Hilderink B N, Juffermans N P, Pillay J
Department of Intensive Care, OLVG Hospital, Amsterdam, The Netherlands.
Laboratory of Translational Intensive Care, Erasmus MC, University Medical Center, Molewaterplein 40, 3000 CA, Rotterdam, The Netherlands.
J Clin Monit Comput. 2025 Apr;39(2):427-434. doi: 10.1007/s10877-024-01249-9. Epub 2024 Dec 26.
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).
线粒体氧张力（MitoPO2）是一种很有前景的新型循环休克非侵入性床边标志物，且与器官衰竭相关。测量MitoPO2需要局部应用5-氨基乙酰丙酸（ALA），以在（表）皮细胞内诱导足够浓度的荧光蛋白原卟啉-IX。目前，其在指导复苏治疗方面的临床潜力受到获取可靠测量信号前较长诱导时间的限制。我们研究了在应用ALA之前对皮肤进行微针预处理是否能使健康人类志愿者更早测量MitoPO2。9名健康人类志愿者作为生理可行性研究的一部分被纳入。所有参与者在清洁后在胸部贴上两片ALA护理贴剂。皮肤的一部分用微针进行预处理，微针可穿透表皮达0.30毫米深度。记录未处理和经微针处理的ALA护理贴剂达到足够信号的时间。诱导后，通过改变不同的吸入氧分数（FiO2）来改变MitoPO2，并记录未处理皮肤和经微针处理皮肤在MitoPO2和线粒体氧耗量（MitoVO2）方面的一致性。与未预处理时3（四分位间距：3-4）小时相比，微针预处理在局部应用ALA后2（四分位间距：2-2）小时诱导出可靠信号（p = 0.02）。在微针处理皮肤和未处理皮肤同时测量的MitoPO2的组内相关系数为0.892（95%置信区间0.821-0.936）。MitoVO2在未处理和微针处理之间的一致性较差，组内相关系数为0.316（0.04-0.55）。我们证明，在局部应用5-氨基乙酰丙酸之前进行微针预处理，在我们的人类志愿者群体中，能够比未处理皮肤至少提前一小时获得可靠且准确的MitoPO2信号。这可能会增加MitoPO2测量在急性情况下的适用性。试验注册号：R21.106（2022年1月1日）。
