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are similar to nsNSAIDs (Argoff, 2005; Savage, 2005). Compared with paracetamol and placebo,
administration of parexocib after orthopaedic surgery resulted in a significant but transient
reduction in creatinine clearance at 2 hours; there was no difference at 4 and 6 hours (Koppert
et al, 2006 Level II).
Longer‐term use of high doses of both coxibs and nsNSAIDs (possibly apart from naproxen)
appear to increase the risk of cardiovascular (CV) and cerebrovascular events and regular use
of nsNSAIDs may interfere with the clinical benefits of low‐dose aspirin (see Section 4.2). Extra
precautions are therefore required in older patients.
There is no consistent evidence on the effect of ageing on clearance of paracetamol but there
is probably no need to reduce the dose given in older people (Divoll et al, 1982; Miners et al,
1988; Bannwarth et al, 2001).
Opioids and tramadol
Despite the age‐related changes listed in Table 11.4, there may be few differences in fentanyl
pharmacokinetics (Scott & Stanski, 1987) or the pharmacokinetics of morphine and oxycodone
(Villesen et al, 2007) and buprenorphine (Kress, 2009) in the older patient.
After oral administration, the bioavailability of some drugs may be increased, leading to
relatively higher blood concentrations (Mangoni & Jackson, 2004).
Opioid dose
Older patients require less opioid than younger patients to achieve the same degree of pain
relief (Macintyre & Jarvis, 1996 Level IV; Woodhouse & Mather, 1997 Level IV; Gagliese et al, 2000
Level IV; Upton et al, 2006), however, a large interpatient variability still exists and doses must
be titrated to effect in all patients. The decrease is much greater than would be predicted by
age‐related alterations in physiology and seems to have a significant pharmacodynamic
component (Macintyre & Upton, 2008).
In the clinical setting there is evidence of an age‐related 2‐ to 4‐fold decrease in morphine and
fentanyl requirements (Macintyre & Jarvis, 1996 Level IV; Woodhouse & Mather, 1997 Level IV;
Gagliese et al, 2000 Level IV). This is in agreement with the findings by Scott and Stanski (Scott &
Stanski, 1987) that the sensitivity of the brain to fentanyl and alfentanil was increased by 50% in
older people. It has been suggested that doses of fentanyl, sufentanil and alfentanil should all
be reduced by up to 50% in older patients (Shafer, 1997); reductions in the doses of other
opioids is also advised (Macintyre & Upton, 2008).
In patients over 75 years the elimination half‐life of tramadol was slightly prolonged (Scott &
Perry, 2000). Lower daily doses have been suggested (Barkin et al, 2005).
Opioid metabolites
Reduced renal function in the older patient could lead to a more rapid accumulation of active CHAPTER 11
opioid metabolites (eg M6G, M3G, hydromorphone‐3‐glucuronide, nordextropropoxyphene,
norpethidine, desmethyl‐tramadol) (see Section 4.1).
Side effects of opioids
The fear of respiratory depression in older people, especially those with respiratory disease,
often leads to inadequate doses of opioid being given for the treatment of their pain.
However, as with other patients, significant respiratory depression can generally be avoided if
appropriate monitoring (ie of sedation) is in place (see Section 4.1).
The incidence of nausea/vomiting and pruritus in the postoperative period lessens with
increasing age (Quinn et al 1994). In older people, fentanyl may cause less postoperative
cognitive dysfunction than morphine (Herrick et al, 1996 Level II) and less confusion
(Narayanaswamy et al, 2006), although administration of an appropriate opioid medication is
Acute pain management: scientific evidence 403