Ethical approval. The study was approved by the Bioethics Commission of the Jerzy Kukuczka Academy of Physical Education in Katowice (Resolution no. 10/2010 of 11 March 2010).
Study enrollment. Patients with PUs screened for the study were the residents of four nursing and care centers in Silesia, Poland between January l, 2009 and September 30, 2011. Study eligibility was determined by the patient’s attending physician based on the following criteria: older than 70 years of age, presence of a Stage II or Stage III PU of at least 1.0 cm2 located on the trunk or in the buttock region, persisting for a minimum of 4 weeks. Patients with two PUs were eligible, and both PUs were evaluated for healing progress; patients with more than two PUs were deemed ineligible. Patients with deep, tunneling, necrotic wounds likely to involve osteomyelitis and requiring surgical intervention; neoplasm; lymphatic system diseases; central nervous system demyelinating diseases; or cirrhosis of the liver also were not eligible for study participation.
Patient demographic information was obtained from standardized interviews with the patients, additional examinations of the patients, and from the history of concomitant diseases available in their medical documentation. Patients’ physical and mental conditions, activity, mobility, and incontinence were assessed using the Norton scale (a score <14 indicated a high risk of PU development). To assess the possibility of friction and shear and wound moisture, as well as sensory perception, physical activity, and mobility, the Braden Scale was applied (a score <16 pointed to a high risk of PU development). Patients’ nutritional status was identified by means of the Nutritional Risk Score (NRS—2002).30 Wound severity at enrollment was assessed according to National Pressure Ulcer Advisory Panel and European Pressure Ulcer Advisory Panel2 criteria: Stage II ulcers = partial-thickness loss of the dermis presenting as a shallow open ulcer with a red pink wound bed, without slough; Stage III ulcers = full-thickness tissue loss; subcutaneous fat may be visible but bone, tendon or muscle are not exposed.
Allocation to main groups/randomization. After the selected patients or their legal guardians gave written consent to take part in the study, patients were randomly divided into the treatment group (TG) or control group (CG). The main investigator in charge of patients’ allocation to groups had 50 envelopes, each containing a piece of paper marked with A (TG) or B (CG). The envelopes were opened one-by-one in the presence of a physiotherapist, and the patient was directed to the appropriate study group.
SWC program administered to both groups. All patients received treatment to prevent the development of additional PUs. Pressure-redistribution surfaces, devices, and pillows were provided as needed. A nurse repositioned patients who could not move unaided at least every 2 hours. Persons who could change position were asked to do so in order to relieve pressure on the ulcer area as often as they could.
Blood analysis was performed to screen for nutritional status markers and metabolic disorders such as anemia (iron deficiency anemia or anemia of chronic disease), thyroid dysfunction, impaired glycemic control, dehydration, protein deficit, and hypoalbuminemia.
Wounds were regularly assessed by the attending physician throughout the period of the study to select topical treatments to appropriately address moisture control, bacterial burden, and debridement needs; microbiological culture and sensitivity testing were provided. A comprehensive, interdisciplinary assessment was conducted by a team consisting of a physician, a nurse, a physical therapist, and a dietitian to develop a SWC program addressing the specific demands of each participant— eg, nutritional intervention, optimization of the wound dressing protocol, and incontinence management. The clinician caregivers were blinded to participant group.
Patients in both groups received similar standard topical care, selected to address the needs of individual patients and to promote moist interactive healing. Wounds were first cleansed with 0.9% sodium chloride, potassium permanganateoroctenidine/phenoxyethanol; the ulcer base then was covered with a dressing. Wound dressings (regardless of the group) included nonadherent gauze pads, dressings moistened with 0.9% sodium chloride, hydrogel, solcoseryl, and calendulae anthodium extractum. If wound debridement was needed or infection was suspected, fibrinolysin/deoxyribonuclease, colistinum, and sulfathiazolumnatricum (only in the CG) were additionally administered.
All immobilized patients received low-molecular-weight heparin (enoxaparin) as a standard therapy. Patients with elevated leukocyte levels were treated with antibiotics selected following microbiological culture and sensitivity testing of the PU swab.
US. The TG was administered SWC in conjunction with HFUS. To generate the acoustic beam, the Intelect Advanced device (Chatanooga Group, Holbrook, NY USA) was used. The periwound and wound areas were stimulated through sterile US gel (Aquasonic, Parker, Fairfield, NJ USA). The effective radiating area (ERA) of the transducer was 4.0 cm2. The beam nonuniformity ratio was maximum 5:1.
Pulsed-wave US of 1 MHz and a duty cycle of 20% were selected (pulse duration was 2 minutes and the interval between pulses was 8 minutes). The spatial average temporal peak intensity (SATP) was 0.5 W/cm2, and the spatial average temporal average intensity (SATA) — obtained by averaging intensity values over the “on” and “off” periods — was 0.1 W/cm2. When the pulsed-wave US is applied, the maximum intensity (SATP) occurs during the pulse and is zero when the sound is off. In this study, pulsed-wave US was used with SATP of 0.5 W/cm2 and a duty cycle of 20%, so SATA was 0.1 W/cm2.
The same frequency (1 MHz) was selected in several other studies where US significantly improved the healing of venous leg ulcers (VLUs)5,8,13-16 and PUs.18 In all clinical studies,7-9,11-18 the pulsed mode of HFUS was used and the duty cycle was usually 20%.5,12-16,18 The current researchers’ decision to use 0.5 W/cm2 SATP was determined by the results of earlier preclinical and clinical studies. In in vitro study, Reher et al31 established the best intensity to promote cytokine release from monocytes, fibroblasts, and osteoblasts was 0.1 or 0.4 W/cm2. In a controlled study on induced wounds in Yucatan pigs, Byl et al32,33 found 1 MHz US with intensity of 0.5 W/cm2 (20% duty cycle) increased hydroxyproline synthesis, collagen deposition, wound breaking strength, and wound closure. The authors of several clinical studies5,8,13-16,18 concluded SATP of 0.5 W/cm2 contributed to a significant decrease in VLU area and a significantly faster healing rate.13 Moreover, the use of 0.5 W/cm2 SATP and 20% pulsed mode eliminated the thermal effects.19
In the current study, patients were provided US for 1 to 3 minutes per cm2 of ulcer area (ie, 1 to 3 minutes per US probe area): 1 minute in week one, 2 minutes in week two, and 3 minutes between week three and the end of treatment. These times are consistent with the times used in other clinical studies, which range between 1 and 5 minutes/cm2.5-18
Patients received HFUS once a day, 5 days in a week. The authors of other studies who also found HFUS to improve the healing of PUs used the same frequency of sessions.18
Before and after each procedure, the US transducer was sterilized in a disinfectant solution. PUs were thoroughly cleansed with 0.9% sodium chloride solution in preparation for the procedure and then covered with the aforementioned dressings immediately afterwards.
The healing progress of ulcers receiving SWC and SWC+US was monitored for 6 weeks or until wounds closed, whichever occurred first.
Primary outcome measures. Researchers sought to determine absolute average change in WSA (cm2) after treatment in relation to its baseline in both groups (showing how effective treatment was in particular groups); and the percentage change/decrease in WSA after 6 weeks of intervention with SWC and US+SWC (to compare changes in PU surface area between the groups).
Secondary outcome measures. The Gilman’s parameter34,35 was calculated to ensure the comparability of healing progress regardless of wound shape. Wound healing rates in terms of average weekly change in wound area (cm2/week) were calculated to compare the groups. Also, the percentage of PUs where WSA was significantly smaller at the end of week 6 of intervention (by at least 50%), healed completely, or increased (WSA greater than the baseline) was determined. Additionally, patients were observed for the possible occurrence of negative effects.
Data collection. Two measurements were performed in each group to establish each individual patient’s WSA (cm2): immediately before treatment and at the end of week 6. For PUs that closed before the end of week 6, the date of closure was recorded. Clinicians performing the measurements were blinded to participant’s group.
WSA was determined using the same method employed in several previous clinical trials.13-16,36 Wound contours were copied using transparent film sheets then measured with the planimeter to establish the surface area of each wound. A digitizer (Mutoh Kurta XGT, Altek, Digitizer Technology Company, LLC, Redmond, WA USA) connected to a personal computer (C-GEO v. 4.0 Nadowski, Poland) was used to process and store resulting data. Measurement errors were addressed similar to the authors’ previous study.36
The formulas used to calculate percentage reduction in WSA against the baseline, the weekly mean absolute healing rates (cm2/week), and the Gilman’s parameter are presented in Table 2.
Statistical analysis. The statistical evaluation was performed by computer analysis using Statistica software (version 8.0, StatSoft Polska Sp. z o.o.). Patient characteristics were analyzed for normality of distribution using the Shapiro-Wilk W-test. Because in some cases the distribution was found not to be normal, the results of the experiment were verified with the nonparametric tests. The distributions of the characteristics also were tested for skewness, kurtosis, and modality. In all cases, skewness and kurtosis were smaller than 4 and the distributions were unimodal, so a mean and a standard deviation were adopted as a measure of central value and dispersion.
The distribution homogeneity of patient characteristics was evaluated in both groups with the Fisher test for independence and the Mann-Whitney U test. The mean wound surface areas before and after treatment in particular groups were compared using the Wilcoxon signed-rank test. The Mann-Whitney U test was used to compare mean percentage changes in wound areas, the values of the Gilman’s parameter, and mean weekly change in WSA between the groups.The healing rates of Stage II and Stage III wounds that significantly improved (decreasing by at least 50%), closed, or worsened (their WSA exceeded its initial value) at the end of intervention (at 6 week) were calculated with the Fisher test.
The level of significance in all statistical tests performed was P 0.05.