Clinical trial NCT05327777
Conditions: Opioid Misuse and Addiction Pain
Sponsor: Thomas Jefferson University
Start date: 2019-11-01; Completion date: 2023-03-15
Enrollment: 129 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Investigators have created an opioid reduction "package" which includes patient education, non-narcotic pain control instructions, and limited (or no) opioid pain prescriptions provided at discharge in an attempt to reduce the number of opioid consumption after outpatient general surgery.

Detailed description:
Between November 2019 and July 2021, patients undergoing elective inguinal hernia repair (IHR) or cholecystectomy were enrolled in the study. Patients were divided into three cohorts: Control, opioid sparing (OS), or zero-opioid (ZO). Control patients did not have any intervention; OS patients had an opioid reduction intervention protocol applied (patient education and perioperative multimodal analgesia) and were provided an opioid prescription at discharge; the ZO had the same protocol, however patients were not provided opioid prescriptions at discharge. Two weeks after discharge patients were interviewed to record opioid consumption, pain scores, and level of satisfaction since discharge.

Arms: arm 1: Normal standard practices arm 2: Providers required to prescribe 10 narcotic pills only arm 3: No narcotic prescription is provided to patient at discharge
Interventions: intervention 1: Oxycodone intervention 2: Zero Opioid Protocol
Intervention descriptions: intervention 1: Investigators provided set opioid prescriptions for 10 pills each patient. intervention 2: Investigators provided no opioid prescriptions at discharge and instead provided information on non-narcotic pain control.

Protocol documents:
Prot_SAP_004.pdf: 
Official Title: Toward Zero Prescribed Opioids for Outpatient General Surgery 
Procedures: a Prospective Cohort Trial 
NCT Number: NCT 05327777 
Date of Document: November 1, 2019


Title of Project: Opioid Free General Surgery 
Introduction and Background: Laparoscopic general surgery is the mainstay of treatment for 
benign biliary disease, including symptomatic gallstones. While laparoscopic cholecystectomy is 
generally considered less painful than open surgery, pain is one of the reasons for delayed 
discharge and overnight admission after outpatient surgery. To optimize same day discharge, 
patients are routinely prescribed narcotic pain medication. There has been a dramatic rise in 
prescription opioid abuse along with the associated morbidity and mortality, with a major 
contributor being the diversion of excess, unused prescriptions. Thomas Jefferson University 
Hospital has recently implemented guidelines for the recommended dosage and length of time of 
opioid pain medications to prescribe after general surgery procedures. 
During the last two decades, there has been an increase in the implementation of Enhanced 
Recovery After Surgery (ERAS) pathways, which includes a focus on multimodal pain 
management. This component allows for the optimization of patient recovery and may assist 
with the reduction of opioid utilization.  
We plan to assess the impact of implementing a new standardized multimodal pain care bundle 
on postoperative pain control and patient satisfaction for elective, outpatient laparoscopic 
cholecystectomy procedures. 
Primary Objective: We aim to assess whether implementation of a multimodal pre-, intra-, and 
postoperative enhanced recovery bundle can result in the decrease of postoperative opioid use in 
patients undergoing elective laparoscopic cholecystectomy.  
Secondary Objective: We will also assess patient satisfaction with the overall quality of pain 
management after the procedure and patient function in the first and second postoperative weeks. 
Patient-reported average pain level in the first 7 postoperative days; patient satisfaction with the 
overall quality of pain management after operation; patient ability to return to daily activities and 
work in the first and second postoperative weeks; phone call to clinic secondary to pain; return to 
the ED secondary to pain, return to the clinic secondary to pain; if prescription is filled, 
morphine equivalents utilized by patients 
Study Design: Prospective, cohort study 
Other Predictors: age, sex, race, Comorbidity/Charlson Comorbidity Index, complications, SSI 
Inclusion Criteria: Elective procedure, urgent/emergent procedure discharged within 24 hours, 
no major cardiac, respiratory, or renal conditions, no advanced liver disease (Child A 
acceptable), opioid naïve, BMI less than 45, previous abdominal surgeries, previous 
cholecystostomy tube, age less than 70 years 
Exclusion Criteria: Open procedure, Child B liver disease or above, opioid tolerant, BMI 
greater than 45, age greater than 70 years 
Methods: 


Patients who undergo elective laparoscopic cholecystectomy or emergent/urgent laparoscopic 
cholecystectomy discharged within 24 hours will be included. We plan to review 25 patients in 
the pre-intervention cohort and 100 patients for the intervention.  
 
The intervention involves the implementation of patient education; healthcare provider education 
(surgeons, anesthetists, residents, nurse practitioners, and nurses); and preoperative, 
intraoperative, and postoperative multimodal analgesia with opioid reduction strategies. Patients 
are to receive verbal and written education on expectations surrounding pain and discomfort after 
the procedure, instructions on optimal use of multimodal analgesic medications, and contact 
information of the provider team if pain is not controlled. Healthcare providers, including 
surgeons, anesthetists, residents, nurse practitioners, and nurses will be educated in large group 
formats (divisional rounds, nursing meetings) and through email. Education will focus on 
understanding the need for opioid reduction, multimodal analgesic strategies, and supporting 
patient/caregiver expectations.  
 
Patients will receive a preoperative multimodal oral pain regimen of ibuprofen 800mg, 
acetaminophen 1000mg, and pregabalin 75 mg in the Short Procedure Unit (SPU) administered 
by nursing.  
 
Intraoperatively, the anesthesiologist will minimize opioid use by utilizing IV lidocaine and IV 
ketamine administration. We will follow along with the agreed upon PONV interventions.  
 
The surgeon will inject local anesthesia into the trocar sites prior to insertion of the trocars. The 
anesthesiologist will administer ketorolac 30 mg IV at the end of the case, once confirmed with 
surgeon that it is appropriate based on difficulty of case.  
 
In the PACU, the patient’s pain will be assessed at one hour and two hours postoperatively by 
the PACU nurse.  
 
Upon discharge, patient will receive detailed instructions on how to utilize ibuprofen and 
acetaminophen postoperatively for 7 days and who to contact if the pain is not well-controlled. A 
prescription for ibuprofen 800 mg tid x 21 pills will be written in addition to acetaminophen  
1,000 mg qid x 28 pills. The patient will receive a phone call at POD 1 and POD 7 from a 
nurse/student and a brief survey will be administered to assess pain, return to daily activity, and 
return to work. The patient will follow-up in the clinic at POD 14. At this time, the patient will 
complete an SF-12 assessment in the clinic waiting room and pain will be assessed by the 
surgeon. A final follow-up call will be made at 30-days postoperatively by nurse/student to 
assess pain, return to daily activity and work. 
 
If patient’s pain is not well-controlled on prescribed regimen, second line treatment can be 
Tramadol 50 mg q6 hours x 8 pills (40 morphine mg equivalents) or oxycodone 5 mg q8 hours x 
6 pills (45 morphine mg equivalents). 
 
A detailed timeline that will be followed for each patient is outlined below: 
 


 
 
 
 
 
 
 
 
 
Baseline Visit – Enrollment and Initiation of ERAS Pathway 
Enrollment 
Measure vitals, height, weight (BMI) 
Demographics 
PMH, PSH, History of opioid use 
Laparoscopic Cholecystectomy (Outpatient Procedure) 
Preoperative Regimen - At Home 
NPO at midnight vs 4-6 hours prior 
Review patient education handout 
Ambulation, breathing exercises 
Laparoscopic Cholecystectomy (Outpatient Procedure) 
Preoperative Regimen – SPU/Holding 
Receive ibuprofen 800 mg x 1 dose, acetaminophen 1,000 mg x 1 
dose, pregabalin 75 mg x 1 dose 
Laparoscopic Cholecystectomy (Outpatient Procedure) 
Intraoperative Regimen 
Anesthesia: dexamethasone 8mg, lidocaine infusion, ketamine 
Trocar site injection with local anesthesia (bupivacaine 0.25-0.5%) 
prior to placement 
Ketorolac (30 mg IV) at end of case 
Laparoscopic Cholecystectomy (Outpatient Procedure) 
Postoperative Regimen 
PACU: 
No fentanyl 
Need to change postop Anesthesia PACU order set 
Pain Assessment at 1 hour, 2 hour by APMS nurse 
Discharge:  
Detailed instructions 


 
 
 
Women/Minorities/Children: All patients who undergo an elective laparoscopic 
cholecystectomy within the eligible time frame are to be included, regardless of age, sex, or 
ethnicity 
 
Human Subjects: Active patient enrollment is needed. There are no risks to the patients 
included in this study. 
 
Data Safety: Data input will be via a dedicated encrypted server. Only key personnel will have 
access to patient identifiers. Local patient identifiers will be stored securely. Data will only be 
shared via encrypted networks. This will facilitate patient data entry at different time points by 
different team members and enable cross checking of data entry by different team members to 
ensure accuracy of data collection. 
 
Statistics Analysis Plan: 
 
Data Collection. Demographic, clinical, and perioperative variables were collected by 
retrospective review of the electronic medical record and included age, sex, race/ethnicity, BMI, 
American Society of Anesthesiologists (ASA) class, smoking status, history of substance abuse, 
procedure, technique (open, laparoscopic, or robotic), whether the minimally invasive inguinal 
repair was trans-abdominal pre-peritoneal (TAPP) or totally extra-peritoneal (TEP), length of 
procedure, estimated blood loss, total intravenous fluid given during the procedure, total local 
anesthetic given during the procedure, total intraoperative morphine milliequivalents 
administered, length of stay after procedure, and patient-reported pain scores at 1 hour after the 
procedure and at discharge. 
Postoperative Follow-up Visits 
Assessment of complications/patient reported outcomes at each 
call/visit 
Nurse/NP/Student (POD 1) 
Phone call, brief survey on pain 
Nurse/NP/Student (POD 7) 
Phone call, brief survey on pain 
Surgeon (2 weeks postop) 
SF12 to be completed in waiting room 
Pain assessment during visit 
Nurse/NP/Student (POD 30) 
Phone call, brief survey on pain 


Outcomes. Outcome variables were obtained by the electronic medical record and/or by 
utilization of a brief telephone survey (intended for internal use only) which was administered by 
members of the study team who contacted the patients 14 days after discharge (Figure S1). 
Outcomes of interest included: total morphine milligram equivalents (MMEs) in the post-
anesthesia care unit (PACU), patient-reported total MMEs after discharge, and patient-reported 
average pain scores and satisfaction scores after discharge. Satisfaction scores were on a scale of 
1 to 10 with 1 being extremely dissatisfied and 10 being extremely satisfied. Additionally, 
number of calls to the surgeon’s office with a complaint of pain and number of pain medication 
refills prescribed were recorded for 30 days following the procedure. For MME calculations, 
patients were asked how many pills of each pain medication they had taken after discharge and 
based on their responses these were converted and recorded by the research team. 
 
Statistical Analysis. Chi-square and analysis of variance (ANOVA) tests were used to compare 
categorical and continuous variables, respectively. For all comparisons two-sided statistical 
significance was set a priori at p<0.05. All statistical analyses were performed using Stata/MP 
17.1 (Statacorp, College Station, TX).