ARTICLE IN PRESS

Journal of Cardiothoracic and Vascular Anesthesia 000 (2024) 19

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Journal of Cardiothoracic and Vascular Anesthesia

journal homepage: www.jcvaonline.com

Original Article
Intraoperative Prophylaxis with Palonosetron for
Postoperative Nausea and/or Vomiting in Adults
Undergoing Cardiothoracic Surgery Under General
Anesthesia: A Single-Center Retrospective Study
1
Carlos E. Estrada Alamo, MD, MBA*, ,
Suejean Hwangpo, PharmDy, Lisa Chamberlain, PharmDy,
Connie Chon, MD*, Bala Nair, PhDz,
Vikas O’Reilly-Shah, MD, PhDx, Sarah E. Bain, MD*,
Justin S. Liberman, MD*
*
Department of Anesthesiology, Virginia Mason Medical Center, Seattle, WA
y
Department of Pharmacy Services, Virginia Mason Medical Center, Seattle, WA
z
Perimatics LLC, Bellevue, WA
x
Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA

Objective: This study assessed the efficacy of palonosetron, alone or with dexamethasone, in reducing postoperative nausea and/or vomiting
(PONV) and its impact on hospitalization duration in patients who undergo adult cardiothoracic surgery (CTS) under general anesthesia.
Design: This retrospective analysis involved 540 adult patients who underwent CTS from a single-center cohort, spanning surgeries between
September 2021 and March 2023. Sensitivity, logistic, and Cox regression analyses evaluated antiemetic effects, PONV risk factors, and
outcomes.
Setting: At the Virginia Mason Medical Center (VMMC), Seattle, WA.
Participants: Adults undergoing cardiothoracic surgery at VMMC during the specified period.
Interventions: Patients were categorized into the following 4 groups based on antiemetic treatment: dexamethasone, palonosetron, dexametha-
sone with palonosetron, and no antiemetic.
Measurements and Main Results: Primary outcomes encompassed PONV incidence within 96 hours postoperatively. Secondary outcomes
included intensive care unit stay duration and postoperative opioid use. Palonosetron recipients showed a significantly lower PONV rate of 42%
(v controls at 63%). The dexamethasone and palonosetron combined group also demonstrated a lower rate of 40%. Sensitivity analysis revealed
a notably lower 0- to 12-hour PONV rate for palonosetron recipients (9% v control at 28%). Logistic regression found decreased PONV risk (pal-
onosetron odds ratio [OR]: 0.24; dexamethasone and palonosetron OR: 0.26). Cox regression identified varying PONV hazard ratios related to
female sex, PONV history, and lower body mass index.
Conclusions: This single-center retrospective study underscored palonosetron’s efficacy, alone or combined with dexamethasone, in managing
PONV among adult patients who undergo CTS. These findings contribute to evolving antiemetic strategies in cardiothoracic surgery, potentially
impacting patient outcomes and satisfaction positively.
Ó 2024 Elsevier Inc. All rights reserved.

POSTOPERATIVE NAUSEA AND VOMITING (PONV)

1
Address correspondence to Carlos E. Estrada Alamo, MD, MBA, Depart- is a common complication that affects up to 80% of surgical
ment of Anesthesiology, Virginia Mason Medical Center, 1100 9th Ave, Seat-
patients.1 It significantly can impact patient satisfaction and
tle, WA, 98101.
E-mail address: carlos_estrada@alumni.harvard.edu contribute to increased postanesthesia care unit length of stay,
(C.E. Estrada Alamo). unanticipated hospital admissions, and healthcare costs.2

https://doi.org/10.1053/j.jvca.2024.01.036
1053-0770/Ó 2024 Elsevier Inc. All rights reserved.
 ARTICLE IN PRESS
2 C.E. Estrada Alamo et al. / Journal of Cardiothoracic and Vascular Anesthesia 00 (2024) 19
Patients undergoing cardiothoracic surgery (CTS) under gen-
eral anesthesia are thought to be particularly susceptible to
PONV due to various factors, including the use of volatile
anesthetics and opioids, prolonged surgery with gut hypoper-
fusion, and endogenous catecholamine surge.3-5
A range of pharmacologic and nonpharmacologic interven-
tions have been developed to address PONV management.
Although prophylactic use of antiemetics such as 5-HT3 recep-
tor antagonists, dexamethasone, and neurokinin-1 receptor
antagonists is common for preventing PONV in high-risk
patients, the optimal approach for adults undergoing CTS
remains uncertain.3,6 Palonosetron, a second-generation 5-
HT3-receptor antagonist, is among the newly developed antie-
metics that hold promise as pharmacologic adjuncts to reduce
the incidence of PONV in high-risk patient populations.7,8 Pal-
onosetron exhibits distinct molecular characteristics compared
to first-generation antagonists like ondansetron. Palonosetron’s
chemical structure includes a tricyclic ring system, contribut-
ing to its longer half-life of approximately 40 hours.9 This pro-
longed half-life, along with higher binding affinity and
selectivity for the 5-HT3 receptor, distinguishes palonosetron
from ondansetron. Ondansetron, in contrast, has a simpler
structure and a shorter half-life of about 4 hours. These molec-
ular differences may underlie the potential advantages of palo-
nosetron, including sustained receptor binding and a more
potent antiemetic effect.
The effectiveness of prophylactic regimens for reduc-
ing PONV in patients who undergo CTS varied across
studies.5,10-12 Further investigation is needed to identify
the optimal approach for minimizing the incidence of
PONV. This particular study examined the impact of palo-
nosetron, both alone and in combination with dexametha-
sone, on PONV incidence in adults undergoing CTS under
general anesthesia. The objective was to evaluate the
effectiveness of this intervention in reducing PONV in
this specific patient population. The findings have the
potential to provide valuable insights into the management
of PONV and improve outcomes for patients undergoing
CTS.
Materials and Methods
Study Design and Study Population Assembly
A retrospective analysis of electronic health records (EHR)
was performed on a cohort of adult patients (>18 years) who
underwent CTS under general anesthesia from September 1,
2021, to March 17, 2023, at Virginia Mason Medical Center
(VMMC). The study included patients who underwent coro-
nary artery bypass grafting, open aortic, mitral, and/or tricus-
pid valve repair or replacement, and open ascending aortic
arch repair. The authors excluded minimally invasive cardiac
procedures from their analysis because these patients did not
undergo cardiopulmonary bypass, had varying exposure to
inhalation anesthesia, and underwent shorter surgeries. The
study received expedited review and was approved by the
Institutional Review Board of the Benaroya Research Institute
at VMMC (IRB22-028). The requirement for written informed
consent was waived by the Institutional Review Board. This
manuscript adheres to the applicable Strengthening the Report-
ing of Observational Studies in Epidemiology guidelines.13
Standardized Guidelines for the Prevention of Postoperative
Nausea and/or Vomiting
In March 2022, VMMC implemented standardized practice
guidelines for preventing PONV in patients undergoing
CTS. The guidelines involved administering palonosetron
(0.075 mg as a single dose) via intravenous infusion 30 minutes
before the expected end of surgery.14 Before this standardiza-
tion, there were no specific departmental guidelines for PONV
prevention in patients who undergo CTS. Both before and after
the implementation of palonosetron, the attending anesthesiol-
ogist had the autonomy to administer additional antiemetics
during the surgery if deemed necessary. Postoperative pain
management was determined at the discretion of the surgical
team.
Ascertainment and Validation of CTS Cases
Perioperative data were obtained from the medical records
of adult patients who underwent CTS at VMMC between Sep-
tember 1, 2021, and March 17, 2023. Custom queries were
written to extract information from the Cerner Millennium
EHR database (Cerner Millennium, Cerner Inc, Kansas City,
MO). Structured elements included patient demographics, date
of surgery, surgical procedure, anesthesia type, PONV risk fac-
tors, PONV events, and both intraoperative and postoperative
analgesic and antiemetic medications administered. Unstruc-
tured information, including text from preoperative anesthesia
evaluation notes, was processed using natural language proc-
essing techniques to extract specific details regarding PONV
risk factors (ie, history of PONV or gastroesophageal reflux
disease [GERD]) and medical conditions. Medication-related
information, such as medication type, dose, and administration
time, was extracted from the Medication Administration
Record within the EHR. To ensure data accuracy, 10% of the
extracted data samples were selected randomly and manually
validated against the source data in the EHR.
Primary Independent Variable
The main independent variable (exposure) in the study was
the intraoperative administration of agents with known anti-
emetic activity, including dexamethasone, midazolam, palono-
setron, ondansetron, metoclopramide, meperidine, haloperidol,
diphenhydramine, propofol infusion (20 mg/kg/min through-
out surgery), and scopolamine.15
Primary Outcome Measure
The primary outcome of interest, defined a priori, was the
incidence of PONV up to 96 hours after surgery. PONV was
determined by the presence of documented instances of nausea
 ARTICLE IN PRESS
C.E. Estrada Alamo et al. / Journal of Cardiothoracic and Vascular Anesthesia 00 (2024) 19
or vomiting or the administration of antiemetic medications
during the postoperative period. The Medication Administra-
tion Record was queried to identify specific antiemetic
medications administered postoperatively, including dexa-
methasone, midazolam, palonosetron, ondansetron, metoclo-
pramide, meperidine, haloperidol, diphenhydramine, propofol
infusion (20 mg/kg/min throughout surgery), and scopol-
amine. Patients who received any of these medications were
deemed to have received a rescue antiemetic and consequently
were classified as having experienced PONV.
Secondary Outcome Measures
Secondary outcomes included intensive care unit (ICU)
length of stay and postoperative opioid use. Duration of ICU
length of stay was determined as the time period commencing
from the anesthesia stop time, denoting the completion of
responsibilities by the primary anesthesia team and concluding
at the time of patient discharge from the ICU, as documented
in the EHR. Postoperative opioid use included the administra-
tion of oxycodone, hydromorphone, morphine, fentanyl
(injection and/or patch), buprenorphine, and meperidine.
Cumulative opioid dosages were converted to oral morphine
milligram equivalents (MME) using established opioid conver-
sion factors.16 The median daily MME administered was cal-
culated by summing the MMEs of opioids administered during
the postoperative period and dividing it by the ICU length of
stay, measured in days.
Risk Factors for Postoperative Nausea and/or Vomiting
Data on potential PONV risk factors, such as demographic,
medical history, and perioperative details, were automatically
extracted from the EHR. Factors considered in both univariate
and multivariate logistic regression analyses included age, sex,
height, weight, body mass index (BMI), American Society of
Anesthesiologists (ASA) physical status, smoking status, his-
tory of PONV or motion sickness, history of GERD, surgical
procedure, type of anesthesia, exposure to inhalation anes-
thetic agents (ie, isoflurane and sevoflurane), cumulative intra-
operative opioid administered, and the duration of surgery and
exposure to inhalation anesthetic agents.
Statistical Analysis
Primary statistical analyses for this study were performed
using SAS software (version 9.4, SAS Institute, Inc, Cary, NC).
Visualizations of Kaplan-Meier plots were generated in R 3.0 (R
Foundation for Statistical Computing, Vienna, Austria). Sum-
mary statistics were used to describe the data, with mean (SD)
and median (IQR) used for normally and nonnormally distrib-
uted data, respectively. Categorical variables were presented as
percentages. To examine associations, chi-square tests were per-
formed for categorical data, and independent sample t tests were
used for continuous data. Missing data were not imputed, and
patient counts were specified when less than the total.
3
The study used multivariate logistic regression analysis to
examine the relationship between variables of interest and the
odds of cumulative 96-hour PONV. Additionally, sensitivity
analyses were performed using similar multivariate regression
models, assessing PONV occurrence in 12-hour intervals up to
96 hours after surgery. Variable selection for these multivari-
ate models was performed using a backward elimination
approach with SAS PROC LOGISTIC to determine indepen-
dent associations while accounting for confounding variables.
To minimize discrepancies caused by noncomparable parame-
ters, variable entry and retention criteria of 0.25 and 0.1,
respectively, were employed.17 The strength and significance
of the associations were assessed by reporting odds ratios
(OR), 95% CI, and p values.
KaplanMeier curves were used to analyze PONV-free sur-
vival, with comparison using the log-rank test (Mantel-Cox).
Univariate and multivariate Cox proportional hazards regres-
sion analysis was used to calculate the hazard ratio (HR) and
95% CI for PONV. In the multivariate analysis, variable entry
and retention criteria of 0.25 and 0.1, respectively, were
employed to reduce inconsistencies from non-comparable
parameters.
Sample Size
An a priori power analysis was performed to determine the
minimum sample size necessary for testing the study hypothe-
sis. Assuming a 50% prevalence of PONV in the CTS popula-
tion and a 20% reduction in PONV incidence by using
palonosetron, the results revealed that a sample size of
N = 248 was required to achieve 90% power at a significance
level of a = 0.05.18,19
Results
Cohort Characteristics
Between September 1, 2021, and March 17, 2023, a total of
34,649 patients underwent surgery at VMMC (Fig 1). Of these,
33,604 patients did not undergo CTS and were thus excluded
from further analysis. Patients who underwent minimally inva-
sive cardiac procedures were also excluded due to differences
in their surgical characteristics, such as the absence of cardio-
pulmonary bypass, varying exposure to inhalation anesthesia,
and shorter surgery durations. The final dataset consisted of
540 adult patients who underwent specific cardiac procedures,
such as coronary artery bypass grafting, open aortic, mitral,
and/or tricuspid valve repair or replacement, or open ascending
aortic arch repair. Table 1 presents the baseline cohort charac-
teristics and PONV risk factors stratified by treatment group
and 96-hour PONV incidence. The average age was 67.1 years
(SD = 10.2), and the majority of patients were male (70%).
The majority of patients had an ASA physical status of IV or
V (96%). The case counts for each group were as follows:
dexamethasone (N = 39/540), palonosetron (N = 198/540),
dexamethasone and palonosetron combined (N = 118/540),
and no antiemetic (N = 185/540). No significant differences
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4 C.E. Estrada Alamo et al. / Journal of Cardiothoracic and Vascular Anesthesia 00 (2024) 19
Fig 1. Case-level flow diagram outlining exclusions and case counts.
were found in demographic, medical history, or preoperative
variables among the groups.
Incidence of Postoperative Nausea and/or Vomiting
In the study cohort, the overall incidence of PONV at
96 hours was 49% (N = 265/540) (Table 2). The majority of
PONV events occurred within the first 24 hours after surgery,
with 62% (N = 164/265) of events reported during this time
frame. Figure 2 presents KaplanMeier plots examining the
relationship between antiemetic administration and the cumu-
lative incidence of PONV. Patients who received intraopera-
tive palonosetron had a significantly lower 96-hour PONV rate
of 42% (N = 83/198) compared to the control group, which
had a higher rate of 63% (N = 116/195; log-rank p < 0.001)
(Table 2). Similarly, the group receiving a combination of
dexamethasone and palonosetron showed a significantly lower
96-hour PONV rate of 40% (N = 47/118) compared to the con-
trol group (log-rank p < 0.001). However, the group receiving
dexamethasone alone exhibited a 96-hour PONV rate of 49%
(N = 19/39), and the difference compared to the control group
was not statistically significant (log-rank p = 0.091).
To obtain a more detailed understanding of the incidence of
PONV rates among treatment groups over various postopera-
tive time intervals, sensitivity analysis was performed using
time bins (eg, 0-12 hours, 12-24 hours, etc) (Supplementary
Table S1). In the control group, the 0- to 12-hour postoperative
PONV rate was 28% (95% CI: 22%-35%), whereas the palo-
nosetron group had a significantly lower rate of 9% (95% CI:
5%-12%, p < 0.001). The results of univariate logistic
regression analysis supported these findings, revealing 76%
lower odds of PONV in the palonosetron group compared to
the control group during the 0- to 12-hour period (OR 0.24,
95% CI: 0.13-0.43, p < 0.001) (Table 3). The group receiving
a combination of dexamethasone and palonosetron also
showed a significantly lower PONV rate of 9% (95% CI: 4%-
15%) during the same time period (p < 0.001), with an OR of
0.26 (95% CI: 0.13-0.53, p < 0.001) The administration of
dexamethasone alone did not show a statistically significant
reduction in the 0- to 12-hour PONV rate (13%, 95% CI: 2%-
23%, p = 0.05), with an OR of 0.38 (95% CI: 0.14-1.01,
p = 0.05). Between 12-to-24 hours, the control group had an
event rate of 17% (95% CI: 12%-23%). The differences in
PONV rates between the control and the dexamethasone, palo-
nosetron, and combination dexamethasone and palonosetron
groups were not statistically significant.
Secondary Outcome Analysis
PONV was significantly associated with a longer ICU length
of stay (Table 1). Patients who experienced PONV had a
median ICU length of stay of 6.0 days (IQR: 4.9-8.3), whereas
those without PONV had a shorter medical ICU length of stay
of 5.1 days (IQR: 4.1-7.7; p = 0.002). There was no notable
association between postoperative opioid usage, adjusted for
ICU length of stay, and the occurrence of PONV within
96 hours of surgery, as reflected by the median opioid usage of
21.4 MME per day (IQR: 11.3-45.3) in patients without
PONV and 23.0 MME per day (IQR: 10.8-34.9) in patients
with PONV (p = 0.530).
 ARTICLE IN PRESS
C.E. Estrada Alamo et al. / Journal of Cardiothoracic and Vascular Anesthesia 00 (2024) 19 5

Table 1
Cohort Characteristics and Risk Factors for PONV Stratified by Treatment Group and 96-Hour PONV Incidence

Intraoperative Antiemetic PONV Within 96 h

None Dex Pal Dex + Pal P-Value No Yes p Value

(N = 185) (N = 39) (N = 198) (N = 118) (N = 275) (N = 265)

Age, y 0.063 0.771

Mean (SD) 65.9 (9.81) 65.9 (11.43) 67.7 (10.29) 68.2 (10.11) 66.8 (10.73) 67.3 (9.63)
BMI 0.749 0.039*
Mean (SD) 28.7 (5.73) 28.7 (5.27) 30.0 (7.61) 29.1 (5.85) 29.9 (7.26) 28.7 (5.58)
ASA physical status, n (%) 0.008 0.731
III 9 (4.86) 1 (2.56) 8 (4.04) 3 (2.54) 11 (4.0) 10 (3.8)
IV 165 (89.19) 38 (97.44) 190 (95.96) 113 (95.76) 256 (93.1) 250 (94.3)
V 11 (5.95) 0 (0) 0 (0) 2 (1.69) 8 (2.9) 5 (1.9)
Operative procedure, n (%) 0.666 0.726
Aneurysm repair aortic thoracic: endolumin 1 (0.54) 0 (0) 0 (0) 0 (0) 0 (0.0) 1 (0.4)
Aneurysm repair aortic thoracic ascend + AVR 20 (10.81) 7 (17.95) 31 (15.66) 15 (12.71) 42 (15.3) 31 (11.7)
CABG + endo vein harvest +AVR 12 (6.49) 3 (7.69) 14 (7.07) 11 (9.32) 18 (6.5) 22 (8.3)
CABG +EVH 106 (57.3) 20 (51.28) 100 (50.51) 58 (49.15) 143 (52.0) 141 (53.2)
CABG +EVH + mitral/tricuspid replacement 8 (4.32) 1 (2.56) 4 (2.02) 2 (1.69) 7 (2.5) 8 (3.0)
Mitral valve replacement/repair 19 (10.27) 4 (10.26) 26 (13.13) 10 (8.47) 28 (10.2) 31 (11.7)
Aortic valve replacement 19 (10.27) 4 (10.26) 23 (11.62) 22 (18.64) 37 (13.5) 31 (11.7)
Sex, n (%) 0.842 0.001*
Male 134 (72.43) 28 (71.79) 138 (69.7) 80 (67.8) 211 (76.7) 169 (63.8)
Female 51 (27.57) 11 (28.21) 60 (30.3) 38 (32.2) 64 (23.3) 96 (36.2)
Nonsmoker, n (%) 0.342 0.518
No 7 (3.78) 1 (2.56) 15 (7.58) 7 (5.93) 17 (6.2) 13 (4.9)
Yes 178 (96.22) 38 (97.44) 183 (92.42) 111 (94.07) 258 (93.8) 252 (95.1)
History of PONV, n (%) 0.637 0.006*
No 173 (93.51) 36 (92.31) 187 (94.44) 114 (96.61) 267 (97.1) 243 (91.7)
Yes 12 (6.49) 3 (7.69) 11 (5.56) 4 (3.39) 8 (2.9) 22 (8.3)
History of GERD, n (%) 0.275 0.050
No 123 (66.49) 31 (79.49) 132 (66.67) 86 (72.88) 200 (72.7) 172 (64.9)
Yes 62 (33.51) 8 (20.51) 66 (33.33) 32 (27.12) 75 (27.3) 93 (35.1)
Surgery duration, min 0.259 0.504
Median (IQR) 237.0 (203.0-275.0) 248.0 (194.0-327.0) 248.5 (212.0-287.0) 251.5 (203.0-294.0) 249.0 (211.0-285.0) 240.0 (202.0-290.0)
Volatile exposure, min 0.118 0.930
Median (IQR) 302.0 (259.0-342.0) 302.0 (260.0-369.0) 312.5 (270.0-355.0) 287.0 (228.0-346.0) 302.0 (265.0-347.0) 305.0 (261.0-351.0)
Intraoperative opioid, MME 0.036 0.306
Median (IQR) 120.0 (75.0-150.0) 135.0 (75.0-165.0) 135.0 (90.0-170.0) 100.0 (75.0-150.0) 122.5 (75.0-150.0) 120.0 (82.5-167.5)
Postoperative opioid, MME/d 0.264 0.530
Median (IQR) 21.6 (11.0-35.3) 28.2 (15.4-58.1) 20.5 (10.6-39.4) 23.0 (10.0-47.1) 21.4 (11.3-45.3) 23.0 (10.8-34.9)
Length of stay, d 0.131 0.002*
Median (IQR) 6.0 (4.9-8.0) 5.7 (4.8-7.9) 6.0 (4.8-8.2) 5.1 (4.0-7.1) 5.1 (4.1-7.7) 6.0 (4.9-8.3)

Abbreviations: ASA, American Society of Anesthesiologists; AVR, aortic valve replacement; BMI, body mass index; CABG, coronary artery bypass graft; Dex,
dexamethasone; EVH, endoscopic vein harvest; GERD, gastroesophageal reflux disease; MME, morphine milligram equivalents; PAL, palonosetron; PONV,
postoperative nausea and vomiting.
* Text here.

Risk Factors Associated with 96-Hour Postoperative Nausea
and/or Vomiting
Table 3 displays the relationship between risk factors
and the likelihood of experiencing PONV within 96 hours
of surgery. Elevated odds of experiencing PONV within
96 hours were observed with a history of PONV (OR: 3.0,
95% CI: 1.3-6.9, p value: p = 0.009) and female sex (OR:
1.9, 95% CI: 1.3-2.7, p = 0.001). Conversely, higher BMI
was associated with decreased odds of 96-hour PONV
(OR: 0.97 per BMI unit, 95% CI 0.94-1.00 p = 0.034).
Other risk factors, including age, nonsmoking status, ASA
Physical Status, surgical procedure, surgery duration, anes-
thesia duration, duration of volatile exposure, total intrao-
perative opioid administered, and postoperative opioid
use, showed no significant association with the odds of
96-hour PONV. Although a history of GERD was associ-
ated with increased odds of 96-hour PONV, it did not
reach statistical significance (OR: 1.4, 95% CI: 1.0-2.1,
p = 0.050).
After controlling for confounding variables using multivari-
ate logistic regression and backward elimination, several asso-
ciations with 96-hour PONV remained statistically significant
(Supplementary Table S2). Female sex demonstrated higher
odds of 96-hour PONV (OR = 2.0, 95% CI: 1.3-3.0,
p = 0.001), as did a history of PONV (OR = 2.4, 95% CI: 1.0-
5.8, p = 0.043). Additionally, there was a slight decrease in the
odds of 96-hour PONV with higher BMI (OR = 0.97, 95% CI:
0.94-1.00, p = 0.036). Intraoperative administration of palono-
setron was significantly associated with lower odds of
experiencing PONV at 96 hours (OR = 0.44, 95% CI: 0.30-
0.64, p < 0.001).
 ARTICLE IN PRESS
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Table 2
Cumulative Incidence of PONV Within 96 Hours by PONV Qualifier

Time, h PONV None Dexamethasone Subtotal Palonosetron Subtotal Dexamethasone Subtotal Grand Total
Qualifier and Palonosetron

0-12, n (%) Nausea 5 (2.7) 5 (2.2) 3 (1.5) 8 (2.1) 2 (1.7) 7 (2.3) 10 (1.9)
Vomiting 1 (0.5) 1 (0.4) 1 (0.3) 1 (0.3) 1 (0.2)
Antiemetic 46 (24.9) 5 (12.8) 51 (22.8) 14 (7.1) 60 (15.7) 9 (7.6) 55 (18.2) 74 (13.7)
Total 52 (28.1) 5 (12.8) 57 (25.4) 17 (8.6) 69 (18) 11 (9.3) 63 (20.8) 85 (15.7)
0-24, n (%) Nausea 6 (3.2) 1 (2.6) 7 (3.1) 6 (3) 12 (3.1) 5 (4.2) 11 (3.6) 18 (3.3)
Vomiting 1 (0.5) 1 (0.4) 1 (0.3) 1 (0.3) 1 (0.2)
Antiemetic 77 (41.6) 11 (28.2) 88 (39.3) 35 (17.7) 112 (29.2) 22 (18.6) 99 (32.7) 145 (26.9)
Total 84 (45.4) 12 (30.8) 96 (42.9) 41 (20.7) 125 (32.6) 27 (22.9) 111 (36.6) 164 (30.4)
0-36, n (%) Nausea 7 (3.8) 1 (2.6) 8 (3.6) 8 (4) 15 (3.9) 5 (4.2) 12 (4) 21 (3.9)
Vomiting 1 (0.5) 1 (0.4) 1 (0.5) 2 (0.5) 1 (0.3) 2 (0.4)
Antiemetic 87 (47) 14 (35.9) 101 (45.1) 41 (20.7) 128 (33.4) 23 (19.5) 110 (36.3) 165 (30.6)
Total 95 (51.4) 15 (38.5) 110 (49.1) 50 (25.3) 145 (37.9) 28 (23.7) 123 (40.6) 188 (34.8)
0-48, n (%) Nausea 7 (3.8) 2 (5.1) 9 (4) 11 (5.6) 18 (4.7) 5 (4.2) 12 (4) 25 (4.6)
Vomiting 1 (0.5) 1 (0.4) 1 (0.5) 2 (0.5) 1 (0.3) 2 (0.4)
Antiemetic 97 (52.4) 14 (35.9) 111 (49.6) 50 (25.3) 147 (38.4) 31 (26.3) 128 (42.2) 192 (35.6)
Total 105 (56.8) 16 (41) 121 (54) 62 (31.3) 167 (43.6) 36 (30.5) 141 (46.5) 219 (40.6)
0-60, n (%) Nausea 7 (3.8) 2 (5.1) 9 (4) 11 (5.6) 18 (4.7) 6 (5.1) 13 (4.3) 26 (4.8)
Vomiting 1 (0.5) 1 (0.4) 1 (0.5) 2 (0.5) 1 (0.3) 2 (0.4)
Antiemetic 99 (53.5) 16 (41) 115 (51.3) 54 (27.3) 153 (39.9) 34 (28.8) 133 (43.9) 203 (37.6)
Total 107 (57.8) 18 (46.2) 125 (55.8) 66 (33.3) 173 (45.2) 40 (33.9) 147 (48.5) 231 (42.8)
0-72, n (%) Nausea 7 (3.8) 2 (5.1) 9 (4) 11 (5.6) 18 (4.7) 7 (5.9) 14 (4.6) 27 (5)
Vomiting 1 (0.5) 1 (0.4) 1 (0.5) 2 (0.5) 1 (0.3) 2 (0.4)
Antiemetic 105 (56.8) 17 (43.6) 122 (54.5) 60 (30.3) 165 (43.1) 37 (31.4) 142 (46.9) 219 (40.6)
Total 113 (61.1) 19 (48.7) 132 (58.9) 72 (36.4) 185 (48.3) 44 (37.3) 157 (51.8) 248 (45.9)
0-84, n (%) Nausea 7 (3.8) 2 (5.1) 9 (4) 11 (5.6) 18 (4.7) 7 (5.9) 14 (4.6) 27 (5)
Vomiting 1 (0.5) 1 (0.4) 1 (0.5) 2 (0.5) 1 (0.3) 2 (0.4)
Antiemetic 106 (57.3) 17 (43.6) 123 (54.9) 65 (32.8) 171 (44.6) 38 (32.2) 144 (47.5) 226 (41.9)
Total 114 (61.6) 19 (48.7) 133 (59.4) 77 (38.9) 191 (49.9) 45 (38.1) 159 (52.5) 255 (47.2)
0-96, n (%) Nausea 7 (3.8) 2 (5.1) 9 (4) 11 (5.6) 18 (4.7) 8 (6.8) 15 (5) 28 (5.2)
Vomiting 1 (0.5) 1 (0.4) 1 (0.5) 2 (0.5) 1 (0.3) 2 (0.4)
Antiemetic 108 (58.4) 17 (43.6) 125 (55.8) 71 (35.9) 179 (46.7) 39 (33.1) 147 (48.5) 235 (43.5)
Total 116 (62.7) 19 (48.7) 135 (60.3) 83 (41.9) 199 (52) 47 (39.8) 163 (53.8) 265 (49.1)

Abbreviation: PONV, postoperative nausea and vomiting.

Table 4 presents statistically significant associations with backward elimination, several associations with the risk of 96-
the risk (HR) of experiencing PONV within 96 hours, as hour PONV remained statistically significant (Supplementary
observed in the time-to-event analysis. After adjusting for con- Table S3). Notably, female sex was associated with a 1.7 times
founding variables using multivariate Cox regression and higher hazard (HR) of PONV compared to male patients (95%

Fig 2. KaplanMeier analysis. Cumulative incidence of postoperative nausea and/or vomiting by antiemetic group. PONV, postoperative nausea and/or vomiting.
 ARTICLE IN PRESS
C.E. Estrada Alamo et al. / Journal of Cardiothoracic and Vascular Anesthesia 00 (2024) 19 7

Table 3 Discussion
Univariate Logistic Regression Analysis of Associations With 96-Hour PONV

N OR OR
The authors’ study examined the associations between the
(95% CI) p Value intraoperative administration of prophylactic antiemetics and
the incidence of PONV in adult patients undergoing CTS
Age, y 540 1.00 (0.99-1.02) 0.611 under general anesthesia at VMMC. Specifically, the authors’
BMI 495 0.97 (0.94-1.00) 0.034
ASA physical status
focus was on palonosetron, a second-generation 5-HT3 anti-
3 21 1.45 (0.36-5.94) 0.602 emetic that offers several advantages over first-generation 5-
4 506 1.56 (0.50-4.84) 0.439 HT3 antagonists such as ondansetron, granisetron, and dolase-
5 13 - - tron. First, palonosetron’s extended half-life of 40 hours sug-
Operative procedure gests the potential for a sustained effect and reduced frequency
Aneurysm repair aortic 1 647182.3 (0.00-I) 0.986
thoracic: endolumin
of dosing.20 Second, it exhibits higher binding affinity and
Aneurysm repair aortic 73 0.88 (0.45-1.71) 0.709 selectivity for the 5-HT3 receptor, resulting in a more potent
thoracic ascend + AVR antiemetic effect compared to other drugs in the same class.21
CABG + eEVH + AVR 40 1.46 (0.67-3.20) 0.346 Lastly, palonosetron has shown a lower incidence of adverse
CABG + EVH 284 1.18 (0.69-2.00) 0.548 effects such as headache and constipation when compared to
CABG + EVH + mitral/ 15 1.36 (0.44-4.18) 0.587
tricuspid replacement
other 5-HT3-receptor antagonists.21 Due to these advantages,
Mitral valve replacement/ 59 1.32 (0.66-2.66) 0.435 palonosetron is increasingly favored as the preferred seroto-
repair nin-receptor antagonist medication for preventing chemother-
Aortic valve replacement 68 - - apy-induced PONV in high-risk patients.22,23
Risk factor, female patients The log-rank test compared 96-hour PONV-free survival
No 380 - -
Yes 160 1.87 (1.29-2.73) 0.001
curves, revealing lower PONV risk in palonosetron recipients.
Risk factor, non-smoking status Sensitivity analysis confirmed this trend within 0-to-12 hours,
No 30 - - with lower PONV rates in palonosetron groups versus the con-
Yes 510 1.28 (0.61-2.68) 0.518 trol. The lack of statistical difference in subsequent 12-hour
Risk factor, history of PONV intervals (eg, 12-24 hours, etc.) may be attributed to several
No 510 - -
Yes 30 3.02 (1.32-6.91) 0.009
factors. First, the effect of palonosetron on PONV risk dimin-
Risk factor, history of GERD ishes over time due to drug metabolism. Secondly, the overall
No 372 - - incidence of PONV may decrease over time, especially in
Yes 168 1.44 (1.00-2.08) 0.05 high-risk patients. Finally, the limited number of patients
Risk factor, postoperative opioid experiencing PONV in each time period made it challenging
use
No 8
to detect statistically significant differences in PONV rates
Yes 532 6.89 (0.84-56.30) 0.072 among the study groups. Larger studies with more participants
Intraoperative palonosetron are required to validate the findings of this study and establish
No 224 - - the optimal palonosetron administration time for preventing
Yes 316 0.46 (0.33-0.65) < 0.001 PONV.
Intraoperative dexamethasone
No 383 - -
The authors’ analysis of cumulative PONV rates in high-risk
Yes 157 0.67 (0.46-0.98) 0.037 patients who underwent CTS unveiled a nuanced yet poten-
Surgery duration, min 540 1.00 (1.00-1.00) 0.365 tially clinically significant distinction in cumulative PONV
Volatile exposure, min 412 1.00 (1.00-1.00) 0.974 incidence between the dexamethasone (49%) and palonosetron
Total intraoperative opioid, 476 1.00 (1.00-1.00) 0.482 (42%) groups compared to the control. Given the intricacies of
MME
Total postoperative opioid, MME 481 1.00 (1.00-1.00) 0.555
these surgeries, even a slight decrease in PONV incidence
Length of stay, d 530 1.02 (1.00-1.04) 0.077 could prove crucial for improving overall patient well-being
and postoperative recovery in individuals undergoing cardio-
Abbreviations: ASA, American Society of Anesthesiologists; AVR, aortic thoracic procedures. This high-risk population, often burdened
valve replacement; BMI, body mass index; CABG, coronary artery bypass
graft; EVH, endovascular vein harvesting; GERD, gastroesophageal reflux
with multiple comorbidities, faces heightened vulnerability to
disease; MME, morphine milligram equivalents; OR, odds ratio; PONV, PONV’s adverse effects, including compromised respiratory
postoperative nausea and vomiting. function and delayed mobilization. Therefore, any reduction,
regardless of its subtlety, holds the potential to significantly
contribute to optimizing patient outcomes in cardiothoracic
CI: 1.3-2.2, p < 0.001), and patients with a history of PONV interventions.
had a 1.9 times higher hazard (HR = 1.9, 95% CI: 1.2-3.0, Analysis of secondary outcome measures revealed that
p = 0.005). Conversely, higher BMI was associated with a patients experiencing PONV within 96 hours of surgery
lower hazard of PONV (HR = 0.97, 95% CI: 0.95-0.99, had a median additional ICU stay of 0.9 days, potentially
p = 0.009). In time-to-event analysis, intraoperative palonose- increasing healthcare costs. Effective personalized PONV
tron demonstrated a statistically significant protective effect, prophylaxis strategies for patients who undergo CTS could
with an HR of 0.51 (95% CI: 0.40-0.65, p < 0.001). lead to cost savings, but more research is needed to
 ARTICLE IN PRESS
8 C.E. Estrada Alamo et al. / Journal of Cardiothoracic and Vascular Anesthesia 00 (2024) 19

Table 4
Univariate Cox Regression Analysis of Associations With 96-Hour PONV

Level N HR (95% CI) HR p Value

Age, y 538 1.00 (0.99-1.02) 0.621

BMI 493 0.98 (0.96-1.00) 0.025*
ASA physical status V 13 0.72 (0.25-2.10) 0.543
IV 506 1.00 (0.53-1.89) 0.99
III 21 - -
Surgery duration, min 538 1.00 (1.00-1.00) 0.156
Volatile exposure, min 410 1.00 (1.00-1.00) 0.754
Risk factor, female sex Yes 160 1.61 (1.25-2.07) < 0.001*
No 380 - -
Risk factor, non-smoking Yes 510 1.26 (0.72-2.20) 0.413
No 30 - -
Risk factor, history of PONV Yes 30 2.14 (1.38-3.32) < 0.001*
No 510 - -
Risk factor, history of GERD Yes 168 1.33 (1.03-1.71) 0.027*
No 372 - -
Risk factor, postoperative opioids Yes 532 5.04 (0.71-35.92) 0.106
No 8 - -
Intraoperative dexamethasone Yes 157 0.73 (0.55-0.97) 0.028*
No 383 - -
Intraoperative palonosetron Yes 316 0.53 (0.41-0.67) < 0.001*
No 224 - -
Intraoperative dexamethasone + palonosetron Yes 118 0.68 (0.50-0.93) 0.017*
No 422 - -

Abbreviations: ASA, American Society of Anesthesiologists; BMI, body mass index; GERD, gastroesophageal reflux disease; HR, hazard ratio; PONV,
postoperative nausea and vomiting.
* Text here.

evaluate the economic impact and cost-effectiveness of tai-
lored PONV management.
In the authors’ study, well-established risk factors for
PONV, such as younger age, nonsmoking status, and dura-
tion of anesthesia, did not significantly predict 96-hour
PONV in their cohort. Several factors may have contributed
to this result. First, the limited sample size of the authors’
study may have affected the detection of statistically signifi-
cant associations between these risk factors and 96-hour
PONV. Additionally, their study focused exclusively on
patients undergoing CTS, and PONV risk factors may vary
by surgical specialty. To enhance patient-specific prophy-
laxis strategies and gain a comprehensive understanding of
PONV risk factors, future studies should involve larger and
more diverse populations.
Limitations
The study was subject to various limitations. Firstly, reli-
ance on EHR data, despite efforts to ensure quality, may intro-
duce issues due to missing, inaccurate, or incomplete
information, potentially influencing the results. The limited
sample size may impede the detection of significant associa-
tions between risk factors and PONV, emphasizing the neces-
sity for larger samples to yield more robust findings. A notable
challenge arose from the uneven distribution of patients across
antiemetic groups, particularly with the dexamethasone group
having a substantially smaller size (n = 39) than the palonose-
tron group (n = 198), potentially introducing nonuniformity in
assessing antiemetic effectiveness, despite statistical analyses
to address this disparity. Although the study indicated a signifi-
cant reduction in PONV with combined dexamethasone and
palonosetron, discerning the specific contributions of each
drug remains uncertain.
Further analyses, such as subgroup assessments or con-
trolled trials, are essential for isolating and understanding the
individual impact of each medication on PONV. Moreover,
the retrospective design introduced the possibility of unmea-
sured confounding factors affecting observed associations.
Additionally, the single-institution focus within a specific sur-
gical subspecialty may introduce selection bias and limit the
findings’ applicability to other surgical specialties. Neverthe-
less, the study offered valuable insights into PONV risk factors
and the benefits of prophylactic antiemetics like palonosetron
in CTS. Prospective studies involving diverse surgical popula-
tions are necessary to validate the findings, address
limitations, and enhance personalized PONV prophylaxis
strategies.
Conclusions
Intraoperative palonosetron, with or without dexametha-
sone, was effective in preventing PONV within the first
12 hours postoperatively. Female sex, lower BMI, and a his-
tory of PONV were identified as significant risk factors for
PONV in patients who undergo CTS. These findings highlight
the importance of including palonosetron in a comprehensive
antiemetic regimen for patients who undergo CTS.
 ARTICLE IN PRESS
C.E. Estrada Alamo et al. / Journal of Cardiothoracic and Vascular Anesthesia 00 (2024) 19
Declaration of competing interest
Vikas O’Reilly-Shah holds equity in Doximity Inc. Bala
Nair is the Chief Technology Officer for Perimatics LLC and
holds equity in the company. The other authors declare no
competing interests.
CRediT authorship contribution statement
Carlos E. Estrada Alamo: Data curation, Formal analysis,
Investigation, Methodology, Project administration, Software,
Supervision, Validation, Visualization, Writing  original
draft, Writing  review & editing, Resources. Suejean
Hwangpo: Data curation, Methodology, Validation. Lisa
Chamberlain: Conceptualization, Methodology, Writing 
review & editing. Connie Chon: Validation, Investigation.
Bala Nair: Data curation, Software, Validation, Writing 
review & editing. Vikas O’Reilly-Shah: Formal analysis,
Methodology, Writing  review & editing. Sarah E. Bain:
Conceptualization, Data curation, Investigation, Methodology,
Validation, Writing  original draft, Writing  review & edit-
ing. Justin S. Liberman: Conceptualization, Data curation,
Formal analysis, Investigation, Methodology, Validation,
Writing  original draft, Writing  review & editing.
Acknowledgments
The authors would like to extend their gratitude to the Peri-
matics data science team for their invaluable assistance in
extracting patient data from the electronic medical record.
Their expertise, efficiency, and dedication to producing accu-
rate results greatly contributed to the success of this study.
Supplementary materials
Supplementary material associated with this article can be
found in the online version at doi:10.1053/j.jvca.2024.01.036.
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