MEBO BURN OINTMENT

HEALTHHEALTH TECHNOLOGY ASSESSMENT UNIT

TECHNOLOGY ASSESSMENT
MEDICAL DEVELOPMENT DIVISION SECTION
MINISTRY OF HEALTH MALAYSIA
MEDICAL DEVELOPMENT DIVISION
SERIAL NO 015 /2011

MINISTRY OF HEALTH MALAYSIA

015/2011
DISCLAIMER
Technology review is a brief report, prepared on an urgent basis, which draws on
restricted reviews from analysis of pertinent literature, on expert opinion and / or
regulatory status where appropriate. It is not subjected to an external review process.
While effort has been made to do so, this document may not fully reflect all scientific
research available. Additionally, other relevant scientific findings may have been
reported since completion of this review.

Please contact: [email protected], if you would like further information.

Health Technology Assessment Section (MaHTAS)

Medical Development Division
Ministry of Health Malaysia
Level 4, Block E1, Precinct 1
Government Office Complex
62590 Putrajaya.

Tel: 603 88831246

Fax: 603 8883 1230

Available at the following website: http://www.moh.gov.my

ii
Prepared by: Puan Noormah Mohd. Darus
Principal Assisstant Director
Health Technology Assessment Section (MaHTAS)
Medical Development Division
Ministry of Health Malaysia

Reviewed by: Datin Dr. Rugayah Bakri

Deputy Director
Health Technology Assessment Section (MaHTAS)
Medical Development Division
Ministry of Health Malaysia

External Reviewer: Miss Lim Lay Hooi

Senior Consultant and Head of Department
Plastic and Reconstructive Surgery
Hospital Pulau Pinang

DISCLOSURE

The author/ authors of this report have no competing interest in this subject and the
preparation of this report is totally funded by the Ministry of Health, Malaysia.

iii
EXECUTIVE SUMMARY

Introduction
Wound healing is a complex series of events characterized by inflammation; however, it does not culminate
in tissue regeneration but rather in tissue restoration. Healing involves three processes: epithelialization,
connective tissue deposition, and contraction. Factors adversely affecting wound healing include advanced
age of patients, poor nutrition, smoking, diabetes, anemia, obesity, cancer, ischemia, uremia and
denervation. Local wound factors such as infection and prolonged periods of pressure greater than tissue
perfusion pressure results in delayed healing as well. There is, however, more recent evidence in literature
that good hydration is an important external factor responsible for optimal wound healing. Superficial and
partial-thickness burns usually heal within 2 weeks unless complications such as infection or chronic
diseases occur. Topical ointments such as Flammazine are commonly used for the treatment of superficial,
and partial thickness burns to keep the wound environment in moist condition, decrease pain, and prevent
bacterial infection.

Moist Exposed Wound Ointment (MEBO) (Julphar Gulf Pharmaceutical Industries, UAE) is the basis of
MEBT (Moist Exposed Burn Therapy). It has been popularized two decades ago by Xu Rongxiang from the
Beijing Chinese Burn Center. It offers the advantages of a moist environment for wound healing in addition
to those of the open treatment technique avoiding cumbersome, bulky, and expensive dressings. Clinical and
experimental studies reported in the Chinese literature have demonstrated that the ointment markedly
reduces evaporation from the wound surface.

This review was requested by the Director of Hospital Kuala Lumpur following a presentation on the MEBO
ointment by Prof Chen Yong Chong, Plastic surgeon and Clinical Director of China National Science &
Technology Centre for Burns, Wounds and Ulcers.

Objective
To assess the effectiveness, safety and cost-effectiveness of MEBO BURN OINTMENT for use in the
medical facilities in Ministry of Heath Malaysia such as for burn therapy, skin graft, wounds and ulcers.

Results and conclusion

The retrieved evidence on clinical trials had small number of patients. Most of the papers were poorly
designed. There was a report on longitudinal case series published in The Chinese Journal of Burns Wounds
& Surface Ulcers from 1989 to 1994 which mentioned only descriptive results of scars and healing time.
However, these longitudinal case series are of low level evidence.

Hence, scientifically more rigorous studies such as randomized control trials with bigger sample size and
standardized outcome measures are needed to show effectiveness of MEBO ointment for wound healing and
treatment of burn injuries (even for partial thickness /second degree burns).

Methods
Literatures were searched through electronic databases specifically PubMed/Medline, Cochrane, OVID,
INAHTA and also in general databases. Google was used to search as additional web-based information. In
addition websites for existing HTA agency, society websites and cross-referencing of the articles retrieved
were also carried out accordingly to the topic.

A critical appraisal of the retrieved papers was performed and the evidence level was graded according to
the US/Canadian Preventive Services Task Force.

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MEBO BURN OINTMENT

1. INTRODUCTION

Wound healing is a complex series of events characterized by inflammation; however, it does not culminate
in tissue regeneration but rather in tissue restoration. 1, 2 Healing involves three processes: epithelialization,
connective tissue deposition, and contraction. The contribution of each process varies according to the type
of wound. Factors adversely affecting wound healing include advanced age of patients, poor nutrition,
smoking, diabetes, anemia, obesity, cancer, ischemia, uremia and denervation. Local wound factors such as
infection and prolonged periods of pressure greater than tissue perfusion pressure results in delayed healing
as well. 1, 3,4 There is, however, more recent evidence in literature that good hydration is an important
external factor responsible for optimal wound healing. 2, 5-13 In the natural course of events, dermis or deeper
subcutaneous tissues devoid of epidermal protection lose water to the atmosphere. The uppermost layers
become dehydrated and incorporated in the scab trapping some of the leukocytes that crowd to the wound
surface.

Superficial and partial-thickness burns usually heal within 2 weeks unless complications such as infection or
chronic diseases occur.14,15 Topical ointments such as Flammazine are commonly used for the treatment of
superficial, and partial thickness burns to keep the wound environment in moist condition, decrease pain,
and prevent bacterial infection. 15, 16, 17

Moist Exposed Wound Ointment (MEBO) (Julphar Gulf Pharmaceutical Industries, UAE) is the basis of
MEBT (Moist Exposed Burn Therapy). It has been popularized two decades ago by Xu Rongxiang from the
Beijing Chinese Burn Center. 2, 18 It offers the advantages of a moist environment for wound healing in
addition to those of the open treatment technique avoiding cumbersome, bulky, and expensive dressings.
Clinical and experimental studies reported in the Chinese literature have demonstrated that the ointment
markedly reduces evaporation from the wound surface.2, 18

This review was requested by the Director of Hospital Kuala Lumpur following a presentation on the MEBO
ointment by Pro Chen Yong Chong, Plastic surgeon and Clinical Director of China National Science &
Technology Centre for Burns, Wounds and Ulcers.

2. OBJECTIVE

To assess the effectiveness, safety and cost-effectiveness of MEBO BURN OINTMENT for use in the
medical facilities in Ministry of Heath Malaysia such as for burn therapy, skin graft, wounds and ulcers.

3. TECHNICAL FEATURES

The MEBO BURN OINTMENT is a registered USA patented formulation since 1995. MEBO is pure
herbal, natural in origin, containing beta-sitosterol phellodendron amurense, scutellaria baicalensis, coptis
chinensi, pheretima aspergillum, Beeswax and sesame oil. 15, 19 The pharmalogical effects are attributable to:
beta-sitosterol, isolated from phellodendron amurense,
flavonoids mainly baicalin isolated from scutellaria baicalensis,
alkaloids mainly berberine, isolated from coptis chinensi,
Beeswax and sesame oil

MEBO was claimed to reduce severe pain of burns, prevents shock, and reduces dermal infections. Wound
healing is promoted by prevention of dermal water loss. Additionally the vendor claimed that MEBO
showed anti-inflammatory, anti-bacterial and analgesic effects. It was claimed that therapy with MEBO

5
induces a fast healing accompanied by a low hazard of infection, and that the use of analgesics can be
reduced or stopped. 15, 19

4. METHODOLOGY
4.1 Search Methods
Literatures were searched through electronic databases specifically PubMed/Medline, Cochrane, OVID,
INAHTA and also in general databases. Google was used to search as additional web-based information.

The search strategy used the terms, which are either singly or in various combinations: MEBO BURN
OINTMENT, phellodendron amurense, scutellaria baicalensis, coptis chinensi, pheretima aspergillum, beta-
sitosterol, isolated from phellodendron amurense, baicalin isolated from scutellaria baicalensis, berberine,
isolated from coptis chinensi MEBO for burns, MEBO for fast healing, effectiveness and cost effectiveness
either singly or in combination with the limits to humans and English. In addition websites for existing HTA
agency, society websites and cross-referencing of the articles retrieved were also carried out accordingly to
the topic.

4.2 Selection of studies

Any primary and secondary papers pertaining to MEBO BURN OINTMENT will be included in this
technology review. Those which full text could not be obtained were excluded. A critical appraisal of the
retrieved relevant papers was performed and the evidence level was graded according to the US/Canadian
Preventive Services Task Force (Appendix 1).

5 RESULTS AND DISCUSSION

5.1 Effectiveness of MEBO BURN OINTMENT

In a study by Hirsh et al, forty patients with 2nd degree thermal burns, with partial-thickness burns < 20%
total body surface area (TBSA) aged 18 to 70 years old were enrolled within 48 hours post- injury. 15 level 1
The patients were randomly divided into two groups, 20 patients in each treatment arm: Study group
received MEBO ointment topical wound treatment. The second group received standard Flammazine based
therapy, and served as positive control. Wound healing was assessed by measuring the transepidermal water
loss (TEWL) using a dermalab device and a wound closure index (calculated by clinical assessment, and
photographic documentation of the epithelialization) was performed additionally. A pain assessment was
performed using visual analogue scale 0 to 10 (0 = no pain; 1-2 = slight pain; 3-4 = mild pain; 5 = moderate
pain; 6-9 = moderately severe pain; 10 = severe pain). The primary endpoint was defined as the change of
epithelization of the wound between baseline, and day 12. Epithelization of the wound was measured as the
difference of transepidermal water loss (TEWL) between intact skin, and the deepest part of the wound.

Transepidermal water loss (TEWL) in the MEBO group was 24.3gr/m2/h, whereas the Flammazine
treated group showed 24.8gr/m2/h on day 0.
There was a mean/median difference of 2.3gr/m2/h between MEBO, and Flammazine in advantage
of MEBO. However, this difference was not statistically significant (p=0.78).
No clinical signs of infection or bacterial contamination occurred, and no positive wound swabs
could be detected in the investigated wounds during this study.
There were no significant differences that could be detected between both groups for the mean
course of Wound Closure Index.
The assessment of pain in the patients according to the visual analogue scale showed a strong
decrease in reported pain from an average of 5 (moderate pain) for both group to 3.8 for the MEBO
study group and 3.5 for Flammazine respectively.

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Allam A.M. et al did a study on 106 patients who had acute partial-thickness burned hand with total burns in
less than 25% body surface area (BSA). 20 level 1 The cases were selected out of 442 burn patients treated
from Burns Unit in Tanta, Egypt. The patients were randomly allocated to one of two groups: Group 1: hand
managed by daily application of 1 % local silver sulphadiazine SSD cream, Group 2: moist exposed burn
ointment MEBO applied as a local agent twice daily. In patients with bilateral burned hands, each hand was
managed separately either in group 1 or in group 2. In both groups, the hand was kept moving freely in a
sterile polyethylene bag. The results were as follows:

There were no significant differences between the two groups regarding either the analgesic effect
after local ointment application or hand movement inside the polyethylene bag.
The daily wound evaluation found more crustation of the agent used over the wound managed by
local 1% SSD cream (69.81%) compared to MEBO
On follow-up, the burned hands healed faster using MEBO (10.48 versus 14.53 days), with fewer
post-burn hand deformities and better active hand movements; however, the total cost until complete
hand burn wound healing was higher with MEBO than with 1% SSD. The cost of the daily topical
agent to dress the burned hands with MEBO was 9.0 Egyptian pounds and 2.17 Egyptian pounds
with 1% SSD cream.
However, the final results were superior, with early return to work, when MEBO was used, with
fewer post-burn complications and more rapid healing as well as with shorter hospital stay.
Healed burned hands treated with MEBO had a more or less normal functional range of movements
with fewer post-burn hand complications, reducing post-burn hand surgery which can compensate
for the cost of the MEBO dressing in the acute burn stage.

In a study by Sakr MF et al, eighty seven patients with 182 chronic pressure ulcers treated at five hospitals
from different areas in world, between January 2003 and January 2009, were randomized into 2 groups;
those in group 1 (n=46) received MEBO while those in group 2 (n=41) received Fucidin. 21 level 1 Data
collected prospectively included demographics, nutritional status, underlying predisposing disease and co-
morbidities. Ulcer surface area (SA) and healing index (HI) were calculated and compared at two-week
intervals for 12 weeks. Results were as follows:
Patients in both groups had similar demographic, clinical, biochemical features, and ulcer
characteristics. There was a significant increase in healing index (HI) and reduction in ulcer surface
area (SA) on weeks two and four respectively, that was maintained through 12 weeks in patients
treated with MEBO.
More than half of ulcers (56.5%) treated with MEBO had complete healing (HI = 1) by 12 weeks, as
opposed to only 19.6% of those treated with Fucidin (P<0.001).
Moreover, none of the patients receiving MEBO had a HI of <50% of their ulcers by 12 weeks as
compared to 26.8% of those receiving Fucidin (P<0.001). No adverse effects or allergic reactions of
topical ointment were encountered in either group.
In addition to its safety, MEBO significantly promotes the healing of chronic pressure ulcers with
significant increase in HI of any given ulcer as early as two weeks following initiation of treatment,
and complete healing of more than 50% of ulcers by 12 weeks.

Ang ES at al did a trial that was conducted in a specialized burn facility located in a tertiary referral hospital
in a developed and industrialized island-state in Southeast Asia. 22 level 1 Patients between the ages of 12 and
80 who had partial-thickness thermal burns covering less than 40% of body surface area (BSA) were
randomly assigned to receive either MEBO or C (burns wounds were cleansed with chlorhexidine 0.05%
and dressed with SSD). Fifty-seven patients were assigned to MEBO and 58 patients to C. The latter group
received twice-daily dressing changes; MEBO patients received MEBO every 4 hours. Patients were
hospitalized until 75% BSA had healed. BSA was determined by visual inspection and charted on Lund and

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Browder charts regularly. Wound healing rate, bacterial infection rate, pain score, and hospitalization costs
were recorded. The results were as follows:
The median time to 75% healing was 17.0 with MEBO and 20.0 days with C, respectively (HR =
0.67, 95% CI = 0.41-1.11, P =.11), suggesting similar efficacy between the 2 modalities.
Bacterial infection rates were similar between the 2 groups (HR = 1.10, 95% CI = 0.59-2.03, P =.76).
MEBO imparted a greater analgesic effect in the first 5 days of therapy and reduced hospital costs by
8% compared with the conventional arm.
The mean cost of both hospitalization and consumables per patient was lower with MEBO, by
Singapore (SGD) $493 and SGD $360, respectively (USD$1 ~ SGD $1.67). The mean dressing time,
however, was higher with MEBO by a mean of 312 minutes or 5 hours. Patients were dressed either
by a Registered or Assistant Nurse on approximately equal numbers of occasions. The additional
dressing time was calculated to cost SGD $43 more per patient on MEBO. However, overall, the
mean cost per patient for MEBO was reduced by 8% compared with the conventional arm.

Atiyeh BS et al did a series of clinical studies conducted in multiple centers (Lebanon, Greece, Italy, France
and Dubai) to demonstrate the validity of using MEBO in clinical practice 23 level II-1.
In Phase I: Clinical study 1, 15 consecutive patients with no underlying medical conditions requiring split
thickness skin grafts were included in this prospective clinical study. A skin graft 0.012 inches thick was
harvested with a Padget Electric Dermatome from the thigh. Moisture retentive ointment (MEBO) was
applied in a thick layer on half of the split thickness skin graft donor site and covered by a thin non-
occlusive semi open dressing. It was reapplied and the dressing changed daily until full re-epithelialization.
On the other half, the standard conventional dressing was applied intra-operatively consisting of antibiotic
impregnated Vaseline gauze, Sofra Tulle, covered by a bulky gauze dressing held in position by an elastic
bandage. Twenty four to forty eight hours later, the bandage was removed and the now adherent gauze was
kept uncovered and undisturbed in place until spontaneous separation occurred. Parameters evaluated
included speed of re-epithelialization, analgesia, and cosmetic appearance of resultant scars. Photographic
documentation at regular intervals was performed. The longest follow up was eighteen months.
Wounds treated by the moisture retentive ointment were completely re-epithelialized within 5-6 days
while the conventionally treated areas required 10-12 days to re-epithelialize and were markedly less
hyperemic and pigmented. Final cosmetic appearance as documented photographically, as well as
patient's satisfaction and preference were much superior for the MEBO treated areas.
In Phase II: Clinical study 2, 20 Split Thickness Skin Grafts (STSG) donor sites in 13 adult patients
requiring skin grafts were included in this study. 0.012in thick skin grafts were harvested uniformly in all
patients by the same investigator using the Padget electric dermatome. Donor sites were assigned randomly
for MEBO (10 fields) or Tegaderm (10 fields) application. The ointment was applied daily in a thick layer
and covered by a simple semi-open dressing. Tegaderm layer, on the other hand, was changed whenever
indicated.
Anatomical healing time for MEBO was 8.9 ± 2.846 days and 13.133 ± 2.258 days for Tegaderm
(significant difference p=0.0185). Three fields of the Tegaderm group developed local wound
complications
Average functional barrier recovery time was 67.4 ± 13.368 days for MEBO and 150 ± 46.476 days
for Tegaderm (extremely significant difference p=0.0005). Significantly better scar quality was also
observed in the MEBO group compared to Tegaderm as evidenced by photographic documentation.
In Phase III: Clinical trial 1, a prospective multicenter clinical trial was conducted between December 1999
and November 2000. 52 patients of both sexes with burn injuries (30 flame burns, 18 scalds and 4 patients
with other causes of thermal injury) with an age range of 12 to 80 years (mean 40.5 y) were entered in the
study according to strict inclusion and exclusion criteria. All patients were seen at the outpatient department.

8
The burned areas were cleansed with physiologic saline solution along with debridement of blisters. The
lesions were subsequently dried before the application of a thick layer of MEBO ointment (1-2 mm).
Whenever it was more convenient, dry sterile gauze with an elastic bandage were applied. Ointment
application was performed once or twice daily after gently removing the previously applied layer. A total of
100 burn sites with a Total Body Surface Area (TBSA) of 0.5% to 15% were evaluated by physical
examination, recording of patients’ satisfaction, and assessment of pain by the visual analogue scale.
Transepidermal water loss and moisture were measured at regular intervals. Swab cultures were also done
regularly.
After the application of MEBO, a rapid and progressive reduction of edema and clinical
inflammation was noticed. It was also observed that topical ointment application contributed to the
debridement of the wound facilitating rapid epithelialization within 2 to 6 days. Prior to MEBO
application, the mean value of the pain scores was 6.92 ± 5.50. Pain scores decreased gradually
following treatment.
During the following assessments at days 6, 9 and 12 the changes in the pain scores became
statistically extremely significant (p<0.001)
After one week of MEBO treatment, bacterial wound colonization decreased to 10% in the
immediate group (started on MEBO application on the first or second post-burn day) and to 61% in
the late group (started on MEBO on the third post-burn day or later). By the second week,
colonization dropped to 5% and 23% respectively. All patients with positive swab cultures
progressed to complete healing.
In Phase IV: Clinical trial 2, forty patients of both sexes between the ages of 5 and 54 years presenting with
superficial partial thickness burns 5–20% TBSA in adults and 5–15% TBSA in children greater than 5 years
of age sustained <24 hrs prior to presentation over a period of 3 months were included in the study. The
study was conducted in five different centers in Egypt where medical care is largely under government
control in order to minimize accounting discrepancies. All patients were admitted to the hospital and
assigned randomly to two comparable study groups. Twenty patients were managed with the moist exposed
method and 20 other patients received the standard local therapy utilized at the given center.
The author mentioned there was a reduction in hospital stay for the moist exposed therapy group.
The author also mentioned that there was a decrease in the average time spent by the treating
physicians and nurses with patients treated by the moisture retaining ointment as compared to time
spent with patients treated by other modalities.
MEBO-treated patients required fewer analgesics.

A prospective clinical trial was conducted from December 1999 to November 2000 in multiple centers from
Italy, France, Greece, and Lebanon in order to evaluate the effect of a newly described moisture retentive
ointment (MEBO) on healing of chronic ulcers affecting mainly the lower extremity by Atiyeh BS et al. 24
level II-1
A total of 47 patients with non-healing wounds and ulcers were entered in the study. Patients with
wounds or ulcers failing to heal for more than 1 month were included in the study. Five additional cases
with problematic wounds of less than one month were also included. Local wound management was
accomplished by daily application of a thick layer of ointment (1-2 mm) using gauze or a blunt instrument
(tongue depressor) after gently removing the previously applied layer. Dry sterile gauze and an elastic
bandage then covered the wound. All wounds and ulcers were evaluated at weekly intervals whether patients
were hospitalized or seen at the outpatient department. Upon each evaluation, a ruler was placed adjacent to
the ulcer and a photograph was taken. Wound surface area was subsequently calculated with computerized
planimetry. Due to the variation in ulcer size between patients (0.4 cm2 - 61.98 cm2), which makes
comparison rather difficult, a healing index was calculated. It was computed by dividing the difference in
ulcer size between days 0 and any given day X by ulcer size at day 0. Healing Index (HI) = (Ulcer size day 0

9
– Ulcer size day X) / Ulcer size day 0 The index ranges between 0 at the initial day of assessment and 1 after
completion of healing irrespective of ulcer size
Considering all types of ulcers together, there was an extremely significant reduction in ulcer surface
area and increase in healing index over the first 3 weeks of treatment.
Looking at the 0.25 healing index curves, it was shown that more than 50% of all ulcers reached 0.25
HI within the first week, more than 80% within the second week, and more than 90% within the third
week.
100% of the non-neurotrophic ulcers reached 0.25 HI by the third week while only 80% of the
neurotrophic ulcers reached the same stage of healing.
50% of all ulcers reached 0.75 HI by the second week, and around 80% by the fourth week, while
85% of non-neurotrophic and about 65% of neurotrophic ulcers reached 0.75 HI by the fourth week.

Atiyeh BS et al presented the results of three clinical comparative prospective studies that were conducted
using MEBO.
Clinical Study I
Fifteen consecutive patients, otherwise healthy, requiring split thickness skin grafting of open wounds were
included in the study. A Padget Electric Dermatome was used in all patients to harvest a skin graft 0.12 thick
from the thigh. To avoid patient to patient variation, the same patient acted as his own control. A thick layer
of MEBO covered by a thin nonocclusive semi-open dressing was applied on half of the split thickness skin
graft donor site surface area. The ointment was reapplied and the dressing was changed daily until full
reepithelialization. The other half was covered by the regular conventional dressing we have been using
routinely. An antibiotic impregnated Vaseline gauze (Sofra-Tulle) was applied at the time of surgery
covered by bulky gauze dressing held in position by an elastic bandage. The bandage was removed 24• 48
hours later, and the now adherent gauze was kept uncovered and undisturbed in place until spontaneous
separation occurred. Photographs taken at regular intervals documented the clinical observation of cosmetic
appearance following healing of the two study areas over a follow-up period of 1 year.
Complete re-epithelialization was observed within 5-6 days in the MEBO-treated areas while the
conventionally treated areas required 10.12 days to heal.
The MEBO-treated areas were markedly less hyperemic and less pigmented. This difference in
appearance persisted all through the observation period and was maintained on long-term follow-up.
The final cosmetic appearance and the patients’ satisfaction were superior for the MEBO-treated
areas.
Hyperemia cleared almost completely from the MEBO-treated areas within 3 months but persisted
for more than 6 months in the Sofra-Tulle treated areas.
In all patients, there was lack of epidermal sliding in the MEBO-treated area similar to normal skin.
Variable degrees of epidermal sliding could, however, be demonstrated in Sofra-Tulle-treated areas.

Clinical Study II
Over a period of 9 months, 13 adult patients with no underlying medical conditions requiring split thickness
skin grafts to cover open defects participated in the second prospective clinical study. Thick skin grafts
(0.012 inches) were harvested uniformly in all patients by the same investigator using the Padget electric
dermalome. A total of 20 donor site study fields were available. They were assigned randomly for MEBO
(10 fields) or Tegaderm (10 fields) application. In 5 patients, MEBO and Tegaderm could be applied
simultaneously on two separate fields and in 1 additional patient, 3 donor fields were available for
investigation. The ointment was applied daily in a thick layer after gently removing the previously applied
layer with sterile gauze, and the site was covered by a simple semi-open dressing. Applied Tegaderm
membrane, on the other hand, was changed whenever indicated, either when excessive fluid had
accumulated or fluid leakage had occurred or whenever the membrane had lost its adherent occlusive
property. Ointment or Tegaderm application was continued until anatomical healing was observed.

10
 Time for anatomical re-epithelialization in the second study as observed clinically for MEBO was
about 8.9 days and about 13.1 days for Tegaderm.
The observed difference between the two study groups was significant (p = 0.0185). Moreover, 3
Tegaderm-covered fields developed local wound complications.
Though initially in the first 3 days, Transepidermal water loss (TEWL) values in the MEBO-treated
group increased sharply from initial base line values, average TEWL at the time of anatomical
healing was not significantly different for the two study groups: 10.58 and 11.93 times greater than
normal for MEBO and Tegaderm, respectively.
However, average functional barrier recovery time was about 67.4 days for MEBO and about 150
days for Tegaderm.
The difference between the two groups was extremely significant (p = 0.0005). Better scar quality
was also observed in the MEBO group as evidenced by photographic documentation and scar
assessment scores at 1, 2, and 6 months.

Clinical Study III

Primary healing was assessed prospectively in 60 consecutive traumatic or surgical facial wounds repaired
by linear closure. The study included 38 patients followed over a period of 9 months. All were Fitzpatrick
skin types III, IV, and V. All wounds were managed by the same surgeon. Patients were clustered on an
alternating basis in to two major groups. Group I: 20 scars treated with MEBO application 3 to 4 times a
day. Application was started immediately postoperatively whenever feasible, or after removal of steri-strips
whenever subcuticaler repair was performed and was continued for 6 weeks. Group II: 25 scars managed
with application of topical antibiotic ointment (Fucidin) until removal of sutures a few days thereafter. A
third additional group of 15 scars that were mainly covered by adhesive tape following suturing did not
receive any topical therapy and were considered a control group.
In the third study evaluating primary healing, cosmetically better scars consistent with lower scores
are observed in group I (MEBO) at 1, 3, and 6 months.
The difference between groups I and II was extremely significant (p < 0.001) at 6 months. The same
significant difference was observed when only scars parallel to the crease lines were considered. This
difference was reduced to a significant level (p < 0.05) for nonparallel scars.
Differences in scores for color, contour, distortion, and aspect between groups I and II were
extremely significant (p < 0.001) in favor of MEBO group at 1 and 3 months.

Al-Meshaan M. et al did a study to assess the role of MEBO (moist exposed burn ointment) in topical
treatment of the wound secondary to surgical debridement. 26 level 1 Eleven patients (age range, 40-75 yr;
mean, 55 yr) were admitted to the clinical facilities of the Department of Urology at Al Sabah Hospital,
Kuwait, suffering from Fournier’s gangrene, in the 31-month period between January 2004 and July 2006.
The patients were treated with triple antibiotic therapy (penicillin, amikacin, and metronidazole) and the
necrotic tissue was immediately and aggressively debrided surgically. The patients were then randomly
divided into two groups: one group (six patients) received MEBO for the topical treatment of the raw area,
while the other group of five patients received only placebo (KY gel). MEBO was applied as a relatively
thick layer (about 3 mm) under a sterile dressing after cleansing of the wound with povidone solution (Figs.
1,2). The placebo was applied in a similar way. All 11 patients suffered from comorbid diseases, as follows:
nine patients were diabetic (82%), six were obese (55%), and two were immunocompromised (18%) (one
due to liver transplantation and one due to kidney transplantation). Chronic urinary tract infection with
urethral strictures was found in two cases (18%) and hyperhydrosis with skin disease in three (27%); eight
patients cases reported chronic perineal itching (72%). Hypercholesterolaemia was detected in seven
patients (64%). The results were as follows:
The duration of hospital stay was reduced by 41.7% in the MEBO-treated group (30 days
compared to 51 days in the control group)

11
 Pain relief was felt faster in the group of patients treated with MEBO, which could be attributed
to the faster control of infection and wound healing in this group.
Hence, a combination of appropriate antibiotic coverage and aggressive surgical therapy is mandatory for
the treatment of Fournier’s gangrene. MEBO promotes the healing of the resulting, quite extensive wound,
reducing pain and controlling infection. It is a also a cost-effective therapy as it accelerates healing and
reduces hospital stay by 41.7%.

Kefei Y et al reported 4954 cases from 1989 to 1994, which were published in the Chinese Journal of Burns
Wounds and Surface and cases collected by the authors for many years in clinical practice. There were 77
kinds of burns wounds and surface ulcers. The cure rate of the 4954 cases was more than 92%, and the
effective rate reached 100%. The average course of disease was 4.36 years. The average healing time was
16.18 days. The age and gender of these patients were: Twenty-five hundred and ninety one males (54.32%)
and 2263 (45.68%) females were included in this study (male: female= 1:0.84); 535 cases were children
(10.80%), 4203 cases (84.84%) were grown-ups, and 216 cases (4.36%) were senile. The types of diseases
the patients had were as in the table 1 below
Table 1: Types of disease and healing time

No Type Case Number Percentage Average

(%) duration (day)
healing time
1 Common wounds in surgery 2675 53.99 23.78

2 Wounds in E.N.T and 953 19.24 17.58

ophthalmology
3 Wounds in gynaecology and 724 14.61 15.78
obstetrics
4 Wounds in dermatology 574 11.59 13.53
5 Wounds in cosmetology 28 0.57 10.24

Total 4954 100 16.18

The results after using MEBO on the 4954 cases were as follows:
There were no scars or few scars left after the wound was healed.
After using MEBO, the scars of third-degree burn wound are thin and soft, and have little influence
on their functions. The main mechanisms of its curative effects include:
o The dermal cells in the survival dermis tissues of the wound regenerate and divide faster
under the effect of MEBO, fill up the impairment of dermis tissues, so as to restore the
wound.
Obvious curative effects were obtained, and the course of treatment was reduced. Based on the
statistical analysis, the shortest average course of disease was 0.63 year, the longest average course
of disease was 8.08 years, the shortest average curing time was 10.59 days, the longest average
curing time was 21.58 days, and the average curing time was 16.18 days.
For the ulcer patients, in the MEBO group, there were 785 cases, the average cure time was
13.41±3.75 days; in the control group with routine treatment, there were 552 cases, and the average
cure time was 33.76±5.8 days. There was significant difference between the 2 groups (P<0.001).

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5.2 Safety

There was no retrievable scientific evidence on the safety or adverse events of MEBO BURN OINTMENT.

5.3 Cost-effectiveness

Atiyeh BS et al (2002) study was conducted in five different centers in Egypt where medical care was
largely under government control and accounting is rather uniform. 27 level 1 Forty patients of both sexes
between 5 and 54 years of age presenting with superficial partial thickness burns sustained <24 h prior to
presentation over a period of 3 months (maximum duration of treatment was 29 days, minimum duration of
treatment was 6 days) were included in the study. All patients entered in the study have been admitted to
hospital and were assigned randomly to two comparable study groups Twenty patients were managed with
MEBO application, while 20 other control patients received the standard local therapy utilized at the given
center [Silversulphadiazine, Sofratulle, Chlorhexidinetulle, Nitrofurazone, Quadriderm (betamethasone +
chlorocresol + clioquinol +gentamicin ,+ tolnaftate), Dexpanthenol, Nitrofurazone, Savlon (cetrimide +
chlorhexidine), Hydrogen peroxide, Povidone–iodine].

Overall cost of therapy was evaluated by estimating both direct and indirect costs. Direct cost included
actual cost of the topical agent used, i.v. fluids, concomitant antibiotics, analgesics and other pharmaceutical
agents and preparations, such as gloves, catheters and dressing materials. Direct cost included also cost of
hospitalization as fixed by authorities as well as the cost of all performed laboratory tests. Indirect cost was
estimated by computing time spent by the treating physicians and nurses in attending to the various needs of
the patients, such as dressing changes, debridement and bathing. Total cost of treatment as well as individual
components (hospitalizations duration and cost, physician/nurse time, topical treatment, systemic antibiotics,
analgesics, other medications, laboratory services and medical materials) were recorded, calculated (as per
course of treatment or per day). The results were as follows:
The reduction in hospital stay for the MEBO-treated group was statistically very significant (P <
0.01) whereby the mean hospital stay for MEBO group was 12.84 days while for the control it was
18.35 days.
The observed decrease in the average time spent by the treating physicians with patients treated by
MEBO (0.21 per day and 2.58 per course) as compared to time spent with patients treated by other
modalities (0.29 per day and 4.82 per course) was significant (P < 0.05). On the other hand the
decrease in average time spent by nurses between the two groups was very significant in favor of
MEBO application (0.51 per day and 6.73per course) as compared to control (0.61 per day and 10.95
per course).
The combination of longer hospitalization and increased cost of conventional dressings clearly
demonstrated the positive benefit of MEBO application in the topical treatment of minor to moderate
second degree burns over conventional standard methods of local treatment whenever early surgical
tangential excision and skin grafting was not feasible or warranted.

Atiyeh BS et al (2004) did a prospective clinical study from September 2003 to December 2003 in 14
different hospitals in the Kingdom of Saudi Arabia. 28 level 1 Fifty two patients with a second degree Total
Body Surface Area (TBSA) burns of 5 to 35% (average 12.55 + 5.77) were included in the study after
obtaining a signed informed consent from the patients or from their legal guardians. All patients were
admitted to the hospital and assigned randomly into two groups. One study group was treated with moist
exposed burn therapy using the moisture retaining ointment (MEBO) under investigationa second control
group received the standard burn treatment for the given hospital. Agents used for local burn wound care
were (Silver Sulfadiazine, Extract cepae 10%, heparin sodium 5000 iu and allantion, Panothenic acid,
Chlorohexidine, Fucidic acid, Bacitracin zinc and neomycin sulphate, Povidone iodine Sofratulle. Overall
cost of therapy was evaluated by estimating both direct and indirect costs. Direct cost included actual cost of

13
the topical agent used, intra−venous fluids, on comitant antibiotics, analgesics and other pharmaceutical
agents and preparations, such as gloves, catheters and dressing materials. Direct cost included also cost of
hospitalization as well as the cost of all performed laboratory tests. Indirect cost was estimated by
computing time spent by the treating physicians and nurses in attending to the various needs of the patients,
such as dressing changes, debridement and bathing. Total cost of treatment as well as individual components
(hospitalizations duration and cost, physician/nurse time, topical treatment, systemic antibiotics, analgesics,
other medications, laboratory services and medical materials) were recorded, calculated (as per course of
treatment or per day). The result showed that:
A reduction of 20.24% in hospitalization time was observed for the study group as compared to
the control group.
The overall reduction in treatment cost for the MEBO study group was significant (p=0.025) per
course of treatment (Total treatment cost. MEBO application resulted in a reduction of 25.7% as
compared to the control group.), but not significant (p=0.5653) per day though a 9.41%
reduction in daily cost was observed.
Difference between the 2 groups in treatment cost excluding hospitalization was not significant
per course (p=0.1381), and per day (p=0.2700) despite a 25% reduction in daily cost achieved
with MEBO application.
On the other hand difference in hospitalization cost including accommodation and physicians and
nurses cost was very significant in favor of the study group (p=0.0051) per course of treatment
[Total hospitalization cost (accommodation, physicians and nurses cost) with MEBO application
resulted in 20% reduction as compared to the control group]. The reduction in total time spent
by physicians attending patients was significant (p=0.0216) per course (39.43% reduction
achieved with MEBO).
The reduction in total time spent by nurses, however, was very significant (p=0.0095) per course
of treatment. (Time spent by physicians and nurses per course of treatment. MEBO application
resulted in 39.43% reduction in physicians’ time and 28.67% nurse’s time).
Cost of topical agent was 9% lower with MEBO per course of treatment and 2.4% per day of
treatment. Similarly, the decrease in material cost including gloves, catheters, canulae, syringes,
IV fluids, dressings, and cleansing solutions observed with MEBO per course or per day was not
significant despite 36.43% and 28.05% reduction respectively.
Reduction in systemic antibiotic cost achieved with MBT was 50.42% per course and 47.72% per
day. These differences statistically were not significant.
The same was observed for the cost of other medications cost. Analgesic cost per day was
reduced by 60.8% with MEBO per course (significant p=0.0135) and 55.88% per day
(significant=0.0271).
Surgical debridement was required in 4.54% (n=1) of the MEBO treatment group, and in 18.18%
(n=4) of the conventional treatment group (P >0.05).
Overall total treatment cost was also significantly reduced by MEBO with a significant reduction
of the physicians’ work load, and a very significant reduction of the nurses’ work load.
Resultant scars following MEBO application may require fewer scars related treatment
modalities and perhaps less secondary corrective procedures that by itself may make MEBO
application a more cost beneficial local burn wound care modality

Ang ES et al did a study to assess the effectiveness of MEBO compared with conventional burn wound
management (CBWM) in patients who have partial-thickness burns. 29 level 1 The study population comprised
all patients with partial-thickness burns who were admitted to the Singapore National Burns Center between
1 April 1997 and 24 October 1998. The study population was aged between 6 and 80 years. The study was a
randomized controlled trial that was carried out at a single centre. The conventional burn wound
management (CBWM)group comprised of 55 patients while 57 patients were in the MEBO group. The

14
direct costs included in the study were those related to the hospital, consumables and the time to dress
wounds. No indirect costs were included in the study. The results showed that:
The time to 75% of initial body surface area (BSA) healing could be assessed for 25 patients in the
CBWM group and 36 patients in the MEBO group. The median time to 75% healing, as shown by
the Kaplan-Meier curves, was 17 days in the MEBO group and 20 days in the CBWM group, (hazard
ratio, HR=0.67, 95% CI: 0.41 - 1.11; p=0.11). A Cox regression model, in which there is an
adjustment comparison for the initial burn BSA at randomization, gave an HR of 0.61 (95% CI: 0.36
- 1.02; =0.061).
In the 2 weeks after randomization, there were 17 patients in the CBWM group with an MRSA
infection and 16 in the MEBO group. At 14 days, the MRSA infection rate was 35.5% for the
CBWM group and 37.4% for the MEBO group.
The mean cost was SGD $10,180 (range: 697 - 79,301) for the CBWM group and SGD $9,697
(range: 990 - 55,533) for the MEBO group.
The mean difference in the cost of consumables per patient was lower in the MEBO group by SGD
$360. The mean cost was SGD $975 (range: 22 - 6,651) for the CBWM group and SGD $595 (range:
22 - 3,027) for the MEBO group.

6 CONCLUSION

The retrieved evidence on clinical trials had small number of patients. Most of the papers were poorly
designed. There was a report on longitudinal case series published in The Chinese Journal of Burns Wounds
& Surface Ulcers from 1989 to 1994 which mentioned only descriptive results of scars and healing time.
However, these longitudinal case series are of low level evidence.

Hence, scientifically more rigorous studies such as randomized control trials with bigger sample size and
standardized outcome measures are needed to show effectiveness of MEBO ointment for wound healing and
treatment of burn injuries (even for partial thickness /second degree burns).

7 REFERENCES

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moisture retentive ointment in the management of cutaneous wounds and ulcers: A multicenter
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 29. Kefei Y, Jianming M, Qi Y, A Comprehensive Report on the Therapeutic Effect of MEBO in
Treating 4954 Cases of Various Wounds and UlcersThe Chinese Journal of Burns Wounds and
Surface Ulcers 1997, 33(4): 15-21

8. APPENDICES
8.1 Appendix 1 - Level of Evidence Table

Level Study design

I Evidence obtained from at least one properly designed randomized controlled trial
II-1 Evidence obtained from well-designed controlled trials without randomization
II-2 Evidence obtained from well-designed cohort or case-control analytic studies,
preferably from more than one centre or research group
II-3 Evidence obtained from multiple time series with or without the intervention.
Dramatic results in uncontrolled experiments (such as the results of the
introduction of penicillin treatment in the 1940s) could also be regarded as this
type of evidence
III Opinions or respected authorities, based on clinical experience; descriptive
studies and case reports; or reports of expert committees

Source: US/CANADIAN PREVENTIVE SERVICES TASK FORCE (HARRIS 2001)

17