Administration Of Inhaled Nitric Oxide Research Articles

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Introduction: Use of inhaled nitric oxide (INO) is a common practice in the treatment of acute respiratory failure in neonatal and pediatric patient populations. The use of INO is associated with a substantial cost and the evidence supporting improved clinical outcome in this population is inconsistent. Hypothesis: We hypothesize that clinical outcomes will demonstrate no statistically significance difference between immediate responders and non-responders in neonatal and pediatric patients who received INO therapy for acute hypoxia. Methods: This is a single-center, non-randomized, retrospective review of non-cardiac, neonatal and pediatric patients who received INO therapy for acute hypoxia between 2004 and 2011. Each eligible patient had pre- and post- arterial (within 1 hour) gases recorded which allowed calculation of PaO2/FiO2 ratios to determine immediate response to INO. ICU outcome was obtained for each eligible patient and predicted mortality (PMort) was calculated through the Vermont Oxford Network (VON) or Virtual PICU (VPS). A total of 142 patients were deemed to be eligible subjects during this time period. Statistical analysis included basic descriptive statistics (mean, median) and group comparison using parametric and non-parametric analysis when appropriate. A p-value of <= 0.05 was used to determine statistical significance between groups. Results: 93 patients demonstrated an immediate, positive response to INO while 50 patients demonstrate no improvement in P/F ratio following initiation on INO. Responders differed significantly from non-responders in pre-P/F ratio (62 vs 80, p=0.004), post-P/F ratio (114 vs 58, p=0.001) and PMort (18 vs 7, p=0.001). We observed no significant difference in ICU mortality between responders and non-responders (27% vs 25%, p=0.815). Conclusions: INO improved P/F ratio following initiation in 65% of the subjects studied. However, INO did not improve ICU outcome even in the responders. Clinical guidelines should be developed to address the administration of INO in this population. Our data suggest that the cost:benefit relationship would not favor the use of INO.

Utilidad del óxido nítrico inhalado en paciente con síndrome de distrés respiratorio agudo y tetralogía de Fallot no intervenida

Utility of inhaled nitric oxide in the treatment of acute respiratory distress syndrome (ARDS) with pulmonary hypertension (PHT) is controversial and there are few studies in the literature that evaluate its effects during prolonged administration. We analyze the case of a 45 day old male patient with un-operated Fallot's tetralogy who developed ARDS and PHT with non-cardiac cause, that required prolonged mechanical ventilation (30 days) and administration of inhaled nitric oxide (INO). Before the INO, the oxygenation index was 19, and at a few minutes of its application it decreased to 15. The patient developed a dependence on INO, tolerating its gradual weaning. Administration could be interrupted at 27 days on onset. We did not observe toxic effects during the administration of INO.

Interaction of endogenous endothelin-1 and inhaled nitric oxide in term and preterm infants.

The peptide endothelin-1 (ET-1) plays an unknown role in the pathogenesis and progression of two important neonatal pulmonary disorders, chronic lung disease (CLD) of prematurity and persistent pulmonary hypertension of the newborn (PPHN). Inhaled nitric oxide (INO) is a proven vasodilator therapy in PPHN and is an experimental therapy in CLD. We sought to determine the effects, if any, of the interaction of inhaled INO with ET-1 in these two separate disorders. Infants (n=21) with PPHN (mean gestation age, 39.4 weeks; mean birth weight, 3470 g) were treated with INO. All infants were <72 h of age at baseline. Plasma obtained at baseline and after 24 h of INO therapy was assessed for ET-1. The change in ET-1 levels with INO was inversely correlated with change in arterial partial pressure of O(2) (r=-0.71, P=0.0003). A separate group of 33 patients with CLD (mean gestational age, 27 weeks; mean birth weight, 740 g; mean age, 19 days) had tracheal aspirate levels of ET-1 obtained before, during, and after 7 days' administration of INO. Values were normalized by soluble secretory component of IgA. Tracheal aspirate ET-1 levels were detectable before INO therapy. There was no significant change during or after treatment with INO. There was not a significant correlation between baseline fractional inspired O(2) and ET-1 levels. There was a non-significant trend in the correlation between the change in ET-1 and the change in interleukin-8 levels in tracheal aspirate. This report confirms the presence of ET-1 in tracheal aspirate of premature infants who are developing CLD and reaffirms the presence of ET-1 in plasma of infants with PPHN. Short-term INO therapy was associated with a decrease in plasma ET-1 levels in PPHN, but did not affect tracheal aspirate ET-1 in CLD. Given the vasconstrictive, profibrotic, and proinflammatory properties of ET-1, specific ET-1 receptor antagonists could be considered as candidates for trials as adjunct therapy in either or both of these disorders.

Outpatient inhaled nitric oxide in a patient with idiopathic pulmonary fibrosis: a bridge to lung transplantation

Inhaled nitric oxide (INO) has been shown to improve oxygenation and decrease intrapulmonary shunt and pulmonary hypertension in various lung diseases. In this study we report a patient with end-stage idiopathic pulmonary fibrosis and pulmonary hypertension who received INO after coronary artery bypass surgery, with significant improvement in arterial oxygenation and pulmonary arterial pressure. Using a pulsing delivery system, the patient continued to receive outpatient INO for 30 months while waiting for lung transplantation. Exercise study and two-dimensional echocardiogram, after 3 months of inhaled NO, demonstrated continued benefits of INO for improvement of arterial oxygenation, pulmonary arterial pressure and exercise tolerance. Inhaled nitric oxide (INO), a selective pulmonary vasodilator, has been shown to improve arterial oxygenation and pulmonary hypertension in the short term in patients with idiopathic pulmonary fibrosis. 1,2 However, long-term use of INO in these patients has not been reported previously. We report here the successful long-term outpatient administration of INO in a patient with idiopathic pulmonary fibrosis and secondary pulmonary hypertension, using a simple pulsed delivery system. The patient demonstrated significant improvement in oxygenation, pulmonary hypertension and exercise tolerance during treatment, allowing him to function independently while awaiting lung transplantation.

The Influence of Inhaled Nitric Oxide on Cerebral Blood Flow and Metabolism in a Child with Traumatic Brain Injury

The Influence of Inhaled Nitric Oxide on Cerebral Blood Flow and Metabolism in a Child with Traumatic Brain Injury

Immunohistochemical localization of protein 3-nitrotyrosine and S-nitrosocysteine in a murine model of inhaled nitric oxide therapy.

Inhaled nitric oxide (INO) therapy is currently used clinically to selectively dilate the pulmonary vasculature and to help treat persistent pulmonary hypertension and bronchopulmonary dysplasia in the neonate. However, in the presence of oxygen or superoxide, nitric oxide forms potentially harmful reactive nitrogen species. Using an experimental mice model, we examined the effects of concurrent hyperoxia and INO on protein tyrosine nitration and cysteine S-nitrosylation in pulmonary tissue. Data showed enhanced 3-nitrotyrosine staining within the airway epithelium and alveolar interstitium of mice lungs treated with hyperoxia, which did not increase significantly with INO administration. Within the alveolar interstitium, 3-nitrotyrosine staining was localized to macrophages. S-Nitrosocysteine staining in airway epithelium was significantly enhanced with INO administration regardless of oxygen content. These data suggest that the formation of protein S-nitrosocysteine is the major protein modification during administration of INO.

Use of nitric oxide in meconium aspiration syndrome: lack of response

To test the hypothesis that inhaled nitric oxide (INO) may not be an effective therapeutic agent in meconium aspiration syndrome (MAS). Prospective, interventional study. The animal research laboratory at The Children's National Medical Center. Seven newborn pigs, 2-7 days old, weighing 2.8 +/- 0.17 kg were used for the study. Animals were anaesthetized, paralysed, intubated and ventilated. Catheters were placed in the jugular vein, carotid artery, and pulmonary artery. After 1 h of recovery 10 ml/kg of 20% meconium in normal saline solution was insufflated into the lungs. Animals were ventilated to maintain ABGs in a normal range, i.e. pH = 7.35-7.45, PaCO2 = 40-45, and PaO2 = 70-90 torr. Ventilator settings were increased as needed until maximum settings of: FiO2 = 1.00, PIP = 40, IMV = 60. After 2 h of conventional ventilation or demonstration of significant lung disease by failure to maintain desired blood gases on maximum ventilator settings, INO was administered for 20 min in concentrations of 10, 20 and 40 ppm. To ensure that there was no additive effect of INO, a 15-min normalization period at 0 ppm was allowed between each dose of INO. Physiologic measurements, ventilatory settings, arterial blood gases, and methemoglobin were recorded at each study period. Measurements were taken after each exposure to INO and after its discontinuation. Arterial saturation (SaO2) and PaO2 were significantly lower ([81 +/- 18] and [54 +/- 14], respectively) and PAP was significantly higher [24 +/- 3] after MAS when compared with baseline. Administration of INO did not improve oxygenation nor decrease PAP at any of the study doses. In this model of MAS, short-term exposure to INO did not decrease PAP nor improve oxygenation. It may be postulated that poor distribution of INO caused by the obstructive nature of this disease may be responsible for the lack of response in this disease state, or that the primary etiology for hypoxia is parenchymal lung disease and not pulmonary hypertension.

INHALED NITRIC OXIDE DOES NOT ADVERSELY AFFECT LUNG MECHANICS IN EXPERIMENTAL RESPIRATORY DISTRESS SYNDROME. 2054

We previously reported brief (30 minutes) administration of inhaled nitric oxide (INO) to premature lambs resulted in worse tidal volume and dynamic compliance. To determine if this effect is sustained, we measured lung mechanics in premature lambs randomized to receive either INO or control gas for four hours. We studied eight sets of premature lamb twins (119 - 126 days gestation, ≅ 0.8 term). Arterial and venous catheters, and tracheal tubes were placed and modified natural surfactant (beractant) was given prior to mechanical ventilation. Lambs were delivered, stabilized and mechanically ventilated for approximately two hours prior to baseline pulmonary function measurements. One twin was randomly assigned to receive 20 ppm INO while the other received control gas (Control) for the next four hours. Pulmonary function measurements (dynamic compliance (Cdyn), respiratory system compliance (Crs), inspiratory tidal volume (VTi), and respiratory system resistance (Rrs)) were made hourly (SensorMedics 2600). One lamb died before entry into the study. There were no significant differences in the pulmonary function measurements between the INO and Control groups. Data in table are mean ± SE at baseline and four hours. We conclude that four hour administration of INO does not adversely affect lung mechanics in preterm lambs with experimental respiratory distress syndrome. We speculate that INO may be used in premature infants without compromising lung mechanical function.

Inhaled nitric oxide in cardiac failure: vascular versus ventricular effects.

Inhaled nitric oxide (INO) is a powerful and selective pulmonary vasodilator in pulmonary hypertension, including that related to cardiac disease. Recently, NO was shown to have a direct negative inotropic action on the myocardium, but whether INO can impair left ventricular (LV) function is not known. We administered INO during right heart catheterisation in 10 subjects with LV failure and secondary pulmonary hypertension. INO was delivered for 10 min at concentrations of 10, 20, and 40 ppm in spontaneous respiration. Average age was 49.9 years (range 19-59 years), and mean LV ejection fraction EF (LVEF) was 19.9% (range 15-27%). INO produced an average decrease in pulmonary vascular resistance (PVR) of 40% as compared with baseline (p < 0.0001) with no significant change in systemic vascular resistance (SVR). There was no significant difference in the haemodynamic response to the three doses of INO. The large decrease in PVR was due mainly to an increase in pulmonary capillary wedge pressure (PCWP). Cardiac index (CI) rose in 7 patients and was unchanged in 2. One patient had a marked increase in PAWP and a marked decrease in CI during administration of INO, which rapidly reversed after discontinuation of INO. This study demonstrates that the administration of INO to patients with impaired cardiac reserve may result in marked increase in ventricular preload with little benefit to pulmonary pressures. In view of the known in vitro effects of NO and the marked haemodynamic changes demonstrated in response to INO in this study, caution should be exercised when using INO in this population.