Challenges and opportunities to change the course of the opioid epidemic: a surgeon’s perspective

KEYWORDS:

• Analgesics, opioid
• combined multimodal therapy
• opioid-related disorders
• pain, postoperative
• prescription drug diversion
• prescription drug misuse

The US opioid epidemic is a public health crisis. Approximately 78 Americans die every day from opioid-related overdoses and prescription opioids are involved in at least half of those deaths [1]. It appears the current crisis may be an unintended consequence of well-intentioned initiatives designed to raise clinicians’ awareness of the problem of inadequate pain management and encourage more aggressive treatment of pain. In the 1990s, the phrase ‘pain as the 5th vital sign’ was coined by the American Pain Society to bring pain management to the forefront of routine patient care [2]. In 2000, Congress declared the next 10 years to be the ‘Decade of Pain Control and Research,’ to encourage advances in pain research and treatment [3]. In 2002, the Centers for Medicare & Medicaid Services and the Agency for Healthcare Research and Quality established the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey of patient satisfaction to improve transparency and develop accountability for the quality of pain management and other aspects of care provided during a patient’s hospital stay [4]. The HCAHPS survey is part of a ‘pay for performance’ model used to calculate reimbursements to hospitals [4]. As a result of heightened awareness and accountability, ‘titrating opioids to effect’ through use of pain rating scales has become the standard of care for pain management. More subtle internal influences, such as pressure to gain favorable HCAHPS patient satisfaction scores and the desire to avoid unfavorable patient ratings and negative comments on web-based physician-rating sites, have also played a role in changing the culture of pain management during the past 20 years. These factors, along with an absence of adequate patient education and insufficient provider knowledge regarding risks of overreliance on prescription opioids, have swung the pendulum from one extreme—the perception that pain should be treated more aggressively, to the other—the exponential increase in demand for opioids that has resulted in the current health-care crisis. Between 1997 and 2007, the average per-person opioid supply in morphine equivalents increased by 700% in the United States [5]. As clinicians, we are now charged with finding ways to achieve good pain management while minimizing opioid use.

Overall, 99% of US surgical patients are given postsurgical opioids [6], an indicator of the current overreliance on opioids. Opioid exposure, even in opioid-naïve surgical patients and when appropriately prescribed for short-term use, puts patients at risk for long-term opioid use [7–9] and abuse [10]. Some of the most commonly performed surgeries (total hip arthroplasty, total knee arthroplasty, laparoscopic or open cholecystectomy, open appendectomy, cesarean delivery, and simple mastectomy) are associated with an increased risk of chronic opioid use [8].

The problem of opioid abuse has prompted pharmaceutical manufacturers to develop abuse-deterrent opioid formulations that are less rewarding or more difficult to use for nonmedical purposes [11]. For example, the current formulation of OxyContin® (extended-release oxycodone) is more difficult to break, dissolve, or crush than the original formulation [11]. Some abuse-deterrent formulations, such as OxyContin, Hysingla® ER (extended-release hydrocodone), and Zohydro® ER (extended-release hydrocodone), form a gel if they are dissolved so they cannot be easily injected through a hypodermic needle [11]. TRV130 (Trevena, Inc, King of Prussia, PA) is a G-protein-biased ligand of the μ-opioid receptor that is being developed for intravenous use as an alternative to fentanyl and morphine [12,13]. TRV130 provides potent analgesia with reduced gastrointestinal and respiratory dysfunctional effects compared with morphine [13].

In 2014, the Drug Enforcement Administration (DEA) rescheduled hydrocodone combination products—the most frequently prescribed opioids—from schedule III to the more restrictive category of schedule II in response to the increasing misuse and diversion of prescription opioids [14]. Ironically, this ruling, which made hydrocodone more difficult to prescribe, may have further contributed to misuse and diversion. Surgeons became more likely to prescribe larger quantities of opioids and/or more refills than needed because of the DEA’s new restrictions on the physicians’ ability to call in opioid prescriptions to pharmacies. Overall, this change in prescribing patterns has produced an accumulation of surplus pills, which facilitates misuse, development of long-term opioid use, and diversion. A 2013 study surveyed 48 patients undergoing wisdom tooth extraction: all 48 received an opioid prescription (median, 20 tablets), and on follow-up, all respondents reported they had leftover medication (median leftover amount, 12 tablets). None reported discarding unused opioid tablets [15]. Efforts to limit inappropriate use of prescription opioids, including policies aimed at restricting diversion and the development of abuse-deterrent opioid formulations, may also have partly contributed to a shift toward heroin use in some individuals with dependence on prescription opioids [16,17]. Because the increase in heroin use pre-dated the implementation of these efforts, however, other factors, including heroin accessibility and price, probably played a larger role in the transition to heroin use [17]. Although additional research is needed to better understand the effects of initiatives to reduce overprescribing and prescription opioid abuse on heroin use [18], it is generally agreed that nonmedical use of prescription opioids is a strong predictor of future heroin use [16,17], with the majority of heroin users reporting that they used prescription opioids for nonmedical purposes before they started using heroin [16].

Use of multimodal analgesic regimens has become a key tool for expediting movement away from opioid-centric prescribing practices for postsurgical pain management. Since postsurgical pain involves multiple pain pathways in both the central and peripheral nervous systems, a multimodal analgesic approach targeting various pain pathways should be more effective than an approach that relies on a single modality [19,20].

The opioid-sparing effects of multimodal analgesia can also reduce the potential for opioid-related adverse events (ORAEs)—a problem that affects one of seven surgical patients exposed to opioids [6]. Some ORAEs, such as nausea, vomiting, or constipation, may seem relatively routine for postsurgical patients but these side effects can have considerable economic and clinical impact [6], and should be avoided, if possible. A large retrospective cohort study showed that patients with ORAEs have 55% longer hospital stays, 47% higher hospitalization costs, 36% higher risk of 30-day readmission, and 3.4-fold higher risk of inpatient mortality compared with patients without ORAEs [6]. The opioid-sparing effects of multimodal analgesia may also reduce the risk of development of opioid-induced hyperalgesia, a phenomenon that is usually associated with patients receiving chronic opioid therapy [21], but can also occur in surgical patients who receive high intraoperative doses of opioids during the perioperative period [22]. In a prospective study, adult patients undergoing open colorectal surgery who received a high-dose infusion of remifentanil and desflurane had more intense postsurgical pain and greater postoperative opioid consumption than patients who received a low-dose infusion [22]. Similar results were observed in another prospective study in women undergoing total abdominal hysterectomy who received a high-dose fentanyl infusion compared with those who received low-dose fentanyl [23].

Pharmacologic agents used in multimodal analgesic regimens for common surgical procedures often include a combination of opioids with nonopioid agents such as acetaminophen, nonsteroidal anti-inflammatory drugs, pregabalin, gabapentin, and intravenous ketamine [20,24]. The regimen should be tailored to the procedure, patient, and setting [20]. In some surgical settings, such as laparoscopic cholecystectomy, laparoscopic sleeve gastrectomy, bariatric surgery, and renal tuberotomy, the successful use of multimodal analgesia that included agents such as dexmedetomidine, propofol, ketamine, and local anesthetics has achieved opioid-free pain management [25–29].

Current clinical practice guidelines recommend the use of multimodal techniques, including use of long-acting local anesthetics whenever possible [20,30]. The duration of action of traditional local anesthetic formulations can be extended via use of continuous infusion pumps or use of a prolonged-release formulation of bupivacaine (bupivacaine liposome injectable suspension; EXPAREL®, Pacira Pharmaceuticals, Inc., Parsippany, NJ), which has been shown to provide up to 72 h of postsurgical analgesia and reduce postsurgical opioid consumption compared with placebo and bupivacaine HCl [31–33].

Until about 10 years ago, opioids were not usually prescribed for postsurgical analgesia following low-risk procedures, such as hernia, podiatric, dental, or minor skin surgery. Since then, prescribing of opioids to control pain after those procedures has increased, despite availability of effective, opioid-sparing, multimodal analgesic regimens. Opioid-naïve patients who undergo minor surgical procedures associated with relatively low levels of postsurgical pain (e.g. cataract surgery, laparoscopic cholecystectomy, prostate resection) and are given opioids postsurgery are 44% more likely to become chronic opioid users compared with those not given opioids [7]. In some cases, opioid prescribing not only continues but also escalates to higher-potency opioids [7]. The effect of unnecessary opioid use for minor surgeries is exacerbated by the fact that low-risk surgeries are far more common than higher-risk surgeries, and the number of ambulatory, same-day surgeries is growing because of medical advances in noninvasive and minimally invasive procedures [34]. Analgesic efficacy can vary depending on surgical procedure type and pain intensity; in some cases, aggressive use of opioids may be warranted [35]. Nevertheless, a one-size-fits-all, opioid-centric approach to controlling postsurgical pain may represent a missed opportunity to reduce ORAE risk and minimize opioid exposure.

We, as clinicians, should do what we can to manage first-time exposure to opioids whenever possible, given the difficulty in weaning patients from chronic opioid use [36]. Preventing initial exposure to opioids should be considered whenever possible and is particularly warranted for minor surgical procedures in which nonopioid modalities can provide effective postsurgical analgesia. Patients with preexisting psychiatric comorbidities or family histories that genetically predispose them to developing opioid dependence would also benefit from opioid-sparing analgesic strategies. There is a significant association between postsurgical chronic opioid use and presence of psychiatric comorbidities; however, additional research is needed to better understand factors that predict opioid dependence [8,9]. In some cases, risk factors in the patient’s history might be unknown. Preventing initial exposure to opioids when pain can be successfully managed with other modalities would render these unknowns inconsequential in postsurgical pain management.

Motivation to curtail opioid prescribing or discuss opioid therapy with patients is sometimes mitigated in cases where patients are not reluctant to use opioids or even insistently request that opioids be prescribed. Through discussions to set achievable goals for pain management, present options for alternatives to opioids, and review benefits and risks of opioid therapy [20,36], we can help patients and their families understand the benefits of a balanced approach. Furthermore, should an opioid prescription be needed at discharge, reviewing appropriate disposal is also important [20]. Educational initiatives for clinicians are needed to address knowledge deficits and additional strategies to reduce overreliance on opioids should be explored, including implementation of user-friendly checklist decision aids, fact sheets, and smartphone apps for clinicians. The Centers for Disease Control and Prevention is implementing these tools to support its guideline for the prescribing of opioids for chronic pain [36]. A corresponding guideline focusing exclusively on the prescribing of opioids for acute postsurgical pain has not yet been developed. However, guidelines on management of acute postsurgical pain are available [20,30] and recommend use of multimodal analgesic regimens whenever possible [20,30].

Improved data sharing and collaboration between surgeons, anesthesiologists, and primary care physicians regarding pain management is also necessary. As a group, surgeons, anesthesiologists, pain specialists, and primary care specialists provide the majority of pain-related care in the United States [37,38]. Since primary care specialists are closer to their patients and know their patients better than any other clinician, the primary care community has the greatest opportunity to make a meaningful improvement in the approach to pain management. During transfers of care, primary care specialists should have the patient’s prescription history and other relevant information to refer to when the patient requests refills for postsurgical opioids. Primary care specialists are often put in the position of being a ‘catch-all,’ responsible for managing pain in patients who were started on an opioid regimen by non–primary care specialists. Collaboration between primary care specialists, surgeons, and anesthesiologists is needed to formulate cohesive plans for multimodal therapy throughout the continuum of care.

Clinicians practicing in the acute care setting have a unique opportunity to help curb the opioid epidemic. A concerted effort to curtail unnecessary reliance on opioids through use of multimodal analgesic approaches to pain management will not only help to optimize patients’ recovery, but could mitigate negative downstream effects of the prescription opioid crisis that currently plagues our country. Moreover, education for both providers and patients can help to reduce overreliance on opioids. Lastly, clear communication between providers in the acute setting, particularly during transitions of care, can help ensure appropriate postsurgical pain management of patients after hospital discharge, especially those at risk for misuse or abuse of prescription opioids.

Declaration of interest

GJ Mancini is a consultant for Medtronic, Intuitive Surgical, and Pacira Pharmaceuticals, Inc. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Acknowledgments

Writing assistance, provided by Michael D Morren, RPh, MBA (Peloton Advantage, LLC), was utilized in the writing of this manuscript and funded by Pacira Pharmaceuticals, Inc. The author was fully responsible for the content, editorial decisions, and opinions expressed in the current article. The author did not receive an honorarium related to the development of this manuscript.

Additional information

Funding

This article was funded by Pacira Pharmaceuticals, Inc.