Effect of cathodal and anodal electrical stimulation on pressure ulcer healing

INTERVENTION: The purpose of this prospective, parallel‐group, randomized, double‐blind, controlled, clinical trial is to evaluate the activity of cytokines, growth factors and healing rates of pressure ulcers (PU) in people with central nervous system injures after 4 weeks of intervention involving standard wound care (SWC), SWC in conjunction with high voltage monophasic pulsed current (HVMPC) delivered by the cathode, and SWC combined with HVMPC delivered by the anode as the treatment electrodes. Demographic information on the patients will be compiled during standardized interviews and physical examinations, as well as from additional examinations of the patients and the documentation of their concomitant diseases. The patients’ physical and mental conditions, activity, mobility and incontinence will be 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 of the patients, their physical activity and mobility the Braden Scale will be applied (a score < 16 pointed to a high risk of PU development). Patients’ nutritional status will be identified by means of the Nutritional Risk Score (NRS‐2002). Wound severity at enrolment will be assessed based on the National Pressure Ulcer Advisory Panel criteria: Category II ulcers = partial‐thickness loss of the dermis presenting as a shallow open ulcer with a red pink wound bed, without slough; Category III ulcers = full‐thickness tissue loss; subcutaneous fat may be visible but bone, tendon or muscle are not exposed; Category IV ulcers = full‐thickness tissue loss with exposed tendon, muscle or bone. Slough or eschar may be present on some parts of the wound bed. Can include undermining and tunnelling. SWC programme administered to both electrical stimulation groups. All patients will be treated to prevent the development of new PUs. Pressure‐redistribution surfaces, devices and pillows will be applied as needed. A nurse or physiotherapist will reposition the immobile patients every 2 hours at the least. Blood tests will be carried out to screen for nutritional status markers and metabolic disorders such as anaemia (iron deficiency anaemia or anaemia of chronic disease), thyroid dysfunction, impaired glycaemic control, dehydration, protein deficit, hypoalbuminemia. Wounds will be regularly assessed by the attending physician over the period of the study to select topical treatments appropriately addressing moisture control, bacterial burden, and debridement needs; microbiological culture and sensitivity tests will also be performed. A team formed of a physician, a nurse, a physical therapist and a dietician will make comprehensive, interdisciplinary assessments of the patients to develop SWC programmes meeting their specific demands, for instance consisting of nutritional intervention, optimization of the wound dressing protocol, and incontinence management. The clinician caregivers will be blinded to participant’s group. Patients in both electrical stimulation groups will receive similar standard topical care, selected to address their individual needs and to promote moist interactive healing. Electrical stimulation with the cathode. In the cathode ES group, patients will be administered HVMPC in addition to SWC. The device for applying HVMPC will be the Intelect Advanced Combo (by Chattanooga, USA). This HVMPC protocol has been adopted following the positive results of earlier clinical trials on patients with PUs and venous leg ulcers.. Over the period o CONDITION: Central nervous system injury Chronic wound healing pressure ulcer Wound healing ; ; ; ; Percentage WSA reduction from baseline at week 4 (PAR4) will be calculated with the following formula: PAR4 = initial WSA (cm2) – WSA (cm2) at week 4 x 100% / Initial WSA (cm2) All immobilized patients will receive low‐molecular‐weight heparin (enoxaparin) as a standard therapy. Patients with elevated leukocyte levels will be treated with antibiotics selected following microbiological culture and sensitivity testing of the PU swab. The device generates a twin‐peak monophasic pulse consisting of two 77‐ microsecond exponential pulses in rapid succession (the twin‐peak pulse duration was 154 microseconds). Pulse frequency will be 100 pps. ES will not cause muscle contractions. Patients who retained the sensory function will only experience sensory effects. Amperage will be applied at a level of 0.36 A. If the sensory experience is too strong (patients with sensory function) the amperage will be reduced but not below 0.25 A. Accordingly, the electrodes will deliver an electrical charge of 250‐ 360 microcoulomb per second. Each patient will have his or her own set of electrodes made of conductive carbon rubber. The treatment electrode (of a size matching the wound surface area) will be placed on an aseptic gauze pad saturated with physiological saline overlaying the wound site. The dispersive electrode (bigger than the treatment electrode) closing the electrical circuit will be positioned at least 20 cm from the PU. Before and after each ES procedure, the electrodes will be sterilized in a disinfectant solution. PRIMARY OUTCOME: Changes in the concentration of anti‐inflammatory cytokines in peripheral blood (IL‐10). Changes in the concentration of polypeptide growth factors in peripheral blood (FGF; IGF‐1; VEGF, EGF, KGF, TGF beta1). Changes in the concentration of pro‐inflammatory cytokines in peripheral blood (IL‐1Beta, IL‐6, TNF‐alpha) SECONDARY OUTCOME: Absolute average change in wound surface area (WSA) (cm2) after treatment in relation to its baseline in all groups (showing how effective treatment will be in particular groups). ; Changes in gene expression for anti‐inflammatory cytokines in the specimen of granulation tissue taken from wound edge.(IL‐10) Changes in gene expression for growth factors and their receptors in the specimen of granulation tissue taken from wound edge (FGF; IGF‐1; VEGF, EGF, KGF, TGF beta1). ; Changes in gene expression for pro‐inflammatory cytokines in the specimen of granulation tissue taken from wound edge.(IL‐1Beta, IL‐6, TNF‐alpha) Percentage change/decrease in WSA after 4 weeks of intervention with SWC + sham ES, SWC + cathode HVMPC, and SWC + anode HVPC (to compare changes in PU surface area between the groups). INCLUSION CRITERIA: Patient eligibility for the experiment will be established by their physician according to the following criteria: patients with either paraplegia or quadriplegia caused by congenital, medical, or traumatic central nervous system injury, over the age of 18 years, hospitalized in rehabilitation centre, with a Category II, III or IV PU of at least 0.5 cm2 in size and of minimal duration 4 weeks.