Excerpts

several recent converging lines of evidence point to the possibility that maladaptive inflammation due to perioperative use of anti-inflammatories, such as dexamethasone or nonsteroidal anti-inflammatory drugs (NSAIDs), may contribute to the development of this chronic postsurgical pain.

the use of NSAIDs early in low back pain has been shown to contribute to pain chronicity. Thus, there may also be disadvantages to reducing inflammation. The use of anti-inflammatories for acute pain has increased with the recent clinical desire to accelerate discharge from hospital, and reduce the use of opioids in perioperative and acute pain scenarios.8 For these reasons, the routine use of anti-inflammatories such as ketorolac and dexamethasone is a strong recommendation by the Enhanced Recovery After Surgery® Society in many surgical subtypes.

While strong evidence shows that this approach is efficacious in reducing opioid use and speeding time to discharge,9 there has been little attention paid to potential long-term consequences of their use. This is partially by system design: with multiple clinical specialties involved in care, the anesthesiologist responsible for perioperative pain control often does not participate in long-term follow-up of their patients, and thus is unable to identify that a problem exists. Study follow-up is often too short to identify the presence of chronic pain, which may or may not be a focus of the studies in any case. This has resulted in limited research prospectively examining the effects of perioperative interventions on long-term pain outcomes

recent studies and meta-analyses have also reported that NSAID or steroid use is associated with increased chronic pain postoperatively.

Altering the early neutrophil response can have significant downstream consequences. Among the first cells recruited to the site of injury/disease, neutrophils are known to control the recruitment and activation of other cells including macrophages and T cells peripherally, and glial cells centrally. Use of high-dose steroids or NSAIDs has been shown to alter neutrophil degranulation and macrophage polarization. This altered polarization is hypothesized to lead to the inability to fully resolve acute inflammation, and the subsequent development of chronic pain. Additionally, and potentially more important for chronic pain development, neutrophils have been shown to contribute to neuronal survival and axon regeneration, suggesting proregenerative neutrophil function promoting repair in peripheral nerves and the spinal cord.

Accumulating scientific evidence suggests potential negative long-term consequences with the use of NSAIDs and steroids; however, these findings are not uniform. Thus, there is equipoise on the topic that would support the value of high-quality, multisite randomized trials including not only clinical outcomes but also physiologic observations to more fully characterize the issues at hand, bringing us closer to true personalized medicine in the perioperative field.

Citation

Clinkard, D., Buckley, N., Diatchenko, L. et al.The role of acute inflammation in pain resolution: is it time to rethink the use of routine anti-inflammatories in surgical practice?. Can J Anesth/J Can Anesth 71, 1349–1352 (2024). https://doi.org/10.1007/s12630-024-02837-8

Link to Full Article