Evaluation and Treatment of Postoperative Pain in Patients With Opioid Use Disorder

Background

Because of the dramatic increase in the number of opioid related deaths since 1999, the opioid epidemic was declared a “public health emergency” in the United States on October 26, 2017. The opioid abuse epidemic arose in part from a lack of acknowledgment about the high addiction potential of opioids along with aggressive widespread pharmaceutical company marketing of prescription opioids for both acute and chronic pain treatment in the late 1990s. ^, This led to pervasive opioid diversion, opioid abuse, and a rapid rise in opioid overdoses, leading to over 47,000 people in the United States dying from an opioid overdose in 2017. As seen in Fig. 27.1 , from 2010–2015 the annual number of deaths from prescription opioids remained relatively stable. However, overdose deaths from illicit opioids (heroin followed by high-potency synthetic opioids such as fentanyl) nearly tripled. This large increase in illicit opioid use was driven in part by people prescribed opioids and who subsequently developed opioid use disorder (OUD). ^,

OUD is defined by the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, criteria as having at least two of the criteria illustrated in Table 27.1 . As of 2015, two million Americans aged 12 years or older had an OUD involving prescription opioids, and nearly 600,000 had an OUD involving heroin. Opioid-attributable deaths increased 292% between 2001 and 2016. In 2016, the approximate person-years of lives lost in the United States from opioid-attributable deaths was 1.68 million (5.2 per 1000 population), and opioid overdose was linked to an average of two-thirds of the 175 daily deaths related to all drug overdoses in the United States. The economic burden of prescription opioid abuse in 2013 was estimated to be almost $80 billion. The global burden of disease from opioid related conditions approaches 11 million life-years lost from health problems, disabilities, and early death.

Some patients are at a higher risk of developing OUD, and widely available scoring systems such as the opioid risk tool (ORT) were developed to screen for the likelihood of aberrant behavior. These criteria included a personal history or family history of illicit substance use, comorbid psychological disorder, age between 16 and 45 years, and history of preadolescent sexual abuse ( Table 27.2 ). One study found that patients who were younger, had comorbid depression, used psychotropic medications, and were impaired by pain had a significantly increased risk of developing OUD (odds ratio of eight).

Comorbid chronic pain (CP) and substance use disorders (SUD) are very common. Chronic non-cancer pain (CNCP) is common among patients treated for SUD, and SUD is common among those treated for CNCP. The lifetime prevalence of CP in patients with SUD is over 50% and as high as 75% in those actively treated for SUD. The overall prevalence of current SUD among patients with CNCP is as high as 48%, and the lifetime prevalence of any SUD in those CNCP is as high as 74%. SUD may result from substances used to cope with pain symptoms, and/or substance use-related injury may lead to CP conditions. ^, However, many experts now believe that a diathesis-stress model best explains these comorbidities. Patients have preexisting, semi-dormant characteristics of the individual before the onset of CP, which are then activated and exacerbated by the stress of this chronic condition, eventually resulting in diagnosable psychopathology. Several studies have examined the chronologic relationship between CNCP and SUD with conflicting evidence.

The management of pain in patients with SUD, specifically OUD, has not been investigated in detail. Studies published on the co-management of OUD and CNCP suggest the use of 1) multi-disciplinary care teams, 2) stepped care models, and 3) multimodal treatments with a combination of nonpharmacologic, non-opioid pharmacologic, and buprenorphine or methadone. In 2012, the Center for Substance Abuse Treatment published a thorough set of recommendations for managing CP in patients with SUD based on expert recommendations.

It is critical to understand that the risk of death in adults with SUD is significantly higher than in those without; even patients undergoing SUD treatment have a mortality rate approximately four times that of the general United States population, while those with OUD also have a significantly elevated mortality rate. Even those with OUD and treated with an opioid agonist have a significantly higher death rate from drug abuse and other causes than the general population. Thus in those patients being actively treated for OUD, relapse may be lethal. Clinicians must be aware that pain management in patients with active addiction or in treatment, especially treatment involving opioids, is perilous.

This chapter will review the latest evidence for the management of acute postoperative pain in patients with comorbid OUD. Given the paucity of published evidence on this topic, recommendations from experts in the field and data from the management of perioperative pain alone are extrapolated to the care of patients with comorbid SUD.

Management of Opioid Use Disorder

The Substance Abuse and Mental Health Services Administration (SAMHSA) has determined that the combination of medication assisted treatment (MAT) and cognitive behavior therapy should be used to manage patients with OUD. The three medications approved by the United States Food and Drug Administration for MAT are methadone, buprenorphine, or naltrexone.

The outcomes of MAT treatment in patients with OUD are dramatic; patients who use methadone have retention rates of 60%–84%, ^, and patients who use buprenorphine have similar results. ^, Importantly, mortality rates also decrease with the use of these medications. In a well-cited randomized placebo control trial comparing buprenorphine to a placebo, the placebo group dropout rate was 100% by the second month, with all subjects demonstrating urine samples positive for drug use and mortality rate of 20%. Buprenorphine-treated patients demonstrated a 75% retention rate and a mortality of 0% at one year. A meta-analysis assessing methadone versus buprenorphine treatment for patients with OUD found that subjects who received 8–12 mg/day buprenorphine had 1.26 times the relative risk of discontinuing treatment and 8.3% more positive urinalyses than subjects receiving 50–80 mg/day methadone. However, different dropout rates have been observed with other doses of methadone. For example, patients who receive doses of less than 60 mg of methadone are significantly more likely to drop off treatment than those who received doses of 80 mg or more.

Acute Pain Treatment Goals

The appropriate management of new-onset pain in patients with OUD depends on the origin of pain (i.e. new postoperative acute pain versus acute on chronic exacerbation). As recommended above, management should include a multispecialty approach and multimodal pharmacologic and nonpharmacologic treatments. The goals of treating acute pain in patients with OUD are to prevent withdrawal, provide adequate analgesia, and avoid triggering a relapse if a patient is in recovery (or worsening of the disorder if a patient has active addiction).

The most common causes of acute pain include surgery, fracture, dental work, cuts, and burns. Patients taking opioids to control CP, OUD, or illegitimately should not be intentionally weaned off opioids during an acute pain episode because of the risk of withdrawal and presumed hyperalgesia. A multimodal regimen, including nonpharmacologic therapies, regional anesthesia, and/or non-opioid medications, may reduce the need for additional opioid medications. Continuous regional anesthesia provides superior perioperative analgesia compared to opioid-based management of acute pain and should be strongly considered when possible as part of the multimodal pain management plan for patients who undergo surgery.

Challenges of Postoperative Pain Management in Patients With Opioid Use Disorder

There are many challenges in treating acute pain in patients with OUD, including withdrawal, tolerance, hyperalgesia because of chronic opioid exposure, and comorbid psychological conditions, including the risk of relapse.

Withdrawal. Withdrawal during hospitalization can occur after underdosing inpatient opioids and/or sudden discontinuation of a misused drug if illicit drug use is not known, such as in an unconscious patient or one who voluntarily withholds details of their history. Withdrawal and severity may be diagnosed using the Clinical Opiate Withdrawal Scale ( Fig. 27.2 ) using symptoms such as dysphoric mood, nausea or vomiting, muscle aches, lacrimation, rhinorrhea, pupillary dilation or piloerection or sweating, diarrhea, yawning, fever, or insomnia. The time to onset of withdrawal symptoms depends on the type of opioid used. Short acting opioids such as heroin have an onset of withdrawal at 8–24 h after last use and may last 4–10 days. Long-acting opioids such as methadone have an onset of withdrawal symptoms 12-48 h after last use and may last 10–20 days.

Hyperalgesia. Hyperalgesia is an increased sensitivity to painful stimuli. Patients with OUD report a pain sensitivity increase of 42%–72% compared with controls. ^, The mechanisms of hyperalgesia can be attributed to central activation of N-methyl-d-aspartate (NMDA) receptors and protein kinase C, upregulation of spinal dynorphin, and apoptosis of spinal dorsal horn neurons. Patients with OUD maintained on methadone may be hyperalgesic and cross-tolerant to the anti-nociceptive effects of very high plasma morphine concentrations. Higher morphine doses may achieve pain relief, although there is a risk of respiratory compromise.

Tolerance. Tolerance is thought to involve opioid receptor desensitization, internalization, and downregulation, whereas dependence and withdrawal are primarily because of opioid receptor counter adaptation. Clinically, which is defined as an increasing requirement of a drug to gain the same effect. However, different opioids develop tolerance at different rates and different degrees; this is called differential tolerance. For opioids, the development of tolerance is most profound for analgesia, followed by respiratory depression, and finally peripheral effects such as decreased gastrointestinal motility. Thus patients with OUD will be tolerant to the analgesic effects of opioids but may still have an increased risk of respiratory depression if the pain is treated with opioids.

Psychological Comorbidities. There is a high association of substance use disorder with CP despite the absence of clear-cut directional causality. ^, Patients with CP often have SUD involving other substances such as benzodiazepines, alcohol, and cannabis. CP patients also have a high incidence of psychological comorbidities, including major depressive disorder, anxiety spectrum disorders, post-traumatic stress disorder, and risk of suicide. Data suggests that CP is a significant independent risk factor for suicidality. Predictors of suicidality included frequent intermittent pain, sleep problems, and feeling negative about self-mental health. Interestingly, pain duration, intensity/severity, or type were unrelated to suicide risk.

Evaluation of Patients With Opioid Use Disorder who Present for Surgery

Evaluation of both inpatients and outpatients with OUD is best accomplished using a multispecialty approach, including psychiatry, psychology, social work, physical therapy, and/or pain management specialists. Similar to the evaluation of patients with CP and SUD, patients should undergo a comprehensive assessment that includes their substance use history, whether they have active addiction or are in treatment, their comorbidities (including CP history and psychiatric history), a physical examination, and the patient’s current mental status. A thorough history and physical examination should include prescription-controlled medication use (which should be verified according to the state’s prescription drug monitoring program), the dose of medications taken, use of recreational drugs, pain goals, withdrawal symptoms such as nausea, vomiting, diarrhea, anxiety, and shivering ( Table 27.3 ), and even potentially a urine toxicology screen for controlled and illicit medications. If the patient had a history of CP, the baseline pain intensity at rest and during activity should also be assessed. In patients admitted for non-elective surgical procedures, perioperative (particularly post-surgical) withdrawal symptoms should be anticipated. For patients who will require postoperative pain management with opioids postoperatively, especially those who will be discharged with an opioid prescription, screening for opioid abuse risk may occur. While it is assumed that a history of OUD predicts increased risk, the degree of risk can be further anticipated with a simple screening tool. For example, the “ORT” scores patients based on their family history of substance use, personal history of substance use, age, history of preadolescent sexual abuse, and psychological disease.

Patients With OUD in Remission who Present for Surgery

Patients with OUD in remission and without medication treatment may no longer have signs and symptoms of physical dependence, but will continue to be susceptible to triggers. Triggers for relapse include stress (i.e. surgery) and administration of the agents of abuse (i.e. opioids). Thus these patients are at a particularly high risk of relapse. Anxiety surrounding surgery, perioperative concerns (e.g. financial, social, and/or professional), and postoperative pain are stressors that can trigger drug cravings and relapse, as may poor pain control, if it occurs perioperatively. ^, An acute pain consultation, even prior to surgery, can help with the development of a safe and effective perioperative pain plan, which may include regional anesthesia, multimodal pharmacologic therapy, and discharge planning. Discharge planning may include storage and disposal of unused opioids and enlisting the help of a responsible friend or family member to assist in managing the patient’s opioid use. Overdose prevention education and naloxone prescription should be considered.

Management of postoperative pain in patients with OUD on MAT should start with the continuation of the home medication treatment regimen. Therapy should be based on the degree of expected pain, which depends on the type of surgery and includes, as appropriate, non-opioid adjuvant therapies, regional anesthesia, and nonpharmacologic therapies. Additional opioids can be added, but only when the benefits are deemed greater than the risk. If additional opioids are added, a postoperative tapering plan should be developed to discontinue them after the perioperative phase. Moreover, clear communication should be undertaken with the patient to set expectations and prevent opioid escalation. Multi-disciplinary discharge planning is critical.

Postoperative Pain Management Techniques for Patients With Opioid Use Disorder