Twenty-five RCTs (n=1,853) involving 33 comparisons were included in the analysis, of which 21 were double-blind.
Methodological quality: the median quality score assigned to included studies was 4 (range: 1 to 5).
Intra-operative blood loss: based on 9 RCTs (12 comparisons), no statistically-significant difference between the NSAID (2.1 +/- 0.91 mL/kg) and control (1.8 +/-0.9 mL/kg) groups was found; the WMD was 0.38 (95% CI: -0.81, -0.06).
Incidence of post-operative bleeding: based on 1,304 patients in 16 RCTs (19 comparisons), no statistically-significant difference between the NSAID and control groups was found, with event rates ranging from 0 to almost 30% (Peto-OR 1.30, 95% CI: 0.89, 1.89). This result was independent of the OR model used and no significant difference was found between studies that reported primary compared with secondary bleeding.
Number of readmissions due to bleeding: based on 506 patients in 8 RCTs (9 comparisons), no statistically-significant difference between the NSAID and control groups was found (Peto-OR 2.10, 95% CI: 0.85, 5.19). This result was independent of the OR model used.
Reoperation due to bleeding: based on 1,626 patients in 21 RCTs (27 comparisons), the likelihood of requiring reoperation due to bleeding was significantly higher in the NSAID group than in the control group (Peto-OR 2.33, 95% CI: 1.12, 4.83, P-value not given). However, when studies with no cases of reoperation due to bleeding were included, there was only a trend towards a statistically-significant difference between the NSAID and control groups (OR 1.92, 95% CI: 1.00, 3.71, P- value not given). The resulting NNT was 60 (95% CI: 34, 277). Sensitivity analyses found the likelihood of reoperation due to bleeding was only statistically significant in patients administered NSAID treatment after surgery (Peto-OR 4.3, 95% CI: 1.69, 11.26); the NNT was 40 (95% CI, 23, 123). This was independent of the OR model used. No statistically-significant difference was found between single- and multiple-dose NSAID regimens.
Pain relief: in 10 of the 11 studies, NSAIDs were associated with statistically-significant improvements in pain relief compared with placebo or no treatment. Compared with opioids, NSAIDs were associated with statistically-significant improvements in pain relief (2 studies) or were no different (5 studies); one study found that opioids were associated with a statistically-significant improvement in pain relief over NSAIDS. No statistically-significant difference in pain relief was found between NSAIDs and acetaminophen (3 studies). Compared with acetaminophen codeine, NSAIDs were associated with statistically-significant improvements in pain relief (1 study) or were no different (1 study); one study found that acetaminophen codeine was associated with a statistically-significant improvement in pain relief over NSAIDS.
PONV: based on 11 RCTs, the risk of PONV was significantly higher in patients receiving an opioid than a NSAID (RR 0.73, 95% CI: 0.63, 0.85); the NNT was 9 (95% CI: 5, 19).