Since 1999, the opioid epidemic has killed around 645,000 people in America—a number that would no doubt be even higher were it not for naloxone, an opioid antagonist that can effectively reverse the effects of an overdose. However, time is critical: if naloxone is not administered promptly, the victim’s chances of survival diminish rapidly. In a paper published August 14 in Device, a team of researchers describe a device designed to detect the signs of an overdose and automatically deliver a dose of naloxone in as little as 10 seconds.
The device–which researchers describe as a “robotic first responder”–is named the “implantable system for opioid safety” (iSOS). It’s implanted under the user’s skin, in the same way as a heart loop recorder. This allows for more accurate monitoring of vital signs than existing wearable devices.
One challenge for any sort of automated device is the question of opiate tolerance: while sampling the level of opiates in a user’s blood might seem to be a simple way to detect the risk of an overdose, a level that would kill an opiate naïve person might barely register with a long-term addict. As such, most overdose detection devices rely on monitoring a user’s heart rate, respiratory rate, or blood oxygen level. Unfortunately, these are all vital signs that are affected by all manner of factors, making these devices vulnerable to detecting false positives.
Giovanni Traverso, one of the co-authors of the paper from Brigham and Women’s Hospital, explains to Popular Science that instead of monitoring a single vital sign, the iSOS uses multiple sensors, including an electrocardiograph, a sensor that monitors blood oxygen level (SpO2), a heart rate monitor, body temperature thermometer, and various other features. These are all coordinated by a 64 MHz ARM CPU, which aggregates and processes all this data. “Fusing multiple sensors together to develop a physiologic biomarker of early opioid poisoning and overdose allows us to accurately detect opioid overdose … and correctly administer naloxone.”
In initial tests carried out on pigs, the iSOS was able to reverse overdoses in 96% of cases. The device can distinguish between “rapid” and “slow-onset” overdoses, which have different symptom profiles. Despite the sophistication of the unit’s design, it’s possible to conceive of situations that might generate false positives. A sleep apnea event, for instance, results in falling blood oxygen levels, reduced heart rate, and other symptoms that resemble the onset of an opioid overdose. Can the device distinguish between someone’s SpO2 falling because their CPAP is about to activate, and it falling because they’re overdosing on fentanyl?
Traverso agrees that false positives could still arise: “Yes, sleep apnea … can produce physiological signals similar to those of an opioid overdose. Other conditions that are relevant include benzodiazepine intoxication, especially since individuals with opioid use disorder may also have other substance use disorders.” He says that the device’s algorithms were designed with such situations in mind: “The algorithms distinguish between these scenarios by analyzing the dynamic response of heart rate and respiratory signals.”
Users do have a short time—between 10 and 30 seconds, depending on whether the device detects a slow or rapid overdose—to cancel the iSOS’s operation if the situation is a false positive. They can do so via the associated smartphone app, and Traverso says, “the device also has a built-in alert system with auditory and tactile signals to wake the user, providing an alternative for those without smartphones or with uncharged devices.”
Otherwise, the iSOS delivers its payload of naloxone: 10mg, administered subcutaneously in as little as 10 seconds. As Traverso explains, this is “significantly higher than typical intranasal doses, such as those in commercial naloxone nasal sprays, which are commonly 4 mg.” He says that the higher dose was chosen to address the growing problem of fentanyl overdoses, which often require more than one administration of nasal spray to reverse. While the iSOS currently carries one such dose, Traverso says that it could potentially carry multiple doses of a more concentrated naloxone solution, allowing it to administer repeated doses if the first fails to revive the user.
Unfortunately, in some cases, even a single 10mg dose can have adverse effects on users: as the dose of naloxone increases, so does the risk of putting the user into precipitated withdrawal. Traverso agrees that this is a risk, but says, “We agree that precipitated withdrawal is unpleasant, but [it] is preferable to the overdose state, which would result in death. The focus of the device is on preventing death from overdose, rather than on modulating withdrawal symptoms.” He also notes, “Even most intranasal rescue naloxone doses may precipitate some opioid withdrawal.”
Whether or not naloxone administration results in precipitated withdrawal, opiate users who are revived by the drug often require medical care in the aftermath of an overdose. Traverso says that while neither the device nor the associated smartphone app currently allows for automated calling of first responders, including such a feature is certainly possible: “While the device itself focuses on overdose detection and naloxone administration, it is implied that integration with a smartphone app could potentially include features like calling first responders… We also envision the device would log overdose detection, which would allow for more personalized behavioral counseling for individuals being treated for opioid use disorder focusing on awareness of overdose events.”
Of course, the elephant in the room discussing a device like this—especially in the context of America’s idiosyncratic health system—is cost. Traverso says that at present, he has no real notion of how much the device might cost: “The exact cost of the device is not yet determined, as future work will focus on refining the manufacturing process and scaling production, which will help to inform the final cost.”
“However,” he adds, “we anticipate that the use of this device will be cost-favorable, especially considering its capacity to save lives and mitigate the morbidity associated with opioid overdoses. The long-term benefits of preventing fatal overdoses and reducing healthcare costs related to overdose treatment are significant factors that support the value of this technology.”