doi: 10.1111/1346-8138.

13276 Journal of Dermatology 2016; 43: 357375

GUIDELINE
The wound/burn guidelines 1: Wounds in general
Yuji INOUE,1 Minoru HASEGAWA,2 Takeo MAEKAWA,3 Andres LE PAVOUX,4 Yoshihide
ASANO,5 Masatoshi ABE,6 Takayuki ISHII,2 Takaaki ITO,7 Taiki ISEI,8 Shinichi IMAFUKU,9
Ryokichi IRISAWA,10 Masaki OHTSUKA,11 Mikio OHTSUKA,12 Fumihide OGAWA,13
Takafumi KADONO,5 Masanari KODERA,14 Tamihiro KAWAKAMI,15 Masakazu
KAWAGUCHI,16 Ryuichi KUKINO,17 Takeshi KONO,18 Keisuke SAKAI,19 Masakazu
TAKAHARA,20 Miki TANIOKA,21 Takeshi NAKANISHI,22 Yasuhiro NAKAMURA,23 Akira
HASHIMOTO,24 Masahiro HAYASHI,16 Manabu FUJIMOTO,3 Hiroshi FUJIWARA,25 Koma
MATSUO,26 Naoki MADOKORO,27 Osamu YAMASAKI,11 Yuichiro YOSHINO,28 Takao
TACHIBANA,29 Hironobu IHN,1 The Wound/Burn Guidelines Committee
1
Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, 2Department of
Dermatology, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Ishikawa,
3
Department of Dermatology, Jichi Medical University, Tochigi, 4Ichige Dermatology Clinic, Ibaraki, 5Department of Dermatology,
Faculty of Medicine, University of Tokyo, Tokyo, 6Department of Dermatology, Gunma University Graduate School of Medicine,
Gunma, 7Department of Dermatology, Hyogo College of Medicine, Hyogo, 8Department of Dermatology, Kansai Medical University,
Osaka, 9Department of Dermatology, Faculty of Medicine, Fukuoka University, Fukuoka, 10Department of Dermatology, Tokyo
Medical University, Tokyo, 11Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and
Pharmaceutical Sciences, Okayama, 12Department of Dermatology, Fukushima Medical University, Fukushima, 13Department of
Dermatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 14Department of Dermatology, Japan Community
Health Care Organization Chukyo Hospital, Aichi, 15Department of Dermatology, St. Marianna University School of Medicine,
Kanagawa, 16Department of Dermatology, Yamagata University Faculty of Medicine, Yamagata, 17Department of Dermatology, NTT
Medical Center Tokyo, 18Department of Dermatology, Nippon Medical School, Tokyo, 19Intensive Care Unit, Kumamoto University
Hospital, Kumamoto, 20Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 21Department
of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, 22Department of Dermatology, Osaka City University Graduate
School of Medicine, Osaka, 23Department of Dermatology, University of Tsukuba, Ibaraki, 24Department of Dermatology, Tohoku
University Graduate School of Medicine, Miyagi, 25Department of Dermatology, Niigata University Graduate School of Medical and
Dental Sciences, Niigata, 26Department of Dermatology, The Jikei University School of Medicine, Tokyo, 27Department of Dermatology,
Mazda Hospital, Hiroshima, 28Department of Dermatology, Japanese Red Cross Kumamoto Hospital, Kumamoto, 29Department of
Dermatology, Osaka Red Cross Hospital, Osaka, Japan

ABSTRACT
The Japanese Dermatological Association determined to prepare the Wound/Burn Guidelines focusing on treat-
ments, catering to needs for the clinical practice of dermatology. Among these guidelines, Wounds in General
was intended to explain knowledge necessary to heal wounds without specifying particular disorders.

Key words: chronic skin wounds, deep wounds, dressing material, shallow wounds, topical agents.

BACKGROUND OF THE DRAFTING OF clinical practice of dermatology. Among these guidelines,

WOUNDS IN GENERAL
Guidelines are documents systematically prepared to support
medical experts and patients for making appropriate judg-
ments in particular clinical situations. The Japanese Dermato-
logical Association determined to prepare the Wound/Burn
Guidelines focusing on treatments, catering to needs for the
Wounds in General was intended to explain knowledge nec-
essary to heal wounds without specifying particular disor-
ders. Its assignment is to establish basic principles of
treatment for wounds before explanations in individual chap-
ters of the Wound/Burn Guidelines. By so doing, it also aims
to improve the level of treatment for wounds in general in
Japan. Its contents cover the entire course of wound healing

Correspondence: Hironobu Ihn, M.D., Ph.D., Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University,
1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan. Email: ihn-der@kumamoto-u.ac.jp
This is the secondary English version of the original Japanese manuscript for The wound/burn guidelines 1: Wounds in general published in the
Japanese Journal of Dermatology 2011; 121(8): 15391559.
Received 18 November 2015; accepted 21 November 2015.

2016 Japanese Dermatological Association 357

Y. Inoue et al.

from an initial stage to recovery. Moreover, most of the TERMINOLOGY

wounds treated at the dermatology clinic are intractable
Wound bed preparation: Management of the wound surface
chronic skin wounds, and the present guidelines also deal
environment to promote wound healing. Specifically, it consists
with chronic skin wounds except in the chapter on burns. In
of removing necrotic tissues, reducing bacterial load, prevent-
treating chronic skin wounds, therapeutic principles differ
ing wound drying, controlling excessive exudates, and treating
between shallow wounds and deep wounds to which necrotic
undermining and wound margins.
tissues and poor granulation tissue attach. Therefore, in
TIME: Practical principles of wound bed preparation based
Wounds in General, treatments for skin wounds are
on the concept of evaluating factors that prevent wound heal-
described by dividing chronic skin wounds into shallow ones
ing from the viewpoints of tissue (T), infection or inflammation
restricted to the upper dermal layers and deep ones extend-
(I), moisture (M) and wound edge (E), and using the results for
ing further.
treatment and care.
Granulation tissue: Tissue newly formed by the repair/inflam-
POSITION OF WOUNDS IN GENERAL mation response to tissue damage. Grossly, it is a reddish soft
tissue, and it consists of newly formed blood vessels, connec-
The Wound/Burn Guidelines Committee (Table 1) consists of
tive tissue, fibroblasts and inflammatory cells.
members commissioned by the Board of Directors of the Japa-
Epithelialization: Covering of defects of the skin or mucosa
nese Dermatological Association. It held several meetings and
by the epithelium, namely, the epidermis or mucosal epithe-
evaluations in writing since October 2008 and drafted a com-
lium, in the healing process. In the skin, the epidermis regener-
mentary on wounds in general and five guidelines for the man-
ates from the epidermis or appendages of the skin around the
agement of particular wounds by taking opinions of the
defect (healing by regeneration). However, in deep skin defects
Scientific Committee and Board of Directors of the Japanese
with no residual appendages, the epidermis extends from
Dermatological Association into consideration. The explana-
peripheries of the defect after the wound surface is replaced
tions about wounds in general in this article show the current
by granulation tissue (cicatricial healing).
standards of the diagnosis and treatment in Japan. However,
Moist wound healing: A method to maintain the wound sur-
patients vary in underlying diseases, severity of symptoms and
face in a moist environment. It retains polynuclear leucocytes,
background including complications. Therefore, the physicians
macrophages, enzymes and cell growth factors on the wound
who conduct the diagnosis and treatment should determine
surface. It also promotes autolysis and contributes to debride-
the approaches to the prevention, care and treatment together
ment and does not interfere with cell migration.
with the patients, and the contents of their decisions are not
Cytokines: Small soluble proteins or glycoproteins with a
required to be in complete agreement with the present guide-
molecular weight of 30 kD or less produced and released by
lines. Also, the guidelines are not relevant for citation in law-
cells. Humoral factors that regulate biological functions of the
suits.
body such as inflammation, immune responses and cell prolif-
eration by binding to receptors on the surface of target cells
SPONSORS AND CONFLICTS OF INTEREST and controlling their differentiation, proliferation and activation
are collectively called cytokines.
All cost needed for drafting the commentary on wounds in
Growth factors: Factors that promote cell proliferation and dif-
general has been borne by the Japanese Dermatological Asso-
ferentiation are collectively called growth factors. Most of them
ciation, and no fund has been received from particular organi-
are peptides and usually act at the site of their production by the
zations, enterprises or pharmaceutical companies. Also, each
paracrine (acting on cells in the neighborhood) or autocrine (act-
member of the committee participating in the preparation of
ing on the cells that produced them) mechanism. Fibroblast
the present guidelines has no conflict of interest to disclose on
growth factor (FGF), epidermal growth factor (EGF), platelet-
drafting the present commentary.
derived growth factor (PDGF), transforming growth factor (TGF)-
a/b and hepatocyte growth factor are typical growth factors.
REVIEWS BEFORE DISCLOSURE Lavage: Removing chemical stimulants, infection sources
and foreign bodies from the skin or wound surface using the
Prior to the disclosure of the commentary, progresses in draft-
hydraulic pressure or lysing effect of a liquid. Lavage may be
ing were presented at the Annual Meetings of the Japanese
performed using physiological saline, tap water, or saline or
Dermatological Association from 2008 to 2011, opinions were
tap water combined with a surfactant such as soap and deter-
invited from the association members, and necessary revisions
gent. The effect of lavage may be derived from the flow volume
were made.
or hydraulic pressure.
Debridement: A therapeutic action to clean the wound by
UPDATING POLICIES removing necrotic tissues, aged cells that have ceased to react
to stimulation by promoters of wound healing such as growth
The present guidelines will be updated in 35 years. However,
factors, foreign bodies and foci of bacterial infection, which are
if partial updating becomes necessary, update information is
often associated with the above. There are methods such as:
presented on the website of the Japanese Dermatological
(i) autolytic debridement induced by occlusive dressing; (ii)
Association when appropriate.

358 2016 Japanese Dermatological Association

Y. Inoue et al.
the bacterial count in local exudates from chronic skin wounds
(diabetic ulcer, venous ulcer, pressure ulcer) is 1 9 106 colony-
forming units or higher per 1 g of sample.8385 They also rec-
ommend prompt discontinuation of disinfection in considera-
tion of the toxicity of disinfectants once infection has been
controlled. However, the same guidelines present a lower rec-
ommendation level for the control of local infection concerning
ischemic ulcer alone (because it is particularly sensitive to the
toxicity of disinfectants).86
In addition, the International Consensus87 recommends
disinfection of infected wounds complicated by systemic infec-
tion, wounds of patients with the risk of increased susceptibility
to infection, and wounds showing exacerbation of signs of
infection treated by methods other than disinfection such as
lavage alone. Iodine preparations are recommended as local
disinfectants. Also, discontinuation of disinfection is recom-
mended when improvements are observed in the wound.
SHALLOW CHRONIC SKIN WOUNDS
In wounds with defects of the epidermis alone or to the upper
layer of the dermis without clear signs of infection, the signifi-
cance of disinfection is small.88 For wounds showing epithelial-
ization, lavage using physiological saline and tap water is
sufficient. There are various cytokines on the wound surface,
and the epidermis being formed is thin. Therefore, they must
be treated protectively, and rubbing during washing is often
unnecessary.
DEEP CHRONIC SKIN WOUNDS
Deep chronic skin wounds accompanied by
infection or necrotic tissue
Usually, necrotic tissue exists to a wide area of the wound
surface. The presence of necrotic tissue increases the risk of
infection, and wounds with necrotic tissue are always con-
sidered to be in a state of critical colonization. Indeed, if the
balance is tilted to infection, systemic symptoms including
fever may be observed in addition to local symptoms such
as a hot feeling, increase in exudates such as pus, redden-
ing, swelling and pain. Wound healing cannot be expected
without controlling infection. Therefore, (i) removal of necrotic
tissue (debridement), (ii) lavage and disinfection, (iii) and sys-
temic administration antibacterial agents are necessary.
Because the presence of necrotic tissue prevents permeation
of disinfectants to the wound, as mentioned above, it is
important to use disinfectants after aggressively removing
necrotic tissue and cleaning the wound by lavage. Also, dis-
infection should be discontinued at an appropriate point
once infection has been controlled, and critical colonization
has been reversed to colonization.89,90 Thus, adherence to
eradication of bacteria by disinfection is unnecessary if
wound infection is not established. However, if infection has
been established, or is about to be established (critical colo-
nization), disinfection to control infection at the cost of some
tissue damage is necessary.91
368
Deep chronic skin wounds in the granulation/
epithelialization stage
In the event of defect of the dermis or full thickness of the
skin, the risk of infection is higher than in superficial
wounds. The state of bacteria is often colonization. Some
more time is needed until epithelialization and granulation is
in progress. Therefore, granulation must not be inhibited by
tissue toxicity of unnecessary disinfection. Lavage is neces-
sary and sufficient for maintaining cleanness of the wound,
and it is necessary to wash the wound surface with some
pressure.70,92
REFERENCES
68 Iwasawa A, Nakamura R. Points to keep in mind in the use of the
povidone iodine preparation. Infection Control 2002; 4: 1824.
69 Fernandez R, Griffiths R, Ussia C. Water for wound cleansing (re-
view).The Cochrane Collaboration Issue 2, The Cochrane Library,
2010.
70 Ohnishi S, et al. Hazardousness of the povidone iodine sterilization
for the wound healing and the effectiveness of the tap water wash-
ing. Nesshyou 2006; 32: 2632.
71 Kobayashi K, Ohkubo K, Oie S. Guideliens for sterilization and dis-
infection. Health Publication 1999.
72 Hatae S, et al. Sterilization and sterilization mainly on the medical care.
povidone iodine solution. Rinshyou to Biseibutsu 2002; 29: 367372.
73 10% povidone iodine solution Attached document. Meiji seika;
2008.July
74 Iijima S, Kuramochi M. Investigation of Irritant skin reaction by
10% povidone-Iodine solution after surgery. Dermatology 2002;
204(suppl 1): 103108.
75 Iijima S. Primary irritating contact dermatitis with the 10% povi-
done iodine solution. Iyaku journal 2002; 38: 513.
76 Sugihara K, et al. Examination of the antisepsis of the wound part
of the skin. Pharma Medica 2003; 21: 7989.
77 Imazawa T, et al. A case that caused anaphylactic shock after glu-
conic acid chlorhexidine use. J Jpn Soc Plastic Reconstr Surg
2003; 23: 582588.
78 Saitou Y. Sterilization and sterilization mainly on the medical care
Gluconic acid chlorhexidine. Rinshyou to Biseibutsu 2002; 29: 377
380.
79 0.05% Chlorhexidine gluconate solution Attached document Mar-
uishi seiyaku 2005.July
80 0.02% Benzethonium chloride solution Attached document Kenei
seiyaku 2008.February
81 Sibbad RG, Woo K, Ayello EA. Increased bacterial burden and
infection: the story of NERDS and STONES. Adv Skin Wound Care
2006; 19: 447461.
82 Kouno T, Taniguchi A. Right or wrong of the wound sterilization
based on the evidence Clinical Dermatorogy 2005. Rinshyohihuka
2005; 59: 117122.
83 Whitney J, Phillips L, Aslam R, et al. Guidelines for the treatment
of pressure ulcers. Wound Rep Reg 2006; 14: 663679.
84 David L, Steed MD, Christopher A, Theodore C, et al. Guidelines
for the treatment of diabetic ulcers. Wound Rep Reg 2006; 14:
680692.
85 Martin C, Robson MD, Diane M, Cooper RN, Aslam R. Guidelines for
the treatment of venous ulcers. Wound Rep Reg 2006; 14: 649662.
86 Hopf HW, Ueno C, Aslam R. Guidelines for the treatment of arterial
insufficiency ulcers. Wound Rep Reg 2006; 14: 693710.
87 Wound Infection in Clinical Practice: an International Consensus
Supported by an unrestricted educational grant from Smith &
Nephew. Int Wound J 2008; 5: s3
88 Ichioka S. Infection management in the wound treatment. Chiryou
2003; 85: 27292733.
2016 Japanese Dermatological Association
Y. Inoue et al.

Table 1. (continued)

Chairperson: Hironobu Ihn (Professor and Chairman, Department of Dermatology and Plastic Surgery, Faculty of Life Science,
Kumamoto University)
Vice-chairperson: Takao Tachibana (General Manager, Department of Dermatology, Osaka Red Cross Hospital)
Keisuke Sakai (Research Associate, Intensive Care Unit, Kumamoto University
Hospital)
Akira Hashimoto (Research Associate, Department of Dermatology, Tohoku University
Graduate School of Medicine)
Masahiro Hayashi (Assistant Professor, Department of Dermatology, Yamagata
University Faculty of Medicine)
Naoki Madokoro (General manager, Department of Dermatology, Mazda Hospital)
Yuichiro Yoshino (General manager, Department of Dermatology, Japanese Red Cross
Kumamoto Hospital)
EBM Takeshi Kono (Associate Professor, Department of Dermatology, Nippon Medical
School)

mechanical debridement (e.g. wet-to-dry dressing, high-pres-
sure lavage, hydrotherapy and ultrasonic lavage); (iii) debride-
ment using proteases; (iv) surgical debridement; and (v)
biological debridement using maggots.
Wet-to-wet dressing (wet gauze dressing with saline): The
dressing method of applying gauze saturated with physiologi-
cal saline to the wound to maintain a moist environment.
Exudates: Intercellular fluid that seeps out from wounds
devoid of the epithelium. It is rich in protein and contains vari-
ous inflammatory cells, cytokines and growth factors involved
in wound healing.
Topical agents: Drugs used for topical treatment through the
skin or by direct application to the focus in the skin. Prepared
by compounding various active agents with a base.
Dressing materials: Modern wound-dressing materials for
creating a moist environment for wounds. Conventional steril-
ized gauze is excluded.
Wound-dressing materials: Wound-dressing materials can be
classified into dressing materials (recent dressing materials)
and medical materials such as gauze (classic dressing materi-
als). The former are medical materials aimed to provide condi-
tions optimal for wound healing by maintaining a moist
environment and must be used selectively depending on the
state of the wound and amount of exudates. The latter allow
the wound to dry and cannot maintain a moist environment if
exudates are insufficient. Medical materials other than conven-
tional gauze that provide an environment optimal for wound
healing by covering the wound and maintaining moisture may
also be called wound-dressing materials or dressing materials.
Occlusive dressing: All dressing methods used to avoid dry-
ing of wounds for moist wound healing are called occlusive
dressing. This is a collective term for dressing using modern
wound-dressing materials other than conventional gauze
dressing.
Surgical therapy: Surgical treatments, surgical debridement
and open treatments of subcutaneous undermining.
Negative pressure occlusive wound therapy: A variation of
physical therapy. The wound is maintained in a closed environ-
ment, and suction is applied to adjust the pressure to 125
150 mmHg, in principle. This directly eliminates bacteria and
exotoxins released from them, promotes angiogenesis and
alleviates edema of granulation tissue.
Undermining: Cavities wider than a skin defect are called
undermining. The wall covering an undermining is called the
cover wall or lid.
Lavage pressure: The pressure applied to remove exudates
or remnants from the wound surface. It is expressed in psis.
Contamination: A state in which bacteria that do not divide
or proliferate are present on the ulcer surface.
Colonization: A state in which bacteria that divide and prolif-
erate are present on the ulcer surface. The immune capacity of
the host and proliferative capacity of bacteria are in equilib-
rium.
Infection: A state in which bacteria that divide and proliferate
on the ulcer surface have increased further and interfere with
wound healing as their proliferative activity surpasses the host
immune capacity.
Critical colonization: Conventionally, the microbial environ-
ment of the wound was classified into infected and aseptic
states, but the current trend is to understand the two condi-
tions as continuous (the concept of bacterial balance). Infection
of the wound is understood as continuous stages of contami-
nation, colonization and infection, and infection is considered
to occur depending on the balance between the bacterial bur-
den on the wound and host resistance. Critical colonization is
a stage between colonization and infection but tilted more to
infection with the number of bacteria exceeding that in colo-
nization.
Ulcer: Cutaneous or mucosal defect extending beyond the
basement membrane (dermoepidermal junction, mucosa). Usu-
ally leaves a scar after healing.
Erosion: Cutaneous or mucosal defect not extending beyond
the basement membrane (dermoepidermal junction, mucosa).
Usually heals without leaving a scar.
Pressure ulcer: External force applied to the body reduces or
blocks the blood flow of the soft tissue between bone and the

360 2016 Japanese Dermatological Association


superficial layer of the skin. If this condition continues for a
period, the tissue sustains irreversible ischemic damage and
develops a pressure ulcer.
Maceration: A state of tissue, particularly the cornified layer
that has absorbed a large amount of water and developed into
a whitish and swollen condition. The barrier function of the skin
is reduced, and erosion and infection are likely to occur.
Frequently observed around pressure ulcers.
Crust: A hard structure formed by drying of exudates, pus
and necrotic tissue. Dried blood is called blood crust. Crusts
are often formed in skin defects with drying of the wound
surface.
QUESTIONS AND ANSWERS
Question 1: How should an environment appropriate for
healing of chronic skin wounds be prepared?
Answer: Wound bed preparation is important to promote
healing of chronic skin ulcers. For this, necrotic tissues
must be removed, excessive exudates controlled and a
moist environment maintained by preventing drying of the
wound. The TIME concept1 has been proposed as a
method for the evaluation of the wound healing environ-
ment. However, healing of contaminated wounds compli-
cated by bacterial or fungal infection may be delayed by
maintaining a moist environment. Therefore, examinations
including observation of the wound and bacterial cultures of
samples from the wound are important.
COMMENTS
Acute and chronic skin wounds
Before the discovery of antibiotics, bacterial infection of
wounds often induced sepsis and resulted in serious out-
comes. Therefore, it has been a long-standing belief that
wounds should be disinfected and dried as the control of
infection is the most important factor of wound healing. For
this purpose, wound dressing using sterilized gauze has been
practiced widely. Recently, however, the idea that gauze
dressing allows the wound surface to dry and is likely to dam-
age granulation tissue and regenerated epithelium at gauze
changes, and to cause a delay in wound healing, has become
Treatment of underlying diseases
Treatment of chronic skin wounds
Treatment of local factors
Figure 1. Treatment plan of chronic skin wounds. PAD, peripheral arterial diseases.
2016 Japanese Dermatological Association
Wound/Burn Guidelines 1
prevalent also in Japan. As a result, moist wound healing,
namely, promoting wound healing by maintaining a moist envi-
ronment, has begun to be advocated.2,3
Skin wounds are classified into acute and chronic wounds.
Acute skin wounds are those in which the mechanism of
wound healing functions normally as in fresh traumas and sur-
gical wounds. Chronic skin wounds are those in which some
causes are preventing the mechanism of wound healing from
functioning normally.4,5 Causes that delay healing of chronic
skin wounds are divided into systemic factors such as underly-
ing diseases and local factors (Fig. 1).
The healing process of chronic skin ulcer is divided into
three phases: the inflammation, proliferation and maturation
phases (Fig. 2).6 Because cells, cytokines and growth factors
that play primary roles in wound healing vary with the phase,7
it is important to prepare a wound healing environment appro-
priate for the phase.8
In the inflammation phase, invasion of pathogenic agents is
prevented by infiltration of neutrophils and macrophages, and
foreign bodies are removed. If the wound is excessively
washed or disinfected in this phase, cells that have infiltrated
are washed off and cells themselves are damaged. For
smoother inflammatory cell infiltration, a clean and moist envi-
ronment should be maintained. However, as excessive inflam-
mation delays wound healing, a poultice with a cooling effect
or wet-to-wet dressing (saline gauze dressing) may be selected
in this phase depending on the condition of the wound.
In the cell proliferation phase, blood vessels and extracellular
matrix are formed, and granulation occurs. Because various
cytokines are introduced in this phase, a moist environment
should be retained over the wound surface to promote cell pro-
liferation. If necrotic tissue attaches to the wound in this period,
it serves as a nest of bacterial infection and prevents maturation
of the extracellular matrix. Therefore, aggressive debridement
or lavage to remove necrotic tissue may be necessary.
In the maturation/reconstruction phase, maturation of the
extracellular matrix and regeneration/migration of epidermal
cells are primary features. Infection should be controlled, and
the wound surface should be maintained in a moist environ-
ment. In this phase, changes of gauze or dressing materials
should be performed carefully, as their frequent changes may
damage regenerated/migrated epidermal cells.
Diabetes mellitus
Collagen disease
PAD
Varix, etc.
Wound bed preparation
Control of TIME
Moist wound healing
361
Y. Inoue et al.

Inflammation phase

Maturation/reconstruction phase
Proliferation phase

Figure 2. Healing processes of chronic skin wounds and parameters related to wound healing. EGF, epidermal growth factor; FGF,
fibroblast growth factor; IL, interleukin; PDGF, platelet-derived growth factor; TGF, transforming growth factor; TNF, tumor necrosis
factor; VEGF, vascular endothelial growth factor.

Table 2. Time

TIME Evaluation item of WBP Treatment Manipulation

Tissue non-viable or deficient
Infection or inflammation
Moisture imbalance
Edge of wound non-advancing
or undermined epidermal margin
Necrotic tissue/inactive Debridement Five kinds of debridement (autolytic,
tissue sharp surgical, enzymatic, mechanical
or biological)
Infection or inflammatory Remove infected foci Local lavage, local or systemic antibiotics
Exudate imbalance Apply moisture-balancing Appropriate dressing materials, negative
dressings pressure occlusive treatment
Delayed wound healing Debridement, Surgical debridement, negative pressure
or pocket formation physiotherapy occlusive dressing

Modified references.5,29 WBP, wound bed preparation.

Treatment for shallow chronic skin wounds
For wound bed preparation for shallow chronic skin wounds
with a depth to the upper dermal level, it is important to create
an environment appropriate for regeneration/migration of epi-
dermal cells. Because bacterial infection is controlled, and
there is no necrotic tissue attached to the wound, disinfection
or excessive lavage should be avoided, and a moist environ-
ment should be maintained, because, in wound healing, a
moist environment is advantageous for epidermal cell growth
and angiogenesis912 as well as for the control of pain13
compared with a dry environment.
Methods to maintain a moist environment for wounds
include: (i) poultice; (ii) wet-to-wet dressing; (iii) application of
an oleaginous ointment; and (iv) occlusive dressing. (i) and (ii)
are useful for the control of wounds in the inflammation phase,
because they are effective for cooling of the wound and
removal of necrotic tissues and exudates as well as maintain-
ing a moist environment, but they are laborious procedures.
They are also impractical for the treatment of large wounds or
wounds that require a long time until healing. Moreover, while
they are effective for dressing of wounds in the inflammation
phase as they also have a cooling effect, warming has been
confirmed to promote wound healing in the proliferation and
maturation/reconstruction phases,14 and cooling may delay
wound healing. Poultice and wet-to-wet dressing should be
used for surgical wounds and wounds complicated by infection
in a limited period.
The application of an oleaginous ointment is useful for the
treatment of shallow skin wounds, because it keeps the wound
moist with periodic mechanical debridement.15 However, the
use of a topical agent is associated with the risk of contact
dermatitis and has the negative effect of removing cells and

362 2016 Japanese Dermatological Association


exudates useful for wound healing from the wound surface by
the application of the ointment. See Question 4 for specific
external medications.
Occlusive dressing has been confirmed to promote wound
healing by a number of papers,16,17 and various materials have
recently been introduced clinically.18,19 However, there is a
systematic review that no clear wound healing promoting effect
was confirmed in dressing materials other than hydrocolloid.20
Among the effects of moist wound healing, the promotion of
re-epithelialization of donor sites of split-thickness skin grafts9
and epithelialization of second-degree burns not requiring sur-
gery was focused upon,21 but there have recently been some
reports of its effectiveness for promoting epithelialization of
deep wounds accompanied by bone exposure22 and after laser
irradiation.23 Occlusive dressing is also recommended from the
viewpoint of medical cost reduction,24 and the effectiveness
and cost-wise advantage of the application of non-medical film
materials to wounds have been suggested.25 However, the use
of such materials for wounds is a deviation from their original
objective and needs caution.26
Treatment for deep chronic skin wounds
Primary concerns in the treatment for deep chronic skin
wounds with infection or necrotic tissues attached them are
debridement of necrotic tissues and the control of exudates. It
is important to make the best possible wound bed preparation
by evaluating the wound according to the TIME concept
(Table 2)5,29 proposed in 2005.
Removal of necrotic tissues
Necrotic tissues not only interfere with epithelialization but also
increase exudates and provide nests for bacterial infection.27
Therefore, it is necessary to perform debridement as early as
possible. Debridement can be achieved by resecting or scrap-
ing off necrotic tissues using a scalpel or scissors (surgical
debridement), lysing necrotic tissues using enzyme prepara-
tions (chemical debridement) or other methods. Surgical or
chemical debridement should be selected in consideration of
the quality and quantity of necrotic tissues.
In surgical debridement, emergency treatment may
become necessary due to exacerbation of the patients gen-
eral condition, or anesthesia may be required if necrotic tis-
sues are present over a wide area. However, for small
chronic skin wounds, debridement limited to an area not
causing bleeding can be performed mostly at the bedside
without anesthesia. Points of attention in performing surgical
debridement are hemorrhagic tendency and the history of
oral anticoagulant/antiplatelet administration. According to the
guidelines by the Japanese Circulation Society, it is desirable
to perform minor surgery while continuing p.o. administration
of warfarin or an antiplatelet agent if postoperative bleeding
is considered manageable.28 However, as some patients tol-
erate suspension of these medications without risks, whether
they should be continued or discontinued should be
determined by consulting with the attending physician and in
consideration of the patients general condition and wound
size.
2016 Japanese Dermatological Association
Wound/Burn Guidelines 1
By chemical debridement, necrotic tissues are lysed using
an enzyme-containing ointment. It takes a longer time than sur-
gical debridement but is advantageous in that it involves a
lower risk of hemorrhage and is less painful. Necrotic tissues
lyse spontaneously by simply maintaining a moist environment
around the wound using an oleaginous ointment or dressing
material. However, in autolysis of necrotic tissues, sufficient
attention to exacerbation of bacterial infection is necessary,
and infection must be controlled using antibiotics. Moreover,
debridement can be performed more smoothly by layering an
enzyme preparation and an oleaginous ointment. Specific
preparations to be used are described in Question 4.
In chronic skin wounds to which infected or necrotic tissues
are attached, necrotic tissues cannot be removed completely
by a single surgical debridement. They can be removed more
safely and efficiently by performing surgical debridement in
several stages and with chemical debridement.
Control of exudates
In a dry environment, epithelialization is prevented as necrotic
tissues adhere to the wound surface and prevent migration of
epidermal cells, and as epidermal cells themselves are
necrosed due to drying. Also, exudates contain large amounts
of not only cells including vascular endothelial cells and blood
cells but also growth factors and cytokines and are useful for
regeneration of damaged tissues.30
In a moist environment, on the other hand, granulation
occurs in the dermal area, providing a condition favorable for
the formation of scaffolds for keratinocyte migration. However,
excessive exudates inhibit wound healing by causing edema of
underlying tissues and promoting bacterial infection.31,34 The
risk of bacterial infection is known to be reduced by appropri-
ate treatments,32,33 and exudates must be controlled at an
appropriate level to promote wound healing. In maintaining a
moist environment, sufficient caution for infection is necessary.
Other treatments
The advantage of the concomitant application of external med-
ications to wounds for objectives other than the promotion of
granulation or epithelialization is unclear. Particularly, the use
of an ointment containing an antibiotic (antibacterial agent)
cannot be recommended, because it may allow bacteria to
acquire resistance.35 Recently, occlusive dressing after sprin-
kling autologous blood36 or bone marrow cells37 over the
wound has been reported to show some wound healing pro-
moting effect, but there are only case reports, and no further
evaluation has been conducted.
REFERENCES
1 Schults G, Mozingo D, Romanelli M, Claxton K. Wound healing
and TIME; new concepts and scientific application. Wound Repair
Regen 2005; 13: S1S11.
2 Hinman CD, Maibach H. Effect of air exposure and occlusion on
experimental human skin wounds. Nature 1963; 200: 377379.
3 Winter GD. Formation of the scab and the rate of epithelization of
superficial wound in the skin of the young domestic pig. Nature
1962; 193: 293294.
363
Y. Inoue et al.
4 Ichioka S, Minamimura A. Update of Wound surgery for sur-
geons; Algorithm of the classification, diagnosis and treatment for
skin ulcer that is hard to be cured. Jpn J Plast Surg 2008; 51:
S105S113.
5 Ooura N, Harii K. Chronic wound. J Treat 2009; 91: 237242.
6 Martin M. Wound healing-aiming for perfect skin regeneration.
Science 1997; 276: 7581.
7 Fujiwara S. Wound-healing mechanism (1) Description about fun-
damental progress, mainly about mediators. Nishinihon J Derma-
tol 2008; 70: 5566.
8 Vaneau M, Chaby G, Guillot B, et al. Consensus panel recommen-
dations for chronic and acute wound dressings. Arch Dermatol
2007; 143: 12911294.
9 Wiechula R. The use of moist wound-healing dressings in the man-
agement of split-thickness skin graft donor sites: a systematic
review. Int J Nurs Pract 2003; 9: S9S17.
10 Field FK, Kerstein MD. Overview of wound healing in a moist envi-
ronment. Am J Surg 1994; 167: 2S6S.
11 Alvarez OM, Mertz PM, Eaglstein WH. The effect of occlusive
dressings on collagen synthesis and reepithelialization in superficial
wounds. J Surg Res 1983; 35: 142148.
12 Dyson M, Young SR, Hart J, Lynch JA, Lang S. Comparison of the
effects of moist and dry conditions on the process of angiogenesis
during dermal repair. J Invest Dermatol 1992; 99: 729733.
13 Eaglstein WH, Mertz PM. New methods for assessing epidermal
wound healing: the effects of triamcinolone acetonide and
polyethelene film occlusion. J Invest Dermatol 1978; 71: 382384.
14 Whitney JD, Wickline MM. Treating chronic and acute wounds with
warming: review of the science and practice implications. J Wound
Ostomy Continence Nurs 2003; 30: 199209.
15 Michie DD. Influence of occlusive and impregnated gauze dress-
ings on incisional healing: a prospective, randomized, controlled
study. Ann Plast Surg 1994; 32: 5764.
16 Heffernan A, Martin AJ. A comparison of a modified form of Granu-
flex(Granuflex Extra Thin)and a conventional dressing in the man-
agement of lacerations, abrasions and minor operation wounds in
an accident and emergency department. J Accid Emerg Med
1994; 11: 227230.
17 Eaglstein WH. Moist wound healing with occlusive dressings: a
clinical focus. Dermatol Surg 2001; 27: 175181.
18 Mizuguchi K, Terashi H, Tahara S, et al. Dressing methods which
paid attention to features of various films. Jpn J Plast Surg 2008;
51: 561568.
19 Hermans MH. Hydrocolloid dressing (DuoDerm) for the treatment
of superficial and deep partial thickness burns. Scand J Plast
Reconstr Surg Hand Surg 1987; 21: 283285.
20 Chaby G, Senet P, Vaneau M, et al. Dressings for acute and
chronic wounds: a systematic review. Arch Dermatol 2007; 143:
12971304.
21 Wyatt D, McGowan DN, Najarian M. Comparison of a hydrocolloid
dressing and silver sulfadiazine cream in the outpatient manage-
ment of second-degree burns. Trauma 1990; 30: 857865.
22 Yamaguchi Y, Sumikawa Y, Yoshida S, Kubo T, Yoshikawa K,
Itami S. Prevention of amputation caused rheumatic diseases fol-
lowing a novel therapy of exosing bone marrow, occlusive dressing
and subsequent epidermal grafting. Br J Dermatol 2005; 152: 664
672.
23 Atiyeh BS, Dham R, Costagliola M, Al-Amm CA, Belhaouari L.
Moist exposed therapy: an effective and valid alternative to occlu-
sive dressings for postlaser resurfacing wound care. Dermatol Surg
2004; 30: 1825.
24 Ubbink DT, Vermeulen H, van Hattem J. Comparison of homecare
costs of local wound care in surgical patients randomized between
occlusive and gauze dressings. J Clin Nurs 2008; 17: 593601.
25 Takahashi J, Yokota O, Fujisawa Y, et al. An evaluation of
polyvinylidene film dressing for treatment of pressure ulcers in
older people. J Wound Care 2006; 15: 449454.
26 Matsunaga K. Wrap therapy-the conclusion of a debate and my
opinion-. Visual Dermatol 2007; 6: 996999.
364
27 Shultz GS, Sibbald RG, et al. Wound bed preparation: a systematic
approach to wound management. Wound Repair Regen 2003; 11:
S1S28.
28 Masuda T, Katoh H, Sone K, et al. Profound bacterial infection of
diabetes foot-clinical features of cases which we treated in two
years. Jpn J Clin Dermatol 2006; 60: 516520.
29 http:__www. j-circ.or.jp_guideline_pdf_JCS2009_hori_d.pdf
30 De MM, Ongaro L, Magaldi S, Gemmati D, Legnaro A, Palazzo A,
et al. Time- and dose-dependent effects of chronic wound fluid on
human adult dermal fibroblasts. Dermatol Surg 2008; 34: 347356.
31 Matsumura H. New aspects of the control for exudation of wound.
Jpn J Plast Surg 2007; 50: 637644.
32 Hutchinson JJ, McGuckin M. Occlusive dressings:a microbiologic
and clinical review. Am J Infect Control 1990; 18: 257268.
33 Weed T, Ratliff C, Drake DB. Quantifying bacterial bioburden dur-
ing negative pressure wound therapy: does the wound VAC
enhance bacterial clearance ?. Ann Plast Surg 2004; 52: 279280.
34 Lawrence JC. Dressing and wound infection. Am J Surg 1994;
167: 21S24S.
35 Dixon AJ, Dixon MP, Dixon JB. Randomized clinical trial of the
effect of applying ointment to surgical wounds before occlusive
dressing. Br J Surg 2006; 93: 937943.
36 Iwayama-Hibino M, Sugiura M, Muro K, Tomita Y. Successful topi-
cal hemotherapy with a new occlusive dressing for an intractable
ulcer on the toe. J Dermatol 2009; 36: 245248.
37 Yamaguchi Y, Yoshida S, Sumikawa Y, et al. Rapid healing of
intractable diabetic foot ulcers with exposed bones following a
novel therapy of exposing bone marrow cells and then grafting epi-
dermal sheets. Br J Dermatol 2004; 151: 10191028.
QUESTION 2: IS LAVAGE RECOMMENDABLE
FOR PROMOTING HEALING OF CHRONIC
SKIN WOUNDS?
Answer: To promote wound healing, it is important first to eval-
uate the condition of the wound. The presence or absence of
underlying disorders, stage of wound healing, depth of wound,
presence or absence of undermining, whether or not the
wound is infected, and presence or absence of necrotic tissue
must be clarified. In lavaging the wound, the use of cytotoxic
disinfectants should be avoided, a sufficient amount of physio-
logical saline, distilled water or tap water should be used, and
the wound surface must be treated protectively. Depending on
the condition of the wound, debridement, increasing the
amount of lavage fluid or lavage pressure and appropriate
warming of the lavage fluid are recommended.
COMMENTARY
Significance of lavage and points of caution
In chronic skin wounds with some causes preventing the nor-
mal mechanism of wound healing from functioning,38,39 lavage
is performed to eliminate local causes. Removing foreign bod-
ies, contaminated materials and microorganisms by lavage
and, thus, promoting wound healing leads to wound bed
preparation.40,42 Recently, the TIME concept (see Question 1)
has been proposed for wound bed preparation.41,43 By improv-
ing each of TIME, the mechanism of wound healing begins to
function normally, and wound bed preparation progresses.
Lavage is a treatment employed for the treatment of all
wounds but is particularly important as a measure against the I
(infection or inflammation) of TIME.
2016 Japanese Dermatological Association

In lavaging wounds, it is important to make sure that causes
of the delay of healing are removed using a sufficient amount
of physiological saline, distilled water or tap water.4450 There
is no difference in the infection or recovery rate according to
differences in the lavage fluid. The number of bacteria and
contamination can be reduced more effectively by using
soap.5153 Also, as damaging the wound surface may lead to a
delay of wound healing, the wound surface must be treated
protectively. While bacteria and residual materials can be
removed by lavaging with pressure,5458 caution is needed as
excessive pressure damages granulation tissue on the wound
surface. It is recommended to warm lavage fluid nearly to the
body temperature.59 Cold lavage fluid should be avoided,
because it not only is less effective for removing contamination
but also may cause vasoconstriction in diabetic ulcer, angiitis
and ulcers associated with collagen disease. If, on the other
hand, lavage fluid is warmed excessively, it may denature pro-
tein on the wound surface. In wounds such as wide burns,
low-temperature lavage fluid may reduce the body tempera-
ture. Also, the use of extremely warm or cold fluid causes
discomfort or pain during lavage.
Methods for lavage
Shallow chronic skin wounds
In erosion and shallow ulcers, the normal mechanism of wound
healing is expected to function as in acute skin wounds. In treat-
ing shallow wounds, it is most important not to allow them to
develop into deep wounds due to infection or necrosis. Wounds
should be kept as clean as possible by reducing the number of
bacteria and removing residual materials such as ointment and
foreign bodies by lavage. Also, as excessive lavage in this stage
reduces cytokines necessary for wound healing and delays it,
caution is needed.
Deep chronic skin wounds accompanied by infection or
necrotic tissue
Infection and necrotic tissue are the most important local fac-
tors that delay wound healing. Lavage is also very significant
for the control of critical colonization, which is a stage immedi-
ately before overt infection. Along with the administration of
antibiotics for infection and debridement for necrotic tissue,
sufficient lavage is indispensable for wound bed prepara-
tion.39,41,6063 In the presence of obvious infection, disinfec-
tants may be used, but lavage after disinfection is expected to
minimize unnecessary tissue damage and prevent sensitization
leading to contact dermatitis.
For lavage in this stage, the use of a sufficient amount of
lavage fluid is important. It is difficult to ensure the removal of
bacteria and contaminants with a small amount of fluid.
Shower and bathing are recommended as simple methods for
sufficient lavage. However, caution is necessary because, in
exceptional cases, lavage of patients with extensive burns by
shower or bath using a shared facility has been reported to
have caused nosocomial infection and increased the number
of bacteria on the normal skin or uninfected wounds.6466
2016 Japanese Dermatological Association
Wound/Burn Guidelines 1
A debriding effect is expected from performing lavage with
an appropriate pressure. Although physiological saline, distilled
water or tap water suffices as lavage fluid, highly acidic
electrolyzed water has been reported have significantly reduced
the number of bacteria compared with physiological saline in
pressure ulcers.67 However, caution is necessary in its use,
because it is approved as a disinfectant of medical equipment
and a bactericidal agent for food additives but not as a drug.
Deep chronic skin wounds in the granulation/epithelialization
phase
If infection is controlled, and necrotic tissue is removed, the
mechanism of wound healing begins to function normally, and
granulation/epithelialization progresses. In this period, it is
important to perform lavage protectively with the objective of
removing ointment or contaminants remaining on the wound
surface without damaging it. Also, in this period, wounds may
be covered with a dressing material for moist wound healing,
and wounds dressed for this purpose need not be washed
daily.
REFERENCES
38 Ichioka S, Minamimura A. Wound surgery for a surgeon update,
the classification of intractable skin ulcers, and diagnosis and a
treatment algorithm (in Japanese) . Jpn J Plastic Reconstr Surg,
2008; 51: S105S113.
39 Ohura N, Harii S. Chronic wound (in Japanese). Japanese J Ther-
apy, 2009; 91: 237243.
40 Chin C, Shult G, Stacey M. Principles of wound bed preparation
and their application to the treatment of chronic wounds. Primary
Intent, 2003; 11: 171182.
41 Ohura N. What is wound bed preparation (in Japanese). Jpn J
Plastic & Reconstr Surgery 2007; 50: 533541.
42 Tachibana T. Pressure ulcers, Local treatment toward protection of
the wound and wound bed preparation and moist wound healing
(in Japanese). J DiagnTreatm 2007; 95: 15591566.
43 Shultz GS, Sibbald RG, et al. Wound bed preparation: a systematic
approach to wound management. Wound Repair Regen 2003; 11:
S1S28.
44 Angeras MH, Brandberg A, Falk A, Seeman T. Comparison
between sterile saline and tap water for the cleaning of acute trau-
matic soft tissue wounds. Eur J Surg 1992; 158: 347350.
45 Griffiths RD, Fernandez RS, Ussia CA. Is tap water a safe alterna-
tive to normal saline for wound irrigation in the community setting?
J Wound Care 2001; 10: 407411.
46 Godinez FS, Grant-Levy TR, McGuirk TD, Lettetle S, Eich M,
OMalley GF. Comparison of normal saline vs tap water for irriga-
tion of lacerations in the emergency department. Acad Emerg Med
2002; 19: 396397.
47 Bansal BC, Wiebe RA, Perkins SD, Abramo TJ. Tap water for irri-
gation of lacerations. Am J Emerg Med 2002; 20: 469472.
48 Valente JH, Forti RJ, Freundlich LF, Zandieh SO, Crain EF. Wound
irrigation in children: saline solution or tap water? Ann Emerg Med
2003; 41: 609616.
49 Moscati RM, Mayrose J, Reardon RF, Janicke DM, Jehle DV. A
multicenter comparison of tap water versus sterile saline for wound
irrigation. Acad Emerg Med 2007; 14: 404409.
50 Fernandez R, Griffiths R. Water for wound cleansing, The Cochrane
Database of Systematic Reviews, retrieved from The Cochrane
Library, 3: no page (Systematic Review Paper), 2009.
51 Sanada H, Ohnishi M, Kitayama Y, et al. Examination of the effec-
tiveness of the soap irrigation in the wound neighborhood skin of
365
Y. Inoue et al.
the elderly person having a pressure ulcer (in Japanese). Jpn J
Pressure Ulcers 2000; 2: 3239.
52 Kitayama Y, Sanada H, Konya C, et al. Analysis of the dirt of the
wound neighborhood skin of the elderly person having a pressure
ulcer (in Japanese). Jpn J wound Osutomy Continence Nurs Soc
2001; 23: 5.
53 Ishiyama S, Togashi H, Tamura S, et al. Influence on pressure
ulcers neighborhood skin by the skin irrigation which contained
synthetic ceramide (in Japanese). Japanese J Pressure Ulcers
2003; 15: 508514.
54 Stevenson TR, Thacker JG, Rodeheaver GT, Bacchetta C, Edger-
ton MT, Edlich RF. Cleansing the traumatic wound by high pres-
sure syringe irrigation. JACEP 1976; 5: 1721.
55 Longmire AW, Broom LA, Burch J. Wound infection following high-
pressure syringe and needle irrigation. Am J Emerg Med 1987; 5:
179181.
56 Grower MF, Bhaskar SN, Horan MJ, Cutright DE. Effect of water
lavage on removal of tissue fragments from crush wounds. Oral
Surg Oral Med Oral Pathol 1972; 33: 10311036.
57 Green VA, Carlson HC, Briggs RL, Stewart JL. A comparison of
the efficacy of pulsed mechanical lavage with that of rubber-bulb
syringe irrigation in removal of debris from avulsive wounds. Oral
Surg Oral Med Oral Pathol 1971; 32: 158164.
58 Stewart JL, Carlson HC, Briggs RL, Green VA. The bacteria-
removal efficiency of mechanical lavage and rubber-bulb syringe
irrigation in contaminated avulsive wounds. Oral Surg Oral Med
Oral Pathol 1971; 31: 842848.
59 Museru LM, Kumar A, Ickler P. Comparisonof isotonic saline, dis-
tilled water and boiled water in irrigation of openfractures. Int
Orthop 1989; 13: 179180.
60 Sibbald RG, Browne AC, Coutts P, Queen D. Screening evaluation
of an ionized nanocrystalline silver dressing in chronic wound care.
Ostomy Wound Manage 2001; 47: 3843.
61 Ichioka S, Ohura N, Nakatsuka T, et al. Usefulness of the simple
local shower in the wound irrigation (in Japanese). Jpn J Pressure
Ulcers 2001; 3: 3237.
62 White RJ, Cutting KF. Critical colonization; The concept under-
scrutiny. Ostomy Wound Manage 2006; 52: 5056.
63 Takeda A, Tachi M. Chronic Wound: pressure ulcers, Condition of
the pressure ulcers and conservative treatment (in Japanese). Jpn
J Plastic Reconstr Surg 2008; 51: S173S176.
64 Embil JM, McLeod JA, Al-Barrak AM et al. An outbreak of methi-
cillin resistant Staphylococcus aureus on a burn unit: potential role
of contaminated hydrotherapyequipment. Burns 2001; 27: 681688.
65 Simor AE, Lee M, Vearncombe M et al. An outbreak due to mul-
tiresistant Acinetobacter baumannii in a burn unit: risk factors for
acquisition and management. Infect Control Hosp Epidemiol 2002;
23: 261267.
66 Tredget EE, Shankowsky HA, Joffe AM et al. Epidemiology of
infections with Pseudomonas aeruginosa in burn patients: the role
of hydrotherapy. Clin Infect Dis 1992; 15: 941949.
67 Ohura T, Haga S, Nakamura H. Irrigation effect of the pressure
ulcers department using the strongly acid water, Comparison with
the saline for the number of bacteria (in Japanese). Jpn J Clin Ther
Med 2006; 22: 541545.
QUESTION 3: HOW SHOULD THE SURFACE
OF CHRONIC SKIN WOUNDS BE
DISINFECTED?
Answer: Generally, shallow skin wounds need no disinfection.
In deep skin wounds, also, if they are not infected, lavage is
performed without the trouble of disinfecting. However, in
wounds in which colonization is advancing to infection, or infec-
tion has been established, it is necessary to disinfect them and
control infection despite the possibility of some tissue damage.
366
COMMENTARY
Disinfection is an action to kill or reduce pathogenic microor-
ganisms (such as bacteria) present on the skin or other objects
and reduce their pathogenicity. Disinfection is performed to
reduce opportunities of latent infection by these microorgan-
isms, generally using disinfectants. Eradicating microorganisms
using heat or other physical or chemical agents, which is called
sterilization, must be distinguished from disinfection.
Disinfectants exert bactericidal effects by protein-coagulat-
ing or oxidative activities, but it must be remembered that they
exert the same effects on the host (wound surface) as well as
microorganisms.6870 However, the histotoxicity of disinfectants
are often evaluated in animal models or in vitro, and applying
the results of such evaluations directly to wounds actually
being treated is questionable. At any rate, disinfection should
not be continued without a clear objective.
There are various types in disinfectants, but not all disinfec-
tants have bactericidal activities against all pathogenic
microorganisms (Table 3).71
Among disinfectants, (i) povidone iodine, (ii) chlorhexidine
gluconate and (iii) benzalkonium chloride are appropriate to be
used for chronic skin wounds.
Types of disinfectants and methods for their use are
described below.
TYPES OF DISINFECTANTS
Povidone iodine: A typical preparation of povidone iodine is
10% Isodine. It is brown, and this color serves as a mark of
the disinfected area. Its bactericidal activity is considered to be
derived from the oxidative power of iodine. A few minutes is
necessary for disinfection, and some consider that it must be
sufficiently dried after the application.72 However, as the pack-
age insert of Isodine states that most of the bacteria are killed
within approximately 30 s,73 there is also the expert opinion
that several tens of seconds suffices. Because povidone iodine
often causes contact dermatitis in a wet environment due to
sweat or exudates,74,75 it is important to wash it off and not to
allow it to remain on the skin after drying. As it is highly irrita-
tive, it must be diluted when applied to the face or mucosa.
Also, caution is needed in its use in patients with thyroid dys-
function as it may affect thyroid hormone-related materials.73
Chlorhexidine gluconate: Hibitane and Maskin are com-
mon chlorhexidine gluconate preparations. Although the agent
is odorless and transparent, some products are dyed. It is less
irritative than povidone iodine and can be applied to the face
and external genitals. Its bactericidal activity is weak, and
some strains survive even after contact for 5 min or longer. It
is used at a concentration of 0.05% for disinfection of skin
wounds.75 Because there are case reports of anaphylactic
shock, its use on the mucosal surface (vaginal, vesical, oral)
and ear is contraindicated.7679
Benzalkonium chloride: In addition to Osvan, there is ben-
zethonium chloride, available as Hyamine and Bezeton Solu-
tion, as its analog. It is almost odorless and non-irritative and
is appropriate for disinfection of the skin/mucosa. It is used at
2016 Japanese Dermatological Association
 Wound/Burn Guidelines 1

Table 3. Disinfectants and activities against all pathogenic microorganisms

Pseudomonas Resistant Pseudomonas Tubercle Bacteria Hepatitis

Bacteria MRSA aeruginosa aeruginosa bacillus Fungi spores virus HIV
Benzalkonium chloride M 9 9 M 9 9 9
Benzethonium chloride M 9 9 M 9 9 9
Chlorhexidine gluconate M 9 9 M 9 9 9
Ethanol for disinfection 9 9
Povidone iodine M 9
Mercurochrome 9 M 9 9 9
Hydrogen peroxide M M M 9 M 9 9 9
(2.53.5%)

MRSA, methicillin-resistant Staphylococcus aureus.

adequate
M little adequate
9 not adequate

a concentration of 0.010.025% for the mucosa and wounds
of the skin. For disinfection of infected skin surfaces, it is used
at 0.01%.80
METHODS FOR DISINFECTION
These disinfectants produce their bactericidal effects by dena-
turing/coagulating bacterial proteins (often proteins of the cell
membrane) and causing bacteriolysis. As they simultaneously
exert the same effect on host cells, they are histotoxic. There-
fore, disinfection continued without a clear reason delays
wound healing. If there are organic materials such as blood,
pus and necrotic tissue, disinfectants denature them and make
them less permeable. This prevents disinfectants from reaching
the wound and attenuates their expected bactericidal activities.
Disinfectants are effective when they are applied after remov-
ing necrotic materials and sufficiently lavaging the wound, but
their bactericidal activities are also reduced by residues of
soap used for lavage.
After the application of a disinfectant, the wound must be
allowed to stand in this state for several tens of seconds to a
few minutes because some time is needed for disinfection. The
disinfectant must be washed off after a sufficient duration of
contact with the wound to minimize the toxicity of residual
disinfectant to host cells.
DISINFECTION OF SKIN WOUNDS
ACCORDING TO THE WOUND TYPE
The activities of bacteria in wounds can be staged into: (i) con-
tamination (no bacterial proliferation); (ii) colonization (bacteria
proliferate but do no harm to the wound); and (iii) infection
(bacteria proliferate and do harm). It is widely accepted that
these stages are continuous and that infection develops as the
balance between the action of bacteria on the wound (bacterial
burden) and host resistance is disrupted.74 Critical colonization
is defined as a transitional state between the stages of (ii) and
(iii). Infected wounds exhibit characteristic clinical features.
NERDS, representing findings observed when the wound sur-
face is suspected to be infected, and STONES, representing
Table 4. NERDS and STONES
NERDS STONES
Superficial increased Deep component infection
bacterial burden
N : non-healing wound S : size is bigger
E : exudative wound T : temperature increased
R : red and bleeding wound O : os/probes to or exposed
bone
D : debris in the wound N : new area of breakdown
S : smell from the wound E : exudates, erythema, edema
S : smell
findings observed in deep infection, provide references for
judgments about local infection (Table 4).81
NERDS stands for non-healing wound (delayed wound
healing; a state in which a 2040% decrease in the wound size
is not observed in the course of 4 weeks), exudative wound
(increase in exudates; a state in which 50% in area of the
dressing material such as gauze is contaminated by exudates),
red and bleeding wound (red granulation that bleeds even by
slight treatment), debris in the wound (necrotic tissue; yellow,
white or black necrotic tissue adhering to the wound) and
smell from the wound (bad smell; a state in which the wound
emits a foul odor). STONES stands for size is bigger (enlarge-
ment of the wound; a state in which increases in the long and
short diameters of the wound are observed), temperature
increased (hot feeling; the temperature around the wound is
elevated by 3C compared with a control such as the oppo-
site side), os/probes to or exposed bone (bone exposure; a
state in which bone is directly visible (exposed) at the wound),
new area of breakdown (breakdown in the vicinity; a state in
which the skin around the existing wound fails, allowing new
ulcers to develop), exudates, erythema, edema and smell.
If the condition is judged to be colonization, disinfection of
the wound is not always necessary. Disinfection is necessary
when signs of infection are observed in the wound, namely, in
the stages of critical colonization and infection.82
The guidelines of the Wound Healing Society strongly
recommend to reduce the microbial mass by disinfection when

2016 Japanese Dermatological Association 367

Y. Inoue et al.
the bacterial count in local exudates from chronic skin wounds
(diabetic ulcer, venous ulcer, pressure ulcer) is 1 9 106 colony-
forming units or higher per 1 g of sample.8385 They also rec-
ommend prompt discontinuation of disinfection in considera-
tion of the toxicity of disinfectants once infection has been
controlled. However, the same guidelines present a lower rec-
ommendation level for the control of local infection concerning
ischemic ulcer alone (because it is particularly sensitive to the
toxicity of disinfectants).86
In addition, the International Consensus87 recommends
disinfection of infected wounds complicated by systemic infec-
tion, wounds of patients with the risk of increased susceptibility
to infection, and wounds showing exacerbation of signs of
infection treated by methods other than disinfection such as
lavage alone. Iodine preparations are recommended as local
disinfectants. Also, discontinuation of disinfection is recom-
mended when improvements are observed in the wound.
SHALLOW CHRONIC SKIN WOUNDS
In wounds with defects of the epidermis alone or to the upper
layer of the dermis without clear signs of infection, the signifi-
cance of disinfection is small.88 For wounds showing epithelial-
ization, lavage using physiological saline and tap water is
sufficient. There are various cytokines on the wound surface,
and the epidermis being formed is thin. Therefore, they must
be treated protectively, and rubbing during washing is often
unnecessary.
DEEP CHRONIC SKIN WOUNDS
Deep chronic skin wounds accompanied by
infection or necrotic tissue
Usually, necrotic tissue exists to a wide area of the wound
surface. The presence of necrotic tissue increases the risk of
infection, and wounds with necrotic tissue are always con-
sidered to be in a state of critical colonization. Indeed, if the
balance is tilted to infection, systemic symptoms including
fever may be observed in addition to local symptoms such
as a hot feeling, increase in exudates such as pus, redden-
ing, swelling and pain. Wound healing cannot be expected
without controlling infection. Therefore, (i) removal of necrotic
tissue (debridement), (ii) lavage and disinfection, (iii) and sys-
temic administration antibacterial agents are necessary.
Because the presence of necrotic tissue prevents permeation
of disinfectants to the wound, as mentioned above, it is
important to use disinfectants after aggressively removing
necrotic tissue and cleaning the wound by lavage. Also, dis-
infection should be discontinued at an appropriate point
once infection has been controlled, and critical colonization
has been reversed to colonization.89,90 Thus, adherence to
eradication of bacteria by disinfection is unnecessary if
wound infection is not established. However, if infection has
been established, or is about to be established (critical colo-
nization), disinfection to control infection at the cost of some
tissue damage is necessary.91
368
Deep chronic skin wounds in the granulation/
epithelialization stage
In the event of defect of the dermis or full thickness of the
skin, the risk of infection is higher than in superficial
wounds. The state of bacteria is often colonization. Some
more time is needed until epithelialization and granulation is
in progress. Therefore, granulation must not be inhibited by
tissue toxicity of unnecessary disinfection. Lavage is neces-
sary and sufficient for maintaining cleanness of the wound,
and it is necessary to wash the wound surface with some
pressure.70,92
REFERENCES
68 Iwasawa A, Nakamura R. Points to keep in mind in the use of the
povidone iodine preparation. Infection Control 2002; 4: 1824.
69 Fernandez R, Griffiths R, Ussia C. Water for wound cleansing (re-
view).The Cochrane Collaboration Issue 2, The Cochrane Library,
2010.
70 Ohnishi S, et al. Hazardousness of the povidone iodine sterilization
for the wound healing and the effectiveness of the tap water wash-
ing. Nesshyou 2006; 32: 2632.
71 Kobayashi K, Ohkubo K, Oie S. Guideliens for sterilization and dis-
infection. Health Publication 1999.
72 Hatae S, et al. Sterilization and sterilization mainly on the medical care.
povidone iodine solution. Rinshyou to Biseibutsu 2002; 29: 367372.
73 10% povidone iodine solution Attached document. Meiji seika;
2008.July
74 Iijima S, Kuramochi M. Investigation of Irritant skin reaction by
10% povidone-Iodine solution after surgery. Dermatology 2002;
204(suppl 1): 103108.
75 Iijima S. Primary irritating contact dermatitis with the 10% povi-
done iodine solution. Iyaku journal 2002; 38: 513.
76 Sugihara K, et al. Examination of the antisepsis of the wound part
of the skin. Pharma Medica 2003; 21: 7989.
77 Imazawa T, et al. A case that caused anaphylactic shock after glu-
conic acid chlorhexidine use. J Jpn Soc Plastic Reconstr Surg
2003; 23: 582588.
78 Saitou Y. Sterilization and sterilization mainly on the medical care
Gluconic acid chlorhexidine. Rinshyou to Biseibutsu 2002; 29: 377
380.
79 0.05% Chlorhexidine gluconate solution Attached document Mar-
uishi seiyaku 2005.July
80 0.02% Benzethonium chloride solution Attached document Kenei
seiyaku 2008.February
81 Sibbad RG, Woo K, Ayello EA. Increased bacterial burden and
infection: the story of NERDS and STONES. Adv Skin Wound Care
2006; 19: 447461.
82 Kouno T, Taniguchi A. Right or wrong of the wound sterilization
based on the evidence Clinical Dermatorogy 2005. Rinshyohihuka
2005; 59: 117122.
83 Whitney J, Phillips L, Aslam R, et al. Guidelines for the treatment
of pressure ulcers. Wound Rep Reg 2006; 14: 663679.
84 David L, Steed MD, Christopher A, Theodore C, et al. Guidelines
for the treatment of diabetic ulcers. Wound Rep Reg 2006; 14:
680692.
85 Martin C, Robson MD, Diane M, Cooper RN, Aslam R. Guidelines for
the treatment of venous ulcers. Wound Rep Reg 2006; 14: 649662.
86 Hopf HW, Ueno C, Aslam R. Guidelines for the treatment of arterial
insufficiency ulcers. Wound Rep Reg 2006; 14: 693710.
87 Wound Infection in Clinical Practice: an International Consensus
Supported by an unrestricted educational grant from Smith &
Nephew. Int Wound J 2008; 5: s3
88 Ichioka S. Infection management in the wound treatment. Chiryou
2003; 85: 27292733.
2016 Japanese Dermatological Association
 Wound/Burn Guidelines 1

89 Sibbald RG, Williamson D, Orsted HL et al. Preparing the wound
bed debridement, bacterial balance and moisture balance. Ost-
omy/Wound Manag 2000; 46: 1435.
90 Sibbald RG, Orsted H, Schultz GS, Coutts P, Keast D. Preparing
the wound BED 2003: focus on infection and inflammation. Ost-
omy/Wound Manag 2003; 49: 2451.
91 Homma K, Ohura T. Treatment of MRSA infection, a pollution ulcer
and the pressure ulcer. Infect Control 2001; 10: 460463.
92 Longmire AW, Broom LA, Burch J. Wound infection following high
pressure syringe and needle irrigation. Am J Emerg Med 1987; 5:
179181.
QUESTION 4: WHAT TOPICAL AGENTS
SHOULD BE USED FOR CHRONIC SKIN
WOUNDS?
Answer: To promote healing of chronic skin wounds, the depth
of the wound, stage of the healing process and factors pre-
venting healing must be clarified. Then, it is recommended to
selectively use topical agents that are useful for removing the
factors preventing healing and promote the healing process in
consideration of the composition and base of the drug.
COMMENTARY
Significance of, and precautions in, the use of
topical agents
Wound healing is delayed if there are factors inhibiting even
part of the wound healing process mentioned above (see
Question 1). To eliminate such factors, or to further accelerate
the normal healing process, topical agents must be selected
according to the state of the wound. The appropriate use of
topical agents is well known to promote wound healing from a
large number of clinical trials of topical agents and reviews by
experts.9399 However, their attachment to the normal skin
around the wound should be avoided as much as possible,
because they may cause contact dermatitis or maceration, and
the skin of such sites must be observed carefully during their
use. Also, the effects of medication should be evaluated
approximately every 2 weeks, drugs must be changed, if
necessary, and the use of ineffective drugs should not be
continued without reason. As for the actual use of topical
agents, an ointment should be spread over gauze evenly at a
sufficient thickness (~13 mm) using an ointment spatula or
tongue depressor with measures to avoid drying of the wound
surface or adhesion of gauze to the wound surface.96 Particu-
larly, if exudates are insufficient, an increased amount of the
ointment may be applied, or the gauze may be covered with
polyurethane film. If there are undermining, topical agents must
be applied into them.
Bases of topical agents
In topical agents, not only the active agent (primary compo-
nent) but also the base plays an important role in their
effects.9399 The bases of ointments frequently used for the
treatment of wounds are classified into oleaginous, emulsion
and water-soluble bases (Table 5).
Oleaginous bases include those derived from minerals such
as white petroleum and plastibase and those prepared from
animal or vegetable oil such as zinc oxide. They have been
used widely through the ages because of their strong protective
and moisture-retaining effects on the skin and low irritativity.
Emulsion bases are prepared by emulsification of oleagi-
nous and water-soluble components with a surfactant and are
classified into oil-in-water (O/W) bases, in which oil is dis-
persed in water, and water-in-oil (W/O) bases, in which water

Table 5. Characters of bases of external medications

Classification of base Representative base Representative ointment Character

Hydrophobic Oleaginous Mineral oil White petrolatum Azuonl ointment Cuticle softening
base base Plastibase Gentacin ointment Crust removal
Fucidin Leo ointment Wound surface protection
Prostandin ointment Low irritation
Animal or Simple ointment Zinc ointment
vegetable oil
Hydrophilic Emulsion Oil-in-water Hydrophilic ointment Olcernon ointment High drug-incorporation
base base type (O/W) Vanishing cream Geben cream property
Water-in-oil Absorption ointment Solcoseryl ointment High permeability
type (W/O) Cold cream Reflap ointment Washable
Hydrophilic petrolatum
Purified lanolin
Water-soluble Macrogol ointment Actosin ointment High water-absorbing
base Cadex ointment (including property
a polymer particle) Aqueous secretion
Bromelain ointment absorption
U-PASTA KOWA ointment Low irritation
(including a saccharose Washable
component)

2016 Japanese Dermatological Association 369

Y. Inoue et al.
Table 6. Choice of topical agents
Shallow and deep Representative topical
skin wounds agents
Shallow chronic skin Dimethyl
wounds isopropylazulene
ointment Ointment
Ointments containing
antibiotics (antibacterial
agents)
Zinc oxide ointments
White petrolatum
Deep chronic skin Cadexomer iodine
wounds (those ointments or powder
accompanied by
infection or necrotic
tissue)
Creams containing silver
sulfadiazine
Dextranomer polymer
Bromelain component
ointment
Povidone iodine gel
Povidone iodine sugar
containing white sugar
Iodine-containing
ointments
Fradiomycin sulfate/
crystalline trypsin
powder
370
Representative
products Remarks
Azunol ointment Wound surface protection and weak anti-
inflammatory effect
Gentacin ointment Antibacterial effects by containing antimicrobial agent
Fucidin Leo ointment such as antibiotics. Avoid using for a long period to
prevent emergence of resistant bacteria
Zinc oxide simple Thin layer application protects wound surface, while
ointment thick layer application dries (or desiccates) wound
surface
White petrolatum Use for wound surface protection. It is an advantage
that it does not induce contact dermatitis
Cadex ointment Released iodine shows strong antimicrobial activity,
Cadex powder while polymer particles absorb exudates and
remove necrotic tissues and bacteria. Not suitable
for dried surface of the wound. Powder shows
higher water absorbability, while macrogol ointment
is easier to use. During washing, old polymer
particles need to be washed out thoroughly. It is
contraindicated in a patient with a history of iodine
hypersensitivity
Geben cream Sulfadiazine and silver to contain show wide
antimicrobial activity for bacteria and fungi. High
tissue permeability and moisture content facilitate
softening and autolysis of necrotic tissues. Not
suitable for wet wounds. Contraindicated in patients
with a history of sulfa hypersensitivity, newborn
infants, low-birthweight babies and mild burn
patients (pain is caused). Pay attention to possible
rise in serum osmolarity in extensive burn patients
Debrisan Polymer particles facilitate exudates absorption and
Debrisan Paste removal of bacteria and their degradation products.
Paste preparation containing macrogol is easier to
use. During washing, polymer particles need to be
washed out thoroughly. Do not apply to ulcers
having difficulties in washing due to undermining.
Not suitable for dried surface of the wound
Bromelain ointment The protease bromelain works on chemical
debridement of necrotic tissue. Preventive ointment
application may reduce flare and pain of
surrounding normal skin. Not suitable for infected
wound.
Isodine Gel Inhibit infection by iodide strong antimicrobial activity.
The base contains macrogol. Contraindicated in
patients with a history of iodine hypersensitivity.
U-PASTA KOWA Iodine exerts strong antimicrobial activity and white
ointment sugar absorbs exudates and reduces edema. Not
suitable for dried surface of the wound. Use after
enough stirring. Contraindicated in patients with a
history of iodine hypersensitivity.
Iodocoat Ointment It exerts similar effects to cadexomer iodine, even
without polymer particle. Contraindicated in patients
with a history of iodine hypersensitivity
Francetin T There are both antibacterial effects by fradiomycin
Powder sulfate and necrotic tissue-lytic effects by trypsin.
Not suitable for dried surface of wound because of
its powdery preparation. Contraindicated for
bleeding surface of the wound and in patients with
liver or renal damage.
2016 Japanese Dermatological Association
 Wound/Burn Guidelines 1

Table 6. (continued)

Shallow and deep Representative topical Representative

skin wounds agents products Remarks

Deep chronic skin Alprostadil alfadex Prostandin ointment Promotes granulation by increasing of blood flow and
wounds (Those in (prostaglandin E1) angiogenesis. Promote epithelization by stimulating
the epithelialization ointment) epidermal cell growth and migration. Suitable for a
period) dried surface of wounds because of plastibase
ointment base. Contraindicated in pregnant women,
in patients with heart failure and bleeding.
Aluminum chlorhydroxy Isalopan (powder) This medicine is aluminum salt of allantoin derivate,
Allantoinate powder which promotes granulation and removal of necrotic
tissues.
Lysozyme Reflap ointment There are tissue-repairing activity such as fibroblast
hydrochloride- Reflap sheet growth and purulent discharge-lytic effects.
containing ointment Contraindicated in patients with a history of
albumen hypersensitivity.
Solcoseryl-containing Solcoseryl This is a calf hemodialysate extract, which promotes
ointments Ointment granulation by activating angiogenesis and fibroblast
Solcoseryl Jelly growth. Contraindicated in patients with a history of
bovine blood products hypersensitivity.
Basic fibroblast growth Fiblast Spray A recombinant human bFGF preparation, which
factor (bFGF) promotes a good-quality granulation through
activation of angiogenesis and fibroblast growth and
migration. Dissolve in a specialized spray bottle and
spray on a wound surface. Contraindicated for the
wound surface with malignant tumor or with a
history of it.
Tretinoin tocopherol Olcernon ointment This strongly promotes granulation by activating
ointment growth and migration of vascular endothelial cells
and fibroblasts. Suitable for dried surface of the
wounds because of emulsion base with much
moisture content. Yellowish wound surface due to
the ointment color is sometimes confused with
infected wound.
Bucladesine sodium Actosin ointment This promotes granulation and epithelialization
ointment through vasodilatation, blood flow improvement,
and growth and migration of vascular endothelial
cells and fibroblasts. It has water absorbability due
to macrogol base. Some may be susceptible to
peculiar odor

is dispersed in oil. The former are called hydrophilic ointments
or vanishing creams, and the latter water-absorbable oint-
ments or cold creams. Their advantage is that they can be
compounded with both water-soluble and oil-soluble drugs.
They are also penetrating and are useful for the preparation
of drugs for deep ulcers and wounds accompanied by necro-
tic tissue, the treatment of which requires highly penetrating
drugs.
Water-soluble bases completely dissolve in water. Macrogol,
a condensation polymer of ethylene oxide and water, is a typi-
cal water-soluble base. While the percutaneous absorbability
of the active component compounded with a water-soluble
base is low, water-soluble bases have little irritativity and very
high water-absorbing property and are useful for wounds rich
in exudates. They are also advantageous in that they can be
readily washed off.
As for other bases, those compounded with white sugar or
absorbent polymer particles show a very high water-absorbing
property and are optimal for wounds rich in exudates. To sum-
marize, oleaginous ointments with high wound-protecting and
moisture-retaining effects are appropriate for shallow wounds
deficient in exudates, but water-soluble bases or bases con-
taining white sugar or polymer particles are appropriate for
deep wounds rich in exudates.
Selection of topical agents (see Table 6)
Shallow chronic skin wounds
As the skin plays an important role in the protection of internal
organs from the external environment and retention of mois-
ture, in the event of partial defect of the skin, the site of the
defect must be protected and, further, maintained in an appro-

2016 Japanese Dermatological Association 371

Y. Inoue et al.
priately moist environment until healing. Therefore, shallow
wounds (erosion and shallow ulcers within the upper layer of
the dermis) are good indications for dressing materials and
topical agents. Ointments using methylpropyl azulene, an
oleaginous base with a strong moisturizing effect, ointments
containing antibiotics (antibacterial agents) (mostly ointments
with an oleaginous base such as sodium fusidate and gen-
tamycin sulfate ointments), zinc oxide ointments and white
petrolatum are used for such wounds. However, the use of
ointments containing antibiotics (antibacterial agents) over
2 weeks or longer should be avoided, because it may induce
the emergence of resistant bacteria.
Deep chronic skin wounds
Those accompanied by infection or necrotic tissue. While
migration of inflammatory cells, which produce growth factors
and cytokines necessary for granulation, to the wound is indis-
pensable for its healing, excessive inflammation or persistence
of inflammation prevents granulation or subsequent epithelial-
ization and delays wound healing. Because foreign bodies,
infection and necrotic tissue thus cause a delay of wound heal-
ing, they must be removed as much as possible by surgical
debridement or sufficient lavage. To promote autolysis of
necrotic tissue, cadexomer iodine ointments or external pow-
der preparations102104 as well as ointments containing brome-
lain, which are enzyme preparations,100 and fradiomycin
sulfate/crystalline trypsin powder101 are frequently selected.
Although it is often difficult to completely remove necrotic tis-
sue by such chemical debridement alone, subsequent surgical
debridement is made safer and easier if necrotic tissue is
softened by these chemical agents. For external treatment of
infected wounds, cadexomer iodine ointments or external
powder preparations with a strong antibacterial
activity,102104,106,107 povidone iodine sugar108,109 and iodine-
containing ointments,109 are used. Creams containing silver
sulfadiazine are also used frequently because of the strong
antibacterial activity.111113 If the wound is abnormally rich in
exudates due to infection or marked inflammation, granulation
may be prevented, or additional infection or inflammation may
develop. Also, the surrounding normal skin is macerated and
becomes vulnerable to erosion due to external stimulation.
Therefore, the use of topical agents that absorb exudates is
necessary. Cadexomer iodine ointments or external powder
preparations containing polymer particles,102105,107 dextra-
nomer polymer114 and povidone iodine sugar containing white
sugar108,109 are typical among them. Iodine-containing oint-
ments,110 which have a bactericidal effect due to continuous
release of iodine and an exudate-absorbing effect and are
easier to handle than polymer-based preparations, are also
considered useful.
Those in the epithelialization stage. Granulation tissue is
formed in wounds after the control of infection and removal
of necrotic tissue. However, for deep ulcers or wounds show-
ing a delay of granulation for some reason, topical agents
that promote granulation should be used. In addition to trafer-
min (basic fibroblast growth factor) preparations with a strong
372
granulation-promoting effect,115118 alprostadil alfadex (prosta-
glandin E1) ointments,119 aluminum chlorohydroxy allantoinate
external powder preparations,120 lysozyme hydrochloride-con-
taining ointments,121 Solcoseryl-containing ointments,122 tre-
tinoin tocopherol ointments123,124 and bucladesine sodium
ointments125,126 are known to promote granulation.
Once the ulcerated area is filled with satisfactory granulation
tissue, epithelialization begins. In this period, protection of the
wound surface and maintenance of a moist environment are
important. Ointments such as those used for the treatment of
superficial chronic skin wounds mentioned above are indicated.
For actively inducing shrinking of the wound by epithelialization,
alprostadil alfadex (prostaglandin E1) ointments119 and bucla-
desine sodium ointments125,126 are considered useful.
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97 Tamura A. Usage of external medicine and wound dressing for
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98 Furuta K. External medicine for pressure ulcers-base, classification,
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99 Japanese society of pressure ulcers-Guideline for prevention and
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100 Ogawa Y, Kurooka S, Katakami S, et al. The evaluation of the
effect of Bromelain ointment on the debridement of eschar of burn,
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48: 13011309.
101 Shibata K, Ezaki R, Sato S. Combined application of antibiotics and
anti-inflammation enzyme. J Therapy 1972; 54: 14471451.
102 Ishibashi K, Ohkawara A, Kukita A, et al. Clinical evaluation of NI-
009 on various cutaneous ulcers-comparative study with
Debrisan. J Clin Therap Med 1990; 6: 785816.
103 Kukita A, Ooura T, Aoki T, et al. Clinical evaluation of NI-009 on
various cutaneous ulcers-comparative study with Elase C oint-
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104 Anzai T, Shiratori A, Ohtomo E, et al. Evaluation of clinical utility of
NI-009 on various cutaneous ulcers comparative study with
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105 Tachibana T, Miyachi Y. Topical treatment for pressure ulcers. Jpn
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venous leg ulcers (Review). In: The Cochrane Collaboration. Pub-
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iodine in the treatment of chronic wounds. Wounds 1997; 9: 6886.
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108 Imamura S, Uchino H, Imura Y, et al. The clinical effect of KT-136
(sugar and povidone-iodine ointment) on decubitus ulcers- a com-
parative study with lysozyme ointment. Jpn Pharmacol Ther 1989;
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109 Saito Y, Furuse Y, Ishii T, et al. A clinical randomized comparative
study of povidone-iodinesugar ointment (U-PASTA KOWA) versus
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ointment) and povidone-iodinesugar ointment (U-PASTA KOWA)
on decubitus. Jpn Pharmacol Ther 1994; 22: 24032413.
110 Hikake S, Kobayashi K, Miwa Y, et al. Development and formula-
tion characteristics of an ointment for skin ulcers including pres-
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2007; 67: 260265.
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sulfadiazine, povidone-iodine and physiologic saline in the
treatment of chronic pressure ulcers. J Am Geriatr Soc 1981; 29:
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controlled comparative study with lysozyme chloride ointment. J
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2016 Japanese Dermatological Association
Wound/Burn Guidelines 1
Question 5: How should dressing materials be
used?
Answer: Basically, dressing materials have a water-retaining
property. However, as their ability to absorb exudates varies
with the product form, a moist environment appropriate for
wound healing can be prepared by selecting them according
to the amount of exudates. Also, their use with sufficient
understanding of the material and morphology of each dress-
ing material is recommended. Cautions against their inappro-
priate use are necessary as it may induce infection or interfere
with wound healing.
COMMENTARY
Significance of, and points of caution in, the use of
dressing materials
The proper use of a dressing material on the basis of the TIME
concept described above (see Question 1) and principles of
moist wound healing is an effective measure for the treatment
of chronic skin wounds.127133 In the present guideline, dress-
ing materials means modern wound-dressing materials aimed
to create a moist environment for wounds, and conventional
sterilized gauze is excluded.
Among dressing materials, polyurethane film used for the
protection of the skin and secondary dressing is not covered
by insurance, and its cost is included in the technical fee.
For wounds reaching the dermis or even deeper areas,
dressing materials for skin defects specified by the National
Health Insurance (NHI; specific insured medical materials)
can be used according to the wound depth. They cannot be
prescribed as they are not drugs, but the NHI points can be
calculated if they are used for the treatment. If multiple
dressing materials are used for the same site, the NHI points
can be calculated for the primary material only. Caution is
needed as they are excluded from the insurance coverage if
they are used for surgical sutured wounds or wounds with a
depth not specified by insurance. Occluding the wound with
a dressing material and creating a moist environment not
only contributes to wound healing by retaining cell growth
factors and cytokines contained in exudates, promoting the
migration of epidermal cells and preventing the spread or
promoting autolysis of necrotic tissue, but also has effects
such as the protection of the skin around the wound,
prevention of contamination, mitigation of pain and heat
retention.
However, dressing materials that prevent observation of the
wound should not be used for infected wounds, because infec-
tion may be exacerbated by maintaining a moist environment.
In using dressing materials, it should also be noted that the
period of insurance coverage is limited (usually for 2 weeks,
3 weeks at the maximum) and that the discretion in the choice
and use of dressing materials belongs exclusively to the physi-
cian. An advantage of dressing materials is that they do not
necessarily require daily change, but it is necessary to check
for signs of infection or contamination of the wound through
the material, and detachment of the material, and to appropri-
ately determine the time of their change or duration of their
373
Y. Inoue et al.

sustained application (1 week at the maximum). The resistance avoided or, if it is used, sufficient precautions such as chang-
to infection is depressed in patients with a deficient blood flow ing the dressing material daily and checking whether or not
to the wound due to peripheral arterial diseases (conventionally infection is developing under the dressing material are neces-
called arteriosclerosis obliterans) and immunocompromised sary. Dressing materials can be an effective means if used
patients. In such patients, occlusive dressing should be appropriately, but it must be remembered that they may pre-
vent wound healing if used without sufficient knowledge about
them or experience in their use.
Table 7. Quantity of exudation and choice of dressing
materials Characteristics of various dressing materials
Exudates Suitable dressing materials Polyurethane film
Moderatelittle Polyurethane film Polyurethane film coated with an adhesive on one side is used
Hydrocolloid for the protection or secondary dressing of shallow wounds
Little (with dry necrotic tissues) Hydrogel deficient in exudates. It is permeable to oxygen and vapor but
Heavy Alginate does not allow the passage of bacteria. Because of its trans-
Chitinous substance parency, it facilitates the observation of the wound.
Hydro-fiber
Hydro-polymer
Hydrocolloid
Polyether foam
Hydrocolloid consists of a waterproof outer layer and an inner
adhesive layer containing hydrophilic colloid particles. It forms

Table 8. Depth of wound and choice of dressing materials

Insurance repayment Materials Representative trade name

Contained into Polyurethane film Opsite wound
technology charge Cutifilm EX
TegadermTM Transparent Film Dressing
Bioclusive
Perme-aid S
(A) For the wound Chitin Beschitin W
reaching dermis Hydrocolloid Absocure Surgical
TegadermTM Light Hydrocolloid Dressing
DuoActive ET
Polyurethane foam Hydrosite slim
Hydrogel ViewGel
NewGel
(B) For the wound (B1) Standard Hydrocolloid Absocure wound
reaching subcutaneous Comfeel Ulcus Dressing
tissue TegadermTM Hydrocolloid Dressing
DuoActive
DuoActive CGF
Hydrogel GelPalm (wet sheath type I, II)
Chitin Beth chikin W-A
Alginate Algoderm (end of sales in March 2013)
Kaltostat
Kurabior FG
ActivHeal (end of sales at 18 August 2011)
Sorbsan
Hydrofiber Aquacel
Aquacel Ag
Hydropolymer Tielle
Polyurethane foam Hydrosite
Hydrosite AD
(B2) Special Hydrocolloid Comfeel Paste
Hydrogel Intrasite Gel System
GranuGEL
GelPalm (granular gel)
(C) For the wound Polyurethane foam Hydrosite Cavity
reaching muscle/bone Chitin Beth chikin F

374 2016 Japanese Dermatological Association


an occluded moist environment not interfering with wound
healing. Because it is gelatinized by absorbing water, it is not
appropriate for wounds rich in exudates. Being translucent, it
facilitates observation of the wound.
Hydrogel
Hydrogel has a matrix structure of hydrophilic polymeric mole-
cules and contains water. It provides moisture to dried necrotic
tissue and promotes its autolysis.
Chitin
Non-woven fabric of chitin, fibrous mucopolysaccharide
extracted from crustacean shell. After it is lightly undermining
in the wound, it must be covered by a dressing material. It has
a wound-cleaning effect due to water-absorbing and adsorbent
actions and a hemostatic effect. It is decomposed even if it
remains at the wound.
Alginate
Alginic acid calcium salt extracted from seaweeds and pre-
pared into fibers. It is lightly packed in the wound and covered
with a dressing material. It has a high exudate-absorbing
capacity and gels by absorbing moisture.
Hydrofiber
Non-woven fabric of fibers of sodium carboxymethyl cellu-
lose. It is lightly packed in the wound and covered by a
dressing material. It has a high exudate-absorbing capacity
and forms gel that does not disintegrate after absorbing
moisture.
Hydropolymer
It is prepared as a pad consisting of hydrophilic polyurethane
foam, and fits into even depressed wounds as it swells by
absorbing excessive exudates. The pad in the center is sur-
rounded by an adhesive tape and can be changed readily as it
does not gel.
Polyurethane foam
It has a three-layer structure of non-adhesive polyurethane,
which comes into contact with the wound, hydrophilic polyur-
ethane foam in the center and polyurethane film on the outer
side. It absorbs excessive exudates by the capillarity. As it is
non-adhesive, it is less likely to damage the wound surface.
Having a sufficient thickness, it provides protection to the
wound, but some skill is needed for its application. Some
products are prepared with an adhesive film and can be
applied directly.
Selection of dressing materials according to the
amount of exudates and wound depth
After considering the functions and characteristics of various
dressing materials, dressing materials should be selected using
the amount of exudates as a criterion (Table 7). Table 8 shows
dressing materials and their representative product names
according to the wound depth.
2016 Japanese Dermatological Association
Wound/Burn Guidelines 1
Selection of dressing materials according to the
stage of chronic skin wounds
Shallow chronic skin wounds
Polyurethane film is often used for erosion and blisters to pro-
tect the wound surface although it is not covered by insurance.
Thin types of hydrocolloid and polyurethane foam are used for
non-infected shallow ulcers to the upper layer of the dermis
also for the protection of the wound surface and preservation
of a moist environment.
Deep chronic skin wounds
Those accompanied by infection/necrotic tissue. As mentioned
above, the control of infection by the removal of necrotic tis-
sue and administration of antibiotics and the management of
exudates are important for chronic skin wounds with infec-
tion or necrotic tissue. Treatment for infection is of particular
importance. In this stage, as infection may be exacerbated
by occluding the wound, occlusive dressing should be
avoided, and primarily topical agents with an antibacterial
action should be used for the treatment. In dried necrotic
tissue, Hydrogel provides moisture and promotes its
autolysis.
Those in the granulation/epithelialization stage. In the stage
of granulation or epithelialization, the latter half of the healing
process of chronic skin wounds, the use of occlusive
dressing materials for moist wound healing is important not
to allow the wound healing mechanism to be impaired by
drying of the wound or granulation tissue or newly formed
epidermis to be damaged by changes of dressing materials.
While many of the external medications used in this
period actively promote granulation or epithelialization,
dressing materials are used to induce wound healing primar-
ily by maintaining a moist environment and preserving cytoki-
nes at the wound. Hydrocolloid is recommended when
effusion is deficient, and alginate, chitin, Hydrofiber,
hydropolymer and polyurethane foam are recommended
when exudate is rich.
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