In recent years, there has been a tremendous increase in opioid prescribing for the purpose of controlling acute and chronic pain. Impressively, the amount of opioid prescribed to US patients increased by 104%, from 43.8 million prescriptions in 2000 to 89.2 million in 2010.1 Recent data do show a leveling off in opioid prescribing, although rates in the United States remain at historically high levels and many times the rates seen in other industrialized Western countries.2 Overall, approximately 4% of US adults consume opioids regularly for pain.3The lack of evidence supporting such practices and the abundant evidence of the risks and harms of opioid use have been highlighted in many reports. The rates of prescription and illicit opioid misuse, overdose, and admissions to drug treatment programs have all increased in parallel to burgeoning opioid prescribing.4 Regrettably, a second equally serious epidemic has emerged in the context of prescription opioid abuse, that being the use of illicit opioids including heroin and fentanyl. These dual opioid-related epidemics together have led to the deaths of more than 30,000 Americans annually, a statistic that is trending upward despite slightly slowing prescription opioid use.4 Though not closely coordinated, responses to the opioid epidemic(s) have come from medical organizations, state agencies, federal agencies, law enforcement groups, and even the White House. Examining opportunities to limit both the supply and demand sides of our opioid-related problems will both foster a comprehensive understanding of the interrelated issues and hopefully assist the multiple stakeholders in coordinating their responses. Such coordination would ideally limit the supply of opioids for nonmedical use, reduce inappropriate demand, and assure availability for legitimate medical indications. Although some of the principles and approaches outlined below are universal to opioid prescribing, the focus of this article is to enhance the anesthesiologist’s understanding on the use of opioids to treat chronic nonmalignant pain and considerations for the treatment of acute pain as they might impact the transition to chronic use.
BURGEONING OPIOID USE AND THE PRACTICE OF ANESTHESIOLOGY
The practice of anesthesiology is in no way immune from the consequences of pervasive opioid use. In fact, the impact of the prescription and illicit opioid epidemics becomes of even greater concern as our field expands its practice model to one of the leading Perioperative Surgical Home. In this model, we ideally become involved in a patient’s care even before the point that a decision is made to operate.5 We evaluate patients for surgical suitability, optimize management, and implement preoperative measures to promote the best possible outcomes. Then, after providing an anesthetic tailored to an individual’s particular needs, we lead pain management efforts both in the immediate postoperative period and in the transition back to primary care. Aside from perioperative medicine, those specializing in chronic pain management may have long-term involvement with patients where opioid use is very frequently an issue.
Several concerns surrounding these patients therefore arise. First, the fraction of patients chronically consuming opioids scheduled for surgery is approximately 20%.6 This fraction may be even larger if we focus on spine or orthopedic surgery where pain from the underlying diseases is frequently treated with opioids before operations being considered. Chronic preoperative opioid use whether medically sanctioned or abuse-related portends many difficulties. These include elevated levels of postoperative pain, high and unpredictable postoperative opioid requirements, and elevated risks of postoperative respiratory depression.7,8 Beyond these immediate risks, a quickly growing body of evidence suggests chronic opioid users experience poorer surgical outcomes than their opioid-free counterparts. Examples include limited restoration of function after joint replacement surgery, poorer quality of recovery after spine surgeries, and higher levels of persistent pain after gynecological procedures.9–11 The contributions of opioid tolerance and opioid-induced hyperalgesia have been discussed by many authors, and both laboratory and clinical evidence support their conclusions.12–14 More broadly, the anesthetic technique and other aspects of perioperative management used may influence the likelihood of developing postoperative pain.15 Lowering the risk of chronic pain may by itself reduce the risk of developing an opioid use disorder (OUD). Less well explored are interactions between opioid use and psychological factors such as depression and anxiety that independently contribute to poor outcomes. Limiting preoperative opioid use to those obtaining medical benefit using conservative doses of drugs is therefore a goal of great importance to anesthesiologists. Whether and when to taper opioids preoperatively is an entirely open question at this point.
ADDRESSING THE OPIOID EPIDEMIC—SUPPLY-SIDE MEASURES
Maintaining availability of opioids to provide pain control for those likely to benefit while limiting access for illicit purposes is a critical goal for physicians, regulators, and law enforcement. Several approaches are available, and while some of these have been implemented, optimal practices will need to be derived from experience and data as we move forward in addressing the opioid crisis. These approaches are not mutually exclusive, and all of the following approaches to reduce the supply of opioids for inappropriate use are being pursued and used to some extent.
Education of Prescribers
The effective management of pain and suffering remains as one of the founding pillars of medical practice. However, despite tremendous advances in numerous fields of medicine including cardiology, endocrinology, and oncology, advances in pain medicine have lagged far behind. Seminal discoveries within the basic science of pain ranging from the detection of painful stimuli to its perception have emerged; however, little of this knowledge has been successfully translated into new strategies or advanced therapeutics. For now, the current clinical practice of pain management is attempting to make the best use of well-established pharmacologic and/or interventional techniques, often in combination, to provide effective analgesia and reduce suffering. The apparent overreliance on opioids alone and their indiscriminate use to manage chronic painful conditions has often placed patients at risk for a wide range of adverse effects including opioid dependence, misuse, and overdose. In the absence of new blockbuster analgesics capable of the potency of opioids without the unwanted adverse effects, we are faced with retraining our health care professional in the art of pain management that is based in multimodal approaches with the goal of achieving a realistic functional end point. How do we attain this? Simply stated, we must provide an up-to-date educational program in pain management and OUD to our present and future health care providers. This will be a difficult hill to climb.
Currently, there is no common pain management curriculum that is broadly utilized for US medical, dental, pharmacy, or nursing schools. Nor is there a consensus as to what constitutes competencies in pain management or the management of OUD for medical school graduates or established providers. An in-depth understanding and coordination of the pain management and substance use disorder curriculum that exists in our nation’s institutions is lacking. As of 2010, a survey of 117 US and Canadian medical schools concluded that pain curriculum was limited in time and scope.16 This translated to as little as 3.8% of responding US medical schools (104) reporting to have a required pain course.16 Although the majority of medical schools contain some pain curriculum, it is primarily embedded in other core course structures and is not generally regarded as a stand-alone topic. In 2010, the National Institutes of Health (NIH) Pain Consortium held a workshop on the state of pain education in the United States and its results were equally sobering—overall there was inadequate education and training in pain management across the country. As little as 9 hours were devoted to pain education throughout the entire 4 years of medical school. As a result, an effort was launched to develop a stronger evidence-based pain curriculum that would serve as a resource for US medical schools. Hosted by the Pain Consortium,17 Centers of Excellence in Pain Education (CoEPE) were established to develop complementary teaching modules on a range of clinically challenging pain management scenarios.18 One such module, “Edna: An Older Adult with Lower Back Pain,”19 is available, as well as other modules on a range of pain management topics. Such modules are intended to compliment an individual institution’s efforts to provide a more interactive and inquiry-based pain curriculum that ultimately leads to clinical competencies in pain management. Although not presented in modular format, a number of other resources are available to support efforts surrounding pain education. These are often found through professional societies dedicated to the research and management of pain such as the International Association for the Study of Pain (IASP) and the American Pain Society (APS) that host a wealth of reference material, curriculum outlines, and/or relevant pain educational links. One may also find some relevant CME-based pain content through the International Anesthesia Research Society (IARS) website.20
In addition to pain education, provider and trainee access to curriculum about diagnosis and treatment of OUD, certainly no less important, appears equally challenged as the lack of an accessible pain education curriculum. Just as it is the goal of all physicians to reduce risk and harm to their patients, the reality is that more than 2 million people in the United States are estimated to suffer from OUD due to prescription opioids. Although OUD treatment protocols have been developed and published through federally mandated efforts such as the Substance Abuse and Mental Health Services Administration (SAMHSA),21 these documents although comprehensive may appear at arm’s length from general practitioners or nonaddiction specialists. Cleary, it is impossible to quickly train up 100,000 or even 1000 additional addiction specialists given that as of 2012, estimates of only about 1200 of the approximately 900,000 plus practicing physicians in the United States were specifically trained in addiction medicine. It follows that caregivers prescribing opioids should be able to recognize opioid misuse, take initial steps, and refer to addiction treatment specialists when necessary.22 In response, societies dedicated to the treatment of substance use disorder have also stepped forward with educational tools and training resources. This has taken the form of local and, for example, national support systems such as the “Provider Clinical Support System For Opioid Therapies” (PCSS-0)23 sponsored by the American Academy of Addiction Psychiatry. Other systems intended to facilitate educational access of physicians in the prescribing of buprenorphine for OUD have been proposed.24
While many physicians may be discouraged by the enormity of the OUD issue, educational approaches may provide physicians more solid footing when dealing with OUD in their practices. In addition to those initiatives and programs described above, a resurgence of evidence-based educational outreach from physician to physician holds promise. Sometimes referred to as academic detailing or systems consultation, this approach has been used successfully to close the gap between evidence-based medicine and clinical practice for conditions such as atrial fibrillation and chronic obstructive pulmonary disease, historically mired in the anecdotal practice of medicine.25,26 Similarly, as providers search for professional guidance in applying emerging evidence to their opioid prescribing practices,27 such educational detailing from trusted colleagues will be critical to separate fact from fiction among the pervasive marketing environment that surrounds the current practice of medicine in the United States. Encouragingly, decision support programming is already becoming an important part of medication ordering through electronic medical record systems. Expanding evidence-based educational links when ordering analgesic therapies or considering an individual patient’s risk for opioid misuse may help provide “on the spot” educational support and improve outcomes.
Opioid Management Guidelines
Guidelines for the treatment of pain due to a multitude of common chronic conditions have been written. Examples include guidelines for the treatment of back pain,28,29 neuropathic pain,30,31 osteoarthritis,32,33 and others. More recently, authored guidelines comment specifically about the position of opioids as the use of these drugs has increased in popularity. These sets of guidelines have been written with the stated or implicit goals of providing effective treatment for qualified patients while avoiding excessive or inappropriate prescribing.34–40 However, the Centers for Disease Control and Prevention (CDC) guidelines for prescribing opioids for chronic pain are some of the most carefully constructed and influential.27
The strength of the CDC guidelines is based on several factors including the broad range of stakeholders included in the effort, the systematic and transparent review process that was used, the inclusion of consideration of public comments, and the well-developed patient and prescriber materials that accompanied the issuance of the guidelines. In general, these guidelines urge a more conservative use of opioids than some have suggested previously. Specific conclusions tending to limit opioid use include the careful selection of patients involving careful history taking and screening, the optimization of nonopioid therapy before a trial of opioids, the use of relatively low doses of opioids, and the recommendation to carefully follow treatment outcome and taper or discontinue opioid prescribing if the goals of therapy are not met. Further tending to limit dose escalation are the recommendations for the use of short-acting formulations generally having smaller dosage unit sizes and the progressive enhancement in monitoring and frequency of reevaluation has been suggested as overall doses increase.27
Prescription Drug Monitoring Programs
Prescription Drug Monitoring Programs (PDMPs) are state-based efforts that collect patient-specific prescribing information for the purpose of enhancing patient safety and reducing the abuse and diversion of controlled substances including opioids. Important information including the identification of prescribers, the specific types, and amounts of opioids a patient is receiving, and the prescription of potentially adversely interacting medications such as benzodiazepines, may be available. These programs are commonly administered by state Departments of Justice, Departments of Health, or Boards of Pharmacy.41 Such programs are now widespread, and as of the time of this writing, only one state, Missouri, had not set up such a program. Information including drugs prescribed, quantities, dates of prescription fills, and prescriber identity are typically available. Information is often updated at least weekly making the records timely. Although highly state-specific, PDMP data may be available to health officials, law enforcement agencies, medical examiners, and others in addition to prescribers. Prescribers may or may not be required to check their state’s PDMP before issuing an opioid prescription, but recent chronic pain management guidelines recommend consulting the PDMP at the time of initiating opioid therapy and subsequently at least every 3 months.27
While advocacy for the use of these databases is strong, it has not been clearly defined how effective these programs have been, who should have access, or how best to use the information to achieve the goal of safer opioid prescribing.42 For example, modest reductions in opioid prescribing were noted after the implementation of Florida’s PDMP and pill mill legislation,43 and a more recent analysis demonstrated an average 30% reduction in the rate of prescribing across 24 states after the implementation of PDMPs.44 However, the implementation of PDMPs has taken place in the midst of a more general rise in the level of concern over opioid use, making it difficult to attribute the reductions in prescribing to the PDMP programs alone. Although prescribers do report that the use of the programs can be cumbersome, one recent report concluded that the availability of a PDMP was deemed very useful by 74% of the physicians surveyed.45 Additional data suggest that states with mandatory prescriber registration in their PDMP program also experience larger reductions in opioid prescribing.46 Registration can otherwise be quite low.
A somewhat related approach for controlling prescribing is the state Medicaid Provider Assignment or “Lock-In” Program. This type of program usually involves the assignment of a specific prescribing provider and pharmacy for all opioid prescriptions. In this way, opioid prescribing can be more carefully controlled and monitored. Enrollees are typically individuals using Medicaid programs who have a record of obtaining opioids from multiple prescribers. Analyses of the outcomes of these programs have been mixed with some investigators identifying reductions in opioid prescribing,47,48 but others paradoxically finding an overall increase in opioid prescribing to enrollees.49 The available information is inadequate at this point to determine the net benefits versus unintended consequences of these programs.50 Such prescribing programs could, of course, expand to private insurers.
Abuse Deterrent Formulations
Abuse deterrent formulations, commonly known as ADFs, reduce the likelihood that an opioid can be abused by crushing, snorting, injecting, or smoking the drug in addition to altering the formulation to make it intrinsically less rewarding or even aversive if used in an unintended manner. The science of creating ADFs is young, and the technologies are rapidly evolving.51 Most currently available ADFs either add an opioid antagonist that is absorbed or activated if tampering occurs or the formulation uses physical and/or chemical measures to hinder the extraction of opioid. Several different ADF formulations are available, a partial list of which appears in the Table.
Despite the advances in our understanding of ADF technology, it should be kept in mind that currently available ADFs do not prevent toxicity from a very common route of administration of abused opioids, the oral route, the same route as is used when the drugs are administered medicinally. Thus, consequences of abuse including overdose and death are possible even with these newly engineered drugs. The Food and Drug Administration (FDA) requires that drug companies collect data on the abuse of their specific products to track the effectiveness of these ADF formulations.
Critically, we do not fully understand the effectiveness of using ADFs. There is reason for optimism in this regard as the reformulation of OxyContin (Purdue Pharma, Stamford, CT) to an ADF resulted in a substantial decline in nonoral abuse. However, the effect of introducing the ADF OxyContin was to shift many abusers to abuse of other opioids, most notably heroin. In addition, about 30% of the pre-ADF abusers continued to abuse the drug by switching to an oral route of abuse or defeating the ADF.52 Other ADFs have not necessarily been as effective in reducing abuse, suggesting that effectiveness may be drug- and formulation-specific.53 Finally, the cost-effectiveness remains undefined for these drugs although many standard formulation drugs are available as generics, and the ADF formulations are relatively expensive.54 Thus, drug costs and the decisions of pharmacy benefit committees may have a major impact on opioid ADF availability.
Reducing Drug Diversion
Drug diversion is said to occur when the normal pathways for supply of a drug, in this case an opioid, is violated leading to the use of a drug for an illegal purpose. Opioids can be diverted at any stage of the supply chain, but much of the diversion occurs in transit between manufacturer and wholesaler or wholesaler and pharmacies, within pharmacies and hospital storage locations, and after prescription to patients. Much of the attention in the lay press and medical journals has been paid to the diversion of drugs obtained through unscrupulous “pill mills” and the theft or sale of unused portions of legitimate prescriptions. In this regard, the passage of legislation such as Florida’s PDMP and pill mill law was associated with modest but significant drops in opioid prescriptions and in morphine equivalents per prescription.43 Those reductions were larger on average for prescribers and patients with high preprogram opioid prescribing and use. Diversion of prescribed drugs from patients’ supplies is also a critical supply route as a large portion of misused prescription opioids are obtained from family and friends.55 Safe storage and careful instructions to safeguard prescribed opioids are therefore important goals.
Complementing the heightened attention on high-volume opioid prescribing has been attention to limiting opioid prescribing after injury or surgery and take-back programs directed at recovering unused opioids. For example, a recent report examining opioid prescribing and use after shoulder surgery showed that the median number of opioid tablets prescribed was 60, but the median number used 90 days after surgery was only 13. A minority of these patients were instructed on what to do with leftover tablets.56 Similarly, Maughan et al57 found that on average patients used less than half of the opioid pills prescribed after outpatient dental surgery. The overprescribing of postoperative opioids is amenable to provider education, however. For example, Hill et al58 reported that after providing recommendations to emphasize the use of nonsteroidal anti-inflmmatory drugs and acetaminophen after general surgery, the number of opioid pills prescribed per patient after surgery decreased by 53% with only 1 of 246 study patients requiring an opioid refill. Take-back programs can consist of drop boxes in pharmacies and other convenient locations, scheduled events, providing materials for mailing unused medications for disposal, and other approaches. Both the FDA and Drug Enforcement Administration (DEA) have supported this type of approach. A recent study involving 5 counties in Central Kentucky showed the potential limitations of this type of approach, as the investigators documented the recovery of only about 0.1% of the opioids annually prescribed in those counties after the installation of permanent drop boxes and several take-back events.59
Controlling the availability of opioids encompasses a critical set of measures, but does not necessarily comprise a complete response. In this regard, reducing the demand for opioids complements the already described supply-side efforts. The range of available options is diverse. As presented below, no single measure or single organization can address demand-side issues. Implementation of multiple simultaneous efforts may, similar to the supply-side approach, provide the greatest impact on overall opioid use. Key goals in reducing opioid demand include better informing the public concerning the harms associated with opioids, treating opioid addiction, and generating fewer individuals chronically using opioids by limiting perioperative exposure.
Treatment of OUD
The number of Americans living with an OUD is enormous. It has been estimated that in 2015 approximately 2 million had a substance use disorder involving prescription pain relievers and 591,000 had a substance use disorder involving heroin. Furthermore, the heroin abuse problem is growing rapidly.60 Clearly, a rational approach to reducing demand for opioids would be to reduce the number of people seeking to misuse them.
Standard therapy for OUD is medication-assisted treatment, a combination of medications along with counseling and behavioral treatment. Both opioid agonists, for example, methadone and buprenorphine, and antagonists, for example, naltrexone, can reduce the frequency of opioid use in those with use disorders.61 The use of buprenorphine has been facilitated by scheduling the drug as DEA Schedule III and by the ability of prescribers to provide the drug for the treatment of use disorder with a reduced requirement for special training. Naltrexone, an opioid antagonist, is available both in tablet form and as depot formulations.62 Behavioral therapies include cognitive behavior therapy, contingency management, motivational interviewing, and drug counseling.63 Recent evidence has added weight to the central role of medications in therapy. For example, a Cochrane review concluded that opioid agonist treatment for opioid misuse was more effective than counseling.64 More recently, the large Prescription Opioid Addiction Treatment Study (POATS) in which patients received buprenorphine, counseling, or the combination demonstrated no additional benefit of counseling when added to medication management.65 Overall, it appears that programs emphasizing pharmacological treatment of OUD might reduce demand for both prescription opioids and heroin alike.
Perisurgical Reduction in Opioid Exposure
Much attention is currently focused on the transition from acute, limited opioid use to chronic opioid use and OUD. It is common for those who eventually develop OUDs to experience a first opioid exposure in the context of a surgery or injury precipitating an emergency room or primary care visit.66,67 One study addressing the question of type of surgery versus the likelihood of prolonged opioid use suggested that some surgeries, for example, joint replacement, conferred an odds ratio of greater than 5 for use at 1 year when compared to nonsurgical patients.68 In addition to prolonged opioid use, perioperative opioid administration is associated with opioid-related adverse drug events in more than 13% of patients.69 Further analysis has identified likelihood of chronic opioid use as being dependent on the number of days of medication supplied with the first prescription, the provision of a second prescription, and the cumulative dose of opioid. If the index prescription was for a long-acting opioid, 1- and 3-year opioid use, although not necessarily abuse, was more likely than if the first prescription was for a short-acting opioid.70 Similarly, a workman’s compensation claims study revealed that those patients receiving an opioid prescription within 15 days of low back pain onset were more likely to be receiving opioids as long as 2 years after the onset of pain compared with patients who did not receive opioids soon after the injuries.71 In light of this and additional evidence, the 2016 CDC opioid prescribing guidelines recommended that opioids be used at the lowest effective doses and for no more than 7 days after acute injuries to reduce the likelihood of transition to chronic use.27
Anesthesiologists being involved in perioperative pain management are in a position to reduce the likelihood of surgical procedures precipitating chronic opioid use and the development of OUDs. In addition to limiting the number of opioid pills provided at the time of discharge as already discussed, the use of multimodal therapy by virtue of limiting opioid exposure may also reduce the patient’s chronic opioid use liability. Relevant measures, depending on the specific surgical procedure, to reduce opioid requirements include the use of pre-, intra-, and postoperative adjuvants, wound area local anesthetic infiltration, and regional anesthesia.72
Public Education on Pain and OUD
Despite the universal experience of pain, the public’s understanding of its causes, treatments, and outcomes remains poorly developed. For most persons who suffer an injury or undergo a surgical procedure, there is an inherent expectation that as healing progresses, pain will decrease proportionately. Fortunately, resolution of pain occurs in the vast majority of cases, but depending on certain factors (some known and unknown), pain may persist serving no useful purpose and often leading to escalating analgesic therapies without further recovery of function. Although anesthesiologists and other physicians are generally comfortable intervening in situations that are driving acute pain, patients along with their physicians should have a better idea of what their role is when acute pain does not resolve in a timely manner. This is particularly important with respect to the additional risks opioids may pose in both the short and the longer-term relative to other therapeutic options. These points were in part summarized in the Institude of Medicine’s report in 2011 that addressed Patient Education in Institute of Medicine Table 4-1 Essential Topics and, more recently, in the National Pain Strategy.73,74 Among the 12 points detailed there, the overarching themes of prevention, personal empowerment, setting realistic expectations, becoming informed consumers, and obtaining adequate information to provide self-care resonate as critical components of any public education program on pain and OUD.74 These are topics that all physicians and importantly anesthesiologists can learn to discuss with their patients.
Beyond the confines of the doctor–patient relationship, there is an increasing need for a broader educational message to be communicated to the public at large. This is especially important given the often conflicting messages the public absorbs from broadcast TV, pharmaceutical marketing, and advertisements. The goal of public education about pain and opioid misuse is to attempt to protect individuals from unnecessary harm while supporting their functional recovery. For those who already are at risk, are opioid dependent, and/or suffer from OUD, targeted web-based educational efforts are emerging to prevent opioid-related overdose and death.75 Nevertheless, in the absence of a coordinated public education effort at the federal level, individual states are at times stepping in to provide public outreach. For example, the state of Oregon provides a focused message on “risk awareness and pain education and care” through its Oregon Pain Guidance serving Southern Oregon website.76 Clearly, much more effort and resources are needed at all levels to begin to match the scope of this national opioid epidemic.
A RESEARCH AGENDA—KEY QUESTIONS
Although the challenges of the US opioid epidemic are formidable, many approaches to reducing the supply of opioids and perhaps reducing demand for them are available. Unfortunately, data concerning the prioritization of particular strategies are not yet available. However, those practicing within the field of anesthesiology may still contribute to control of the opioid epidemic in many ways, including helping to limit the supply of the drugs through leadership in the pain management community and reducing demand by limiting perioperative exposure and using analgesic techniques creatively. We are also in a position to take leadership roles in addressing several basic research questions:
- How do surgical injury, the experience of pain, and exposure to opioids interact to affect the probability of chronic use of opioids? Questions here begin with basic neurobiological questions bringing together the fields of pain and addiction research. We would hope to define the neurobiological basis of possible interactions; identify targetable receptors, cells, and brain centers to reduce long-term opioid use; and identify environmental or patient-specific factors causing vulnerability or providing protection from long-term opioid use after short-term exposure.
- How do we balance our approach to analgesia in the perioperative period to meet the dual goals of providing substantial levels of pain relief while minimizing the risk of contributing to a chronic opioid use problem? Studies in this area might focus on the benefits versus risks and costs of multimodal analgesia. Hopefully, as new generation opioids with improved side-effect profiles and perhaps reduced abuse liability become available,77–79 we will be in a position to determine how best to incorporate them into perisurgical medical practice.
- How do we interface optimally with patients, surgeons, and regulators to promote understanding of the risks of exposure to opioids while assuring their availability as one component of the treatment of perioperative pain? For decades, many fields of medicine including anesthesiology, emergency medicine, surgery, and others have emphasized the use of opioids for severe pain. We now need to change provider beliefs and patient expectations in this regard. We will need to learn how best to implement guidelines and identify factors limiting the adoption of best practices for opioid prescribing.
While medical providers working in many specialty areas are responsible for the management of pain that may involve the use of opioids, anesthesiologists have particularly prominent roles in perioperative and chronic pain management. Our roles in addressing the US opioid epidemic will likely become more prominent as regulatory and political focus on the issue heightens and the role of anesthesiologists in the perioperative surgical home broadens. We are in a position to reduce the excessive use of opioids by educating ourselves, colleagues, and patients. We must promote the evidence-based guideline-compliant prescribing of opioids and reduce demand by limiting perioperative opioid exposure and therefore the risk of developing OUDs. While the challenges posed by the opioid epidemic are formidable, we are also in a position to lead research efforts to generate the information required to optimize the use of opioids in pain management while limiting risks for patients and community members.
The authors thank Ms Morgen Ahearn for her expert editing of this manuscript.
Name: David J. Clark, MD, PhD.
Contribution: This author helped conceive and write major sections of the manuscript.
Name: Mark A. Schumacher, MD, PhD.
Contribution: This author helped conceive and write major sections of the manuscript.
This manuscript was handled by: Honorio T. Benzon, MD.
1. Sites BD, Beach ML, Davis MA. Increases in the use of prescription opioid analgesics and the lack of improvement in disability metrics among users. Reg Anesth Pain Med. 2014;39:6–12.
2. van Amsterdam J, van den Brink W. The misuse of prescription opioids: a threat for Europe? Curr Drug Abuse Rev. 2015;8:3–14.
3. Volkow ND, McLellan AT. Opioid abuse in chronic pain—misconceptions and mitigation strategies. N Engl J Med. 2016;374:1253–1263.
4. Rudd RA, Seth P, David F, Scholl L. Increases in drug and opioid-involved overdose deaths—United States, 2010-2015. MMWR Morb Mortal Wkly Rep. 2016;65:1445–1452.
5. Alem N, Kain Z. Evolving healthcare delivery paradigms and the optimization of ‘value’ in anesthesiology. Curr Opin Anaesthesiol. 2017;30:223–229.
6. Mudumbai SC, Oliva EM, Lewis ET. Time-to-cessation of postoperative opioids: a population-level analysis of the Veterans Affairs Health Care System. Pain Med. 2016;17:1732–1743.
7. Chan FJ, Schwartz AM, Wong J, Chen C, Tiwari B, Kim SJ. Use of chronic methadone before total knee arthroplasty. J Arthroplasty. 2017;32:2105–2107.
8. Rapp SE, Ready LB, Nessly ML. Acute pain management in patients with prior opioid consumption: a case-controlled retrospective review. Pain. 1995;61:195–201.
9. Lee D, Armaghani S, Archer KR, et al. Preoperative opioid use as a predictor of adverse postoperative self-reported outcomes in patients undergoing spine surgery. J Bone Joint Surg Am. 2014;96:e89.
10. VanDenKerkhof EG, Hopman WM, Goldstein DH. Impact of perioperative pain intensity, pain qualities, and opioid use on chronic pain after surgery: a prospective cohort study. Reg Anesth Pain Med. 2012;37:19–27.
11. Zywiel MG, Stroh DA, Lee SY, Bonutti PM, Mont MA. Chronic opioid use prior to total knee arthroplasty. J Bone Joint Surg Am. 2011;93:1988–1993.
12. Angst MS, Clark JD. Opioid-induced hyperalgesia: a qualitative systematic review. Anesthesiology. 2006;104:570–587.
13. Bekhit MH. Opioid-induced hyperalgesia and tolerance. Am J Ther. 2010;17:498–510.
14. Chu LF, Angst MS, Clark D. Opioid-induced hyperalgesia in humans: molecular mechanisms and clinical considerations. Clin J Pain. 2008;24:479–496.
15. Richebé P, Julien M, Brulotte V. Potential strategies for preventing chronic postoperative pain: a practical approach: Continuing Professional Development. Can J Anaesth. 2015;62:1329–1341.
16. Mezei L, Murinson BB; Johns Hopkins Pain Curriculum Development Team. Pain education in North American medical schools. J Pain. 2011;12:1199–1208.
18. Doorenbos AZ, Gordon DB, Tauben D. A blueprint of pain curriculum across prelicensure health sciences programs: one NIH Pain Consortium Center of Excellence in Pain Education (CoEPE) experience. J Pain.2013;14:1533–1538.
21. Substance Abuse and Mental Health Services Administration. Managing Chronic Pain in Adults With or in Recovery From Substance Use Disorders. 2012.Rockville, MD: Center for Substance Abuse Treatment.
22. Crowley R, Kirschner N, Dunn AS, Bornstein SS; Health and Public Policy Committee of the American College of Physicians. Health and Public Policy to Facilitate Effective Prevention and Treatment of Substance Use Disorders Involving Illicit and Prescription Drugs: An American College of Physicians Position Paper. Ann Intern Med. 2017;166:733–736.
24. Egan JE, Casadonte P, Gartenmann T, et al. The Physician Clinical Support System-Buprenorphine (PCSS-B): a novel project to expand/improve buprenorphine treatment. J Gen Intern Med. 2010;25:936–941.
25. Quanbeck A, Brown RT, Zgierska A, Johnson RA, Robinson JM, Jacobson N. Systems consultation: protocol for a novel implementation strategy designed to promote evidence-based practice in primary care. Health Res Policy Syst. 2016;14:8.
26. Trotter Davis M, Bateman B, Avorn J. Educational outreach to opioid prescribers: the case for academic detailing. Pain Physician. 2017;20:S147–S151.
27. Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain—United States, 2016. JAMA. 2016;315:1624–1645.
28. Chou R, Deyo R, Friedly J, et al. Systemic pharmacologic therapies for low back pain: a systematic review for an American College of Physicians Clinical Practice Guideline. Ann Intern Med. 2017;166:480–492.
29. Qaseem A, Wilt TJ, McLean RM, Forciea MA; Clinical Guidelines Committee of the American College of Physicians. Noninvasive treatments for acute, subacute, and chronic low back pain: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2017;166:514–530.
30. Deng Y, Luo L, Hu Y, Fang K, Liu J. Clinical practice guidelines for the management of neuropathic pain: a systematic review. BMC Anesthesiol. 2016;16:12.
31. Moulin D, Boulanger A, Clark AJ, et al; Canadian Pain Society. Pharmacological management of chronic neuropathic pain: revised consensus statement from the Canadian Pain Society. Pain Res Manag. 2014;19:328–335.
32. Bruyère O, Cooper C, Pelletier JP, et al. An algorithm recommendation for the management of knee osteoarthritis in Europe and internationally: a report from a task force of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). Semin Arthritis Rheum. 2014;44:253–263.
33. McAlindon TE, Bannuru RR, Sullivan MC. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartilage. 2014;22:363–388.
34. Chou R, Fanciullo GJ, Fine PG, et al; American Pain Society-American Academy of Pain Medicine Opioids Guidelines Panel. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain. 2009;10:113–130.
35. Franklin GM; American Academy of Neurology. Opioids for chronic noncancer pain: a position paper of the American Academy of Neurology. Neurology. 2014;83:1277–1284.
36. Hegmann KT, Weiss MS, Bowden K, et al; American College of Occupational and Environmental Medicine. ACOEM practice guidelines: opioids for treatment of acute, subacute, chronic, and postoperative pain. J Occup Environ Med. 2014;56:e143–e159.
37. Lall MP. Opioid therapy for chronic low back pain: prescribing considerations for advanced practice registered nurses. J Neurosci Nurs. 2014;46:361–366.
38. Manchikanti L, Kaye AM, Knezevic NN, et al. Responsible, safe, and effective prescription of opioids for chronic non-cancer pain: American Society of Interventional Pain Physicians (ASIPP) Guidelines. Pain Physician. 2017;20:S3–S92.
39. Subera LE, Brandenburg MA, Doran-Redus A, Archer P; Opioid Prescribing Guidelines for Oklahoma Workgroup. Opioid prescribing guidelines for Oklahoma health care providers in the office-based setting. J Okla State Med Assoc. 2014;107:416–430.
40. Trescot AM, Boswell MV, Atluri SL. Opioid guidelines in the management of chronic non-cancer pain. Pain Physician. 2006;9:1–39.
41. Prescription Drug Monitoring Program Training and Technical Assistance Center (PDMP TTAC) at Brandeis University. Available at: http://www.pdmpassist.org
. Accessed April 26, 2017.
42. Gugelmann H, Perrone J, Nelson L. Windmills and pill mills: can PDMPs tilt the prescription drug epidemic? J Med Toxicol. 2012;8:378–386.
43. Rutkow L, Chang HY, Daubresse M, Webster DW, Stuart EA, Alexander GC. Effect of Florida’s prescription drug monitoring program and pill mill laws on opioid prescribing and use. JAMA Intern Med. 2015;175:1642–1649.
44. Bao Y, Pan Y, Taylor A, et al. Prescription drug monitoring programs are associated with sustained reductions in opioid prescribing by physicians. Health Aff (Millwood). 2016;35:1045–1051.
45. Lin DH, Lucas E, Murimi IB, et al. Physician attitudes and experiences with Maryland’s prescription drug monitoring program (PDMP). Addiction. 2017;112:311–319.
46. Wen H, Schackman BR, Aden B, Bao Y. States with prescription drug monitoring mandates saw a reduction in opioids prescribed to Medicaid enrollees. Health Aff (Millwood). 2017;36:733–741.
47. Dreyer TR, Michalski T, Williams BC. Patient outcomes in a Medicaid managed care lock-in program. J Manag Care Spec Pharm. 2015;21:1006–1012.
48. Skinner AC, Ringwalt C, Naumann RB. Reducing opioid misuse: evaluation of a Medicaid controlled substance lock-in program. J Pain. 2016;17:1150–1155.
49. Roberts AW, Farley JF, Holmes GM. Controlled substance lock-in programs: examining an unintended consequence of a prescription drug abuse policy. Health Aff (Millwood). 2016;35:1884–1892.
50. Roberts AW, Gellad WF, Skinner AC. Lock-in programs and the opioid epidemic: a call for evidence. Am J Public Health. 2016;106:1918–1919.
51. Webster LR, Markman J, Cone EJ, Niebler G. Current and future development of extended-release, abuse-deterrent opioid formulations in the United States. Postgrad Med. 2017;129:102–110.
52. Cicero TJ, Ellis MS. Abuse-deterrent formulations and the prescription opioid abuse epidemic in the United States: lessons learned from OxyContin. JAMA Psychiatry. 2015;72:424–430.
53. Cicero TJ, Ellis MS, Kasper ZA. A tale of 2 ADFs: differences in the effectiveness of abuse-deterrent formulations of oxymorphone and oxycodone extended-release drugs. Pain. 2016;157:1232–1238.
54. Keast SL, Owora A, Nesser N, Farmer K. Evaluation of abuse-deterrent or tamper-resistant opioid formulations on overall health care expenditures in a state Medicaid program. J Manag Care Spec Pharm. 2016;22:347–356.
55. Shei A, Rice JB, Kirson NY, et al. Sources of prescription opioids among diagnosed opioid abusers. Curr Med Res Opin. 2015;31:779–784.
56. Kumar K, Gulotta LV, Dines JS. Unused opioid pills after outpatient shoulder surgeries given current perioperative prescribing habits. Am J Sports Med. 2017;45:636–641.
57. Maughan BC, Hersh EV, Shofer FS. Unused opioid analgesics and drug disposal following outpatient dental surgery: a randomized controlled trial. Drug Alcohol Depend. 2016;168:328–334.
58. Hill MV, Stucke RS, McMahon ML, Beeman JL, Barth RJ Jr.. An educational intervention decreases opioid prescribing after general surgical operations. Ann Surg. 2017 Mar 6 [Epub ahead of print].
59. Egan KL, Gregory E, Sparks M, Wolfson M. From dispensed to disposed: evaluating the effectiveness of disposal programs through a comparison with prescription drug monitoring program data. Am J Drug Alcohol Abuse. 2017;43:69–77.
60. Quality CfBHSa, ed. Key substance use and mental health indicators in the United States: Results from the 2015 National Survey on Drug Use and Health. In: NSDUH Series H-51. 2016.Vol. SMA 16-4984. Rockville, MD: Health and Human Services.
61. Ayanga D, Shorter D, Kosten TR. Update on pharmacotherapy for treatment of opioid use disorder. Expert Opin Pharmacother. 2016;17:2307–2318.
62. Lobmaier PP, Kunøe N, Gossop M, Waal H. Naltrexone depot formulations for opioid and alcohol dependence: a systematic review. CNS Neurosci Ther. 2011;17:629–636.
63. Carroll KM, Onken LS. Behavioral therapies for drug abuse. Am J Psychiatry. 2005;162:1452–1460.
64. Mattick RP, Breen C, Kimber J, Davoli M. Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database Syst Rev. 2009:CD002209.
65. Weiss RD, Rao V. The prescription opioid addiction treatment study: what have we learned. Drug Alcohol Depend. 2017;173(suppl 1):S48–S54.
66. Dobscha SK, Morasco BJ, Duckart JP, Macey T, Deyo RA. Correlates of prescription opioid initiation and long-term opioid use in veterans with persistent pain. Clin J Pain. 2013;29:102–108.
67. Edlund MJ, Martin BC, Russo JE, DeVries A, Braden JB, Sullivan MD. The role of opioid prescription in incident opioid abuse and dependence among individuals with chronic noncancer pain: the role of opioid prescription. Clin J Pain. 2014;30:557–564.
68. Sun EC, Darnall BD, Baker LC, Mackey S. Incidence of and risk factors for chronic opioid use among opioid-naive patients in the postoperative period. JAMA Intern Med. 2016;176:1286–1293.
69. Kessler ER, Shah M, Gruschkus SK, Raju A. Cost and quality implications of opioid-based postsurgical pain control using administrative claims data from a large health system: opioid-related adverse events and their impact on clinical and economic outcomes. Pharmacotherapy. 2013;33:383–391.
70. Shah A, Hayes CJ, Martin BC. Characteristics of initial prescription episodes and likelihood of long-term opioid use—United States, 2006-2015. MMWR Morb Mortal Wkly Rep. 2017;66:265–269.
71. Webster BS, Verma SK, Gatchel RJ. Relationship between early opioid prescribing for acute occupational low back pain and disability duration, medical costs, subsequent surgery and late opioid use. Spine (Phila Pa 1976). 2007;32:2127–2132.
72. Helander EM, Menard BL, Harmon CM, et al. Multimodal analgesia, current concepts, and acute pain considerations. Curr Pain Headache Rep. 2017;21:3.
74. Institute of Medicine Committee on Advancing Pain Research, Care, and Education. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. 2011.Washington, DC: Institute of Medicine.
75. Dunn KE, Yepez-Laubach C, Nuzzo PA, et al. Randomized controlled trial of a computerized opioid overdose education intervention. Drug Alcohol Depend. 2017;173suppl 1S39–S47.
77. Manglik A, Lin H, Aryal DK, et al. Structure-based discovery of opioid analgesics with reduced side effects. Nature. 2016;537:185–190.
78. Spahn V, Del Vecchio G, Labuz D, et al. A nontoxic pain killer designed by modeling of pathological receptor conformations. Science. 2017;355:966–969.
79. Violin JD, Crombie AL, Soergel DG, Lark MW. Biased ligands at G-protein-coupled receptors: promise and progress. Trends Pharmacol Sci. 2014;35:308–316.