The clinical management of postoperative pain has undergone a paradigm shift toward multimodal analgesia, primarily driven by the imperative to mitigate the systemic impact of the opioid epidemic. Within this framework, nonsteroidal anti-inflammatory drugs (NSAIDs) are an important pillar for non-opioid pharmacological analgesia. Despite strong recommendations from major clinical guidelines, adoption remains hindered by persistent concerns regarding adverse effects such as acute kidney injury (AKI), perioperative bleeding, and impaired tissue healing. However, a critical evaluation of the literature suggests an excellent safety profile for NSAIDs when used in short courses for acute postoperative analgesia.
Renal dysfunction is a primary concern when using NSAIDs, as they inhibit prostaglandins that regulate glomerular filtration, particularly via constriction of the afferent arterioles. While some observational data suggest a slight increase in the odds of AKI immediately following surgery, comprehensive reviews of randomized controlled trials indicate that these effects are typically transient and clinically insignificant in patients with normal baseline renal function. Short-term administration, particularly of parenteral agents like ketorolac for five days or less, has not been shown to increase the incidence of renal failure compared to opioid monotherapy. Nevertheless, caution is still warranted in patients with pre-existing chronic kidney disease, hypovolemia, or those receiving concomitant nephrotoxic agents.
The perceived risk of perioperative bleeding similarly lacks robust clinical substantiation when drugs are used appropriately. While nonselective NSAIDs inhibit platelet aggregation via thromboxane A2 suppression, prospective data involving over 11,000 patients found no difference in surgical site bleeding between ketorolac, diclofenac, and ketoprofen when administered according to approved labels. Meta-analyses further demonstrate that ketorolac and ibuprofen do not significantly increase the risk of hematoma formation compared to placebos or opioids when used postoperatively. While postoperative anticoagulants do increase bleeding risk, this effect is equal across patients receiving NSAIDs and those receiving other analgesics. Conversely, preoperative or intraoperative administration may pose a higher risk and should be approached with greater selectivity.
Controversies regarding bone union and tissue healing largely stem from animal models and low-quality retrospective studies. Current clinical evidence does not consistently demonstrate that short-term postoperative NSAID use impairs fracture healing or graft survival in orthopedic procedures. However, specific surgical contexts, such as arthroscopic rotator cuff repairs, may necessitate the avoidance of COX-2 selective inhibitors due to potential interference with tendon-to-bone healing.
Cardiovascular and gastrointestinal complications, while well-documented safety concerns in chronic NSAID therapy, appear minimally during short-term perioperative analgesia. For instance, cardiovascular events do not show a significant increase in non-cardiac surgical populations when NSAIDs are used for seven to ten days. Despite class-wide black box warnings, certain agents like naproxen may be relatively safe even in post-cardiac surgery populations. In the gastrointestinal tract, short courses of less than seven days are not associated with increased ulceration or bleeding in most populations. A notable exception exists in colorectal surgery, where multiple studies have identified a significant association between NSAID use and an increased rate of anastomotic leakage.
The safety profile of NSAIDs for postoperative analgesia is generally favorable for the majority of the surgical population. When administered at the lowest effective dose for limited durations, the benefits of reduced opioid consumption and improved patient satisfaction outweigh the potential for serious adverse events. Clinical practice should transition toward the routine inclusion of NSAIDs in multimodal regimens, reserving avoidance only for patients with well-founded contraindications such as severe renal impairment, acute cardiovascular disease, or specific high-risk gastrointestinal procedures.
References
1. Chang, R. W., Tompkins, D. M., & Cohn, S. M. (2020). Are NSAIDs Safe? Assessing the Risk-Benefit Profile of Nonsteroidal Anti-inflammatory Drug Use in Postoperative Pain Management. The American Surgeon. https://journals.sagepub.com/home/asu
2. Forrest, J. B., et al. (2002). Ketorolac, diclofenac, and ketoprofen are equally safe for pain relief after major surgery. British Journal of Anaesthesia. https://academic.oup.com/bja
3. Joshi, G. P., Kehlet, H., & Lobo, D. N. (2025). Nonsteroidal anti-inflammatory drugs in the perioperative period: current controversies and concerns. British Journal of Anaesthesia. https://doi.org/10.1016/j.bja.2024.10.018
4. Gupta, A., & Bah, M. (2016). NSAIDs in the Treatment of Postoperative Pain. Current Pain and Headache Reports. https://link.springer.com/journal/11916