Pathogenesis Of Pressure Ulcers Research Articles

Predictors of COVID-19 disease severity augment the Braden scale in the prediction of pressure ulcer development among COVID-19–positive intensive care unit patients: A case-control study

Predictors of COVID-19 disease severity augment the Braden scale in the prediction of pressure ulcer development among COVID-19–positive intensive care unit patients: A case-control study

Protective effect of dimethyl fumarate for the development of pressure ulcers after cutaneous ischemia-reperfusion injury.

Ischemia-reperfusion (I/R) is associated with various pathogenic conditions, and there has been increasing evidence that cutaneous I/R injury is associated with the pathogenesis of pressure ulcers (PUs), especially at the early stage presenting as non-blanchable erythema. Several studies demonstrated that oxidative stress is a key player in I/R injury, and the inhibition of oxidative stress may be capable of protecting tissue damage after I/R injury in various organs including skin. Dimethyl fumarate (DMF) approved by the Food and Drug Administration is Nrf2 activator, and recent studies revealed the antioxidative and anti-inflammatory effects of DMF on I/R injury in animal models. Our objective was to assess the effects of oral administration of DMF on the development of PUs after cutaneous I/R injury in mice. We found that DMF administration significantly decreased the size of PUs after cutaneous I/R. Cutaneous I/R-induced oxidative stress was also significantly inhibited by DMF in OKD48 mice, in which oxidative stress can be visually assessed. In addition, DMF treatment decreased hypoxic area, the numbers of apoptotic cells, and vascular loss in I/R area. DMF treatment suppressed the infiltration of MPO+ neutrophils and the production of proinflammatory cytokines in I/R site after cutaneous I/R injury. in vitro experiments, DMF treatment suppressed the production of reactive oxygen species in pericyte-like cells. These results suggest that DMF treatment might prevent the formation of PUs induced by cutaneous I/R injury via suppressing oxidative stress and subsequent inflammation. DMF treatment during the early phase of decubitus ulcers might protect against further progression.

Topical betamethasone butyrate propionate exacerbates pressure ulcers after cutaneous ischemia-reperfusion injury.

Ischaemia-reperfusion (I/R) is involved in the development of various organ diseases. There has been increasing evidence that cutaneous I/R injury is associated with the pathogenesis of pressure ulcers (PUs), especially at the early stage presenting as non-blanchable erythema. However, there is no evidence-based treatment for early-stage PUs. Our objective was to assess the effects of topical steroid on the development of PUs after cutaneous I/R injury in mice. Cutaneous I/R was performed by trapping the dorsal skin between two magnetic plates for 12 h, followed by plate removal. Topical application of betamethasone butyrate propionate (BBP) in I/R areas significantly increased the size of PUs after I/R. The number of thromboses was increased, and CD31(+) vessels were decreased in the I/R area treated with topical BBP. The number of oxidative stress-associated DNA-damaged cells and apoptotic cells in the I/R area was increased by topical BBP treatment. In addition, the mRNA level of NADPH oxidase 4 (Nox4), the essential enzyme that produces reactive oxygen species, was significantly increased and that of NF-E2-related factor 2 (Nrf2), a transcription factor that regulates the expression of antioxidant proteins, was inhibited in the I/R area treated by BBP. The number of CD68(+) macrophages and the level of transforming growth factor-beta in lesional skin were also decreased by BBP. These results suggest that a topical steroid might accelerate the formation of PUs induced by cutaneous I/R injury by aggravating oxidative stress-induced tissue damage. Topical steroids might not be recommended for the treatment of acute-phase decubitus ulcers.

Potential efficiency of antioxidants to prevent pressure ulcers. A neglected hypothesis

Pressure ulcers are necrotic lesions mainly due to capillary hypoperfusion. It is well known that hypoxia and also subsequent oxygenation at reperfusion provoke the formation of reactive oxygen species (ROS) responsible for cell death. The hypothesis of their participation in the pathogenesis of pressure ulcers has already been tested; several antioxidants have the capacity to inhibit skin necrosis in animal models but their efficiency in preventing bedsores has never been demonstrated in patients. The failure of clinical trials to show the protective activity of some antioxidants does not rule out the involvement of ROS in ischemic ulcers and the potential efficacy of other antioxidants in preventing their formation remains possible.

Weight-bearing-induced changes in the microtopography and structural stiffness of human skin in vivo following immobility periods.

Pressure ulcers (PUs) are injuries to the skin and underlying tissues, caused by sustained deformations and occur frequently in aged patients. Skin microtopography and stiffness affect the interaction of skin with contact surfaces contributing to PU development. We simulated immobility in 20 healthy females (mean age 69.9 years). Skin microtopography and stiffness were measured at the PU predilection sites before and after loading. Skin roughness decreased at the heels by 18.1% after 90 minutes (p = 0.022), but remained unchanged at the sacrum and the upper back. Structural elasticity and elastic deformations increased at all skin areas; changes over time were significant at the sacrum (p = 0.005) and the heel, (p = 0.002). The residual skin deformation increased at all skin areas after loading significantly at the sacrum (32.0%, p = 0.013) and upper back (20.6%, p = 0.007). The structural "biological" elasticity of the skin decreased significantly at the upper back after loading, but remained unchanged at the heels. All skin changes recovered after unloading. Results indicate that prolonged loading causes structural skin changes in humans in vivo in PU predilection sites. The pathogenesis of PUs is different at the heels, the sacral and upper back skin.

Trauma and thrombosis in the pathogenesis of pressure ulcers

It was surprising to discover at a recent conference on the pathophysiology of pressure ulcers that the etiology of pressure lesions was considered by many speakers to be rather mysterious. Such a state of affairs may well exist because the pathogenesis of pressure lesions (bed sores) has been insufficiently debated to weed out inadequate causal hypotheses. One reason could be that few people who study pressure ulcers are perceived to be acceptably qualified in the various disciplines now involved: engineering, medicine, nursing, physiotherapy, and so forth. The treatment of pressure ulcers is similarly diverse, with dermatologists, geriatricians, nurses, physiatrists, plastic surgeons, and others being concerned. Perhaps there are few people who are willing to challenge the work of specialists from different disciplines? Admittedly, pressure ulcers can have more than one cause, and this complicates any discussion about their etiology. In consequence, I shall mainly focus on small to medium ulcers that are uncomplicated by bacterial infection and have every appearance of being caused by sustained point (uniaxial) pressure rather than an angled (shearing) force and/or a frictional effect. Also, I shall assume that the point pressure is vertical or bnormalQ (at right angles) to the body part concerned. These lesions will be called normal pressure ulcers (NPUs).

Development of a Simple, Noninvasive, Clinically Relevant Model of Pressure Ulcers in the Mouse

The formation of pressure ulcers and other skin wounds is considered to be a multifactorial process. Cycles of ischemia–reperfusion have been considered to be significant contributing factors in the pathogenesis of pressure ulcers. This study reports the development of a reproducible murine model of ischemia–reperfusion injury by the external application of magnets. Mice were sedated with 50% CO2:50% O2 for 50–60 s. Dorsal hair was shaved and the area cleaned. The skin was gently pulled and placed between two round ceramic magnetic plates (5 × 12 mm diameter, 2.4 g weight, 1000 G magnetic force). The resultant “pinch” procedure was designed to leave a 5-mm skin bridge between the magnets, creating 50 mm Hg pressure between the plates. Three 12-h ischemia–reperfusion cycles were employed to cause pressure ulcer formation. Animals tolerated the procedure well. They returned to normal activity a few minutes after magnet placement. The lesions reached their maximum at 10 days postinjury. Full-thickness skin loss with damage and necrosis of subcutaneous tissue (ulcer stage 3) was observed in all cases, reaching a mean stage score of 3.6 ± 0.6 of based on a 0–5 scale for extent of injury by visual assessment. Thus, an inexpensive, reproducible murine pressure ulcer model was developed, which results in graded injury without long-term immobilization of the animals. This method will facilitate the development of new prevention and management strategies.

The Role of Allopurinol and Deferoxamine in Preventing Pressure Ulcers in Pigs

Ischemia and reperfusion may be important in the pathogenesis of pressure ulcers. On the basis of this hypothesis, the effects of intermittent pressure and the antifree radical agents allopurinol and deferoxamine were studied in a pig model in which a pressure of 150 mmHg was applied intermittently to the scapulae. Cutaneous blood flow, transcutaneous oxygen tension, skin and muscle damage, and muscle levels of adenosine triphosphate were quantified. A control group of pigs (n = 6) was untreated, the allopurinol group (n = 6) received oral allopurinol beginning 2 days before the experiment, and the deferoxamine group (n = 6) received an intramuscular injection of deferoxamine 2 hours before the experiment. Pressure (150 mmHg) was applied to the scapulae for 210 minutes, and it was relieved for 30 minutes. This 4-hour cycle was repeated continuously for 48 hours, and it resulted in pressure injuries in all animals. Allopurinol and deferoxamine improved cutaneous blood flow and tissue oxygenation, but only deferoxamine could significantly reduce cutaneous and skeletal muscle necrosis (p < 0.001). This study suggests a future role for antifree radical agents in the reduction of pressure-induced injury. (Plast. Reconstr. Surg. 105: 1408, 2000.)

The role of allopurinol and deferoxamine in preventing pressure ulcers in pigs.

Ischemia and reperfusion may be important in the pathogenesis of pressure ulcers. On the basis of this hypothesis, the effects of intermittent pressure and the anti-free radical agents allopurinol and deferoxamine were studied in a pig model in which a pressure of 150 mmHg was applied intermittently to the scapulae. Cutaneous blood flow, transcutaneous oxygen tension, skin and muscle damage, and muscle levels of adenosine triphosphate were quantified. A control group of pigs (n = 6) was untreated, the allopurinol group (n = 6) received oral allopurinol beginning 2 days before the experiment, and the deferoxamine group (n = 6) received an intramuscular injection of deferoxamine 2 hours before the experiment. Pressure (150 mmHg) was applied to the scapulae for 210 minutes, and it was relieved for 30 minutes. This 4-hour cycle was repeated continuously for 48 hours, and it resulted in pressure injuries in all animals. Allopurinol and deferoxamine improved cutaneous blood flow and tissue oxygenation, but only deferoxamine could significantly reduce cutaneous and skeletal muscle necrosis (p < 0.001). This study suggests a future role for anti-free radical agents in the reduction of pressure-induced injury.