Enzymatic Debridement Agent Research Articles

714 Our Experience with Enzymatic Debriding Agent, Anacaulase, for Burn Injuries: A 14 Patient Case Series

714 Our Experience with Enzymatic Debriding Agent, Anacaulase, for Burn Injuries: A 14 Patient Case Series

771 Enzymatic Burn Wound Debridement: The Learning Curve

Abstract Introduction The European Medicines Agency (MEA) approved the use of a proteolytic enzymatic debriding agent enriched in bromelain in 2012. It has become a widely used non-surgical treatment alternative for the debridement of deep partial thickness to full thickness thermal burns. We will present our early experience with this product candidly. We will outline our sequential learning. Moreover, we will describe the pitfalls and lessons learned as well as demonstrate the evolution of our current practice guidelines. Methods This is a retrospective analysis of all patients treated with a bromelain based enzymatic debridement agent at a regional burn unit. 17 patients with a mean age of 44.53 years were treated with enzymatic debridement between April 2017 and April 2022. This period includes an 18 month pause where we did not use the product. We reviewed analgesia requirements, efficacy of debridement using the product, wound care post debridement (including the use of skin substitutes), skin grafting post application and overall outcomes. Results 17 patients were treated during this period. Nine patients had burns involving less than 5% TBSA, three patients had burns between 5 and 15% TBSA and five had burns greater than 15% TBSA. Of the 17 patients, 10 had the enzymatic debridement agent applied on the ward and seven had it applied in theatre. For the application of the product three patients had general anaesthesia, two had a combination of general and regional anaesthesia (e.g. spinal, axillary block), three had regional analgesia alone, seven received oral analgesia and ward based sedation and two received oral analgesia and ward based Methoxyflurane. 10 patients required skin grafting. One patient was treated with allograft post enzymatic debridement. One patient had their post enzymatic debridement wounds covered with Xenograft. The remainder had their post debridement wounds treated with dressings. There were three cases where the proteolytic agent failed to debride the burns. In the skin grafted group, 1 patient had complete graft loss. We will provide a narrative description and outline how each case contributed to the development of our current treatment algorithm. Conclusions We now believe that enzymatic debridement does have a real place within the armamentarium of burn wound excision with dermal preservation. Undoubtedly, there is a learning curve associated with its use. This must be considered by any service intending to adopt its use. Applicability of Research to Practice We support the use of bromelain enriched proteolytic enzymatic debriding agent in appropriate cases. With experience, it is likely to be useful in the management of many patients who sustain deep partial thickness to full thickness burns.

Preliminary evidence supporting a new enzymatic debridement product for use in chronic wounds.

A new recombinant proteolytic enzyme, isolated from maggot saliva, with fibrinolytic action has been investigated through a series of non-clinical toxicology and in-vitro/in-vivo pharmacology studies to explore its potential safety and efficacy as an enzymatic debridement agent for use in chronic wounds. Studies indicate that the enzyme has a good safety profile. When locally administered, it is not detrimental to wound healing, is non-sensitising and is rapidly inactivated in the systemic circulation. Adverse effects are limited, at very high concentrations, to transient erythema at the site of application. In-vitro testing indicates that the enzyme, whilst selective for fibrin, has additional proteolytic action against collagen and elastin, with enzymatic action for all three substrates being dose dependent. In-vivo, we used an established MRSA biofilm model, in which microbiological counts were used as a surrogate for debridement efficacy. Here, we showed that higher concentrations of the enzyme in a formulated proprietary gel, significantly reduced MRSA counts over a period of 2 to 14 days, and significantly improved the vascularity of the wound at 14 days. Together, these data support the potential for this maggot-derived proteolytic enzyme as a clinically effective debriding agent.

The Results of a Phase ⅢClinical Trial for a Novel Enzymatic Debridement Agent KMW-1 in Japanese Patients with Deep Dermal Burn and Deep Burn

The Results of a Phase ⅢClinical Trial for a Novel Enzymatic Debridement Agent KMW-1 in Japanese Patients with Deep Dermal Burn and Deep Burn

402EMF Comparison of the Effects of a Bromelain and Collagenase-based Enzymatic Agent on Inflammation and Eschar Debridement in a Partial Thickness Porcine Model

Thousands of people are admitted to the hospital each year with burns. Many such burns are deep partial or full-thickness and require some form of debridement to allow burn depth assessment, enhance healing and reduce scarring. At present, most deep burns are treated surgically, with a minority of patients treated with the only commercially available enzymatic debridement agent in the US, collagenase. However, there are few if any studies that demonstrate the efficacy of a collagenase-based enzymatic agent.

Development of a porcine hard-to-heal wound model: evaluation of a bromelain-based enzymatic debriding agent.

We describe the development of a novel porcine eschar model and compare the debridement efficacy of various concentrations of a novel bromelain-based enzymatic agent with collagenase. Full thickness excisional wounds were created on pigs and injected intradermally with various doses of doxorubicin. Wounds were monitored for a period of 46 days for the development of eschar and wound closure. After determining the optimal concentration and dose of doxorubicin resulting in non-healing eschars, these conditions were used to create additional wounds on another set of animals. The resulting eschars were treated with various concentrations of a novel bromelain-based enzymatic agent (EscharEx-02) or collagenase. The primary endpoint was greater than 95% removal of the central eschar. Consistent eschars composed of two distinct areas (a central area of exudate and slough representing the hard-to-heal wound bed, and a peripheral area of full-thickness mummified necrosis) were seen after injection of doxorubicin (0.5 ml/cm2 of stock solution 0.75mg/ml) at one and six days after wound creation. Complete removal of the central eschar was achieved in all wounds after five and eight treatments with 5% and 2% EscharEx-02 respectively. Complete removal of the central eschar with collagenase was achieved in 0% and 82% of the wounds after 10 and 16 treatments respectively. We describe a porcine model for creating eschars similar to hard-to-heal wounds in humans. A novel bromelain-based enzymatic debridement agent was more effective than a commercially available collagenase in removing eschars in this wound model.

Bromelain‐based enzymatic debridement of chronic wounds: Results of a multicentre randomized controlled trial

Chronic wounds are estimated to affect over 6 million people annually in the United States with an estimated annual cost of $25 billion. Debridement represents a key step in their management and is considered a basic necessity to induce the functional process of tissue repair. However, there is an unmet need for an efficient rapid acting non-surgical debridement agent. Bromelain-based enzymatic debridement has been proven to provide an effective, selective and safe non-surgical debridement in deep burns. EscharEx (MediWound Ltd, Yavne, Israel), is a bromelain-based enzymatic debridement agent currently in development for chronic wounds. The aim of this study was to assess its safety and efficacy in chronic wounds. Seventy-three patients suffering from a lower extremity ulcer of diabetic/venous insufficiency/post-surgical/traumatic aetiology were enrolled in a multicentre, assessor blinded, randomized controlled trial. Patients were randomized to topical treatment by either EscharEx or its gel vehicle for up to 10 daily 4 hour applications, and then continued follow-up for up to 6months. The EscharEx arm achieved a significantly higher incidence of complete debridement compared to the gel vehicle arm; 55 versus 29% (p= .047), thus meeting the primary endpoint of this study. The EscharEx and gel vehicle arms achieved similar reductions in wound area, non-viable tissue area and wound healing scores during the debridement period. There were no significant differences between the arms in the incidence of complete wound closure (41% in the EsxcharEx arm vs. 53% in the gel vehicle arm) and in the mean time to complete wound closure (70.0± 32.8 days in the EsxcharEx arm vs. 65.7± 38.4 days in gel vehicle arm). There were no significant safety issues and EscharEx demonstrated a favourable benefit to risk profile.

Rapid enzymatic burn debridement: A review of the paediatric clinical trial experience.

NexoBrid (NXB) has been proven to be an effective selective enzymatic debridement agent in adults. This manuscript presents the combined clinical trial experience with NXB in children. Hundred and ten children aged 0.5 to 18 years suffering from deep thermal burns of up to 67% total body surface area were treated with NXB in three clinical trials. Seventy-seven children were treated with NXB in a phase I/II study, where 92.7% of the areas treated achieved complete eschar removal within 0.9 days from admission. Thirty-three children (17 NXB, 16 standard of care [SOC]) participated in a phase III randomized controlled trial. All wounds treated with NXB achieved complete eschar removal. Time to complete eschar removal (from informed consent) was 0.9 days for NXB vs 6.5 days for SOC (P < .001). The incidence of surgical excision was 7.9% for NXB vs 73.3% for SOC (P < .001). Seventeen of these children participated in a phase III-b follow-up study (9 NXB and 8 SOC). The average long-term modified Vancouver Scar Scale scores were 3.4 for NXB-treated wounds vs 4.4 for SOC-treated wounds (NS). There were no significant treatment-related adverse events. Additional studies are needed to strengthen these results.

Instantaneous Specific Burn Debridement With an Enzymatic Debriding Agent: A New Resource for the Treatment of Burns

Nexobrid is a new resource for debridement that has emerged in recent years and is gaining relevance in the treatment of all kinds of thermal injuries. This product is an ointment (formed with a mixture of pineapple-derived enzymes enriched with bromelain) that is directly applied over the burn. With a single application, it performs a burned tissue-specific debridement in less than 4 hr, leaving a vital and completely debrided wound bed. In this article, we describe our experience with this product, and through a representative case, we explain the management of these patients in our Burns unit in consonance with national and international consensus.

PSS14 - Economic Burden of Burn Injuries Treated With An Enzymatic Debriding Agent In Spain

PSS14 - Economic Burden of Burn Injuries Treated With An Enzymatic Debriding Agent In Spain

Use of a selective enzymatic debridement agent (Nexobrid®) for wound management: Learning curve

Use of a selective enzymatic debridement agent (Nexobrid®) for wound management: Learning curve

Cost Analysis of a Novel Enzymatic Debriding Agent for Management of Burn Wounds.

Introduction. Given its efficacy and safety, NexoBrid™ (NXB) has become part of our therapeutic options in burns treatment with satisfactory results. However, no cost analysis comparing NXB to the standard of care (SOC) has been carried out as of today. Aim. To assess the cost of treatment with NXB and compare it to the SOC cost. Methods. 20 patients with 14–22% of TBSA with an intermediate-deep thermal burn related injury were retrospectively and consecutively included. 10 of these patients were treated with the SOC, while the other 10 with NXB. The cost analysis was performed in accordance with the weighted average Italian Health Ministry DRGs and with Conferenza Stato/Regioni 2003 and the study by Tan et al. For each cost, 95% confidence intervals have been evaluated. Results. Considering the 10 patients treated with NXB, the overall savings (total net saving) amounted to 53300 euros. The confidence interval analysis confirmed the savings. Discussion. As shown by our preliminary results, significant savings are obtained with the use of NXB. The limit of our study is that it is based on Italian health care costs and assesses a relative small cohort of patients. Further studies on larger multinational cohorts are warranted.

Identification and Characterization of Novel Matrix-Derived Bioactive Peptides: A Role for Collagenase from Santyl® Ointment in Post-Debridement Wound Healing?

Debridement, the removal of diseased, nonviable tissue, is critical for clinicians to readily assess wound status and prepare the wound bed for advanced therapeutics or downstream active healing. Removing necrotic slough and eschar through surgical or mechanical methods is less specific and may be painful for patients. Enzymatic debridement agents, such as Clostridial collagenase, selectively and painlessly degrade devitalized tissue. In addition to its debriding activities, highly-purified Clostridial collagenase actively promotes healing, and our past studies reveal that extracellular matrices digested with this enzyme yield peptides that activate cellular migratory, proliferative and angiogenic responses to injury in vitro, and promote wound closure in vivo. Intriguingly, while collagenase Santyl® ointment, a sterile preparation containing Clostridial collagenases and other non-specific proteases, is a well-accepted enzymatic debridement agent, its role as an active healing entity has never been established. Based on our previous studies of pure Clostridial collagenase, we now ask whether the mixture of enzymes contained within Santyl® produces matrix-derived peptides that promote cellular injury responses in vitro and stimulate wound closure in vivo. Here, we identify novel collagen fragments, along with collagen-associated peptides derived from thrombospondin-1, multimerin-1, fibronectin, TGFβ-induced protein ig-h3 and tenascin-C, generated from Santyl® collagenase-digested human dermal capillary endothelial and fibroblastic matrices, which increase cell proliferation and angiogenic remodeling in vitro by 50–100% over controls. Using an established model of impaired healing, we further demonstrate a specific dose of collagenase from Santyl® ointment, as well as the newly-identified and chemically-synthesized ECM-derived peptides significantly increase wound re-epithelialization by 60–100% over saline-treated controls. These results not only confirm and extend our earlier studies using purified collagenase- and matrix-derived peptides to stimulate healing in vitro and in vivo, but these Santyl®-generated, matrix-derived peptides may also represent exciting new opportunities for creating advanced wound healing therapies that are enabled by enzymatic debridement and potentially go beyond debridement.

A novel rapid and selective enzymatic debridement agent for burn wound management: A multi-center RCT

ObjectivesExcisional debridement followed by autografting is the standard of care (SOC) for deep burns, but is associated with serious potential complications. Conservative, non-surgical and current enzymatic debridement methods are inefficiently slow. We determined whether a non-surgical option of rapid enzymatic debridement with the debriding enzyme NexoBrid™ (NXB) would reduce need for surgery while achieving similar esthetic and functional outcomes as SOC. MethodsWe conducted a multi-center, open-label, randomized, controlled clinical trial including patients aged 4-55 years with deep partial and full thickness burns covering 5-30% of their total body surface area (TBSA). Patients were randomly assigned to burn debridement with NXB (applied for 4h) or SOC, which included surgical excisional or non-surgical debridement. ResultsNXB significantly reduced the time from injury to complete débridement (2.2 vs. 8.7 days, P<0.0001), need for surgery (24.5% vs. 70.0%, P<0.0001), the area of burns excised (13.1% vs. 56.7%, P<0.0001) and the need for autografting (17.9% vs. 34.1%, P=0.01). Scar quality and quality of life scores were similar in both study groups as were the rates of adverse events. ConclusionsEnzymatic débridement with NXB resulted in reduced need for and extent of surgery compared with SOC while achieving comparable long-term results in patients with deep burns. Trial registration: Clinical Trials.gov NCT00324311.

SANTYL® Collagenase as an effective debriding agent for burn wounds

Purpose: To demonstrate the effectiveness of using SANTYL® Collagenase in conjunction with mechanical debridement as the primary source of treatment for burn patients. This case report was on 61-year-old male with uncontrolled Type II Diabetes Mellitus, diabetic peripheral neuropathy, hypertension, and other comorbidities who presented with 1st degree burns on dorsum of 1st interdigital space of right foot. Methods: Mechanical debridement was performed initially at every encounter. Sterile Saline was then applied to clean the wound. Application of enzymatic debridement agent SANTYL® Collagenase (2mm thick) over the wound daily to obtain good clean granular base. Apply clean, dry and sterile dressingwithAquaphor® spray daily for moisture management. Patient was put into partial immobilization device to decrease forces to area of concern. Results: Baseline: The wound measured 0.8 cm×2.5 cm×0.1 cm. Wound had an eschar present, no drainage, erythematous base, and peeling of wound margins. Day 8: The wound measured 0.4 cm×1.25 cm×0.05 cm after sharp and enzymatic debridement (Santyl® Collagenase). There was no drainage present, decrease in erythematous base, no eschar present, and clear margins Day 15: The wound had fully healed without any presence of eschar or debris. Conclusions: The overall results show that using Santyl® Collagenase in conjunction with mechanical debridement was effective in treating burn wounds. Santyl® Collagenase is quick acting, removes devitalized tissue, results in full clearance, and causes less discomfort to the patient. The combination of this therapy allowed complete closure of the burnwound in under 28 days time. Further research should be conducted to support the efficacy of Santyl® Collagenase on different types of wounds.

Selectivity of a bromelain based enzymatic debridement agent: A porcine study

BackgroundDebridement of the burn eschar is a cornerstone of burn wound care. Rapid enzymatic debridement with a bromelain-based agent (Debriding Gel Dressing-DGD) has recently been investigated. The current study was designed to further investigate the selectivity of DGD to burned eschar in a larger number and more varied types of wounds. MethodsA systematic animal experiment was conducted to determine the effects of DGD on normal, non-injured skin, burns, exposed dermis of donor sites, and skin punch biopsy wells. Partial thickness dermal burns and partial thickness skin graft donor sites were created on a pig and treated with a 4-h application of DGD or its control hydrating vehicle that does not have any activity except hydration. Punch biopsy samples were taken before and after treatment and microscopically assessed for evidence of tissue viability and its respective components thickness. ResultsRapid dissolution of the burn eschar was noted in all DGD but not vehicle treated burns. There was no apparent damage to the underlying sub eschar dermis, donor sites, normal skin or punch biopsy wells after exposure to DGD. While the thickness of the treated tissues slightly increased due to edema, the increase in dermal thickness was similar after treatment with DGD or its vehicle. The increase in the cross section surface area of the treated punch biopsy wells was similar after treatment with DGD and its control vehicle. ConclusionsExposure of the burn eschar to DGD results in its rapid dissolution. Exposure of normal skin or non-burned dermis to DGD has no effects demonstrating its selectivity to eschar.

Escharotomy Using an Enzymatic Debridement Agent for Treating Experimental Burn-Induced Compartment Syndrome in an Animal Model

In patients with deep circumferential burns, adequate resolution of burn-induced compartment syndrome (BICS) is achieved by surgical escharotomy. Surgical escharotomy is traumatic, may cause considerable blood loss, does nothing toward debridement of the burn wound, and entails possible morbidity and complications. Debridase is a Bromelain derived enzymatic preparation capable of lysing the burn eschar within 4 hours, obviating the need for surgical debridement. It has an affinity to burned necrotic tissue and does not damage healthy skin. In our clinical assessment of the Debridase efficacy, we found in several cases of deep burns of the limbs that the measured IC pressure subsided after 2-4 hours of Debridase application and none of the enzymatic escharotomy treated patients suffering from circumferential burns developed BICS. To confirm these observations we conducted this controlled study. to assess the efficacy of Debridase for treating BICS in an animal model. A model for BICS was developed by making circumferential burns to pig legs and monitoring the anterior compartment the legs. BICS was induced in the legs of 5 pigs, 20 legs. 10 legs were treated with Debridase and 10 served as nontreated controls, treated by surgical escharotomy at the conclusion of the experiment. Debridase reduced BICS within 30 minutes from application. Debridase was as effective as a standard surgical escharotomy. Escharectomy using an effective enzymatic debriding agent is potentially an adequate, simple, fast and effective procedure to treat BICS, it has the added benefit of burn debridement without surgical escharotomy.

001 A Novel Model for the Assessment of Formulated Enzymatic Debriding Agents

In order to closely mimic the actual mechanism of wound debridement by an enzymatic debriding agent, a synthetic wound eschar substrate (SWES) has been developed. The SWES is prepared by the enzymatic conversion of fibrinogen to fibrin in the presence of fibrous bovine collagen and elastin, to form an insoluble planar matrix composed of the three major proteins present in wound eschar. Each of the proteinaceous components is uniquely labeled prior to formation of SWES with different dye, and the debridement test is conducted using a Franz Diffusion System. The debriding agent is applied to the SWES mounted on the donor compartment of the cell, and the digested hydrolysate containing dye‐labeled peptide fragments is sampled from the receptor compartment. Accordingly, the progress of digestion is obtained in real time. Since the three proteins are labeled with spectrally distinct dyes, data on the hydrolysis of the substrates can be collected simultaneously. This method facilitates the testing of formulated debriding products in a manner that closely mimics application to a wound and provides a powerful tool for the evaluation of formulated enzymatic debriding agents.

Effect of vibriolysin, an enzymatic debriding agent, on healing of partial‐thickness burn wounds

Vibriolysin, a new agent for enzymatic debridement, was recently shown to rapidly and thoroughly hydrolyze burn wound eschar within full-thickness wounds. The safety of this agent and its subsequent effect on wound healing processes have yet to be established and are addressed in this study. Within the context of a porcine partial-thickness burn wound model, the enzyme was shown to digest desiccated eschar after two applications, whereas four applications of another enzymatic preparation were required. Computerized morphometric analysis of dermal and epidermal growth from histologic sections on wounds harvested at day 7 and 10 was used to assess wound healing. The data indicate that wounds treated with Vibriolysin exhibited significant dose-responsive stimulation of granulation tissue (neodermis) as compared with control treatment groups. Repeated protease applications did not convert partial-thickness burns to full-thickness wounds, and no adverse inflammatory responses were detected between 1 and 10 days. The results suggest that in addition to its documented efficacy in the debridement of burn eschar, Vibriolysin may have beneficial effects on dermal reparative events.

Preliminary evaluation of vibriolysin, a novel proteolytic enzyme composition suitable for the debridement of burn wound eschar.

Vibriolysin, a proteolytic enzyme secreted by the marine microorganism Vibrio proteolyticus, was evaluated for its efficacy as an enzymatic debridement agent. Initial in vitro experiments revealed that the protease readily hydrolyzed proteinaceous components of eschar (e.g., fibrin, elastin, and in particular, collagen). Enzyme selectivity towards the digestion of denatured proteins but not viable elements was demonstrated in vitro and in vivo by treatment of full-thickness burn wounds with a porcine model. The full-thickness wound eschar was rapidly hydrolyzed by a hydrophilic vibriolysin composition with a resultant wound bed that appeared pink and viable. Vibriolysin exhibited desirable properties heretofore not described for the enzymatic debridement agents, in particular, its selective hydrolysis of dead but not viable tissue, debridement in the absence of bleeding, compatibility with adjunct therapies, and its unique shelf-life stability in a hydrophilic composition at ambient temperature.