International Journal of Surgery 44 (2017) 260e268

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International Journal of Surgery

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Review

Povidone iodine in wound healing: A review of current concepts and

practices
Paul Lorenz Bigliardi a, b, c, *, Syed Abdul Latiff Alsagoff d, Hossam Yehia El-Kafrawi e,
Jai-Kyong Pyon f, Chad Tse Cheuk Wa g, Martin Anthony Villa h
a
National University of Singapore, YLL School of Medicine, Singapore
b
National University Hospital, Division of Rheumatology, University Medicine Cluster, 119228, Singapore
c
Experimental Dermatology, Institute of Medical Biology, Agency for Science Technology & Research (A*STAR), 138648, Singapore
d
Ampang Puteri Specialist Hospital, Orthopaedic Surgery, Selangor, Malaysia
e
Department of Plastic and Reconstructive Surgery, University of Alexandria, Alexandria, Egypt
f
Department of Plastic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
g
University of Hong Kong, Pokfulam, Hong Kong
h
Division of Vascular Surgery, Institute of Surgery, St. Luke's Medical Center, Quezon City, Philippines

h i g h l i g h t s

In wound care, topical antiseptics may limit the potential for antibiotic resistance.

Povidone iodine is an effective antiseptic that does not impede wound healing.

Povidone iodine is bactericidal against Gram-positive and -negative organisms.

No acquired bacterial resistance or cross-resistance has been reported for iodine.

Povidone iodine aids healing in a range of acute and chronic wounds.

a r t i c l e i n f o a b s t r a c t

Article history: Background: Of the many antimicrobial agents available, iodophore-based formulations such as povi-
Received 6 March 2017 done iodine have remained popular after decades of use for antisepsis and wound healing applications
Received in revised form due to their favorable efficacy and tolerability. Povidone iodine's broad spectrum of activity, ability to
31 May 2017
penetrate biofilms, lack of associated resistance, anti-inflammatory properties, low cytotoxicity and good
Accepted 20 June 2017
Available online 23 June 2017
tolerability have been cited as important factors, and no negative effect on wound healing has been
observed in clinical practice. Over the past few decades, numerous reports on the use of povidone iodine
have been published, however, many of these studies are of differing design, endpoints, and quality. More
recent data clearly supports its use in wound healing.
Methods: Based on data collected through PubMed using specified search criteria based on above topics
and clinical experience of the authors, this article will review preclinical and clinical safety and efficacy
data on the use of povidone iodine in wound healing and its implications for the control of infection and
inflammation, together with the authors' advice for the successful treatment of acute and chronic
wounds.
Results and conclusion: Povidone iodine has many characteristics that position it extraordinarily well for
wound healing, including its broad antimicrobial spectrum, lack of resistance, efficacy against biofilms,
good tolerability and its effect on excessive inflammation. Due to its rapid, potent, broad-spectrum
antimicrobial properties, and favorable risk/benefit profile, povidone iodine is expected to remain a
highly effective treatment for acute and chronic wounds in the foreseeable future.
© 2017 The Authors. Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd. This is an open
access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction
* Corresponding author. Medical Center National University Hospital, 3rd floor, 5
Lower Kent Ridge Road 119074, Singapore.
Virtually all wounds are colonized with microorganisms, often
E-mail address: paul_bigliardi@nuhs.edu.sg (P.L. Bigliardi).

http://dx.doi.org/10.1016/j.ijsu.2017.06.073
1743-9191/© 2017 The Authors. Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd. This is an open access article under the CC BY-NC-ND license (http://
creativecommons.org/licenses/by-nc-nd/4.0/).
 P.L. Bigliardi et al. / International Journal of Surgery 44 (2017) 260e268
without clinical consequence and the presence of some microor-
ganisms may even aid healing [1,2]. However, contamination with
pathogenic microbial flora can lead to infection and sepsis, which
disrupts the healing continuum [3,4]. The development of infection
is determined by complex interactions between the host and mi-
croorganisms, and further influenced by the environment and
therapeutic interventions [3,5].
Although inflammation occurs as a physiological response to
wounding and is required for the healing process, microbial
infection can induce excessive inflammation [4]. Prolonged
inflammation together with defective remodeling of the extracel-
lular matrix and a failure of re-epithelialization are hallmark
characteristics of chronic wounds [2]. Microbial colonies in chronic
wounds often produce biofilms that interact with host tissue in a
parasitic manner [3,4]. The reduced metabolic state induced by
biofilms can also enhance resistance to antibiotics and aid the
evasion of host defense mechanisms. Biofilms are found in
approximately 60% of chronic wounds and 6% of acute wounds,
with eradication of the resident bacteria remaining difficult [4].
Therefore, effective antiseptics for wound healing should ideally
address both inflammation and biofilm formation.
Few antimicrobial substances are generally considered for
wound therapy. Of these, povidone iodine has continued to be
broadly applied [7e9].
The aim of this article is to clarify the current role and use of
povidone iodine in wound healing from both diverse regional and
specialist's perspectives.
Data were collected through PubMed using specified search
criteria based on preselected topics. For clinical use, focus was put
on model indications as surgical site infection, burns and chronic
wounds e.g. diabetic foot ulcer. Articles from personal bibliography
and the clinical experience of the authors were also taken into
account, especially in areas of limited published information.
2. Importance of antibiotics and antiseptics in wound healing
An increasing emergence of resistance to topical and systemic
antibiotics is observed [4,6]. Antiseptics, as an alternative for topical
wound treatment, tend to be microbicidal and have a broader
spectrum of antimicrobial activity than antibiotics [6]. Further-
more, in comparison to most antibiotics, antiseptics reduce the
likelihood of resistance emerging due to their multiple mechanisms
of action targeting various aspects of cell biology in microbes [4].
Therefore, the use of topical antibiotics should be discouraged if
appropriate antiseptics are available [7]. Furthermore, a recent
WHO guideline advocates the use of good antisepsis peri-
operatively while reducing the use of systemic antibiotics [8,9].
Overall, the properties of an ideal antiseptic include a broad
spectrum of activity [5,6,10], the ability to penetrate biofilms [4],
necrotic tissue, and eschar [4,6,10], a low potential for acquired
resistance [1,5,6,10], supportive effects for wound healing by
Table 1
Properties of ideal antiseptics.

Antimicrobial activity against a wide range of micro-organisms [5,6,8]
including pathogens within biofilms [4]

Limited inactivation by organic compounds [6]

Good penetration, including into necrotic tissue and eschar [6,8] with mini-
mal systemic absorption [1]

No risk of acquired microbial resistance [1,5,6,8]

Good local and systemic tolerability [1,5,6,8]

Supportive effect through the suppression of excessive inflammation [5]

Facilitation of wound healing (desirable cosmetic and functional outcomes)
[1]

Low cost [1] and ease of application
261
impeding excessive inflammation [5,11], and good local tolerability
[5,6,10] (Table 1). Few antiseptics remain to be relevant for the
prevention and treatment of infection in wound care. These include
iodine carriers (iodophores) with polyvinylpyrrolidone (PVP or
povidone) iodine (which will be discussed in detail as the most
prominent representative), as well as silver, chlorhexidine, ben-
zalkonium chloride, triclosan, octenidine, and polihexanide
(PHMB) and selected dyes such as Eosine.
3. Povidone iodine
The role of iodine in wound care is primarily as an antimicrobial
agent. Povidone iodine has been used and tested in wound healing
for many decades [4,10]. As with other antiseptics, in vitro, animal,
and clinical data using various formulations and concentrations in
studies of differing design, endpoints, and quality continuously
accumulates, while some questions still remain to be answered
[12,13].
In povidone iodine, iodine forms a complex with the synthetic
carrier polymer povidone, which itself has no microbicidal activity
[10]. In an aqueous medium, free iodine is released into solution
from the povidone iodine complex and an equilibrium is estab-
lished, with more free iodine being released from the povidone
iodine reservoir as iodine-consuming germicidal activity proceeds
(Fig. 1) [14,15].
The formulation-, concentration- and temperature-dependent
equilibrium of povidone-bound iodine to free iodine serves to
minimize safety and tolerability issues associated with skin expo-
sure to earlier elemental iodine formulations [10], and appears to
protect against inhibition of granulation tissue formation [16].
3.1. Mode of action
The microbicidal activity of iodine appears to involve the inhi-
bition of vital bacterial cellular mechanisms and structures, and
oxidizes nucleotides fatty/amino acids in bacterial cell membranes,
in addition to cytosolic enzymes involved in the respiratory chain,
causing them to become denatured and deactivated (Fig. 1) [17].
However, the precise sequence of events occurring at the molecular
level has yet to be fully elucidated [6,14,15,18,19]. Cytotoxicity
studies have shown that the bactericidal effect occurs even before
individual human cells are affected (see below).
In vitro evidence suggests that iodine not only has broad spec-
trum antibacterial effects, but also counteracts inflammation eli-
cited by both pathogens and the host response [20]. These anti-
inflammatory effects appear to be multifactorial (Table 2)
[5,16,21,22] and have been shown to be clinically relevant [21,23].
3.2. Preclinical efficacy data
3.2.1. Spectrum of activity
Povidone iodine is one of the few topical antimicrobial shown to
be effective against bacteria, several viruses, fungi, spores, pro-
tozoa, and amoebic cysts (Table 3) [6,10,11,14,24].
In classical antimicrobial testing, povidone iodine has been
shown to kill a variety of bacterial strains known to commonly
cause nosocomial infections, including methicillin-resistant
Staphylococcus aureus (MRSA) and other antibiotic-resistant
strains within 20e30 s of exposure [25,27]. In contrast, compara-
tors such as chlorhexidine require much longer exposure times, and
residual bacteria persist for most species [25,27].
3.2.2. Resistance and cross-resistance
The global prevalence of hospital- and community-acquired
infections is rapidly increasing, together with increasing
262 P.L. Bigliardi et al. / International Journal of Surgery 44 (2017) 260e268

Fig. 1. Mechanism of action of povidone iodine in equilibrium with free iodine.

The active moiety is iodine, oxidising pathogen nucleotides and fatty/amino acids and thus deactivates proteins as well as DNA/RNA.

Table 2
Povidone iodine effects contributing to anti-inflammatory properties.

Host parameters Pathogen parameters

Modulation of redox potential (antioxidant/free radical scavenging activity) [18,19]
Inhibition of production and release of bacterial exotoxins such as a-hemolysin,

Inhibitory effect on human inflammatory effector cells and mediators of phospholipase C, and lipase [5]
inflammation such as TNF-a and b-galactosidase [5,20]
Suppression of bacterial enzymes such as elastase and b-glucuronidase [5]

Reduction in plasmin activity [20]

Inhibition of metalloproteinase production [14,20]

Enhancement of healing signals from proinflammatory cytokines by activation
of monocytes, T-lymphocytes, and macrophages [14]

Table 3
Antimicrobial spectra for four commonly-used antiseptics.

Antiseptic Vegetative bacteria Spores Fungi Viruses

Gram-positive Gram-negative Actinobacteria

Povidone iodine 10% BC þþþ, LS BC þþþ, LS BC þþ SC þþ FC þþþ, LS VC þþ, LS

Polihexanide BC þþþ, LS BC þþþ, LS NA NA FC þþ, IS VC þ, IS
Chlorhexidine BC þþþ, LS BC þþþ, IS NA NA FC þþ, IS VC þ, IS
Octenidine BC þþ, LS BC þþ, IS NA NA FC þþ, IS VC þ, IS
Ethanol 70% BC þ, LS BC þ, LS BC þ NA FC þ, LS VC þ

þ: Weak; þþ: Medium; þþþ: High.

BC: Bactericidal; FC: Fungicidal; IS: Incomplete spectrum; LS: Large spectrum; NA: No activity; SC: Sporicidal; VC: Virucidal.
Adapted from Ref. [8].

resistance to topical antibiotics such as mupirocin, fusidic acid, and
gentamicin, as well as systemic antibiotics [6,28e30]. This poses a
major medical challenge, and appears to be partially attributable to
the overuse and misuse of antibiotics [31,32].
Most data exists on bacterial resistance and cross-resistance to
antiseptics, including chlorhexidine, quaternary ammonium salts,
silver and triclosan, as reported in strains isolated from clinical
settings [6,16,26,27,33]. Evidence of cross-resistance between an-
tiseptics and antibiotics has also been documented [16,34].
Furthermore, resistance to povidone iodine has not been induced in
systematic testing to date [35]. Thus, in contrast to other antiseptics
(with the apparent exception of an absence of cross-resistance to
silver), no acquired resistance or cross-resistance has been reported
for iodine in over 150 years of use [6,14,16,26,27]. This lack of
resistance is likely due to iodine's multiple mechanisms of action
[36].
3.2.3. Activity against biofilms
Biofilms are known to delay wound healing and can promote
bacterial survival in the presence of antimicrobial therapies [37].
The sustained efficacy of povidone iodine on wound healing in the
presence of biofilms has been recently reviewed [38]. Studies have
confirmed the in vitro efficacy of povidone iodine against
S. epidermidis and S. aureus growth, as well as the inhibition of
staphylococcal biofilm formation at sub-inhibitory concentrations
[39]. Furthermore, in a CDC-reactor model, povidone iodine was
efficacious in the presence of biofilms grown in a mixed culture
comprising MRSA and C. albicans, even at highly diluted concen-
trations [40]. The biofilm removal in this assay was greater than
observed with e.g. PHMB, octenidine, chlorhexidine, mupirocin and
fusidic acid [40].
 P.L. Bigliardi et al. / International Journal of Surgery 44 (2017) 260e268 263

3.2.4. Toxicity, tolerability, and allergenicity
A number of cytotoxicity studies have been conducted to
investigate the potential detrimental effects of povidone iodine and
other antiseptics on wound healing typically fibroblasts, keratino-
cytes and other cell lines. While all antiseptics may have a measure
of cytotoxicity due to nonspecific effects, this may not necessarily
be clinically relevant to the wound healing process [41]. Cytotox-
icity data from tests performed on isolated cells must be considered
in perspective. In vitro cytotoxicity can be more pronounced than in
a biological system with a three-dimensional matrix and vascular
system, and not necessarily reflective of in vivo or clinical settings
[16,41]. Interestingly, recent cytotoxicity tests have shown that
povidone iodine has very low cytotoxicity compared to other an-
tiseptics when tested on skin (vs. PHMB, octenidine, chlorhexidine
and hydrogen peroxide) [41] and oromucosal (same as octenidine
but superior to chlorhexidine) cell lines [42]. However, other
studies have reached different conclusions. The inconsistency in
translation may be further due to the multitude of protocols, cell
types and species involved in the testing.
Clinical experience reveals increasing contact allergies to topical
antibiotics such as neomycine [43] or fusidic acid [44], and anti-
septics such as chlorhexidine [45,46]. In addition, sensitisation
through topical applications of antibiotics can induce severe
generalized allergic reactions if these antibiotics are later used
systemically and vice versa [47]. On the other hand proven allergies
against povidone iodine or silver are rare [46]. Sensitisations
against PVP-I are sometimes cross-reacting to iodinated contrast
media [48]. However, these important cross-reactivities can be
discovered by prick, intradermal and/or patch skin tests skin tests.
Interestingly, a recent study has shown povidone iodine to
enhance wound healing via TGF b, not only by increasing granu-
lation but also enhancing neovascularization [55].
3.4. Data on povidone iodine safety
Data on the systemic absorption of antiseptics are scant [1].
Iodine seems to be absorbed from the skin, but more so from
mucosa [56]. However, the condition of the skin barrier will
determine transdermal iodine absorption. The absorption will be
increased if the skin barrier is broken as in wounds and also
dependent on skin age and surface area of application (Fig. 2).
Safety information in povidone iodine product labeling includes
general warnings against use in patients allergic to povidone iodine
or excipients, thyroid disorders, in very low birth weight infants,
and in patients receiving radio-iodine therapy [6,57].
4. Clinical evidence of povidone iodine efficacy
Human trials of povidone iodine in wound healing have varied
widely in regards to inclusion criteria, demographic characteristics,
underlying pathologies, medical interventions, and trial endpoints
[10,52]. Povidone iodine products have been available in many
countries without prescription for decades [56], and are generally

3.3. Non-clinical models

Animal models can sometimes lack clinical relevance, and

appreciable differences exist between the dermal architecture in
animal and human skin. Pig skin can compare closest to human skin
and is therefore the most suitable non-human model. Rodent skin,
in contrast, differs from humans considerably, as it is much thinner,
the epidermis is synchronized to follicular cycles in the furry skin
and it heals mainly by contraction rather than by migration of
epidermal cells [49]. Animal models may further lack applicability
to chronic wound care in clinical settings, as human patients often
have underlying medical conditions that complicate healing [1].
These issues warrant caution when attempting to extrapolate
preclinical data to clinical settings, and suggest that non-clinical
data should be considered in conjunction with robust clinical
evidence.
While some in vitro studies have suggested that povidone iodine
may have a measure of cytotoxic effect [50], no consistent delete-
rious effects on various measures of wound healing have been
demonstrated in in vivo studies, particularly at lower povidone
iodine concentrations [41,51]. A number of animal studies of
povidone iodine in wound healing were published over thirty years
ago [41,52], and the majority demonstrated that concentrations of
up to 10% generally do not inhibit the granulation and epithelial-
ization processes [41].
Several animal studies have also investigated the effect of
povidone iodine on wound microcirculation, with inconsistent Fig. 2. Schematic representation of iodine pharmacokinetics after application of
povidone.
findings. In rabbit ear chamber wounds, the use of a 5% povidone
Absorption: Depends on site the site and area of application, with an intact stratum
iodine solution was associated with an early but rapidly transient corneum being the major barrier (thus higher absorption from mucosa and wounds)
decrease in blood flow [51,53]. However, in the 10% povidone iodine [51,67].
study mentioned earlier, wounds showed faster neovascularization Distribution: Volume of distribution is approximately 23 L; biological half-life
with povidone iodine treatment compared with silver nitrate, so- approximately 2 days [51]; active uptake into the thyroid, intra thyroidal iodine has
a half-life of 7 weeks.
dium hypochlorite, and untreated controls [54]. Another rat model Metabolism: Iodine is rapidly converted into iodide. Iodide is incorporated into
demonstrated no negative effects on capillary blood flow after up to thyroxine (thyroid produces approx. 100 mg/dL).
60 min exposure to a 1% povidone iodine solution [51]. Excretion: 97% are excreted renally with a half-life of 2 days [51].
264 P.L. Bigliardi et al. / International Journal of Surgery 44 (2017) 260e268
considered to be effective antiseptics that do not impede wound
healing [12,52]. A range of povidone iodine products have been
formulated to suit specific medical needs, with current uses and
benefits for various indications discussed below (summarized in
Table 4) [10].
The concentration of free iodine determines the germicidal ac-
tion of povidone iodine [15], and the color of povidone iodine can
be used as an indicator of maintenance of efficacy, and as a
reminder to reapply the product [13]. In addition, color gradation
can aid the practitioner in distinguishing between superficial and
deep burns to guide wound debridement [58]. The frequency of
dressing changes and type of povidone iodine formulation needed
are dependent on the nature and behavior of the wound bed.
In therapeutic use, treatment should stop when symptoms
subside. However, wound healing is more than antisepsis [2,4] and
a good choice of dressings and procedures is essential for the
outcome. Therefore, povidone iodine antisepsis is one important
measure amongst others. This includes good debridement, cleaning
and choice of an appropriate dressing. Negative wound pressure
therapy is getting increasingly popular, but also not a single solu-
tion as infection is a constant threat. Povidone iodine can be used
both prophylactically during wound cleaning and therapeutically as
leave-on application in contaminated chronic and acute wounds. A
typical regimen for cleaning is a soaking time of 20 min each, using
cycle frequencies of four to eight cycles per day [59].
4.1. Prevention of surgical site infection
Surgical site infections (SSI) continue to be a significant source
of increased morbidity, mortality, hospital length of stay, and care
costs [60]. As the majority of infections acquired during surgery
originate from the patient's own commensal flora, disinfection of
the surgical site prior to incision is imperative [61]. A large Amer-
ican study in 7669 clean-contaminated surgical patients [61], as
well as a recent Cochrane review [60], confirmed the value of
preoperative skin antisepsis with povidone iodine as a feasible
clinical option. While there appeared to be little benefit from the
addition of alcohol to povidone iodine [60,61], one study of 200
healthy volunteers showed that the use of 70% isopropyl alcohol
before or after 10% povidone iodine was more effective in reducing
bacterial skin counts than disinfection with a single agent [62]. The
Table 4
Selected commercially-available formulations of povidone iodine and clinical wound healing applications.
Level of exudation High PU foam with 3%
Medium PU foam with 3%
Low Liposomal 3% Hydrogel
Dry Liposomal 3% Hydrogel
Contamination
Increasing level of infection
PU, polyurethane.
a
Plus absorbant dressing.
recent WHO guideline prefers alcoholic chlorhexidine solution over
povidone iodine for pre-surgical use [8,9] However, some recent
studies [63] were possibly not included due to a cut-off date leading
to a recommendation in contrast to recent Cochrane Reviews.
As well as surgical site preparation, intraoperative flushing with
povidone iodine has been shown to reduce infection rates in sen-
sitive indications including breast surgery (at a 4% dilution) [64],
spinal surgery (0.35% dilution) [65], total joint arthroplasty (0.35%
dilution) [66], and intraperitoneal irrigation (1% dilution) during
laparotomy [67]. Such wound irrigation with diluted povidone
iodine has been advocated by a recent WHO guideline [8,9]. In
some countries, the use of povidone iodine dilutions represents
approved usage except for pre-operative skin prepping, where full
concentrations are needed to eliminate resident microflora.
4.2. Povidone iodine in acute wounds
Depending on severity, acute traumatic wounds may be subject
to OTC treatment with clear guidance on when to invoke physician
referral [68]. Such wounds may benefit from the use of povidone
iodine, especially when contaminated or infected [69].
Dry powder sprays may be better tolerated in sensitive wounds
while having a hemostatic effect on some superficial bleeding, and
can be applied without the need for wound dressing. However,
ointments can increase the efficacy and absorption of Iodine by
occlusion effects and can be used in dry wounds or skin and to
prevent adhesion, but it is less indicated if oozing or exudate is
predominant.
4.3. Surgical wounds
In a clinical trial of patients undergoing split skin grafts, the use
of povidone iodine ointment medicated gauze did not delay wound
healing when compared to simple vaseline gauze, and evidence for
a possible earlier onset of epithelialization with povidone iodine
was observed [23]. In addition, wounds treated with povidone
iodine trended toward lower bacterial counts in comparison to the
gauze controls.
In graft wounds, the efficacy of liposomal povidone iodine
hydrogel has been demonstrated to significantly enhance antiseptic
efficacy, wound epithelialization, healing quality, and graft take
PU foam with 3% Dry powder spraya/solution Dry powder spraya/solution
PU foam with 3% Dry powder spraya/solution Dry powder spraya/solution
Ointment 10% Ointment 10% Ointment 10%
Ointment 10% Ointment 10% Ointment 10%
Colonization Critical colonization Spreading/invasive
infection (sepsis)
 P.L. Bigliardi et al. / International Journal of Surgery 44 (2017) 260e268
when compared with chlorhexidine gauze, with no clinically-
relevant topical or systemic adverse effects reported [69,70].
In contaminated and dirty wounds requiring surgical attention
(class III and IV), antisepsis (together with systemic antibiosis and a
check on the tetanus immunization status) is warranted. Intense
debridement and wound cleaning, together with suitable wound
treatment devices such as polyurethane foams may facilitate long
term healing. Dressing changes and antisepsis can be delegated to
family members, allowing for easier follow-up in countries with
slim medical infrastructure. Dry powder sprays for exuding wounds
and ointments for drier wounds allow differentiated treatment.
Patients have reported the additional benefit of a cooling effect
experienced from dry powder sprays, likely due to the evaporating
propellant.
4.4. Burn wounds
The potential for microbial infection is high in burn wounds, and
infection can cause partial thickness burns to progress to full
thickness, with severe consequences [21]. Burns precipitate a
mediator-induced response, with evidence of both local and sys-
temic oxidative changes, increased oxygen free radical activity, lipid
peroxidation, and a reduction in antioxidant scavenging capacity
[21].
In a study of 38 patients with varying burn sizes, the addition of
povidone iodine ointment to a standard hospital antibiotic protocol
alone or in combination with daily systemic vitamins E and C
improved markers of oxidative stress and wound healing. These
effects were accompanied by a 15.3% decrease in the incidence of
infection after 4 days of treatment compared with zero time, a
reduction in the mortality rate from 87.5% for those receiving
standard care to 5.9% in povidone iodine-treated patients, a faster
wound healing time, and reduced hospital cost burden [21].
Furthermore, no adverse systemic effects were observed. The effect
of povidone iodine on neutrophils [5] and oxygen radicals [20] is
potentially of significant value in burns patients due to the limita-
tions imposed by collateral tissue damage [71].
A 5% povidone iodine cream was reported to be superior to
silver sulfadiazine in terms of application and wound healing [72].
This formulation was also shown to be effective and well tolerated
in an uncontrolled pediatric trial [73].
In another randomized trial involving 213 patients with partial
thickness burns, treatment with a povidone iodine dressing was
associated with reduced treatment times, lower analgesia re-
quirements, fewer hospital visits, and less time off work compared
with chlorhexidine dressing treatment [74]. Interestingly, a trend
toward less pain and bleeding on dressing removal was also
observed with povidone iodine [74]. Another trial in a similar pa-
tient population demonstrated faster wound healing and a more
favorable cosmetic result with liposomal povidone iodine hydrogel
versus silver sulfadiazine [75].
The authors' clinical experience with the use of povidone iodine
in patients with burn wounds is detailed in Table 5.
4.5. Povidone iodine in chronic wounds
Chronic skin wounds affect 1e3% of the population [76] and
represent a significant clinical and financial burden to healthcare
systems [22], with approximately 50% of outpatients requiring
nursing services [77]. In most cases, chronic underlying disease
undermines normal tissue repair, preventing wounds from healing
as expected even after intense treatment for an extended amount of
time [2,4,22].
Chronic wounds often harbor biofilms that render the infection
more difficult to detect, diagnose and treat [4,32,37]. A shift
265
towards anaerobic and gram negative bacteria seems to occur with
increasing chronicity of wounds [3].A lack of perfusion in these
chronic wounds with insufficiency of the arterial and/or venous
system does not support the routine use of systemic antibiotics to
promote the healing of chronic wounds. Consensus suggests that
systemic antibiotics should only be used in cases of established
clinical infection [7,78]. In addition, about half patients with
chronic wounds develop allergic contact eczemas to topical prod-
ucts applied, particularly to preservatives, emollients, dressing
adhesives, antibiotics (e.g. fucidic acid or neomycine) and anti-
septics (e.g. chlorhexidine). Therefore, the use of hypoallergenic
formulations and active ingredients are important to avoid sensi-
bilisations through the treatment of wounds. Povidone iodine and
silver have in this aspect a very good safety profile.
The benefits of povidone iodine in chronic wound healing, as in
burn wounds [23], may extend beyond its antimicrobial properties
[74].
4.5.1. Venous and arterio-venous leg ulcers
In an intra-individual comparison study, 51 patients with at
least two similar chronic leg ulcers were treated with hydrocolloid
dressings. One ulcer in each patient received additional topical
application of povidone iodine, silver sulfadiazine, or chlorhexi-
dine. While comparable antimicrobial activity was observed with
all three agents, povidone iodine exposure resulted in a highly
significant 2e9 week improvement in healing time, with superior
microvascularity and dendrocyte density [79]. In another study of
female patients with at least two chronic venous leg ulcers treated
with hydrocolloid dressings, daily application of povidone iodine
solution resulted in a faster reduction in ulcer size, a lower bacterial
load, and less pronounced inflammatory effects versus hydrocolloid
dressing alone [80]. Long-term local application of povidone iodine
solution and ointment in a study of 25 patients with venous leg
ulcers (VLUs) secondary to chronic primary lymphedema also
resulted in excellent local tolerability and clinical efficacy, with no
evidence of resistance [81].
In a further study of 63 patients with VLUs, 42 had compression
bandages applied, of whom 21 with superficial infection were
treated locally with povidone iodine, and 21 received systemic
antibiotics [76]. The remaining 21 patients were treated locally
with povidone iodine without compression. Unsurprisingly,
compression increased the ulcer healing rate; furthermore, healing
rates among patients receiving systemic antibiotics were compa-
rable to those treated with topical povidone iodine, but the use of
systemic antibiotics increased the risk of relapse with superficial
bacterial infections (impetigo and folliculitis) compared with local
povidone iodine application (32% vs. 11%, respectively).
4.5.2. Diabetic foot ulcers
In a retrospective study of 30 patients with a total of 42 wounds,
primarily diabetic foot ulcers, 29% of wounds achieved full closure
and 45% achieved partial closure within 6 months with regular
topical povidone iodine application [77]. Another study in ulcer
patients (the majority being diabetic) revealed less pain associated
with povidone iodine dressings compared with cadexomer-iodine
and silver dressings [82]. Under some conditions, diabetic foot ul-
cers may be treated by split thickness skin grafting or allografts, and
povidone iodine antisepsis can help ensure graft success by
reducing the bacterial load in cost-sensitive environments [83].
However, the detailed effects of these antiseptics on skin grafts
require further evaluation in standardized clinical trials.
4.5.3. Pressure ulcers
In a randomized study of 27 spinal cord injury patients with
pressure ulcers, 84% of ulcers treated with povidone iodine
266 P.L. Bigliardi et al. / International Journal of Surgery 44 (2017) 260e268

Table 5
Use of PVP-I in burn wounds: clinical experience.

Burn degree Treatment approach PVP-I formulation used Posology (thickness) Dressing Frequency of change Comment

Superficial second Conservative PVP- I ointment Thick layer Vaseline gauze, and Twice weekly
cotton dressing
Deep second Conservative PVP- I ointment Thick layer Vaseline gauze, and 2 -3 times weekly Optional addition of
cotton dressing corticosteroid may hasten
healing
Third degree split skin graft PVP eI solution as Wet-to-dry dressing Daily During preparation of the
soaked packs as a debriding method wound for grafting

Table 6
Use of PVP-I in chronic wounds: clinical experience.

Type of ulcer (stage) PVP-I product used Application (thickness etc.) Dressing (frequency of change) Comments

Clean diabetic ulcer
Superficially infected or
unhealed chronic diabetic
ulcers
Locally infected diabetic ulcers
with biofilm
Pressure ulcers (various stages)
Venous and arterio-venous
ulcers (locally infected)
Liposomal PVP-I hydrogel
PVP-I ointment Thick layer
PVP-I solution Irrigation/disinfection during
dressing changes (not normally
left on wound surface)
Liposomal hydrogel with 3% Fine film of gel
PVP-I after wound debridement
Diluted PVP-I solution (1:1 with Twice daily for disinfection (not
saline) usually left on wounds)
PVP-I solution
Typically twice weekly As Solution (optionally rinsed off
needed before dressing)Hydrogel
covered with a polyurethane
foam and/or hydrofiber
dressing, optionally thick layer
applied under VAC therapy
Negative pressure dressing2
times per week
PVP-I soaked gauze; Once good granulation is
hydrofiber/hydropolymer achieved, change to occlusive,
dressings; negative pressure moisture retentive dressings
dressingsDaily changes as
required, or at least 2 times per
week
Gel covered with hydrofiber Wounds with biofilm require
and/or hydropolymer initial debridement.Systemic
dressing1-2 times per week antibiotic use is
important.Radiographic
examination to explore access
for drainage may be important
to prevent sepsis.
After cleaning and
debridement, apply negative
pressure dressings or those
filled with hydrofibers or
hydropolymers with/without
silver2-3 times per week

hydrogel achieved re-epithelialization, versus 54% treated with
povidone iodine solution and gauze; however, there was no sig-
nificant difference in the speed of healing (measured in cm2/day)
between the two groups. The authors concluded that the moist
environment created by the hydrogel, rather than the use of a dry
gauze dressing, was the most likely reason for the higher rate of
epithelialization raising questions with respect to the experimental
design [84]. In another study, 18 outpatients with pressure ulcers
and stasis ulcers received daily application of povidone iodine
ointment under and within the dressing, which resulted in a
reduced level of infection and inflammation, and apparent pro-
motion of healing [85].
The authors' general clinical experiences with povidone iodine
use in the treatment of chronic wounds have been summarized in
Table 6. It is acknowledged that an individualized approach should
be taken, depending upon specific wound and patient
characteristics.
5. Summary
healing, including its broad antimicrobial spectrum, lack of resis-
tance, efficacy against biofilms, good tolerability and its effect on
excessive inflammation. Clinical alternatives include chlorhexidine,
silver-containing products, PHMB, octenidine and the old antiseptic
dyes, although they all have different overall profiles that must be
taken into consideration when making a chosing an antiseptic. Of
clinical relevance, wound healing in clean wounds is not impeded
and in colonised wounds is supported [22,67]. Its use is especially
important for sensitive and difficult to treat wounds and in the case
of chronic wounds where an extended duration of therapy is likely.
Some combinations as medicated gauzes make known formula-
tions easier to apply. Newer application methods and formulations,
such as inclusion in wound healing devices or carrier systems such
as liposomes have extended the reach of existing formulations by
combining iodine with modern wound treatment concepts. Due to
its rapid, potent, broad-spectrum antimicrobial properties, and
favorable risk/benefit profile, povidone iodine is expected to
remain a highly effective treatment for acute and chronic wounds
in the foreseeable future.

Mounting evidence suggests that antiseptics should be used in

preference to topical and systemic antibiotics for localized skin Ethical approval
infections. Povidone iodine, the most commonly used iodophor, has
many characteristics that position it extraordinarily well for wound No ethical approval for this review.
 P.L. Bigliardi et al. / International Journal of Surgery 44 (2017) 260e268
Funding
This review was received public funding through A*STAR and
NUH Singapore, and was supported by an educational grant from
Mundipharma Pte Ltd, Singapore.
Author contribution
The Authors: Paul Lorenz Bigliardi, Syed Abdul Latiff Alsagoff,
Hossam Yehia El-Kafrawi, Jai-Kyong Pyon, Chad Tse Cheuk Wa and
Martin Anthony Villa were all involved with (1) the conception and
design of the study, or acquisition of data, or analysis and inter-
pretation of data, (2) drafting the article and revising it, and (3) final
approval of the version to be submitted.
Conflicts of interest
No Conflicts.
Paul Lorenz Bigliardi confirms that I have given academic pre-
sentations for Mundipharma on wound healing and was consulting
them.
Research registration unique identifying number (UIN)
No research registration unique identifying number for this
review.
Guarantor
Professor Paul Lorenz Bigliardi.
Acknowledgements
The authors thank Lee Farrand for providing medical editorial
support, which was funded by Mundipharma Pte Ltd, Singapore.
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