TY - JOUR
T1 - Decreased surfactant phosphatidylcholine synthesis in neonates with congenital diaphragmatic hernia during extracorporeal membrane oxygenation
AU - Janssen, Daphne J.
AU - Zimmermann, Luc J.
AU - Cogo, Paola
AU - Hamvas, Aaron
AU - Bohlin, Kajsa
AU - Luijendijk, Ingrid H.
AU - Wattimena, Darcos
AU - Carnielli, Virgilio P.
AU - Tibboel, Dick
N1 - Funding Information:
Acknowlegdments We thank Roel Venrooij (medical student, Erasmus MC, Rotterdam, The Netherlands) for technical support, Wim van den Berg (Internal Medicine, Erasmus MC-Dijkzigt, Rotterdam, The Netherlands) for technical support, and the nursing staff, neonatologists and intensivists of the neonatal and surgical intensive care units of the Erasmus MC-Sophia for their help and support during the study. We appreciate the Sophia Foundation for Medical Research (SSWO 245), Rotterdam, The Netherlands (LJZ and DT) and NIH R01 HL 65385 (AH).
PY - 2009/10
Y1 - 2009/10
N2 - Purpose: 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). Methods: 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-13C] glucose. The 13C-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. Results: 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. Conclusion: 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.
AB - Purpose: 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). Methods: 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-13C] glucose. The 13C-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. Results: 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. Conclusion: 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.
KW - Congenital diaphragmatic hernia
KW - Lung injury
KW - Stable isotopes
KW - Surfactant metabolism
KW - Surfactant phosphatidylcholine
UR - http://www.scopus.com/inward/record.url?scp=72449198469&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=72449198469&partnerID=8YFLogxK
U2 - 10.1007/s00134-009-1564-7
DO - 10.1007/s00134-009-1564-7
M3 - Article
C2 - 19582395
AN - SCOPUS:72449198469
VL - 35
SP - 1754
EP - 1760
JO - Intensive Care Medicine
JF - Intensive Care Medicine
SN - 0342-4642
IS - 10
ER -