Historical Perspectives on the Development of Current Standards of Care for Enzymatic Debridement

Abstract

Background and Objective: The use of plant-based products for burn treatment dates back to 1600 BC. Enzymatic debridement, which can be achieved as non-surgical or conservative debridement, has recently gained increasing attention. Several reviews have been published thus far. However, there has been no historical article including the achievements of the last 20 years, and this is the first review to present the achievements made in the field of enzymatic debridement in the last 20 years. This study aimed to present a historical overview of the development of enzymatic debridement until the present day. Methods: Enzymes from bacteria and plants were initially used for full-thickness burn treatment; however, they did not gain attention. Papain-derived products were the first plant-based products used for enzymatic debridement. Sutilains gained broad use in the 70s and 80s but came off market in the 1990s. Bromelain has been used for burn treatment owing to its strong debriding properties. NexoBrid™ is used as a minimally invasive approach for enzymatic debridement of deep dermal burns. However, its use has been limited due to commercially available bromelain and the presence of four distinct cysteine proteinases. NexoBrid™ involves faster eschar removal together with reduced blood loss, leading to improved long-term outcomes. However, research on nonoperative enzymatic debridement of burns has taken decades and is still ongoing. Results: Overall, the results of our study indicate that necrectomy, which has been used for a long time, remains the standard of care for burns. However, enzymatic debridement has several advantages, such as faster eschar removal, reduced blood loss, and reduced need for skin grafting, especially in cases of facial and hand burns. Enzymatic debridement cannot replace surgical intervention, as the enzyme only works on the surface of the eschar. Enzymatic debridement is not recommended in the early phase of scald burns. Conclusions: Enzymatic debridement has become an integral part of burn therapy and the standard of care in specific burn centers.

Enzymatic Debridement (Nexobrid) on Burned Hands: Retrospective Review from a Burn Referral Center in Spain

“…15 Bromelain, the active ingredient in Nexobrid, is a proteolytic enzyme derived from pineapple fruit, initially described by Heinicke et al 16 Nearly 30 years later, Klein et al 17 conducted the first randomized clinical trial on the enzyme's use for burn debridement, whereas Boswick et al 18 published a multicenter study investigating the efficacy of enzymatic debridement with bromelain the same year. However, results varied, potentially due to the lack of standardization in the product composition, 15 leading to uncertainty about the actual proportion of bromelain present and the discovery of up to four different proteolytic enzymes. 19 In December 2012, Nexobrid, a bromelain-based product with standardized composition (0.09 g of bromelain per gram of product), received approval in Europe.…”

Efficiency of Bromelain-Enriched Enzyme Mixture (NexoBrid™) in the Treatment of Burn Wounds

“…The need for non-surgical burn debridement resulted in the development of bromelainbased agents. In 1957, Heinicke and Gortner described a new protease from pineapple fruit [14]. In 1971, Levine demonstrated the therapeutic properties of bromelain [15].…”

“…Since 2012, NexoBrid™ has been approved as a minimally invasive treatment [14]. The instructions for bromelain use recommend for it to be applied to less than 15% TBSA in one session.…”

Role, Development, and Value of Enzymatic Debridement as Integral Component in Initial Treatment of Burn Injuries Exemplified by NexoBrid®

“…In the 1970s, Levine et al observed promising results with good debriding effects in animal tests by using a pineapple-derived enzyme mix, called "Bromelain" [34,35]. Still, the analysis of the exact chemical composition as well as standardized manufacturing remained major barriers for the establishment of bromelain-derived approaches in the wide market [36]. With current technologies, these impediments were easily overcome.…”