Wound, Pressure Ulcer, and Burn Guidelines (2023)‐6: Guidelines for the Management of Burns, Third Edition

ABSTRACT

The third edition of the Guidelines for the Management of Burns is a fully revised set of guidelines developed by the Wound/Pressure Ulcer/Burn Guidelines Committee of the Japanese Dermatological Association. The guidelines were developed in a systematic and transparent manner using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. For three clinical questions examined through meta‐analyses―systemic antibiotic prophylaxis, dressing materials, and trafermin―weak recommendations were received for the treatment of burns. The guidelines also provide general information on burn severity assessment, systemic management, infection control, and topical treatment.

Contents
Wound/Burn/Pressure Ulcer Guidelines Revising Committee
Chapter 1	Guidelines for the management of burns.
Chapter 2	Outline of burn treatment
Chapter 3	Guidelines for the management of burns Clinical questions (CQ) and recommendations
CQ1	Is systemic antibiotic prophylaxis for burns early after injury useful for preventing wound infection?
CQ2	Are dressing materials useful for the treatment of second‐degree burns?
CQ3	Is trafermin useful for the treatment of second‐degree burns?
Chapter 4	Definition of terms
Chapter 5	Explanation
Explanation 1	Severity assessment
Explanation 2	Systemic management 1: Fluid resuscitation
Explanation 3	Systemic management 2: Inhalation injury (burn)
Explanation 4	Systemic management 3: Electric injury
Explanation 5	Systemic management 4: Chemical injury
Explanation 6	Infection control
Explanation 7	Topical treatment 1: Escharotomies and fasciotomies
Explanation 8	Topical treatment 2: Topical agents
Chapter 6	Details of a systematic review for each CQ
List of the members of the Wound/Burn/Pressure Ulcer Guidelines Revising Committee COI reporting criteria for participants in the Wound/Pressure Ulcer/Burn Guidelines Supervising and Drafting Committees, participation/non‐participation criteria, and a list of the COI disclosed

1. Chapter 1 General Information

1.1. Background of the Drafting of the Guidelines for the Management of Burns, Third Edition

Burns are a common type of skin injury encountered at all levels of medical facilities from private clinics to core hospitals. Minor burns heal by topical treatment alone, but moderate to severe burns require systemic management, and skin grafting is often necessary also for topical treatment. Inappropriate initial treatment or delay of initial treatment may have adverse effects on the subsequent treatment and course. Therefore, accurate evaluation of the severity and initiation of appropriate treatment are necessary.

As guidelines for the management of burns, the “Clinical Practice Guidelines for Management of Burn Care” were published by the Japanese Society for Burn Injuries in March 2009, and the 3rd Edition in 2021. These guidelines cover severe burns requiring hospital treatment for approximately 4 weeks (intensive care unit/burn care unit/general ward) at all ages, but not burns for which outpatient treatment is possible. For this reason, the present guidelines aim to start adequate diagnosis/initial treatment in burn patients whom physicians often encounter, including minor burn patients in addition to severely burned patients. Therefore, concerning surgical therapy, individual techniques, excluding acute‐phase escharotomies and fasciotomies, are not recommended/explained based on the purpose of the present guidelines.

1.2. Position of the Guidelines for the Management of Burns

The Wound/Burn/Pressure Ulcer Guidelines Revising Committee was composed of members delegated by the Board of Directors of the Japanese Dermatological Association. It held several meetings and online meetings after the 1st meeting on June 3, 2018 and has drafted the explanations on wounds in general, and five other related guidelines, including these guidelines, by taking into consideration the opinions of the Scientific Committee and the Board of Directors of the Japanese Dermatological Association. The present guidelines for the management of burns represent current standard burn care in Japan, but individual background factors, such as underlying disease, extent of injury/site/burn depth, and complications, vary among burn patients. Therefore, the physician responsible for treatment should determine a therapeutic strategy with the patient. It is unlikely that treatment optimized for individual patients is completely consistent with the present guidelines. These guidelines are not intended to serve as a legal standard and may not be directly cited in legal proceedings.

On the other hand, the current situation in which treatment guidelines are actually quoted on court decision must also be considered.

1.3. Major Updated Points in the Third Edition

• To improve transparency, we newly prepared guidelines according to the GRADE approach.

• Clinical question (CQ): A quantitative systematic review (meta‐analysis) was performed with respect to 3 CQs (prophylactic antibiotic administration, dressing materials, trafermin) that the Wound/Pressure Ulcer/Burn Guidelines Drafting Committee members consider the most important.

• To ensure the convenience of the guidelines, an outline of the diagnosis and treatment of burn was divided into general remarks and detailed explanations with respect to diseases. A form to refer to a commentary with respect to the details of important points was adopted.

1.4. Financial Support

All expenses required for drafting these guidelines have been borne by the Japanese Dermatological Association, and no aid or financial support has been provided by organizations, enterprises or pharmaceutical companies.

1.5. Collection of Evidence

The systematic review team for each CQ performed preliminary searching according to the Minds Handbook for clinical practice guideline development 2020. The Japan Medical Library Association was responsible for searching.

• Databases used: PubMed, Cochrane Database of Systematic Reviews, and Japanese Medical Abstracts Society

• Search period: Between January 1980 and the end of December 2020

1.6. Systematic Review Methods

According to the Minds Handbook for clinical practice guideline development 2020, accompanying working templates were used.

1.6.1. Evaluation of Individual Reports (Step 1)

Systematic review teams responsible for individual CQs evaluated the bias risk (selection bias, performance bias, detection bias, patient attrition bias, other biases) and indirectness (differences in the study subject population/intervention/comparison/outcome measurement) of each study design (interventional study, observational study) with respect to the outcome‐based literature, and extracted the number of subjects. When effect‐index‐presenting methods differed, they were unified to the risk ratio or risk difference, and described as total evidence.

1.6.2. Summary on Total Evidence (Step 2)

The total evidence integrated across outcomes was assessed with respect to a summary on total evidence, and the certainty of evidence was decided on one. The bias risk and indirectness were again evaluated. In addition, inconsistency, inaccuracy, and publication bias were assessed. The certainty (strength) of evidence was classified, as shown in Table 1.

TABLE 1.

Certainty of evidence.

A (strong)	There is strong confidence in the estimated value of effect.
B (moderate)	There is moderate confidence in the estimated value of effect.
C (weak)	Confidence in the estimated value of effect is limited.
D (very weak)	There is little confidence in the estimated value of effect.

1.6.3. Quantitative Systematic Review (Meta‐Analysis)

When the study design was similar, with the high‐degree similarity of each item of PICO, a meta‐analysis to quantitatively integrate effect indices was performed, and the integrated one was considered as an item for examining the strength of total evidence.

1.6.4. Preparation of a Systematic Review Report

The results of the above quantitative systematic review were summarized in a systematic review report as the strength of total evidence, and used as materials for preparing recommendations with a summary on total evidence.

1.7. Recommendation‐Determining Methods

1.7.1. Review in Persons In Charge of Each CQ

We prepared a summary of findings, considering the certainty of total evidence regarding outcomes and balance between favorable (advantages) and adverse effects (harm and burden).

The importance (weighting) of favorable and adverse effects was re‐evaluated based on the importance of outcomes and certainty of total evidence. The direction and strength of recommendation were comprehensively considered, and submitted to a recommendation decision meeting through discussion by persons in charge of each CQ.

1.7.2. Recommendation Decision Meeting

At a recommendation decision meeting (panel meeting), each systematic review team reported the results of examination based on the materials (evaluation sheets/total evidence, systematic review reports) submitted in advance. Subsequently, the members of the panel meeting voted for one of the following options:

• Recommended (strong recommendation)

• Proposed (weak recommendation)

• Not proposed (weak recommendation)

• Not recommended (strong recommendation)

For voting, the Delphi method was adopted. The recommendation level was determined with a consistency of ≥ 80%. When there was no consistency of ≥ 80% on 3 sessions of voting, the result was regarded as “no recommendation”.

Immediately before voting on each CQ, the presence or absence of COI was reconfirmed, and panel‐meeting members receiving COI did not vote. The results of voting are presented in the explanatory text for each CQ.

1.8. CQ Changes in the Process of Preparation

There was no CQ change in the process of preparation.

1.9. Work for Revising the Guidelines

The Wound/Pressure Ulcer/Burn Guidelines Revising Committee held the 1st General Guideline Meeting on June 3, 2018, and started the revision. Subsequently, the supervising committee and 6 guideline‐drafting committees held online/mail meetings during the COVID‐19 pandemic. The committee for preparing the guidelines for the management of burns held an online recommendation decision meeting (panel meeting) on June 12, 2022 after a few sessions of mail meeting, and determined the recommendation level. On the basis of the results, each drafting‐committee member prepared a draft for the above guidelines, and the present guidelines were prepared through evaluation by the members of the Japanese Dermatological Association.

1.10. Committee for Revising the Guidelines for the Management of Burns, Third Edition

Refer to a list of drafting‐committee members.

1.11. Review Before Publication

Before the publication of these guidelines, opinions were invited from the association members on the homepage of the Japanese Dermatological Association from 2022 to 2023, and necessary revisions were made.

1.12. Promotion of Utilization After Publication

The present guidelines will be announced at a general meeting of the Japanese Dermatological Association, and published in the Japanese Journal of Dermatology. Furthermore, anyone will be able to download them free of charge on the website of the Japanese Dermatological Association for widespread use. Furthermore, An English version of the guidelines will be published the year after publication.

1.13. Plans for Revision

The present guidelines are scheduled to be revised in the next 5 years. However, if a partial update becomes necessary, it will be presented on the website of the Japanese Dermatological Association when appropriate.

Committee for Preparing the Guidelines for the Management of Burns, Third Edition

	Name	Affiliation, profession	Apportionment
Chairman of the supervising committee	Takao TACHIBANA	Department of Dermatology, Hoshigaoka Medical Center, physician	Supervision
Vice‐chairman of the supervising committee	Minoru HASEGAWA	Department of Dermatology, University of Fukui, physician	Supervision
Vice‐chairman of the supervising committee	Manabu FUJIMOTO	Department of Dermatology, Osaka University, physician	Supervision
Supervising members	Yoshihide ASANO	Department of Dermatology, Tohoku University, physician	Supervision
	Takeshi NAKANISHI	Department of Dermatology, Meiji University of Integrative Medicine, physician	Supervision
	Hiroshi FUJIWARA	Department of Dermatology, Niigata University, physician	Supervision
	Takeo MAEKAWA	Department of Dermatology, Jichi Medical University Saitama Medical Center, physician	Supervision
	Sei‐ichiro MOTEGI	Department of Dermatology, Gunma University, physician	Supervision
Representative of the drafting committee	Yuichiro YOSHINO	Department of Dermatology, Japanese Red Cross Kumamoto Hospital, physician	Outline writing, panel meeting
Drafting committee	Masahiro AMANO	Department of Dermatology, University of Miyazaki	Outline/explanation writing, panel meeting
	Shiro IINO	Department of Dermatology, University of Fukui	Outline/CQ explanation writing, panel meeting
	Youichi OMOTO	Department of Dermatology, Omoto Skin Clinic	Outline/CQ explanation writing, panel meeting
	Masato KAKEDA	Department of Dermatology, Saiseikai Matsusaka General Hospital	Outline/CQ explanation writing, panel meeting
	Ko KAGOYAMA	Department of Dermatology, University of Toyama	Outline/explanation writing
	Toru SAITO	Department of Dermatology, Yamagata University	Outline/explanation writing, panel meeting
	Keisuke SAKAI	Department of Dermatology, National Sanatorium Kikuchi Keifuen	Outline/explanation writing, panel meeting
	Naotaka DOI	Department of Dermatology, Doi Skin Clinic	Outline/explanation writing, panel meeting
	Akira HASHIMOTO	Department of Dermatology, Tohoku University	Outline/explanation writing, panel meeting
	Masahiro HAYASHI	Department of Dermatology, Shin‐Nakamichi Dermatology Clinic	Outline/CQ explanation writing, panel meeting
	Katsunari MAKINO	Department of Dermatology, Kumamoto University	Outline/explanation writing, panel meeting
	Naoki MADOKORO	Department of Dermatology, NHO Higashihiroshima Medical Center	Outline/CQ explanation writing
	Naoya MIKITA	Department of Dermatology, Mikita Dermatology Clinic	Outline/explanation writing, panel meeting
	Masahito YASUDA	Department of Dermatology, Gunma University	Outline/explanation writing, panel meeting
	Katsuhiro YAMADA	Department of Dermatology, Aoi Dermatology Clinic	Outline/CQ explanation writing, panel meeting
	Michiru MASUDA	Nurse, Kumamoto University, WOC	Panel meeting

Systematic review team		Panel meeting members
CQ1	Masahiro HAYASHI, Katsuhiro YAMADA	Masahiro AMANO, Shiro IINO, Youichi OMOTO, Masato KAKEDA, Toru SAITO, Keisuke SAKAI, Akira HASHIMOTO, Katsunari MAKINO, Naoya MIKITA, Masahito YASUDA, Yuichiro YOSHINO, Michiru MASUDA
CQ2	Youichi OMOTO, Masato KAKEDA	Masahiro AMANO, Shiro IINO, Toru SAITO, Keisuke SAKAI, Naotaka DOI, Akira HASHIMOTO, Masahiro HAYASHI, Katsunari MAKINO, Naoya MIKITA, Masahito YASUDA, Katsuhiro YAMADA, Yuichiro YOSHINO, Michiru MASUDA
CQ3	Shiro IINO, Naoki MADOKORO	Masahiro AMANO, Youichi OMOTO, Masato KAKEDA, Toru SAITO, Keisuke SAKAI, Naotaka DOI, Akira HASHIMOTO, Masahiro HAYASHI, Katsunari MAKINO, Naoya MIKITA, Masahito YASUDA, Katsuhiro YAMADA, Yuichiro YOSHINO, Michiru MASUDA

1.14. Monitoring After Announcement

After guideline announcement, the widespread use of the present guidelines and changes in the contents of diagnosis/treatment will be investigated by a questionnaire survey.

1.15. Summary of Clinical Questions (CQ)

CQ1 Is Systemic Antibiotic Prophylaxis for Burns Early After Injury Useful for Preventing Wound Infection?

Recommendation level	Remarks on recommendation
Weak recommendation	Currently, it cannot be recommended to uniformly perform systemic antibiotic prophylaxis for burns early after injury for the prevention of wound infection, because there is no sufficient evidence on its efficacy. Therefore, it is proposed that such administration should be avoided.

CQ2 Are Dressing Materials Useful for the Treatment of Second‐Degree Burns?

Recommendation level	Remarks on recommendation
Weak recommendation	The use of dressing materials [silver‐containing Hydrofiber, silver‐containing polyurethane foam/soft silicone, hydrocolloid, polyurethane film, non‐adhesive gauze (soft silicone)] is proposed for the treatment of second‐degree burns.

CQ3 Is Trafermin Useful for the Treatment of Second‐Degree Burns?

Recommendation level	Remarks on recommendation
Weak recommendation	The use of trafermin in patients with second‐degree burns is proposed.

2. Chapter 2. Outline of Burn Treatment (Figure 1)

FIGURE 1.

Diagnostic and therapeutic algorithm for burn injury.

2.1. Severity Assessment (Explanation 1)

Severity assessment is the important first step of burn treatment, and two parameters: burn depth and area are necessary to determine therapeutic strategies and predict the prognosis.

As a method of estimating the burn depth, clinical symptom‐based classification is useful. Furthermore, it may be combined with laser Doppler blood flow measurement or video microscopy (Explanation 1.1). As methods to estimate the burn area, the Rule of Nine, Rule of Five, and Lund and Browder chart are useful. Furthermore, as a method of locally estimating the burn area, the palmar method is used (Explanation 1.2). As tools for evaluating the severity of burns, Artz’ criteria and modified criteria (Moylan's criteria) are useful (Explanation 1.3). Prognostic factors for burns include the burn area (as a percentage of the total body surface area: %TBSA), presence or absence of inhalation injury, third‐degree burn area, prognostic burn index (PBI), age, and burn index (Explanation 1.4).

2.2. Systemic Management 1: Fluid Resuscitation (Explanation 2)

In patients with extensive burns, inflammation‐related enhancement of systemic vascular permeability, a decrease in the vascular content, massive edema, an increase in the peripheral vascular resistance, and a decrease in the cardiac output are observed in addition to body fluid loss from the wound surface, leading to so‐called burn shock. This reaction occurs the most markedly within 24 h after injury. In burned patients, initial fluid resuscitation is particularly important for maintaining circulation in the burn shock period. The necessity of this treatment should be promptly evaluated (Explanation 2.1), and it should be started as early as possible (Explanation 2.2). One of several formulae for estimating the infusion volume and dosing rate based on the burn area and body weight is routinely used (Explanation 2.3), but the components (Explanation 2.4) and volume of infusion must be adjusted in individual cases (Explanation 2.5).

2.3. Systemic Management 2: Inhalation Injury (burn) (Explanation 3)

As respiratory failure threatens all trauma patients' lives in the early stage, the necessity of initial evaluation involving the airway and respiration is not controversial. It must be considered that combustibles or toxic gas may coexist in addition to heat‐related damage. If flame‐related injury or facial burns are present, concomitant inhalation injury should be suspected, and physical findings must be confirmed (Explanation 3.1). When inhalation injury is suspected, high‐concentration oxygen administration should be promptly started, and the necessity of respiratory care including endotracheal intubation should be examined (Explanation 3.2). To evaluate the severity of inhalation injury, bronchoscopy is useful, but treatment should not be delayed due to this examination (Explanation 3.3).

2.4. Systemic Management 3: Electric Injury (Explanation 4)

Concerning electric injury, an electric current that passes through the body may damage various organs/tissues in addition to the skin. The mechanism of injury, site, route of current passage, and contact time differ among individual cases, and it is difficult to compare them among patients; therefore, no severity classification has been established. Usually, in the case of electric injury, hospital fluid resuscitation (Explanation 4.1) and continuous monitoring are performed for the management of organ damage (Explanation 4.2).

2.5. Systemic Management 4: Chemical Burns (Explanation 5)

For the initial management of chemical burns, washing with a sufficient volume of water should be performed (Explanation 5.1), excluding some exceptions. However, specific management is required for phenol, cement, quicklime, and hydrogen fluoride (Explanation 5.2).

2.6. Infection Control (Explanation 6, CQ1)

It is not recommended to uniformly perform systemic antibiotic prophylaxis for the prevention of wound infection in patients with burns early after injury. However, systemic antibiotic prophylaxis may be considered after setting target bacteria in consideration with wound culture and the peculiarity of the institution/area in patients with contaminated wounds, compromised patients including diabetics, children, and perioperative‐period patients (CQ1). For contaminated burns, the administration of tetanus toxoid (Tt) or tetanus immunoglobulin (TIG) is recommended (Explanation 6.1). Hydrotherapy is recommended for patients with relatively minor burns that do not require hospitalization. Among patients with severe extensive burns, hydrotherapy may be performed under infection control in those in whom hydrotherapy is considered to be appropriate (Explanation 6.2). For disinfection, the causative bacteria for infection, antibacterial spectrum of each drug, and wound state should be comprehensively considered (Explanation 6.3). A tube for the management of fecal diversion may be used because the frequency of fecal contamination‐related gauze exchange at the perianal wound site and frequency of wound infection or urinary tract infection may be reduced. However, the patient's general condition and wound state must be considered (Explanation 6.4).

2.7. Topical Treatment (Explanations 7 and 8, CQ2 and 3)

Circumferential or mostly circumferential deep burns of the limbs or anterior thorax have no extensibility, and fluid resuscitation may induce peripheral circulatory disorder of the limbs or respiratory disorder; therefore, escharotomies and fasciotomies for decompression should be considered (Explanation 7).

It is difficult to accurately evaluate the depth of burn wounds in the initial phase. In addition, first‐degree to deep second‐degree burns are mixed in many cases, and it is difficult to limit topical agents to be used. Therefore, for the initial treatment of burns, topical agents, such as white petrolatum, zinc oxide, dimethyl isopropylazulene, and grease‐based ointments including ones containing various antibiotics, should be selected as a rule to protect the wound surface. If the depth of burns is clear, topical agents may be selected in accordance with respective depths.

For first‐degree burns, topical steroids may be used early after injury to obtain anti‐inflammatory actions (Explanation 8.1). For second‐degree burns, of which the depth has been clarified, dressing materials (CQ2), trafermin (CQ3), tretinoin tocoferil, bucladesine sodium, and prostaglandin E1 should be used (Explanation 8.2). For chronic‐phase ulcers with necrotic tissue resulting from deep second‐degree burns, bromelain ointment, cadexomer iodine, dextranomer, and silver sulfadiazine should be used to remove the necrotic tissue (Explanation 8.3). Third‐degree burns refer to tissue damage/necrosis involving all layers of the corium, and surgical or chemical debridement is necessary. Therefore, topical agents, such as bromelain ointment, cadexomer iodine, dextranomer, and silver sulfadiazine, may be used to prevent infection and soften/lyse the necrotic tissue until debridement rather than wound‐surface protection (Explanations 8.3 and 8.4).

3. Chapter 3. Guidelines for the Management of Burns—Clinical Questions (CQ) and Recommendations

CQ1 Is Systemic Antibiotic Prophylaxis for Burns Early After Injury Useful for Preventing Wound Infection?

Recommendation level	Remarks on recommendation	Results of voting
Weak recommendation	Currently, it cannot be recommended to uniformly perform systemic antibiotic prophylaxis for burns early after injury for the prevention of wound infection, because there is no sufficient evidence on its efficacy. It is proposed to avoid such administration. On the other hand, there are data on the usefulness of systemic antibiotic prophylaxis under/in perioperative or specific conditions/patient groups. Systemic antibiotic prophylaxis may be considered after setting target bacteria in consideration with wound culture and the peculiarity of the institution/area in patients with contaminated wounds, compromised patients including diabetics, children, and perioperative‐period patients.	Weak recommendation 12/12 (100%)

3.1. Background/Purpose

An important factor influencing the prognosis of burned patients is various wound site‐ and burn‐associated infectious diseases. Whether prophylactic antibiotic administration to burned patients is advantageous has been examined from various viewpoints. However, due to the characteristics of the disease (trauma) “burn”, the site of injury, area, and underlying disease markedly differ among patients, and there is no evidence on antibiotic prophylaxis.

In previous analyses/reports, various items, such as wound infection, prognosis, sepsis/bacteremia, pneumonia, urinary tract infection, all‐cause mortality, and admission period, were investigated as outcomes. The timing of antibiotic administration was established as early after injury and a perioperative period. The routes of administration include selective digestive decontamination‐targeting administration and airway administration in addition to oral and intravenous routes. In the present guidelines, we aim to examine whether systemic antibiotic prophylaxis for burns early after injury reduces the risk/frequency of wound infection.

3.2. Scientific Basis

We searched for reports examining the frequency of wound infection after systemic antibiotic administration for burns early after injury. As a result, one RCT [1] as an interventional study and four observational studies [2, 3, 4, 5] corresponded to this CQ. In the RCT [1] by Durtschi et al., the number of patients was small (n = 51), and there were marked differences in the severity among the analyzed patients (1%–91% TBSA). Even in the intervention group, intravenously and orally penicillin‐treated patients were mixed. An observational study investigated only outpatients [2]. Another study analyzed only children with extensive burns [3]. Another study examined children with relatively minor burns [4]. Concerning antibiotics, the routes of administration were similarly mixed [2, 3], and antibiotics differed among patients [4, 5]; bias risks were found. In the RCT [1] by Durtschi et al., the risk ratio was 1.324 (0.750–2.2335), and wound infection was slightly more frequent in the prophylactic antibiotic administration group. A meta‐analysis of the observational studies showed a risk ratio of 0.83 (0.46–1.48, p = 0.49). Wound infection was slightly less frequent in the prophylactic antibiotic administration group, but there was no significant difference.

3.3. Explanation

Concerning the usefulness of antibiotic administration for burns early after injury, much data with various study designs have been reported. However, many studies presented negative opinions regarding uniform systemic antibiotic prophylaxis.

Ergün et al. [3] divided 77 children with extensive burns into two groups: prophylactic systemic antibiotic administration (n = 47) and non‐administration (n = 30) groups, compared the results, and reported that the incidence of wound infection was significantly higher in the former (administration group: 21.3%, non‐administration group: 16.7%), and that 7 of 8 patients with sepsis belonged to the administration group. They found that the admission period was longer in the administration group, and that administration was associated with secondary infection in other sites (respiratory system, urinary tract).

In a multicenter cooperative study in Italy [6], silver sulfadiazine was used as a topical agent, and pefloxacin (quinolone antibiotic) was administered to 634 patients with extensive burns (mean age: approximately 40 years, mean burn area: 35% TBSA) for 4 days. Infection did not occur in 104 patients (16%). In the other patients, conditions were relatively mild, and quinolone‐ and aminoglycoside‐resistant bacteria had increased after administration. It was concluded that the usefulness of systemic antibiotic prophylaxis in this protocol could not be confirmed.

Concerning minor burns, Boss et al. [2] retrospectively examined the incidence of wound infection by dividing 294 outpatients with burns into two groups: systemic antibiotic administration (n = 133) and non‐administration (n = 161) groups, and reported that there was no difference in the incidence of wound infection (3.8 and 3.1%, respectively). When investigating the results with respect to the burn area, they found that the rate of patients treated with antibiotics in the ≥ 5% TBSA group was significantly higher than in the < 5% TBSA group, whereas administration did not reduce the incidence of wound infection.

Thus, currently, there is no data demonstrating that uniform antibiotic prophylaxis for burns early after injury decreases the risk/frequency of wound infection.

A meta‐analysis of four observational studies [2, 3, 4, 5] showed bias risks, such as the age, burn area, type of antibiotics, and administration method. Factors that reduce the certainty of evidence (bias risk‐2, indirectness‐1) were present, and the strength of evidence was established as “very weak”. At a panel meeting, it was weakly recommended that uniform systemic antibiotic prophylaxis for burns early after injury for preventing wound infection should be avoided. On the other hand, there are many reports showing the efficacy of prophylactic administration in high‐risk or perioperative‐period patients and many opinions recommending prophylactic administration. Rashid et al. [4] administered antibiotics to children with burns to prevent toxic shock syndrome (TSS), and reported that there was a decrease in the incidence of TSS.

Tagami et al. [7] extracted 2893 severe burn patients with a burn index of ≥ 10 from the DPC data in Japan, and compared the mortality rate and rate at which anti‐MRSA drugs were used between a group in which antibiotic administration was started within 2 days after admission (injury) and a non‐administration group. Among ventilator‐assisted patients, the hospital mortality rate within 28 days in the prophylactic antibiotic administration group was significantly lower than in the non‐administration group. On the other hand, among non‐ventilator‐assisted patients, there was no difference in the mortality rate between the two groups. Furthermore, there was no increase in the frequency of adopting anti‐MRSA drugs even when antibiotics were prophylactically administered in the early stage.

Concerning perioperative antibiotic prophylaxis, Ramos et al. [8] examined its influence on skin graft survival. With respect to 90 sessions of skin grafting in 77 patients who underwent split‐thickness skin grafting for burn wounds (mean age: 41.7 years, mean burn area: 21.8% TBSA), they compared the survival rate between a group in which polymyxin was applied to the skin graft site and systemic antibiotic prophylaxis was performed (44 sessions) and a non‐administration group (46 sessions), and reported that the partial skin graft failure rates in the administration and non‐administration groups were 23% and 50%, respectively, and that the ≥ 10% area failure rates were 9% and 35%, respectively, showing significant differences in the two parameters.

Thus, there are data on the usefulness of systemic antibiotic prophylaxis under/in perioperative or specific conditions/patient groups. Systemic antibiotic prophylaxis may be considered after setting target bacteria in consideration with wound culture and the peculiarity of the institution/area in patients with contaminated wounds, compromised patients including diabetics, children, and perioperative‐period patients.

3.4. Precautions for Clinical Use

Among previous studies, there are no data demonstrating that uniform antibiotic prophylaxis for burns early after injury reduces the risk/frequency of wound infection. However, the risk of infectious disease at burn or trauma sites may be high in compromised patients with underlying diseases, such as diabetes mellitus; therefore, systemic antibiotic prophylaxis may be considered after setting target bacteria in consideration with wound culture and the peculiarity of the institution/area.

As there are no guidelines for patient groups requiring antibiotic prophylaxis early after injury, they must be comprehensively evaluated, considering the patient background and wound state.

3.5. Possibility of Future Research

The site of injury, severity, and underlying disease markedly differ among patients. Medical environments and drugs that are available differ among countries. For this reason, it is not easy to standardize a study design, but various infectious diseases associated with wounds and burns are an important factor influencing the prognosis of burned patients; therefore, it may be important to accumulate data/findings in the future.

CQ2 Are Dressing Materials Useful for the Treatment of Second‐Degree Burns?

Recommendation level	Remarks on recommendation	Results of voting
Weak recommendation	The use of dressing materials [silver‐containing Hydrofiber, silver‐containing polyurethane foam/soft silicone, hydrocolloid, polyurethane film, non‐adhesive gauze (soft silicone)] is proposed for the treatment of second‐degree burns.	Weak recommendation 13/13 (100%)

3.6. Background/Purpose

Usually, surgery is not indicated for superficial second‐degree burns, and adequate topical therapy leads to healing. Concerning deep second‐degree burns, a thin necrotic tissue layer is observed on the wound surface, but, if the extent is small, conservative treatment after necrotic tissue lysis by adequate topical therapy or surgical debridement may result in healing. Dressing materials for burn wounds are applied to second‐degree burns, such as superficial second‐degree burns and deep second‐degree burns after necrotic tissue removal. Third‐degree burns have thick necrotic tissue, and surgical treatment is indicated for them; therefore, usually, dressing materials are not applied.

Dressing materials maintain a moist environment on the ulcer wound surface, providing an optimal environment for wound healing. In clinical practice, they are also routinely used for burn treatment. There are many kinds of dressing materials available for second‐degree burns: hydrophilic fiber, hydrocolloid, hydrogel, polyurethane foam, non‐adhesive gauze (soft silicone), and polyurethane film. They are selected in accordance with the wound site/state and exudate volume. The number of dressing materials, including silver‐containing materials that exhibit antimicrobial effects, has increased in comparison with that previously reported. However, scientific evidence on the efficacy and safety of respective dressing materials has not been clearly presented. It may be important to accumulate previously obtained evidence and examine whether the use of dressing materials should be recommended for the treatment of second‐degree burns.

When investigating the efficacy and safety of respective dressing materials, various items, such as the interval until wound healing, incidence of infection, pain level, costs, number of hospital visits until healing, admission period, patients' satisfaction, necessity of surgery, and adverse events, are established as outcomes. Outcomes to be compared vary among references. Of these, the interval until wound healing, incidence of infection, and pain on treatment were selected at a panel meeting as outcomes that may be important for decision making, and a systematic review for these outcomes was performed. Concerning the other items, only explanations were presented. Furthermore, we excluded dressing materials (including control materials) that had been approved only overseas so that the results of this review may be suitable for treatment in Japan.

3.7. Scientific Basis

To confirm the efficacy of dressing materials for second‐degree burns, we searched for the literature on randomized controlled trials (RCT), establishing subjects as patients with “second‐degree burns” and controls as those receiving “other treatments”. Of the literature, we adopted 18 studies [9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26] describing the interval until wound healing, incidence of infection, and pain on treatment, which were established as primary outcomes for this CQ. Concerning the number of studies per dressing material, there are five studies on silver‐containing Hydrofiber [9, 10, 11, 12, 13], four on hydrocolloid [14, 15, 16, 17], two on polyurethane film [18, 19], two on silver‐containing polyurethane foam/soft silicone [20, 21], two on non‐adhesive gauze (soft silicone) [22, 23], and three on hydrogel [24, 25, 26].

There are five RCT in which silver‐containing Hydrofiber was used for the treatment of second‐degree burns: 3 using silver sulfadiazine in the control group [9, 10, 11], 1 using chlorhexidine‐containing tulle glasses [12], and 1 using physiological saline dressing [13]. A meta‐analysis of three RCT [9, 12, 13] was performed with respect to the interval until wound healing. In the intervention group, the interval until wound healing was significantly shortened (mean value difference: −3.46, 95% confidence interval: −5.19 to −1.74, p < 0.0001). Concerning the incidence of infection, there is one RCT [10], and there was no significant difference. Concerning pain on treatment, there are five RCT [9, 10, 11, 12, 13], but outcomes for pain on treatment differ among the studies (differences in the day of evaluation or pain‐evaluating methods), and a meta‐analysis could not be performed. However, pain in the dressing material group was significantly relieved in comparison with the control group in most RCT.

There are four RCT in which hydrocolloid was used for the treatment of second‐degree burns: 1 using silver sulfadiazine in the control group [14], 2 using chlorhexidine‐containing tulle glasses [15, 16], and 1 using silver sulfadiazine and chlorhexidine‐containing tulle glasses [17]. A meta‐analysis of two RCT [16, 17] was performed with respect to the incidence of infection. There was no significant difference between the intervention and control groups (risk ratio: 0.93, 95% confidence interval: 0.17–5.24, p = 0.94). Concerning the interval until wound healing, a meta‐analysis could not be performed, but one RCT [14] showed a significant reduction in the interval until healing, whereas three RCT [15, 16, 17] did not show any significant difference. Concerning pain, a meta‐analysis could not be performed, but one RCT [14] showed a significant difference. In three RCT [15, 16, 17], there was no significant difference.

There are two RCT in which polyurethane film was used for the treatment of second‐degree burns: 1 using paraffin gauze in the control group [18] and 1 using chlorhexidine‐saturated paraffin gauze [19]. A meta‐analysis was performed with respect to the incidence of infection. There was no significant difference between the intervention and control groups (risk ratio: 0.88, 95% confidence interval: 0.23 to 3.37, p = 0.85). Concerning the interval until wound healing, one RCT [19] showed a significant reduction in the interval until healing, whereas the other RCT [18] did not show any significant difference. Concerning pain on treatment, one RCT [19] showed a significant difference, whereas the other RCT [18] did not show any significant difference.

There are two RCT in which silver‐containing polyurethane foam/soft silicone were used for the treatment of second‐degree burns, and silver sulfadiazine was adopted in the control group [20, 21]. A meta‐analysis was performed with respect to the incidence of infection. There was no significant difference between the intervention and control groups (risk ratio: 5.53, 95% confidence interval: 0.66–46.13, p = 0.11). Concerning the interval until wound healing, the cured area and healing rate differ among the references, and a meta‐analysis could not be performed. However, one RCT [20] showed that the cured area and healing rate 1 week after injury were significantly greater/higher in the intervention group. In the other RCT [21], there was no significant difference. In the two RCT [20, 21], pain on treatment was significantly relieved at all observation points.

There are two RCT in which non‐adhesive gauze (soft silicone) was used for the treatment of second‐degree burns, and silver sulfadiazine was adopted in the control group [22, 23]. A meta‐analysis showed a significant reduction in the interval until wound healing in the intervention group (mean value difference: −4.08, 95% confidence interval: −6.43 to −1.73, p = 0.0007). There was no significant difference in the incidence of infection between the intervention and control groups (risk ratio: 1.42, 95% confidence interval: 0.07–30.83, p = 0.82). Concerning pain on treatment, there was no significant difference in one RCT [23].

There are five RCT in which hydrogel was used for the treatment of second‐degree burns: 3 using silver sulfadiazine in the control group [24, 25, 26] and 2 using paraffin gauze [24, 26]. A meta‐analysis could not be performed, but two RCT [25, 26] showed a significant reduction in the interval until wound healing. In one RCT [24], there was no significant difference. Although a meta‐analysis could not be performed, pain on treatment was significantly relieved in three RCT [24, 25, 26]. In one RCT [25], there was no significant difference in the incidence of infection.

Chitin has been used as a dressing material for wounds, including burns, in Japan. However, few studies have examined its efficacy for burn wounds, and there is only one case‐series study in 120 patients including those with skin graft donor sites or trauma [27]. Of these patients, 21 had burns, and the efficacy was evaluated as effective/extremely effective in 80%. However, hemostatic and analgesic effects were also evaluated, and effects on wound healing are unclear.

3.8. Explanation

Dressing materials vary, and the concentration, three‐dimensional structure, and contained materials differ even among some products consisting of the same component. Therefore, dressing materials primarily covered by health insurance in Japan were investigated. Concerning outcomes, the interval until wound healing, incidence of infection, and pain on treatment were examined. When several descriptions were present, respective ones were reviewed. When searching for studies to be adopted for a meta‐analysis, systematic reviews and randomized controlled trials were extracted. A meta‐analysis was possible with respect to two outcomes: the interval until wound healing and incidence of infection. There are some reports on adverse events related to dressing materials, but the incidence of adverse events was low in these studies; they were excluded. Concerning the cost and frequency of dressing exchange, many studies reported that the frequency of exchange and that of hospital visit in the dressing material group were lower than in the control group, reducing the cost. However, personnel expenses must be considered in addition to the cost of materials. It may be difficult to examine the cost in studies in countries other than Japan.

Concerning silver‐containing Hydrofiber, a meta‐analysis was performed, and the results showed that the use of silver‐containing Hydrofiber significantly shortened the interval until wound healing. Although a meta‐analysis could not be performed, there was no increase in the incidence of infection, and many studies found that pain on treatment was relieved. However, there are many factors that reduce the certainty of evidence (bias risk‐2, imprecision‐1), and the strength of evidence was established as “very weak”. At a panel meeting, it was determined that the use of silver‐containing Hydrofiber should be weakly recommended for the treatment of second‐degree burns.

Concerning hydrocolloid, a meta‐analysis regarding the incidence of infection was possible. There was no significant difference between the intervention and control groups. With respect to the interval until wound healing and pain on treatment, one RCT each showed a significant difference in comparison with the control group. However, finally, there are many factors that reduce the certainty of evidence (bias risk‐2, imprecision‐1, indirectness‐1, others‐1), and the strength of evidence was established as “very weak”. At a panel meeting, it was determined that the use of hydrocolloid should be weakly recommended for the treatment of second‐degree burns.

Concerning polyurethane film, a meta‐analysis regarding the incidence of infection was possible. There was no significant difference between the intervention and control groups. With respect to the interval until wound healing and pain on treatment, one RCT each showed a significant difference in comparison with the control group. However, finally, there are many factors that reduce the certainty of evidence (bias risk‐2, imprecision‐1, others‐1), and the strength of evidence was established as “very weak”. At a panel meeting, it was determined that the use of polyurethane film should be weakly recommended for the treatment of second‐degree burns.

Concerning silver‐containing polyurethane foam/soft silicone, a meta‐analysis regarding the incidence of infection was possible. There was no significant difference between the intervention and control groups. With respect to pain on treatment, two RCT showed a significant difference in comparison with the control group. With respect to wound healing, the cured area and healing rate 1 week after injury were significantly greater/higher in the intervention group, but there was no significant difference in the interval until wound healing. Finally, there are many factors that reduce the certainty of evidence (bias risk‐1, imprecision‐1), and the strength of evidence was established as “very weak”. At a panel meeting, it was determined that the use of silver‐containing polyurethane foam/soft silicone should be weakly recommended for the treatment of second‐degree burns.

Concerning non‐adhesive gauze (soft silicone), a meta‐analysis showed that the use of non‐adhesive gauze significantly shortened the interval until wound healing, and that there was no increase in the incidence of infection. However, there are many factors that reduce the certainty of evidence (bias risk‐1, others‐1), and the strength of evidence was established as “very weak”. At a panel meeting, it was determined that the use of non‐adhesive gauze (soft silicone) should be weakly recommended for the treatment of second‐degree burns.

Concerning hydrogel, two RCT showed a significant reduction in the interval until wound healing. With respect to pain on treatment, three RCT showed the significant relief of pain. In one RCT [25], there was no significant difference in the incidence of infection. However, a meta‐analysis could not be performed, and the use of hydrogel was not recommended in the present guidelines.

Concerning chitin, there is one case‐series study, but the number of patients was small; the evidence level is low. The use of chitin was not recommended in the present guidelines.

Based on these results, all dressing materials were weakly recommended for the treatment of second‐degree burns. In the RCT cited this time, a dressing material was selected for burn wounds in the intervention group, and silver sulfadiazine, chlorhexidine‐containing tulle glasses, or paraffin gauze was used in the control group to compare the results between the two groups. Therefore, in most studies, blinding in participants and evaluators was impossible. In addition, the wound state, such as the burn site or wound area, differed among respective studies. Thus, the quality or uniformity of individual RCT is low, reducing the reliability of meta‐analyses. All dressing materials were weakly recommended for the treatment of second‐degree burns.

3.9. Precautions for Clinical Use

The dressing materials on which the literature was searched this time include products that are not approved as medicines by the Ministry of Health, Labour and Welfare in Japan. No clinical trial of these products has been performed in Japanese patients, and results from the foreign literature are not always adaptable for Japanese. Furthermore, in Japan, a period during which dressing materials are available under health insurance coverage is limited, excluding non‐adhesive gauze. The cost is uniformly determined in accordance with the dressing area. Therefore, neither the dressing period nor cost in the foreign literature applies to health insurance treatment in Japan. Furthermore, it must be considered that health insurance coverage of silver‐containing polyurethane foam/soft silicone for burn wounds is limited to wounds reaching the subcutaneous tissue.

3.10. Possibility of Future Research

When performing RCT of dressing materials, silver sulfadiazine was used as a control agent in many references. No study has examined the superiority or inferiority among dressing materials. Silver sulfadiazine effectively functions in preventing infection in patients with second‐degree burns, but is not particularly effective in achieving epithelialization or shortening the interval until wound healing. It is natural that dressing materials are evaluated as significantly more effective in shortening the interval until wound healing when compared with silver sulfadiazine. If more RCT for comparing different dressing materials are performed, a clear answer on effective dressing materials may be obtained. In the future, the superiority or inferiority among different dressing materials or between dressing materials and fixed topical agents or basic wound dressing should be examined.

CQ3 Is Trafermin Useful for the Treatment of Second‐Degree Burns?

Recommendation level	Remarks on recommendation	Results of voting
Weak recommendation	The use of trafermin in patients with second‐degree burns is proposed.	Weak recommendation 14/14 (100%)

3.11. Background/Purpose

With respect to the effects of trafermin (bFGF: basic fibroblast growth factor) on second‐degree burns, a reduction in the interval until epithelialization (healing) and improvement in scars are commonly recognized, and a consensus regarding its usefulness has been reached in Japan from the viewpoint of safety. In the present guidelines, a meta‐analysis was performed with respect to the interval until healing, and the usefulness of trafermin was comprehensively evaluated after reviewing previous meta‐analyses on scar improvements and reports on adverse events.

3.12. Scientific Basis

The usefulness of trafermin for the treatment of second‐degree burns was examined. We searched for systematic reviews or reports from RCT in which trafermin was used to treat early burn ulcers. One systematic review [28] and four RCT [29, 30, 31, 32] were hit. In this systematic review, all growth factors for second‐degree burns were analyzed, and bFGF was analyzed based on the above studies [29, 30, 31, 32]. Concerning the interval until healing for FGF in this study, a meta‐analysis of 5 studies: one study [33] on acidic fibroblast growth factor (aFGF) and the above studies [29, 30, 31, 32] was performed. For this reason, we performed a meta‐analysis of references on bFGF alone, excluding the study on aFGF. As a result, the interval until healing was significantly shortened in the trafermin‐treated group (mean value difference: −3.49 days, 95% confidence interval: −4.31 to −2.68 days, p = 0.02).

In the systematic review [28], a meta‐analysis regarding the scar‐reducing effects of trafermin on second‐degree burns was performed using 3 of the above studies [29, 30, 31]. It was concluded that scars were significantly reduced in the trafermin‐treated group on scar assessment with the Vancouver scar scale [34]. There is only one RCT (Fu et al. [31]) describing its safety. It was reported that there was no adverse event in any patient treated with trafermin.

3.13. Explanation

Concerning the effects of trafermin on second‐degree burns, a meta‐analysis of four reports from RCT [29, 30, 31, 32] was performed with respect to the interval until healing. In the trafermin‐treated group, the interval until healing was significantly shortened. With respect to an improvement in scars, in the systematic review [28], a meta‐analysis was performed using RCT [29, 30, 31], and it was reported that scars were significantly reduced in the trafermin‐treated group on scar assessment with the Vancouver scar scale (height, p = 0.01; pliability, p < 0.01; vascularity, p < 0.01). These results suggested that trafermin administration to patients with second‐degree burns is effective to some extent in shortening the interval until healing and reducing scars. However, concerning trafermin administration, blinding could not be implemented due to the nature of the intervention. In these studies, the performance bias (−2) and detection bias (−2) were confirmed, and the strength of evidence on its effects was finally established as “very weak”. Concerning safety, there is only one RCT describing adverse events, as described above. Although statistical analysis was not performed, as another study, Ahn et al. [35] reported a retrospective analysis regarding adverse events in 1630 trafermin‐treated patients with deep second‐degree burns. In this study, adverse events occurred in 37 patients (2.3%): pain (1.7%) and dermatitis (0.6%) at the site of trafermin administration. However, these adverse events were mild, and it is described that there may have been no relationship with trafermin administration. Comprehensively considering the above effects and safety, the use of trafermin for second‐degree burns was weakly recommended through a panel meeting.

3.14. Precautions for Clinical Use

Trafermin is a spray‐type liquid preparation, and must be combined with some topical agent or dressing material to maintain a moist environment for second‐degree burns.

3.15. Possibility of Future Research

As trafermin is a relatively expensive topical agent, it is also necessary to examine outcomes established from medicoeconomical aspects in the future. Second‐degree burns are lesions with acute topical inflammation, differing from stable chronic ulcers; therefore, the adequate timing of administration and severity/site of second‐degree burns for which trafermin is indicated should be discussed in the future.

4. Chapter 4. Definition of Terms

In the present guidelines, terms to be used in the guidelines were defined as follows based on review articles and descriptions in textbooks in Japan. Some terms were quoted from the Burn Terminology prepared by the Japanese Society for Burn Injuries and terminology prepared by the terminology committee of the Japanese Society of Pressure Ulcers, and the uniformity in the Wound/Pressure Ulcer/Burn Guidelines was considered.

First‐degree burn: Epidermal burn that shows only reddening of the injured area and cures without scars.

Second‐degree burn: Usually classified into two types according to the depth.

• Superficial dermal burn (SDB): A burn that forms a blister. The dermis at the floor of the blister is red. Usually cures after epithelialization in 1–2 weeks. Generally, leaves no hypertrophic scar.

• Deep dermal burn (DDB): A burn that forms a blister. The dermis at the floor of the blister is white and anemic. The injury requires 3–4 weeks until cure by epithelialization but is likely to leave hypertrophic scar or cicatricial keloid.

Third‐degree burn: Deep burn causing necrosis of the full thickness of the skin to subcutaneous tissue. It includes burns with a white or brown leather‐like appearance and burns with completely charred skin. Because epithelialization progresses only from the margins of the injury, 1–3 months or longer is needed until cure, and hypertrophic scar or cicatricial contracture occurs without skin grafting.

Burn index (BI): An index devised by representing the severity of burns, developed by Schwarz et al. (1963). Calculated as 1/2 x area of second‐degree burn (%) + area of third‐degree burn (%). A BI of 10–15 or higher is considered severe.

Prognostic burn index (PBI): An index representing the severity of burns. Calculated as age (years) + BI.

Inhalation injury (burn): Damage of the pharyngeal/laryngeal or tracheal/bronchial mucosa or the pulmonary alveoli caused by inhalation of smoke, high‐pressure vapor and toxic gas due to fire or explosion.

Chemical injury (burn): Injury associated with various corrosion phenomena with tissue destruction related to attachment/contact of chemicals, such as acid, alkali, heavy metal, and toxic gas, to the skin or mucosa.

Electric injury (burn): Injury associated with electric disorders, such as electric shock, lightning strike, electric spark, and arc light. Electric injury is classified into electric current‐related disturbance, Joule heat generation‐related injury, and spark‐related injury.

Total body surface area (TBSA): Total body surface area.

Topical agents: Drugs applied through the skin or directly to skin lesions for topical treatment. Prepared by compounding various active components with a base.

Dressing materials: Modern wound‐dressing materials aimed to create a moist environment around wounds. Conventional sterilized gauze is excluded.

Wound‐dressing materials: Wound‐dressing materials are divided into dressing materials (modern wound‐dressing materials) and medical materials including gauze (classic wound‐dressing materials). The former are medical materials that provide an optimal environment for wound healing with maintaining moist environment and must be used selectively depending on the condition of the wound and amount of exudates. The latter allow drying of the wound and cannot maintain a moist environment if effusion is insufficient. Wound‐dressing materials cover the wound, retain moisture and provide an optimal environment for wound healing. Medical materials other than conventional gauze may be called wound‐dressing materials or dressing materials.

Wound bed preparation: Management of the wound surface environment to promote wound healing. Specifically, necrotic tissues are removed, bacterial load is reduced, drying of the wound is prevented, excessive effusion is controlled, and pockets and wound margins are treated.

TIME: Practical principles of wound bed preparation based on the concept of evaluating factors that prevent wound healing from the viewpoints of tissue (T), infection or inflammation (I), moisture (M) and wound edge (E), and using the results for treatment and care.

Moist wound healing: Maintaining the wound surface in a moist environment. This retains multinucleated leukocytes, macrophages, enzymes and cell growth factors contained in effusion on the wound surface. Such an environment promotes autolysis and removal of necrotic tissues and does not interfere with cell migration.

Escharotomies and fasciotomies: Also called decompression incision. It is performed to prevent swelling‐related circulatory disorder at the distal portions of the extremities and respiratory dyskinesia at the cervix/trunk in patients with circumferential/deep burns of the trunk, limbs, and cervix. Escharotomy to fasciotomy is performed in accordance with the depth of burns.

5. Chapter 5. Explanation

5.1. Explanation 1. Severity Assessment

Severity assessment is the important first step of burn treatment. Two parameters, burn depth and area, are necessary to determine therapeutic strategies and prognosis.

5.1.1. Clinical symptom‐based classification is useful for estimating the depth of burns. Furthermore, it may be combined with laser Doppler blood flowmetry or video microscopy

• Clinical finding‐based depth assessment (Table 2) is based on experts' opinions [36], and has also been long adopted in textbooks. Furthermore, no specific instruments are required, and this method is widely used.

TABLE 2.

Classification of depth based on clinical symptoms.

Classification	Clinical symptoms
First‐degree burn (epidermal burn)	Erythema, painful
Superficial second‐degree burn (superficial dermal burn)	Erythema, blisters, painful Compression of blisters leads to the disappearance of flare.
Deep second‐degree burn (deep dermal burn)	Erythema, purpura to white spots, blisters, hypoesthesia Compression of blisters does not lead to the disappearance of flare.
Third‐degree burn (deep burn)	Black, brown, or white blisters (−), painless

Note: Cited and partially modified from Comprehensive Handbook of Clinical Dermatology (2). Nakayama Shoten Co. Ltd., Tokyo: 2003; 241.

• Concerning burn depth‐estimating methods, there is one prospective non‐randomized controlled trial comparing laser Doppler blood flowmetry with video microscopy [37]. The sensitivity of each method for detecting superficial dermal burns (SDB) was compared in 27 patients within 72 h after injury. The sensitivity of the two methods was 100%, and healing was achieved within 3 weeks in patients diagnosed with SDB. Furthermore, there are analytical epidemiological studies or case reports on laser Doppler blood flowmetry or video microscopy [38, 39, 40, 41]. However, instruments are not widely introduced, and these methods are not routinely used.

5.1.2. The Rule of Nines, Rule of Five, and Lund‐Browder chart are useful for estimating the burn area. Furthermore, the Palmar method is used to topically estimate the burn area

• A method to estimate the burn area using the Rule of Nines, Rule of Five, and Lund‐Browder chart (Figure 2) is based on experts' opinions [42, 43, 44]. However, it is widely used in clinical practice, being useful for estimating the burn area.

• In the palmar method, the palm is calculated as approximately 1% of the body surface in adults. There are analytical epidemiological studies [45, 46, 47] concluding that an approximately 1% (0.7 to 0.95) burn area can be estimated although there are slight differences among methods to calculate the body surface area as a reference. This method is clinically practical and useful.

FIGURE 2.

Calculation of burn area.

5.1.3. As tools for evaluating the severity of burns, Artz’ criteria and modifications (Moylan's criteria) are useful

• Both Artz’ criteria and modifications (Moylan's criteria) (Table 3) for evaluating the severity of burns are based on experts' opinions [48, 49]. However, they are the most commonly used in clinical practice, being practical as the definition of severity assessment.

TABLE 3.

Artz's criteria.

Artz’ criteria
Severe burns
Grade II: ≥ 30% TBSA
Grade III: ≥ 10% TBSA
Third‐degree burns of the face, hands and feet
Burns complicated by inhalation injury
Burns complicated by soft tissue injury or fractures
Electric injury
Moderate burns (requiring hospital care in a general hospital)
Grade II: 15%–30% TBSA
Grade III: ≤ 10% TBSA (excluding the face, hands and feet)
Minor burns (outpatient care is possible)
Grade II: ≤ 15% TBSA
Grade III: ≤ 2% TBSA
TBSA: total body surface area
Cited and partially modified from Ref. [48]

5.1.4. Prognostic factors for burns include the burn area (percentage of the total body surface area: % TBSA), presence or absence of inhalation injury, third‐degree burn area, prognostic burn index (pbi), age, and burn index

• The burn area (% TBSA) is based on experts' opinions, but is a basic parameter for evaluating the severity of burns in the literature and the prognosis of burned patients [50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65]. Furthermore, there are many opinions that it is useful for determining the outcome.

• There are many articles describing that age [50, 51, 52, 54, 56, 57, 60, 61] and inhalation injury [51, 57, 59, 61, 62, 65] are prognostic factors. There are also some articles describing that the third‐degree burn area [60, 62] is a prognostic factor. These studies investigated a few hundred to a few thousand patients with burns. The burn index [62] and PBI [53] are routinely used in clinical practice in Japan. Furthermore, according to some references, self‐inflicted burn injury [63] and concomitant psychiatric diseases [60] are involved in the mortality rate.

5.2. Explanation 2. Systemic Management 1: Fluid Resuscitation

5.2.1. If the burn area is ≥ 20% TBSA in adults or ≥ 10% TBSA in children, fluid resuscitation should be performed. However, even if it is lower than the values, initial fluid resuscitation may be started, considering the general condition

• No study has examined whether fluid resuscitation should be performed with respect to the extent (area) of injury. However, in clinical practice, initial fluid resuscitation has been performed in patients with extensive burns, and its usefulness is widely recognized [48, 66, 67, 68, 69, 70, 71, 72].

• In patients with a burn area of ≥ 15% TBSA, burn shock and systemic inflammatory response syndrome (SIRS), which increases the burn shock‐related mortality rate, occur, and initial fluid resuscitation may be necessary [73].

• Concerning guidelines in various regions, it is described that fluid resuscitation should be performed based on the body weight and burn area in adults/children with a burn area of ≥ 20% TBSA in the Advanced Burn Life Support Course 2018 (ABLS 2018) prepared by the American Burn Association (ABA), and in adults with a burn area of ≥ 20% TBSA or children with a burn area of ≥ 10% TBSA in the International Society for Burn Injuries (ISBI) Practice Guidelines for Burn Care 2016 (ISBI guidelines 2016) and European Practice Guidelines for Burn Care 2017 established by the European Burns Association (EBA)(EBA guidelines 2017) [74, 75, 76].

• A survey in the ISBI/ABA members showed that the burn area at which fluid resuscitation was started ranged from 10% to 20% TBSA [77]. Currently, fluid resuscitation may be necessarily performed in patients with a burn area of ≥ 20% TBSA.

5.2.2. Fluid resuscitation should be initiated as early as possible in patients in whom its necessity is suggested

• There is no RCT on the timing of starting initial fluid resuscitation. There are only case control studies.

• Among 76 burned adults with renal failure, survivors were compared with patients who died. There was a significant difference in the interval until the start of initial fluid resuscitation (1.7 ± 1.0 vs. 4.4 ± 2.1 h, respectively) [78].

• Concerning children with burns, a study compared two groups: a group consisting of patients who were treated between 1966 and 1983 (n = 24) and a group consisting of those who were treated between 1984 and 1997 (n = 36), and reported that the interval from injury until the start of fluid resuscitation was 8.6 ± 1.7 h in the former and 3.0 ± 0.5 h in the latter. Furthermore, the mortality rates in the former and latter were 100 and 56%, respectively, showing a decrease. Of the 36 patients after 1984, in survivors, fluid resuscitation had been started earlier than in those who died (1.7 ± 0.5 vs. 4.8 ± 0.9 h, respectively) [79].

• A retrospective study showed that the incidence of sepsis, incidence of kidney damage, and mortality rate in children in whom fluid resuscitation was started within 2 h after burn injury were lower than in those in whom it was started 2 to 12 h after burn injury [80].

• In the ABLS 2018, guidelines for initial fluid resuscitation based on the body weight and age in patients with ≥ 20% TBSA burns before ambulance transport are presented [74].

• Thus, it may be necessary to start fluid resuscitation as promptly as possible in patients requiring it.

5.2.3. Usually, the rate of initial fluid resuscitation is established using a formula with the body weight and burn area (% tbsa), and lactate Ringer (lr) solution at 2 to 4 ml/kg/% TBSA is administered over 24 h after injury. The rate at which a half of the volume is administered over the first 8 h should be established as the initial rate of fluid replacement

• For initial fluid resuscitation, several formulae, such as the Parkland (Baxter), Modified Brooke, and Advanced Burn Life Support (ABLS)‐based formulae, have been used. However, there is no high‐quality comparative study, and a conclusion has not been reached.

• Baxter evaluated circulatory kinetics using isotopes in the acute phase of burns in an animal experiment, and reported that fluid infusion at 3.7 to 4.3 mL/kg/% TBSA was necessary, and that the functional extracellular fluid (ECF) level rapidly decreased in accordance with the burn area after injury, whereas LR administration prevented burn shock, reducing the mortality rate [81]. According to a study, LR was administered using the urine volume (40 mL/h) and consciousness level in burn patients as indices, and the fluid volume over 24 h after injury ranged from 3.7 to 4.3 mL/kg/% TBSA in 70% of adults and in 98% of children aged ≤ 12 years [82].

• However, recent studies showed that an initial fluid volume larger than in the Parkland method was required [82, 83, 84]. Excessive fluid infusion‐related enhancement of edema and limb/abdominal compartment syndrome were reported, being called “fluid creep” [85, 86]. According to a study, 50 patients with ≥ 20% TBSA burns were randomly divided into two groups: a group treated using the Parkland method and a group treated under invasive intrathoracic blood flow monitoring, and the fluid volume over the first 24 h was significantly greater in the latter. In the former, intravascular dehydration within 48 h was noted, but there were no differences in the preload or cardiac output. There were also no differences in the mortality rate or incidence of complications [87]. Briefly, electrolyte fluid administration at a more excessive volume than in the Parkland method did not improve the preload or cardiac output.

• Another study compared the results of initial fluid resuscitation between two groups: 2‐mL/kg/% TBSA and 4‐mL/kg/% TBSA groups, and reported that the total fluid volume was minimized in the former, whereas there were no differences in the results, such as the mortality rate [88]. In the ISBI guidelines 2016 and EBA guidelines 2017, it is recommended that fluid resuscitation at 2 to 4 mL/kg/% TBSA should be performed in 24 h after injury while paying attention to excessive fluid infusion. In the ABLS 2018, it is described that the initial dose of LR in adults should be established as 2 mL/kg/% TBSA, and a method to add glucose‐containing maintenance fluid to LR at 3 mL/kg/% TBSA in children is presented [74, 75, 76].

• There are marked individual differences in the response to fluid resuscitation. Even when adopting any formula for fluid replacement, the volume should be regulated so that it may not be too large or small while continuously evaluating the urine volume and circulatory kinetics [89].

5.2.4. As an initial fluid, an isotonic electrolyte fluid, lactate Ringer (LR) solution, is routinely used. To prevent excessive fluid replacement, albumin preparations, hypertonic lactated saline (HLS), and hydroxyethyl starch (HES) are used, but an obvious conclusion has not been reached

• As initial treatment for burns, the use of isotonic electrolyte fluids, as represented by LR, is widely accepted. In representative formulae for fluid replacement, such as the Parkland (Baxter) and Modified Brooke formulae, and those for children, such as the Cincinnati and Galveston formulae, LR is established as an initial fluid. In the ABSL 2018, a method to use LR is also presented [74]. Furthermore, the use of salt‐containing fluids is recommended in the ISBI guidelines 2016 [75], and the use of electrolyte fluids is recommended in the EBA guidelines 2017 [76].

• Isotonic electrolyte fluids, as represented by LR, are superior from the viewpoint of availability and cost, and are widely used as an initial fluid for severely burned patients [90].

• The massive‐dose administration of physiological saline induces hypernatremia or metabolic acidosis, and its use for initial fluid resuscitation should be avoided [91, 92].

• Colloids, such as albumin, may increase the osmotic pressure, maintaining the intravascular volume. However, vascular permeability is enhanced early after burn injury, and their use for initial fluid resuscitation has been avoided. On the other hand, there is a meta‐analysis showing that the use of albumin within 24 h after injury is involved in decreases in the incidence of compartment syndrome and mortality rate [93]. Another meta‐analysis found that albumin decreased the fluid infusion volume, whereas there was no difference in the mortality rate [94]. However, excluding two studies with a high bias risk, albumin administration was associated with decreases in the mortality rate and incidence of compartment syndrome. In these reports, the quality of evidence is limited, suggesting the necessity of an additional study; a conclusion has not been reached. However, albumin preparations may be useful as an option for suppressing excessive fluid infusion. In the Japanese Society for Burn Injuries (JSBI) Clinical Practice Guidelines for Management of Burn Care (3rd Edition) (2021), it is described that the use of albumin preparations for initial fluid resuscitation in 1‐ to 12‐year‐old patients with a burn area of 15 to 45% TBSA may decrease the fluid volume, shortening the admission period [95].

• HLS is prepared by adding sodium to LR. It was devised to replenish extracellular fluid/sodium loss after burn injury and reduce the total fluid volume in comparison with isotonic fluid. Fourteen patients in the HLS group were compared with 22 in the LR group while maintaining the urine volume at 0.5 to 1.0 mL/kg/h. Fluid infusion at 3.1 ± 0.9 and 5.2 ± 1.2 mL/24 h/kg x % TBSA in the former and latter, respectively, was required. In the HLS group, the urine volume was maintained with a smaller fluid volume, and the intra‐abdominal pressure (IAP) and maximum expiratory pressure were significantly lower. In addition, the incidence of intra‐abdominal hypertension (IAH) was lower (HLS group: 14%, LR group: 50%) [96]. However, another study reported that the incidence of renal failure and mortality rate in the HLS group were higher than in the LR group, and that there was no decrease in the total fluid volume [97]. According to a meta‐analysis examining whether HLS reduces the mortality rate in patients with hypovolemia, the relative risks of death were 0.84 in trauma patients, 1.49 in burn patients, and 0.51 in surgically treated patients in the HLS group when comparing hypertonic + isotonic fluid administration with isotonic fluid administration in trauma, burn, and surgically treated patients [98]. In conclusion, HLS is reportedly effective in decreasing the total fluid volume and inhibiting an increase in the intra‐abdominal pressure, but it increases the relative risk of death. In addition, dispensing in each institution is necessary. No study has demonstrated the superiority of HLS to LR.

• HES is an artificial colloid to be used as a plasma substitute. It is used to maintain circulation in the case of massive hemorrhage, but high‐dose continuous use leads to kidney damage, raising an issue [99]. A study randomly divided burn patients into two groups: a group in which electrolyte fluids were used for initial fluid resuscitation and a group in which one‐thirds of the volume was substituted for 6% HES, and compared the results. The fluid volume required over 24 h after injury and weight gain were significantly smaller in the HES group, suggesting that HES is useful for decreasing the total fluid volume [100]. However, in 2013, a study in a population primarily consisting of non‐burn patients and a meta‐analysis showed that the use of HES was associated with increases in the mortality rate and incidence of acute kidney injury [101]. The European Medicines Agency (London, UK) prohibited the use of HES in burn patients [72].

5.2.5. The urine volume per hour is used as a parameter for establishing the rate of initial fluid administration. The rate of fluid administration should be regulated so that the urine volume may be maintained at ≥ 0.5 mL/kg/h in adults, 1.0 mL/kg/h in children weighing ≤ 30 kg, and 0.5 ml/kg/h in children weighing > 30 kg. In addition, it should be regulated based on hemodynamic parameters

• The urine volume per hour is the most commonly used as the simplest parameter. In adults, the rate of fluid administration has been regulated so that the urine volume may be maintained at 0.5 to 1 mL/kg (ideal body weight)/h [70, 71, 102]. and the fluid volume has been adjusted in consideration with the assessment of vital signs (e.g., blood pressure, pulse rate, peripheral circulation, and tachypnea).

• In the ABLS 2018, it is recommended that a urine volume of ≥ 0.5 mL/kg/h in adults, ≥ 1 mL/kg/h in children weighing ≤ 30 kg, or ≥ 0.5 mL/kg/h in 17‐year‐old or younger children weighing >30 kg should be established as a parameter for fluid resuscitation [74]. In the EBA guidelines 2017, target urine volumes are established as 0.5 mL/kg/h in adults and 1 mL/kg/h in children [76]. In the ISBI guidelines 2016, they are established as 0.3 to 0.5 mL/kg/h in adults and 1 mL/kg/hr. in children [75].

• Formulae for fluid replacement provide an initial estimated value to compensate for water loss related to burn injury. However, the actual rate of administration must be regulated in accordance with the clinical response and circulatory kinetics to avoid excessive or insufficient fluid resuscitation. According to a systematic review for investigating adequate fluid resuscitation parameters that replace the urine volume per hour, there was a decrease in the mortality rate when adopting hemodynamics with alternative endpoints (primarily, cardiac index and intrathoracic blood volume) to adjust the rate of fluid administration, but not the urine volume per hour (risk ratio, 0.77; 95% CI, 0.42 to 0.85; p < 0.004) [89].

• In patients who do not respond to fluid resuscitation or those in whom the urine volume is continuously small, circulatory kinetics are assessed using arterial pressure monitoring, central venous pressure (CVP) monitoring, measurement of the arterial blood lactic acid level, echocardiography, and cardiac output monitoring [76, 102].

• Various studies examined the rate of administration on fluid resuscitation, but a clear conclusion has not been reached.

5.3. Explanation 3. Systemic Management 2: Inhalation Injury (Burn)

5.3.1. As findings suggestive of the presence of inhalation injury, a fire in a closed space, facial burns/soot attachment, hoarseness, dyspnea, wheezing, pulmonary murmurs, black sputum, and consciousness disorder are used

• There are many experts' opinions that the presence of inhalation injury should be suspected based on the mechanism of injury and physical findings [74, 102, 103, 104].

• In patients who required intubation due to inhalation injury, oral soot (p < 0.001), facial burns (p = 0.025), and trunk burns (p = 0.025) were positively correlated with inhalation injury. A study reported their correlations stronger than that of vocal cord edema on laryngoscopy [103].

5.3.2. If inhalation injury is suspected, high‐concentration oxygen administration should be started, and the necessity of intubation should be examined

• In the case of inhalation injury, carbon monoxide or toxic gas may have been inhaled in addition to airway injury, and high‐concentration oxygen administration should be started without waiting for results on the blood CO hemoglobin level. The blood half‐life of carbon monoxide is approximately 4 h under room air, but is shortened to approximately 1 h under 100% oxygen administration; therefore, oxygen administration should be continued until the CO hemoglobin level is normalized [74].

• When a history of smoke exposure, shock, consciousness disorder, or cardiopulmonary arrest is observed, hydroxocobalamin is administered, considering the possibility of hydrogen cyanide poisoning [105, 106]. However, it remains to be clarified whether hydroxocobalamin reduces the mortality rate after smoke inhalation; therefore, some opinions recommend that administration should be limited to adults in whom severe cyanide poisoning is suspected and children in whom moderate cyanide poisoning is suspected among smoke‐inhaling patients [102].

• If inhalation injury of the upper airway is present, edema‐related rapid airway obstruction may occur. In the ABLS 2018, it is described that intubation should be performed even before arrival at the hospital if the presence of pharyngeal burns, hoarseness, or wheezing is observed [74]. However, a study pointed out that intubation was unnecessary in one‐thirds of patients in whom it was performed before arrival at the hospital [107].

• As experts' opinions, it is described that intubation should not be performed based on the presence of facial or cervical burns alone, and that intubation is necessary in patients meeting one or more of the following criteria in addition to burns of the entire face: (1) the presence of deep circumferential cervical burns, (2) symptoms of airway obstruction (e.g., changes in the voice, wheezing, laryngeal dyspnea), and (3) extensive (≥ 40% TBSA) burns [102].

5.3.3. Bronchoscopy is useful for making a diagnosis of inhalation injury and evaluating the severity, but the start of treatment must not be delayed due to diagnosis

• There are experts' opinions that findings directly obtained using bronchoscopy are useful for making a diagnosis of inhalation injury and evaluating the severity [104, 108, 109, 110, 111, 112, 113, 114]. Some studies reported that severity classification in lesions observed on bronchoscopy using evaluation scores [109, 110, 111] was correlated with the morbidity rate, length of stay in the intensive care unit, duration of mechanical ventilation, and severity of hypoxemia [104, 109, 110, 111, 112, 113, 114]. However, no method for evaluating the severity has been established. A study pointed out the possibility that the mortality rate, admission period, and incidence of pneumonia‐related complications may be increased by unnecessarily performing diagnostic bronchoscopy [115]. Its influence on the prognosis of patients or treatment is uncertain, and patient transfer to a burn center must not be delayed by prioritizing bronchoscopy [102].

5.4. Explanation 4. Systemic Management 3: Electric Injury

5.4.1. Patients with electric injury require fluid resuscitation at a volume greater than that estimated from the burn area of the skin

• Electric shock‐related myopathy may induce myoglobinemia or kidney damage, and fluid resuscitation at a volume greater than in patients with burns was necessary according to several studies [116, 117]. In the ABLS 2018, a method to administer lactate Ringer (LR) solution at a half of 4 mL/kg/% TBSA over 8 h after injury and at the remainder over the next 16 h is adopted at all ages in the case of high‐voltage electric injury. In children, glucose‐containing maintenance fluid is added. Target urine volumes in adults and children are 30 to 50 mL/h and 1 mL/kg/h, respectively. However, if red urine is observed, as represented by myoglobinuria, a target urine volume should be increased to 75–100 mL/h until the urine color becomes clear. If there is a > 1/3 increase/decrease in the urine volume per hour from a target value of 1 mL/kg/h, the rate of fluid administration should be regulated by decreasing/increasing one‐thirds at maximum [74].

5.4.2. In patients with electric injury, electrocardiographic monitoring, blood testing, and urinalysis should be performed to continuously examine latent internal injury or compartment syndrome

• In patients with electric injury, the deep area may be greatly damaged even when the skin surface is normal. In the heart, electric injury may cause fatal arrhythmia, and initial electrocardiography should be performed in all patients [117, 118]. However, when electrocardiograms are normal in the absence of consciousness disorder, cardiac arrest, or abnormal heart beats, long‐term monitoring is not necessary [119].

• If the muscle is greatly damaged, abnormalities may be detected by performing blood testing/urinalysis. It is necessary to evaluate whether early debridement should be performed [120].

5.5. Explanation 5. Systemic Management 4: Chemical Injury

5.5.1. Lavage with a sufficient volume of water should be performed for the initial management of chemical injury, excluding some exceptions

• The clinical course of chemical injury differs from that of flame‐ or boiling water‐related burns, depending on a chemical substance involved in injury. For initial management, lavage with water has been conventionally performed. Some retrospective cohort studies compared an adequately treated group with a non‐adequately‐treated group, and showed that there were decreases in the mortality rate and admission period in the group in which treatment was promptly started or sufficient lavage was performed, and that the depth of burns was superficial [121, 122, 123].

• Prompt treatment refers to treatment within 10 min after injury. Sufficient lavage refers to lavage with water for ≥ 15 min. However, long‐time lavage (30 min to 2 h) may be necessary in some cases, depending on the acid/alkali concentration or extent of injury [123, 124].

5.6. Chemical burns requiring special initial management include phenol, cement, quicklime, and hydrogen fluoride burns

• Special initial management is necessary for some chemical substances involved in injury. Management should be performed as follows: [124].

Phenol: It is not water‐soluble, and polyethylene glycol should be used.

Cement: It has strong water absorption and strongly alkaline properties, and water lavage should be performed after removing clothes and sufficiently brushing it off.

Quicklime: It reacts with water, generating heat. Therefore, it should be sufficiently brushed off before lavage.

Hydrogen fluoride: The topical application of calcium gluconate and arterial injection (2%–5% calcium gluconate) should be selected [125]. The administration of calcium gluconate relieves pain.

5.7. Explanation 6. Infection Control

5.7.1. For contaminated burns, the administration of tetanus toxoid (Tt) or tetanus immunoglobulin (TIG) is recommended

• Concerning anti‐tetanus therapy for wounds in general including burns, there are three descriptive studies reviewing the literature [126, 127, 128]. It is recommended to treat contaminated burns similarly to other wounds in general [126]. Currently, there are no criteria for indicating anti‐tetanus therapy for burn patients in Japan. However, the onset of tetanus could be fatal, and anti‐tetanus therapy is recommended for contaminated burn wounds [129]; therefore, Tt or TIG should also be administered to patients with contaminated burn wounds.

• Clostridium tetani is an anaerobic bacterium widely distributed in nature including rice paddies, vegetable fields and house gardens [130], and tetanus may occur following burns [131, 132]. There is a report that an 18‐month‐old girl who had undergone anti‐tetanus vaccination three times and was considered to have complete immunity against tetanus developed the disease 11 days after sustaining a burn of 25% TBSA [133]. For the prevention of tetanus at the time of injury including burns, topical treatment of wounds including the removal of foreign bodies and debridement is considered essential. In addition to it, Church et al. recommended, “at burn centers, to usually administer TIG at 250–500 U and to administer Tt to patients who have not acquired complete primary immunity or those more than 10 years after the last vaccination” [126]. Concerning wounds in general including burns, the American Academy of Pediatrics Advisory Committee on Immunization Practices and Advisory Committee on Immunization Practices recommend the administration of Tt or TIG depending on the patient's history of inoculation of Tt and condition of the wound (whether it is a tetanus‐prone wound) [127, 134].

• Clinically, it is difficult to strictly distinguish between “tetanus‐prone” and “non‐tetanus‐prone” wounds, and tetanus occurs not infrequently from a minor wound such as a scratch sustained during gardening and a burn of 1% TBSA or less [135] or even without a clear wound. Therefore, Rhee et al. recommended to “administer Tt and TIG to those more than 10 years after the last vaccination and those with an unclear state of immunity regardless of the severity of the wound” [127], but, in the present medical circumstances in Japan, it is considered difficult to administer Tt or TIG to all patients with traumas including minor ones. Also, according to the survey of five emergency medical facilities in the USA, none of the 504 patients with “tetanus‐prone wounds” in a state of incomplete primary immunity was administrated both Tt and TIG, suggesting a gap between the guidelines and actual use of TIG [128]. Furthermore, TIG administration increases the anti‐tetanus antibody titer within 24 h, whereas at least 4 days are required until a Tt‐administration‐related increase in the antibody titer; therefore, Tt may not be effective in acute‐phase prevention, but Tt administration may prevent the onset of tetanus through an increase in the antibody titer if vaccination‐related basic immunity is completed [136]. In Japan, the recent annual number of patients is reportedly approximately 100, and the mortality rate is approximately 10%. Therefore, the administration of Tt or TIG is recommended for patients with incomplete or unclear primary immunity against tetanus and those with contaminated burn wounds more than 5 or 10 years after the last vaccination, depending on the degree of wound contamination in accordance with anti‐tetanus therapy for trauma (refer to Table 4).

• In Japan, Takeuchi et al. [137] performed anti‐tetanus preventive treatment in 89 trauma patients (TIG in 60, Tt in 9, both in 20) and reported no occurrence of tetanus or adverse reactions, but, according to our review, there is no evaluation or report concerning burns.

• The frequency of additional Tt vaccination depends on the patient's age or immune state. Therefore, it is necessary to confirm the package inserts of Tt.

TABLE 4.

Anti‐tetanus therapy for trauma.

Immune state	Type of wound
	Clean, minor	Other wounds
Previous Tt vaccination: ≥ 3 times	No TIG	No TIG
	When the interval from the final session of Tt vaccination is ≥ 10 years, Tt vaccination at 0.5 mL should be performed.	When the interval from the final session of Tt vaccination is ≥ 5 years, Tt vaccination at 0.5 mL should be performed.
Previous Tt vaccination: ≤ 3 times or unclear	No TIG	TIG at 500 units
	Tt vaccination at 0.5 mL	Tt vaccination at 0.5 mL

Note: Cited and partially modified from Ref. [127].

Abbreviations: Tt: Tetanus toxoid, TIG: Human tetanus immunoglobulin.

5.8. Hydrotherapy for extensive burns may increase the risk of wound infection, and sufficient infection control, such as avoiding the use of shared bathing/shower equipment, is necessary

• Hydrotherapy for wounds (taking a shower/bath, lavage) is routinely performed for the prevention of infection, promotion of wound healing, and refreshing.

• To obtain similar effects in burn patients, hydrotherapy is often performed especially in patients with minor burns not requiring hospitalization. However, few studies have examined its usefulness, and expert opinions comprise the greater portion of the published work on hydrotherapy [138, 139, 140, 141]. There is no RCT regarding the prevention of infection on hydrotherapy (taking a shower/bath) in patients with extensive burns.

• Hydrotherapy for extensive burns has been performed at many facilities. A burn unit survey in the United States and Canada in 1994 showed that hydrotherapy was performed in 94.8% of 153 facilities [142]. In 81.4%, treatment by bathing was performed. In 82.8%, it was performed in all burned patients regardless of the burn area. In 86.9%, it was continuously performed during the admission period. Later, according to a survey in 2010, hydrotherapy was routinely performed in 83% of 59 facilities [143]. Furthermore, a survey in the United Kingdom and Ireland showed that hydrotherapy was performed in 27 of 28 facilities responsible for burn treatment [144]. However, there were indication criteria for hydrotherapy in 11 facilities (41%), and a protocol had been established in 4 (15%).

• Hydrotherapy for extensive burns using shared equipment, such as bathtubs, may cause nosocomial infection with Pseudomonas aeruginosa, Staphylococcus aureus, or MRSA [145, 146, 147, 148, 149, 150, 151, 152]. A systematic review [147] of two case control studies [145, 146] examined the risk of infection with Acinetobacter, and showed that hydrotherapy by bathing increased the risk of infection with this type of bacteria (OR: 3.29, 95% CI: 1.64–6.63). In 12 burn patients with MRSA infection, the same strain was detected from a hand shower and stretcher as equipment for hydrotherapy, suggesting their involvement in transmission [148]. Hydrotherapy was discontinued, and switched to bedside treatment with strict infection control. Subsequently, there was no MRSA infection. Furthermore, another study compared a group in which bathing with shared equipment was performed with a group in which bedside lavage with sterilized water and chlorhexidine was performed, and reported that the mortality rate, sepsis‐associated mortality rate, and Pseudomonas aeruginosa‐associated mortality rate were significantly lower in the latter, and that the resistance of Pseudomonas aeruginosa to aminoglycosides reduced [149]. Concerning mass infection with Pseudomonas aeruginosa in burn wards, an environmental survey and cohort study were performed [150]. Mass infection with Pseudomonas aeruginosa was controlled by sterilizing contaminated equipment for hydrotherapy. An analysis with regular bacterial culture from burn wounds, bathtubs for hydrotherapy, and water after use showed that Staphylococcus aureus and Klebsiella pneumoniae were frequently detected from wound sites and bathtubs, and that there was an increase in the number of multidrug‐resistant bacteria in bathtubs. However, no bacteria were detected from water samples [151].

• Thus, shared bathing equipment increases the incidence of horizontal infection with bacteria, and it has been eliminated step by step at many burn centers [143]. These bacteria are also settled in areas that are difficult to sterilize, such as a water pipe and hose, in addition to a treatment table/bathtub as a part of equipment for hydrotherapy [146, 152], and complete prevention is difficult. However, Akin et al. performed hydrotherapy on a stretcher with a sterile, disposable plastic sheet, and reported that no bacteria were detected from the stretcher, suggesting the effectiveness of this method in preventing infection [152].

• As hydrotherapy, especially with shared equipment, for extensive burns may induce infection, sufficient infection control, such as avoiding the use of shared equipment, is necessary. Although the demerits of hydrotherapy in the prevention of infection are emphasized, no study has examined the effects of hydrotherapy on factors other than infection, such as wound healing or an admission period. Therefore, it is necessary to comprehensively evaluate whether hydrotherapy should be performed based on the wound site and patient condition while paying attention to infection.

5.8.1. For disinfection, the causative bacteria for infection, antibacterial spectra of various drugs, and wound condition should be considered

• There are various opinions and reports concerning disinfection of burns, and the matter still remains controversial. In Japan, some investigators consider that chlorhexidine or povidone iodine should be used for disinfection of burns [129, 140, 143, 144], but others consider that disinfection itself should be avoided from the viewpoint of delayed wound healing [153, 154]. For example, as for povidone iodine, there is a report that it is toxic to fibroblasts and epidermal keratinized cells in vitro at clinically used concentrations [155], but there is another report that there was no significant difference in the interval of wound healing when comparing povidone iodine with petrolatum topically applied to split‐thickness mesh skin grafts [156].

• Concerning disinfection of burns, there is one systematic review [157]. However, reports on silver‐containing dressing materials, dressing materials/topical agents containing disinfectants that are not approved as products in Japan, honey, and aloe comprise the greater portion, and there are few reports on the effects of povidone iodine or chlorhexidine application, that is, disinfection available in Japan.

• Concerning the effectiveness of burn disinfection available in Japan, there is one RCT comparing silver sulfadiazine alone with silver sulfadiazine plus chlorhexidine [135]. Snelling et al. investigated 253 patients with a mean burn area of approximately 20% TBSA, and reported that the frequency of Staphylococcus aureus colonization in a group in which 1% silver sulfadiazine was mixed with 0.2% chlorhexidine gluconate or the burn site was washed with 4% chlorhexidine gluconate‐containing soap on changing gauze was lower than in a group in which 1% silver sulfadiazine alone was applied. However, it remains to be clarified to what extent a decrease in the frequency of Staphylococcus aureus colonization at the wound site improves the prognosis.

• As relevant guidelines, it is described that disinfectants should be used for the topical treatment of second‐degree burn wounds within 1 week after injury as an expert opinion due to little evidence in the Clinical Practice Guidelines for Management of Burn Care (3rd Edition) [95] prepared by the Japanese Society for Burn Injuries. Internationally, the guidelines concerning burn of New South Wales, Australia [158], recommend that burns should be washed with 0.05% chlorhexidine gluconate, sponge saturated with chlorhexidine gluconate, or sterile saline.

• Caution is necessary in applying povidone iodine over an extensive area in patients with kidney or thyroid dysfunction, elderly patients, and children because of its absorption from the wound surface (iodine poisoning) [159].

• In conclusion, few studies have examined the advantage of disinfection of burn wounds, and there is little evidence. However, burn injury is a type of wound/trauma, and disinfection may be considered, reviewing wound conditions, such as contaminated or infected wounds, causative bacteria for infection, and antibacterial spectra of various drugs in accordance with the management of wounds in general.

5.8.2. In patients with perianal burns, a fecal diversion tube may be used because it may reduce the frequency of gauze change due to contamination by stools and the incidence of wound or urinary tract infection. However, the patient's general condition and wound state must be considered

• There is one non‐randomized comparative trial concerning the use of the fecal diversion tube for burn patients [160].

• In patients with gluteal, femoral or perineal burns, contamination of the wound associated with defecation often poses problems, and the patients are exposed to the risk of infection and loss of skin grafts. Also, sedated patients have fecal incontinence and require gauze change at each bowel movement, and patients with fecal incontinence are reported to increase the risk of nosocomial infection including Clostridium difficile infection [161].

• To avoid wound contamination, defecation control has been performed using various methods, such as colostomy, fasting, and narcotics. Recently, the fecal diversion tube has been reported to be useful for the management of skin detachment and wounds around the anus. When it was used in 42 patients with fecal incontinence discharging liquid or semi‐liquid stools, the treatment was effective for maintaining or improving the condition of the gluteal and perianal skin in 92% or more of patients even with risk factors of skin vulnerability [162]. When 106 patients with perianal burns managed with the fecal diversion tube were compared with a previous 106 patients managed without it, no significant difference was observed in the mortality rate, but the incidences of subcutaneous and urinary tract infections were reduced significantly from 46.2% to 19.8% and from 27.4% to 14.2%, respectively, and the treatment was also advantageous cost wise [161].

• In a prospective study in 7 perianal burns and 13 with severe perianal excoriations, the severity score of perianal skin damage was significantly reduced after intubation, the mean frequency of gauze change was reduced from 3.3 to 1.5 times/day, and the frequency of changes of bed linen for patients with fecal incontinence was reduced from 9.3 to 1.2 times/day [163]. In Japan, Nishibori et al. anally intubated five burn patients (three after surgery for gluteal burns and two with extensive burns) and reported that the treatment was effective in defecation control with no wound contamination [164]. The fecal diversion tube is recommended as a noninvasive treatment that should be considered before ostomy [163].

• As complications, anal laxity, anal ulcers [165], rectal ulcers [166], and lower gastrointestinal bleeding [162, 166] of which the association with the tube cannot be ruled out in patients receiving anticoagulant therapy have been reported. The patient condition must be considered.

5.9. Explanation 7. Topical Treatment 1: Escharotomies and Fasciotomies

Circumferential or mostly circumferential deep burns of the extremities or anterior chest may induce peripheral circulatory disturbance of extremities or respiratory disorder, and escharotomies and fasciotomies should be considered for decompression.

• There is no systematic review or RCT on the usefulness of escharotomies and fasciotomies.

• Escharotomies and fasciotomies should be considered based on the presence or absence of peripheral circulatory disturbance of extremities and respiratory state within 48 h after injury, when edema reaches a peak, in patients with circumferential or mostly circumferential deep second‐ or third‐degree burns of the extremities/trunk. In addition to escharotomy involving the subcutaneous tissue, fasciotomy is sometimes necessary, depending on the depth of burns.

• In patients with circumferential third‐degree burns of extremities, extremities are longitudinally incised for decompression [167]. Salisbury et al. [168] performed a prospective study regarding escharotomies and fasciotomies of extremities and fingers in patients with circumferential third‐degree burns of extremities, and reported that the incidence of digital necrosis in a group in which escharotomies and fasciotomies of fingers was added was significantly lower than in a group in which escharotomies and fasciotomies of extremities alone was performed (7.5 vs. 20.8%, respectively). Furthermore, a study showed that escharotomies and fasciotomies led to oxygen saturation recovery to a normal value in circumferential extremity burn patients with an oxygen saturation of < 95% on a pulse oximeter [169]. Saffle et al. [170] measured the intramuscular pressure (IMP) in patients with circumferential third‐degree burns of the upper extremities, reported that IMP was more accurate than Doppler findings, and recommended escharotomies and fasciotomies for patients with an IMP of ≥ 30 mmHg.

• Escharotomies and fasciotomies is frequently performed in patients with high‐voltage electric injury [171]. Internationally, bromelain‐based enzymatic debridement is performed, and the opportunity to perform escharotomies and fasciotomies has decreased [172].

• Concerning anterior thoracic burns, Demling et al. [173] used a 30% third‐degree scald burn sheep model, and found that escharotomies and fasciotomies of the anterior chest significantly improved the pulmonary compliance, urine volume, and cardiac output in the anterior thoracic burn group.

5.10. Explanation 8. Topical Treatment 2: Topical Agents

5.10.1. For first‐degree burns, topical steroids may be used early after injury to obtain anti‐inflammatory actions

• Concerning the usefulness of topical steroids for burn treatment, there are only expert opinions [174, 175, 176]. On the other hand, there are three RCT (including double‐blind RCT) showing that there are no anti‐inflammatory effects of topical steroids on the physically damaged (burned) skin [177, 178, 179]. However, in Japan, many topical steroids have been used to treat burns, and most expert opinions pointed out the usefulness of topical steroids for the treatment of first‐degree burns; the use of topical steroids may be considered in the initial phase of first‐degree burns.

• Yamanaka et al. recommended the use of very strong or stronger topical steroids immediately after injury to over a short period for removing tissue destruction and inflammation in the early stage in patients with first‐degree burns [174]. Takuma et al. recommended the use of topical steroids at marked flare/pain sites in patients with first‐degree burns [175]. Furthermore, Hitoshi et al. reported that topical steroids were effective in inhibiting flare/edema in the acute phase and relieving pain in patients with first‐ or second‐degree burns, whereas they delayed wound healing, suppressing epithelialization. They recommended that the application period should be restricted to 2 days after injury [176].

• On the other hand, Pederson et al. performed a double‐blind RCT by artificially creating first‐degree burns or superficial second‐degree burns in 12 healthy volunteers and compared the anti‐inflammatory effect between clobetasol propionate and placebo according to the severity of pain and erythema and reported no significant difference between the two groups [177]. Faurschou et al. [178] examined the effects of an topical steroid preparation on sun burn (ultraviolet B irradiation) in 20 healthy volunteers but observed no clinical usefulness when it was applied after irradiation.

• Also, Muramatsu et al. carried out a double‐blind trial concerning the effects of betamethasone valerate/gentamycin sulfate on fresh second‐degree burns using gentamycin sulfate as a control drug [179]. According to this study, no difference was observed in the alleviation of swelling or pain between the two groups, and betamethasone valerate/gentamycin sulfate promoted epithelialization until 2 days from the beginning of their use but suppressed it after 4 days or more. They also treated one group by using gentamycin sulfate after topical application of betamethasone valerate/gentamycin sulfate for 3 days but another group by using gentamycin sulfate alone from the beginning and observed no significant difference in the comprehensive evaluation of objective findings, number of days until completion of epithelialization or overall pharmacological effect.

5.10.2. To treat second‐degree burns of which the depth is clear, tretinoin tocoferil, bucladesine sodium, and prostaglandin E1 should be used

• For chronic ulcers caused by burns, topical agents should be selected for wound bed preparation based on the TIME concept or moist wound healing. It is also important to appropriately select not only the principal agent but also the base according to the condition of the wound surface. The following topical treatments are explained in the Guidelines for the Management of Pressure Ulcers (3rd edition) as topical agents appropriate for wound bed preparation, but the topical agents used for T (removal of necrotic tissue) and M (maintenance of the moist environment) in burns are the same:

  • T (removal of necrotic tissue): Cadexomer iodine, silver sulfadiazine, dextranomer, bromelain ointment.
  • I (control/elimination of infection): Cadexomer iodine, silver sulfadiazine, povidone‐iodine sugar, povidone‐iodine gel, iodine ointment.
  • M (maintenance of the moist environment): When effusion is excessive, cadexomer iodine, dextranomer and bucladesine sodium; when effusion is deficient, tretinoin tocoferil, prostaglandin E1, and oil‐based ointments such as white petrolatum.
  • E (management of wound edges): No recommendable topical agents.

• Regarding tretinoin tocoferil, there is one double‐blind RCT comparing it with bendazac in patients with various skin ulcers including those caused by burns [180] and one non‐blinded RCT comparing it with lysozyme hydrochloride [181]. Concerning bucladesine sodium, there is one double‐blind RCT each comparing it with the base and lysozyme hydrochloride in patients with various skin ulcers including those caused by burns [182, 183]. As for prostaglandin E1, there is a non‐blinded RCT comparing it with lysozyme hydrochloride in patients with various skin ulcers including those due to burns [184]. However, it must be considered that there is no detailed description on the state of burn‐related ulcers, such as the depth of burns, in these reports.

• Ointments containing antibiotics (antibacterial agents) are oil‐based ointments. They may be used for the protection of the wound surface and maintenance of the moist environment, but their use should be restricted to a short period, because their long‐time use may lead to the development of resistant bacteria.

• If ulcers accompanied by necrotic tissue develop as a result of deep second‐degree burns, the above topical agents should be selected after surgical debridement. If the general condition is poor, or if the necrotic tissue is thin, making surgical debridement impossible, the topical application of bromelain, silver sulfadiazine, cadexomer iodine or dextranomer for the removal of necrotic tissue should be considered (refer to Explanations 8.3 and 8.4).

• A double‐blind RCT comparing tretinoin tocoferil with bendazac was performed in 152 patients with various skin ulcers including 44 with ulcers due to burns by the L‐300 Clinical Trial Group [180]. While there is no mention of the depth of burns or time after injury, granulation 1 week after the application of the test drugs was reported to be significantly better in the tretinoin tocoferil group. There is also a non‐blinded RCT comparing tretinoin tocoferil with lysozyme hydrochloride in 217 patients with various skin ulcers including 36 with ulcers due to burns, but no detailed description is provided concerning the depth of burns or time after injury, and it was reported that there was no significant difference between the two groups among the patients with ulcers due to burns [181].

• Niimura et al. performed a double‐blind RCT comparing bucladesine sodium with the base in 150 patients with pressure ulcers/skin ulcers including 20 with ulcers due to burns and comparing bucladesine sodium with lysozyme hydrochloride in 275 patients with pressure ulcers/skin ulcers including 40 with ulcers due to burns [182, 183]. According to these reports, bucladesine sodium was significantly superior in the ulcer area reduction rate, granulation and epithelialization, but no detailed information is provided concerning the depth of burns or time after injury. There is, however, a report that the blood concentration of bucladesine sodium increased and remained elevated for a period after its topical application [185], so attention to the general condition including the blood pressure, urine volume and blood glucose level is necessary when it is topically applied to a wide area.

• Imamura et al. performed a non‐blinded RCT comparing prostaglandin E1 with lysozyme hydrochloride in 171 patients with pressure ulcers/skin ulcers including 26 with ulcers due to burns [184]. According to their report, there is no detailed mention of the depth of burns or time after injury, but the response rate in the prostaglandin E1‐applied group was significantly higher among the patients with ulcers due to burns. On the other hand, there was no significant difference in the rate of reduction in the ulcer area between the two groups. Note As of February 2023, when the publication of the present guidelines is being prepared, the shipment of tretinoin tocoferil is stopped.

5.10.3. Bromelain, cadexomer iodine, dextranomer, and silver sulfadiazine should be used as topical agents to remove necrotic tissue from small third‐degree burns

• Concerning bromelain, there is one RCT evaluating its debriding effect on third‐degree burns [186].

• Concerning cadexomer iodine and dextranomer, there are non‐randomized comparative trials in patients with various skin ulcers including ulcers due to burns [187, 188], and a case series study [189]. In these reports, the improvement rating, involving debriding effects, was high, but burns were not focused, and the number of patients was small.

• Concerning silver sulfadiazine, there is no article evaluating the debriding effect except for expert opinions about pressure ulcers [190, 191]. However, there has been rich experience in the clinical use of silver sulfadiazine for burns, and it may prevent infection (refer to Explanation 8.4).

• Anzai et al. performed an RCT using bromelain and a placebo prepared by mixing inactivated bromelain with the same base in 33 patients with deep second‐ or third‐degree burns (7–10 days after injury) [186]. They separated the wound of each patient into halves, applied the true drug or placebo topically to each half, and compared the degree of lysis of necrotic tissue, hemorrhage and pain, reporting that the true drug showed a significantly greater debriding effect in third‐degree burns. There are many other case reports showing the usefulness of bromelain. Ogawa et al. evaluated the debriding effect of bromelain in ulcer patients including 28 with ulcers due to burns and reported that a response rate of 86% was obtained in ulcers due to burns [192]. In using bromelain, attention to pain, which occurs frequently, is necessary. Also, as highly water‐absorbing macrogol is used as the base, its debriding effect is attenuated when effusion or the moisture of the wound surface is reduced [190].

• Silver sulfadiazine is considered to produce a wound surface cleaning effect as its emulsion base with high water content causes softening and lysis of necrotic tissue due to its permeation characteristics [191]. However, there are a few points that need attention in its use: it may cause edema on the wound surface in wounds rich in effusion, its effect is attenuated when it is used with povidone iodine, and its concomitant use with other drugs, particularly topical cutaneous enzyme preparations, should be avoided [190].

5.10.4. Silver sulfadiazine should be applied to extensive third‐degree burns

• Third‐degree burns refer to tissue injury/necrosis involving the full‐thickness dermis. Surgical or chemical debridement is necessary. Therefore, topical agents, such as bromelain, cadexomer iodine, dextranomer and silver sulfadiazine, which prevent infection until debridement and soften/lyse the necrotic tissue rather than the protection of the wound surface, should be used.

• Concerning the topical use of silver sulfadiazine for the treatment of third‐degree burns, there are two non‐randomized comparative trials [193, 194]. The primary objective of topical agents for extensive third‐degree burns is to prevent infection from the wound surface until surgical debridement. Silver sulfadiazine is widely used in Japan and abroad for the treatment of burns, and there are multiple reports showing an excellent antibacterial action. Also, it is convenient for application to a wide area because of the emulsion base.

• Pegg et al. performed a non‐randomized comparative trial in patients with burns of various degrees by treating 314 with silver sulfadiazine, 156 with maphenide (not marketed in Japan), and 175 historical controls with gentamycin sulfate [193], and reported that the mortality rate, positive rate of bacterial cultures, and detection rates of P. aeruginosa, staphylococci, Proteus and Candida were significantly reduced in the silver sulfadiazine group compared with the control and maphenide groups. In Japan, Oyama et al. carried out a non‐randomized comparative trial evaluating the effects of silver sulfadiazine and gentamycin sulfate in 31 patients with moderate to severe burns according to Artz's criteria [194], and reported that silver sulfadiazine was markedly effective against Klebsiella, Serratias, other Gram‐negative bacteria and Candida.

• Ono et al. evaluated the minimum inhibitory concentrations (MIC) of various antibacterial agents against P. aeruginosa, because its detection rate increases with time among bacteria isolated from burns. As no strain resistant to silver sulfadiazine or maphenide was observed, they recommended them as topical antibacterial agents for burns [195]. Also, Yura et al. performed resistance‐acquisition and bactericidal studies using silver sulfadiazine against P. aeruginosa and reported infrequent development of resistance and a satisfactory bactericidal action of the drug [196]. On the other hand, there have been reports of infections resistant to silver preparations including silver sulfadiazine [197]. According to the report by Li et al. [198], bacteria are shown to acquire resistance to silver in the presence of silver at a low concentration, and Atiyeh et al. suggested the necessity to maintain an appropriate silver concentration at the wound, because resistance to silver develops at concentrations near the MIC but not at a sufficient concentration [199]. Also, in extensive burns with a large amount of exudates, silver sulfadiazine is reported to be inactivated with a marked decrease in its effect [200]. Therefore, repeated applications should be considered under such circumstances.

• Because an emulsion base is used in silver sulfadiazine preparations, they have high tissue permeability and are expected to produce a debriding effect by promoting autolysis of necrotic tissue (refer to Explanation 8.3).

• As adverse effects of silver sulfadiazine, leukocytopenia, methemoglobinemia, silver deposition, and allergic reaction to sulfonamides have been reported. Sufficient attention to these adverse effects is considered necessary, particularly when silver sulfadiazine is topically applied to extensive burns. However, leukocytopenia is also occasionally observed in the use of other drugs, and there is the opinion that it should not be regarded as a side‐effect specific to silver sulfadiazine [201]. There is also the opinion that the use of silver sulfadiazine should be avoided as much as possible for wounds showing active proliferation of epidermal keratinized cells such as donor site wounds and superficial second‐degree burns, because the cytotoxicity of silver delays wound healing [199].

6. Chapter 6. Details of a Systematic Review for Each CQ

CQ1 Is Systemic Antibiotic Prophylaxis for Burns Early After Injury Useful for Preventing Wound Infection?

Recommendation level	Remarks on recommendation
Weak recommendation	Currently, it cannot be recommended to uniformly perform systemic antibiotic prophylaxis for burns early after injury for the prevention of wound infection, because there is no sufficient evidence on its efficacy. It is proposed to avoid such administration.

6.1. Literature search

The Japan Medical Library Association was requested to search for the literature. (refer to Supporting Information with respect to the retrieval style and search results).

• Databases used: PubMed, Cochrane Database of Systematic Reviews, Japan Medical Abstracts Society.

• Search period: January 1980 to December 2020.

To investigate the literature as much as possible, reports, including review articles and systematic reviews on burn treatment, were extensively searched, and the references quoted in articles were also searched.

There is 1 RCT on prophylactic systemic antibiotic administration for burns early after injury. There are 4 retrospective observational studies.

6.2. Outcome

Various interventions/items: the timing of antibiotic administration (early after injury, perioperative period) and influence on the prognosis of patients, sepsis/bacteremia, and skin graft survival as outcomes, have been examined. However, the present guidelines aim to provide adequate initial treatment for burns, and “early after injury” was adopted as the timing of administration through a review by the systematic review team, and the incidence of wound infection (importance of outcome: 4) as an outcome.

The importance of outcome was determined by all guideline‐drafting members' agreement (consistency rate: 100%).

6.3. Literature screening

Primary screening was performed using “burn” and “antibiotic administration” as key words. PubMed: 839 studies, Cochrane Database of Systematic Reviews: 2, and Japan Medical Abstracts Society: 3 were found. Many reports on corneal (chemical) burns were included. On secondary screening, the above reports were focused to 25 articles written in English on antibiotic administration to patients with burns. Of these, 1 RCT and 4 observational studies (total: 5) were used for analysis regarding antibiotic administration early after injury. A flowchart of literature search is presented (Figure 3).

FIGURE 3.

CQ1 Prophylactic antibiotics for burns: Flowchart of literature search.

6.4. Evaluation of individual references

With respect to the 4 observational studies selected on secondary screening, the selection bias, performance bias, detection bias, attrition bias, and other biases were assessed based on the Minds Manual for Guideline Development 2020.

6.5. Evaluation of the outcome

For outcome assessment, the integrated value and 95% confidence interval of effect measures for respective outcomes were calculated using statistical software “R” and its metafor package, as described in the Minds Manual for Guideline Development 2020, and a meta‐analysis was performed.

6.6. Results

Incidence of wound infection: The integrated value of effect measures was 0.83, and the 95% confidence interval was 0.46 to 1.48. The strength of evidence was established as very weak (D).

A forest plot and total evidence are presented (Figures 4, 5) (with respect to assessment sheets for each outcome, refer to Supporting Informations).

FIGURE 4.

CQ1 Forest plot.

FIGURE 5.

CQ1 Total evidence.

Based on these results, a summary of the results (SoF) was prepared and presented at a panel meeting.

CQ2 Are Dressing Materials Useful for the Treatment of Second‐Degree Burns?

Recommendation level	Remarks on recommendation
Weak recommendation	The use of dressing materials [silver‐containing Hydrofiber, silver‐containing polyurethane foam/soft silicone, hydrocolloid, polyurethane film, non‐adhesive gauze (soft silicone)] is proposed for the treatment of second‐degree burns.

6.7. Literature search

The Japan Medical Library Association was requested to search for the literature. (refer to Supporting Informations with respect to the retrieval style and search results).

• Databases used: PubMed, Cochrane Database of Systematic Reviews, Japan Medical Abstracts Society.

• Search period: January 1980 to December 2020.

With respect to dressing materials that are used for ulcer treatment in Japan [silver‐containing Hydrofiber, silver‐containing polyurethane foam/soft silicone, hydrocolloid, polyurethane film, hydrogel, non‐adhesive gauze (soft silicone), chitin], preliminary searching was performed. A systematic review on silver‐containing Hydrofiber, silver‐containing polyurethane foam/soft silicone, polyurethane film, hydrocolloid, and non‐adhesive gauze was performed. When searching the literature for evidence more reliable than systematic reviews and RCT, PubMed: 19 studies on silver‐containing Hydrofiber, Cochrane Database of Systematic Reviews: 1, and Japan Medical Abstracts Society: 0 were found. Concerning silver‐containing polyurethane foam/soft silicone, PubMed: 12 studies, Cochrane Database of Systematic Reviews: 1, and Japan Medical Abstracts Society: 0 were found. Concerning hydrocolloid, PubMed: 60 studies, Cochrane Database of Systematic Reviews: 1, and Japan Medical Abstracts Society: 0 were found. Concerning polyurethane film, PubMed: 38 studies, Cochrane Database of Systematic Reviews: 1, and Japan Medical Abstracts Society: 0 were found. Concerning non‐adhesive gauze, PubMed: 19 studies, Cochrane Database of Systematic Reviews: 1, and Japan Medical Abstracts Society: 0 were found.

6.8. Outcome

As a result of consideration by the systematic review team, the healing rate (importance of outcome: 5) and incidence of infection (importance of outcome: 5) were adopted as outcomes. The importance of outcome was determined by all guideline‐drafting members' agreement (consistency rate: 100%).

6.9. Literature screening

Silver‐containing Hydrofiber: Reports describing the above outcomes were selected from the 20 studies collected on literature searching (primary screening). As a result, 5 RCT were selected. As a result of secondary screening, the 5 RCT were used for analysis. A flowchart of literature search is presented (Figure 6).

FIGURE 6.

CQ2 Silver‐containing Hydrofiber Flowchart of literature search.

6.10. Silver‐containing polyurethane foam/soft silicone

Reports describing the above outcomes were selected from the 13 studies collected by literature searches (primary screening). As a result, 2 RCT were selected. As a result of secondary screening, the 2 RCT were used for analysis. A flowchart of literature search is presented (Figure 7).

FIGURE 7.

CQ2 Silver‐containing polyurethane foam/soft silicone flowchart of literature search.

6.11. Hydrocolloid

Reports describing the above outcomes were selected from the 61 studies collected by literature searches (primary screening). As a result, 4 RCT were selected. As a result of secondary screening, the 4 RCT were used for analysis. A flowchart of literature search is presented (Figure 8).

FIGURE 8.

CQ2 Hydrocolloid Flowchart of literature search.

6.12. Polyurethane film

Reports describing the above outcomes were selected from the 39 studies collected by literature searches (primary screening). As a result, 2 RCT were selected. As a result of secondary screening, the 2 RCT were used for analysis. A flowchart of literature search is presented (Figure 9).

FIGURE 9.

CQ2 Polyurethane film flowchart of literature search.

6.13. Non‐adhesive gauze

Reports describing the above outcomes were selected from the 20 studies collected by literature searches (primary screening). As a result, 2 RCT were selected. As a result of secondary screening, the 2 RCT were used for analysis. A flowchart of literature search is presented (Figure 10).

FIGURE 10.

Non‐adhesive gauze (soft silicone): Flowchart of literature search.

6.14. Evaluation of individual references

With respect to the 2 RCT selected on secondary screening, the selection bias, performance bias, detection bias, attrition bias, and other biases were assessed based on the Minds Manual for Guideline Development 2020 ver. 3.0. Dressing materials are recognized by subjects or investigators, and performance/detection blinding is impossible. These RCT were evaluated as having a bias risk.

6.15. Evaluation of the outcome

For outcome assessment, the integrated value and 95% confidence interval of effect measures for respective outcomes were calculated using Review Manager 5.4, and a meta‐analysis was performed.

6.16. Results

6.16.1. Silver‐containing Hydrofiber

Interval until wound healing: Integrated value of effect measures, −3.46; 95% confidence interval, −5.19 to −1.74; strength of evidence, very weak (D) (Figures 11, 12).

FIGURE 11.

CQ2 Silver‐containing Hydrofiber Healing rate Forest plot.

FIGURE 12.

CQ2 Silver‐containing polyurethane foam/soft silicone Total evidence.

6.16.2. Silver‐containing polyurethane foam/soft silicone

Incidence of infection: Integrated value of effect measures, 5.53; 95% confidence interval, 0.66 to 46.13; strength of evidence, very weak (D) (Figures 13, 14).

FIGURE 13.

CQ2 Silver‐containing polyurethane foam/soft silicone Incidence of infection Forest plot.

FIGURE 14.

CQ2 Silver‐containing Hydrofiber Total evidence.

6.16.3. Hydrocolloid

Incidence of infection: Integrated value of effect measures, 0.93; 95% confidence interval, 0.17 to 5.24; strength of evidence, very weak (D) (Figures 15, 16).

FIGURE 15.

CQ2 Hydrocolloid Incidence of infection Forest plot.

FIGURE 16.

CQ2 Hydrocolloid Total evidence.

6.16.4. Polyurethane film

Incidence of infection: Integrated value of effect measures, 0.88; 95% confidence interval, 0.23 to 3.37; strength of evidence, very weak (D) (Figures 17, 18).

FIGURE 17.

CQ2 Polyurethane film Incidence of infection Forest plot.

FIGURE 18.

CQ2 Polyurethane film Total evidence.

6.16.5. Non‐adhesive gauze

Interval until wound healing: Integrated value of effect measures, −0.71; 95% confidence interval, −1.07 to −0.35; strength of evidence, very weak (D).

Incidence of infection: Integrated value of effect measures, 1.76; 95% confidence interval, 0.34 to 9.20; strength of evidence, very weak (D) (Figures 19, 20).

FIGURE 19.

CQ2 Non‐adhesive gauze Interval until wound healing Forest plot.

FIGURE 20.

CQ2 Non‐adhesive gauze Incidence of infection Forest plot.

Based on these results, a summary of the results (SoF) was prepared and presented at a panel meeting. (Figures 15, 16, 21).

FIGURE 21.

CQ2 Non‐adhesive gauze Total evidence.

CQ3 Is Trafermin Useful for the Treatment of Second‐Degree Burns?

Recommendation level	Remarks on recommendation
Weak recommendation	The use of trafermin in patients with second‐degree burns is proposed.

6.17. Literature Search

The Japan Medical Library Association was requested to search for the literature. (refer to Supporting Informations with respect to the retrieval style and search results).

• Databases used: PubMed, Cochrane Database of Systematic Reviews, Japan Medical Abstracts Society.

• Search period: January 1980 to December 2020.

There are 4 RCT on second‐degree burns and bFGF. These studies were analyzed.

6.18. Outcome

As a result of consideration by the systematic review team, the interval until healing (importance of outcome: 5) was adopted as an outcome. An improvement in scars and adverse events were also nominated as candidates for outcomes, but there was a conventional systematic review using articles from the above RCT with respect to an improvement in scars, and there was only 1 study describing adverse events; therefore, these items were not newly analyzed. The importance of outcome was determined by all guideline‐drafting members' agreement (consistency rate: 100%).

6.19. Literature Screening

Primary screening was performed using “burn” and “bFGF” as key words. 4 RCT and 1 systematic review were selected. This systematic review analyzed articles from the 4 RCT and other articles on aFGF, and was excluded on secondary screening. The 4 RCT were analyzed. A flowchart of literature search is presented (Figure 22).

FIGURE 22.

CQ3 Flowchart of literature search.

6.20. Evaluation of Individual References

With respect to the 4 RCT selected on secondary screening, the selection bias, performance bias, detection bias, attrition bias, and other biases were assessed based on the Minds Manual for Guideline Development 2020 ver. 3.0. Due to the bFGF administration procedure, performance/detection blinding is impossible. These RCT were evaluated as having a performance bias (−2) and detection bias (−2).

6.21. Evaluation of the Outcome

For outcome assessment, the integrated value and 95% confidence interval of effect measures for respective outcomes were calculated using EZR version 1.55, and a meta‐analysis was performed.

6.22. Results

Interval until healing: Integrated value of effect measures, −3.49 (Random effect model); 95% confidence interval, −4.38 to −1.30; strength of evidence, very weak (D).

A forest plot and total evidence are presented below (Figures 23, 24). (with respect to assessment sheets for each outcome, refer to Supporting Informations).

FIGURE 23.

CQ3 Forest plot.

FIGURE 24.

CQ3 Total evidence.

Based on these results, a summary of the results (SoF) was prepared and presented at a panel meeting.

7. List of the members of the Wound/ Burn/Pressure Ulcer Guidelines Revising Committee

7.1. Supervising committee

Chairperson: Takao TACHIBANA (Hoshigaoka Medical Center).

Vice‐chairperson: Minoru HASEGAWA (University of Fukui), Manabu FUJIMOTO (Osaka University).

Members: Yoshihide ASANO (Tohoku University), Takeshi NAKANISHI (Meiji University of Integrative Medicine), Hiroshi FUJIWARA (Niigata University), Takeo MAEKAWA (Jichi Medical University Saitama Medical Center), Sei‐ichiro MOTEGI (Gunma University), Yuichiro YOSHINO (Japanese Red Cross Kumamoto Hospital).

7.2. Drafting committee

7.2.1. Wounds in General

Sei‐ichiro MOTEGI (Gunma University), Masaru ARIMA (Fujita Health University), Toshio ICHIKI (Kyushu University), Ikuko UEDA (Osaka University), Katsuyuki OKADA (Kiryu Kosei General Hospital), Sakae KANEKO (Japanese Red Cross Masuda Hospital), Hiroyuki KANO (Gifu Municipal Hospital), Yuta KURASHIGE (Kurashige Dermatology Clinic), Akira SHIMIZU (Kanazawa Medical University), Yasuyuki SUMIKAWA (Hokutoukai Sumikawa Dermatology Allergy Clinic), Hidenori TAKAHASHI (Japan Community Health care Organization (JCHO) Fukui Katsuyama General Hospital), Zenshiro TAMAKI (Saitama Prefectural Children's Medical Center), Jun TSUJITA (Social Insurance Inatsuki Hospital), Michio TOKUYAMA (Tokai University), Hideki FUJITA (Nihon University), Koji HABE (Mie University).

7.2.2. Pressure Ulcers

Hiroshi FUJIWARA (Niigata University), Ryokichi IRISAWA (Tokyo Medical University), Masaki OTSUKA (Chutoen General Medical Center), Tomoko KAKO (Mie Prefectural General Medical Center), Tatsuya KAJI (Hiroshima City Hiroshima Citizens Hospital), Takafumi KADONO (St. Marianna University School of Medicine), Monji KOGA (Fukuoka University), Kuninori HIROSAKI (Hokkaido Medical Center).

7.2.3. Diabetic Ukin ulcer/Gangrene

Takeshi NAKANISHI (Meiji University of Integrative Medicine), Ryuta IKEGAMI (Ikegami Clinic), Shun OMORI (Kokura Daiichi Hospital), Hiroshi KATO (Nagoya City University), Toshifumi KOMORI (Kyoto Prefectural University of Medicine), Tomomichi SHIMIZU (Tokai University), Kazunari SUGITA (Saga University), Hideaki TANIZAKI (Kansai Medical University), Hideki NAKAJIMA (Kochi University), Shujiro HAYASHI (Dokkyo Medical University), Risa MATSUO (Asahikawa Medical University), Hiroshi MITSUI (University of Yamanashi), Hiroto YANAGISAWA (Saitama Medical University), Michiya YAMAGUCHI (Yamaguchi University), Osamu YAMASAKI (Shimane University).

7.2.4. Connective Tissue Diseases and Vasculitis

Yoshihide ASANO (Tohoku University), Jun ASAI (Kyoto Prefectural University of Medicine), Takayuki ISHII (Toyama Prefectural Central Hospital), Yohei IWATA (Fujita Health University), Akihiko UCHIYAMA (Gunma University), Ken OKAMURA (Yamagata University), Yoichi OGAWA (University of Yamanashi), Mari KISHIBE (Asahikawa Medical University), Yuta KOIKE (Nagasaki University), Masanari KODERA (Japan Community Health care Organization (JCHO) Chukyo Hospital), Yorihisa KOTOBUKI (Kotobuki Dermatology Clinic), Noriki FUJIMOTO (Shiga University of Medical Science), Takuya MIYAGI (University of the Ryukyus), Chie MIYABE (Tokyo Women's Medical University), Yukie YAMAGUCHI (Yokohama City University), Ayumi YOSHIZAKI (The University of Tokyo).

7.2.5. Leg Ulcers/Varices

Takeo MAEKAWA (Jichi Medical University Saitama Medical Center), Takaaki ITO (Hyogo Medical University), Takeo IDEZUKI (NTT Medical Center Tokyo), Mayumi OTA (The Jikei University School of Medicine), Hiroshi SAKAI (Osaka University), Yasuko SARAYAMA (Kobe Rosai Hospital), Takamitsu TANAKA (Teikyo University), Hiroyuki NIHARA (Shimane University), Takayuki FUSUMAE (Tokyo Medical Center), Koji MAKINO (National Hospital Organization Kumamoto Medical Center), Hiroshi YATSUSHIRO (Fukui‐ken Saiseikai Hospital).

7.2.6. Burns

Yuichiro YOSHINO (Japanese Red Cross Kumamoto Hospital), Masahiro AMANO (University of Miyazaki), Shiro IINO (University of Fukui), Youichi OMOTO (Omoto Skin Clinic), Masato KAKEDA (Saiseikai Matsusaka General Hospital), Ko KAGOYAMA (University of Toyama), Toru SAITO (Yamagata University), Keisuke SAKAI (National Sanatorium Kikuchi Keifuen), Naotaka DOI (Doi Skin Clinic), Akira HASHIMOTO (Tohoku University), Masahiro HAYASHI (Shin‐Nakamichi Dermatology Clinic), Katsunari MAKINO (Kumamoto University), Michiru MASUDA (Kumamoto University, Certified Nurse in Wound, Ostomy and Continence Nursing (WOCN)), Naoki MADOKORO (Higashihiroshima Medical Center), Naoya MIKITA (Mikita Dermatology Clinic), Masahito YASUDA (Gunma University), Katsuhiro YAMADA (Aoi Dermatology Clinic).

COI reporting criteria for participants in the Wound/Pressure Ulcer/Burn Guidelines Supervising and Drafting Committees, participation/non‐participation criteria, and a list of the COI disclosed (Prepared in reference to JAMS Guidelines on COI Management in Medical Research (in March 2017, Japanese Association of Medical Sciences, https://jams.med.or.jp/guideline/index.html)).

Criteria for Judgment of COI Disclosure

Participants

1. Presence or absence of officers and advisors in companies and for‐profit organizations and the amounts of their remunerations.

Standard amount: 1 million yen/company/year classification of pension amounts: (1) 1 million yen ≤ (2) 5 million yen ≤ (3) 10 million yen ≤.

• 2Ownership of stocks and profits derived from the stocks (profits for the previous year presented in this format).

Standard amount: 1 million yen/company/year classification of pension amounts: (1) 1 million yen ≤ (2) 5 million yen ≤ (3) 10 million yen ≤.

• 3Royalty payments for patents by companies and for‐profit organizations.

Standard amount: 1 million yen/company/year classification of pension amounts: (1) 1 million yen ≤ (2) 5 million yen ≤ (3) 10 million yen ≤.

• 4Remunerations, such as daily allowances and lecture fees, paid by a company and for‐profit organization for attending a conference (presentations, advice).

Standard amount: 0.5 million yen/company/year classification of pension amounts: (1) 0.5 million yen ≤ (2) 1 million yen ≤ (3) 2 million yen ≤.

• 5Fees paid by a company and for‐profit organization for the creation of pamphlets, roundtable discussion articles.

Standard amount: 0.5 million yen/company/year classification of pension amounts: (1) 0.5 million yen ≤ (2) 1 million yen ≤ (3) 2 million yen ≤.

• 6Research funds (industry‐academia collaborative research, contract research, clinical trials) provided by a company and for‐profit organization.

Standard amount: 1 million yen/company/year classification of pension amounts: (1) 1 million yen ≤ (2) 10 million yen ≤ (3) 20 million yen ≤.

• 7Donations for scholarships and incentives offered by a company and for‐profit organization.

Standard amount: 1 million yen/company/year classification of pension amounts: (1) 1 million yen ≤ (2) 5 million yen ≤ (3) 10 million yen ≤.

• 8Endowed courses provided by companies, including those sponsored by companies, with donations of ≥ 1 million yen.
• 9Other remunerations (travel, gifts, not directly related to research).

Standard amount: 50 thousand yen/company/year classification of pension amounts: (1) 50 thousand yen ≤ (2) 200 thousand yen ≤ (3) 500 thousand yen ≤.

Participants' spouses, first‐degree relatives, or those who share income or property interests with participants

1. Presence or absence of officers and advisors in companies and for‐profit organizations and the amounts of their remunerations.

Standard amount: 1 million yen/company/year classification of pension amounts: (1) 1 million yen ≤ (2) 5 million yen ≤ (3) 10 million yen ≤.

• 2Ownership of stocks and profits derived from the stocks (profits for the previous year presented in this format).

Standard amount: 1 million yen/company/year classification of pension amounts: (1) 1 million yen ≤ (2) 5 million yen ≤ (3) 10 million yen ≤.

• 3Royalty payments for patents by companies and for‐profit organizations.

Standard amount: 1 million yen/company/year classification of pension amounts: (1) 1 million yen ≤ (2) 5 million yen ≤ (3) 10 million yen ≤.

Organizations that participants belong and those related to departments

1. Research funds (industry‐academia collaborative research, contract research, clinical trials) provided by a company and for‐profit organization.

Standard amount: 10 million yen/company/year classification of pension amounts: (1) 10 million yen ≤ (2) 20 million yen ≤ (3) 40 million yen ≤.

• 2Donations for scholarships and incentives offered by a company and for‐profit organization.

Standard amount: 2 million yen/company/year classification of pension amounts: (1) 2 million yen ≤ (2) 10 million yen ≤ (3) 20 million yen ≤.

Criteria for exclusion

1. Members of the guideline drafting committee, their spouses, first‐degree relatives, or those who share income or property interests if they fall under any of the following:

2. Incomes of the officers and advisors of companies and for‐profit organizations (≥ 1 million yen/company/year);

3. Ownership of stocks and profits generated from the stocks (≥ 5% of all stocks/company or ≥ 1 million yen/company/year);

4. Receipt of patent royalties from companies and for‐profit organizations (≥ 1 million yen/company/year); and.

5. Affiliations of endowed courses provided by companies and for‐profit organizations.

Criteria that should be met by the chairperson of the guideline drafting committee

Both individual and organizational COI are classified into Category (1) or below.

Criteria that should be met by the members of the guideline supervisory and drafting committees

Both individual and organizational COI are classified into Category (2) or below. However, the number of persons in Category (2) shall not exceed half of the members of the guideline drafting committee.

List of the COI

Takeo MAEKAWA (member of the guideline supervising committee), financial COI Ono Pharmaceutical Co. Ltd. (Category (2) or below), Taiho Pharmaceutical Co. Ltd. (Category (2) or below), Maruho Co. Ltd. (Category (2) or below).

Minoru HASEGAWA (member of the guideline supervising committee), financial COI Maruho Co. Ltd. (Category (2) or below), Ono Pharmaceutical Co. Ltd. (Category (2) or below).

Manabu FUJIMOTO (member of the guideline supervising committee), financial COI Maruho Co. Ltd. (Category (2) or below).

Nonfinancial COI

Takafumi KADONO is the Editor‐in‐Chief of Journal of Dermatology and a co‐author of this article. Dr. Kadono is excluded from editorial decision‐making related to the acceptance and publication of this article.

Minoru HASEGAWA, Hideki FUJITA, Mari KISHIBE, and Dr. Ken OKAMURA are Editorial Board members of Journal of Dermatology and a co‐author of this article. To minimize bias, they were excluded from all editorial decision‐making related to the acceptance of this article for publication.

Funding

This work was supported by the Japanese Dermatological Association.

Conflicts of Interest

According to the JAMS Guidelines on COI Management in Medical Research (https://jams.med.or.jp/guideline/index.html) published by the Japanese Association of Medical Sciences in March 2017, the members of the guideline‐revising committee disclosed the conflicts of interest (COI) during the past 3 years back to the previous year on assumption as a member and guideline announcement. For reporting, (1) the members' COI, their spouses' COI, (2) first‐degree relatives' or income/financial profit‐sharing persons' COI, and (3) COI of organizations/divisions to which the members belong were reported with an amount classification using the COI self‐disclosure form established in the JAMS Guidelines on COI Management in Medical Research.

Yoshino Y., Amano M., Iino S., et al., “Wound, Pressure Ulcer, and Burn Guidelines (2023)‐6: Guidelines for the Management of Burns, Third Edition,” The Journal of Dermatology 53, no. 9 (2026): e688–e732, 10.1111/1346-8138.70357.

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.