Bromelain-based enzymatic burn debridement: A systematic review of clinical studies on patient safety, efficacy and long-term outcomes

In 2012 the European Medicines Agency approved a pineapple stem-derived Bromelain-based debridement concentrate of proteolytic enzymes (NexoBrid & REG;, MediWound Ltd, Yavne, Israel) for adult deep burns. Over 10 000 patients have been successfully treated with NexoBrid & REG; globally, including in the US. The aim of our study is to perform a systematic review of the current literature on Nexobrid & REG; outcomes. We conducted a literature search in PubMed, Google Scholar, Embase, and other search engines (2013-2023). The online screening process was performed by two independent reviewers with the Covidence tool. The protocol was reported using the Preferred Reporting Items for Systematic Review and Meta-Analyses, and it was registered at the International Prospective Register of Systematic Reviews of the National Institute for Health Research. We identified 103 relevant studies of which 34 were found eligible. The included studies report the positive effects of Nexobrid & REG; on burn debridement, functional and cosmetic outcomes, scarring, and quality of life. Also, they validate the high patient satisfaction thanks to enhanced protocols of analgosedation and/or locoregional anaesthesia during Bromelain-based debridement. Two studies investigate potential risks (coagulopathy, burn wound infection) which concluded there is no strong evidence of these adverse events. NexoBrid & REG; is a safe, selective, non-surgical eschar removal treatment modality. The benefits of Bromelain-based debridement are faster debridement and healing times, reduced operations, length of stay, cases of sepsis, blood transfusions, and prevention of compartment syndrome. Existing evidence suggests that the indications and the role of Bromelain-based debridement are expanding to cover "off-label" cases with significant benefits to the global healthcare economy.