The Chinese Journal of Burns Wounds and Surface Ulcers 2000, 12(2): 26~29.

Report of Clinical Trial of MEBO

Duan Yan-fang Yichang TCM Hospital, Yichang, Hubei 443003, China INTRODUCTION During the year of 1998, our hospital treated 80 patients suffering various types of burns with Moist Exposed Burn Ointment (MEBO) under the direction of Moist Exposed Burn Therapy (MEBT). The main clinical observation index comprised healing modes for different extent burns, the incidence of scar formation in three months after healing, systemic treatment results, drug analgesic effect and possible toxicity and side effects. Meanwhile, a contrast study of 20 burn cases treated with conventional silver sulfadiazine (SD-Ag) was conducted as control. MATERIALS AND METHODS General information: One hundred patients totally were observed in this trial, including 80 patients receiving MEBO treatment (MEBO group) and 20 SD-Ag treatment (control group). Distribution of sex and average ages were 61 male and 19 female patients with an average age of 23.517.9 in MEBO group and 17 male, 3 female with age 30.512.7 in SD-Ag group. The causes of injury in MEBO group were mainly hot liquid and direct flame, accounting for 41.4 % and 40.0 % respectively, which compared to electricity (12 cases), chemicals and others. In control group, 50 % (10/20) patients sustained flame burn, 45.0 % (9/20) hot liquid scalds and 1 electrical burns. Severity of the burn injury: The average total body surface area (TBSA) and the largest TBSA of burns were 22.619.0 % and 90 % in MEBO group and 21.615.5 % and 75 % in SD-Ag group. The superficial II degree burns in two groups were 8.96.0 % and 8.33.8 % respectively, and there was no statistical difference between groups. Deep II degree burns were 17.9512.5 % and 13.57.7 %, and there showed significant difference between two groups (t=6.243, P<0.01), indicating deep II degree burns in MEBO group was obviously larger than that in SD-Ag group. However, according to Classification Standard of Chinese Burn Association established in 1970, the comprising proportions of the severity of burn injury in both groups were 21.3 % and 20.0 % (mild), 41.35 % and 55.0 % (moderate), 17.5 % and 15.0 % (severe), 20.0 % and 10.0 % (extremely severe), showing no statistical difference. Therefore, two groups were comparable in terms of TBSA and severity of burn injuries. In MEBO group, 18 patients were associated mild or moderate inhalation injury, accounting for 22.5 % and 8 patients (10 %) developed shock on admission. The incidences of inhalation injury and complication in SD-Ag group were similar to those in MEBO

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The Chinese Journal of Burns Wounds and Surface Ulcers 2000, 12(2): 26~29.

group, 15 % and 10 % respectively. In MEBO group, there were 26 patients (adult, 32.5%) whose arterial systolic pressures were lower than 12 Kpa on admission comparing to 4 patients (20 %) in SD-Ag group. The results of 2 test was P<0.01 (2=11.887), indicating the severity of burn shock in MEBO treating group was severer than that in SD-Ag control group. Frequency of burned regions: In Table 1, it was shown that in both groups, the burn wounds often involved trunk, head & face, arm, hand and neck regions of the body. The most easily exposed regions as head and face and upright nature of the human being of isolating from injury sources by hands may explain the predilection for these smaller anatomic areas sustaining the majority of the burns. Injury to trunk was mostly attributable to the larger anatomic areas.
Table 1. The frequency of burned regions in two groups
Right Hand Genitalia & Right Foot Head/face Right Arm

Left Hand

Right leg

Left Foot

buttocks

Left Arm

Left Leg

MEBO Group

SD-Ag Group

Management: Topical treatment: The exposure therapy was adopted in both groups and superficial and deep partial thickness wounds were advocated to heal spontaneously. While the skin grafting could be performed for repairing full thickness burn wound at appropriate time. Patients in MEBO treating group received standard Moist Exposed Burn Therapy (MEBT) through the whole treatment procedure, as the wounds were applied with MEBO ointment to a thickness of 0.5 mm~1 mm every 4 hours while no conventional debridement was needed. In SD-Ag control group, the wounds were treated with 1 % SD-Ag suspension according to the guideline of direction after debridement. Systemic treatment: Patients in both groups received similar anti-shock regime as recommended by standard resuscitation proposal of burn surgery. Total volume of fluid infusion at first 24-hour postburn = 1.5 ml (crystalloid & colloid fluid)/TBSA/kg body weight (2 ml/TBSA/kg body weight for child)+daily physiological water needs. However, for extremely extensive burn patients, the volume of fluid infusion were

Group No % No %

Trunk

Neck

48 60.0 9 45.0

31 38.8 6 30.0

43 53.8 8 40.0

44 55.0 8 40.0

39 48.8 7 35.0

37 46.3 5 25.0

54 67.5 9 45.0

52 65.0 8 40.0

19 23.8 4 20.0

14 17.5 5 25.0

38 47.5 11 55.0

22 27.5 5 25.0

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The Chinese Journal of Burns Wounds and Surface Ulcers 2000, 12(2): 26~29.

larger than that recommended by the formula on the condition that volume of urine output kept balance with infusion velocity. The fluid in the second 24-hour was half of first 24-hour actual infusion while physiological water needs maintained same. The amount of urine output was required to be 30~50 ml/hour in adult or 1 ml/hour/kg body weight in child. RESULTS 1. Wound healing area without skin grafting, days and incidence of scar formation of superficial II degree wound: All superficial II degree wounds in both groups healed without skin grafting. Although no statistical difference in healing area, the healing time in MEBO treating group decreased obviously. Two patients in SD-Ag control group developed apparent scar with an incidence of 10 %. The four-fold table was used to perform 2 test: 2 =8.163, P<0.01, indicating that superficial II degree wounds in SD-Ag control group had potential to scar formation (Table 2).
Table 2. Comparison of wound healing size without skingrafting, time and incidence of scar formation of superficial II degree wound in two groups (xs)

Group (Number) MEBO group (80) SD-Ag group (20)

Healing area (% TBSA) 8.96.0 8.33.8

Healing days 9.32.2 * 14.10.7

Scar formation (%) 0 ** 10.0 (2/20)

Compared with SD-Ag group: t=8.865, P<0.01

2 Compared with SD-Ag group: =8.163, P<0.01

2. Wound healing area without skin grafting, days and incidence of scar formation of deep II degree wound: All patients in MEBO treating groups healed without skin-grafting while 2 cases in control group by skin grafting (Table 3).
Table 3. Comparison of wound healing size without skingrafting, time and incidence of scar formation of deep II degree wound in two groups (xs) Group (Number) MEBO group (80) SD-Ag group (20) Healing area (% TBSA) 17.912.5 13.57.7 Healing days 22.53.0 * 28.33.6 Scar formation (%) 21.3 (17/80) ** 95.0 (19/20)

Compared with SD-Ag group: t=6.243, P<0.01

2 Compared with SD-Ag group: =17.783, P<0.01

3. Healing mode, time and incidence of scar formation of III degree wound: Fifteen patients in MEBO group sustained III degree wound with a average area of

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The Chinese Journal of Burns Wounds and Surface Ulcers 2000, 12(2): 26~29.

14.112.5 % BSA and healing time of 42.96.2 days. There were 6 patients receiving skin grafting. All patients developed scars. In SD-Ag control group, only 1 involved III degree burn (75 % TBSA, 45 % III degree). Superficial II degree wound of this patient healed on day 14 postburn and on day 35 there were still 5 % deep II and 45 % III degree granulation wounds unhealed, which responded to skin grafting at last. The total skin grafting BSA was 50 % and healed on day 60 with large area of scar left. 4. Evaluation of analgesic effect: Table 4 presented 5 degrees to assess analgesic effect after drug application in both groups. The results indicated that scales of excellent and good in MEBO treating group were higher than those in SD-Ag control group.
Table 4. Comparison of analgesic effect between two groups

Group (Number) MEBO group (80) SD-Ag group (20)

Excellent 43 0 **

Good 37 0 **

Fair 0 15

Poor 0 5

Very poor 0 0

Compared with MEBO treating group: **P<0.01

5. Assessment of pain intensity during changing dressing: See Table 5.

Table 5. Comparison of pain intensity on drug renewal

Group (Number) MEBO group (80) SD-Ag group (20)

0 17 0 **

I 56 2 **

II 7 18

III 0

Compared with MEBO treating group: **P<0.01

6. Incidence of wound infection: Because of few cases of wound infection development, a statistic analysis on the total incidence of wound infection based on three infectious index was conducted (Table 6). The results showed that the incidence of wound infection of MEBO treating group was significantly lower than that of SD-Ag control group (2=12.255, P<0.01), confirming treatment with MEBO could control wound infection effectively.
Table 6. Comparison of wound infection between two groups

Group (Number)

Wound cellulitis

Sub-crust empyema

Necrosis of newly regenerated tissues or delay repair

Wound infection (%)

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The Chinese Journal of Burns Wounds and Surface Ulcers 2000, 12(2): 26~29.

MEBO group (80) SD-Ag group (20)

4 1

2 7

1 0

7 (8.75) 8 (40.0) **

Compared with MEBO treating group: **P<0.01

7. Lab examination: During the whole treatment procedure, the changes of hemoglobin, white blood cells (WBC), renal and liver functions were examined. Among them, WBC showed obvious changes (Table 7). WBC in MEBO treating group kept linear progressive descent during shock, liquefaction and recovery periods while no elevation tendency in liquefaction period. In SD-Ag control group, WBC maintained as high as 15109/L during shock and liquefaction periods.
Table 7. Comparison of peripheral venous WBC count between two groups (109/L, xs)

Group (Number) MEBO group (80) SD-Ag group (20)

Shock period 21.15.2 15.64.1 **

Liquefaction period 12.94.3 15.23.2

Recovery period 7.81.5 8.51.4

Compared with MEBO treating group: ** t=2.690, P<0.01

8. Largest TBSA and III degree area treated and cured: In MEBO treating group, the largest cured TBSA was 90 % (50 % III degree) without disability comparing to 75 % TBSA (45 % III degree) with disability left in SD-Ag control group. 9. Toxicity and side effects: In this trial, no skin rash, urticaria or other allergic reactions were found in both groups. DISCUSSION Since MEBO could improve microcirculation of wound, loose spasm of arrectores pilorum and isolate wounds from air, it had very satisfactory analgesic effect, which was verified by evaluation of analgesic effect in MEBO treating group in this trial. While in SD-Ag control group, patients complained of obvious pains as it was showed as fair or poor in analogue scale. The comparison indicated the analgesic effect of MEBO was superior to that of SD-Ag. The average healing time for superficial II degree wound in MEBO treating group was 9.32.2 days comparing to 14.10.7 days in SD-Ag control group. There was significant difference between two groups (P<0.01), indicating that MEBO could

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The Chinese Journal of Burns Wounds and Surface Ulcers 2000, 12(2): 26~29.

greatly shorten the healing time of superficial partial-thickness burn wound. For deep partial-thickness burn wound, the average healing time in two groups were 22.53.0 and 28.33.6 days respectively. The significant difference between two groups (0.01<P<0.05) again validated the above conclusion. As far as full-thickness burn wound concerned, MEBO could promote III degree wound to heal spontaneously in a physiological environment and facilitate the sweat gland residing in viable subcutaneous layer to heal wound by epithelialization, which was far reached by SD-Ag. In this trial, no pain or less pain was reported in MEBO treating group during changing dressing. However, in SD-Ag control group, patients complained of great pains and sometimes analgesic was needed. MEBO was proven to be dramatically superior to SD-Ag with regard to causing further pains to patients. In some reports, the unscientific treating condition misled some medical staff to draw a mistaken conclusion that MEBO predisposed to wound infection. So we complied with standardized and strict requirement to carry out this trial to compare MEBO with SD-Ag treatment. The results showed that the incidence of wound infection in MEBO group was obviously decreased than that in SD-Ag control group (P<0.01). This may be attributed to the following two reasons: (1) Since the first appearance of SD-Ag about thirty years ago, some microorganisms are becoming resistant to SD-Ag because of its wide application in clinic, which greatly weakens its bactericidal effect. (2) The causative bacteria of burn wound infection become more and more diversified as rare bacteria such as Grams negative bacilli have predominated currently. However, the available spectrum of antibacterial activity prevents SD-Ag from killing all pathogen. (3) The application method of SD-Ag is basically against the treatment principle in surgery of preventing infection by drainage. Besides therapeutic effects, the toxicity and side effects should also be investigated to assess advantages and limitations of any medicine. Therefore, the comparison of toxicity and side effects between MEBO and SD-Ag was an important clinical observation index included in this trial. In MEBO treating group (80 patients), liver and renal functions under dynamic monitoring maintained normal and no systemic toxicity or side effects was found except 2 cases developing local allergic reaction. In SD-Ag control group (20 patients), great pains were reported and 2 patients were found to involve leukocytopenia with an incidence of 10 %. Leukocyte is well known as the most important immunocyte in human body and leukocytopenia may directly impair the patients ability to defend against infection. Especially for extensive burn patient, hypoleukocytosis predisposes to early fulminant septicemia or wound sepsis, which has close correlation to whether patients can be cured or not. The above observations and contrasts gave strong proofs that MEBO preceded SD-Ag. It is a commonly accepted conception in burn management that the general therapeutic effects of any new technique and medication should be assessed by the results of treating extensive burn patients since burns are the essential of all kinds of traumas. The success of treating extensive burns can validate the absolute effect of new technique and medication. The results in this trial verify not only the success of

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The Chinese Journal of Burns Wounds and Surface Ulcers 2000, 12(2): 26~29.

MEBO in treating extensive burns, but also satisfactory functions rehabilitation after healing from extensive burns, which are beyond the capacity of contemporary burn medical society.

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