Dexamethasone vs Ondansetron as the First-line Antiemetic to Prevent Postoperative Nausea and Vomiting After Cesarean Delivery
Phase: PHASE4
Conditions: Nausea and Vomiting, Postoperative, Cesarean Section Complications
Sponsor: Beth Israel Deaconess Medical Center

(CCI) Committee on Clinical Investigations 
Page 1 of 6 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 1/9/2022 
PART B 
STUDY DESCRIPTION 
 
TITLE OF PROTOCOL 
Dexamethasone vs Ondansetron as the First-Line Antiemetic 
to Prevent Postoperative Nausea and Vomiting after 
Cesarean Delivery 
Principal Investigator 
Philip E. Hess, MD 
 
 
B1. 
PURPOSE OF PROTOCOL 
To determine whether dexamethasone or ondansetron should be used as a first-line antiemetic 
for prophylaxis against postoperative nausea and vomiting after cesarean delivery. To 
investigate whether dexamethasone will provide additional analgesic benefit when compared 
to ondansetron. 
  
 
 
B2. 
SIGNIFICANCE AND BACKGROUND FOR THE STUDY 
Cesarean delivery is the most common surgical procedure performed in the United States, 
with approximately 1.2 million cesarean deliveries performed in 2020.(1) Cesarean delivery 
is preferentially performed under neuraxial anesthesia (spinal or epidural anesthesia) to 
allow mothers to be awake during the delivery of their child and to improve maternal safety. 
Despite the routine use of neuraxial techniques for most cesarean deliveries in the United 
States, many patients experience nausea and/or vomiting either during surgery 
(intraoperative nausea and vomiting, IONV) or after surgery (postoperative nausea and 
vomiting, PONV).  
 
PONV has traditionally been associated with female gender, history of motion sickness, 
nonsmoking status, and opioid use.(2) Other authors have shown increased PONV risk with 
younger age, type of surgery, and general anesthesia as opposed to regional or neuraxial 
anesthesia.(3,4) Intrathecal opioids, are the gold standard for pain relief after cesarean 
delivery, and are part of the Society for Obstetric Anesthesia and Perinatology’s (SOAP) 
Early Recover After Cesarean (ERAC) guideline. However, these medications have been 
implicated in increased rates of PONV.(5) Given the prevalence of cesarean delivery and 
the importance of maternal well-being, prophylaxis of nausea and vomiting remains an 
important issue to address.  
 
Medications from multiple classes are commonly administered to prevent and treat PONV 
after cesarean delivery. These include 5-HT3 antagonists, dopaminergic antagonists, 
corticosteroids, antihistamines, and anticholinergics. Ondansetron, a 5HT3 antagonist, and 
dexamethasone, a corticosteroid, are among the most commonly administered medications 
due to their efficacy and long track record of safety during pregnancy. Indeed, the SOAP 
ERAC guideline recommends that at least two agents from different classes be administered 
perioperatively to decrease the rates of IONV and PONV.(6) They further suggest 
metoclopramide for IONV prophylaxis, ondansetron or dexamethasone for PONV 
prophylaxis.  
 
The safety and efficacy of ondansetron and dexamethasone are further supported by a 2021  
Cochrane Systematic review analyzing medical prophylaxis against IONV and PONV in 
cesarean delivery.(6) Both ondansetron and dexamethasone decreased postoperative 

(CCI) Committee on Clinical Investigations 
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Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 1/9/2022 
nausea (Ond: RR 0.45; 10 RCT, 1340 total subjects; Dex: RR 0.59; 6 studies, 733 women) 
and vomiting rates (Ond: RR 0.47, 10 studies, 1450 women; Dex: RR 0.68; 7 RCT, 793 
women). No adverse events from 5HT3 blocking agents or corticosteroids were identified.  
 
Dexamethasone is intriguing as a first-line agent for cesarean delivery since it may have the 
added benefit of improved pain control and/or decreased postoperative opioid requirement. 
Several studies have addressed the role of dexamethasone in pain management. A 2008 
study by Jaafarpour et al.(8) found a decrease in composite rates of nausea and vomiting, 
as well reduction of ~1 point on the VAS pain scale for 24 hours following surgery. Data from 
other studies have been mixed (9, 10, 11). 
 
In conclusion, there is a gap in knowledge in defining the optimal first-line antiemetic for 
prophylaxis of PONV in patients undergoing cesarean delivery. Our goal is to evaluate the 
effectiveness of ondansetron vs. dexamethasone on PONV rates and postoperative pain 
control. 
 
References 
1. CDC, National Vital Statistics Reports, Vol. 70, No. 17, Feb 7 2022 
2. Apfel CC, Läärä E, Koivuranta M, Greim CA, Roewer N. A simplified risk score for 
predicting postoperative nausea and vomiting: conclusions from cross-validations 
between two centers. Anesthesiology. 1999 Sep;91(3):693-700. doi: 
10.1097/00000542-199909000-00022. PMID: 10485781. 
3. Sinclair DR, Chung F, Mezei G. Can postoperative nausea and vomiting be 
predicted? Anesthesiology. 1999 Jul;91(1):109-18. doi: 10.1097/00000542-
199907000-00018. PMID: 10422935. 
4. Gan TJ, Meyer T, Apfel CC, Chung F, Davis PJ, Eubanks S, Kovac A, Philip BK, 
Sessler DI, Temo J, Tramèr MR, Watcha M; Department of Anesthesiology, Duke 
University Medical Center. Consensus guidelines for managing postoperative 
nausea and vomiting. Anesth Analg. 2003 Jul;97(1):62-71, table of contents. doi: 
10.1213/01.ane.0000068580.00245.95. PMID: 12818945. 
5. Dahl JB, Jeppesen IS, Jorgensen H, Wetterslev J, Moiniche S. Intraoperative and 
postoperative analgesic efficacy and ad- verse effects of intrathecal opioids in 
patients undergoing cesarean section with spinal anesthesia: a qualitative and 
quantitative systematic review of randomized controlled trials. Anesthesiology 
1999;91:1919 –27  
6. Bollag L, Lim G, Sultan P, Habib AS, Landau R, Zakowski M, Tiouririne M, 
Bhambhani S, Carvalho B. Society for Obstetric Anesthesia and Perinatology: 
Consensus  
7. Griffiths JD, Gyte GM, Popham PA, Williams K, Paranjothy S, Broughton HK, Brown 
HC, Thomas J. Interventions for preventing nausea and vomiting in women 
undergoing regional anaesthesia for caesarean section. Cochrane Database Syst 
Rev. 2021 May 18;5(5):CD007579. doi: 10.1002/14651858.CD007579.pub3. PMID: 
34002866; PMCID: PMC8130052.Statement and Recommendations for Enhanced 
Recovery After Cesarean. Anesth Analg. 2021 May 1;132(5):1362-1377. doi: 
10.1213/ANE.0000000000005257. PMID: 33177330. 
8. Jaafarpour M, Khani A, Dyrekvandmoghadam A, Khajavikhan J, Saadipour Kh. The 
Effect Of Dexamethasone On Nausea, Vomiting And Pain In Parturients Undergoing 

(CCI) Committee on Clinical Investigations 
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Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 1/9/2022 
Caesarean Delivery Journal Of Clinical And Diagnostic Research [Serial Online] 2008 
June [Cited: 2008 June 2];3:854- 858  
9. Mehdiratta JE, Dominguez JE, Li YJ, Saab R, Habib AS, Allen TK. Dexamethasone 
as an Analgesic Adjunct for Postcesarean Delivery Pain: A Randomized Controlled 
Trial. Anesthesiol Res Pract. 2021 Sep 24;2021:4750149. doi: 
10.1155/2021/4750149. PMID: 34603442; PMCID: PMC8486547. 
10. Selzer A, Pryor KO, Tangel V, O'Connell K, Kjaer K. The effect of intravenous 
dexamethasone on postoperative nausea and vomiting after Cesarean delivery with 
intrathecal morphine: a randomized-controlled trial. Can J Anaesth. 2020 
Jul;67(7):817-826. English. doi: 10.1007/s12630-020-01582-y. Epub 2020 Jan 27. 
PMID: 31989472. 
11. Ituk U, Thenuwara K. The effect of a single intraoperative dose of intravenous 
dexamethasone 8 mg on post-cesarean delivery analgesia: a randomized controlled 
trial. Int J Obstet Anesth. 2018 Aug;35:57-63. doi: 10.1016/j.ijoa.2018.03.008. Epub 
2018 Mar 26. PMID: 29773484 
 
B3. 
DESCRIPTION OF RESEARCH PROTOCOL 
A. 
Study Design – Overview, Methods, Procedures 
 
Study Design 
Prospective, randomized, double-blind, controlled trial. 
 
Endpoints:  
Primary outcome: Composite need for treatment of nausea and vomiting, pain, and pruritus in 
the 24 hours following cesarean delivery.  
 
Secondary outcomes: visual analogue scores for pain, PONV, pruritus in the PACU at 0 and 2 
hours, and at 24 hours. Obstetric quality of recovery score (OBQoR-11).  
 
Brief Study Protocol: 
Standard care pathway: 
Patients will receive standard care for their cesarean and post-cesarean care. This includes 
preoperative intravenous catheter placement with preoperative IV fluid, standard American 
Society of Anesthesiologists monitoring, and neuraxial anesthesia (either spinal or combined 
spinal-epidural) in a sterile fashion. Each patient will receive standard cesarean neuraxial 
anesthesia dose of intrathecal medication consisting of 1.5 ml of 0.75% hyperbaric 
bupivacaine, fentanyl 25 mcg, and 150 mcg of morphine. At end of surgery, all patients will 
receive standard dose of ketorolac 30 mg IV and acetaminophen 1 gm IV and continue with 
redosing every 6 and 8 hours (respectively) for 24 hours. On arrival to PACU, all patients will 
receive standard nursing care with standard monitoring of side effects. On discharge from 
PACU, patients will be transferred to postpartum floor and receive standard nursing care and 
monitoring.  
 
Over the following 24 hours, all standard post-cesarean medications will be used.  
For treatment of breakthrough pain: 
• oxycodone 5-10 mg PO every four hours PRN for pain.  
For treatment of PONV: 
• promethazine 6.25 mg IV as first-line for nausea/vomiting,   

(CCI) Committee on Clinical Investigations 
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Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 1/9/2022 
• haloperidol 0.5-1 mg IV for refractory nausea/vomiting.  
For treatment of pruritus: 
• naloxone 0.04 mg IV for refractory pruritus. 
 
Study Procedures: 
After induction of spinal anesthesia, patients will receive either dexamethasone 8 mg or 
ondansetron 4 mg in a randomized and blinded fashion.  
 
Study measurements will all be recorded by a blinded investigator. Patients will be asked 
to score their nausea, pain, and pruritus on a Visual Analog Scale (10 cm, unmarked line) 
on arrival to PACU, 2 hours postoperatively, and 24 hours postoperatively. At 24 hours, 
patients will be asked to complete Quality of Recovery Score following Cesarean Delivery 
Questionnaire (ObsQoR-11). 
 
The primary outcome is the total rescue medication dose. The incidence of any side effects 
will be recorded, as will the time to first rescue medications.   
 
 
B. 
Statistical Considerations 
a. Sample Size Justification:   
The sample size for this trial was determine using the two-sample Mann-Whitney U-
Test, based on the Alpha (two-sided) = 0.05 and Power = 0.8 with an assumed 
P(X>Y) 0.67. The required sample size per group is 46. We plan to increase to 50 
patients per group to account for drop outs. Thus, we will enroll 100 patients. 
 
b. Data Analysis:   
 
Descriptive statistics of the demographics will be performed. Data will be graphed and 
assessed for normality using histograms, QQ plots and the Shapiro-Wilk test. Continuous 
data, such as age, pain scores, and opioid consumption, will be presented as mean (SD) or 
median [interquartile range], as appropriate. Between-group comparisons will be assessed 
using the unpaired t-test and Mann-Whitney U test, as appropriate. Categorical data, such as 
the proportion of patients who successfully completed the study protocol, will be presented as 
frequencies or proportions and analyzed using a chi-square or Fisher’s Exact test. All two-
sided p-values ≤0.05 will be considered statistically significant. 
 

(CCI) Committee on Clinical Investigations 
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Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 1/9/2022 
C. 
Subject Selection 
All patients will be selected from the schedule or add-on list of cesarean deliveries at BIDMC. 
All patients will meet inclusion and exclusion criteria. 
 
Inclusion criteria:  
• Healthy women (ASA 2)  
• Between 18 and 45 years old  
• Singleton term pregnancies  
• Scheduled or non-labor cesarean delivery 
• Neuraxial (spinal or combined-spinal epidural) anesthesia 
 
Exclusion criteria:  
• Refusal to participate  
• Known allergy or contraindication to any medication used in the study 
• Significant medical or obstetrical disease (ASA ≥ 3) 
• Antiemetic use within 24 hours preceding cesarean delivery 
• Insulin dependent diabetes 
• Hyperemesis gravidarum or chronic antiemetic use 
• History of daily or near-daily steroid use during pregnancy 
• Opioid use disorder or other chronic pain syndrome 
• Opioid use during pregnancy 
• Use of antipruritus medication, pruritic urticarial papules of pregnancy, or cholestasis of 
pregnancy 
  
 
 
B4. 
POSSIBLE BENEFITS 
All patients in the study will benefit from receiving an antiemetic medication. It is unknown if 
inclusion in the study will provide additional analgesic benefit to those assigned to the 
dexamethasone arm. The study will provide benefit to future patients to determine which 
medication is more efficacious as first-line agent for PONV prophylaxis.  
 
 
 
B5. 
POSSIBLE RISKS AND ANALYSIS OF RISK/BENEFIT RATIO 
There are no additional risks for being enrolled in this study as patients would routinely be 
receiving ondansetron and/or dexamethasone per provider preference. Both medications are 
routinely administered during cesarean delivery. 
 

(CCI) Committee on Clinical Investigations 
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Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 1/9/2022 
B6. 
RECRUITMENT AND CONSENT PROCEDURES 
Recruitment 
All patients will be identified from the schedule and add-on list of cesarean deliveries at BIDMC. 
The pateints will be approached by a study investigator who will determine the patient’s 
willingness to participate and if the patient may meet inclusion and exclusion criteria. The 
investigator will present the study to the patient and perform informed consent for enrollment in 
the study.  
  
 
Consent 
The study investigator will obtain written informed consent from the potential subject in the 
preoperative holding area. This is a secure location that is currently used for all medical 
conversations with patients, including informed consent. The patient’s support person(s) (e.g. 
spouse, parent, etc.) may remain for the informed consent procedure. 
 
 
Subject Protection 
We do not anticipate that any subjects would be vulnerable to coercion or undue influence. No 
consent will be obtained from patients needing an urgent or stat cesarean delivery, as 
institutionally defined, in order to ensure that patients have enough time for the consent process 
and are not in an adverse emotional state at the time of consent. Furthermore, it will be made 
clear to the patients of the Principal and Co-Investigators that their participation is entirely 
voluntary and will not affect their clinical care with their physicians if they decline participation. 
Patients will also have the ability to discontinue their participation at any time.  
 
B7. 
STUDY LOCATION 
 Privacy  
All conversations will be had in the secured area currently used for private medical 
conversations. No information will be shared outside of the study personnel and BIDMC. 
Patient information will extracted from the medical record and entered into a REDCap 
database. Any paper notes containing patient data will be kept in locked cabinets and 
rooms. 
 
 Physical Setting 
All conversations and consent discussions will be help in the preoperative area designed 
for this type of interaction. The patient will be cared for on the labor and delivery unit for the 
cesarean delivery, and on the postpartum unit for their recovery. These are the typical 
locations for these women, whether participating in a study or not. 
 
 
B8. 
DATA SECURITY 
Initial study documents including consent and enrollment documentation will be stored in the 
Obstetric anesthesia office in a secured location, accessible to research investigators. Any 
notes recorded on paper being destroyed in a HIPAA compliant manner.  
 
Research data will be stored on data-encrypted files on a secure server behind the BIDMC 
firewall. It will be password protected. Only research staff will have access to this data. 
 
Study data will be collected and managed using REDCap electronic data capture tools 
hosted at Beth Israel Deaconess Medical Center. No identifiable information with be shared 

(CCI) Committee on Clinical Investigations 
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Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 1/9/2022 
outside of BIDMC and all non-identifiable information will be pooled and released as a group 
for the final study after statistical analysis is complete. Identifiers will be kept until completion 
of data analysis to allow for review of additional information that may become necessary 
during the statistical analysis phase. After the completion of the statistical analysis phase 
and a sufficient length of time, the file containing the patients' MRNs and study specific 
unique numerical identifiers will be deleted. No identifiable information with be shared 
outside of BIDMC. Identifiers will be kept until completion of data analysis to allow for review 
of additional information that may become necessary during the statistical analysis phase. 
Data will be destroyed 3 years after publication. 
 
B9 
Multi-Site Studies 
 
Is the BIDMC the coordinating site?        Yes     No  
 
Is the BIDMC PI the lead investigator of the multi-site study?      Yes     No  
 
      
 
B10 
Dissemination of Research Results 
 
Please explain whether you will be able to thank subjects and provide research results and, if so, how this will 
be accomplished. If you do not think this is feasible, appropriate or applicable to this research, please specify 
why. 
 
Patients will be thanked at time of enrollment, however research results will not be routinely 
distributed to the patients at completion of the study. If a patient specifically requests their 
individual results or the aggregated results, this will be performed on an individual basis.