Composition of Wound Fluid from Pressure Ulcers
The purpose of this pilot study was to characterize changes in concentrations of tumor necrosis factor (TNF)-a, interleukin (IL)-1b, matrix metalloproteinase (MMP)-3, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-1 in wound fluid collected from pressure ulcers in adults treated with negative pressure wound therapy (NPWT; V.A.C.® Therapy, KCI, San Antonio, Tex). Wound fluids were collected from 8 patients with Stage III or IV pressure ulcers in home care and extended care settings. Concentrations of analytes were measured immediately prior to initiation of NPWT (Day 0) and at Days 1, 3, and 7 continuous NPWT. There were statistically significant (P < 0.05) decreases from baseline in the levels of MMP-3 (Day 0 > [Day 1 ~ Day 3 ~ Day 7]), MMP-9 (Day 0 > [Day 1 ~ Day 3]), and MMP-3:TIMP-1 ratios (Day 0 > [Day 1 ~ Day 3 ~ Day 7]). No other significant differences were detected. Previous studies have shown a consistent decrease in protease levels to have prognostic value for healing. Thus, the change in composition of fluids from pressure ulcers treated with NPWT may be beneficial to wound healing.
Pressure ulcers develop when persistent pressure on soft tissue over a bony site obstructs capillary flow, leading to tissue necrosis. Physiological response to tissue injury initiates a cascade of overlapping events that may last from days to months, depending on the ability of the wound to proceed through the healing process in an orderly and timely manner. An acute wound becomes chronic when it fails to heal properly in an appropriate timeframe. Some of the key regulators of wound healing include pro-inflammatory cytokines, growth factors, proteases, and protease inhibitors. Wound chronicity is thought to be, in part, a result of disruption in the temporal sequence and the concentrations of these biomolecules.
Negative pressure wound therapy (NPWT; V.A.C.® Therapy, KCI, San Antonio, Tex) has been shown to help promote healing of wounds, including pressure ulcers. One postulate is that modulation of key mediators of wound healing contribute to the clinical success associated with NPWT. Previous studies in pigs have shown that NPWT can have an effect on systemic levels of inflammatory cytokines within the first few hours of application. Stechmiller et al showed that wound fluid from NPWT-treated pressure ulcers in patients in an acute care setting exhibited significant decrease in the levels of tumor necrosis factor (TNF)-α from pre-therapy levels but presented no differences in protease levels. It is thought that the inpatients in that study had acute inflammation (as demonstrated by elevated initial TNF-α levels) but may have had lower initial levels of proteases because of better attention to debridement, treatment compliance, and nutritional support than in non-inpatient care settings. Thus, the current study focused on pressure ulcer patients in home care and extended care settings. The purpose of this pilot study was to test the hypothesis that pro-inflammatory cytokine, matrix metalloproteinase (MMPs), and tissue inhibitor of metalloproteinase (TIMP) levels in wound fluid from pressure ulcers treated with NPWT change over a period of 7 days.
Abstract and Introduction
Abstract
The purpose of this pilot study was to characterize changes in concentrations of tumor necrosis factor (TNF)-a, interleukin (IL)-1b, matrix metalloproteinase (MMP)-3, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-1 in wound fluid collected from pressure ulcers in adults treated with negative pressure wound therapy (NPWT; V.A.C.® Therapy, KCI, San Antonio, Tex). Wound fluids were collected from 8 patients with Stage III or IV pressure ulcers in home care and extended care settings. Concentrations of analytes were measured immediately prior to initiation of NPWT (Day 0) and at Days 1, 3, and 7 continuous NPWT. There were statistically significant (P < 0.05) decreases from baseline in the levels of MMP-3 (Day 0 > [Day 1 ~ Day 3 ~ Day 7]), MMP-9 (Day 0 > [Day 1 ~ Day 3]), and MMP-3:TIMP-1 ratios (Day 0 > [Day 1 ~ Day 3 ~ Day 7]). No other significant differences were detected. Previous studies have shown a consistent decrease in protease levels to have prognostic value for healing. Thus, the change in composition of fluids from pressure ulcers treated with NPWT may be beneficial to wound healing.
Introduction
Pressure ulcers develop when persistent pressure on soft tissue over a bony site obstructs capillary flow, leading to tissue necrosis. Physiological response to tissue injury initiates a cascade of overlapping events that may last from days to months, depending on the ability of the wound to proceed through the healing process in an orderly and timely manner. An acute wound becomes chronic when it fails to heal properly in an appropriate timeframe. Some of the key regulators of wound healing include pro-inflammatory cytokines, growth factors, proteases, and protease inhibitors. Wound chronicity is thought to be, in part, a result of disruption in the temporal sequence and the concentrations of these biomolecules.
Negative pressure wound therapy (NPWT; V.A.C.® Therapy, KCI, San Antonio, Tex) has been shown to help promote healing of wounds, including pressure ulcers. One postulate is that modulation of key mediators of wound healing contribute to the clinical success associated with NPWT. Previous studies in pigs have shown that NPWT can have an effect on systemic levels of inflammatory cytokines within the first few hours of application. Stechmiller et al showed that wound fluid from NPWT-treated pressure ulcers in patients in an acute care setting exhibited significant decrease in the levels of tumor necrosis factor (TNF)-α from pre-therapy levels but presented no differences in protease levels. It is thought that the inpatients in that study had acute inflammation (as demonstrated by elevated initial TNF-α levels) but may have had lower initial levels of proteases because of better attention to debridement, treatment compliance, and nutritional support than in non-inpatient care settings. Thus, the current study focused on pressure ulcer patients in home care and extended care settings. The purpose of this pilot study was to test the hypothesis that pro-inflammatory cytokine, matrix metalloproteinase (MMPs), and tissue inhibitor of metalloproteinase (TIMP) levels in wound fluid from pressure ulcers treated with NPWT change over a period of 7 days.
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