Acute pain management in hospitalized adult patients with opioid dependence: a narrative review and guide for clinicians

Up to 40% of Americans experience chronic pain of some kind.¹ In the United States, opioid analgesics are the most prescribed class of medications,² with 245 million prescriptions filled in 2014 alone. Thirty-five percent of these prescriptions were for long-term therapy.³ It is now apparent that opioid pain medication use presents serious risks. In 2014, 10.3 million persons reported using prescription opioids for nonmedical reasons.⁴ Between 1999 and 2014, more than 165,000 people in the United States died of overdose related to opioid medication.⁵ In addition, heroin use in the United States has increased over the past decade.⁶ Opioid agonist maintenance therapy is also increasingly used to treat patients with opioid use disorder.

Given the prevalence of opioid use in the United States, it is important for hospitalists to be able to appropriately and safely manage acute pain in patients who have been exposed long-term to opioids, whether it is therapeutic or non-medical in origin. Although nonopioid medications and nondrug treatments are essential components of managing all acute pain, opioids continue to be the mainstay of treatment for severe acute pain in both opioid-naïve and opioid-dependent patients.

Given the paucity of published trials meeting the typical criteria, we did not perform a structured meta-analysis but, instead, a case-based narrative review of the relevant published literature. Our goal in performing this review is to guide hospitalists in the appropriate and safe use of opioid analgesics in treating acute pain in hospitalized patients who are opioid-dependent.

When managing acute pain in patients with opioid dependence it is important to have a clear understanding of the definitions related to opioid use. Addiction, physical dependence and tolerance have been defined by a joint consensus statement of the American Society of Addiction Medicine, American Academy of Pain Medicine, and American Pain Society⁷: Addiction is a primary, chronic, biological disease, with genetic, psychosocial and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving.

Physical Dependence is a state of adaptation that is manifested by a drug class specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist.

Tolerance is the 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 over time.

Opioid use disorder (OUD) is defined as a problematic pattern of opioid use leading to clinically significant impairment or distress with symptoms including a strong desire for opioids, inability to control or reduce use of opioids, continued use despite adverse consequences, and development of tolerance and withdrawal symptoms.⁸

Physical dependence and tolerance are common consequences of long-term opioid use. In contrast, OUD has been reported to affect only 2% to 6% of individuals exposed to opioids.⁹ The underlying mechanisms that lead an individual to abuse or become addicted to opioids largely due to the effects opioids have on endogenous μ-opioid receptors. As analgesics, opioids exert their effects by binding primarily to these μ-opioid receptors, with a large concentration in the brain regions regulating pain perception.^10,11 There is also a large concentration of μ-opioid receptors in the brain reward regions, leading to perceptions of pleasure and euphoria. Repeated administration of opioids conditions the brain to a learned association between receiving the opiate and euphoria.^12,13 This association becomes stronger as the frequency and duration of administration increases over time, ultimately leading to the desire or craving of the opioid’s effect.