The efficacy and clinical safety of various analgesic combinations forpost-operative dental pain: a systematicreview

Abstract

Background Various analgesics are available for post-operative pain after third molar surgery. Combinations of different classes of analgesics may improve the overall efficacy of pain control as they covers different pain pathways. A great variation of combinations and dosages of analgesics have been suggested in the literature, yet it was still unclear what combination(s) and dosages were the most effective for acute post-operative dental pain. A systematic review of randomized clinical trials would help clinicians to make clinical judgment of which analgesic combination(s) would be the best for their patients for acute post-operative dental pain in terms of efficacy and safety.

Aim To conduct a systematic review of randomized clinical trials to answer the clinical question “which analgesic combination and dosage is potentially the most effective and safe for acute post-operative dental pain control?”

Methods A structured systematic literature search, with predefined inclusion and exclusion criteria, of the relevant computer databases and journals was performed. The search and the evaluations of articles were done by 2 independent reviewers in 3 rounds. Studies that fulfilled the pre-set criteria were included to enter the final review. The analgesic efficacy of the analgesic combinations reported in the included studies were presented by the objective pain measurements, sum of pain intensity at 6 hours (SPID6) and total pain relief at 6 hours (TOTPAR6). The SPID6 and TOTPAR6 of various combinations were adjusted after deducting from the effect of placebos of the respective studies. The adverse effects of the different analgesic combinations were also presented.

Results There were 13 studies with 2843 subjects included in the final review. Eight groups of drug combinations with 13 different dosages were reported. The efficacies of the reported analgesic combinations have SPID6 scores ranged from 1.46 to 6.44 and TOTPAR6 scores ranged from 3.24 – 10.3. Among the analgesic combinations, ibuprofen 400mg + oxycodone HCL 5mg had the highest adjusted SPID6 (6.44), and a very higher adjusted TOTPAR6 (9.31), representing its efficacy could be superior to the other different analgesic combinations reported in this study. Nausea was the most common adverse effect of the analgesic combinations, with prevalence ranged from 0-55%. Most of the common adverse effects were related to the use of opioids in the combination. Three combinations of different dosages containing ibuprofen and caffeine were reported with the lowest prevalence of adverse effect. Conclusions This systematic review of randomized clinical trials has presented the efficacy and adverse effects of the various analgesic combinations for acute post-operative dental pain control. We have identified ibuprofen 400mg with oxycodone 5mg was more effective when compared to the other 12 combinations. Nausea was the most common adverse effects in an analgesic combination containing an opioid. Ibuprofen 200mg with caffeine 100mg or 200mg has a reasonable analgesic effect with fewer side effects when compared to the other analgesic combinations.