Role of paracetamol and NSAIDs in addition to step III
opioids
Findings
The first step of the WHO analgesic ladder recommends
the use of paracetamol or NSAIDs without opioids;
combination with opioids is possible as part of step II and
step III. Our recommendation, however, only addresses
use of these drugs in combination with step III opioids.
In a Cochrane review updated to March, 2003,
42 eligible trials were identified. The evidence supported
the superiority of NSAIDs and paracetamol to placebo,
but no diff erence could be found between diff erent
NSAIDs. Concerning the addition of NSAIDs or
paracetamol to step III opioids, fi ve placebo-controlled,
double-blind RCTs were identifi ed. Another review32
found seven further articles, giving a total of 12 eligible
studies (seven of NSAIDs and fi ve of paracetamol). Three
studies showed increased analgesia and two a decrease
in opioid consumption with combined NSAIDs and
opioids. In one study a mean diff erence of 0·4 on a
0–10 numerical pain-intensity rating scale was found in
favour of paracetamol. One study showed a higher
prevalence of gastrointestinal side-eff ects in patients
treated with opioids and NSAIDs than in patients treated
with opioids alone. In general, trial design and duration
of reviewed studies were not adequate to enable
assessment of the side-eff ects of long-term NSAID use
in this population, but caution was recommended,
particularly the high-risk elderly population, because of
these drugs’ known gastrointestinal, renal, and cardiovascular
toxic eff ects.91
All these studies had substantial limitations because of
the heterogeneity in designs, populations, and outcome
measures and the lack of long-term evaluation.