Evaluation of a Single Intra-operative Dose of Dexmedetomidine on Post-operative Narcotic Requirements and Pain Scores in Bariatric Surgery Patients
Phase: PHASE4
Conditions: Pain
Sponsor: West Virginia University

Does Single Intraoperative Bolus Dexmedetomidine Significantly Reduce 
Narcotic Requirements During Postoperative Period in Bariatric Patients? 
NCT02604940 
April 09, 2014 
 
Protocol 
 
 

West Virginia University IRB Protocol #1306055796 
Does Single Intraoperative Bolus Dexmedetomidine Significantly Reduce 
Narcotic Requirements During Postoperative Period in Bariatric Patients? 
Contact Information:  
Pavithra Ranganathan  
 
 
 
Michael Kyle Ritchie 
Assistant Professor 
 
 
 
 
PGY-3, CA-2 Resident 
WVU Dept. of Anesthesiology 
 
 
 
WVU Dept. of Anesthesiology 
ranganathanp@wvuhealthcare.com 
 
 
ritchiem@wvuhealthcare.com 
Introduction: This study will evaluate the postoperative opioid sparing effects of dexmedetomidine 
given as single bolus dose intraoperativley.  Dexmedtomidine is an agonist of α2-adrenergic receptors 
sedative medication used by intensive care units and anesthesiologists and is unique in its ability to 
provide sedation without causing respiratory depression.  Recently, it has received attention for its 
potential for additive analgesia.   The study population will be patients undergoing gastric bypass 
surgery.  The study population of bariatric surgery patients was chosen due to high prevalence of sleep 
apnea and Pickwickian component that can be worsened with opioid analgesia in the postoperative 
period.  The purpose of the study is to test whether the use of a single bolus dose dexmedetomidine in 
addition to standard dose pain regimen decreases postoperative narcotic requirements when compared 
to standard dose pain regimen alone.  The secondary purpose is to study whether single bolus dose 
dexmedetomidine reduces respiratory rate, heart rate, systolic and mean blood pressure, patient PCA 
demand bolus requests and VAS pain scores in the postoperative period.  Our overall goal of the study is 
to establish evidence of dexmedetomidine's role in multimodal pain relief in the bariatric surgery 
population with the possibility of other patient subgroups to follow.  
Primary Objective:   The primary objective of the study is to assess if the use of a single bolus dose 
dexmedetomidine in addition to standard pain regimen given intraoperatively decreases postoperative 
narcotic requirements when compared to standard pain regimen alone. 
Secondary Objective:   The secondary objective of the study is to assess if the use of single bolus dose 
dexmedetomidine decreases respiratory rate, heart rate, systolic and mean blood pressure, patient PCA 
demand bolus requests and VAS pain scores in the postoperative period. 
Potential Benefits to Subjects 
a. Increased patient satisfaction and comfort 
b. Decreased narcotic requirements 
c. Decreased narcotic related side effects including nausea, constipation and respiratory 
depression 
d. Decreased stress response 
e. Reduced postoperative blood pressure  and heart rate 

f. 
Patient anxiolysis    
Study Design:  After informed consent is obtained in the Bariatric Surgery Center, patients will be 
enrolled in the study and assigned a code for the remainder of study.  The code will used by 
pharmacy for block randomization.  The code will be associated with MRN for patient identification 
and data entry by Co-investigators after patient has been discharged from study.  On the day of the 
procedure, preoperative nursing will place sticker on front of patient hard chart clearly marking 
participation in trial.  The control group will receive 1-2 mcg/kg fentanyl IV plus 1000 mg IV tylenol 
as well 60mL saline delivered over 15 minutes in OR upon notification of surgical closure.  The 
experimental group will receive 1-2 mcg/kg fentanyl IV plus 1000mg IV acetaminophen and 1mcg/kg 
IV dexmedetomidine deliver over 10 minutes from 60 mL syringe upon notification of surgical 
closure. Pharmacy will be notified of patient enrollment in trial, use block randomization sheet for 
assignment to treatment or control group, and prepare medication syringes.  Syringes will be 
delivered to OR for administration by anesthesia personnel upon notification of surgical closure.  
The investigators, patient, anesthesia staff, PACU nursing OR staff and surgeon will be blinded to 
medication being administered.  Pharmacy will not be blinded to medication as they will have block 
randomization sheet and assign patient by MRN to a given code. Time interval to extubation from 
procedure stop will be recorded in EMR by anesthesia personnel.  Upon arrival to PACU, patient will 
immediately receive hydromorphone and be instructed on its usage by PACU nursing.  PACU nursing 
will record HR, RR, BP, and VAS score q15min per PACU routine into EMR.  PCA will be interrogated 
at 30 minute, 1 hour, 90 minute, 2 hour and 4 hour mark by PACU nursing and usage in milligrams 
will be recorded in chart as nursing note for later review by researchers.  Included in PCA data will 
be total mg of hydromorphone used, number of demand doses given by pump, and number of times 
patient pushes demand button.  Patient will be discharged from study after 4 hour mark per OSA 
guidelines.  Results will be recorded into Redcap online statistics program to ensure data safety.  
Code and MRN block randomization sheet will be kept under lock and key in pharmacy. 
 
Patient Risk Management:  
a. Identification of Risk:  Because medication is to be given in this study, more than minimal risk 
will be incurred by the patient.  Participation is completely voluntary.  Risks include possible 
allergy or other unanticipated reaction to dexmedetomidine or hydromorphone.  Specific side 
effects to dexmedetomidine include symptomatic bradycardia, sinus arrest, hypertension, 
hypotension, and excessive sedation. Specific side effects related to hydromorphone are 
common to all narcotics and include sedation, respiratory depression, upper airway obstruction, 
constipation, illeus, bradycardia, nausea, and vomiting.   
 
b. Management of Risk:  :   During study period, syringes will be covered with opaque label as to 
blind surgeon and anesthesia personnel to contents.  Label can be peeled off at any time by 
anesthesia personnel to reveal syringe content in the event of an emergency and medication 
identification would be necessary for patient safety.  Patient would be disqualified from trial if 
this were to occur.  Atropine and glycopyrolate will be in syringes and ready for use as part of 
standard emergency drug regimen in case of hypotension or bradycardia experienced by patient 
throughout study period.  Dexmedetomidine or saline will not be administered to patient if 
systolic blood pressure is less the 90mmHg, mean arterial pressure less than 60, or if heart rate 
less than 50 bpm.  Rescue hydromorphone will be available in form of IV hydromorphone 2mg 
PRN q5mins if PCA dosing fails to control pain.  Patient will be disqualified from study if rescue 
medication was given. Medications will only be administered by trained anesthesia personnel.  

Trained PACU nurses under guidance of staff anesthesiologist will oversee PCA usage.  Trained 
pharmacy staff will prepare all medications for use.  Emergency resuscitation equipment and 
drugs including atropine and narcan will be immediately available at all.  
 
c. Confidentiality:  The records of this study will be kept confidential. The investigators will not 
include the name of any patient involved in the research.  Patients will be assigned a code 
number upon enrollment in study.  Code numbers will be used for block randomization in 
pharmacy to randomly assign patient to treatment groups.  Pharmacy staff will have access to 
patient chart and MRN for purpose of recording which drug was given, control or experimental.  
Block randomization sheet containing MRN and code numbers for patient will be kept under 
lock in key by pharmacy personnel.  The sheet will be kept for official study documentation.  A 
document listing the code associated with a specific patient and their MRN will be stored in 
redcap only to be viewed by the co-investigators for data analysis. The patient’s code number 
will be used on all other documentation to protect patient privacy. The investigators and 
statistician will be the only person who will have access to this data.   
 
d. Patient Data Safety Plan:  Researchers will access the code sheet at 25, 50, 75, and 100 patient 
enrolment points to record pertinent clinical data for analysis.  Included in the interval analysis 
will be medical futility and critical detrimental patient events to assure patient safety 
throughout trial.  Times.  Specifically, study personnel will look for instances of symptomatic 
bradycardia or other heart rhythm disturbances, oversedation, respiratory failure, hypotension 
or other unforeseen critical event.  Patients will be provided with study personnel contact 
information in case adverse event possibly related to study were to occur after discharge from 
study All data will be entered and safely stored in redcap, an online secured server maintained 
by School of Public Health 
 
Number of Subjects: 100 subjects (50 subjects assigned to control group and 50 to treatment group) 
a. Subject Characteristics:  The participants in the study will include 100 bariatric surgery patients 
at WVUH Ruby Memorial Hospital who choose to participate in the study after informed consent 
is obtained.    
 
b. Selection Criteria:  Patients must be undergoing bariatric surgery at WVUH Ruby Memorial.  
They must be ASA class III of lower.  They must be between the age of 18 to 65 years old. 
 
c. Exclusion Criteria:  Hydromorphone or dexmedetomidine allergy.  ASA class IV or higher.  
Emergency surgery.  Long term narcotics usage defined as > 2 weeks.  Long term sedative 
(benzodiazepine, clonidine, hydroxyzine) usage defined as greater than 2 weeks  Bradycardia 
defined as HR < 50bpm, SBP < 100mmHg, Tachy-Brady Syndrome, 1st, 2nd or 3rd degree heart 
block, Junctional Rhythm. Severe renal or hepatic dysfunction.  Protected populations will be 
excluded from study including obstetrical patients, prisoners, students, or mentally 
handicapped.  
 
d. Recruitment Source:  Bariatric surgery patients at WVUH Ruby Memorial will be recruited in 
bariatric surgery clinic or pre-operatively by anesthesia personnel.  Dr. Quinlin performs 3 to 4 
laproscopic gastic bypasses per week with a conservative estimate of 200 operations year.  Our 

goal is 50% patient participation after voluntary participation rights and exclusion criteria have 
been applied.    
 
e. Recruitment Methods:  Subjects that meet above criteria will be asked if they wish to participate 
in study.  Risks and benefits of the study will be explained. 
 
f. 
Potential Problems:  Problems involving subject identification and recruitment by anesthesia 
personnel should be minimum.  Education  post-operative staff on PCA usage data recording will 
likely be the largest barrier. 
 
Informed Consent: Patients undergoing bariatric surgery at WVUH Ruby Memorial will be asked about 
voluntary participation in the study during preoperative visit to Bariatric Surgery Center.  Risks and 
benefits relating to the study will be explained to patient by Kristen Rosati, Physician Assistant at WVU 
Bariatric Surgery Center.  Information will be given to patient after all questions and concerns have been 
addressed.  Patient will be given opportunity to consider trial participation and informed consent 
process would take place on subsequent visit.  After inclusion and exclusion criteria have been assessed, 
the patient will then have informed consent form reviewed with them and sign informed consent form if 
they wish to participate.  Patient will be enrolled in study from this point forward. 
 
Statistical Methods: Descriptive statistics will be calculated for both groups, including means (SD) and 
frequencies (percentages) where appropriate.  Comparisons between the two groups with respect to 
binary outcomes will be done via chi-square tests, and odds ratios (95% confidence intervals) will be 
reported to quantify the magnitude of the differences observed.  The majority of the primary outcomes 
are continuous in nature, and more than likely many will be skewed, including cumulative 
hydromorphone usage.  However, given the sample size (over 30 per group), t-tests comparing the 
means of these outcomes will be able to be used.  In the event sample size targets are not reached, 
nonparametric tests (i.e., Mann-Whitney U) will be utilized.  Statistical significance will be set at alpha = 
0.05.  All data will be exported from REDCap and analyzed via SAS (version 9.3).  Power analysis reveals 
50 enrolled patients per group will provide 90% power (alpha = 0.05) to detect a difference of 0.66 
standard deviations between the two groups.  Unfortunately, no reliable standard deviation estimates 
of our primary outcome, cumulative hydromorphone at 240 minutes post-arrival to PACU, are available 
in the literature.  A conservative estimate from the Tufanogullari et al. paper (Anesthesia and Analgesia, 
2008, 106: 1741-1748) for the standard deviation of cumulative morphine in one day (not 
hydromorphone) is about 30 in either group.  Given our calculations for this hypothetical outcome, we 
would have sufficient power to see a difference of 20mg in cumulative morphine between the two 
groups, which would amount to a 40% reduction given a mean morphine level of 50mg in the control 
group.  Since we will be focusing on hydromorphone and not morphine over a shorter period of time, 
both the mean and SD of our primary outcome should be considerably smaller in a similar fashion, but 
the percent reduction that we would be able to detect statistically should remain the same.  For our 
secondary outcome of the VAS pain score, which is known to have a SD of about 3 in this population, 
100 patients will provide 90% power to detect a difference of 2 units in pain score at any given time 
point.     

Primary Endpoint: The primary endpoint will be cumulative patient hydromorphone PCA usage in the 4 
hour postoperative period. 
Secondary Endpoints:  Respiratory rate, heart rate, systolic and mean blood pressure, patient PCA 
demand bolus requests and VAS pain scores in the postoperative period. 
Timeline to Endpoints:  We anticipate a one year course for data collection to achieve our goal sample 
size.   Twelve weeks are estimated to be need for statistical calculation and results analysis.  
Costs: The subjects of this study will not incur any costs as a result of their participation.   Funding for 
dexmedetomidine will be provided by Hospira.  
Compensation and Incentives: There will be no compensation or incentives offered for anyone involved 
in this research project. 
Literature Review 
 
Bakhamees, H. S., El-Halafawy, Y. M., El-Kerdawy, H. M., Gouda, N. M., & Altemyatt, S. (2007). Effects of 
dexmedetomidine in morbidly obese patients undergoing laproscopic gastric bypass. Middle 
Eastern Journal of Anesthesia, 19(3), 537-552.  
Dholakia C, Beverstein G, Garren M, Nemergut C, Boncyk J, Gould JC.  (2007) The impact of perioperative 
dexmedetomidine infusion on postoperative narcotic use and duration of stay after laparoscopic 
bariatric surgery. J Gastrointest Surg. Nov;11(11):1556-9. Epub 2007 Aug 21. 
Schnabel, A., Meyer-Frießem, C. H., Reichl, S. U., Zahn, P. K., & Pogatzki-Zahn, E. M. (2013). Is 
intraoperative dexmedetomidine a new option for postoperative pain treatment? a meta-
analysis of randomized controlled trials. Pain, 154, 1140-1149.  
Tufanogullari, B., White, P. F., Mariana, P. P., Kianpour, D., Lacour, T., Griffin, J., Skrivanek, G., & 
Macaluso, A. (2008). Dexmedetomidine infusion during laparoscopic bariatric surgery: The effect 
on recovery outcome variables. Anesthesia and Analgesia, 106(6), 1741-1748.