Clinical trial NCT03435003
Conditions: Post-operative Nausea and Vomiting Laparoscopic Sleeve Gastrectomy
Keywords: Bariatric Procedure
Sponsor: Stony Brook University
Start date: 2017-08-28; Completion date: 2019-04-01
Enrollment: 83 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Bariatric surgery remains the most effective therapy for obesity. Postoperative nausea and vomiting (PONV) are commonly reported following bariatric surgery. The proposed study focuses on the most common bariatric procedure performed, laparoscopic sleeve gastrectomy (LSG), and aims to assess the effect of a post-operative nausea and vomiting-specific intervention. The investigators hypothesize that the intervention group will experience a reduction of nausea-related prolonged hospital stay and significantly improve patient-reported quality of recovery from surgery and quality of life.

Detailed description:
To test this hypothesis, participants undergoing sleeve gastrectomy will be randomized to two groups: control vs Nausea specific-intervention group. All subjects will be assessed with a nausea specific questionnaire at 1, 4, 12, 24 hours and 3 weeks after surgery. Patient satisfaction with recovery will be assessed using specialized questionnaires at baseline, 24 hrs. and 3 weeks following surgery. Serial assessments of nausea, vomiting, quality of life and quality of recovery, will allow the investigators to identify an effect on incidence and severity of Post-operative Nausea and Vomiting. Importantly, the investigators will evaluate for an impact in patient-reported measures of quality of life.

The total sample size is 83. This study will provide valuable insight on the epidemiology of post-operative nausea and vomiting after hospital discharge following Sleeve gastrectomy, which is currently poorly characterized. By allowing the investigators to assess the overall incidence of nausea and vomiting at different time points, this study will afford the opportunity to identify a time period of high incidence and further adjust our prevention efforts accordingly in future studies.

Arms: arm 1: A) Pre-operatively: aprepitant 80 mg oral capsule and scopolamine transdermal patch.

B) Intra-operatively: total intravenous anesthesia (TIVA) will be maintained with IV infusions of propofol, and dexmedetomidine infusion or intermittent bolus dosing of fentanyl after induction. Sugammadex (2-4 mg/Kg IV) will be used for reversal of neuromuscular blockade in both groups. A single dose of dexamethasone 8 mg IV will be administered after induction, and a single dose of ondansetron 4 mg IV will be administered approximately 20 minutes prior to the end of operation.

C) Post-operatively: Scheduled ondansetron and Raglan every 6 hours, using Compazine as a rescue medication. arm 2: A) Pre-operatively: No intervention

B) Intra-operatively: inhalation anesthetics (sevoflurane or desflurane) and intermittent opioid boluses will be used for maintenance of anesthesia, as standard practice in the institution of the investigators and across the country. PONV prevention measures in the control group will be limited to dexamethasone 8 mg and ondansetron 4 mg.

C) Post-operatively: Scheduled ondansetron and Raglan every 6 hours, using Compazine as a rescue medication.
Interventions: intervention 1: Aprepitant 80 mg Oral Capsule intervention 2: scopolamine transdermal intervention 3: Total intravenous anesthesia intervention 4: Dexamethasone intervention 5: Ondansetron intervention 6: Reglan intervention 7: Ondansetron intervention 8: Compazine intervention 9: Sugammadex intervention 10: Propofol intervention 11: dexmedetomidine intervention 12: Fentanyl intervention 13: Sevoflurane intervention 14: Desflurane
Intervention descriptions: intervention 1: aprepitant 80 mg orally one hour prior to scheduled surgery intervention 2: scopolamine transdermal patch one hour prior to scheduled surgery intervention 3: Maintenance of anesthesia without the use of inhaled anesthetics. intervention 4: Dexamethasone 8 mg intraoperatively intervention 5: Ondansetron 4 mg intraoperatively. Ondansetron will be given twice. Once intraoperatively and then post- operatively. intervention 6: Postoperatively scheduled Reglan intervention 7: Postoperatively scheduled ondansetron intervention 8: Postoperatively as needed compazine for breakthrough PONV intervention 9: Reversal with sugammadex intervention 10: Intravenous anesthesia will be maintained through IV propofol intervention 11: maintenance of anesthesia in the intervention arm intervention 12: intermittent bolus dosing of fentanyl will be used after induction for anesthesia maintenance intervention 13: inhalational anesthesia intervention 14: inhalational anesthesia

Protocol documents:
ICF_001.pdf: 
 
 
 
 
 
RESEARCH CONSENT FORM 
 
 
Project Title: Designing optimal prevention and management of postoperative nausea and 
emesis for patients undergoing Laparoscopic Sleeve Gastrectomy. 
Principal Investigator: Dr. Konstantinos Spaniolas1. 
Co-Investigators: Dr. Aurora Pryor1, Dr. Daryn Moller2 , Dr. Andrew Bates1, Dr. Salvatore 
Docimo1, Dr. Tyler Cohn1, Darragh Herlihy NP1. 
Department: Surgery, Anesthesiology 
 
You are being asked to be a volunteer in a research study.  
PURPOSE  
The purpose of this study is:  
 Bariatric surgery remains the most effective therapy for obesity. Nausea and vomiting are 
commonly reported following bariatric surgery.  
 The proposed study focuses on the laparoscopic sleeve gastrectomy (LSG) which is most 
common bariatric procedure performed.  It aims to assess the effect of a specific 
intervention on post-operative nausea and vomiting. 
 We hypothesize that the group that will receive this specific intervention will experience a 
reduction of prolonged hospital stay and significantly improve quality of recovery from 
surgery. 
 Subjects undergoing surgery will be randomized to two groups: control vs Nausea specific-
intervention group.  
 An effect on the presence and degree of Post-operative Nausea and Vomiting will be 
measured by serial questionnaires of nausea, vomiting, quality of life and quality of 
recovery. 
 The total sample size is 82.  
 
 
Approved: May 10, 2018
Expiration Date: May 9, 2019
Stony Brook University IRB (CORIHS A)


 
 
PROCEDURES : 
 If you decide to be in this study, your part will involve:  
 You will be assessed in the outpatient clinic on the basis of inclusion and exclusion 
criterion. Patients enrolled in this study will be randomized by a computer generated 
number to controll group and Post-operative nausea and vomiting specific intervention 
group .  
 All subjects will be assessed with a nausea specific questionnaire at 1, 4, 12, 24 hours and 
3 weeks after surgery.  
 Patient satisfaction with recovery will be assessed using specialized questionnaires at 
baseline, 24 hours and 3weeks following surgery. 
RISKS / DISCOMFORTS 
The following risks/discomforts may occur as a result of you being in this study:  
The risk related to the conduct of this study is due to possible adverse events from medication 
use. All the medications proposed in this study are commonly used in the clinical setting for 
perioperative care, with minimal risk. The proposed study does not introduce a new therapy or 
medication in this clinical setting, but it attempts to assess a protocol of care for a specific patient 
population. In terms of each medication specifically, all the medications proposed are currently 
often used for the perioperative care of bariatric patients 
(Aprepitant, Scopolamine, Dexamethasone, Ondansetron, Propofol, Sugammadex, and 
Promethazine). Serious adverse events are not common for any of the medications used in the 
study: 
Aprepitant - The minor adverse events include hiccups, heartburn, diarrhea, headache, fatigue, 
constipation and abdominal pain.   
Scopolamine – Contraindicated in patients with closed angle glaucoma. Adverse events are 
uncommon and can include hallucinations, confusion and dizziness. The most common is dry 
mouth, which is well tolerated in this patient population. 
Ondansetron – The most common adverse events for ondansetron when used for prevention of 
postoperative nausea is headache and hypoxia. QT interval prolongation can occur, so patients 
with a history of congenital long QT syndrome will be excluded. This medication is used as first 
line for prevention and treatment of postoperative nausea for most patients. 
Propofol - Common adverse events include cough, burning sensation around IV site, anxiety, 
muscle pain, urine discoloration; all of these are self-limited and non-serious. Hypotension 
related to propofol will be assessed for and treated in real-time by the anesthesiology team as per 
clinical practice.  
Sugammadex - Use in patients with renal failure is not recommended, so patients with 
creatinine clearance less than 30 will be excluded from the study.  
Compazine–  The most common AEs include dizziness, drowsiness, anxiety;sleep problems 
(insomnia), strange dreams;dry mouth, stuffy nose , blurred vision , constipation, breast 
swelling or discharge, a missed menstrual period.  
 
 
Approved: May 10, 2018
Expiration Date: May 9, 2019
Stony Brook University IRB (CORIHS A)


 
 
All medications will be administered in a monitored setting (tertiary care referral center). In 
current clinical practice, all these medications, often in combination, are being used for the 
prevention and treatment of postoperative nausea. AEs are not common, and are overall minor in 
severity. 
 
Being a part of this study while pregnant may expose the unborn child to significant risks 
that are not justified, given the purpose of the study. Therefore, pregnant females will be 
excluded from the study. If you are a female who can become pregnant, a pregnancy test 
must be done, and must be negative before you can enter this study.  
 
BENEFITS  
There may be no direct benefit to you as a result of being in this study. 
Our hope is that the study will provide valuable insight on the causes of post-operative nausea 
and vomiting after hospital discharge following Sleeve gastrectomy, which is currently poorly 
characterized. By allowing us to assess the overall incidence of nausea and vomiting at different 
time points, this study will afford us the opportunity to identify a time period of high incidence 
and further adjust our prevention efforts accordingly in future studies. 
PAYMENT TO YOU:  You will not be paid for this study.  
PAYMENT TO THE INSTITUTION This project is funded, in part, by a grant or contract 
from The Research Committee of the Society for Surgery of the Alimentary Tract to the 
Research Foundation of Stony Brook University, in support of the Investigators' work on this 
study.  
CONFIDENTIALITY   
We will take steps to help make sure that all the information we get about you is kept 
confidential. Your name will not be used wherever possible. We will use a code instead. All the 
study data that we get from you will be kept locked up. The code will be locked up too. If any 
papers and talks are given about this research, your name will not be used.  
We want to make sure that this study is being done correctly and that your rights and welfare are 
being protected. For this reason, we will share the data we get from you in this study with the 
study team, the sponsor of the study (and those who work for them), Stony Brook University's 
Committee on Research Involving Human Subjects, applicable Institutional officials, and certain 
federal offices, including the Office for Human Research Protections (OHRP), and, where 
applicable, the Food and Drug Administration (FDA). However, if you tell us you are going to 
hurt yourself, hurt someone else, or if we believe the safety of a child is at risk, we will have to 
report this.  
In a lawsuit, a judge can make us give him the information we collected about you.  
While you are in this study we will get data about your health from your medical record. We will 
also get health data from the results of the tests you will have done in this study. You have a 
right to privacy but the data we get about your health in this study can be shared with the people 
 
Approved: May 10, 2018
Expiration Date: May 9, 2019
Stony Brook University IRB (CORIHS A)


 
 
referenced above (the study team, the sponsor of this study, those who work for the sponsor, 
Stony Brook University's Committee on Research Involving Human Subjects, applicable 
institutional officials, and federal offices such as OHRP, FDA) as well as: 
 
your insurance company  
 
your medical doctor  
Your health data are shared to make sure the study is being done correctly, costs are charged 
correctly, and to make sure your rights and safety are protected. Not all of these people are 
required by law to protect your health data. They might share it with others without your 
permission but no identifiers will be used.   
You have the right to stop allowing us to use or give out your health data. You can do this at any 
time by writing to Dr. Konstantinos Spaniolas. If you do this, we will stop collecting any new 
health data from you, except if we need to keep an eye on a bad side effect you were having in 
the study. We will use any data we collected before you wrote your letter. When you sign the 
consent form at the end, it means:  
 
That you have read this section.  
 
That you will allow the use and reporting of your health data as described above.  
 
You have received a form from the University Hospital. It is called the Notice of Privacy 
Practices form.  
Clinical Trial Registry: A description of this clinical trial will be available on 
http://www.ClinicalTrials.gov, as required by U.S. Law. This Web site will not include 
information that can identify you. At most, the Web site will include a summary of the results. 
You can search this Web site at any time. 
COSTS TO YOU   
There are no foreseeable costs to you.  
ALTERNATIVES  
 
Your alternative to being in this study is to simply not participate.  
IN CASE OF INJURY  
If you are injured as a result of being in this study, please contact Dr. Konstantinos 
Spaniolas at telephone # 631-444-7298. The services of Stony Brook University Hospital 
will be open to you in case of such injury.  
However, you and/or your insurance company will be responsible for payment of any 
resulting treatment and/or hospital stay. 
 
 
 
Approved: May 10, 2018
Expiration Date: May 9, 2019
Stony Brook University IRB (CORIHS A)


 
 
YOUR RIGHTS AS A RESEARCH SUBJECT   
 
Your participation in this study is voluntary. You do not have to be in this study if you 
don't want to be. 
 
You have the right to change your mind and leave the study at any time without giving 
any reason, and without penalty. 
 
Any new information that may make you change your mind about being in this study will 
be given to you. 
 
You will get a signed and dated copy of this consent form to keep. 
 
You do not lose any of your legal rights by signing this consent form. 
QUESTIONS ABOUT THE STUDY OR YOUR RIGHTS AS A RESEARCH SUBJECT    
 
If you have any questions, concerns, or complaints about the study, you may contact [Dr. 
Konstantinos Spaniolas], at telephone # (631-444-7298). 
 
If you have any questions about your rights as a research subject or if you would like to 
obtain information or offer input, you may contact the Stony Brook University Research 
Subject Advocate, Ms. Lu-Ann Kozlowski, BSN, RN, (631) 632-9036, OR by e-mail, lu-
ann.kozlowski@stonybrook.edu 
 
Visit Stony Brook University’s Community Outreach page, 
http://research.stonybrook.edu/orc/community.shtml#overview-of-volunteering-in-
research  for more information about participating in research, frequently asked 
questions, and an opportunity to provide feedback, comments, or ask questions related to 
your experience as a research subject. 
If you sign below, it means that you have read (or have had read to you) the information given in 
this consent form, and you would like to be a volunteer in this study. 
 
___________________________          _____________________________________________ 
Subject Name (Printed)                           Subject Signature                    Date            Time 
 
 
 
 
___________________________            ___________________________________________ 
Name of Person Obtaining Consent        Signature of Person Obtaining         Date           Time  
(printed)                                                                   Consent 
 
 
Approved: May 10, 2018
Expiration Date: May 9, 2019
Stony Brook University IRB (CORIHS A)

Prot_SAP_002.pdf: 
TITLE: DESIGNING OPTIMAL PREVENTION AND MANAGEMENT OF POSTOPERATIVE NAUSEA AND 
EMESIS FOR PATIENTS UNDERGOING LAPAROSCOPIC SLEEVE GASTRECTOMY. 
PRINCIPAL INVESTIGATOR: Konstantinos Spaniolas, MD 
Co-investigator: Dr. Pryor Aurora, Dr. Daryn Moller
I. SUMMARY 
Bariatric surgery remains the most effective therapy for obesity and the metabolic syndrome. Postoperative nausea and
vomiting (PONV) are commonly reported following bariatric surgery; our preliminary results suggest that 90.8% of 
patients report PONV during their index hospital stay, and 30.4% of readmitted patients report PONV as the reason for re-
hospitalization. Importantly, we have previously found that 49% of patients are unable to be discharged on time due to 
oral intake intolerance attributed to PONV. Multiple small studies have attempted to introduce single-level intervention to 
decrease PONV with limited success in this patient population. The proposed study focuses on the most common bariatric 
procedure performed, laparoscopic sleeve gastrectomy (LSG), and aims to assess the effect of a PONV-specific 
intervention using a multimodal contemporary approach. We hypothesize that the PONV-intervention group will 
experience a more than 50% relative risk reduction of PONV-related prolonged hospital stay and significantly improve 
patient-reported quality of recovery from surgery and quality of life. To test this hypothesis, subjects undergoing LSG will 
be prospectively randomized to two groups: control (physician driven prophylaxis) vs PONV-intervention group (two 
anti-emetic agents prior to surgery, total intravenous anesthesia, two additional anti-emetic agents during surgery, and 
sugammadex as reversal agent). The primary end-point will be PONV-related prolonged hospital length of stay, using 
postoperative day 1 as the target for hospital discharge as per clinical pathway. Serial assessments of PONV, quality of 
life and quality of recovery, will allow us to identify an effect of the PONV-intervention on PONV incidence and severity. 
Importantly, we will evaluate for an impact in patient-reported measures of quality of life. Our proposal is extremely 
innovative, because it addresses a high impact topic, evaluates the effect of PONV-intervention in all phases of recovery, 
and includes instruments to measure self-reported patient experience with surgery. 
II. SPECIFIC AIMS
PONV is associated with delayed hospital discharge and readmissions following LSG. The impact of PONV on patient 
experience, self-reported outcomes, and overall recovery is unknown for this patient population. The proposed study aims 
to assess the effect of a PONV-specific intervention using a multimodal contemporary approach in subjects undergoing 
LSG. The PONV intervention will include specific steps using total intravenous anesthesia and staged anti-emetic 
medications, in the pre-, intra- and post-operative phase of care. We hypothesize that a comprehensive multi-level PONV 
intervention will decrease the incidence and severity of PONV, increase successful patient hospital discharge on 
postoperative day (POD) 1, facilitate late phase postoperative recovery and positive patient experience. 
Specific Aim 1: Evaluate the impact of a PONV-specific intervention on PONV-related prolonged length of 
hospital stay following LSG surgery. Subjects will be serially assessed for the presence and scale of nausea and emesis 
during their early, intermediate and late phases of recovery, measured with a PONV-specific survey. Time from 
completion of the index procedure until patient hospital discharge will be assessed; subjects who remain in the hospital 
past POD 1 due to PONV will be considered as having a prolonged length of stay, which is the primary endpoint for this 
aim. We will also assess the effect of a PONV-specific intervention on post-discharge PONV-related resource utilization 
following LSG. Patients will be followed to capture hospital readmissions, emergency department visits and outpatient 
intravenous hydration for PONV. We hypothesize that the PONV-intervention group will experience a higher rate of 
successful POD 1 discharge, and a decrease in incidence and severity of both nausea and emesis. 
Specific Aim 2: Assess the effect of a PONV-specific intervention on patient reported outcomes (PRO). Patient-
reported outcome measures will be collected to evaluate recovery from surgery and health-related quality of life at 2- and 
4-weeks following LSG. We hypothesize that a PONV-specific intervention will allow patients to have improved self-
assessed recovery and quality of life during the first 30-days following surgery. 
Approved: 5/22/2019
Expiration Date: 5/21/2020
Stony Brook University Human Subjects Committee (IRB)


III. SIGNIFICANCE 
Bariatric surgery is the most effective method to treat obesity and associated diseases. Currently, the LSG is the most 
common bariatric procedure performed (1). In this patient population, however, PONV occurs commonly. Published 
studies suggest a 59-87% incidence of PONV during the hospital stay following LSG (2, 3). 
The burden of PONV in the bariatric population, and specifically after LSG, is particularly high. We have previously 
demonstrated that PONV is the most common cause for hospital readmission following LSG, with 30.4% of readmitted
LSG patients reporting PONV and oral intake intolerance as their primary reason for readmission (4). This is markedly 
different in gastric bypass patients, where only 18% of readmitted patients reported PONV as their primary complaint. 
Additionally, our preliminary data suggest that half of LSG patients experience a delay in pathway-expected hospital 
discharge due to PONV (see Preliminary Data section under Approach). With the drive to minimize hospital length of 
stay, PONV control is paramount to achieve safe early hospital discharge. 
The impact on PONV on PRO is unclear. One third of patients who received double PONV prophylaxis and routine anti-
emetics for the first two days at home following ambulatory laparoscopic surgery reported that nausea had a negative 
effect on their quality of life, during self-assessment on POD 5 (5). Following ambulatory surgery, the incidence of PONV 
increases over time; 16.1% of patients experience PONV in early recovery, and 31.2% of patients report PONV on POD 
5, during late recovery at home (6). These rates are almost double for patients undergoing ambulatory laparoscopic surgery, 
suggesting that PROs after discharge are of high value for the assessment of a PONV-related effect. Importantly, PONV 
at home significantly impairs the ability to perform activities of daily living, which is an important goal of recovery for 
patients (7). Since PONV is reported commonly in LSG patients, we anticipate that improvement in PONV will affect 
PROs and overall experience during the intermediate (from post-anesthesia care unit until hospital discharge) and late 
(from hospital discharge to return to usual activity) phases of recovery. 
Although the benefit of a multimodal approach to PONV prevention has been well established (8), evidence in the 
bariatric, and specifically the LSG population is not clear. A study evaluating a triple-agent protocol in 96 LSG patients, 
using ondansetron, dexamethasone and haloperidol, demonstrated improvement in PONV incidence, but no effect on 
hospital length of stay (3). The lack of effect on hospital discharge may be related to the use of short half-life preventive 
agents, the lack of aggressive postoperative anti-PONV management or the implementation of a post-care pathway with 
less emphasis in early hospital discharge. This would possibly underline the value of longer lasting antiemetic agents, as 
prevention. The only study to date evaluating the use of aprepitant, an agent with half-life exceeding 12 hours, in bariatric 
surgery demonstrated significant decrease in the rate of emesis compared to controls (3.1% vs 15%, p=0.021), but is 
limited by the non-inclusion of LSG patients, and the lack of triple prophylaxis as control (9). Furthermore, the use of 
sugammadex has emerged as a modality to decrease pain and PONV. A randomized study of 88 bariatric surgery patients 
assigned to this agent vs neostigmine demonstrated a significant decrease in the early incidence of PONV (6.8% vs 
18.2%, p<0.05)(10). Studies evaluating the longer-term effect of this reversal approach to PONV in this patient population 
are not available.  
Recently published recommendations from European societies for the enhanced recovery of bariatric surgery include 
multimodal PONV prevention, but the evidence, as also noted in the article, is lacking (11). Despite the significant impact 
of PONV in this patient population, there is no consensus on the optimal approach in PONV prevention. Given the 
proportion of LSG procedures performed, the effect of PONV in this patient population and the paucity of high quality 
data, the proposed study will allow us to advance science in bariatric surgery, change the standard of care and improve 
patient experience. A standardized anti-PONV intervention with proven efficacy could minimize length of stay and 
readmissions after LSG, minimizing costs and improving patient experience. 
Approved: 5/22/2019
Expiration Date: 5/21/2020
Stony Brook University Human Subjects Committee (IRB)


IV. INNOVATION  
Multiple studies suggest that PONV is a significant postoperative problem for bariatric surgery patients (4). Despite this, 
no studies have addressed PONV in this patient population in a systematic fashion, or using a multilevel approach. 
Furthermore, PONV is this patient population has likely different pathophysiology compared to similar symptoms in 
colectomy and other gastrointestinal patients. Development of a program specific to bariatric surgery for the prevention 
and management of PONV using interventions before, during and following surgery is a novel approach to this clinical
problem. Furthermore, the current proposal is innovative in a three-fold way: 
a. Evaluation of PONV during the late phase of recovery from surgery for patients undergoing LSG hasn’t been 
previously reported. The proposed study will try to fill this knowledge gap, which is especially important given that 
PONV is the most common cause for hospital readmission in this group. 
b. Although PONV has a significant impact on patient experience during recovery from surgery, this hasn’t been 
explored, especially in patients undergoing LSG, despite the high incidence of PONV in this setting. Using standardized 
questionnaires, patients following LSG will be able to provide PROs on quality of life and quality of recovery. The use of 
PROs, including instruments of quality of life assessment, for the evaluation of PONV is novel, and will afford us the 
ability to assess if a PONV-specific intervention can have a patient-centered impact. 
V. APPROACH 
Overall design: We will conduct a randomized controlled trial to evaluate the effect of a multi-level PONV-specific 
intervention (pre-, intra- and post-operative) for patients undergoing LSG. Patients will be followed for 30 days to assess 
the benefit of this intervention on all phases of postoperative recovery (early, intermediate and late). 
Pre-op
Intra-op
Post -op
Patients Scheduled for Sleeve 
Gastrectomy
Randomization 1:1
Control
None
Dexamethasone 8mg
Ondansetron 4mg
PONV 
Intervention
Apprepitant 80mg
Scopolamine patch
TIVA
Dexamethasone 8mg
Ondansetron 4mg
Sugammadex reversal
Ondansentron 4mg q6
Metoclopramide 10mg q6
Compazine 10mg oral 
Approved: 5/22/2019
Expiration Date: 5/21/2020
Stony Brook University Human Subjects Committee (IRB)


Human Subjects: Adult patients (18 years and older) undergoing LSG will be assessed for eligibility to participate in this 
study. Subjects will be recruited at the Stony Brook University Bariatric and Metabolic Weight Loss Center by study 
personnel. Patients with documented allergy to the study medications, history of chronic nausea and emesis requiring 
medication, poorly controlled diabetes (HgA1c>9 mg/dl), or history of previous bariatric or gastro-esophageal surgery 
will be excluded from this study. 
Study Groups: Eligible subjects for this study will be randomized to two groups using an online random number 
generator. Randomization will occur during the last outpatient visit prior to undergoing LSG. Subjects will be assigned to 
two groups: control vs PONV-intervention (Figure). 
Intervention: A) Pre-operatively: The experimental group will undergo treatment with aprepitant 80 mg orally and 
scopolamine transdermal patch one hour prior to scheduled surgery (figure 1). 
B) Intra-operatively: Anesthetic parameters: Induction of anesthesia will be performed with propofol (1-2.5 mg/Kg IV) 
and succinylcholine (1-1.5 mg/Kg IV) or rocuronium (0.5-1 mg/Kg IV) after pre-oxygenation as standard practice for 
both groups. In the PONV-intervention group, total 
intravenous anesthesia (TIVA) will be maintained with 
IV infusions of propofol, and dexmetomidate infusion 
or intermittent bolus dosing of fentanyl after induction. In the control group, inhalation anaesthetics (sevoflurane or 
desflurane) and intermittent opioid boluses will be used for maintenance of anesthesia, as standard practice in our 
institution and across the country. Muscle relaxation will be maintained with boluses of rocuronium (10-20 mg) or 
vecuronium (1-2 mg) to provide optimal surgical conditions for both groups. Sugammadex (2-4 mg/Kg IV) will be used 
for reversal of neuromuscular blockade in both groups. Anti-emetic regimen: In the PONV-intervention group, a single 
dose of dexamethasone 8 mg IV will be administered after induction, and a single dose of ondansetron 4 mg IV will be 
administered approximately 20 minutes prior to the end of operation. PONV prevention measures in the control group will 
be limited to dexamethasone 8 mg and ondansetron 4 mg. This contrasts with the PONV-intervention group, which will 
undergo multimodal therapy (8, 12). At any point during the study, clinical mandates by either surgeon or anesthesiologist 
can allow for subject cross-over, or subject withdrawal from the study. 
C) Post-operatively: PONV control will include scheduled ondansetron and metoclopramide every 6 hours, using 
Compazine as a rescue medication (Figure 1). This step will be common for both groups. 
Surgery will be performed in a standardized way: antral division will commence at 4 cm from the pylorus, and the gastric 
sleeve will be calibrated over a 38 Fr bougie (or double channel endoscope, equivalent to 37.6 Fr). All patients will be in 
the current standardized LSG pathway that includes: avoidance of routine nasogastric decompression or surgical drainage, 
avoidance of routine urinary catheter placement, early ambulation the same day, early initiation of oral intake as soon as 
patient is awake, and no routine contrast radiologic studies. Per pathway design, all patients who undergo non-revisional 
LSG are planned for hospital discharge on POD 1. Pain control consists of scheduled acetaminophen and as needed IV 
opioids for the day of surgery, followed by as needed oral opiods starting on early morning POD 1. 
Specific Aim 1: Evaluate the impact of a PONV-specific intervention on PONV-related prolonged length of 
hospital stay following SG surgery. 
Hypothesis: We hypothesize that the PONV-intervention group will experience a more than 50% relative risk reduction 
of PONV-related prolonged hospital stay. We hypothesize that a PONV-specific intervention will lead to decrease in 
incidence and severity of PONV. 
Figure 1: Study protocol for PONV prevention
Approved: 5/22/2019
Expiration Date: 5/21/2020
Stony Brook University Human Subjects Committee (IRB)


Rationale: All patients undergoing LSG are high-risk for PONV (13). By implementing a series of interventions that 
individually have been proven efficacious in decreasing nausea or emesis, we anticipate a significant reduction in the 
incidence of PONV in the experimental group. The impact of nausea and emesis individually on the ability of LSG 
patients to tolerate oral intake and maintain hydration is unclear. Inability to tolerate oral intake and subsequent 
dehydration pronounce the effects of PONV, so we anticipate that an early intervention to prevent the incidence and 
severity of PONV will allow for early hospital discharge without an increased risk for hospital readmission. All items on
the PONV-intervention program have been suggested to decrease PONV in bariatric or other high-risk populations (2, 3, 9, 
10, 14).  
Preliminary data: We have previously completed a prospective cohort study of 65 patients undergoing isolated non-
revisional laparoscopic bariatric surgery (subjects undergoing concurrent procedures were excluded), and serially assessed 
for PONV using a 10-point Likert scale (presented at 2017 SAGES Annual Conference). Using a standardized 
postoperative PONV management algorithm, we identified that 59 of 65 (90.8%) of patients experienced PONV at some 
point during their hospitalization following LSG. The study was conducted in a clinical setting with routine radiographic 
imaging on POD 1 and pathway-targeted hospital discharge on POD 2. We identified that 20.7% of LSG patients 
experienced a prolonged hospital length of stay (past POD 2) and 6.9% were re-admitted within 30-days for PONV. In a 
more contemporary clinical practice without routine imaging and early oral intake initiation, the effect of PONV is more 
pronounced. In our current pathway with these elements of care, patients undergoing LSG are expected to meet criteria for 
hospital discharge on postoperative day 1. In the 2015-2016 academic year, we identified that 49% of SG patients were 
unable to be discharged to home on POD 1. 
Experimental design: This is a prospective randomized trial of subjects undergoing LSG for morbid obesity. Subjects 
will be randomized to two groups (control vs PONV-intervention) as described above. Assessments: Subjects will be 
assessed for the presence and severity of PONV at 1, 4, 12, 24 hours, and 3 weeks following the end of the surgical 
procedure (table 1). Nausea will be defined as an unsettled feeling in the stomach and urge to vomit. Vomiting will be 
defined as oral expulsion of gastric contents, and retching as expulsive attempts without any oral content. We will use a 
10-point verbal rating scale (VRS) for the assessment of nausea as used previously (3, 9). Vomiting and retching will be 
assessed in a binary way. The Rhodes Index of nausea and emesis, an 8-question survey (composite score range 0-32), 
will be used as an additional assessment instrument at the later time points (12 h and later) since it evaluates PONV over 
12-hour intervals (15). This index has been previously used for the assessment of PONV following LSG (16). At each time 
point, total opioids (converted to morphine equivalents) and rescue anti-emetics used will be noted. Visits to the 
emergency room and hospital re-admissions will be captured; these will be considered PONV-related if the patient 
presents with inability to tolerate oral intake secondary to PONV, and/or signs and symptoms of dehydration, who are not 
found to have other pathology during evaluation (i.e. readmission for a patient with nausea due to a systemic infection will 
not be considered PONV-related). Outcome measures: Primary outcome for this aim will be PONV-related delay in 
hospital discharge, defined as inability to be discharged from the hospital on POD 1 due to PONV. Secondary outcomes 
will be hospital length of stay (measured as hours from the end of the surgical procedure), incidence of PONV (incidence 
of nausea and emesis will also be assessed separately), severity of PONV (based on the VRS and Rhodes Index), PONV-
related resource utilization (individually measured presentation to the emergency room and hospital readmission for 
PONV). 
Interpretation, Potential Pitfalls and Alternative 
Strategies:  We anticipate a significant reduction 
in PONV incidence and PONV-related delayed 
hospital discharge in the PONV-intervention 
group. Although unlikely, it is possible that we will 
be unable to identify a difference in POD1 
discharge, as the time of performance of LSG may 
be a confounder and bias the results (i.e. patients 
undergoing SG earlier in the day may be more likely 
Time points
Specific Aim 1: PONV 
Specific Aim 2: PRO
Baseline
VRS, Rhodes Index
GIQLI, EQ-5D 
1 hr
VRS
4 hr 
VRS 
12 hr 
VRS, Rhodes Index
24 hr 
VRS, Rhodes Index
QoR-15, GIQLI
3 wk 
VRS, Rhodes Index
QoR-15, GIQLI, EQ-5D
Table 1: Patient study assessments for each time point.
Approved: 5/22/2019
Expiration Date: 5/21/2020
Stony Brook University Human Subjects Committee (IRB)


to be discharged to home on POD1). In our current practice, LSG procedures are performed earlier in the operating room 
day, to facilitate earlier hospital discharge the following day. Despite this, we have identified a 49% failure rate for POD1 
discharge. In addition, our secondary measures, including incidence/severity of PONV and length of stay (measured in 
hours from the end of surgery) are not affected by operating room timing, and will allow for efficacy assessment of our 
PONV-intervention, independent of time of day of LSG completion. It is also possible that we identify no difference 
between the groups in terms of longer term PONV incidence. Our study will still provide valuable insight on the
epidemiology of PONV after hospital discharge following LSG, which is currently poorly characterized. By allowing us 
to assess the overall incidence of PONV at different timepoints, this study will afford us the opportunity to identify a time 
period of high incidence and further adjust our prevention efforts accordingly in future studies. 
Specific Aim 2: Assess the effect of a PONV-specific intervention on patient reported outcomes (PRO). 
Hypothesis: We hypothesize that a PONV-specific intervention will significantly improve patient-reported quality of 
recovery from surgery and quality of life. 
Rationale: PONV significantly affects the late phase of recovery (from hospital discharge to return to baseline), because 
it impairs the ability to perform activities of daily living, which patients value as an important goal of recovery (7). In a 
postoperative survey of 469 patients evaluated two weeks after abdominal surgery, visceral function (including PONV) 
correlated with physical and functional impairment during recovery.  Additionally, one third of patients following 
ambulatory laparoscopic surgery reported that nausea had a negative effect on their quality of life, during self-assessment 
on POD 5 (5). Since PONV is reported commonly in LSG patients, we anticipate that improvement in PONV will 
significantly improve quality of life and overall experience during the intermediate (from post-anesthesia care unit until 
hospital discharge) and late phases of recovery. Additionally, the ability to resume physical activity is an important 
outcome of patient recovery (17). This is particularly important after bariatric surgery, as an adjunct for weight loss, and 
recommended as part of clinical practice guidelines (18). It is plausible that improvements in PONV for SG patients would 
have a significant benefit in terms of progressive physical activity and resumption of activities of daily living.  If the 
PONV intervention is associated with improved patient experience and PROs, it could improve clinical decision making 
for patients considering LSG. 
Experimental design: Subjects randomized to control versus PONV-intervention from Specific Aim 1, will be assessed 
in terms of quality of recovery and quality of life at the intermediate and late phases. Assessments: PROs will be obtained 
at 24 hours, and 3 weeks following LSG surgery (table 1). The Gastrointestinal Quality of Life Index (GIQLI) is a 
validated instrument for the assessment of quality of life following gastrointestinal surgery, previously used in bariatric 
surgery research (19-23). The QoR-15 is a validated reliable instrument to assess the quality of a patient’s postoperative 
recovery (24). This survey has been also used for quality of recovery assessment in the late phase, up to 30 days following 
gastrointestinal surgery (25, 26). The Part A of QoR-15 assesses overall patient experience, as well as physical and 
functional status without direct assessment of symptoms (e.g. nausea) which are evaluated in Part B. Broad coherent 
assessment of quality of life will be performed using the EQ-5D index. This is a validated standardized brief instrument 
that provides a simple descriptive profile in five domains (mobility, self-care, usual activities, pain and anxiety) and a 
single index value for health status, designed for self-completion. The EQ-5D Crosswalk index calculator will be used to 
convert the descriptive profiling into a single index. EQ-5D has been extensively used for quality of life assessment in 
bariatric surgery (27-29). 
Outcome measures: Primary outcome from this aim will be difference in the GIQLI index at 2 weeks postoperatively. 
Secondary outcomes will be difference in GIQLI at 24 hours and 3 weeks, difference in QoR-15 at each time point, 
difference in QoR-15 Part A at each time point, difference in EQ-5D self-assessed visual score, difference in EQ-5D 
profiling (score in each category), and difference in EQ-5D index at 3 weeks. 
Interpretation, Potential Pitfalls and Alternative Strategies:  We anticipate a significantly higher GIQLI in the PONV-
intervention group. It is likely that an improvement in PONV will a priori lead to improvements in the quality of life 
indices selected, since these surveys include assessment of PONV. Although this could be considered bias, we believe that 
Approved: 5/22/2019
Expiration Date: 5/21/2020
Stony Brook University Human Subjects Committee (IRB)


improvement in these validated indices would remain a significant finding. However, to further assess for global 
improvements in quality of life, we will be separately analyzing Part A of the QoR-15 survey, which doesn’t capture 
severity and presence of PONV. Additionally, the EQ-5D instrument includes no direct measurement of PONV, and 
would allow us to control for bias. It is also possible that the PONV-intervention group experiences no significant 
improvement in quality of life. If we identify an improvement in PONV incidence and severity (specific aim 1) without a 
concomitant improvement in quality of life after recovery, this finding would suggest the limited impact of PONV on
quality of life early after LSG. Such finding would allow us to focus our subsequent PONV intervention methods in the 
intermediate phase of recovery. The EQ-5D instrument was used over the more widely used Short Form-36 due to the 
ease of use for patients (five vs 36 questions) and the non-inferiority for postoperative patients. 
Statistical analysis: For continuous variables, data distribution will be assessed using the Shapiro-Wilk test. Two-sided t-
test (means, standard deviation) and Wilcoxon rank sum test (median, 25th-75th percentiles) will be used accordingly. 
Categorical variables will be compared using chi-square testing. VRS assessments for all time points combined will be 
compared using repeated measures ANOVA. 
Sample Size Considerations: The primary outcome of the study will be incidence of PONV-related delay of hospital 
discharge following LSG. Change in proportion will be assessed with chi-square testing. We expect a decrease in delay of 
POD1 discharge from 49% to 20% (3, 8). Based on the data above, with two-tailed a=0.05 and b=0.2, we would require 41 
subjects per group (total N=82) to detect a significant difference with the PONV-prevention. The Stony Brook Bariatric 
and Metabolic Weight Loss Center performs 100-150 LSG procedures annually, so we anticipate that the proposed study 
will be completed within 2 years. 
VI. TIMELINE 
Months
Milestones
  1-3   4-6   7-9
 9-12
13-15
16-18
19-21
22-24
IRB approval
X
Study staff training 
X
Subject recruitment 
X
X
X
X
X
X
Data analysis 
X
X
Manuscript preparation 
X
X
VII. INSTITUTIONAL APPROVALS  
Institutional approval will be obtained from the Stony Brook University Institutional Review Board. The review board 
meets regularly on a bi-monthly basis. 
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Approved: 5/22/2019
Expiration Date: 5/21/2020
Stony Brook University Human Subjects Committee (IRB)


Approved: 5/22/2019
Expiration Date: 5/21/2020
Stony Brook University Human Subjects Committee (IRB)