The USA has recorded unprecedented increases in drug overdose mortality over the past 30 years, especially related to the class of opioids that includes prescription analgesics (e.g., oxycodone), heroin, and fentanyl [1]. According to the Centers for Disease Control and Prevention (CDC), 47,600 people died of an opioid overdose in the USA in 2017 alone, representing over two-thirds of all drug overdose deaths [2].
Rates of fatal overdose due to synthetic opioids have risen 10% between 2017 and 2018 in the USA [2], owing to increased contamination of opioid supplies with fentanyl, a drug that is 30 to 50 times more powerful than heroin [3]. The CDC reports that the number of overdose deaths attributable to fentanyl increased by over 1100% between 2013, when the increase began, and 2016 [4].
The rising rates of overdose have become particularly pronounced over the course of the COVID-19 pandemic, as rates of relapsing opioid use disorder (OUD) soar [5]. Non-fatal overdoses also cause significant physiological complications, including brain hypoxia, and have been correlated with decreased cognitive performance, increased depressive symptoms, and increased suicidal ideation [6].
Those who experience a non-fatal overdose are at greater risk of experiencing a subsequent overdose, both fatal and non-fatal. Harm reduction efforts to mitigate the long-term effects of opioid overdose are essential, with estimates of overdose rates—including both fatal and non-fatal—among people who inject drugs as high as one in five each year [7].
Opioid overdoses cause morbidity and mortality by depressing an individual’s respiratory drive, leading to hypoxemia and eventually death. The current standard of care for severe opioid overdose is administering naloxone, an opioid-receptor antagonist that counteracts opioid-induced respiratory depression [8].
Naloxone is FDA-approved for intranasal, intramuscular, intravenous, and subcutaneous delivery and can reliably reverse opioid overdoses within minutes. In states most affected by the opioid epidemic, initiatives to reduce opioid overdose mortality have focused on promoting judicious opioid prescribing practices and the widespread distribution of lay and first-responder naloxone kits. Prior work suggests programs for community-delivered naloxone are safe public health measures that have the potential to reduce rates of fatal overdoses [9].
However, one major limitation of existing naloxone distribution efforts is that the successful reversal of an opioid overdose currently requires identification and reversal by another person. One study found that 51.8% of fatal overdoses were not witnessed by another individual, while 27.4% of fatal overdoses were witnessed by a bystander who failed to recognize the symptoms of opioid overdose [10].
Even when an overdose is detected, first responders may not arrive until it is too late, especially in rural areas [11]. Surprisingly, there is no current means to address opioid overdoses in cases where people use alone [12, 13]. Previous efforts to target such populations have relied on mobile applications, which, while potentially beneficial, still require bystander intervention and high community trust [14,15,16,17].
Reliable methods of detecting severe opioid overdoses in community settings could address these challenges. In pursuit of advanced medical devices and analytics, the FDA launched a Innovation Challenge in May 2018 to incentivize development of technologies to address the addiction crisis [18].
Alternative device-based strategies to eliminate the need for bystander intervention are being actively studied, including the use of biosensors to detect physiological changes after opioid use [19,20,21,22,23] and autoinjectors to reverse overdose [24], but user acceptability of such solutions remains an open question.
A research team at the University of Washington has developed a wearable device to detect and reverse an opioid overdose.
The results demonstrate the proof-of-concept of a wearable naloxone injector system, according to the paper published Nov. 22 in Scientific Reports.
“The opioid epidemic has become worse during the pandemic and has continued to be a major public health crisis,” said lead author Justin Chan, a UW doctoral student in the Paul G. Allen School of Computer Science & Engineering. “We have created algorithms that run on a wearable injector to detect when the wearer stops breathing and automatically inject naloxone.”
Co-author Jacob Sunshine, an associate professor of anesthesiology and pain medicine at the UW School of Medicine, said one of the unique aspects of opioid overdoses is that naloxone, a benign drug, is highly effective and can save lives if it can be administered in a timely fashion.
The UW team is looking to make these devices widely available, which would first require approval by the U.S. Food and Drug Administration.
In a multiyear collaboration, the UW investigators worked on the prototype with West Pharmaceutical Services of Exton, Penn, which developed a wearable subcutaneous injector that safely administers medications.
The research team combined this injector system with sensors and developed an algorithm to detect the life-threatening pattern of respirations that occur when people experience opioid toxicity.
Co-author Shyam Gollakota, a UW professor in the Allen School, said the device could help people at different stages of opioid-use disorder to avoid accidental death.
The pilot device includes a pair of accelerometers that measure respiration and an onboard processor that detects the halt of motion associated with breathing. The wearable system, which has received regulatory approval in the United States, activates the injector in the presence of prolonged apneic events.
The pilot device also can transmit data about breathing rates and apneic motion to a nearby smartphone via Bluetooth.
To test the device, a clinical study was conducted with volunteers in a supervised injection facility in Vancouver, B.C., and a parallel clinical trial was conducted in a hospital environment among volunteers who manifested signs of apnea by holding their breath.
The team recruited 25 participants at the Vancouver site. The sensors were able to accurately track respiration rates among people with opioid-use disorder. Further, the device was able to detect non-medical, opioid-induced apnea, a breathing pattern that commonly precedes a potentially fatal overdose.
The testing in Vancouver measured breathing patterns only to develop the respiratory algorithm and did not involve injection of naloxone, which was administered only in the second study involving healthy human volunteers who did not take opioids.
In the second study, 20 participants simulated overdose events in a hospital setting by breathing normally, then performing a breath hold for 15 seconds to mimic an apneic event. When the wearable system detected that the subject had not moved for at least 15 seconds, it activated and injected naloxone into the participant.
Following device actuation, blood draws taken from study participants confirmed that the system could deliver the antidote into the circulatory system, showing its potential to reverse opioid overdoses.
“We have enjoyed collaborating with the UW research team at bringing together this expertise in cutting-edge biosensing and wearable drug-delivery technologies,” said Alex Lyness, senior manager of research and technology at West Pharmaceuticals. “We are pleased to have been able to contribute to this project and prototype system that is intent on solving such a significant unmet need.”
Researchers said further studies are needed to assess the comfort and discreteness of the device over longer time periods, particularly in unsupervised settings. And, they said, additional study of the device is needed to evaluate naloxone injection in people who use opioids for nonmedical purposes.
More information: Closed-loop wearable naloxone injector system, Scientific Reports (2021). DOI: 10.1038/s41598-021-01990-0
