Oxygenation Status in Chronic Leg Ulcer After Topical Hemoglobin Application May Act as a Surrogate Marker to Find the Best Treatment Strategy and to Avoid Ineffective Conservative Long-term Therapy.

Abstract

Chronic leg ulcers can be a challenge to treat and long-term therapy a significant cost factor in western public health budgets. Objective wound assessment assays enabling selection of appropriate wound therapy regimes would be desirable. Oxygenation status in ulcer tissue has obtained increased attention as a relevant factor in wound healing. To increase oxygenation in wounds, a topical hemoglobin spray was developed. Although favorable results have been noted, the link between clinical efficacy and the mode of action has not been demonstrated. The aims were to determine if changes in tissue oxygenation can be measured after topical application of hemoglobin on chronic wounds and to evaluate the findings in terms of therapy strategies. Photoacoustic imaging was used to measure the local oxygen saturation (StO2) in leg ulcers before and after hemoglobin spray treatment. Sclerosis of the leg ulcers was histopathologically graded and the change in wound size was documented in a follow-up examination. Measuring 49 patients, an increase in StO2 after topical hemoglobin application from on average 66.1 to 71% (p=0.017) after 20min was observed. Depending on the increase in StO2 (>10% or <10%) patients were stratified into a Responder and a Non-Responder group. Wound size significantly decreased in the Responder Group (p=0.001), while no significant difference in the Non-Responder group (p=0.950) was noted. Our findings suggest that the likelihood of wound healing under conservative therapy can be predicted by measuring changes in StO2 after topical hemoglobin application. This assay may reduce treatment time and costs by avoiding ineffective conservative long-term therapy. German Clinical Trials Register: DRKS00005993.