The Effect of an Opioid-free Anesthetic on Post-operative Opioid Consumption After Laparoscopic Bariatric Surgery: a Prospective, Single-blinded, Randomized Controlled Trial
Phase: PHASE3
Conditions: Opioid Use, Unspecified, Bariatric Surgery Candidate, Anesthesia
Sponsor: Christine Oryhan

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Study Title: The effect of an opioid-free anesthetic on post-operative opioid consumption after 
laparoscopic bariatric surgery: a prospective, single-blinded, randomized controlled trial.  
 
Principal Investigator: Christine Oryhan, MD 
 
Co-Investigators:  
Joseph Strunk, MD 
Josiah Perez, MD 
Lily Chang, MD 
Mohan Mallipeddi, MD 
Nam Nguyen, MD 
Shanley Deal, MD 
Angela Hirsh, MD 
 
Table of Contents: 
 
A. Specific Aims…………………………………………………………………………....Page 1 
B. Background & Significance……………………………………………………….…...Page 1 
C. Preliminary Studies……………………………………………………………….…….Page 2 
D. Research Design & Methods………………………………………………………….Page 2 
E. Protection of Human Subjects………………………………………………………...Page 4 
F. References/Literature Citations……………………………………………………….Page 9 
G. Consultants……………………………………………………………………………...Page 9 
H. Facilities Available……………………………………………………………………....Page 9 
I. 
Appendix…………………………………………………………………………………Page 9 
 
A. Specific Aims 
 
To test the hypothesis that an opioid-free anesthetic technique, compared with a more 
traditional opioid-based technique for laparoscopic gastric bypass surgery, decreases 24 hour 
post-operative opioid consumption. We propose a study of 196 subjects randomized into two 
groups. The control group will receive a traditional opioid restrictive general anesthetic. The 
study group will receive an opioid-free anesthetic technique. 
 
B. Background & Significance 
 
- 
Obese patients may be sensitive to the respiratory depressant effect of opioids and more 
likely to require non-invasive ventilatory support to avoid hypoxic episodes. Furthermore, 
bariatric surgery patients are at high risk for post-operative nausea and vomiting.  
- 
Opioid-related adverse events increase treatment costs, length of stay, and readmission 
rates. 
- 
Studies have demonstrated benefits of various opioid-free and opioid-sparing techniques 
on post-operative pain control and opioid requirements. However, many study protocols 
have utilized high intraoperative opioids, which does not reflect our current practice at 

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Virginia Mason. We are trying to compare an opioid-free technique to a more traditional 
opioid-based technique that reflects our relatively more restrictive intraoperative opioid 
administration.1,2  
- 
Data suggests that 6% of all opioid naive patients who are discharged with a prescription 
for opioids are still using opioids 1 year after surgery.3,4  
- 
Few studies have looked at how anesthetic technique can affect the development of 
persistent post-operative pain, which is difficult and expensive to treat. None of these 
studies, to our knowledge, have specifically looked into the possibility of an opioid-free 
anesthetic technique influencing the incidence of persistent post-operative pain in the 
bariatric surgery population. 
 
C. Preliminary Studies 
 
This study will be the first of its kind to be carried out at Virginia Mason Medical Center. The 
principal investigator is Dr. Christine Oryhan, a staff anesthesiologist and pain physician, who 
has considerable knowledge in the evolving topic of opioid-free anesthesia.   
 
D. Research Design and Methods (including data analysis) 
 
Patient selection: 
We plan to enroll 196 subjects at VMMC that are undergoing laparoscopic bariatric surgery. 
Patients who volunteer to be involved in our study will be randomized to either the opioid free or 
traditional anesthetic arm, with a computer generated arm assignment. They will be blinded 
from which arm they are randomized to. Group A will receive a traditional opioid restrictive 
general anesthetic and group B will receive an opioid-free anesthetic technique.  
 
Data will be recorded on human subjects as part of their preoperative workup, the perioperative 
period, and routine postoperative follow-up as far as three months after surgery. Preoperatively, 
we will gather routine data on patient age, sex, BMI, and smoking status. We will also gather 
information from each patient’s preoperative routine psychological assessment, including history 
of depression, history of anxiety, history of substance abuse, PHQ-9 score, and GAD-7 score. 
Additionally, we will gather information on baseline pain score in patient’s abdomen. 
Perioperatively, we will gather data on ASA classification, type of surgery performed, duration of 
general anesthesia, volume of intraoperative fluids given, estimated blood loss, duration of 
PACU stay, intraoperative and PACU hemodynamic modulating medication requirements, 
lowest intraoperative heart rate, intraoperative and postoperative opioid and antiemetic 
requirements, hospital length of stay, numeric pain rating scale pain scores, postoperative 
oxygen requirements, and any complications. After discharge from the hospital, we will gather 
data taken from the 30-day follow-up phone call, and 3-month follow-up clinic visit that are 
already part of routine care. These data include Emergency Department visits for abdominal 
pain, any surgical complications, opioid medication refills, abdominal pain scores, and 
characteristics of any ongoing opioid use.  Patients will be blinded from which anesthetic 
technique is utilized for the patient’s care. All surgical ward nurses, clinic nurses making follow-
up phone calls, and bariatric surgeons will be able to identify which patient received with type of 

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anesthetic care. All of the above data will be recorded and subsequently abstracted from the 
electronic medical record (EMR).  
 
Subjects will only be enrolled to the study when laparoscopic surgery is planned, as stated in 
the inclusion criteria. In the event the decision is made intraoperatively for conversion of 
laparoscopic surgery to open, these subjects will remain on the trial and remaining follow-up 
data will be collected, however, they will be excluded from the main study group analysis. The 
anesthetic plan after conversion to open will then be at the discretion of the anesthesiology 
team. 
 
Statistical Sample Size Calculation: 
In order to demonstrate a 40% reduction in 24 hour opioid consumption based on clinical 
relevance, we first analyzed the typical postoperative opioid consumption from a sample of 
patients who underwent laparoscopic bariatric surgery at Virginia Mason Hospital in 2018. We 
found that the mean opioid use in MED for the first 24 hours following laparoscopic bariatric 
surgery was 134.4mg, with a standard deviation of 106.9mg. Using these numbers, with a 
significance level of 5% and a power of 90%, our required sample size is 83 subjects per group. 
We plan on recruiting 98 per group (196 total) to account for inter-subject variability and drop 
out (15%). 
 
Procedure:  
Control Group A- Opioid-based regimen:  
- 
Preop: 
- 
Multimodals unless contraindicated (i.e. APAP oral sol & gabapentin) 
- 
Scopolamine patch 
- 
Induction 
- 
Fentanyl (50mcg IV) 
- 
Lidocaine 1.5mg/kg IV bolus using IBW 
- 
Propofol 2-3mg/kg IV bolus 
- 
Neuromuscular blockade per Anesthesiology team discretion 
- 
Maintenance 
- 
Sevoflurane 
- 
Neuromuscular blockade at the discretion of anesthesiology team 
- 
May use fentanyl to treat SBP or HR > 20% of baseline 
- 
Emergence 
- 
Neuromuscular reversal, dosed according to VM protocol 
- 
May titrate fentanyl per anesthesiology team throughout the case 
- 
Pt extubated and brought to PACU 
- 
PACU opioid orders per anesthesiology team 
- 
PONV Prophylaxis 
- 
4mg dexamethasone, 1mg haloperidol, Scopolamine patch 
 
Experimental Group B- Opioid-free regimen:  
- 
Preop: 

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- 
Multimodals unless contraindicated (i.e. APAP oral sol & gabapentin) 
- 
Scopolamine patch 
- 
Induction: 
- 
Dexmedetomidine 1mcg/kg IV bolus over 10 minutes using IBW 
- 
Lidocaine 1.5mg/kg IV bolus using IBW 
- 
Propofol 2-3mg/kg IV bolus 
- 
Neuromuscular blockade per Anesthesiology team discretion 
- 
Ketamine 0.5mg/kg IV bolus (based on IBW) 
- 
Maintenance 
- 
Sevoflurane  
- 
Dexmedetomidine 0.4 mcg/kg/hr IV infusion using IBW (may titrate based on 
patient response between 0.3-0.5mcg/kg/hr) 
- 
Lidocaine 2mg/kg/hr IV infusion using IBW 
- 
May use esmolol as needed to treat SBP or HR > 20% of baseline 
- 
Neuromuscular blockade at the discretion of anesthesiology team 
- 
Emergence 
- 
Dexmedetomidine infusion turned off during laparoscopic desufflation 
- 
Lidocaine infusion turned off at skin closure 
- 
Neuromuscular reversal, dosed according to VM protocol 
- 
Pt extubated and brought to PACU 
- 
PACU opioid orders per anesthesiology team 
- 
PONV Prophylaxis 
- 
4mg dexamethasone, 1mg haloperidol, Scopolamine patch 
 
 
This is a prospective, single-center, single-blinded, randomized controlled trial comparing the 
effect of an opioid-free general anesthetic versus a traditional anesthetic with a restricted 
quantity of opioid on postoperative pain following laparoscopic bariatric surgery. Our primary 
outcome will be 24-hour opioid consumption after surgery. Secondary outcomes include: 
numeric pain scores, time from induction to emergence, opioid-related side effects (nausea, 
vomiting, pruritus, and respiratory depression), time to diet advancement to full liquid diet, time 
to first bowel movement, 30-day and 3 month pain scores and opioid requirements, cost to OR 
Pharmacy, time from arrival to PACU to “ready for PACU discharge”, length of hospital stay, 30 
day opioid prescription refills after surgery, patient satisfaction, lowest intraoperative heart rate, 
and intraoperative and postoperative treatment of bradycardia and hypotension. 
 
E. Protection of Human Subjects 
 
1. Risks to the subjects: 
a. Human Subject involvement and characteristics 
i. 
Human subjects will undergo general anesthesia for elective laparoscopic 
bariatric surgery according to one of two study protocols 
ii. 
Human subjects will be adults ≥18 years old, undergoing elective 
laparoscopic bariatric surgery at Virginia Mason Medical Center, as 

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deemed appropriate by our bariatric surgeons. We anticipate enrolling 
196 human subjects in this study, including patients with ASA class I-III.  
 
2. Consent: 
a. Subjects may provide written consent in surgery clinic after a discussion with 
their bariatric surgeon. They may also be contacted by telephone prior to the day 
of surgery by one of the investigators. They will also receive additional 
explanation and be given the opportunity to provide written consent on the day of 
surgery if not obtained prior. 
b. Subjects may also be consented over the phone and sign the informed consent 
form electronically via DocuSign. Their surgeon or one of the investigators will 
contact the subject by telephone prior to the patient’s scheduled surgery. The 
surgeon and/or investigator will go over the consent, giving detailed description 
of the study, the procedures to be followed and the risks and benefits of 
participation. The subject will have adequate time to address any questions or 
concerns regarding the consent. The subject will then be able to give 
documented consent. The person obtaining consent will document the consent 
process in the subject’s chart. A copy of the signed consent form will be available 
to the patient via the DocuSign website.  
 
3. Inclusion/Exclusion Criteria 
a. Inclusion criteria: Adult (≥18 years old) patients undergoing planned elective 
laparoscopic gastric bariatric surgery (i.e. laparoscopic roux-en-Y gastric bypass, 
laparoscopic sleeve gastrectomy), able to provide informed consent.  
b. Exclusion criteria: Any opioid use within 4 weeks prior to surgery, chronic 
antiemetic use, hypersensitivity or contraindication to any study drug, ASA class 
IV,      , patients unable to provide post-operative pain scores, pregnancy or 
lactating, <18 years old, refusal or inability to provide informed consent.  
c. Ethnic / Racial Category: Will not be assessed.  
 
4. Sources of Materials: 
a. All research material obtained from living humans involved in the project will be 
collected as they normally would according to current standard work at Virginia 
Mason’s Bariatric Surgery Program. During initial surgical consultation and any 
other necessary preoperative clinic visits, patients will undergo routine laboratory 
workup. This will include a blood draw, from which we will measure, as a part of 
normal standard of care, patient HbA1c. 
b. Data will be recorded on human subjects as part of their preoperative workup, 
the perioperative period, and routine postoperative follow-up as far as three 
months after surgery. Specific data to be collected is listed under section D.   
c. All blood samples, records, and data will be collected as part of standard of care 
at Virginia Mason.  
d. Limited PHI linking the subject to the data will be maintained to assure source 
documentation is accurate and study is conducted per protocol and regulations.  

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No data will be linked directly to the subject and the randomization envelope will 
contain a unique study subject number. Access to collected data will be limited to 
key study personnel. All data will be kept on password protected computers. 
 
5. Potential Risks:  
a. There are risks associated with any general anesthetic. Side effects can occur 
with different medications. All of the below listed medications involved in the 
general anesthetic techniques are commonly used in surgical patients 
intraoperatively, subjects will not have an undue burden of risk associated with 
their participation in this study. Risks associated with dexmedetomidine use 
include bradycardia and hypotension requiring pharmacologic treatment, 
transient hypertension during loading, atrial fibrillation, sinus arrest, nausea, and 
fever. The dexmedetomidine as an adjuvant during surgery is an “off label,” but 
well-established use. Additional risks associated with lidocaine include CNS 
effects (tinnitus, perioral tingling, metallic taste, restlessness, vertigo, and 
seizures), and cardiovascular effects (hypotension, PR prolongation, QRS 
widening, and dysrhythmias). Additional risks associated with ketamine include 
delirium, diplopia, nystagmus, tachycardia, hypertension, hypersalivation, 
nausea, vomiting, nightmares, and hallucinations. However these risks occur at 
anesthetic doses, and only subanesthetic doses will be used during this study. 
Risks associated with intraoperative opioids include postoperative nausea and 
vomiting, delirium, delayed return of bowel function and respiratory depression.  
 
6. Adequacy Of Protection Against Risks 
a. Recruitment and Informed Consent: Potential study participants will be asked by 
the bariatric surgeon if they would like to be involved in the study during their 
preoperative visit, whether it be initial consultation or any subsequent 
preoperative visit. If time allows, the surgeon themselves will discuss the study, 
and obtain informed consent. If clinic time does not allow, then patients will be 
given an information packet containing details of the planned study, and will later 
receive a phone call during which informed consent can be obtained. If this is the 
case, then all informed consent will be documented on the day of surgery. The 
investigators will answer any questions the subjects have. 
b. Protection against Risk: All data will be recorded and abstracted from the 
electronic medical record. As such, this data will be protected by all HIPPA rules. 
All abstracted data will be coded and recorded in password protected 
spreadsheets on the Virginia Mason Medical Center G-Drive. This plan should be 
as effective at minimizing risks to confidentiality as the electronic medical record 
and Virginia Mason server themselves. Even if our data on the G-drive is 
breached, the data will be de-identified to the degree that no persons or sensitive 
information should be identifiable.  
c. Subjects will have access to any and all medical care if an adverse event were to 
occur. We can ensure necessary medical or professional intervention in the 
event of adverse effects to the subjects.  

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7. Potential Benefits Of the Proposed Research To The Subjects And Others 
a. This study has the potential to help answer important questions regarding post-
operative pain control, decreasing postoperative opioid consumption, and 
modulating the incidence of persistent postoperative pain in our bariatric surgery 
patients. Namely, we can potentially demonstrate our hypothesis that an opioid-
free anesthetic helps decrease postoperative opioid consumption and the 
incidence of persistent postoperative pain. The bariatric surgery population is 
being specifically studied in the case because as it currently stands, they are 
most accurately being tracked with excellent postoperative follow-up.  
b. We believe the risks are reasonable in relation to the anticipated benefits 
because prior studies have already demonstrated the safety profile of the drugs 
as administered during a general anesthetic. Furthermore, all of the study drugs 
in our treatment arm will be administered in relatively low doses, and are already 
part of standard of care at other institutions1. Patients in the experimental 
treatment arm will also benefit from avoiding known adverse side effects of 
intraoperative opioids, as outlined above.  
 
8. Importance Of The Knowledge To Be Gained 
a. This study aims to provide an evidence-based strategy for reducing 
postoperative opioid consumption, which has important implications in the setting 
of our national opioid epidemic. Additionally, our study hopes to provide a cost-
analysis of this strategy, now that dexmedetomidine is available in generic forms.  
 
9. Subject Safety And Minimizing Risks 
a. All risks pertinent to this study design are anticipated to be encountered in the 
intraoperative and immediate postoperative period, during which all study 
participants will be directly cared for by an anesthesiologist, anesthesiology 
resident, nurse anesthetist, and/or PACU nurse. Intraoperatively, all vital signs 
including heart rate and blood pressure will be monitored continuously 
throughout the duration of the operation in accordance with American Society of 
Anesthesiology standards. All episodes of bradycardia and/or hypotension will be 
treated appropriately and the treatment recorded in the anesthetic record. 
Postoperatively, patient vital signs, mental status, pain, and nausea will all be 
continuously monitored by PACU nurses as part of standard of care. All 
assessments and treatments will be recorded in the electronic medical record.  
b. Study endpoints regarding these risks will include intraoperative and 
postoperative blood pressure and heart rate, and any pharmacologic 
interventions made to maintain hemodynamic stability (MAP > 65mmHg and 
heart rate/MAP no greater than 20% above baseline before induction). 
 
10. Quality Assurance - Site Monitoring 
a. An independent review of the records will be conducted by the Benaroya 
Research Institute’s Regulatory Compliance and Education Department.  The 

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Compliance Department shall assist the investigator(s) in the maintenance of 
complete, accurate, legible, and well-organized clinical study data.  In addition 
the study monitors will explain, interpret, and ensure the investigator’s continued 
understanding of all applicable regulations concerning the proper execution of 
the protocol and the investigator’s reporting responsibilities.  The data collection 
forms will be monitored periodically for accuracy, completeness, and adherence 
to the protocol, regulatory compliance, and the maintenance of comprehensive 
clinical records.  These data will be checked against medical records to verify 
completeness and accuracy. 
 
11. Audit and Inspection 
a. Internal quality audits may be performed pre-, throughout or post-study by the 
Compliance Department. Furthermore, the Investigator agrees to inform the 
Regulatory Compliance Department immediately of any known or suspected 
inspection by authorities and agrees to provide access to the required subject 
records and other study documentation. 
 
12. Data Collection 
a. All records associated with the study will be maintained for approximately 10-15 
years.  Those documents may include the following: 
i. 
Subject files including the completed data collection form, supporting 
source documentation and the informed consent. 
ii. 
The protocol with all amendments, the investigator brochure or package 
insert (if applicable), 
iii. 
Copies of all regulatory documentation, e.g., Delegation of Authority Log, 
iv. 
All correspondence with the IRB, Scientific Merit, Data Safety Monitoring 
and regulatory authority. 
v. 
The database and any statistical analyses conducted for the study. 
 
13. Subject Confidentiality 
a. All records will be kept in a locked file cabinet.  All computer entry and 
networking programs will be done using SID’s only.  Clinical information will not 
be released without written permission of the subject, except as necessary for 
monitoring by IRB, the FDA, the OHRP or designee. 
 
14. Institutional Review Board 
a. Institutional Review Board (IRB) Review and Informed Consent: This protocol 
and the informed consent document and any subsequent modifications will be 
reviewed and approved by the BRI IRB.  A signed consent form will be obtained 
from each subject.  The consent form will describe the purpose of the study, the 
procedures to be followed, and the risks and benefits of participation. A copy of 
the signed consent form will be given to the subject. 

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b. Study Modifications/Discontinuation: The study may be modified or discontinued 
at any time by the IRB, Sponsor, OHRP, FDA, or other Government agencies, as 
part of their duties to ensure that research subjects are protected. 
c. Adherence to Protocol: Revisions to the protocol will only be made when 
changes have been approved by the principal investigator, sponsor and 
regulatory authority, as applicable. Changes must also be approved by the IRB of 
record, preferably, before implementation unless subject safety is at risk. 
Protocol deviations (minor items that do not impact subject safety or data 
integrity) will be avoided, but if necessary, they should be approved by the 
principal investigator and acknowledged by the IRB of record prior to their 
occurrence.  If consistent deviations are noted, the PI will determine if a 
preventative action plan is necessary, working or whether another solution   will 
be sought.  Protocol violations (impact subject safety or data integrity) should be 
avoided, but if they occur, must be reported to the PI within 24-48 hours of 
learning of the event.  Prompt reporting to the IRB of record is also mandatory. 
 
F. Reference/Literature Citations 
 
1. Mauermann E, Ruppen W, Bandschapp O. Different protocols used today to achieve 
total opioid-free general anesthesia without locoregional blocks. Best Pract Res Clin 
Anesthesiol 2017;31:533-45. 
2. Hoehn RS, Seitz AP, Singer KE, et al. Enhanced recovery protocol for laparoscopic 
sleeve gastrectomy: Are narcotics necessary? J Gastrointest Surg 2019 Jan 28; epub 
ahead of print. 
3. Raebel MA, Newcomer SR, Bayliss EA, et al. Chronic opioid use emerging after bariatric 
surgery. Pharmacoepidemiology and Drug Safety 2014;23:1247-1257. 
4. Brummett CM, Waljee JF, Goesling J, et al. New Persistent Opioid Use After Minor and 
Major Surgical Procedures in US Adults. JAMA Surg. 2017;152(6):e170504. 
 
G. Consultants 
 
All investigators work in the Department of Anesthesiology or Department of Surgery at Virginia 
Mason Medical Center and will be actively involved in subject recruitment, study design, and 
analysis. 
 
H. Facilities Available 
 
Following the standard work at VMMC, all general anesthetics will be performed in the operating 
room at Virginia Mason Medical Center. 
 
J. Appendix- none