Thirty-six double-blind RCTs (3,362 patients, excluding the number of patients receiving placebo) were included.
The methodological quality scores ranged from 2 to 5 (out of a possible 5). There was no statistically significant difference between the studies showing a difference in analgesic effect and studies showing a negative effect (p=1.0).
The methodological flaws included: baseline difference between the treatment groups; use of a relatively insensitive pain scale; the possibility of low study sensitivity (suggested by no significant difference between the active drugs and placebo); low bioavailability of rectal paracetamol; and the use of insufficient doses of paracetamol.
Paracetamol versus NSAIDs (33 RCTs).
Major surgery (5 RCTs, 398 patients): 4 of the 5 RCTs showed no significant difference between paracetamol and NSAID in pain scores or post-operative morphine requirements.
Orthopaedic surgery (3 RCTs, 270 patients): none of the 3 studies showed any differences on pain sores at rest. One of the 3 RCTs showed reduced pain on movement after disk surgery with ketoprofen, compared with paracetamol.
Gynaecological surgery (3 RCTs, 178 patients): 2 of the 3 RCTs showed that NSAIDs improved pain scores in two different surgical procedures in comparison with paracetamol.
Ear, nose and throat surgery (6 RCTs, 408 children): 5 of the 6 studies included no placebo control and showed no difference between paracetamol and NSAIDs. One RCT with a placebo control showed that ketorolac was superior to a relatively low dose of paracetamol (10 mg/kg).
Dental surgery (16 RCTs): the results were inconsistent. Eight RCTs showed NSAIDs were associated with lower pain scores than paracetamol; 5 RCTs showed no difference; 2 RCTs showed that 1,000 mg paracetamol was superior to 650 mg aspirin and 100 mg diclofenac; and one study did not compare the two treatments statistically.
Paracetamol plus NSAIDs versus paracetamol (7 RCTs): each study involved a different surgical procedure. Four of the 7 RCTs showed that combinations of paracetamol with NSAIDs (aspirin, ketoprofen and diclofenac) were associated with lower pain scores than paracetamol alone; 2 RCTs involving gynaecological surgery showed no differences between the treatment groups; and in one study, the pain scores were not measured. Five of the 7 RCTs showed significant reductions in opioid consumption for combinations of drugs when compared with paracetamol alone; and one RCT showed no difference between the treatment groups.
Paracetamol plus NSAIDs versus NSAIDs (4 RCTs, 190 patients): one of the 4 RCTs showed a reduction in pain scores at rest and on movement for the combination of paracetamol and ketoprofen, compared with ketoprofen alone; one RCT showed diclofenac plus paracetamol reduced pain after dental surgery in comparison with diclofenac alone; and 2 RCTs showed no difference between the treatment groups.
Relatively few studies compared the adverse effects of NSAIDs with paracetamol. Adverse reactions that have been reported in the literature were discussed. These related to gastrointestinal hepatic, renal and haematological effects, allergic reactions and miscellaneous. The latter included heterotopic bone formation, sleep disturbance, modification of body temperature, and drug interactions.