This is a standardized dressing protocol for patients with toxic epidermal necrolysis. This robust protocol utilizes silver ion dressings designed to accelerate healing and alleviate pain, minimizing hospital stays.

Toxic epidermal necrolysis (TEN) is a severe cutaneous adverse drug reaction with high mortality rates, demanding specialized wound care to address epidermal detachment and bullae formation. This study summarizes a standardized dressing management protocol to enhance the healing process, reduce complications, and improve patient comfort during dressing changes for TEN patients. The protocol emphasizes a systematic approach to patient preparation, environmental control, and the utilization of silver-ion-based dressing materials. Specifically, it integrates gentle cleansing techniques with a warmed povidone-iodine saline solution, precise necrotic tissue removal, and silver sulfadiazine lipid hydrocolloid dressings to maintain an optimal healing environment. The effectiveness of this protocol was further validated through a retrospective analysis, which showed a significant reduction in the onset of re-epithelization, wound healing time, and hospital stays, resulting in diminished pain during dressing changes. Furthermore, this protocol also provides tailored strategies for dressing changes in sensitive areas, ensuring comprehensive care. The standardized protocol streamlines the dressing process and contributes to more efficient allocation of healthcare resources, establishing a robust foundation for TEN treatment that can be adopted in clinical practice and inform future research.

Toxic epidermal necrolysis (TEN) is a severe cutaneous adverse drug reaction, distinguished by widespread epidermal detachment and bullae formation, which confers an increased susceptibility to complications such as infections and derangements in fluid and electrolyte balance¹. This condition invariably precipitates a host of complications, notably infection and fluid and electrolyte imbalances, with the severity of TEN being inextricably linked to the manifestation and progression of such complications. The literature has documented that TEN mortality rates span from 12% to 30%². Areas of diffuse erythema are seen in TEN, with individual macular lesions at the periphery. Large, flaccid blisters are formed from the detachment of the epidermis from the underlying dermis. The roofs of the blisters turn necrotic and large 5 cm sheets show denudation of the epidermis³. The efficacious management of TEN is predicated upon the prompt discontinuation of the inciting drug regimen and meticulous wound care⁴. Of particular note, wound care assumes a central position in the treatment paradigm for TEN patients. Its principal objectives are to stanch occult fluid loss, forestall the onset of sepsis, and foster epithelial regeneration⁵. The overarching principles governing wound care encompass safeguarding the underlying exposed dermis, attenuating the potential for infection, mitigating the risks of pigmentary alterations and scarring, and optimizing the process of epithelial reformation. More specifically, wound care resides within the purview of surgical debridement, and its operational modalities entail selecting either debridement procedures or supportive dressings. This translates into either the excision of detached and necrotic epidermal tissues or the retention of viable epidermis as a biological dressing, followed by the application of supportive dressings to facilitate epithelial reformation⁴.

The extensive skin lesions associated with TEN are particularly susceptible to being invaded by microbes such as bacteria, fungi, and other pathogens⁶. Conventional dressings, such as gauze and cotton pads, exhibit limited water absorption capabilities and have a propensity to adhere to wound surfaces, leading to iatrogenic trauma, exacerbated pain levels, and bleeding during dressing changes⁷. These materials provide inadequate air permeability, which impedes wound healing⁸. Furthermore, traditional dressings are ineffective at preventing and managing infections, increasing the risk of wound sepsis⁹. Their inability to facilitate wound healing results in prolonged convalescence, increased patient discomfort, and higher healthcare costs¹⁰.

Novel dressings, such as zinc oxide talcum powder wraps and silver ionic dressings, have been investigated for TEN management¹¹. Notably, silver sulfadiazine lipid hydrocolloid dressings dressing, a typical silver ionic dressing that sustains the release of silver sulfadiazine, has shown promise in maintaining adequate antibacterial levels, promoting a moist healing environment, and decreasing irritation and pain during dressing changes^12,13,14,15. Recent studies suggest that silver sulfadiazine lipid hydrocolloid dressings can reduce healing time, infection rates, and patient discomfort compared to traditional dressing^16,17. However, standardized dressing change protocols still need to be developed for TEN patients.

At present, there is a lack of standardized protocols for the wound care of patients with toxic epidermal necrolysis (TEN). Moreover, wound management practices differ among various medical units. Consequently, the establishment of standardized wound management for TEN patients constitutes a crucial yet unfulfilled clinical priority¹⁸. The primary aim of this research is to standardize the wound dressing change procedures for TEN patients. Specifically, it endeavors to compare the wound healing time between two different dressing change regimens: one centered around silver sulfadiazine liposome hydrocolloid dressing, and the other being the conventional dressing change approach. The secondary objective is to investigate the efficacy of silver sulfadiazine liposome hydrocolloid dressing in facilitating wound healing in these patients.

All procedures performed in this study comply with the ethical standards of the First Affiliated Hospital of Chongqing Medical University and the Declaration of Helsinki and its later amendments or similar moral standards. This study was approved by the ethics committee of Chongqing Medical University (Number: 2024-155-01), Participants were informed of the process, content, and possible medical phenomena before the start of the trial to ensure their right to know. Patients and their families were consulted to determine their willingness to participate in the trial activities. Before the enrollment of this patient, their informed consent for the use of photographs and participation in this research was obtained. This dressing management protocol was primarily designed for patients diagnosed with TEN. However, this protocol is also applicable for patients with extensive body areas of epidermolysis, such as pemphigus, bullous pemphigoid, and epidermolysis bullous.

1. Preparations

1. Environmental preparation
   1. House the patient in a single room with protective isolation, maintaining it at 25-28 °C and 40-50% humidity, with daily UV irradiation and ventilation. Place a far-infrared grill 30-50 cm from the patient for 30-60 min sessions to treat trauma; allow them to adjust their position for optimal exposure.
   2. Disinfect the room, including the floor and bed, using a 500 mg/L chlorine solution twice daily.
   3. Ensure that the bed is an antibedsore inflatable mattress with sterile sheets, sterile cotton pads, and disposable nursing pads. Use whole-body exposure therapy with disinfected quilt frames during dressing changes to minimize epidermal stripping.
      NOTE: Disposable nursing pads were used to prevent fluid seepage.
2. Patient preparation
   1. For bedridden patients, carefully rinse and dress localized skin breaks without moving them from the bed.
   2. For ambulatory patients who can stand by the bedside, place a medical waste bag beneath their feet to ensure that garbage and liquids are collected and flushed.
      NOTE: This precaution prevents the ward floor from getting wet due to rinsing fluid.
3. Material preparation
   1. Keep essential items ready, including a treatment trolley, sterile gauze rolls, gloves (both sterile and film), empty needles, a dressing change box with sterile scissors, and medical swabs.
      1. Ensure the dressing change box contains large and small gauze blocks, Bactroban ointment, fu fang comfrey oil, povidone-iodine, 0.9% sodium chloride in 500 mL bottles, silver sulfadiazine lipid hydrocolloid dressings, rb-bFGF, sterile cotton pads, duvet covers, pillowcases, and petroleum jelly oil gauze.
   2. Keep personal protective equipment ready-disposable sterile surgical gowns, caps, shoe covers, masks, and household and medical garbage bags.

2. Skin cleansing and disinfection

1. Prepare the cleaning solution by mixing povidone-iodine with bottled saline in a 1:9 ratio. Warm the mixture in hot water to achieve a temperature of approximately 35 °C.
   NOTE: The mixture's temperature should be based on the patient's comfort. Iodophor primarily functions as a disinfectant and sterilizing agent. If a patient is allergic to iodophor, its use can be selectively considered depending on the severity of the allergy. Nevertheless, chlorhexidine can serve as an alternative.
2. Assess the patient's condition to ensure the cleaning technique is suitable.
3. Remove the previous dressing by moistening it with ozone water to facilitate detachment from the skin.
4. Clean the patient's entire body using the prepared povidone-iodine saline solution and gently dry the patient's skin using a large sterile gauze.
   1. For the first dressing change, rinse the lesion area with the povidone-iodine saline solution.
      NOTE: There is no need to remove all the necrotic epidermis entirely. Just wait for them to fall off naturally. When removing previous dressings, if the dressing adheres to the skin tightly, avoid forceful separation to prevent damage to the delicate neonatal epithelium.
5. Use far-infrared thermal retention devices throughout the process to warm the patient and protect against chill¹⁹.

3. Dressing change procedures

1. Dressing change at the erythema and bullae stage
   NOTE: Preserve the skin's integrity to improve the protective barrier and prevent secondary skin infections. Avoid forcibly removing extensive bullae and loosened epidermis; leave them in place to serve as biological dressings.
   1. In cases in which the epidermis has been shed and there is debris, gently remove necrotic tissue and debris that can be easily detached without force.
      NOTE: In step 2.3, when the previous dressing is moistened with ozone water, the necrotic, detached epidermis would come off with the removal of gauze or can be gently removed by hand.
   2. Preserve the unpeeled skin tissue (the ruptured epidermis that is not removable along with gauze). Use sterilized scissors to remove any loose or peeling skin tissue.
   3. Leave small bullae and those with minimal exudate untreated, keeping the bullae wall intact for natural absorption.
   4. For large bullae >2 cm in diameter filled with fluid, apply iodophor for sterilization. Then, use a 2 mL sterile syringe to aspirate the fluid from the bullae through a low puncture, and send the fluid for bacterial and fungal cultures. Alternatively, use a surgical blade to make a small incision at the lowest point of the bullae for natural drainage.
   5. Overlay with sterile gauze.
2. Dressing change at the exfoliation stage
   1. Confirm that the patient's epidermis is loose and exfoliated, with associated exudation and increased pain.
   2. Use the Numerical Rating Scale to assess the patient's pain level.
   3. To alleviate discomfort, administer 100 mg of Tramadol intramuscularly 30 min before dressing changes.
   4. Measure the dimensions and contour of the skin lesion to determine the appropriate dressing size.
   5. Apply Silver Sulfadiazine Lipid Hydrocolloid dressing, ensuring complete coverage and extending 0.5 to 1 cm beyond the wound margin.
   6. Saturate a substantial sterile gauze block with comfrey oil and Bactroban ointment and place it on the silver ion dressing.
   7. Overlay with sterile gauze and secure with sterile cotton pads.
      NOTE: Avoid using tapes that adhere directly to the skin, which will tear the skin when changing dressing. Instead, sterile cotton pads, like clothes, should cover the whole body.
3. Dressing change at the reepithelization stage
   1. Observe that the skin is in the reepithelization stage, showing a tendency to heal but remaining fragile.
   2. Discontinue using silver sulfadiazine lipid hydrocolloid dressings and switch to rb-bFGF to accelerate the healing process.
      NOTE: Protect the newly formed skin tissues by avoiding any actions that could cause dragging, pulling, or tugging.
   3. Implement a bi-hourly axial turnover to reduce the risk of developing pressure ulcers due to prolonged contact pressure.

4. Efficacy and number of dressing changes

1. In cases of profuse exudates, replace the dressing 1-2x daily. Conversely, if the exudate is scant, change the dressing every 2-3 days.
2. The three stages mentioned above could exist simultaneously. Monitor the patient's skin condition and adjust care procedures to support the healing process effectively.
3. Closely monitor the exudate from cutaneous lesions, documenting its volume, color, and odor. Repeat the previous procedures if necessary. Adhere to the following standardized protocol during dressing changes: initial disinfection, subsequent cleansing, thorough drying, and applying a new dressing.

5. Dressing change at particular sites

1. Mouth and lips
   1. To alleviate oral discomfort, use a 5% sodium bicarbonate solution and lidocaine for gargling.
   2. Apply thick Bactrim or erythromycin ointment to the lips for local antiseptic and protective effects.
   3. Oral hygiene practices
      1. Advise patients to avoid keeping their lips closed for long durations.
      2. Encourage patients to open their mouths frequently to reduce the risk of secondary chapping and promote healing.
2. Ocular area
   1. In cases where a patient presents ocular symptoms, advise them to consult an ophthalmologist to assess the condition.
   2. Flush the conjunctival sac of the eyelid daily with 0.9% sodium chloride to maintain cleanliness.
   3. Cleanse the eye promptly of pseudo membranes and inflammatory secretions using sterile cotton swabs.
   4. Administer Tobramycin and levofloxacin eye drops 4x daily to treat ocular infections and inflammation.
   5. Cover both eyes with petroleum jelly gauze for a patient incapable of closing their eyes.
      NOTE: Regularly covering both eyes with petroleum jelly gauze is also recommended for regular patients.
3. Perineum
   1. Perform daily perineal irrigation with a saline solution to maintain hygiene.
   2. After irrigation, apply silver sulfadiazine lipid hydrocolloid dressings dressing to the affected skin lesions.
   3. Wrap the area with comfrey oil gauze.
   4. Advise male patients to use comfrey oil gauze to separate the penis from the scrotum to prevent adhesion and facilitate healing.

We retrospectively compared the outcomes of this new method (based on silver sulfadiazine lipid hydrocolloid dressings dressing) with the conventional method (which did not involve silver sulfadiazine lipid hydrocolloid dressings dressing or sterile cotton pads) throughout the years 2023-2024. Sixty patients with toxic epidermal necrolysis (TEN) from the Dermatology Department of the First Affiliated Hospital of Chongqing Medical University were enrolled for statistical analysis. Mean values, standard deviations (SD), and the Wilcoxon rank-sum test were applied to contrast the demographic details, rash control duration, wound desiccation time, skin healing period, and average hospitalization stay of patients in the experimental group treated with silver sulfadiazine liposome hydrocolloid dressing and those in the control group using common petrolatum gauze. P < 0.05 was regarded as indicative of a statistically significant difference.

Figure 1 shows the critical dressing change steps and outcomes in a patient with TEN. On admission, the patient's epidermis becomes loose and exfoliated (Figure 1A). The detached epidermis and the necrotic tissue or debris adhering to the wound are removed gently using sterile scissors (Figure 1B). Then, silver sulfadiazine lipid hydrocolloid dressings dressing is used based on the size of the skin lesion. An appropriate-sized silver sulfadiazine lipid hydrocolloid dressings dressing was gently applied to ensure complete coverage, extending 0.5-1 cm beyond the wound margin (Figure 1C). A large gauze block soaked in comfrey oil and Bactroban mixture was used to cover the silver sulfadiazine lipid hydrocolloid dressings. Finally, sterile gauze and cotton pads were fixed on top (Figure 1D). Figure 1E,F show the outcomes for this patient on day 7 (after two dressing changes) and day 11 (after three dressing changes). The skin was re-epithelized.

Table 1 compares patients' demographic characteristics and outcomes between this new and conventional method. There was no significant difference in age, sex, and exfoliation area between the two groups (P > 0.05). However, the re-epithelization start time, wound healing time, and length of stay were significantly shorter using our new method than the conventional method (P < 0.001). Besides, when changing dress, patients feel less pain using our new method (P < 0.001).

Figure 1: Key dressing change steps and outcomes in a patient with toxic epidermal necrolysis. (A) The exfoliated and necrotized epidermis on admission. (B) The back of the patient after removing the detached epidermis and necrotic tissue. (C) The use of silver sulfadiazine lipid hydrocolloid dressings dressing. (D) Final cover with sterile gauze and fixation with a sterile cotton pad. (E) Outcome at day 7. (F) Outcome at day 11. Please click here to view a larger version of this figure.

Table 1: Comparison of demographic and outcome results. Abbreviation: BSA = body surface area.

TEN is a rare but devastating drug reaction characterized by extensive skin detachment affecting more than 30% of the body's surface area and the mucous membranes¹⁸. TEN is associated with severe complications, like sepsis with a mortality rate of 14%-30%. It has been reported that mortality is strongly linked with the areas of detached skin because the widespread skin bullae significantly increases the risk of infection due to the loss of the protective skin barrier²⁰.

TEN poses a significant threat to patients' physical and mental well-being, highlighting the importance of efficient dressing management in promoting skin healing, alleviating pain, decreasing hospital stays, and enhancing treatment efficiency²¹. Effective dressing management plays a crucial role in treatment, as it can promote skin healing, significantly reduce patient pain, shorten hospital days, and comprehensively improve treatment. Third-level centers usually have more advanced medical equipment and technology, which can provide more comprehensive treatment services, while local hospitals focus more on initial treatment and patient stability. Understanding the previous practice standards for all categories listed in the new plan helps medical institutions better develop and implement treatment plans, ensuring that patients receive the best treatment outcomes. This study aimed to evaluate. the effectiveness of a standardized dressing management protocol in the treatment of TEN.

Critical steps in the protocol
The critical steps in managing skin conditions involve a systematic approach to environmental and patient preparation, including a single-occupancy room with controlled temperature and humidity, disinfection protocols, and using sterile materials to prevent infection. The process encompasses patient-specific care, such as maintaining oral and ocular hygiene and managing perineal health, with particular attention to non-ambulatory patients. Cleaning solutions, such as a warmed povidone-iodine saline mixture, are meticulously prepared for gentle and effective skin cleansing. The dressing change frequency must be adjusted according to the patient's exudate from the skin lesion. The silver sulfadiazine lipid hydrocolloid dressings dressing has the potential for antibacterial and anti-inflammatory properties and minimizes skin adhesion and discomfort. The benefits of comfrey oil include muscle regeneration, anti-inflammatory, antiviral, antioxidant, and vasodilatory effects. The comfrey oil and Bactroban combination form a protective lipid barrier on the skin, reducing the risk of wound infection and promoting rapid recovery of damaged areas²².

Iodine allergy patients should be cautious when using povidone-iodine (usually referred to as povidone-iodine). Due to the differences in chemical structure and bioavailability of different iodine preparations and iodine's slow and sustained release characteristics in povidone-iodine, its irritation to the skin is reduced, and its bactericidal effect is enhanced²³. However, for iodine allergy patients, using povidone-iodine depends on the severity and mechanism of the allergic reaction. Individuals with mild allergies not caused by specific components of povidone-iodine may use it with caution under close medical supervision. Still, those with a history of severe allergies should be highly vigilant, as even small doses of iodine may cause severe reactions. Therefore, professional medical personnel must assess the patient's allergy history and health status before use. In case of uncertainty, it is advisable to avoid its use to prevent risks.

Infrared light, as a non-invasive physical therapy, has shown potential in TEN treatment. It is located between visible light and microwave, with solid penetration and the ability to penetrate deep into the skin. Near-infrared and far-infrared light have attracted medical attention due to their mild therapeutic effects. Infrared light can promote blood circulation, accelerate the delivery of nutrients and oxygen to wounds, facilitate healing, alleviate inflammatory response, decrease the release of inflammatory mediators, and relieve pain and discomfort²⁴. It can also promote cell proliferation and collagen synthesis, accelerate skin regeneration and repair, and indirectly reduce the risk of infection by promoting blood circulation and reducing inflammation²⁵. In TEN treatment, infrared light serves as an auxiliary treatment method. Doctors must develop personalized plans based on the patient's condition and wound status, use professional treatment equipment for irradiating the wound, and follow medical advice for treatment time and frequency. However, infrared therapy is not all-powerful, and various factors influence its effectiveness. It should be combined with other treatment methods to form a comprehensive treatment plan to achieve the best results.

Modifications and troubleshooting of the method
The dressing management protocol utilized in this study represents an advancement over prior methodologies. A pivotal innovation is the selection of dressing materials. Historically, using Vaseline-impregnated gauze for dressing changes often posed difficulties, such as patient discomfort, wound bleeding, or secondary damage to newly formed tissue caused by gauze removal, thereby prolonging the wound healing process²⁶. In contrast, silver sulfadiazine dressings offer a range of beneficial properties, including non-adherence to the wound bed, bacteriostatic effects, promotion of wound repair, absorption of exudates, and protection against skin injury²⁷. Moreover, this protocol's approach of tailoring dressing frequency according to the condition of skin exudates exemplifies the principle of personalized care. This approach not only ensures the efficacy of the dressing but also minimizes the irritation caused by unnecessary dressing changes.

Consequently, it contributes to a reduction in the duration of hospital stays. Additionally, we proposed different methods for particular sites to tailor care for different patients. Since patients with TEN often have Nikolsky's Sign, protecting undetached but fragile skin from further damage during the dressing change process is crucial.

Limitations of the method
This study has some limitations to address. First, the successful application of the protocol was confined to a single hospital setting, and multicenter studies have yet to demonstrate the findings. The generalizability of the results may be constrained, as different healthcare environments with diverse patient demographics and varying resource availability levels could produce divergent outcomes. Second, the performance of this protocol was concluded based on a retrospective analysis. The effectiveness and rigor of this method should be evaluated in prospective randomized controlled trials-besides, this method's core procedure involved applying silver ion dressings. While positive effects were observed with this dressing category, alternative dressing types' potential efficacy and interchangeability remain unexplored. Furthermore, a comprehensive comparative analysis of different varieties was not undertaken within the silver ion dressing category. This could have yielded more granular and nuanced insights into the optimal dressing options.

Significance of the method
Wound care is of great importance in TEN management; however, no consensus steps for dressing change for TEN have been proposed to date^4,6. Some principles have been established, like anti-shear strategies, and careful drainage of large or painful bullae, but the application of these principles into clinical practice needs further investigation⁶. Here, we for the first time proposed practical wound care strategies and dressing change procedures in the management of patients with TEN. This dressing change strategy is especially applicable for patients with large areas of skin detachment. We believe that this protocol could provide nurses or doctors with limited wound care experience, with practical guidelines to operate, and easy to start. We also hope that this protocol can support the establishment of a consensus on intact and effective operating procedures for TEN patients in further studies.

The authors declare that they have no competing interests.

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