Evidence gap for acute pain outcomes in opioid use disorder

1. In this systematic review, evidence for the efficacy of acute pain interventions on individuals with opioid use disorder was generally limited.

2. Studies involving individuals already on buprenorphine showed that continuing the agent during episodes of acute pain may reduce pain severity.

Evidence Rating Level: 2 (Good)

Study Rundown:  Effective management of acute pain episodes among individuals with opioid use disorder (OUD) can be challenging due to the potential for increased opioid tolerance and opioid-induced hyperalgesia. Individuals with OUD are often on pharmacologic treatment with agents such as buprenorphine, methadone, and suboxone, whose activity on the μ-opioid receptor can further complicate acute pain interventions. Current clinical guidance on the management of acute pain in individuals with OUD is generally informed by expert opinion, and many practitioners continue to endorse lack of knowledge and confidence in navigating these clinical scenarios. Hence, this systematic review aimed to synthesize and analyze the available evidence on the benefits and risks of acute pain interventions among persons with OUD, including those on pharmacologic management. The review demonstrated a significant evidence gap on the effect of acute pain interventions on pain outcomes in individuals with OUD. Among individuals already on buprenorphine, continuing the agent during episodes of acute pain generally appeared to render lower or similar pain severity versus discontinuation. However, evidence regarding acute pain interventions among people prescribed methadone was insufficient to assess their effectiveness, and there were no comparative studies evaluating pain or OUD outcomes among adults prescribed naltrexone. For people not on any pharmacologic management for OUD, agents such as oral clonidine, intramuscular (IM) haloperidol and IM midazolam with intravenous (IV) morphine were associated with improved pain outcomes. The results of this review were limited by a high contribution from observational evidence and a reliance on comparative data collected before the current era of high-potency synthetic opioids. Overall, this study described the limited characterization of acute pain management in patients with OUD.

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Relevant Reading: Acute pain and self-directed discharge among hospitalized patients with opioid-related diagnoses: a cohort study

In-Depth [systematic review]: This systematic review investigated the evidence on the benefits and harms of acute pain interventions among individuals with OUD. Studies of any design including persons 18 years of age or older with OUD and evaluating pain or OUD outcomes were included. Overall, 115 articles were included in the final review, including 17 clinical trials, 20 controlled observational studies, 24 uncontrolled observational studies, and 54 case reports. A total of 12 retrospective cohort studies conducted in the United States assessed a pain-related outcome in individuals on buprenorphine for OUD. Among 10 controlled cohort studies evaluating pain severity, 6 found that post-operative pain scores were lower among those who continued sublingual (SL) buprenorphine while 4 found no difference between continuation and discontinuation. Among 12 cohorts comparing the use of opioid analgesics as an outcome, 7 found that those who continued SL buprenorphine received lower full-agonist opioid doses while the other 5 found no difference. There were only single comparative studies on acute pain interventions among individuals with OUD on methadone, which was insufficient to assess effectiveness. However, there were 16 randomized-controlled trials (RCTs) including adults with OUD not on pharmacologic treatment evaluating 14 acute pain interventions, with most of these studies being conducted in Iran. One RCT assessing acute pain due to orthopedic fracture showed oral clonidine may decrease pain severity and opioid use. Another RCT assessing acute limb or abdominal pain showed the combination of IM haloperidol and IM midazolam with IV morphine may improve pain outcomes compared to morphine alone. Moreover, another RCT demonstrated that intraoperative IV lidocaine may decrease post-operative pain severity versus IV ketamine or placebo. Overall, more evidence is needed to better elucidate the efficacy of acute pain interventions on individuals with OUD.

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