TY - JOUR
AU - Vermeulen, H
AB - Abstract Background Decisions on local and systemic wound treatment vary among surgeons and are frequently based on expert opinion. The aim of this meta-review was to compile best available evidence from systematic reviews in order to formulate conclusions to support evidence-based decisions in clinical practice. Methods All Cochrane systematic reviews (CSRs), published by the Cochrane Wounds and Peripheral Vascular Diseases Groups, and that investigated therapeutic and preventive interventions, were searched in the Cochrane Database up to June 2011. Two investigators independently categorized each intervention into five levels of evidence of effect, based on size and homogeneity, and the effect size of the outcomes. Results After screening 149 CSRs, 44 relevant reviews were included. These contained 109 evidence-based conclusions: 30 on venous ulcers, 30 on acute wounds, 15 on pressure ulcers, 14 on diabetic ulcers, 12 on arterial ulcers and eight on miscellaneous chronic wounds. Strong conclusions could be drawn regarding the effectiveness of: therapeutic ultrasonography, mattresses, cleansing methods, closure of surgical wounds, honey, antibiotic prophylaxis, compression, lidocaine–prilocaine cream, skin grafting, antiseptics, pentoxifylline, debridement, hyperbaric oxygen therapy, granulocyte colony-stimulating factors, prostanoids and spinal cord stimulation. Conclusion For some wound care interventions, robust evidence exists upon which clinical decisions should be based. Introduction Many healthcare professionals are involved in the treatment and prevention of acute or chronic wounds. Decisions are made daily that affect wound healing, pain and costs. Acute and chronic wounds (Fig. 1) form a substantial problem in different healthcare settings: emergency departments, nursing homes, home care and family practices1–3. Approximately €30 million is spent on (local) wound care in the Netherlands, and in the UK the costs of wound care in 2005–2006 were estimated to be between £ 15 and £ 18 million (European Wound Management Association and A. Nelson, personal communication)4,5. Because wounds have a considerable impact on patient morbidity, mortality, daily functioning and quality of life6–8, they deserve high-quality local and systemic treatment. Fig. 1 Open in new tabDownload slide Leg ulcer with slough Ideally, treatment decisions concerning these wounds should be based on the best available evidence, integrated with patients' concerns and priorities, and accounting for the local situation, resources and skills. In reality, however, treatment decisions are generally based on personal opinion, experience and the preference of healthcare professionals9–11. This is due partly to the overwhelming amount of literature available, which often shows conflicting results12. Although the total body of evidence concerning wound care is substantial, high-level evidence to guide decisions on treatment, such as meta-analyses and randomized clinical trials (RCTs), is relatively scarce13–15. Nevertheless, the best available evidence should be identified and applied to decisions in daily practice. This meta-review of Cochrane systematic reviews (CSRs) was conducted for both local and systemic treatment options for open wounds to assist healthcare professionals involved in wound care. Methods Searching and selecting For this meta-review, all CSRs on local and systemic wound care were included, because these are considered the highest level of evidence for effectiveness of treatments in the hierarchy of study designs16. Eligible CSRs dealt with the treatment or prevention of open wounds of any type and aetiology, in adults as well as in children. Reviews on prevention of surgical-site infection were excluded because these primarily comprise closed wounds. All systematic reviews in the Cochrane Database of Systematic Reviews up to June 2011, as published by the Cochrane Wounds Group and the Cochrane Peripheral Vascular Diseases Group, were retrieved and screened independently by two researchers, and by a third in case of any disagreement. Appraising the strength of evidence Because all CSRs undergo clinical and methodological scrutiny, formal appraisal of their internal validity was not needed. Instead, two researchers independently classified each CSR into one of five levels of evidence of effect (Table 1). For this classification, each prevention or treatment comparison and outcome was graded by taking into account the number of trials and participants included, consistency of results, and potential for pooling of the results. In the case of apparent methodological flaws or contradictory results in the individual trials, the level of evidence of the intervention studied was downgraded. A third arbiter resolved any disagreement. If the outcome did not show strong evidence of effect (level 5), a more tentative conclusion was given if the majority of the trials showed consistent results towards a positive or negative effect. Table 1 Definition of categories to grade the strength of evidence of effect Levels of evidence of effect . Criteria . 1. Strong evidence of effect Significant results in favour of new treatment, based on pooled data of trials totalling over 100 patients 2. Strong evidence of no effect Significant results in favour of control treatment or non-significant differences, based on pooled data of studies totalling over 100 patients 3. Limited evidence of effect Significant results in favour of new treatment, based on one or more large (over 100 patients) but unpoolable studies, or pooled results from small studies totalling less than 100 patients 4. Limited evidence of no effect Significant results in favour of control treatment or non-significant difference, based on one or more large (over 100 patients) but unpoolable studies, or pooled results from small studies totalling less than 100 patients 5. Neither strong nor limited evidence of effect No large or poolable trials available. These small trials may show:  a) Significantly positive treatment effect (++)  b) Trend towards positive treatment effect (+)  c) No significant differences (0)  d) Trend towards negative treatment effect (−)  e) Significantly negative treatment effect (−−) Levels of evidence of effect . Criteria . 1. Strong evidence of effect Significant results in favour of new treatment, based on pooled data of trials totalling over 100 patients 2. Strong evidence of no effect Significant results in favour of control treatment or non-significant differences, based on pooled data of studies totalling over 100 patients 3. Limited evidence of effect Significant results in favour of new treatment, based on one or more large (over 100 patients) but unpoolable studies, or pooled results from small studies totalling less than 100 patients 4. Limited evidence of no effect Significant results in favour of control treatment or non-significant difference, based on one or more large (over 100 patients) but unpoolable studies, or pooled results from small studies totalling less than 100 patients 5. Neither strong nor limited evidence of effect No large or poolable trials available. These small trials may show:  a) Significantly positive treatment effect (++)  b) Trend towards positive treatment effect (+)  c) No significant differences (0)  d) Trend towards negative treatment effect (−)  e) Significantly negative treatment effect (−−) Open in new tab Table 1 Definition of categories to grade the strength of evidence of effect Levels of evidence of effect . Criteria . 1. Strong evidence of effect Significant results in favour of new treatment, based on pooled data of trials totalling over 100 patients 2. Strong evidence of no effect Significant results in favour of control treatment or non-significant differences, based on pooled data of studies totalling over 100 patients 3. Limited evidence of effect Significant results in favour of new treatment, based on one or more large (over 100 patients) but unpoolable studies, or pooled results from small studies totalling less than 100 patients 4. Limited evidence of no effect Significant results in favour of control treatment or non-significant difference, based on one or more large (over 100 patients) but unpoolable studies, or pooled results from small studies totalling less than 100 patients 5. Neither strong nor limited evidence of effect No large or poolable trials available. These small trials may show:  a) Significantly positive treatment effect (++)  b) Trend towards positive treatment effect (+)  c) No significant differences (0)  d) Trend towards negative treatment effect (−)  e) Significantly negative treatment effect (−−) Levels of evidence of effect . Criteria . 1. Strong evidence of effect Significant results in favour of new treatment, based on pooled data of trials totalling over 100 patients 2. Strong evidence of no effect Significant results in favour of control treatment or non-significant differences, based on pooled data of studies totalling over 100 patients 3. Limited evidence of effect Significant results in favour of new treatment, based on one or more large (over 100 patients) but unpoolable studies, or pooled results from small studies totalling less than 100 patients 4. Limited evidence of no effect Significant results in favour of control treatment or non-significant difference, based on one or more large (over 100 patients) but unpoolable studies, or pooled results from small studies totalling less than 100 patients 5. Neither strong nor limited evidence of effect No large or poolable trials available. These small trials may show:  a) Significantly positive treatment effect (++)  b) Trend towards positive treatment effect (+)  c) No significant differences (0)  d) Trend towards negative treatment effect (−)  e) Significantly negative treatment effect (−−) Open in new tab To check the robustness of the classification, a sensitivity analysis was performed by applying different definitions of a large study population, referring to the total number of patients available for each treatment per comparison. By default, large was defined as comprising at least 100 patients, because this number was representative of larger studies in the included CSRs. Extracting and presenting data Data were extracted by two researchers and checked by a third for interventions, comparisons and outcome as reported by the authors of the CSRs. Subsequently, the CSRs were grouped into those addressing local, systemic or preventive measures for the various wound types, acute and chronic wounds. When a CSR covered two or more wound types, for example miscellaneous chronic wounds and diabetic ulcers, only the relevant parts of the same review were included in the category. Traumatic and surgical wounds were classified as acute wounds. Chronic wounds were defined as those characterized by delayed healing despite comprehensive re-evaluation and appropriate adjustment of treatment. Examples of chronic wounds are pressure ulcers, arterial or venous leg ulcers, and diabetic foot ulcers. Results After screening 68 and 82 abstracts from the Cochrane Wounds Group and the Cochrane Peripheral Vascular Disease Group, 41 and three relevant CSRs respectively were identified. Not all therapeutic or preventive measures in these 44 CSRs reflected first-choice clinical treatment options. The present conclusions therefore discuss treatment options as described by CSRs, despite their position as first, second or last resort choice, and clinical relevance. From the 44 CSRs, there were 52 reviews of different wound types from which evidence-based conclusions could be extracted. Thirteen of these addressed acute wounds, and the remaining 39 addressed chronic wounds: 14 venous ulcers, eight pressure ulcers, seven diabetic ulcers, five arterial ulcers and five miscellaneous chronic wounds. The acute wounds contained surgical incisions, traumatic lacerations, surgical (infected) wounds and burns. Owing to the limited number of CSRs dealing with various acute wounds, these results are reported as a single category. A total of 33 conclusions with strong evidence of effect and 18 conclusions with fairly strong evidence of effect could be drawn from the CSRs, whereas evidence was not available or insufficient in the remaining 58. The majority (79 of 109, 72·5 per cent) of the conclusions referred to chronic wounds. The conclusions based on the evidence found in the CSRs were divided into preventive, systemic and local treatments. The strongest conclusions are summarized as recommendations (Table 8). Sensitivity analysis To assess a possible effect on the results, the number of strong, fairly strong and weaker levels of evidence were recalculated using n = 40, n = 60, n = 80 and n = 120 as alternative definitions of a large study population. The number of strong recommendations (level 1 and 2) did not change substantially until a patient population of 60 or fewer was used. Hence, the validity the proposed 100-patient threshold was considered sufficient. Acute wounds (Table 2) Preventive systemic treatment in the form of prophylactic antibiotics proved to be ineffective in preventing infection after dog bites, with the exception of human and dog bites located on hands27. Availability of antibiotics and familiarity with their use should lead to the implementation of this preventive option in clinical care. Table 2 Treatment recommendations for acute wounds based on the grading system (Table 1) Reference . Year of last update of review . Intervention . Level of evidence . Evidence by reviewers . Local care  Fernandez et al.17 2010 Water for wound cleansing 2 No difference between drinkable tap water or other solution to cleanse wounds to prevent wound infection 2 Effectiveness of cleaning wounds as a routine is questionable 5c No difference in infection rate when using water versus procaine spirit  Coulthard et al.18 2009 Tissue adhesives for closure of surgical incisions excluding high-tension areas 2 No difference between sutures, adhesive tape and tissue adhesives for wound healing 3 Cosmetic appearance rated higher when using tissue adhesives than with tissue adhesive tape 5d Tissue adhesives may cause more wound dehiscence  Farion et al.19 2007 Tissue adhesives for traumatic lacerations in children and adults 1 Tissue adhesives are a reasonable alternative to close traumatic lacerations, despite a slightly increased rate of wound dehiscence 1 Less erythema and pain when using tissue adhesives compared with standard wound care  Jull et al.20 2008 Honey as a topical treatment for wounds 1 Honey improves healing time in moderate superficial and partial thickness burns 5d Mean time to healing in acute wounds may be shorter for SSG compared with honey as topical treatment  Wasiak et al.21 2008 Dressings for superficial and partial-thickness burns 5a Biosynthetic and hydrocolloid dressings may reduce wound healing time 5c Other fibre dressings and antimicrobial (silver) dressings may have no effect on, or even prolong, healing  Vermeulen et al.22 2003 Dressings and topical agents for surgical wounds healing by secondary intention 5c No evidence to support the effectiveness of foam, alginate, hydrocolloid or bead dressing 3 Gauze therapy could lead to greater discomfort but lower costs 5a Plaster cast may reduce healing time compared with elastic compression 5d Aloe vera may delay wound healing compared with gauze  Wasiak and Cleland23 2010 TNP for partial-thickness burns 5b A reduction in burn size at day 5 was seen when TNP was compared with SSD  Dryburgh et al.24 2011 Debridement for surgical wounds 5c Insufficient evidence for the effectiveness of debridement alone or the choice of different methods to achieve a clean wound bed 5b Controversial evidence concerning dextranomer, but could reduce the time to a clean wound bed when using enzymatic agent Systemic care  O'Mathuna and Ashford25 2010 Therapeutic touch for healing acute wounds 2 No effect of therapeutic touch for healing of wounds after minor surgery  Eskes et al.26 2010 HBOT for acute surgical and traumatic wounds 5a HBOT may increase complete wound healing in crush injuries compared with sham HBOT Prevention  Medeiros and 2001 Antibiotic prophylaxis for 2 Strong evidence that prophylactic antibiotics for dog bites do not prevent Saconato27  mammalian bites 1  infection, except when the bite is located on the hand 5a Prophylactic antibiotics after bites of humans may prevent infection  Lethaby et al.28 2008 Pin-site care for preventing 2 Cleansing versus no cleansing showed no difference in infection rate  infections associated with 5c Saline versus alcohol or frequency of cleansing showed no difference  external bone fixators and pins 5b Xeroform treatment versus other dressings may reduce the incidence of infection  Storm-Versloot 2010 Topical silver for preventing 3 Contradictory limited evidence of increased and decreased infection et al.29  wound infection 4  rates when using SSD cream 5c No evidence for effectiveness of topical silver for preventing wound infection in terms of wound healing and wound infection Reference . Year of last update of review . Intervention . Level of evidence . Evidence by reviewers . Local care  Fernandez et al.17 2010 Water for wound cleansing 2 No difference between drinkable tap water or other solution to cleanse wounds to prevent wound infection 2 Effectiveness of cleaning wounds as a routine is questionable 5c No difference in infection rate when using water versus procaine spirit  Coulthard et al.18 2009 Tissue adhesives for closure of surgical incisions excluding high-tension areas 2 No difference between sutures, adhesive tape and tissue adhesives for wound healing 3 Cosmetic appearance rated higher when using tissue adhesives than with tissue adhesive tape 5d Tissue adhesives may cause more wound dehiscence  Farion et al.19 2007 Tissue adhesives for traumatic lacerations in children and adults 1 Tissue adhesives are a reasonable alternative to close traumatic lacerations, despite a slightly increased rate of wound dehiscence 1 Less erythema and pain when using tissue adhesives compared with standard wound care  Jull et al.20 2008 Honey as a topical treatment for wounds 1 Honey improves healing time in moderate superficial and partial thickness burns 5d Mean time to healing in acute wounds may be shorter for SSG compared with honey as topical treatment  Wasiak et al.21 2008 Dressings for superficial and partial-thickness burns 5a Biosynthetic and hydrocolloid dressings may reduce wound healing time 5c Other fibre dressings and antimicrobial (silver) dressings may have no effect on, or even prolong, healing  Vermeulen et al.22 2003 Dressings and topical agents for surgical wounds healing by secondary intention 5c No evidence to support the effectiveness of foam, alginate, hydrocolloid or bead dressing 3 Gauze therapy could lead to greater discomfort but lower costs 5a Plaster cast may reduce healing time compared with elastic compression 5d Aloe vera may delay wound healing compared with gauze  Wasiak and Cleland23 2010 TNP for partial-thickness burns 5b A reduction in burn size at day 5 was seen when TNP was compared with SSD  Dryburgh et al.24 2011 Debridement for surgical wounds 5c Insufficient evidence for the effectiveness of debridement alone or the choice of different methods to achieve a clean wound bed 5b Controversial evidence concerning dextranomer, but could reduce the time to a clean wound bed when using enzymatic agent Systemic care  O'Mathuna and Ashford25 2010 Therapeutic touch for healing acute wounds 2 No effect of therapeutic touch for healing of wounds after minor surgery  Eskes et al.26 2010 HBOT for acute surgical and traumatic wounds 5a HBOT may increase complete wound healing in crush injuries compared with sham HBOT Prevention  Medeiros and 2001 Antibiotic prophylaxis for 2 Strong evidence that prophylactic antibiotics for dog bites do not prevent Saconato27  mammalian bites 1  infection, except when the bite is located on the hand 5a Prophylactic antibiotics after bites of humans may prevent infection  Lethaby et al.28 2008 Pin-site care for preventing 2 Cleansing versus no cleansing showed no difference in infection rate  infections associated with 5c Saline versus alcohol or frequency of cleansing showed no difference  external bone fixators and pins 5b Xeroform treatment versus other dressings may reduce the incidence of infection  Storm-Versloot 2010 Topical silver for preventing 3 Contradictory limited evidence of increased and decreased infection et al.29  wound infection 4  rates when using SSD cream 5c No evidence for effectiveness of topical silver for preventing wound infection in terms of wound healing and wound infection SSG, superficial skin grafts; TNP, topical negative pressure; SSD, silver sulfadiazine; HBOT, hyperbaric oxygen therapy. Open in new tab Table 2 Treatment recommendations for acute wounds based on the grading system (Table 1) Reference . Year of last update of review . Intervention . Level of evidence . Evidence by reviewers . Local care  Fernandez et al.17 2010 Water for wound cleansing 2 No difference between drinkable tap water or other solution to cleanse wounds to prevent wound infection 2 Effectiveness of cleaning wounds as a routine is questionable 5c No difference in infection rate when using water versus procaine spirit  Coulthard et al.18 2009 Tissue adhesives for closure of surgical incisions excluding high-tension areas 2 No difference between sutures, adhesive tape and tissue adhesives for wound healing 3 Cosmetic appearance rated higher when using tissue adhesives than with tissue adhesive tape 5d Tissue adhesives may cause more wound dehiscence  Farion et al.19 2007 Tissue adhesives for traumatic lacerations in children and adults 1 Tissue adhesives are a reasonable alternative to close traumatic lacerations, despite a slightly increased rate of wound dehiscence 1 Less erythema and pain when using tissue adhesives compared with standard wound care  Jull et al.20 2008 Honey as a topical treatment for wounds 1 Honey improves healing time in moderate superficial and partial thickness burns 5d Mean time to healing in acute wounds may be shorter for SSG compared with honey as topical treatment  Wasiak et al.21 2008 Dressings for superficial and partial-thickness burns 5a Biosynthetic and hydrocolloid dressings may reduce wound healing time 5c Other fibre dressings and antimicrobial (silver) dressings may have no effect on, or even prolong, healing  Vermeulen et al.22 2003 Dressings and topical agents for surgical wounds healing by secondary intention 5c No evidence to support the effectiveness of foam, alginate, hydrocolloid or bead dressing 3 Gauze therapy could lead to greater discomfort but lower costs 5a Plaster cast may reduce healing time compared with elastic compression 5d Aloe vera may delay wound healing compared with gauze  Wasiak and Cleland23 2010 TNP for partial-thickness burns 5b A reduction in burn size at day 5 was seen when TNP was compared with SSD  Dryburgh et al.24 2011 Debridement for surgical wounds 5c Insufficient evidence for the effectiveness of debridement alone or the choice of different methods to achieve a clean wound bed 5b Controversial evidence concerning dextranomer, but could reduce the time to a clean wound bed when using enzymatic agent Systemic care  O'Mathuna and Ashford25 2010 Therapeutic touch for healing acute wounds 2 No effect of therapeutic touch for healing of wounds after minor surgery  Eskes et al.26 2010 HBOT for acute surgical and traumatic wounds 5a HBOT may increase complete wound healing in crush injuries compared with sham HBOT Prevention  Medeiros and 2001 Antibiotic prophylaxis for 2 Strong evidence that prophylactic antibiotics for dog bites do not prevent Saconato27  mammalian bites 1  infection, except when the bite is located on the hand 5a Prophylactic antibiotics after bites of humans may prevent infection  Lethaby et al.28 2008 Pin-site care for preventing 2 Cleansing versus no cleansing showed no difference in infection rate  infections associated with 5c Saline versus alcohol or frequency of cleansing showed no difference  external bone fixators and pins 5b Xeroform treatment versus other dressings may reduce the incidence of infection  Storm-Versloot 2010 Topical silver for preventing 3 Contradictory limited evidence of increased and decreased infection et al.29  wound infection 4  rates when using SSD cream 5c No evidence for effectiveness of topical silver for preventing wound infection in terms of wound healing and wound infection Reference . Year of last update of review . Intervention . Level of evidence . Evidence by reviewers . Local care  Fernandez et al.17 2010 Water for wound cleansing 2 No difference between drinkable tap water or other solution to cleanse wounds to prevent wound infection 2 Effectiveness of cleaning wounds as a routine is questionable 5c No difference in infection rate when using water versus procaine spirit  Coulthard et al.18 2009 Tissue adhesives for closure of surgical incisions excluding high-tension areas 2 No difference between sutures, adhesive tape and tissue adhesives for wound healing 3 Cosmetic appearance rated higher when using tissue adhesives than with tissue adhesive tape 5d Tissue adhesives may cause more wound dehiscence  Farion et al.19 2007 Tissue adhesives for traumatic lacerations in children and adults 1 Tissue adhesives are a reasonable alternative to close traumatic lacerations, despite a slightly increased rate of wound dehiscence 1 Less erythema and pain when using tissue adhesives compared with standard wound care  Jull et al.20 2008 Honey as a topical treatment for wounds 1 Honey improves healing time in moderate superficial and partial thickness burns 5d Mean time to healing in acute wounds may be shorter for SSG compared with honey as topical treatment  Wasiak et al.21 2008 Dressings for superficial and partial-thickness burns 5a Biosynthetic and hydrocolloid dressings may reduce wound healing time 5c Other fibre dressings and antimicrobial (silver) dressings may have no effect on, or even prolong, healing  Vermeulen et al.22 2003 Dressings and topical agents for surgical wounds healing by secondary intention 5c No evidence to support the effectiveness of foam, alginate, hydrocolloid or bead dressing 3 Gauze therapy could lead to greater discomfort but lower costs 5a Plaster cast may reduce healing time compared with elastic compression 5d Aloe vera may delay wound healing compared with gauze  Wasiak and Cleland23 2010 TNP for partial-thickness burns 5b A reduction in burn size at day 5 was seen when TNP was compared with SSD  Dryburgh et al.24 2011 Debridement for surgical wounds 5c Insufficient evidence for the effectiveness of debridement alone or the choice of different methods to achieve a clean wound bed 5b Controversial evidence concerning dextranomer, but could reduce the time to a clean wound bed when using enzymatic agent Systemic care  O'Mathuna and Ashford25 2010 Therapeutic touch for healing acute wounds 2 No effect of therapeutic touch for healing of wounds after minor surgery  Eskes et al.26 2010 HBOT for acute surgical and traumatic wounds 5a HBOT may increase complete wound healing in crush injuries compared with sham HBOT Prevention  Medeiros and 2001 Antibiotic prophylaxis for 2 Strong evidence that prophylactic antibiotics for dog bites do not prevent Saconato27  mammalian bites 1  infection, except when the bite is located on the hand 5a Prophylactic antibiotics after bites of humans may prevent infection  Lethaby et al.28 2008 Pin-site care for preventing 2 Cleansing versus no cleansing showed no difference in infection rate  infections associated with 5c Saline versus alcohol or frequency of cleansing showed no difference  external bone fixators and pins 5b Xeroform treatment versus other dressings may reduce the incidence of infection  Storm-Versloot 2010 Topical silver for preventing 3 Contradictory limited evidence of increased and decreased infection et al.29  wound infection 4  rates when using SSD cream 5c No evidence for effectiveness of topical silver for preventing wound infection in terms of wound healing and wound infection SSG, superficial skin grafts; TNP, topical negative pressure; SSD, silver sulfadiazine; HBOT, hyperbaric oxygen therapy. Open in new tab There is strong evidence that systemic treatment with therapeutic touch does not have any additional effect on wound healing compared with placebo or non-treatment after minor surgery25. Cleansing of pin-site wounds associated with orthopaedic fixators using saline, alcohol, hydrogen peroxide or antibacterial soap to prevent infections was not effective when compared with no cleansing28. For the local care of burn wounds, the effectiveness on wound healing of topical negative pressure compared with silver sulfadiazine remains unclear, owing to insufficient evidence23. For burn wounds the use of silver sulfadiazine should be discouraged, as several trials showed a trend towards wound healing delay and increased pain and infection rates21,29. Conversely, topical honey was strongly proven to reduce wound healing time compared with film or gauze-based dressings for burn wounds20. If acute wounds, such as lacerations or soft tissue wounds, need cleansing, the use of drinkable tap water is strongly effective in reducing wound infections compared with saline solutions17. For closing traumatic lacerations, tissue adhesives compared with standard wound care were strongly effective19. Despite a slightly increased rate of wound dehiscence and higher cost, tissue adhesives can be considered a reasonable alternative19. This seems particularly relevant as the improved cosmetic outcome is gaining in importance18,19. Venous ulcers (Table 3) No trials were found comparing compression therapy with no compression to prevent recurrence of healed venous leg ulcers42. Table 3 Treatment recommendations for venous ulcers based on the grading system (Table 1) Reference . Year of last update of review . Intervention . Level of evidence . Evidence by reviewers . Local care  O'Meara et al.30 2008 Compression for venous leg ulcers 1 Elastic compression improves wound healing more than inelastic compression 1 High compression improves wound healing more than low compression 3 Multilayered compression could improve wound healing more than single-layered compression and there seems no difference between the effect of two- and four-layer compression 5a Compression may increase ulcer healing rates more than no compression  Palfreyman et al.31 2006 Dressings for healing venous leg ulcers 2 Type of wound dressing beneath compression does not influence healing (trials included hydrocolloids, foam dressings, alginates, low-adherent dressings and hydrogels)  Briggs and Nelson32 2010 Topical agents or 1 Lidocaine–prilocaine cream decreases pain during ulcer  dressings for pain in  debridement (not clear whether this affects healing)  venous leg ulcers 2 Ibuprofen slow-release foam dressing has no effect on pain relief  Jones and Nelson33 2009 Skin grafting for venous leg ulcers 1 Bilayer artificial skin increases the proportion of ulcer healing more than standard care 4 Single-layer skin replacement probably does not improve healing rates more than standard care 4 Allografting seems to improve healing rates more than standard care 5a Pinch grafts may increase ulcer healing more than xenografts  Al-Kurdi et al.34 2010 Therapeutic ultrasound for 3 Therapeutic ultrasound could decrease ulcer area  venous leg ulcers 4 No difference between therapeutic ultrasound and sham treatment in ulcer healing  O'Meara et al.35 2010 Antibiotics and antiseptics for venous leg ulcers 1 Cadexomer iodine increases ulcer healing compared with standard care both with, and without compression therapy 3 Ethacridine lotion added to compression could reduce ulcer area by 20% 5c Contradictory results for ulcer healing concerning povidone 5b Peroxide 10% could support area reduction of venous leg ulcers  Nelson et al.36 2011 IPC for venous leg ulcers 2 IPC with compression does not contribute to ulcer healing compared with compression treatment alone 5a IPC with dressing versus dressing alone may have a positive effect on ulcer healing 5b Rapid IPC may improve ulcer healing more than slow IPC  Flemming and Cullum37 2011 Laser therapy for venous leg ulcers 4 No difference in wound healing between laser therapy and sham therapy  Aziz et al.38 2011 Electromagnetic therapy for venous leg ulcers 5c Insufficient evidence for the effectiveness of electromagnetic therapy on ulcer healing Systemic care  Jull et al.39 2010 Pentoxifylline for venous 1 Pentoxifylline increases ulcer healing with, or without compression  leg ulcers 1 More adverse (mainly gastrointestinal) events occur during pentoxifylline treatment  Wilkinson and Hawke40 2010 Oral zinc for arterial and venous leg ulcers 2 Oral zinc has no effect on ulcer healing  Kranke et al.41 2003 HBOT for chronic wounds 5b Insufficient evidence for effectiveness of HBOT on healing  O'Meara et al.35 2010 Antibiotics and antiseptics 4 No difference in healing between ciprofloxacin and standard care  for venous leg ulcers 5c Insufficient evidence for effectiveness of routine use of antibiotics to promote healing Prevention  Nelson et al.42 2000 Compression for 5c No trials found comparing compression versus no compression  preventing recurrence of venous ulcers 5b High compression may lead to fewer recurrences Reference . Year of last update of review . Intervention . Level of evidence . Evidence by reviewers . Local care  O'Meara et al.30 2008 Compression for venous leg ulcers 1 Elastic compression improves wound healing more than inelastic compression 1 High compression improves wound healing more than low compression 3 Multilayered compression could improve wound healing more than single-layered compression and there seems no difference between the effect of two- and four-layer compression 5a Compression may increase ulcer healing rates more than no compression  Palfreyman et al.31 2006 Dressings for healing venous leg ulcers 2 Type of wound dressing beneath compression does not influence healing (trials included hydrocolloids, foam dressings, alginates, low-adherent dressings and hydrogels)  Briggs and Nelson32 2010 Topical agents or 1 Lidocaine–prilocaine cream decreases pain during ulcer  dressings for pain in  debridement (not clear whether this affects healing)  venous leg ulcers 2 Ibuprofen slow-release foam dressing has no effect on pain relief  Jones and Nelson33 2009 Skin grafting for venous leg ulcers 1 Bilayer artificial skin increases the proportion of ulcer healing more than standard care 4 Single-layer skin replacement probably does not improve healing rates more than standard care 4 Allografting seems to improve healing rates more than standard care 5a Pinch grafts may increase ulcer healing more than xenografts  Al-Kurdi et al.34 2010 Therapeutic ultrasound for 3 Therapeutic ultrasound could decrease ulcer area  venous leg ulcers 4 No difference between therapeutic ultrasound and sham treatment in ulcer healing  O'Meara et al.35 2010 Antibiotics and antiseptics for venous leg ulcers 1 Cadexomer iodine increases ulcer healing compared with standard care both with, and without compression therapy 3 Ethacridine lotion added to compression could reduce ulcer area by 20% 5c Contradictory results for ulcer healing concerning povidone 5b Peroxide 10% could support area reduction of venous leg ulcers  Nelson et al.36 2011 IPC for venous leg ulcers 2 IPC with compression does not contribute to ulcer healing compared with compression treatment alone 5a IPC with dressing versus dressing alone may have a positive effect on ulcer healing 5b Rapid IPC may improve ulcer healing more than slow IPC  Flemming and Cullum37 2011 Laser therapy for venous leg ulcers 4 No difference in wound healing between laser therapy and sham therapy  Aziz et al.38 2011 Electromagnetic therapy for venous leg ulcers 5c Insufficient evidence for the effectiveness of electromagnetic therapy on ulcer healing Systemic care  Jull et al.39 2010 Pentoxifylline for venous 1 Pentoxifylline increases ulcer healing with, or without compression  leg ulcers 1 More adverse (mainly gastrointestinal) events occur during pentoxifylline treatment  Wilkinson and Hawke40 2010 Oral zinc for arterial and venous leg ulcers 2 Oral zinc has no effect on ulcer healing  Kranke et al.41 2003 HBOT for chronic wounds 5b Insufficient evidence for effectiveness of HBOT on healing  O'Meara et al.35 2010 Antibiotics and antiseptics 4 No difference in healing between ciprofloxacin and standard care  for venous leg ulcers 5c Insufficient evidence for effectiveness of routine use of antibiotics to promote healing Prevention  Nelson et al.42 2000 Compression for 5c No trials found comparing compression versus no compression  preventing recurrence of venous ulcers 5b High compression may lead to fewer recurrences IPC, intermittent pneumatic compression; HBOT, hyperbaric oxygen therapy. Open in new tab Table 3 Treatment recommendations for venous ulcers based on the grading system (Table 1) Reference . Year of last update of review . Intervention . Level of evidence . Evidence by reviewers . Local care  O'Meara et al.30 2008 Compression for venous leg ulcers 1 Elastic compression improves wound healing more than inelastic compression 1 High compression improves wound healing more than low compression 3 Multilayered compression could improve wound healing more than single-layered compression and there seems no difference between the effect of two- and four-layer compression 5a Compression may increase ulcer healing rates more than no compression  Palfreyman et al.31 2006 Dressings for healing venous leg ulcers 2 Type of wound dressing beneath compression does not influence healing (trials included hydrocolloids, foam dressings, alginates, low-adherent dressings and hydrogels)  Briggs and Nelson32 2010 Topical agents or 1 Lidocaine–prilocaine cream decreases pain during ulcer  dressings for pain in  debridement (not clear whether this affects healing)  venous leg ulcers 2 Ibuprofen slow-release foam dressing has no effect on pain relief  Jones and Nelson33 2009 Skin grafting for venous leg ulcers 1 Bilayer artificial skin increases the proportion of ulcer healing more than standard care 4 Single-layer skin replacement probably does not improve healing rates more than standard care 4 Allografting seems to improve healing rates more than standard care 5a Pinch grafts may increase ulcer healing more than xenografts  Al-Kurdi et al.34 2010 Therapeutic ultrasound for 3 Therapeutic ultrasound could decrease ulcer area  venous leg ulcers 4 No difference between therapeutic ultrasound and sham treatment in ulcer healing  O'Meara et al.35 2010 Antibiotics and antiseptics for venous leg ulcers 1 Cadexomer iodine increases ulcer healing compared with standard care both with, and without compression therapy 3 Ethacridine lotion added to compression could reduce ulcer area by 20% 5c Contradictory results for ulcer healing concerning povidone 5b Peroxide 10% could support area reduction of venous leg ulcers  Nelson et al.36 2011 IPC for venous leg ulcers 2 IPC with compression does not contribute to ulcer healing compared with compression treatment alone 5a IPC with dressing versus dressing alone may have a positive effect on ulcer healing 5b Rapid IPC may improve ulcer healing more than slow IPC  Flemming and Cullum37 2011 Laser therapy for venous leg ulcers 4 No difference in wound healing between laser therapy and sham therapy  Aziz et al.38 2011 Electromagnetic therapy for venous leg ulcers 5c Insufficient evidence for the effectiveness of electromagnetic therapy on ulcer healing Systemic care  Jull et al.39 2010 Pentoxifylline for venous 1 Pentoxifylline increases ulcer healing with, or without compression  leg ulcers 1 More adverse (mainly gastrointestinal) events occur during pentoxifylline treatment  Wilkinson and Hawke40 2010 Oral zinc for arterial and venous leg ulcers 2 Oral zinc has no effect on ulcer healing  Kranke et al.41 2003 HBOT for chronic wounds 5b Insufficient evidence for effectiveness of HBOT on healing  O'Meara et al.35 2010 Antibiotics and antiseptics 4 No difference in healing between ciprofloxacin and standard care  for venous leg ulcers 5c Insufficient evidence for effectiveness of routine use of antibiotics to promote healing Prevention  Nelson et al.42 2000 Compression for 5c No trials found comparing compression versus no compression  preventing recurrence of venous ulcers 5b High compression may lead to fewer recurrences Reference . Year of last update of review . Intervention . Level of evidence . Evidence by reviewers . Local care  O'Meara et al.30 2008 Compression for venous leg ulcers 1 Elastic compression improves wound healing more than inelastic compression 1 High compression improves wound healing more than low compression 3 Multilayered compression could improve wound healing more than single-layered compression and there seems no difference between the effect of two- and four-layer compression 5a Compression may increase ulcer healing rates more than no compression  Palfreyman et al.31 2006 Dressings for healing venous leg ulcers 2 Type of wound dressing beneath compression does not influence healing (trials included hydrocolloids, foam dressings, alginates, low-adherent dressings and hydrogels)  Briggs and Nelson32 2010 Topical agents or 1 Lidocaine–prilocaine cream decreases pain during ulcer  dressings for pain in  debridement (not clear whether this affects healing)  venous leg ulcers 2 Ibuprofen slow-release foam dressing has no effect on pain relief  Jones and Nelson33 2009 Skin grafting for venous leg ulcers 1 Bilayer artificial skin increases the proportion of ulcer healing more than standard care 4 Single-layer skin replacement probably does not improve healing rates more than standard care 4 Allografting seems to improve healing rates more than standard care 5a Pinch grafts may increase ulcer healing more than xenografts  Al-Kurdi et al.34 2010 Therapeutic ultrasound for 3 Therapeutic ultrasound could decrease ulcer area  venous leg ulcers 4 No difference between therapeutic ultrasound and sham treatment in ulcer healing  O'Meara et al.35 2010 Antibiotics and antiseptics for venous leg ulcers 1 Cadexomer iodine increases ulcer healing compared with standard care both with, and without compression therapy 3 Ethacridine lotion added to compression could reduce ulcer area by 20% 5c Contradictory results for ulcer healing concerning povidone 5b Peroxide 10% could support area reduction of venous leg ulcers  Nelson et al.36 2011 IPC for venous leg ulcers 2 IPC with compression does not contribute to ulcer healing compared with compression treatment alone 5a IPC with dressing versus dressing alone may have a positive effect on ulcer healing 5b Rapid IPC may improve ulcer healing more than slow IPC  Flemming and Cullum37 2011 Laser therapy for venous leg ulcers 4 No difference in wound healing between laser therapy and sham therapy  Aziz et al.38 2011 Electromagnetic therapy for venous leg ulcers 5c Insufficient evidence for the effectiveness of electromagnetic therapy on ulcer healing Systemic care  Jull et al.39 2010 Pentoxifylline for venous 1 Pentoxifylline increases ulcer healing with, or without compression  leg ulcers 1 More adverse (mainly gastrointestinal) events occur during pentoxifylline treatment  Wilkinson and Hawke40 2010 Oral zinc for arterial and venous leg ulcers 2 Oral zinc has no effect on ulcer healing  Kranke et al.41 2003 HBOT for chronic wounds 5b Insufficient evidence for effectiveness of HBOT on healing  O'Meara et al.35 2010 Antibiotics and antiseptics 4 No difference in healing between ciprofloxacin and standard care  for venous leg ulcers 5c Insufficient evidence for effectiveness of routine use of antibiotics to promote healing Prevention  Nelson et al.42 2000 Compression for 5c No trials found comparing compression versus no compression  preventing recurrence of venous ulcers 5b High compression may lead to fewer recurrences IPC, intermittent pneumatic compression; HBOT, hyperbaric oxygen therapy. Open in new tab The following systemic treatment options are available when first-choice options fail, and should be considered alongside patient preferences, costs and wound type. For instance, pentoxifylline was strongly effective in promoting wound healing compared with placebo, in combination with compression therapy39. This was true for people of all ages with a venous ulcer and in any care setting, with a duration varying from 4 to 26 months39. Despite controversy about its clinical indications, pentoxifylline is an inexpensive drug with few side-effects and a number needed to treat (NNT) of four patients to improve wound healing significantly. One small trial, in which 18 venous ulcers were included with treatment failure for over 1 year, did not provide sufficient evidence on the effectiveness of hyperbaric oxygen therapy (HBOT) versus sham therapy41. Oral zinc was strongly ineffective for ulcer healing compared with placebo40. None of the 25 trials comparing the routine use of antibiotics and antiseptics with standard care, other antibiotics or placebo provided strong or consistent fairly strong evidence on quicker wound healing35. Therefore, no antimicrobial drug should be used without evidence of colonization or infection. For local treatment, skin grafting compared with standard care was not effective for venous ulcer healing, except for bilayer artificial skin treatment of ‘hard to heal’ ulcers33. The high cost of this treatment is an important factor to consider when interpreting these results. Laser therapy showed limited evidence of effect compared with sham or (infra)red light37, and electromagnetic therapy showed insufficient evidence of effect compared with sham or standard therapy38. Strong evidence of effect was shown for high compression versus low compression, whereas elastic bandages were more effective than inelastic bandages30. Limited evidence of effect was shown when comparing multicomponent and single-component systems30. Seven small trials showed significantly positive effects in terms of quicker ulcer healing when comparing compression therapy, as either bandages or pneumatic devices, with no compression therapy30,36. A simple, comfortable local dressing, such as low-adherent knitted viscose, can be used beneath compression bandages, as there was strong evidence that no dressing type had an additional beneficial effect over any other31. For sharp debridement, there was strong evidence that a eutectic mixture of local anaesthetic (lidocaine–prilocaine), as opposed to placebo, provided effective pain relief (although the impact of debridement on healing was unclear and lidocaine–prilocaine is not licensed for use in open wounds in all settings)32. In contrast, there was strong evidence of no effect on pain relief for ibuprofen slow-release foam dressing compared with other foam dressings32. Limited evidence of effect is available for the following local antimicrobial therapies in addition to compression therapy to increase healing rates: slow-release iodine, cadexomer, compared with standard care or hydrocolloid, and ethacridine lotion 0·1 per cent versus placebo35. Systemic side-effects from the potential absorption of iodine should be considered when using iodine for the treatment of wounds. Ethacridine lotion is seldom used in practice as a wound disinfectant; this could be due to poor accessibility. Diabetic ulcers (Table 4) For the prevention of diabetic ulcers, patient education, as opposed to usual care or brief education, had limited effectiveness in developing foot care knowledge and behaviour that might decrease the incidence of subsequent ulceration or amputation47. Pressure-relieving interventions, such as orthotic devices or therapeutic shoes, tend to reduce the incidence of ulceration and callus formation compared with standard therapy, although there was insufficient evidence to draw a strong conclusion45. Table 4 Treatment recommendations for diabetic ulcers based on the grading system (Table 1) Reference . Year of last update of review . Intervention . Level of evidence . Evidence by reviewers . Local care  Edwards and Stapely43 2009 Debridement for diabetic foot ulcers 1 Strong evidence for effectiveness of hydrogel on healing rate of diabetic foot ulcers 1 Fewer complications occur when using hydrogel 5b Surgical or larval debridement may decrease healing time compared with conventional treatment or hydrogel  Bergin and Wraight44 2010 Silver-based wound dressings and topical agents for treating diabetic foot ulcers 5c No eligible studies identified so no evidence for effectiveness of silver-based wound dressings  Spencer45 2000 Pressure-relieving interventions for preventing and treating diabetic foot ulcers 5a Total contact casts in treatment of diabetic foot ulcers may be effective Systemic care  Kranke et al.41 2003 HBOT for chronic wounds 1 HBOT decreases the risk of major amputation versus control treatment 5b Difference in healing after 1 year was seen in contrast to results directly after HBOT  Cruciani et al.46 2011 G-CSF as adjunctive therapy for diabetic foot infections 3 G-CSF could decrease the need for surgical intervention, especially amputation, and duration of hospitalization 5b May be effective, especially in life-threatening infection Prevention  Dorresteijn et al.47 2010 Patient education for preventing diabetic foot ulceration 3 Limited evidence of effectiveness for patient education on foot care knowledge and behaviour 5c Incidence of foot ulceration did not differ in the trials  Spencer45 2000 Pressure-relieving interventions for 5a Manufactured shoes may help to reduce the incidence of ulceration  preventing and treating diabetic foot ulcers 5b Orthotic interventions tended to result in less callus formation after 1 year 5a Significantly more callus resolution than with standard podiatry Reference . Year of last update of review . Intervention . Level of evidence . Evidence by reviewers . Local care  Edwards and Stapely43 2009 Debridement for diabetic foot ulcers 1 Strong evidence for effectiveness of hydrogel on healing rate of diabetic foot ulcers 1 Fewer complications occur when using hydrogel 5b Surgical or larval debridement may decrease healing time compared with conventional treatment or hydrogel  Bergin and Wraight44 2010 Silver-based wound dressings and topical agents for treating diabetic foot ulcers 5c No eligible studies identified so no evidence for effectiveness of silver-based wound dressings  Spencer45 2000 Pressure-relieving interventions for preventing and treating diabetic foot ulcers 5a Total contact casts in treatment of diabetic foot ulcers may be effective Systemic care  Kranke et al.41 2003 HBOT for chronic wounds 1 HBOT decreases the risk of major amputation versus control treatment 5b Difference in healing after 1 year was seen in contrast to results directly after HBOT  Cruciani et al.46 2011 G-CSF as adjunctive therapy for diabetic foot infections 3 G-CSF could decrease the need for surgical intervention, especially amputation, and duration of hospitalization 5b May be effective, especially in life-threatening infection Prevention  Dorresteijn et al.47 2010 Patient education for preventing diabetic foot ulceration 3 Limited evidence of effectiveness for patient education on foot care knowledge and behaviour 5c Incidence of foot ulceration did not differ in the trials  Spencer45 2000 Pressure-relieving interventions for 5a Manufactured shoes may help to reduce the incidence of ulceration  preventing and treating diabetic foot ulcers 5b Orthotic interventions tended to result in less callus formation after 1 year 5a Significantly more callus resolution than with standard podiatry HBOT, hyperbaric oxygen therapy; G-CSF, granulocyte-colony-stimulating factor. Open in new tab Table 4 Treatment recommendations for diabetic ulcers based on the grading system (Table 1) Reference . Year of last update of review . Intervention . Level of evidence . Evidence by reviewers . Local care  Edwards and Stapely43 2009 Debridement for diabetic foot ulcers 1 Strong evidence for effectiveness of hydrogel on healing rate of diabetic foot ulcers 1 Fewer complications occur when using hydrogel 5b Surgical or larval debridement may decrease healing time compared with conventional treatment or hydrogel  Bergin and Wraight44 2010 Silver-based wound dressings and topical agents for treating diabetic foot ulcers 5c No eligible studies identified so no evidence for effectiveness of silver-based wound dressings  Spencer45 2000 Pressure-relieving interventions for preventing and treating diabetic foot ulcers 5a Total contact casts in treatment of diabetic foot ulcers may be effective Systemic care  Kranke et al.41 2003 HBOT for chronic wounds 1 HBOT decreases the risk of major amputation versus control treatment 5b Difference in healing after 1 year was seen in contrast to results directly after HBOT  Cruciani et al.46 2011 G-CSF as adjunctive therapy for diabetic foot infections 3 G-CSF could decrease the need for surgical intervention, especially amputation, and duration of hospitalization 5b May be effective, especially in life-threatening infection Prevention  Dorresteijn et al.47 2010 Patient education for preventing diabetic foot ulceration 3 Limited evidence of effectiveness for patient education on foot care knowledge and behaviour 5c Incidence of foot ulceration did not differ in the trials  Spencer45 2000 Pressure-relieving interventions for 5a Manufactured shoes may help to reduce the incidence of ulceration  preventing and treating diabetic foot ulcers 5b Orthotic interventions tended to result in less callus formation after 1 year 5a Significantly more callus resolution than with standard podiatry Reference . Year of last update of review . Intervention . Level of evidence . Evidence by reviewers . Local care  Edwards and Stapely43 2009 Debridement for diabetic foot ulcers 1 Strong evidence for effectiveness of hydrogel on healing rate of diabetic foot ulcers 1 Fewer complications occur when using hydrogel 5b Surgical or larval debridement may decrease healing time compared with conventional treatment or hydrogel  Bergin and Wraight44 2010 Silver-based wound dressings and topical agents for treating diabetic foot ulcers 5c No eligible studies identified so no evidence for effectiveness of silver-based wound dressings  Spencer45 2000 Pressure-relieving interventions for preventing and treating diabetic foot ulcers 5a Total contact casts in treatment of diabetic foot ulcers may be effective Systemic care  Kranke et al.41 2003 HBOT for chronic wounds 1 HBOT decreases the risk of major amputation versus control treatment 5b Difference in healing after 1 year was seen in contrast to results directly after HBOT  Cruciani et al.46 2011 G-CSF as adjunctive therapy for diabetic foot infections 3 G-CSF could decrease the need for surgical intervention, especially amputation, and duration of hospitalization 5b May be effective, especially in life-threatening infection Prevention  Dorresteijn et al.47 2010 Patient education for preventing diabetic foot ulceration 3 Limited evidence of effectiveness for patient education on foot care knowledge and behaviour 5c Incidence of foot ulceration did not differ in the trials  Spencer45 2000 Pressure-relieving interventions for 5a Manufactured shoes may help to reduce the incidence of ulceration  preventing and treating diabetic foot ulcers 5b Orthotic interventions tended to result in less callus formation after 1 year 5a Significantly more callus resolution than with standard podiatry HBOT, hyperbaric oxygen therapy; G-CSF, granulocyte-colony-stimulating factor. Open in new tab Systemic additional treatment with HBOT, as opposed to sham or control treatment, is strongly effective in decreasing major amputations, with a NNT of four patients41. There is insufficient evidence that systemic treatment with granulocyte-colony-stimulating factor (G-CSF) can help cure infections or heal ulcers46. On the other hand, G-CSF, compared with standard care, had limited effectiveness in decreasing the need for surgical intervention, especially amputation46. However, the small therapeutic bandwidth and high costs mean that this therapy should not be used as a first treatment option, but only when other treatment options fail. There is strong evidence of benefit for the local application of hydrogels after debridement compared with standard treatment after debridement, gauze-based dressings or standard care to promote wound healing43. There is a lack of relevant trials comparing silver-based wound dressings in diabetic foot ulcers44. Evidence on the effectiveness of total costs as pressure-relieving treatment is very limited45. Arterial ulcers (Table 5) No evidence-based conclusions can be drawn concerning preventive actions. Table 5 Treatment recommendations for arterial ulcers based on the grading system (Table 1) Reference . Year of last update of review . Intervention . Level of evidence . Evidence by reviewers . Local care  Nelson and Bradley48 2006 Dressings and topical agents 5c Insufficient evidence for ulcer healing or area reduction for any dressing or topical agent for arterial leg ulcers Systemic care  Wilkinson and Hawke40 2010 Oral zinc for treating ulcers 5b Oral zinc may increase healing of arterial and venous leg ulcers  Ruffolo et al.49 2009 Prostanoids for CLI 2 No effect for long-term effectiveness and safety in patients with CLI, despite 1  strong evidence of rest pain relief and ulcer healing 1 Oral iloprost reduces amputation 2 Prostanoids do not differ from placebo when comparing amputation rates  Ubbink and Vermeulen50 2008 SCS for NR-CCLI 1 SCS improves limb salvage and clinical situations in patients with NR-CCLI 5a SCS may increase ulcer healing and pain relief  Fowkes and Leng12 2007 Bypass surgery for chronic lower limb ischaemia 3 Compared with thrombolysis, surgery could result in fewer amputations and has a lower incidence of ongoing or recurrent ischaemia 3 Primary graft patency was higher compared with PTA after 1 year 3 More surgical complications (thrombosis) versus exercise 5c Compared with PTA, mortality rates after thrombolysis, thromboendarterectomy and exercise did not differ Reference . Year of last update of review . Intervention . Level of evidence . Evidence by reviewers . Local care  Nelson and Bradley48 2006 Dressings and topical agents 5c Insufficient evidence for ulcer healing or area reduction for any dressing or topical agent for arterial leg ulcers Systemic care  Wilkinson and Hawke40 2010 Oral zinc for treating ulcers 5b Oral zinc may increase healing of arterial and venous leg ulcers  Ruffolo et al.49 2009 Prostanoids for CLI 2 No effect for long-term effectiveness and safety in patients with CLI, despite 1  strong evidence of rest pain relief and ulcer healing 1 Oral iloprost reduces amputation 2 Prostanoids do not differ from placebo when comparing amputation rates  Ubbink and Vermeulen50 2008 SCS for NR-CCLI 1 SCS improves limb salvage and clinical situations in patients with NR-CCLI 5a SCS may increase ulcer healing and pain relief  Fowkes and Leng12 2007 Bypass surgery for chronic lower limb ischaemia 3 Compared with thrombolysis, surgery could result in fewer amputations and has a lower incidence of ongoing or recurrent ischaemia 3 Primary graft patency was higher compared with PTA after 1 year 3 More surgical complications (thrombosis) versus exercise 5c Compared with PTA, mortality rates after thrombolysis, thromboendarterectomy and exercise did not differ CLI, critical limb ischaemia; SCS, spinal cord stimulation; NR-CCLI, non-reconstructable chronic critical leg ischaemia; PTA, percutaneous transluminal angioplasty. Open in new tab Table 5 Treatment recommendations for arterial ulcers based on the grading system (Table 1) Reference . Year of last update of review . Intervention . Level of evidence . Evidence by reviewers . Local care  Nelson and Bradley48 2006 Dressings and topical agents 5c Insufficient evidence for ulcer healing or area reduction for any dressing or topical agent for arterial leg ulcers Systemic care  Wilkinson and Hawke40 2010 Oral zinc for treating ulcers 5b Oral zinc may increase healing of arterial and venous leg ulcers  Ruffolo et al.49 2009 Prostanoids for CLI 2 No effect for long-term effectiveness and safety in patients with CLI, despite 1  strong evidence of rest pain relief and ulcer healing 1 Oral iloprost reduces amputation 2 Prostanoids do not differ from placebo when comparing amputation rates  Ubbink and Vermeulen50 2008 SCS for NR-CCLI 1 SCS improves limb salvage and clinical situations in patients with NR-CCLI 5a SCS may increase ulcer healing and pain relief  Fowkes and Leng12 2007 Bypass surgery for chronic lower limb ischaemia 3 Compared with thrombolysis, surgery could result in fewer amputations and has a lower incidence of ongoing or recurrent ischaemia 3 Primary graft patency was higher compared with PTA after 1 year 3 More surgical complications (thrombosis) versus exercise 5c Compared with PTA, mortality rates after thrombolysis, thromboendarterectomy and exercise did not differ Reference . Year of last update of review . Intervention . Level of evidence . Evidence by reviewers . Local care  Nelson and Bradley48 2006 Dressings and topical agents 5c Insufficient evidence for ulcer healing or area reduction for any dressing or topical agent for arterial leg ulcers Systemic care  Wilkinson and Hawke40 2010 Oral zinc for treating ulcers 5b Oral zinc may increase healing of arterial and venous leg ulcers  Ruffolo et al.49 2009 Prostanoids for CLI 2 No effect for long-term effectiveness and safety in patients with CLI, despite 1  strong evidence of rest pain relief and ulcer healing 1 Oral iloprost reduces amputation 2 Prostanoids do not differ from placebo when comparing amputation rates  Ubbink and Vermeulen50 2008 SCS for NR-CCLI 1 SCS improves limb salvage and clinical situations in patients with NR-CCLI 5a SCS may increase ulcer healing and pain relief  Fowkes and Leng12 2007 Bypass surgery for chronic lower limb ischaemia 3 Compared with thrombolysis, surgery could result in fewer amputations and has a lower incidence of ongoing or recurrent ischaemia 3 Primary graft patency was higher compared with PTA after 1 year 3 More surgical complications (thrombosis) versus exercise 5c Compared with PTA, mortality rates after thrombolysis, thromboendarterectomy and exercise did not differ CLI, critical limb ischaemia; SCS, spinal cord stimulation; NR-CCLI, non-reconstructable chronic critical leg ischaemia; PTA, percutaneous transluminal angioplasty. Open in new tab Systemic treatment with prostanoids compared with placebo in patients with critical leg ischaemia (CLI) was shown to be strongly effective in relieving rest pain and improving ulcer healing, but had no clear effect on late amputation rates49. Prostanoids can be considered a last-resort treatment option because of the high costs and the fact that the dose has to be increased until side-effects appear in order to obtain maximum treatment effect. For patients with CLI, the focus is often on limb salvage rather than ulcer healing. Spinal cord stimulation (SCS) for the treatment of non-reconstructable CLI showed strong evidence of effectiveness, and resulted in an improved limb salvage rate, compared with findings in patients treated conservatively50. On the other hand, costs, patient selection and experience with the treatment need to be taken into account when considering treatment with SCS. Bypass surgery showed evidence of effectiveness, albeit limited, in the prevention (or postponement) of major amputation, but other outcomes did not differ significantly from exercise or SCS in patients with CLI12. Lack of available trials preclude any evidence-based conclusions to be drawn on which local topical agents or dressings should be used for the healing of arterial ulcers48. Pressure ulcers (Table 6) Strong evidence for the effectiveness of high-specification foam mattresses (contoured-foam support surfaces comprising foam of different densities) and limited evidence for low air-loss mattresses was found over standard hospital foam mattresses and standard beds for prevention of pressure ulcers56,58. In one large trial, limited evidence was found for a mixed nutritional supplement diet to reduce the development of pressure ulcers more than a standard hospital diet54. Table 6 Treatment recommendations for pressure ulcers based on the grading system (Table 1) Reference . Year of last update of review . Intervention . Level of evidence . Evidence by reviewers . Local care  Baba-Akbari Sari et al.51 2008 Therapeutic ultrasound for pressure ulcers 2 Strong evidence for ineffectiveness of therapeutic ultrasound for ulcer healing 5c Ultrasound versus laser did not show a difference in ulcer healing  Aziz et al.52 2010 Electromagnetic therapy for treating pressure ulcers 5b Small trials describe that electromagnetic therapy may be effective for ulcer healing  Moore and Cowman53 2010 Wound cleansing for pressure ulcers 5c No trials found comparing cleansing versus no cleansing 5d Saline versus water cleansing, and whirlpool versus no 5d  whirlpool cleansing technique may be less effective in terms of ulcer healing Systemic care  Langer et al.54 2003 Nutritional interventions for preventing and treating pressure ulcers 5b Small trials show no difference when adding ascorbic acid supplementation 5c High-protein diet reported contradictory results for ulcer healing 5d Zinc supplementation may be ineffective for prevention of pressure ulcers  Moore and Cowman55 2008 Repositioning for treating pressure ulcers 5c No trials found on this subject Prevention  McInnes et al.56 2010 Support surfaces for pressure ulcer prevention 1 High-specification foam mattresses better than standard hospital foam mattresses to prevent ulcers 1 No difference in effectiveness of alternating-pressure and constant low-pressure mattresses 1 Pressure-relieving overlays on operating table are effective in prevention of postoperative pressure ulcers  Moore and Cowman57 2010 Risk assessment tools for prevention of pressure ulcers 5c One underpowered trial showed no difference when Braden risk assessment tool and training was compared with unstructured risk assessment and training or unstructured risk assessment alone  Langer et al.54 2003 Nutritional intervention for prevention of pressure ulcers 3 Mixed diet reduced development of pressure ulcers versus hospital diet Reference . Year of last update of review . Intervention . Level of evidence . Evidence by reviewers . Local care  Baba-Akbari Sari et al.51 2008 Therapeutic ultrasound for pressure ulcers 2 Strong evidence for ineffectiveness of therapeutic ultrasound for ulcer healing 5c Ultrasound versus laser did not show a difference in ulcer healing  Aziz et al.52 2010 Electromagnetic therapy for treating pressure ulcers 5b Small trials describe that electromagnetic therapy may be effective for ulcer healing  Moore and Cowman53 2010 Wound cleansing for pressure ulcers 5c No trials found comparing cleansing versus no cleansing 5d Saline versus water cleansing, and whirlpool versus no 5d  whirlpool cleansing technique may be less effective in terms of ulcer healing Systemic care  Langer et al.54 2003 Nutritional interventions for preventing and treating pressure ulcers 5b Small trials show no difference when adding ascorbic acid supplementation 5c High-protein diet reported contradictory results for ulcer healing 5d Zinc supplementation may be ineffective for prevention of pressure ulcers  Moore and Cowman55 2008 Repositioning for treating pressure ulcers 5c No trials found on this subject Prevention  McInnes et al.56 2010 Support surfaces for pressure ulcer prevention 1 High-specification foam mattresses better than standard hospital foam mattresses to prevent ulcers 1 No difference in effectiveness of alternating-pressure and constant low-pressure mattresses 1 Pressure-relieving overlays on operating table are effective in prevention of postoperative pressure ulcers  Moore and Cowman57 2010 Risk assessment tools for prevention of pressure ulcers 5c One underpowered trial showed no difference when Braden risk assessment tool and training was compared with unstructured risk assessment and training or unstructured risk assessment alone  Langer et al.54 2003 Nutritional intervention for prevention of pressure ulcers 3 Mixed diet reduced development of pressure ulcers versus hospital diet Open in new tab Table 6 Treatment recommendations for pressure ulcers based on the grading system (Table 1) Reference . Year of last update of review . Intervention . Level of evidence . Evidence by reviewers . Local care  Baba-Akbari Sari et al.51 2008 Therapeutic ultrasound for pressure ulcers 2 Strong evidence for ineffectiveness of therapeutic ultrasound for ulcer healing 5c Ultrasound versus laser did not show a difference in ulcer healing  Aziz et al.52 2010 Electromagnetic therapy for treating pressure ulcers 5b Small trials describe that electromagnetic therapy may be effective for ulcer healing  Moore and Cowman53 2010 Wound cleansing for pressure ulcers 5c No trials found comparing cleansing versus no cleansing 5d Saline versus water cleansing, and whirlpool versus no 5d  whirlpool cleansing technique may be less effective in terms of ulcer healing Systemic care  Langer et al.54 2003 Nutritional interventions for preventing and treating pressure ulcers 5b Small trials show no difference when adding ascorbic acid supplementation 5c High-protein diet reported contradictory results for ulcer healing 5d Zinc supplementation may be ineffective for prevention of pressure ulcers  Moore and Cowman55 2008 Repositioning for treating pressure ulcers 5c No trials found on this subject Prevention  McInnes et al.56 2010 Support surfaces for pressure ulcer prevention 1 High-specification foam mattresses better than standard hospital foam mattresses to prevent ulcers 1 No difference in effectiveness of alternating-pressure and constant low-pressure mattresses 1 Pressure-relieving overlays on operating table are effective in prevention of postoperative pressure ulcers  Moore and Cowman57 2010 Risk assessment tools for prevention of pressure ulcers 5c One underpowered trial showed no difference when Braden risk assessment tool and training was compared with unstructured risk assessment and training or unstructured risk assessment alone  Langer et al.54 2003 Nutritional intervention for prevention of pressure ulcers 3 Mixed diet reduced development of pressure ulcers versus hospital diet Reference . Year of last update of review . Intervention . Level of evidence . Evidence by reviewers . Local care  Baba-Akbari Sari et al.51 2008 Therapeutic ultrasound for pressure ulcers 2 Strong evidence for ineffectiveness of therapeutic ultrasound for ulcer healing 5c Ultrasound versus laser did not show a difference in ulcer healing  Aziz et al.52 2010 Electromagnetic therapy for treating pressure ulcers 5b Small trials describe that electromagnetic therapy may be effective for ulcer healing  Moore and Cowman53 2010 Wound cleansing for pressure ulcers 5c No trials found comparing cleansing versus no cleansing 5d Saline versus water cleansing, and whirlpool versus no 5d  whirlpool cleansing technique may be less effective in terms of ulcer healing Systemic care  Langer et al.54 2003 Nutritional interventions for preventing and treating pressure ulcers 5b Small trials show no difference when adding ascorbic acid supplementation 5c High-protein diet reported contradictory results for ulcer healing 5d Zinc supplementation may be ineffective for prevention of pressure ulcers  Moore and Cowman55 2008 Repositioning for treating pressure ulcers 5c No trials found on this subject Prevention  McInnes et al.56 2010 Support surfaces for pressure ulcer prevention 1 High-specification foam mattresses better than standard hospital foam mattresses to prevent ulcers 1 No difference in effectiveness of alternating-pressure and constant low-pressure mattresses 1 Pressure-relieving overlays on operating table are effective in prevention of postoperative pressure ulcers  Moore and Cowman57 2010 Risk assessment tools for prevention of pressure ulcers 5c One underpowered trial showed no difference when Braden risk assessment tool and training was compared with unstructured risk assessment and training or unstructured risk assessment alone  Langer et al.54 2003 Nutritional intervention for prevention of pressure ulcers 3 Mixed diet reduced development of pressure ulcers versus hospital diet Open in new tab No conclusions from available Cochrane evidence can be made regarding the effectiveness of systemic treatments. Regarding local treatments, there is strong evidence that therapeutic ultrasound is ineffective compared with sham ultrasound, with ulcer healing as the main outcome51. The possible positive effect on ulcer healing of electromagnetic therapy remains unproven, as only two small trials have been performed, with no convincing evidence for effectiveness52. Furthermore, no particular wound cleansing solution or technique has shown any substantial effect on ulcer healing53. Miscellaneous chronic wounds (Table 7) Insufficient evidence is available for the use of topical silver for the treatment of infected or contaminated wounds29,60. A trend towards a positive effect on healing time was seen in a small trial of honey at the cost of more adverse events in comparison with Edinburgh University Solution of Lime (EUSOL)20. Table 7 Treatment recommendations for miscellaneous chronic wounds based on the grading system (Table 1) Reference . Year of last update of review . Intervention . Level of evidence . Evidence by reviewers . Local care  Jull et al.20 2008 Honey as topical treatment for 5a Shorter healing time for honey treatment compared with EUSOL  wounds 5e More adverse events reported in the honey-treated groups compared with other wound dressings.  Adderley and Smith59 2011 Topical agents and dressings for fungating wounds 5c Quality of life was not reported for any dressing or topical agent for managing wound symptoms associated with fungating wounds 5a Longer duration until treatment failure was seen for miltefosine 6%  Vermeulen et al.60 2006 Topical silver for treating infected wounds 5c Silver-containing dressings or topical agents for treatment of infected or contaminated chronic wounds may have no effect on wound healing Systemic care  Ubbink et al.61 2007 TNP for treating chronic wounds 5b Insufficient evidence for effectiveness of TNP in healing of chronic wounds, although there was a trend towards positive treatment effects in favour of TNP Prevention  Storm-Versloot et al.29 2010 Topical silver for preventing wound infection 5c Insufficient evidence for effectiveness of silver-containing dressings or topical agents to promote wound healing or prevent wound infection 5d Aquacel® Ag had a longer healing time and more infections compared with Algosteril® Reference . Year of last update of review . Intervention . Level of evidence . Evidence by reviewers . Local care  Jull et al.20 2008 Honey as topical treatment for 5a Shorter healing time for honey treatment compared with EUSOL  wounds 5e More adverse events reported in the honey-treated groups compared with other wound dressings.  Adderley and Smith59 2011 Topical agents and dressings for fungating wounds 5c Quality of life was not reported for any dressing or topical agent for managing wound symptoms associated with fungating wounds 5a Longer duration until treatment failure was seen for miltefosine 6%  Vermeulen et al.60 2006 Topical silver for treating infected wounds 5c Silver-containing dressings or topical agents for treatment of infected or contaminated chronic wounds may have no effect on wound healing Systemic care  Ubbink et al.61 2007 TNP for treating chronic wounds 5b Insufficient evidence for effectiveness of TNP in healing of chronic wounds, although there was a trend towards positive treatment effects in favour of TNP Prevention  Storm-Versloot et al.29 2010 Topical silver for preventing wound infection 5c Insufficient evidence for effectiveness of silver-containing dressings or topical agents to promote wound healing or prevent wound infection 5d Aquacel® Ag had a longer healing time and more infections compared with Algosteril® EUSOL, Edinburgh University Solution of Lime; TNP, topical negative pressure. Open in new tab Table 7 Treatment recommendations for miscellaneous chronic wounds based on the grading system (Table 1) Reference . Year of last update of review . Intervention . Level of evidence . Evidence by reviewers . Local care  Jull et al.20 2008 Honey as topical treatment for 5a Shorter healing time for honey treatment compared with EUSOL  wounds 5e More adverse events reported in the honey-treated groups compared with other wound dressings.  Adderley and Smith59 2011 Topical agents and dressings for fungating wounds 5c Quality of life was not reported for any dressing or topical agent for managing wound symptoms associated with fungating wounds 5a Longer duration until treatment failure was seen for miltefosine 6%  Vermeulen et al.60 2006 Topical silver for treating infected wounds 5c Silver-containing dressings or topical agents for treatment of infected or contaminated chronic wounds may have no effect on wound healing Systemic care  Ubbink et al.61 2007 TNP for treating chronic wounds 5b Insufficient evidence for effectiveness of TNP in healing of chronic wounds, although there was a trend towards positive treatment effects in favour of TNP Prevention  Storm-Versloot et al.29 2010 Topical silver for preventing wound infection 5c Insufficient evidence for effectiveness of silver-containing dressings or topical agents to promote wound healing or prevent wound infection 5d Aquacel® Ag had a longer healing time and more infections compared with Algosteril® Reference . Year of last update of review . Intervention . Level of evidence . Evidence by reviewers . Local care  Jull et al.20 2008 Honey as topical treatment for 5a Shorter healing time for honey treatment compared with EUSOL  wounds 5e More adverse events reported in the honey-treated groups compared with other wound dressings.  Adderley and Smith59 2011 Topical agents and dressings for fungating wounds 5c Quality of life was not reported for any dressing or topical agent for managing wound symptoms associated with fungating wounds 5a Longer duration until treatment failure was seen for miltefosine 6%  Vermeulen et al.60 2006 Topical silver for treating infected wounds 5c Silver-containing dressings or topical agents for treatment of infected or contaminated chronic wounds may have no effect on wound healing Systemic care  Ubbink et al.61 2007 TNP for treating chronic wounds 5b Insufficient evidence for effectiveness of TNP in healing of chronic wounds, although there was a trend towards positive treatment effects in favour of TNP Prevention  Storm-Versloot et al.29 2010 Topical silver for preventing wound infection 5c Insufficient evidence for effectiveness of silver-containing dressings or topical agents to promote wound healing or prevent wound infection 5d Aquacel® Ag had a longer healing time and more infections compared with Algosteril® EUSOL, Edinburgh University Solution of Lime; TNP, topical negative pressure. Open in new tab No evidence-based conclusions for systemic treatments can be drawn. Topical negative-pressure therapy was not shown to be effective for healing chronic wounds in seven small trials. Despite the absence of evidence from CSRs, topical negative-pressure therapy is frequently used in practice61,62. Discussion Useful conclusions can be drawn from CSRs to support evidence-based decisions in wound care. They mostly involve the care of patients with chronic or venous leg ulcers, and are thus relevant to a range of healthcare professionals. The conclusions presented here are of the highest level available and healthcare professionals involved in wound care should be aware of them (Table 8). Table 8 Summary of strong levels (1 and 2) of evidence and recommendations for wound care Wound type . Recommendation and effect size of the treatment . Acute wounds  Mammalian bites27 Prevent infection with prophylactic antibiotics, particularly in hands; NNT 4 (3, 8)  Superficial and partial-thickness burns20,29 Apply local honey for quick healing, as WMD of 5 (−5·1, − 4·3) days is reported compared with conventional dressings In acute wounds do not use silver sulfadiazine as topical agent; NNH 13 (7, 1667)  Laceration and soft tissue wounds17 When in need of cleansing, use tap water of drinking quality rather than sterile saline solutions; NNT 3 (3, 7) Chronic wounds  Venous ulcers30,36,39 Systemic treatment with pentoxifylline increases complete wound healing; NNT 4 (3, 7) Use compression therapy for wound healing, adding high compression; multicomponent systems or elastic bandages are the most effective  Diabetic ulcers41,43 Use hyperbaric oxygen therapy to decrease major amputation rate; NNT 5 (3, 12) Use local hydrogels to promote complete wound healing; NNT 5 (3, 10)  Arterial ulcers in patients with critical leg ischaemia49,50 Use systemic prostanoids in patients with critical leg ischaemia to relieve rest pain, NNT 11 (7, 28), and improve ulcer healing, NNT 9 (6, 17) Use spinal cord stimulation to improve limb salvage; NNT 9 (5, 45)  Pressure ulcers51,56 Use high-specification foam mattresses, NNT 13 (10, 21), and low air-loss mattresses, NNT 5 (3, 9), to prevent pressure ulcers on the ward, and pressure-relieving overlays on the operating table; NNT 17 (10, 54) Do not use local therapeutic ultrasound to heal pressure ulcers Wound type . Recommendation and effect size of the treatment . Acute wounds  Mammalian bites27 Prevent infection with prophylactic antibiotics, particularly in hands; NNT 4 (3, 8)  Superficial and partial-thickness burns20,29 Apply local honey for quick healing, as WMD of 5 (−5·1, − 4·3) days is reported compared with conventional dressings In acute wounds do not use silver sulfadiazine as topical agent; NNH 13 (7, 1667)  Laceration and soft tissue wounds17 When in need of cleansing, use tap water of drinking quality rather than sterile saline solutions; NNT 3 (3, 7) Chronic wounds  Venous ulcers30,36,39 Systemic treatment with pentoxifylline increases complete wound healing; NNT 4 (3, 7) Use compression therapy for wound healing, adding high compression; multicomponent systems or elastic bandages are the most effective  Diabetic ulcers41,43 Use hyperbaric oxygen therapy to decrease major amputation rate; NNT 5 (3, 12) Use local hydrogels to promote complete wound healing; NNT 5 (3, 10)  Arterial ulcers in patients with critical leg ischaemia49,50 Use systemic prostanoids in patients with critical leg ischaemia to relieve rest pain, NNT 11 (7, 28), and improve ulcer healing, NNT 9 (6, 17) Use spinal cord stimulation to improve limb salvage; NNT 9 (5, 45)  Pressure ulcers51,56 Use high-specification foam mattresses, NNT 13 (10, 21), and low air-loss mattresses, NNT 5 (3, 9), to prevent pressure ulcers on the ward, and pressure-relieving overlays on the operating table; NNT 17 (10, 54) Do not use local therapeutic ultrasound to heal pressure ulcers Values in parentheses are 95 per cent confidence intervals. NNT, number needed to treat; WMD, weighted mean difference; NNH, number needed to harm. Open in new tab Table 8 Summary of strong levels (1 and 2) of evidence and recommendations for wound care Wound type . Recommendation and effect size of the treatment . Acute wounds  Mammalian bites27 Prevent infection with prophylactic antibiotics, particularly in hands; NNT 4 (3, 8)  Superficial and partial-thickness burns20,29 Apply local honey for quick healing, as WMD of 5 (−5·1, − 4·3) days is reported compared with conventional dressings In acute wounds do not use silver sulfadiazine as topical agent; NNH 13 (7, 1667)  Laceration and soft tissue wounds17 When in need of cleansing, use tap water of drinking quality rather than sterile saline solutions; NNT 3 (3, 7) Chronic wounds  Venous ulcers30,36,39 Systemic treatment with pentoxifylline increases complete wound healing; NNT 4 (3, 7) Use compression therapy for wound healing, adding high compression; multicomponent systems or elastic bandages are the most effective  Diabetic ulcers41,43 Use hyperbaric oxygen therapy to decrease major amputation rate; NNT 5 (3, 12) Use local hydrogels to promote complete wound healing; NNT 5 (3, 10)  Arterial ulcers in patients with critical leg ischaemia49,50 Use systemic prostanoids in patients with critical leg ischaemia to relieve rest pain, NNT 11 (7, 28), and improve ulcer healing, NNT 9 (6, 17) Use spinal cord stimulation to improve limb salvage; NNT 9 (5, 45)  Pressure ulcers51,56 Use high-specification foam mattresses, NNT 13 (10, 21), and low air-loss mattresses, NNT 5 (3, 9), to prevent pressure ulcers on the ward, and pressure-relieving overlays on the operating table; NNT 17 (10, 54) Do not use local therapeutic ultrasound to heal pressure ulcers Wound type . Recommendation and effect size of the treatment . Acute wounds  Mammalian bites27 Prevent infection with prophylactic antibiotics, particularly in hands; NNT 4 (3, 8)  Superficial and partial-thickness burns20,29 Apply local honey for quick healing, as WMD of 5 (−5·1, − 4·3) days is reported compared with conventional dressings In acute wounds do not use silver sulfadiazine as topical agent; NNH 13 (7, 1667)  Laceration and soft tissue wounds17 When in need of cleansing, use tap water of drinking quality rather than sterile saline solutions; NNT 3 (3, 7) Chronic wounds  Venous ulcers30,36,39 Systemic treatment with pentoxifylline increases complete wound healing; NNT 4 (3, 7) Use compression therapy for wound healing, adding high compression; multicomponent systems or elastic bandages are the most effective  Diabetic ulcers41,43 Use hyperbaric oxygen therapy to decrease major amputation rate; NNT 5 (3, 12) Use local hydrogels to promote complete wound healing; NNT 5 (3, 10)  Arterial ulcers in patients with critical leg ischaemia49,50 Use systemic prostanoids in patients with critical leg ischaemia to relieve rest pain, NNT 11 (7, 28), and improve ulcer healing, NNT 9 (6, 17) Use spinal cord stimulation to improve limb salvage; NNT 9 (5, 45)  Pressure ulcers51,56 Use high-specification foam mattresses, NNT 13 (10, 21), and low air-loss mattresses, NNT 5 (3, 9), to prevent pressure ulcers on the ward, and pressure-relieving overlays on the operating table; NNT 17 (10, 54) Do not use local therapeutic ultrasound to heal pressure ulcers Values in parentheses are 95 per cent confidence intervals. NNT, number needed to treat; WMD, weighted mean difference; NNH, number needed to harm. Open in new tab Obviously, the conclusions given here do not offer treatment solutions for every wound type, because strong evidence is not yet available for all situations. When systematic reviews do not present strong evidence or suggest that more research is needed, clinicians have to rely on practical and pragmatic advice given in consensus guidelines. Some of the present conclusions, such as compression therapy for venous ulcers, may seem obvious. However, the availability of such strong evidence turns best practice into evidence-based practice. Other recommendations may be contrary to common practice or counterintuitive, such as the lack of evidence for silver dressings or negative-pressure therapy for certain types of wound. This may imply that current practice is not evidence-based and needs to change in order to ensure best quality care. Another example is pentoxifylline. Despite the strong evidence available regarding its effectiveness for venous ulcers, it is seldom used in clinical practice. Clinicians are not familiar with this drug and the manufacturer is reluctant to change its advice on the indications for pentoxifylline. Nevertheless, modern caregivers are compelled to offer their patients best available care with proven effectiveness. The medical profession is changing rapidly, and all too often new evidence emerges that contradicts standard routines; yet it can take a considerable time to be implemented and for the old routine to be abolished63. Some treatment practices, for which strong evidence is lacking, may still be warranted by other, lower levels of evidence not presented here. Sometimes, when evidence is lacking, choices need to be made based on personal or peer expertise, which is still in agreement with evidence-based practice. Besides, some conclusions made in this meta-review belong to the last-resort options of the therapeutic ladder. Furthermore, lack of evidence of benefit is not the same as evidence of lack of benefit. Hence, the absence of robust evidence of effectiveness does not exclude a potentially beneficial effect. Research in the form of large RCTs is needed to identify whether any benefit actually exists. The 44 CSRs with firm conclusions show that a body of knowledge exists in the area of wound care. However, only one-third of these recommendations are strong and based on high-quality evidence. This confirms the disappointing overall level of evidence available in wound care, as already noted by others13–15. This could be due to the fact that wound care products merely require trials to demonstrate safety and performance in order to obtain CE (Conformité Européene) marking, a persistent reluctance to perform high-quality research in wound care, the profitable and unrestricted market for new wound products without corresponding evidence, or the relentless power of case reports and personal opinion. Nevertheless, convincing evidence currently available about wound care should be used by all healthcare professionals and should therefore be readily accessible. This could help more effective, comprehensive and coherent wound care to be organized in the future. There were limitations to the present study. First, only Cochrane reviews were included in this meta-review, and the omission of other systematic reviews or primary studies may have resulted in underrepresentation of the available evidence on certain types of wound care. Nevertheless, CSRs are considered the highest level of evidence in the hierarchy of study designs and are likely to correspond with other systematic reviews16. Conclusions in the present review were based on effectiveness rather than the (overall) effect sizes found in the reviews. For this information, the reader is referred to the particular Cochrane reviews. Second, the classification system of the evidence used here combined elements of different grading methods in order to summarize the broad topic of both local and systemic wound care. As no validated grading system exists as yet, key elements of Grading of Recommendations Assessment, Development and Evaluation (GRADE)63 and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)64 guidelines were combined in this meta-review in order to evaluate levels of evidence of effect. The original instruments did not suffice, because these grading systems lean upon the original trials. Third, the majority (72·5 per cent) of the conclusions referred to chronic wounds, especially venous ulcers (30 of the 79 conclusions for chronic wounds). This shows the existing niches in treatment choice, whereas some important questions, mainly concerning acute wounds, have not yet been addressed. New research should therefore stem from clinical dilemmas rather than the researchers' or manufacturers' interest. Evidence-based medicine has developed into a lasting need rather than a passing fad for wound care practice13,65. This overview of systematic reviews can contribute to effective wound care management. When gaps in knowledge or best practice exist, an analysis of consensus documents may offer pragmatic and practical advice until adequate scientific clinical research provides the missing answers. Acknowledgements The authors thank Sally Bell-Syer, Professor David Leaper, Professor Piet J. M. Bakker and Dr Miranda W. 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TI - Evidence-based decisions for local and systemic wound care
JF - British Journal of Surgery
DO - 10.1002/bjs.8810
DA - 2012-08-02
UR - https://www.deepdyve.com/lp/oxford-university-press/evidence-based-decisions-for-local-and-systemic-wound-care-rtYWitxfCg
SP - 1172
EP - 1183
VL - 99
IS - 9
DP - DeepDyve
ER -