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Reduced oxygen concentration for the resuscitation of infants with congenital diaphragmatic hernia

Journal of Perinatology volume 38, pages 834–843 (2018)Cite this article

Subjects

Abstract

Objective:

To evaluate whether infants with congenital diaphragmatic hernia (CDH) can be safely resuscitated with a reduced starting fraction of inspired oxygen (FiO2) of 0.5.

Study design:

A retrospective cohort study comparing 68 patients resuscitated with starting FiO2 0.5 to 45 historical controls resuscitated with starting FiO2 1.0.

Results:

Reduced starting FiO2 had no adverse effect upon survival, duration of intubation, need for ECMO, duration of ECMO, or time to surgery. Furthermore, it produced no increase in complications, adverse neurological events, or neurodevelopmental delay. The need to subsequently increase FiO2 to 1.0 was associated with female sex, lower gestational age, liver up, lower lung volume–head circumference ratio, decreased survival, a higher incidence of ECMO, longer time to surgery, periventricular leukomalacia, and lower neurodevelopmental motor scores.

Conclusion:

Starting FiO2 0.5 may be safe for the resuscitation of CDH infants. The need to increase FiO2 to 1.0 during resuscitation is associated with worse outcomes.

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References

  1. Gosche JR, Islam S, Boulanger SC. Congenital diaphragmatic hernia: searching for answers. Am J Surg. 2005;190:324–32.

    Article  Google Scholar 

  2. DiFiore JW, Fauza DO, Slavin R, Wilson JM. Experimental fetal tracheal ligation and congenital diaphragmatic hernia: a pulmonary vascular morphometric analysis. J Pediatr Surg. 1995;30:917–23.

    Article  CAS  Google Scholar 

  3. Bloss RS, Aranda JV, Beardmore HE. Congenital diaphragmatic hernia: pathophysiology and pharmacologic support. Surgery. 1981;89:518–24.

    CAS  PubMed  Google Scholar 

  4. Lotze A, Knight GR, Anderson KD, Hull WM, Whitsett JA, O’Donnell RM, et al. Surfactant (beractant) therapy for infants with congenital diaphragmatic hernia on ECMO: evidence of persistent surfactant deficiency. J Pediatr Surg. 1994;29:407–12.

    Article  CAS  Google Scholar 

  5. Kumar VHS. Current concepts in the management of congenital diaphragmatic hernia in infants. Indian J Surg. 2015;77:313–21.

    Article  Google Scholar 

  6. Masumoto K, Teshiba R, Esumi G, Nagata K, Takahata Y, Hikino S, et al. Improvement in the outcome of patients with antenatally diagnosed congenital diaphragmatic hernia using gentle ventilation and circulatory stabilization. Pediatr Surg Int. 2009;25:487–92.

    Article  Google Scholar 

  7. te Pas AB, Kamlin CO, Dawson JA, O’Donnell C, Sokol J, Stewart M, et al. Ventilation and spontaneous breathing at birth of infants with congenital diaphragmatic hernia. J Pediatr. 2009;154:369–73.

    Article  Google Scholar 

  8. Kays DW, Langham MR Jr., Ledbetter DJ, Talber JL. Detrimental effects of standard medical therapy in congenital diaphragmatic hernia. Ann Surg. 1999;230:340–8.

    Article  CAS  Google Scholar 

  9. Ijsselstijn H, Tibboel D, Hop WJ, Molenaar JC, de Jongste JC. Long-term pulmonary sequelae in children with congenital diaphragmatic hernia. Am J Respir Crit Care Med. 1997;155:174–80.

    Article  CAS  Google Scholar 

  10. ECC Guidelines. Neonatal resuscitation. Circulation. 2000;102:I-343–57.

    Google Scholar 

  11. van den Hout L, Sluiter I, Gischler S, De Klein A, Rottier R, Ijsselstijn H, et al. Can we improve the outcome of congenital diaphragmatic hernia? Pediatr Surg Int. 2009;25:733–43.

    Article  Google Scholar 

  12. Perrone S, Bracciali C, Di Virgilio N, Buonocore G. Oxygen use in neonatal care: a two-edged sword. Front Pediatr. 2017;4:143.

    Article  Google Scholar 

  13. Ozxurekci Y, Aykac K. Oxidative stress related diseases in newborns. Oxid Med Cell Longev. 2016;2016:1–9.

    Article  Google Scholar 

  14. Sola A, Rogido MR, Deulofeut R. Oxygen as a neonatal health hazard; call for détente in clinical practice. Acta Paediatr. 2007;96:801–12.

    Article  Google Scholar 

  15. Saugstad OD, Sejersted Y, Solberg R, Wollen EJ, Bjørås M. Oxygenation of the newborn: a molecular approach. Neonatology. 2012;101:315–25.

    Article  CAS  Google Scholar 

  16. Minoo P, Segura L, Coalson JJ, King RJ, DeLemos RA. Alterations in surfactant protein gene expression associated with premature birth and exposure to hyperoxia. Am J Physiol. 1991;261:L386–392.

    CAS  PubMed  Google Scholar 

  17. Northway WH, Rosan RC, Porter DY. Pulmonary disease following respiratory therapy of hyaline-membrane disease. N Engl J Med. 1998;267:357–67.

    Google Scholar 

  18. Bancalari E, Gerhardt T. Bronchopulmonary dysplasia. Pediatr Clin North Am. 1986;33:1–23.

    Article  CAS  Google Scholar 

  19. Deulofeut R, Sola A. Risk for late bacterial sepsis in infants ≤ 1,000 grams: another beneficial effect of avoiding hyperoxia?. J Investig Med. 2006;54:S276

    Google Scholar 

  20. Victor VM, Rocha M, Esplugues JV, De la Fuente M. Role of free radicals in sepsis: antioxidant therapy. Curr Pharm Des. 2005;11:3141–58.

    Article  CAS  Google Scholar 

  21. Lin PW, Stoll BJ. Necrotising enterocolitis. Lancet. 2006;368:1271–83.

    Article  Google Scholar 

  22. Guven A, Gundogdu G, Vurucu S, Uysal B, Oztas E, Ozturk H, et al. Medical ozone therapy reduces oxidative stress and intestinal damage in an experimental model of necrotizing enterocolitis in neonatal rats. J Pediatr Surg. 2009;44:1730–5.

    Article  Google Scholar 

  23. Wheatley CM, Dickinson JL, Mackey DA, Craig JE, Sale MM. Retinopathy of prematurity: recent advances in our understanding. Arch Dis Child Fetal Neonatal Ed. 2002;87:F78–82.

    Article  CAS  Google Scholar 

  24. Saldeño YP, Favareto V, Mirpuri J. Prolonged persistent patent ductus arteriosus: potential perdurable anomalies in premature infants. J Perinatol. 2012;32:953–8.

    Article  Google Scholar 

  25. Perrone S, Tataranno LM, Stazzoni G, Ramenghi L, Buonocore G. Brain susceptibility to oxidative stress in the perinatal period. J Matern Fetal Neonatal Med. 2015;28:2291–5.

    Article  Google Scholar 

  26. Volpe JJ. Neurobiology of periventricular leukomalacia in the premature infant. Pediatr Res. 2001;50:553–62.

    Article  CAS  Google Scholar 

  27. Ramani M, van Groen T, Kadish I, Bulger A, Ambalavanan N. Neurodevelopmental impairment following neonatal hyperoxia in the mouse. Neurobiol Dis. 2013;50:69–75.

    Article  Google Scholar 

  28. Saugstad OD. Take a breath—but do not add oxygen (if not needed). Acta Paediatr. 2007;96:789–800.

    Google Scholar 

  29. Naumburg E, Bellocco R, Cnattingius S, Johnson A, Ekbom A. Supplementary oxygen and risks of childhood lymphatic leukaemia. Acta Pediatr. 2002;91:1233–328.

    Article  Google Scholar 

  30. Spector LG, Klebanoff MA, Feussner JH, Georgieff MK, Ross JA. Childhood cancer following neonatal oxygen supplementation. J Pediatr. 2005;147:27–31.

    Article  Google Scholar 

  31. Paneth N. The evidence mounts against use of pure oxygen in newborn resuscitation. J Pediatr. 2005;147:4–6.

    Article  Google Scholar 

  32. The Neonatal Inhaled Nitric Oxide Study Group (NINOS). Inhaled nitric oxide and hypoxic respiratory failure in infants with congenital diaphragmatic hernia. Pediatrics. 1997;99:838–45.

    Article  Google Scholar 

  33. Porta NFM, Steinhorn RH. Pulmonary vasodilator therapy in the NICU: inhaled nitric oxide, sildenafil, and other pulmonary vasodilating agents. Clin Perinatol. 2012;39:149–64.

    Article  Google Scholar 

  34. Lakshminrusimha S, Russell JA, Steinhorn RH, Swartz DD, Ryan RM, Gugino SF, et al. Pulmonary hemodynamics in neonatal lambs resuscitated with 21%, 50%, and 100% oxygen. Pediatr Res. 2007;62:313–8.

    Article  CAS  Google Scholar 

  35. Lakshminrusimha S, Swartz DD, Gugino SF, Ma CX, Wynn KA, Ryan RM, et al. Oxygen concentration and pulmonary hemodynamics in newborn lambs with pulmonary hypertension. Pediatr Res. 2009;66:539–44.

    Article  Google Scholar 

  36. Farrow KN, Groh BS, Schumacker PT, Lakshminrusimha S, Czech L, Gugino SF, et al. Hyperoxia increases phosphodiesterase 5 expression and activity in ovine fetal pulmonary artery smooth muscle cells. Circ Res. 2008;102:226–33.

    Article  CAS  Google Scholar 

  37. Snoek KG, Reiss IK, Greenough A, Capolupo I, Urlesberger B, Wessel L, et al. Standardized postnatal management of infants with congenital diaphragmatic hernia in Europe: The CDH EURO Consortium Consensus – 2015 Update. Neonatology. 2016;110:66–74.

    Article  Google Scholar 

  38. Sola A. Oxygen saturation in the newborn and the importance of avoiding hyperoxia-induced damage. NeoReviews. 2015;16:e393–405.

    Article  Google Scholar 

  39. Danzer E, Gerdes M, Bernbaum J, D’Agostino J, Bebbington MW, Siegle J, et al. Neurodevelopmental outcome of infants with congenital diaphragmatic hernia prospectively enrolled in an interdisciplinary follow-up program. J Pediatr Surg. 2010;45:1759–66.

    Article  Google Scholar 

  40. Leeuwen L, Walker K, Halliday R, Fitzgerald DA. Neurodevelopmental outcome in congenital diaphragmatic hernia survivors during the first three years. Early Hum Dev. 2014;90:413–5.

    Article  Google Scholar 

  41. Danzer E, Gerdes M, D’Agostino JA, Hoffman C, Bernbaum J, Bebbington W, et al. Longitudinal neurodevelopment and neuromotor outcome in congenital diaphragmatic hernia patients in the first 3 years of life. J Perinatol. 2013;33:893–8.

    Article  CAS  Google Scholar 

  42. Danzer E, Zarnow D, Gerdes M, D’Agostino JA, Siegle J, Bebbington MW, et al. Abnormal brain development and maturation on magnetic resonance imaging in survivors of severe congenital diaphragmatic hernia. J Pediatr Surg. 2012;47:453–61.

    Article  Google Scholar 

  43. Bernbaum J, Schwartz IP, Gerdes M, D’Agostino JA, Coburn CE, Polin RA. Survivors of extracorporeal membrane oxygenation at 1 year of age: the relationship of primary diagnosis with health and neurodevelopmental sequelae. Pediatrics. 1995;96:907–13.

    CAS  PubMed  Google Scholar 

  44. D’Agostino JA, Bernbaum JC, Gerdes M, Schwartz IP, Coburn CE, Hirschl RB, et al. Outcome for infants with congenital diaphragmatic hernia requiring extracorporeal membrane oxygenation: the first year. J Pediatr Surg. 1995;30:10–15.

    Article  Google Scholar 

  45. Stolar CJ, Crisafi MA, Driscoll YT. Neurocognitive outcome for neonates treated with extracorporeal membrane oxygenation: are infants with congenital diaphragmatic hernia different? J Pediatr Surg. 1995;30:366–71.

    Article  CAS  Google Scholar 

  46. Kapadia VS, Chalek LF, Sparks JE, Allen JR, Savani RC, Wyckoff MH. Resuscitation of preterm neonates with limited versus high oxygen strategy. Pediatrics. 2013;132:e1488–e1496.

    Article  Google Scholar 

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Acknowledgements

Research reported in this study was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number TL1TR001880 for author JSR.

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Authors and Affiliations

  1. The Center for Fetal Diagnosis and Treatment, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    John S. Riley, Ryan M. Antiel, Natalie E. Rintoul, Anne M. Ades, Lindsay N. Waqar, Lisa M. Herkert, William H. Peranteau, Alan W. Flake, N. Scott Adzick & Holly L. Hedrick

  2. Division of Neurology, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Nan Lin

  3. Neonatal Follow-up Program, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Jo Ann D’Agostino & Casey Hoffman

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  1. John S. Riley
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Correspondence to Holly L. Hedrick.

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Riley, J.S., Antiel, R.M., Rintoul, N.E. et al. Reduced oxygen concentration for the resuscitation of infants with congenital diaphragmatic hernia. J Perinatol 38, 834–843 (2018). https://doi.org/10.1038/s41372-017-0031-5

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