Closed-loop wearable naloxone injector system

Abstract

Overdoses from non-medical use of opioids can lead to hypoxemic/hypercarbic respiratory failure, cardiac arrest, and death when left untreated. Opioid toxicity is readily reversed with naloxone, a competitive antagonist that can restore respiration. However, there remains a critical need for technologies to administer naloxone in the event of unwitnessed overdose events. We report a closed-loop wearable injector system that measures respiration and apneic motion associated with an opioid overdose event using a pair of on-body accelerometers, and administers naloxone subcutaneously upon detection of an apnea. Our proof-of-concept system has been evaluated in two environments: (i) an approved supervised injection facility (SIF) where people self-inject opioids under medical supervision and (ii) a hospital environment where we simulate opioid-induced apneas in healthy participants. In the SIF (n = 25), our system identified breathing rate and post-injection respiratory depression accurately when compared to a respiratory belt. In the hospital, our algorithm identified simulated apneic events and successfully injected participants with 1.2 mg of naloxone. Naloxone delivery was verified by intravenous blood draw post-injection for all participants. A closed-loop naloxone injector system has the potential to complement existing evidence-based harm reduction strategies and, in the absence of bystanders, help make opioid toxicity events functionally witnessed and in turn more likely to be successfully resuscitated.

Overdose Alert and Response Technologies: State-of-the-art Review

“…We classified technologies into 3 main groups according to their main function, namely, “OD alert,” “OD response,” and “combined OD alert and response.” These are shown in Tables 1 - 3 . Multimedia Appendix 2 [ 24 - 38 , 40 - 47 ] displays more detailed information about each study (ie, intervention, function, focus, device, theme, and study design). Although there is frequently a degree of overlap between the first 2 groups, as all devices ultimately need to combine OD alert and response, this classification is based on the main focus of the study.…”

“…There are some devices being developed that attempt to cover both functions by acting as a closed-loop system. In this case, the device uses a sensor that, if detecting an OD, sends a signal to an automatic antidote dispenser attached to the body in the form of either an injection [ 24 , 39 , 45 , 48 , 49 ] or an implant [ 25 ]. At present, the studies we identified are in the prototype phase and are more focused on the antidote dispenser than on the sensor.…”

“…Other countries might also be concerned by other substances causing or contributing to OD, such as benzodiazepines, GABAergic substances, or stimulants such as methamphetamine, or DRDs caused by cocaine-induced cardiac effects [ 4 ]. Moreover, some studies presented (9/23, 39%) were conducted by just a few groups, with 6 of them headed by a group led by researchers largely based in Philadelphia, Pennsylvania, United States, and Drexel University accounting for 26% (6/23) of the papers [ 27 , 29 , 32 , 34 , 38 , 40 ] and a group led by researchers at the University of Washington accounting for 13% (3/23) of the papers [ 24 , 33 , 35 ]. More research on user needs and preferences from other countries and on other substances is encouraged, and new literature reviews should be conducted in a few years to update the state of the art.…”

“…Of the 23 selected papers, 17 (74%) studies conducted primary research [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] using mixed methods [26,29,38], qualitative [27,28,41], and quantitative research [24,25,[30][31][32][33][34][35][36][37]40]; 1 (4%) was a protocol for a clinical trial study [42]; 2 (9%) described proof-of-concept devices [41,43]; and 4 (17%) were literature reviews [44][45][46][47]. All studies were conducted in North America (United States and Canada) except for one that was based in Israel but used data from the United States [37].…”

Perceptions on wearable sensor-based interventions for monitoring of opioid therapy: A qualitative study

“…Other approaches have described the use of digital health tools to facilitate harm reduction, including opioid overdose detection and automatic delivery of the antidote naloxone (13,14). For example, Chan et al evaluated the computational and mechanical functionality of a novel closed-loop, on-body sensor designed to automatically inject naloxone after detecting an opioid overdose (15).…”