Opioid Use Disorders in the Postsurgical Period: A Review of the Past, Present, and Future

Over the past 10 years, addiction to opioid analgesics has emerged as a major issue, recently reaching epidemic status. Many factors have contributed to this trend, including changes in medication-prescribing habits, changes in drug formulations, ease of illegal access to drugs over the Internet, and an overall increase in the number of opioid prescriptions filled annually.(1,2) Every day in the United States, 650,000 opioid prescriptions are filled, with a significant portion of these due to inappropriate prescription by medical professionals.(2) In 2015, 97.5 million patients used prescription pain relievers, representing more than one third (36.4%) of the population older than 12 years of age. In the same year, 12.5 million individuals older than 12 misused pain medications, with 2.1 million of those being first-time misusers of pain medications.(3)

The use of opioids in the treatment of chronic pain is one of the most controversial topics in medicine today.(4) Although opioid analgesic use in acute pain management seems benign, long-term use of opioids for pain management is associated with a clinically significant burden of opioid use disorders.(1) The sale of opioids has increased, in particular for the management of non-cancer pain,(5,6) and many experts have postulated that there is a correlation between this finding and the increase in opioid overdoses and deaths.(7,8) Furthermore, the scant evidence for the long-term efficacy of opioids does not support their widespread use in the management of chronic pain and raises concerns for patients’ greater physical and psychosocial problems.(9)

An inherent difficulty in the study of opioid abuse, chronic opioid use, and opioid misuse is the seeming interchangeability of these and related terms.(4) Terms such as “opioid abuse,” “opioid misuse,” and “opioid dependence” make up a group of distinct disorders that have been described in detail and clearly defined. However, throughout the literature, various definitions of each term may be used, depending on when and where the paper was published and, seemingly, the authors’ preference. For simplicity, this article refers to each of these opioid-related conditions as an opioid use disorder (OUD). An OUD is defined by the CDC as an opioid use pattern that causes significant impairment or distress. Diagnosis of OUD requires fulfillment of specific criteria, such as unsuccessful efforts to reduce or control use, or use resulting in social problems and failure to perform at work, school, or home, among other criteria.(10)

The study of postsurgical pain management is sparse, despite the fact that 51 million Americans have surgery annually,(9) and 80% of these patients experience acute postsurgical pain.(11,12) Furthermore, opioid medications remain a primary modality for postoperative pain relief, with 80% of patients receiving opioids after low-risk surgeries.(9) Many studies have proposed that the postoperative period is a vulnerable time for patients at risk of developing an OUD.(13-15) This vulnerability is the result not only of the re-exposure of some patients who have experienced adverse events related to opioid use in the past (including tolerance, overdose, and misuse), but also to the high number of patients prescribed opioids for the first time after surgery and the high proportion of patients who use opioids for a long duration postsurgically.(9) Many patients who are exposed to opioids postsurgically develop an OUD or experience relapse of OUD. In 2017, Brummett and colleagues(16) reported that general postsurgical patients were at increased risk for chronic opioid use. Although current studies vary in their findings, about 1 in 30 patients exposed to opioids after major surgery continue to use them after three months.(14) Of patients surveyed in orthopedic or neurosurgery clinics of a tertiary academic center, 14.7% reported using opioids without a prescription, in greater amounts, or longer than prescribed, far exceeding the reported national prevalence of OUD amongst U.S. adults.(17) Other sources have cited chronic postoperative opioid use in the surgical population as ranging between 9.2 and 13%.(9)

Reduction of the incidence of OUD has become a national priority and, as a result, there has been a large-scale effort to better define the path that led to the opioid crisis. This has spawned the development of several guidelines from different—and occasionally conflicting—sources regarding best management of the epidemic at several levels. The purpose of this article is to consolidate information regarding the path leading to widespread OUD, as well as summarize guidelines and findings from several recent studies regarding the prevention of OUD in the postsurgical period.

Methods

We used the search terms opioid, postoperative, surgery, addiction, tolerance, abuse, misuse, and opioid use disorder (OUD). Further search terms were adopted as identified in relevant papers. A comprehensive list of databases was accessed, including EBSCOhost, PsychInfo, PubMed, and Medline, with the same terms used to ensure that a representative body of work could be found from articles written within the past 15 years. Due to the specific focus of our study, otherwise relevant articles that focused on pediatric patients or treatment of cancer-related pain were excluded.

To create a comprehensive overview of the opioid epidemic today, we focused our search in several areas:

• The first literature search focused on the history of pain management with opioids from 1980 to today.

• The next search reviewed opioid prescription for pain management after surgeries and their contribution to the opioid epidemic.

• The final search queried the latest literature for proposed solutions to the epidemic from the federal, state, city, hospital, and pharmaceutical levels.

The articles included in this study were chosen to portray the modern history of the use of opioids in the United States and the evolution of their status as a controlled substance (both with regard to their abuse potential and their role in pain management). We focused on the body of knowledge regarding risk factors for developing OUD and the perioperative time period due to the high level of perceived risk during this time. We also chose to review the current established interventions and evidence-based recommendations for management of this epidemic of OUD. We identified 13,174 papers that were topically related to opioid use disorders and then screened them for their relation to postsurgical pain management. A total of 460 relevant papers were identified.

Definitions of Opioid Use Disorders

An inherent difficulty in the study of opioid abuse and misuse is the seeming interchangeability of these and related terms.(4) This adds confusion for medical practitioners when discussing the issue and prevents researchers from efficiently comparing studies for a unified body of research. For simplicity, in this article this group of disorders will be referred to as opioid use disorders (OUD). Some of the relevant terms that are used throughout the literature are presented in the following list, with definitions based on those derived by Denisco et. al.:(18)

• Misuse: Use of a medication (prescribed for a medical purpose) other than as directed or as indicated, whether willfully or unintentionally and whether or not harm results.

• Abuse: Any use of an illegal drug or the intentional self-administration of a medication for a nonmedical purpose such as altering one’s state of consciousness (e.g., “getting high”).

• Addiction: A primary, chronic, neurobiological disease, with genetic, psychosocial, and environmental factors influencing its development and manifestations, characterized by behaviors that include impaired control over drug use, compulsive use, continued use despite harm, and craving, or a combination of these.

• Physical dependence: A state of adaptation manifested by a drug class–specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, or administration of an antagonist.

• Tolerance: A state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug’s effects across time.

These definitions are consistent with the DSM-5 criteria.(19)

History of the Opioid Epidemic

Some sources trace the opioid epidemic to 1980, when a five-sentence letter written by the manufacturer of OxyContin was published in the New England Journal of Medicine stating that, “despite widespread use of narcotic drugs in hospitals, the development of addiction is rare in patients with no history of addiction.”(20) This brief letter subsequently was cited extensively without review or criticism and greatly influenced the prescription patterns of medical professionals as well as patient expectations regarding pain management.(21) However, today’s opioid crisis cannot be attributed exclusively to this letter.

In the 1990s, a new wave of research suggested that patients’ pain was not being managed effectively, driving the demand for better drugs and novel methods to satisfy patients. In one such study, Max and colleagues(22) highlighted the lack of advancement in pain management between 1970 and 1990. This study specifically cited the aforementioned New England Journal of Medicine article and its lack of detail about study methods and revised the recommendations for managing pain.(22) Using Max’s recommendations, the American Pain Society developed quality assurance standards for the relief of acute pain and pain secondary to malignancy, and The Joint Commission announced standards that included the 1-to-10 pain scale commonly used today. (23)

In the following years, The Joint Commission cyclically updated its standards in response to studies claiming that patient pain relief was inadequate, adding pain as the fifth vital sign, calling for compulsory evaluation of pain in all patients, and encouraging use of opioids to relieve pain. In 2000, The Joint Commission officially updated these standards to encourage an initiative for the aggressive treatment of pain.(23) Concurrently, Congress passed a bill establishing the next ten years as the “Decade of Pain Control and Research” in an attempt to formally recognize the apparent problems in pain control.(1)

The failure to address the opioid epidemic at its initial signs allowed it to not only persist, but grow, for more than 18 years.

By 2002, the question was being raised whether physicians had unintentionally crossed a threshold in their attempts to eradicate patients’ pain, leading to The Joint Commission’s withdrawal of many of the standards put into practice during the previous 40 years. In 2002, the 2001 standard of “pain is considered the fifth vital sign in a patient’s care” was changed to “pain used to be considered the fifth vital sign,” and in 2004 the phrase was deleted entirely. In 2009, the requirement that all patients’ pain be assessed was lifted.(23) Despite the withdrawal of many of these standards, the failure of committees and professionals to address the opioid epidemic at its initial signs allowed it to not only persist, but grow, for more than 18 years.(24)

In 2007, long after recognition of the growing number of patients suffering OUDs, OxyContin’s manufacturer and three senior executives pleaded guilty to federal criminal charges, confirming that they misled regulators, doctors, and patients about the risk of dependence and addiction to the medication in their original letter to the New England Journal of Medicine.(21) It was the beginning of an era of scrutiny. Today, the U.S. legislature maintains classes (Class I through V) for categorization of drugs based on their dangerous and/or addictive properties.(25) Opioids are placed in Class II, meaning they have a “high potential for abuse which may lead to severe psychological or physical dependence.”(26) In addition, prescription drug monitoring programs (PDMPs) have been established to record physicians’ and patients’ habits in regard to the writing and filling of prescriptions, respectively, for controlled-substance medications. However, although 49 out of 50 states have such programs, not all are operational, and the differences in reporting patterns, infrastructure, and oversight make it difficult to consolidate data.(25) Of the 49 states that participate, 47 have a physician-accessible PDMP, but 32 do not have an enrollment mandate for physicians. Only eight states mandate prescribers to review the state PDMP prior to prescribing controlled substances. PDMPs, their use, and the variables between PDMPs are discussed later in this article (see Solutions for OUD).(27,28)

In 2015, approximately 58.3 million people in the United States used hydrocodone products, whereas only 828,000 people used heroin.(29) Deaths from unintentional opioid overdose more than quadrupled from 1999 to 2017, and opioid use now is the leading cause of accidental death in the United States.(30,31) The opioid-related death rate has increased by 285%, from 0.7 per 100,000 between 2002 and 2004 to 2.7 per 100,000 between 2011 and 2014.(32) The increased availability of opioids through both legitimate and illicit means results in summation of doses, which can lead to respiratory depression and death. This is particularly problematic in elderly patients, in whom increased sensitivity to the toxic effects of opioids is well established.(1)

Furthermore, approximately $55.7 billion in annual health and societal costs is related to prescription OUDs, with $20 billion in spending due to related emergency department visits and hospitalizations for overdoses, and complications related to intravenous abuse of opioid medications, including cellulitis, abscess formation, bacteremia, sepsis, endocarditis, and osteomyelitis.(33,34) Other side effects, such as opioid-induced hyperalgesia, a phenomenon in which animals who are acutely and chronically exposed to opioids can experience a net increase in pain sensitivity (usually during withdrawal), are becoming more prevalent as opioid use continues to become more widespread.(35) Many more Americans may be experiencing states of dependence in which they require regular dosing of opioid medications to prevent withdrawal and maintain baseline function.

Postsurgical Pain Management

Many patients are first exposed to these controlled substances postsurgically to control acute pain.(18) An estimated 100 million surgical procedures are performed in the United States every year,(36) and 80% of surgical patients experience acute pain postoperatively.(11,12) According to surveys of postsurgical patients by Gan and colleagues,(36) analgesia after surgery has failed to improve between 1993 and 2013, despite advances in pain management and heightened awareness to the under management of pain. These surveys found that the most common presurgical concern for patients was pain, and that 75% experienced moderate or extreme pain during the immediate postsurgical period, and 74% still were experiencing the same level of pain after discharge. Eighty-eight percent of patients receive analgesic medications after surgery, and 39% report moderate to severe pain after receiving their first dose of medication. Of that 88%, 57% prefer nonnarcotic over narcotic pain medications, and 30% fear becoming addicted to narcotic pain medications.

Management of postsurgical pain is an undeniably important part of the postoperative period.

Some sources continue to suggest that postoperative pain relief is inadequate due to the failure to educate patients regarding what to expect and request from medical staff. For example, if a lower level of pain is expected by the patient, it may be reasonable for that patient to request an increased dosage of analgesic medication to lower his or her pain to the expected postoperative pain level. Additionally, it has been suggested that medical and nursing staff require more education pertaining to the prescription and administration of analgesia, especially in relation to individual drug response.(37)

Management of postsurgical pain is an undeniably important part of the postoperative period. Postsurgical pain is not merely uncomfortable for patients—it also carries with it a significantly increased risk for pulmonary and cardiovascular complications. These complications are the most common reasons for delayed discharge and carry significant morbidity and mortality risks for patients. In addition, severe postsurgical pain is the most common reason for unexpected hospital admission after ambulatory surgery, leading to prolonged recovery time and increased risk of chronic pain. Aggressive treatment of postoperative pain may be particularly important for patients with preoperative chronic pain, because they are more vulnerable to complications, particularly postsurgical chronic pain superimposed on their previous chronic pain.(38)

Opioid Use Disorders in the Postsurgical Setting

Although there is a relative dearth of information regarding OUDs in postsurgical patients, it is known that 1 in 30 patients exposed to opioids after major surgery continue to use them after three months.(14) Between 60% and 70% of patients prescribed opioids for the treatment of legitimate pain later use drugs of the same class to get high.(39) Characteristics of preoperative patients that are associated with increased risk of OUD after surgery include valid prescribed opioid use, feared personal risk of drug abuse, and depressive symptoms. Each of these factors independently is more predictive of new-onset OUD than postoperative pain duration or severity.(40) Risk factors for new persistent use of opioid medications after major and minor surgical procedures also echoed risk factors for OUDs seen in the non-perioperative population. These risks include male sex, history of drug abuse, alcohol abuse, depression, benzodiazepine use, or antidepressant use.(41) Notably, patients suffering OUD were shown not only to require higher doses of opioids to control their postsurgical pain but also to report higher levels of pain when compared to their opioid-naïve counterparts.(14)

Due to the high number of patients prescribed opioids for the first time after surgery, and the high proportion of patients who use opioids for a long duration postsurgically, it is likely that many patients who are exposed to opioids for the first-time following surgery will develop OUDs. Sun and colleagues(41) found that, in general, postsurgical patients were at increased risk for chronic opioid use (defined as having filled 10 or more prescriptions or more than a 120-day supply of an opioid excluding the first 90 days after the surgery was performed). All of the surgical procedures studied were found to have an increased risk of chronic opioid use. Furthermore, Brummett and colleagues(16) found that postoperative opioid misuse could not be accounted for based on whether patients underwent minor versus major surgical procedures. Interestingly, this is associated with behavioral and pain disorders in conjunction with the previously cited patient-derived variables of male sex, history of drug abuse, alcohol abuse, depression, benzodiazepine use, and antidepressant use,(41) suggesting that prolonged opioid use in the postsurgical period is due not to surgical pain but, rather, to patient-level predictors.

Current Treatment Regimens and Proposed Solutions for Opioid Use Disorders

Since the beginning of the opioid epidemic in the 1980s, the United States has seen millions of lives lost and billions of dollars discarded due to mismanaged opioid distribution. The initial goal of pain-free living effectively catalyzed the opioid epidemic. In the past 20 years, the problem has accelerated, despite frequent changes in pain management guidelines and advancements in drug formulation. The recent shift in medicine’s focus from pain relief to pain management is an important first step in preventing the next generation from succumbing to the opioid crisis we know today. Unfortunately, the opioid epidemic had become firmly anchored in American medicine by the time this shift was made.

Even though millions of Americans are diagnosed with and succumb to OUD every year, established treatment protocols are fraught with recidivism and relapse. A significant body of research has shown that effective treatment of OUDs can require many years of rehabilitation and that long-term recovery is lifelong. At this time, only three medications (methadone, buprenorphine, and extended-release naltrexone) are approved for the treatment of opioid use disorder. The current optimal care regimen is to couple these medications with psychosocial support to reduce illicit opioid use, relapse risk, and overdoses, while improving social function. The effectiveness of this regimen is limited by inconvenience, cost, and lack of availability to patients who may not be able to relocate for their care.(42) Methadone treatment initially requires patients to come to a dispensing facility every day for weeks to months before they are given multiple doses to take as outpatients at their own discretion. Although as effective as methadone therapy, buprenorphine fails to prevent recidivism at lower doses with the same efficacy as methadone regimens. Both treatment options place significant burden on patients who probably are facing many other struggles resulting from addiction.(43) Furthermore, Smyth and colleagues(44) showed that as many as 91% of patients who seek inpatient treatment for opiate dependence experience relapse, with initial relapse occurring within one week in 59% of cases.

There is a large amount of research concerning OUD in general and in the postsurgical population, with most papers listing their findings in the form of guidelines and suggestions for medical practitioners. However, these guidelines and recommendations have not been translated into policy changes at the federal, state, and hospital levels. Many guidelines are readily available from the CDC and various other organizations. It is beyond the scope of this paper to reiterate these in full. Rather, this article highlights and cites critical issues to consider for a meaningful impact on the opioid epidemic.

Federal Regulations

Federal regulations have the potential to unify drug history databases, implement broader opioid regulations, and provide federal funding for opioid research, recovery programs, and public education. The enforcement of these requirements for state- and city-level guidelines may also play an important role in the response to the opioid crisis.

PDMPs record controlled substance prescription medication writing and filling habits. Although 49 out of 50 states have such programs, not all are operational, and the differences in reporting patterns, infrastructure, and oversight make it difficult to consolidate data.(25) Furthermore, overall utilization of PDMPs is low.(27) A study conducted by the Bureau of Justice Assistance (a division of the U.S. Department of Justice) analyzed 20 state-level PDMPs between 2009 and 2012 and found that the median registration rate for the PDMP program among prescribers licensed to provide at least one controlled substance was 35%, with varying and often disappointing levels of use after registration.(28)

Researchers suggest state PDMPs be consolidated to form a cohesive national database. Creation of a single, nationwide PDMP would follow patients as they cross state lines and form a comprehensive reporting and investigative resource for physicians who use PDMPs.(27)

As a result of low adherence, 22 out of the 49 states that maintain a PDMP now legally require a prescriber to reference the PDMP prior to writing a prescription for a controlled substance, a step many providers view as an unnecessary burden. Implementation of a mandate would require physicians to consider their patients’ history prior to prescription of opioid medications (postsurgically and otherwise) and make changes in treatment plans accordingly.(27)

Overall, research revolving around the usefulness and effectiveness of these statewide PDMPs is controversial. This may explain some hesitance on the part of medical professionals to adopt the PDMP system. Supporters of PDMP systems state that inconsistencies in conclusions from these studies may be due to differences in PDMPs themselves, the laws surrounding the PDMPs, lack of data available to describe the opioid prescription patterns prior to PDMP implementation, and limited use of the PDMP. Nonetheless, most believe that supplying providers with information regarding a patient’s prescription history will lead to the identification of patients who may suffer from an OUD, avoidance of polypharmacy, and a decrease in the amount of opioids available in the nonprofessional market.(27)

We recommend further studies of established state PDMPs for effectiveness and possible integration into health system electronic medical records. Before any such changes are implemented, more research should be conducted on a smaller scale, with close attention paid to control for the issues just discussed. This research could help to tailor a larger-scale program with national and comprehensive coverage.

It has been suggested that some opioid formulations are less compatible with abuse. For example, crush-resistant formulations have been found to have a lower street price than crushable varieties, leading to the conclusion that they are less desirable to persons selling them illegally.(45) Federal funding could allow for research facilitating the creation of more options for pain control that are resistant to misuse and abuse.

Programs such as the Screening, Brief Interventional, and Referral to Treatment (SBIRT), a trial program enforced in 13 states, have created reimbursable ICD10 codes. This gives physicians an incentive to comprehensively screen and treat patients for substance abuse, including opioid use disorders.(46) Federal support could allow formal implementation of the SBIRT at the national level. This could be taken even a step further to allow for the creation of ICD10 codes that reward physicians who screen patients for their risk of developing OUD (risk factors are discussed later in this article).

Population education with regard to risks related to both legal and illegal opioid use has been glaringly inadequate. Public school and general population education need to add more comprehensive education in already required health curriculums to address the many risks of opioid use. Cigarette companies have been in charge of financially supporting anti-smoking ad campaigns since 1998(47)—a similar federal initiative could require the pharmaceutical companies responsible for selling opioids to fund informative ad campaigns about the dangers of misuse of these drugs. Although this is a problem that needs to be addressed on all levels, it is important that it start nationally.

State and City Regulations

Regulation at the state and city level allows for the tuning of programs and interventions to the specific needs of that geographic area. We believe that education of the public, education of physicians, maintenance of prescription narcotic databases, pill recovery programs, and pain clinic oversight are best suited to being managed on the state level.

Education of the public needs to be tailored to the needs of individual states and cities. Some states, such as West Virginia (with an opioid overdose death rate of 35.5 per 100,000 in 2014), may require an extensive public education campaign to counter the huge effect of the opioid epidemic.(33) This education could focus on the signs and symptoms of an opioid overdose, administration of naloxone, prevention of opioid recreational use, and proper storage and disposal of prescribed opioids.(48) This level of jurisdiction also can modify the curriculum of public school drug education programs and health classes to better address the opioid epidemic by appropriate age groups.

As of 2016, only 14 states had implemented any specific continuing medical education (CME) requirements regarding opioid prescribing or pain management.(49) We believe that all states should require physicians to complete some degree of CME regarding the current opioid epidemic, and that an increased amount of continuing education should be required for those with opioid prescription authority, covering:

• Current opioid prescribing recommendations;

• How to assess risk factors for chronic OUDs; and

• The effect of the epidemic in their state.

The amount and frequency of the required hours of education would be scaled to the severity of the opioid epidemic in that state. Each state could work in tandem with the board-certifying bodies of the specialties that are highly involved with pain management or opioid prescriptions to further enforce these CME requirements during recertification.

State legislation can increase the level of detail of regulations over many areas that could modify the course of the opioid epidemic. These might include:

• Support for the creation of a state PDMP that can interface with the national PDMP;

• Restriction of classical opioid formulations and support for abuse-resistant opioid formulations;

• Required risk factor assessment for opioid abuse as part of preoperative assessment; and

• Increased funding for further research on the treatment of OUDs.

In 2009, leftover prescription medications supplied by a friend or family member were responsible for 1.44 million people’s first exposure to opioids.(46) State- and city-supported pill recovery programs with convenient drop-off points in communities (e.g., hospitals, fire stations, health clinics, pharmacies, post offices), coupled with educational campaigns, could have drastically reduced this exposure. In rural locations, where physical drop-off points may be impractical, increased education on proper disposal could help.

There must be more efficient statewide regulation of pain clinics. Some possible approaches would include:

• Establishing evidence-based, tiered guidelines for multimodal pain management;

• Increasing the number of required continued education units for physicians who desire to have opioid prescription authority; or

• Creating a monitoring function of the PMDP to allow for financial incentives for physicians who follow opioid prescription guidelines more than, for example, 90% of the time.

Hospitals, Anesthesiology, and Patient Care Settings

Regulation at the hospital level is uniquely poised to have the highest impact and the greatest flexibility to make vital changes in both the short and long term. This grassroots level of policy will facilitate cooperation with local policymakers and care providers for definitive outcomes and the sustainability of postsurgical pain management. Such reform must include use of alternative pre- and intraoperative analgesia, multimodal pain management, direct patient preoperative education, patient screening, management of established formularies, and creation of local-level awareness campaigns.

Regional anesthesia has been found to decrease opioid requirements, postoperative pain, nausea, vomiting, and sedation, while improving patient satisfaction.

Use of opioid-sparing modalities for perioperative pain management (i.e., alternative intravenous, oral, and local analgesic medications) can significantly affect patient recovery in a manner similar to preoperative cardiac and pulmonary optimization.(50)

Notably, regional anesthesia has been found to decrease opioid requirements, postoperative pain, nausea, vomiting, and sedation, while improving patient satisfaction. Adjuvant medications (intravenous, oral, or transdermal) used either before, during, or soon after surgery have shown some promising pain-modulating and opioid-sparing effects. The adjuvant medications found to attenuate opioid use are dexmedetomidine, clonidine, tizanidine, ketamine, dextromethorphan, duloxetine, lidocaine, esmolol, and caffeine.(50)

Compared with general anesthesia, regional anesthesia (whether lower extremity, upper extremity, truncal, or neuraxial) is associated with improved perioperative analgesia and decreased opioid use; decreased postoperative nausea, vomiting, and patient sedation; and increased patient satisfaction. However, more research in control of rebound pain after regional anesthesia wears off is needed. (50)

Overall, there is a strong need for further research due to the relatively limited research in each modality discussed, especially with regard to effects on long-term opioid use.(50)

The quantity and duration for which opioids are prescribed is directly proportional to the risk of development of opioid abuse or dependence.(51) Current recommendations for the prescription of opioids are based on the “start low and go slow” approach.(52) Other recommendations apply more specifically to postsurgical patients and suggest optimal lengths of opioid-based pain management. Specifically, Scully and colleagues(53) aimed to describe an optimal length of time somewhere between the median prescription length and the early nadir. Their findings were as follow:

• For general surgery procedures: 4 to 9 days;

• For women’s health procedures: 4 to 13 days; and

• Musculoskeletal procedures: 6 to 15 days.

Another study, by Howard and colleagues,(51) sought to define the optimal dose of opioid medication for patients undergoing elective laparoscopic cholecystectomy. Data were collected from patients in a pre-intervention group to discern the optimal prescribed amount for each patient, and then that amount was provided to those patients. Howard and colleagues found that their evidence-based prescription approach lowered prescription size by 63% without increasing the need for refills. Furthermore, patients reported that the smaller prescription size led to decreased consumption of pills. Guidelines and findings such as these should be considered by physicians who may prescribe pain relief post surgically based on narrative evidence or believe that prescribing a hefty amount of opioid medications will allow patients to better control their pain.

Patients should be screened preoperatively for risk factors for developing OUDs.

Multimodal pain management combines different pain management methods, both medical and nonmedical, to manage patient pain. The goal is to provide effective analgesia while reducing the use of opioids and opioid-related adverse effects.(36) Examples include alternative pain therapies such as scheduled pain medications, as-needed pain medications, and nonpharmacologic pain management such as patient education.(54) Patients who have used multimodal pain therapy have “fewer adverse effects, lower pain scores, lower narcotic usage, higher satisfaction scores and earlier physical therapy milestones. Multimodal pain management protocol decreases narcotic usage, improves pain scores, increases satisfaction and enhances early recovery.”(55) This is a pivotal step toward combating the current opioid epidemic.

At the hospital level, physicians must counsel patients on the fact that they will experience postsurgical pain and that the goal is not to eradicate, but rather to manage, their pain at a reasonable level. This goal can be achieved through balance of preventing the physical effects of severe pain (e.g., tachycardia, hypertension, and pulmonary compromise) with the risks of adverse effects from analgesic medications.(38) Furthermore, patient anxiety about postsurgical pain must be addressed by their care team, because studies show that increased presurgical anxiety is associated with increased postsurgical pain and consequent increased need for pain medication.(36)

Patients should be screened preoperatively for risk factors for developing OUDs, and individualized pain management regimens should be developed accordingly. Many tools are available for assessing the risk that a patient may become addicted to opioids, including:

• The Opioid Risk Tool (ORT);

• The Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R); and

• The Brief Risk Interview (BRI).

Unfortunately, due to the limited amount of significant research, a clinically recognized gold standard test to evaluate this risk has not yet been identified. The current CDC recommendation is that all physicians exercise caution when prescribing opioid medications for chronic non-cancer pain (except for those used for palliative or end-of-life care). The CDC is wary of the possible overestimation of the efficacy of existing OUD risk assessors’ ability to rule out the risks related to opioid prescriptions in individual patients. (56)

The CDC suggests that the most important risk factor to be assessed before opioids are prescribed is a history of substance abuse.(56) To curtail patient self-reporting errors and omissions, urine drug testing may be useful in objectively deducing which patients use drugs. Under-reporting is a major contributor to the risk of developing an OUD postsurgically. To further encourage this reimbursable intervention, hospitals must educate their physicians on the ICD10 codes for opioid screening and for counseling opioid-misusing patients.

Other risk factors for developing addiction to all substances, including opioids, have been extensively researched. The phenotypic factors predictive of opioid addiction include age between 16 and 45 years, alcohol abuse history, illegal drug abuse history, prescription drug abuse history, and a history of mental health disease, including attention deficit disorder, obsessive compulsive disorder, bipolar disorder, and schizophrenia.(31) In fact, 45.3% of patients who chronically use opioids have a diagnosis of some mental illness, and 7.6% have previously been given a non-opioid substance abuse diagnosis.(51) Alternatively, it has been suggested that substance abuse and mental health disorders often are comorbid, leading some experts to suggest preexisting mental health disease may have not a causative effect but, rather, a high evidence of comorbidity. It has been suggested that any causative relationship between the two variables is due primarily to attempts to self-medicate.(51)

Young, white men are more likely to abuse prescription drugs than their counterparts.(39) Reduced hours of sleep is another risk factor that has been associated with opioid abuse.(9) Edlund et al.(51) reported that many chronic conditions may put patients at risk of prolonged opioid use, including arthritis, non-arthritic back pain, and (in a minority of patients) headaches.

Patients who report more severe pain and more serious limitation of activity due to pain also are more likely to develop an OUD. Additionally, patients with a tendency to catastrophize pain (i.e., “a mental set related to pain that is characterized by feelings of helplessness and persistent unrealistic beliefs about pain and its consequences”(9)) are more vulnerable to opioid misuse.

Some genetic markers have been isolated that are thought to increase the propensity for either drug abuse generally or heroin (opioid) addiction in particular, as follows:

• Catechol-O-methyltransferase (COMT), SNP marker rs4680 has been associated with alcohol and drug abuse;

• Dopamine DI receptor (DRD I), SNP marker rs4532 and Opioid receptor Mu 1 (OPRMI),

• SNP marker rs1799971 have been associated with heroin addiction; and

• Serotonin receptor 2A (HTR2A), SNP marker rs7997012 has been associated with drug abuse and depression.(31)

An individualized and dynamic exit strategy must be created for each patient (and discussed with that patient) and clearly established for each pain management case upon initiation of opioid-based therapy. The exit strategy should consider the patient’s goals as well as his or her individual risk factors.

The inclusion of a pharmacist is integral to a functioning pain management team. Pharmacists’ contributions enhance patient care with their intimate knowledge of the local formulary and obscure options for complementary care while avoiding drug interactions. They may suggest use of multimodal pain control via non-opioid analgesics or alternate-mechanism-of-action medications for patients’ pain. As a part of the care team, pharmacists will be expected to strictly adhere to updated, tiered guidelines and work closely with physicians to offer their expertise in managing patients’ pain.

Pharmaceutical Companies

Pharmaceutical companies have long faced scrutiny for their role in the development of the opioid epidemic.(20) Government officials have claimed that pharmaceutical companies oversaturated the market with opioid drugs while failing to control against misuse and diversion. This is reminiscent of firearm manufacturers who were accused of knowing that many of their guns would fill demand on the black market.(57)

Litigation to change industry practices and build public awareness began in the early 2000s but has increased in frequency in recent years. In most states, a drug manufacturer’s duty to warn about risks related to a drug is only to issue a warning to prescribers, who are then responsible for communicating these risks to patients. Many pharmaceutical companies have been charged with making misleading claims regarding the lack of addictive properties of opioid medications or overstating the safety of these drugs.(57) Many argue that public education, similar to that which resulted from litigation surrounding tobacco products, should be enforced as a penalty for the spread of false information from pharmaceutical companies.

The government has claimed injury and seeks restitution for the rebuilding of social systems damaged by the opioid epidemic. Funds from several government suits have been instrumental in providing OUD treatment to communities and also have provided support to law enforcement.(57)

Pharmaceutical companies could contribute to decreasing the impact of the opioid epidemic by developing additional formulations that include safety mechanisms such as an antagonist agent or tamper-resistant formulation and encouraging their use at the level of the prescriber.(57)

Conclusion

The postsurgical period is a vulnerable time for patients who are at risk for developing OUDs, despite the strides forward that have been made since the pain eradication goals of the 1990s. The potential for abuse of opioids is now better understood, regardless of the reason for first exposure. However, more research in this field must be conducted. We recommend vigilance on the part of physicians when prescribing opioids and education of patients regarding the potential for developing an OUD connected with the management of postoperative pain. Issues regarding OUDs in the postoperative period should be confronted, including preoperative risk screening and a tiered pain management approach, with interdisciplinary teams using multimodal approaches to pain control. On a broader front, creation and use of a national PDMP and creation of non-crush opioid medications also may prove useful.

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