Auricular field nerve stimulation using the NSS-2 BRIDGE? device as an alternative to opioids following kidney donor surgery
Received Date: Jan 04, 2021 / Accepted Date: Jan 20, 2021 / Published Date: Jan 28, 2021
Introduction: The purpose of this study was to investigate what the role that the NSS-2 BRIDGE® device, an auricular field nerve stimulator, may play in reducing opioid requirement and pain in kidney donor surgery. Electrophysiologic studies have demonstrated that the stimulation of the cranial nerves produced by the NSS-2 BRIDGE® device modulates the ascending/descending spinal pain pathways, especially at the level of the limbic system.
Materials and methods: The design compared the effects of the NSS-2 BRIDGE® device (NSS 2-BRIDGE® device group; n=10) to a control group (n=10). In both groups, the surgery was performed using the same standard Enhanced Recovery after Surgery (ERAS) protocol based on the use of a multimodal analgesic approach. For the active treatment group, the NSS-2 BRIDGE® device was placed in the post anesthesia care unit. The primary endpoint was opioid requirement (oral morphine equivalent; OME) at 24 hrs. Post-surgery. Secondary end-points included pain (0 to 10), at 24hrs and 48hrs., time to discharge from the recovery room, incidence of post-operative nausea and vomiting at 24 hrs., time to oral intake, time to ambulation, and time to discharge from the hospital. Data was analyzed using unpaired t-test and presented as mean ± Standard Deviation (SD).
Results: Compared to control, the use of the NSS-2 BRIDGE® was associated with a 75.4% reduction in OME (33.6 vs 8.3 mg; p=0.03) and 57% reduction in pain (5.8 vs 2.5; p<0.05) at 24 hrs and a 73.3% difference in pain at 48 hrs. (1.6 ± 1.6, vs 6.0 ± 2.8; p=0.0004). There was no difference in non-opioid analgesics administration between groups.
Conclusion: The tolerability of NSS-2 BRIDGE® device was reported by most to be excellent. This study suggests that the NSS-2 BRIDGE® device may represent a complementary approach to minimize the postoperative requirement for opioid.
Keywords: Opioids, Auricular neurostimulation, Auriculotherapy, Nephrectomy donor, Pain management, Kidney transplant, Anesthesiology
Kidneys obtained from a live donor are frequently used for kidney transplantation . Despite the introduction of Enhanced Recovery after Surgery (ERAS) protocols which are based on a multimodal approach to perioperative pain management, the use of opioids are still required following kidney donor surgery. (RM Planinsic, personal communication) Opioids have established serious side effects including respiratory depression, postoperative nausea and vomiting and expose the donors to an unnecessary risk of Opioid Use Disorder (OUD), considering that these patients undergo surgery for organ donation .
Percutaneous Nerve Field Stimulation is a technique that has been shown to be of interest for the management of various pain conditions . However, its clinical applications have been limited by the requirement of bulky non-disposable stimulators or the need for surgical implantation, as in the case for treatment of epilepsy . In the past few years, the NSS-2 BRIDGE® device was developed . It is a small, battery operated and disposable percutaneous nerve stimulator that stimulates the various nerves present in the ear, including branches of the vagal, the trigeminal, facial and glossopharyngeal nerves (Figure 1). The stimulation is transmitted to the corresponding nucleus of these cranial nerves located in the brain stem. These structures are involved in the modulation the pain pathway via the limbic system . Recently, the FDA approved the use of the NSS-2 BRIDGE® device for the treatment of clinical symptoms associated with opioid withdrawal . Since pain, nausea and vomiting are symptoms associated with opioid withdrawal, it is possible that the NSS-2 BRIDGE® device may also be of benefits during the perioperative period.
A preliminary report published by Lim et al. suggests that the NSS-2 BRIDGE® device was associated in significant reduction of opioid consumption and pain following a cesarean section . We hypothesized that the NSS-2 BRIDGE® device may play a role in minimizing perioperative pain and the requirement for opioids in patients undergoing kidney donation surgery.
Materials and Methods
This study received Institutional Review Board approval from the University of Pittsburgh Human Research Protection Office and was registered to ClinicalTrials.gov prior to beginning enrollment (Clinicaltrials.gov NCT03834142, date of registration: February 06, 2019). Written informed consent was obtained from prior to surgery to use the NSS-2 BRIDGE® device postoperatively for the potential purpose of managing postoperative pain in prospective kidney donor subjects. Inclusion criteria were ≥ 18 yrs. old, scheduled to undergo donor kidney surgery. Exclusion criteria included history of active depression, anxiety, active alcoholism or drug abuse, chronic pain condition requiring daily opioid. Exclusion for the use of the NSS-2 BRIDGE® device included, history of hemophilia, subjects with cardiac pacemakers or other implanted devices (e.g. vagal nerve simulators), patients with psoriasis vulgaris diagnosis and women who are pregnant or breastfeeding.
The NSS-2 BRIDGE® device, which includes 3 active electrodes and one ground, was placed on the ear of the subject’s preference in the post-anesthesia care unit. The three active electrodes of the NSS- 2 BRIDGE® device were fixed at the level of the tragus, the anterior scaphoid fossa, and the posterior aspect of the helix. The fourth electrode, functioning as the ground, was placed on the lobule. Each electrode was covered after placement (Figure 2). The electronic and battery component of the device was fixed with adhesive behind the ear (Figure 2). Each research coordinator involved in the placement of the device was qualified by the trainer instructor of Innovative Health Solutions. Each of them received an in-person demonstration and viewed the training module provided by Innovative Health Solutions. Once the NSS-2 BRIDGE® device was placed, it remained active for 120 hrs. (five days). Each subject was instructed on how to remove and dispose of the device at home. Controls were obtained concurrently during the same period and extended from September 2019 to January 2020. At the time of discharge from the surgery, each subject in the active group was instructed to report pain, opioid use, tolerability of the NSS-2 BRIDGE® device and any side effects during a daily telephone call.
Each control was identified based on the inclusion and exclusion for the use of NSS-2 BRIDGE® device.
Both active treatment subjects and controls were managed according to the established ERAS protocol which includes general anesthesia induction with propofol (1-2mg/kg), muscle relaxant, and maintenance with sevoflurane or propofol. The protocol also included the use of ketamine (0.4 mg/kg/hr. IV) and lidocaine (1.8 mg/kg/hr. IV). Lidocaine infusion was decreased to 1 mg/kg/hr. at the end of surgery and emergence from anesthesia. It was continued into the post-operative period for 2 days or until discharge from the hospital. Ketorolac 15mg IV was administered at the end of the case. Once the subject reached the recovery room, the post-operative pain management was based on the use of both non-opioids and opioids. Non-opioid analgesics consisted of lidocaine infusion at 1 mg/kg/hr. x 48hrs. Or less if the subject was discharged earlier, acetaminophen 1 g IV q 6hrs. For 24hrs. Then PO and ketorolac 15 mg IV q6hrs for 24 hrs. Opioid administration was titrated to the level of pain (using a verbal analog scale; VAS) mild pain (1-3 VASA): tramadol 100 mg po q6hrs. prn; moderate pain (4-6): oxycodone 5 mg po q4hrs. prn; severe pain (7-10): oxycodone 10 mg po q4hrs. prn; hydromorphone 0.5 mg IV q2hrs. prn was allowed for breakthrough pain.
Primary and secondary end points
The primary endpoint was opioid consumption at 24 hrs following surgery. Secondary end points included pain at 24 hrs. and 48 hrs., using a verbal scale ( 0 = no pain to 10 = worst possible pain), incidence of post-operative nausea and vomiting at 24 hrs. and 48hrs., time to oral intake, time to ambulation, time to discharge from the recovery room, time to discharge from the hospital and the tolerability of the device using a 10 scale measurement ( 10-8 excellent; 7-5 good, 4-2 fair and 2-0 poor) and obtained on a follow up phone call 7 days after the surgery.
Descriptive statistics are present as mean ± SD. Using SPSS, a one tailed unpaired t-test was performed to assess the significance of the difference in opioid consumption at 24hrs. as well as all secondarily end points. Alpha was set up at 0.05.
(Table 1) presents the patients demographics. There was not significance difference between the groups with respect to race, gender, age, and BMI.
|Group Active (N=10)||Group Control (N=10)|
|Age (years)||43.5 ± 12.7SD||42 ± 11.7SD|
|Body mass index||28.0 ± 4.4SD||27.3 ± 3.0SD|
Table 1: Age and BMI are median values. Percentages represent the percent of patients to which the variable pertains.
Following surgery, the time spent in the recovery room by the subjects of both groups was similar (NSS 2-BRIDGE® group (197 min ± 152min vs 133 min ± 364min vs; p=0.11).
A significant 75.4% reduction in opioid consumption (mg of morphine PO equivalent; (OME; mg) was recorded at 24 hrs. Postoperatively in the NSS 2-BRIDGE® group vs the control group (8.3 ± 9.6 vs 33.5 ± 37.3, respectively; p=0.03 ;). (Figure 3) represents the mean opioid consumption at 24 hrs in the NSS-2 BRIDGE® device group versus the control. This reduction in opioids requirement occurred in the context of a significant 58.3% reduction in pain scores at 24 hrs. Postoperatively was recorded in the NSS 2-BRIDGE® group vs the control group, which (2.5 ± 2.0 vs 6 ± 1.4 respectively; p<0.001).
Although at 48 hrs. Opioid consumption was similar in the active treatment group and the control groups at 48 hrs. post-operatively (22.4mg OME ± 19.5mg vs 26.7mg OME ± 21.9mg, respectively p=0.33), pain was 73.3% lower in the NSS 2-BRIDGE® group compared to the control group 1.6 ± 1.6, vs 6.0 ± 2.8; p=0.0004 (Figure 4).
The use of the NSS 2-BRIDGE® device was also associated with a downward trend in post-operative nausea and vomiting (PONV) with a reduction of the required milligram of ondansetron for treatment of PONV the NSS-2 BRIDGE® device group vs the controls (0.4mg ± 1.26mg vs 3.2mg ± 3.9mg; p=0.06).
Although the time to oral intake was similar in both groups (5.3hrs ± 2.6hrs vs 4.2 hrs. ± 2.7hrs.w; p=0.19), the subjects in the NSS-2 BRIDGE® device group ambulated 50% earlier than those in the control, which was found to be significant (11.6 hrs. ± 7.4hrs vs 18.9 hrs. ± 6.9hrs, respectively; p=0.02).
The time to hospital discharge was similar in both groups (2.1 days± 2.9 SD vs 0.53 days vs 2.2 ± 0.33 days, respectively: p=0.32).
Finally, the tolerability of the device was reported to be excellent in 7/9 (78%) of participants, 1/9 (11%) and 1/9 fair (11%). We were not able to reach 1 patient for the 7 day follow up.
Limitations include the following: 1. although all subjects underwent the same surgery using the same approach, the subjects were not randomized, and a placebo device was not applied to the subjects.
The proposed mechanism of action of the NSS-2 BRIDGE® device is that the auricular percutaneous electrical nerve field stimulation directly stimulates the cranial and spinal nerve branches, innervating the four regions of the external ear. The stimulation is transmitted to the corresponding nucleus structure of these cranial nerves, which allows modulation of the pain pathways . This concept is supported by animal model studies which investigated the role of the NSS-2 BRIDGE® device in reducing post-inflammatory hyper analgesia in rats. This hyper analgesic condition was introduced by way of trinitrobenzene sulfonic acid-induced colitis, and also following inflammation in a compressed paw model. In these animal models, it was demonstrated that the auricular percutaneous electrical nerve field stimulation induced by the NSS-2 BRIDGE® device led to specific electro firing in the central nucleus of the amygdala, and also in the lumbar spinal cord and associated therapeutic properties . In this regard, it is important to understand that the ear is uniquely innervated due to its embryological origin. In the sixth week of gestation, development of the external ear is initiated by the rise of two pharyngeal arches that contain six aural hillocks or hillocks . Following rotations and migration, the first three hillocks from the first pharyngeal arch form the tragus, the helix, and the cymba concha, while the remaining 3 hillocks the second pharyngeal arch migrate to complete the concha and generate the antihelix and the antitragus. Each hillock includes tissues of mesodermic or endodermic origin as well as tissue of ectodermic origin . This explains the unique ear innervation of the external ear, which include branches of the trigeminal, facial, glossopharyngeal and vagus cranial nerves and the lesser occipital and greater auricular regions, superficial cervical plexus, and originating from spinal nerves at the level of C2 and C3 . The nucleus of these cranial nerves are located in the brainstem and closely connected to a number of structures including the tractus solitarious and the structure involved in the limbic system such as the thalamus and hypothalamus, amygdala, rostral ventral medulla . This part of the brain stem is established to modulate the autonomic nervous system and the pain pathway.
The study suggests that the postoperative placement of the NSS- 2 BRIDGE® device significantly reduces opioid requirement at 24 hrs. Post-surgery and reduces pain scores for 48 hrs. Post-operatively. Furthermore, this study also confirms that the NSS-2 BRIDGE® device tolerability is excellent in most subjects. In this study, the NSS-2 BRIDGE® device was placed in the recovery room following surgery to focus on the postoperative use of opioids and to avoid having to account for arbitrary use of opioids during surgery. Furthermore, it should be recognized that in non-anesthetized subjects the placement of the NSS-2 BRIDGE® device may be associated with some impression of “tickling” during the first 30-45 min following the placement of electrodes and activation of the NSS-2 BRIDGE® device. Although most patients do not report this as a problem, there are some patients who report this as uncomfortable (Chelly, personal communication).
Subjects who received the NSS-2 BRIDGE® device were asked to wear it for five days (120 hours) and received daily follow-up telephone calls every day after discharge from the hospital to record their daily pain scores and opioid use. Since the majority of subjects were discharge from the hospital following two days of hospitalization and that only subjects implanted with the NSS-2 BRIDGE® device were followed after discharged, we chose to focus on data obtained at 24 hrs. and 48 hrs. However, the review of the follow-up data indicated that pain and postoperative use of opioids following discharge were like the ones reported during hospitalization, suggesting that there are long- lasting benefits of the NSS-2 BRIDGE® device.
This study suggests that the NSS-2 BRIDGE® device may be of significant value in controlling postoperative opioid consumption and pain. This is especially interesting in the context of the current opioid epidemic and associated risk of opioid use disorder (OUD) in surgical patients. However, a prospective randomized placebo control design is required to confirm our findings.
Funding: Department of Anesthesiology and Perioperative Medicine, 3550 Terrace Street, A-1305 Scaife Hall, Pittsburgh, Pennsylvania, 15213
Author confirmation statement: All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.
Authorship: Amy Monroe, MPH, MBA: Development of the protocol, IRB submission, conduct of the study, data analysis, statistical analysis and development the manuscript.
Raymond M. Planinsic, MD, FASA: Development of the protocol, conduct of the study, and review of the manuscript
Amit Tevar, MD: Conduct of the study, review of the manuscript
Jacques Chelly, M.D. PhD, MBA: Development of the protocol, IRB submission, conduct of the study, data analysis, statistical analysis and development the manuscript
Amy Monroe, Jacques Chelly, Raymond Planinsic and Amit Tevar declare that they have no conflict of interest.
Compliance with ethics guidelines:
This study was approved by the University of Pittsburgh’s Human Research Protection Office’s Institutional Review Board
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
The abstract portion of this manuscript was shared as a poster at the American Society of Anesthesiologists Annual Meeting on October 2-5, 2020.
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Citation: Monroe AL, Planinsic RM, Tevar A, Chelly JE (2021) Auricular field nerve stimulation using the NSS-2 BRIDGE® device as an alternative to opioids following kidney donor surgery. J Pain Relief 10: 365. DOI: 10.4172/2167-0846.1000365
Copyright: © 2021 Monroe AL, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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