Pressure Injuries Treated With Anodal and Cathodal High-voltage Electrical Stimulation: the Effect on Blood Serum Concentration of Cytokines and Growth Factors in Patients With Neurological Injuries. A Randomized Clinical Study.

It remains unclear whether electrical currents can affect biological factors that determine chronic wound healing in humans. PURPOSE: The aim of this study was to determine whether anodal and cathodal high-voltage monophasic pulsed currents (HVMPC) provided to the area of a pressure injury (PI) change the blood level of cytokines (interleukin [IL]-1ß, IL-10, and tumor necrosis factor [TNF]-α) and growth factors (insulin-like growth factor [IGF]-1 and transforming growth factor [TGF]-ß1) in patients with neurological injuries and whether the level of circulatory cytokines and growth factors correlates with PI healing progression. METHODS: This study was part of a randomized clinical trial on the effects of HVMPC on PI healing. All patients with neurological injuries (spinal cord injury, ischemic stroke, and blunt trauma to the head) and a stage 2, stage 3, or stage 4 PI of at least 4 weeks' duration hospitalized in one rehabilitation center were eligible to participate if older than 18 years of age and willing to consent to donating blood samples. Exclusion criteria included local contraindications to electrical stimulation (cancer, electronic implants, osteomyelitis, tunneling, necrotic wounds), PIs requiring surgical intervention, patients with poorly controlled diabetes mellitus (HbA1C > 7%), critical wound infection, and/or allergies to standard wound treatment. Participants were randomly assigned to 1 of 3 groups: anodal (AG) or cathodal (CG) HVMPC treatment (154 µs; 100 Hz; 360 µC/sec; 1.08 C/day) or a placebo (PG, sham) applied for 50 minutes a day, 5 days per week, for 8 weeks. TNF-α, IL-1ß, IL-10, TGF-ß1, and IGF-1 levels in blood serum were assessed using the immunoenzyme method (ELISA) and by chemiluminescence, respectively, at baseline and week 4. Wound surface area measurements were obtained at baseline and week 4 and analyzed using a digitizer connected to a personal computer. Statistical analyses were performed using the maximum-likelihood chi-squared test, the analysis of variance Kruskal-Wallis test, the Kruskal-Wallis post-hoc test, and Spearman's rank order correlation; the level of significance was set at P ≤.05. RESULTS: Among the 43 participants, 15 were randomized to AG (mean age 53.87 ± 13.30 years), 13 to CG (mean age 51.08 ± 20.43 years), and 15 to PG treatment (mean age 51.20 ± 14.47 years). Most PIs were located in the sacral region (12, 74.42%) and were stage 3 (11, 67.44%). Wound surface area baseline size ranged from 1.00 cm2 to 58.04 cm2. At baseline, none of the variables were significantly different. After 4 weeks, the concentration of IL-10 decreased in all groups (AG: 9.8%, CG: 38.54%, PG: 27.42%), but the decrease was smaller in the AG than CG group (P = .0046). The ratio of pro-inflammatory IL-10 to anti-inflammatory TNF-α increased 27.29% in the AG and decreased 26.79% in the CG and 18.56% in the PG groups. Differences between AG and CG and AG and PG were significant (AG compared to CG, P = .0009; AG compared to PG, P = .0054). Other percentage changes in cytokine and growth factor concentration were not statistically significant between groups. In the AG, the decrease of TNF-α and IL-1ß concentrations correlated positively with the decrease of PI size (P <.05). CONCLUSION: Anodal HVMPC elevates IL-10/TNF-α in blood serum. The decrease of TNF-α and IL-1ß concentrations in blood serum correlates with a decrease of PI wound area. More research is needed to determine whether the changes induced by anodal HVMPC improve PI healing and to determine whether and how different electrical currents affect the activity of biological agents responsible for specific wound healing phases, both within wounds and in patients' blood. In clinical practice, anodal HVMPC should be used to increase the ratio of anti-inflammatory IL-10 to pro-inflammatory TNF-α , which may promote healing.

A Randomized, Controlled Clinical Study to Assess the Effect of Anodal and Cathodal Electrical Stimulation on Periwound Skin Blood Flow and Pressure Ulcer Size Reduction in Persons with Neurological Injuries.

The use of electrical stimulation (ES) should be considered for treating nonhealing pressure ulcers (PUs), but optimal ES wound treatment protocols have yet to be established. A randomized, controlled, double-blind clinical study was conducted to evaluate the effects of cathodal and anodal high-voltage monophasic pulsed current (HVMPC) on periwound skin blood flow (PSBF) and size reduction of Stage 2 to Stage 4 PUs of at least 4 weeks' duration. Persons >18 years of age, hospitalized with neurological injuries, at high risk for PU development (Norton scale <14 points; Waterlow scale >15 points), and with at least 1 Stage 2 to Stage 4 PU were eligible to participate in the study. Persons with necrotic wounds, osteomyelitis, electronic or metal implants in the PU area, PUs in need of surgical intervention, acute wound inflammation, diabetes (HBA1c >7%), diabetic neuropathy, cancer, and/or allergies to standard wound treatments were excluded. Patients were randomly assigned to 1 of 3 groups: anodal (AG), cathodal (CG), or placebo (PG) ES. All groups received individualized PU prevention and standard wound care. In the PG, sham ES was applied; the AG and CG were treated with anodal and cathodal HVMPC, respectively (154 µs 100 Hz; 360 µC/second; 1.08 C/day), 50 minutes per day, 5 days per week, for a maximum of 8 weeks. PSBF was measured using laser Doppler flowmetry at baseline, week 2, and week 4, and wound surface area measurements were obtained and analyzed using a digitizer connected to a personal computer. Data analysis utilized the maximum-likelihood chi-squared test, the analysis of variance Kruskal-Wallis test, the Kruskal-Wallis post-hoc test, and Spearman's rank order correlation. Nonlinear approximation based on exponential function was used to calculate treatment time needed to reduce the wound area by 50%. In all tests, the level of significance was set at P ≤.05. Of the 61 participating patients, 20 were in the AG (mean age 53.2 ± 13.82 years), 21 in the CG (mean age 55.67 ± 17.83 years), and 20 in the PG (mean age 52.5 ± 13.18 years). PUs (baseline size range 1.01 cm2 to 59.57 cm2; duration 4 to 48 weeks) were most frequently located in the sacral region (73.77%) and classified as Stage 3 (62.29%). PSBF at week 2 was significantly higher in the AG and CG than in the PG (P <.05). Week 4 differences were not statistically significant. Wound percentage area reduction calculated at week 8 for the AG (64.10% ± 29.22%) and CG (74.06% ± 23.23%) were significantly different from PG ulcers (41.42% ± 27.88%; P = .0391 and P = .0024, respectively). In both ES groups, PSBF at week 4 and percent wound surface area reductions between weeks 4 and 8 were positively correlated, but only the AG correlation was statistically significant (P = .049). In this study, both ES modalities improved blood flow and wound area reduction rate. Studies examining optimal ES treatment times for healing to occur, the effect of comorbidities and baseline wound variables on ES outcomes, and the nature of the relationship between blood flow and healing are necessary.

Evaluation of the Healing Progress of Pressure Ulcers Treated with Cathodal High-Voltage Monophasic Pulsed Current: Results of a Prospective, Double-blind, Randomized Clinical Trial.

OBJECTIVE: To investigate the effectiveness of high-voltage monophasic pulsed current (HVMPC) as an adjunct to a standard wound care for the treatment of Stage II and III pressure ulcers (PrUs). DESIGN: Prospective, randomized, double-blind, controlled clinical study. SETTING: Two nursing and care centers. PATIENTS: Patients with PrUs that did not respond to previous treatment for at least 4 weeks were randomly assigned to the electrical stimulation (ES) group (25 patients; mean age of 79.92 ± 8.50 years; mean wound surface area [WSA] of 10.58 ± 10.57 cm) or to the control group (24 patients; mean age of 76.33 ± 12.74 years; mean WSA of 9.71 ± 6.70 cm). INTERVENTIONS: Both the ES and control groups received standard wound care and respectively, cathodal HVMPC (154 microseconds; 100 pulses per second; 0.24 A; 250 µ/s) applied continuously for 50 minutes once a day, 5 times a week, or sham HVMPC. MAIN OUTCOME: Percentage area reduction over 6 weeks of intervention. MAIN RESULTS: In the ES group, there was a statistically significant decrease in WSA after 1 week of treatment (35% ± 30.5%) compared with 17.07% ± 34.13% in the control group (P = .032). After treatment, at week 6, percentage area reduction in the ES group was 80.31% ± 29.02% versus 54.65% ± 42.65% in the control group (P = .046). CONCLUSIONS: Cathodal HVMPC reduces the WSA of Stage II and III PrUs. The results are consistent with the results of other researchers who used HVMPC to treat PrUs.