Mark Wefers Bettink

Mitochondrial oxygen monitoring during surgical repair of congenital diaphragmatic hernia or esophageal atresia: 9 173 Discussion This is the first study showing feasibility of mitoPO 2 measurements in neonates, and importantly, in a clinically relevant high-risk perioperative setting. Measurements with the COMET monitor proved feasible and safe in terms of local damage to the skin. Furthermore, pathophysiological disturbances led to perturbations in mitoPO 2 . In twelve out of fifteen patients mitoPO 2 measurements were successful. Failures were caused by external and potentially preventable factors, disabling detection of an adequate delayed fluorescence signal. In one case infrared warming lamp heat or radiation interfered with the priming of the skin with ALA. Aluminum foil is a strong infrared reflector and was successfully used to shield the ALA plaster against infrared radiation during priming of the skin in the following cases. In the two other failed cases colored substances on the skin interfered with measurements, chlorohexidine with pink pigment and skin marker are both significant sources of delayed fluorescence and thereby potent disturbers of the mitochondrial PpIX light emission. Safety of ALA administration with Alacare plasters was a major concern for the ethics committee due to the off-label use of ALA for measuring mitoPO 2 with the COMET. The reaction of the neonatal skin on ALA administration was unknown and consequently we only obtained approval to perform this feasibility and safety study. ALA makes the skin sensitive for light, consequently it is frequently used for photodynamic therapy in different sorts of dermatologic pathology. In children of five years and older, the administration of ALA up to 354 mg, which is over 40 times higher than de 8mg ALA that was applied on the skin in this study, did not have any 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). Systemic effects of topical/local administration of ALA on the skin have not been reported and in this study, we focused on potential local side effects in neonatal skin. There is a risk for erythema and burns when the skin is exposed to (day)light after the administration of ALA. Therefore, precautionary measures were taken to shield the skin for light for 48 hours after the measurement with the COMET was ended and the skin sensor was removed. In none of the cases local damage or irritation of the skin was observed, so the combination of ALA-plaster and COMET measurements seems safe. The pharmacokinetic properties of topical ALA administration with Alacare in neonates are unknown, but in adults the reported skin priming time with ALA takes 4 till 8 hours (13). In this study, the same priming times were maintained for neonates. In a following

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