Systemic and Histopathological Effects of Bromelain-Based Enzymatic Debridement in Human Burns—A Systematic Review

Background/Objectives: Bromelain-based enzymatic debridement (NexoBrid®) is an established tissue-preserving alternative to tangential excision in deep partial-thickness burns. Its clinical efficacy is supported by randomised trials, but its systemic effects are inconsistently described and its effects at tissue level in humans are largely unknown. The objective was to synthesise the human evidence on both domains and to determine, as a prespecified endpoint, whether any study has evaluated them in the same patients. Methods: PubMed, Embase and Scopus were searched between 2016 and 2026 using two stream-specific strategies that shared their intervention and population blocks and differed only in their outcome block: Stream A, clinical outcomes reported with systemic biological parameters; Stream B, clinical outcomes reported with histopathological findings. Eligible studies were original human investigations published in the last ten years. Risk of bias was assessed with ROBINS-I and the JBI checklists, and the synthesis was narrative, following PRISMA 2020 and SWiM. Results: Of 559 records, twelve studies were included: ten in Stream A (970 patients) and two in Stream B (nine patients); no study identified by the present search met the criteria of both. C-reactive protein and procalcitonin were significantly higher after enzymatic than after surgical debridement throughout the first week, and, in the single study that analysed the treated area as a continuous exposure, the probability of a post-debridement coagulation alteration rose with the area treated (odds ratio 1.158 per percentage point of body surface). Early fever occurred in 14% of patients and predicted later wound infection. Both histological studies were purely qualitative: neither reported a thickness, a percentage or a cell count, and neither reported any laboratory value. Conclusions: Enzymatic debridement is associated with a measurable systemic response whose proposed mechanisms are all statements about tissue that has never been examined. The two literature fields describe the same process at two levels of observation, in different patients and at incompatible times. No validated instrument exists for quantifying the human burn biopsy after debridement.