## 2 Materials and Methods  
The current study included 30 patients aged 20 to 56 years, treated between September 2019 and September 2020. The study patients were diagnosed with flame burns (10 cases) and scalp burns (20 cases) covering 5% to 30% of the skin surface, burn degree IIB (deep partial-thickness)--III (full-thickness) (Table 1). The cases included in this study were randomly divided into two groups. The intern protocol of enzymatic debridement was initiated once the patients of the first group were assessed from the point of view of inclusion and exclusion criteria and if they were eligible. The patients of the second group were treated with the actual gold-standard protocol of early surgical excision with or without split-thickness skin grafting (STSG). Inclusion criteria: (a) age over 18 years; (b) burn degrees IIB or III that have surgical indication; (c) burns greater than 1% of total body surface area (TBSA); (d) flame or scalp burns; (e) patient consent (Figure 1). \begin{table}
\begin{tabular}{c c c c} \hline \hline \multicolumn{2}{c}{**Criteria**} & \multicolumn{2}{c}{**Total Number of Patients—30**} \\ \hline \hline \multicolumn{2}{c}{**Gender**} & \multicolumn{2}{c}{**Females—12**} & **Males—18** \\ \hline \multirow{4}{*}{Age (years)} & 20–30 & 2 & 2 \\ \cline{2-4}  & 31–40 & 0 & 6 \\ \cline{2-4}  & 41–50 & 4 & 8 \\ \cline{2-4}  & 51–54 & 6 & 2 \\ \hline \multirow{2}{*}{Cause of burn} & Flame & 4 & 10 \\ \cline{2-4}  & Scald & 8 & 8 \\ \hline \multirow{2}{*}{Burn degree} & II B & 8 & 12 \\ \cline{2-4}  & III & 4 & 6 \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Demographics and burn wound characteristics of patients included in the study. Exclusion criteria: (a) absence of consent; (b) women during pregnancy or lactation; (c) confirmed allergy to bromelain, pineapple, or papaya; (d) coagulation disorders; (e) patients with chemical or electrical burns; (f) patients on chronic corticosteroid treatment. Burn depth was determined by clinical examination: color, sensitivity, capillary refilling, thrombotic vessels, skin pliability, and laboratory examination using a skin scanner. As enzymatic debridement is seen as a painful procedure, it requires pre-, intra-, and postprocedural pain management. The type of analgesia or anesthesia was chosen depending on the anatomical region of the lesions. In most cases, continuous locoregional anesthesia and intravenous sedation, epidural anesthesia, were used. NexoBrid(tm) was used for enzymatic debridement. NexoBrid(tm) is presented as a package of powder and gel that needs to be mixed. It is a concentrate of proteolytic enzymes enriched in bromelain, extracted from the stem of Ananas comosus. It is used in the first 72 h after the burn injury and is limited to an area of no more than 15% TSBA. In patients with a burn area over 15% TSBA, enzymatic debridement is done in two sessions. For the treatment of every 1% TSBA burn, we used NexoBrid(tm) 2 g of sterile powder in 20 g of sterile gel, which are mixed till homogenization just prior to administration, no more than 15 min. Considering that the substance does not act on dry wounds, the pre-soaking phase is very important and, according to the instructions, must take at least 2 h. We used a modified internal protocol in which the enzymatic debridement process was divided into three stages, with an extension of the pre-soaking period to >6 h (Figure 2). In the second stage, after enzymatic debridement, burn depth was reassessed (Figure 3). In the case of full-thickness burns, we used split-thickness skin autografts harvested from an anatomical area with intact skin and as little exposure as possible to ensure minimum morbidity. Excision and grafting were early or delayed, depending on the bleeding pattern. If the pattern of bleeding after enzymatic debridement shows pinpoint capillary bleeding, it is the sign of a possible spontaneous re-epithelialization within 3 weeks.