SUMMARY. In the Pirogov Medical Institute Burns and Plastic Surgery Centre in Sofia, Bulgaria, the medical preparation Contractubex® gel manufactured by Merz was used for the treatment of superficial burns and for prophylactics and treatment of hypertrophic scars and keloids. In the period 1997-2001 Contractubex® gel was administered to 211 patients (169 children and 42 adults). The patients were divided into two groups on the basis of the treatment strategy: one group, composed of 121 children and 28 adults, received medication by simple spreading or gentle massage; the other group, consisting of 48 children and 14 adults, was subjected to ultraphonophoresis with Contractubex® gel. Nine variables were monitored for comparison. Superficial burns were found to heal in the same terms as expected with classical treatment. However, the cicatrices that formed looked different: they were pink rather than reddish, their involution was faster, and their elasticity was greater. It was found that fresh cicatrices regressed more quickly than older scars and keloids, although general complaints were considerably reduced. Massage twice a day was preferred to massage once a day. Ultrasound accelerated the action, with good results appearing notably earlier. We report very good results in 161 patients (76 %), good in 39 (19%), and unsatisfactory in 11 (5%).
One of the tasks of reconstructive and plastic surgery is the treatment and restoration of shape and function in the affected human body. Prior to operative treatment, various conservative methods for the prevention and treatment of pathological cicatrization are used.
Both in surgically treated and in superficial burns, certain processes develop in the skin that lead to severe alterations in the newly formed cicatrices (such processes are less marked in surgically treated burns and more marked in superficial ones). Young connective tissue is less elastic, extensively vascularized, and pigmented. This abnormal process of wound healing can occur following both minor disease and trauma, e.g. piercing and acne, and severe accidents, e.g. burns. Excessive growth and deposition of collagen in the tissues characterize keloids and hypertrophic scars. This may be a result of insufficient decomposition of proteins and their consequential deposition in tissues.
The difference between keloid scars, hypertrophic scars, and normotrophic scars is a matter of histological morphology, cell function and growth factors. Fibroblasts stimulate the formation of collagen filaments, which instead of being parallel are often scattered chaotically. In time, fibres and cells decrease in number and the wound begins to shrink, this process depending on the severity of the injury. At best, a normotrophic cicatrix develops; otherwise, a hypo- or hypertrophic cicatrix or keloid is formed.
The reasons for the formation of these cicatrices are complex. Mechanical, local, physical, racial, and other factors have their importance. Treatment modalities also have to be considered.1,2 Surgery, drugs, and physiotherapy have been used in the attempt to find the most suitable treatment for these abnormal growths, but results have been unsatisfactory - hence the various methods and preparations that have been implemented in the treatment of this persistent condition. According to some researchers, compressive dressings and garments are an essential element in the prophylaxis and treatment of burn sequelae.3,4 Compressive silicon plaques and gels are also widely used.5-13 However, despite current advances in plastic surgery, their use in the treatment of scars and keloids is not always possible or effective. The progress of science has now made it possible to use laser therapy as well, although as yet with variable success.14-18 The use of cortisone in different forms (i.v., i.m. solution, creams, etc.) is widespread.19 Extensive use is made of gels and unguents for topical treatment, especially those that prevent or reduce pathological cicatrization and favour the involution of scars.20,21 Contractubex®, an onion-extract-containing gel manufactured by Merz, is such a preparation.22-29 This is a gel for the topical treatment of cicatrices, containing 10% Bulbus allii cepae extract, heparin sodium 5000 IU, allantoin 1 g, and methyl-4-hydroxybenzoate 150 mg. The composition of the extract is ether oils (0.005-0.15%), cyclo-alin-methyl-alein, propylalin, thiopropional-camphophelol, quartz derivatives, phloroglucin peptides, protocatechin acid, ferulic acid, amino acids, pectin phytohormones, vitamin C up to 33 mg/%, and vitamin B1 up to 60 mg. The gel is supplied in tubes of 20, 50, and 100 g.
During the period 1997-2001, Contractubex® was applied to 211 patients in the Department of Burns and Plastic Surgery at the NIEM Pirogov Medical Institute. Age distribution is shown in Table I.
The patients were divided into two groups (A and B) on the basis of the method of application.
Group A. Contractubex® gel was applied to 149 patients (121 children and 28 adults).
Superficial burns and burns after full epithelialization: the wounds were dressed every day and Contractubex® gel was applied in a layer of 1 mm by simple spreading on the skin. Patients with wound surfaces on the extremities with no bacterial growth were considered appropriate for this kind of medication.
Hypertrophic scars and keloids: the preparation was applied twice daily (morning and evening) with light rubbing massage.
In relation to the treated surface, Group A was divided into subgroups including superficial burns, freshly epithelialized superficial burns, skin autografts, hypertrophic cicatrices, and keloids (Table II).
<% createTable "Table II","Group A",";Superficial burns;Fresh epithelialized superficial burns;Skin autografts;Hypertrophic scars;Keloids;Total@;24;48;18;48;11;149@;16%;32%;12%;32.5%;7.5%;100%","",4,300,true %>Patients with IIAB degree burns had wound surfaces of up to 3% TBSA.
Patients with hypertrophic scars and keloids were divided into three groups, the first comprising patients with fresh hypertrophic cicatrices (one month after complete epithelialization); the second, patients with scars 2 to 10 months after epithelialization; and the third, patients with “old”, mature, untreated hypertrophic scars and keloids (Table III).
The shortest application period of Contractubex® gel was 3 months and the longest, 12 months. Patients were observed and results were compared at monthly follow-up examinations.
Group B. In 62 patients (48 children and 14 adults) Contractubex® gel was applied by ultraphonophoresis.
In both groups, we observed the following eight variables:
In patients with fresh, epithelialized burns and in autografts, only the kind of consequence and its evolution were evaluated.
In the first group (24 patients), epithelialization was achieved in the familiar terms known with other therapeutic means (Figs. 1, 2). However, the cicatrices that formed differed: their elasticity was considerably greater, with full mobility being preserved in zones near the large joints. The scars were pink rather than reddish as in other cases, and their involution was faster than that of scars treated differently. In these patients Contractubex® gel was used for an average period of 4 months.
| <% immagine "Fig. 1","gr0000001.jpg","Child with superficial burn.",230 %> | <% immagine "Fig. 2","gr0000002.jpg","Results after 30 days' treatment with Contractubex® gel.",230 %> |
In the remaining 125 patients in the first group, we applied Contractubex® gel locally, rubbing it on with light superficial massage, initially once daily and later twice daily.
In patients with fresh autografts (18 in number), these looked as if they were 6 months old after the preparation had been used for only about 60 days. Marginal scars were soft and normotrophic. We report only one unsatisfactory result, with slight corrugation and decreased autograft elasticity (Figs. 3, 4).
| <% immagine "Fig. 3","gr0000003.jpg","Fresh palmar autograft.",230 %> | <% immagine "Fig. 4","gr0000004.jpg","After 60 days' treatment with Contractubex® gel.",230 %> |
In patients with fresh hypertrophic cicatrices (one month or less after epithelialization), itching decreased after the third week of application of Contractubex® gel (21 patients). In 2-3 months the colour changed from intense red to pink. The primary juiciness and tension of the scar decreased visibly.
Average scar size in cm2 (80 cm2) decreased by 5.92 cm2 (7.8%) and average scar height (0.4 cm2) by 0.08 cm2 (4.4%) (Figs. 5, 6).
| <% immagine "Fig. 5","gr0000005.jpg","Fresh hypetrophic cicatrix after chemical burn.",230 %> | <% immagine "Fig. 6","gr0000006.jpg","Three months after use of Contractubex® gel.",230 %> |
The use of Contractubex® gel in this group continued on average for 6 months.
In the 2- to 10-month-old scar group, the decrease in cm2 was 6.24 cm2 (7.8%); scar height (0.7 cm on average) decreased by 0.1 cm (14.28%).
In 18 patients (72%), itching started to decrease and was tolerable and irregular at the end of the fourth week of gel application. In 5 patients (20%) itching decreased but remained constant, and in 2 cases (8%) the clinical effect was poor. Scar colour began to fade at the end of sixth week in 20 patients (80%).
The elasticity and softness of the scars began to change at week 24 of Contractubex® gel application, which is approximately 2 months earlier than with other medicines (Figs. 7-9).
| <% immagine "Fig. 7","gr0000007.jpg","Untreated post-burn hypertrophic scars and graft. Scars 6 months after last surgery.",230 %> | <% immagine "Fig. 8","gr0000008.jpg","Three months after Contractubex® gel treatment.",230 %> |
Old untreated cicatrices remained unchanged. In 80 patients from group A, the influence of Contractubex® gel on skin temperature was evaluated at the beginning and at the end of the application period.
Table IV presents the skin temperature of 56 children and 24 adults.
<% createTable "Table IV","Skin temperature results after Contractubex® gel application (45 days on average)",";Subjects;N°;I;II;Difference;p@;Children;66;38.02.00;37.06.00;0.06;0.01@;Adults;24;37.09.00;37.02.00;0.07;0.001@;Total;90;0.03;0.04;0.01;0.01","",4,300,true %>The average skin temperature of children at the first measurement was 38.2 °C. After a mean application of 45 days of Contractubex® gel, the skin temperature mean value was 37.6 °C, with an average decrease of 0.6 °C. The difference between the first and the second measurement was statistically significant (p < 0.01).
It is important to notice that the baseline skin temperature values in epithelialized regions and fresh cicatrices were higher than normal values (cf. I. I. Gurina’s table, 1959). The decrease in mean values after gel application indicated that beneficial changes had taken place in the cicatricial skin cells, improving peripheral haemodynamic elasticity.
Table V shows the results obtained with Contractubex® gel application via ultraphonophoresis. In 62 patients
(48 children and 14 adults), 10 to 26 procedures (mean number, 18) were performed.
<% createTable "Table V","Skin temperature changes after Contractubex® gel application by ultrasound",";Subjects;N°; I; II; Difference;p@; Before ultrasound; After ultrasound;Before ultrasound; After ultrasound; @;Children;48;33.08.00; 34.03.00;36.05.00; 37.03.00;2.07;0.01@;Adults;14;32.04.00; 32.08.00;34.08.00; 35.09.00;2.04;0.01@;Total;62; ","",4,300,true %>Skin temperature was measured before and after each procedure at the beginning and at the end of treatment.
Skin temperature increased by a mean value of 1.1 °C after each procedure in both children and adults. This was attributed to ultrasound, which has a moderate tissue hyperthermy effect.
At the end of the treatment period, skin temperature increased by an average value of 2.7 °C in children and 2.4 °C in adults. By then, skin temperature in the hypertrophic cicatricial region was already similar to normal skin temperature. Subjective complaints after ultrasound application abated in 40 patients (65%) and stopped completely in 22 patients (35%).
Good permanent results were achieved in subjects who underwent the maximum number of procedures, i.e. two or three series, each of ten procedures followed by a 15-20 day pause between each series and application of Contractubex® gel locally with light rubbing massage in between the rest periods. No allergic reactions to Contractubex® gel were observed during the study.
In 204 patients (97%), light epithelium desquamation was observed, but this stopped after discontinuation of gel application. With regard to the study population (211 subjects), we report very good results in 161 patients (76%), good in 39 (19%), and unsatisfactory in 11 (5%).
Skin cicatrices, regardless of the initial cause of their occurrence, always constitute a considerable problem for patients. Prophylaxis therefore has to begin in the acute trauma phase, even if this may be a stage when the physician’s primary concern is to save the patient’s life. Wound care, the type of dressing, and treatment strategies always influence the formation of post-burn cicatrices and keloids. The full set of procedures applied - physiotherapy, compression, and local medication - is of great importance.
The preparation Contractubex® gel by Merz is a perfect choice for local treatment, giving very good results in the treatment and prophylaxis of post-burn cicatrization. In our opinion application should start as soon as possible - before epithelialization is complete or immediately after wound defects have been covered. This applies both to spontaneously epithelialized superficial burns and to deeper burns covered by plastic surgery.
The preparation may be applied over epithelialized donor sites as well. Treatment should persevere throughout the course of cicatrix formation. Healing is a slow process - it sometimes takes years to be complete and it requires an accurate clinical approach. Tolerance by the patient is also essential.
Contractubex® gel can be used to treat old, mature cicatrices, although application is prolonged and the results are inconclusive. Chadzynska,22 Chadzynska and Jablonska,23 Willital et al.,25 and Jackson et al.26 confirm the effect of Contractubex® gel treatment.
Involution of fresh hypertrophic cicatrices is faster. In IIB degree burns, the resulting scars are softer and more elastic. Patients have fewer general complaints, which disappear after initiation of Contractubex® application.
No allergic reactions to Contractubex® gel were observed during the trial.
The decrease of cicatricial size accelerated considerably compared with treatment using routine preparations.
No side effects like those observed in long-term treatment with corticosteroids were encountered.
Massage twice a day was preferred to massage once a day. Contractubex® ultrasound application boosted its action and good results occurred considerably earlier, as confirmed by skin temperature findings.
RESUME. A l’Institut Médical Pirogov de Brûlures et de Chirurgie Plastique à Sofia, Bulgarie, les Auteurs ont utilisé la préparation médicale gel Contractubex®, fabriquée par Merz, dans le traitement des brûlures et pour la prophylaxie et le traitement des cicatrices hypertrophiques et des chéloïdes. Dans la période 1997-2001 ils ont administré le gel Contractubex® à 211 patients (169 enfants et 42 adultes). Les patients ont été divisés en deux groupes sur la base de la stratégie du traitement: un groupe, composé de 121 enfants et 28 adultes, a été traité avec un simple étalement ou un délicat massage; l’autre groupe (48 enfants et 14 adultes) a été traité avec l’ultraphonophorèse moyennant le gel Contractubex®. Neuf variables ont été contrôlées pour la comparaison. Les Auteurs ont trouvé que les brûlures superficielles guérissaient dans les mêmes termes que l’on trouve avec le traitement classique. Cependant, les cicatrices qui se formaient étaient différentes: elles étaient de couleur rose plutôt que rouge, leur involution était plus rapide et leur élasticité était majeure. Ils ont observé que les cicatrices neuves régressaient plus rapidement par rapport aux cicatrices et aux chéloïdes moins récentes, même si les affections générales étaient notamment réduites. Le massage deux fois par jour a été préféré au massage une fois par jour. L’ultrason a accéléré l’action, avec de bons résultats qui se manifestaient plus précocement. Selon les Auteurs, les resultants étaient très bons dans 161 patients (76 %), bons dans 39 (19%) et peu satisfaisants dans 11 (5%).