Inhaled nitric oxide in neonates and children with pulmonary hypertension

Lönnqvist, Per Arne; Winberg, P.; Lundell, Bo; Selldén, Hans; Olsson, GL

doi:10.1111/j.1651-2227.1994.tb18265.x

Cited by 37 publications

(25 citation statements)

References 21 publications

(21 reference statements)

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“…The improvement in P a O 2 was observed earlier and at lower IPGE 1 dose in Group I patients compared with Group II patients. Previous studies have referred to the benefits of earlier institution of therapy for hypoxemic respiratory failure (1,35). The improvement in P a O 2 was predicted by both dose and time in study for Group I but only by time in study for Group II.…”

Section: Inhaled Pge1 In Neonatal Pphnmentioning

confidence: 75%

Aerosolized PGE1: A Selective Pulmonary Vasodilator in Neonatal Hypoxemic Respiratory Failure Results of a Phase I/II Open Label Clinical Trial

et al. 2004

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Twenty term/near term neonates with hypoxemic respiratory failure and oxygenation index Ն20 were enrolled in a Phase I/II feasibility, safety and dose escalation study of inhaled PGE 1 (IPGE 1 ). Incremental doses of IPGE 1 , delivered by a jet nebulizer over a 2-h period, followed by weaning over 1 h, were given to 13 patients before receiving inhaled nitric oxide (INO) (Group I), and to seven patients, who failed to respond to INO (Group II). Response was defined as an increase in P a O 2 of either Ն 25 (full) or 10 -25 (partial) torr. Exit criteria included an acute deterioration in oxygenation status, a persistent oxygenation index above 35 in Group I, or the availability of extracorporeal membrane oxygenation (ECMO) Hypoxemic respiratory failure in the newborn is usually associated with potentially reversible pulmonary hypertension that causes right-to-left shunting and profound hypoxemia. The goal of therapy is to selectively lower the pulmonary vascular resistance (PVR). Intravenously administered vasodilators lack pulmonary selectivity leading to systemic side effects. Inhaled nitric oxide (INO), a selective pulmonary vasodilator, has revolutionized the treatment of hypoxemic respiratory failure. However, there is lack of sustained improvement in 30 -46% of infants (1-4); moreover, INO is a highly toxic molecule requiring expensive monitoring and scavenging systems for administration, making the treatment expensive and limiting availability. Aerosolized prostaglandins I 2 and E 1 have been reported to be effective selective pulmonary vasodilators in animals and human adults (5-19). In addition, inhaled PGI 2 (IPGI 2 ) has also been reported to be effective in preterm and term newborns and children with pulmonary hypertension (20 -26). Although i.v. PGE 1 is widely used in neonates, the use of the inhaled form has not been reported in newborns with Received October 3, 2003; accepted June 18, 2004

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Section: Inhaled Pge1 In Neonatal Pphnmentioning

confidence: 75%

Aerosolized PGE1: A Selective Pulmonary Vasodilator in Neonatal Hypoxemic Respiratory Failure Results of a Phase I/II Open Label Clinical Trial

et al. 2004

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“…Although such difference did not reach statistical significance, this was presumably due to the small number of subjects. Some authors have proposed to use NO in an earlier phase of the disease in order to limit further iatrogenic damage to the lung [30]. However, the risk-benefit ratio of an earlier use of inhaled NO has not yet been clarified, and concerns have been raised as to the potential toxicity of NO in the neonatal [31].…”

Section: Discussionmentioning

confidence: 99%

Inhaled nitric oxide in hypoxaemic newborns who are candidates for extracorporeal life support

Biban

Trevisanuto²,

Pettenazzo³

et al. 1998

Eur Respir J

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Term and preterm newborns suffering from severe hypoxaemic respiratory failure, either due to persistent pulmonary hypertension (PPHN) or respiratory distress syndrome (RDS), still account for a relatively high morbidity and mortality [1,2]. Several treatments have been attempted in these patients, such as exogenous surfactant replacement, i.v. vasodilators such as tolazoline and prostacyclins, inhaled prostacyclins, magnesium sulphate, highfrequency ventilation and liquid ventilation, although rarely has their efficacy been confirmed by controlled studies [3][4][5][6]. Extracorporeal membrane oxygenation (ECMO) constitutes a valid therapeutic option in neonates with refractory hypoxaemia [7,8], as recently confirmed by the UK ECMO collaborative trial [9]. However, ECMO remains a complex and expensive technique that requires systemic anticoagulation and cannulation of major vessels. Inhaled nitric oxide (NO) has been shown to be a promising novel treatment in hypoxaemic newborns with severe PPHN, either idiopathic or secondary to various cardiopulmonary diseases. In using this therapy several authors have observed a marked improvement of oxygenation in most patients and a decline of ECMO cases [10][11][12]. It is still unclear, however, why in some patients gas exchange during NO therapy is not improved and whether, in cases of positive response, a rapid improvement of oxygenation is necessarily associated with a favourable outcome. The objectives of this study were: 1) to assess the acute physiological effect of inhaled NO on systemic oxygenation in newborns with acute respiratory failure approaching ECMO criteria; and 2) to evaluate whether survival without ECMO support was correlated to an acute and sustained response to inhaled NO and, conversely, whether death or need for ECMO could be anticipated by a poor or absent response. MethodsThis study was approved by the Ethics and Scientific Review Board at the Department of Paediatrics, University of Padova. Informed parental consent was obtained prior to initiation of NO therapy. All newborns admitted at A cohort of newborns with a gestational age of ≥34 weeks and an oxygenation index (OI) >25 were prospectively evaluated. Patients were given NO at an initial dose of 10 parts per million (ppm). Oxygenation parameters were evaluated prior and during NO inhalation. From January 1994 to December 1996, 20 infants were en-rolled in the study. Based upon their outcome, patients were divided into two groups: survivors with no need for ECMO, group A (n=8) and survivors requiring ECMO or nonsurvivors, group B (n=12).All infants approached or met ECMO criteria before NO inhalation. Eight patients (40%) were successfully managed with NO and conventional treatment (group A). Newborns in this group showed a rapid and sustained improvement of systemic oxygenation during NO inhalation. Mean arterial oxygen tension (Pa,O 2 ) increased significantly from 4.5 kPa (34 mmHg) (95% confidence interval (95% CI) 1.9-7.1 kPa (14.4-53.7 mmHg)) to 10.1 kPa (75.7 mmHg) (95% CI 6.5-13.6 kP...

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“…Low arginine levels could mean that endogenous NO levels were inadequate and explain why iNO can be an effective vasodilator in PHN of the newborn. The response to iNO, however, is variable [7], and dosages required to optimize oxygenation differ between individuals [8,9]. One possible explanation for such results is that the arginine levels and hence the endogenous NO levels vary.…”

Section: Introductionmentioning

confidence: 90%

Plasma Arginine Levels and the Response to Inhaled Nitric Oxide in Neonates

Kavvadia

Greenough²,

Lilley³

et al. 1999

Neonatology

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Inhaled nitric oxide (iNO) can be an effective vasodilator in pulmonary hypertension of the newborn (PHN). The aim of this study was to determine whether differences in arginine levels, from which endogenous NO is produced, explain the variability in response to NO and whether the arginine levels were lower in term and preterm infants with PHN than in infants without PHN (controls). We prospectively studied 30 infants (17 born preterm) with clinically diagnosed PHN and treated with iNO and 22 controls (14 born preterm). Three NO levels (10, 20, 40 ppm) were administered to the PHN infants to identify that associated with maximum oxygenation. Twenty-seven infants with PHN improved following iNO and had lower arginine levels than those infants who did not respond to iNO (p < 0.05). No significant relationship, however, was noted between the arginine levels and either the magnitude of change in the oxygenation index in response to iNO or the NO level associated with maximum oxygenation. The median plasma arginine level prior to iNO of the PHN infants was 12.5 (range 2–53) μmol/l, but not significantly lower than that of the controls (median 24, range 3–82 μmol/l). We conclude that differences in plasma arginine levels are unlikely to explain the variation in response to iNO and that, although arginine levels tended to be lower in infants with PHN, this is not a consistent finding in either the term or preterm infants.

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Inhaled nitric oxide in neonates and children with pulmonary hypertension

Cited by 37 publications

References 21 publications

Aerosolized PGE1: A Selective Pulmonary Vasodilator in Neonatal Hypoxemic Respiratory Failure Results of a Phase I/II Open Label Clinical Trial

Aerosolized PGE1: A Selective Pulmonary Vasodilator in Neonatal Hypoxemic Respiratory Failure Results of a Phase I/II Open Label Clinical Trial

Inhaled nitric oxide in hypoxaemic newborns who are candidates for extracorporeal life support

Plasma Arginine Levels and the Response to Inhaled Nitric Oxide in Neonates

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