Mark Wefers Bettink

Chapter 9 168 in the heme-biosynthetic pathway, synthesized inside the mitochondria. Under normal (non-sensitized) conditions PpIX concentrations in human skin are very low and non- detectable with COMET. Administration of 5-aminolevulinic acid (ALA) increases mitochondrial PpIX concentrations and ensures the mitochondrial origin of the delayed fluorescence signal (15). Therefore, to enable measurements with the COMET monitor, ALA needs to be applied on skin to induce PpIX, the latter acting as mitochondrially located oxygen-sensitive dye (17,18). ALA is registered for use in adults, for example for photodynamic therapy in dermatologic pathology (19,20) and to visualize brain tumors during fluorescence-guided surgery (21,22) and was not used in pediatric patients until recently. Research with cutaneous ALA administration up to 354 mg in infants of 5 years and older reported no side effects.(23) Oral administration of 20 mg/kg ALA in infants of 1 year and older showed a transient increase of alanine aminotransferase (24)(25)(26). Rarely, the administration of 5-aminolevulinic acid led to an allergic reaction, in here contact dermatitis are the only reported allergies.(27) Therefore, we assumed the safety on a systemic level of a very low dosage of ALA – 8mg – on the skin of neonates, providing an opportunity to use COMET monitoring in neonates for the first time. Primary outcomes of this study were feasibility and safety, especially local (photo)toxicity, of cutaneous ALA administration in combination with using the COMET monitor in neonates perioperatively. A secondary outcome was preliminary evaluation of anesthesiologic and surgical procedures influencing mitoPO 2 . Material and Methods The institutional research board approved a feasibility study of 15 neonates (MEC 2017- 145). After obtained informed consent from both parents, measurements were performed during surgical treatment of neonates with congenital diaphragmatic hernia (CDH) or esophageal atresia (EA). Surgery took place in the operating theater, unless the neonate was on extracorporeal membrane oxygenation (ECMO), in which case the surgery was performed in the pediatric intensive care unit due to logistics. In this study the feasibility was defined as the possibility of priming the skin with ALA and to measure mitoPO 2 in neonates. The safety was defined as (the lack of) any adverse event of the skin after cutaneous administration of ALA and measurement with COMET until 48 hours after the COMET-skin sensor was removed.