Expanding the Boundaries of Enzymatic Debridement: Short-Term Laboratory and Metabolic Responses to On-Label and Off-Label NexoBrid Application in Acute Burn Care

Background Enzymatic debridement with NexoBrid® is increasingly used beyond current label restrictions, particularly in patients with extensive burns. However, data on systemic safety and metabolic effects in large-area applications remain limited. This study aimed to evaluate short-term laboratory and metabolic changes following on-label and off-label use. Methods In this retrospective single-center cohort study, 167 adult burn patients treated with NexoBrid between 2020 and 2024 were included. Patients were stratified into on-label (≤15% TBSA treated, n=110) and off-label (>15% TBSA treated, n=57) groups. Laboratory parameters including electrolytes, pH, base excess, lactate, hemoglobin, and hematocrit were analyzed at predefined time points from baseline to day 3–4 post-application. Results Off-label patients had significantly larger burns (mean TBSA 35% vs. 14%) and higher mortality (17.9% vs. 13%). Electrolyte changes were transient, with a temporary increase in potassium and decrease in calcium, both normalizing rapidly without clinical relevance. Metabolic parameters remained stable, with improving base excess and no sustained lactate elevation. In contrast, hemoglobin and hematocrit decreased significantly over time, more pronounced in the off-label group, consistent with burn severity and treatment extent rather than a direct effect of enzymatic debridement. Conclusions In this retrospective cohort, no major short-term electrolyte or metabolic derangements were observed following enzymatic debridement, including patients undergoing off-label (>15% TBSA treated) treatment. The observed hematologic decline likely reflects overall burn severity rather than a treatment-specific effect. However, substantial differences in burn severity between groups and the absence of a non-NexoBrid control cohort preclude causal conclusions regarding overall systemic safety.