Efficacy of proteolytic enzyme bromelain on health outcomes after third molar surgery. Systematic review and meta-analysis of randomized clinical trials

Background: Bromelain is a cysteine protease isolated from pineapple with a range of biological properties including platelet aggregation inhibition and anti-inflammatory effects. Recent studies have evaluated the clinical implications of bromelain in reducing postoperative inflammatory complications after third molar surgery, but the results are contrasting. This systematic review and meta-analysis evaluated the effects of bromelain on health outcomes in patients submitted to third molar surgery. Material and methods: The study was conducted following the PRISMA statement. Searches were conducted in six electronic databases and Google Scholar from inception to May 2018. The following elements were used to define eligibility criteria: (1) population: patients undergoing third molar surgery; (2) intervention and controls: bromelain vs placebo or no-treatment control group; (3) outcomes: quality of life, postoperative pain, rescue analgesic consumption, facial swelling, and trismus; and (4) study type: randomized clinical trials (RCTs). Treatment effects were defined as weighted (WMD) or standardized mean difference (SMD) and 95% CIs. Results: Six RCTs were included in the meta-analysis. There was large effect size of bromelain on improving physical appearance (SMD -0.77, CI% 95 -1.11 to -0.42), social isolation (SMD -0.97, CI% 95 -1.74 to -0.21), and sleep quality (SMD -1.19, CI% 95 -1.97 to -0.40) during the first postoperative week. Differences in pain intensity were found during the first 24h (SMD -0.49, CI 95% -0.82 to -0.17) and 7 days after surgery (SMD -0.52, CI 95% -0.79 to -0.24). No evidence was found that bromelain was effective in reducing trismus and facial swelling. Conclusions: The currently available evidence suggests that bromelain has a beneficial effect in reducing pain and has a positive impact on patient quality of life after third molar surgery. However, therapeutic advances for the use of bromelain need a high level of evidence and further head-to-head RCTs are needed to inform clinical choices.