitigate the emetic effects of
gastrointestinal, brainstem, and vestibular hypoperfusion [55]. Supplemental intravenous crystal-
loid administration has been shown to reduce PONV and the need for antiemetic treatment [55],
but it is unclear if this applies to parturients undergoing cesarean delivery with neuraxial
anesthesia.
Patient risk factors
In nonobstetric patients, risk factors for PONV include female sex, history of PONV, history of motion
sickness, nonsmoking, younger age, postoperative opioids, and longer anesthetic duration [56e58], but
data specific to the obstetric population are limited. This knowledge gap is significant because two risk
factors (female sex and opioid administration) are present by default in parturients receiving neuraxial
morphine, while other potential obstetric-specific contributors to PONV have not been evaluated.
Recently, our group examined the association of various pregnancy-specific and perioperative factors
with PONV after cesarean delivery and reported that two factors: nonsmoking during pregnancy, and a
history of PONV after cesarean delivery and/or morning sickness were associated with increased PONV
risk [59].
Pharmacological and nonpharmacological options for prophylaxis and the treatment of nausea
and vomiting
Central control of nausea/vomiting is through the chemoreceptor trigger zone and the vomiting
center [60], which are densely populated with serotonergic, dopaminergic, muscarinic, histaminergic,
neurokinin-1, and opioid receptors. Data on the antiemetic efficacy of pharmacological agents targeting
these receptors in the obstetric patient population derived from meta-analyses are summarized in
Table 1.
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Table 1
Common antiemetic agents used in parturients undergoing cesarean delivery. Data presented as risk ratio (95% confidence intervals). Abbreviations: NNT e number needed to treat.
Drug Intraoperative Postoperative Potential adverse effects
Nausea Vomiting Nausea Vomiting Maternal Fetal
Ondansetron 4 mg 0.60 (0.40e0.89) [62] 0.60 (0.30e1.18) [62] 0.39 (0.21e0.75) [62] 0.45 (0.27e0.77) [62] No increase in arrhythmia, No increased risk of
Ondansetron 8 mg 0.45 (0.20e1.01) [62] 0.14 (0.02e1.03) [62] 0.44 (0.18e1.09) [62] 1.0 (0.19e5.15) [62] headache, or adverse fetal outcomes
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Granisetron 1 mg 1.14 (0.59e2.20) [62] 0.67 (0.19e2.28) [62] extrapyramidal side effects when given during
Granisetron 3 mg 1.07 (0.47e2.44) [61] 0.61 (0.19e1.94) [61] [61,62]. gestation [63].
Data are inconclusive

regarding breast milk
transfer risk.
Dexamethasone From 2.5 to 0.31 (0.15e0.64) [62] 0.35 (0.14e0.86) [62] 0.73 (0.44e1.22) [64] 0.70 (0.52e0.96) [64] No increase in delayed Inconclusive safety data
10 mg 0.75 (0.52e1.07) [62] 0.78 (0.54e1.12) [62] wound healing, wound in neonates.
infection, sedation, or
extrapyramidal side effects Corticosteroids used to
[64]. accelerate fetal lung
maturation
Metoclopramide 10 mg 0.36 (0.13e0.96) [62] 0.45 (0.20e0.99) [62] 0.58 (0.36e0.94) [62] 0.65 (0.24e1.73) [62] Data are limited. Metoclopramide does
Metoclopramide 20 mg 0.27 (0.10e0.75) [62] No increase in anxiety, not increase fetal
Metoclopramide 0.15 mg kg1 0.32 (0.12e0.90) [62] 0.09 (0.01e1.54) [62] 0.40 (0.16e1.02) [62] 0.32 (0.12e0.90) [62] headaches, dizziness, adverse outcomes
Droperidol 0.5 mg 0.33 (0.17e0.65) [62] 0.34 (0.09e1.23) [62] hypotension, or pruritus when used during
Droperidol 0.625 mg 0.36 (0.15e0.90) [62] 0.29 (0.07e1.17) [62] was noted with gestation [71].
Droperidol 1.25 mg 0.44 (0.17e1.15) [62] 0.37 (0.10e1.27) [62] 1.67 (0.43e6.51) [62] 0.55 (0.32e0.94) [62] metoclopramide or Metoclopramide is
droperidol [62]. secreted in breast milk
Droperidol has an FDA [71].
black box warning for
increased risk of torsades
de pointes [72].
Dimenhydrinrate 50 mg 0.38 (0.21e0.69) [62] 0.52 (0.19e1.42) [62] Very limited data available. Appears safe when
Dimenhydrinate 100 mg 0.17 (0.05e0.57) [62] used in gestation [78].
Cyclizine 50 mg 0.50 (0.28e0.88) [62] 0.50 (0.27e0.93) [62] Secreted in breast milk
[2].
Glycopyrrolate 0.2 mg 0.49 (0.22e1.09) [62] 0.45 (0.12e1.62) [62] Very limited data available. Neonatal safety and
Scopolamine patch 0.71 (0.51e0.97) [62] 0.96 (0.36e2.59) [62] 0.55 (0.41e0.74) [62] breast milk transfer
unclear.
Scopolamine use
during gestation does
not increase fetal
adverse outcomes [76].
5
Serotonin antagonists
5HT3 receptor antagonists such as ondansetron are commonly used for antiemetic prophylaxis.
Based on data from two meta-analyses, ondansetron 4 mg significantly reduces the risk of intra-
operative nausea (but not vomiting) and PONV [61,62]. Increasing the dose to 8 mg results in no further
reduction in IONV or PONV [61,62]. The number needed to treat (NNT) for ondansetron is between 7
and 8 for PONV [61]. Very few studies investigated granisetron, but those studies reported no signif-
icant reduction in IONV or PONV [61,62].
Ondansetron is considered safe at common antiemetic doses [58], with no significant adverse ef-
fects reported [61,62]. Nonetheless, ondansetron is associated with QTc prolongation, and the Food and
Drug Administration (FDA) recommends that the dose should not exceed 16 mg [58]. The number
needed to harm is 36 for headache and 23 for constipation in the nonobstetric population [58].
Ondansetron has been used to treat severe nausea during pregnancy, with no significant increase in
adverse fetal outcomes [63].
Corticosteroids
Dexamethasone at doses ranging from 2.5 mg to 10 mg reduces PONV with an NNT ranging from 5
to 9 in obstetric and gynecological patients receiving neuraxial anesthesia and neuraxial morphine
[64]. These results contrast with another meta-analysis reporting that dexamethasone reduced IONV
but not PONV, although authors noted that the component studies were of questionable quality [62].
Furthermore, these findings are not consistent with the delayed onset of antiemetic effect (approxi-
mately 2 h) after intravenous administration, which makes dexamethasone more appropriate for
preventing PONV [65,66]. In addition, dexamethasone is a suitable antiemetic when long-acting
neuraxial opioids are used because of its long duration of action [65,66]. There was no
doseeresponse benefit reported for reducing PONV from increasing the dexamethasone dose from
2.5 mg to 10 mg [62,64].
Dexamethasone is not associated with delayed wound healing, wound infection, or extrapyramidal
side effects [64], although hyperglycemia was noted in nonobstetric patients receiving dexamethasone
8 mg [67,68]. Doses ranging from 4 mg to 5 mg have been recommended for PONV prophylaxis [58],
but the latest consensus guidelines recommend 8 mg, as it may be associated with improved quality of
recovery [69].
Dopaminergic antagonists
A meta-analysis reported that, compared to placebo, metoclopramide and droperidol are effective
in preventing IONV and PONV in women undergoing cesarean delivery, although several studies did
not include the use of intrathecal morphine [62]. A subsequent trial investigated metoclopramide alone
or in combination with ondansetron in parturients receiving neuraxial morphine 150 mg and reported
that metoclopramide alone reduced IONV with NNT ¼ 6, compared to placebo [3]. Combining meto-
clopramide with ondansetron 4 mg further reduced IONV with NNT ¼ 4 [3]. Metoclopramide alone did
not reduce PONV, while its combination with ondansetron reduced PONV rates for only 2 h after
surgery [3].
Metoclopramide use has been associated with dizziness, drowsiness, fatigue, and rarely, extrapy-
ramidal side effects [70], but no significant increase in maternal adverse effects were found in meta-
analyses [3,62]. Despite crossing the placenta and being secreted in breast milk, the use of metoclo-
pramide is not associated with increased fetal adverse effects [71]. In contrast, droperidol is associated
with the risk of QTc prolongation and torsades de pointes, and has an FDA “black box” warning [72]. Of
note, amisulpride is an atypical D2/D3-antagonist with no QTc prolongation or extrapyramidal effects
at antiemetic doses [73]. Compared to placebo, amisulpride significantly reduces PONV in the non-
obstetric surgical population, with no significant CNS or cardiac side effects [73]. It is also effective for
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the treatment of established PONV [74]. However, its efficacy and safety in the obstetric population
have not been evaluated.
Antihistamines
While the efficacy of antihistamines in preventing IONV is unclear, they appear effective for
PONV prophylaxis [62]. Dimenhydrinate 25e50 mg is commonly used, with no benefit associated
with higher doses [62], while cyclizine 50 mg may be more effective than dexamethasone 8 mg for
PONV prophylaxis [75]. Dimenhydrinate and diphenhydramine are commonly used to treat
hyperemesis gravidarum and appear safe when used in pregnancy [76], although they are secreted
in breast milk [2].
Anticholinergics
Scopolamine patch 1.5 mg is efficacious in reducing PONV after cesarean delivery [77,78]. Within
6 h after surgery, scopolamine significantly reduced nausea compared to placebo or ondansetron.
From 6 to 24 h, scopolamine was effective in reducing vomiting e an effect not seen with
ondansetron, which could possibly be due to its longer duration of action [77]. Nonetheless,
scopolamine use increased the incidence of blurred vision and dry mouth [77]. Glycopyrrolate
0.2 mg was reported to reduce postoperative nausea in an early study [79]. However, meta-analysis
of glycopyrrolate 0.2 mg and scopolamine was inconclusive regarding their antiemetic efficacy,
because of the small number of studies available [62]. The safety of anticholinergics with breast-
feeding is unknown, but scopolamine has been used during pregnancy without increase in fetal
adverse effects [76].
Neurokinin 1 (NK1) antagonists
Stimulation of NK1 receptors in gastrointestinal vagal afferents and central vomiting centers
causes nausea/vomiting [80], and NK1 antagonists like aprepitant were found to reduce PONV,
with higher efficacy against vomiting compared to ondansetron [58]. Aprepitant 40 mg is the
FDA-approved dose, with no further benefit of increasing doses up to 125 mg [81]. At present,
there are no studies investigating the efficacy and safety of NK1 antagonists in the obstetric
population.
P6 stimulation
Stimulation of the pericardium 6 (P6) Neiguan point is as effective as pharmacological agents in

treating chemotherapy-induced nausea/vomiting [82], and preventing PONV [83]. In a meta-
analysis of studies of women undergoing cesarean delivery, P6 stimulation reduced intra-
operative nausea, but not intraoperative vomiting or PONV [62], but there was significant hetero-
geneity among included studies. The mechanism of action is unclear, but may involve beta
endorphin release, alteration of serotonin and vagal levels, and increased gastric emptying [84].
Regardless, P6 stimulation appears to be safe and avoids concerns of secretion of pharmacological
agents in breast milk. However, its use is limited because of the lack of conclusive data about its
effectiveness in the obstetric population, as well as the lack of familiarity and possible poor
tolerance of acupoint stimulation [85].
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Combination of antiemetics
Data from nonobstetric patients suggest that multimodal antiemetic therapy-utilizing agents acting
at different receptor sites is more effective than monotherapy, particularly in high-risk patients
[58,86,87]. Similarly, results of several studies support using multimodal antiemetic therapy in women
undergoing cesarean delivery. For instance, Voigt et al. reported that tropisetron þ metoclopramide
were more effective in preventing IONV compared to dimenhydrinate þ dexamethasone and tropi-
setron alone [88]. In other studies, dexamethasone þ droperidol were more effective than either agent
alone [89], and dexamethasone þ ondansetron reduced PONV incidence compared to dexamethasone
alone in parturients receiving spinal anesthesia with intrathecal morphine [90]. Further research is
needed to establish the most efficacious antiemetic combination regimen in obstetric patients. Pending
further studies, the limited efficacy and safety data available in the obstetric population suggest that a
combination of 5-HT3 antagonists and dexamethasone may be a reasonable choice. Addition of
metoclopramide will confer further prophylaxis against IONV.
Treatment of PONV
Most studies focus on preventing PONV, with relatively little research into its treatment overall,
particularly in the obstetric population. Therefore, principles learned from the general surgical pop-
ulation can be applied to obstetric patients. In patients who do not receive prophylaxis, 5HT3 antag-
onists are recommended as a first-line treatment [58]. Patients who develop PONV within 6 h of
antiemetic prophylaxis, should receive treatment with an agent of a different pharmacological class,
excluding those with a delayed onset of action (e.g., dexamethasone, aprepitant, and scopolamine)
[91e93]. After 6 h, the repeated administration of the prophylactic agent is reasonable, with the
exception of long-acting agents (e.g., scopolamine, dexamethasone, and aprepitant) [58]. Low-dose
naloxone or propofol 20 mg have shown effectiveness in treating intractable PONV following cesar-
ean delivery [94,95], and isopropyl alcohol inhalation reduces nausea severity faster than ondansetron
or promethazine [58]. In addition to rescue treatment, evaluation to identify and minimize inciting
factors for PONV should be performed.
Antiemetic prophylaxis versus reactive management
While the safety of antiemetic use in pregnant or lactating mothers is a justified concern, mounting
data on the safety, efficacy, and cost-effectiveness of commonly used antiemetics have shifted the risk-
benefit ratio in favor of prophylactic administration [96]. Furthermore, nausea and vomiting are
incorporated in the obstetric quality of recovery score [97], and remain as one of the top concerns for
women undergoing cesarean delivery [4]. Consequently, prophylactic antiemetic therapy is incorpo-
rated into the National Institute for Health and Care Excellence (NICE) guidelines [98] and Enhanced
Recovery after Cesarean delivery (ERAC) [5,99,100] protocols. As combination antiemetic therapy is
more effective than monotherapy, and women undergoing cesarean delivery represent a population at
high-risk for PONV, the routine administration of a combination of antiemetics is recommended. This is
particularly relevant given the lack of PONV risk scores specific to obstetric patients. We recommend
the administration of a combination of metoclopramide (for IONV prophylaxis), ondansetron (for
IONV/PONV prophylaxis), and dexamethasone (for PONV prophylaxis). Given the multifactorial etiol-
ogy of IONV and PONV, other interventions may be needed to reduce the risk of IONV and PONV, which
are summarized in the practice points box.
Summary
The high incidence of IONV and PONV associated with cesarean delivery adversely impacts
maternal recovery. However, many intraoperative and postoperative emetogenic triggers can be
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avoided or mitigated by optimizing various aspects of perioperative anesthetic and surgical manage-
ment. Additionally, the cost-effectiveness, efficacy, and accumulating safety data of antiemetic therapy
support the use of multimodal prophylaxis in this high-risk patient population. Further research is
needed to elucidate the optimal antiemetic combination, and the risk of adverse effects in this specific
patient population.
Funding source
This work did not receive any specific grant from funding agencies in the public, commercial, or not-
for-profit sectors.
Declaration of Competing Interest
Dr. Habib has previously received research support and honoraria from Acacia Pharma, and research
support from Pacira Biosciences.
Practice points
Minimizing intraoperative nausea/vomiting.
Optimize neuraxial blockade with intrathecal fentanyl 10e15 mg or epidural fentanyl 50 mg.
Maintain SBP >90% of baseline with prophylactic phenylephrine infusion initiated at 25
e50 mg min1 and titrated to clinical effect.
Intravenous crystalloid coload.
Slow administration of prophylactic cephazolin, consider adding to IV fluid infusion.
Avoid uterine exteriorization, peritoneal irrigation, and excessive visceral manipulation.
Administer oxytocin through slow infusion using the minimal effective dose to minimize
hypotension.
Minimizing postoperative nausea/vomiting.
Optimize postoperative analgesia using a multimodal analgesic strategy with scheduled

acetaminophen and NSAIDs.
Lowest effective dose of neuraxial morphine (e.g., 100 mg intrathecal or 3e4 mg epidural).
Truncal blocks in parturients not receiving intrathecal morphine.
Antiemetic prophylaxis.
Combination therapy with agents acting on different receptos is superior to monotherapy,

e.g., metoclopramide (for IONV) þ ondansetron (for IONV and PONV) þ dexamethasone (for
PONV).
Treatment of PONV.
Nausea/vomiting within 6 h of prophylaxis should be treated using a drug with different

mechanism of action from the prophylactic agent, excluding those with delayed onset of
action (e.g., dexamethasone, scopolamine, and aprepitant).
Repeated dose of prophylactic agent is reasonable if nausea/vomiting occurs after 6 h of
prophylaxis (excluding longer-acting prophylactic agents).
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Research agenda
Patient and perioperative factors associated with IONV/PONV in cesarean delivery should be
identified, and obstetric-specific risk prediction models should be formulated to guide anti-
emetic prophylaxis.
Agents with a favorable side effect profile in the nonobstetric population (e.g., aprepitant,
palonosetron, and amisulpride) need to be investigated in the obstetric population.
The optimal combination antiemetic therapy in the obstetric population should be
determined.
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Contents lists available at ScienceDirect

Best Practice & Research Clinical

The optimum management of nausea and

Minimizing risk factors associated with intraoperative nausea and vomiting

Uterotonic agents and antibiotics

Uterine exteriorization signiﬁcantly increases IONV by two-fold [33,34], while intra-abdominal

Minimizing risk factors associated with postoperative nausea and vomiting

Pain and opioid use

Patient risk factors

Drug Intraoperative Postoperative Potential adverse effects

Nausea Vomiting Nausea Vomiting Maternal Fetal

Data are inconclusive

Neurokinin 1 (NK1) antagonists

Stimulation of the pericardium 6 (P6) Neiguan point is as effective as pharmacological agents in

Antiemetic prophylaxis versus reactive management

Declaration of Competing Interest

Minimizing postoperative nausea/vomiting.

Optimize postoperative analgesia using a multimodal analgesic strategy with scheduled

Combination therapy with agents acting on different receptos is superior to monotherapy,

Nausea/vomiting within 6 h of prophylaxis should be treated using a drug with different

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