Preoperative preemptive drug administration for acute postoperative pain: A systematic review and meta-analysis

Although it is widely recommended that clinical trials undergo some type of quality review, the number and variety of quality assessment scales that exist make it unclear how to achieve the best assessment. To determine whether the type of quality assessment scale used affects the conclusions of meta-analytic studies. Meta-analysis of 17 trials comparing low-molecular-weight heparin (LMWH) with standard heparin for prevention of postoperative thrombosis using 25 different scales to identify high-quality trials. The association between treatment effect and summary scores and the association with 3 key domains (concealment of treatment allocation, blinding of outcome assessment, and handling of withdrawals) were examined in regression models. Pooled relative risks of deep vein thrombosis with LMWH vs standard heparin in high-quality vs low-quality trials as determined by 25 quality scales. Pooled relative risks from high-quality trials ranged from 0.63 (95% confidence interval [CI], 0.44-0.90) to 0.90 (95% CI, 0.67-1.21) vs 0.52 (95% CI, 0.24-1.09) to 1.13 (95% CI, 0.70-1.82) for low-quality trials. For 6 scales, relative risks of high-quality trials were close to unity, indicating that LMWH was not significantly superior to standard heparin, whereas low-quality trials showed better protection with LMWH (P<.05). Seven scales showed the opposite: high quality trials showed an effect whereas low quality trials did not. For the remaining 12 scales, effect estimates were similar in the 2 quality strata. In regression analysis, summary quality scores were not significantly associated with treatment effects. There was no significant association of treatment effects with allocation concealment and handling of withdrawals. Open outcome assessment, however, influenced effect size with the effect of LMWH, on average, being exaggerated by 35% (95% CI, 1%-57%; P= .046). Our data indicate that the use of summary scores to identify trials of high quality is problematic. Relevant methodological aspects should be assessed individually and their influence on effect sizes explored.

The usefulness of intravenous patient-controlled analgesia (PCA) with opioids for postoperative analgesia is not well defined. We systematically searched (MEDLINE, EMBASE, Cochrane Library, bibliographies, any language, to January 2000) for randomised trials comparing opioid-based PCA with the same opioid given intramuscularly, intravenously, or subcutaneously. Weighted mean differences (WMD) for continuous data, relative risks (RR) and numbers-needed-to-treat (NNT) for dichotomous data were calculated with 95% confidence intervals (CI) using fixed and random effects models. Data from 32 trials were analysed: 22 (1139 patients) were with morphine, five (682) with pethidine, three (184) with piritramide, one (47) with nalbuphine and one (20) with tramadol. In three morphine and one pethidine trial (352 patients), more patients preferred PCA (89.7% vs. 65.8%, RR 1.41 (95%CI 1.11 to 1.80), NNT 4.2). Combined dichotomous data on pain intensity and relief, and the need for rescue analgesics from eight morphine, one pethidine, one piritramide, and one nalbuphine trial (691 patients), were in favour of PCA (RR 1.22 (1.00 to 1.50), NNT 8). In two morphine trials (152), pulmonary complications were more frequently prevented with PCA (100% vs. 93.3%, RR 1.07 (1.01 to 1.14), NNT 15). There was equivalence for cumulative opioid consumption, pain scores, duration of hospital stay, and opioid-related adverse effects. These trials provide some evidence that in the postoperative pain setting, PCA with opioids, compared with conventional opioid treatment, improve analgesia and decrease the risk of pulmonary complications, and that patients prefer them.