Rapid non-invasive measurement of mitochondrial oxygen tension after microneedle pre-treatment: a feasibility study in human volunteers.

Abstract

Mitochondrial oxygen tension (MitoPO2) is a promising novel non-invasive bedside marker of circulatory shock and is associated with organ failure. The measurement of mitoPO2 requires the topical application of 5-aminolevulinc acid (ALA) to induce sufficient concentrations of the fluorescent protein protoporphyrin-IX within (epi)dermal cells. Currently, its clinical potential in guiding resuscitation therapies is limited by the long induction time prior to obtaining a reliable measurement signal. We investigated whether microneedle pre-treatment of the skin before ALA application allows for earlier measurement of mitoPO2 in healthy human volunteers. 9 healthy human volunteers were included as part of physiological feasibility study. All participants had two ALA-care plasters administered on the chest after cleaning. One part of the skin was pretreated with microneedling, which perforates the epidermis with a depth of 0.30 mm. The time-to-sufficient signal was recorded for both untreated and microneedled ALA-care application. After induction mitoPO2 was varied using different FiO2 and the agreement between untreated and microneedled skin for mitoPO2 and mitoVO2 was recorded. Pre-treatment with microneedling induced reliable signal at 2 (IQR: 2-2) hours after topical ALA administration compared to 3 (IQR: 3-4) hours without pre-treatment (p = 0.02). The intraclass correlation of mitoPO2 simultaneously measured on microneedling and untreated skin was 0.892 (95%CI 0.821-0.936). MitoVO2 showed poor agreement between untreated and microneedling with an ICC of 0.316 (0.04-0.55). We demonstrate that pre-treatment with microneedling before topical application of 5-aminolevulinic acid enables obtaining a reliable and accurate mitoPO2 signal at least an hour faster than on untreated skin in our population of human volunteers. This potentially increases the applicability of mitoPO2 measurements in acute settings.Trial registration number: R21.106 (01-01-2022).