Efeitos do tratamento com Hidrogel na cicatrização de

Transcription

UNIVERSIDADE FEDERAL DO RIO GRANDE DO NORTE
CENTRO DE CIÊNCIAS DA SAÚDE
PROGRAMA DE PÓS-GRADUAÇÃO EM FISIOTERAPIA
Efeitos do tratamento com Hidrogel na cicatrização de úlceras
venosas de membros inferiores: Revisão Sistemática
Cibele Teresinha Dias Ribeiro
Natal
2014
Cibele Teresinha Dias Ribeiro
Dissertação apresentada à Universidade
Federal do Rio Grande do Norte –
Programa de pós-graduação em
Fisioterapia, para a obtenção do
título de Mestre em Fisioterapia.
Orientador: Guilherme A. F. Fregonezi
Natal
2014
Universidade Federal do Paraná
Sistema de Bibliotecas
Ribeiro, Cibele Teresinha Dias
Efeitos do tratamento com Hidrogel na cicatrização de úlceras venosas de
membros inferiores: revisão sistemática. / Cibele Teresinha Dias Ribeiro. –
Natal, 2014.
96f: il.; 30cm.
Orientador: Guilherme Augusto de Freitas Fregonezi
Dissertação (Mestrado) – Programa de Pós-Graduação em Fisioterapia.
Centro de Ciências da Saúde. Universidade Federal do Rio Grande do Norte.
1. Úlcera venosa. 2. Insuficiência venosa. 3. Hidrogel. I. Título II.
Fregonezi, Guilherme Augusto de Freitas. III Universidade Federal do Rio
Grande do Norte. Centro de Ciências da Saúde. Programa de PósGraduação em Fisioterapia.
CDU 616-002.44
Coordenador do Programa de Pós-Graduação em Fisioterapia:
Jamilson Simões Brasileiro
iii
BANCA EXAMINADORA
Prof. Dr. Guilherme Augusto Freitas Fregonezi
Presidente - UFRN
Prof. Drª Selma Sousa Bruno
UFRN – Membro Interno
Prof. Drª Andrea Lemos Bezerra de Oliveira
UFPE – Membro externo
Aprovada em 04/02/2014
iv
Dedicatória
Ao meu esposo, Fernando e a minha filha Bianca.
v
Agradecimentos
Inicialmente quero agradecer a Deus e a minha família por me amparar nos
momentos difíceis, me dar força interior para superar as dificuldades, me mostrar o
caminho certo nas horas incertas e me suprir em todas as minhas necessidades.
Aos meus pais, pela educação, pelos valores, pelo que sou hoje. Ao meu pai, que
tenho certeza estar comemorando comigo mais esta vitória. De onde você estiver,
pai, agradeço tudo o que fez por mim e por ter mostrado a todos que viver vale a
pena e temos que lutar até os últimos segundos de nossas vidas pelo e por quem
mais amamos!! A minha mãe, amor incondicional, por sempre me apoiar, ajudar em
todos os momentos e estar presente nos momentos mais especiais e importantes da
minha vida. A todos os familiares, em especial a minhas irmãs, Danielle e Franciele,
as quais sempre estiveram ao meu lado, me apoiando e que, apesar da distância,
nossa união e cumplicidade sempre estiveram presentes. A minha tia Solange, que
teve uma participação especial na minha educação como minha professora também.
Ao meu professor mais especial, esposo, companheiro, amigo, meu “porto
seguro”, Fernando Dias, obrigada por tudo! Agradeço por toda a sua paciência em
sempre estar pronto a passar o seu conhecimento de maneira clara e com
entusiasmo. Você é um exemplo de professor e pesquisador. São admiráveis a sua
dedicação ao ensino e a forma como contagia a todos a também querer aprender
cada vez mais. E a minha filha Bianca, que é a razão da minha vida.
Agradeço ao Professor Guilherme Fregonezi, pela orientação. Obrigada pelas
oportunidades oferecidas pelo senhor antes mesmo de iniciar o mestrado e pelos
ensinamentos que foram fundamentais durante todo esse tempo.
Agradeço a oportunidade de ter participado do curso de Revisão Sistemática
com a Prof.ª Andrea Lemos e a sua presença na banca. Seus ensinamentos foram
primordiais para que eu conseguisse aprimorar os conhecimentos em revisão
sistemática.
vi
Agradeço também às pessoas que fazem parte do grupo de Feridas da
Colaboração Cochrane, Sally Bell-Syer e Ruth Foxlee. Vocês também foram
essenciais para a realização desta revisão, pois sempre responderam aos meus emails prontamente, resolvendo minhas dúvidas e enviando sugestões.
A todos os colegas de mestrado, principalmente a Fernando Macedo, que nos
deixou tão inesperadamente, mas que tive a oportunidade de conhecer melhor no
laboratório 6, ajudando-o nos pilotos do projeto por ele desenvolvido. Que você
esteja em paz!
A todos os amigos que faziam e ainda fazem parte do laboratório 6, pelo
convívio e aprendizagem.
As pessoas especiais que sempre serão lembradas durante o período no qual
vivi em Natal: à professora e amiga Vanessa Resqueti, pela amizade, por todos os
momentos juntas, principalmente os de convívio familiar; à Diana Freitas e Gabriela
Chaves, por compartilharmos sempre dúvidas dos nossos trabalhos e pelos ótimos
momentos que vivenciamos no departamento; à Jaqueline Andruchak, pela amizade;
à professora Ana Raquel, uma das primeiras pessoas a qual conheci em Natal e
que sempre me apoiou na realização desse mestrado além de ter convivido com ela
em muitos momentos em família.
Aos funcionários do departamento de Fisioterapia da UFRN, principalmente a
Edriene e a D. Eudione, por sempre estarem dispostas a me ajudar, servindo como
“babás” para que eu conseguisse participar de cursos e aulas.
E a todos que, de alguma forma, fizeram parte de mais essa etapa, o meu
sincero Obrigada por tudo!!
vii
SUMÁRIO
Dedicatória
v
Agradecimentos
vi
Listas
Lista de abreviaturas
x
Lista de figuras
xi
Lista de gráficos
xii
Resumo
xiii
Abstract
xiv
1 INTRODUÇÃO
1
1.1 Doença venosa crônica
2
1.2 Úlceras venosas
5
1.2.1 Processo de cicatrização de uma úlcera
7
1.2.2 Curativos de carboximetilcelulose
8
1.3 Justificativa
11
1.4 Objetivos
12
1.4.1 Objetivo principal
12
1.4.2 Objetivos secundários
12
2 MATERIAIS E MÉTODOS
13
2.1 Caracterização da pesquisa
14
2.2 Etapas de uma revisão pela Colaboração Cochrane
14
2.3 Critérios para considerar os estudos para a revisão
17
3 RESULTADOS
19
viii
3.1 Descrição dos estudos
38
3.1.1 Resultados da busca
38
3.1.2 Estudos incluídos
40
3.2 Risco de viés dos estudos incluídos
41
3.3 Efeitos do hidrogel
44
3.3.1 Comparação entre hidrogel, Quitosana, e gaze com solução salina (He e col. 2008)
44
3.3.2 Comparação entre hidrogel, Intrasite, e gel de alginato (de la
Brassine e col. 2006)
46
3.3.3 Comparação entre hidrogel, Intrasite, e mel de Manuka (Gethin e
col. 2008)
47
3.3.4 Comparação entre hidrogel e hidrocolóide (Grotewohl, 1994) 48
4 DISCUSSÃO
50
5 CONSIDERAÇÕES FINAIS E CONCLUSÃO
53
6 REFERÊNCIAS BIBLIOGRÁFICAS
55
ANEXOS
61
ANEXO 1: Protocolo publicado-Hydrocolloid for healing venous leg ulcer 62
ANEXO 2: Estudos excluídos e justificativas para exclusão
80
ANEXO 3: Características dos estudos incluídos
87
ix
Lista de Abreviaturas
DVC- Doença Venosa Crônica
IC- Intervalo de Confiança
ITB- Índice Tornozelo-Braquial
IVC- Insuficiência Venosa Crônica
NPF- Nurse Prescriber´s Formulary
RevMan- Review Manager
RR- Risco Relativo
TVP- Trombose Venosa Profunda
x
Lista de figuras
Figura 1: Fluxograma da estratégia de elaboração de uma revisão sistemática pela
Colaboração Cochrane.
Figura 2: Diagrama com o resultado da seleção dos estudos.
Figura 3: Avaliação do risco de viés de todos os estudos incluídos na revisão
Figura 4: Avaliação do risco de viés de cada estudo incluído na revisão: julgamento
dos autores de cada item para cada estudo incluído.
xi
Lista de gráficos
Gráfico 1: Forest plot representando a comparação do hidrogel com gaze com
solução salina para o desfecho cicatrização completa das úlceras.
Gráfico 2: Forest plot representando a comparação do hidrogel com o gel de alginato
para o desfecho porcentagem de redução da úlcera em 4 semanas de tratamento.
Gráfico 3: Forest plot representando a comparação do hidrogel com o mel de
Manuka para o desfecho cicatrização completa das úlceras.
Gráfico 4: Forest plot representando a comparação do hidrogel com o mel de
Manuka para o desfecho incidência de infecção.
xii
Resumo
A doença venosa crônica (DVC) evidencia-se entre as doenças crônicas por
acometer a população idosa e ser a principal responsável pelas úlceras de membros
inferiores nesta população. O uso de adesivos no cuidado de uma úlcera venosa é
parte fundamental no tratamento para a cicatrização, no entanto, as evidências para
auxiliar na escolha do melhor adesivo são escassas. O objetivo principal do estudo
foi avaliar a eficácia do tratamento com o hidrogel na cicatrização de úlceras
venosas mediante métodos de busca, síntese de informação e análise estatística
através de uma revisão sistemática com meta-análise. Foram selecionados estudos
controlados randomizados nas seguintes bases de dados: CENTRAL; DARE; NHS
EED; MEDLINE; EMBASE; CINAHL. Além dessas bases foram consultados três
websites para identificar estudos em andamento: ClinicalTrials.gov, OMS ICTRP e
ISRCTN. Os desfechos primários analisados foram: cicatrização completa das
úlceras e incidência de infecção das úlceras e os secundários foram: alterações no
tamanho da úlcera, tempo de cicatrização das úlceras, recorrência das úlceras,
qualidade de vida dos participantes, dor e custos do tratamento. Quatro estudos
estão atualmente incluídos na revisão com um total de 250 pacientes. O uso do
hidrogel parece ser superior ao curativo convencional, gaze embebida em salina,
para a cicatrização de úlceras venosas de membros inferiores; 16/30 pacientes
apresentaram cicatrização completa das úlceras (RR 5,33, 95%CI [1,73,16,42]). O
gel de alginato demonstrou ser mais efetivo quando comparado ao hidrogel quanto à
redução da área da úlcera; 61,2% (± 26,2%) com o alginato e 19,4% (± 24,3%) com
o hidrogel ao final das quatro semanas de tratamento. O mel de Manuka demonstrou
ser similar ao hidrogel em relação à porcentagem de redução da área. Esta revisão
mostrou que não existem evidências disponíveis a respeito da eficácia do hidrogel
em relação aos outros tipos de curativo na cicatrização de úlceras venosas de
membros inferiores, demonstrando assim a necessidade de futuras pesquisas para
auxiliar os profissionais da saúde na escolha do adesivo correto.
Palavras-chave: Insuficiência Venosa Crônica; úlcera venosa; curativo de
hidrogel; revisão sistemática.
xiii
Abstract
Chronic venous disease (CVD) is evident among the chronic diseases and
affects the elderly population and primarily is responsible for leg ulcers in this
population. The use of dressings in the care of a venous ulcer is a fundamental part
of the treatment for healing, however, evidence to assist in choosing the best
dressing is scarce. The main objective of this study was to evaluate the effectiveness
of treatment with hydrogel in the healing of venous ulcers using search methods,
synthesis of information and statistical research through a systematic review and
meta-analysis. Randomized controlled trials were selected in the following
databases: CENTRAL; DARE; NHS EED; MEDLINE; EMBASE; CINAHL. Beyond
these databases three websites were consulted to identify ongoing studies:
ClinicalTrials.gov, OMS ICTRP e ISRCTN. The primary outcomes were analyzed:
complete wound healing, incidence of wound infection and the secondary were:
changes in ulcer size, time to ulcer healing, recurrence of ulcer, quality of life of
participants, pain and costs of treatment. Four studies are currently included in the
review with a total of 250 participants. The use of hydrogel appears to be superior to
conventional dressing, gauze soaked in saline, for the healing of venous leg ulcers;
16/30 patients showed complete healing of ulcers (RR 5,33, 95%CI [1,73,16,42]).
The alginate gel was shown to be more effective when compared to the hydrogel
dressing in reduction of the wound area; 61,2% (± 26,2%) with alginate e 19,4% (±
24,3%) with hydrogel at the end of four weeks of treatment. Manuka honey has
shown to be similar to the hydrogel dressings in percentage of area reduction. This
review demonstrated that there is no evidence available about the effectiveness of
the hydrogel compared to other types of dressings on the healing of venous leg
ulcers of the lower limbs, thus demonstrating the need of future studies to assist
health professionals in choosing the correct dressing.
Keywords: chronic venous insufficiency, venous ulcers, hydrogel dressings,
systematic review.
xiv
1INTRODUÇÃO
2
As úlceras venosas de membros inferiores são frequentes e recorrentes, em
especial, em idosos. É uma ferida complexa associada a um custo considerável para
os pacientes e para saúde pública. O uso de adesivos no cuidado de uma úlcera
venosa é parte fundamental no tratamento para a cicatrização, no entanto, as
evidências para auxiliar a escolha do melhor adesivo são escassas. Atualmente
buscam-se intervenções terapêuticas que possam acelerar o processo de
cicatrização das feridas diminuindo assim, a morbidade, as complicações e os
gastos oriundos da doença.
O presente estudo trata-se de uma revisão sistemática com o objetivo de
sintetizar o resultado de pesquisas selecionadas sobre a eficácia do tratamento do
hidrogel na cicatrização de úlceras venosas mediante métodos de busca, síntese de
informação e análise estatística através de uma revisão sistemática com metaanálise.
1.1 Doença Venosa Crônica
A doença venosa crônica (DVC) destaca-se entre as doenças crônicas que
acometem a população idosa e é a principal responsável pelas úlceras de membros
inferiores nesta população1;2. A DVC refere-se a uma doença que afeta o
funcionamento do sistema venoso dos membros inferiores decorrentes de uma
hipertensão venosa de longa duração, causada por insuficiência valvular com ou
sem obstrução do fluxo venoso podendo afetar o sistema venoso superficial, sistema
venoso profundo, ou ambos3. Essa condição abrange uma série de apresentações
clínicas que podem variar de telangiectasias a úlceras abertas.
A classificação da DVC dos membros inferiores surgiu a partir de um
consenso estabelecido por um comitê de especialistas de vários países4 e
posteriormente ela foi revisada e atualizada por alguns autores do mesmo comitê5.
Ela é classificada segundo a classificação Clinical-Etiology-Anatomy-Patophysiology
(CEAP) onde C refere-se aos sinais clínicos da doença; E à etiologia; A refere-se à
localização anatômica da doença e P à fisiopatologia. Todas as formas de
apresentação clínica da DVC estão divididas em sete categorias que variam de
acordo com a gravidade, sendo C0 a ausência de sinais; C1 telangiectasias e/ou
veias reticulares; C2 varizes tronculares; C3 edema; C4a pigmentação e/ou eczema
3
dos membros; C4b lipodermatosclerose e/ou atrofia branca; C5 úlcera venosa
cicatrizada e C6 úlcera venosa ativa.
Em relação à etiologia, a DVC divide-se em três classes: congênita (Ec),
primária (Ep), secundária (Es) ou sem causa venosa identificável (Em). No que diz
respeito à anatomia venosa do membro inferior, esta se divide em três sistemas:
superficial (As), profundo (Ad), perfurante (Ap) e local venoso não identificável (An).
Por fim, em termos fisiopatológicos, a DVC poderá resultar de um refluxo (Pr), de
uma obstrução (Po), de ambos os processos (refluxo e obstrução – Pr,o) e
patofisiologia não identificada (Pn)5.
Tendo como base a classificação CEAP, a doença venosa crônica é definida
como qualquer forma de doença venosa desde C0 a C6. Existe uma sobreposição
de termos, pois alguns autores consideram o termo insuficiência venosa crônica
(IVC) como sinônimo de DVC abrangendo assim todas as classes da doença. Por
outro lado, alguns consideram IVC apenas casos avançados da doença como
aqueles pacientes que apresentam edema (C3), alterações subcutâneas (como
lipodermatoesclerose C4b) e úlcera venosa (C5-C6)6.
A prevalência da IVC tende a aumentar com a idade7. Um único estudo
realizado no Brasil, interior de São Paulo, sobre alterações venosas de membros
inferiores estimou a prevalência de varizes em 39,5% e de formas mais graves da
IVC, no caso as úlceras abertas ou cicatrizadas em 1,5%8.
Nos Estados Unidos estima-se que aproximadamente 2,5 milhões de pessoas
tenham IVC, das quais 20% chegam a desenvolver úlcera venosa9. Uma revisão
com 11 estudos de prevalência realizados na Austrália e Europa estimou a
prevalência de úlceras venosas de membros inferiores em 0,1% a 0,3% na
população adulta10. Os dados epidemiológicos têm consistentemente sugerido que
a prevalência aumenta com a idade e é maior entre as mulheres11-14. Tem sido
estimado que a incidência de úlceras venosas na terceira idade seja de 0,76/100
pessoas por ano em homens e de 1,42/100 pessoas por ano em mulheres13.
As úlceras venosas estão associadas a um custo considerável para o
paciente e para os profissionais da saúde e apresentam um grande problema para a
4
saúde pública por ser progressiva e apresentar propensão à recorrência15. Duas
revisões sistemáticas sobre qualidade de vida em pacientes com úlceras de perna
reportaram que a presença de ulceração na perna estava associada com dor,
restrição às atividades de trabalho e lazer, mobilidade reduzida, perturbação do
sono, redução do bem-estar psicológico e isolamento social16;17
O custo do tratamento de uma úlcera de perna não cicatrizada no Reino
Unido foi estimado em cerca de EUR 1,3 mil por ano (valores calculados em 2001)18.
Um estudo realizado na Alemanha revelou que o custo médio por ano com um
paciente com uma úlcera venosa crônica é de EUR 9569 dos quais 92% estão
relacionados a custos diretos como gastos com exames, curativos, taxas médicas e
8% estão relacionados a custos indiretos como perda da produtividade no trabalho19.
Um estudo de coorte realizado no USA registrou que os custos diretos com um
paciente com uma úlcera venosa de membros inferiores seria em media $2400 por
mês (valor estimado em 1997)20.
Como descrito, a IVC provém da disfunção do sistema venoso dos membros
inferiores decorrentes de uma hipertensão venosa de longa duração. Os fatores
predisponentes da hipertensão venosa incluem história de trombose venosa
profunda (TVP), tromboflebite, trauma na perna, artrite, obesidade, gravidez e vida
sedentária. Esses fatores podem resultar em danos às válvulas nas veias das
pernas21;22. Em condições normais, o fluxo de sangue nos vasos venosos ocorre em
uma única direção, das veias do sistema superficial para as veias do sistema
profundo, orientado pelas inúmeras válvulas contidas no interior das veias desses
sistemas e auxiliado pela musculatura dos membros inferiores especialmente das
pernas e dessas desembocando no átrio direito. Esse mecanismo faz com que a
pressão venosa, que em posição ortostática pode atingir valores de até 80mmHg a
90mmHg seja reduzida para 30 mmHg em resposta a ação valvular e à contração
muscular; portanto, uma falha no funcionamento dessas válvulas pode desencadear
a hipertensão venosa21;23.
Durante a progressão da insuficiência venosa, observam-se alterações da
microcirculação representadas pela diminuição do número de capilares associado às
alterações morfológicas dos capilares remanescentes que se tornam contorcidos,
convolutos e dilatados; concomitantemente ocorre diminuição da pressão tissular de
5
O2 local24-26. Uma teoria importante e provavelmente mais aceita atualmente para a
fisiopatologia da ulceração venosa é a teoria do encarceramento dos leucócitos26;27.
A estase venosa favorece a marginalização dos leucócitos e a interação endotélioleucocitária, com consequente infiltração leucocitária e produção de citocinas e
substâncias químicas por parte destes. Estes fatores contribuirão para a lesão
tissular (semelhante ao que ocorre na inflamação crônica)27;28.
1.2 Úlceras venosas
A complicação mais importante da IVC é a úlcera venosa representando
cerca de 70% de todas as úlceras de perna. Elas apresentam-se como feridas
abertas, geralmente irregulares e superficiais nos membros inferiores, predominando
no terço inferior da perna e caracteristicamente tendem a se cronificar, serem
recidivantes e apresentarem cicatrização lenta, especialmente quando não tratadas
prontamente e adequadamente. Estão associadas à hipertensão venosa sustentada
e alterações da microcirculação decorrentes de insuficiência venosa crônica26-28;29.
Essa condição causa problemas físicos, psicológicos e financeiros que
impactam a qualidade de vida dos pacientes. O impacto das úlceras venosas na
rotina diária dos pacientes tem sido descrito em vários estudos quantitativos e
qualitativos. Os maiores problemas reportados pelos pacientes são: dor, imobilidade,
distúrbios do sono, falta de energia, limitações nas atividades de trabalho e lazer,
preocupações, frustações e falta de autoestima16;17.
A duração de uma úlcera venosa pode variar de algumas semanas a mais de
10 anos e em algumas pessoas elas nunca cicatrizam14;30;31. O tamanho da úlcera
bem como a sua duração (tempo maior que 18 meses) são fatores que contribuem
para o risco de uma úlcera não cicatrizar32. Outros fatores também estão associados
a um atraso da cicatrização das úlceras, como: lipodermatoesclerose, evidência de
trombose venosa profunda, tromboflebite superficial e baixa mobilidade do
tornozelo33.
Margolis et al.
34
mostraram, através de um estudo de coorte com 260
pacientes que apresentavam úlcera venosa e foram tratados por um período de 2
anos com terapia compressiva, os fatores independentes associados com o
6
insucesso da cicatrização de uma úlcera com 24 semanas de duração que foram:
tamanho inicial da ferida, duração da ferida no início do tratamento, história de
ligadura venosa, história de cirurgia para colocação de prótese de joelho ou quadril,
ITB (índice tornozelo-braquial) <0,8, ferida coberta com fibrina em uma área >50%
no início do tratamento.
O diagnóstico da úlcera venosa é basicamente clínico realizado através da
anamnese e do exame clínico. Na anamnese deve-se observar: queixa e a duração
dos sintomas; doenças anteriores como a trombose venosa; traumatismos prévios
dos membros e a existência de doença varicosa e principalmente a aparência e
localização da úlcera. Os sintomas incluem sensação de peso nas pernas e dor nos
membros inferiores principalmente ao final do dia35. O diagnóstico clínico juntamente
com os exames complementares tem como objetivo estabelecer as possíveis causas
da IVC, se ela ocorre por obstrução do retorno venoso, por refluxo ou por ambos.
Dentre os exames complementares existentes os mais usados são: o Doppler de
ondas contínuas, o eco-Doppler venoso e a pletismografia venosa35;36. Todo
paciente que apresenta uma úlcera precisa realizar o índice tornozelo-braquial (ITB)
para investigar a presença de doença arterial obstrutiva periférica. É um teste não
invasivo, de baixo custo, determinado pelo Doppler vascular que é calculado através
da maior pressão sistólica aferida no tornozelo aferida nas artérias tibial posterior ou
pediosa dividida pela maior pressão sistólica aferida no membro superior utilizando a
artéria braquial. Índices iguais ou menores que 0,9 caracterizam o diagnóstico de
doença arterial periférica37. Índices maiores que 0,8 são geralmente usados para
afastar a coexistência de doença arterial periférica como causa da úlcera levando ao
diagnóstico de úlcera devido a insuficiência venosa38.
Devido às características de cronicidade e alta reincidência das úlceras
venosas, atualmente buscam-se intervenções terapêuticas que possam acelerar o
processo de cicatrização das feridas diminuindo assim, a morbidade, as
complicações e os gastos oriundos da doença. Embora o uso de compressão por
enfaixamento e cuidados com a ferida seja o tratamento padrão
1;39
, o uso de
agentes físicos como o ultrassom40;41, o laser associado à outras terapias como led
infravermelho42 e correntes pulsadas de alta voltagem (HVPC)43 tem sido sugerido
7
para a aceleração da cicatrização das feridas além do tratamento promovido pela
Fisioterapia através dos exercícios físicos44.
De acordo com as Diretrizes sobre Diagnóstico, Prevenção e Tratamento da
Doença Venosa Crônica da Sociedade Brasileira de Angiologia e Cirurgia Vascular
(SBACV)36, durante o tratamento de uma úlcera venosa é necessário aliar a terapia
compressiva com a elevação do membro durante o repouso. Para o tratamento de
uma úlcera venosa são necessárias medidas que almejem a rápida cicatrização da
úlcera através de cuidados básicos de limpeza do local afetado, uso de curativos,
terapia compressiva, uso de agentes físicos, exercícios.
1.2.1 Processo de cicatrização de uma úlcera
O processo de cicatrização envolve vários fenômenos entre os mais
importantes estão os bioquímicos e fisiológicos que podem atuar de forma
harmoniosa para garantir a reconstituição tecidual. A cicatrização depende de vários
fatores locais e gerais, como: localização anatômica, tipo de pele, raça, idade, etc.
O processo de cicatrização das úlceras envolve três estágios. Inicialmente
existe o estágio inflamatório, que é precedido por uma fase de coagulação que se
inicia após o surgimento da ferida. Esta fase depende da atividade plaquetária e da
cascata de coagulação. Ocorre uma série de liberação de produtos como,
substâncias vasoativas, proteínas adesivas, fatores de crescimento e proteases que
são liberadas e estabelecem o desenvolvimento de outras fases. A formação do
coágulo serve não apenas para coaptar as bordas da ferida, mas também para
cruzar a fibronectina, oferecendo uma matriz provisória, em que os fibroblastos,
células endoteliais e queratinócitos possam ingressar na ferida45.
No estágio inflamatório o macrófago aparece como a célula mais importante,
pois ele fagocita as bactérias, desbrida corpos estranhos e direciona o
desenvolvimento do tecido de granulação. A fase de proliferação é responsável pelo
fechamento da lesão e finalizando o processo ocorre a etapa de reparo tecidual em
um estágio de remodelamento45;46.
Todo o processo de cicatrização depende da proliferação de fibroblastos e da
síntese de colágeno para a reparação tecidual. Os colágenos do tipo I e III são
8
encontrados em abundância no tecido de granulação, sendo o colágeno tipo III em
maior
quantidade
nas
bordas
da
lesão
dérmica47.
A
resposta
inicial
imunohistoquímica para a cicatrização tecidual depende basicamente da presença
de ambos os tipos de colágeno. No entanto são vários os fatores que influenciam o
processo de cicatrização, retardando o mesmo e tornando as feridas crônicas. Entre
eles interferem a idade, o estado nutricional do paciente e a existência de doenças
como a diabetes45.
Phillips e colaboradores48 citaram em seu estudo que a área da úlcera bem
como sua duração é preditora significativa da cicatrização completa e do tempo para
cicatrização total em uma úlcera. O percentual de cicatrização e a área da úlcera na
terceira semana são bons preditores de uma cicatrização completa da úlcera.
1.2.2 Curativos de carboximetilcelulose
Os curativos em geral são aplicados nas feridas diretamente ou sobre outro
adesivo ou bandagem. O ambiente ideal para a cicatrização é aquele no qual a
ferida é mantida coberta e úmida. Existem vários tipos de adesivos que promovem
esse meio úmido com o objetivo de reepitelização da ferida, promover conforto ao
paciente, controlar o exudato da ferida, prevenir que as bandagens não
permaneçam em contato direto com a ferida, minimizar o número de trocas dos
adesivos e o risco de maceração49.
De acordo com a Nurse Prescriber´s Formulary (NPF)49, o adesivo apropriado
para o tratamento das feridas não depende somente do tipo de ferida, mas do
estágio em que se encontra o processo de cicatrização da mesma. A NPF classifica
os adesivos em quatro categorias:
Básicos: Esta categoria é subdividida em adesivos absorventes e adesivos de baixa
aderência. Os de baixa aderência são compostos de algodão e podem ser
colocados diretamente em contato com a ferida. Eles podem conter algum
medicamento como a clorexidina ou não apresentar medicamento como a gaze de
parafina. Os adesivos absorventes são aplicados diretamente na ferida e podem ser
usados como uma camada secundária a um tratamento com feridas com muito
exudato, exemplo: Primapore (Smith & Nephew).
9
Avançados - Esta categoria é composta por oito tipos de adesivos:
- Adesivos de Hidrogel: será descrito com mais detalhes abaixo por ser o
adesivo utilizado como tratamento proposto pela revisão.
- Adesivos de Hidrocolóide: são geralmente compostos por uma matriz
absorvente de hidrocolóide sobre uma película permeável ao vapor ou espuma de
apoio, exemplo: Granuflex (ConvaTec).
- Adesivos de alginato: esses adesivos são altamente absorventes e possuem
em sua composição alginato de cálcio ou alginato de cálcio de sódio que podem ser
combinados com o colágeno. O alginato forma um gel quando em contato com a
superfície da ferida. Esse gel pode ser retirado no momento da troca do adesivo ou
lavado com solução salina estéril, exemplo: Curasorb (Covidien).
- Adesivos de espuma: esses adesivos contém espuma de poliuretano
hidrofílica e são designados para absorver o exudato da ferida e manter a superfície
da mesma úmida. Existem vários tipos, algumas, por exemplo, contém material
absorvente adicional como a viscose e fibras de acrilato, exemplo: Allevyn (Smith &
Nephew).
- Adesivos macios de polímero: são compostos de um polímero de silicone
macio mantidos em uma camada não aderente. Eles são moderadamente
absorventes, exemplo: Urgotul (Urgo).
- Adesivos de membrana e filmes permeáveis: esses adesivos são
permeáveis ao vapor de água e oxigênio, mas não são permeáveis a água no
estado líquido ou micro-organismos, exemplo: Opsite (Smith & Nephew).
- Adesivos de efeito capilar: esses adesivos contem um núcleo absorvente de
fibras hidrofílicas mantidas entre duas camadas de contato de baixa aderência,
exemplo: Vacutx (Protex).
- Adesivos de absorção de odores: esses adesivos contem carvão na sua
composição e são usados para absorver o odor das feridas. Eles são usados
10
frequentemente com um adesivo secundário para melhorar a absorção, exemplo:
CarboFLEX (ConvaTec).
Anti-microbial - Existem três tipos nessa subdivisão:
- Adesivos impregnados com mel: esses adesivos contém mel de pureza
médica com propriedades anti-inflamatórias e anti-microbiais. Podem ser usados em
feridas agudas e crônicas, exemplo: Medihoney (Medihoney).
- Adesivos impregnados com prata: eles são usados para tratar feridas
infectadas, exemplo: Acticoat (Smith & Nephew).
- Adesivos impregnados com iodo: esses adesivos liberam iodo livre no qual
pode agir como um antiséptico para a ferida quando esta é exposta ao exudato,
exemplo: Iodozyme (Insense).
Existem ainda outros tipos de adesivos antimicrobiais compostos de gaze ou
adesivos de baixa aderência impregnados com solução oleosa que apresentam
propriedades antimicrobiais.
Adesivos especializados - Nessa categoria existem dois tipos:
- Adesivos de silicone para queloides: esses adesivos reduzem ou previnem a
cicatriz hipertrófica ou queloides, exemplo: Cica-Care (Smith & Nephew).
- Adesivos de matriz moduladora de proteinase: eles alteram a atividade de
enzimas proteolíticas em feridas crônicas, exemplo: Promogran (Systagenix).
O hidrogel utilizado como curativo primário (curativo usado em contato direto
com a ferida) é um adesivo que pode apresentar-se sob a forma de gel transparente,
amorfo ou placa. As placas são geralmente compostas por água, propileno glicol e
carboximetilcelulose ou água e polivinilpirridona. A NPF49 descreve os hidrogéis
como adesivos compostos de polímeros de amido possuindo até 96% de água.
Os hidrogéis bem como os adesivos em geral, têm como objetivo proteger a
ferida promovendo um ambiente úmido visando a cicatrização da mesma. Eles são
usados em feridas secas ou com pouco exudato e deve ser evitado o uso em feridas
11
com muito exudato, pois, o excesso de hidratação pode provocar a maceração do
tecido ao redor da ferida. É necessário um curativo secundário (usado sobre o
curativo primário; não aderente) para cobrir a ferida (NPF). As trocas deste tipo de
curativo não necessitam ser diárias, porém dependem do curativo secundário e
podem ocorrer entre um período de cinco a sete dias. Elas devem ser feitas quando
for observado um extravasamento de exsudato para fora do curativo45.
Além da vantagem da manutenção do meio úmido, os hidrogéis favorecem a
angiogênese e promovem o desbridamento autolítico. Esse último processo é
responsável pela digestão das células mortas através de enzimas sendo favorecido
pela manutenção do meio úmido50. Outra vantagem dos curativos de hidrogéis é que
eles protegem as terminações nervosas reduzindo assim a dor dos pacientes51 e
causando menos desconforto durante as trocas.
1.3 Justificativa
O uso de curativos no cuidado de uma úlcera venosa é parte fundamental no
tratamento para a cicatrização. Existem muitos tipos disponíveis no mercado e os
custos variam consideravelmente. Para a escolha correta do uso do curativo para
cada paciente deve-se levar em consideração além do tipo da ferida e suas
características o estágio de cicatrização.
No entanto, a base de evidências para guiar qual o curativo correto para o
tratamento ideal da úlcera é escassa. São necessárias orientações para ajudar os
profissionais de saúde a tomar decisões a respeito do melhor curativo disponível
para o tratamento visando uma rápida cicatrização da úlcera.
Além disso, apesar do uso de diversos curativos ainda existe carência de
análises sistemáticas que avaliem a efetividade do uso destes na cicatrização de
úlceras venosas, incluindo o uso de hidrogel e adesivos de carboximetilcelulose
(hidrocolóides) embora estes sejam amplamente utilizados na rotina clínica.
Portanto, este estudo propôs avaliar a evidência clínica sobre a efetividade do
tratamento do hidrogel para a cicatrização de úlceras venosas através de uma
revisão sistemática. Além disso, a fisioterapia aplicada às doenças vasculares
periféricas tem aumentado sua abrangência e este profissional está cada vez mais
12
em contato com pacientes acometidos por úlceras de pele; portanto necessitando
conhecer a indicação e a efetividade destes curativos.
1.4 Objetivos
1.4.1 Objetivo principal
Avaliar o resultado de estudos sobre a eficácia do hidrogel comparado com
outros tratamentos e outros adesivos para a cicatrização de úlceras venosas.
1.4.2 Objetivos secundários
- Selecionar, avaliar e incluir os ensaios clínicos controlados e randomizados
no qual apresentem os efeitos dos tratamentos de hidrogel para a cicatrização de
úlceras venosas comparados com outros nas alterações do tamanho da úlcera,
tempo até a cicatrização bem como sua recorrência;
- Avaliar a eficácia do tratamento de hidrogel na melhora da qualidade de vida
e da dor;
- Avaliar os custos do tratamento das úlceras venosas.
13
2 Materiais e Métodos
14
2.1 Caracterização da pesquisa
O presente estudo trata-se de uma revisão sistemática com metanálise
desenvolvida
em
parceria
com
a
Colaboração
Cochrane
(The
Cochrane
Collaboration). A revisão seguiu as recomendações para realização de revisões
sistemáticas e meta-análise propostas pelo Cochrane Handbook for Systematic
Reviews of Interventions disponível no site da Colaboração Cochrane52.
2.2 Etapas de uma revisão pela Colaboração Cochrane
A Colaboração Cochrane, fundada em 1992 no Reino Unido é uma
organização internacional sem fins lucrativos cujos objetivos são preparar, manter e
assegurar o acesso a revisões sistemáticas sobre efeitos de intervenções na área da
saúde. A estrutura organizacional da Colaboração Cochrane divide-se em: rede de
consumidores, centros, comitê diretor, campos, grupos de metodologia e grupos de
revisão. Os grupos de revisão, por sua vez, estão divididos nas diversas áreas da
saúde. A presente revisão faz parte do “Grupo de Feridas” (Wounds Group), com
sede localizada na cidade North Yorkshire, York, United Kindom.
Para iniciar uma revisão sistemática pela Colaboração Cochrane é necessário
inicialmente contatar o (a) coordenador (a) do grupo de interesse a fim de discutir
possíveis títulos para a revisão, os quais não entrem em choque com outros títulos
já existentes nos grupos de revisões e assegurar a viabilidade da revisão proposta.
O site da Colaboração Cochrane disponibiliza todas as informações e dados do
corpo editorial e coordenadores de cada grupo, além das revisões já existentes.
Após checar a viabilidade do tema sugerido, é então necessário preencher o
formulário de registro do título ou o formulário de atualização, os quais contém uma
breve descrição sobre a revisão, bem como algumas informações dos autores. O
formulário é então submetido ao corpo editorial do grupo o qual é responsável pelo
aceite da revisão sugerida.
Para iniciar a presente revisão, os autores contataram a coordenadora do
Grupo de Feridas e enviaram uma proposta de titulo. O grupo então sugeriu dividir
uma revisão já publicada53 e que precisava ser atualizada em quatro outras revisões.
A partir desse consenso foi então enviado a proposta através do formulário de
15
registro de dois títulos sugeridos no qual foi aprovado pelos editores do grupo.
Todas as etapas a seguir foram realizadas de acordo com o Cochrane Handbook for
Systematic Reviews of Interventions52 fornecido pela Colaboração Cochrane.
Devido ao tempo necessário para desenvolvimento de uma revisão
sistemática e alguns atrasos durante o desenvolvimento do estudo, o resultado de
uma das revisões está sendo apresentado aqui nesta dissertação54 (Hidrogel
dressings for venous leg ulcers) e a outra revisão ainda se encontra em andamento55
(Anexo 1).
A Colaboração Cochrane recomenda que a revisão sistemática seja efetuada
em sete passos: formulação da pergunta; localização e seleção dos estudos;
avaliação crítica dos estudos; coleta de dados; análise e apresentação dos dados e
aprimoramento e atualização da revisão52. Segue abaixo o fluxograma completo com
todas as etapas para a realização da revisão sistemática pela Colaboração
Cochrane:
16
Formulação
da pergunta
Contato com o
grupo de
feridas
Registro do
título
Pesquisador
1
Seleção dos
estudos
Estudos excluídos e
elaboração da tabela
com a justificativa para
a exclusão
Necessidade
da revisão
Elaboração
protocolo para
Colaboração
Cochrane
Busca e
identificação
dos artigos
Reunião de
consenso
Pesquisador
1
Pesquisador
2
Seleção dos
estudos
Estudos
incluídos
Pesquisador
1
Extração dos dados e
dos estudos incluídos
Aprovação e
publicação do
protocolo
Pesquisador
2
Reunião de
consenso
Avaliação do
risco de viés
dos estudos
incluídos
Extração dos dados e
dos estudos incluídos
Pesquisador
2
Reunião de
consenso
Tabulação e análise
dos dados
Interpretação dos
dados e Redação do
manuscrito
Figura 1: Fluxograma da estratégia de elaboração de uma revisão sistemática pela
Colaboração Cochrane.
17
2.3 Critérios para considerar os estudos para a revisão
Os seguintes critérios foram considerados para a inclusão dos estudos na
revisão: tipos de estudos; tipos de participantes; tipos de intervenções; tipos de
desfecho (primários e secundários); métodos de busca para identificação dos
estudos (busca eletrônica e outras fontes de pesquisa). Para a coleta e análise dos
dados foi considerada a avaliação do risco de viés; mensuração do efeito do
tratamento; dados incompletos ou ausentes; avaliação da heterogeneidade; análise
de subgrupo e análise de sensibilidade.
Foram incluídos estudos controlados randomizados que apresentassem os
efeitos do hidrogel na cicatrização de úlceras venosas de membros inferiores em
pacientes de qualquer idade. Os desfechos primários analisados foram: cicatrização
completa da ferida medida pelo número de úlceras completamente cicatrizadas
durante a duração de cada estudo e a incidência de infecção na ferida. Os
desfechos secundários foram: mudanças no tamanho da úlcera medidas pela
redução no seu tamanho original expresso em valores absolutos (cm²) ou relativos
(%); tempo de cicatrização da úlcera; recorrência da úlcera; qualidade de vida
avaliada através de questionários genéricos padronizados como o SF-36, SF-12 ou
SF-6; dor avaliada no momento da troca do adesivo ou durante o tratamento através
de instrumentos validados como questionários ou escala visual analógica; e custos.
Foram pesquisados estudos nas seguintes bases de dados eletrônicas: CENTRAL
2013, Issue 8; DARE 2013, Issue 8; NHS EED 2013, Issue 8; MEDLINE (1948 a
agosto de 2013); EMBASE (1980 a setembro de 2013); CINAHL (1982 a agosto de
2013). Além dessas bases foi consultado 3 websites para identificar estudos em
andamento: ClinicalTrials.gov, OMS ICTRP e ISRCTN. A busca de artigos foi
realizada pela própria equipe do grupo de revisão de acordo com o protocolo préestabelecido (Wounds group). No entanto a escolha dos descritores e a decisão de
quais estudos entrariam para a revisão foi função dos autores.
Foi utilizado o software Review Manager (RevMan) versão 5.2 disponível para
download no site da Colaboração Cochrane para a combinação e análise dos dados.
Os seguintes dados foram extraídos dos estudos e inseridos no RevMan de maneira
independente por dois autores: detalhes metodológicos como design do estudo,
18
método de randomização e sigilo de alocação, mascaramento dos participantes e
dos avaliadores, desistências e exclusões, entre outros. Foram extraídos também
descrição dos participantes, como: amostra total, idade, tipo e duração da úlcera,
critérios de inclusão e exclusão. Na descrição da intervenção foi extraído o tipo de
adesivo usado como tratamento, duração do tratamento e a descrição dos
resultados.
Na intenção de evitar a possibilidade de viés, aumentando assim a qualidade
dos resultados, foi utilizada uma tabela para avaliação do risco de viés (The
Cochrane Collaboration´s tool for assessing risk of bias) fornecida pela Colaboração
Cochrane, no qual inclui os seguintes itens: sequência de randomização (random
sequence generation), sigilo de alocação (allocation concealment), mascaramento
dos participantes e dos avaliadores (blinding of participantes and personnel),
mascaramento dos avaliadores envolvidos com a análise dos desfechos de cada
estudo (blinding of outcome assessment), descrição seletiva do desfecho (selective
reporting) e outros vieses (other bias). Cada item recebeu uma das seguintes
classificações: “alto risco de viés”, “baixo risco de viés” ou “risco incerto de viés” de
acordo com o Handbook for Systematic Reviews of Interventions da Colaboração
Cochrane. A avaliação do risco de viés foi realizada de maneira independente por
dois autores.
Para a análise estatística foi utilizado o software RevMan 5.2 onde a
mensuração do efeito do tratamento foi analisada através das variáveis contínuas
que foram expressas como diferença de média com um intervalo de confiança (IC)
de 95% e das variáveis dicotômicas foram expressas através da estimativa do risco
relativo (RR) também com um intervalo de confiança de 95%.
Todos os critérios citados acima estão descritos detalhadamente na seção de
resultados na publicação que descreve o protocolo intitulado: Hydrogel dressings for
venous leg ulcers que foi publicado na Cochrane Database of Systematic Reviews54.
19
3 RESULTADOS
20
Os resultados estão divididos em duas partes: na primeira encontra-se o
protocolo publicado na base de dados da Colaboração Cochrane e em seguida a
análise dos dados e discussão descritiva dos resultados que ainda não foram
publicados.
21
Hydrogel dressings for venous leg ulcers (Protocol)
Ribeiro CTD, Dias FAL, Fregonezi GAF
This is a reprint of a Cochrane protocol, prepared and maintained by The Cochrane Collaboration and published in The Cochrane
Library 2013, Issue 9
http://www.thecochranelibrary.com
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
22
TABLE OF CONTENTS
HEADER . . . . . . . . . .
ABSTRACT . . . . . . . . .
BACKGROUND . . . . . . .
OBJECTIVES . . . . . . . .
METHODS . . . . . . . . .
ACKNOWLEDGEMENTS
. . .
REFERENCES . . . . . . . .
APPENDICES . . . . . . . .
CONTRIBUTIONS OF AUTHORS
DECLARATIONS OF INTEREST .
SOURCES OF SUPPORT . . . .
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1
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6
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15
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[Intervention Protocol]
Hydrogel dressings for venous leg ulcers
Cibele TD Ribeiro1 , Fernando AL Dias2 , Guilherme AF Fregonezi3
1 Graduate
Program in Physiotherapy, Federal University of Rio Grande do Norte, Natal, Brazil. 2 Department of Physiology, Federal
University of Paraná, Curitiba, Brazil. 3 Department of Physical Therapy, Federal University of Rio Grande do Norte, Natal, Brazil
Contact address: Guilherme AF Fregonezi, Department of Physical Therapy, Federal University of Rio Grande do Norte, Avenida
Senador Salgado Filho, 3000, Lagoa Nova, Natal, Rio Grande do Norte, 59078-470, Brazil. [email protected].
Editorial group: Cochrane Wounds Group.
Publication status and date: New, published in Issue 9, 2013.
Citation: Ribeiro CTD, Dias FAL, Fregonezi GAF. Hydrogel dressings for venous leg ulcers. Cochrane Database of Systematic Reviews
2013, Issue 9. Art. No.: CD010738. DOI: 10.1002/14651858.CD010738.
ABSTRACT
This is the protocol for a review and there is no abstract. The objectives are as follows:
To assess the effects of hydrogel wound dressings for healing venous leg ulcers in people in any care setting.
BACKGROUND
A glossary of medical terms is available in Appendix 1.
Description of the condition
Venous leg ulcers (VLU) present as open wounds generally irregular and shallow or sores on the lower limb. They are associated with
sustained venous hypertension and microcirculatory alterations
resulting from chronic venous insufficiency (Grey 2006; Wollina
2006).This condition has psychological and financial impact and
also impacts on the physical functioning of affected patients. The
impact of leg ulcers on patient’s daily life is described in many
quantitative and qualitative studies. The major problems reported
from the patients are: pain, immobility, sleep disturbance, lack of
energy, limitations in work and leisure activities, worry, frustration and lack of self-esteem (Herber 2007; Persoon 2004). Thus,
venous leg ulcers will ultimately impact quality of life. Venous leg
ulceration is a chronic health problem that can take years to heal
completely, and, as it has a high rate of recurrence, often requires
life-long treatment (Margolis 2002; Van Hecke 2011). Wound
size and wound duration (greater than 18 months) were major
contributors to a risk of not healing (Margolis 2004). Additionaly, the presence of lipodermatosclerosis, evidence of deep vein
thrombosis, superficial thrombophlebitis or poor ankle mobility
were individually associated with delayed healing (Lantis 2013).
The incidence of venous ulceration rises with increasing age (De
Araujo 2003; Wipke-Tevis 2000). The primary risk factors are
aging, gender (more common in women), obesity, previous leg
injuries, deep venous thrombosis (clots in veins) and phlebitis (inflammation of veins) (Collins 2010). Insufficiency of the superficial, perforating or deep veins of the leg is also a risk factor for leg
ulceration (Valencia 2001). Venous leg ulcers have been estimated
to afflict between 0.2% and 1% of the total population and between 1% and 3% of the elderly population in the United States
(USA) and Europe (Margolis 2002).The estimated incidence of
venous leg ulcers in the elderly (i.e. aged 65 years or older) per
100 person-years is around 0.76 for males and 1.42 for females
(Margolis 2002). The estimated prevalence of venous leg ulcers
ranges between 0.6 and 1.9 per cent in the adult population of
the UK, USA, and Europe (Briggs 2003). Epidemiological studies
estimate that venous leg ulcers affect 1 million people in the USA,
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accounting for 70 to 80 per cent of all ulcers of the lower limbs
(De Araujo 2003). A cohort study calculated that direct medical
care costs attributable to a VLU averaged $2400 (in 1997 value
US dollars) per month (Olin 1999). Up to 10 per cent of the population in Europe and North America has valvular incompetence,
with 0.2 per cent developing venous ulceration. Venous ulceration
represents the most prevalent form of difficult-to-heal wounds,
and treating these problematic wounds requires significant healthcare resources. Recent data from Germany revealed that the mean
total cost per year for a patient with chronic venous leg ulceration
was EUR 9569, of which 92% was estimated to be direct costs
(non drug treatment, inpatients costs and outpatient care) and 8%
indirect costs (inability to work) (Purwins 2010).
The physiopathology of venous ulcers starts as a macrovascular
problem due to valve incompetence. Aetiological (causative) factors such as venous thrombosis could cause valve insufficiency that
results in venous stasis and reflux, which are the predominant factors in chronic venous insufficiency (Raju 2010). In the normal
venous system, pressure decreases during exercise as a result of
the action of the muscles pumping the blood vessels. In a system
where the valves are incompetent, the venous pressure remains
high (Grey 2006). Sustained venous hypertension will ultimately
lead to microcirculatory dysfunction and cause alterations in skin
perfusion, which can then lead to ulceration.
Alterations in the microcirculation are described as a decrease in
the capillary density, which can also be reduced by dilation, tortuosity and convolution of the remaining capillaries (Howlader
2003; Incandela 2001; Junger 2000). This impacts the nutrition
and clearance of by-products in the tissue, leading to skin changes
observed in the form of swelling, eczema, hyperpigmentation (skin
coloration), lipodermatosclerosis (hard, tight skin) and, ultimately,
tissue ulceration. Part of the pathway leading to tissue damage and
ulceration is due to leucocyte interaction with endothelial cellsurface binding molecules that facilitate their migration into tissue. Once leucocytes are in the tissue they become active and produce a series of molecules that lead to tissue damage (Smith 2006;
Wollina 2006).
The diagnosis of venous ulceration is usually based on clinical examination. Additional tests such as colour duplex ultrasonography
(measurement of blood flow in the veins and arteries of the leg),
plethysmography (measures variations in the size or volume of a
limb), venography ( x-ray test that provides an image of the leg
veins) and ankle brachial pressure index (ABPI- provides the ratio
of systolic blood pressure at the ankle to that in the arm) (Cochrane
Wounds Group Glossary; The Free Medical Dictionary) may be
helpful if the diagnosis is unclear (Collins 2010; Robson 2006).
All patient that present an ulcer should be screened for peripheral
arterial disease (PAD) by Doppler measurement of ABPI. An index equal or lower than 0.9 is the diagnosis criterion for peripheral arterial disease (Rooke 2011); however, ABPI measurement
greater than 0.8 is generally used to exclude peripheral arterial disease as the cause of a leg ulceration, leaving the most likely diag-
nosis venous ulceration (RCN 2006). Venous ulcers are generally
irregular and shallow, and often occur over bony prominences,
particularly in the gaiter area (over the medial malleolus). Skin alterations surrounding the ulcer such as hyperpigmentation, lipodermatosclerosis and fibrosis are usually present (Collins 2010).
Frequent symptoms for venous ulceration include pain, odour and
drainage from the wound (Valencia 2001). Arterial ulcers can be
distinguished from venous ulcers because the former typically have
round and well-demarcated borders and the presence of necrotic
tissue in the wound bed. Physical symptoms of arterial leg ulcers
include: loss of leg hair; atrophic skin (wasting of skin); cold feet;
absence of, or decrease in, arterial pulses; and symptoms such as
intermittent claudication (pain on walking that goes away with
rest). Neuropathic ulcers are more common in, but are not limited to, patients with diabetes mellitus. These differ from venous
leg ulcers in having defined borders, they are usually deeper than
venous ulcers and are associated with foot numbness, burning and
paraesthesia (sensation of “pins and needles”) (Valencia 2001).
The standard treatment for venous leg ulcer is compression therapy. It has been shown that compression increases the healing rates of venous leg ulcers compared with no compression
(O’Meara 2009). This treatment is often applied with other interventions, such as debridement (Tang 2012), topical agents (Briggs
2012; Robson 2006), physical agents (Aziz 2011; Cullum 2010;
Flemming 1999), dressings (Palfreyman 2007).
Description of the intervention
The optimal wound healing environment is one where the wound
is kept covered and moist, rather than left open to the air. Standard
treatment for venous leg ulcers should include therapeutic compression (may be applied by bandages) in addition to a dressing,
except when otherwise indicated (O’Meara 2009; Robson 2006).
Dressings are applied underneath bandages or stockings with the
aim of protecting the wound and providing a moist environment
to aid healing. Nowadays, several types of dressing seek to achieve
a moist environment, the aim of which is to promote re-epithelialisation of the wound, providing comfort, controlling exudate and
helping to prevent bandages and stockings adhering to the wound
bed. The ideal conditions required for wound healing in terms of
dressing application have been explained as follows: maintenance
of a moist wound environment without risk of maceration; avoidance of toxic chemicals, particles or fibres in the dressing fabric;
minimisation of number of dressing changes; and maintenance of
an optimum pH level (NPF 2011).
The primary intervention of interest in this review is hydrogel
dressings used in the treatment of venous leg ulcers. The aim of
hydrogel dressings is to promote pain relief, comfort and also to
favour autolytic debridement (natural enzymic removal of dead
tissue) (Mandelbaum 2003). The dressings consist of a starch
polymer and up to 96% water. They are supplied in two forms;
flat sheets (e.g. ActiFormCool (Activa)), or amorphous hydro-
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gel (e.g. Aquaflo (Covidien)). Some of the hydrogels are associated with alginates (e.g. Nu-Gel, Purilon Gel) (NPF 2011), which
have a higher capacity for absorption and chemical debridement
(Mandelbaum 2003). The advantages of hydrogel dressings are
that they can be used during several phases of healing, and may promote relief and comfort, however, they do require a secondary covering. Hydrogel dressings also may reduce pain in painful wounds
(Bradbury 2008). The interval between dressing changes varies
according to the type of hydrogel dressing: amorphous hydrogel
may require daily changes (Mandelbaum 2003), while hydrogel
sheet dressings may last for up to seven days.
There is a broad choice of dressings available to treat wounds
such as venous leg ulcers. For ease of comparison this review has
classed dressings into groups according to the broad categories
of the Nurse Prescribers’ Formulary 2011 (NPF 2011), that is,
basic, advanced, anti-microbial and specialist wound dressings (see
Appendix 2). Dressing names, manufacturers and distributors may
vary between countries.
To assess the effects of hydrogel wound dressings for healing venous
leg ulcers in people in any care setting.
METHODS
Criteria for considering studies for this review
Types of studies
Randomised controlled trials (RCTs), either published or unpublished, that have evaluated the effects of any type of hydrogel
wound dressing in the treatment of venous leg ulcers irrespective
of publication status or language will be included. Trials reported
in abstract form only will be eligible for inclusion, provided adequate information is either presented in the abstract or available
from the trial author. Studies using quasi-randomisation will be
excluded.
How the intervention might work
The most appropriate dressing for wound management depends
not only upon the type of wound but also on the stage of the
healing process. Dressings for moist wound healing need to ensure
that the wound remains moist, and free of clinical infection and
excessive slough (dead tissue), but avoid peri-wound maceration
(NPF 2011).
Hydrogel dressings, classified as an advanced wound dressing by
the Nurse Prescribers’ Formulary, are designed to control the environment for wound healing by donating fluids to dry sloughy
wounds, and by facilitating autolytic debridement of necrotic tissue. Some hydrogel dressings also have the ability to absorb limited amounts of exudate or rehydrate a wound, depending on the
wound’s moisture levels (NPF 2011).
Why it is important to do this review
Chronic venous ulcer healing is a complex clinical situation that
causes considerable economic impact, and adversely affects the
quality of life for those who suffer from them.
Hydrogel dressings can be used to deslough wounds by promoting
autolytic debridement through moisture to re-hydrate, soften and
liquefy non-viable tissue present on the wound surface. There is no
current up-to-date evidence to inform clinicians of the effects of
hydrogel dressings in treating venous leg ulcers (Palfreyman 2007).
The effect of hydrogel dressings compared with other dressings
and conventional methods of care for venous ulcers needs to be
established.
OBJECTIVES
Types of participants
We will include people of any age in any care setting with a diagnosed venous leg ulcer determined either by clinical evaluation,
or complementary laboratory tests (e.g. duplex ultrasonography,
plethysmography and venography), or both (Collins 2010), using
the definition of a positive diagnosis given by the authors. Trials
that include people with wounds of other aetiology (e.g. pressure
ulcers), or trials of mixed populations (venous ulcers along with
arterial or diabetic ulcers) will be excluded, unless the results for
the subgroup of people with venous leg ulcers are reported separately or if the majority of participants (≥ 75% in each arm)
have leg ulcers of venous aetiology. The review authors will attempt to contact trial authors to obtain the relevant data, if data
from subgroups of people with venous leg ulcers are not reported
separately. Studies of people with infected wounds will not be included, because hydrogel dressings are not indicated (prescribed)
for this type of wound.Trials evaluating skin grafting are covered
elsewhere and will be excluded from this review (Jones 2007).
Types of interventions
The intervention will be hydrogel dressings used as a treatment
for venous leg ulcers. Comparators will be any other dressing, no
dressing or another hydrogel dressing. For ease of comparison we
will categorise dressings according to the Nurse Prescribers’ Formulary (NPF 2011). We will use generic names where possible,
also providing trade names and manufacturers where these are
available. It is important to note, however, that manufacturers and
distributors of dressings may vary from country to country, and
dressing names may also differ.We will not include trials evaluating hydrogel dressings impregnated with antimicrobial, antiseptic
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or analgesic agents as these interventions are evaluated in other
Cochrane reviews (Briggs 2012; O’Meara 2010). Trials that use
larval therapy will be excluded.
We will include any RCT in which the presence or absence of a hydrogel dressing is the only systematic difference between treatment
groups; and in which a hydrogel dressing is compared with other
wound dressings, non-dressing treatments (for example, topical
applications) or another hydrogel dressing. We will include RCTs
of hydrogel dressings, irrespective of whether compression therapy
is reported as a concurrent therapy.
Types of outcome measures
Primary outcomes
1. Complete wound healing measured by the number of ulcers
completely healed within the duration of the trial.
2. Incidence of wound infection, using diagnosis of infection as
described in individual trials.
Secondary outcomes
1. Changes in ulcer size measured by reduction in original wound
area within the duration of the trial expressed as absolute (e.g. surface area changes in cm2 since baseline) or relative (e.g. percentage
change in area relative to baseline) changes.
2. Time to ulcer healing
3. Recurrence of ulcer.
4. Health-related quality of life (measured using a standardised
generic questionnaire such as EQ, SF-36 , SF-12 or SF-6 (http:
//www.sf-36.org/) or disease-specific questionnaire). We will not
include ad-hoc measures of quality of life that are likely to be un
validated and will not be common to multiple trials.
5. Pain (e.g. at dressing change, between dressing changes, or over
the course of treatment) will be included only if measured by
reliable and validated instruments such as surveys, questionnaires,
data capture process or visual analogue scale)
6. Costs (including measurements of resource use, such as number
of dressing changes, nurse time or health professional time costs,
or both, if reported by the authors).
Search methods for identification of studies
• Ovid MEDLINE (1948 to present);
• Ovid EMBASE (1974 to present);
• EBSCO CINAHL (1982 to present)
We will search the Cochrane Central Register of Controlled Trials
(CENTRAL) using the following MESH headings and keywords:
#1 MeSH descriptor Leg Ulcer explode all trees
#2 (varicose NEXT ulcer*) or (venous NEXT ulcer*) or (leg NEXT
ulcer*) or (stasis NEXT ulcer*) or (crural NEXT ulcer*) or “ulcus
cruris”
#3 (#1 OR #2)
#4 MeSH descriptor Hydrogel explode all trees
#5 hydrogel* or intrasite or curafil or dermagran or duoderm or
hydrosorb or hypergel or normlgel or nu-gel or nugel or purilon
or “suprasorb gel” or hypligel or elasto-gel or elastogel or tegagel
or aquaform or granugel or curasol or curatec
#6 (#4 OR #5)
#7 (#3 AND #6)
We will adapt this strategy to search Ovid MEDLINE, Ovid EMBASE and EBSCO CINAHL. The Ovid MEDLINE search will
be combined with the Cochrane Highly Sensitive Search Strategy
for identifying randomised trials in MEDLINE: sensitivity- and
precision-maximizing version (2008 revision) (Lefebvre 2011). We
will combine the EMBASE and CINAHL searches with the trial
filters developed by the Scottish Intercollegiate Guidelines Network (SIGN 2011).
We will also search the following Trial Search Registries, as sources
of ongoing or, as yet, unpublished trials:
• The Current Controlled Trials http://www.controlledtrials.com/;
• ClinicalTrials.gov http://www.clinicaltrials.gov/; and
• WHO International Clinical Trials Registry Platform
(ICTRP) http://www.who.int/ictrp/en/.
Searching other resources
The bibliographies of all retrieved and relevant publications identified by the above strategies will be searched for further studies.
We will attempt to contact researchers to obtain additional information whenever necessary, along with manufacturers to request
information about ongoing or as yet unpublished trials. We will
attempt to obtain registered trial protocols for all published trial
reports identified for inclusion.
Electronic searches
Data collection and analysis
We will search the following electronic databases to identify reports
of relevant randomised clinical trials:
• The Cochrane Wounds Group Specialised Register;
• The Cochrane Central Register of Controlled Trials
(CENTRAL) (The Cochrane Library) (Latest issue);
Selection of studies
Two review authors (CR and FD), working independently, will
screen the titles and abstracts of the studies identified from the
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search strategy against the inclusion criteria. Full versions of articles
that appear to fulfil the inclusion criteria will be obtained for
further assessment. Another review author (GF) will evaluate any
discrepancies, if necessary, and will advise in case of disagreement.
We will record all reasons for exclusion of trials for which the fulltext has been obtained.
Data extraction and management
Two review authors (CR and FD), working independently, will
extract data into Revman 5.2 and summarise details of trials using
a standard data extraction sheet (Revman 2012). We will resolve
any discrepancies by discussion with a third review author (GF).
According to methods described in the Cochrane Handbook for
Systematic Reviews of Interventions, the following information
will be extracted (Higgins 2011a):
• Country of origin.
• Study authors and year of publication.
• Care setting.
• Type of ulcer.
• Unit of investigation (per patient) - single ulcer or foot or
patient, or multiple ulcers on the same patient.
• Number of participants randomised to each treatment
group.
• Eligibility criteria and key baseline participant data (gender,
age, ethnicity, baseline ulcer area, ulcer duration, prevalence of
co-morbidities such as diabetes).
• Details of the dressing/treatment regimen received by each
group.
• Details of any co-interventions.
• Primary and secondary outcome(s) (with definitions).
• Outcome data for primary and secondary outcomes (by
group).
• Overall sample size and methods used to estimate statistical
power (relates to the target number of participants to be
recruited, the clinical difference to be detected and the ability of
the trial to detect this difference).
• Duration of treatment.
• Duration of follow-up.
• Number of withdrawals (by group with reasons).
• Statistical methods used for data analysis.
• Risk of bias criteria (sequence generation, allocation
concealment, blinding, incomplete outcome data, selective
outcome reporting).
• Source of funding.
Assessment of risk of bias in included studies
Two review authors will independently assess each eligible study
for risk of bias using the Cochrane Collaboration ‘Risk of bias
assessment tool’. This tool addresses six specific domains, namely
sequence generation, allocation concealment, blinding of partic-
ipants and care providers; blinding of outcome assessors, incomplete outcome data, selective outcome reporting and other issues
which may potentially bias the study (Appendix 3). For this review, we will consider other risk of bias issues as follows: comparability of treatment groups in relation to baseline ulcer surface area;
choice of analysis where multiple ulcers on the same individuals(s)
are studied; and choice of analysis in cluster randomised trials.
We will complete a ‘Risk of bias’ table for each eligible study and
each study will be classified as being at overall high, low or unclear
risk of bias, according to the methods described in chapter 8 of
the Cochrane Handbook for Systematic Reviews of Interventions
(Higgins 2011b). Blinding and completeness of outcome data will
be assessed for each outcome separately. We will discuss any disagreement amongst all authors to achieve a consensus. We will
present the findings using a ‘Risk of bias’ summary figure, which
presents all of the judgments in a cross-tabulation of study by
risk of bias domain. This display of internal validity will indicate
the weight the reader may give the results of each study. We will
classify trials as being at high risk of bias overall if they are rated
high for any of three key criteria, namely, allocation concealment,
blinding of outcome assessors and completeness of outcome data.
For trials that have at least one of the three key domains rated as
’unclear’ but none of these judged at high risk of bias, the trial
will be classified as being at overall unclear risk of bias. Trials can
only be classified as being at low risk of bias overall if all three key
domains are rated as low risk individually.
Measures of treatment effect
Data analysis will be performed according to the guidelines of
the Cochrane Collaboration. One review author will enter quantitative data into Review Manager 5.2, another will check it, and
the data will be analysed using the Cochrane Collaboration’s associated software. We will present the outcome results for each
trial with 95% confidence intervals (CI). We will report estimates
for dichotomous outcomes (e.g. ulcers healed during time period,
number of infected ulcers) as risk ratios (RR). Continuous outcomes (such as absolute or relative changes in ulcer area) will be
expressed as mean differences (MD) and overall effect size (with
95% CI calculated). For time to event data, we plan to plot estimates of hazard ratios with associated 95% CIs where available
from trial reports.
Unit of analysis issues
We will treat the number of ulcers as the unit of analysis in this
review; however, we will record whether outcomes in relation to an
ulcer were measured on a per-participant or per-ulcer basis, and,
in studies where multiple ulcers on a person were treated as being
independent, we will record that as part of our risk of bias assessment. The authors will include data from cluster-randomised trials if the information is available. For cluster-randomised trials, we
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will adjust results when the unit of analysis in the trial is presented
as the total number of individual participants instead of the number of clusters. Results will be adjusted using the mean cluster size
and intra-cluster correlation co-efficient (ICC) (Higgins 2011c).
Data from cross-over trials will be assessed at the point of crossover if available. For meta-analysis, data will be combined from
individually randomised trials using the generic inverse-variance
method as described in chapter 16.3 of the Cochrane Handbook
for Systematic Reviews of Interventions (Higgins 2011d).
Dealing with missing data
The authors will contact the trial investigators in cases of incomplete or missing data. Where trials report complete healing outcomes for only those participants who complete the trial (i.e. participants withdrawing and lost to follow-up are excluded from the
analysis), we will treat the participants who are not included in
the analysis as if their wound did not heal. Where trials report
results for participants who complete the trial without specifying
the numbers initially randomised per group, we will present only
complete case data. For other outcomes the same analysis will be
applied.
Assessment of heterogeneity
We will consider clinical heterogeneity (that is where trials appear
similar in terms of participant characteristics, intervention type
and duration and outcome type) and statistical heterogeneity. We
will assess statistical heterogeneity using the Chi² test (a significance level of P < 0.10 is considered to indicate significant heterogeneity) in conjunction with the I² statistic (Higgins 2003). The
I² statistic estimates the percentage of total variation across trials
due to heterogeneity rather than variation due to chance (Higgins
2003). Heterogeneity will be categorized as follow: I² values ≤
40% to indicate a low level of heterogeneity and ≥75% to represent very high heterogeneity (Deeks 2011).
Assessment of reporting biases
If sufficient studies (i.e. more than ten) are identified, an attempt
will be made to check for publication bias using a funnel plot,
as described in the Cochrane Handbook for Systematic Reviews
of Interventions (Higgins 2011e). If asymmetry is present we will
explore possible causes including publication bias, poor methodological quality and true heterogeneity.
alternative hydrogel dressings or other types of dressings. The decision to include studies in a meta-analysis will depend on the availability of treatment effect data and assessment of heterogeneity.For
comparisons where there is no apparent clinical heterogeneity and
the I2 value is ≤ 40%, we will apply a fixed-effect model. Where
there is no apparent clinical heterogeneity and the I2 value is >
40%, we will apply a random-effects model. However, we will not
pool data where heterogeneity is very high (I2 values ≥ 75%).
For the dichotomous outcomes we will present the summary estimate as a risk ratio (RR) with 95% confidence intervals (CI).
Where continuous outcomes are measured in the same way across
trials, we will present a summary mean difference (MD) with 95%
CI. We will present a standardised mean difference (SMD) where
trials measure the same outcome using different methods. For time
to event data, we plan to plot, and if feasible pool, estimates of
hazard ratio and 95% CI as presented in the trial reports using the
generic inverse variance method in RevMan 5.2.
The authors will grade the quality of the evidence for each primary outcome using four levels of quality: high, moderate, low
and very low (Schünemann 2011a). We plan to record the quality in a “Summary of findings” table using the GRADE system,
as described in the Cochrane Handbook for Systematic Reviews
of Interventions (Schünemann 2011b), for the first primary outcome. Quality will be based in the following factors:
1. Limitations in the design and implementation of available studies suggesting high likelihood of bias.
2. Indirectness of evidence (indirect population, intervention, control, outcomes).
3. Unexplained heterogeneity or inconsistency of results (including problems with subgroup analyses).
4. Imprecision of results (wide confidence intervals).
5. High probability of publication bias.
Subgroup analysis and investigation of heterogeneity
Subgroup analysis will be carried out according to the presence
or absence of compression therapy independent of type (elastic or
inelastic) or level (moderate or high) compression. If is not clearly
indicated in the trial report the presence or absence of compression
therapy, we will not include these trials in this subgroup analysis.
Sensitivity analysis
Data synthesis
Where data are available, sensitivity analyses will be performed for
each comparison that has a meta-analysis, according to the overall
risk of bias of each included RCT. RCTs with overall high or unclear risk of bias will be excluded and the difference between estimates of treatment effect from this analysis and the main analysis
considered.
We will present a narrative overview of the studies reviewed and
the authors will use Revman 5.2 to combine outcomes when it is
possible (Revman 2012). Included trials will be grouped according
to the comparator intervention which may include no dressing,
ACKNOWLEDGEMENTS
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The authors would like to acknowledge the contribution of the
Wound’s Group editorial base staff: Sally Bell-Syer for advice on
the protocol and editorial assistance and Ruth Foxlee for designing the search strategy. In addition Elizabeth Royle for copy editing and the referees; Wounds Group Editors Joan Webster, Marian Brady, Statistical advisor Marialena Trivella and referees Mark
Corbett, Una Adderley, Vicki Pennick and Amy Zelmer.
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∗
Indicates the major publication for the study
APPENDICES
Appendix 1. Glossary of Terms
alginate = a salt of alginic acid.
capillary convolution = a rolled up or coiled condition of the capillary vessels.
debridement = is the medical removal of dead, damaged, or infected tissue to improve the healing potential of the remaining healthy
tissue. It is thought to be an important part of the healing process for wounds.
macrovascular = the portion of the vasculature of the body comprising the larger vessels.
polymer = a large molecule (macromolecule) composed of repeating structural units.
re-epithelialisation = growth of the epithelium across a wound from the wound edges.
skin perfusion = the process of nutritive delivery of arterial blood to a capillary bed in the biological tissue.
thrombosis = formation of a thrombus (blood clot) within the heart or blood vessels.
tortuosity = condition of being twisted or crooked.
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valvular incompetence = inability of the valves to keep blood flowing in the direction it should be.
vein incompetence = venous insufficiency, that leads to abnormal (inadequate) blood flow through veins.
venous stasis = reduction in blood flow or stoppage of blood flow through a vein.
venous reflux = blood moving in the wrong direction in veins due to valvular incompetence.
Definitions taken from The Free Medical Dictionary and Cochrane Wounds Group Glossary.
Appendix 2. Nurse Prescribers Formulary 2011 categories of dressings
Basic wound contact dressings
Low-adherence dressings and wound contact materials
These dressings are usually cotton pads that are placed directly in contact with the wound. They can be either non-medicated (e.g.
paraffin gauze dressing) or medicated (e.g. containing povidone iodine or chlorhexidine). Examples include paraffin gauze dressing, BP
1993 and Xeroform (Covidien) dressing - a non-adherent petrolatum blend with 3% bismuth tribromophenate on fine mesh gauze.
Absorbent dressings
These dressings are applied directly to the wound and may be used as secondary absorbent layers in the management of heavily exuding
wounds. Examples include Primapore (Smith & Nephew), Megapore (Molnlycke) and absorbent cotton gauze (BP 1988).
Advanced wound dressings
Hydrogel sheet and amorphous dressings
These dressings consist of a starch polymer and up to 96% water. They can absorb wound exudate or rehydrate a wound, depending
on the wound moisture levels. They are supplied in either flat sheets or amorphous hydrogel. Examples of hydrogel sheet dressings
include: Actiformcool (Activa) and Aquaflo (Covidien). Examples of amorphous hydrogel dressings include: Purilon Gel (Coloplast)
and NuGel (Systagenix).
Films-permeable film and membrane dressings
These dressings are permeable to water vapour and oxygen, but not to liquid water or micro-organisms. Examples include Tegaderm
(3M); Opsite (Smith & Nephew).
Soft polymer dressings
These dressings are composed of a soft silicone polymer held in a non-adherent layer. They are moderately absorbant. Examples include:
Mepitel (Molnlyckye) and Urgotul (Urgo).
Hydrocolloid dressings
These dressings are usually composed of an absorbant hydrocolloid matrix on a vapour-permeable film or foam backing. Examples
include: Granuflex (Conva Tec). NU DERM (Systagenix). Fibrous alternatives have been developed that resemble alginates and are
not occlusive: Aquacel (Conva Tec).
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Foam dressings
These dressings contain hydrophilic polyurethane foam and are designed to absorb wound exudate and maintain moist wound surface.
There are various versions; some include additional absorbent materials, such as viscose and acrylate fibres, or particles of superabsorbent polyacrylate, while some are silicone-coated for non traumatic removal. Examples include: Allevyn (Smith & Nephew); Biatain
(Coloplast); Tegaderm (3M).
Alginate dressings
These dressings are highly absorbent and consist of calcium alginate or calcium sodium alginate, which can be combined with collagen.
The alginate forms a gel when in contact with wound surface. This gel can be lifted off at dressing removal, or rinsed away with sterile
saline. Bonding to a secondary viscose pad increases absorbency. Examples include: Curasorb (Covidien); SeaSorb (Coloplast); Sorbsan
(Unomedical).
Capillary-action dressings
These dressings consist of an absorbant core of hydrophilic fibres held between two low-adherent contact layers. Examples include:
Advadraw (Advancis); Vacutx (Protex).
Odour-absorbent dressings
These dressings contain charcoal and are used to absorb wound odour. Often this type of dressing is used in conjunction with a
secondary dressing to improve absorbency. Examples include: CarboFLEX (Conva Tec).
Anti-microbial dressings
Honey-impregnated dressings
These dressings contain medical-grade honey, which is supposed to have antimicrobial and anti-inflammatory properties, and can be
used for acute or chronic wounds. Examples include: Medihoney (Medihoney) and Activon Tulle (Advancis).
Iodine-impregnated dressings
These dressings release free iodine, which is thought to act as a wound antiseptic, when exposed to wound exudate. An example is
Iodozyme (Insense).
Silver-impregnated dressings
These dressings are used to treat infected wounds, as silver ions are thought to have antimicrobial properties. Silver versions of most
dressing types are available (e.g. silver foam, silver hydrocolloid etc). Examples include: Acticoat (Smith & Nephew) and Urgosorb
Silver (Urgo).
Other antimicrobial dressings
These dressings are composed of a gauze or low-adherent dressing impregnated with an ointment thought to have antimicrobial
properties. Examples include: chlorhexidine gauze dressing (Smith & Nephew) and Cutimed Sorbact (BSN Medical).
Specialist dressings
Protease-modulating matrix dressings
These dressings alter the activity of proteolytic (protein-digesting) enzymes in chronic wounds. Examples include: Promogran (Systagenix) and Sorbion (H & R).
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Silicone keloid dressing
These dressings reduce or prevent hypertrophic or keloid scarring. Examples include: Cica-Care (Smith & Nephew) and Ciltech (Sumed).
Appendix 3. The Cochrane Collaboration’s tool for assessing risk of bias
1. Was the allocation sequence randomly generated?
Low risk of bias
The investigators describe a random component in the sequence generation process such as: referring to a random number table; using
a computer random number generator; coin tossing; shuffling cards or envelopes; throwing dice; drawing of lots.
High risk of bias
The investigators describe a non-random component in the sequence generation process. Usually, the description would involve some
systematic, non-random approach, for example: sequence generated by odd or even date of birth; sequence generated by some rule
based on date (or day) of admission; sequence generated by some rule based on hospital or clinic record number.
Unclear
Insufficient information about the sequence generation process to permit judgement of low or high risk of bias.
2. Was the treatment allocation adequately concealed?
Low risk of bias
Participants and investigators enrolling participants could not foresee assignment because one of the following, or an equivalent
method, was used to conceal allocation: central allocation (including telephone, web-based and pharmacy-controlled randomisation);
sequentially-numbered drug containers of identical appearance; sequentially-numbered, opaque, sealed envelopes.
High risk of bias
Participants or investigators enrolling participants could possibly foresee assignments and thus introduce selection bias, such as allocation
based on: using an open random allocation schedule (e.g. a list of random numbers); assignment envelopes without appropriate
safeguards (e.g. if envelopes were unsealed or non opaque or not sequentially numbered); alternation or rotation; date of birth; case
record number; any other explicitly unconcealed procedure.
Unclear
Insufficient information to permit judgement of low or high risk of bias. This is usually the case if the method of concealment is not
described or not described in sufficient detail to allow a definite judgement, for example if the use of assignment envelopes is described,
but it remains unclear whether envelopes were sequentially numbered, opaque and sealed.
3. Blinding - was knowledge of the allocated interventions adequately prevented during the study?
1. Blinding of participants and care providers;
2. Blinding of outcome assessors;
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Low risk of bias
Any one of the following:
• No blinding, but the review authors judge that the outcome and the outcome measurement are not likely to be influenced by
lack of blinding.
• Blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.
• Either participants or some key study personnel were not blinded, but outcome assessment was blinded and the non-blinding of
others unlikely to introduce bias.
High risk of bias
• No blinding or incomplete blinding, and the outcome or outcome measurement is likely to be influenced by lack of blinding.
• Blinding of key study participants and personnel attempted, but likely that the blinding could have been broken.
• Either participants or some key study personnel were not blinded, and the non-blinding of others likely to introduce bias.
Unclear
Either of the following:
• Insufficient information to permit judgement of low or high risk of bias.
• The study did not address this outcome.
4. Were incomplete outcome data adequately addressed?
Low risk of bias
• No missing outcome data.
• Reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing
bias).
• Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups.
• For dichotomous outcome data, the proportion of missing outcomes compared with observed event risk was not enough to have
a clinically relevant impact on the intervention effect estimate.
• For continuous outcome data, plausible effect size (difference in means or standardised difference in means) among missing
outcomes was not enough to have a clinically relevant impact on observed effect size.
• Missing data have been imputed using appropriate methods.
High risk of bias
• Reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing
data across intervention groups.
• For dichotomous outcome data, the proportion of missing outcomes compared with observed event risk was enough to induce
clinically relevant bias in intervention effect estimate.
outcomes was enough to induce clinically relevant bias in observed effect size.
• ‘As-treated’ analysis done with substantial departure of the intervention received from that assigned at randomisation.
• Potentially inappropriate application of simple imputation.
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Unclear
• Insufficient reporting of attrition/exclusions to permit judgement of low or high risk of bias (e.g. number randomised not stated,
no reasons for missing data provided).
5. Are reports of the study free of suggestion of selective outcome reporting?
Low risk of bias
• The study protocol is available and all of the study’s pre-specified (primary and secondary) outcomes that are of interest in the
review have been reported in the pre-specified way.
• The study protocol is not available but it is clear that the published reports include all expected outcomes, including those that
were pre-specified (convincing text of this nature may be uncommon)
High risk of bias
• Not all of the study’s pre-specified primary outcomes have been reported.
• One or more primary outcomes is reported using measurements, analysis methods or subsets of the data (e.g. subscales) that
were not pre-specified.
• One or more reported primary outcomes were not pre-specified (unless clear justification for their reporting is provided, such as
an unexpected adverse effect).
• One or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a meta-analysis.
• The study report fails to include results for a key outcome that would be expected to have been reported for such a study.
Unclear
Insufficient information to permit judgement of low or high risk of bias. It is likely that the majority of studies will fall into this category.
6. Other sources of potential bias
For example:
• comparability of treatment groups in relation to baseline ulcer surface area;
• choice of analysis where multiple ulcers on the same individuals(s) are studied;
• choice of analysis in cluster randomised trials;
Low risk of bias
The study appears to be free of other sources of bias.
High risk of bias
There is at least one important risk of bias. For example, the study:
• had a potential source of bias related to the specific study design used; or
• had extreme baseline imbalance; or
• has been claimed to have been fraudulent; or
• had some other problem.
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Unclear
There may be a risk of bias, but there is either:
• insufficient information to assess whether an important risk of bias exists; or
• insufficient rationale or evidence that an identified problem will introduce bias.
Guilherme Fregonezi: conceived the review question and secured funding; advised on and developed the protocol; completed part of
the first draft of the protocol; made an intellectual contribution to the protocol, and approved the final version prior to submission.
Fernando Dias: developed and coordinated the protocol; advised on, completed the first draft of the protocol; approved the final version
of the protocol prior to submission; made an intellectual contribution to the protocol.
Cibele Ribeiro: developed and coordinated the protocol; advised on, completed and edited the first draft of the protocol; approved the
final version of the protocol prior to submission; made an intellectual contribution to the protocol.
Contributions of editorial base:
Nicky Cullum: edited the protocol; advised on methodology, interpretation and protocol content.
Susan O’Meara, Editor: commented on, edited and approved the final protocol prior to submission.
Sally Bell-Syer: coordinated the editorial process. Advised on methodology, interpretation and content. Edited the protocol.
Ruth Foxlee: designed the search strategy and edited the search methods section.
DECLARATIONS OF INTEREST
None.
SOURCES OF SUPPORT
Internal sources
• No sources of support supplied
External sources
• MCT/CT-Saúde and Decit/SCTIE/MS (CNPq - process 559416/2009-1), Brazil.
Research grant
• NIHR/Department of Health (England), (Cochrane Wounds Group), UK.
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3.1 Descrição dos estudos
3.1.1 Resultados da busca
Os resultados abaixo estão descritos de acordo com a formatação requerida
pela Colaboração Cochrane para a submissão da revisão utilizando o RevMan.
Foram identificados um total de 460 estudos dos quais 218 estudos foram
identificados através de busca em base eletrônica de dados bibliográficos, sendo
essas: Cochrane Wounds Group Specialised Register, Central, Medline, Embase e
Ebsco Cinhal. Os 242 estudos restantes foram identificados através de buscas
realizadas em sites de registros de ensaios controlados, como: controlled-trials,
clinicaltrials.gov, who ictrp e nenhum desses estudos foi incluído por não
apresentarem informações relevantes aos critérios propostos. Foram contatadas 16
empresas fabricantes de adesivos de carboximetilcelulose para a confirmação da
existência ou não de estudos em andamento ou recentemente finalizados, sendo
essas: 3M, A1 Pharmaceuticals, Activa, Aspen Medical, Braun, BSN Medical,
Coloplast, Convatec, Covidien, Hartmann, MedLogic, Molnlycke, Protex, Synergy
Healthcare, Smith & Nephew Healthcare e Systagenix. Das 16 empresas apenas
cinco (3M, Activa, Synergy Healthcare, Smith & Nephew Healthcare e Systagenix)
responderam ao contato confirmando a não existência de estudos em andamento ou
recentemente finalizados. As empresas restantes não responderam ao contato
enviado. Não foi obtido nenhum estudo a partir do contato com os fabricantes de
adesivos.
Após a seleção dos estudos foram excluídos 103 estudos dos 218 restantes
baseado nos títulos e resumos por não atenderem aos critérios de inclusão. Outros
80 estudos foram eliminados por serem duplicatas na lista de estudos presentes
após a busca. Assim, ao final da seleção restaram 35 estudos dos quais foram
obtidas a versão completa para a confirmação dos critérios de elegibilidade. A figura
2 apresenta um diagrama com os detalhes do resultado da busca. As razões de
exclusão dos estudos estão descritas no Anexo 2.
39
Figura 2 – Diagrama com o resultado da seleção dos estudos
Dos 35 estudos restantes foram excluídos mais 27 estudos por não
apresentarem os critérios de elegibilidade propostos. Segue abaixo as razões de
exclusão baseada nos critérios de elegibilidade:
- 10 estudos não eram estudos controlados randomizados;
40
- 5 estudos eram resumos de conferências com informação limitada;
- 5 estudos não apresentavam o hidrogel como tratamento para as úlceras
venosas;
- 3 estudos utilizavam úlceras de diferentes etiologias, mas não apresentavam
a descrição dos resultados separados para os participantes com úlcera venosa. Os
autores foram contatados, mas não houve resposta;
- 3 estudos apresentavam o hidrogel não sendo a única diferença sistemática
entre os grupos;
- 1 estudo apresentou uma quantidade menor que 75% para participantes com
úlcera venosa não tendo sido reportado os valores apenas para pacientes com
úlcera venosa.
3.1.2 Estudos incluídos
Quatro estudos foram incluídos apresentando um total de 250 participantes.
Dos quatro estudos um foi realizado na China (He e col., 2008)56, um na Alemanha
(Grotewohl 1994)57, na Bélgica (de la Brassinne e col., 2006)58 e o último na Irlanda
(Gethin e col., 2008)59. Três estudos foram publicados em inglês (Grotewohl 1994,
de la Brassinne e col. 2006, Gethin e col. 2008) e um estudo foi publicado em chinês
(He e col. 2008). Este último estudo foi traduzido para a língua portuguesa pela
empresa All Tasks – Serviço de traduções para análise dos dados para o estudo.
Todos os estudos incluídos foram randomizados controlados dos quais dois
estudos foram multicêntricos (Gethin e col., 2008; Grotewohl 1994).
Em relação à população incluída dos estudos, a média de idade foi entre 45 a
70 anos. Somente um estudo, o de Grotewohl (1994) não reportou a idade dos
pacientes incluídos. Em relação aos critérios de inclusão e exclusão dos
participantes dos estudos incluídos somente um deles Gethin e col. (2008) reportou
o resultado do ITB como critério de diagnóstico para a participação ou não no
estudo.
41
As comparações dos adesivos usadas nos estudos incluídos foram as
seguintes:
- Hidrogel, Opragel, com um hidrocolóide Grotewohl (1994).
- Hidrogel, Quitosana, com gaze contendo solução salina (He e col. 2008).
- Hidrogel, Intrasite, com um gel de alginato, Flaminal (de la Brassinne e col.
2006).
- Hidrogel, Intrasite, com um adesivo composto de mel de Manuka, “Manuka
honey” (Gethin e col. 2008).
Foi utilizada a terapia compressiva associada ao tratamento com os adesivos
em dois estudos (Gethin e col. 2008, Grotewohl 1994). Somente um estudo reportou
o uso do adesivo secundário (Allevyn – curativo de espuma hidrocelular)59. A
duração do tratamento foi de 12 semanas em um estudo (Gethin e col. 2008), quatro
semanas em dois estudos (de la Brassinne e col. 2006, Grotewohl 1994) e 2
semanas em um estudo (He e col. 2008). No Anexo 3 encontram-se todas as
características dos estudos incluídos, como: detalhes da metodologia, dos
participantes, das intervenções utilizadas por cada estudo e dos desfechos
analisados por cada estudo.
3.2 Risco de viés dos estudos incluídos
Alocação dos participantes
Três estudos (He e col. 2008, Grotewohl 1994 e de la Brassinne e col. 2006)
não descrevem o método da sequência de randomização dos pacientes somente
citam que foram randomizados por isso foram classificados como risco incerto de
viés. Somente um estudo (Gethin e col. 2008) apontou corretamente a sequência de
randomização que foi realizada através de telefone remoto sendo assim classificado
como baixo risco de viés.
Em relação ao sigilo de alocação dos pacientes somente um estudo (Gethin e
col. 2008) descreve corretamente que foi realizada através de envelopes opacos
42
numerados em série e foi então classificado como baixo risco de viés. Os outros três
estudos não reportaram o sigilo de alocação dos pacientes sendo classificados
como risco incerto de viés.
Mascaramento
Dos quatro estudos incluídos (He e col. 2008, Grotewohl 1994, de la
Brassinne e col. 2006 e Gethin e col. 2008) nenhum estudo reportou o
mascaramento dos participantes, dos profissionais envolvidos com o tratamento e
dos profissionais envolvidos com a análise dos desfechos de cada estudo. Sendo
assim todos os estudos foram classificados para esse item como alto risco de viés.
Dados incompletos
Três estudos (He e col. 2008, Grotewohl 1994 e de la Brassine e col. 2006)
foram considerados como risco incerto de viés pois não reportaram nenhuma
desistência ou perda durante o tratamento. Um estudo (Gethin e col. 2008) registrou
as perdas dos participantes do estudo e para a análise dos dados o número de
participantes foi mantido o mesmo (n=54) entre os grupos de intervenção e, portanto
foi considerado um estudo com baixo risco de viés, pois a análise foi realizada com
intenção de tratar.
Descrição seletiva do desfecho
Para a análise desse item é necessário o acesso ao protocolo proposto pelos
estudos para ser considerado como evidência definitiva. Porém não foi possível
obter o protocolo de pesquisa dos estudos incluídos através do contato com os
autores. Foi feito uma busca nos sites de registros de protocolos de pesquisa e não
foi encontrado nenhum registro. Sendo assim para classificar o grau de viés desse
item foi feito uma análise baseada na metodologia e nos resultados reportados por
cada estudo.
Um estudo (He e col. 2008) foi considerado com alto risco de viés, pois
reportou um desfecho (tempo de cicatrização) nos resultados no qual não foi
descrito na metodologia do estudo. Os outros três estudos (Grotewohl 1994, de la
43
Brassinne e col. 2006 e Gethin e col. 2008) foram considerados estudos com baixo
risco de viés pois apresentaram os resultados para os desfechos descritos na
metodologia proposta.
As figuras abaixo 3 e 4 apresentam todos os critérios analisados para a
análise dos vieses dos quatro estudos incluídos com a classificação para cada
estudo.
Figura 3 – Avaliação do risco de viés de todos os estudos incluídos na revisão
44
Figura 4 – Avaliação do risco de viés de cada estudo incluído na revisão: julgamento dos
autores de cada item para cada estudo incluído.
3.3 Efeitos do hidrogel
Foram incluídos quatro estudos que avaliaram os curativos de hidrogéis para
o tratamento de úlceras venosas (He e col. 2008, de la Brassine e col. 2006, Gethin
e col. 2008, Grotewhol 1994). Os resultados serão apresentados por comparações
dos tratamentos aplicados em cada estudo com descrição detalhada por desfechos
(primários e secundários) propostos na revisão.
3.3.1 Comparação entre hidrogel, Quitosana, e gaze com solução salina (He e
col. 2008)
Desfechos primários:
45
1. Cicatrização completa das úlceras: o grupo do hidrogel cicatrizou completamente
em 16 participantes nos 14 dias de tratamento enquanto que o grupo controle a
cicatrização completa ocorreu em 3 participantes, havendo diferença estatística
entre os grupos (RR 5,33, 95%CI 1,73 a 16,42). O gráfico 1 apresenta a análise da
comparação do hidrogel com gaze com solução salina para o desfecho cicatrização
completa das feridas.
Gráfico 1 – Forest plot representando a comparação do hidrogel com gaze com solução
salina para o desfecho cicatrização completa das úlceras.
2. Incidência de infecção: esse desfecho não foi analisado pelo estudo.
Desfechos secundários:
1. Alterações no tamanho da úlcera: As medidas das úlceras foram realizadas no 7°
e no 14° dia de tratamento. No grupo do hidrogel a área da úlcera diminui de 3,4 ±
0,6 cm2 para 1,1 ± 0,2 cm2; e no grupo controle a área da úlcera diminuiu de 3,1 ±
0,4 cm2 para 2,3 ± 0,7 cm2.
2. Tempo de cicatrização: O tempo de cicatrização no grupo do hidrogel foi de 12,0 ±
1,7 dias e no grupo controle foi de 31,0 ± 2,9 dias tendo sido reportado diferença
estatística entre os grupos pelos autores (p < 0,05).
3. Recorrência da úlcera: esse desfecho não foi analisado pelo estudo.
4. Qualidade de vida dos participantes: esse desfecho não foi analisado pelo estudo.
5. Dor: esse desfecho não foi analisado pelo estudo.
46
6. Custos do tratamento: esse desfecho não foi analisado pelo estudo.
3.3.2 Comparação entre hidrogel, Intrasite, e gel de alginato (de la Brassinne
e col. 2006)
1. Cicatrização completa das úlceras: esse desfecho não foi analisado pelo estudo.
1. Alterações no tamanho da úlcera: as medidas das úlceras foram realizadas antes
de iniciar o tratamento, no 7° dia, 14° e no final das quatro semanas. A área de
superfície da úlcera diminuiu com o tempo de tratamento nos dois grupos tratados. A
porcentagem de redução da área da úlcera no grupo do gel de alginato foi de 27,3%
± 20,6% no 14° dia e de 61,2% ± 26,2% ao final das quatro semanas. No grupo
tratado com o hidrogel a porcentagem de redução foi de 3,2% ± 13,3% no 14° dia e
de 19,4% ± 24,3% ao final das quatro semanas. O gráfico 2 apresenta a análise da
comparação do hidrogel com o gel de alginato para o desfecho porcentagem de
redução da úlcera em quatro semanas de tratamento.
47
Gráfico 2 – Forest plot representando a comparação do hidrogel com o gel de alginato para
o desfecho porcentagem de redução da úlcera em 4 semanas de tratamento.
2. Tempo de cicatrização: esse desfecho não foi analisado pelo estudo.
3.3.3 Comparação entre hidrogel, Intrasite, e mel de Manuka (Gethin e col.
2008).
1. Cicatrização completa das úlceras: esse desfecho foi analisado com 12 semanas
de tratamento. No grupo do mel de Manuka 24/54 (44%) pacientes cicatrizaram
completamente e no grupo do hidrogel 18/54 (33%) apresentaram uma cicatrização
completa da úlcera. O gráfico 3 apresenta a análise da comparação do hidrogel com
o mel de Manuka para o desfecho cicatrização completa das úlceras.
Gráfico 3 - Forest plot representando a comparação do hidrogel com o mel de Manuka para
o desfecho cicatrização completa das úlceras.
48
2. Incidência de infecção: o grupo que foi tratado com o mel de Manuka apresentou
seis perdas por infecção na ferida e o grupo de hidrogel apresentou 12 perdas por
infecção na ferida (Gráfico 4). A análise dos dados desse estudo foi por intenção de
tratar, pois foram incluídas as perdas dos dois grupos na análise estatística para
proteger o estudo de um possível viés de seguimento.
Gráfico 4 – Forest plot representando a comparação do hidrogel com o mel de Manuka para
o desfecho incidência de infecção.
1. Alterações no tamanho da úlcera: o grupo do mel de Manuka apresentou uma
redução de 34% e a redução no grupo do hidrogel foi de 13% havendo diferença
estatística entre os grupos (p< 0.001).
3.3.4 Comparação entre hidrogel e hidrocolóide (Grotewohl 1994)
49
1. Cicatrização completa das úlceras: esse desfecho não foi analisado pelo estudo.
1. Alterações no tamanho da úlcera: o grupo do hidrogel reduziu 44,6% e o grupo do
hidrocolóide reduziu 33,3% do tamanho da ferida com quatro semanas de
tratamento.
Não foi possível realizar uma meta-análise devido à falta de dados e de estudos
que apresentassem comparações de um mesmo tratamento. Devido à escassez de
informações não foi possível também realizar a análise de sensibilidade e análise de
subgrupo como foi proposto na metodologia da revisão.
50
4 DISCUSSÃO
51
Nesta revisão foi possível analisar os efeitos do tratamento com o hidrogel na
cicatrização de úlceras venosas de membros inferiores. Quatro estudos controlados
e randomizados envolvendo 250 participantes foram incluídos na revisão. Vários
desfechos propostos pela revisão não foram reportados pelos estudos, sendo estes:
qualidade de vida, dor, recorrência da úlcera e custos para o tratamento. Embora
alguns desfechos avaliados nos estudos incluídos tenham demonstrado uma
melhora na cicatrização das úlceras dos pacientes que receberam o hidrogel como
tratamento, não foi possível realizar uma meta-análise devido à falta de dados e de
estudos que apresentassem comparações de um mesmo tratamento.
O uso do hidrogel parece ser superior ao curativo convencional no caso, gaze
embebida em salina, para a cicatrização de úlceras venosas de membros inferiores.
No entanto, esta análise foi baseada em apenas um estudo que apresentou risco de
viés incerto e onde a seleção dos pacientes foi feita baseado no tamanho da úlcera
(menor que 4 cm2); portanto, dificultando o extrapolamento dos dados para úlceras
crônicas de maior tamanho inicial. A carência de estudos de qualidade relativos a
esta comparação não permite a conclusão definitiva da superioridade do hidrogel
sobre o curativo convencional para guiar a prescrição clínica. Esta prescrição deverá
ser feita levando-se em consideração outras condições clínicas individuais como a
acessibilidade ao hidrogel, conforto nas trocas de curativos e presença de tecido
necrótico na ferida.
A comparação do uso do hidrogel com outros tratamentos, como o mel de
Manuka, demonstrou que o efeito do hidrogel é similar em relação à porcentagem de
redução da área das úlceras embora exista uma tendência à melhora no
debridamento autolítico nas fases iniciais de cicatrização (quatro semanas) para o
mel de Manuka que, contudo, não persistiu no “follow up” final do estudo (12
semanas). Apesar do estudo do mel de Manuka apresentar um alto risco de viés
(devido ao fato de não ter sido descrito o mascaramento dos avaliadores, embora
para os outros critérios ele tenha sido considerado de baixo risco), pode-se
considerar em termos metodológicos como o melhor estudo entre os quatro
incluídos, pois houve a preocupação de reportar a correta seleção e alocação dos
participantes bem como a intenção de tratar os participantes que foram excluídos
por motivos descritos pelos autores do estudo. Em relação ao outro tratamento
52
analisado, o gel de alginato demonstrou ser mais eficaz quando comparado ao
hidrogel quanto à redução da área e volume da ferida.
Em revisão de Palfreyman e col. (2007)53 foram analisados todos os curativos
para o tratamento de úlceras venosas de membros inferiores e concluiu-se que não
haviam dados suficientes para afirmar que um tipo de curativo foi mais eficaz do que
outro na cicatrização de úlceras venosas. Neste estudo os desfechos analisados
foram tempo até a completa cicatrização das úlceras ou proporção das úlceras
completamente cicatrizadas e porcentagem de cicatrização das úlceras e foram
incluídos quatro estudos com hidrogéis dos quais dois estudos comparavam o
hidrogel com adesivos de baixa aderência, um estudo comparou o hidrogel com o
cadexomer iodine e o último comparou o hidrogel com o dextranômero. Os
resultados obtidos na presente revisão sistemática estão de acordo com Palfreyman
e col. (2007)53 no qual os desfechos analisados foram os mesmos nas duas revisões
sugerindo que não há nenhuma evidência para os hidrogéis como sendo melhor ou
pior do que outros curativos para a cicatrização de úlceras venosas.
A escolha correta do adesivo ideal para o tratamento com os pacientes que
apresentem úlceras venosas depende de estudos que avaliem a dor e a qualidade
de vida através de instrumentos de avaliação válidos e confiáveis e que os
resultados sejam reportados na íntegra e de maneira clara para que se possa fazer
uma correta análise de todos os parâmetros (a avaliação desses dois itens não foi
reportada em nenhum dos estudos incluídos).
Os resultados obtidos nessa revisão sistemática mostram claramente a
necessidade de mais estudos controlados randomizados de alta qualidade
metodológica abordando o uso do hidrogel no tratamento de pacientes com úlceras
venosas de membros inferiores. Os dados dos estudos não apontam consistência
para suportar o uso de um ou outro adesivo. Parte dessa inconsistência é dada pela
baixa qualidade dos artigos. Estudos futuros devem relatar aspectos metodológicos,
como, randomização e alocação dos participantes do estudo e mascaramento dos
avaliadores dos resultados, e considerar outros critérios importantes como o
tamanho adequado da amostra a fim de detectar os efeitos do tratamento para que
se possa orientar de maneira correta e clara a decisão pelos profissionais da saúde
do tratamento adequado para cada paciente.
53
5 CONSIDERAÇÕES FINAIS E CONCLUSÃO
54
Sugere-se, baseado nas evidências atuais pela presente revisão sistemática
que, os curativos de hidrogéis podem ser melhores que gaze embebida em solução
salina para a cicatrização de úlceras venosas de membros inferiores e menos efetivo
que o gel de alginato para a redução da área e volume da ferida, porém ainda
existem incertezas em relação a essa decisão. Não existem evidências disponíveis a
respeito da efetividade do hidrogel em relação aos outros tipos de curativo na
cicatrização de úlceras venosas de membros inferiores, por isso há a necessidade
de futuras pesquisas para auxiliar os profissionais da saúde na escolha do adesivo
correto. Estudos futuros devem apresentar melhor rigor metodológico, clara
definição dos critérios de inclusão e exclusão dos estudos, descrição detalhada dos
desfechos que serão analisados para que se possa fazer ou não a indicação do uso
do curativo para o tratamento.
55
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61
6 ANEXOS
62
ANEXO 1: Protocolo publicado – Hydrocolloid dressings for venous leg ulcers
63
Hydrocolloid dressings for healing venous leg ulcers (Protocol)
Ribeiro CTD, Fregonezi GAF, Resqueti VR, Dornelas de Andrade A, Dias FAL
This is a reprint of a Cochrane protocol, prepared and maintained by The Cochrane Collaboration and published in The Cochrane
Library 2014, Issue 1
http://www.thecochranelibrary.com
64
TABLE OF CONTENTS
HEADER . . . . . . . . . .
ABSTRACT . . . . . . . . .
BACKGROUND . . . . . . .
OBJECTIVES . . . . . . . .
METHODS . . . . . . . . .
ACKNOWLEDGEMENTS
. . .
REFERENCES . . . . . . . .
APPENDICES . . . . . . . .
DECLARATIONS OF INTEREST .
SOURCES OF SUPPORT . . . .
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[Intervention Protocol]
Hydrocolloid dressings for healing venous leg ulcers
Cibele TD Ribeiro1 , Guilherme AF Fregonezi2 , Vanessa R Resqueti3 , Armele Dornelas de Andrade4 , Fernando AL Dias5
1 Graduate
Program in Physiotherapy, Federal University of Rio Grande do Norte, Natal, Brazil. 2 PhD Program in Physical Therapy,
Federal University of Rio Grande do Norte, Natal, Brazil. 3 Master Degree Program, Department of Physical Therapy, Federal University
of Pernambuco, Recife, Brazil. 4 Physical Therapy, Master Degree Program in Physical Therapy, Federal University of Pernambuco,
Recife, Brazil, Recife, Brazil. 5 Department of Physiology, Federal University of Paraná, Curitiba, Brazil
Contact address: Guilherme AF Fregonezi, PhD Program in Physical Therapy, Federal University of Rio Grande do Norte, Avenida
Senador Salgado Filho, 3000, Bairro Lagoa Nova, Natal, Rio Grande do Norte, 59078-970, Brazil. [email protected].
Editorial group: Cochrane Wounds Group.
Publication status and date: New, published in Issue 1, 2014.
Citation: Ribeiro CTD, Fregonezi GAF, Resqueti VR, Dornelas de Andrade A, Dias FAL. Hydrocolloid dressings for healing venous
leg ulcers. Cochrane Database of Systematic Reviews 2014, Issue 1. Art. No.: CD010918. DOI: 10.1002/14651858.CD010918.
ABSTRACT
This is the protocol for a review and there is no abstract. The objectives are as follows:
To determine the effects of hydrocolloid dressings compared with other wound dressings, non-dressing treatments or another hydrocolloid dressing on the healing of venous leg ulcers, and also the effects on health-related quality of life, pain, medical costs and recurrence
of ulcers.
BACKGROUND
Description of the condition
Venous leg ulcers present as open wounds on the lower limb. They
are usually associated with sustained venous hypertension which
causes chronic venous insufficiency (impaired venous blood flow)
(Grey 2006; Wollina 2006). This condition has psychological and
financial impacts, and also impairs the physical functioning of affected patients. The impact of leg ulcers on the patient’s daily life is
described in many quantitative and qualitative studies. The major
problems reported by patients are: pain, immobility, sleep disturbance, lack of energy, limitations in work and leisure activities,
worry, frustration and lack of self-esteem (Herber 2007; Persoon
2004). Thus, venous leg ulcers will ultimately impact quality of
life. Venous leg ulceration is a chronic health problem that can take
years to heal completely, and, as it has a high rate of recurrence, of-
ten requires life-long treatment (Margolis 2002; Van Hecke 2011).
Wound size and wound duration (longer than 18 months) are major contributors to the risk of not healing (Margolis 2004). Additionaly, the presence of lipodermatosclerosis (inflammation of
subcutaneous fat layers), evidence of deep vein thrombosis (blood
clot lodged in a leg vein), superficial thrombophlebitis (inflammation of surface veins) or poor ankle mobility are individually
associated with delayed healing (Lantis 2013).
The incidence of venous leg ulcers rises with increasing age (De
Araujo 2003; Wipke-Tevis 2000). The primary risk factors are aging, gender (venous leg ulcers are more common in women), obesity, previous leg injuries, deep venous thrombosis and phlebitis
(inflammation of veins) (Collins 2010). Venous leg ulcers have
been estimated to afflict between 0.2% and 1% of the total population, and between 1% and 3% of the elderly population in the
United States and Europe (Margolis 2002). The estimated prevalence of venous leg ulcers ranges between 0.6% and 1.9% in the
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66
adult population of the UK, USA, and Europe (Briggs 2003). Epidemiological studies estimate that venous leg ulcers affect one million people in the USA, accounting for 70% to 80% of all ulcers
of the lower limbs (De Araujo 2003). A cohort study calculated
that monthly direct medical care costs attributable to a venous leg
ulcer averaged USD 2400 (at 1997 values) (Olin 1999). Venous
ulceration represents the most prevalent form of difficult-to-heal
wounds, and treating these problematic wounds requires significant healthcare resources. Recent data from Germany revealed
that the mean total cost per year for a person with chronic venous
leg ulceration was EUR 9569, 92% of which was estimated to be
direct costs (that is, non-drug treatment, inpatients costs and outpatient care) and 8% indirect costs (inability to work) (Purwins
2010).
The pathophysiology of venous leg ulcers starts as a macrovascular
(see Appendix 1) problem attributable to valve incompetence. In
the normal venous system, blood pressure decreases during exercise as a result of the action of muscles pumping blood though
the vessels. In a system where the valves are incompetent, venous
pressure remains high (Grey 2006). Sustained venous hypertension (high blood pressure) will ultimately lead to microcirculatory
dysfunction and cause alterations in skin perfusion (transport of
oxygen and other substances), which can then lead to ulceration.
A diagnosis of venous leg ulceration is usually based on clinical examination. Additional tests such as colour duplex ultrasonography
(measurement of blood flow in the veins and arteries of the leg),
plethysmography (measurement of variations in the size or volume
of a limb), and venography (X-ray test that provides an image of
the leg veins) may be helpful (Cochrane Wounds Group Glossary;
Collins 2010; Robson 2006; The Free Medical Dictionary). All patients that present with an ulcer should be screened for peripheral
arterial disease (PAD) by Doppler measurement of ankle brachial
pressure index (ABPI). An ABPI measurement greater than 0.8
is generally considered as eliminating PAD as the cause of a leg
ulceration, leaving the most likely diagnosis as venous ulceration
(RCN 2006). Venous leg ulcers are generally irregular and shallow,
and often occur over bony prominences, particularly over the medial malleolus (inner ankle). Skin alterations surrounding the ulcer, such as hyperpigmentation (discolouration), lipodermatosclerosis and fibrosis (scarring) are usually present (Collins 2010). Frequent symptoms for venous ulceration include pain, odour and
drainage from the wound (Valencia 2001). Arterial ulcers can be
distinguished from venous ulcers because the former typically have
round and well-demarcated borders and the presence of necrotic
tissue in the wound bed. Physical symptoms of arterial leg ulcers
include: loss of leg hair; atrophic skin (wasting of skin) in the
segment; cold feet; absence of, or decrease in, arterial pulses; and
symptoms such as intermittent claudication (pain on walking that
is relieved by rest). Neuropathic ulcers (due to diseased nerves)
are more common in, but are not limited to, people with diabetes
mellitus. These differ from venous leg ulcers in having defined
borders, usually being deeper than venous ulcers, and are associ-
ated with foot numbness, burning and paraesthesia (sensation of
’pins and needles’) (Valencia 2001).
The standard treatment for venous leg ulcers is compression therapy. It has been shown that compression increases the healing rates
of venous leg ulcers compared with no compression (O’Meara
2012). The healing rates can range from 30% to 60% after 24
weeks of treatment, and up to 70% to 85% after one year of treatment (Margolis 2000). The maintenance of compression therapy
may reduce the risk of recurrence of the ulcer (Phillips 2000).
Compression therapy also reduces oedema and pain (Fletcher
1997). In the presence of compression, healing occurs more rapidly
in younger people, and those with a smaller initial ulcer area;
shorter duration of ulceration; and no deep vein involvement
(Skene 1992). This treatment is often applied with other interventions, such as debridement (removal of dead material) (Tang
2012), topical agents (e.g. creams) (Briggs 2010; Robson 2006),
physical agents (Aziz 2011; Cullum 2010; Flemming 1999), and
dressings (Palfreyman 2006).
Description of the intervention
The optimal wound healing environment is one in which the
wound is kept covered and moist, rather than left open to the
air. Standard treatment for venous leg ulcers should include therapeutic compression (this may be applied by bandages) in addition to a dressing, except when otherwise indicated (O’Meara
2012; Robson 2006). Dressings are applied underneath bandages
or stockings with the aim of protecting the wound and providing
a moist environment to aid healing. Nowadays, several types of
dressing seek to achieve a moist environment, the aim of which is
to promote re-epithelialisation of the wound, providing comfort,
controlling exudate and helping to prevent bandages and stockings from adhering to the wound bed. The ideal conditions required for wound healing in terms of dressing application have
been explained as follows: maintenance of a moist wound environment without risk of maceration (tissue breakdown); avoidance of
toxic chemicals, particles or fibres in the dressing fabric; a minimal
number of dressing changes; and maintenance of an optimum pH
level (NPF 2011).
The primary intervention of interest in this review is hydrocolloid
dressings used in the treatment of venous leg ulcers. The aim of
these dressings is to promote pain relief, comfort and also to favour
autolytic debridement (natural enzymic removal of dead tissue)
(Mandelbaum 2003). They are usually presented as a hydrocolloid layer that is composed of sodium carboxymethylcellulose (or a
similar material that forms a gel when wet) on a vapour-permeable
film or foam pad. Examples include Granuflex (ConvaTec) and
NU DERM (Systagenix). Fibrous hydrocolloids are a sub-set of
dressings that are designed for use in wounds with heavy exudate
instead of alternate dressing types such as alginates, e.g. Aquacel (ConvaTec). Hydrocolloid dressings have also been shown to
reduce pain in painful wounds (Meaume 2004). The purported
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benefits of hydrocolloid dressings include that they reduce the risk
of infection and do not require daily changes,. However, it has also
been suggested that they can cause maceration of the adjacent tissue and can provoke an unpleasant odour through the reaction of
exudate with the primary active ingredient in the dressing. Dressing changes should be done whenever leakage is observed or the
dressing loses its adherence (Mandelbaum 2003).
There is a broad choice of dressings available to treat wounds
such as venous leg ulcers. For ease of comparison this review will
class dressings into groups according to the broad categories of
the Nurse Prescribers’ Formulary 2011 (NPF 2011), that is, basic, advanced, anti-microbial and specialist wound dressings (see
Appendix 2). Dressing names, manufacturers and distributors may
vary between countries.
How the intervention might work
Animal models suggest that a moist wound environment can aid
wound healing. Wound dressings are used to maintain such an
environment; they may also keep wounds free of clinical infection
and excessive slough (dead tissue)(NPF 2011).
Hydrocolloid dressings, classified as an advanced wound dressing by the Nurse Prescribers’ Formulary, are designed to control
the environment for wound healing, for example maintaining hydration, and by facilitating autolytic debridement of necrotic tissue. They are semi-permeable to water vapour and oxygen. These
dressings form a gel in the presence of exudate to facilitate rehydration in lightly to moderately exuding wounds and promote
autolytic debridement of dry, sloughy or necrotic wounds (NPF
2011). There is no current up-to-date evidence to inform clinicians of the effects of hydrocolloid dressings in treating venous
leg ulcers (Palfreyman 2006). The effect of hydrocolloid dressings
compared with other dressings and conventional methods of care
for venous ulcers needs to be established.
hydrocolloid dressings. The current review will establish the current level of evidence of hydrocolloid dressings for the treatment
of venous ulcers.
OBJECTIVES
To determine the effects of hydrocolloid dressings compared with
other wound dressings, non-dressing treatments or another hydrocolloid dressing on the healing of venous leg ulcers, and also
the effects on health-related quality of life, pain, medical costs and
recurrence of ulcers.
METHODS
Criteria for considering studies for this review
Types of studies
We will include randomised controlled trials (RCTs), either published or unpublished, that have evaluated the effects of any type
of hydrocolloid wound dressing in the treatment of venous leg ulcers, irrespective of language of publication or publication status.
Trials reported in abstract form only will be eligible for inclusion,
provided adequate information is presented in the abstract or is
available from the trial author. Studies using quasi-randomisation
will be excluded.
Why it is important to do this review
Types of participants
Chronic venous leg ulcer ulceration is a complex clinical situation
that causes considerable economic impact, and adversely affects
the quality of life of those who suffer from them.
Interventions that aim to shorten healing time or improve quality
of life and comfort are desired, and several dressings have been
designed to achieve this; however, there are several dressing types
available to decision makers and the evidence based has previously
been shown to be sparse (Palfreyman 2006). There is no current
up-to-date evidence to inform clinicians of the effects of hydrocolloid dressings in treating venous leg ulcers. This review will now
update part of the previous Cochrane review (Palfreyman 2006),
and will be one of several Cochrane reviews investigating the use
of dressings in the treatment of venous leg ulcers. Each review will
focus on a particular dressing type which, in this review, will be
RCTs recruiting people described in the primary report as having
venous leg ulcers, managed in any setting, are eligible for inclusion.
As the method of diagnosis of venous ulceration may vary, we will
accept definitions as used in the RCTs.Collins 2010 Trials that include people with wounds of other aetiology (causes, e.g. pressure
ulcers), or trials of mixed populations (venous ulcers along with
arterial or diabetic ulcers) will be excluded, unless the results for
the subgroup of people with venous leg ulcers are reported separately, or if the majority of participants (75% or more in each arm)
have leg ulcers of venous aetiology. When data from subgroups
of people with venous leg ulcers are not reported separately, the
review authors will attempt to contact trial authors to obtain the
relevant data. Trials evaluating skin grafting are covered elsewhere
and will be excluded from this review (Jones 2007).
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Types of interventions
The intervention will be hydrocolloid dressings used as a treatment for venous leg ulcers. Comparators will include any other
dressing, no dressing or another hydrocolloid dressing. For ease
of comparison we will categorise dressings according to the Nurse
Prescribers’ Formulary 2011 (NPF 2011). We will use generic
names where possible, also providing trade names and manufacturers where these are available. It is important to note, however,
that manufacturers and distributors of dressings may vary from
country to country, and dressing names may also differ. We will
not include trials evaluating hydrocolloid dressings impregnated
with antimicrobial, antiseptic or analgesic agents, as these interventions are evaluated in other Cochrane reviews (Briggs 2010;
O’Meara 2013). Trials that use larval therapy will be excluded.
We will include any RCT in which the presence or absence of
a hydrocolloid dressing is the only systematic difference between
treatment groups; and in which a hydrocolloid dressing is compared with other wound dressings, non-dressing treatments (for
example, topical applications) or another hydrocolloid dressing.
We will include RCTs of hydrocolloid dressings, irrespective of
whether compression therapy is reported as a concurrent therapy.
Types of outcome measures
Primary outcomes
1. Complete wound healing measured by:
• time to complete wound healing (correctly analysed using
survival, time-to-event approaches, ideally with adjustment for
relevant covariates such as baseline size);
• the proportion of ulcers healed during follow up (frequency
of complete healing) during the study.
2.Rate of adverse events (as defined by the trial authors).
Secondary outcomes
1. Changes in ulcer size measured by reduction in original
wound area within the duration of the trial expressed as absolute
(e.g. surface area changes in cm2 since baseline) or relative (e.g.
percentage change in area relative to baseline) changes.
2. Incidence of wound infection
3. Recurrence of ulcer.
4. Health-related quality of life (measured using a standardised
generic questionnaire such as EQ, SF-36, SF-12 or SF-6 (http://
www.sf-36.org/) or a disease-specific questionnaire). We will not
include ad-hoc measures of quality of life that are likely to be
unvalidated and will not be common to multiple trials.
5. Pain (e.g. at dressing change, between dressing changes, or
over the course of treatment) will be included only if measured
by reliable and validated instruments such as surveys,
questionnaires, data capture process or a visual analogue scale.
6. Costs (including measurements of resource use, such as
number of dressing changes, nurse time or health professional
time costs, if reported by the trial authors).
Search methods for identification of studies
Electronic searches
The following electronic databases will be searched for potentially
relevant studies without any language or date restrictions:
1. The Cochrane Wounds Group Specialised Register;
2. The Cochrane Central Register of Controlled Trials
(CENTRAL) (latest issue);
3. Ovid MEDLINE (1946 to present);
4. Ovid EMBASE (1974 to present);
5. EBSCO CINAHL (1982 to present).
We will search the Cochrane Central Register of Controlled Trials
(CENTRAL) using the following exploded MeSH headings and
keywords:
#1 MeSH descriptor Leg Ulcer explode all trees
#2 ((varicose NEXT ulcer*) or (venous NEXT ulcer*) or (leg
NEXT ulcer*) or (stasis NEXT ulcer*) or (crural NEXT ulcer*)
or “ulcus cruris” or “ulcer cruris”)
#3 (#1 OR #2)
#4 MeSH descriptor Bandages, Hydrocolloid explode all trees
#5 (hydrocolloid* or activheal or alione or askina or comfeel or
duoderm or flexigran or granuflex or hydrocoll or “nu derm” or
tegaderm or “ultec pro” or aquacel or versiva or cutinova or medihoney or tegasorb or dermafilm or signadress)
#6 (#4 OR #5)
#7(#3 AND #6)
We will combine the Ovid MEDLINE search with the Cochrane
Highly Sensitive Search Strategy for identifying randomised trials in MEDLINE: sensitivity- and precision-maximising version
(2008 revision) (Lefebvre 2011). We will combine the EMBASE search with the Ovid EMBASE filter developed by the UK
Cochrane Centre (Lefebvre 2011). We will combine the CINAHL
searches with the trial filters developed by the Scottish Intercollegiate Guidelines Network (SIGN 2011).
We will also search the following Trial Search Registries, as sources
of ongoing or, as yet, unpublished trials:
1. World Health Organization International Trials Registry
Platform (http://www.who.int/ictrp/en/);
2. ISRCTN (International Standard Randomised Controlled
Trial Number) (http://www.controlled-trials.com/isrctn/).
Searching other resources
The bibliographies of all relevant publications identified by the
above strategies will be searched for further studies. We will attempt to contact study authors to obtain additional information
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whenever necessary, along with manufacturers to request information about ongoing or as yet unpublished trials. We will attempt
to obtain registered trial protocols for all published trial reports
identified for inclusion.
16. Statistical methods used for data analysis.
17. Risk of bias criteria (sequence generation, allocation
concealment, blinding, incomplete outcome data, selective
outcome reporting).
18. Adverse events.
19. Source of funding.
Data collection and analysis
Assessment of risk of bias in included studies
Selection of studies
Two review authors (CR and GF), working independently, will
screen the titles and abstracts of the studies identified from the
search strategy against the inclusion criteria. Full versions of articles
that appear to fulfil the inclusion criteria will be obtained for
further assessment. Another review author (VR) will evaluate any
discrepancies, if necessary, and will advise in case of disagreement.
We will record all reasons for exclusion of trials for which the fulltext has been obtained.
Data extraction and management
Two review authors (CR and GF), working independently, will
extract Revman 2012and summarise details of trials using a standard data extraction sheet. Data will then be entered into Revman
5.2 (Revman 2012), We will resolve any discrepancies by discussion with a third review author (VR). According to methods described in the Cochrane Handbook for Systematic Reviews of Interventions, the following information will be extracted (Higgins
2011a):
1. Country of origin.
2. Study authors and year of publication.
3. Care setting.
4. Type of ulcer.
5. Unit of investigation (per participant) - single ulcer or foot
or participant or multiple ulcers on the same participant.
6. Number of participants randomised to each trial.
7. Eligibility criteria and key baseline participant data (gender,
age, ethnicity, baseline ulcer area, ulcer duration, prevalence of
co-morbidities such as diabetes).
8. Details of the dressing/treatment regimen received by each
group.
9. Details of any co-interventions.
10. Primary and secondary outcome(s) (with definitions).
11. Outcome data for primary and secondary outcomes (by
group).
12. Overall sample size and methods used to estimate statistical
power (relates to the target number of participants to be
recruited, the clinical difference to be detected and the ability of
the trial to detect this difference).
13. Duration of treatment.
14. Duration of follow-up.
15. Number of withdrawals (by group, with reasons).
Two review authors will independently assess each eligible study
for risk of bias using the Cochrane Collaboration ‘Risk of bias’
assessment tool. This tool addresses six specific domains, namely
sequence generation, allocation concealment, blinding of participants and care providers and blinding of outcome assessors, incomplete outcome data, selective outcome reporting and other
issues which may potentially bias the study (Appendix 3). For
this review, we will consider the other risk of bias issues as follows: comparability of treatment groups in relation to baseline
ulcer surface area; choice of analysis when studying multiple ulcers on the same individuals(s); and choice of analysis in cluster
randomised trials. We will complete a ‘Risk of bias’ table for each
eligible study according to the methods described in Chapter 8 of
the Cochrane Handbook for Systematic Reviews of Interventions
(Higgins 2011b). Blinding and completeness of outcome data will
be assessed for each outcome separately. We will discuss any disagreement amongst all authors to achieve a consensus. We will
present the findings using a ‘Risk of bias’ summary figure, which
presents all of the judgments in a cross-tabulation of study by
risk of bias domain. This display of internal validity will indicate
the weight the reader may give the results of each study. We will
classify trials as being at high risk of bias overall if they are rated
high for any of three key criteria, namely, allocation concealment,
blinding of outcome assessors and completeness of outcome data.
For trials that have at least one of the three key domains rated as
’unclear’ but none of these judged as being at high risk of bias, the
trial will be classified as being at unclear risk of bias overall. Trials
can only be classified as being at low risk of bias overall if all three
key domains are rated as being at low risk individually.
Measures of treatment effect
Data analysis will be performed according to the guidelines of the
Cochrane Collaboration. One review author will enter quantitative data into Review Manager 5.2, another will check it, and the
data will be analysed using RevMan 5.2. We will present the outcome results for each trial with 95% confidence intervals (CI). We
will report estimates for dichotomous outcomes (e.g. ulcers healed
during time period, number of infected ulcers) as risk ratios (RR).
Continuous outcomes (such as absolute or relative changes in ulcer area) will be expressed as mean differences (MD) and overall
effect size (with 95% CI calculated) or as standardised mean differences (SMDs) if different methods of measurement are used in
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the studies. For time-to-event data, we plan to plot, and, if feasible, pool, estimates of hazard ratio and 95% CI as presented in the
trial reports using the generic inverse variance method in RevMan
5.2.
Unit of analysis issues
We will treat the individual ulcer as the unit of analysis in this
review. We will record whether outcomes relating to an ulcer were
measured on a per-participant or per-ulcer basis and will note
whether the trial authors have analysed the data appropriately. If
the number of ulcers appears to be equal to the number of participants, we will assume that the ulcer is the unit of analysis, unless otherwise stated. The authors will include data from clusterrandomised trials if the information is available. For cluster-randomised trials, we will adjust results when the unit of analysis in
the trial is presented as the total number of individual participants
instead of the number of clusters. Results will be adjusted using the
mean cluster size and intra-cluster correlation co-efficient (ICC)
(Higgins 2011c). Data from cross-over trials will be assessed at
the point of cross-over, if available. For meta-analysis, data will be
combined from individually randomised trials using the generic
inverse-variance method as described in Chapter 16 (section 16.3)
of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011e).
Dealing with missing data
The authors will contact the trial investigators in cases of incomplete or missing data. Where trials report complete healing outcomes for only those participants who complete the trial (i.e. participants withdrawing and lost to follow-up were excluded from
the analysis), we will treat the participants who were not included
in the analysis as if their wound did not heal. Where trials report
results for participants who complete the trial without specifying
the numbers initially randomised per group, we will present only
complete case data. For other outcomes the same analysis will be
applied.
Assessment of heterogeneity
We will consider clinical heterogeneity (that is where trials appear
different in terms of participants characteristics, intervention type
and duration and outcome type) and statistical heterogeneity. We
will assess statistical heterogeneity using the Chi² test (P values
less than 0.10 will be considered to be indicative of significant
heterogeneity) in conjunction with the I² statistic (Higgins 2003).
The I² statistic estimates the percentage of total variation across
trials due to heterogeneity rather than variation due to chance
(Higgins 2003). Heterogeneity will be categorised as follows: I²
values of 40% or less will indicate a low level of heterogeneity,
and values of 75% or above will represent very high heterogeneity
(Higgins 2011c).
Assessment of reporting biases
If a sufficient number of studies (i.e. more than ten) are identified,
an attempt will be made to check for publication bias using a funnel plot (Higgins 2011d). Publication bias is one of a number of
possible causes of ’small study effects’: a tendency for estimates of
the intervention effect to be more beneficial in smaller RCTs. Funnel plots allow a visual assessment of whether small study effects
may be present in a meta-analysis. A funnel plot is a simple scatter plot of the intervention effect estimates from individual RCTs
against some measure of each trial’s size or precision. If asymmetry is present, the effect calculated in a meta-analysis will tend to
overestimate the intervention effect. The more pronounced the
asymmetry, the more likely it is that the amount of bias will be
substantial. We will also explore other possible causes of asymmetry, for example poor methodological quality of included studies.
Data synthesis
We will present a narrative overview of the studies reviewed and
the authors will use RevMan 5.2 to combine outcomes when it is
possible (Revman 2012). Included trials will be grouped according to the comparator intervention, which may include no dressing, alternative hydrogel dressings or other types of dressings. The
decision to include studies in a meta-analysis will depend on the
availability of treatment effect data and assessment of heterogeneity. For comparisons where there is no apparent clinical heterogeneity and the I2 value is 40% or less, we will apply a fixed-effect
model. Where there is no apparent clinical heterogeneity and the I
2 value is greater than 40%, we will apply a random-effects model.
However, we will not pool data where heterogeneity is very high
(I2 values of 75% and above).
The authors will grade the quality of the evidence for each primary
outcome (complete wound healing measured by the number of
ulcers completely healed within the duration of the trial and adverse events, e.g. incidence of wound infection) using four levels of
quality: high, moderate, low and very low (Schünemann 2011a).
We plan to record the quality in a ’Summary of findings’ table using the GRADE system, as described in the Cochrane Handbook
for Systematic Reviews of Interventions (Schünemann 2011b).
Quality will be based in the following factors.
1. Limitations in the design and implementation of available studies suggesting high likelihood of bias.
2. Indirectness of evidence (indirect population, intervention, control, outcomes).
3. Unexplained heterogeneity or inconsistency of results (including problems with subgroup analyses).
4. Imprecision of results (wide confidence intervals).
5. High probability of publication bias.
Subgroup analysis and investigation of heterogeneity
Subgroup analysis will be carried out according to the presence
or absence of compression therapy independent of type (elastic
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or inelastic) or level (moderate or high) of compression. Trials in
which the presence or absence of compression therapy is not clearly
indicated in the trial report will not be included in this subgroup
analysis.
main analysis.
ACKNOWLEDGEMENTS
Sensitivity analysis
Where data are available, we will perform sensitivity analyses for
each comparison that has a meta-analysis, according to the overall
risk of bias of each included RCT. We will exclude RCTs with
overall high or unclear risk of bias, and consider the difference
between estimates of treatment effect from this analysis and the
The authors would like to acknowledge the contribution of the
Wound’s Group editorial base staff: Sally Bell-Syer for advice on
the protocol and editorial assistance and Ruth Foxlee for designing the search strategy. In addition the referees: Wounds Group
Editor, Andrew Jull; Statistical advisor, Giovanni Casazza; and referees Marissa Martyn-St James, Una Adderley, Nancy Munoz and
Shirley Manknell.
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∗
Indicates the major publication for the study
APPENDICES
Appendix 1. Glossary of terms
alginate = substance derived from algic acid, found in seaweed, used as a component in some dressings for wounds.
debridement = is the medical removal of dead, damaged, or infected tissue to improve the healing potential of the remaining healthy
tissue. It is an important part of the healing process for wounds.
deep = situated far beneath the surface; not superficial.
dressing = pieces of material, traditionally made of cloth, that act as a contact layer between a wound and outside environment.
exudate = fluid that leaks out of a wound.
fibrosis = formation of fibrous tissue.
hydrocolloid = dressing that reacts with wound exudate to maintain a moist environment at the surface of a wound.
hydrophilic = readily absorbing moisture.
lipodermatosclerosis = area of pigmentation and hardened skin caused by leakage of red blood cells into the skin. Seen in people with
chronic venous insufficiency.
macerate/maceration = the softening and breaking down of skin resulting from prolonged exposure to moisture.
macrovascular = the larger vessels in the blood system.
macrovascular disease = disease of the large veins.
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medial malleolus = inner area of the lower leg, between the ankle and calf muscle.
microcirculation = the flow of blood or lymph through the smallest vessels of the body, especially the venules, capillaries, and arterioles.
necrotic tissue = dead or dying tissue, which may be caused by interruption of the blood supply.
occlusive dressings = a dressing that seals a wound from air or bacteria.
perfusion = the transfer of fluid through tissue.
polymer = a large molecule (macromolecule) composed of repeating structural units.
pressure ulcer = area of inflamed skin/broken skin, caused by excessive or prolonged pressure, shear, or friction. This prevents adequate
blood flow to the skin and finally the death of skin and underlying tissues.
skin perfusion = the process of arterial blood, carrying nutrients (oxygen, glucose etc) to a capillary bed in the biological tissue.
slough = a layer, or mass, of dead tissue separated from surrounding living tissue, as in a wound, a sore, or an inflammation.
superficial vein = one of a number of veins in the subcutaneous tissue that empty into deep veins.
thrombosis = formation of a thrombus (blood clot) within the heart or blood vessels.
thrombophlebitis = inflammation of a vein associated with the formation of a thrombus.
valvular incompetence = inability of the valves to keep blood flowing in the correct direction.
venous stasis = ’pooling’ of blood in a vein, this occurs when the blood vessel’s valves are inactive and its walls inelastic.
venous reflux = reversed flow of blood within the veins. Occurs in veins in which the valves have become inactive or incompetent.
Definitions taken from The Free Medical Dictionary and Cochrane Wounds Group Glossary.
Appendix 2. Nurse Prescribers’ Formulary 2011 Categories of dressings
Basic wound contact dressings
Low-adherence dressings and wound contact materials: usually cotton pads that are placed directly in contact with the wound,
these can be non-medicated (e.g. paraffin gauze dressing) or medicated (e.g. containing povidone iodine or chlorhexidine). Examples
include paraffin gauze dressing, BP 1993 and Xeroform (Covidien) dressing - a non-adherent petrolatum blend with 3% bismuth
tribromophenate on fine mesh gauze.
Absorbent dressings: applied directly to the wound and may also be used as secondary absorbent layers in the management of heavilyexuding wounds. Examples include Primapore (Smith & Nephew), Megapore (Mölnlycke) and absorbent cotton gauze (BP 1988).
Advanced wound dressings
Hydrocolloid dressings: usually composed of an absorbant hydrocolloid matrix on a vapour-permeable film or foam backing. Examples
include: Granuflex (Conva Tec), NU DERM (Systagenix). Fibrous alternatives have been developed that resemble alginates and are
not occlusive: Aquacel (Conva Tec).
Hydrogel sheet and amorphous dressings: consist of a starch polymer and up to 96% water. These dressings can absorb wound exudate
or rehydrate a wound depending upon the moisture levels. They are supplied as either flat sheets or amorphous hydrogel. Examples of
hydrogel sheet dressings include: Actiformcool (Activa) and Aquaflo (Covidien). Examples of amorphous hydrogel dressings include:
Purilon Gel (Coloplast) and NuGel (Systagenix).
Films - permeable film and membrane dressings: permeable to water vapour and oxygen, but not to liquid water or micro-organisms.
Examples includeTegaderm (3M); Opsite (Smith & Nephew).
Soft polymer dressings: dressings composed of a soft silicone polymer held in a non-adherent layer, these are moderately absorbant.
Examples include: Mepitel (Mölnlycke) and Urgotul (Urgo).
Foam dressings: contain hydrophilic polyurethane foam and are designed to absorb wound exudate and maintain a moist wound
surface. A variety of versions exists, some of which include additional absorbent materials such as viscose and acrylate fibres, or particles
of super-absorbent polyacrylate, or are silicone-coated for non-traumatic removal. Examples include: Allevyn (Smith & Nephew);
Biatain (Coloplat); Tegaderm (3M).
Alginate dressings: highly absorbent dressings composed of calcium alginate or calcium sodium alginate, which can be combined with
collagen. The alginate forms a gel while in contact with the wound surface, this can be lifted off at dressing removal or rinsed away with
sterile saline. Bonding to a secondary viscose pad increases absorbency. Examples include: Curasorb (Covidien); SeaSorb (Coloplast);
Sorbsan (Unomedical).
Capillary-action dressings: consist of an absorbant core of hydrophilic fibres held between two low-adherent contact layers. Examples
include: Advadraw (Advancis); Vacutx (Protex).
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Odour absorbent dressings: dressings that contain charcoal and are used to absorb wound odour. Often this type of dressing is used
in conjunction with a secondary dressing to improve absorbency. Examples include: CarboFLEX (ConvaTec)
Anti-microbial dressings
Honey-impregnated dressings: contain medical-grade honey which is proposed to have antimicrobial and anti-inflammatory properties
and can be used for acute or chronic wounds. Examples include: Medihoney (Medihoney) and Activon Tulle (Advancis).
Iodine-impregnated dressings: these release free iodine, which is thought to act as a wound antiseptic, when exposed to wound
exudate. One example is Iodozyme (Insense).
Silver-impregnated dressings: used to treat infected wounds, as silver ions are thought to have antimicrobial properties. Silver versions
of most dressing types are available (e.g. silver foam, silver hydrocolloid etc). Examples include: Acticoat (Smith & Nephew) and
Urgosorb Silver (Urgo).
Other antimicrobial dressings: these dressings are composed of a gauze or low-adherent dressing impregnated with an ointment
thought to have antimicrobial properties. Examples include: chlorhexidine gauze dressing (Smith & Nephew) and Cutimed Sorbact
(BSN Medical).
Specialist dressings
Protease-modulating matrix dressings: designed to alter the activity of proteolytic enzymes (i.e. breakdown of protein or dead skin)
in chronic wounds. Examples include: Promogran (Systagenix) and Sorbion (H & R).
Silicone keloid dressing: designed to reduce or prevent hypertrophic or keloid scarring. Examples include: Cica-Care (Smith &
Nephew) and Clitech (Su-med).
Appendix 3. The Cochrane Collaboration’s tool for assessing risk of bias
1. Was the allocation sequence randomly generated?
Low risk of bias
The investigators describe a random component in the sequence generation process such as: referring to a random-number table; using
a computer random-number generator; coin tossing; shuffling cards or envelopes; throwing dice; drawing of lots.
High risk of bias
The investigators describe a non-random component in the sequence generation process. Usually, the description would involve some
systematic, non-random approach, for example: sequence generated by odd or even date of birth; sequence generated by some rule
based on date (or day) of admission; sequence generated by some rule based on hospital or clinic record number.
Unclear
Insufficient information about the sequence generation process to permit a judgement of low or high risk of bias.
2. Was the treatment allocation adequately concealed?
Low risk of bias
Participants and investigators enrolling participants could not foresee assignment because one of the following, or an equivalent
method, was used to conceal allocation: central allocation (including telephone, web-based and pharmacy-controlled randomisation);
sequentially-numbered drug containers of identical appearance; sequentially-numbered, opaque, sealed envelopes.
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High risk of bias
Participants or investigators enrolling participants could possibly foresee assignments and thus introduce selection bias, such as allocation
based on using: an open random allocation schedule (e.g. a list of random numbers); assignment envelopes without appropriate
safeguards (e.g. if envelopes were unsealed or non opaque or not sequentially-numbered); alternation or rotation; date of birth; case
record number; or any other explicitly unconcealed procedure.
Unclear
Insufficient information to permit a judgement of low or high risk of bias. This is usually the case if the method of concealment is not
described, or not described in sufficient detail to allow a definite judgement to be made, for example if the use of assignment envelopes
is described, but it remains unclear whether envelopes were sequentially-numbered, opaque and sealed.
3. Blinding: was knowledge of the allocated interventions adequately prevented during the study?
Two types of blinding are considered here:
(1) blinding of participants and care providers; and
(2) blinding of outcome assessors.
Low risk of bias
• No blinding, but the review authors judge that the outcome and the outcome measurement are not likely to be influenced by
lack of blinding.
• Blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.
• Either participants or some key study personnel were not blinded, but outcome assessment was blinded and the non-blinding of
others was unlikely to introduce bias.
High risk of bias
Any one of the following.
• No blinding or incomplete blinding, and the outcome or outcome measurement is likely to be influenced by lack of blinding.
• Blinding of key study participants and personnel attempted, but likely that the blinding could have been broken.
• Either participants or some key study personnel were not blinded, and the non-blinding of others was likely to introduce bias.
Unclear
Either of the following.
• Insufficient information provided to permit judgement of low or high risk of bias.
4. Were incomplete outcome data adequately addressed?
Low risk of bias
• No missing outcome data.
• Reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing
bias).
• Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups.
• For dichotomous outcome data, the proportion of missing outcomes compared with observed event risk was not enough to have
a clinically relevant impact on the intervention effect estimate.
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outcomes was not enough to have a clinically relevant impact on observed effect size.
• Missing data have been imputed using appropriate methods.
High risk of bias
• Reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing
data across intervention groups.
• For dichotomous outcome data, the proportion of missing outcomes compared with observed event risk enough to induce
clinically relevant bias in intervention effect estimate.
• For continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing
outcomes enough to induce clinically relevant bias in observed effect size.
• ’As-treated’ analysis done with substantial departure of the intervention received from that assigned at randomisation.
• Potentially inappropriate application of simple imputation.
Unclear
• Insufficient reporting of attrition/exclusions to permit a judgement of low or high risk of bias (e.g. number randomised not
stated, no reasons for missing data provided).
5. Are reports of the study free of suggestion of selective outcome reporting?
Low risk of bias
• The study protocol is available and all of the study’s pre-specified (primary and secondary) outcomes that are of interest in the
review have been reported in the pre-specified way.
• The study protocol is not available, but it is clear that the published reports include all expected outcomes, including those that
were pre-specified (convincing text of this nature may be uncommon).
High risk of bias
• Not all of the study’s pre-specified primary outcomes have been reported.
• One or more primary outcomes is reported using measurements, analysis methods or subsets of the data (e.g. subscales) that
were not pre-specified.
• One or more reported primary outcomes were not pre-specified (unless clear justification for their reporting is provided, such as
an unexpected adverse effect).
• One or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a meta-analysis.
• The study report fails to include results for a key outcome that would be expected to have been reported for such a study.
Unclear
Insufficient information provided to permit a judgement of low or high risk of bias. It is likely that the majority of studies will fall into
this category.
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6. Other sources of potential bias
Low risk of bias
The study appears to be free of other sources of bias.
High risk of bias
There is at least one important risk of bias. For example, the study:
• had a potential source of bias related to the specific study design used; or
• stopped early due to some data-dependent process (including a formal-stopping rule); or
• had extreme baseline imbalance; or
• has been claimed to have been fraudulent; or
• had some other problem.
Unclear
There may be a risk of bias, but there is either:
• insufficient information to assess whether an important risk of bias exists; or
• insufficient rationale or evidence that an identified problem will introduce bias.
Guilherme Fregonezi: conceived the review question and secured funding; advised on and developed the protocol; completed part of
the first draft of the protocol; made an intellectual contribution to the protocol, and approved the final version prior to submission.
Fernando Dias: developed and co-ordinated the protocol; advised on, completed the first draft of the protocol; approved the final
version of the protocol prior to submission; made an intellectual contribution to the protocol.
Cibele Ribeiro: developed and co-ordinated the protocol; advised on, completed and edited the first draft of the protocol; approved
the final version of the protocol prior to submission; made an intellectual contribution to the protocol.
Vanessa Resqueti: made an intellectual contribution to the protocol and approved the final version of the protocol prior to submission.
Armele de Andrade: made an intellectual contribution to the protocol and approved the final version of the protocol prior to submission.
Contributions of editorial base:
Jo Dumville, Editor: approved the final protocol prior to submission.
Sally Bell-Syer: coordinated the editorial process. Advised on methodology, interpretation and content. Edited the protocol.
Ruth Foxlee: designed the search strategy and edited the search methods section.
Rachel Richardson: edited the protocol.
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DECLARATIONS OF INTEREST
Guilherme Fregonezi: none known.
Fernando Dias: none known.
Cibele Ribeiro: none known.
Vanessa Resqueti: none known.
Armele de Andrade: none known.
SOURCES OF SUPPORT
Internal sources
• No sources of support supplied
External sources
• MCT/CNPQ/CT- Saúde/MS/SCTIE/DECIT n. 67/2009, process 559416/2009-1), Brazil.
• The National Institute for Health Research (NIHR) is the sole funder of the Cochrane Wounds Group, UK.
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ANEXO 2: Características dos estudos excluídos e justificativa para exclusão
81
Characteristics of excluded studies (Reasons for exclusion):
Altman 1993: Did not report sufficient information to be judged as eligible for
inclusion in this review. Unable to obtain the necessary information to make a
judgment (no response to email sent trial author). Uncertain if venous leg ulcers was
reported separately.
Anonymous 1994: Not an RCT (Study translated form German).
Anonymous 1997: Not an RCT (Review article translated from German about
dermatomycoses).
Argoff 2013: Not a treatment of interest.
Barbaud 2009: Not treatment of interest.
Berard 1986: Not treatment of interest (Evaluation of hydrocolloid).
Blume 2008: Study includes ulcers of diabetic aetiology.
Bolton 2003: Not an RCT.
Bradley 1999: Not an RCT (review article).
Brandrup 1990: Not a treatment of interest (RCT comparing zinc oxide medicated
and hydrocolloid dressings in people with venous and arterial leg ulcers).
Caprio 1995: Not a treatment of interest (Study evaluation of hydrocolloid vs
collagen dressing).
Chraibi 1994: Not an RCT.
Coerper 2004: Not a treatment of interest.
Cordts 1992: Not a treatment of interest (Study evaluation of Unna's boot vs
hydrocolloid dressing).
Couilliet 2001: Not an RCT.
D'Alicandro 2003: Includes ulcer of mixed aetiology with no separate reporting by
ulcer type.
Davis 2010: Not a treatment of interest (Larval therapy no hydrogel dressings).
Dereure 2012: Not a treatment of interest.
Driver 2009: Not a treatment of interest (Evaluation of vacuum therapy vs advanced
moist wound therapy in ulcers of diabetic aetiology).
Dumville 2009: Not a treatment of interest (Larval therapy no hydrogel dressings).
82
Dumville 2011: Not an RCT (Review article).
Eneroth 2008: Not an RCT (Review article).
Farah 2010: Not an RCT (Review article).
Farina 1997: Insufficient information to be judged as eligible for inclusion in this
review. Unable to obtain the necessary information to make a judgement (no
response to email sent trial author).
Flanagan 1995: Not an RCT.
Fonder 2008: Not an RCT (Review article).
Friedman 1984: Not a treatment of interest (Evaluation of hydrocolloid).
Gago 2002: Conference abstract with limited information. Unable to obtain the
necessary information to make a judgement (no response to email sent trial author).
Gibson 1995: Leg ulcers with mixed aetiology presenting less than 75% of venous
leg ulcer on each arm study.
Guerin 2012: Not an RCT.
Hamerlinck 1989: Not a treatment of interest (Study evaluates hydrocolloid vs
unitulle- primary wound contact layer impregnated with white soft paraffin).
Hampshire 2000: Not a treatment of interest (Study evaluates larval therapy no
hydrogel dressings).
Hampton 2004: Study did not randomize participants.
Hansson 1998: Not a treatment of interest (Study evaluation of iodine vs.
hydrocolloid dressing).
Harding 1996: Not a treatment of interest (Study evaluation of hydrocellular
adhesive dressing vs hydrocolloid).
Harding 2001: Not a treatment of interest (Study evaluation of hydrofiber vs. alginate
dressings).
Hinchliffe 2008: Not an RCT (Review article).
Hofman 1994: Conference abstract with limited information. Unable to obtain the
necessary information to make a judgment (no response to email sent trial author).
Hofman 1996: Not an RCT (Case study and expert opinion).
Hoppe 2012: Not an RCT.
83
HQO 2006: Not an RCT (Review article about negative pressure wound therapy).
Hu 2011: Not an RCT (Review article).
Hunt 2003: Not an RCT (Review article).
Hutchinson 1997: Not a treatment of interest.
Isner 1996: Not a treatment of interest.
Jansen 2009: Not a population of interest.
Jensen 1998: Not a population of interest.
JNMA 2007: Not an RCT (Info poems - Expert opinion).
Jones 2009: Not an RCT (Review article).
Karlsmark 2002: Not a treatment of interest.
Kaya 2005: Not a population of interest.
Kerstein 2001: Not an RCT (Review article of cost effectiveness of venous and
pressure ulcer protocols).
Kikta 1988: Hydrogel is not the only systematic difference between groups. Not a
valid comparison for inclusion in the review.
La Grenade 1993: Not a population of interest (Evaluation of sickle cell no venous
ulcers).
Lammoglia 2012: Not a treatment of interest.
Larsen 1997: Conference abstract with limited information. Unable to obtain the
necessary information to make a judgment (no response to email sent trial author).
Lawall 2012: Not an RCT (Review article).
LeBon 2009: Not an RCT (Review article).
Lee 2011: Not and RCT (Review about effects of honey in venous leg ulcers).
Leite 2011: Not an RCT.
Lewis 2001: Not an RCT (Review article).
Limova 2002: Not a treatment of interest (study evaluation of two hydrocolloid
dressings).
Lindholm 1995: Not a treatment of interest.
84
Lyon 1998: Not a treatment of interest.
Mansson 1996: Not a treatment of interest (Study evaluation of Iodosorb dressing
vs. Hydrocolloid vs. Jenolet).
Mason 1999: Not an RCT (Review article).
Meaume 2005: Not a treatment of interest (Study evaluation of soft polymer dressing
vs. hydrocolloid).
Mekkes 2001: Not a treatment of interest.
Meyer 1995: Not an RCT.
Moffatt 1992: Not a treatment of interest.
Mulder 1989: Not a treatment of interest (Evaluation of three hydrocolloid dressings).
Mulder 1993: Not a treatment of interest.
Nelson 2006: Not an RCT (Review article).
Nowak 1996: Conference abstract with limited information. Unable to obtain the
necessary information to make a judgement (no response to email sent trial author).
O'Donnell 2006: Not an RCT (Review article).
O'Meara 2000: Not an RCT (Review article).
Ohlsson 1994: Not a treatment of interest.
Palfreyman 2007: Not an RCT (Review article).
Perez 2000: Not a treatment of interest.
Peters 2001: Not a treatment of interest (Evaluation of electric stimulation on diabetic
ulcers).
Petherick 2006: Not a treatment of interest (Evaluation of larval therapy).
Pfeffer 2005: Not an RCT.
Phillips 2000: Not a treatment of interest.
Pierard 1995: Not a treatment of interest (Study evaluation of hydrocolloid vs.
compressive bandages).
Pittler 2007: Not a treatment of interest.
Raymond 2008: Not an RCT.
85
Raynor 2004: Evaluation of larval therapy (Not a treatment of interest).
Renner 2013: Not an RCT. Assessment of contact sensitization and not healing
effect of the dressings.
Rivera-Arce 2007: Not a treatment of interest. Use of a topical agent concomitant to
hydrogel.
Robinson 1996: Not separeted report for venous leg ulcer.
Romanelli 1999: Not a treatment of interest (Study evaluation of hydrocellular
dressing vs. hydrocolloid).
Sackheim 2006: Not an RCT (Review article).
Samson 1992: Not an RCT. Letter to the editor limited presentation of results.
Sandison 2008: Not a population of interest.
Scanlon 2003: Not an RCT (Review article).
Schulze 2003: Not an RCT.
Senet 2011: Not a treatment of interest.
Senet 2012: Not a treatment of interest.
Sibbald 2003: Not a treatment of interest.
Sironi 1994: The hydrogel dressing is not the only systematic difference between
groups.
Smith 1997: Not a treatment of interest.
Soares 2009: Not a treatment of interest (Evaluation of larval therapy).
Sparholt 2002: Not enough information to be judged as eligible for inclusion in this
review. Unable to obtain the necessary information to make a judgement (no
response to email sent trial author).
Spilsbury 2008: Evaluation of larval therapy. Not a treatment of interest.
Tang 2012: Not an RCT (Review article).
Thomas 1997: Not a treatment of interest. Study evaluation of hydrocolloid vs.
Polyurethane foam.
Valencia 2001: Not an RCT (Review article).
Varghese 1986: Not a treatment of interest.
86
Veraart 1994: Evaluation of hydrocolloid.
Vernassiere 2005: Not a treatment of interest. Evaluation of topical application of
morphine on skin ulcers.
Vin 1997: Not a treatment of interest.
Walker 1996: Not a treatment of interest. Evaluation of bandage system no hydrogel
dressings. The difference between groups is not the hydrogel.
Wang 2012: Not a population of interest.
Wayman 2000: Not a treatment of interest (Evaluation of larval therapy).
Werner 1994: Not a treatment of interest. Use of topical agent.
Westerhof 1995: Not a treatment of interest.
Zarchi 2012: Not a treatment of interest.
Zuccarelli 1992: Not a treatment of interest. Study evaluation of foam dressing vs.
hydrocolloid.
87
ANEXO 3: Características dos estudos incluídos
88
Characteristics of included studies
1- de la Brassine 2006
Methods
Design: open; Pilot study; RCT.
Country: Belgium.
Setting: hospital.
Sample size calculation: not reported.
Ethical approval: was reported. It was granted
after the medical ethics committee approved the
project.
Participants
Informed consent: was obtained after the patients
being fully advised about the purpose and
consequences of the study.
Total sample: 20 hospitalized patients with
chronic leg ulcers of venous origin.
Inclusion criteria: males and females, mobile, 4070 years and ulcers with exudate.
Exclusion criteria: none specified.
Numbers randomized:
Group 1 (hydrogel dressing): 10 participants.
Group 2 (alginate dressing): 10 participants.
Gender of the participants: 13 female and 7 male
from the 20 patients.
Mean participant age: 61 years (45-70).
ABPI: not reported.
Unit of analysis: participant.
Ulcer infection: not reported.
Participant ulcer duration (current):
years(0,5-10 years) in both groups.
2,25
89
Baseline ulcer surface:
Group 1 (hydrogel dressing): 20.9 ± 7.5 cm² (p=
0.826).
Group 2 (alginate dressing): 20.3 ± 7.6 cm² (p=
0.826).
Baseline volume measurement:
Group 1 (hydrogel dressing): 128.4 ± 55.2 mm³.
Group 2 (alginate dressing): 124.7 ± 49.9 mm³.
Interventions
Data collected: diagnosis, sex, age, ulcer
dimension and volume.
Group 1: hydrogel dressing (Intrasite gel) (control
group).
Group 2: alginate dressing (Flaminal gel).
*Both groups had the wound debrided and
cleaning with saline before the dressing was
applied.
Description of compression therapy: not reported.
Length of treatment: 4 weeks.
Follow-up: 4 weeks (endpoint).
Comments:
* The surface measurement of the ulcer was
made using acetate tracing (Opsite Flexigrid from
Smith and Nephew Healtcare).
Outcomes
* The volume measurement of the ulcer was
made using high algin impression material
(Jeltrate
mould
from
Dentsply
Caulk
International).
Reporting of outcomes relevant to this review:
Complete wound healing: reported.
Incidence of wound infection: not reported.
Change in ulcer size: reported, planimetry used to
measure the wound at baseline, day 7, 14 and 28
days of treatment and also volume measured at
90
the same days.
Time to ulcer healing: not reported.
Recurrence of ulcer: not reported.
Quality of life: not reported.
Pain: not reported.
Notes
Costs: not reported.
Number of participants withdrawing and reasons:
trial authors did not report on participant
withdrawal.
2- Gethin 2009
Methods
Design: open; multicentre; RCT.
Country: Ireland.
Setting: Participants from 10 sites, including
vascular centres, acute and community care
hospitals and leg ulcer clinics.
Sample size calculation: a sample size of 156
participants randomly allocated to two equal
groups of 78 estimated as having 80% power to
detect a minimum difference of 20% at the 5%
two-sided significance level.
Ethical approval: was reported.
Participants
Informed consent: was obtained.
Total sample: 108 participants.
Inclusion criteria: having a venous ulcer, being
over 18 years of age, able to provide written
informed consent, having ≥50% of wound bed
covered in slough, ulcer size < 100cm², ABPI
≥0.8.
Exclusion criteria: less than 18 years, unable to
provide written informed consent, having an ulcer
> 100 cm², ulcer diagnosed as being malignant,
having a cavity wound, clinical diagnosis of
91
wound infection, currently taking antibiotics for
any
reason,
currently
taking
oral
immunosuppressant, having poorly controlled
diabetes, having previously enrolled into the
study, pregnant women or lactating mothers.
Mean participant age: not reported.
ABPI: results not reported.
Baseline data collected: gender, age, wound size
and duration, ulcer location and history of
recurrence.
Medical information collected: history of deep
venous thrombosis (DVT), hypertension, trauma
or surgery to the affected limb, diabetes,
immunosuppression and current medications
Numbers randomized:
Group 1 (hydrogel dressing): 54 participants
Group 2 (Manuka honey dressing): 54
participants
Unit of analysis: ulcer.
Ulcer infection: was reported.
Interventions
Comments: The trial authors reported that each
participant could only contribute with one ulcer
(the upper most ulcers or the largest ulcer was
selected if more than one was present).
Group 1: hydrogel dressing (IntraSite Gel, Smith
& Nephew).
Group 2:
Lohmann).
Manuka
honey
dressing
(Opr,
*All participants were subjected to a compression
therapy.
Outcomes
Follow-up: was reported (at week 12).
Complete wound healing: reported that some
ulcers were completely healed after 28 days and
several participants after 28 days (no reporting of
92
numbers).
Incidence of wound infection: reported.
measure the wound at baseline; weeks 4, 8 and
12.
Pain: not reported.
Notes
Number of patients withdrew:
Group 1 (hydrogel dressing): 17 participants
Group 2 (Manuka honey dressing): 9 participants
Reasons: infection in reference wound and
elsewhere; patient request; did not attend followup.
3- Grotewhol 1994
Methods
Design: multicenter; RCT.
Country: Germany.
Setting: not reported.
Ethical approval: not reported.
Participants
Informed consent: was obtained.
Total sample: 84 participants with ulcera crurum.
Inclusion criteria: none specified.
Numbers randomized:
93
Group 1 (hydrocolloid dressing): 24 participants
Group 2 (hydrogel dressing): 39/41 participants
Mean participant age: not reported.
ABPI: not reported.
Unit of analysis: ulcer.
Baseline ulcer size cm2 (mean) (before
treatment):
Group
1
(hydrocolloid
dressing):
6.3
Group 2 (hydrogel dressing): 10.1
Data collected: diagnosis,
sex,
age,
ulcer
Participant ulcer duration: not reported.
Data collected: ulcer dimension by planimetry.
Comments: The study started with 84 participants
but only 62 participants followed for 28 days of
the study.
Interventions
The trial author reported that 3 patients from the
Hydrogel group had double-sided ulcers; 1 of
these patients was treated with hydrogel and
hydrocolloid at once.
Group 1: hydrocolloid dressing (proprietary name
not reported, manufacturer not reported) (control
group).
Group 2: hydrogel dressing (Opragel, Lohmann).
therapy.
Outcomes
Follow-up: not reported.
94
numbers).
measure the wound at day 14 and day 28 of the
treatment.
Pain: not reported.
Notes
No details of total number of ulcers healed at end
of trial provided.
Exclusions post-randomization: 22 no reasons
provided or from which group patients withdrew.
The trial author reported that did not observe
cases of irritation or allergic reactions with the use
of dressings.
No details provided from imbalance in allocation
to treatment groups.
Group 1: 3 ulcers did not demonstrated signs of
healing.
Group 2: 4 ulcers did not demonstrated signs of
healing.
4- He 2008
Methods
Design: RCT.
Country: China.
Setting: not reported.
Ethical approval: not reported.
Informed consent: not reported.
95
Participants
Total sample: 60 patients with chronic venous
ulcer of lower extremities.
Inclusion criteria: age ≥ 18 years; required to
have a venous insufficiency ulcer for more than 1
month of duration, with area ≤ 4cm²; woman not
pregnant; not immunosuppression; no history of
allergy to polysaccharides (glycans).
Group 1 (gaze in saline): 30 participants.
Group 2 (hydrogel dressing): 30 participants.
Gender of the participants:
Group 1 (gaze in saline): 20 males and 10
females
Group 2 (hydrogel dressing): 24 males and 6
females.
Side of the ulcers: 32 ulcers from the left side and
28 ulcers from the right side.
Baseline ulcer size cm2
treatment): 2.5 – 4.0 cm².
(mean)
(before
Group 1 (gaze in saline): 3.1±0.4 cm².
Group 2 (hydrogel dressing): 3.4±0.6 cm².
Mean participant age:
Group 1 (gaze in saline): 60.1±7.4 years.
Group 2 (hydrogel dressing): 57.3±6.8 years.
Participant ulcer duration:
Group 1 (gaze in saline): 3.3 ±0.9 years.
Group 2 (hydrogel dressing): 2.9±0.7 years.
ABPI: not reported.
Unit of analysis: patient.
96
Data collected: diagnosis,
sex,
age,
ulcer
Participant ulcer duration: not reported.
Data collected: ulcer dimension by planimetry.
Comments: The study started with 84 participants
but only 62 participants followed for 28 days of
the study.
Interventions
The trial author reported that 3 patients from the
Hydrogel group had double-sided ulcers; 1 of
these patients was treated with hydrogel and
hydrocolloid at once.
Group 1: gaze in saline (control group).
Group 2: hydrogel dressing (Chitosan, Xangai
Qisheng).
therapy.
Length of treatment: 5 months.
Outcomes
Follow-up: not reported.
numbers).
measure the wound at day 14 and day 28 of the
treatment.
Pain: not reported.

Efeitos do tratamento com Hidrogel na cicatrização de

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