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Skin Integrity and Pressure Injuries

Recombinant Human Erythropoietin

Chronic ulcers experienced by individuals, such as those with SCI, with hemoglobin values less than 100 g/L may be difficult to heal because of impaired tissue oxygenation. It is important to distinguish between iron deficiency anemia and anemia of chronic disease. This condition occurs in individuals with chronic inflammatory and/or infectious processes; a chronic non-healing pressure injury is a chronic inflammatory condition. Anemia of chronic disease is thought to be the result of impaired red blood cell production because of persistently elevated levels of circulating inflammatory cytokines (Spivak 2002). The endogenous hormone erythropoietin and recombinant human erythropoietin (rHuEPO) play crucial roles in the regulation of hematopoiesis and induce red blood cell production. It has direct hemodynamic and vasoactive effects and modulates the inflammatory process, thereby potentially reversing the conditions believed to underlie chronic pressure injuries. Treatment with rHuEPO has been shown to be effective in increasing hemoglobin values in five individuals with stage IV pressure injuries related to anemia of chronic disease (Turba et al. 1992) and in the complete healing of a chronic leg ulcer in a single case report (Al-Momen 1991). One study has been performed that investigated the value of rHuEPO in the healing of chronic wounds among those with SCI.

Author Year
Country
Research Design
PEDro Score
Sample Size

Methods

Outcome

Vair et al. 2015
Canada
Pre-post
N=4
Population: Mean age=57 yr; Gender: males=2, females=2; Pressure injury stage: III=3, IV=1.
Intervention: Participants with nonhealing ulcers and low hemoglobin levels received recombinant human erythropoietin (rhuEPO) injections of 75 IU/kg, 3 times/wk, for 6 wk in addition to regular care.
Outcomes: Wound surface area; Wound depth.
1. Wound healing results were variable among participants, with no significant differences from baseline to 8 and 20 wk follow-up in terms of wound surface area and wound depth.
Keast & Fraser 2004
Canada
Pre Post
N=4
Population: Mean age: 59 yr; Gender: males=4, females=0.
Intervention: Six wk of recombinant human erythropoietin (75 IU/kg, three times per wk), in addition to regular rehabilitation practice (inpatient and outpatient).
Outcome Measures: Hemoglobin count; Pressure injury quantity, area, and depth.
1. Day 1: Mean hemoglobin=88g/L; Mean ulcer surface area=42.3cm2 ; Mean ulcer depth=2.3cm.
2. End of wk 6: Mean hemoglobin=110g/L. Mean ulcer surface=38.4cm2; Mean ulcer depth=1.2cm.

Discussion

A prospective pilot study was designed to estimate the prevalence of anemia of chronic disease (ACD) in outpatients with spinal cord injury (SCI) and chronic PIs and examine the impact of rhuEPO on PI healing (Vair et al. 2015). Four patients had wound area, depth, and cytokines measured before, during, and after 6 weeks of treatment with rhuEPO, with a 3-month follow-up. Wound surface area and depth had mean decreases of 1.35 cm² 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). 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 PIs is at least 35%, and increased vigilance of patient nutrition is recommended.

A retrospective chart review of four individuals with SCI and stage IV chronic pressure injuries was performed by Keast and Fraser (2004). Following treatment with 75 IU/kg of rHuEPO subcutaneously thrice weekly for six weeks, the mean baseline hemoglobin for the subjects increased from 88±7.4 g/L to 110±3.7 g/L. Mean ulcer surface area decreased from 42.3±40.2 cm2 to 38.4±44.3 cm2 over six weeks of treatment despite the fact that one of the subjects showed a significant increase in WSA as a result of surgical de-roofing performed to eliminate all undermining. All subjects showed a decrease in the depth of the target ulcer from 2.3±1.2 cm to 1.2±1.0 cm. Observations suggested that some of the subjects demonstrated increased ability to fight recurrent infections; all subjects reported that they felt more energetic and better able to participate in their rehabilitation activities. No adverse effects were observed. rHuEPO shows promise not only in resolving the anemia of chronic disease associated with stage IV pressure injuries but also in the healing of these wounds in persons with SCI although further study is warranted.

Conclusion

There is level 4 evidence (from two pre-post tests: Keast & Fraser 2004; Vair et al. 2015) that recombinant human erythropoietin aids in the healing of stage IV chronic non-healing pressure injuries post SCI.

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