J. Koller; P. Bukovčan; M. Orság; R. Kvalténi; I. Gräffinger
Department of Burns and Reconstructive Surgery, University Hospital Bratislava, Ružinov Hospital, Bratislava
; Slovak Republic
Vyšlo v časopise:
ACTA CHIRURGIAE PLASTICAE, 50, 4, 2008, pp. 109-114
excision has become the method of choice for treatment of acute deep
burns over the last few decades (1, 2). One of the major drawbacks of
the surgical removal of necrotic tissues is that much healthy, viable
tissue is removed together with the necrotic areas. Therefore a more
selective method for necrotic tissue removal, which would preserve
and not harm the viable tissues, has been sought. One of the most
promising options seems to be enzymatic debridement. In 1943 Cooper
(3) published an article on enzymatic debridement of burns by
a mixture of papain, cystein hydrochloride and sodium
salicylate. Various proteolytic enzymes of bacterial origin, such as
clostridial collagenase, streptokinase and streptodornase, were used
for enzymatic debridement in the 1950s (4, 5, 6) with controversial
efficacy. Proteases derived from B.
subtilis were used in the 1970s and were
marketed as Travase®,
manufactured by Flint Laboratories (7, 8). The results of all the
above methods have been highly variable. The enzymes were effective
only in a moist environment, and the debridement took quite
a considerable time – which varied from days to weeks. Hence,
under these conditions, the spread of infection was facilitated, and
infection was found to be the most frequent complication of such
debridements. Enzymatic debridement with these agents was slow, not
effective enough, could not be used for large surfaces, and was
accompanied by high frequency of adverse events and complications
reports on the use of a pineapple stem-derived proteolytic
enzyme mixture (bromelain) for burn debridement were published by
Klein (10, 11). He used commercially available lyophilized enzyme
with good but inconsistent results. With the development of more
effective extraction methods (12), the pineapple stem enzyme mixture
known as Debridase was used by Rosenberg (13) for burn debridement in
a group of 130 patients during the years from 1984 to 1999.
Bratislava Burn Department participated in two multicenter
prospective randomized clinical studies with a new enzymatic
debriding agent under a name of Debrase Gel DressingTM
(DGD) assigned for early debridement of acute deep burns. The
clinical trials were approved by the Ethical Committee of the Ružinov
Hospital. The first study, which was performed during the years 2002
and 2003 and which was focused on the efficacy and safety of the
drug, included 15 patients. The second study, which started in 2006
and which is still ongoing, has so far included 7 patients.
Altogether 22 patients have been included in the two studies.
criteria for both the studies included acute deep partial thickness
and full thickness burns from 5% to 30% of the total body surface
area, which were indicated for treatment by early excision. The age
of eligible patients in the first study was between 18 and 60 years;
in the second study it was between 4 and 55 years. Patients with
burns older than 48 hours, with serious concomitant diseases, and
those with severe allergies were excluded, as were alcoholics and
drug users. Patients with severe inhalation injuries and women in
fertile age with positive pregnancy tests were also excluded. In the
first study only one target wound (TW) could be treated, and burns of
the face and hands could not be included among target wounds.
(MediWound Ltd) is a purified substance derived from
specially-made bromelain raw material. The enzyme is supplied as
a sterile purified freeze-dried substance. DGD contains very
active proteolytic enzymes isolated and purified from pineapple stems
and fruits. The enzymes are capable of dissolving and removing
necrotic tissue within a couple of hours and at the same time
they do not damage the potentially viable tissue. DGD consists of
Debrase powder, which is mixed and rehydrated just before application
by a hydrating agueous gel. Two or five grams of Debrase powder
are mixed with 20 or 50 grams of hydrating gel directly before
application and used to treat 100 cm2
or 250 cm2 of burn
written consent was obtained from each eligible patient before
randomization. Online electronic management of patient case record
files (eCRFs) was used. This also applies to randomization of the
patients for the study, which was provided online centrally. In the
first study there were three arms – DGD application, standard of
care (SOC), and gel only application. In the second study there were
two arms only – DGD application and SOC groups. Baseline vital
functions and blood samples for biochemistry and hematology
investigations were obtained before treatment in either of the
care before application
SOC groups standard wound care of the department was employed,
followed by either surgical interventions (tangential excision
followed by autograft wound closure), or use of biological skin
substitutes for coverage and/or promotion of autolytic debridement of
deep partial thickness burns. All the full thickness areas were
treated by early excision and autograft closure. Late autografting
was done in areas which did not heal within 3 weeks.
the DGD and/or gel only group (first study only) the wounds assigned
for treatment were cleansed several times by mild antiseptic solution
(Betadine soap) which was followed by complete removal of all the
remnants of devitalized epidermis. Thereafter wet sterile saline or
antibacterial solution soaks were applied to the wound for 2 hours
was applied at the bedside, or in a special room for dressing
changes for burn patients. Following removal of the dressing used for
initial soaking, the wound edges were covered by a protective
layer of sterile vaseline and the wound surface covered by a layer
of DGD 1.5 to 3 mm thick, spread evenly with a sterile
wooden spatula. The treated area was then covered by a sterile
occlusive film spread over the wound and fixed with a loose
sterile fluffy gauze outer dressing, held in place by elastic
bandages. This dressing was left in place for 4 hours. The treated
area needed to be kept warm (35–37°C).
of DGD from the wound
dressing was aseptically removed followed by removal of the
protective vaseline barrier with the use of a sterile spatula.
In thicker eschar another spatula was used to remove the dissolved
parts of the eschar from the wound by scraping. The wound was rinsed
several times with sterile saline followed by scraping of the wound
with sterile gauze. The efficacy of debridement was evaluated and new
soaking dressing with antibacterial solution was applied for 2 hours.
of post-debridement soaking dressing and assessment of debridement
removal of the post-treatment soaking dressing, the efficacy of
debridement was estimated as a percentage of the necrosis
removed. Debridement efficacy more than 90% was judged as excellent,
efficacy between 65% and 90% as good,
and less than 65% as poor.
If debridement was less than 65% the debridement could be repeated
once more with a new application of DGD followed by another 2
hours of soaking.
management post debridement offered quite a wide range of
options, depending on the decision of the surgeon. The options
included topical antibacterial treatment by silversulfadiazine cream
(SSD), wound coverage by allografts, xenografts, cultured allogenic
keratinocytes. Selective partial autografting of the very deep dermal
and full thickness areas was possible as well, leaving the more
superficial areas to heal spontaneously. We used all the above
methods except SSD. Continuous wound monitoring with adequate
therapeutic response to changes in the healing process was provided.
debridement was compared with the standard of care methods used at
the facilities participating at the multicenter clinical trial.
Primary endpoint of the study included the percentage of the original
wound which required surgical excision following enzymatic
debridement. Secondary endpoint was the time to complete wound
closure and the extent of the original wound which required
autologous skin grafting. Other investigations included measurement
of basic vital signs, pain assessment by a 10-grade visual
analogue scale, measurements of blood loss (number of blood
transfusions required), basic hematological and biochemical
parameters, occurrence of local and systemic adverse reactions and
take of eventually applied skin autografts.
22 patients were selected for the study. One patient was eliminated
from the study following selection because he fell out of the time
frame, and one patient was excluded during the study due to
development of delirium tremens of alcoholic origin.
age range was between 19 and 69 years (with exceptional approval for
the oldest patient). The DGD group included 10 patients, the SOC
group 7 patients, and the gel only group 3 patients (Table1).
only group of patients
all the three patients who received just gel instead of DGD no
debridement was achieved. All these patients were, according to the
study protocol, treated exactly the same way as the SOC patients.
group of patients
the DGD group of patients (Table 2) the debridement efficacy varied
between 50% and 100%. In 8 out of 10 patients the efficacy was more
than 90% (excellent). In one patient (No. 1) it was 80%, and in this
case the only repeated debridement was provided, with an efficacy of
30%. In this patient an additional surgical debridement of 15% of the
target wound was required as well, and almost the entire target wound
(TW) needed closure by autograft. The lowest efficacy – 50% (TW1)
and 70% (TW2) was observed in one patient (No. 10) where it was
assumed that the burns were more superficial than they appeared
clinically. This fact was also confirmed by the observation that the
wounds healed within 19 (TW1) and 32 (TW2) days
respectively, without the need for surgical intervention.
most of the patients the pain score during debridement was mild
(range 1 to 3); in 3 patients it was moderate (range 4 to 5) and
could easily be handled by the administration of analgetic
medications. The scar score was assessed after complete healing at
monthly follow-up visits. The scores in the table were estimated at
the 3rd monthly
visit. In most of the cases scarring was mild, while in only 2 cases
it was moderate. The most common adverse reaction (AR) was
temperature elevation – in almost all the patients. The second most
frequent AR was deepening of parts of the treated wound from deep
dermal to full thickness injuries, which required finally moderate
amounts of skin grafting. No severe infectious or other complications
were observed. The progress of wound healing was comparable to the
standard of care treatment patients.
group of patients
standard of care patients were treated according to the protocols
used in our burn department (Table 3). Initial wound care consisted
of surgical wound cleansing and debridement of loose devitalized
remnants of epidermis. Wound areas with dermal burns which were not
excessively deep were temporarily covered by non-meshed fresh frozen
xenografts, which were kept in place until most of the wounds were
healed. In areas where deepening of the wounds was observed and
necrotic skin was present, the patients were subjected to surgical,
mostly tangential excisions and wound closure by autologous skin
grafts. All the subdermal (third degree) burns were excised
surgically and grafted by skin grafts. The wound care and follow up
was identical to the DGD group.
enzymes have been used in order to remove necrotic tissues from the
wounds of different origin. The enzymes were derived from plants such
as papain and bromelain; from bacteria-like sutilains,
streptokinase-streptodornase and various other bacterial
collagenases. However, this type of debridement had many limitations.
The efficacy of all the above-mentioned enzymes was usually not
sufficient for early removal of all the necrotic tissues, which
resulted in necessity of prolonged exposures and repeated
applications. The wound surface assigned for debridement was also
limited due to the possible toxicity of the products. Moreover, the
use of enzymes was not recommended in the early phases of wound
treatment. Prolonged and repeated exposures led to increased risk of
severe wound infections, as has been observed during the treatment.
All these factors led to considerable prolongation of healing of the
wounds and more scarring (9, 14, 15, 16, 17).
treatment of deep burns by early excision became more popular in the
last few decades and was used preferentially in most of the burn
centers. The advantages included considerable shortening of
morbidity, reduction of mortality and reduction of infection and
hypermetabolic response. The overall healing time was reduced
significantly (1, 2). The drawbacks of surgical excision are that it
is an invasive procedure accompanied by significant perioperative
blood loss and postoperative pain. Selectivity of the procedure is
low, since surgical excision entails the removal of a considerable
amount of healthy viable tissue along with the necrotic tissues.
Compared to surgical excision, enzymatic debridement was more
selective but much more time consuming in the past.
to Rosenberg (13), the ideal debridement agent or method should have
the following attributes:
Safety; i.e. without any systemic adverse effects
and minimal, if any, bleeding.
Selectivity; resulting in removal of the necrotic
eschar without affecting the surrounding viable tissue, thus
permitting accurate diagnosis of the extent of the original damage.
Effective; removing the entire eschar, preferably in
a single application.
Rapid; resulting in rapid reduction of the infection
risk and permitting sequential debridement of large areas over
a short time span.
Simple to use and cost-effective.
study (13) of 130 burn patients with 332 deep dermal and full
thickness burns proved good safety, selectivity, efficacy and
rapidity of the debridement. In our study on a more limited
number of patients the similar favorable effects of DGD debridement
have been observed. In most of the DGD group patients the entire burn
eschar was digested within 4 hours following application. Selectivity
of the debridement was proved, particularly in deep partial thickness
burns, where enzymatic debridement could be used also as a diagnostic
procedure to differentiate between partial and full thickness burns
(Fig. 1–6). This would prevent unnecessary surgical procedures,
which could also remove much of the potentially viable tissues and
create full thickness injuries instead of partial thickness wounds
with a good potential for spontaneous healing enhanced by
biological dressings. In our patients all the three types of
post-debridement wound coverage (i.e. meshed skin allografts,
xenografts, or cultured allogeneic keratinocytes) together with
meticulous wound care provided good healing for the selectively
debrided partial thickness wounds. In full thickness injuries the
graft take at the debrided areas was comparable with the take of
grafts following excision procedures. The number of patients treated
at our department by DGD was not yet sufficient for statistical
evaluation of the results.
study was sponsored by MediWound Ltd.
of interest declaration
of the authors had any financial interests in
Prof. Ján Koller, M.D., Ph. D.
Department for Burns and Reconstructive Surgery
Hospital Bratislava, Ružinov Hospital
06 Bratislava, Slovak Republic
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