International Journal of Obstetric Anesthesia (2020) 44, 126–130

0959-289X/$ - see front matter Ó 2020 Elsevier Ltd. All rights reserved.
https://doi.org/10.1016/j.ijoa.2020.08.008

SHORT REPORT
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A risk score for postoperative nausea and/or vomiting

in women undergoing cesarean delivery with intrathecal
morphine
H.S. Tan,a M. Cooter,a R.B. George,b A.S. Habiba
a
Department of Anesthesiology, Division of Women’s Anesthesia, Duke University Medical Center, Durham, NC, USA
b
Department of Anesthesia and Perioperative Care, UCSF, San Francisco, CA, USA

ABSTRACT
Background: Postoperative nausea and/or vomiting affects up to 80% of parturients undergoing cesarean delivery, but there is a
lack of obstetric-specific risk-prediction models. We performed this study to identify postoperative nausea/vomiting risk factors in
parturients undergoing cesarean delivery, formulate an obstetric-specific prediction model (Duke score), and compare its perfor-
mance against the Apfel score.
Methods: A post-hoc analysis of data from two randomized controlled trials studying nausea/vomiting in women undergoing
cesarean delivery with intrathecal morphine. Potential risk factors for postoperative nausea/vomiting within 24 h of surgery with
univariate associations with P 0.20 were considered for inclusion in the multivariable analysis. After identifying the final mul-
tivariable model, we derived our Duke score by assigning points to the selected factors. We then tested the association of the Duke
and Apfel scores with postoperative nausea and vomiting, and compared the area-under-the-receiver operating characteristic
curve.
Results: Analysis included 260 parturients, of whom 146 (56.2%) experienced postoperative nausea/vomiting. Non-smoking dur-
ing pregnancy (OR 2.29 [95% CI 1.12 to 4.67], P=0.023), and history of postoperative nausea/vomiting after cesarean delivery
and/or morning sickness (2.09 [1.12 to 3.91], P=0.021) were independent predictors of postoperative nausea/vomiting and included
in the Duke score. Both Duke and Apfel scores trended linearly with postoperative nausea/vomiting risk (Duke P=0.001; Apfel
P=0.049) and had comparable areas-under-the-receiver operating characteristic curve (Duke 0.63 [0.57 to 0.70]; Apfel 0.59 [0.52 to
0.65], P=0.155).
Conclusions: Both Duke and Apfel scores exhibited similar but poor predictive performance. Until better tools are developed,
routine prophylactic anti-emetics appears to be a reasonable approach in this patient population.
Ó 2020 Elsevier Ltd. All rights reserved.

Keywords: Apfel score; Cesarean delivery; Intrathecal opioids; Neuraxial anesthesia; Postoperative nausea/vomiting

Introduction cesarean delivery. The most commonly used, the Apfel

Postoperative nausea and/or vomiting (PONV) affects
up to 80% of parturients undergoing cesarean delivery
under spinal anesthesia with intrathecal morphine,1
and is a major cause of dissatisfaction with surgery.2
Accurate prediction of PONV risk after cesarean
delivery is challenging, given the lack of obstetric-
specific risk-prediction models. Although several risk-
scoring systems for PONV are available,3–5 none has
been developed specifically for pregnant women or
Accepted August 2020
Correspondence to: A.S. Habib, Department of Anesthesiology, Duke
University Medical Center, Box 3094, Durham, NC 27710, USA.
E-mail address: ashraf.habib@duke.edu
score, assesses PONV risk based on: female sex; receipt
of postoperative opioids; non-smoking status; and his-
tory of PONV and/or motion sickness. The Apfel score
was developed in a diverse surgical population receiving
general anesthesia.3 Since all parturients undergoing
cesarean delivery are female and usually receive postop-
erative opioids by default, applying the Apfel score in
this situation may limit its predictive performance.
Furthermore, factors specific to pregnancy and cesar-
ean delivery might contribute to PONV, including
morning sickness, intra-operative nausea and vomiting
(IONV), and uterine exteriorization,6,7 but these
factors have not been assessed for inclusion in current
H.S. Tan et al.
risk-prediction models. Hence, the study aim was to
develop an obstetric-specific PONV prediction model
(Duke score) by examining the association of
pregnancy-specific patient and peri-operative factors
with PONV after cesarean delivery, and then to com-
pare its predictive performance with the Apfel score.
Methods
This is a post-hoc analysis of two multicenter random-
ized controlled trials studying nausea and vomiting dur-
ing and after cesarean delivery, conducted at Duke
University (Durham, NC, USA) and IWK Health Cen-
tre (Halifax, NS, Canada).1,8 Institutional Review
Board approvals were obtained at both sites, and both
studies were registered with clinicaltrials.gov
(NCT01216410 and NCT01481740).
Both studies had similar inclusion and exclusion cri-
teria. Non-laboring parturients, American Society of
Anesthesiologists (ASA) physical status II or III, single
gestation 36 weeks, and scheduled for cesarean deliv-
ery under spinal or combined spinal-epidural anesthesia
with intrathecal morphine, were enrolled. We excluded
parturients <152 cm or >180 cm tall, in labor, needing
emergency cesarean delivery, receiving anti-emetics
<24 h prior to cesarean delivery, or allergic to ondanse-
tron, metoclopramide, or phenylephrine. We also
excluded parturients with hypertensive disease of preg-
nancy, cardiac disease, and type I diabetes mellitus.
The sole difference in inclusion criteria was body mass
index (BMI); the first study1 excluded BMI >45 kg/m2,
whereas the second8 included parturients with BMI 35
–55 kg/m2.
Standardized anesthetic management included spinal
anesthesia with 12 mg hyperbaric bupivacaine, 15 mg
fentanyl and 150 mg morphine. Intra-operative systolic
blood pressure (SBP) was maintained within 20% of
baseline using a prophylactic phenylephrine infusion in
one study,1 while the second study8 randomized parturi-
ents to receive prophylactic phenylephrine infusion or
phenylephrine boluses for treatment of hypotension.
Only parturients not receiving prophylactic anti-
emetics were included in this analysis. In both studies,
IONV unrelated to hypotension was treated with
ondansetron 4 mg.
The primary outcome of this analysis was the inci-
dence of PONV within 24 h of surgery, with data col-
lected by independent blinded investigators at 2, 6,
and 24 h after surgery.
Potential risk factors for PONV collected in these
studies included history of PONV after cesarean deliv-
ery, PONV after other surgery, motion sickness, morn-
ing sickness, hyperemesis gravidarum, smoking during
or prior to pregnancy, pre-operative nausea, presence
of IONV, intra-operative SBP reduction >20% from
baseline, use of intra-operative rescue anti-emetics, exte-
127
riorization of the uterus, and method of phenylephrine
administration (bolus versus infusion).
Univariate associations of potential risk factors with
PONV were assessed. We then constructed a multivari-
able mixed model, via variable selection among terms
univariably associated with PONV at P 0.20, by back-
wards selection based on Bayesian Information criteria,
with PONV as the outcome and a random effect for
study membership. Our Duke score was derived by
assigning points to the selected factors in the final mul-
tivariable model by rounding the quotient of the esti-
mated odds ratios (OR) and the smallest value to the
nearest integer. The linear association of Duke and
Apfel scores with PONV was assessed with Cochrane-
Armitage Trend tests. We then compared the scores
using Mann-Whitney U test for paired difference in
the area-under-the-receiver operating characteristic
curve (AUC ROC), as well as Integrated Discrimination
Improvement (IDI). The IDI may be interpreted as
improvement in average (integrated) sensitivity cor-
rected for changes in specificity.9 Differences between
observed and predicted outcome probabilities were
assessed with calibration curves, and the degree of
over-optimization was assessed via bootstrapped esti-
mates and 95% confidence intervals (CI) with 2000 repli-
cates. Statistical significance was assessed at the a=0.05
level and analyses were performed in SAS (v9.4 SAS Inc,
Cary NC).
Results
We analyzed 260 parturients out of the 460 enrolled in
the two studies (Supplementary Fig. 1), with 146
(56.2%) experiencing PONV. There was no site-specific
difference in baseline PONV rate (Duke 60%, IWK
54%, P=0.304). Univariate associations of patient
demographics, Apfel risk factors and other investigated
risk factors with PONV are presented in Table 1.
In the multivariable mixed model, non-smoking
during pregnancy, and history of PONV after cesar-
ean delivery and/or morning sickness were indepen-
dently associated with PONV (Table 1). As ORs for
those two risk factors were approximately equal, we
created the Duke score by assigning one point for
the presence of each risk factor (maximum score of
2). There was a significant linear relationship between
PONV risk and increasing Duke and Apfel scores
(P=0.001 and P=0.049, respectively). The incidence
of PONV for each level of Duke and Apfel scores is
shown in Table 2.
The Duke score had an AUC ROC (95%CI) of 0.633
(0.57 to 0.70), compared with 0.586 (0.52 to 0.65) for the
Apfel score (P=0.15, Supplementary Fig. 2), although
the Duke score improved PONV prediction by 2.4%
based on IDI. Analysis of the Duke score with the addi-
tion of bootstrapping resulted in a similar AUC ROC of
 128
Table 1 Patient characteristics and peri-operative risk factors for postoperative nausea and/or vomiting (PONV) stratified by PONV outcome status, univariable
mixed model associations with PONV, and final multivariable mixed model
PONV status Univariable analysis Final multivariable modela
PONV Present (n=146) PONV Absent (n=114) OR (95% CI) P-value OR (95% CI) b (SE) P-value
Patient Demographics
Age (y) 32.0 [28.0, 36.0] 32.0 [28.0, 35.0] 1.02 (0.97 to 1.07) 0.448
Body mass index (kg/m2) 37.6 [33.0, 40.7] 38.7 [35.1, 41.8] 1.00 (0.95 to 1.04) 0.833
Surgical duration (min) 47.0 [39.0, 62.0] 47.0 [37.0, 61.0] 1.00 (0.99 to 1.02) 0.519

A risk score for postoperative nausea and/or vomiting after cesarean delivery
Previous cesarean delivery 110/146 (75.3%) 93/114 (81.6%) 0.73 (0.40 to 1.36) 0.320
Apfel Risk Factors*
Non-smoker in pregnancy 131/146 (89.7%) 90/114 (78.9%) 2.29 (1.13 to 4.64) 0.021 2.29 (1.12 to 4.67) 0.83 (0.36) 0.023
History of PONV and/or motion sickness 57/146 (39.0%) 39/114 (34.2%) 1.16 (0.69 to 1.95) 0.573
Other Risk Factors
Any history of PONV 53/146 (37.1%) 31/114 (27.2%) 1.56 (0.91 to 2.68) 0.104
History of motion sickness 41/146 (28.5%) 34/114 (29.8%) 0.95 (0.55 to 1.64) 0.858
History of morning sickness 116/146 (79.5%) 81/114 (71.7%) 1.56 (0.88 to 2.79) 0.131
History of PONV after cesarean delivery 66/146 (45.2%) 45/114 (39.5%) 1.31 (0.79 to 2.17) 0.294
and/or motion sickness
History of PONV after cesarean 124/146 (84.9%) 83/114 (72.8%) 2.09 (1.13 to 3.88) 0.020 2.09 (1.12 to 3.91) 0.74 (0.32) 0.021
delivery and/or morning sickness
Phenylephrine infusion 104/146 (71.2%) 77/114 (67.5%) 0.93 (0.51 to 1.70) 0.822
History of hyperemesis gravidarum 2/146 (1.4%) 2/114 (1.8%) 0.94 (0.10 to 5.41) 0.762
Pre-operative nausea 27/146 (18.8%) 22/114 (19.3%) 0.98 (0.52 to 1.84) 0.947
Intra-operative nausea and/or vomiting 84/146 (57.5%) 61/114 (53.5%) 1.23 (0.75 to 2.04) 0.410
Systolic blood pressure fall >20% 60/146 (41.1%) 40/114 (35.1%) 1.57 (0.91 to 2.70) 0.102
Intra-operative rescue antiemetic given 49/146 (33.6%) 33/114 (28.9%) 1.28 (0.75 to 2.18) 0.373
Uterus exteriorized 82/146 (56.2%) 63/114 (55.3%) 0.90 (0.54 to 1.52) 0.700
Total fluids given (L) 2.0 [1.9, 2.5] 2.0 [1.8, 2.4] 1.00 (1.00 to 1.00) 0.130
PONV: postoperative nausea and/or vomiting. Potential variables were included in the multivariable model based on univariable association of variables (p 0.20) with PONV, followed by backward
selection based on Bayesian Information Criteria. The intercept of the multivariable mixed model is 1.00 (SE 0.48), P=0.283.*The Apfel score includes four risk factors: female gender, non-smoking
status, history of PONV or motion sickness and receipt of postoperative opioids (female gender and receipt of postoperative opioids [intrathecal morphine] are present by default in all patients in this
cohort).
H.S. Tan et al.
Table 2 Incidence of postoperative nausea and/or vomiting (PONV) associated with the Duke score and Apfel score
Score Duke Score
PONV Present PONV Absent Total
0 2 (22.2%) 7 (77.8%) 9 –
1 33 (44.6%) 41 (55.4%) 74
2 111 (62.7%) 66 (37.3%) 177
3 – – –
4 – – –
PONV: postoperative nausea and/or vomiting. In the Duke score, one point was assigned for the presence of each risk factor. In the Apfel score,
one point was assigned by default for female gender and receipt of postoperative opioids, respectively, and one point was assigned for the presence
of each additional risk factor.
0.63 (0.57 to 0.70) and low over-optimization (mean
0.0004, 95% CI 0.063 to 0.064).
Calibration plots suggest that both Duke and Apfel
scores were adequately calibrated as the reference line
is within the 95% confidence band, but the Duke score
produced predicted probabilities over a broader range
(0.2 to 0.7), compared with to the restricted range (0.4
to 0.7) for the Apfel score, indicating limited utility.
The Duke score had considerably more wobble com-
pared to the Apfel score (Supplementary Fig. 3).
Discussion
Two variables independently predicted PONV in
parturients undergoing cesarean delivery under spinal
anesthesia, and were included in the Duke score: non-
smoking during pregnancy, and history of PONV after
cesarean delivery and/or morning sickness. Both Duke
and Apfel scores exhibited similar, but poor, predictive
performance.
In non-obstetric PONV risk scores, patient and anes-
thetic variables appear to carry the greatest emetogenic
risk.10 For instance, postoperative opioids and female
sex had respective OR of 4.78 and 2.44 in the Apfel
score,3 however, both are present by default in parturi-
ents receiving neuraxial morphine, potentially limiting
its predictive performance in this population. Con-
versely, several pregnancy-related and cesarean
delivery-related factors might be associated with PONV
risk,11–14 but their predictive performance has not been
evaluated for inclusion in PONV risk scores.
To develop an obstetric-specific risk score, we utilized
prospectively-collected information of patient and peri-
operative risk factors. We also included a number of risk
factors associated with IONV, since it is not clear if
those risk factors or the occurrence of IONV increases
PONV risk. However, only non-smoking and history
of PONV after previous cesarean delivery and/or morn-
ing sickness were independently associated with PONV.
The latter was combined into a composite variable
because: (1) history of PONV after cesarean delivery
was only applicable to 78% of parturients who had pre-
vious cesarean delivery; and (2) separate consideration
of history of PONV after cesarean delivery would
129
Apfel Score
PONV Present PONV Absent Total
– –
– – –
11 (36.7%) 19 (63.3%) 30
82 (57.3%) 61 (42.7%) 143
53 (60.9%) 34 (39.1%) 87
require stratification in three ways: parturients who
never had cesarean delivery; parturients who had cesar-
ean delivery without PONV; and parturients who had
cesarean delivery with PONV. This would increase
model complexity. The Apfel score was chosen as a
benchmark as it is the most commonly used and vali-
dated PONV risk score,11 but it performed poorly in
obstetric patients with an AUC ROC of 0.59, compared
with 0.753 in non-obstetric populations. This supports
our hypothesis that the default presence of two of the
four Apfel risk factors in all patients (female sex and
receipt of postoperative opioids) may diminish the pre-
dictive performance of the Apfel score in obstetric
patients undergoing cesarean delivery with intrathecal
morphine.
The major limitation of our study is the lack of exter-
nal validation. External validation of the Apfel score
reported miscalibration and significant degradation in
PONV prediction, with an AUC of 0.63,4 during exter-
nal validation compared to 0.75 during derivation.3 Our
study has a relatively small sample size, which might
have prevented assessment of rare factors such as hyper-
emesis gravidarum. The strength of our study includes
the detailed prospective collection of potential risk fac-
tors in two studies that used a standardized anesthetic
technique and nausea and/or vomiting as primary
outcomes.
In summary, as expected, the Apfel score performed
poorly in this cohort of women undergoing cesarean
delivery with neuraxial morphine. Identification of inde-
pendent PONV predictors specific to this patient popu-
lation and their incorporation into a risk-scoring model
resulted in only a small improvement in PONV predic-
tion using the Duke score, and an overall poor predic-
tive performance. Given the high incidence of PONV
in this patient population, and the lack of tools to ade-
quately risk-stratify parturients, routine multimodal
anti-emetic prophylaxis seems justified.
Funding
This research did not receive any specific grant from
funding agencies in the public, commercial, or not-for-
profit sectors.
130 A risk score for postoperative nausea and/or vomiting after cesarean delivery

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Declaration of interests trial of phenylephrine infusion versus bolus dosing for nausea and
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None. 2018;65:254–62.
9. Pencina MJ, D’Agostino Sr RB, D’Agostino Jr RB, Vasan RS.
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