• Tissue injury and inflammation results in peripheral mediator release and stimulation of nociceptors on peripheral nerve endings.
• NSAIDs work by blocking cyclooxygenase enzymes, COX-1 and COX-2, which are responsible for producing prostaglandins that stimulate pain receptors. They are protein-bound and renally excreted.
  • Non-selective NSAIDs inhibit both COX-1 and COX-2 enzymes, posing a higher risk of gastrointestinal bleeding due to COX-1’s protective role in the stomach.
  • COX-2 inhibitors offer reduced gastrointestinal toxicity but may have a heightened risk of cardiovascular side effects compared to non-selective NSAIDs.
• When the COX enzyme sites become saturated, surpassing the ceiling dose of an NSAID increases the concentration of unbound drug in the body, raising the risk of adverse events without providing additional therapeutic benefits.

Patient specific factors to consider:

• Consider alternative diagnoses and pain modalities, neuropathic and chronic nociplastic pain that require a modified approach.
• Use a validated pain assessment score: numerical rating scale.
• Have a patient-centered discussion and consider minimising NSAIDs if:
  • Age greater than 65 years old.
  • History of:
    • ulcer or gastrointestinal bleeding.
    • cardiovascular disease.
    • pediatric brittle asthma which may be precipitated by NSAIDs.
    • renal disease (acute kidney injury or chronic kidney disease) or factors predisposing to AKI such as dehydration or rhabdomyolysis.
    • sulfonamide allergy.
    • concurrent anticoagulant, antiplatelet, glucocorticoid, or SSRI use (increased bleed risk).

Agent Selection, Dosing, and Duration

• Mild to moderate pain: ibuprofen, naproxen, diclofenac.
• Moderate to severe pain: ketorolac.
• Maximum individual NSAID ceiling doses:
  • Ibuprofen: 400 mg PO
  • Naproxen: 440 mg PO (recommended dose: 250-375 mg PO BID)
  • Diclofenac: 50 mg PO
  • Ketorolac: 10 mg IM/IV (15 mg might be most practicable depending on vial size)
    • To minimize UGIB risk: < 65 y, maximum 10 mg/day, max duration: 5 days.
• Duration of use: reassessment after 5 days.
• Duration of action: based on trial data, patients should be informed that 70% of people will experience pain relief for at least 6 hours.
• Higher daily doses of NSAIDs, particularly ketorolac, are associated with an increased risk of bleeding, including UGIB and/or perforation, beyond the above ceiling doses.

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3. Motov S, Yasavolian M, Likourezos A, et al. Comparison of Intravenous Ketorolac at Three Single-Dose Regimens for Treating Acute Pain in the Emergency Department: A Randomized Controlled Trial. Ann Emerg Med. 2017;70(2):177-184. doi:10.1016/j.annemergmed.2016.10.014

   
   

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