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Abstract
The use of iodine in wound management can be traced back hundreds of years and yet continues to divide and create debate
amongst todays clinicians. Is there a place for this agent in either infected or non-infected wounds? The body of evidence and
pharmacopeia of iodine-based products available can prove daunting. This review outlines the properties of iodine-based products
and seeks to examine the relevant clinical studies in an attempt to provide an evidence-based structure to facilitate the choice of
iodine-based product. The authors reviewed both animal and human studies. Over 50 studies have been conducted on the use
of iodine in wound care. Analysis of the literature reveals that there does appear to be a place for iodine in wound management,
particularly in the presence of infection. However, the literature highlights iodine may cause harm, therefore a sound knowledge
of the factors that contribute to the activity of iodine and its potential for cytotoxicity is required for its judicious use.
RN BN PGDip MRCNA Iodine is a natural element of the halogen group which is also
A/Clinical Nurse Consultant, Wound Management, an essential nutrient in the body. It has been used throughout
Royal Perth Hospital history in wound care for its antiseptic properties but modern
clinicians have concerns regarding its use over fears of
Patrice Mwipatayi
its systemic absorption, impact on metabolic function and
MMed (Surg) FCS (SA) Cert Vasc Surg (SA)
wound healing. With the emergence of multi-resistant stains
Vascular & Endovascular Surgeon,
of organisms and a better understanding of the dynamics
Royal Perth Hospital
of wound healing, the use of topical iodine in wound
*Corresponding author care has taken a different profile. This paper outlines the
properties of iodine-based products and reviews the relevant
research in this field. This will provide the clinician with an Povidone-iodine or polyvinylpyrrolidone iodine complex
evidence-based framework to facilitate the choice of when (PVP-I) is a combination of molecular iodine and
it is appropriate to use iodine-based products in relation to polyvinylpyrrolidone surfactant/iodine complex. It is a water-
wound care. soluble complex with elemental iodine bound to a synthetic
polymer 10% solution in water 17. The bactericidal component
Iodine is free iodine, approximately one part per million (1ppm) 18.
Iodine has been used in wound care since the Greek age (4th Even at low concentrations, the action of iodine is rapid, yet
century BC). Theophrastus, Aristotles pupil, described the the exact mode of action remains unknown 15. Iodine swiftly
use of seaweeds and other plants enriched with iodine in penetrates micro-organisms and attacks key protein groups
relieving pain after sunburn wounds 12. Wounded soldiers (which are essential for bacteria survival free sulphur amino
were first treated with plants enriched with iodine during acids cysteine and methionime), nucleotides and fatty acids;
Napoleons Egyptian campaign 13. Davis, in 1839, also reported this results in bacteria cell death 16. The antiviral activity is
similar to that bacteria, although there is less known about
using iodine for treating wounds during the American Civil
the antiviral action of iodine 15. Table 1 gives a summary of the
War 14. Despite being used for treatment of wounds for over a
antimicrobial spectrum of iodine.
century, the natural element iodine was not discovered until
1811 by the Dijon chemist Bernard Courtois. The name came
Iodine formulations
from the Greek word iodides meaning violet coloured
Povidone-iodine is available in a 7.5% concentration
because of the violet colours of its vapours 13.
scrub with detergent for pre-operative and post-operative
Iodine is a dark non-metallic crystalline solid. The solubility of scrubbing and a germicidal wash, a 5% water-soluble first
elementary iodine in water can be vastly increased by the addition aid cream, and a 10% water-soluble ointment. The most
of potassium iodide 12. Aqueous or alcoholic solutions of iodine commonly manufactured form is a 10% solution in water,
are toxic to tissue and cause skin discoloration, pain, irritation for application as a paint, spray, or wet soak 18.
and inflammation. Aqueous solutions of iodine are also unstable Inadine consists of a knitted viscose fabric impregnated
in solution 15. This resulted in the development of iodophors with a polyethylene glycol base containing 10% povidone-
(iodine carriers or iodine-releasing agents), formulations which iodine equivalent to 1% available iodine.
decreased the free available iodine. Iodophors are complexes of
Cadexomer-iodine contains 0.9% iodine within a
iodine and a solubilising carrier which acts as a reservoir of the
three dimensional starch lattice, formed into spherical
active free iodine 16. The most widely used are povidone-iodine
microbeads and is available as a paste, powder and sheet.
and cadexomer-iodine. Povidone-iodine was first introduced
into Anglo-American countries in the 1960s 13 and cadexomer- Table 2 summarises iodine-based products from a
iodine in the early 1980s. pharmacological perspective.
Povidone-iodine (Inadine TM) Johnson & Johnson Cadexomer-iodine (Iodosorb TM) Smith & Nephew
Composition
Polyvinylpyrrolidone an iodophor (PVP-I), Cadexomer-iodine available in a pad, paste and powder, 50% w/w
which increases the solubility of iodine (equivalent available iodine 0.9%)
and provides its sustained release Composed of a three dimensional starch lattice formed into
This is a chemically bound product spherical microbeads
Inadine consists of a knitted viscose fabric Iodine is released slowly with absorption of wound exudate as the beads
impregnated with a polyethylene glycol (PEG) take up fluid (requires the presence of wound exudate to maximise action)
base containing 10% PVP-I
equivalent to 1% available iodine
Action
Antimicrobial. Antimicrobial
Highly absorbent (1gm 6ml)
Facilitates desloughing
Pharmaco-kinetics
Systemically absorbed Systemically absorbed
Excreted in the urine Excreted in the urine
Biodegradable by amylases normally present in wound fluid
Indications
As an antiseptic dressing for ulcerative wounds Chronic exuding (moderate to high) wounds including leg ulcers,
(e.g. heavily colonised and infected) where there pressure ulcers and diabetic ulcers, particularly when infection
is a small amount of exudate is present or suspected
Prevention of infection in minor burns and Where slough, infection, or the risk of infection is an issue
minor traumatic skin loss
Precautions
Treatment of kidney problems Severely impaired renal function
Pregnant and breastfeeding women Past history of thyroid disorder (more susceptible to
Cases of Duhrings herpetiform dermatitis alterations in thyroid metabolism)
Contraindications
Known iodine hypersensitivity Known or suspected iodine sensitivity
Before and after use of radio-iodine Hashimotos thyroiditis and in cases of non-toxic nodular goitre
Children under 12 years of age
Pregnant and breastfeeding women
Adverse reactions
Contact allergy Contact allergy
Transient pain within first hour of application may be described as
stinging or smarting.
Dosage and administration
Not more than four dressings at any one time Clean the wound do not dry the surface.
(i.e. 9.5 x 9.5 cm). Apply sufficient to cover the wound to a depth of 3mm (ung)
Frequency of dressing change Frequency of change dependent on exudate, change when loss of colour.
May be daily initially, then 2-3 times/week.
A single application should not exceed 50gm
Not more than 150gm/week
Not more than 3/12 continuous treatments.
Interactions
There is a potential interaction between lithium, sulphurazoles
and the sulphonylureas so co-administration is not recommended.
Medical supervision
Suggested for any patient with thyroid disorders
In newborn babies and infants to the age of 6/12
To treat ulcerative wounds, burns, or large injuries
If used for more than one week
Connell S (1991) 20 Chart review of acute wounds requiring suturing in the Infection rates decreased from 11.9% to 6% with the elimination of
emergency department (n=92) povidone-iodine
Darczy J (2002) 21 Chronic ulcers (n=25). Cleaning the wound with PVP-1 solution No significant improvement in wound size or depth. Reduced number of
and PVP-1 ointment placed in the ulcer bacterial colonies within 4 weeks. Infection, satellite ulcer, erythema and
oedema significantly improved after 6 weeks
DeKock et al. (1989) 22 Human burn wounds (n=60) compares povidone-iodine to Fewer bacteria cultured in the povidone-iodine group.
silver sulphadiazine Statistical significance not calculated
Eming et al. (2006) 24 Chronic venous leg ulcers (n=7). Effect of PVP-1 on metalloprotease, Inhibition of metalloprotease activity. Dose-dependent inhibition of
neutrophil elastase and plasmin activity in wound fluid neutrophil elastase activity. Less pronounced for plasmin activity
Fumal et al. (2002) 25 Three groups of 17 patients with at least two similar chronic ulcers. Modest improvement in healing rates at the sties receiving chlorhexidine
Treatment with hydrocolloid dressings (control). One ulcer in digluconate or silver sulfadiazine. PVP-1 significantly increased
each patient received applications of PVP-1, silver sulfadiazine healing rate (p<0.01)
or chlorhexidine digluconate
12
Gordon et al. (1989) 26 Contaminated wounds in emergency department requiring Infection rates 18% with povidone-iodine. No significant difference
suturing (n=248). Compares betadine dry powder vs. savlodil
Georgiade et al. (1973) 27 50 patients with burns treated with betadine ointment 77% of wound cultures did not have bacterial growth after QID application
vs. 42% and 33% for the BID/TID and QOD/QD application groups (p<0.001)
Gravett et al. (1987) 28 500 patients prior to suturing lacerations treated with 11 became infected in the treatment group
normal saline irrigation and 1% povidone-iodine and scrubbing 30 became infected in the control (p<0.01)
vs. same treatment without scrubbing (control)
Hopf et al. (1991) 29 Superficial wounds (n=25). Compares betadine cream vs. Faster epithelization with betadine cream (p<0.01)
Silvadene cream vs. no treatment
Knutson et al. (1981) 30 Burns, chronic wounds (n=759). Treated with povidone-iodine Decrease in infection. Increase in wound healing rates
and sugar (n=90), povidone-iodine ointment and sugar (n=515),
Vol. 16 No. 1
standard treatment (n=154)
Kucan et al. (1981) 31 Compares povidone-iodine (n=15), vs. silver sulfadiazine (n=15), Effect on wound healing not studied. Effect on infection 60% of patients
vs. saline (n=14) in pressure ulcers responded to treatment after 14 days vs. 60% and 90% at the saline and
SSD groups
Lammers et al. (1982) 32 Compared 33 acute wounds soaked in 1% povidone-iodine or No difference in wound infection between the control and povidone-iodine
FEBRUARY 2008
Iodine in wound care: a review of the literature
normal saline vs. no treatment (control) groups. Normal saline group had increased bacterial counts (p<0.0001)
Lee et al. (1979) 33 18 chronic wounds treated povidone-iodine 10% 67% were clinically cured, 33% showed improvement
Two wounds continued to be infected (p<0.001)
Lineaweaver et al. (1985) 6 In vitro comparison of 1% povidone-iodine, 0.5% sodium At full strength all four agents killed 100% of fibroblasts. 0.25% acetic acid
hypochlorite, 0.25% acetic acid, and 3% hydrogen peroxide decreased bacterial survival, the other three agents were equally toxic
on human cells and bacteria
Lineaweaver et al. (1985) 5 In vitro comparison of three topical antibiotics and four All four were cytotoxic to fibroblasts
antiseptic agents (1% povidone-iodine, 0.25% acetic acid, 3%
hydrogen peroxide, and 0.5% sodium hypochlorite) to assess
their cytotoxicity to cultured human fibroblasts
McKenna et al. (1991) 7 0.005% sodium hypochlorite, 0.001% povidone-iodine, 0.005% sodium hypochlorite effective topical antibacterial without inhibiting
McLure et al. (1992) 34 In vitro comparing povidone-iodine 10% and chlorhexidine Povidone-iodine significantly reduced the logarithmic reduction factors than
against 33 clinical isolates chlorhexidine (p<0.001) at full and diluted strengths
Pirard-Franchimont Treatment of hydrocolloid dressing alone or in combination Increase in wound healing rates in povidone-iodine group in first 4 weeks
et al. (2002) 35 with povidone-iodine in venous ulcers (n=30) (p<0.05). Decrease in infection (neutrophilic vasculitis, and bacterial clumps
in povidone-iodine group, significance not calculated
13
Rodeheaver et al. (1982) 36 In vitro testing comparing bactericidal activity of aqueous iodine, Bactericidal activity of antiseptic solution was inferior to aqueous iodine.
povidone-iodine antiseptic solution (Betadine), and povidone- Aqueous iodine significantly potentiated infection, no therapeutic benefit
iodine surgical scrub solution (Betadine), normal saline as control compared with saline. Higher infection rates in the surgical scrub group
compared with control
Saydak S (1990) 37 Pressure ulcers (n=11), two ulcers per patient. Compares Slower healing in the iodine group. No significant difference
povidone-iodine with absorption dressing
Sindelar et al. (1979) 38 Surgical wounds irrigated with either povidone-iodine (n=242) Decrease in wound infection rates in the povidone-iodine group 2.9% vs.
or saline (n=258) 15.1% (p<0.001)
Stringer et al. (1983) 39 Acute wounds (n=80) cleansed with either hydrogen Reduction of wound sepsis with the use of povidone-iodine (p<0.05)
peroxide (n=20), normal saline (n=20), Savlon (n=20),
or povidone-iodine (n=20)
Takahashi et al. (2002) 40 Nine adults bacteriological evaluation of povidone-iodine Dressing changes can be avoided for at least 3 days postoperatively
Vol. 16 No. 1
under opsite dressing
Teepe et al. (1993) 9 In vitro investigation of 35 antimicrobial and antiseptic agents Under certain conditions cultured epithelial cells may be exposed to clinical
on cultured human keratinocytes concentrations of 0.1% povidone-iodine
Vijanto et al. (1980) 8 Surgical paediatric wounds (n=294) compares povidone-iodine No effect on wound healing in any group. Decrease in infection 2.6% with
5%, povidone-iodine 1%, or saline (control) 1% povidone-iodine vs. 8.5% of the control group. Increase in infection
FEBRUARY 2008
Iodine in wound care: a review of the literature
Archer et al. (1990) 41 Porcine model (n=3), four sites surgically incised treated with either, Impaired healing in the povidone-iodine group.
0.8% povidone-iodine, semi-permeable film, or sugar paste Statistical significance not stated
Bennett et al. (2001) 42 Porcine model, six wounds treated with either 5% mafenide Re-epithelialisation not significantly influenced in any group. Mafenide acetate
acetate, 10% povidone with 1% free iodine, 0.25% sodium and sodium hypochlorite increased neodermal thickness (p<0.05),
hypochlorite, 3% hydrogen peroxide, 0.25% acetic acid, and hydrogen peroxide and acetic acid inhibited neodermal formation (p<0.001.
one untreated control Apart from hydrogen peroxide all treatments increased fibroblast proliferation.
Mafenide acetate and betadine enhanced angiogenesis (p<0.05)
eusol, povidone-iodine 5%, povidone-iodine 1%, hydrogen Eusol and chloramine T the formation of granulation tissue ceased.
peroxide, chloramine T, and chlorhexidine gluconate 0.05%
Geronemus et al. (1979) 43 Multiple wounds on domestic pigs treated with either Neosporin Neosporin significantly increased re-epithelialisation rates by 25%. Furacin
ointment, Furacin, silvadine cream, pharmadine (contains 9% to retarded healing rates. Pharmadine did not affect the healing rate. Both Silvadene
12% free iodine), or no treatment and its vehicle increased re-epithelialisation by 28% and 21% respectively
14
Gruber et al. (1975) 44 Rat model multiple partial and full thickness wounds treated with No effect on wound healing, 12.2 and 9.3 days mean healing time for betadine
0.25% acetic acid, povidone-iodine, and 3% hydrogen peroxide, vs. 12.4 and 9.5 for saline in partial-thickness wounds in rats and humans;
with a control of normal saline. Ten human donor sites half the 19.2 vs. 19.5 in full-thickness wounds in rats, non-significant difference
donor site no treatment (control), the other half received one of
the antiseptic agents
Howell et al. (1993) 45 Lacerations in a guinea pig model contaminated with S. aureus Effect on wound healing not studied. No effect on bacteria levels
(n=48) vs. saline; cefazoline; no treatment
Kashyap et al. (1995) 46 Incision wounds (n=60) in mice randomly assigned to one of four Povidone-iodine as well as steroid group had significantly reduced wound
(A-D) treatment groups. A and B received either povidone-ointment strength/no effect on collagen
and ointment vehicle with no povidone-iodine. Group D no
ointments (control), Group C received cortisone acetate
Vol. 16 No. 1
Kjoselth et al. (1994) 47 Full thickness wounds on mice. Comparing bacitacin, 0.25% Control wounds and wounds treated with silver sulfadiazine and mafenide
sodium hypochlorite, 1% silver sulfadiazine, 8.5% mafenide acetate epithelialised faster (p<0.01). Povidone-iodine epithelialised the slowest
acetate, 10% povidone-iodine, and control no treatment
Malloy et al. (1993) 48 Male rats (n=50), surgical incisions compares povidone-iodine Prolonged impairment of healing in povidone-iodine group (p<0.05)
FEBRUARY 2008
Iodine in wound care: a review of the literature
No effect on tensile strength (17.52 gm/mm2 tensile strength after I week vs.
the animal used for wounding, and clearly describe methods
Decrease in bacteria (S. aureus) 5.94 log bacterial counts after 24 hours and products used in treating the wounds. Different types
Apelqvist et al. (1996) 54 Diabetic foot ulcers (n=250, 12 treated with cadexomer-iodine, No difference in wound healing in either group
13 with standard treatment
Danielsen et al. (1997) 55 Venous leg ulcers (n=17) treated with cadexomer-iodine for the Decrease in bacterial counts (65% of patients had negative P. aeruginosa
effectiveness in the treatment of Pseudomonas aeruginosa cultures after 1 week
Floyer et al. (1988) 56 Venous leg ulcers (n=30) treated with cadexomer-iodine to Wound healing increased (15 out of 18 healed or reduced in size, 3 increased in
establish the effectiveness in wound healing, infection and size). Decrease in clinical signs of infection. 11 were withdrawn from the trial
sensitivity (pain n=8, increase in size n=4, new ulcers n=3, unrelated n=1). No allergies
developed
hydrocolloid dressing, or paraffin gauze in the hydrocolloid and paraffin gauze groups)
Harcup et al. (1986) 58 Venous leg ulcers (n=72) cadexomer-iodine vs. standard treatment Increase in wound healing. Ulcers reduced by 36% after 4 weeks of treatment
vs. 10% in standard treatment (p<0.01%). Decrease in infection (p<0.05-p<0.001)
Hillstm (1988) 59 Venous leg ulcers treated with cadexomer-iodine (n=38) vs. Increase in wound healing in cadexomer-iodine group, 34% reduction in ulcer
standard treatment (n=36) size vs. 5%. Decrease in wound infection
Holloway et al. (1989) 60 Venous leg ulcers treated with either cadexomer-iodine (n=38) Increase in wound healing rates in cadexomer-iodine group (p<0.0025).
16
or standard treatment of wet to dry dressings (n=37) No statistical significance on infection
Laundanska et al. (1988) 61 Venous leg ulcers treated with cadexomer-iodine (n=30) vs. Increase in wound healing 74% mean reduction of size after 6 weeks vs.
standard treatment cleaning with hydrogen peroxide and zinc 54% in standard treatment (p<0.01)
paste dressing (n=30)
Moberg et al. (1983) 62 Decubitus ulcers (n=34) treated with cadexomer-iodine (18) vs. Increase in wound healing in cadexomer-iodine group (76% decrease in ulcer
standard treatment; saline dressing, debriding agent or size vs. 57%) (p< 0.05%)). Decrease in pain, pus and debris (p<0.005%)
non-adhesive dressing (n=16)
Moss et al. (1987) 63 Venous ulcers (n=21) treated with cadexomer-iodine vs. No significant difference in wound healing rates.
debrisan (n=21) Neither therapy significantly reduced colonisation
Ormiston et al. (1985) 64 Venous leg ulcers (n=60), cadexomer-iodine (n=30) vs. standard Increase in wound healing (0.89cm2/wk ulcer healing vs. 0.46 in the
treatment; gentian violet, and polymyxin-bacitracin ointment (n=30) standard treatment (p<0.0001). Non-significant effect on infection
Skog et al. (1983) 65 Venous leg ulcers (n=74) cadexomer-iodine (n=36) vs. standard Decrease in ulcer size 34% after 6 weeks treatment vs. 5% increase in size in
Vol. 16 No. 1
treatment at each centre (n=38) standard treatment group. Decrease in infection in treatment group
Steele et al. (1986) 66 Venous leg ulcer (n=38) cadexomer-iodine vs. standard No difference in wound healing rates. No statistical significance at 1, 4, or 6 weeks
treatment (n=36)
Stewart et al. (1987) 567 Venous leg ulcer (n=46) cadexomer-iodine vs. Intrasite (n=49) No statistical difference in wound healing rates
Travainen (1988) 68 Venous ulcers (n=27) cadexomer-iodine (n=14) vs. Increase in wound healing (64% healed vs. 50% of dextranomer group after 8
FEBRUARY 2008
Iodine in wound care: a review of the literature
Malloy & Brady 48 used a rat model (n=50) with two incised povidone-iodine. Clean lacerated experimental wounds in
full thickness wounds each comparing normal saline wick to 60 mice were randomly assigned to one of four treatment
povidone-iodine wicks, and found that healing was delayed groups (povidone-iodine, ointment vehicle, cortisone acetate
for 30 days in the povidone-iodine group compared to 15 or no treatment), in research by Kashyap et al. 46 designed to
days for the saline wick wounds. With a larger sample size measure the effect of povidone-iodine on tensile strength.
(n=341), Mulliken et al. 51 compared povidone-iodine with The groups treated with povidone-iodine and steroids had
Ringers solution also in experimental incision wounds in significantly reduced tensile strength in comparison to the
rats. Their results demonstrated that brief irrigation with other groups. Kjoseth et al.s 47 results demonstrated earlier
povidone-iodine solution does not affect factors important in neovascularisation in the groups treated with povidone-
the recovery of tensile strength during wound healing, such iodine and silver sulfadiazine than with other antiseptic
as fibroplasia and collagen cross-linking in the clean incised agents, (control, silver sulfadiazine, mafenide acetate, silver
wound. nitrate, bacitracin and povidone-iodine) in full thickness
wounds on mice. However, epithelialisation was significantly
A marked difference of toxicity was established when Severyns
slower with povidone-iodine than with any of the other
et al. 53 compared irrigation of the femoral vessel in rats with
agents tested.
saline, chlorhexidine or povidone-iodine. Irrigation with
povidone-iodine caused the more damage to the vascular
Cadexomer-iodine
endothelium and thrombosis than the other agents tested.
The majority of studies involving cadexomer-iodine are on
This supported the work of Brennan et al. 4 that, under
human subjects. Three studies used the experimental porcine
experimental conditions, chlorhexidine was the safer agent to
model. Mertz et al. 71 demonstrated that, unlike povidone-
use as a wound irrigation fluid.
iodine, cadexomer-iodine applied daily in comparison to
Two studies have been conducted using mice 46, 47, both cadexomer ointment (the vehicle without iodine), or no
demonstrating impaired wound healing with use of treatment control, was able to accelerate the rate of epidermal
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Lamme et al. (1998) 69 Full thickness pig wounds, treated with Increase in re-epithelialisation at 6 and 9 days in
cadexomer-iodine (n=12), iodine with starch cadexomer-iodine group (p<0.05)
(n=120 or saline (n=12)
Mertz et al. (1999) 70 Partial thickness pig wounds, inoculated with Cadexomer-iodine reduced the bacteria (p<0.004)
methicillin-resistant S. aureus.
Assigned to three groups; air exposed untreated
control, cadexomer (vehicle) dressing with starch
no iodine, or cadexomer-iodine dressing
Mertz et al. (1994) 71 Partial thickness pig wounds (n=120). Three Increase in epithelisation in the cadexomer-iodine
treatment groups; cadexomer-iodine, air exposed, group vs. controls (4.6 days vs. 4.9 and 4.7 days).
and ointment base control Decrease in bacterial count in treatment group
migration and reduce the number of pathogens, including cadexomer-iodine group. Only one of the standard treatment
methicillin-resistant Staphylococcus aureus (MRSA), in partial group healed compared with six in the cadexomer-iodine
thickness wounds in pigs inoculated with MRSA and other group.
pathogens. The author replicated this study in 1999 70,
Thirteen human studies with an English translation have been
inoculating the partial thickness pig wounds with MRSA
conducted comparing the clinical outcomes of cadexomer-
only. The effect of wound healing was not examined in this
iodine with other dressing modalities in the treatment of
study. Again, the results demonstrated the effectiveness
venous leg ulcers. Danielson et al. 55 examined the effects
of cadexomer-iodine in preventing proliferation of MRSA.
of cadexomer-iodine in venous leg ulcers colonised with
Epidermal regeneration and epithelisation was also increased
Pseudomonas aeruginosa. The sample size was small, with
in full thickness pig wounds in research conducted by Lamme
only 19 patients entered into the study, and there was not a
et al. 69. This group compared cadexomer-iodine with normal
control group. Negative cultures were found in 65% and 75%
saline 12 pigs were allocated to each group, statistical
of patients after 1 and 12 weeks of treatment respectively. The
significance was reached (p<0.05).
median ulcer area reduction obtained at 12 weeks was 32.9%.
Human clinical studies using cadexomer-iodine in chronic All patients had a short stretch bandaging system in place.
wounds such as diabetic foot ulcers, venous leg ulcers or
Two separate studies 57, 67 examined the effects of cadexomer-
pressure ulcers have demonstrated a positive effect on
iodine and wound healing rates with conflicting results.
wound healing. There was no difference in outcomes when Hansson 57 conducted a randomised, multi-centre trial
comparing cadexomer-iodine with gentamicin solution, comparing cadexomer-iodine (n=56) with either a hydrocolloid
streptodornase/streptokinase or saline gauze in diabetic foot dressing (n=48) or paraffin gauze (n=49) as an adjunct to
ulcers 54. The study was small, with 12 patients treated with compression therapy. There was a mean reduction in ulcer size
cadexomer-iodine and 12 treated with standard treatment of 62% versus 42% and 24% in the hydrocolloid and paraffin
(as outlined). The weekly costs were lower in the treatment gauze groups. Statistically significant difference in wound
group. Perhaps the outcomes would have been different healing rates was not reached by Stewart & Leaper 67 when
by comparing silver impregnated dressing which were not comparing cadexomer-iodine (n=49) with Intrasite gel (n=46) in
available at the time of the study. chronic leg ulcers. The ulcers studied were of various aetiology,
including venous, arterial, traumatic, diabetic and mixed/
A randomised study of the treatment of pressure ulcers
other, with the majority (n=42) being venous. Compression
was undertaken by Moberg et al. 62. This group compared
bandaging was not used in patients with venous leg ulcers; this
cadexomer-iodine (n=16) to patients receiving standard
may account for the lack of difference in healing rates in either
treatment (n=18) which comprised of saline, enzyme-based or
of these groups.
non-adhesive dressings. There was a considerable reduction
in pus, debris and pain of the ulcers in the cadexomer-iodine Of the remaining 10 studies examining the effects of
group as well as accelerated wound healing. The ulcers were cadexomer-iodine in patients with venous leg ulcers, eight
reduced by 76% versus 57% after 8 weeks of treatment in the recorded an improvement in wound healing rates and
infection 56, 58-61, 64, 65, 68, whilst the remaining two did not find 34% decrease in ulcer size compared with 5% in the other
this to be the case 63, 66. Moss et al. 63 compared cadexomer- treatment groups. In the standard treatment group there
iodine with dextranomer in 42 patients. The patients were was no effect on infection in 18 patients. However, in 16
observed for 6 weeks on standard outpatient therapy, and out of 23 patients in the cadexomer-iodine group, infection
then randomly allocated to either agent, after which time cleared. Overall, in this study, there was a reduction of pain,
ulcers not responding to treatment could be changed to removal of pus and debris, removal of exudate, stimulation
the other treatment. At the end of the study there was no of granulation and reduction of surrounding erythema in the
significant reduction in wound size or bacterial colonisation group randomised to cadexomer-iodine. Similarly designed
in either group. The authors do not clearly indicate if studies 56, 58-61, 64, 68 have also concluded that cadexomer-iodine
appropriate compression bandaging was in place, as this has a positive effect on wound healing, reducing the bacterial
would also impact on wound healing rates. Steele et al. 66 load and decreasing infections.
recruited their patients from general practice and compared
multiple standard therapies with cadexomer-iodine in 57 Discussion
patients. There was no difference in healing rates. This group
Evaluation of the results of numerous in vivo studies
did not examine the effect on bacteria.
demonstrate overwhelmingly that there is enough evidence
The most commonly quoted study demonstrating the to support the use of cadexomer-iodine in the chronic
effectiveness of cadexomer-iodine is by Skog et al. 65, a multi- wound environment. There is a lack of evidence to suggest
centre study of 93 patients with recalcitrant venous leg that cadexomer-iodine would have a negative impact on
ulcers. Patients were randomised to either cadexomer-iodine wound healing and infection; on the contrary, wound-healing
or one of various standard therapies (enzyme preparations, rates are improved. There are no studies demonstrating the
dextranomer, fucidic acid, trypure powder, polymix or silver effectiveness of cadexomer-iodine in acute wounds. However,
nitrate) combined with compression bandaging. After 6 with the correct set of circumstances such as infection, slough
weeks of treatment with cadexomer-iodine, there was a and exudate, one would expect this to transpire in acute
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wounds, although there does need to be further study in this effects on tissue. As illustrated, the systemic effects must
area to substantiate this. always be considered.
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