Michael Stacey

Wound bed preparation: a systematic approach to wound management

The healing process in acute wounds has been extensively studied and the knowledge derived from these studies has often been extrapolated to the care of chronic wounds, on the assumption that nonhealing chronic wounds were simply aberrations of the normal tissue repair process. However, this approach is less than satisfactory, as the chronic wound healing process differs in many important respects from that seen in acute wounds. In chronic wounds, the orderly sequence of events seen in acute wounds becomes disrupted or “stuck” at one or more of the different stages of wound healing. For the normal repair process to resume, the barrier to healing must be identified and removed through application of the correct techniques. It is important, therefore, to understand the molecular events that are involved in the wound healing process in order to select the most appropriate intervention. Wound bed preparation is the management of a wound in order to accelerate endogenous healing or to facilitate the effectiveness of other therapeutic measures. Experts in wound management consider that wound bed preparation is an important concept with significant potential as an educational tool in wound management.

Analysis of the acute and chronic wound environments: the role of proteases and their inhibitors

To assess the differences in proteolytic activity of acute and chronic wound environments, wound fluids were collected from acute surgical wounds (22 samples) and chronic wounds (25 samples) of various etiologies, including mixed vessel disease ulcers, decubiti and diabetic foot ulcers. Matrix metalloproteinase (MMP) activity measured using the Azocoll assay was significantly elevated by 30 fold in chronic wounds (median 22.8 μg MMP Eq/ml) compared to acute wounds (median 0.76 μg MMP Eq/ml) (p < 0.001). The addition of the matrix metalloproteinase inhibitor Illomostat decreased the matrix metalloproteinase activity by approximately 90% in all samples, confirming that the majority of the activity measured was due to matrix metalloproteinases. Gelatin zymograms indicated predominantly elevated matrix metalloproteinase‐9 with smaller elevations of matrix metalloproteinase‐2. In addition tissue inhibitor of metalloproteinase‐1 levels were analyzed in a small subset of acute and chronic wounds. When tissue inhibitor of metalloproteinase‐1 levels were compared to protease levels there was an inverse correlation (p = 0.02, r = – 0.78). In vitro degradation of epidermal growth factor was measured by addition of 125I labelled epidermal growth factor to acute and chronic wound fluid samples. There was significantly higher degradation of epidermal growth factor in chronic wound fluid samples (mean 28.1%) compared to acute samples (mean 0.6%). This also correlated to the epidermal growth factor activity of these wound fluid samples (p < 0.001, r = 0.64). Additionally, the levels of proteases were assayed in wound fluid collected from 15 venous leg ulcers during a nonhealing and healing phase using a unique model of chronic wound healing in humans. Patients with nonhealing venous leg ulcers were admitted to the hospital for bed rest and wound fluid samples were collected on admission (nonhealing phase) and after 2 weeks (healing phase) when the ulcers had begun to heal as evidenced by a reduction in size (median 12%). These data showed that the elevated levels of matrix metalloproteinase activity decreased significantly as healing occurs in chronic leg ulcers (p < 0.01). This parallels the processes observed in normally healing acute wounds. This data also supports the case for the addition of protease inhibitors in chronic wounds in conjunction with any treatments using growth factors.

Mitogenic activity and cytokine levels in non-healing and healing chronic leg ulcers

The cause of impaired healing in chronic leg ulcers is not known. However, recent attempts to modify the healing process have focused on adding growth factors to stimulate healing and have failed to produce dramatic improvements in healing. This study used a unique model of chronic wound healing in humans to obtain wound fluid samples from chronic venous leg ulcers that had changed from a nonhealing to a healing phase. These samples were used to assess cytokine and growth factor levels, and mitogenic activity in these nonhealing and healing chronic wounds. The pro‐inflammatory cytokines interleukin‐1, interleukin‐6 and tumor necrosis factor‐αwere found to be present in significantly higher concentrations in wound fluid from nonhealing compared to healing leg ulcers. There were detectable levels but, no significant change in the levels of platelet derived growth factor, epidermal growth factor, basic fibroblast growth factor or transforming growth factor‐βas ulcers healed. Wound fluid was added to fibroblasts in vitro to assess mitogenic activity. There was a significantly greater proliferative response to healing wound fluid samples compared to nonhealing samples. These results suggest that healing may be impaired by inflammatory mediators rather than inhibited by a deficiency of growth factors in these chronic wounds.

Biochemical analysis of wound fluid from nonhealing and healing chronic leg ulcers

The purpose of this study was to determine the biochemical composition of fluid taken from chronic wounds, to compare these values with that of serum, and therefore to assess whether the wound fluid is representative of the extracellular environment of the wound. Paired wound fluid and blood samples were collected from eight patients with chronic leg ulcers in a nonhealing and healing phase. Wound fluid and serum samples were screened for a profile of general biochemical analyses, including electrolytes, lactate, glucose, and protein analyses. Electrolyte levels were essentially identical in wound fluid and serum samples. Lactate and lactate dehydrogenase levels were significantly greater and glucose and bicarbonate levels were significantly lower in wound fluid when compared with the paired serum samples. Albumin and total protein levels in wound fluid were on average half those of serum levels. In this small sample of eight patients, wound fluid collected from chronic leg ulcers is an exudate with the biochemical composition expected in extracellular fluid. In addition, bicarbonate and glucose levels increase and C‐reactive protein levels decrease in wound fluid, but remain unchanged in serum, during healing. These results suggest changes in the state of hypoxia and the inflammatory process in the healing wound.

Aetiology of Chronic Leg Ulcers

This study was undertaken to determine the relative prevalence of the factors causing chronic ulceration of the leg in the general population. Two hundred and fifty-nine patients with chronic ulceration of the leg were found on screening a Western Australian population of 238,000. (The prevalence of chronic ulceration of the leg was 1.1 per 1000 population.) Two hundred and forty-two of these patients (93%) with 286 chronically ulcerated limbs were fully assessed to determine the factors contributing to ulceration. In 239 limbs (84%) ulceration involved the leg; in these limbs venous disease was the most prevalent cause of ulceration (160 limbs). Arterial disease was found in 66 limbs, with both venous and arterial disease present in 35 limbs. Rheumatoid arthritis was a causative factor in 27 limbs and diabetes was found with 29 limbs with ulceration involving the leg. In 47 limbs (16%) ulceration was confined to the foot; arterial disease (35 limbs) and diabetes (23 limbs) were the most prevalent causes of ulceration in these limbs. Venous disease was infrequent (three limbs). No disorder of the circulation was found in 48 limbs (20%) with ulceration involving the leg, and in 58 (20%) of all ulcerated limbs. More than one aetiological factor was present in 93 limbs (33%). A cause for ulceration was not found in 10 limbs (3.5%).

THE EFFECT OF BACTERIAL COLONIZATION ON VENOUS ULCER HEALING

To determine the effect of bacterial colonization on venous ulcer healing, 82 patients with 100 venous ulcerated limbs were each studied prospectively for six months. Despite bacteriological swab results, topical or systemic antibiotics were not administered unless cellulitis supervened. Initial ulcer size, length of ulcer history and time to complete healing of colonized and uncolonized ulcers were determined and compared.

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Incisional hernias are more common in aneurysmal arterial disease

OBJECTIVE To test the hypothesis that incisional hernia was a more frequent complication following aortic reconstructive surgery in patients with aneurysmal as opposed to occlusive aortic disease. DESIGN A retrospective review. MATERIALS AND METHODS All patients having aortic reconstructive surgery at a teaching hospital between 1988 and 1992 were identified and recalled to be examined for evidence of an incisional hernia. RESULTS Of the 134 patients having aortic reconstructive surgery, 87 were available to be examined by an independent clinician. The overall incisional hernia rate was 28%. Patients with aneurysmal disease were significantly more likely to develop an incisional hernia after elective surgery than patients with occlusive disease (p = 0.04). None of the other variables investigated, including age, chronic obstructive airways disease, diabetes, smoking, wound infection, obesity, length of intensive care unit stay and number of units of blood transfused, were significantly related to the complication of incisional hernia. CONCLUSION Incisional hernia is a common complication of aortic reconstructive surgery, especially in patients with aneurysmal disease.

The influence of dressings on venous ulcer healing — A randomised trial

OBJECTIVE To assess the effect of different dressings on venous ulcer healing. DESIGN A randomised clinical trial. MATERIALS Patients were randomised to treatment with one of three dressings: a zinc oxide impregnated bandage, a zinc oxide impregnated stockingette, or an alginate dressing. All patients were treated as outpatients and had compression bandaging with two minimal stretch bandages (Elastocrepe) and a stockingette (Tubigrip) to keep the bandages in place. METHODS One hundred and thirteen patients (133 ulcerated limbs) with chronic ulceration of the leg due to venous disease alone, and attending Fremantle Hospital Leg Ulcer Clinic, Western Australia were entered into the study. Healing was measured as complete healing of the ulcerated limb or failure of the limb to heal within 9 months. RESULTS There was no significant difference between the three groups in ulcer size, duration, and other parameters compared. Healing was affected significantly by ulcer size and which leg was ulcerated. There was significantly faster healing with the paste bandage. CONCLUSION The use of a paste bandage significantly improved the healing of chronic venous ulcers when used in combination with compression bandaging, and compared to an alginate dressing and a zinc oxide impregnated stockingette.

Prediction and monitoring the therapeutic response of chronic dermal wounds

A significant proportion of chronic wounds fail to heal in response to treatment of underlying pathologies combined with good wound care practice. Current prognostic tests to identify these wounds rely on the use of algorithms based on clinically measurable parameters such as wound dimensions and wound duration. Venous leg ulcers may be stratified into healing/non healing at 24 weeks of compression therapy and diabetic foot ulcer treatment outcome assessed using a 3‐parameter algorithm. Accurate and reproducible measurement of wound area is required for these algorithms to have clinical utility. Whilst a number of attempts have been made to develop computerised wound‐assessment techniques, wound tracing by clinicians combined with planimetry remains the standard methodology. Once treatment has been initiated, it is important to continuously monitor the wound to assess efficacy of treatment. This can be achieved by measuring wound area change over the first weeks of treatment to identify whether re‐assessment of treatment strategy is required. A number of algorithms for assessing rate of wound area change have been evaluated to determine a surrogate endpoint for healing. Retrospective analysis of large patient groups indicates that approximately 75% correct prediction of healing outcome can be achieved.