Dose‐response to inhaled nitric oxide in acute hypoxemic respiratory failure of newborn infants: A preliminary report

Bührer, Christoph; Merker, G; Falke, K. J.; Versmold, Hans T.; Obladen, Michael

doi:10.1002/ppul.1950190508

Cited by 13 publications

(8 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In particular, two large controlled multicentre trials have recently demonstrated that NO therapy improves systemic oxygenation and may reduce the need for more invasive treatments in these patients, even if, in both studies, the mortality rate observed by the authors was similar in the treated and controlled groups [14,15]. However, the reason why some patients show a seldom or unsustained response to NO therapy remains unclear.…”

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

View full text Add to dashboard Cite

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...

show abstract

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

View full text Add to dashboard Cite

show abstract

“…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: 89%

“…All the infants with PHN included in this study had lung pathology, and this may have obscured any relationship between the arginine and iNO levels. The response to iNO is also relatively diagnosis specific; poor responses are seen in infants with meconium aspiration syndrome or congenital diaphragmatic hernia [7], and tolerance can develop in the latter group [21].…”

Section: Discussionmentioning

confidence: 99%

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

Kavvadia

Greenough²,

Lilley³

et al. 1999

Neonatology

View full text Add to dashboard Cite

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.

show abstract

“…According to several publications this is not only the case in term infants [4,5,22], but also in premature neonates [7][8][9]. Although it still has to be regarded as an experimental treatment and a variety of potential side-effects have to be looked at, iNO has emerged as a very promising therapeutic approach in PPHN.…”

Section: Discussionmentioning

confidence: 99%

High-frequency ventilation augments the effect of inhaled nitric oxide in persistent pulmonary hypertension of the newborn

Hoehn¹,

Krause²,

Hentschel³

1998

Eur Respir J

View full text Add to dashboard Cite

aaHigh-frequency ventilation (HFV) is widely used for rescue treatment of hypoxaemic neonates and premature infants [1]. Although its role as a first-line mode of ventilation has not been established, it is often applied in newborns with respiratory failure, who cannot be successfully managed with conventional mechanical ventilation (CMV). The results of recent studies investigating the theoretically diminished baro-and volutrauma remain equivocal. Nonetheless there is evidence for a decreased secretion of inflammatory mediators [2] and a reduced amount of lung oedema [3] using high-frequency oscillatory ventilation (HFOV) with or without additional application of exogenous surfactant.Inhaled nitric oxide (iNO) as a treatment for neonatal pulmonary hypertension has been in use for the past few years, both in premature infants and in term neonates [4][5][6][7][8][9]. It is worth noting that the first published application of iNO in a premature infant, and the subsequent improvement of oxygenation, occurred during HFOV [10]. Although still an experimental treatment, NO inhalation plays an important therapeutic role in severe hypoxaemia of the newborn due mainly to extrapulmonary shunting [11,12].Recently, a randomized, multicentre trial showed that the combination of iNO and HFOV was superior in term neonates, as compared to either treatment alone [13]. We report a similar experience in a full-term neonate, but also in a premature infant of 29 weeks of gestation. Case 1The term infant was delivered by caesarean section because of maternal hypertension. There was no maternal history of infection. The infant was male and had a birth weight of 3,810 g and Apgar 9,10,10 (1',5',10'); he became symptomatic at the age of 15 min with intercostal retractions and grunting. At that stage, capillary blood gases were: pH 7.23, capillary carbon dioxide tension (Pc,CO 2 ) 8.0 kPa (60 mmHg), capillary oxygen tension (Pc,O 2 ) 4.0 kPa (30 mmHg) in combination with an increasing inspiratory oxygen fraction (FI,O 2 ). At the age of 2 h the neonatal transport team was called, which arrived about 1 h later. The infant was intubated and ventilated because of persistent cyanosis, antibiotic treatment was started and he was transferred to our neonatal intensive care unit. Upon arrival, bovine surfactant (100 mg·kg -1 ) was applied; in order to achieve adequate oxygenation, peak inspiratory pressures (PIPs) up to 4.6 kPa were required (positive endexpiratory pressure (PEEP) 0.5 kPa, rate 70 breaths·min -1 , inspiratory time 0.35 s, mean airway pressure (MAP) 1.8 kPa, FI,O 2 1.0). After approximately 6 h a sudden deterioration of oxygenation and arterial blood pressure occurred, caused by a pneumopericard, which was relieved by drainage. During this event, profound hypoxia occurred for about 15 min, the continuously recorded arterial oxygen saturation (Sa,O 2 ) (measured by pulsoximetry) was approximately 20%. Following drainage of the pneumopericard We report two cases of newborn infants with profound hypoxaemia, who did not respond with ...

show abstract

Dose‐response to inhaled nitric oxide in acute hypoxemic respiratory failure of newborn infants: A preliminary report

Cited by 13 publications

References 31 publications

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

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

High-frequency ventilation augments the effect of inhaled nitric oxide in persistent pulmonary hypertension of the newborn

Contact Info

Product

Resources

About