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

Abstract

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...

Neonatal pulmonary hypertension treated with inhaled nitric oxide and high-frequency ventilation

“…Inhaled nitric oxide decreases the need for ECMO in patients with PPHN, 3,4,6,7 and following its approval for clinical use, the number of patients entered in the national registry of ECMO patients with a diagnosis of sepsis, idiopathic PPHN or meconium aspiration declined by about 50%. 16 In a randomized trial, improvement in oxygenation occurred more frequently in infants with PPHN treated with HFOV plus iNO as compared to infants treated with either HFOV or iNO alone.…”

“…5 iNO has been shown to reduce the need for ECMO in term and near-term neonates with pulmonary hypertension. 3,4,6,7 High-frequency ventilation (HFV) has been used with increasing frequency for PPHN, 8 and when combined with iNO results in an acute rise in arterial oxygen saturation, 9 and reduces the likelihood of ECMO treatment. 10 Studies of iNO delivered by HFV have, to date, utilized high-frequency oscillatory ventilation (HFOV).…”