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13. Coxibs given in addition to PCA opioids reduce opioid consumption but do not result in a
decrease in opioid‐related side effects (N) (Level I).
14. Coxibs and non‐selective NSAIDs have similar adverse effects on renal function (U)
(Level I).
15. Non‐selective NSAIDs do not significantly increase blood loss after tonsillectomy but do
increase the need for reoperation due to bleeding (N) (Level I).
16. Parecoxib and/or valdecoxib compared with placebo do not increase the risk of
cardiovascular adverse events after non‐cardiac surgery (N) (Level I).
17. Coxibs and non‐selective NSAIDs are associated with similar rates of adverse cardiovascular
effects, in particular myocardial infarction; naproxen may be associated with a lower risk
than other non‐selective NSAIDs and celecoxib may be associated with a lower risk than
other coxibs and non‐selective NSAIDs overall (N) (Level I).
18. Perioperative non‐selective NSAIDs increase the risk of severe bleeding after a variety of
other operations compared with placebo (N) (Level II).
19. Coxibs do not impair platelet function; this leads to reduced perioperative blood loss in
comparison with non‐selective NSAIDs (S) (Level II).
20. Short‐term use of coxibs results in gastric ulceration rates similar to placebo (U) (Level II).
21. Use of parecoxib followed by valdecoxib after coronary artery bypass surgery increases the
incidence of cardiovascular events and is therefore contraindicated (S) (Level II). CHAPTER 4
The following tick boxes represent conclusions based on clinical experience and expert
opinion.
Adverse effects of NSAIDs are significant and may limit their use (U).
The risk of adverse renal effects of non‐selective NSAIDs and coxibs is increased in the
presence of factors such as pre‐existing renal impairment, hypovolaemia, hypotension, use
of other nephrotoxic agents and ACE inhibitors (U).
4.3 ADJUVANT DRUGS
4.3.1 Inhalational agents
Nitrous oxide
Nitrous oxide (N 2O) has been used since the inception of anaesthesia for its modest analgesic
and sedative properties, with minimal respiratory and cardiovascular depression. In many
countries it is available as a 50% N 2O /50% oxygen mixture called Entonox®. While it has a long
history of use, there is a paucity of good studies examining its effectiveness in comparison
with other analgesics.
In adults, N 2O in oxygen has some analgesic efficacy in labour (Rosen, 2002 Level I) and is
effective during painful procedures such as bone marrow aspiration (Gudgin et al, 2008
Level III‐3), venous cannulation (Gerhardt et al, 2001 Level II), sigmoidoscopy (Harding & Gibson,
2000 Level II) and liver biopsy (Castera et al, 2001 Level II), and in relieving acute ischaemic chest
pain (O'Leary et al, 1987 Level II). In elderly patients (median age 84 years), N 2O provided better
analgesia than morphine during bed sore and ulcer care (Paris et al, 2008 Level II).
In children, N 2O was effective in reducing pain associated with IV cannulation (Henderson et al,
1990 Level II; Hee et al, 2003 Level III‐2; Ekbom et al, 2005 Level III‐2), urethral catheterisation (Zier et
Acute pain management: scientific evidence 79
