Serum Selenium-Binding Protein 1 (SELENBP1) in Burn Injury: A Potential Biomarker of Disease Severity and Clinical Course.

Oxidative stress, systemic inflammation, and metabolic derangements are hallmarks of burn pathophysiology. Severely burned patients are highly susceptible to infectious complications. Selenium-binding protein 1 (SELENBP1) modulates intracellular redox homeostasis, and elevated serum concentrations have been associated with adverse clinical outcomes in trauma patients. We hypothesized that serum SELENBP1 at hospital admission and during hospitalization may constitute a meaningful biomarker of disease severity and the clinical course in burn injury, with pulmonary infection as primary endpoint. To this end, we conducted a prospective cohort study that included 90 adult patients admitted to the Burn Center of the University Hospital Zurich, Switzerland. Patients were treated according to the local standard of care, with high-dose selenium supplementation during the first week. Serum SELENBP1 was determined at nine time-points up to six months postburn and the data were correlated to clinical parameters. SELENBP1 was initially elevated and rapidly declined within the first day. Baseline SELENBP1 levels correlated positively with the Abbreviated Burn Severity Index (ABSI) (R = 0.408; p < 0.0001). In multiple logistic regression, a higher ABSI was significantly associated with increased pulmonary infection risk (OR, 14.4; 95% CI, 3.2-88.8; p = 0.001). Similarly, baseline SELENBP1 levels constituted a novel but less accurate predictor of pulmonary infection risk (OR, 2.5; 95% CI, 0.7-8.9; p = 0.164). Further studies are needed to explore the additional value of serum SELENBP1 when stratifying patients with respect to the clinical course following major burns and, potentially, for monitoring therapeutic measures aimed at reducing tissue damage and oxidative stress.

[Implementation of treatment by enzymatic debridement in burns: results of an interprofessional German-speaking expert workshop]. / Implementierung der Behandlung durch enzymatisches Debridement bei Verbrennungen ­ Ergebnisse eines interprofessionellen, deutschsprachigen Expertenworkshops.

INTRODUCTION: Since its introduction in 2013 Bromelain-based Enzymatic Debridement (ED) is increasingly used in burn centers. Published evidence shows its efficiency in eschar removal as well as a superiority in blood loss and necessity of further surgical procedures compared to standard-of-care. While the procedure is safe and shows reliable results in experienced hands, some practical and logistical issues must be challenged that are not described sufficiently in available literature. METHOD: A multi-professional panel, consisting of experienced users of ED from German-speaking burn units has been invited to an expert workshop. Topics concerning indication, definition of treatment pathways, practical issues, post-treatment and handling of complications have been coordinated in advance to allow discussion during the workshop. RESULTS: To each topic practical recommendations were developed and consented. Summarizing key messages have been additionally highlighted. They aim on helping to achieve optimal results after establishing the technique by new users as well as optimizing results by experienced users. Amongst others, the resulting recommendations deal with indications for ED beyond the classic domain, different treatment pathways depending on burn depth and primary result after ED with adapted post-treatment, management of treatment failure and implementation of infrastructural conditions. DISCUSSION: While efficiency of ED as well as superiority in some aspects of treatment of burn wounds could be shown in available literature, user-oriented recommendations for practical implementation are scarce. Although the recommendations and experts opinions published here are only partly evidenced based, they are still based on the pooled experienced of the panelists that easily outnumbers the cases published in literature so far and allow valuable support for a successful implementation of the technique.

Safety of enzymatic debridement in extensive burns larger than 15% total body surface area.

OBJECTIVES: Bromelain-based enzymatic debridement has emerged as an alternative to surgical eschar removal. Indications include partial thickness, mixed pattern, and full-thickness burns. Enzymatic debridement has been approved by the European Medicines Agency for treating burn wounds affecting <15% total body surface area (TBSA). Data and evidence for the treatment of areas >15% TBSA in one session is scarce. The aim of this retrospective study was to retrospectively analyze off-label use of enzymatic debridement in a single burn center for large TBSA burns. METHODS: Between 01/2017 and 12/2018, 59 patients with partial- to full-thickness burns underwent enzymatic debridement in a single center study. Patients were categorized into two groups: the regular use group with a treated area less than 15% TBSA and the off-label group (OG) with larger TBSA debrided in one session. Treatment was evaluated for systemic inflammatory reaction, bleeding, hemodynamic instability and electrolyte shifts. RESULTS: In total, 49 patients were treated in the regular use group with a median application area of 6% (IQR 2.5-9.5) and 10 patients were treated in the off-label group with a median application area of 18% (IQR 15-19) TBSA. We found no significant differences regarding blood pressure, body temperature or hemodynamic stability during and after enzymatic debridement. No treatment-related serious adverse events were observed in either group. Catecholamine use was similar in both groups. No differences in leukocyte counts, CRP, PCT and lactate prior to application and during the following three days were observed. Sodium, potassium, chloride and phosphate levels did not differ. We found no evidence of an electrolyte shift. Survival was 49 of 49 patients (100%) in the RG and 7 of 10 patients (70%) in the OG (p = 0.004). CONCLUSION: Enzymatic debridement did not result in any expected or unexpected side effects in the patient groups investigated. These preliminary results indicate the potential safety of bromelain-based enzymatic debridementin the treatment of burns greater than 15% TBSA.

Eschar removal by bromelain based enzymatic debridement (Nexobrid®) in burns: European consensus guidelines update.

INTRODUCTION: Bromelain-based Enzymatic Debridement has been introduced as an additional concept to the burn surgeon's armamentarium and is best indicated for mid-to deep dermal burns with mixed patterns. Increasing evidence has been published focusing on special regions and settings as well as on limitations of Enzymatic Debridement to improve patient care. To better guide Enzymatic Debridement in view of the increasing experience, there is a need to update the formerly published consensus guidelines with user-orientated recommendations, which were last produced in 2017. METHODS: A multi-professional expert panel of plastic surgeons and burn care specialists from twelve European centers was convened, to assist in developing current recommendations for best practices with use of Enzymatic Debridement. Consensus statements were based on peer-reviewed publications and clinical relevance, and topics for re-evaluation and refinement were derived from the formerly published European guidelines. For consensus agreement, the methodology employed was an agreement algorithm based on a modification of the Willy and Stellar method. For this study on Enzymatic Debridement, consensus was considered when there was at least 80 % agreement to each statement. RESULTS: The updated consensus guidelines from 2019 refer to the clinical experience and practice patterns of 1232 summarized patient cases treated by the panelists with ED in Europe (2017: 500 cases), reflecting the impact of the published recommendations. Forty-three statements were formulated, addressing the following topics: indications, pain management and anesthesia, large surface treatment, timing of application for various indications, preparation and application, post-interventional wound management, skin grafting, outcome, scar and revision management, cost-effectiveness, patient´s perspective, logistic aspects and training strategies. The degree of consensus was remarkably high, with consensus in 42 out of 43 statements (97.7%). A classification with regard to timing of application for Enzymatic Debridement was introduced, discriminating immediate/very early (≤12 h), early (12-72 h) or delayed (>72 h) treatment. All further recommendations are addressed in the publication. CONCLUSIONS: The updated guidelines in this publication represent further refinement of the recommended indication, application and post-interventional management for the use of ED. The published statements contain detailed, user-orientated recommendations aiming to align current and future users and prevent pitfalls, e.g. for the successful implementation of ED in further countries like the USA. The significance of this work is reflected by the magnitude of patient experience behind it, larger than the total number of patients treated in all published ED clinical trials.

[Burn wound treatment through enzymatic debridement: First experience in Switzerland]. / Enzymatisches Débridement zur Behandlung von Brandverletzungen: Erste Erfahrungen in der Schweiz.

INTRODUCTION: Thermal injuries are frequent and can be associated with relevant morbidity and mortality in severe cases. Excisional debridement followed by autografting is the standard of care for deep burns, but is associated with serious potential complications. Clinical results of a novel enzymatic debridement based on Bromelain raw material extracted from the pineapple plant (Nexobrid™) were published in 2014. At the Center for Burns at the University Hospital Zürich enzymatic debridement was introduced in 2016. Our experience and interpretation of the first 12 cases are reported. PATIENTS AND METHODS: Patients of at least 18 years of age with second and third degree burns were included in this study. Pregnant or breast feeding women were excluded. After so-called "pre-soaking" with saline solution, the Nexobrid™ gel was applied for 4 hours with occlusive sealing. After abrasion of the debris, "post-soaking" with Prontosan® followed and definite wound dressings were applied. RESULTS: The mean age of the patients was 51 (19-78) years, the length of hospital stay was 38 (1-92) days. The amount of burns was 25 (1-67) % of the total body surface area (TBSA). On average, 11 (1-18) % of the TBSA was debrided with Nexobrid™ after 7 (1-19) days. In 8 patients, the defects completely healed without scarring after Nexobrid™ treatment. In 4 patients additional surgical measures were necessary to complete the debridement as well as to cover the defect. The treatment with Nexobrid™ was efficient in difficult treatment areas such as back, hands and feet, where preservation of the demis prevented joint contracture through scarring. CONCLUSION: Treatment with Nexobrid™ extends the armamentarium to treat partial second-degree thermal injuries with good long-term results. It can be applied in analgosedation in an intensive care setting and reduces the need for surgical treatment.

Eschar removal by bromelain based enzymatic debridement (Nexobrid®) in burns: An European consensus.

Early debridement and/or eschar removal is regarded as a significant step in the treatment of deep partial and full thickness burns. It aims to control wound bioburden and allows early wound closure by conservative treatment or skin grafting. Preservation of viable dermis accompanied by early wound closure, is regarded as a necessary step to reduce scar related complication, e.g. functional limitations and/or unaesthetic scar formation. Aside from the classical techniques of surgical excision as tangential excision for eschar removal, hydro-surgery, maggot therapy, laser, enzymatic debridement have been described as additional techniques in the burn surgeon's armamentarium. It is widely accepted that early eschar removal within 72h improves the outcome of burn wound treatment by reducing bacterial wound colonization, infection and length of hospital stay. In contrast, the right technique for eschar removal is still a matter of debate. There is increasing evidence that enzymatic debridement is a powerful tool to remove eschar in burn wounds, reducing blood loss, the need for autologous skin grafting and the number of wounds requiring surgical excision. In order to assess the role and clinical advantages of enzymatic debridement by a mixture of proteolytic enzymes enriched in Bromelain (Nexobrid®) beyond the scope of the literature and in view of users' experience, a European Consensus Meeting was scheduled. The aim was to provide statements for application, based on the mutual experience of applying enzymatic debridement in more than 500 adult and pediatric patients by the consensus panelists. Issues to be addressed were: indications, pain management and anesthesia, timing of application, technique of application, after-intervention care, skin grafting after enzymatic debridement, blood loss, training strategies and learning curve and areas of future research needs. Sixty-eight (68) consensus statements were provided for the use of enzymatic debridement. The degree of consensus was remarkably high, with a unanimous consensus in 88.2% of statements, and lowest degree of consensus of 70% in only 3 statements. This consensus document may serve as preliminary guideline for the use of enzymatic debridement with user-oriented recommendations until further evidence and systematic guidelines are available.