Review

Evidence-based decisions for local and systemic wound care
1 ¨ F. E. Brolmann , D. T. Ubbink1,2 , E. A. Nelson6 , K. Munte5 , C. M. A. M. van der Horst3 and H. Vermeulen1,4 Departments of 1 Quality Assurance and Process Innovation, 2 General Surgery, and 3 Plastic, Reconstructive and Hand Surgery, Academic Medical Centre, and 4 Amsterdam School of Health Professions, Amsterdam, 5 Department of Dermatology, Erasmus Medical Centre, Rotterdam, The Netherlands, and 6 School of Healthcare, University of Leeds, Leeds, UK Correspondence to: Dr D. T. Ubbink, Department of Quality Assurance and Process Innovation, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands (e-mail: d.ubbink@amc.nl)

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 evidencebased 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.

Paper accepted 12 April 2012 Published online in Wiley Online Library (www.bjs.co.uk). DOI: 10.1002/bjs.8810

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
© 2012 British Journal of Surgery Society Ltd Published by John Wiley & Sons Ltd

and quality of life6 – 8 , they deserve high-quality local and systemic treatment. 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
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Fig. M.bjs. because these are considered the highest level of evidence for effectiveness of treatments in the hierarchy of study designs16 . 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. 1 Leg ulcer with slough best available evidence should be identified and applied to decisions in daily practice. in adults as well as in children. Instead. or pooled results from small studies totalling less than 100 patients No large or poolable trials available. A third arbiter resolved any disagreement. two researchers independently classified each CSR into one of five levels of evidence of effect (Table 1). because this number was representative of larger studies in the included CSRs. a sensitivity analysis was performed by applying different definitions of a large study population. all CSRs on local and systemic wound care were included. E. All systematic reviews in the Cochrane Database of Systematic Reviews up to June 2011. Nelson. In the case of apparent methodological flaws or contradictory results in the individual trials. as published by the Cochrane Wounds Group and the Cochrane Peripheral Vascular Diseases Group. formal appraisal of their internal validity was not needed. Limited evidence of no effect 5. Strong evidence of effect 2. Brolmann. For this classification. Munte. Neither strong nor limited evidence of effect © 2012 British Journal of Surgery Society Ltd Published by John Wiley & Sons Ltd www. each prevention or treatment comparison and outcome was graded by taking into account the number of trials and participants included. the level of evidence of the intervention studied was downgraded. or pooled results from small studies totalling less than 100 patients Significant results in favour of control treatment or non-significant difference.co. Vermeulen prevention of surgical-site infection were excluded because these primarily comprise closed wounds. Appraising the strength of evidence Because all CSRs undergo clinical and methodological scrutiny. Reviews on Table 1 Definition of categories to grade the strength of evidence of effect Criteria Significant results in favour of new treatment. C. large was defined as comprising at least 100 patients. based on pooled data of trials totalling over 100 patients Significant results in favour of control treatment or non-significant differences. were retrieved and screened independently by two researchers. and potential for pooling of the results. A. A. D.¨ F. To check the robustness of the classification. Methods Searching and selecting For this meta-review. consistency of results. Strong evidence of no effect 3. K. based on one or more large (over 100 patients) but unpoolable studies. Ubbink.uk British Journal of Surgery . M. referring to the total number of patients available for each treatment per comparison. If the outcome did not show strong evidence of effect (level 5). van der Horst and H. Eligible CSRs dealt with the treatment or prevention of open wounds of any type and aetiology. E. Limited evidence of effect 4. based on one or more large (over 100 patients) but unpoolable studies. and by a third in case of any disagreement. a more tentative conclusion was given if the majority of the trials showed consistent results towards a positive or negative effect. based on pooled data of studies totalling over 100 patients Significant results in favour of new treatment. By default. 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 1. T.

For the local care of burn wounds.bjs. despite their position as first. such as lacerations or soft tissue wounds. eight pressure ulcers. Hence. tissue adhesives can be considered a reasonable alternative19 . and diabetic foot ulcers. For closing traumatic lacerations.Evidence-based decisions for local and systemic wound care Extracting and presenting data Data were extracted by two researchers and checked by a third for interventions. Cleansing of pin-site wounds associated with orthopaedic fixators using saline. acute and chronic wounds. the validity the proposed 100patient threshold was considered sufficient. 72·5 per cent) of the conclusions referred to chronic wounds. arterial or venous leg ulcers. and the remaining 39 addressed chronic wounds: 14 venous ulcers. The following systemic treatment options are available when first-choice options fail. Thirteen of these addressed acute wounds. Venous ulcers (Table 3) No trials were found comparing compression therapy with no compression to prevent recurrence of healed venous leg ulcers42 . When a CSR covered two or more wound types. systemic and local treatments. Despite a slightly increased rate of wound dehiscence and higher cost. traumatic lacerations. The number of strong recommendations (level 1 and 2) did not change substantially until a patient population of 60 or fewer was used. surgical (infected) wounds and burns. need cleansing. 41 and three relevant CSRs respectively were identified. the number of strong. 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. After screening 68 and 82 abstracts from the Cochrane Wounds Group and the Cochrane Peripheral Vascular Disease Group. only the relevant parts of the same review were included in the category. n = 80 and n = 120 as alternative definitions of a large study population. owing to insufficient evidence23 . whereas evidence was not available or insufficient in the remaining 58. Availability of antibiotics and familiarity with their use should lead to the implementation of this preventive option in clinical care. For burn wounds the use of silver sulfadiazine should be discouraged. second or last resort choice.19 . The acute wounds contained surgical incisions. costs and wound type. 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 . as several trials showed a trend towards wound healing delay and increased pain and infection rates21. From the 44 CSRs. Subsequently. the CSRs were grouped into those addressing local. Chronic wounds were defined as those characterized by delayed healing despite comprehensive re-evaluation and appropriate adjustment of treatment. hydrogen peroxide or antibacterial soap to prevent infections was not effective when compared with no cleansing28 . For instance. Acute wounds (Table 2) Preventive systemic treatment in the form of prophylactic antibiotics proved to be ineffective in preventing infection after dog bites. for example miscellaneous chronic wounds and diabetic ulcers. systemic or preventive measures for the various wound types. Traumatic and surgical wounds were classified as acute wounds. alcohol. and should be considered alongside patient preferences.uk British Journal of Surgery Sensitivity analysis To assess a possible effect on the results. and clinical relevance.co. five arterial ulcers and five miscellaneous chronic wounds. This seems particularly relevant as the improved cosmetic outcome is gaining in importance18. The conclusions based on the evidence found in the CSRs were divided into preventive. tissue adhesives compared with standard wound care were strongly effective19 . comparisons and outcome as reported by the authors of the CSRs. n = 60. pentoxifylline was strongly effective in promoting www. The present conclusions therefore discuss treatment options as described by CSRs. fairly strong and weaker levels of evidence were © 2012 British Journal of Surgery Society Ltd Published by John Wiley & Sons Ltd . with the exception of human and dog bites located on hands27 . The strongest conclusions are summarized as recommendations (Table 8). The majority (79 of 109. seven diabetic ulcers. there were 52 reviews of different wound types from which evidence-based conclusions could be extracted. Examples of chronic wounds are pressure ulcers.29 . the effectiveness on wound healing of topical negative pressure compared with silver sulfadiazine remains unclear. If acute wounds. these results are reported as a single category. topical honey was strongly proven to reduce wound healing time compared with film or gauze-based dressings for burn wounds20 . Not all therapeutic or preventive measures in these 44 CSRs reflected first-choice clinical treatment options. Results recalculated using n = 40. Owing to the limited number of CSRs dealing with various acute wounds. Conversely. the use of drinkable tap water is strongly effective in reducing wound infections compared with saline solutions17 .

Brolmann. hyperbaric oxygen therapy.22 2003 Dressings and topical agents for surgical wounds healing by secondary intention 5c Wasiak and Cleland23 Dryburgh et al.20 2008 Honey as a topical treatment for wounds 1 5d Wasiak et al. Ubbink. E. K. adhesive tape and tissue adhesives for wound healing Cosmetic appearance rated higher when using tissue adhesives than with tissue adhesive tape Tissue adhesives may cause more wound dehiscence Tissue adhesives are a reasonable alternative to close traumatic lacerations. Munte.¨ F. © 2012 British Journal of Surgery Society Ltd Published by John Wiley & Sons Ltd www.26 Prevention Medeiros and Saconato27 Lethaby et al.bjs.17 Intervention Level of evidence Evidence by reviewers 2010 Water for wound cleansing 2 2 5c 2 Coulthard et al. TNP.29 2010 SSG.21 2008 Dressings for superficial and partial-thickness burns 5a 5c Vermeulen et al. Vermeulen Table 2 Treatment recommendations for acute wounds based on the grading system (Table 1) Year of last update of review Reference Local care Fernandez et al. A. healing No evidence to support the effectiveness of foam. except when the bite is located on the hand Prophylactic antibiotics after bites of humans may prevent infection Cleansing versus no cleansing showed no difference in infection rate Saline versus alcohol or frequency of cleansing showed no difference Xeroform treatment versus other dressings may reduce the incidence of infection Contradictory limited evidence of increased and decreased infection rates when using SSD cream No evidence for effectiveness of topical silver for preventing wound infection in terms of wound healing and wound infection 3 5d 1 Farion et al.18 2009 Tissue adhesives for closure of surgical incisions excluding high-tension areas No difference between drinkable tap water or other solution to cleanse wounds to prevent wound infection Effectiveness of cleaning wounds as a routine is questionable No difference in infection rate when using water versus procaine spirit No difference between sutures.co. E.uk British Journal of Surgery . hydrocolloid or bead dressing Gauze therapy could lead to greater discomfort but lower costs Plaster cast may reduce healing time compared with elastic compression Aloe vera may delay wound healing compared with gauze A reduction in burn size at day 5 was seen when TNP was compared with SSD Insufficient evidence for the effectiveness of debridement alone or the choice of different methods to achieve a clean wound bed Controversial evidence concerning dextranomer. alginate. van der Horst and H. SSD. C. Nelson. M. or even prolong. D. but could reduce the time to a clean wound bed when using enzymatic agent No effect of therapeutic touch for healing of wounds after minor surgery HBOT may increase complete wound healing in crush injuries compared with sham HBOT Strong evidence that prophylactic antibiotics for dog bites do not prevent infection.24 2010 2011 TNP for partial-thickness burns Debridement for surgical wounds 3 5a 5d 5b 5c 5b Systemic care O’Mathuna and Ashford25 Eskes et al.28 2010 2010 Therapeutic touch for healing acute wounds HBOT for acute surgical and traumatic wounds Antibiotic prophylaxis for mammalian bites Pin-site care for preventing infections associated with external bone fixators and pins Topical silver for preventing wound infection 2 5a 2001 2008 2 1 5a 2 5c 5b 3 4 5c Storm-Versloot et al. topical negative pressure. T. A. despite a slightly increased rate of wound dehiscence Less erythema and pain when using tissue adhesives compared with standard wound care Honey improves healing time in moderate superficial and partial thickness burns Mean time to healing in acute wounds may be shorter for SSG compared with honey as topical treatment Biosynthetic and hydrocolloid dressings may reduce wound healing time Other fibre dressings and antimicrobial (silver) dressings may have no effect on. superficial skin grafts. HBOT. silver sulfadiazine.19 2007 Tissue adhesives for traumatic lacerations in children and adults 1 Jull et al. M.

and without compression therapy Ethacridine lotion added to compression could reduce ulcer area by 20% Contradictory results for ulcer healing concerning povidone Peroxide 10% could support area reduction of venous leg ulcers IPC with compression does not contribute to ulcer healing compared with compression treatment alone IPC with dressing versus dressing alone may have a positive effect on ulcer healing Rapid IPC may improve ulcer healing more than slow IPC No difference in wound healing between laser therapy and sham therapy Insufficient evidence for the effectiveness of electromagnetic therapy on ulcer healing Pentoxifylline increases ulcer healing with. low-adherent dressings and hydrogels) Lidocaine–prilocaine cream decreases pain during ulcer debridement (not clear whether this affects healing) Ibuprofen slow-release foam dressing has no effect on pain relief Bilayer artificial skin increases the proportion of ulcer healing more than standard care Single-layer skin replacement probably does not improve healing rates more than standard care Allografting seems to improve healing rates more than standard care Pinch grafts may increase ulcer healing more than xenografts Therapeutic ultrasound could decrease ulcer area No difference between therapeutic ultrasound and sham treatment in ulcer healing Cadexomer iodine increases ulcer healing compared with standard care both with. HBOT.35 2010 Nelson et al. or without compression More adverse (mainly gastrointestinal) events occur during pentoxifylline treatment Oral zinc has no effect on ulcer healing Insufficient evidence for effectiveness of HBOT on healing No difference in healing between ciprofloxacin and standard care Insufficient evidence for effectiveness of routine use of antibiotics to promote healing No trials found comparing compression versus no compression High compression may lead to fewer recurrences 2010 1 1 2 5b 4 5c Wilkinson and Hawke40 Kranke et al. © 2012 British Journal of Surgery Society Ltd Published by John Wiley & Sons Ltd www.35 2010 2003 2010 Prevention Nelson et al.39 2011 2011 Laser therapy for venous leg ulcers Electromagnetic therapy for venous leg ulcers Pentoxifylline for venous leg ulcers Oral zinc for arterial and venous leg ulcers HBOT for chronic wounds Antibiotics and antiseptics for venous leg ulcers Elastic compression improves wound healing more than inelastic compression High compression improves wound healing more than low compression Multilayered compression could improve wound healing more than single-layered compression and there seems no difference between the effect of two.Evidence-based decisions for local and systemic wound care Table 3 Treatment recommendations for venous ulcers based on the grading system (Table 1) Year of last update of review Level of evidence Reference Local care O’Meara et al.41 O’Meara et al.co. intermittent pneumatic compression.uk British Journal of Surgery . alginates.31 2006 Dressings for healing venous leg ulcers Topical agents or dressings for pain in venous leg ulcers Skin grafting for venous leg ulcers 2 Briggs and Nelson32 2010 1 2 1 4 4 5a 3 4 1 3 5c 5b 2 5a 5b 4 5c Jones and Nelson33 2009 Al-Kurdi et al.36 2011 IPC for venous leg ulcers Flemming and Cullum37 Aziz et al.and four-layer compression Compression may increase ulcer healing rates more than no compression Type of wound dressing beneath compression does not influence healing (trials included hydrocolloids.42 2000 Compression for preventing recurrence of venous ulcers 5c 5b IPC.30 Intervention Evidence by reviewers 2008 Compression for venous leg ulcers 1 1 3 5a Palfreyman et al.bjs. hyperbaric oxygen therapy. foam dressings.34 2010 Therapeutic ultrasound for venous leg ulcers Antibiotics and antiseptics for venous leg ulcers O’Meara et al.38 Systemic care Jull et al.

M. Nelson. Therefore. Seven small trials showed significantly positive effects in terms of quicker ulcer healing when comparing compression therapy. G-CSF.46 Prevention Dorresteijn et al. especially amputation. Munte. M. Ubbink.uk British Journal of Surgery .41 2003 1 5b Cruciani et al. E. C. in combination with compression therapy39 . Brolmann. and duration of hospitalization May be effective. van der Horst and H.co. whereas elastic bandages were more effective than inelastic bandages30 .bjs. A. comfortable local dressing. www.¨ F. For local treatment. in which 18 venous ulcers were included with treatment failure for over 1 year. no antimicrobial drug should be used without evidence of colonization or infection. such as low-adherent knitted viscose. and electromagnetic therapy showed insufficient evidence of effect compared with sham or standard therapy38 . Oral zinc was strongly ineffective for ulcer healing compared with placebo40 . For sharp debridement. E. One small trial. The high cost of this treatment is an important factor to consider when interpreting these results. as either bandages or pneumatic devices. Despite controversy about its clinical indications. T.36 . other antibiotics or placebo provided strong or consistent fairly strong evidence on quicker wound healing35 . granulocyte-colony-stimulating factor. None of the 25 trials comparing the routine use of antibiotics and antiseptics with standard care. with no compression therapy30. wound healing compared with placebo. hyperbaric oxygen therapy. with a duration varying from 4 to 26 months39 . pentoxifylline is an inexpensive drug with few side-effects and a number needed to treat (NNT) of four patients to improve wound healing significantly. © 2012 British Journal of Surgery Society Ltd Published by John Wiley & Sons Ltd except for bilayer artificial skin treatment of ‘hard to heal’ ulcers33 . can be used beneath compression bandages. especially in life-threatening infection Limited evidence of effectiveness for patient education on foot care knowledge and behaviour Incidence of foot ulceration did not differ in the trials Manufactured shoes may help to reduce the incidence of ulceration Orthotic interventions tended to result in less callus formation after 1 year Significantly more callus resolution than with standard podiatry 2010 Patient education for preventing diabetic foot ulceration Pressure-relieving interventions for preventing and treating diabetic foot ulcers 3 5c 5a 5b 5a 2000 HBOT. Strong evidence of effect was shown for high compression versus low compression. as there was strong evidence that no dressing type had an additional beneficial effect over any other31 . Limited evidence of effect was shown when comparing multicomponent and single-component systems30 . Laser therapy showed limited evidence of effect compared with sham or (infra)red light37 . K. Vermeulen Table 4 Treatment recommendations for diabetic ulcers based on the grading system (Table 1) Year of last update of review Reference Local care Edwards and Stapely43 Intervention Level of evidence Evidence by reviewers 2009 Debridement for diabetic foot ulcers 1 1 5b Bergin and Wraight44 Spencer45 2010 2000 Silver-based wound dressings and topical agents for treating diabetic foot ulcers Pressure-relieving interventions for preventing and treating diabetic foot ulcers HBOT for chronic wounds 5c Strong evidence for effectiveness of hydrogel on healing rate of diabetic foot ulcers Fewer complications occur when using hydrogel Surgical or larval debridement may decrease healing time compared with conventional treatment or hydrogel No eligible studies identified so no evidence for effectiveness of silver-based wound dressings Total contact casts in treatment of diabetic foot ulcers may be effective 5a Systemic care Kranke et al. A. D.47 Spencer45 2011 G-CSF as adjunctive therapy for diabetic foot infections 3 5b HBOT decreases the risk of major amputation versus control treatment Difference in healing after 1 year was seen in contrast to results directly after HBOT G-CSF could decrease the need for surgical intervention. This was true for people of all ages with a venous ulcer and in any care setting. did not provide sufficient evidence on the effectiveness of hyperbaric oxygen therapy (HBOT) versus sham therapy41 . A simple. there was strong evidence that a eutectic mixture of local anaesthetic (lidocaine–prilocaine). skin grafting compared with standard care was not effective for venous ulcer healing.

There is insufficient evidence that systemic treatment with granulocyte-colony-stimulating factor (GCSF) can help cure infections or heal ulcers46 . critical limb ischaemia. the small therapeutic bandwidth and high costs mean that this therapy should not be used as a first treatment option.bjs. There is a lack of relevant trials comparing silver-based wound dressings in diabetic foot ulcers44 . and ethacridine lotion 0·1 per cent versus placebo35 . had limited effectiveness in decreasing the need for surgical intervention. had limited effectiveness in developing foot care knowledge and behaviour that might decrease the incidence of subsequent ulceration or amputation47 . However.49 Intervention Level of evidence Evidence by reviewers 2006 Dressings and topical agents Oral zinc for treating ulcers Prostanoids for CLI 5c Insufficient evidence for ulcer healing or area reduction for any dressing or topical agent for arterial leg ulcers Oral zinc may increase healing of arterial and venous leg ulcers No effect for long-term effectiveness and safety in patients with CLI. Pressure-relieving interventions. compared with standard care.uk British Journal of Surgery . © 2012 British Journal of Surgery Society Ltd Published by John Wiley & Sons Ltd Systemic additional treatment with HBOT. Diabetic ulcers (Table 4) For the prevention of diabetic ulcers. this could be due to poor accessibility. as opposed to placebo. gauze-based dressings or standard care to promote wound healing43 . surgery could result in fewer amputations and has a lower incidence of ongoing or recurrent ischaemia Primary graft patency was higher compared with PTA after 1 year More surgical complications (thrombosis) versus exercise Compared with PTA. although there was insufficient evidence to draw a strong conclusion45 . SCS. 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.Evidence-based decisions for local and systemic wound care Table 5 Treatment recommendations for arterial ulcers based on the grading system (Table 1) Year of last update of review Reference Local care Nelson and Bradley48 Systemic care Wilkinson and Hawke40 Ruffolo et al. as opposed to usual care or brief education. cadexomer. In contrast. mortality rates after thrombolysis.co. is strongly effective in decreasing major amputations. thromboendarterectomy and exercise did not differ 2010 2009 5b 2 1 1 2 1 5a 3 3 3 5c Ubbink and Vermeulen50 Fowkes and Leng12 2008 2007 SCS for NR-CCLI Bypass surgery for chronic lower limb ischaemia CLI. spinal cord stimulation. Arterial ulcers (Table 5) No evidence-based conclusions can be drawn concerning preventive actions. but only when other treatment options fail. with a NNT of four patients41 . Systemic side-effects from the potential absorption of iodine should be considered when using iodine for the treatment of wounds. PTA. Limited evidence of effect is available for the following local antimicrobial therapies in addition to compression therapy to increase healing rates: slow-release iodine. NR-CCLI. despite strong evidence of rest pain relief and ulcer healing Oral iloprost reduces amputation Prostanoids do not differ from placebo when comparing amputation rates SCS improves limb salvage and clinical situations in patients with NR-CCLI SCS may increase ulcer healing and pain relief Compared with thrombolysis. patient education. On the other hand. Evidence on the effectiveness of total costs as pressure-relieving treatment is very limited45 . as opposed to sham or control treatment. 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 . G-CSF. there was strong evidence of no effect on pain relief for ibuprofen slow-release foam dressing compared with other foam dressings32 . such as orthotic devices or therapeutic shoes. percutaneous transluminal angioplasty. There is strong evidence of benefit for the local application of hydrogels after debridement compared with standard treatment after debridement. but had no clear effect on late www. Ethacridine lotion is seldom used in practice as a wound disinfectant. non-reconstructable chronic critical leg ischaemia. tend to reduce the incidence of ulceration and callus formation compared with standard therapy. especially amputation46 . compared with standard care or hydrocolloid.

in the prevention (or postponement) of major amputation. On the other hand. as only two small trials have been performed. and resulted in an improved limb salvage rate. A.co. Vermeulen Table 6 Treatment recommendations for pressure ulcers based on the grading system (Table 1) Year of last update of review Reference Local care Baba-Akbari Sari et al. K. C. D.uk British Journal of Surgery . No conclusions from available Cochrane evidence can be made regarding the effectiveness of systemic treatments. costs. T. © 2012 British Journal of Surgery Society Ltd Published by John Wiley & Sons Ltd 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. E.54 2003 Nutritional intervention for prevention of pressure ulcers 3 High-specification foam mattresses better than standard hospital foam mattresses to prevent ulcers No difference in effectiveness of alternating-pressure and constant low-pressure mattresses Pressure-relieving overlays on operating table are effective in prevention of postoperative pressure ulcers 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 Mixed diet reduced development of pressure ulcers versus hospital diet amputation rates49 . The possible positive effect on ulcer healing of electromagnetic therapy remains unproven. compared with findings in patients treated conservatively50 . with ulcer healing as the main outcome51 . but other outcomes did not differ significantly from exercise or SCS in patients with CLI12 . M. Brolmann. A. Regarding local treatments. For patients with CLI. Ubbink.¨ F. Bypass surgery showed evidence of effectiveness.54 2003 Nutritional interventions for preventing and treating pressure ulcers 5b 5c 5d Moore and Cowman55 Prevention McInnes et al.58 . Spinal cord stimulation (SCS) for the treatment of non-reconstructable CLI showed strong evidence of effectiveness. albeit limited. Nelson. Prostanoids can be considered a lastresort 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. Munte.bjs. patient selection and experience with the treatment need to be taken into account when considering treatment with SCS. M. the focus is often on limb salvage rather than ulcer healing.52 Moore and Cowman53 2010 2010 Electromagnetic therapy for treating pressure ulcers Wound cleansing for pressure ulcers 5b 5c 5d 5d Strong evidence for ineffectiveness of therapeutic ultrasound for ulcer healing Ultrasound versus laser did not show a difference in ulcer healing Small trials describe that electromagnetic therapy may be effective for ulcer healing No trials found comparing cleansing versus no cleansing Saline versus water cleansing. E. and whirlpool versus no whirlpool cleansing technique may be less effective in terms of ulcer healing Small trials show no difference when adding ascorbic acid supplementation High-protein diet reported contradictory results for ulcer healing Zinc supplementation may be ineffective for prevention of pressure ulcers No trials found on this subject Systemic care Langer et al.51 Intervention Level of evidence Evidence by reviewers 2008 Therapeutic ultrasound for pressure ulcers 2 5c Aziz et al.56 2008 Repositioning for treating pressure ulcers Support surfaces for pressure ulcer prevention 5c 2010 1 1 1 Moore and Cowman57 2010 Risk assessment tools for prevention of pressure ulcers 5c Langer et al. van der Horst and H. with no convincing evidence for www. limited evidence was found for a mixed nutritional supplement diet to reduce the development of pressure ulcers more than a standard hospital diet54 . there is strong evidence that therapeutic ultrasound is ineffective compared with sham ultrasound. In one large trial. 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 .

co. Another example is pentoxifylline.bjs.60 Systemic care Ubbink et al. Edinburgh University Solution of Lime. because strong evidence is not yet available for all situations. effectiveness52 . Discussion Useful conclusions can be drawn from CSRs to support evidence-based decisions in wound care. However.62 . it is seldom used in clinical practice. although there was a trend towards positive treatment effects in favour of TNP Insufficient evidence for effectiveness of silver-containing dressings or topical agents to promote wound healing or prevent wound infection Aquacel® Ag had a longer healing time and more infections compared with Algosteril® 2007 TNP for treating chronic wounds 5b Prevention Storm-Versloot et al. When systematic reviews do not present strong evidence or suggest that more research is needed. and all too often new evidence emerges that contradicts standard routines. Topical negative-pressure therapy was not shown to be effective for healing chronic wounds in seven small trials. 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 .uk British Journal of Surgery . Quality of life was not reported for any dressing or topical agent for managing wound symptoms associated with fungating wounds Longer duration until treatment failure was seen for miltefosine 6% Silver-containing dressings or topical agents for treatment of infected or contaminated chronic wounds may have no effect on wound healing Insufficient evidence for effectiveness of TNP in healing of chronic wounds. the conclusions given here do not offer treatment solutions for every wound type. such as the lack of evidence for silver dressings or negative-pressure therapy for certain types of wound.61 2011 2006 Shorter healing time for honey treatment compared with EUSOL More adverse events reported in the honey-treated groups compared with other wound dressings.60 . may seem obvious.29 2010 Topical silver for preventing wound infection 5c 5d EUSOL. Obviously. Clinicians are not familiar with this drug and the manufacturer is reluctant to change its advice on the indications for pentoxifylline.20 Intervention Level of evidence Evidence by reviewers 2008 Honey as topical treatment for wounds Topical agents and dressings for fungating wounds Topical silver for treating infected wounds 5a 5e 5c 5a 5c Adderley and Smith59 Vermeulen et al. topical negative pressure. No evidence-based conclusions for systemic treatments can be drawn. yet it can take a considerable time to be implemented and www. topical negative-pressure therapy is frequently used in practice61. clinicians have to rely on practical and pragmatic advice given in consensus guidelines. the availability of such strong evidence turns best practice into evidence-based practice. They mostly involve the care of patients with chronic or venous leg ulcers. Despite the absence of evidence from CSRs. The conclusions presented here are of the © 2012 British Journal of Surgery Society Ltd Published by John Wiley & Sons Ltd highest level available and healthcare professionals involved in wound care should be aware of them (Table 8). Furthermore. Miscellaneous chronic wounds (Table 7 ) Insufficient evidence is available for the use of topical silver for the treatment of infected or contaminated wounds29. such as compression therapy for venous ulcers. TNP.Evidence-based decisions for local and systemic wound care Table 7 Treatment recommendations for miscellaneous chronic wounds based on the grading system (Table 1) Year of last update of review Reference Local care Jull et al. modern caregivers are compelled to offer their patients best available care with proven effectiveness. Despite the strong evidence available regarding its effectiveness for venous ulcers. Some of the present conclusions. Other recommendations may be contrary to common practice or counterintuitive. and are thus relevant to a range of healthcare professionals. Nevertheless. The medical profession is changing rapidly. no particular wound cleansing solution or technique has shown any substantial effect on ulcer healing53 . This may imply that current practice is not evidence-based and needs to change in order to ensure best quality care.

comprehensive and coherent wound care to be organized in the future. 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. 8) Apply local honey for quick healing. as WMD of 5 (−5. C. NNT 3 (3. Second. Sometimes. 7) Use compression therapy for wound healing. CSRs are considered the highest level of evidence in the hierarchy of study designs and are likely to correspond with other systematic reviews16 . Hence. key elements of Grading of Recommendations Assessment.56 Values in parentheses are 95 per cent confidence intervals. 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. only Cochrane reviews were included in this meta-review. NNT 5 (3. WMD. A. 9). and pressure-relieving overlays on the operating table. 12) Use local hydrogels to promote complete wound healing. NNT 13 (10. lack of evidence of benefit is not the same as evidence of lack of benefit.bjs. The original instruments did not suffice. NNT 11 (7. Nevertheless. This shows www. and low air-loss mattresses. 1667) When in need of cleansing.43 Arterial ulcers in patients with critical leg ischaemia49. Nevertheless. This confirms the disappointing overall level of evidence available in wound care. Vermeulen Table 8 Summary of strong levels (1 and 2) of evidence and recommendations for wound care Recommendation and effect size of the treatment Wound type Acute wounds Mammalian bites27 Superficial and partial-thickness burns20. Research in the form of large RCTs is needed to identify whether any benefit actually exists. As no validated grading system exists as yet. 54) Do not use local therapeutic ultrasound to heal pressure ulcers Diabetic ulcers41. lower levels of evidence not presented here. particularly in hands. van der Horst and H. convincing evidence currently available about wound care should be used by all healthcare professionals and should therefore © 2012 British Journal of Surgery Society Ltd Published by John Wiley & Sons Ltd be readily accessible. This could be due to the fact that wound care products merely require trials to demonstrate safety and performance in order to obtain CE (Conformit´ e Europ´ eene) marking.1. some conclusions made in this meta-review belong to the last-resort options of the therapeutic ladder. when evidence is lacking. adding high compression. number needed to treat. NNH. the reader is referred to the particular Cochrane reviews. multicomponent systems or elastic bandages are the most effective Use hyperbaric oxygen therapy to decrease major amputation rate. For this information. The 44 CSRs with firm conclusions show that a body of knowledge exists in the area of wound care. to prevent pressure ulcers on the ward. −4. E. Some treatment practices. This could help more effective. M. A. E. the absence of robust evidence of effectiveness does not exclude a potentially beneficial effect. Besides. First. M. 10) Use systemic prostanoids in patients with critical leg ischaemia to relieve rest pain. Furthermore. NNT 4 (3. Third. choices need to be made based on personal or peer expertise. Munte. NNT 9 (5. may still be warranted by other.co. 21). 7) Systemic treatment with pentoxifylline increases complete wound healing. because these grading systems lean upon the original trials. number needed to harm. only one-third of these recommendations are strong and based on high-quality evidence. 45) Use high-specification foam mattresses. 17) Use spinal cord stimulation to improve limb salvage.39 Prevent infection with prophylactic antibiotics. and improve ulcer healing.uk British Journal of Surgery . NNH 13 (7.29 Laceration and soft tissue wounds17 Chronic wounds Venous ulcers30. especially venous ulcers (30 of the 79 conclusions for chronic wounds). the majority (72·5 per cent) of the conclusions referred to chronic wounds. Brolmann. Ubbink. D. There were limitations to the present study. Nelson. NNT.3) days is reported compared with conventional dressings In acute wounds do not use silver sulfadiazine as topical agent. use tap water of drinking quality rather than sterile saline solutions. a persistent reluctance to perform high-quality research in wound care. K.36. for the old routine to be abolished63 . weighted mean difference. the profitable and unrestricted market for new wound products without corresponding evidence. for which strong evidence is lacking. 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.¨ F. NNT 4 (3. NNT 17 (10. NNT 5 (3. Conclusions in the present review were based on effectiveness rather than the (overall) effect sizes found in the reviews. NNT 5 (3. T. 28). or the relentless power of case reports and personal opinion. which is still in agreement with evidence-based practice.50 Pressure ulcers51. NNT 9 (6. as already noted by others13 – 15 . However.

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