Skip to main content
PMC home page
Archives of Disease in Childhood. Fetal and Neonatal Edition logoLink to Archives of Disease in Childhood. Fetal and Neonatal Edition
. 1997 Nov;77(3):F185–F190. doi: 10.1136/fn.77.3.f185

Open randomised controlled trial of inhaled nitric oxide and early dexamethasone in high risk preterm infants

N Subhedar, S Ryan, N Shaw
PMCID: PMC1720712  PMID: 9462187

Abstract

AIM—To determine whether treatment with inhaled nitric oxide (NO) and/or dexamethasone reduces the incidence of chronic lung disease (CLD) and/or death in high risk preterm infants.
METHODS—Infants below 32 weeks of gestation were recruited at 96 hours of age if they were deemed to be at high risk of developing CLD. Infants were randomly assigned to one of four treatment groups using a factorial design: (1) 5-20 parts per million inhaled NO for 72 hours; (2) 0.5-1 mg/kg/day intravenous dexamethasone for 6 days; (3) both drugs together; (4) continued conventional management.
RESULTS—Forty two infants were randomised: 10 infants received inhaled NO alone; 11 dexamethasone alone; 10 both treatments; and 11 neither treatment. There was no difference in the combined incidence of CLD and/or death before discharge from hospital between either infants treated with inhaled NO and controls (RR 1.05, 95% CI 0.84-1.25), or those treated with dexamethasone and controls (RR 0.95, 95% CI 0.79-1.18).
CONCLUSIONS—At 96 hours of age, neither treatment with inhaled NO nor dexamethasone prevented CLD or death.

 Keywords: randomised controlled trial; nitric oxide; dexamethasone; chronic lung disease

Full Text

The Full Text of this article is available as a PDF (109.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abman S. H., Kinsella J. P. Inhaled nitric oxide therapy of pulmonary hypertension and respiratory failure in premature and term neonates. Adv Pharmacol. 1995;34:457–474. doi: 10.1016/s1054-3589(08)61103-5. [DOI] [PubMed] [Google Scholar]
  2. Abman S. H., Kinsella J. P., Schaffer M. S., Wilkening R. B. Inhaled nitric oxide in the management of a premature newborn with severe respiratory distress and pulmonary hypertension. Pediatrics. 1993 Oct;92(4):606–609. [PubMed] [Google Scholar]
  3. Barefield E. S., Karle V. A., Phillips J. B., 3rd, Carlo W. A. Inhaled nitric oxide in term infants with hypoxemic respiratory failure. J Pediatr. 1996 Aug;129(2):279–286. doi: 10.1016/s0022-3476(96)70255-x. [DOI] [PubMed] [Google Scholar]
  4. Barnes P. J. Nitric oxide and airway disease. Ann Med. 1995 Jun;27(3):389–393. doi: 10.3109/07853899509002592. [DOI] [PubMed] [Google Scholar]
  5. Bührer C., Merker G., Falke K., Versmold H., Obladen M. Dose-response to inhaled nitric oxide in acute hypoxemic respiratory failure of newborn infants: a preliminary report. Pediatr Pulmonol. 1995 May;19(5):291–298. doi: 10.1002/ppul.1950190508. [DOI] [PubMed] [Google Scholar]
  6. Cooke R. W. Early and late cranial ultrasonographic appearances and outcome in very low birthweight infants. Arch Dis Child. 1987 Sep;62(9):931–937. doi: 10.1136/adc.62.9.931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Evans N. J., Archer L. N. Doppler assessment of pulmonary artery pressure and extrapulmonary shunting in the acute phase of hyaline membrane disease. Arch Dis Child. 1991 Jan;66(1 Spec No):6–11. doi: 10.1136/adc.66.1_spec_no.6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Evans N. J., Archer L. N. Doppler assessment of pulmonary artery pressure and extrapulmonary shunting in the acute phase of hyaline membrane disease. Arch Dis Child. 1991 Jan;66(1 Spec No):6–11. doi: 10.1136/adc.66.1_spec_no.6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Finer N. N., Etches P. C., Kamstra B., Tierney A. J., Peliowski A., Ryan C. A. Inhaled nitric oxide in infants referred for extracorporeal membrane oxygenation: dose response. J Pediatr. 1994 Feb;124(2):302–308. doi: 10.1016/s0022-3476(94)70324-8. [DOI] [PubMed] [Google Scholar]
  10. Foubert L., Fleming B., Latimer R., Jonas M., Oduro A., Borland C., Higenbottam T. Safety guidelines for use of nitric oxide. Lancet. 1992 Jun 27;339(8809):1615–1616. doi: 10.1016/0140-6736(92)91886-d. [DOI] [PubMed] [Google Scholar]
  11. Heal C. A., Spencer S. A. Methaemoglobinaemia with high-dose nitric oxide administration. Acta Paediatr. 1995 Nov;84(11):1318–1319. doi: 10.1111/j.1651-2227.1995.tb13558.x. [DOI] [PubMed] [Google Scholar]
  12. Högman M., Frostell C., Arnberg H., Hedenstierna G. Bleeding time prolongation and NO inhalation. Lancet. 1993 Jun 26;341(8861):1664–1665. doi: 10.1016/0140-6736(93)90802-n. [DOI] [PubMed] [Google Scholar]
  13. Iyer P., Evans N. Re-evaluation of the left atrial to aortic root ratio as a marker of patent ductus arteriosus. Arch Dis Child Fetal Neonatal Ed. 1994 Mar;70(2):F112–F117. doi: 10.1136/fn.70.2.f112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kavanagh B. P., Mouchawar A., Goldsmith J., Pearl R. G. Effects of inhaled NO and inhibition of endogenous NO synthesis in oxidant-induced acute lung injury. J Appl Physiol (1985) 1994 Mar;76(3):1324–1329. doi: 10.1152/jappl.1994.76.3.1324. [DOI] [PubMed] [Google Scholar]
  15. Kinsella J. P., Neish S. R., Shaffer E., Abman S. H. Low-dose inhalation nitric oxide in persistent pulmonary hypertension of the newborn. Lancet. 1992 Oct 3;340(8823):819–820. doi: 10.1016/0140-6736(92)92687-b. [DOI] [PubMed] [Google Scholar]
  16. Kubes P., Granger D. N. Nitric oxide modulates microvascular permeability. Am J Physiol. 1992 Feb;262(2 Pt 2):H611–H615. doi: 10.1152/ajpheart.1992.262.2.H611. [DOI] [PubMed] [Google Scholar]
  17. Mulligan M. S., Hevel J. M., Marletta M. A., Ward P. A. Tissue injury caused by deposition of immune complexes is L-arginine dependent. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6338–6342. doi: 10.1073/pnas.88.14.6338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rastogi A., Akintorin S. M., Bez M. L., Morales P., Pildes R. S. A controlled trial of dexamethasone to prevent bronchopulmonary dysplasia in surfactant-treated infants. Pediatrics. 1996 Aug;98(2 Pt 1):204–210. [PubMed] [Google Scholar]
  19. Roberts J. D., Jr, Fineman J. R., Morin F. C., 3rd, Shaul P. W., Rimar S., Schreiber M. D., Polin R. A., Zwass M. S., Zayek M. M., Gross I. Inhaled nitric oxide and persistent pulmonary hypertension of the newborn. The Inhaled Nitric Oxide Study Group. N Engl J Med. 1997 Feb 27;336(9):605–610. doi: 10.1056/NEJM199702273360902. [DOI] [PubMed] [Google Scholar]
  20. Roberts J. D., Polaner D. M., Lang P., Zapol W. M. Inhaled nitric oxide in persistent pulmonary hypertension of the newborn. Lancet. 1992 Oct 3;340(8823):818–819. doi: 10.1016/0140-6736(92)92686-a. [DOI] [PubMed] [Google Scholar]
  21. Rozé J. C., Storme L., Zupan V., Morville P., Dinh-Xuan A. T., Mercier J. C. Echocardiographic investigation of inhaled nitric oxide in newborn babies with severe hypoxaemia. Lancet. 1994 Jul 30;344(8918):303–305. doi: 10.1016/s0140-6736(94)91341-2. [DOI] [PubMed] [Google Scholar]
  22. Ryan S. W., Nycyk J., Shaw B. N. Prediction of chronic neonatal lung disease on day 4 of life. Eur J Pediatr. 1996 Aug;155(8):668–671. doi: 10.1007/BF01957150. [DOI] [PubMed] [Google Scholar]
  23. Sanders R. J., Cox C., Phelps D. L., Sinkin R. A. Two doses of early intravenous dexamethasone for the prevention of bronchopulmonary dysplasia in babies with respiratory distress syndrome. Pediatr Res. 1994 Jul;36(1 Pt 1):122–128. doi: 10.1203/00006450-199407001-00022. [DOI] [PubMed] [Google Scholar]
  24. Shaw N., Gill B., Weindling M., Cooke R. The changing incidence of chronic lung disease. Health Trends. 1993;25(2):50–53. [PubMed] [Google Scholar]
  25. Shennan A. T., Dunn M. S., Ohlsson A., Lennox K., Hoskins E. M. Abnormal pulmonary outcomes in premature infants: prediction from oxygen requirement in the neonatal period. Pediatrics. 1988 Oct;82(4):527–532. [PubMed] [Google Scholar]
  26. Shinwell E. S., Karplus M., Zmora E., Reich D., Rothschild A., Blazer S., Bader D., Yurman S., Dolfin T., Kuint J. Failure of early postnatal dexamethasone to prevent chronic lung disease in infants with respiratory distress syndrome. Arch Dis Child Fetal Neonatal Ed. 1996 Jan;74(1):F33–F37. doi: 10.1136/fn.74.1.f33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Yeh T. F., Torre J. A., Rastogi A., Anyebuno M. A., Pildes R. S. Early postnatal dexamethasone therapy in premature infants with severe respiratory distress syndrome: a double-blind, controlled study. J Pediatr. 1990 Aug;117(2 Pt 1):273–282. doi: 10.1016/s0022-3476(05)80547-5. [DOI] [PubMed] [Google Scholar]

Articles from Archives of Disease in Childhood Fetal and Neonatal Edition are provided here courtesy of BMJ Publishing Group

RESOURCES