Acute Pain Management in Patients With Opioid Tolerance

Adebola Adesoye, PharmD, BCPS; Nakia Duncan, PharmD, BCGP, BCPS


US Pharmacist. 2017;42(3):28-33. 

In This Article

Special Populations and Acute Pain Management


Currently, older adults comprise the fastest-growing segment of the world's population. The number of people worldwide aged 65 years and older was estimated at 508 million in 2008, and by 2040 that number will increase to 1.3 billion.[21] With increasing age, the incidence and prevalence of certain pain syndromes also increase. According to the CDC, more than 2.8 million injuries treated annually in emergency departments result from falls.[22]

Older adults are frequently untreated or undertreated for pain.[23] Barriers to effective pain management in older adults include difficulty in adequately assessing pain, underreporting of pain, atypical manifestations of pain, and misconceptions about tolerance and addiction to opioids.[23] Additionally, treatment of acute pain in older adults can be challenging given changes in pharmacodynamics and pharmacokinetics.[23] Older adults have increased fat mass, decreased muscle mass, and decreased body water, all of which have important implications for drug distribution. A predictable age-related decline in CYP450 function plays a major role in drug metabolism. In addition, polypharmacy is a well-known issue in this population. Multidisciplinary and multimodal approaches to treatment are recommended to optimize treatment response without jeopardizing safety. It is also important to consider the frailty of older adults and the risk of falls.

The medication lists of all older adults should be reviewed comprehensively for drug interactions and CNS-altering agents. In 2015, the Beers Criteria were updated to note that opioids should be avoided if the patient has a history of falls and fractures or is taking three or more CNS-active drugs concomitantly, which increases the risk of falls.[24] It is also important to assess renal and/or hepatic function when designing a pain regimen. The maxim "Start low and go slow" should be followed. Perhaps the most important element is to reassess and continue to titrate up or down based on the patient's response, as well as tolerability.

Additionally, an understanding of the different types of pain (nociceptive vs. neuropathic) will guide the use of nonopioids versus adjuvant medications. Adjuvants and topical agents are ideal for geriatric patients to reduce the opioid requirement and associated risks.[23] Table 2 outlines considerations for acute pain management in older adults.[21,24] Using a variety of nonopioid agents can result in favorable outcomes in the treatment of pain in older adults.

Opioid Abuse

Opioid misuse and dependence among prescription-opioid patients continues to rise in the U.S. Opioid addiction is driving this epidemic, with 20,101 overdose deaths related to prescription pain relievers.[25] Clinicians should be aware of factors associated with opioid abuse that can help predict opioid dependence. Boscarino and colleagues, in a study involving patients receiving long-term opioid therapy, found that opioid dependence is associated with five main factors: age <65 years (odds ratio [OR] 2.33, P= .001), depression (OR 1.29, P= .022), psychotropic medication (OR 1.73, P= .006), history of severe dependence (OR 1.85, P= .001), and previous opioid abuse (OR 3.81, P<.001).[26] It is critically important to obtain thorough patient histories in order to be better equipped to detect aberrant behaviors. These risk factors have also been noted to promote perceptions among healthcare providers that can lead to the undertreatment of true pain.

Given the growing epidemic of opioid abuse and misuse, several state boards of pharmacy have implemented prescription-monitoring programs that can help providers identifying aberrant behaviors in the acute-care setting. Additionally, the FDA is encouraging the development of opioid formulations with abuse-deterrent (AD) properties and mixed agonist-antagonist opioids ( Table 3 ) to help combat the opioid epidemic.[27] Formulations with AD properties target the known or expected routes of abuse, such as crushing in order to snort and dissolving in order to inject. However, most of these newer formulations are extended-release (ER) and are more appropriate for patients requiring long-term opioid use. The FDA notes that long-acting and ER opioid formulations are appropriate only for opioid-tolerant patients.[3] ER opioid formulations with AD properties, although usually more expensive than generic opioids, are excellent for managing pain in patients at risk for opioid abuse or misuse.

Long-term Opioid Agonist Therapy

Increasing numbers of patients with opioid addiction are receiving opioid agonist therapy (OAT) with methadone and buprenorphine, and some are receiving OAT combined with naloxone or simply naltrexone alone. (Naloxone and naltrexone are pure opioid antagonists that block all types of opioid receptors; they can be orally administered and have a long duration of action.) As a result, providers will more frequently encounter OAT patients who have developed painful conditions that need effective treatment strategies. Long-term OAT patients are at increased risk for pain undertreatment.[28] NSAIDs and acetaminophen are recommended for treating acute pain; however, if the pain is moderate-to-severe, opioid analgesics may be required for effective control.[28]

Although it is known that opioid-dependent patients have a reduced pain threshold,[28–30] several misconceptions impede effective pain management: 1) maintenance opioids (e.g., methadone) provide analgesia; 2) addiction relapse may occur with the use of opioids for analgesia; 3) respiratory and CNS depression will likely develop with additional opioid use; and 4) reporting of pain may be a manipulation attempt.[28] In reality, many patients are reluctant to take opioid analgesics in legitimate situations because of fear of relapse.[30] It is suggested that the stress associated with unrelieved pain is more likely than adequate analgesia to trigger relapse.[31]

This poses a challenge for acute pain treatment but also creates opportunities for education, which is crucially important for both patients and clinicians. A thorough understanding of the mechanisms of action of agents used to treat pain and to manage addiction is paramount. This is particularly true in patients in opioid-substitution programs. For example, patients on extremely high doses of methadone may receive little benefit from additional opioids because opioid receptors are occupied by methadone, and analgesia from methadone does not last long.[17] However, splitting the daily methadone dose for administration every 8 hours may be considered to achieve analgesic benefit.[17] Another consideration is the use of small doses of methadone as needed in opioid-addicted patients who are currently using illicit opioids to prevent withdrawal symptoms.[17]

Providers should build a relationship of trust with these patients. The patient's pain-management plan should be discussed in a nonjudgmental, reassuring manner. The patient should be encouraged to provide a detailed medication history, including prescribed and illicit drugs, in order to promote effective pain management in acute situations. Also, opioid cross-tolerance and increased pain sensitivity, which likely will lead to higher opioid doses required in shorter intervals, should be assessed. Use of a mixed agonist-antagonist opioid for acute pain management should be avoided because these agents can precipitate acute withdrawal symptoms. Maintenance dosing of methadone or buprenorphine should be continued. Any additional analgesia should be provided using a multimodal approach, including nonopioids such as NSAIDs or IV acetaminophen, adjuvant therapies that enhance opioids' effect, and short-acting opioids.[4,32] Adjuvants include ketamine, which has opioid-sparing effects due to N-methyl-D-aspartate receptor antagonism, and alpha2-adrenoceptor stimulators such as clonidine, to reduce opioid-withdrawal symptoms.[5,28–30,32] Other treatment strategies for patients in opioid-abuse programs are given in Table 4 (available at[30,32]