What to do when clinical trials are lacking? Pharmacokinetic-guided treatment of nonsteroidal anti‑inflammatory drugs for painful chronic wounds

What is it about?

Regarding systemic analgesic treatment for painful chronic wounds, current guidelines recommend following the WHO analgesic ladder. However, to the best of the author’s knowledge, clinical studies supporting this recommendation are lacking. From a pharmacokinetic perspective, the main problem is the prescription of nonsteroidal anti-inflammatory drugs (NSAIDs) as first-line analgesics for all types of wounds, including those with poor blood supply. NSAIDs are primarily local acting agents and must reach the site of inflammation to produce their main clinical effect by inhibiting the cyclooxygenase-2 enzyme. The intensity of the analgesic effect would be compromised in wounds with any degree of ischemia in which blood supply is reduced, as the drugs would be unable to adequately reach their pharmacological target. In contrast, NSAIDs are always able to target and inhibit the cyclooxygenase-1 enzyme, which is responsible for their well-known adverse effects. Therefore, the risk-benefit balance of NSAIDs would be unbalanced in favor of risk in ischemic wounds. In general, it is clear that clinical trials are needed to determine the role of NSAIDs and other systemic analgesics in the treatment of different types of wounds. In particular, the role of NSAIDs as systemic analgesics in poorly perfused wounds should be addressed. Meanwhile, clinicians should guide analgesic treatment with NSAIDs based on their clinical judgement and, where possible, perhaps with the support of noninvasive new technologies, such as infrared thermography.

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