losartan-potassium and Pressure-Ulcer

Anemia of chronic disease (ACD) is thought to impair the responsiveness of erythroid progenitor cells, but research has shown treatment with recombinant human erythropoietin (rhuEPO) can improve patient hemoglobin levels and, subsequently, overall patient health status and quality of life. A prospective pilot study was designed to estimate the prevalence of ACD in outpatients with spinal cord injury (SCI) and chronic pressure ulcers (PUs) and examine the impact of rhuEPO on PU healing in this population. The charts of 49 SCI patients with PUs were reviewed; of those, 17 had anemia (hemoglobin <110 g/L). The prevalence of anemia in SCI patients with PUs was found to be approximately 35%. From these 17 potential participants, 5 had improved hemoglobin levels during the screening period (rendering them ineligible), 1 withdrew due to illness, and 7 died, leaving 4 participants to complete the study. Four patients (2 men, 2 women, average age 57 ± 16.5 years) ultimately were enrolled. Wound area and depth and cytokines were measured before, during, and after 6 weeks of treatment with rhuEPO, with a 3-month follow-up. Laboratory tests measuring hemoglobin, C-reactive protein, and prealbumin were used to monitor nutritional status and treatment response. No statistically significant changes were observed with treatment. Wound surface area and depth had mean decreases of 1.35 cm(2) and 0.58 cm, respectively, immediately post-treatment. Participants' elevated C-reactive protein levels (91.1-14.2 mg/L) decreased with rhuEPO treatment, but returned to baseline levels post-treatment (83.2-14.3 mg/L). Prealbumin levels were consistently low (range of 0.1-0.21 g/L). This research indicates rhuEPO treatment may improve some outcomes for ACD-SCI PU patients, but larger randomized controlled trials are required. The results of this study suggest the prevalence of ACD in the SCI outpatient population with PUs is at least 35%, and increased vigilance of patient nutrition is recommended.

Topics: Adult; Aged; Anemia; Chronic Disease; Erythropoietin; Female; Humans; Male; Middle Aged; Pilot Projects; Pressure Ulcer; Prevalence; Prospective Studies; Quality of Life; Recombinant Proteins; Spinal Cord; Wound Healing

An increased risk of skin pressure ulcers (PUs) is common in patients with sensory neuropathies, including those caused by diabetes mellitus. Recombinant human erythropoietin (rhEPO) has been shown to protect the skin against PUs developed in animal models of long-term diabetes. The aim of this work was to determine whether rhEPO could prevent PU formation in a mouse model of drug-induced SFN. Functional SFN was induced by systemic injection of resiniferatoxin (RTX, 50 µg/kg, i.p.). RhEPO (3000 UI/kg, i.p.) was given the day before RTX injection and then every other day. Seven days after RTX administration, PUs were induced by applying two magnetic plates on the dorsal skin. RTX-treated mice expressed thermal and mechanical hypoalgesia and showed calcitonin gene-related peptide (CGRP) and substance P (SP) depletion without nerve degeneration or vascular dysfunction. RTX mice developed significantly larger stage 2 PUs than Vehicle mice. RhEPO prevented thermal and mechanical hypoalgesia and neuropeptide depletion in small nerve fibers. RhEPO increased hematocrit and altered endothelium-dependent vasodilatation without any effect on PU formation in Vehicle mice. The characteristics of PUs in RTX mice treated with rhEPO and Vehicle mice were found similar. In conclusion, RTX appeared to increased PU development through depletion of CGRP and SP in small nerve fibers, whereas systemic rhEPO treatment had beneficial effect on peptidergic nerve fibers and restored skin protective capacities against ischemic pressure. Our findings support the evaluation of rhEPO and/or its non-hematopoietic analogs in preventing to prevent PUs in patients with SFN.

Topics: Animals; Disease Models, Animal; Diterpenes; Erythromelalgia; Erythropoietin; Mice; Neuroprotective Agents; Pressure Ulcer

Pressure-induced vasodilatation (PIV), a cutaneous physiological neurovascular (C-fiber/endothelium) mechanism, is altered in diabetes and could possibly contribute to pressure ulcer development. We wanted to determine whether recombinant human erythropoietin (rhEPO), which has protective neurovascular effects, could prevent PIV alteration and pressure ulcer formation. We developed a skin pressure ulcer model in mice by applying two magnetic plates to the dorsal skin. This induced significant stage 2 ulcers (assessed visually and histologically) in streptozotocin-treated mice with 8 weeks of diabetes compared with very few in controls. Control and streptozotocin mice received either no treatment or systematic rhEPO (3,000 UI kg(-1) intraperitoneally, twice a week) during the last 2 weeks of diabetes. After 8 weeks of diabetes, we assessed ulcer development, PIV, endothelium-dependent vasodilation, C-fiber-mediated nociception threshold, and skin innervation density. Pretreatment with rhEPO fully prevented ulcer development in streptozotocin mice and also fully restored C-fiber nociception, skin innervation density, and significantly improved PIV, but had no effect on endothelium-dependent vasodilation. Our finding that rhEPO treatment protects the skin against pressure-induced ulcers in diabetic mice encourages evaluation of the therapeutic potential for non-hematopoietic analogs of EPO in preventing neuropathic diabetic ulcers.

Topics: Animals; Diabetes Mellitus, Experimental; Disease Models, Animal; Dose-Response Relationship, Drug; Erythropoietin; Injections, Intraperitoneal; Magnetics; Male; Mice; Nerve Fibers, Unmyelinated; Pressure Ulcer; Recombinant Proteins; Skin; Streptozocin; Treatment Outcome

Patients with hemoglobin greater than or equal to 100 g/L may have difficulty healing pressure ulcers because of impaired tissue oxygenation. Decreased hemoglobin is often anemia of chronic disease and may be due to the effects of inflammatory cytokines on erythroid progenitor cells. Recombinant human erythropoietin has been found to reverse anemia of chronic disease and may act as a growth factor in wound healing. To review the effect of 6 weeks of subcutaneous recombinant human erythropoietin 75 IU/kg administered 3 times weekly to resolve refractory anemia of chronic disease and heal Stage IV pressure ulcers, a retrospective chart review was conducted of four spinal cord injured patients (all men, mean age 59 years +/- 19) with Stage IV pressure ulcers and multiple comorbid conditions. The patients received recombinant human erythropoietin either through an inpatient spinal cord rehabilitation unit or an outpatient wound management clinic as part of interdisciplinary care. Mean hemoglobin increased from 88 +/- 7.4 g/L to 110 +/- 3.7 g/L. Mean ulcer surface area decreased from 42.3 cm2 (+/- 40.2) to 37.3 cm2 (+/- 44.3) despite extensive deroofing of one ulcer and subsequent increase in size. Mean ulcer depth decreased from 2.3 cm (+/- 1.2) to 1.2 cm (+/- 1.0). Human recombinant erythropoietin shows promise in resolving the refractory anemia of chronic disease associated with Stage IV pressure ulcers. Further study is suggested.

Topics: Adult; Aged; Anemia; Chronic Disease; Cost-Benefit Analysis; Drug Administration Schedule; Drug Costs; Erythropoietin; Hemoglobins; Humans; Injections, Subcutaneous; Male; Middle Aged; Pressure Ulcer; Recombinant Proteins; Retrospective Studies; Risk Factors; Severity of Illness Index; Spinal Cord Injuries; Treatment Outcome; Wound Healing

Anemia in patients with grade IV pressure sores is usually refractory to therapy with iron salts, and red cell transfusions are commonly required when reconstructive surgery is performed. The anemia is characterized by hypoferremia, reticulocytopenia, and normal-to-increased serum ferritin. Five patients with this anemia were treated with recombinant human erythropoietin (rHuEPO) in doses of 50 to 100 U/kg, given subcutaneously three times per week. The hemoglobin increased in every patient; the mean (+/- SD) value at the initiation of treatment was 8.8 +/- 1.0 g/dL, and after a median of 4 weeks of therapy, it was 12.4 +/- 1.6 g/dL (p less than .001). No adverse effects of treatment were observed. It is concluded that rHuEPO is a promising new agent for pressure sore anemia, but randomized, controlled clinical trials will be required to firmly establish its place in the management of patients with this type of anemia.

Topics: Adult; Aged; Anemia, Hypochromic; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Pressure Ulcer; Recombinant Proteins