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Keywords: Randomized Clinical Study of SilvaSorb® Gel in
Comparison to Silvadene® Silver Sulfadiazine Cream
in the Management of Partial-Thickness Burns
Paul M. Glat, MD, Wade D. Kubat, DO, John F. Hsu, DO, Tarek Copty, MD,
Brooke A. Burkey, MD, Wellington Davis, MD, Isak Goodwin, MD
This prospective, randomized study assessed the clinical, microbiological, and patient comfort
characteristics of two silver-based topical agents in the management of partial-thickness
burn wounds. Pediatric patients were randomly assigned to treatment with either Silva-
Sorb® Gel (Medline Industries, Munedelein, IL) or Silvadene® silver sulfadiazine cream
(King Pharmaceuticals, Bristol, TN) for up to 21 days or to the point of full reepithelialization
of the wound. Inclusion criteria were patients ranging in age from 2 months to 18
years with TBSA ranging from 1 up to 40%. A total of 24 patients were enrolled and completed
the study. Findings demonstrated that the use of SilvaSorb Gel was associated with
less pain and greater patient satisfaction when compared with Silvadene. No statistically significant
differences were found when assessing the rate of infection, time to reepithelialization,
or the number of dressings changes required during treatment. The reduction of pain
and improved overall patient satisfaction with the use of SilvaSorb Gel compared with
Silvadene indicates an important role for SilvaSorb Gel in treatment of partial-thickness
burns in a pediatric population. (J Burn Care Res 2009;30:262–267)
Topical antimicrobials are the standard of care in the
treatment of burn wounds because of their ability to
reduce the incidence of wound sepsis. Silver sulfadiazine
(SSD) cream is the definitive standard in the
treatment of burns because of their relative ease of
application, wide efficacy profile, and availability in
most hospital formularies. SSD cream is a soft, white,
and water-soluble topical, which contains 10 mg of
active silver antimicrobial (silver sulfadiazine). Aside
from the active antimicrobial, SSD contains amixture
of white isopropyl myristrate petrolatum, sorbitan
monooleate, stearols, polyoxyl 40 stearate, propylene
glycol, and water. SSDcream is generally considered
a good choice for partial-thickness wounds as it
allows wounds to heal without the need for surgical
intervention or skin grafting. Offsetting the benefits
of SSD topical treatments are the reported side
effects that include allergic reactions or sensitivity,
frequent and painful dressing changes, delayed
healing, and staining/discoloration of the wound
bed, which confound wound evaluation and depth
determination.1
Advances in burn management have greatly improved
survivability from severe burn injuries, with
new wound care products focusing on effective moisture
management,2 control of infection and improved
healing, while resolving limitations and/or
side effects of current treatments. Newer topical treatments
such as SilvaSorb® Gel (Medline Industries) have
been developed to address the potential side effects of
SSD, while maintaining rapid healing, increasing ease
in application, ability to reduce bioburden, and improving
patient comfort.3 SilvaSorb Gel is an amorphous,
biocompatible hydrogel with a unique Micro-
Lattice structure in which the scaffolding stabilizes
the silver ions. The product is effective for 3 days thus
not requiring daily dressing changes.3 The hydrogel
has the advantage of being transparent, nonirritating,
nonsensitizing, and excellent with fluid management.
The product has also been shown in vitro to possess
excellent fluid management and wound healing
properties, while controlling wound bioburden
From the Department of Plastic Surgery, St. Christopher’s Hospital
for Children, Philadelphia, Pennsylvania.
Address correspondence to Paul M. Glat, MD, St. Christopher’s
Hospital for Children, Erie Ave at Front Street, Philadelphia,
PA 19134.
This research was supported through Drexel University School of
Medicine by Medline Industries.
Copyright © 2009 by the American Burn Association.
1559-047X/2009
DOI: 10.1097/BCR.0b013e318198a2e8
262
without being toxic to host cells such as fibroblasts
and keratinocytes.4,5 It also functions without staining
the surrounding skin and wound or forming a
pseudoeschar. However, SilvaSorb Gel has not been
extensively studied in a clinical burn setting. As a
result, this study was designed to compare SilvaSorb
Gel to the standard of care topical burn treatment,
SSD, in the treatment of partial-thickness burn
wounds in pediatric patients.
METHODS
Pediatric patients presenting to our unit with superficial
and mid-dermal burn wounds were considered
eligible if they were at least 2 months of age and not
greater than 18 years of age and sustained their burn
injuries within 36 hours of enrollment. The burn size
needed to range from 1% but not greater than 40% of
TBSA and the patients or their parents were able to
consent to both inclusion in the study and treatment
until their wounds were completely healed. The study
was designed to be carried out for 21 days, but all
patients were followed until complete healing. Major
exclusions included burn wounds associated with either
electrical or chemical injury, deep or full-thickness
burns, the subject’s prognosis was unlikely for survival
past the study duration, the patient’s burn site had
been previously treated with an antimicrobial agent
or a debriding with an enzymatic agent, the patient
had been previously entered into a similar study, or
was pregnant. Burn injuries progression with an increase
in burn depth requiring wound closure or surgical
intervention was criteria to withdraw patients
from further participation in the study. All patients
were recruited into the study from a population of
patients at the Burn Unit at St. Christopher’s Hospital
for Children, Philadelphia, Pennsylvania. Patients
were provided with informed consent to participate in
the study and the protocol was approved by the institutional
review board.
A total of 24 patients were prospectively enrolled
into the study, with a goal of at least 20 patients
meeting the definition of “protocol correct,” prior
to randomization into either a control group with
treatment with Silvadene® silver sulfadiazine
cream (King Pharmaceuticals) or into a study arm
with treatment with SilvaSorb Gel. Eligibility was
established by completion of the written informed
consent, fulfillment of the inclusion criteria, and
with no exclusions being met. The study was scheduled
until full reepithelialization of the wound
occurred.
After eligibility was established, an initial evaluation
was performed on each patient, which included
subject demographics, medical history, and a baseline
assessment of the burn injury with photographic documentation.
TBSA standard formulas, as appropriate
for the age of the subject, along with Lund and Browder
charts were provided in the Clinical Research Form and
used in the determination of the extent of the burn
injury.
Patients were randomly assigned to a protocol of
care that included either SSD cream or SilvaSorb
Gel, without blinding of the physician investigator or
other medical personnel to the type of treatment. Figure 1
summarizes the treatment protocol for each arm of the
study.
Under the study protocol, patients received an initial
evaluation that included medical history, subject
demographics, and baseline assessment of the burn
Figure 1. Treatment Protocol—SilvaSorb gel vs silver sulfadiazine (SSD). Each product was used in a similar fashion with daily
dressing changes until complete reepithelialization was observed.
Journal of Burn Care & Research
Volume 30, Number 2 Glat et al 263
injury. Dressing changes were scheduled to continue
until complete healing. Subjects were instructed to
visit the clinic for evaluation once every 2 to 3 days
and complete requisite dressing change forms. Outpatients
and/or their guardians were allowed to
change their own dressing and were provided with
general practice instructions of the burn center and
on the use of the topical treatments.
The initial treatments as well as each dressing
change were documented on the wound assessment,
dressing change, home dressing change forms and
included in the CRF. Data were recorded during the
initial treatment and subsequent changes included
details on the treatment application, status of the
burn, number of dressing changes between evaluations
and any adverse findings or events. Study endpoints
that were recorded included the following: a)
time to full reepithelialization, b) pain during dressing
changes utilizing an age-specific pain rating scale
measured just after the first postdebridement dressing
change, c) number of dressing changes, and d) patient
satisfaction as assessed by a parental or patient
questionnaire.
A descriptive statistical analysis was used to examine
the distribution of continuous variables and included
frequency histograms for categorical variables
for each of the treatment groups. In nonnormal distributions,
transformations were used to normalize
the data for statistical analysis. In some cases, exact
methods were employed when the expected frequencies
were small. Statistical significance was defined as
a two-sided P-value with 95% confidence intervals.
For all study endpoints, a P-value of less than or equal
to 0.05 was considered significant. Substantial equivalence
of the treatment groups with respect to wound
infection was assessed via Blackwelder’s method of
testing equivalence. The percentage of patients achieving
full reepithelialization within 21 days was assessed
utilizing a chi-square test, with exact test being used in
cases where expected frequencies are small. The percentage
of reepithelialization at 21 days was compared
between groups using t-test or Wilcoxon’s rank sum
test, with the time to full reepithelialization compared
utilizing Kaplan-Meier estimates and a log-rank test.
The number of dressing changes was assessed via the use
of Wilcoxon method.
RESULTS
A total of 24 pediatric patients were enrolled into the
study and randomly assigned to a protocol of care
that included either SSD cream (n 12) or SilvaSorb
gel (n 12). Baseline characteristics were comparable
between the treatment and control arms of
the study with the exception of patient age. Overall
mean age of the patients in the Silvadene arm was
22.78 months, with a standard deviation of 13.51
months, compared with the mean age of patients in
the SilvaSorb arm at 43.00 months, with a standard
deviation of 29.10 months with a significant difference
being noted (P 0.0291). Patients ranged in
age from 13 months to 5 years in the SSD treatment
arm compared with 9 months to 9 years in the
SilvaSorb arm. TBSA for the wound injury site was
comparable for both study arms and ranged from 1
to 10% TBSA.
Overall pain ratings were recorded based on an
age-specific pain rating scale. In older children, the
patient’s were asked directly to rate their pain on a
scale of 1 to 10 or using the Wong-Baker Pain Scale
(Figure 2).6 In infants and toddlers, pain was determined
by the observational pain assessment scale.7
Pain ratings were found to be significantly less in the
SilvasorbGel group when compared with SSD (Table
1), and the results were statistically significant (2.33
vs 5.33, P 0.0001). Also relevant was that proportionately
more patients (50%) in the SilvaSorb cohort
experienced less pain as registered by a rating between
Figure 2. Wong/Baker Faces Pain Scale.
Journal of Burn Care & Research
264 Glat et al March/April 2009
1 and 4, when compared with the same range in the
SSD group (17%). Although there is no specific definitive
standard infantile or toddler pain assessment
tools, the two scales that were used in this study have
been extensively used in previous studies in the burn
literature.8
The study was designed to be carried out for 21
days but all patients were followed until complete
healing was observed. When comparing patients in
the SilvaSorb Gel treatment group, proportionately
more reached reepithelialization within the 21-day
study duration than those in the SSD treatment
group, although the difference in mean time to reepithelialization
between groups was not significantly
different with a P-value of 0.949 (Table 2). In two
cases, patients in the SSD treatment group reached
reepithelialization after the 21-day study duration,
(26 and 28 days) whereas all patients in the SilvaSorb
Gel cohort experienced healing within the study duration.
In contrast, the furthest point of reepithelialization
occurred at only 18 days in one patient in the
SilvaSorb Gel group. However, because of small sample
sizes, these differences were not demonstrated in
the statistical comparisons.
Dressing changes were documented throughout
the course of treatment, whether administered within
the context of inpatient or outpatient care. Dressing
change forms included in the CRF included wound
assessment, dressing change (inpatient care), and
home (outpatient) dressing change forms. The distribution
of the number of dressing changes by treatment
arm varied slightly, although there were virtually no
differences seen in the total number of dressing
being applied, as evidenced in the nonstatistically
significant P-value of 0.449 (Table 3).
Patient satisfaction was evaluated by questionnaire
using a 1 to 4 point scale, with 1 equating to being
“unsatisfied” and 4 being “extremely satisfied,” reflective
of the highest possible evaluation. Patients in
the SSD treatment arm were found to have a lower
satisfaction rating when compared with the patients
in the SilvaSorb (Table 4). These data were found to
be statistically significant (P 0.004).
Finally, neither group had any burn wound infections
or adverse events occur during the course of the
study.
DISCUSSION
Topical antimicrobials remain the standard of care in
the treatment of partial-thickness burn wounds because
of their ability to reduce the incidence of wound
sepsis. SSD cream has been the definitive standard in
the treatment of burns.1 However, in this study, the
use of SSD was associated with significantly more pain
and patient discomfort when compared with the study
medication, SilvaSorb Gel.Not surprisingly, this translated
to a patient satisfaction rating which was higher
with the use of SilvaSorb Gel. The comfort and satisfaction
profile are likely due to the unique polymer
microlattice composition of SilvaSorb, which provides
more moisture to the wound while simultaneously
controlling the amount of exudate.3 In addition,
the formation of pseudoeschar with the use of
SSD would account for increased pain upon removal
of the pseudoeschar during the dressing changes.
The microlattice structure of SilvaSorb gel is unique.
It is composed of polyacrylamide, cross linker, water,
glycerol, and polysaccharide. These components together
serve to provide scaffolding for silver stabilization
and regulating the moisture within the gel. The
Table 1. Pain rating
Treatment Mean Median SD
SilvaSorb (n 12) 2.33 2.00 1.07
Silver sulfadiazine (n 12) 5.33 5.00 1.44
Total (n 24) 3.83 4.00 1.97
t(22) 5.80; P .0001.
Table 2. Days to re-epithelialization
Treatment Mean Median SD
SilvaSorb (n 12) 12.42 12.50 3.58
Silver sulfadiazine (n 12) 12.75 9.50 7.45
Total (n 24) 12.58 10.50 5.72
S 136.50; P .449.
Table 3. Number of dressing changes
Treatment Mean Median SD
SilvaSorb (n 12) 13.50 13.00 4.70
Silver sulfadiazine (n 12) 13.42 10.00 8.26
Total (n 24) 13.46 11.50 6.57
S 165.50; P .383.
Table 4. Patient satisfaction rating
Treatment Mean Median SD
SilvaSorb (n 12) 3.25 3.00 0.75
Silver sulfadiazine (n 12) 2.17 2.00 0.72
Total (n 24) 2.71 3.00 0.91
S 198.00; P .004.
Journal of Burn Care & Research
Volume 30, Number 2 Glat et al 265
microlattice allows oxygen to penetrate to the wound
surface while minimizing the moisture from escaping
to the surface. Moisture enters the gel and interacts
with the silver within the scaffold. The interaction
mobilizes the silver component and allows the silver
to be diffused to the wound site. Previous study demonstrated
ionic silver reservoir release at an average
rate of 1.5 ppm. SilvaSorb gel maintains a level of
ionic silver that is effective against a wide-spectrum of
microbes without harming healthy tissues within and
around the wound site.4,5,9
This study measured the number of dressing changes
for each patient was recorded, with the goal of comparing
the cost of each treatment. Two previous studies
authored by Caruso et al previously demonstrated the
cost effectiveness of utilizing a 7-day burn dressing
compared with SSD in partial-thickness burns.10,11
The cost savings are related to decreased nursing and
physician time associated with fewer dressing changes
needed with the 7-day product, despite the increased
cost of the product itself. In this study, the number of
dressing changes was relatively equivalent; however,
SilvaSorb Gel is normally prescribed as a 3-day product
and can potentially be left in place for up to 7 days.
This study was designed to allow each group to
change dressings on a daily basis in order to maintain
consistency between groups. The direct costs for this
study were not calculated. It can be extrapolated that,
similar to the Caruso studies,10,11 SilvaSorb Gel when
used as recommended every 3 days would have a significant
cost savings due to less manpower required
for dressing changes. This is despite a slightly increased
product cost for the SilvaSorb Gel when compared
with SSD.
Reepithelialization rates were found to be equivalent
between the two study groups. Because of the abovementioned
recommended 3-day wear time, less frequent
dressing changes would occur in clinical practice
and this could impact rates of reepithelialization. Less
frequent dressing changes allows reepithelialization
to progress without disruption, and therefore may
correlate with a decrease in the overall time for healing.
It must be stressed, however, that in the case of
time to reepithelialization (in days) and the number
of dressing changes in this study neither endpoint
yielded a significant difference. Improvement in these
parameters can only be hypothesized in clinical practice
with a less frequent dressing change regimen. The
small cohort of patients enrolled in this study makes it
difficult to compare reepithelialization rates as well as
complications between the two groups. However,
there were no adverse events seen in this study (including
no infections) and there was no significant
difference in rates of reepithelialization. Therefore,
for these two variables the two groups demonstrated
equivalency. Larger study size would be required to
demonstrate significant differences in these areas.
The authors also acknowledge the potential bias created
from patients changing their own dressings but
this should be balanced against the beneficial advantages
of data collection and limitations encountered
in patient follow-up logistics.
CONCLUSIONS
SilvaSorb Gel was safe and effective at treating partial
thickness burns and was associated with significantly
less pain and greater patient satisfaction over the
course of treatment. Proportionately more patients in
the SilvaSorb Gel study group reached reepithelialization
within the 21-day study duration when compared
with those in the Silvadene treatment group,
although the difference in mean time to reepithelialization
between groups was not significantly different
(P 0.949). All patients in the SilvaSorb Gel cohort
reached full reepithelialization before the scheduled
21-day study duration, whereas two patients in the
Silvadene arm reached this healing endpoint at 26
days and 28 days. No differences were seen in either
the number of dressings. Although no significant differences
were noted in the infection rates between the
two study groups, this data demonstrated that Silvasorb
Gel showed equivalence with the standard of
care in this regard.
Given the sensitive nature of treatment required for
burn wounds, especially in the pediatric population,
the ability to reduce pain associated with dressing
changes and to decrease the number of dressing
changes is extremely valuable. This, combined with
the ability to improve patient comfort with the use of
SilvaSorb Gel, warrants additional investigation of
this product in the care of the burn patient. Further
analysis in larger patient populations is necessary and
should provide more data, including cost analyses,
which may prove beneficial in the treatment of burn
wounds with this product.
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