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

Abstract

In 2012 the European Medicines Agency approved a pineapple stem‐derived Bromelain‐based debridement concentrate of proteolytic enzymes (NexoBrid®, MediWound Ltd, Yavne, Israel) for adult deep burns. Over 10 000 patients have been successfully treated with NexoBrid® globally, including in the US. The aim of our study is to perform a systematic review of the current literature on Nexobrid® 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® 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® 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.

Current Uses of Bromelain in Children: A Narrative Review

“…Some studies have confirmed the safety of NexoBrid in the treatment of adult and pediatric burns [ 71 ], while Shoham et al [ 73 ] showed better results in children than in adults. Given the higher prevalence of burns in children (approximately 60%) and the important emotional and health significance of this condition, the use of enzymatic debridement for early eschar removal in the pediatric population is an important challenge to achieve a good long-term outcome [ 73 ].…”

“…Several studies have demonstrated the efficacy of NexoBrid in selectively removing burn eschar in a single 4-hour application, thus reducing the necessity for surgical excision of necrotic tissue [ 73 ] by at least 3.5 times [ 71 ] and preserving dermal tissue [ 72 ]. In addition, NexoBrid provided faster wound healing with better long-term outcomes [ 73 ] and improved quality of life [ 72 ].…”

“…Several studies have demonstrated the efficacy of NexoBrid in selectively removing burn eschar in a single 4-hour application, thus reducing the necessity for surgical excision of necrotic tissue [ 73 ] by at least 3.5 times [ 71 ] and preserving dermal tissue [ 72 ]. In addition, NexoBrid provided faster wound healing with better long-term outcomes [ 73 ] and improved quality of life [ 72 ]. One of the most important advantages is the selective action of NexoBrid with intact underlying tissue: this is useful for thin skin in children [ 73 ] and for deep and full-thickness burns where the depth of the lesion can be difficult to determine [ 71 ], reducing the risk of bleeding and hemodynamic instability [ 72 ].…”

“…In addition, NexoBrid provided faster wound healing with better long-term outcomes [ 73 ] and improved quality of life [ 72 ]. One of the most important advantages is the selective action of NexoBrid with intact underlying tissue: this is useful for thin skin in children [ 73 ] and for deep and full-thickness burns where the depth of the lesion can be difficult to determine [ 71 ], reducing the risk of bleeding and hemodynamic instability [ 72 ]. In partial-thickness burns, it has resulted in spontaneous re-epithelialization, reducing graft risk, improving functional and aesthetic outcomes [ 72 ], and reducing hospital costs [ 71 ].…”

Assessing the Effect of Enzymatic Debridement on the Scar Quality in Partial-Thickness Burns to Deep Dermal Burns of the Hand: A Long-Term Evaluation

“…Although EDNX has become a standard procedure in many burn centers worldwide during the past ten years, surprisingly, our recent extensive search of the literature showed limited valid data on the long-term scarring after the enzymatic debridement of the hands. Shoham et al conducted a systematic review in 2023, finding 103 relevant studies, of which 34 were found eligible [ 10 ]. Among these, there were several studies investigating the long-term outcomes of hand burns after enzymatic debridement.…”