Nitric oxide in paediatric respiratory disorders: novel interventions to address associated vascular phenomena? (original) (raw)
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Low-dose inhaled nitric oxide for neonates with pulmonary hypertension
Journal of Paediatrics and Child Health, 1996
Objective: Inhaled nitric oxide (iNO) has been shown to cause selective pulmonary vasodilatation and improve ventilationperfusion matching and may be an important therapeutic option for the treatment of persistent pulmonary hypertension of the newborn (PPHN). We report our experience on the use of iNO in neonates with severe PPHN. Methodology: Inhaled NO was administered to 10 infants with PPHN and persistent hypoxaemia (meconium aspiration syndrome, n = 9; pneumonia, n = 1) after failure of conventional therapy to improve oxygenation. With the exception of one infant, iNO was commenced at 10 ppm. Results: After 30 min exposure to iNO, the arterial oxygen tension (PaO,) rose from a median of 49 mmHg (6.5 kPa) [range 12-82mmHg (1.6-10.9 kPa)] to 75mmHg (10 kPa) [range 17-450mmHg (2.3-60 kPa)] (P = 0.005), while the median oxygenation index fell (pre-iNO of 37 vs post-iN0 20) (P = 0.005) and median systemic arterial pressure rose (pre-iNO 46.5 mmHg (6.2 kPa) [range 32-63 mmHg (4.3 to 8.4 kPa vs post-iN0 54.5 mmHg (7.3 kPa) [range 36-74 kPa]) P = 0.005). All infants subsequently continued to receive iNO with the duration of exposure to iNO ranging from 12 to 168 h (median duration 100 h). Three infants died despite showing an initial beneficial response to iNO. The mean duration of intubation for survivors was 11.9k2.6 days. Methaemoglobinaemia and toxic levels of nitrogen dioxide were not seen during iNO administration. Of the seven survivors, 12 month follow up in two infants and 4 month follow up in four infants showed age-appropriate neurodevelopmental skills, with one infant having very mild hearing loss. Conclusions: Inhaled NO reduces the oxygenation index by improving the PaO, and decreasing ventilation pressures, and appears to be clinically useful in severely hypoxaemic infants with PPHN refractory to conventional treatment.
Current status of inhaled nitric oxide therapy in the perinatal period
Early Human Development, 1997
The recent discovery of nitric oxide (NO) and the elucidation of its biological roles has been accompanied by significant advances in our understanding of several physiological and pathological processes. Impaired NO synthesis and / or release may underlie the pathophysiology of several cardiopulmonary disorders characterised by hypoxemia and pulmonary hypertension. Inhaled NO produces selective pulmonary vasodilation and appears to be an effective new therapy for infants with pulmonary vasospasm or hypoxemia associated with ventilation-perfusion imbalance. Although formal reports from current randomised and controlled clinical trials of inhaled NO therapy are awaited, preliminary results suggest an improved outcome. NO is, however, still an investigational drug. The limitations of this therapy and its toxicology are reviewed.
Inhaled nitric oxide in persistent pulmonary hypertension of the newborn
The Lancet, 1992
Background: This study was designed to evaluate the effect of nitric oxide (NO) on the management of neonates with severe persistent pulmonary hypertension refractory to high-frequency oscillatory ventilation. Methods: The birth weight and the gestational age of infants were 3125.5 ± 794 g (mean ± SD) and 39 ± 2.4 weeks, respectively. All neonates were ventilated for an average of 137.5 min (range 90-180 min) prior to NO therapy. The mean oxygenation index (OI) of all neonates prior to NO was 46.3 ± 5 (mean ± SEM). NO was initially administered at 20 parts per million (ppm) for at least 2 h and increased gradually by 2 ppm to a maximum of 80 ppm. Results: Eighteen infants (75%) responded and six (25%) did not respond to the treatment. Three neonates died in the responding group, while all the nonresponders died (P = 0.0001). The survival rate was 62.5% among all neonates. NO significantly decreased OI (P < 0.0001) and improved the arterial/alveolar (a/A) oxygen ratio (P < 0.0001) within the first 2 h of NO therapy in 61.1% of the responders. However, the OI and the a/A oxygen ratio remained almost the same throughout the treatment in the non-responders and the non-survivors. Conclusion: Inhaled NO at 20 ppm, following adequate ventilation for 2 h without significant response, could be used to identify the majority of the nonresponders in order to seek other alternatives.
Inhaled nitric oxide therapy for persistent pulmonary hypertension of the newborn
Acta paediatrica Japonica; Overseas edition, 1995
Increasing evidence suggests that the pulmonary vascular endothelium is an important mediator of resting pulmonary vascular tone through the synthesis and release of a variety of vasoactive substances including nitric oxide (NO). In addition, pulmonary endothelial dysfunction (such as impairment of NO synthesis) is present in lung injury and may contribute to the pathophysiology of pulmonary hypertensive disorders. Recently, exogenously administered NO gas has been utilized to treat infants with persistent pulmonary hypertension of the newborn (PPHN). These preliminary studies suggest that inhaled NO is a promising new therapy for the treatment of infants with PPHN. Controlled clinical trials must now be performed to determine if the use of inhaled NO improves the long-term outcome of patients with PPHN. Long-term exposure must be monitored closely for potential toxicity which includes methemoglobinemia and lung injury secondary to peroxynitrite and nitrogen dioxide production.
Inhaled nitric oxide therapy in neonates and children: reaching a European consensus
Intensive Care Medicine, 2004
Inhaled nitric oxide (iNO) was first used in neonatal practice in 1992 and has subsequently been used extensively in the management of neonates and children with cardiorespiratory failure. This paper assesses evidence for the use of iNO in this population as presented to a consensus meeting jointly organised by the European Society of Paediatric and Neonatal Intensive Care, the European Society of Paediatric Research and the European Society of Neonatology. Consensus Guidelines on the Use of iNO in Neonates and Children were produced following discussion of the evidence at the consensus meeting.
Journal of Perinatal Medicine, 2006
Aim: To determine whether inhaled nitric oxide might reduce the need for excessive respiratory alkalosis to maintain systemic oxygenation in infants with persistent pulmonary hypertension of the newborn (PPHN). Materials and methods: A retrospective historical cohort study of 34 infants with PPHN with oxygenation index (OI) of 25 or more, including 19 infants without inhaled nitric oxide (i-NO) therapy (control group) and 15 infants with inhaled nitric oxide therapy (i-NO group) was performed. The initial dose of 10 ppm of i-NO was administered and no responders received the maximum dose of 25 ppm. We evaluated the mortality rate and the change of OI index and PaCO 2 during the first 6 days. Results: There were no significant differences in characteristics between groups. Two of 15 in the i-NO group and 6 of 19 infants in the control group died during the first 48 h. Baseline OI, PaCO 2 and arterial pH were similar in the two groups. OI in the i-NO group was significantly higher than in the control group between 12 and 96 h. PaCO 2 in the i-NO group was higher than in the control group between 24 and 144 h. Conclusion: i-NO therapy for PPHN might improve systemic oxygenation without excessive hypocapnia. However there was no reduction in duration of ventilation support or oxygen supply.