Table 1.

Concerns and evidence relating to NSAIDs for acute pain management in the inpatient setting.

Concern	Evidence	Recommendation
Bleeding/antiplatelet effects	Bleeding times and perioperative bleeding events are not significantly affected by NSAIDs at usual doses; GI complications from NSAID-induced prostaglandin inhibition are not increased by short-term use (<7 days); These risks may be further mitigated by using a COX-2 selective agent since antiplatelet effects are mediated by COX-1 inhibition	Do not withhold NSAIDs in acute pain due to bleeding concerns as long as usual analgesic doses and short-term durations are employed; selective COX-2 inhibitors or concomitant gastroprotective agents may be considered in patients at high GI bleed risk
Wound healing issues or orthopedic/spinal nonunion after fracture or fusion surgery	Older data from animal and limited retrospective studies suggested these concerns, however more recent and higher quality prospective studies have not replicated	NSAIDs, especially COX-2 selective agents, appear efficacious and safe for short-term use in orthopedic and spinal surgery and should be routinely considered based on risks/benefits
Anastomotic leak after GI surgery	Some studies have suggested increased risk of anastomotic leakage with nonselective NSAIDS, but selective COX-2 inhibitors were not associated with this risk in recent meta-analyses	Do not withhold COX-2 selective NSAIDs in GI surgery patients
MACE after cardiac surgery	COX-2 selective inhibitors have been associated with increased rates of MACE after cardiac surgery, likely due to an unfavorable effect on pro-thrombotic pathways	COX-2 selective agents should be avoided in cardiac surgery, however, nonselective NSAIDs have been used safely in cardiac surgery, and COX-2 selective agents have been used safely in patients with cardiac disease undergoing noncardiac surgery
Sulfa allergy	While some NSAIDs contain a sulfur-containing moiety, these are not structurally the same as sulfa antibiotics; patients with sulfa allergies have been found to be no more likely to have allergic reactions to NSAIDs than patients without sulfa allergies	Do not withhold NSAIDs, including celecoxib, in patients with sulfa (sulfonamide antibiotic) allergies
Gastritis/pouchitis in patients s/p bariatric surgery	Patients s/p bariatric surgery should avoid chronic NSAID exposure, however, short-term use is supported by current guidelines as safe and beneficial	Do not withhold short-term NSAIDs in acute pain in patients s/p bariatric surgery; use of a COX-2 selective agent and/or temporary PPI therapy may be considered to decrease GI risk
Kidney injury	NSAIDs inhibit prostaglandin-dependent mechanisms of preserving renal perfusion and GFR in times of decreased renal blood flow, increasing risk for acute and chronic kidney injury in at-risk populations	All NSAIDs and COX-2 inhibitors should generally be avoided in patients with AKI or CKD
Large doses must be used for analgesia	The maximum effective analgesic dose of ketorolac is approximately 10–15 mg and is approximately 400 mg for ibuprofen based on available dose-finding studies, though higher doses may confer additional anti-inflammatory benefit	When using NSAIDs primarily to treat pain, doses should generally not exceed their analgesic ceiling in order to limit adverse effects

Legend: AKI-acute kidney injury, CKD = chronic kidney disease, COX = cyclooxygenase enzyme, GI = gastrointestinal, MACE = major adverse cardiac events, NSAID = non-steroidal anti-inflammatory drug, PPI = proton pump inhibitor, s/p = status post. References: [45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72].