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000). Figure?6 Forest plot of side effects. Discussion This quantitative meta-analysis involving 12 RCTs11�C22 showed that the combination therapy of single-dose IA bupivacaine and morphine is effective for pain relief after knee arthroscopic surgery. There was no significant difference between the two groups in terms of side effects. Separate IA administration of bupivacaine or morphine alone has been reported to provide good postoperative analgesia after arthroscopic knee surgery.27�C29 Eroglu et al30 further demonstrated the efficacy and safety of low-dose IA bupivacaine and morphine for spinal anaesthesia in outpatients after knee arthroscopic surgery. However, the efficacy and safety of combination therapy with IA bupivacaine and morphine remain controversial. This meta-analysis suggests that the administration of single-dose IA bupivacaine plus morphine is effective for pain relief after knee arthroscopic surgery, while its short-term side effects are similar to those of saline placebo. The results described above are supported by some studies11�C19 but not by others.20�C22 The conflicting findings may be due to various factors. Ruwe et al31 suggested that patients with preoperative pain were more likely to experience postoperative pain, so they regarded preoperative pain as a significant variable. Epinephrine may be another confounding factor. Haynes et al32 reported that the addition of epinephrine could decrease the effectiveness of morphine in the combination group. However, Allen's study27 indicated that the addition of epinephrine did not weaken the analgesic effect of IA bupivacaine plus morphine, but could rather prolong the duration of analgesia. Furthermore, Reuben and Sklar33 suggested that inflammation at the site of surgical trauma would cause increased postoperative pain, but this was not considered in our study. The findings of this meta-analysis suggest that there was no significant difference (WMD 3.46; 95% CI ?1.81 to 8.72; p=0.20) between the bupivacaine plus morphine group and the placebo group in terms of time to first analgesic request. However, McSwiney et al34 reached an opposite conclusion. They considered that the combination therapy of single-dose IA bupivacaine plus morphine should provide longer duration of analgesia. However, the small number of see more studies included in their report may have influenced this finding. In this meta-analysis, three studies11 12 21 reported the rate of side effects in both the bupivacaine plus morphine group and the placebo group. Most of the included studies13 14�C20 22 suggested that side effects were infrequent, and there was no statistically significant difference between the two groups.