Management of chronic pressure ulcers: an evidence-based analysis

Abstract

In April 2008, the Medical Advisory Secretariat began an evidence-based review of the literature concerning pressure ulcers.Please visit the Medical Advisory Secretariat Web site, http://www.health.gov.on.ca/english/providers/program/mas/tech/tech_mn.html to review these titles that are currently available within the Pressure Ulcers series.PRESSURE ULCER PREVENTION: an evidence based analysisThe cost-effectiveness of prevention strategies for pressure ulcers in long-term care homes in Ontario: projections of the Ontario Pressure Ulcer Model (field evaluation)MANAGEMENT OF CHRONIC PRESSURE ULCERS: an evidence-based analysis

Objective: The Medical Advisory Secretariat (MAS) conducted a systematic review on interventions used to treat pressure ulcers in order to answer the following questions: Do currently available interventions for the treatment of pressure ulcers increase the healing rate of pressure ulcers compared with standard care, a placebo, or other similar interventions?Within each category of intervention, which one is most effective in promoting the healing of existing pressure ulcers?

Background: A pressure ulcer is a localized injury to the skin and/or underlying tissue usually over a bony prominence, as a result of pressure, or pressure in conjunction with shear and/or friction. Many areas of the body, especially the sacrum and the heel, are prone to the development of pressure ulcers. People with impaired mobility (e.g., stroke or spinal cord injury patients) are most vulnerable to pressure ulcers. Other factors that predispose people to pressure ulcer formation are poor nutrition, poor sensation, urinary and fecal incontinence, and poor overall physical and mental health. The prevalence of pressure ulcers in Ontario has been estimated to range from a median of 22.1% in community settings to a median of 29.9% in nonacute care facilities. Pressure ulcers have been shown to increase the risk of mortality among geriatric patients by as much as 400%, to increase the frequency and duration of hospitalization, and to decrease the quality of life of affected patients. The cost of treating pressure ulcers has been estimated at approximately $9,000 (Cdn) per patient per month in the community setting. Considering the high prevalence of pressure ulcers in the Ontario health care system, the total cost of treating pressure ulcers is substantial.

Technology: Wounds normally heal in 3 phases (inflammatory phase, a proliferative phase of new tissue and matrix formation, and a remodelling phase). However, pressure ulcers often fail to progress past the inflammatory stage. Current practice for treating pressure ulcers includes treating the underlying causes, debridement to remove necrotic tissues and contaminated tissues, dressings to provide a moist wound environment and to manage exudates, devices and frequent turning of patients to provide pressure relief, topical applications of biologic agents, and nutritional support to correct nutritional deficiencies. A variety of adjunctive physical therapies are also in use.

Method: Health technology assessment databases and medical databases were searched from 1996 (Medline), 1980 (EMBASE), and 1982 (CINAHL) systematically up to March 2008 to identify randomized controlled trials (RCTs) on the following treatments of pressure ulcers: cleansing, debridement, dressings, biological therapies, pressure-relieving devices, physical therapies, nutritional therapies, and multidisciplinary wound care teams. Full literature search strategies are reported in appendix 1. English-language studies in previous systematic reviews and studies published since the last systematic review were included if they had more than 10 subjects, were randomized, and provided objective outcome measures on the healing of pressure ulcers. In the absence of RCTs, studies of the highest level of evidence available were included. Studies on wounds other than pressure ulcers and on surgical treatment of pressure ulcers were excluded. A total of 18 systematic reviews, 104 RCTs, and 4 observational studies were included in this review. Data were extracted from studies using standardized forms. The quality of individual studies was assessed based on adequacy of randomization, concealment of treatment allocation, comparability of groups, blinded assessment, and intention-to-treat analysis. Meta-analysis to estimate the relative risk (RR) or weighted mean difference (WMD) for measures of healing was performed when appropriate. A descriptive synthesis was provided where pooled analysis was not appropriate or not feasible. The quality of the overall evidence on each intervention was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) criteria.

Findings: Findings from the analysis of the included studies are summarized below: CLEANSING: There is no good trial evidence to support the use of any particular wound cleansing solution or technique for pressure ulcers. DEBRIDEMENT: There was no evidence that debridement using collagenase, dextranomer, cadexomer iodine, or maggots significantly improved complete healing compared with placebo.There were no statistically significant differences between enzymatic or mechanical debridement agents with the following exceptions:Papain urea resulted in better debridement than collagenase.Calcium alginate resulted in a greater reduction in ulcer size compared to dextranomer.Adding streptokinase/streptodornase to hydrogel resulted in faster debridement.Maggot debridement resulted in more complete debridement than conventional treatment.There is limited evidence on the healing effects of debridement devices. DRESSINGS: Hydrocolloid dressing was associated with almost three-times more complete healing compared with saline gauze. There is evidence that hydrogel and hydropolymer may be associated with 50% to 70% more complete healing of pressure ulcers than hydrocolloid dressing.No statistically significant differences in complete healing were detected among other modern dressings.There is evidence that polyurethane foam dressings and hydrocellular dressings are more absorbent and easier to remove than hydrocolloid dressings in ulcers with moderate to high exudates.In deeper ulcers (stage III and IV), the use of alginate with hydrocolloid resulted in significantly greater reduction in the size of the ulcers compared to hydrocolloid alone.Studies on sustained silver-releasing dressing demonstrated a tendency for reducing the risk of infection and promoting faster healing, but the sample sizes were too small for statistical analysis or for drawing conclusions. BIOLOGICAL THERAPIES: The efficacy of platelet-derived growth factors (PDGFs), fibroblast growth factor, and granulocyte-macrophage colony stimulating factor in improving complete healing of chronic pressure ulcers has not been established.Presently only Regranex, a recombinant PDGF, has been approved by Health Canada and only for treatment of diabetic ulcers in the lower extremities.A March 2008 US Food and Drug Administration (FDA) communication reported increased deaths from cancers in people given three or more prescriptions for Regranex.Limited low-quality evidence on skin matrix and engineered skin equivalent suggests a potential role for these products in healing refractory advanced chronic pressure ulcers, but the evidence is insufficient to draw a conclusion. ADJUNCTIVE PHYSICAL THERAPY: There is evidence that electrical stimulation may result in a significantly greater reduction in the surface area and more complete healing of stage II to IV ulcers compared with sham therapy. No conclusion on the efficacy of electrotherapy can be drawn because of significant statistical heterogeneity, small sample sizes, and methodological flaws.The efficacy of other adjunctive physical therapies [electromagnetic therapy, low-level laser (LLL) therapy, ultrasound therapy, ultraviolet light therapy, and negative pressure therapy] in improving complete closure of pressure ulcers has not been established. NUTRITION THERAPY: Supplementation with 15 grams of hydrolyzed protein 3 times daily did not affect complete healing but resulted in a 2-fold improvement in Pressure Ulcer Scale for Healing (PUSH) score compared with placebo.Supplementation with 200 mg of zinc three times per day did not have any significant impact on the healing of pressure ulcers compared with a placebo.Supplementation of 500 mg ascorbic acid twice daily was associated with a significantly greater decrease in the size of the ulcer compared with a placebo but did not have any significant impact on healing when compared with supplementation of 10 mg ascorbic acid three times daily.A very high protein tube feeding (25% of energy as protein) resulted in a greater reduction in ulcer area in institutionalized tube-fed patients compared with a high protein tube feeding (16% of energy as protein).Multinutrient supplements that contain zinc, arginine, and vitamin C were associated with a greater reduction in the area of the ulcers compared with standard hospital diet or to a standard supplement without zinc, arginine, or vitamin C.Firm conclusions cannot be drawn because of methodological flaws and small sample sizes. MULTIDISCIPLINARY WOUND CARE TEAMS: The only RCT suggests that multidisciplinary wound care teams may significantly improve healing in the acute care setting in 8 weeks and may significantly shorten the length of hospitalization. However, since only an abstract is available, study biases cannot be assessed and no conclusions can be drawn on the quality of this evidence.

Figures

Figure 1:. Common Locations of Pressure Ulcers

Figure 2:. Forest Plot of Ulcers Healed – Tap Water Versus Normal Saline Cleansing

Figure 3:. Forest Plot of Mean Percentage Change in Volume of Ulcers – Collagenase Versus Placebo

Figure 4:. Forest Plot of Ulcers Healed – Collagenase Versus Placebo

Figure 5:. Forest Plot of Ulcers Healed – Collagenase Versus Hydrocolloid

Figure 6:. Forest Plot of Mean Change in Necrotic Area – Collagenase Versus Fibronolysin/DNAase

Figure 7:. Forest Plot of Ulcers Healed – Dextranomer Versus Collagenase

Figure 8:. Forest Plot of Complete Debridement – Dextranomer Paste Versus Topical Hydrogel

Figure 9:. Forest Plot of Ulcer Area Reduction – Calcium Alginate Versus Dextranomer

Figure 10:. Forest Plot of Ulcers Healed – Maggot Debridement Versus Conventional Therapy

Figure 11:. Forest Plot of Pressure Ulcers Healed – Topical Collagen Versus Hydrocolloid Treatment

Figure 12:. Forest Plot of Ulcers Healed – Hydrocolloid Dressing Versus Saline Gauze (6–12 Weeks Treatment)

Figure 13:. Forest Plot of Ulcers Healed – Hydrocolloid Dressing Versus Saline Gauze (6 Months Treatment)

Figure 14:. Forest Plot of Ulcers Healed – Hydrocolloid versus Gauze Soaked in Antiseptic Solution

Figure 15:. Forest Plot Comparing Healing of Grade 2 Pressure Ulcers – Polyurethane Dressing Versus Saline Gauze

Figure 16:. Forest Plot of Ulcers Healed – Hydrogel versus Traditional Dressing

Figure 17:. Forest Plot of Percent Epithelialization – Hydrogel versus Gauze Soaked in Providone Iodine

Figure 18:. Forest Plot of Ulcers Healed – Hydrogel versus Hydrocolloid

Figure 19:. Percent Change per Week in Surface Area of Ulcer – Hydrogel Versus Hydrocolloid

Figure 20:. Forest Plot of Ulcers Healed – Hydrogel Dressing Versus Hydrocolloid Dressing

Figure 21:. Forest Plot of Complete Healing – Polyurethane Dressing Versus Hydrocolloid Dressing

Figure 22:. Forest Plot of Ulcers Healed – Hydropolymer Dressing Versus Hydrocolloid Dressing

Figure 23:. Ulcers Healed – Hydrocellular Dressing Versus Hydrocolloid Dressing

Figure 24:. Absolute Reduction in Ulcer Area (cm2) – Sequential Calcium Alginate and Hydrocolloid Versus Hydrocolloid

Figure 25:. Ulcers Healed: Noncontact Normothermic Dressing Compared With Moisture Retentive Dressing

Figure 26:. Forest Plot of Complete Healing – Recombinant Platelet-Derived Growth Factor (100 µg/ml) Versus Placebo at 4 Weeks

Figure 27:. Forest Plot of Complete Healing (300 µg/ml) Versus Placebo at 4 Weeks Recombinant Platelet-Derived Growth Factor

Figure 28:. Forest Plot of Complete Healing (100 µg/ml BID) Versus Placebo at 4 Weeks Recombinant Platelet-Derived Growth Factor

Figure 29:. Forest Plot of Complete Healing – Fibroblast Growth Factor Versus Placebo at 6 Weeks

Figure 30:. Forest Plot of Complete Healing Versus Placebo at 6 Weeks Granulo Macrophage Colony Stimulating Factor

Figure 31:. Forest Plot of Sequential Fibroblast Growth Factor and Granulo Macrophage Colony Stimulating Factor Versus Placebo at 6 Weeks

Figure 32:. Forest Plot of Complete Healing – Nerve Growth Factor Versus Placebo at 6 Weeks

Figure 33:. Forest Plot of Complete Healing – Growth Factor Versus Placebo (All Studies)

Figure 34:. Nursing Time per Patient (Minutes) – Air Fluidized Bed Versus Standard Hospital Bed

Figure 35:. Forest Plot of Improved Ulcers – Air-Fluidized Bed versus Conventional Therapy (Hospital) All Ulcers

Figure 36:. Forest Plot of Improved Large Ulcers (>7.8 cm2) – Air-Fluidized Bed versus Conventional Mattresses (Hospital)

Figure 37:. Forest Plot of Improved Ulcers – Air-Fluidized Bed Versus Conventional Therapy

Figure 38:. Pressure Ulcer Related Hospital Days – Air-Fluidized Bed Versus Conventional

Figure 39:. Forest Plot of Improved Ulcers – Air-Fluidized Bed Versus Conventional (Hospital and Home Setting)

Figure 40:. Forest Plot of Ulcers Improved by One Grade – Low-Air-Loss Mattress versus Convoluted Foam Mattresses

Figure 41:. Forest Plot of Ulcers Completely Healed at 12 Weeks – Low-Air-Loss Beds Versus Convoluted Foam Mattresses

Figure 42:. Forest Plot of Ulcers Healed – Airwave Alternating Pressure Mattress versus Nimbus I Alternating Pressure Mattress

Figure 43:. Forest Plot of Patients With Overall Improvement in Pressure Ulcer – Cairwave Alternating Pressure Mattress Plus Proactive Cushion Versus Nimbus 3 Alternating Pressure Mattress Plus Aura Cushion

Figure 44:. Forest Plot of Sacral Ulcers Healed – Cairwave AP/Proactive Cushion Versus Nimbus 3 AP/Aura Cushion

Figure 45:. Forest Plot of Heel Ulcers Healed 3 AP/Aura Cushion

Figure 46:. Forest Plot of Healed Ulcers – Nimbus 3 Alternating Pressure Mattress Versus Another Alternating Pressure Mattress Replacement or Overlay

Figure 47:. Nimbus Alternating Pressure Mattresses Versus Another Alternating Pressure Mattress Replacement or Overlay in Hospital Setting

Figure 48:. Overall Improved Ulcers – Nimbus 3 Alternating Pressure Mattress Versus RIK Static Fluid Mattresses

Figure 49:. Improved Worst Ulcers – Nimbus 3 Alternating Pressure Mattress Versus RIK Static Fluid Mattresses*

Figure 50:. Forest Plot of Ulcers Healed – Alternating Pressure Mattress Overlay Versus Alternating Pressure Mattress Replacement

Figure 51:. Forest Plot of Ulcers Healed – Constant Low Pressure Foam Mattress versus Water Mattress

Figure 52:. Forest Plot of Ulcers Healed – Profiling Bed Versus Flat-Based Bed

Figure 53:. Forest Plot of Ulcers Healed – Alternating Pressure Seat Cushion Versus Static Seat Cushion

Figure 54:. Forest Plot of Rate of Change in Area of Ulcer – Alternating Pressure Seat Cushion Versus Static Air Seat Cushion

Figure 55:. Forest Plot of Rate of Change in Volume of Ulcer – Alternating Pressure Seat Cushion Versus Static Air Seat Cushion

Figure 56:. Forest Plot of Ulcers Healed – Total Contact Seat Versus Low-Air-Loss Bed

Figure 57:. Forest Plot of Ulcers Healed – Total Contact Seat Versus Low Pressure Foam Mattress Overlay

Figure 58:. Mean Weekly Change in Ulcer Size – Whirlpool Versus Conventional Therapy

Figure 59:. Proportion of Patients That Experienced a Mean Reduction in Ulcer Measurements per Week – Whirlpool Versus Conventional Therapy

Figure 60:. Forest Plot of Ulcers That Deteriorated During the Study – Whirlpool Therapy Versus Conventional Therapy

Figure 61:. Forest Plot of Ulcers Healed – Electrotherapy Versus Sham (ITT data) – Fixed Effects Model

Figure 62:. Forest Plot of Pressure Ulcer Healed – Electrotherapy Versus Sham Electrotherapy (Random Effect Model)

Figure 63:. Comparison of Complete Healing – Electromagnetic Therapy Versus Sham Therapy

Figure 64:. Forest Plot of Ulcers Healed – Low-Level Laser Therapy Versus Conventional Therapy

Figure 65:. Forest Plot of Ulcers Healed – Low-Level Laser Therapy Versus Sham Laser Therapy

Figure 66:. Forest Plot of Ulcers Healed – Low-Level Laser Therapy Versus Sham Therapy or Standard Care

Figure 67:. Forest Plot of Ulcers Healed – Ultrasound Therapy Versus Sham Therapy

Figure 68:. Forest Plot of Complete Healing at 12 Weeks – Ultrasound/Ultraviolet C Therapy Versus Low-Level Laser Therapy

Figure 69:. Forest Plot of Complete Healing at 12 Weeks – Ultrasound and Ultraviolet C Therapy Versus Standard Care

Figure 70:. Ulcers Healed – Negative Pressure Therapy Versus HealthPoint Gels

Figure 71:. Forest Plot of Ulcers Healed – Zinc Supplement Versus Placebo

Figure 72:. Forest Plot of Ulcers Healed – Multinutrient Supplement Versus Standard Diet

Figure 73:. Forest Plot of Weighted Mean Difference of Change in PUSH Scores Before and After Treatment for Each of the Study Arms