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Decreased surfactant phosphatidylcholine synthesis in neonates with congenital diaphragmatic hernia during extracorporeal membrane oxygenation.

ABSTRACT: Congenital diaphragmatic hernia (CDH) may result in severe respiratory insufficiency with a high morbidity. The role of a disturbed surfactant metabolism in the pathogenesis of CDH is unclear. We therefore studied endogenous surfactant metabolism in the most severe CDH patients who required extracorporeal membrane oxygenation (ECMO).Eleven neonates with CDH who required ECMO and ten ventilated neonates without significant lung disease received a 24-h infusion of the stable isotope [U-(13)C] glucose. The (13)C-incorporation into palmitic acid in surfactant phosphatidylcholine (PC) isolated from serial tracheal aspirates was measured. Mean PC concentration in epithelial lining fluid (ELF) was measured during the first 4 days of the study.Fractional surfactant PC synthesis was decreased in CDH-ECMO patients compared to controls (2.4 +/- 0.33 vs. 8.0 +/- 2.4%/day, p = 0.04). The control group had a higher maximal enrichment (0.18 +/- 0.03 vs. 0.09 +/- 0.02 APE, p = 0.04) and reached this maximal enrichment earlier (46.7 +/- 3.0 vs. 69.4 +/- 6.6 h, p = 0.004) compared to the CDH-ECMO group, which reflects higher and faster precursor incorporation in the control group. Surfactant PC concentration in ELF was similar in both groups.These results show that CDH patients who require ECMO have a decreased surfactant PC synthesis, which may be part of the pathogenesis of severe pulmonary insufficiency and has a negative impact on weaning from ECMO.

SUBMITTER: Janssen DJ

PROVIDER: S-EPMC2749174 | biostudies-other | 2009 Oct

REPOSITORIES: biostudies-other

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Project description:Background and aim: Neonatal brain monitoring is increasingly used due to reports of brain injury perioperatively. Little is known about the effect of sedatives (midazolam) and anesthetics (sevoflurane) on cerebral oxygenation (rScO2) and cerebral activity. This study aims to determine these effects in the perioperative period. Methods: This is an observational, prospective study in two tertiary pediatric surgical centers. All neonates with a congenital diaphragmatic hernia received perioperative cerebral oxygenation and activity measurements. Patients were stratified based on intraoperatively administrated medication: the sevoflurane group (continuous sevoflurane, bolus fentanyl, bolus rocuronium) and the midazolam group (continuous midazolam, continuous fentanyl, and continuous vecuronium). Results: Intraoperatively, rScO2 was higher in the sevoflurane compared to the midazolam group (84%, IQR 77-95 vs. 65%, IQR 59-76, p = < 0.001), fractional tissue oxygen extraction was lower (14%, IQR 5-21 vs. 31%, IQR 29-40, p = < 0.001), the duration of hypoxia was shorter (2%, IQR 0.4-9.6 vs. 38.6%, IQR 4.9-70, p = 0.023), and cerebral activity decreased more: slow delta: 2.16 vs. 4.35 μV 2 (p = 0.0049), fast delta: 0.73 vs. 1.37 μV 2 (p = < 0.001). In the first 30 min of the surgical procedure, a 3-fold increase in fast delta (10.48-31.22 μV 2) and a 5-fold increase in gamma (1.42-7.58 μV 2) were observed in the midazolam group. Conclusion: Sevoflurane-based anesthesia resulted in increased cerebral oxygenation and decreased cerebral activity, suggesting adequate anesthesia. Midazolam-based anesthesia in neonates with a more severe CDH led to alarmingly low rScO2 values, below hypoxia threshold, and increased values of EEG power during the first 30 min of surgery. This might indicate conscious experience of pain. Integrating population-pharmacokinetic models and multimodal neuromonitoring are needed for personalized pharmacotherapy in these vulnerable patients. Trial Registration: https://www.trialregister.nl/trial/6972, identifier: NL6972.

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Decreased surfactant phosphatidylcholine synthesis in neonates with congenital diaphragmatic hernia during extracorporeal membrane oxygenation.

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