Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Drugs
Published in: Drugs 1/2001

01-01-2001 | Review Article

Response to Inhaled Nitric Oxide in Premature and Term Neonates

Authors: Dr Thomas Hoehn, Martin F. Krause

Published in: Drugs | Issue 1/2001

Login to get access

Abstract

Inhaled nitric oxide (iNO) has emerged as a promising therapeutic agent in the treatment of persistent pulmonary hypertension of the newborn. Several theories exist regarding causes of both response and nonresponse to iNO. Clinical trials differentiate disease entities (primary vs secondary persistent pulmonary hypertension associated with meconium aspiration syndrome, pneumonia or congenital diaphragmatic hernia) and their specific response rates. iNO combined with high-frequency ventilation appears to be superior to inhalation of nitric oxide (NO) during conventional ventilation. Little is known regarding the role of the degree of lung expansion and its modification — no matter what mode of ventilation is applied. Gestational age plays an important role in relation to the potential adverse effects of NO. Of particular concern in the premature neonate is the effect of NO on bleeding time and the inhibition of platelet aggregation. Those potentially hazardous effects need to be carefully weighed against early intervention with iNO at a comparably low oxygenation index in order to prevent the vicious cycle of hypoxaemia and subsequent increased right-to-left shunting. Further studies are required to determine the optimal timing, mode of delivery and mode of ventilation used with iNO therapy in order to optimise the response of premature and term neonates.
Literature
1.
Roberts JD, Polaner DM, Lang P, et al. Inhaled nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 1992; 340: 818–9PubMedCrossRef
2.
Kinsella JP, Neish SR, Shaffer E, et al. Low-dose inhalation nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 1992; 340: 819–20PubMedCrossRef
3.
Roberts Jr JD, Fineman JR, Morin 3rd FC, et al. Inhaled nitric oxide and persistent pulmonary hypertension of the newborn: the Inhaled Nitric Oxide Study Group. N Engl J Med 1997; 336: 605–10PubMedCrossRef
4.
Neonatal Inhaled Nitric Oxide Study Group (NINOS). Inhaled nitric oxide and hypoxic respiratory failure in neonates with congenital diaphragmatic hernia. Pediatrics 1997; 99: 838–45CrossRef
5.
Neonatal Inhaled Nitric Oxide Study Group. Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure. N Engl J Med 1997; 336: 597–604CrossRef
6.
Wessel DL, Adatia I, Van Marter LJ, et al. Improved oxygenation in a randomized trial of inhaled nitric oxide for persistent pulmonary hypertension of the newborn. Pediatrics 1997; 100: E7PubMedCrossRef
7.
Subhedar NV, Ryan SW, Shaw NJ. Open randomised controlled trial of inhaled nitric oxide and early dexamethasone in high risk preterm infants. Arch Dis Child Fetal Neonatal Ed 1997; 77: F185–90PubMedCrossRef
8.
Van Meurs KP, Rhine WD, Asselin JM, et al. Response of premature infants with severe respiratory failure to inhaled nitric oxide. Preemie NO Collaborative Group. Pediatr Pulmonol 1997; 24: 319–23
9.
Skimming JW, Bender KA, Hutchison AA, et al. Nitric oxide inhalation in infants with respiratory distress syndrome. J Pediatr 1997; 130: 225–30PubMedCrossRef
10.
Hogman M, Frostell C, Arnberg H, et al. Bleeding time prolongation and NO inhalation. Lancet 1993; 341(8861): 1664–5PubMedCrossRef
11.
Samama CM, Diaby M, Fellahi JL, et al. Inhibition of platelet aggregation by inhaled nitric oxide in patients with acute respiratory distress syndrome. Anesthesiology 1995; 83: 56–65PubMedCrossRef
12.
Cheung PY, Salas E, Etches PC, et al. Inhaled nitric oxide and inhibition of platelet aggregation in critically ill neonates. Lancet 1998; 351: 1181–2PubMedCrossRef
13.
George TN, Johnson KJ, Bates JN, et al. The effect of inhaled nitric oxide therapy on bleeding time and platelet aggregation in neonates. J Pediatr 1998; 132: 731–4PubMedCrossRef
14.
Miller OI, Gaynor JW, Macrae DJ, et al. Inhaled nitric oxide for pulmonary hypertension after repair of exomphalos. Arch Dis Child 1993; 69: 518–20PubMedCrossRef
15.
Schranz D, Huth R, Wippermann CF, et al. Nitric oxide and prostacyclin lower suprasystemic pulmonary hypertension after cardiopulmonary bypass. Eur J Pediatr 1993; 152: 793–6PubMedCrossRef
16.
Journois D, Pouard P, Mauriat P, et al. Inhaled nitric oxide as a therapy for pulmonary hypertension after operations for congenital heart defects. J Thorac Cardiovasc Surg 1994; 107: 1129–35PubMed
17.
Karamanoukian HL, Glick PL, Zayek M, et al. Inhaled nitric oxide in congenital hypoplasia of the lungs due to diaphragmatic hernia or oligohydramnios. Pediatrics 1994; 94: 715–8PubMed
18.
Hoffman GM, Ross GA, Day SE, et al. Inhaled nitric oxide reduces the utilization of extracorporeal membrane oxygenation in persistent pulmonary hypertension of the newborn. Crit Care Med 1997; 25: 352–9PubMedCrossRef
19.
Day RW, Lynch JM, White KS, et al. Acute response to inhaled nitric oxide in newborns with respiratory failure and pulmonary hypertension. Pediatrics 1996; 98: 698–705PubMed
20.
Barefield ES, Karle VA, Phillips 3rd JB, et al. Inhaled nitric oxide in term infants with hypoxemic respiratory failure. J Pediatr 1996; 129: 279–86PubMedCrossRef
21.
Kinsella JP, Truog WE, Walsh WF, et al. Randomized, multicenter trial of inhaled nitric oxide and high-frequency oscillatory ventilation in severe, persistent pulmonary hypertension of the newborn. J Pediatr 1997; 131: 55–62PubMedCrossRef
22.
Davidson D, Barefield ES, Kattwinkel J, et al. Inhaled nitric oxide for the early treatment of persistent pulmonary hypertension of the term newborn: a randomized, double-masked, placebo-controlled, dose-response, multicenter study: the I-NO/PPHN Study Group. Pediatrics 1998; 101: 325–34PubMedCrossRef
23.
Finer NN, Barrington KJ. Nitric oxide in respiratory failure in the newborn infant. Semin Perinatol 1997; 21: 426–40PubMedCrossRef
24.
Finer NN, Barrington KJ. Nitric oxide in respiratory failure in full-term and nearly full-term newborn infants (Cochrane review). Cochrane Library [CDROM and online]. Issue 1. Oxford: The Cochrane Collaboration, 1999: review no. 000399
25.
Goldman AP, Tasker RC, Haworth SG, et al. Four patterns of response to inhaled nitric oxide for persistent pulmonary hypertension of the newborn. Pediatrics 1996; 98: 706–13PubMed
26.
Rais Bahrami K, Rivera O, Seale WR, et al. Effect of nitric oxide in meconium aspiration syndrome after treatment with surfactant. Crit Care Med 1997; 25: 1744–7PubMedCrossRef
27.
Mercier JC, Lacaze T, Storme L, et al. Disease-related response to inhaled nitric oxide in newborns with severe hypoxaemic respiratory failure: French Paediatric Study Group of Inhaled NO. Eur J Pediatr 1998; 157: 747–52PubMedCrossRef
28.
Steinhorn RH, Cox PN, Fineman JR, et al. Inhaled nitric oxide enhances oxygenation but not survival in infants with alveolar capillary dysplasia. J Pediatr 1997; 130: 417–22PubMedCrossRef
29.
Adler SM, Clark RH. Premature and term neonates have similar responses to inhaled nitric oxide (iNO) [abstract]. Pediatr Res 1998; 43: 272ACrossRef
30.
Watchko JF. Persistent pulmonary hypertension in a very low birthweight preterm infant. Clin Pediatr (Phila) 1985; 24: 592–5CrossRef
31.
Amato M, de Roche B, von Muralt G. Persistent pulmonary hypertension in preterm-infants. Padiatr Padol 1986; 21(1): 25–30PubMed
32.
Gommers D, Hartog A, van ’t Veen A, et al. Improved oxygenation by nitric oxide is enhanced by prior lung reaeration with surfactant, rather than positive end-expiratory pressure, in lung-lavaged rabbits. Crit Care Med 1997; 25: 1868–73PubMedCrossRef
33.
Peliowski A, Finer NN, Etches PC, et al. Inhaled nitric oxide for premature infants after prolonged rupture of the membranes. J Pediatr 1995; 126: 450–3PubMedCrossRef
34.
Banks BA, Seri I, Ischiropoulos H, et al. Changes in oxygenation with inhaled nitric oxide in severe bronchopulmonary dysplasia. Pediatrics 1999; 103: 610–8PubMedCrossRef
35.
Cheung PY, Peliowski A, Robertson CM. The outcome of very low birth weight neonates. J Pediatr 1998; 133: 735–9PubMedCrossRef
36.
Kinsella JP, Walsh FW, Bose CL, et al. Inhaled nitric oxide in premature neonates with severe hypoxaemic respiratory failure: a randomised controlled trial. Lancet 1999; 354: 1061–5PubMedCrossRef
37.
Franco-Belgium Collaborative NO Trial Group. Early compared with delayed inhaled nitric oxide in moderately hypoxaemic neonates with respiratory failure: a randomised controlled trial. Lancet 1999; 354: 1066–71CrossRef
38.
Barrington KJ, Finer NN. Inhaled nitric oxide in preterm newborn infants with respiratory failure (Cochrane review). Cochrane Library [CDROM and Online]. Issue 1. Oxford: The Cochrane Collaboration, 1999: review no. 000509
39.
Chang LY, Graham JA, Miller FJ, et al. Effects of subchronic inhalation of low concentrations of nitrogen dioxide: the proximal alveolar region of juvenile and adult rats. Toxicol Appl Pharmacol 1986; 83: 45–61PubMedCrossRef
40.
Hallman M, Bry K, Turbow R, et al. Pulmonary toxicity associated with nitric oxide in term infants with severe respiratory failure. J Pediatr 1998; 132: 827–9PubMedCrossRef
41.
Hoehn T, Huebner J, Paboura E, et al. Effect of therapeutic concentrations of nitric oxide on bacterial growth in vitro. Crit Care Med 1998; 26: 1857–62PubMedCrossRef
42.
Christou H, Magnani B, Morse DS, et al. Inhaled nitric oxide does not affect adenosine 5′-diphosphate-dependent platelet activation in infants with persistent pulmonary hypertension of the newborn. Pediatrics 1998; 102: 1390–3PubMedCrossRef
43.
Crow JP, Beckman JS. The role of peroxynitrite in nitric oxide-mediated toxicity. Curr Top Microbiol Immunol 1995; 196: 57–73PubMedCrossRef
44.
Gries A, Bode C, Peter K, et al. Inhaled nitric oxide inhibits human platelet aggregation, P-selectin expression, and fibrinogen binding invitroand invivo. Circulation 1998; 97(15): 1481–7PubMedCrossRef
45.
Varela AF, Runge A, Ignarro LJ, et al. Nitric oxide and prostacyclin inhibit fetal platelet aggregation: a response similar to that observed in adults. Am J Obstet Gynecol 1992; 167: 1599–604PubMed
46.
Bassenge E. Antiplatelet effects of endothelium-derived relaxing factor and nitric oxide donors. Eur Heart J 1991; 12 Suppl. E: 12–5PubMedCrossRef
47.
Huang QW, Sun B, Gao F, et al. Effects of inhaled nitric oxide and high-frequency ventilation in rabbits with meconium aspiration. Biol Neonate 1999; 76: 374–82PubMedCrossRef
48.
Gessler P, Nebe T, Birle A, et al. A new side effect of inhaled nitric oxide in neonates and infants with pulmonary hypertension: functional impairment of the neutrophil respiratory burst. Intens Care Med 1996; 22: 252–8CrossRef
49.
Iha S, Orita K, Kanno T, et al. Oxygen-dependent inhibition of neutrophil respiratory burst by nitric oxide. Free Radic Res 1996; 25: 489–98PubMedCrossRef
50.
Hogman M, Frosteil CG, Hedenstrom H, et al. Inhalation of nitric oxide modulates adult human bronchial tone. Am Rev Respir Dis 1993; 148: 1474–8PubMedCrossRef
51.
Hogman M, Frostell C, Arnberg H, et al. Inhalation of nitric oxide modulates methacholine-induced bronchoconstriction in the rabbit. Eur Respir J 1993; 6: 177–80PubMed
52.
Dupuy PM, Shore SA, Drazen JM, et al. Bronchodilator action of inhaled nitric oxide in guinea pigs. J Clin Invest 1992; 90: 421–8PubMedCrossRef
53.
Folkerts G, van der Linde HJ, Nijkamp FP. Virus-induced airway hyperresponsiveness in guinea pigs is related to a deficiency in nitric oxide. J Clin Invest 1995; 95: 26–30PubMedCrossRef
54.
Kinsella JP, Parker TA, Galan H, et al. Effects of inhaled nitric oxide on pulmonary edema and lung neutrophil accumulation in severe experimental hyaline membrane disease. Pediatr Res 1997; 41: 457–63PubMedCrossRef
55.
Abman SH, Kinsella JP. Inhaled nitric oxide for persistent pulmonary hypertension of the newborn: the physiology matters! Pediatrics 1995; 96: 1153–5PubMed
56.
Hoehn T, Krause M, Hentschel R. High-frequency ventilation augments the effect of inhaled nitric oxide in persistent pulmonary hypertension of the newborn. Eur Respir J 1998; 11: 234–8PubMedCrossRef
57.
Hoehn T, Krause MF. Synergistic effects of high-frequency ventilation and inhaled nitric oxide in the treatment of hypoxemic respiratory failure in infancy. Pediatr Pulmonol 1998; 26: 228–30PubMedCrossRef
58.
Putensen C, Rasanen J, Downs JB. Effect of endogenous and inhaled nitric oxide on the ventilation-perfusion relationships in oleic-acid lung injury. Am J Respir Crit Care Med 1994; 150: 330–6PubMed
59.
Putensen C, Rasanen J, Lopez FA, et al. Continuous positive airway pressure modulates effect of inhaled nitric oxide on the ventilation-perfusion distributions in canine lung injury. Chest 1994; 106: 1563–9PubMedCrossRef
60.
Puybasset L, Rouby JJ, Mourgeon E, et al. Factors influencing cardiopulmonary effects of inhaled nitric oxide in acute respiratory failure. Am J Respir Crit Care Med 1995; 152: 318–28PubMed
61.
62.
Saugstad OD. Inhaled nitric oxide for preterm infants: still an experimental therapy. Lancet 1999; 354: 1047–8PubMedCrossRef
Metadata
Title
Response to Inhaled Nitric Oxide in Premature and Term Neonates
Authors
Dr Thomas Hoehn
Martin F. Krause
Publication date
01-01-2001
Publisher
Springer International Publishing
Published in
Drugs / Issue 1/2001
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI
https://doi.org/10.2165/00003495-200161010-00004

Other articles of this Issue 1/2001

Drugs 1/2001 Go to the issue

Adis New Drug Profile

Budesonide/Formoterol Combination

Adis Drug Evaluation

Fluoxetine

Leading Article

The Role of Fluoroquinolones in Tuberculosis Today

Therapy in Practice

Treatments for Androgenetic Alopecia and Alopecia Areata

Review Article

Cholinesterase Inhibitors for Alzheimer’s Disease

Current Opinion

Emergence of Methicillin-Resistant Staphylococcus aureus with Intermediate Glycopeptide Resistance