Efficiency of Therapeutic Ultrasound for Healing Venous Leg Ulcers in Surgically-treated Patients

Abstract: The aim of this study was to evaluate the efficiency of therapeutic ultrasound (US) for healing of venous leg ulcers in surgically treated patients. Study endpoints were the number of completely healed wounds and the clinical parameters predicting the outcome. Seventy patients with venous leg ulcers were included in this study, and ultimately allocated into two comparative groups. Group A consisted of 33 patients (21 women, 12 men). They were treated with the US, compression stockings, and drug therapy. Group B (control) consisted of 37 patients (22 women, 15 men). They were treated with the compression stockings and drug therapy only, administered just as in group A. Ten patients in group A and 12 in group B healed completely (P > 0.05). Comparison of Gilman Index and relative change of the total surface area, length, width, and volume did not demonstrate any difference (P > 0.05) between the groups. A more statistically efficient decrease of pus (P = 0.03) and greater promotion of granulation (P = 0.03) were observed in group A compared to group B. However, the noted changes did not have an influence on acceleration of therapy or final stage of the wound healing process because no differences were detected in the epidermization rate of the ulcers in either group. There are no specific indications that US application promotes healing in patients after surgical operation.

Address correspondence to: Jakub Taradaj, PhD, MD Department of Medical Biophysics Medical University of Silesia ul. Medyków 18, bud. C2 40-752 Katowice, Ligota Poland Phone: 48 32 252 8422 E-mail: jtaradaj@slam.katowice.pl


   Leg ulcers are a major complication of chronic venous insufficiency (CVI). The disease mainly affects people between 60- and 80-years-old, with women affected 3 times more frequently than men.¹ Venous leg ulcers are typically chronic conditions with periods of ulceration followed by healing and then recurrence; 50% of ulcers in the long-term outcomes have been open for more than 10 years, and 60% of patients have experienced previous episodes of ulceration. 1,2    Whenever possible, surgical treatment is provided, as it seems to be the most efficient option. The effect of the operation is to eliminate the transmission of hypertensive blood from superficial and deep veins to microcirculation. 3    Despite surgical repair of blood reflux, which is the main factor in CVI, many difficulties provoking complete wound closure remain. Therefore, modern and effective methods in postoperative therapy are needed. ^4–7    Ultrasound (US) has been employed therapeutically for decades and is currently used by clinicians to treat a wide variety of soft tissue disorders. Application of US may produce a number of biophysical effects that are relevant to wound healing. These include alternations in cellular protein synthesis and release, blood flow and vascular permeability, angiogenesis, and collagen content and alignment. Such effects have been suggested to provide a rationale for the use of therapeutic US at each stage of the wound-healing process. In the management of cutaneous wounds, frequencies from 0.5 MHz–3 MHz have been found to enhance the healing process in incisional lesions, and diabetic and venous ulcers. ^8,9    All of the published clinical studies involved application of US only in conservative therapy of venous leg ulcers. ^10–18 The researchers never applied the US in patients with leg ulcers following a surgical procedure, thus it was estimated whether promising results could be expected in postoperative therapy.    The aim of this study was to evaluate the efficiency of therapeutic US for healing of venous leg ulcers in surgically treated patients. Study endpoints were number of completely healed wounds and clinical parameters used to predict outcomes.

Methods

   The methods, the plan and scope of therapy, inclusion of patients into the groups, and other procedures of the scientific research were reviewed, approved, and accepted by the Bioethical Commission of the Medical University of Silesia (Katowice, Poland).    A prospective, randomized, controlled clinical trial was conducted from September 2005 to February 2007. Seventy patients with venous leg ulcers were included and allocated into two comparative groups. Inclusion and exclusion criteria are presented in Table 1. Group A consisted of 33 patients (21 women, 12 men). They were treated with the US, compression stockings, and drug therapy. Group B consisted of 37 patients (22 women, 15 men). They were only treated with the compression stockings and drug therapy administered identically as in group A. Other details of the examined persons and ulcers are shown in Tables 2 and 3. Patients were evaluated using the CEAP classification of CVI (Table 4).    All ulcers in both groups were diagnosed as venous. Patients were examined by duplex scanning (EUB 555, Hitachi Inc, Japan) to rule out the arterial component and to verify the localization of CVI.    All patients had symptoms of CVI—ie, edema, hyperpigmentation, and lipodermatosclerosis of the affected limb. The number of smokers was recorded as well. Body mass index (BMI) was calculated for all patients by the following equation: According to international norms, a BMI greater than 30 kg/m² indicates obesity.    All operative procedures were performed in the Department of General, Vascular, and Transplant Surgery at the University of Medicine in Katowice. The spectrum of the following procedure included crossectomy, partial (short) stripping of the greater (GSV) or lesser (LSV) saphenous vein, local phlebectomy, and ligation of insufficient perforators.    Patients in group A were treated with US therapy (5 days after surgical intervention). The US beam was generated by a Sonicator 730 apparatus (Mettler Electronics Inc, Anaheim, CA). The power density was 0.5 W/cm2 (spatial average, temporal average). A pulsed wave was with a duty cycle of 1/5 (impulse time = 2 ms, interval = 8 ms) and 1-MHz frequency was used. The procedures were performed in a water bath with a temperature of 34˚C; the US probe had an area of 10 cm² and was placed 2 cm above the wound (Figure 1). The time duration of a single procedure was dependent on the ulcer size. An ulcer of 5 cm² or less was exposed for 5 minutes; for every ulcer 1 cm² in excess of 5 cm², the time was lengthened by 1 minute. For ulcers larger than 20 cm2, the total area was divided into two parts and exposed for the corresponding time. The procedures were repeated once daily for 6 days a week (from Monday to Saturday) over 7 weeks.    All patients in both groups were treated with elastic compression stockings (Sigvaris, Winterthur, Switzerland), providing pressure between 30 mmHg–40 mmHg at the ankle. The stockings were put on the leg at the outpatient clinic every morning and worn for about 10 to 12 hours and were removed at night. The drug therapy followed a standard regimen. All patients received micronized flavonoid fraction (450-mg diosmin, 50-mg hesperidin) and 2 tablets of 500-mg Daflon once daily (Servier Laboratories, France). The ulcer ground was covered with wet dressings (Sterilux®, Hartmann, Germany) of 0.9% sodium chloride. Dressings were changed once a day exclusively at the clinic. The therapy in group B lasted 7 weeks as well.    Treatment progress was evaluated by observing the number of completely healed ulcers, and measuring the area and isolated areas (covered with pus or granulation) of the ulceration by planimetry of congruent projections of the wounds onto transparent paper using a digitized pallet. Depth of the ulceration was precisely measured at various points by micrometer. These findings were then transferred to computer software. The electronic equipment for the measurement of areas and volumes of the ulcers consisted of the digitizer (Kurta™ XGT, Altek Inc, Silver Spring, MD) wired to a personal computer with modified software (C-GEO v. 4.0, Geodezja Nadowski, Poland), which facilitated calculation of these parameters. Measurements of areas and volumes were performed on each patient before therapy, every week during treatment, and after therapy. From these data, the software calculated the area and volume of tissue deficiency in the ulcers. Measurements were also made of length and perpendicular width dimensions (for observation, the correlation between surface area and linear dimensions). The observation of the healing process was supported by precisely calculated parameters, such as Gilman Index¹⁹ and relative changes. These indicators were defined as follows:    The chi-squared independence test (greatest reliability level) was used for analysis of indicators, which characterized patients in all comparative groups. Mean values of the Gilman Index, total area (isolated pus-covered and granulation areas), length, width, and volume of the ulcers before and after therapy were compared between groups by a Wilcoxon matched pairs signed-rank test. Differences in number of completely healed ulcers and relative changes between groups were evaluated with a Mann-Whitney U test. A two-sided P value < 0.05 was considered statistically significant.

Results

   The examined groups were homogeneous in terms of the patients’ characteristics (Tables 2–4). Treatment proved effective in both groups. The 10 (30.3%) patients in group A and 12 (32.4%) in group B healed completely (no difference between groups; P > 0.05). After therapy, there was a statistically significant reduction (P ≤ 0.001) of the total area, length, width, and volume of ulcers in both groups (Table 5). The Gilman Index increased from 0.22 cm to 0.79 cm (P ≤ 0.001) in group A, and in group B from 0.18 cm to 0.92 cm (P ≤ 0.001).    Comparison of relative change of the total surface area (60.01% in group A versus 60.06% in group B), length (39.9% in group A versus 43.01% in group B), width (42.76% in group A versus 46.22% in group B), and volume (80.33% in group A versus 82.41% in group B) did not demonstrate any difference (P > 0.05) between the groups.    The statistically more efficient decrease of pus (P = 0.03) and greater promotion of granulation degree (P = 0.03) were observed in group A (∆R = 92.93%, ∆Z = 68.17%) than in group B (∆R = 71.45%, ∆Z = 53.09%). However, the noted changes did not have an influence on acceleration of therapy and the final stage of the wound healing process, because no differences were detected in the epidermization rate of the ulcers in either group.    The change in wound area occurred simultaneously with changes in linear dimensions in both groups, and was beneficial for wound healing, which ultimately progressed steadily.

Discussion

   Ultrasound has been used for the conservative treatment of a variety of cutaneous wounds, particularly venous ulcers. Much of the published research applies conservative therapies and demonstrate that US strongly accelerates the healing process of venous leg ulcers. ^{10–12,15,16} The investigators were not interested in applying this conservative method to the surgical patients. The present study is the first to implement US for surgical patients. Therefore, the present results can only be compared to conservative treatment reports.    Our results indicate that US applied in group A to venous leg ulcers reduced the initial wound surface area by 60.01% and wound volume by 80.33%. In group B (control), wound surface area decreased by 60.06% and wound volume by 82.41%.    The results from group A appeared to correspond (mainly even more promising) to other clinical studies from conservative treatment of venous leg ulcers in which authors also gained significant reduction of the measurements prior to the start of experiment (Table 6). A good number of these studies were conducted on a small number of patients, which makes scientific analysis difficult.    The literature on the effects of conservative US therapy on soft tissue defects was thoroughly reviewed before the experiment was planned. A significant increase in ulcer healing was expected, especially after the surgical procedures had been performed. However, the results did not confirm these expectations. There was no statistical difference in healing rates between the groups.    The present study was conducted with similar, sometimes identical, doses and parameters as in other clinical trials. Therefore, the authors believe it is not likely that the method of US application would cause differences between US and conservative therapies.    The beneficial effects of healing in group B strongly interfered with the results of this experiment. The healing rates observed in group B were much better compared to control groups treated with conservative therapy. ^{10–12,15,16} The present results demonstrate that vein surgery and leg compression after operation are efficient methods, and that US did not improve venous leg ulcer healing.    These findings are consistent with two critical randomized controlled trials that utilized conservative therapy. Eriksson et al13 observed that after 2 weeks wound size reduction was only 7% better in the US group than in the control group (compression bandaging). After 1 month of therapy, the difference between both groups was 8%, and after 2 months the difference was 6%. Lundeberg et al¹⁴ also did not report any particular influence of US therapy on the healing process when compared with standard compression bandages and stockings. After 1 month of observation, the authors noted 2 completely healed ulcers in the US group and 1 in the control group. After 3 months, 10 ulcers in the US group and 8 in the control group had healed completely.    In conservative therapy, US accelerates movement to the next phases of healing (from decontamination, through granulation, to epidermization), which corresponds with greater decreases in total wound surface area and volume. In surgical procedures, the main purpose of therapy is to remove the cause of the disorder, meaning that in surgical and compression cases, the healing process is more closely connected to improvement of hemodynamics within the venous system than it is to phenomena outside the wound. This belief is supported by the presented results—all ulcers in group B compared to exposed ulcers healed similarly and at the same rate, despite having a larger pus-covered area and smaller granulated area inside the wound. Based on the promising results seen with the therapy in the control group, the authors believe that successful surgical procedures with standard compression and drug therapy after operation can lead to wound closure without using US as an enhancement.

Conclusion

   There are no particular reasons why one should apply US to aid in the healing process after a surgical procedure. Ultrasound efficiently cleanses ulcers of pus and promotes granulation, but it does not influence acceleration of the overall therapy or the final wound healing outcome. These findings require confirmation in other randomized clinical trials.