Participants who required operative repair (N = 7) ingested a median of 8 (range: 6–11) oxycodone digital pills (60-mg morphine equivalents); 84% of the cumulative dose was ingested in the first 72 hours. Six of the 7 participants (86%) with operative fractures remained on oxycodone at 1 week, while 1 participant did not ingest opioids during the study period. Most participants with operative fractures ingested oxycodone digital pills every 8 hours for the first 24 hours before tapering down to every 24 hours at 48 hours after discharge.
Participants with nonoperative fractures (N = 8) ingested a median of 5 (range: 1.5–7) oxycodone digital pills (37.5-mg morphine equivalents); 80% of the cumulative dose was ingested in the first 72 hours. On average, participants ingested oxycodone digital pills once daily for the first 24 hours and had stopped taking oxycodone digital pills 96 hours after their injury. No participants who were managed nonoperatively continued to ingest opioids at the end of the study period.
Most participants (N = 12) self-reported that their pain was well controlled during the study. Ten participants (66%) reported pain that was severe (eg, in the range of 7–10/10), prompting them to use the oxycodone digital pill for the first 72 hours. Although most participants reported they continued to feel pain after 3 days, 10 reported that the intensity of pain had decreased until it was adequately managed with nonsteroidal antiinflammatory drugs and acetaminophen. Of note, 6 participants reported even after their pain had subsided, they continued to ingest oxycodone digital pills in the evening before bedtime as “prophylaxis” against potential episodes of pain in the morning.
The findings of this pilot study indicate that most opioid-naive patients self-administer opioids to manage the pain from acute fracture for only a brief period, even among patients with fractures requiring surgical management. Furthermore, most patients stopped self-administering opioids in advance of exhausting their opioid supply. The point at which most of our patients completely stopped taking opioid analgesics after fracture, 96 hours, is far shorter than the week-long duration of opioid analgesia for the management of acute pain often prescribed by physicians.5 , 6 In addition, we observed that the majority of participants, whether they had operative and nonoperative fractures, tapered (increasing the length of intervals in their dosing schedule) the dose of opioid analgesic. These findings therefore may be used to improve the precision with which physicians prescribe opioids. Rather than prescribing medications on a PRN basis, we propose that clinicians consider instructing patients to begin tapering the dose of opioid analgesics beginning at 24 hours after injury, which would also reduce the number of pills dispensed, and ultimately wasted or made available for diversion.
Interestingly, patients only ingested a median of 6 pills, despite being given 21 pills to each participant, suggesting that even a week-long duration of therapy after fracture may represent overprescribing opioids. Overprescribing may lead to several important problems. First, it may encourage increased opioid use by that patient. A recent study of postoperative patients showed an association between a larger number of tablets dispensed and the number consumed, independent of patient characteristics or pain, suggesting that patients may take more pills just because they are given more, and that this does not lead to improved pain control or satisfaction.21 , 22 Our results showing that most patients stopped use within 3 days are especially significant in light of data from the Centers for Disease Control and Prevention that correlate opioid therapy of >3 days duration with long-term nonmedical opioid use.23 , 24 Limiting the availability of unused opioids through evidence-based prescribing is an effective strategy in preventing downstream opioid abuse.25
Investigators have proposed limiting the number of opioid dosage units to the amount truly needed for a specific clinical indication.26 , 27 Unfortunately, previous methods of assessing medication-taking behavior (which only infer but do not measure ingestion) are easily manipulated, suffer from user bias, provide aggregated information regarding opioid ingestion, and thus cannot provide information on patterns of opioid ingestion. Consequently, the precise number of dosage units and duration of therapy have remained undefined. Our data suggest that approximately six 5-mg oxycodone tablets, when properly tapered, may be sufficient to control pain from acute fractures in the majority of patients, and may serve to support governmental policies directed toward limiting the number of prescribed dosage units of opioid analgesics. Additionally, the mismatch between what was prescribed and what was self-administered underscores the importance of directed teaching to promote nonopioid analgesia (nonsteroidal antiinflammatory drugs and acetaminophen) among providers, despite it being potentially time consuming in a busy ED setting. Physicians should consider providing patients with anticipatory guidance regarding the expected duration of opioid use and the amount of opioids required. Understanding that patients likely need considerably fewer opioid dosage units that are commonly dispensed is important in preventing both downstream long-term opioid use and opioid diversion.23 Our data regarding actual opioid utilization are consistent with other studies demonstrating that physicians significantly overprescribe opioids in response to acute pain.1 , 5 , 28
Participants’ practice of ingesting opioid analgesics before sleep is concerning. Patients reported the concern of waking up at night with pain as the rationale for ingesting opioids before sleep, and indeed, this is a common informal instruction that patients receive from providers in recovery. This approach carries considerable risk, however, because of the respiratory depressant effect of opioids, which may exacerbate preexisting obstructive sleep apnea. Discharge instructions given to patients receiving opioid prescriptions should therefore include explicit warnings regarding the risk of new or worsening sleep apnea that may culminate in death.
Our ultimate goal is not to prevent physicians from prescribing opioids. Instead, our intent is to provide guidelines, based on direct observation, on how to best manage acute pain while preventing overdose and long-term misuse. Pain is not merely distressing; it is also therapeutic. Acute pain promotes healing by limiting an individual’s activity after injury. A careful balance must be struck between functional analgesia and opioid prescribing to avoid long-term nonmedical opioid use. Our data from digital pills that can detect patterns of opioid use are a novel and important step toward responsible and evidence-based opioid prescribing.
This study has several limitations. First, it was conducted at a single academic tertiary ED. The demographics of individuals presenting to our ED and their preferences for opioid analgesics may not be generalizable to other EDs in different settings. Second, the small number of participants enrolled in the study limits the ability to draw conclusions regarding the median number of opioid analgesics required to control acute pain. Despite this, our data suggest that individuals ingesting opioids for acute pain may use less opioids than previously thought. Future investigations will investigate opioid ingestion patterns after more homogenous painful conditions (eg, acute pain after a specific surgical procedure). Third, this study focused on opioid-naive individuals with acute fractures. Individuals with a history of opioid use may respond differently to acute exacerbations of pain producing different ingestion patterns. Fourth, we selected a single painful condition—acute fractures. Our results, while important, may be different in individuals with other painful conditions.
Implications for Further Research
With increasing restrictions on opioid prescribing, detecting opioid ingestion patterns in individuals provide greater precision in determining the numbers of opioid dosage units needed to treat pain while minimizing the threat of misuse. As an investigational tool, the digital pill provides not only a direct measure of opioid ingestion but also evidence of more dynamic changes in medication-taking behavior. Additionally, use of a digital pill technology, when linked to ecologic momentary assessments, can define affective and environmental contexts that surround opioid-taking behavior, such as whether opioid ingestion is linked to subjective notions of increasing pain or periods of stress.
We recognize that the technology associated with the digital pill described here may appear cumbersome and difficult to use. Despite this, we demonstrated that individuals, with short instruction in the ED, can operate digital pills in the real world. Iterative improvements in the technology will make digital pills more seamless; we project that there will be 2 major advances. First, we have witnessed, even during our study period, iterative improvement in energy harvesting in the digital pill. This is significant because improved energy harvesting allows the digital pill to transmit ingestion data across a larger distance. Second, because of improved detection capabilities of the digital pill, the most cumbersome components of the digital pill (eg, the reader and associated patch) will miniaturize and integrate into other on-body technology like a smartwatch or the patient’s smartphone. We believe that these advances will improve the overall acceptability of digital pills and allow expansion of this technology to observe opioid ingestion in disparate populations. The improved technology can also be used in future trials to observe differences in opioid use between different age groups, individuals with disparate risk factors and among various types of surgical procedures.
Clinically, the wireless delivery of opioid ingestion information allows interventions to be delivered to patients at the precise moment they are needed. The discovery of behaviors consistent with the development of tolerance—either an escalation of opioid dose or an increase in dosing frequency—can trigger interventions by clinicians in real time. The development of real-time interventions that are linked to specific patterns of opioid ingestion is an area of urgent need.
Name: Peter R. Chai, MD, MMS.
Contribution: This author helped in conceiving the study, recruiting the participants, completing the data analysis, and was principally responsible for the study as a whole and drafting the manuscript.
Name: Stephanie Carreiro, MD.
Contribution: This author helped in conceiving and completing the data analysis in this study and was also instrumental in providing key edits to the manuscript.
Name: Brendan J. Innes, BS.
Contribution: This author helped recruiting the participants, was primarily responsible for data analysis in the study, and providing key edits in the manuscript.
Name: Brittany Chapman, BS.
Contribution: This author helped in recruiting the participants, completing the data analysis, and providing key edits in the manuscript.
Name: Kristin L. Schreiber, MD, PhD.
Contribution: This author helped in drafting the manuscript and providing key edits in revisions of the manuscript and technical assistance in preparing figures and visualizing data for the manuscript.
Name: Robert R. Edwards, PhD.
Contribution: This author helped in drafting the manuscript and providing key edits in revisions of the manuscript.
Name: Adam W. Carrico, PhD.
Contribution: This author helped in drafting key portions of the manuscript and providing key edits in the revisions of the manuscript.
Name: Edward W. Boyer, MD, PhD.
Contribution: This author helped in conceiving the study, recruiting the participants, mentoring Peter R. Chai and Stephanie Carreiro in data analysis, drafting the manuscript, and providing the principle funding through 5K24DA037109 to acquire materials to perform the study.
This manuscript was handled by: Honorio T. Benzon, MD.
1. Kumar K, Gulotta LV, Dines JSUnused opioid pills after outpatient shoulder surgeries given current perioperative prescribing habits. Am J Sports Med. 2017;61:636–641.
2. Bates C, Laciak R, Southwick A, Bishoff JOverprescription of postoperative narcotics: a look at postoperative pain medication delivery, consumption and disposal in urological practice. J Urol. 2011;185:551–555.
3. Lewis ET, Cucciare MA, Trafton JAWhat do patients do with unused opioid medications? Clin J Pain. 2014;30:654–662.
4. Kim N, Matzon JL, Abboudi J, et alA prospective evaluation of opioid utilization after upper-extremity surgical procedures: identifying consumption patterns and determining prescribing guidelines. J Bone Joint Surg Am. 2016;98:e89.
5. Maughan BC, Hersh EV, Shofer FS, et alUnused opioid analgesics and drug disposal following outpatient dental surgery: a randomized controlled trial. Drug Alcohol Depend. 2016;168:328–334.
6. Hill MV, McMahon ML, Stucke RS, Barth RJ JrWide variation and excessive dosage of opioid prescriptions for common general surgical procedures. Ann Surg. 2017;265:709–714.
7. Woster P, Ko M, Smith T(207) Predictors of medication adherence assessed by urine drug monitoring in patients prescribed opioid medications: relationship with opioid dose. J Pain. 2016;17:S27.
8. Osterberg L, Blaschke TAdherence to medication. N Engl J Med. 2005;353:487–497.
9. Tacke U, Uosukainen H, Kananen M, Kontra K, Pentikänen HA pilot study about the feasibility and cost-effectiveness of electronic compliance monitoring in substitution treatment with buprenorphine-naloxone combination. J Opioid Manag. 2009;5:321–329.
10. Schwarz DA, George MP, Bluth MHToxicology in pain management. Clin Lab Med. 2016;36:673–684.
11. Compton PThe role of urine toxicology in chronic opioid analgesic therapy. Pain Manag Nurs. 2007;8:166–172.
12. Chai PR, Castillo-Mancilla J, Buffkin EUtilizing an ingestible biosensor to assess real-time medication adherence. J Med Toxicol. 2015;11:439–444.
13. Chai PR, Carreiro S, Innes BJ, et alDigital pills to measure opioid ingestion patterns in emergency department patients with acute fracture pain: a pilot study. J Med Internet Res. 2017;19:e19.
14. Browne SH, Behzadi Y, Littlewort GLet visuals tell the story: medication adherence in patients with type II diabetes captured by a novel ingestion sensor platform. JMIR Mhealth Uhealth. 2015;3:e108.
15. Frias J, Virdi N, Raja P, Kim Y, Savage G, Osterberg LEffectiveness of digital medicines to improve clinical outcomes in patients with uncontrolled hypertension and type 2 diabetes: prospective, open-label, cluster-randomized pilot clinical trial. J Med Internet Res. 2017;19:e246.
16. Flores GP, Peace B, Carnes TC, et alPerformance, reliability, usability, and safety of the ID-Cap system for ingestion event monitoring in healthy volunteers: a pilot study. Innov Clin Neurosci. 2016;13:1–8.
17. Chai PR, Rosen RK, Boyer EWIngestible biosensors for real-time medical adherence monitoring: MyTMed. Proc Annu Hawaii Int Conf Syst Sci. 2016;2016:3416–3423.
18. Belknap R, Weis S, Brookens A, et alFeasibility of an ingestible sensor-based system for monitoring adherence to tuberculosis therapy. PLoS One. 2013;8:e53373.
19. Kane JM, Perlis RH, DiCarlo LA, Au-Yeung K, Duong J, Petrides GFirst experience with a wireless system incorporating physiologic assessments and direct confirmation of digital tablet ingestions in ambulatory patients with schizophrenia or bipolar disorder. J Clin Psychiatry. 2013;74:e533–e540.
20. Des Jarlais DC, Lyles C, Crepaz NTREND Group. Improving the reporting quality of nonrandomized evaluations of behavioral and public health interventions: the TREND statement. Am J Public Health. 2004;94:361–366.
21. Bateman BT, Franklin JM, Bykov K, et alPersistent opioid use following cesarean delivery: patterns and predictors among opioid-naïve women. Am J Obstet Gynecol. 2016;215:353.e1–353.e18.
22. Prabhu M, McQuaid-Hanson E, Hopp S, Kaimal A, Leffert L, Bateman BT817: shared decision-making for opioid prescribing after cesarean delivery. Am J Obstet Gynecol. 2017;216:S469.
23. Shah A, Hayes CJ, Martin BCCharacteristics of initial prescription episodes and likelihood of long-term opioid use—United States, 2006-2015. MMWR Morb Mortal Wkly Rep. 2017;66:265–269.
24. Substance Abuse and Mental Health Services Administration. National Survey on Drug Use and Health 2015. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2016.
25. Volkow ND, McLellan TACurtailing diversion and abuse of opioid analgesics without jeopardizing pain treatment. JAMA. 2011;305:1346–1347.
26. Cicero TJ, Ellis MS, Harney JShifting patterns of prescription opioid and heroin abuse in the United States. N Engl J Med. 2015;373:1789–1790.
27. Dart RC, Bronstein AC, Spyker DA, et alPoisoning in the United States: 2012 emergency medicine report of the National Poison Data System. Ann Emerg Med. 2015;65:416–422.
© 2017 International Anesthesia Research Society
28. Harris K, Curtis J, Larsen B, et alOpioid pain medication use after dermatologic surgery: a prospective observational study of 212 dermatologic surgery patients. JAMA Dermatol. 2013;149:317–321.