Opioids: Limited Relief for Acute Pain, Increased Risk of Adverse Events

The commonly held belief that opioids are indispensable for managing acute pain is being challenged by a comprehensive review of existing research. Published in Drugs, the analysis indicates that opioids offer only small, short-lived relief – or are entirely ineffective – for many common acute pain conditions, including certain types of abdominal pain. The use of opioids was linked to an increased risk of adverse events, particularly when used for acute musculoskeletal pain.

Limited Relief, Potential Harms

For decades, pain associations globally have positioned opioids as essential tools for short-term pain management. This perception, according to lead author Christina Abdel Shaheed, PhD, of the University of Sydney School of Public Health in Australia, has fostered a widespread assumption that these drugs are potent pain relievers. “The demand for adequate pain management has not altered over time, and the judicious use of opioid analgesics remains paramount to providing patients with optimal care,” she stated. However, Dr. Abdel Shaheed also emphasized the lack of a comprehensive overview identifying which opioids work for specific acute conditions and where the evidence remains uncertain.

The review, encompassing 59 systematic reviews and meta-analyses of randomized trials since 2010, assessed the efficacy of opioids compared to placebo or no treatment across over 50 acute pain conditions in both adults and young people. The findings suggest a more nuanced picture than previously understood.

Specific Pain Conditions and Opioid Effectiveness

Researchers found high-certainty evidence that oxycodone, morphine, tramadol, and papaveretum provided some reduction in acute abdominal pain at immediate term (within 3 hours) compared to placebo, with a mean difference of 18.4 (95% CI, 31.9 to 5). Moderate-certainty evidence supported immediate pain reduction for 12 other conditions, including pain following myringotomy (ear tube insertion), sciatica, traumatic limb injuries, and dental surgery. For example, opioids reduced pain from myringotomy by a mean difference of 15 (95% CI, 19.6 to 10.4).

However, the evidence was less conclusive for other conditions. Low-certainty evidence suggested potential benefits for labor pain (mean difference of 4.1; 95% CI, 4.6 to 3.6) and post-bunionectomy pain (mean difference of 9.2; 95% CI, 11.4 to 7.1) at immediate term. Notably, the review revealed a surprising lack of trial data for some conditions despite long-standing historical use, such as pain in newborns undergoing therapeutic hypothermia and elective craniotomy.

Perhaps most concerning, the study found moderate-certainty evidence that oral opioids provided only very small pain relief for acute musculoskeletal pain at intermediate term (mean difference of 8.9; 95% CI, 13.5 to 4.3) and simultaneously increased the risk of adverse events (risk difference = 0.1; 95% CI, 0-0.2). The risk of these adverse events also increased when opioids were used for traumatic limb pain (relative risk = 3; 95% CI, 1.9-4.7) and postsurgical pain (relative risk = 1.4; 95% CI, 1.2-1.6).

Increased Awareness of Opioid-Related Harms

This research arrives at a time of heightened awareness regarding the dangers associated with opioid use. The FDA has recently mandated changes to opioid safety labels to better reflect these risks, including overdose, misuse, and death. The current opioid crisis has been significantly influenced by aggressive marketing tactics employed by pharmaceutical companies in the late 20th century, as highlighted in recent legal settlements with Purdue Pharma and the Sackler family.

Implications for Clinical Practice

Study co-first author Josh Zadro, PhD, an assistant professor at the University of Sydney’s Institute for Musculoskeletal Health and School of Health Sciences, explained that while opioids can provide some pain relief for specific conditions like ear procedures, stomach pain, traumatic limb pain, and post-childbirth pain, “the effects are likely to be small or very small and short-lived, thereby challenging the widely held belief that opioids are ‘powerful’ pain relievers for acute pain.”

He further cautioned that opioids “may also be associated with increased risk for harms when used for conditions like acute musculoskeletal pain.” Zadro advocates for a more holistic approach to pain management, suggesting that relying solely on opioids for moderate-to-severe acute pain is unlikely to deliver the desired level of relief. He also pointed out the inconsistencies in opioid efficacy across different conditions and over time, attributing this to variations in trial design and individual patient responses.

Co-first author Stephanie Mathieson, PhD, a senior research fellow at the University of Sydney, noted the surprising lack of data on harms reported in the trials analyzed. “We weren’t surprised to spot that opioids do not provide consistent results over time. This is because of differences in trial conduct and participants’ response to medicines, even for the same pain condition.”

What This Means for Patients

The findings underscore the importance of a careful and individualized approach to pain management. Patients experiencing acute pain should discuss all available options with their healthcare provider, considering both the potential benefits and risks of opioid therapy. Whole-person integrative care, which addresses physical, emotional, and social factors, may offer a more effective and safer approach to managing acute pain for many individuals.

Future Research and Guidance Updates

The researchers identified several areas where further investigation is needed. Specifically, more research is required to determine the efficacy and safety of opioids for conditions where current evidence is inconclusive. Future trials should prioritize the reporting of detailed information on opioid dosages and potential harms. The study’s findings are likely to inform ongoing reviews of clinical guidelines related to acute pain management, potentially leading to updated recommendations regarding the appropriate use of opioid analgesics. The authors can be reached at [email protected] for further information.