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4.2.2 Non-selective non-steroidal anti-inflammatory drugs
The term NSAIDs is used to refer to both nsNSAIDs and coxibs (COX‐2 selective inhibitors).
NSAIDs have a spectrum of analgesic, anti‐inflammatory and antipyretic effects and are
effective analgesics in a variety of acute pain states. Many effects of NSAIDs can be explained
by inhibition of prostaglandin synthesis in peripheral tissues, nerves, and the CNS (Botting,
2006). However, NSAIDs and aspirin may have other mechanisms of action independent of any
effect on prostaglandins, including effects on basic cellular and neuronal processes.
Prostaglandins are produced by the enzyme prostaglandin endoperoxide (PGH) synthase,
which has both cyclo‐oxygenase and hydroperoxidase sites. Two subtypes of cyclo‐oxygenase
enzyme have been identified – the ‘constitutive’ COX‐1, the ‘inducible’ COX‐2: a COX‐3 is also
being investigated (Simmons et al, 2004; Gajraj & Joshi, 2005; Botting, 2006; Kam & So, 2009).
Prostaglandins have many physiological functions including gastric mucosal protection, renal
tubular function and intrarenal vasodilation, bronchodilatation, production of endothelial
prostacyclin that leads to vasodilation and prevents platelet adhesion, and platelet
thromboxane that results in platelet aggregation and vessel spasm. Such physiological roles
are mainly regulated by COX‐1 and are the basis for many of the adverse effects associated
with nsNSAID use. Tissue damage induces COX‐2 production leading to synthesis of
prostaglandins that result in pain and inflammation, and COX‐2 induction within the spinal
cord may play a role in central sensitisation. COX‐2 may also be ‘constitutive’ in some tissues,
including the kidney, cardiovascular system and brain (Kam & So, 2009). NsNSAIDs are ‘non‐
selective’ cyclo‐oxygenase inhibitors that inhibit both COX‐1 and COX‐2. Aspirin acetylates and CHAPTER 4
inhibits cyclo‐oxygenase irreversibly but nsNSAIDs are reversible inhibitors of the enzymes.
The coxibs have been developed to inhibit selectively the inducible form (Simmons et al, 2004;
Gajraj & Joshi, 2005; Botting, 2006).
Efficacy
Single doses of nsNSAIDs are effective in the treatment of pain after surgery (Derry et al, 2009a
Level I; Derry et al, 2009b Level I; Derry et al, 2009c Level I), low back pain (Roelofs et al, 2008 Level I),
renal colic (Holdgate & Pollock, 2004 Level I) and primary dysmenorrhoea (Marjoribanks et al, 2003
Level I). For a list of NNTs for each drug see Table 6.1.
NsNSAIDs are integral components of multimodal analgesia (Kehlet, 1997; Brodner et al, 2001;
Barratt et al, 2002). However, while useful analgesic adjuncts, they are inadequate as the sole
analgesic agent in the treatment of severe postoperative pain. When given in combination
with opioids after surgery, nsNSAIDs resulted in better analgesia, reduced opioid consumption
5
5
and a lower incidence of PONV and sedation (Elia et al, 2005 Level I ; Marret et al, 2005 Level I ).
There was no effect on pruritus, urinary retention and respiratory depression (Marret et al, 2005
5
Level I ). Similarly, in patients less than 70 years of age undergoing cardiothoracic surgery, the
use of nsNSAIDs reduced pain scores and opioid requirements (Bainbridge et al, 2006 Level I)
although the use of these drugs in patients following coronary artery bypass surgery is
controversial (see below).
5
This meta‐analysis includes a study or studies that have since been withdrawn from publication. Please refer to the
Introduction at the beginning of this document for comments regarding the management of retracted articles.
Expert advice suggested that withdrawal of the retracted articles would not influence the conclusions but that
reanalysis would be required for this to be confirmed. Marret et al (Marret et al, Anesthesiology 2009; 111:1279–89)
reanalysed the data included in this meta‐analysis after excluding that obtained from the retracted publications.
They concluded that removal of this information did not significantly alter the results.
Acute pain management: scientific evidence 73
