The process to obtain reimbursement for enzymatic debridement in clinically deep burns.

INTRODUCTION: Burn eschar removal by enzymatic debridement with NexoBrid® (EDNX) results in a maximum preservation of all viable tissue, which is the main advantage over traditional tangential excision. The authors participated in a marketing authorization holder process to obtain reimbursement from the national health authorities in Belgium. MATERIAL AND METHODS: The reimbursement process consisted of three phases, as specified by the reimbursement regulations required by the Belgian National Institute for Health and Disability Insurance (NIHDI). RESULTS: Forty-one patients with clinically deep 2nd and 3rd degree burns, treated with EDNX in two Belgian burn centers, were included in the registry for the first phase of the reimbursement process. The total success rate of the EDNX treatment was 95.1% (39/41). Over half of the burn wounds treated with NexoBrid® (55.2%) did not require any additional surgical debridement or skin grafting. To obtain definitive reimbursement, an extra 16 patients were included. In this population, 51.4% did not require any surgical intervention. The total success rate of the EDNX debridement in this group was 100%. Based on an estimated market share of 12% and around 75 patients in the third year after final reimbursement, a market access consultant calculated that NexoBrid® will realize yearly savings for the Belgian Healthcare budget of at least €30.000. CONCLUSION: Based on the results of this Belgian registry study in combination with the yearly healthcare budget savings, the NIHDI granted a final reimbursement for EDNX treatment in adults, endorsed by the Minister of Health on November 5th, 2019.

Helpful hints in deciding what and when to operate after enzymatic debridement.

INTRODUCTION: In recent years, it has become clear that the burn eschar in deep burns can be selectively removed using the enzymatically debriding agent NexoBrid® (EDNX). In deep partial-thickness burns, such selective debridement preserves all non-injured dermis, which is sometimes sufficient for spontaneous re-epithelization. Nevertheless, it can be extremely challenging to determine exactly what and when to operate after an EDNX procedure. In this manuscript, we sought to investigate the clinical aspect of the enzymatically debrided wound bed of laser Doppler imaging (LDI)-confirmed deep dermal and full-thickness burns after NexoBrid® application. This to evaluate the residual wound healing capacity and implement specific indications for surgical therapy after enzymatic debridement. MATERIAL AND METHODS: Mainly LDI-blue areas, determined between 48 h and 5d after burn and afterwards treated with EDNX were selected. Six practical and three expert EDNX users evaluated the high-quality digital images of the wound beds immediately post NexoBrid® removal and after a 2 h wet-to-dry (WTD) dressing period. RESULTS: One hundred and two mainly LDI-blue areas in 32 patients were analyzed. Regarding the early decision-making, there were no significant differences in the wound bed evaluations, wound healing assessment and treatment decision of all 9 EDNX users post EDNX removal versus post WTD. Moreover, there was a good to excellent consensus between the practical and expert EDNX users in the individual wound bed evaluations. Even in the evaluation of a newly developed wound bed color code, with 7 different colors/patterns to choose from, the consensus was 80%. There was also an 84% consensus on the decision whether or not to operate. All mainly LDI-blue areas with incomplete enzymatic debridement, determined during clinical investigation by expert EDNX users, required surgery. Additionally, the expert investigators demonstrated that the following wound bed characteristics were independent predictors of the need for surgical treatment: visible fat lobules (p = 0.028), translucent fat lobules (p < 0.001), dermal step-off in the wound bed (p < 0.001), visible blood vessels (p < 0.001) and coagulated blood vessels (p = 0.023). Also, higher color code ranges on our own developed wound bed classification were significantly related to a surgical intervention (p = 0.006). When including the LDI flux values, the perfusion units were significantly different (p < 0.001) between the exclusively LDI-blue areas treated conservatively (mean 145.7) and the areas ultimately treated with autografts (mean 119.5). CONCLUSION: To the best of our knowledge, this study is the first to address the clinical wound bed evaluation of LDI-confirmed deep burns after NexoBrid® application. Based on our results, it is recommended to evaluate the wound bed twice: immediately after removing NexoBrid® to assess the viability of the wound bed and after the WTD period to reach a more complete decision. During these evaluations, wound bed characteristics such as incomplete debridement, visible and/or translucent fat lobules, visible and/or coagulated blood vessels and a dermal step-off in the wound bed combined with a higher range (4-5) in the newly developed wound bed color code should lead to an early and reliable decision for skin grafting. For burn centers using LDI, mean flux values below 119.5PU - in addition to the above-mentioned wound bed evaluation - are a clear indicator for surgical therapy.

Enzymatic debridement: past, present, and future.

INTRODUCTION: Early surgical debridement of the deep second and third-degree burns is still the standard of care (SOC) to prepare the wound bed for skin grafting. However, this technique has some drawbacks that explain the growing interest in enzymatic debridement as an alternative. In this article, we provide a historic overview as well as the current state-of-the-art and future prospective of this type of non-surgical debridement. MATERIALS AND METHODS: A narrative review of the available literature was conducted using a systematic search. RESULTS: A total of 32 articles were included. The only enzyme mixture still used nowadays for burn eschar removal is bromelain-based. There is increasing evidence that this type of enzymatic debridement is a powerful tool to selectively remove the eschar in deep burns, thereby reducing the need for autologous skin grafting compared to surgical SOC. Moreover, off-label use of enzymatic debridement with NexoBrid® (facial, pediatric, and >15%TBSA burns) has proven to be effective and safe. CONCLUSION: There is increasing evidence that bedside administered NexoBrid®, preferably under regional anesthesia, is a powerful tool for selective burn eschar removal. However, the clinical wound bed evaluation post-NexoBrid® procedure in relation to the optimal treatment decision-conservative treatment vs. surgery-is not yet completely elucidated. More high-quality prospective clinical trials are necessary to compare enzymatic debridement of objectively confirmed deep burns with the current standard treatment and assess the effectiveness of the eschar removal, the need for surgery, the healing time of such wounds, and the long-term scar quality.

Pain management during a bromelain-based selective enzymatic debridement in paediatric and adult burn patients.

BACKGROUND: Pain associated with surgical or enzymatic burn wound debridement prevents many burn centres from working outside an operating theatre, creating a burden. Alternatives for general anaesthesia to manage pain in burn patients treated with enzymatic debridements, such as regional anaesthesia, have not been studied in detail. This study explores the different possibilities for pain management during a bedside NexoBrid™ procedure. MATERIAL AND METHODS: We performed a single-centre retrospective study that included 82 paediatric, adolescent, and adult patients with deep dermal and full-thickness burns treated bedside with NexoBrid™ under regional or general anaesthesia. Outcome measures were pain during the NexoBrid™ procedure, the safety of the anaesthesia and the NexoBrid™ procedure, logistics of the bedside NexoBrid™ procedure, and time to wound closure. RESULTS: Forty-three patients in the adult group (43/67, 64%) only presented with burn wounds on one upper or the one or two lower extremities. In 29 of them (29/43, 67%), a NexoBrid™ procedure was performed under regional anaesthesia, which resulted in low pain levels without any adverse events. All seven patients in the paediatric group, where only one upper or one or two lower limbs were involved (7/15, 47%), underwent a NexoBrid™ procedure performed under regional anaesthesia where no adverse events were reported. In these children, the use of regional anaesthesia was associated with a significant decrease in time to wound closure (average treatment effect on the treated = -22.5 days, p = 0.021). CONCLUSION: This study highlights that regional anaesthesia administered at the bedside should be the method of choice for pain management during NexoBrid™ procedures because often, it can be adequately and safely performed in all age groups. This approach will reduce the burden on operating theatres. A flow chart has been developed to guide pain management during a NexoBrid™ procedure.

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.

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.