Effect of Intraoperative and Post-operative Opioids on Persistent Opioid Use in the Surgical Patient
Phase: PHASE2
Conditions: Analgesic Drug Dependence, Colectomy
Sponsor: University of South Florida

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Effect of intraoperative and post-operative opioids on persistent opioid 
use in the surgical patient 
 
NCT#: Not Assigned 
 

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Study Protocol Title:  
Effect of intraoperative and post-operative opioids on persistent opioid 
use in the surgical patient 
List of Abbreviations:  
OFA: Opioid Free Anesthesia 
 
Principal Investigator, Research Team, and Study Site: 
 
Principal investigator:   
Name  
Enrico Camporesi, MD 
 
 
 
 
 
 
TeamHealth Anesthesia, Tampa General Hospital 
 
 
 
 
 
 
Morsani College of Medicine, University of South Florida 
 
 
 
 
Address 
1 Tampa General Circle, Suite A327 
 
 
 
 
 
 
Tampa, Florida 33606 
 
 
 
 
Telephone 
813-600-9094 
 
 
 
 
Fax 
 
813-844-4467 
 
 
 
 
Email 
 
ecampore@health.usf.edu  
 
Research team and contact information:  
 
 
Study Coordinator:  
 
Name  
Garrett Enten, BS 
Address 
1 Tampa General Circle, Suite A327 
 
 
 
 
 
 
Tampa, Florida 33606 
 
 
 
 
Telephone 
863-513-9885 
 
 
 
 
Fax 
 
813-844-4467 
 
 
 
 
Email 
 
garrett_enten@teamhealth.com   
 
Co-investigator: 
 
 
 
Dr. Sanchez  
 
Study site:  
 
 
 
 
 
 
 
 
 
 
 
Tampa General Hospital (TGH) 
 
 
 
 
 
 
1 Tampa General Circle 
 
 
 
 
 
 
Tampa, Florida 33606 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Research Synopsis: 
 
 
Background and Significance: 
 
Much has been written about the correlation of opioid prescriptions and rates of opioid 
overdose. (1)  Last year the CDC made recommendations which focused initially on primary care 
physicians and chronic pain. (2)  Recent literature finds that 6-8% of postoperative patients have 
prolonged postoperative opioid prescription use. (3,4) There is no correlation with postoperative pain or 
extent of surgical procedure.  (3) Prescription opioids remain the mainstay of postop pain management.  
Surgeons continue to overprescribe opioids, leading to the potential for continued use or diversion of 
the unused pills. (5)   The roll of intraoperative use of opioids during opioid anesthesia has largely been 
ignored by those studying the opioid crisis. (6) Fentanyl remains the most commonly used intraoperative 
opioid, considered by most anesthesiologists to be an integral component.  Evidence has been mounting 
that fentanyl results in acute tolerance and opioid induced hyperalgesia. (7)  Our study looks at the 
effect of removing all intraoperative opioids on the rate of prolonged postoperative opioid prescription 
use. 
 
Objective: 
Primary Objective 
 To compare post-operative opioid use in a verified sample population of patients who had 
Laparoscopic Colectomy  at TGH  
 
Study design:  
 
Randomized Controlled Trial 
 
Endpoints 
 
Upon Consent 
 
Patient demographics (age, race, gender, BMI) 
 
Hx depression 
 
Hx anxiety 
 
Hx PTSD 
 
Hx smoking 
Study Title 
Effect of intraoperative and post-operative opioids on persistent opioid use 
in the surgical patient 
Study Population 
Patients admitted for Laparoscopic Colectomy  at TGH   
Study Design 
Randomized Controlled Trial  
Sample Size 
100 
Study Duration 
Total length of time: 30 months 
Primary Objective 
To report post-operative opioid use in a sample population at 3, 6, and 12 
months respectively. 

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 
Hx substance abuse 
 
Brief Pain Inventory (BPI) 
 
Screener and Opioid Assessment for Patients with Pain (SOAPP-R 24) 
 
Post-op 
 
Pain Scores in the PACU(10cm on visual analogue scale) 
 
Nausea Scores in the PACU (0-4 PONV scale) 
 
Pain scores Floor Stay 24hr 
 
Opioid Use in Morphine Equivalents 
 
 
Follow up for 12 months 
 
Length of Stay 
 
Post-surgical opioid prescription use 
 
BPI  
 
Patient Satisfaction 
 
 
Methodology:  
 
Overview: 
 
The study population will be composed of 100 patients total, 50 opioid-free anesthesia 
laparoscopic colectomy patients and 50 opioid anesthesia laparoscopic colectomy patients at Tampa 
General Hospital. After consent is obtained patients will be electronically randomized using REDCap in a 
1:1 ratio and assigned to a opioid anesthesia or opioid free anesthesia group. Patients will also consent 
to be asked survey questions preoperatively and be followed for 12 months postoperatively at specific 
intervals to evaluate pain, satisfaction, and opioid prescription use. This will be done through a data 
mining platform and service known as REDCap. REDCap is partnered with USF to allow for subject 
management, data collection and the distribution of surveys via mobile phone. All data collected by 
REDCap is stored on a HIPPA compliant server. Patients will receive automated push notifications to 
their mobile phones to fill out surveys regarding their pill usage, pain, and satisfaction for a year or until 
cessation of opioid use is confirmed. Confirmation of opioid cessation will be performed on a case by 
case basis by the principal investigator, Dr. Camporesi. In addition to the surveys performed, nausea and 
pain scores will be collected prospectively from observation in the PACU 
 
Patient name and MRN will be utilized to access medical records for patient medical history and 
demographical data. Persistent prescription opioid use will be determined using these records and 
REDCap surveys. Collected data will be stored on a REDCap HIPPA compliant server. The HIPPA 
compliant server is stored in a secure access restricted location on USF campus and maintained by Dr. 
Anthony Green, Ph.D, a USF appointed sysadmin of the REDCap server. Data can only be accessed by 
staff participating in the research study. No identifying information about the participants will be 
disclosed. Medical record numbers and patient names will be necessary to access medical records. After 
all the data are collected patient identifiers e.g. patient name, medical record number, date of birth etc. 
will be deleted. The de-identified data will be analyzed to represent outcomes before and after surgery 
using SPSS 17.0.  

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Inclusion Criteria 
 
 
Patients admitted to TGH for laparoscopic colectomy  under Dr. Sanchez’s care   
 
Adults aged 18 and older 
 
Exclusion Criteria 
 
 
Patients who are pregnant 
 
Patients that are not registered within Epic 
 
Patients without smart phone capabilities 
 
Patients younger than 18 years  
 
Patients who cannot speak or read English 
 
Consent Process 
 
All patients that are scheduled to have laparoscopic colectomy at Tampa General Hospital (TGH) 
will be evaluated for study eligibility preoperatively during their visit with the anesthesiologist. The pre-
operative assessment will take place 3-7 days prior to the scheduled surgery. Patients who qualify for 
the study and give informed consent will be entered into the study during their pre-operative visit. All 
study discussions will take place in a private exam room. All subjects will be given the opportunity to ask 
questions. If the investigator feels that the subject understands the research parameters and the subject 
is willing to sign the consent form, the patient will be enrolled in the study.  On the day of the surgical 
procedure the subject will be re-evaluated for willingness to participate.  Any additional questions will 
be answered prior to surgery.  
 
Screening & Baseline Visit 
 
Patients who have signed consent and meet the study criteria will be given the Brief Pain 
Inventory (BPI) and Screener and Opioid Assessment for Patients with Pain (SOAPP-R 24) surveys to 
determine base line pain, opioid use, and self-reported susceptibility to addiction.  
Table 2 Study Groups 
 
 
 
 
Study 
Group 
ANESTHESIA TYPE 
OFA 
Opioid free Anesthesia (n  = 50) 
OA 
Opioid Anesthesia (n = 50) 

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Preoperative Management  
 
The preoperative course will comply with TGH’s standard of care practices with the 
addition of baseline surveys upon consent. 
Intraoperative Management   
 
 (OA): 
 
The intraoperative course will follow our standard of care practices.  Doses/concentration of 
medications/agents used for the anesthetic management of the subjects enrolled in this trial may be 
adjusted when necessary to provide optimal subject care.  Anesthesia will be induced with rocuronium, 
propofol, intravenous opioids, and other medication(s)/agent(s) at a concentration range/dose(s) based 
on the clinical need of the subject. 
Depth of anesthesia will be measured with BIS-monitoring of all patients and a standard 
approaching 50% suppression will be maintained throughout the main duration of surgery. Reversal 
agent will be administered at a post-tetanic count of 1 or 2 (PTC 1,2 defined as deep block). 
Anesthesia will be maintained with intravenous opioids, propofol and/or medication(s)/agent(s), 
including inhalation anesthetic agents, at a concentration range/dose(s) based on the clinical need of 
the subject. 
Tracheal extubation will be performed at the end of anesthesia after administration of reversal 
agent. After extubation, the investigator will determine when the subject is OR discharge ready (subject 
is extubated, wound dressing is in place, and vital signs are stable). 
 
 (OFA): 
 
The intraoperative course will follow our standard of care practices for OFA.  
Doses/concentration of medications/agents used for the anesthetic management of the subjects 
enrolled in this trial may be adjusted when necessary to provide optimal subject care. Acetaminophen 
1g will be given prior to induction.  Anesthesia will be induced with rocuronium 1mg, propofol 3-6 
mg/kg, and succinylcholine 1.5 mg/kg  
Depth of anesthesia will be measured with BIS-monitoring of all patients and a standard 
approaching 50% suppression will be maintained throughout the main duration of surgery. Reversal 
agent will be administered at a post-tetanic count of 1 or 2 (PTC 1,2 defined as deep block). 
Anesthesia will be maintained with Sevoflurane, Magnesium, Lidocaine, Ketamine, Decadron, 
Ondansetron, and Ketorolac at a concentration range/dose(s) based on the clinical need of the subject. 
Tracheal extubation will be performed at the end of anesthesia after administration of reversal 
agent. After extubation, the investigator will determine when the subject is OR discharge ready (subject 
is extubated, wound dressing is in place, and vital signs are stable). 
 
 
 
 
 
 

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Postoperative Management 
 
Upon arrival in the PACU, the (sub)investigator, using the visual analog scale, will clinically assess 
post-operative pain. Assessment of patient pain levels involve a series of VAS testing postoperatively 
(upon arrival and every 15 minutes postoperatively until discharge from the PACU) using a 10 cm line.  
Patients that complain of pain intensity >5 cm/10 cm, will be given a standardized rescue intravenous 
dilaudid regimen, IV dilaudid at 0.4mg  up to a max dose of 2mg prn q 2 hours or until a VAS of <5 is 
obtained. Post-operative PACU narcotic consumption will be recorded and quantified.   
Post-operative nausea and vomiting (PONV) will be assessed using a PONV rating scale every 15 
ŵiŶutes uŶtil PACU disĐharge.  PONV ǁill ďe rated as Ϭ, Ŷo Ŷausea; ϭ, ŵild Ŷausea ч ϭ5 ŵiŶutes; Ϯ, 
Ŷausea ш 5 ŵiŶutes aŶd ϯ, ǀoŵitiŶg.  PONV ǁill ďe treated ǁith ondanestron 4 mg intravenously and, if 
persistent, with metoclopramide 10 mg intravenously.    
All patients will be monitored with continuous pulse-oximetry. All post-operative complications 
will be captured.   
 
Follow-up  
 
Upon discharge, patients will be provided with weekly surveys via the REDCap application on 
their mobile device. A weekly push notification will be sent at a patient designated time, at which point 
patients will fill out a BPI survey, satisfaction of care survey, and pill count. Patients will be sent weekly 
survey for 12 months after discharge or until cessation of opioid use is confirmed by the PI.  
 
Sample Size and Justification: 
Based off of ĐoŶserǀatiǀe reĐruitŵeŶt expeĐtatioŶs aŶd Dr. SaŶĐhez’s ĐurreŶt through rate of 
laparoscopic colectomy patients, we expect to evaluate a total of approximately 100 patients who 
received laparoscopic colectomy  to determine opioid use over 12 months post-op.  
 
Statistical Analysis Plan: 
We will look for opioid prescription use trends with-in subsets of the sample:  patient 
demographics, medical history, and self-reported addiction by performing Chi-square analysis and 
Fisher’s exaĐt tests where applicable. For significant variables, univariate and multivariate logistic 
regression analysis will be performed to look for any independent variables that are linked to continued 
opioid use at 3, 6, 9, and 12 months.  
 
 
 
 
 
 

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Privacy:  
 
The collection of personal patient information will be limited to the amount necessary to 
achieve the aims of the research, so that no unneeded sensitive information is being collected.  
 
Only study personnel will collect data. Hard copy documents will be retained for the duration of 
the study until data entry. All hard copy documents will be kept in a locked cabinet in the research 
ĐoordiŶator’s offiĐe. All eleĐtroŶiĐ data ǁill ďe reĐorded iŶ a passǁord proteĐted ExĐel spreadsheet aŶd 
data analysis will be recorded in a password protected Excel spreadsheet and data analysis will be 
conducted using de-identified data in SPSS statistical software. All hard copy documents will be 
shredded within five years after completion of the study.  
 
Confidentiality precautions: 
Confidentiality is an extension of the concept of privacy; it refers to the ways identifiable 
information will be stored and shared. Identifiable information can be printed information or electronic 
information. The precautions that we will use to maintain the confidentiality of identifiable information 
are: 
 
Paper-based records (data sheets) will be kept in a secure location and only be accessible to 
personnel involved in the study.  
 
Computer-based files will only be made available to personnel involved in the study through the 
use of access privileges and passwords.  
 
Whenever feasible, identifiers will be removed from study-related information.  
 
Risk/Benefit: 
Risk to participants:  
The risks to patients with this project involve the use of PHI for the initial access to study-related data 
and collection of de-identified health information. Anytime such data is accessed and stored by handlers 
outside the domain of clinical routine, the risk of breached data security is increased; however, all 
means necessary have been inputted to secure the information. Medical record numbers and patient 
Ŷaŵes ǁill ďe used to aĐĐess the patieŶt’s ŵediĐal reĐord. 
 
Both Anesthesia protocols are TGH standard of care for OA and OFA, standard level of risk for this 
procedure under each respective anesthesia regimen apply. 
 
Benefits to participants: 
Benefits for subject participation in this study include the retention of Dr. Enrico Camporesi for pain 
consultation for 12 months post-operatively or until cessation of opioid use as confirmed by him.  
 
Patients will be incentivized to fill out every survey with $50 compensation upon completion of the final 
survey if every prior survey has also been filled 
 
 
 
 
 

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Data Safety Monitoring: 
Monitoring throughout the study will be conducted by Enrico Camporesi, MD; and Garrett Enten, BS.  
Any action resulting in a temporary or permanent suspension of the study will be reported to the IRB.  
 
Conflict of Interest: 
There are no conflicts of interest.  
 
Publication and Presentation Plans: 
We anticipate writing a manuscript to discuss our results and submitting to a peer-reviewed journal. We 
also plan to present our findings at any relevant meetings or conferences. 
 
Study Personnel and Roles: 
 
 
Enrico Camporesi, MD  
PI 
Responsible for all study related 
issues 
Dr. Sanchez 
Sub-I 
Surgeon 
Data interpretation/analysis 
Consent Interview 
Dr. Rasheid 
Sub-I 
Surgeon, 
Data interpretation/analysis 
Consent Interview 
Garrett Enten, BS 
Research Coordinator 
Data management and analysis 
Addresses IRB issues 
Communicates with IRB 
Consent Interview 
 
 
 

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References:  
 
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United States, 2010–2015. MMWR Morb Mortal Wkly Rep. ePub: 16 December 2016 
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States, 2016 JAMA. 2016;315(15):1624-1645 
3. Carroll I, Barelka R et al: A pilot study of the determinants of longitudinal opioid use after 
surgery Anesth Analg 2012; 115: 694-702 
4. Brummett C, Waljee J et al: Jama Surgery New persistent opioid use after minor and major 
surgical procedures in US adults JAMA Surg. 2017 Apr 12 :e170504. doi: 
10.1001/jamasurg.2017.0504. [Epub ahead of print] 
5. Waljee J, Li L Brummett C: Iatrogenic opioid dependence in the United States:  Are surgeons the 
gatekeepers? Ann Surg 2017;265:728–730 
6. Kharasch ED, Brunt LM. Perioperative Opioids and Public Health. Anesthesiology. 
2016;124(4):960-965.  
7. Mauermann E, Filitz J et al: Does fentanyl lead to opioid-induced hyperalgesia in healthy 
volunteers? Anesthesiology 2016; 124(2):453-463