Download ACTICOAT : A Unique Nanocrystalline Silver Delivery

ACTICOAT: A Unique Nanocrystalline Silver
Delivery System for Burns and Wounds
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TABLE OF CONTENTS
I.
HISTORICAL OVERVIEW OF SILVER
II.
PROPERTIES OF SILVER
III.
NANOCRYSTALLINE SILVER DELIVERY SYSTEM (ACTICOAT™)
IV.
ANTIMICROBIAL PROPERTIES OF NANOCRYSTALLINE SILVER
(ACTICOAT™)
V.
PROHEALING PROPERTIES OF NANOCRYSTALLINE SILVER
(ACTICOAT™)
VI.
ANTI-INFLAMMATORY PROPERTIES OF NANOCRYSTALLINE
SILVER (ACTICOAT™)
VII.
 AND OTHER SILVER
CLINICAL COMPARISON OF ACTICOAT
COMPOUNDS IN BURNS
VIII.
 IN DIFFICULT TO HEAL AND CHRONIC
USE OF ACTICOAT
WOUNDS
XI.
REFERENCES
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I. HISTORICAL OVERVIEW OF SILVER
Silver has long been used for its antimicrobial properties. However, the delivery systems
available, often in the form of a salt, have been the limiting factor to successful biological
use of this noble metal.
Nanotechnology and the ability to deliver silver from a nanocrystalline structure has and
will markedly improve the biologic value of silver. These advances in crystal chemistry
will likely have a dramatic impact on the microbiology, as well as biology of wound
healing and control of inflammation.
We will describe the past, present and future uses of silver in biologic systems focusing
on its biological properties on “wounds”.
Silver has been used for centuries to prevent and treat a variety of diseases, most
notably infections. Silver has extremely potent antimicrobial properties with levels in
solutions exceeding 10 parts per million. Silver ions appear to kill micro-organisms
instantly by blocking the respiratory enzyme system (energy production), as well as
altering microbe DNA and the cell wall, while having no toxic effect on human cells in
vivo.
Free silver ions, or radicals, are known to be the active antimicrobial agent. In order to
achieve a bactericidal effect, silver ions must be available in solution at the bacterial
surface. Efficacy depends on the aqueous concentration of these ions.
However, crystalline silver is quite insoluble in water and in dilute acids making the
available silver cation concentration, inadequate for use as an antimicrobial on a wound
surface.
Beginning in the 1920’s, a small electrical charge was passed through water and silver
crystals in order to obtain an effective silver (electrocolloidal) ion solution to be used
topically on wounds. The charged silver solutions (electro-colloidal) were approved in
the 1920’s by the FDA for use as an antibacterial agent. These solutions are very
unstable and the concentration of silver may be inadequate for an ideal antimicrobial
agent.
Prior to 1940, pure silver in the colloidal form was being commonly used for wound
infection as this period predated the use of antibiotics. After 1940, systemic antibiotics
became prevalent.
Carl Moyer in 1965 introduced the use of a 0.5% silver nitrate solution for burn wound
management. The silver nitrate was a more stable compound and replaced colloidal
silver. During the same time period, Dr. Charles Fox developed another silver
compound for wounds and burns, silver sulfadiazine. The sulfadiazine is composed of
propylene glycol, stearyl alchohol and isopropanolol. This compound was formulated as
a water soluble cream to be applied twice a day to a wound surface instead of a
continuous soak required of silver nitrate for continued silver delivery.
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Over the past 40 years silver sulfadiazine has become a very popular anti-microbial
silver delivery system. However, both nitrate and sulfadiazine impair fibroblast and
epithelial proliferation, impairing healing.
Advances in the field of nanotechnology were required before a new form of pure silver
was available for use in biological systems.
Toxicity of Silver Compounds
Silver Sulfadiazine Cream
•
•
•
•
•
Can produce bone marrow suppression
Pro-inflammatory response
Toxic to fibroblasts
Can lead to propylene glycol toxicity
Allergic reactions reported
Silver Nitrate 0.5% Solution
•
•
•
Nitrate can produce oxidant injury
Binds chloride
Can retard epithelialization
Pure Silver
•
•
No local or systemic toxicity described
No impairment of healing
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II. PROPERTIES OF SILVER
A) Safety
Silver itself is considered to be non-toxic to human cells in vivo. The only reported
complication is the cosmetic abnormality argyria caused by precipitation of silver salts in
the skin and leading to a blue-gray color. Although not yet defined there remains some
concerns about the potential of high tissue levels of silver altering enzyme function.
Silver nitrate in vitro has been shown to have a negative impact on fibroblasts,
hepatocytes and lymphocytes, but studies on anodically generated silver ions show no
impact on mammalian cells in culture. Clinical evaluations carried out by Bador and
Coombs et al. found no tissue toxicity. The major complications attributed to silver
compounds are due to the complex or anion namely the nitrate and sulfadiazine not the
silver itself. Both nitrate and sulfadiazine have been shown to impair fibroblast and
epithelial cell proliferation impairing healing allergic reactions to topical silver are rare.
Overview of Silver and Wounds
•Potent antimicrobial
-kills instantly
-blocks respiratory enzymes
•Non-toxic to human tissue
•Pro-healing properties
•Anti-inflammatory properties
B) Antimicrobial Effects of Silver
Silver exerts its antimicrobial effects by interfering with the respiratory chain at the
cytochromes (3). Silver ions also interfere with components of the microbial electron
transport system, bind DNA and inhibit DNA replication.
Silver is effective against a broad range of aerobic, anaerobic, Gram-negative and
Gram-positive bacteria, yeast, filamentous fungi and viruses.
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In order for silver to be biologically active, it must be in a soluble form such as Ag+ or
Ag0 clusters. Ag+ is the only form present in silver nitrate, silver sulfadiazine and other
ionic silver compounds. Ag0 is the metallic or uncharged form of silver found as one of
the silver species in nanocrystalline, silver structures. In solution, the Ag° exists in a
sub-crystalline form, less than 8 atoms in size. Silver nitrate and silver sulfadiazine
release silver at concentrations up to 3,200 ppm (silver release from silver sulfadiazine is
much slower than that from silver nitrate) but most of this is rapidly inactivated through
the formation of chemical complexes.
Early silver formulations compensated for the rapid loss of silver ions by frequent
replacement. Although this was effective, it created problems for healthcare
professionals and patients, and resulted in large excesses of silver being delivered to the
wound. In burns units, silver sulfadiazine is commonly applied twice a day and silver
nitrate up to 12 times a day. Repeated applications increase discomfort and wound
trauma.
The nature of the solute also affects the biological activity of silver. In complex organic
biological fluids, continuous concentrations of silver >50 ppm and as high as 60.5 ppm
are needed to kill microbes.
Therefore in wound management, quantities of silver ion should be sufficient to provide
sustained bactericidal action. Acticoat with nanocrystalline silver also provides the Ag0
form of silver, which is far less rapidly deactivated by chloride or organic matter than the
ionic form.
In addition to it’s recognized antibacterial properties,
silver delivered to a wound, has been reported to also
have anti-inflammatory and pro-healing properties.
C) Pro-healing Properties
Although silver in an electro colloidal form, had been reported to improve the healing of
indolent wounds in the early 20th century, that finding disappeared with the use of silver
salts and complexes. Recently there have been several reported studies of improved reepithelialization rates across wounds with silver in the nanocrystalline form. The
mechanism, although unknown at present, does not appear to be due to silver’s
antimicrobial action. Controlling the pro-inflammatory cytokines and proteases may be a
factor.
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D) Anti-inflammatory Properties
Increased wound inflammation not only accentuates pain but markedly impairs healing.
Several heavy metals have been reported to decrease surface inflammation, the most
recognized being gold. Wound surface inflammation has been reported to be decreased
with the use of nanocrystalline silver. Excess metalloproteinases (MMP) are known to
increase inflammation by both increasing inflammatory cell exudates and also leading to
a non-healing chronic wound.
A characteristic of this type of wound is excess surface MMP activity, decreased
inhibitory MMP activity and degradation of growth factors by the MMP’s.
Nanocrystalline silver has been shown both in vitro and in vivo to decrease but not totally
prevent MMP activity as some activity is needed to remove devitalized tissue.
The mechanism for this action also remains unknown. Decreasing the necessary zinc
activity required for MMP’s is one possibility. The other is an effect on the expression or
release of pro-inflammatory cytokines. Silver in the nanocrystal form also decreases
wound release of TNFα.
III. NANOCRYSTALLINE SILVER DELIVERY SYSTEM (ACTICOAT™)
A) Nanotechnology
The property of matter depends on size and many of the chemical and physical
characteristics change significantly when matter is reduced in size. Nanotechnology is a
general term that refers to a relatively new frontier of scientific endeavor. The prefix
“nano” signifies one-billionth. Therefore, a nanometer is one-billionth of a meter, a
nanogram is one billionth of a gram. Ten hydrogen atoms placed side by side measures
one nanometer in length. Silver crystals sputtered under normal vapor deposit
conditions result in tightly adherent crystals of 100-900nm in diameter. Decreasing
crystal volume by nanotechnology markedly increases the exposed surface area of the
crystal which increases the available surface for chemical reactions to take place over a
shorter time period.
Decreasing the particle size will also, in general, change the physical/chemical
properties of the material. Examples of changed properties resulting from nano-sized
metals, include increased superconductivity and increased optical and electrical
properties. Nanosizing can also lead to a more economical utilization of expensive
materials-meaning that can use less material because the reactions are more efficient.
Although not yet specifically defined, it is clear that some of the properties of silver in a
nanocrystal are quite different than the typical crystal. A large portion of the silver is
available as grain or interphase boundaries, considered by some to be a new form of
matter. Orientation relationships are very different for the silver. Also some of the silver
appears to be in an oxidized form. Increasing the variety of oxidized silver species
would be expected to increase solubility and lead to a much higher overall reactivity.
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Nanotechnology
•Nanometer (one billionth)
•Nanosilvercrystals (10
-20 nm)
•Huge surface area
•Crystal properties very different
-much more reactive
-higher energized state
-increasing silver penetration
•Burrell R. An electrochemical analysis of thin silver
films produced by reactive sputtering.
Electrochem
Soc 2001:148; 791.
•OvingtonL. Nanocrystalline
silver; where the old and
familiar meets a new frontier. Wounds 2001:13; 5.
Normal Silver Crystals
Normal crystallization is shown micron sized
particles closely adherent, decreases surface
area for water exposure and silver release.
Nanocrystalline Silver
The structure of the silver system Acticoat
is evident using scanning electron
microscopy. The silver coating consists of
nonacrystals, which allow for rapid
exposure to water and subsequent silver ion
and silver radical release.
There is a marked increase in surface area for water to reaction with silver in the
nanocrystalline form. In addition, other reactive silver species are released from the
more unstable nanocrystal.
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B) Physical Properties Of Acticoat™ Nanocrystalline Silver Delivery System
The method of making the nanocrystalline material on Acticoat is called physical vapour
deposition. Argon gas is introduced into a vacuum chamber that contains a silver
cathode, the chamber acting as the anode. When an electric current is passed through
the gas, positive argon ions are created which accelerate towards the negatively
charged silver cathode. On impact, the argon ions knock out silver atoms that travel
towards the substrate to be coated where they deposit and develop into nanocrystals
when energy inputs are limited. These are only about 15 nanometres across, which is
between 30 a 50 atoms. Thus a nanocrystalline structure is created with a significant
grain-boundary component and increased surface area.
These changes to the physical properties of the crystal lattice result in a meta-stable,
high-energy form of elemental silver. Normal silver placed in water will not dissolve, but
nanocrystalline silver dissolves to provide a continuous concentration in solution of
around 70 ppm. Both Ag+ and Ag0 are released: it is thought that Ag0 does not react
with chloride as quickly as Ag+ and does not require a carrier. As the ions in solution
are depleted, the equilibrium shifts and more Ag+ and Ag0 ions are released. By
contrast, silver nitrate provides a huge immediate concentration of silver ions which, two
hours after application, have virtually all been chemically consumed by chloride.
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C) Silver Nanocrystalline Delivery Dressing (ACTICOAT™)
The silver delivery dressing developed by Dr. Burrell is a 3 layer wound dressing
consisting of an absorbent rayon/polyester core laminated between an upper and lower
layer of silver coated high density polyethylene mesh. The laminations are held in place
with ultrasound welds. The silver coating, which consists of 0.25±0.4 mg silver per mg
high-density polyethylene, is a binary allow of silver and oxygen with negligible
contaminants (content is 99.99% silver).
The coatings are highly porous and consist of nanocrystals organized into coarse
columnar structures.
This unique physical structure, in combination with the oxygen atoms/molecules that are
trapped in the crystal lattice, contribute to the enhanced solubility of the films which
continue to release silver until the concentration in solution reached 66mg/L a level that
is 50 to 100 times higher than is expected from typical bulk pieces of silver metal.
The silver crystals coat both sides of the product with a polyester core between the
sheets to maintain the moisture needed for silver release. Either side of the silver
dressing can be placed onto the wound surface. The silver coating when wet with sterile
water, produces a continual release of Ag+ and likely other silver radicals for days. The
delivery system readily olds to the wound producing wound occlusion as well as
maintaining a wound surface moisture layer. Current published data indicates that this
silver release product produces a rapid and complete killing of essentially all pathogens
found on a wound.
The silver delivery system is represented.
Both silver layers release the silver ion exposure to water.
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REACTIVE SPECIES OF SILVER RELEASED FROM
SILVER PRODUCTS
Medical Name
Initial forms of Silver Species in
Silver
Solution
Nanocrystal Silver Metallic Ag
Ag+AgOH
Delivery
Nanocrystal
Ag° clusters
1% SSD
Ag+
Ag+
(0.5%) Silver
Nitrate
Arglaes
Ag+
Ag+
AgKzPO4
Ag+
Note the different silver species released by the
nanocrystals, ACTICOAT™ System
Note: the release of silver with the nanocrystalline pure silver delivery system is constant
for over 48 hours when exposed to water. The silver concentration on the wound
surface is 20-30 times greater than the concentration required to kill microbes.
(The concentration of Ag+ required to kill pseudomonas is comparable to that required
for killing of other microbes. This constant silver release is unique and quite different
from the initial pulse release of silver Ag+ from other products.
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Silver Delivery Systems (ACTICOAT)
Nanocrystal Silver Delivery System
(ACTICOAT)
A three ply dressing consisting of inner
rayon/polyester core between two layers
of silver coated mesh
•Nanocrystalline silver placed onto a
bilayer of polyethylene for controlled
release
•Ionic silver and silver radicals released in
ideal concentrations when exposed to wate
•Active silver release up to 7 days
•Maintains moisture layer for healing betwe
wound and silver membrane
Highly bacteriocidal fungicidal
•Nanocrystal coating contains 0.841.34mg silver/cm2
Silver concentration in current silver products
•
Silver Nitrate 0.5% solution
-Silver concentration 3180 µg Ag+/mL water
-Ag+ availability 318µ g Ag+/mL water
-Immediate release
•
Silver sulfadiazine 1% cream
Silver concentration 3030Ag+/gram
-Silver availability 3030 µg Ag+/gram
-Release over 12-24 hours
•
Silver delivery (Nanocrystals)
-Silver concentrations 13%
-Silver availability 100 µg Ag+/mL water
-Stable release for at least 48 hours
Although the nanocrystal silver delivery membrane has less total silver, a more rapid and
sustained release appears to occur due to the nanocrystalline structure. This process
markedly increases the surface area of the silver when exposed to the wound. This
physical property may explain its more rapid bacteriocidal action. Less total silver (Ag+)
released by the nanocrystals should decrease any potential toxicity.
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The large sheets of Acticoat™ nanocrystal silver is shown form fitting to a large wound
One side of the sheet is typically darker than the other, but both sides actively
release silver when water is added.
The Acticoat 7 dressing releases silver for 7 days and
comes in a variety of sizes to fit different wound pages
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IV. ANTIMICROBIAL PROPERTIES OF NANOCRYSTALLINE SILVER
As can be seen in Table 3 of Nanocrystal Silver, the aqueous concentration of silver ions
released from the nanocrystalline film is approximately 3% of that released from a 0.5%
silver nitrate or a 1% silver sulfadiazine cream. However, the biological properties of the
silver released from nanocrystals are much greater. Silver resistance has been reported
in the literature and is mediated through one of two pathways. Either the silver is tied up
in the cell wall and membranes, or it is actively transported out of the cell. Bacterial
organisms that have either one of these resistance mechanisms, which are effective up
to 1000 g/mL Ag+.have been tested against the nanocrystalline silver coated dressing.
These tests showed that these organisms were susceptible to the silver produced by the
nanocrystals but not to Ag+ from silver nitrate. These findings, as will be described,
strongly suggest that other species of silver besides Ag+ are released from the
nanocrystals. (ACTICOAT™).
MRSA death curve comparing different silver
compounds. Note increased killing with Acticoat
silver.
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VRE death curve comparing different silver
compounds. Note increased killing with Acticoat
silver.
The lower amount Ag+ released should also decrease the potential of silver toxicity to
cells, if it exists, by a substantial margin when compared to the other silver agents.
In another study nanocrystalline silver was extracted from the silver delivery system
Acticoat by incubating the dressing in pure water at 37°C in a shaking incubator, and
silver concentrations were measured using atomic absorption spectrophotometry. The
minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC)
were determined using five bacterial isolates of clinical interest, and results were
compared for nanocrystal silver, silver nitrate and silver sulfadiazine, based upon total
silver. Nanocrystalline silver had similar MIC and MBC values when compared to three
silver containing agents. Kill kinetics were also studied, using 2.0 cm x 2.0 cm of pieces
of silver dressing, and the same sized pieced of dressing impregnated with either silver
nitrate or silver sulfadiazine.
Bacterial survival was measured using a plate counting technique. Nanocrystal silver
demonstrated the fastest kill times for the five bacteria used. In most instances with
Nanocrystal silver, bacterial survival was undetectable 30 minutes after inoculation,
whereas at least 2-4 hours elapsed before no viable cells were detected with silver
nitrate or silver sulfadiazine.
These findings strongly suggest that silver species in addition to Ag+, released from the
nanocrystalline film are responsible for the more potent antimicrobial properties. To date
the nanocrystalline silver system kills all microbes found in a wound including fungi and
all current antibiotic resistant organisms such as Vancomycin resistant enterococcus
(VRE) and methicillin resistant staphylococcus aureus (MRSA).
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The susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) to a range of
silver preparations: silver sulfadiazine, silver nitrate, silver calcium phosphate (Arglaes™
dressing; Medline Industries Inc., IL, USA), metallic silver film (Silverlon®; Argentum
Medical, IL, USA) and nanocrystalline silver (Acticoat™) was tested. After 30 minutes,
nanocrystalline silver had reduced the number of viable bacteria to very low levels
(102CFU/mL) while after 2 hours the other dressings had still not reduced the levels to
below 105CFU/mL.
Similar results are seen with vancomycin-resistant enterococcus (VRE). The Acticoat™
dressing has been shown to inhibit the growth of Pseudomonas aeruginosa and
S.aureus for a minimum of nine days while a silver film dressing was only able to inhibit
the growth of P. aeruginosa for four days of repetitive challenge, and S. aureus for one
day. This may be due to the presence of phosphate in the film dressing which is known
to reduce the bactericidal properties of silver.
Sustained release of silver is important in reducing bacterial burden. Silver nitrate has to
be applied every two hours to be effective, and the cream base in silver sulfadiazine
reacts with serous exudates to form a pseudo-eschar that must be removed before the
cream can be re-applied. Acticoat™ can be left in place for up to seven days, meaning
that the wound does not have to be manipulated during this period, which may cause
trauma to the new epithelial growth and may spread bacteria into the blood stream.
Resistance to silver is rare, but not unknown. There are two forms of resistance: silver
can be bound by cells in the form of an intracellular complex: and it can also be excreted
from microbes using cellular efflux systems.
Resistance can be induced using low concentrations of silver. Exposure of various E.
coli strains to silver nitrate started at half the minimum inhibitory concentration (MIC)
value (2-4 mg Ag+/L) produced resistance which increased with each generation.
Bactericidal levels of silver do not produce resistance as dead cells cannot mutate, but
MIC and sub-MIC levels can result in the development of resistance. Resistant cells
appear to have reduced permeability of the outer membrane to silver combined with an
ability to pump silver out of the cell – an active efflux mechanism.
This emphasizes the importance of using clinically relevant levels of silver particularly as
a range of silver dressings are now in widespread use. Non-controlled use of silver
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(sub-lethal levels) may result in bacteria developing resistance in the way that antibiotic
and biocide-resistant bacteria have emerged.
V. PROHEALING PROPERTIES OF NANOCRYSTALLINE SILVER

ACTICOAT
Past observations and recent studies using a pure silver delivery system have
demonstrated an increased rate of healing in wounds and burns compared to other
wound care products.
The direct healing effect of pure silver has yet to be defined. Silver has a number of
effects which would indirectly increase healing, namely controlling infection, decreasing
excess inflammation, maintaining moist healing and decreasing wound surface
mechanical trauma caused by frequent dressing changes.
Mechanisms for Pro-Healing Effect of Nanocrystalline Silver
.
•
•
•
•
•
Direct effect in wound biology
Controlling surface microbes
Moist wound healing maintained
Decreasing mechanical trauma during dressing
changes
Decreasing excess wound inflammation
A) Direct Effect of Silver on Healing
Silver has a number of biological effects on the wound surface. It remains to be
determined whether any of these effects produces a healing stimulus.
Several studies comparing silver released from a silver nanocrystal delivery system with
other topical antibiotics have demonstrated increased re-epithelialization of partial
thickness wounds and meshed skin grafts. A comparison was made of the rate of reepithelialization of 2:1 meshed skin grafts on excised burn wounds. The nanocrystal
silver group re-epithelialized at a significantly faster rate. No infection was noted in
either group, both using moist wound healing.
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Re-epithelialization rate of Meshed Skin graft.
Typical meshed skin graft (2:1) studied
(Acticoat vs. Neosporin).
Treatment with Acticoat in one group.
Comparison with meshed graft
continuously moistened with Neosporin
solution.
Methods
20 burn patients with bilateral extremity burns
Excised and covered mesh graft (2:1)
One group skin graft covered with Acticoat
Other group skin graft kept moist using Neosporin solution
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The meshed graft re-epithelialized much faster using topical silver (Acticoat) compared
to neomycin solution. (Demling R., et al, The rate of re-epithelialization across meshed
skin graft is increased with exposure to silver, Burns 2002:28; 264)
B) Controlling Surface Microbes
Increasing evidence has demonstrated that wound colonization can result in a bacterial
burden to healing. The concept that one needs 105 organisms per gram of tissue to be
deleterious is no longer considered accurate. Certainly 105 organisms or greater is
destructive to healing but fewer bacteria can also impede healing as the immune
defenses of a wound and of a patient vary considerably, e.g. the elderly diabetic versus
the healthy young adult.
Improved antimicrobial activity should therefore assist healing independent of any direct
healing property of silver.
C) Maintaining Moist Wound Healing
Numerous studies followed which demonstrated that wound occlusion and moisture
improved all phases of healing. The data demonstrating that a moist wound surface
increases re-epithelialization and all other components of wound healing, is now well
established. Any surface desiccation leads the risk of further tissue damage.
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Problems of Surface Dessication
•
•
•
•
•
Increased depth of surface tissue necrosis
Impediment to surface epithelial cell migration
Decreased surface oxygen available for healing
and bacterial killing
Impaired nutrient flow to surface
Increased infection risk
In general, research has shown that a moist wound environment is associated with less
severe and prolonged inflammation; more rapid keratinocyte proliferation and migration;
earlier differentiation of keratinocytes to restore surface barrier function; more rapid
fibroblast proliferation, increase in collagen synthesis; earlier, angiogenesis; and earlier
full-thickness wound contraction. A more rapid decrease in wound volume and surface
area has also been well documented with moisture.
This use of a moist healing environment has not routinely been used in burns because of
the concern for infection. Also the antibiotic creams do not produce a moist healing
environment. In fact, the creams silver sulfadiazine and sulfamylon, will extract water
from the wound surface as a result of the hyperosmolarity of the cream, especially with
drying of the cream.
Advantages of a Moist Wound Surface
•
•
•
•
•
•
•
•
Reduction in wound surface conversion
Decrease in surface desiccation and eschar
formation
Increase in local growth factor production
Activation of surface proteases to remove
devitalized tissue
Decreased surface inflammation
Enhanced wound surface immune defenses
Increased rate of angiogenesis and fibroblast
proliferation
Increased proliferation and migration of
epithelial cells along thin water layer
Silver nitrate solution maintains a moist surface but this approach is not very popular
because of increased nursing care demands as the dressings must be constantly
moistened.
The nanocrystal silver delivery system maintains a moisture layer between the wound
surface and the inner silver membrane. This moisture layer is also a potent antimicrobial
silver solution on the wound surface. Moisture is maintained on a deep burn by wetting
the surface of the Acticoat™. Moisture on a partial thickness wound is provided by the
wound itself under the Acticoat, which is covered with a secondary dressing.
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The ability to maintain both a moist healing environment and an antimicrobial
environment is a unique property of this silver system, especially beneficial for burns and
wounds.
Clean Wound Bed
Addition of Nanocrystalline
silver delivery maintains
moisture layer on wound
surface.
Use of silver cream results
in a pseudo eschar and can
withdraw fluid from this
wound surface.
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Acticoat on Burn (Day 3). Note
moisture layer and lack of exudates when
silver dressing is peeled back.
D) Decreasing Mechanical Trauma
Frequent dressing change and wound manipulation create not only systemic toxicity but
also local wound trauma. The high rates of bacteremias with wound manipulation have
been well described as has the typical pyrogen release and post-dressing change
hyperthermia. Also wound surface manipulation especially on the re-epithelializing
wound will injure new tissue formation Mechanical removal of creams, ointments and
dressings will all cause local trauma. The nanocrystalline silver dressing can remain in
place for days and if wetted prior to removal, mechanical trauma is minimal. In addition,
the exudates beneath is usually minimal and there is no film or byproduct, which
requires mechanical removal.
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VI. ANTI-INFLAMMATORY PROPERTIES OF NANOCRYSTALLINE SILVER
)
(ACTICOAT
Some inflammation is needed for wound healing. However, excess inflammation on a
wound surface will retard healing by several mechanisms.
A) Problem of excess neutrophils and byproducts
By products of dead and dying neutrophils releasing toxins damaging to local
cells impair the healing process
Typically when neutrophils die, in the process of necrosis or exudates formation,
proteases and oxidants are released. The controlled cell death known as
APOPTOSIS occurs without cell rupture. Increasing the process of apoptosis in
neutrophils would be a protective advantage to the wound bed.
B) What are Metalloproteases (MMP’s) and How do they alter Healing?
The metalloproteases are a family of proteases (enzymes which break down tissue)
characterized by:
a. dependence of the metal zinc for activation
b. present in wounds where their role is to break down damaged tissue,
denatured protein and matrix, in order to make way for new tissue
initiated by growth factors
c. high sulfur content including sulfhydryl and disulfide bonds
d. present in highest concentration on the wound surface and in matrix
e. can inactivate growth factors
The wound healing process is recognized to be a dynamic balance between growth
factors, or the synthetic aspects, and proteases, which produce tissue breakdown and
remodeling.
These proteases therefore break down the elements of a wound namely collagen,
elastin, and matrix. In addition, these proteases will inactivate growth factors if present
in excess as in a chronic wound or an acute burn wound.
There is present a counteraction system to maintain optimum balance in the wound
called endogenous tissue inhibitors of MMP’s or TIMP’s.
There are a number of TIMP’s, released by macrophages and fibroblasts, in response to
MMP production which protect tissue from protease breakdown by a competitive binding
to tissue protease sites.
This system is limited to a finite production, which can be overwhelmed by the greater
potential for protease production with inflammation. At present, considerable research is
underway to increase TIMP’s activity. Presently, there are no clinically available
protease inhibitors.
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Excess wound matrix metalloproteinases (MMP’s) have also been shown to impede
healing by breaking down growth factors and new cells. These MMP’s are activated and
produced in excess as a result of pro-inflammatory cytokines and the other activators of
excess inflammation.
There are several types of wounds where there is a recognized MMP imbalance.
Infected wound logically because bacterial promotes inflammation
The acute burn wound likely due to the massive tissue insult (mostly seen in the
partial thickness burn)
The chronic non-healing wound where excess inflammation is known to be the
cause of the lack of healing
There are many documented mechanisms for the excess MMP’s produced by:
• increased tissue neutrophils
• increased neutrophil, macrophage and fibroblast gene expression for MMP’s
• oxidant and other mediator induced increase in MMP production by all wound cell
types
• increase in pro-inflammatory cytokines
Metalloprotease Profile
MMP’s involved in Wounds
Characteristics of MMP’s
•
Collagenase (MMP-1, MMP-8
•
Breakdown collagen, elastin and
matrix
•
Gelatinases (MMP-2, MMP-9)
•
Should be in balance with natural
inhibitors and with Growth Factors
•
Elastase (MMP-13)
•
Can degrade growth factors and
also wound tissue if in excess
•
Dependent on zinc to activate
•
Need sulfhydryl bonds
24
Exudate buildup on wound
surface increases local
neutrophils & byproducts.
Excess MMP’s breakdown new
collagen and denature new growth
factors and can increase the depth of
the wound (conversion).
Burn Wound
Immediately after initial cleaning
Wound Conversion
Presence of inflammation induced
pseudo eschar.
25
C) Anti-inflammatory Properties of Silver Released from Nanocrystals
(Acticoat™)
Silver from Acticoat, has been shown to decrease wound surface inflammation by at
least two known mechanisms. The first is by a decrease in excess surface MMP’s. The
nanocrystal silver has been shown to decrease MMP activity in an in vitro model as well
as on the surface of non-healing wounds (in animals and man).
In the first five days after wounding, the wounds were dressed daily and the dressing
materials from each of the experimental groups and the controls were collected and the
wound fluid extracted for analysis. The wounds covered with inactive control and silvernitrate-soaked dressings (4 to 6) reached high levels of MMP activity from day 3
onwards which were maintained throughout the duration of the experiment. The woundfluid samples were assayed for total MMP activity. The Acticoat™ wound MMP levels of
activity remained steady. More rapid healing and reduced inflammation was also noted.
The levels of total proteases mirrored those of the MMP’s. Of particular importance was
the observation that MMP levels in wounds dressed with the Acticoat™ nanocrystalline
silver dressings were normalized but did not fall to zero. Total inhibition of MMP activity
might delay healing.
26
Protease release from wounds in swine.
Note: Decreased wound MMP’s using Acticoat
silver in swine model.
27
Patient with chronic wound treated with nanocrystalline silver.
28
In addition to MMP suppression the Acticoat silver was shown to increase wound
surface neutrophil apoptosis. Apoptosis is a programmed form of cell death in which
cells are fragmented into membrane-bound particles that are then eliminated through
phagocytosis, avoiding the necrotic pathway and reducing inflammation. This response
of silver would also protect the wound from damage by excess neutrophil products.
Overall, the reduced inflammation in the wounds treated with Acticoat™ contributed to
more rapid healing. This was demonstrated by the marked decrease in time to develop
granulation tissue.
Increased healing rate in an experimental wound using the Acticoat silver.
29
VII. CLINICAL COMPARISON OF ACTICOAT™ AND OTHER SILVER
COMPOUNDS IN BURNS
A. Antimicrobial Effects and Infection Control
A number of clinical trials have been performed comparing antibacterial efficacy of
the nanocrystal silver delivery system.
Tredget et al performed a randomized prospective trial in burns comparing
nanocrystal silver delivery versus silver nitrate 0.5%. The nanocrystal silver
significantly decreased wound colonization. In addition, there was a significant
decrease in burn wound infection (> 105 organisms per gram tissue) and
bacteremias.
Stephens et al compared nanocrystal silver delivery and silver sulphadiazine on
deep burns in 20 patients. There was no evidence of infections in either group but
nanocrystalline silver (Acticoat) was reported to produce less pain, and nursing time
due to less frequent dressing changes, i.e. twice a day versus every three days.
In a study reported by Honori et.al., randomized prospective trial, nanocrystal
delivery use resulted in a 0% infection rate compared to 5.2% with the use of silver
sulfadiazine on donor sites in burn patients. Another study on superficial partial
thickness burns reported a 50% decrease in local infections with the use of
nanocrystal silver versus xeroform gauze, a common treatment for superficial burns.
A study in toxic epidermal necrolysis patients reported nanocrystal silver to be as
effective as silver nitrate in controlling infection. There was much less pain and less
nursing time required with the silver membrane.(34)
In summary to date, clinical studies on burns have demonstrated that use of the
nanocrystal silver delivery system is either better or at least as effective an
antimicrobial as the currently used silver compounds. However, every study
demonstrated less patient pain and considerably less nursing time with use of the
silver membrane.
B. Improved Healing
Several clinical trials have identified that nanocrystal silver delivery improves healing
of partial thickness wounds. These wounds include donor sites, partial thickness
skin slough disorders and re-epithelialization of meshed skin grafts.
30
Table 14:
Efficacy Studies on Nanocrystal Silver Use
(Increased Re-epithelialization Rate)
Donor Sites Acticoat vs Xeroform
-Increased healing with nanocrystal silver
Acticoat vs SSD+
-improved healing with nanocrystal
silver
Skin Slough Acticoat vs Silver Nitrate
(TENS)
-improved healing
Meshed Grafts Acticoat vs Neosporin Solution
-30% reduction with Acticoat in
time to re-epithelialization
+ silver sulfadiazine
* nanocrystal silver
The donor site studies comparing nanocrystal silver versus xeroform also compared,
a moist healing used with the silver dressing with a dry environment seen with
xeroform making it difficult to determine what component of the silver or the moisture
was responsible. The study, by Demling, et.al., on mesh graft re-epithelialization
compared the silver moist healing environment with that of a standard diluted
Neosporin solution. In this study, the only difference in the wound environment was
the presence of the nanocrystalline release of silver. The study was performed on
the rate of re-epithelialization across a standard meshed graft on an excised wound,
both approaches being used on the same patient. The significant increase in healing
with pure silver more clearly reflects silver healing properties. The mechanisms are
yet to be defined.
C. Versatility
Because of the potent antimicrobial pro-healing properties and ease of use, the
nanocrystal silver delivery system has been effectively used on a variety of burns
with success.
31
Currently Acticoat has been reported to be effective and efficient in managing the
wounds described below.
Uses of nanocrystalline silver delivery in burns
• Deep dermal to full thickness: prior to and
after excision
• Partial thickness burns
- usually large with a potential for infection
• Large skin sloughs (TENS)
• Donor sites
• Meshed skin grafts
The ability to use one effective silver product from admission of a deep burn to
coverage of meshed grafts and donor sites has many clinical uses and cost effective
advantages.
The data on antimicrobial efficacy in deep burns has been described. The data on
donor sites indicates decreased infections as well as decreased pain with Acticoat,
especially compared to xeroform gauze. The data on use over meshed skin grafts
indicates a prohealing as well as antimicrobial effect.
One wound which deserves special attention is the partial thickness skin slough
wound as seen, e.g. in Toxic Epidermal Necrolysis (TENS). Typically, the wounds
are partial thickness but very large in size and extremely painful. In addition, these
wounds are often present in immunocompromised patients and therefore require
antimicrobial coverage.
The major problems in these patients are control of severe pain, infection and
healing. The standard use of antimicrobials with frequent dressing changes typically
leads to not only severe pain and high narcotic needs but wound manipulation
induced endotoxemia, bacteremia, increased inflammation and immense nursing
resources.
Less pain, fewer wound related side effects, and negative effects of narcotics have
been well documented with nanocrystal silver use. Increased rate of reepithelialization has also been reported likely due to the ability to maintain an
undisturbed optimum healing environment.
32
 to cover meshed skin graft
Use of Acticoat
Acticoat in place day 3
Note excellent comformability
TENS Patient
Wound Coverage with

Acticoat
33
 changed every
Acticoat
3-5 days.
D) Patient Comfort and Decreased Toxicity
The major cause of pain in the burn patient is the dressing change. This problem is
of less concern with deep burns. However, wound manipulation does lead to
increased bacteremias, cytokine release and an inevitable pyrogen response in the
post-dressing change period. The increased body temperature also corresponds with
lethargy, hemodynamic instability and increased oxygen demands. Increased CO2
production also occurs.
A number of studies have demonstrated less pain with dressing changes compared
to the use of other products. Honari et.al., compared the pain of a donor site treated
with nanocrystal silver dressing versus SSD and noted a significant decrease in pain
using the silver dressing. Stephens et.al., reported a significant decrease in pain in
deep burns using the silver delivery system compared to silver sulfadiazine SSD.
Tredget et al, reported a similar decrease in pain with dressing changes in burn
wounds with nanocrystal silver delivery versus silver nitrate solution. A decrease in
pain has been reported in TENS patients using the silver delivery membrane
compared to silver nitrate solution.
It is quite evident that wetting the outer surface of the silver dressing is much less
painful than removal and replacement of SSD or use of silver nitrate in burns or
xeroform in donor sites.
Decreasing the toxicity of wound manipulation is another significant benefit of the
nanocrystalline silver delivery system, where wound manipulation is minimal.
Demling et.al., recently reported a study comparing the burn care response of
nanocrystalline silver versus SSD in deep burns. A randomized prospective study
was undertaking looking at pain, cost effectiveness and wound care side effects of
silver delivery compared to SSD.
34
Clinical Response to Dressing Changes+
SSD
(n=25)
Silver
Delivery
Burn
Dressing
Increased T°°
Size
Changes
(> 101 F°)
25±8%
42±10
100%
28±9%
36±9
10%*
Hemodynamic
Changes
BP
Pulse
20%
5%*
100%
40%*
* significantly different from silver delivery
+ time period from onset to 3 hrs post dressing
A significant decrease in wound care related complications were noted using the
nanocrystalline silver.
E) Cost Effectiveness
Several clinical studies on burns and skin sloughs have demonstrated a
significant decrease in cost using the nanocrystal silver delivery system.
Demling, et.al.(67) recently reported a significant decrease in actual cost (not
charges) for deep burn wound care due mainly to the marked decrease in
nursing care and pain medication required.
Cost Comparison SSD versus Nanocrystal Silver Delivery
per week in Major Burns
(a randomized prospective trial)
Nursing
Times/w
k
Nursing
cost
Supplies Medication
Cost++
Pain/
sedation
Total
SSD+
(n=25)
20±2
$760±50
$720±40
$1800±290
Acticoat
(n=26)
7±2*
$280±40* $650±50* $1275±30*
$350±40
$1050±240*
*significant decrease in wound care costs compared to
SSD
35
Other studies have reported a similar cost effectiveness due mainly to at least a 60%
decrease in nursing time for wound care. The decrease in wound manipulation also
markedly decreases pain, pain medications and narcotic induced morbidity.The
studies include the management of skin slough disorders, deep burns.
All studies demonstrated cost effectiveness with a cost saving of 15-25% compared
to standard of care.
CASE 1
Patient is a 40year old male injured in a plane crash. He suffered deep burns to 60%
of TBS plus a fractured pelvis. He weighed 350 pounds and any turning was very
difficult for him and the staff. After initial resuscitation, all burns were covered with
ACTICOAT until excision and grafting could be performed.
Initial assessment of back and buttock burns was that of a deep dermal burn which
may require grafting. Back and buttock care was markedly simplified by the use of
ACTICOAT and buried catheters to rewet. The wound beneath the
ACTICOAT was clean and moist with minimal exudates. Of interest was the fact
that the back did not require excision but healed in 21 days. Bacterial count was
always scant growth.
Burn Admission
Note: burn is deep dermal to full
thickness.
Burn Day 3
Note: adherence presence of
moisture layer and lack of exudates.
36
Burn Day 21
Burn completely re-epithelialized
With return of pigment
Case 2
Patient is a 12 month old boy suffering deep dermal burns to chest, neck,
arms in addition to smoke inhalation. Burn wounds were managed with
Acticoat™ changed every 3-4 days. Wounds were healed by 14 days. Pain
management was much easier with the decrease in need for wound
manipulation.
Admission burn
Burn at 10 days
Note nice adherence of the
Acticoat to the burn wound.
37
Burn at 14 days
Note: re-epithelialization
Summary
is beneficial for the
Nanocrystalline silver delivery by Acticoat
management of :
Partial and Full Thickness burn
Donor sites
Excised and grafted wounds
The mechanism is likely multifactorial:
Eliminating toxic complexes
Decreasing bacteria and inflammation
Moist wound healing
Decreased mechanical trauma
Direct healing effect of nanocrystal silver
38
VIII
Use of Acticoat in Difficult to Heal and in Chronic Wounds
A. Overview
There are several types of wounds which characteristically are much more difficult to
heal than the acute traumatic wounds. The major reasons are the typical presence of
impaired perfusion as seen, e.g. with venous hypertension or diabetes and an underlying
disorder such as immobility as seen in the population with pressure ulcers.
Typically, these wounds begin healing by the normal acute healing process, with the
process simply being prolonged into months instead of weeks. There is also an
increased risk of wound complications due to the underlying impediments to healing.
These wounds are also at high risk for evolving into a chronic wound, which fit into the
difficult to heal category are a diabetic, venous stasis and pressure ulcer.
Difficult to heal wounds
Diabetic Ulcer
Venous Stasis Ulcer
Pressure Ulcer
Each have distinct properties which make them difficult to heal. All of them share the
characteristics of impaired perfusion and increased risk of infection, increased bacterial
burden and inflammation.
Chronic wounds differ substantially from an acute wound. The wound no longer follows
the normal healing processes. The term “non-healing wound” is often used to describe
the chronic wound. Characteristics are presented. However, the exact distinction
between acute and chronic is still somewhat arbitrary and often based on the cause of
the wound and physical status of the patient.
Chronic Wound Characteristics
Wound which fails the normal healing process
Lack of any significant healing over a 3 month period despite good local care
Excess wound inflammation is present
Wound surface often contains necrotic tissue and increased exudates
Colonization with bacteria is usually present
Increased levels of wound metalloproteases which can damage any new
tissue formation
Decreased protease inhibitors
Decreased surface growth factors
39
The time period most commonly used to define a chronic wound is usually
3 months of lack of healing. The most common chronic wounds are pressure ulcers,
diabetic ulcers and venous stasis ulcers. The 3 categories account for 70% of chronic
wounds. However, any acute wound, which fails to follow the normal healing process
can become a chronic wound. It is important that criteria for determining when an acute
wound becomes a chronic wound be met before calling a wound “chronic”. For example,
a pressure ulcer characteristically heals slower than an acute surgical wound but a
pressure ulcer can progressively heal by the normal healing process. It only becomes a
chronic wound if there is failure of the normal healing process. Successful treatment of
the chronic wound depends on a thorough understanding of the pathophysiologic
mechanisms underlying the failure of the normal wound healing process.
Common Types of Chronic Wounds
Pressure Ulcers
Vascular Insufficiency: Chronic Venous Hypertension, Arterial Insufficiency
Metabolic: Diabetes Mellitus, Gout
Infection: Vasculitis
Malignant Cutaneous Wounds
RadiationBurns
These wounds cause a major disability due to the chronicity and frequent recurrence
and therefore negatively impact quality of life in addition to producing an enormous
health care cost (3billion/yr in the U.S.).
B. Etiology
A number of etiologic factors have been identified which impede the normal healing
process allowing a chronic wound to develop. Systemic factors such as malnutrition and
chronic illness prevent the acute wound from healing due to inadequate protein
synthesis needed for new tissue development. Other factors such as impaired perfusion,
hypoxia, do not allow healing to occur because of inadequate oxygen. Other systemic
factors such as infection, diabetes and corticosteroids directly impede healing.
The most common local factors which allow a chronic wound to develop are continued
mechanical trauma to the wound and/or the use of wound care products toxic to the cells
of the wound bed. Repeated loss of the new tissue synthesis will eventually lead to a
chronically inflamed wound.
Etiologic Factors Leading to Chronic Wounds
Malnutrition (protein-calorie) especially with involuntary weight loss
Micronutrient deficiency
Tissue hypoxia
Infection
Diabetes Mellitus
Chronic disability: elderly, chronic disease
Use of toxic wound care products
Inadequate care of the acute wound
Mechanical Injury (repetitive): pressure, shear force, friction
Radiation Therapy
40

C. Treatment of the Difficult to Heal and Chronic Wounds with Acticoat
There is increasing evidence that nanocrystalline silver Acticoat is very effective in the
management of difficult to heal and chronic wounds.
Difficult to Heal and Chronic Wounds
1. Sibbald R. Screening evaluation of an ionized nanocrystalline silver
dressing in chronic wound care. Ostomy Wound Management 2001:47;38.
2. Dousett C. An overview of Acticoat dressing in wound management.
Br. J Nurs 2003:12;44
3. Fromantin I. Use of nanocrystalline silver in cancer wounds. Soins
2003:678;31
The nanocrystalline silver is very effective at:
Decreasing bacterial burden
Controlling excess inflammation
Decreasing excess MMP activity
Maintaining moist healing environment
41
The Chronic Wound
42
Management of Difficult to heal ulcers with a new silver dressing: A clinical
evaluation. (Poster presentation, EWMA, Grenada, 2002)
Romanelli M, et al (Dept Dermatology, University Hospital of Pisa, Italy)
Venous Leg Ulcer
Treated with Acticoat, results after 4 weeks.
Case Study:
The Use of Acticoat on an infected thigh stump
(EVEAN Thiuszorg, Wondevrepleegkundige, Netherlands)
An infected thigh stump in a patient with vascular disease
Infected amputation site with massive
fat necrosis.
Wound dressed with Acticoat and
covered with an absorbent secondary
dressing.
43
Heavily exuding wound during first few
days.
At 7 days P. aeruginosa, S. aureus,
and Streptococci colonization was
reduced. After 12 days wound swabs
were clear. Wound healed in 7 weeks.
Case Study:
/ Acticoat
 7 on infected ulcers of the foot and lower
The use of Acticoat
leg
(Dr. Huuk, Kath. Krankenhaus gem. GmbH (Catholic Hospital,non-profit limited
company) Dr. Winkelhoff, Head of the hospital surgical department. St.JohnnesHospital
Infected ulcers on the anterior and posterior aspects of both legs.
44
1. Treatment with Acticoat
2. Acticoat used in conjunction
with a secondary dressing
3. Acticoat and secondary
dressing are under the
compression dressing
After 64 days the ulcers had clearly improved with treatment.
45
Case Study:
 7 on an acutely infected leg ulcer
The use of Acticoat
Stephen Cook, Tissue Viability Nurse, The Queen Elizabeth Hospital, Norfolk,UK
Patient was an 82 year old admitted with a
fracture of the left distal femur, suspected
DVT (deep vein thrombosis) and cellulitis.
Pictured is his extremely inflamed and
painful right leg.
On exam, infection was seen tracking up the
leg. Systemic antibiotics were begun, and
Acticoat 7 was used to dress the wound.
The wound had greatly improved by day 7
and the patient was now pain free. Some
over-granulation was noted, Acticoat 7
treatment continued in combination with a
secondary pressure dressing.
The over-granulation was stopped and the
wound had healed by 95%. The combined
effect of systemic antibiotics and
Acticoat 7 had a dramatic effect on the
ulcer by controlling infection and improving
healing.
46
D. Diabetic Ulcers
Incidence:
Approximately 15-20% of the estimated 16 million diabetics in the United States will be
hospitalized for a foot complication, usually an ulcer, during the course of their disease.
Progression of these ulcers are the leading cause of foot amputations.
Etiology
Impaired perfusion leading to
ischemia
Foot neuropathy
High risk of infection
Characteristics
Full thickness wound usually
surrounded by a rim of callous
caused by compression of soft
tissues against bony prominences:
feet are most common
Presence of diabetic neuropathy
High risk of infection
Characteristics:
The ulcer is usually full thickness, therefore extracellular matrix components are initially
absent. The most common site is on the foot, especially over bony prominences and on
the heel. The ulcers are typically full thickness and difficult to heal, often becoming
chronic wounds. An adequate description of ulcer characteristics is necessary for
selection of appropriate treatment. Description includes size, depth, appearance and
location. In addition, it must be determined whether the ulcer is the result of neuropathy,
ischemia or typically both. Gentle probing with a blunt sterile probe will detect the
presence of an undermining ulcer and the presence of sinus tracts.
One classification system uses wound color as a marker of wound status.
Red wounds are usually the healthiest and need wound coverage for protection and to
maintain moisture.
Yellow wounds indicate the presence of non-viable but moist tissue. Wounds need to
be debrided to remove necrotic tissue and reduce the bacterial load. Frank infection
does not need to be present to retard healing, simply an increased bacterial burden
which overwhelms the wounds defenses.
Black wounds indicate dead, dehydrated tissue or eschar on the wound surface. The
eschar needs to be removed to be able to assess the wound, prevent infection and
promote healing.
Treatment:
The primary goal of treatment is to obtain wound closure. Treatment is multifaceted due
to the complex nature of the wound. Relief of pressure on the ulcer is critical to the
wound healing process. This endpoint often requires pressure relieving interventions.
Total contact casting reapplied weekly is the optimum management of pressure offloading. Treatment of any underlying ischemia is required. Distal vascular reconstruction
may be required to restore pulsatile flow to the foot. When infection is present,
47
appropriate aerobic and anaerobic antibiotic therapy is necessary. Adequate insulin
availability to the wound is needed to stimulate healing. Also, blood sugar control is
important for healing.
Debridement of all necrotic tissue and callous is also required. Debridement should be
performed to bleeding tissue. Moist wound healing should then be initiated along with
protection from external contamination. Nanocrystalline silver (Acticoat) should
improve healing by:
1. Decreasing bacteria
2. Decreasing inflammation
3. Providing a moist healing environment
Treatment of Diabetic Ulcer
Relief of pressure on the ulcer
Correction of ischemia, if possible
Debridement of necrotic tissue
Control of bacterial burden and infection
Maintain moist wound healing
Adequate insulin therapy, control of blood glucose and increase anabolic
activity
Modulate excess inflammation
Generally infections can be detected by the presence of surrounding cellulitis. Cultures
should be obtained from purulent drainage or curetted material from the wound bed.
Palpation of foot pulses should be performed as well as non-invasive Doppler blood flow
studies. Radiographs of extensive ulcers should be performed to assess for underlying
osteomyelitis.
Evidence of Excessive Bacterial Content:
1.
2.
3.
4.
Wound not healing despite appropriate optimum care
Increased wound drainage
Increase in very friable granulation tissue
Increasing pain, edema, peri-wound redness
48
Case Study:
The use of Acticoat on a diabetic ulcer
Patient is an 80 year old diabetic with an ulcer on his
left heel present for 1 year. Wound dimensions were
6cm wide, 7 cm long and 1 cm deep. Note the
periwound redness, maceration and edema, with
exudates and malordor.
The wound was covered with Acticoat 7 and an
absorbant secondary dressing applied.
After 4 weeks, the wound had significantly reduced in
size to 0.8cm wide, 3.7cm long and 0.2cm deep, a
reduction of 93%. The patient no longer experienced
pain and the wound was free of signs of infection.
The patient had approximately 12 months of
conventional treatment for his diabetic ulcer, and the
ulcer remained unhealed, at a cost of $14,500.00.
A 4 piece course of Acticoat 7 resulted in an ulcer
reduced in size within 4 weeks at a cost of $1,700.00.
Conclusion: The nanocrystalline silver improved healing while decreasing cost.
49
 in treating Venous Stasis Ulcer
E. Experience with Acticoat
Definition and Etiology
Venous stasis ulcer is a partial or full thickness wound on the lower extremities often
over the malleolus caused by venous insufficiency, local stasis, edema and resulting
ischemia. Venous ulcers occur when the superficial leg veins become dilated from
inadequate valve function leading to stasis and venous hypertension.
There are several theories as to the etiology and the difficulty of healing.
1. Calf venous pump failure
2. Peri-capillary fibrin cuffs which impair oxygen diffusion to the wound
3. Macromolecules like fibrinogen leak into the dermis, due to venous hypertension,
and trap Growth Factors and Matrix Proteins making them unavailable for the
repair process.
4. Decrease in nutritive skin capillary blood flow
5. Combination of the above
Incidence:
Venous ulcers account for over 70% of chronic leg ulcers with the incidence increasing
with age. The prevalence in the adult population either active or healed is about 1-2%.
Characteristics:
The classic presentation is an irregularly shaped wound with well defined borders
surrounded by erythematous or hyper-pigmented skin. A yellow to white exudates is
commonly observed. The lower leg is typically edematous. Varicosities are often
present, and a dilated vein may be near the base of the ulcer. The surrounding skin
change is known as lypodermatosclerosis. This process is caused by chronic changes in
the soft tissue from edema and inflammation. The skin is often tender and can be
mistaken for infection.
Characteristics of Venous Ulcers
Irregularly shaped wound with well defined borders
Found on the lower leg often over the medial malleolus
Yellowish exudates often at base
Lower leg and foot edema usually present
Surrounding skin brawny, erythematous or hyper-pigmented
Lower leg venous hypertension
50
Treatment:
The treatment goals for venous ulcers are first and foremeost to decrease tissue edema
with compression therapy, followed by healing of the ulcer, control of pain and
prevention of recurrence, the latter by controlling edema. Local care to the ulcer includes
optimizing the healing environment. Initiation of moist wound healing while minimizing
infection risk, and environmental insults is the standard of care. Controlling excess
inflammation and MMP would also be very advantageous for healing. As with any tissue
ulcer, debridement of necrotic tissue along with control of exudates is necessary. A
variety of hydrogels and alginates are used inckuding a nanocrystalline silver alginate, in
addition to the Acticoat.
Treatment of Venous Ulcers
Control of tissue edema with compression therapy
Correction of any ischemia
Debridement of necrotic tissue
Control infection
Maintain moist wound healing
Control inflammation
Case Study:
Patient is a 45 year old international businessman with a non healing venous
stasis ulcer for 2 years, despite compression therapy. Edema management was
made difficult by traveling. The ulcer was 4cm x 6cm prior to treatment with
Acticoat 7 (Figure 1). Initial cultures grew 2+ staph Aureus. He was then
managed with Acticoat 7 followed by a soft moist gauze, followed by
compression. The dressing was changed weekly (Figure 2).
Figure 1
Figure 2
51
The ulcer healed by 50% in 4 weeks and by 85% 8 weeks (Figure 3, 4). The
ulcer was healed by 12 weeks.
Figure 3
Figure 4
Wound is
85% healed
The use of Acticoat 7 on a venous leg ulcer present for 13 months
(Kerrie Coleman, Clinical Nurse Specialist, Outpatient Services, Royal Brisbane
Hospital, Australia)
The patient was 74 years old with a longstanding
history of leg ulceration and deep venous
disease. The ulcer was heavily exuding,
malodorous and composed of slough and
granulating tissue.
52
At day 6 the wound was responding quickly to the
treatment, which consisted of a moistened. Acticoat
7 and a multi layer compression bandage.
Initially, the dressings were change twice weekly
for exudates management.
Note continued improvement of the ulcer, after 6
weeks.
The ulcer had improved further and by 8 weeks
the ulcers were close to healing.
53
X. References:
54
55
56
57