Inhaled nitric oxide for premature infants after prolonged rupture of the membranes

doi:10.1016/S0022-3476(95)70467-1

The Journal of Pediatrics

Volume 126, Issue 3, March 1995, Pages 450-453

https://doi.org/10.1016/S0022-3476(95)70467-1 Get rights and content

Abstract

We evaluated the use of inhaled nitric oxide in eight premature infants (520 to 1440 gm, 24 to 31 weeks of gestation) who failed to respond to conventional management and who had prolonged rupture of the membranes and oligohydramnios. All infants had a significant improvement in oxygenation and a fall in mean airway pressure with inhaled nitric oxide. Further studies are required to determine the safety and efficacy of this form of therapy. (J PEDIATR 1995;126:450-3)

Section snippets

METHODS

Premature infants eligible to receive INO were infants whose condition was deteriorating and who were unresponsive to what was considered maximal therapy. All infants were receiving a fraction of inspired oxygen of 1.0, all were supported by conventional ventilation and/or high-frequency oscillation (Infant Star; Infrasonics Inc., San Diego, Calif.), and all were treated with either a bovine surfactant (bLES; bLES Biochemicals Inc., London, Ontario, Canada) or Exosurf (Burroughs Wellcome Co.,

RESULTS

Eight premature infants were treated with INO after what was considered to be failure of conventional management. All infants were inborn; birth weights ranged from 520 to 1440 gm and gestations between 24 to 31 weeks (Table ). All infants had an antepartum history of oligohydramnios and PROM for more than 3 days. The mothers of all infants had received dexamethasone and antibiotics antenatally. Four of the eight infants had a cranial ultrasound study before INO therapy, and all had findings

DISCUSSION

Our observations add to the report by Abman et al.⁶ that premature infants with severe respiratory disease, hypoxemia, and right-to-left shunting at the ductal and/or foramen level may have significant improvement in oxygenation after treatment with INO, a result that allows a reduction in MAP. All infants had received what we consider to be maximal ventilatory and other supportive therapy. The eight infants were thought to be at very high risk of having hypoplastic lungs because of the PROM

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Cited by (130)

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To describe current treatment practices of preterm infants with early hypoxemic respiratory failure (HRF) and pulmonary hypertension (PH) and their association with patient outcomes.
We developed a prospective, observational, multicenter clinical registry of preterm newborns <34 weeks' gestation with HRF and PH, based on either clinical or echocardiographic evidence during the first 72 hours of life, from 28 neonatal intensive care units in the US from 2017 through 2022. The primary end point was mortality among those who did or did not receive PH-targeted treatment, and the secondary end points included comparisons of major morbidities. Variables were compared using t tests, Wilcoxon rank-sum tests, Fisher exact tests, and χ² tests.
We analyzed the results of 224 preterm infants enrolled in the registry. Of which, 84% (188/224) received PH-targeted treatment, most commonly inhaled nitric oxide (iNO). Early mortality in this cohort was high, as 33% (71/224) of this sample died in the first month of life, and 77% of survivors (105/137) developed bronchopulmonary dysplasia. Infants who received PH-targeted treatment had higher oxygenation indices at the time of enrollment (28.16 [IQR: 13.94, 42.5] vs 15.46 [IQR: 11.94, 26.15]; P = .0064). Patient outcomes did not differ between those who did or did not receive PH-targeted therapy.
Early-onset HRF with PH in preterm infants is associated with a high early mortality and a high risk of developing bronchopulmonary dysplasia. iNO is commonly used to treat early-onset PH in preterm infants with HRF. In comparison with untreated infants with lower oxygenation indices, iNO treatment in severe PH may prevent poorer outcomes.
When to say no to inhaled nitric oxide in neonates?
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Inhaled nitric oxide (iNO) was approved for use in critically ill term and near-term neonates (>34 weeks gestational age) in 1999 for hypoxic respiratory failure (HRF) with evidence of pulmonary hypertension. In 2011 and 2014, the National Institutes of Health and American Academy of Pediatrics respectively recommended against the use of iNO in preterm infants <34 weeks. However, these guidelines were based on trials conducted with varying inclusion criteria and outcomes. Recent guidelines from the American Thoracic Society/American Heart Association, the Pediatric Pulmonary Hypertension Network (PPHNet) and European Pediatric Pulmonary Vascular Disease Network recommend the use of iNO in preterm neonates with HRF with confirmed pulmonary hypertension. This review discusses the available evidence for off-label use of iNO. Preterm infants with prolonged rupture of membranes and pulmonary hypoplasia appear to respond to iNO. Similarly, preterm infants with physiology of pulmonary hypertension with extrapulmonary right-to-left shunts may potentially have an oxygenation response to iNO. An overview of relative and absolute contraindications for iNO use in neonates is provided. Absolute contraindications to iNO use include a ductal dependent congenital heart disease where systemic circulation is supported by a right-to-left ductal shunt, severe left ventricular dysfunction and severe congenital methemoglobinemia. In preterm infants, we do not recommend the routine use of iNO in HRF due to parenchymal lung disease without pulmonary hypertension and prophylactic use to prevent bronchopulmonary dysplasia. Future randomized trials evaluating iNO in preterm infants with pulmonary hypertension and/or pulmonary hypoplasia are warranted. (233/250 words).
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Persistent pulmonary hypertension is the term used to describe a spectrum of pathophysiological changes that result in hypoxic respiratory failure. A number of underlying physiologies contribute to this overarching syndrome, and understanding the individual components of the disorder potentially allows the clinician to better target therapy and achieve the desired response with a greater success rate and in a shorter time frame. Understanding the underlying patient variance genetically and physiologically allows individualization and targeting of care to each patient, which is an integral part of the concept of precision medicine.
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Pulmonary hypoplasia
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To survive the transition to extrauterine life, newborn infants must have lungs that provide an adequate surface area and volume to allow for gas exchange. The dynamic activities of fetal breathing movements and accumulation of lung luminal fluid are key to fetal lung development throughout the various phases of lung development and growth, first by branching morphogenesis, and later by septation. Because effective gas exchange is essential to survival, pulmonary hypoplasia is among the leading findings on autopsies of children dying in the newborn period. Management of infants born prematurely who had disrupted lung development, especially at the pre-glandular or canalicular periods, may be challenging, but limited success has been reported. Growing understanding of stem cell biology and mechanical development of the lung, and how to apply them clinically, may lead to new approaches that will lead to better outcomes for these patients.

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^☆: From the Departments of Newborn Medicine and Pediatrics, Royal Alexandra Hospital, University of Alberta, Edmonton, Alberta, Canada

^☆☆: Reprint requests: Neil Finer, MD, Royal Alexandra Hospital, 10240 Kingsway, Edmonton, Alberta T5H 3V9, Canada.

^★: 0022-3476/95/$3.00 + 0 9/24/60454

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Inhaled nitric oxide for premature infants after prolonged rupture of the membranes☆,☆☆,★

Abstract

Section snippets

METHODS

RESULTS

DISCUSSION

Lancet

J PEDIATR

J PEDIATR

Lancet

Persistent pulmonary hypertension in premature neonates with severe respiratory distress syndrome

Pediatrics

Pulmonary and systemic arterial pressure in hyaline membrane disease

Arch Dis Child

Inhaled nitric oxide in the management of a premature newborn with severe respiratory distress and pulmonary hypertension

Pediatrics