Do NSAIDs Really Interfere with Healing after Surgery?

Abstract

Perioperative analgesia should be multimodal to improve pain relief, reduce opioid use and thereby adverse effects impairing recovery. Non-steroidal anti-inflammatory drugs (NSAIDs) are an important non-opioid component of this approach. However, besides potential other adverse effects, there has been a longstanding discussion on the potentially harmful effects of NSAIDs on healing after surgery and trauma. This review describes current knowledge of the effects of NSAIDs on healing of bones, cartilage, soft tissue, wounds, flaps and enteral anastomoses. Overall, animal data suggest some potentially harmful effects, but are contradictory in most areas studied. Human data are limited and of poor quality; in particular, there are only very few good randomized controlled trials (RCTs), but many cohort studies with potential for significant confounding factors influencing the results. The limited human data available are not precluding the use of NSAIDs postoperatively, in particular, short-term for less than 2 weeks. However, well-designed and large RCTs are required to permit definitive answers.

Longitudinal peripheral tissue RNA‐Seq transcriptomic profiling, hyperalgesia, and wound healing in the rat plantar surgical incision model

“…In our dataset, Ptgs2 was sharply upregulated prior to the upregulation of S100a8 and S100a9 (Figure 4C). These sequential observations suggest that cyclooxygenase 2 (COX2) is necessary to initiate and maintain wound healing process associated with S100A8 and S100A9, and that NSAIDs which inhibit COX1 and 2 possibly negatively affect wound healing as reported previously 49,50 . We found a strikingly consistent expression pattern among transcripts encoding enzymes that synthesize prostanoids (Figure 5B,C), with expression of all but one of these transcripts being elevated from baseline at 6‐hours post‐incision indicating that these genes are induced locally as opposed to being imported from infiltrating immune cells.…”

“…These sequential observations suggest that cyclooxygenase 2 (COX2) is necessary to initiate and maintain wound healing process associated with S100A8 and S100A9, and that NSAIDs which inhibit COX1 and 2 possibly negatively affect wound healing as reported previously. 49 , 50 We found a strikingly consistent expression pattern among transcripts encoding enzymes that synthesize prostanoids (Figure 5B,C ), with expression of all but one of these transcripts being elevated from baseline at 6‐hours post‐incision indicating that these genes are induced locally as opposed to being imported from infiltrating immune cells. Taken together, the present data suggest that S100A8 and S100A9 are key regulators of wound healing process in skin, and the sequential expression of Ptgs2 followed by S100a8 , and S100a9 is important for regulation of inflammation and pain because the protein complex formed by S100A8 and S100A9 is involved in AA metabolism.…”

Effect of Vitamin C on Tendinopathy Recovery: A Scoping Review

“…It is important to note that NSAIDs may affect the healing of the tissues that take part in the structure of the musculoskeletal system, affecting specifically the proliferation of tenocytes after injury [67]. Therefore, the existing scientific references do not provide enough evidence for or against the use of NSAIDs after an acute injury or surgical repair of the tendon-bone interface [68][69][70]. However, the combination with supplements containing VC [71] or other compounds, such as hyaluronic acid [72], could mitigate the effects exerted by NSAIDs.…”

Lessons from 20 years with COX‐2 inhibitors: Importance of dose–response considerations and fair play in comparative trials

“…Two conditions that have attracted special attention are fracture healing [28] and the risk of anastomotic leakage after gastrointestinal surgery [29,30]. However, most of the evidence regarding fracture healing is derived from animal studies [31,32]. Human data are limited and generally of low quality with few randomized controlled trials [32].…”