Article 1
Establishing Consensus of Best Practice for CEA Use in Treatment of Severe Burns: A US Burn Provider Delphi Study. Glat P, Quirk L, Hultman S, et al. J Burn Care Res. 2024 Mar 19; Online ahead of print.
Cultured epithelial autograft (CEA) is a product consisting of autologous laboratory-grown keratinocytes used to treat severely burned patients. CEA is marketed in the United States under the tradename Epicel® by the Vericel Corporation. While the technology is marketed as a humanitarian device, acknowledging that efficacy has not yet formally been demonstrated, it is widely accepted in the burn community as one of the most viable routes to achieve wound closure in patients with very large total body surface area (TBSA) thermal injuries. CEA is indicated for adult and pediatric patients with a TBSA ? 30%, though, given cost considerations, most surgeons reserve use for significantly larger TBSA injuries. Several centers have published on their experience with CEA and related protocols, but significant center-to-center variability makes it challenging to glean best practices from the current available body of literature. As such, Vericel initiated and funded this consensus study, and an independent consulting company was used. The study utilizes a modified Delphi technique to collect expert opinion and obtain consensus. Three rounds of consensus-building were performed: 1. a qualitative 60-minute virtual interview by a trained moderator, 2. a 20-minute online quantitative survey, and 3. a moderator-led virtual round table. Prior to the first round, literature review identified four primary domains of variability: preoperative planning / surgical planning, immediate postoperative care, rehabilitation, and long-term care. Burn surgeons and nurses experienced in performing CEA procedures in the US were invited to participate. Inclusion criteria included working in an American Burn Association verified burn center, minimum 3 years working post-residency, and treatment of at least 2 patients with CEA over the previous 2 years.
Consensus was reached on all discussed subtopics between rounds 2 and 3, with the following notable recommendations being made. CEA use was recommended for minimum TBSA 30-50% (with utilization at the lower range for pediatric and elderly patients due to thinner dermis). Biopsies should be sent as soon as possible (1-2 days after admission or decision to use CEA). Dermal substitutes are uniformly utilized under CEA, and split thickness skin graft (STSG) underlay is consistently utilized (RECELL epidermal autograft vs. 4:1 vs. 6:1). CEA grafted areas should be left open to air a minimum of 6 hours a day with performance of daily dressing changes all at once, down to the level of the bridal veil primary dressing. Backing removal is recommended on postoperative day 10-14, with lifting of activity restrictions 10 days later. Compression garments may be introduced 2 months postoperatively, and laser therapy may be introduced 3-6 months postoperatively.
Overall, the Delphi method was successful in achieving consensus and the authors were able to produce a set of clear and useful guidelines for surgeons. Acknowledged limitations of the study include the small number of experts available to participate (due largely to the small population of individuals with significant CEA experience) and the potential for the virtual roundtable to introduce a bias in the form of tendency to conform to group opinion when face-to-face.
Article 2
Early Enzymatic Burn Debridement: Results of the DETECT Multicenter Randomized Controlled Trial.
Shoham Y, Rosenberg L, Hickerson W, et al. J Burn Care Res. 2024 Mar 4;45(2):297-307.
Anacaulase-bcdb, marketed as NexoBrid®, has been shown to achieve enzymatic, selective debridement of burn eschar. It is touted to provide a nonsurgical modality for debridement which may reduce the need for skin grafting. Proponents cite benefit in both routine burn care and mass casualty incidents (where burn surgical expertise may be more limited). This BARDA-funded Phase 3 multicenter, randomized, controlled DEbride and proTECT (DETECT) trial was performed to assess safety and efficacy of NexoBrid® for US FDA approval. At the time this study was initiated NexoBrid® was approved for use in Europe and other regions outside the United States. The authors hypothesized that NexoBrid would remove eschar and, therefore, reduce the need for excisional surgery while achieving long-term outcomes comparable to standard of care. Included in the study were adult patients with deep partial and full thickness burns covering 3-30% total body surface area (TBSA). Those with circumferential limb burns, infected burns, inhalation injury, pregnancy, or major comorbidities were excluded. The studied intervention of NexoBrid® treatment was compared to a placebo control (gel vehicle, GV) and standard of care (SOC, nonsurgical and surgical). Prior to treatment, patients were randomized in a 3:3:1 ratio to receive NexoBrid®, SOC, or GV, with all care beyond eschar removal stage equivalent. The primary endpoint of interest was complete (>95%) eschar removal at the end of the debridement phase (NexoBrid® vs. GV). Secondary efficacy assessment (NexoBrid® vs. SOC) was performed for the need for surgical excision, time to complete eschar removal, and estimated blood loss associated with eschar removal. Safety endpoints evaluated included time to wound closure as well as cosmesis considerations at 12 and 24 month follow up visits (using the modified Vancouver Scar Scale, MVSS). Levels of sedation, pain, and adverse events were also examined.
During the study period 175 patients were randomized: 75 to NexoBrid®, 75 to SOC, and 25 to GV, with study treatment administered to 169. There were no significant differences between groups with regard to patient characteristics and burn etiologies. Rates of complete eschar removal were significantly higher with NexoBrid® vs GV (93% vs. 4%, P < 0.001), demonstrating efficacy. Median time to eschar removal was 1.0 and 3.8 days for NexoBrid® and SOC (P < 0.001). 72% of SOC patients and 4% of NexoBrid® patients required surgical excision to achieve complete eschar removal. Significantly less acute blood loss was seen with the NexoBrid® group than SOC (14 vs. 800 mL, P < 0.001). Time to complete wound closure was similar between the NexoBrid® and SOC arms. Comparison of MVSS scores yielded noninferiority of NexoBrid® as compared to SOC at 12 and 24 months.
Clinical experience within the burn community largely seems to concur with the study's findings of efficacy, with eschar removal achieved and reduction in need for surgical intervention. Although the study superficially addresses required levels of procedural sedation and patient self-reported pain scores, the study notably downplays these concerns as compared to substantial anecdotal evidence. Implementation of this technology for eschar removal requires robust protocols for analgesia and sedation with appropriate monitoring that may prove challenging for some centers and units (and in the setting of a mass casualty incident).
Article 3
Implementation Evaluation of Tiered Tele-Triage Pathways for Burn Center Consultations and Transfers.
Agoubi L, Clark N, Gibbs S, et al. J Trauma Acute Care Surg. 2024 Mar 1;96(3):409-417.
Each year in the United States nearly 500,000 patients are treated for burn injury. Approximately 130 burn centers staffed by approximately 300 burn surgeons work to care for the most severely injured patients with the use of only 2000 (approximate) specialty burn beds; more minor burns are cared for at non-specialty centers. Appropriately triaging patients whose needs cannot be sufficiently met at non-specialty centers is imperative to improving burn patient outcomes in the United States. With this study, the University of Washington, Harborview Medical Center, sought to evaluate their tele-triage protocol which was developed to allow specially trained “transfer nurses” to evaluate burn center referrals with the use of imaging.
The protocol called for the tele-triage of burn patients into four categories:
- Green – low acuity, amenable to outpatient follow-up
- Blue – low acuity, potential for local care and discharge
- Red – low acuity, consulting provider requests transfer (referring hospital cannot provide adequate wound care and/or resuscitation)
- Black – high acuity, severe burns (>5% TBSA, airway compromise, any full-thickness, electrical/chemical mechanism, concern for non-accidental trauma).
Burn providers were consulted for all blue, red, and black pathway patients. The designated transfer RNs were specially trained bi-annually and additional training was provided with over 30 videos produced by the burn center staff. The transfer RNs were encouraged to share the video training with referring providers (videos published to YouTube and readily available at: https://www.youtube.com/watch?v=QPZN13a9CtI&list=PLFEMTIzjmLeUC-tONmpxadXa_7rusm_B6
With the implementation of the protocol, the transfer RNs triaged 5272 burn referrals from 2017 to 2019. By September 2017, more than 90% of referrals were assigned to a pathway. The protocol implementation reduced the number of calls to burn providers by a mean of 40 per month (green pathway patients). In addition, the authors found the protocol reduced transfers with transfers steadily decreasing over the study period. Overall, the authors found that 74% of referrals were assigned to lower acuity pathways (green/blue). The pathway assignment reliably predicted final disposition in more than 85% of cases; after provider review, the remaining cases were either upgraded or downgraded.
Limitations included non-standardization of transfer data (as the data was not initially intended to be used for research), single-center nature, performance during the COVID-19 pandemic, and lack of outcomes data for patients triaged to outpatient follow up and for patients who were up-triaged after burn surgeon review.
While numerous limitations do exist for the wide-spread adoption of this protocol, trauma surgeons readily recognize the scarcity of resources which exist for caring for burn patients in our country. The integration of protocols such as this are key to ensuring our nation’s severely burned patients receive specialty care to improve outcomes.
