Oxycodone Ingestion Patterns in Acute Fracture Pain With Digital Pills

Chai, Peter R. MD, MMS; Carreiro, Stephanie MD; Innes, Brendan J. BS; Chapman, Brittany BS; Schreiber, Kristin L. MD, PhD; Edwards, Robert R. PhD; Carrico, Adam W. PhD; Boyer, Edward W. MD, PhD


Anesth Analg. 2017;125(6):2105-2112. 

In This Article

Abstract and Introduction


Background Opioid analgesics are commonly prescribed on an as-needed (PRN) basis for acute painful conditions. Uncertainty of how patients actually take PRN opioids, coupled with a desire to completely cover pain, leads to variable and overly generous opioid prescribing practices, resulting in a surplus of opioids. This opioid surplus becomes a source for diversion and nonmedical opioid use. Understanding patterns of actual opioid ingestion after acute painful conditions can help clinicians counsel patients on safe opioid use, and allow timely recognition and intervention when escalating opioid self-dosing occurs, to prevent tolerance and addiction.

Methods We used a novel oxycodone digital pill system (ingestible biosensor within a standard gelatin capsule combined with 5-mg oxycodone) that when ingested, is activated by the chloride ion gradient in the stomach thereby emitting a radiofrequency signal captured by a wearable reader. The reader relays ingestion data to a cloud-based server that displays ingestion events to the study team. We deployed the oxycodone digital pill among opioid-naive individuals discharged from the emergency department with acute fracture pain. Participants were trained on digital pill operation and discharged with twenty-one 5-mg oxycodone digital pills. They were instructed to take digital pills PRN for pain on discharge. We conducted a brief interview 7 days after study enrollment, at which point participants returned the digital pill system. We identified oxycodone ingestion events in real time by data from the digital pill system and performed pill counts at the return visit to validate digital pill reporting of medication ingestion.

Results In this study, 26 individuals were approached; 16 enrolled with 15 completing the study. Participants ingested a median of 6 (3–9.5) oxycodone digital pills over the course of 7 days, with 82% of the oxycodone dose ingested in the first 3 days. In individuals who required operative repair, 86% (N = 6) continued to ingest opioids at 1 week. There was substantial variability in ingestion patterns between individuals.

Conclusions The utilization patterns of individuals with acute fracture pain could be captured using a digital pill system and revealed a median opioid ingestion of 45-mg morphine equivalents for acute pain over 7 days. Seven participants ceased using opioids within 4 days after discharge from the emergency department, although operative repair was associated with longer use. This digital pill system was able to measure changes in and patterns of opioid self-dosing, which varied between patients.


Opioids are commonly prescribed on an as-needed (PRN) basis, meaning that in the outpatient setting, patients make all decisions regarding opioid dose and frequency relatively independently, and not according to any predefined schedule. Data on how patients actually take PRN opioids (eg, the timing, number, and frequency of dosage units ingested) are unknown. Wide variation exists in how clinicians prescribe opioids in response to acute pain, and providers often err on the side of too many to avoid the inconvenience of refilling prescriptions, a practice that contributes to excess opioid dosage units in the community.[1] Prior investigations suggest that 42%–72% of prescription opioids are left unused after outpatient surgical procedures.[1–6] Although several investigations have demonstrated a large portion of prescribed opioids are unused, previously used methods consist of pill counts (often at a single timepoint), prohibiting any description of the patterns by which individuals ingest PRN opioids.

Current methods to measure medication ingestion are indirect; they rely on pill counts, pharmacy refills, Micro-Electro-Mechanical Systems caps that detect opening of pill bottles, patient diaries, and urine drug screens.[7–9] Long-term opioid adherence monitoring uses urine or hair drug screening, methods that suffer from difficulty in interpretation, varying analytic techniques, and inaccurate results depending on the relationship between opioid ingestion and sample acquisition.[10,11] These monitoring methods describe opioid use in aggregate, are easily manipulated, and fraught with user bias. Aggregate measures of opioid ingestion miss important dynamic information such as the dose per ingestion as well as changes in dosing interval. Real-time changes in dosing interval, or increased dose per ingestion, may indicate problems with pain control or important changes in the nature of opioid use, and thus represent an opportunity for assessment and early intervention—a phenomenon that is difficult to detect through current measures.

Digital pills—where a medication is incorporated into a gelatin capsule containing a biosensor that activates in the stomach—can provide direct and definitive evidence of medication ingestion.[12–17] Iterative improvements in data transmission and signal strength have made digital pills feasible and acceptable to patients.[13] Formative data on the use of digital pills have demonstrated the ability to detect ingestion of antidiabetic agents, antipsychotics, and antituberculosis medications.[14,18,19] Although used to measure medication adherence, direct ingestion monitoring through digital pills creates a new opportunity to measure more than just adherence. In the setting of opioid use, knowledge of real-time ingestion can produce relevant information regarding the opioid dose (number of pills ingested) as well as the timing interval between opioid ingestions. Patterns of escalating dosage or increased interval dosing or conversely, patterns of decreased dosing and tapering can help clinicians manage acute exacerbations of pain. In the present study, we report data on opioid ingestion patterns detected by a digital pill in emergency department (ED) patients discharged after treatment for acute fractures. We additionally report qualitative user acceptance of digital pills to monitor opioid ingestion patterns after acute fracture pain.