Clinical Challenge

Test your clinical knowledge on persistent post-operative opioid use with these 4 questions. Hit submit to see the answers.

1. Persistent post-operative opioid use (PPOU) is commonly defined as filling any opioid prescription between __ and 365 days after surgery.
2. What is the rough estimate of the incidence rate of PPOU in opioid-naïve patients?
3. Among patients who do not take all of their prescribed opioids, what percentage keep rather than dispose of the excess pills?
4. Which state has applied evidence-based guidelines on a large scale for post-discharge opioid prescribing?

The United States continues to be in an opioid epidemic. There are an estimated 2 million people with opioid use disorder (OUD), and overdose deaths related to opioids reached 80,000 in 2021. Tens of billions of dollars are spent annually on related healthcare costs such as medical care and addiction treatment, which in the past directly correlated with the overprescribing of opioids.1-3

While chronic pain specialists and primary care physicians have been scrutinized for opioid-prescribing practices (leading to the 2016 CDC guideline on Prescribing Opioids for Chronic Pain in 2016 and its 2022 revision), less attention has been drawn to post-operative/post-discharge opioid prescribing practices.4

What Is Persistent Post-Operative Opioid Use?

Although definitions for persistent post-operative opioid use (PPOU) vary, it is commonly defined as filling any opioid prescription between 90 and 365 days after surgery. PPOU is common, with meta-analyses pooling incidence rates of over 4% in opioid-naïve patients and higher rates in opioid-experienced patients.5-7 One very large study (over 300,000 subjects) following veterans in the Veterans Health Administration database for a median of 5.6 years following surgery between 2008 and 2018 found that PPOU was statistically and clinically significantly associated with an increased risk of developing both OUD and overdose.8

Risk Factors for Persistent Post-Operative Opioid Use

Risk factors correlated with the development of PPOU in opioid-naïve patients include those specific to the patient, surgery, and perioperative pain management plan. Patient-specific factors include pre-existing chronic pain, substance use disorders, and mood disorders.9,10

Many surgical procedures putting patients at risk for PPOU are especially common, such as total knee arthroplasty and Cesarean section. Others include simple mastectomy, open abdominal procedures such as cholecystectomy and appendectomy, and cardiothoracic surgery.9,11

Heavily prioritizing opioids as part of the perioperative pain management plan rather than a multimodal pain regimen is also associated with PPOU. Unsurprisingly, the dosage and duration of post-operative opioid prescriptions is associated with PPOU as well.11-14

Opioid Use Trends After Surgery

A systematic review analyzing outpatient use of prescription opioids for varying types of surgeries found that the percentage of prescribed opioids actually taken was only 11% to 58% (with the exception of pediatric spinal fusion patients at 90.1%).16 Patients who underwent abdominal surgery took fewer than 15 opioid pills, shoulder surgery patients took 35.2 pills but left 20 pills unused, and hand surgery patients averaged more than 16 unused opioid pills.16-18 Most dermatologic and breast lumpectomy patients took fewer than 5 pills.16

Leftover Pills

Among patients who do not take all of their prescribed opioids, more than 65% keep the excess pills.16,20 Even among studies analyzing opioid overprescribing for different types of surgery, almost half did not report on planned or completed methods of disposal for the leftover pills, further suggesting that physicians do not appropriately emphasize opioid disposal.16

Steps to Reduce Persistent Post-Operative Opioid Use

Although this article centers on post-surgical opioids and PPOU, the first steps toward improved prescribing practices begin before the post-operative stage. Pre-operatively, educating patients on their post-operative recovery and setting proper expectations for their post-operative pain management has been demonstrated to result in decreased opioid prescriptions with reduced opioid consumption – without significant changes to patient satisfaction or refill requests.21,22

Perioperatively, Chou et al published guidelines for the management of acute post-operative pain. While it provides 32 recommendations, only four were considered “high-quality evidence.” Those four included multimodal analgesia (and opioid-sparing analgesia if appropriate), including acetaminophen and/or NSAIDs as part of the multimodal regimen, providing peripheral regional anesthesia when applicable, and neuraxial anesthesia for major thoracic and abdominal cases when possible.15

The Michigan Example

Regarding post-discharge opioid prescriptions, prescribers should work to refine their practices according to procedure-specific, evidence-based guidelines. Multiple studies have proved that opioid-prescribing guidelines decrease opioid prescriptions, opioid consumption, and resulting leftover opioid pills without affecting patient satisfaction.21,22

One large study investigated opioid-native patients who underwent one of six common surgeries that Michigan OPEN had published guidelines for, studying nearly 25,000 patients in Michigan and 120,000 patients outside of Michigan. It found that adhering to the OPEN guidelines resulted in statistically and clinically significant reductions in PPOU, from 3.29% to 2.51%, and opioid prescription quantity from 199.5 oral morphine equivalents (OME) to 88.6, both of which were also markedly larger decreases than those found in patients outside of Michigan.27

Clinical Takeaways

The United States has been challenged by an opioid epidemic for years, and it has been shown that PPOU is associated with an increased risk of OUD and overdose. Risk factors associated with developing PPOU depend on the individual patient, the surgery, and the pain management plan. Although more physicians are acutely aware of the nationwide problem, many still overprescribe opioids. Such prescribing predisposes patients towards developing PPOU. Further, due to a lack of patient education on proper disposal methods, many individuals do not dispose of their leftover pills and some give them to unprescribed family and friends, putting them at risk of OUD and overdose as well.

The process to prevent PPOU begins pre-operatively by educating the patient on the recovery process and setting pain management expectations. It continues perioperatively and immediately post-operatively with a multimodal pain regimen and the utilization of peripheral regional or neuraxial anesthesia when possible. Finally, it concludes with an evidence-based post-discharge pain protocol dependent on the type of surgery performed.

By providing evidence-based guidelines for acute care opioid prescribing, post-discharge prescribing, and educational brochures for patients on topics such as managing pain after surgery and safe storage and disposal of used medications, they have been shown to reduce the number of excessive opioids in circulation and the incidence of post-operative opioid use.

  1. Wilson N, Kariisa M, Seth P, et al. Drug and opioid-involved overdose deaths – United States, 2017-2018. MMWR Morb Mortal Wkly Rep. 2020;69(11):290-297. doi:10.15585/mmwr.mm6911a4
  2. Lipari R. Key substance use and mental health indicators in the United States: results from the 2018 National Survey on Drug Use and Health. SAMHSA. 2019.
  3. Florence C, Luo F, Rice K. The economic burden of opioid use disorder and fatal opioid overdose in the United States, 2017. Drug Alcohol Depend. 2021;218:108350. doi:10.1016/j.drugalcdep.2020.108350
  4. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016. MMWR Recomm Reports. 2016;65(1):1-49. doi:10.15585/mmwr.rr6501e1
  5. Jivraj NK, Raghavji F, Bethell J, et al. Persistent postoperative opioid use: A systematic literature search of definitions and population-based cohort study. Anesthesiology. 2020;132(6):1528-1539. doi:10.1097/ALN.0000000000003265
  6. Lawal OD, Gold J, Murthy A, et al. Rate and risk factors associated with prolonged opioid use after surgery: A systematic review and meta-analysis. JAMA Netw Open. 2020;3(6):e207367. doi:10.1001/jamanetworkopen.2020.7367
  7. Mohamadi A, Chan JJ, Lian J, et al. Risk factors and pooled rate of prolonged opioid use following trauma or surgery: A systematic review and meta-(regression) analysis. J Bone Joint Surg Am. 2018;100(15):1332-1340. doi:10.2106/JBJS.17.01239
  8. Aalberg JJ, Kimball MD, McIntire TR, McCullen GM. Long-term outcomes of persistent post-operative opioid use: A retrospective cohort study. Ann Surg. 2022;Publish Ah. doi:10.1097/SLA.0000000000005372
  9. Kent ML, Hurley RW, Oderda GM, et al. American Society for Enhanced Recovery and Perioperative Quality Initiative-4 Joint Consensus Statement on Persistent Postoperative Opioid Use: Definition, Incidence, Risk Factors, and Health Care System Initiatives. Anesth Analg. 2019;129(2):543-552. doi:10.1213/ANE.0000000000003941
  10. Brummett CM, Waljee JF, Goesling J, et al. New persistent opioid use after minor and major surgical procedures in US adults. *JAMA Surg*. 2017;152(6):e170504. doi:10.1001/jamasurg.2017.0504
  11. Hah JM, Bateman BT, Ratliff J, et al. Chronic opioid use after surgery: Implications for perioperative management in the face of the opioid epidemic. *Anesth Analg*. 2017;125(5):1733-1740. doi:10.1213/ANE.0000000000002458
  12. Calcaterra SL, Yamashita TE, Min S-J, et al. Opioid prescribing at hospital discharge contributes to chronic opioid use. *J Gen Intern Med*. 2016;31(5):478-485. doi:10.1007/s11606-015-3539-4
  13. Alam A, Gomes T, Zheng H, et al. Long-term analgesic use after low-risk surgery: a retrospective cohort study. *Arch Intern Med*. 2012;172(5):425-430. doi:10.1001/archinternmed.2011.1827
  14. Brown CR, Chen Z, Khurshan F, et al. Development of persistent opioid use after cardiac surgery. *JAMA Cardiol*. 2020;5(8):889-896. doi:10.1001/jamacardio.2020.1445
  15. Chou R, Gordon DB, de Leon-Casasola OA, et al. Management of postoperative pain: A clinical practice guideline from the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists’ Committee on Regional Anesthesia, Executive Commi. *J Pain*. 2016;17(2):131-157. doi:10.1016/j.jpain.2015.12.008
  16. Feinberg AE, Chesney TR, Srikandarajah S, et al. Opioid use after discharge in postoperative patients. *Ann Surg*. 2018;267(6):1056-1062. doi:10.1097/SLA.0000000000002591
  17. Kumar K, Gulotta L V, Dines JS, et al. Unused opioid pills after outpatient shoulder surgeries given current perioperative prescribing habits. *Am J Sports Med*. 2017;45(3):636-641. doi:10.1177/0363546517693665
  18. Rodgers J, Cunningham K, Fitzgerald K, Finnerty E. Opioid consumption following outpatient upper extremity surgery. *J Hand Surg Am*. 2012;37(4):645-650. doi:10.1016/j.jhsa.2012.01.035
  19. Uhrbrand P, Helmig P, Haroutounian S, et al. Persistent opioid use after spine surgery. *Spine* (Phila Pa 1976). 2021;46(20):1428-1435. doi:10.1097/BRS.0000000000004039
  20. Lewis ET, Cucciare MA, Trafton JA. What do patients do with unused opioid medications? *Clin J Pain*. 2014;30(8):654-662. doi:10.1097/01.ajp.0000435447.96642.f4
  21. Kaafarani HMA, Eid AI, Antonelli DM, et al. Description and impact of a comprehensive multispecialty multidisciplinary intervention to decrease opioid prescribing in surgery. *Ann Surg*. 2019;270(3):452-462. doi:10.1097/SLA.0000000000003462
  22. Patel HD, Faisal FA, Patel ND, et al. Effect of a prospective opioid reduction intervention on opioid prescribing and use after radical prostatectomy: results of the Opioid Reduction Intervention for Open, Laparoscopic, and Endoscopic Surgery (ORIOLES) Initiative. *BJU Int*. 2020;125(3):426-432. doi:10.1111/bju.14932
  23. University of Michigan. Acute opioid prescribing (ACOP) guide. 2022. Available at: []( Accessed March 2023. 
  24. University of Michigan. OPEN: Opioid Prescribing Engagement Network. OPEN prescribing recommendations-adult. 2023. Available at:   []( Accessed March 2023.
  25. University of Michigan. Managing pain after surgery. 2022. Available at: []( Accessed March 2023.
  26. University of Michigan. Opioids safe storage and disposal. 2023. Available at: []( Accessed March 2023. 
  27. Howard R, Ryan A, Hu HM, et al. Evidence-based opioid prescribing guidelines and new persistent opioid use