SYSTEMATIC REVIEW OF TOPIC TREATMENT FOR VENOUS ULCERS

Disponible en castellano/Disponível em língua portuguesa SciELO Brasil www.scielo.br/rlae 1 RN, PhD in Nursing, Professor, Minas Gerais Federal University, College of Nursing, Brazil, e-mail: eborges@ufmg.br; 2 RN, Free-Lecturer Professor, e-mail: mhcaliri@eerp.usp.br; 3 PhD in Sciences, Professor, e-mail: haas@eerp.usp.br. University of São Paulo at Ribeirão Preto, College of Nursing, WHO Collaborating Center for Nursing Research Development, Brazil Artigo de Revisão Rev Latino-am Enfermagem 2007 novembro-dezembro; 15(6):1163-70 www.eerp.usp.br/rlae


INTRODUCTION
Leg ulcers can be caused by several factors, such as vascular, metabolic and hematological alterations, while the main cause in industrialized countries is chronic venous insufficiency, with the consequent appearance of venous leg ulcers (1) .
The physiopathologic disorder determines venous hypertension, secondary varices, edema and trophic changes, whose ultimate expression is the ulcer, which represents approximately 70% to 90% of the total of leg ulcers (1)(2) .
Although it is difficult to determine the exact number of leg ulcers in the North American population over 65, an increase is estimated from 12% in 1988 to around 22% in 2030.The incidence of chronic venous insufficiency is approximately 5.9% and the prevalence of venous ulcers is around 1% in the Western world, and more frequent in the elderly (3) .
The study performed in Harrow, United Kingdom, identified a global prevalence of leg ulcers of 0.18%, while 38% presented evidence of deep venous system incompetence, 43% superficial venous system, 31% presented signs of ischemia and only 10% did not show signs of arterial or venous insufficiency (4)   .
There are few studies on the prevalence or incidence of leg ulcers in Brazil.One of the them was performed in Botucatu, SP, Brazil and its prevalence was approximately 1.5% of cases of venous active or healed ulcers (5)   . .

OBJECTIVE
This research aimed to perform a systematic review of primary studies and meta-analysis on topical treatment of leg venous ulcers, aiming to answer a set of questions presented in clinical practice, including: Inverse search was also used, which is a method to select documents based on the bibliography of primary documents recovered in the previous search (6) .
The following descriptors or key words were used -Results or measured outcomes The following dependent variables were considered measures to evaluate efficacy: reduction of the damaged area (cm 2 ), healing rate, average time of coverage duration, number of bacteria in the lesion, relapse, reduction of ankle circumference, level of pressure provided by the compression therapy.
-Study Design Studies of various designs were selected, classified according to the level of evidence proposed by Stetler and collaborators (7) : level I -meta-analysis

Review methods
To systematize the analysis of the quality of primary studies, an instrument based on methodological guidelines was created (8-9)   .Data were collected regarding the journal (title, language, date of publication), author (nationality, education, work place) and study (research funds, type of study, objective, sample characteristics, design, intervention, variables, analysis, results, according to elected outcomes, limitations and recommendations).For the critical evaluation of secondary studies (systematic reviews), besides data about the journal, author and study, the articles were classified into descriptive analysis or meta-analysis, according to the type of synthesis used in the data analysis (10) . The

Study Characterization
The sample was composed of 33 primary studies and two meta-analyses, totaling 35.The studies addressed a diversity of topical treatments for venous ulcer.Nineteen (54.3%) referred to compression therapy and 16 (45.7%)were related to topical therapy (Table 1).From the total of studies, six (17.1%) were about the use of the four-layer bandage system.However, studies on other forms of compressive therapy were also found, three (8.6%) of which were on short extension bandage, three (8.6%) on pneumatic compression and two (5.7%) on the use of the Unna boot.
Regarding the research design, the majority of studies were experimental with randomization (54.3%), followed by quasi-experimental studies (20%).Only two studies were meta-analyses (5.7%).
Considering the design and type of treatment, from the 19 experimental studies, six (31.58%) were about compression therapy and 13 (68.42%)about topical therapy.Four (21.1%) studies were on hydrocolloid, two (10.5%) on hydrofiber, two (10.5%) on Essaven gel and two (10.5%) on the Unna boot.In the quasi-experimental design group, seven studies were found, five of which referred to compression therapy and two to topical therapy.In the descriptive exploratory category, all four studies discussed treatment with the four-layer bandage system.As to case reports, two addressed treatment with short extension bandage or pneumatic compression and one the use of hydrocolloid.
The two metanalyses were related to compressive therapy.One of them, with a sample of 22 studies, evaluated the effectiveness and costeffectiveness of compression bandage and hosiery in ulcer treatment (11) .The other, with a sample of two studies, evaluated the effect of compression bandage in relapse prevention (12) .
The category of studies on compression therapy also included six randomized clinical studies.
The number of patients in these studies varied from 22 to 80.The studies compared several compression therapies, such as: long extension compression bandages compared to short extension compression bandages (13) ; Unna boot associated to intermittent pneumatic compression to Unna boot only (14)   ; fourlayer compression bandage to short extension compression bandage (15) ; Charing Cross four-layer compression bandages to an alternative compression bandage with a three-layer system (16) ; Unna boot with minimally invasive surgery (17) and Unna boot and compression bandage (18) .The main outcomes evaluated were ulcer healing rate (four studies) and the level of compression offered by the bandage (one study).
In the five quasi-experimental studies on compressive therapy, the number of participants varied from 17 to 44 in four, while one study considered the number of patient legs (n=42) as a sample.These studies compared intermittent pneumatic compression, provided by 30' and 60' (19)   , application or not of radiant heat (20) , elastic compression bandage, long extension with inelastic compression, short extension with fourlayer compression (21) , two alternative systems of multilayer compression (22) and comparison of three types of compression hosiery class II, with 25 to 35mmHg (23) .
As the main outcome, they evaluated the level of compression provided by the bandage or hosiery, healing rate, skin blood flow at rest, venous volume and capillary refill time and reduction of damaged area.
The four studies on compressive therapy with a descriptive-exploratory design proposed to: evaluate the relation between the pattern of venous incompetence and wound healing in patients using fourlayer compression bandages (24) ; determine the healing rate and cost of compression therapy (25) ; determine the healing rate with the use of the four-layer compression bandage system, Charing Cross (26) and evaluate the efficacy of the four-layer bandage system, Parema (27) .The study samples varied from 50 to 438 subjects and one counted 198 legs as a sample.
Among the case reports, one described two cases of intermittent pneumatic compression (28) and the other the use of short extension bandage (29)   .
One of the studies that addressed the topical therapy of venous ulcer was a case report and 15 were prospective controlled clinical trials.Two of these were quasi-experimental studies.The study samples were composed by venous ulcers or by the patients with venous ulcer.
Treatments were diversified and compared: hydrofiber dressing with calcium alginate (30) ; nonadhesive polyurethane with hydrocolloid, both associated to high compression bandage (33) ; hydrocolloid with gauze, both associated to Unna's boot (34) ; hydrofiber with calcium alginate, both associated to class C3 compression bandage (35) ; application of ultrasound with placebo, both associated to hydrocolloid (36)   ; topical treatment associated to laser stimulation compared with topical treatment associated to placebo, compared with topical treatment only (37) ; cryopreserved cultured epidermal graft with Systematic review of topic treatment... Borges EL, Caliri MHL, Haas VJ.
The two non-randomized studies compared essaven gel with placebo (43) and the association of hydrocolloid with PVP-I . The case study was a pilot study evaluating the properties of the hydrocolloid (45) .

Level of evidence
The majority of the studies analyzed (54.3%) showed evidence of level II and a minority (5.7%) level I. Regarding

DISCUSSION
Aiming for venous ulcer healing, the treatment for improving venous return must be delivered by physicians, nurses and other health professionals with the patient's cooperation and the use of compression therapy is essential, since it increases the healing rate of venous ulcers, when compared to the treatment without compression (11) .
The compression therapy must be consistently applied in order improve the care effectiveness and reduce treatment cost (11,24)   .Professionals who use the system must be trained (15) , since inadequate application of compression can lead to complications.
Graduated compression can control or reduce venous insufficiency (1) , though it must be used to heal non-complicated venous ulcers (11,25) , that is, patients who present an ankle/arm pressure index ≥0.8 (15).
There are situations in which graduated compression is counter-indicated, like in moderated and severe blood insufficiency, carcinoma, as well as in patients who are developing deep venous thrombosis (1) .
A better healing rate was obtained with the use of high compression bandage (40mmHg) instead of low compression or non-elastic compression bandages (11)   .The graduated high compression with a multilayer system capable of sustaining compression (40mmHg) must be used at least once a week (11) as the first choice treatment for non-complicated venous ulcers.So far, when compared with other multilayer compression bandage systems, using the same compression levels, the original four-layer Charing Cross compression system did not present differences in benefits like healing rate, comfort and time of permanence (11,15-16,27)   .Some studies presented similar healing rates of venous ulcers using four-layer and short extension bandages (11,(20)(21) , considering that the latter needs external support of one retention layer, such as the self adherent bandage, which can cause complications in members with extreme dimensions (21,28) .Other studies demonstrated better rates with the four-layer bandages when compared to Unna's paste associated to self-adherent bandage (11) .
Regarding intermittent pneumatic compression, results suggest that it favors the treatment of venous ulcer and must be considered as adjunct therapy.However, this recommendation is not a consensus, since its use did not produce differences in all analyzed studies (28) .
The use of radiant heat bandage shows to be safe and efficient for hospitalized patients with recalcitrant venous ulcer, but it requires more evaluations in order to investigate its efficacy in outpatient treatment (19) .
There were no evidences indicating the best topical therapy.The study results suggest the use of a simple, non-adherent coverage, of low cost and acceptable by patients.Polyurethane foam, hydrocolloid and calcium alginate are presented as treatment options (30)(31)(32)(33)(34)(35) .Hydrofiber or calcium alginate dressings must be used in intensively exudative (29,34) venous ulcers and polyurethane foam or hydrocolloid in ulcers with a low to moderate volume of exudate (30-32)   .
In case hydrocolloid coverage is used in association with zinc oxide paste (Unna's boot), at the end, a gradient compression bandage should be applied (34) .
In summary, dressings must be associated to compressive therapy in venous ulcer treatment.It is affirmed that a reduction of more than 30% in the wound area in the first two weeks of treatment is a prediction of healing (34) .
Patients with extensive ulcer or associated to arterial commitment can be favored with adjunct healing techniques, such as human skin and arterial revascularization, when possible (25)   .Minimally invasive surgical procedures are suggested for patients with primary commitment of the superficial venous system (17) .

CONCLUSION
The results suggest that compression treatment increases the healing rate of venous ulcers when compared to treatment without compression and results in reliable and cost effective healing in the majority of patients.Thus, it must be used to treat patients with venous ulcers.High compression must be used only in patients without arterial commitment.Lack of use of compression hosiery is associated to ulcer relapse.The study results do not permit conclusions about the best topical treatment for venous ulcer either.
Studies varied in terms of designs and used various products.In most studies, the sample was not calculated and the size, generally small, did not permit statistical tests.Several outcomes were evaluated in the same study and different ones between studies.Follow-up and treatment evaluation times were short, generally varying from days to weeks.Several studies presented limitations, such as the lack of explanation about the application method of the compression system or topical treatment, as well as the professional responsible for the procedure, lack of data related to the study site and patients' characteristics.
More randomized and controlled clinical trials need to be performed, with a priori determined samples, based on the primary outcome and with objective result measures, preferably evaluating only one main outcome.
for the bibliographic search: leg ulcer/ venous ulcer/ stasis ulcer/ varicose ulcer and similar terms in Portuguese and Spanish.The search delimitation considered the term topical treatment.The search was performed between March and June 2003 and the first selection of the articles was made through the analysis of abstracts.National libraries' bibliographic commuting service was used for locating publications, in addition to CAPES Journal Portal, the search engine Google and private collections of researchers in the theme area.To select the publications, the following criteria were considered: focus on human beings; Portuguese, Spanish and English; period of publication from 1993 to 2003 and the limit to locate the publication in Brazil was October 2003.Criteria for selecting studies for review -Subjects Only studies were included whose sample was composed of adult and elderly subjects with venous ulcer or described as stasis or varicose ulcer, except for arterial, mixed, diabetic etiology or purpura, schoenlein-Henoch.-Intervention Studies were included which evaluated treatments aimed at the improvement of venous return, such as compression hosiery or bandaging, as well as topical treatment with occlusion of the damaged area.Studies on topical treatment not commercially available in Brazil, such as the use of growth factors and cell culture, or studies whose results were not declared or explicit in the publication, were excluded.Systematic review of topic treatment... Borges EL, Caliri MHL, Haas VJ.

Table 1 -
Type of treatment and design of the studies analyzed.Ribeirão Preto, 2005