Opioids and Public Health: The Prescription Opioid Ecosystem and Need for Improved Management

Evan D. Kharasch, M.D., Ph.D.; J. David Clark, M.D., Ph.D.; Jerome M. Adams, M.D., M.P.H.

Disclosures

Anesthesiology. 2022;136(1):10-30. 

In This Article

Managing the Size of the Opioid Pool

There are three general approaches to managing the size of the opioid pool. These are supply-side, demand-side, and disposal (Figure 2).

Figure 2.

The prescription opioid ecosystem. The pool of unused prescription opioids available for diversion, misuse, and overdose is influenced by supply, demand, and return or disposal. Overprescription of opioids, while providing sufficient supply to treat pain, risks potential patient overuse or residual unused opioids, and underprescription risks undertreated acute and chronic pain. Reducing supply alone has not been successful at reducing opioid overdose rates. Reducing demand through better pain treatment, and enhancing disposal and return, are additional approaches to reducing the opioid pool and mitigating opioid misuse and overdose deaths. Postop, postoperative.

Supply-side Opioid Management

Supply-side regulation targeting restricted prescribing has been the overwhelmingly predominant focus of efforts to combat the opioid crisis. U.S. opioid prescribing is influenced by myriad laws, regulations, policies and guidelines, from numerous federal government agencies (e.g., Centers for Disease Control and Prevention, Atlanta, Georgia; Veterans Affairs Healthcare System; Department of Defense; Centers for Medicare and Medicaid Services, Baltimore, Maryland), state and local governments (all 50 states have some form of opioid prescribing guidelines or restrictions, as do some cities), state medical boards, professional societies, health insurers, pharmacy benefit managers, pharmacies, and local hospitals and healthcare systems.[45] Broad policies and targeted interventions to reduce opioid prescribing include improved medical student curricula; compulsory provider education; electronic medical record systems defaults, warnings, and limits; prescription drug monitoring programs; naloxone access laws; pain clinic laws; and stringent numerical restrictions on opioid prescribing.[31,77]

There are clear pitfalls of bowing to pressures that would result in seemingly attractive and expedient but ill-advised one-size-fits-all solutions. Many of these are outlined in the National Academies of Sciences, Engineering, and Medicine (Washington, D.C.) report "Pain management for people with serious illness in the context of the opioid use disorder epidemic."[78] Overall, the nation's response to the oral opioid crisis has been to tighten patient supplies and impose institutional and practitioner quality indicators based on pill counts. Governments, payers, and pharmacies have assumed authority for limiting opioid prescribing, often in indiscriminate ways, based on misinterpretation of Centers for Disease Control guidelines or based on no real guidance at all.[79] Pill counts have become de facto standards employed by healthcare organizations to highlight their success in reducing opioid use, yet there is no discussion of how those reductions are affecting patient outcomes.[78] One crucial problem is that agencies mandating policy restrictions do not measure, nor are they accountable for, patient outcomes.[78] Mandated opioid prescribing limits may be too low to adequately control pain, or too high to reduce oversupply.[80]

Another crucial problem is that supply-side restrictions focus on intermediate outcomes while ignoring patient-centric and population health outcomes. Intermediate outcomes include prescription pill counts, amounts of opioid used, number of unused pills left over, refill requests, opioid misuse, opioid diversion, health costs, and patterns of healthcare utilization (Figure 3). Patient-centric outcomes, arguably more important, include pain, adverse effects, function, recovery from illness, return to work or school, quality of life, morbidity, and mortality, and their implications for population health. Intermediate outcome statistics can also be misleading. For example, opioid prescriptions to opioid-naïve patients declined by 54% from 2012 to 2017,[32] and mean amounts (milligrams) prescribed per person decreased 13% from 2006 to 2017,[81] but average prescription duration and the number of prescriptions for greater than 30 days both increased 38%.[81]

Figure 3.

Analytic framework for prescribing opioids for acute pain and evidence linkages necessary to support the development of clinical practice guidelines for opioid prescribing. The framework begins with the patient population with acute pain (e.g., postoperative pain). The wide arrow indicates evidence evaluating the effects of an opioid prescribing strategy on a health or intermediate outcome. The dotted lines indicate linkages between different outcomes (e.g., association between a lesser amount of opioid used and risk of long-term use or quality of life), not between an intervention and an outcome (or, in the case of intermediate outcomes and long-term opioid use, between one intermediate and another intermediate outcome). Short- and long-term health outcomes, both beneficial and harmful, may be seen at the patient and community or population levels. Reproduced from Framing Opioid Prescribing Guidelines for Acute Pain: Developing the Evidence 45 with permission of the National Academy of Sciences, courtesy of the National Academies Press, Washington, D.C.

One example of opioid prescribing guidelines hyperfocused on supply-side restriction and their consequence is cancer, where pill count policies may adversely affect patient care. Opioid prescribing guidelines intended for noncancer populations are being inappropriately applied to cancer patients and cancer survivors, with concern about reduced access to effective pain management.[82] A recent survey of cancer patients and survivors found that one third were refused opioids by their physician, and one half were told that their pain treatment was limited by laws, guidelines, or insurance coverage.[82] The expressed fear was that while concerns about opioid misuse were certainly warranted, appropriate pain management was equally as critical.

Another focus of guidelines is on postoperative opioid prescribing, where calls for guidelines have been met with a plethora of recommendations by professional societies and healthcare institutions. Yet these are highly disparate (not surprising, given the above-described variability in interpatient pain experiences and analgesic responses). Among just one surgical type (abdominopelvic surgery), a recent review identified 15 clinical practice guidelines and 26 other pertinent documents containing 98 recommendations for discharge opioid prescribing, and there was substantial variability between them in the amount of recommended discharge opioid—even for the same procedure.[83] Moreover, in addition to the heterogeneity of the recommendations, only a tiny fraction (11%) of recommended interventions were supported by an assessment of strength or level of evidence.[83] Beyond surgery more broadly, there is prescribing variability within many other specific indications, by geographic region, provider type, provider, hospital, and within and between patient populations.[45]

Despite well-established interpatient variability in pain and recovery trajectories, several studies have attempted to identify the one right number of opioid pills needed by all patients postoperatively, with the goal of identifying the one right amount to prescribe.[84–86] Less stringent individualized approaches, such as those based on predischarge in-hospital opioid use, may be more successful,[85,87] but they are only applicable to hospital inpatients, and not more broadly to ambulatory surgery and emergency department visits. Numerable publications have rightly recognized the need to reduce excessive postsurgical opioid prescribing and promoted various approaches. Recent examples of local success in reducing postsurgical opioid pills counts are very promising.[88–91] However, patient effects beyond this intermediate outcome are yet unknown. Enhanced recovery after surgery protocols that promote opioid-sparing if not opioid-free anesthesia have become widely implemented.[92] Nevertheless, such protocols did not affect discharge opioid prescribing.[93] Some reductions in opioid amounts prescribed at discharge after surgery have even been associated with worse postoperative pain control.[86] Risks of inadequate pain control include increased morbidity, care costs, progression to chronic pain and opioid use, delayed recovery, physical and emotional distress, and impaired physical functioning, daily activities, sleep, and return to work or school.[45]

Protocols that aim to "right-size" opioid prescribing in order to narrow the gap between opioid prescribing and amount used and thus reduce "leftovers" to decrease the storage and disposal burden on patients are highly laudable, yet challenged by the problem of variability. Such protocols can represent tradeoffs between opioid prescribing, use, and inadequate pain relief, as limiting discharge prescriptions to the amounts sufficient for the majority of patients means that some will have inadequate pain control.[45,94] Currently, one-size-fits-all opioid prescribing epitomizes the dynamic tension between protocolized and individualized medicine.[95]

In addition, the opioid supply chain now has two parts—the one the healthcare system controls, and a larger portion used for abuse that is illicit at its source. Decades ago this situation was the reverse, with most abused opioids originating in our medical supply. Restricting access with ill-considered policies may take pills from people who need them while leaving intact the main supply lines of the opioid crisis—primarily illicit fentanyl.

It is now recognized that supply-side approaches alone are not succeeding. Broad prescribing restrictions may be suboptimally effective because nearly half of all opioid doses and one quarter of all opioid prescriptions are accounted for by only 1% of providers.[77] In contrast, among the remaining 99% of providers, more than 85% of prescriptions were for less than the Centers for Disease Control recommendation of 50 mg morphine equivalents per day.[77] Since only a tiny fraction of providers account disproportionately for overprescribing, while most prescriptions written by the majority appear more appropriate, further broad increases in prescribing restrictions and more rigid dosing thresholds are considered unlikely to be beneficial, and more likely to reduce appropriate than inappropriate opioid use.[77]

In the realm of acute pain, restrictive opioid prescribing limits have not substantially reduced actual opioid prescribing, nor have they been the primary driver for the overall downward trend in opioid prescribing in the United States that has occurred over the last decade.[96] Greater restrictions on opioid prescribing are thought unlikely to be effective—and certainly not without the risk of inadequate pain treatment.[96] Moreover, sudden and/or involuntary discontinuation of chronic opioid therapy for pain due to clinician decision or supply restriction is not without potential consequence, such as withdrawal, increased or uncontrolled pain, psychologic distress, increased risk of suicidal ideation, opioid-related adverse events, and overdose death (particularly illicit opioids)—the very things we are trying to prevent.[86,97–101]

Legislative, regulatory, and insurer limitations on opioid prescribing alone have not met their intended goals and are considered unlikely to achieve them. One reason is that they impose tight restrictions on an extremely heterogeneous patient population.[78,80] Moreover, they focus more on intermediate outcomes, which are easily quantifiable but less important than the health outcomes that are more important to patients and population health (Figure 3).[45,102] Since the publication of the Centers for Disease Control guidelines with strict thresholds for opioid prescribing, enthusiasm has waned for such supply-side management in some quarters. The American Medical Association (Chicago, Illinois), in its essay "8 keys to end the nation's drug-overdose epidemic," suggests eliminating ineffective opioid prescribing restrictions and shifting focus to the illicit opioid overdose epidemic.[103] Even the authors of the Centers for Disease Control opioid prescribing guidelines have expressed dismay at the misapplication of their guidance.[104] While supply-side opioid policy has stayed or reduced prescription opioid misuse and associated overdose deaths, it appears to have had the unintended consequence of motivating opioid users to switch to illicit drugs and the associated consequence of increased overdose and death (Figure 1).[31,105]

It is clear that patients could benefit from better-informed practices and education regarding pain, oral opioid prescribing, and oral opioid use, and from a reduction in excessive overall and posthospital opioid prescribing. However, supply-side restriction alone is confounded by the problem of variability, and appears neither fully effective nor optimal, and further restrictions risk greater patient pain.

Demand-side Opioid Management

Demand-side (patient need) reduction in the opioid pool offers a more promising path forward if properly executed—that is, reducing pain and the need for opioids.[105] From the perspective of acute postoperative pain, the majority of patients (80%) report that their pain was not adequately managed.[46,106–108] Acute surgical pain not only causes suffering and diminished patient satisfaction[109,110] but also is associated with postoperative surgical complications (i.e., surgical site and urinary tract infections),[43,111,112] and even engenders regret for having had surgery.[110] The problem of chronic postoperative pain affects up to 80% of patients,[113–115] and may lead to persistent postoperative opioid use.[102,116–118] Postoperatively, "one-third of adults receiving long-term opioid therapy report that their first opioid prescription came from a surgeon, indicating that postsurgical prescribing is important…in the opioid epidemic,"[119] and this is cited to suggest that opioids per se are the sole culprit. However, this ignores the fact that all chronic postoperative pain started as acute postoperative pain, and acute postoperative pain was the reason for this one third of patients to be prescribed opioids in the first place. It is well-established that in opioid-naïve patients, acute postoperative pain is the greatest risk factor for chronic postsurgical pain.[120] Moreover, chronic pain is not limited to surgical patients. The incidence of new chronic pain in 1,840 1-yr survivors of critical illness (requiring intensive care unit care) was 18%,[121] and a systematic review of nine studies including 1,755 patients reported a 28 to 77% incidence of persistent pain after intensive care.[122] Neither found any difference between medical versus surgical patients in the incidence of persistent pain.

The target of greatest potential influence on the need for postoperative opioids is reducing acute perioperative pain and the potential consequence of transition to chronic postoperative pain.[115,120,123,124] As summarized recently, current therapeutic modalities such as multimodal analgesia, epidural analgesia, peripheral nerve blocks, perioperative gabapentinoids, intravenous ketamine, and intravenous lidocaine, while often effective in the immediate perioperative period, do not prevent chronic postoperative pain and/or persistent postoperative opioid use.[124–128] While pharmacologic innovations await, care model innovations may hold promise, such as the transitional pain service to provide continuity of pain care, education, and management to complicated patients after hospital discharge.[129–132] It is imperative to find more successful methods and practices than currently available, and this unmet need should be a pressing research focus.[95,102,124,133]

In the immediate, anesthesiologists should focus on carefully tailoring perioperative therapeutic regimens to the needs and circumstances of individual patients, and with the longest lasting benefit, preferably beyond just the immediate perioperative period and their time in hospital. If the prescribing of postoperative oral take-home opioids is to be right-sized, patients must feel confident that they will receive an adequate take-home supply to treat their pain and must receive the amount prescribed, and surgical prescribers must feel confident that they are providing enough to assure adequate analgesia and patient satisfaction, to minimize unwanted calls by patients for more, and to minimize the amount of unused leftover opioid pills. It has been recommended that perioperative initiatives focus more on reducing pain than on just reducing opioids per se.[95]

Pool-size Opioid Management

Last, and least illuminated or pursued, is the objective of shrinking the pool of opioids present in the community, to prevent diversion and misuse. Shrinking the opioid pool represents an unfulfilled opportunity for public health benefit at scale. The pool size depends not only on supply (inflow) but also on outflow, with the latter determined by voluntary disposal and take-back of unused and leftover opioids. The size of the opioid pool has major implications for potential misuse and adverse events. For example, among U.S. adults (older than 12 yr) who misused prescription pain relievers in 2019, 51% received them from a friend or relative (the pool), compared with 37% by prescription from a healthcare provider.[38]

Most patients with unused opioids plan to keep them for potential future need.[60] People keep unused medications because (1) it takes effort to discard them but no effort to leave them where they are, and (2) a natural inclination is to keep something that might be useful later on, such as a drug that once served a purpose (pain relief) and might do so again, particularly if future procurement is uncertain, inconvenient, or expensive.[134] Indeed, the most common reason for patients to retain unused opioids is to have them available should they need to treat pain in the future—theirs or that of others.[74,135] Among U.S. adults (older than 12 yr) who misused prescription pain relievers in 2019, the vast majority (66%) did so to relieve physical pain.[39] This again highlights the importance of the problem of undertreated pain, well-recognized in adults,[20] and more recently in children.[136] Among adults who kept unused opioids and then shared them (one of the definitions of misuse), 73% did so to help another person manage their pain.[58] Hence a major motivation for retaining unused opioids, and a barrier to shrinking the opioid pool, is patients' fear of pain and of their inability to receive proper future treatment. Another major reason patients retain unused opioids is the barriers to disposing or returning them.

Compared with the unremitting focus on restricting opioid prescribing, opioid disposal and return (take-back) have received scant attention. Patient storage of unused medications, lack of return, and lack of education by healthcare providers about disposal have remained unchanged for more than a decade, even in the face of the opioid crisis.[137] Patient education about opioid disposal has been called staggeringly low.[135]

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