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Non Steroidal Anti-inflammatory Drugs & Cyclo-oxygenase-2 inhibitors for management of postoperative pain

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Mechanism of action and positioning in postoperative analgesia

Non-steroidal anti-inflammatory drugs (NSAIDs) and cox-2 inhibitors (coxibs) are systemic analgesics. They have spectrum of analgesic, anti-inflammatory and anti-pyretic effects. Studies demonstrate their clinical efficacy for a variety of acute, postoperative, pain conditionsExamples of NSAIDs include ibuprofen, diclofenac, naproxen and indomethacin.

Coxibs were introduced to negate the gastrointestinal (GI) side effects of NSAIDs. Examples of coxibs include celecoxib and paracoxib.

Recent controversy has surrounded the use of NSAIDs and coxibs due to an increasedcardiovascular risk profile.

NSAIDs and cox-2 inhibitors reversibly inhibit the enzyme cyclooxygenase now recognized to consist of two isoforms, COX-1 and COX-2, mediating production of prostaglandins and thromboxane A2.

Prostaglandins mediate a variety of physiological functions such as maintenance of gastric mucosa, regulation of renal blood flow and regulation of platelet function. They play an important role in nociceptive processing. ANZCA, chapter 4.2.2, page 73.

Specific perioperative issues

  • NSAIDs and coxibs may be used as sole agents or part of a multimodal analgesic strategy for acutepostoperativepain ANZCA, chapter 4.2.2, page 73. ASA, chapter V, page 254.
  • They are inadequate as the sole treatment for severe postoperativepain ASA chapter 4, p 75.
  • Unless contraindicated, NSAIDs or coxibs or paracetamol should be given after surgery on an around-the clock basis ASA, chapter V, page 254.
  • Side effects of NSAIDs and coxibs are more common in long term use.
  • NSAIDs and coxibs have the potential for adverse effects particularly in risks groups such as patients with cardiac disease or the elderly population.
  • GI, cardiovascular and renal insufficiency complications are recognized risks of this class of medication in the postoperative period.
  • With proper patient selection and monitoring, the incidence of NSAID-induced perioperative renal impairment is low.
  • NSAIDs and coxibs confer dose-dependent elevated cardiovascular risk, with rofecoxib and diclofenac conferring the highest risk, and ibuprofen and naproxen the lowest ANZCA, chapter 4.2.3, page 77.
  • Controversy exists as to whether or not NSAIDs and coxibs effect bone fracture healing. ANZCA, chapter 4.2.2, page 75, Bandolier.
  • Perioperative non-selective NSAIDs increase the risk of severe bleeding after a variety of other operations compared with placebo and following tonsillectomy increase the risk of reoperation due to re-bleeding in adults, though not in children ANZCA, chapter 4, page 74; ANZCA, chapter 4, page 78.
  • Platelets produce COX-1 only, thus, coxibs do not impair platelet function. Use of rofecoxib reduced surgical blood loss compared to diclofenac ANZCA chapter 4.2.3, p 77.
  • According to the FDA, ‘short term use of NSAIDs to relieve acute pain, particularly in low doses, does not appear to confer an increased risk of serious cardiovascular events (with the exception of parecoxib and valdecoxib after coronary artery bypass graft surgery, where treatment is contraindicated). ANZCA chapter 4.2.3, p 77.

Recommendations specific to the treatment

Circumstances when the treatment is not recommended:ANZCA, chapter 4, p 78-79.

NSAID or coxibs, in the postoperative period, should be used with caution in patients with a history of thrombotic events such as ischaemic heart disease or stroke.

Patients with active upper gastrointestinal pathology should avoid NSAIDs in the acutepostoperativeperiod.

Patients with acute or chronic renal insufficiency/injury should avoid NSAIDs and coxibs in thepostoperativeperiod.

Consultation with the orthopaedic team may be prudent before commencing NSAIDs in patients with bone fractures pending further evidence.

Summary

NSAIDs and coxibs are integral components of multi-modal analgesia. Judicious use of NSAIDs with careful consideration of current clinical guidelines provides the most appropriate pharmacological treatment for postoperative pain patients. Thorough patient assessment combined with regular clinical review and pharmacovigilance are key to ensuring optimal efficacy and safety in prescribing NSAIDs and coxibs.

Recommended reading

  1. Clarke R, Derry S, Moore RA. Single dose oral etoricoxib for acute postoperative pain in adults. Cochrane Database Syst Rev. 2012 Apr 18;4:CD004309.
  2. Derry S, Moore RA. Single dose oral aspirin for acute postoperative pain in adults. Cochrane Database Syst Rev. 2012 Apr 18;4:CD002067.
  3. Pogatzki-Zahn EM, Schnabel A, Zahn PK. Room for improvement: unmet needs in postoperative pain management. Expert Rev Neurother. 2012 May;12(5):587-600.
  4. Smith HS. Perioperative intravenous acetaminophen and NSAIDs. Pain Med. 2011 Jun;12(6):961-81.
  5. Wickerts L, et al. Coxibs: is there a benefit when compared to traditional non-selective NSAIDs in postoperative pain management? Minerva Anestesiol. 2011 Nov;77(11):1084-98.