A Pilot Study Investigating the Post-Operative Analgesic Effect of NSS-2 BRIDGE Device in Subjects Undergoing Major Abdominal Oncologic Surgery: A Double-Blind, Randomized, Placebo-Controlled Trial
Phase: NA
Conditions: Acute Pain, Surgery, Abdominal Cancer
Sponsor: Jacques E. Chelly

Shadyside Hospital Foundation Grant Proposal 
 
Jacques E. Chelly, MD, PhD, MBA 
 
 
David Bartlett, MD
 
 
 
1 of 12 
 
Project Title: A Pilot Study Investigating the Post-Operative Analgesic Effect of NSS-2 BRIDGE device in 
Subjects Undergoing Major Abdominal Oncologic Surgery: A Randomized, Double-Blind, Placebo 
Controlled Trial 
NCT03555266 
Date: August 1, 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Shadyside Hospital Foundation Grant Proposal 
 
Jacques E. Chelly, MD, PhD, MBA 
 
 
David Bartlett, MD
 
 
 
2 of 12 
 
The purpose of this proposal is to request funds to support a pilot study investigating the use of 
a Percutaneous Auricular Nerve Field Stimulation device called the NFF-2 BRIDGE, which will be applied 
to sixty patients undergoing abdominal oncologic surgery with surgeon David Bartlett at Shadyside 
Hospital. The data collected from this pilot trial will be used to supplement a future grant application to 
the NIH/NIDA to fund a large-scale randomized, placebo-controlled trial. 
Statement of Problem 
The current opioid epidemic has led to a renewed interest in exploring non-pharmacological 
techniques to treat post-operative pain. An increasing number of patients are suffering from the adverse 
effects of opioid use following surgery, including post-operative nausea and vomiting, respiratory 
depression, immunosuppression, constipation, and most recently, addiction. In the United States, over 
$600 billion is spent every year on opioid addiction, including $79 billion related to opioid addiction 
following surgery. Despite many initiatives to decrease the use of opiates in the preoperative setting, 
opioids continue to be regularly prescribed before, during and after surgery. Although the risk of opioid 
addiction following surgery is recognized, the percentage of patients becoming addicted to opioids 
following surgery is not well understood. To date, there has been virtually no agreement regarding the 
duration and dosage that qualify for opioid dependence following surgery, nor that a clear estimation of 
the factors such as biological, psychosocial and socioeconomic that increase the risk of using opioids for 
extended periods of time after surgery. Therefore, in order to combat this growing health crisis at the 
ground level, it is incumbent upon the medical community to explore alternative methods of pain 
control to treat the surgical population in order to reduce the incidence of post-operative opioid 
addiction.  
Project Aims/Goals 

Shadyside Hospital Foundation Grant Proposal 
 
Jacques E. Chelly, MD, PhD, MBA 
 
 
David Bartlett, MD
 
 
 
3 of 12 
 
Percutaneous Nerve Field Stimulation (PNFS) is one of these recognized methods that ongoing 
research has shown to be effective as a complementary method of pain management.   While PNFS is 
not a novel concept, clinical indications of auricular field stimulation have been limited in the past due 
to requirement of bulky, stationary and non-disposable stimulators and electrodes. These technological 
limitations made it difficult to establish the real clinical potential of auricular stimulation for the 
perioperative management of pain in surgical patients, despite the demonstration that auriculotherapy 
has been shown to relieve pain in the postoperative setting.   
The NSS-2 BRIDGE (Appendix 1) is a battery operated and disposable percutaneous auricular nerve field 
stimulator (Innovative Health Solutions, Versailles, IN, USA), that was recently cleared by the FDA and 
assigned a Class II Risk Designation; a class which includes surgical drapes, pumps and power 
wheelchairs. The indication for the NSS-2 BRIDGE is for the treatment of clinical symptoms related to 
opioid consumption and opioid withdrawal. These symptoms include abdominal pain, anxiety and post-
operative nausea and vomiting; conditions which are also present following major oncologic abdominal 
surgery.  The use of the NSS-2 BRIDGE device has been demonstrated to provide significant analgesia in 
patients with abdominal pain syndrome, and clinical trials are ongoing to assess the benefit of this 
approach for post-operative pain management. As compared to the present use of opioids for 
perioperative pain management, the use of a complementary, non-pharmacologic approach offers the 
advantage of analgesia without the associated side effects. Mechanism of action of the Auricular 
Percutaneous Electrical Nerve Field 
The NSS-2 BRIDGE devise allows for stimulation to branches of Cranial Nerves V, VII, IX and X, 
and the occipital nerves, identified by transillumination. Such a stimulation is transmitted to the central 
nervous and especially the limbic system, which is known to be a key component of the central nervous 
system response to stress, anxiety and the pain pathway. The nucleus involved by the stimulation 

Shadyside Hospital Foundation Grant Proposal 
 
Jacques E. Chelly, MD, PhD, MBA 
 
 
David Bartlett, MD
 
 
 
4 of 12 
 
include the amygdala (structure involved in the response to fear and anxiety), the thalamus (structure 
involved in the management of visceral and somatic pain, addiction), the nucleus of tractus solitarie 
(structure involved in the control blood pressure) etc…. The stimulation of these nucleus produces a 
decrease in the transmission of pain impulses from visceral and/or somatic structures to supraspinal 
areas, a reduction in anxiety and control of blood pressure and associated changes of the sympathetic 
and parasympathetic nervous system. 
The Shadyside Foundation Grant will allow for the purchase of sixty NSS-2 BRIDGE devices (30 
active, 30 placebo), and will support a research coordinator in the execution of a pilot study 
investigating the possible benefit of the device to supplement post-operative pain management. This 
pilot study will assess the possible benefit of using this non-invasive PNFS device as a way to reduce 
opioid consumption in patients undergoing abdominal debulking procedures with surgeon Dr. David 
Bartlett. Preliminary data analysis has demonstrated that in the absence of the NSS-2 BRIDGE device, 
the average opioid consumption following major abdominal surgery using the current ERAS multimodal 
protocol is 100 mg IV morphine equivalent. It is expected that the use of the NSS-2 BRIDGE will be 
associated with a reduction of 50-70% opioid consumption following surgery. The primary endpoint for 
this pilot study will be overall opioid consumption and will constitute the basis of a National Institute of 
Drug Abuse (NIDA) proposal on opioid-free surgery. The expected timeline for this trial will be one year, 
from the start of enrollment to manuscript draft.  
Specific Aims 
1. 
This pilot study will prospectively investigate the efficacy of the NSS-2 BRIDGE device in reducing 
perioperative opioid consumption in opioid-naïve patients undergoing major abdominal surgery using 
the current SHY ERAS anesthesia protocol  

Shadyside Hospital Foundation Grant Proposal 
 
Jacques E. Chelly, MD, PhD, MBA 
 
 
David Bartlett, MD
 
 
 
5 of 12 
 
2. 
To prospectively investigate the incidence of post-operative complications between the 
standard ERAS anesthesia protocol + active NSS-2 BRIDGE vs. ERAS anesthesia protocol + placebo (in-
active) NSS-2 BRIDGE 
3. 
To prospectively investigate role that the NSS-2 BRIDGE device may have in reducing opioid 
consumption after discharge and facilitating functional recovery 
Study Design 
The proposed pilot study will be conducted as a single-center prospective randomized double-blind, 
placebo-controlled trial at the University of Pittsburgh Medical Center (UPMC) Shadyside Hospital. 
Institutional review board approval will be obtained before eligible patients are recruited and 
consented. Trial will be registered at www.clinicaltrial.gov before beginning recruitment.  
Recruitment 
Potential subjects will be recruited in the pre-surgical clinic of Dr. David Bartlett once they are scheduled 
for abdominal debulking surgery. Patients will be asked for their interest in pursuing a research study 
that involves wearing a percutaneous, auricular field stimulator for five days as a supplementary method 
of post-operative pain control. Patients who agree to participate in the trial will sign an IRB approved 
Informed Consent Form. 
Randomization Process 
Participating patients will be randomized by computer generated random numbers to either the control 
or intervention group. 
Inclusion Criteria: 
 
Over 18 years of age 

Shadyside Hospital Foundation Grant Proposal 
 
Jacques E. Chelly, MD, PhD, MBA 
 
 
David Bartlett, MD
 
 
 
6 of 12 
 
Open abdominal debulking procedure as per our institution’s Enhanced Recovery After Surgery 
(ERAS) anesthetic protocol. 
Exclusion Criteria: 
 
History of active depression, anxiety or catastrophizing  
 
Active alcoholism or drug abuse  
 
Severe chronic pain condition that requires daily preoperative opioid dependence 
History of hemophilia 
Patients with cardiac pacemakers  
Patients with psoriasis vulgaris diagnosis 
Treatment Groups 
Control Arm: Control group will receive approved ERAS multimodal anesthesia protocol (Appendix 2) 
plus an inactive placebo NSS-2 BRIDGE device. 
Interventional Arm: Intervention group will receive approved ERAS multimodal anesthesia protocol 
(Appendix 2) plus an active NSS-2 BRIDGE device 
 
Data Collection and Outcome Measures 
Once patient has signed the Informed Consent to participate in this pilot study, demographic 
information and medical history will be collected from each participant on the day of surgery. The NSS-2 
BRIDGE device will be applied to the ear by trained researcher in the immediate post-operative setting 
(PACU), as the research team has completed the necessary training required by the company to apply 
the device. Rescue analgesia will be permitted as per the approved ERAS multi-modal anesthetic 

Shadyside Hospital Foundation Grant Proposal 
 
Jacques E. Chelly, MD, PhD, MBA 
 
 
David Bartlett, MD
 
 
 
7 of 12 
 
protocol (Appendix 2), however, the patient will be made aware at the time of consent and throughout 
the trial that they can drop out of the study at any time if they do not like wearing the NSS- 2 BRIDGE 
device.  
The patient will be assessed 12, 24, 48, 72, 96 and 120 hours post-operatively to collect total opioid 
consumption, incidence of adverse events, and level of comfort while wearing the NSS-2 BRIDGE device. 
When the patient is discharged from the hospital, they will be asked to complete a patient satisfaction 
survey. For patients discharged with the device attached, removal instructions and pre-paid return 
envelope will be given to patient to remove the device at 120 hours and send back to the hospital. The 
patient will be contacted 3 months post-operatively to again assess patient satisfaction with the pain 
management after surgery, and to assess functional recovery.   
 
Pre-and-Post Metric Evaluation 
The use of a non-pharmacological NSS-2 BRIDGE has the possibility of providing analgesia to 
post-surgical patients and reducing the number of opioids required following abdominal surgery. This 
will significantly impact patient outcomes, as patients will experience fewer opioid-related side effects 
(such as respiratory depression, post-operative nausea and vomiting, constipation and delirium). This 
will also impact clinicians caring for post-operative patients, as there is the real potential they will have 
fewer conditions to monitor and treat as the patient recovers from surgery. The projected number of 
patients served by this project will initially be sixty enrolled participants at Shadyside Hospital, however, 
the data collected from this trial will serve countless patients and the community at large as physicians 
strive to move away from opioid use following surgery.  Data collected from this pilot study will support 
a future proposal to the National Institute of Drug Abuse (NIDA) to fund a full-scale, randomized, 
placebo-controlled trial using the NSS-2 BRIDGE device. 

Shadyside Hospital Foundation Grant Proposal 
 
Jacques E. Chelly, MD, PhD, MBA 
 
 
David Bartlett, MD
 
 
 
8 of 12 
 
Perhaps most importantly, the investigative use of the non-invasive NSS-2 BRIDGE device has 
the ability to significantly increase patient satisfaction in individuals who are opioid naïve or adverse to 
taking opioids as a method of pain control. Being able to offer the cancer patients at UPMC Shadyside 
such an alternative represents a great opportunity to increase patient satisfaction, outcomes and 
compliance as many patients increasingly fear the use of opioids. The NSS-2 BRIDGE will remain effective 
on the participant for five days, and will have lasting effects even after discharge from the hospital, 
which is a time when many patients turn to opioids to control pain. The way the efficacy of this device 
will be measured will be by comparing total perioperative opioid consumption between the intervention 
group (Standard of Care ERAS protocol + active NSS-2 BRIDGE) and control group (Standard of Care ERAS 
protocol + inactive NSS 2 BRIDGE), and total opioid consumption after discharge between the two 
groups. Other outcome measures include the incidence of respiratory depression, PONV, constipation 
and length of stay between the intervention and control groups.   
 
 
 
 
Appendix 1: NSS- 2 BRIDGE device 

Shadyside Hospital Foundation Grant Proposal 
 
Jacques E. Chelly, MD, PhD, MBA 
 
 
David Bartlett, MD
 
 
 
9 of 12 
 
 
 
 
 
 
 
Appendix 2:  ERAS ANETHESIA PROTOCOL---SHADYSIDE HOSPITAL 

Shadyside Hospital Foundation Grant Proposal 
 
Jacques E. Chelly, MD, PhD, MBA 
 
 
David Bartlett, MD
 
 
 
10 of 12 
 
 
1. Patients will undergo general anesthesia. 
 
Encourage 1 month or more of abstinence from smoking and alcohol 
and 30 min walking/exercise every day leading up to surgery 
Protein and carbohydrate rich diet for 1 week prior to surgery 
Regular diet until midnight day before surgery, then clear liquids 
encouraged until arrival to hospital. 
OSA screening 
Pre-op multimodal analgesia ordered by surgeon to include oral 
Neurontin, Acetaminophen, and +/-Celebrex depending on case 
PONV risk stratification  
(PONV history, female, non-smoker, opiod/inhalation anesthetic use, 
emetogenic procedure 1 point each) 
• Day of Surgery 
DAS Nursing Staff: Heplock IV (KVO), DVT prophylaxis (SQ heparin), Bair 
Hugger 
Pain Service: Avoid narcotics for block placement 
- Continuous Quadratus Lumborum blocks for post op analgesia .  
Ropivicaine 0.5% 20 ml (single shot bilat) 
- Decadron 4mg  
- Dexmedetomidine (Precedex)  40 mcg  
- 500 cc IV fluid bolus with block 
- PONV prophylaxis, according to risk score (Attending 
Anesthesiologist order) 
- Low: no prophylaxis 
- Medium (1-2 risk factors): Scop patch or Perphenazine or Emend 
- High (>2 risk factors): Emend and Scop patch 
- Anesthesia   
- Warm IV fluids, underbody warming blanket, and Bair Hugger 

Shadyside Hospital Foundation Grant Proposal 
 
Jacques E. Chelly, MD, PhD, MBA 
 
 
David Bartlett, MD
 
 
 
11 of 12 
 
- Antibiotics per protocol according to procedure 
- Induction – (Guidelines only)  Adjust doses as clinically relevant. 
Propofol (2 mg/kg), Ketamine (0.3 mg/kg), Precedex 0.3 mcg/kg,  
muscle relaxant, and NO OPIOIDS. 
- Spinal 
- Maintenance - TIVA to include separate infusions of Propofol, 
Ketamine (0.2 mg/kg/hr), Precedex (0.2-0.8 mcg/kg/hr) titrated to 
effect.  concentration is NOT in the Alaris library – must be 
programmed for 100 mg/100cc** 
- NO OPIOIDS; avoid use of Nitrous Oxide 
- Magnesium 2-4 gm IV 
- Ketorlac 15 mg IV at end of case if approved by surgeon 
- NO IV Acetaminophen (unless not given po pre-op) 
- Ondonsatron 4 mg (save Haldol for rescue in PACU). There is NO 
need to give IV Decadron 
- Tidal Volumes recommended at <6-8 cc/kg; PEEP 6-8, FiO2 <80%, 
recruit lungs 
- Fluid Management via Goal Directed Therapy with SVV (Vigileo) if 
aline in place.  
- Avoid NSS (PLtye preferred or LR if not available).  Avoid replacement 
of fluid deficit.  8-10 cc/kg/hr + replacement of EBL as guideline.  IVF 
not to exceed >2L above expected losses. 
- Emergence - Discontinue Ketamine/Precedex 45-60 min prior to 
emergence, then titrate Propofol to closure and emergence. 
PACU 
- Clear liquid intake to start ASAP in PACU; if aspiration risk, IVF 
maintenance at 75 cc/hr. 
- 
Ketamine 30 mg PO 
 
The postop orders in the surgeon’s care plan include 
   Oral opiates, IV rescue opiates, acetaminophen, toradol, Celebrex, 
  
The AIPPS orders should be only for 

Shadyside Hospital Foundation Grant Proposal 
 
Jacques E. Chelly, MD, PhD, MBA 
 
 
David Bartlett, MD
 
 
 
12 of 12 
 
   Ketamine infusion 
   Neurontin at bedtime 
   PCA if needed (goal is to not use PCA unless necessary such as chronic 
opiate users, big open cases, etc). 
   
QL block 
  
Age <60  Ropi 0.5% 20 mL, dexmedetomidine 30 mcg, dexamethasone 4 
mg  per side 
Age >60 Ropi 0.5 % 20 mL, dexmedetomidine 20 mcg, dexamethasone 4 mg 
per side 
  
Plus several hundred mL fluid bolus 
Plus glycopyrrolate 0.2 mg IV