Inhaled Nitric Oxide in very preterm infants with severe respiratory distress syndrome

Department of Surgical and Medical Critical Care, Section of Neonatology, Careggi University Hospital of Florence, Florence, Italy.
Acta Paediatrica (Impact Factor: 1.67). 10/2006; 95(9):1116-23. DOI: 10.1080/08035250600702594
Source: PubMed


To test the hypothesis that inhaled nitric oxide therapy can decrease the incidence of bronchopulmonary dysplasia and death in preterm infants with severe respiratory distress syndrome; to evaluate the possible predictive factors for the response to inhaled nitric oxide therapy.
Preterm infants (less than 30 weeks' gestation) were randomized to receive during the first week of life inhaled nitric oxide, or nothing, if they presented severe respiratory distress syndrome. Then, the treated infants were classified as non responders and responders.
Twenty infants were enrolled in the inhaled nitric oxide therapy group and 20 in the control group. Bronchopulmonary dysplasia and death were less frequent in the inhaled nitric oxide group than in the control group (50 vs. 90%, p=0.016). Moreover, nitric oxide treatment was found to decrease as independent factor the combined incidence of death and BPD (OR=0.111; 95% C.I. 0.02-0.610). A birth weight lower than 750 grams had a significant predictive value for the failure of responding to inhaled nitric oxide therapy (OR 12; 95% C.I. 1.3-13.3).
Inhaled nitric oxide decreases the incidence of bronchopulmonary dysplasia and death in preterm infants with severe respiratory distress syndrome. Birth weight may influence the effectiveness of inhaled nitric oxide therapy in promoting oxygenation improvement in preterm infants.

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    • "In recent years, many studies have focused on the role of inhaled nitric oxide (iNO) for the prevention and treatment of BPD. A number of multicenter clinical trials have shown that iNO therapy reduces the incidence of BPD [11]–[13]. However, Mercier JC et al demonstrated that early use of iNO had not reduced the incidence of BPD in preterm infants [14]. "
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    ABSTRACT: Impairment of endothelial progenitor cells (EPCs) has been shown to contribute to the development of bronchopulmonary dysplasia (BPD). In the current study, the relationship between EPC changes of after birth and the development of BPD was investigated, and the effects of inhaled nitric oxide (iNO) on EPCs were evaluated. Sixty infants with a gestational age of less than 32 weeks and a birth weight of less than 1500 g were studied. NO was administered to infants who were receiving mechanical ventilation or CPAP for at least 2 days between the ages of 7 and 21 days. EPC level was determined by flow cytometry at birth, 7, 21 and 28 days of age and 36 weeks' postmenstrual age (PMA), before and after the iNO treatment. Plasma concentrations of vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 and granulocyte-macrophage colony-stimulating factor were determined via immunochemical assay. Twenty-five neonates developed BPD, 35 neonates survived and did not develop BPD. EPC level was decreased on day 7 and 21 in infants who later developed BPD compared with infants that did not develop BPD. From birth to 21 days of age, BPD infants had a persistently lower VEGF concentration compared with non-BPD infants. No difference was found between the two groups at day 28 or 36 weeks PMA. In infants that later developed BPD, iNO raised the KDR(+)CD133(+) and CD34(+)KDR(+)CD133(+) EPC numbers along with increasing the level of plasma VEGF. EPC level was reduced at 7 days of age in infants with BPD, and iNO increased the EPC number along with increasing the level of VEGF. Further studies are needed to elucidate the mechanism leading to the decrease of EPCs in infants with BPD and to investigate the role of iNO treatment in the prevention of BPD.
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    ABSTRACT: Neonatal intensive care represents a unique environ- ment where the full measure of modern medicine and technology is applied to the tiniest and most fragile pa- tients. Clearly, the advances in neonatal care, pharma- cology, and mechanical ventilation are among the most impressive in medicine over the last few decades. Yet, as answers and solutions are advanced, new questions arise. Along with questions of what actions to take right now, neonatal care teams must also look to the future in terms of how what we do now affects the future for this infant. Of course no discussion of medical care is complete without a discussion of current costs and fu- ture financial burdens. With a long life ahead of them, the financial burden of chronic care for infants with long term disabilities can easily eclipse what appears to be expensive neonatal intensive care. The introduction of inhaled nitric oxide to neonatal intensive care has focused these issues, of appropriate care, current costs, and long term outcomes as much as perhaps any treatment since the introduction of extra- corporeal membrane oxygenation. Evidenced based re- views are helpful, but individual clinicians must make decisions that are not always easily answered by a meta-analysis and grading of the evidence. In an effort to simulate these real world scenarios, this case-based breakfast symposium was held at the 53rd International Respiratory Congress of the American Association for Respiratory Care on December 3rd, 2007 at the Marriott
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    ABSTRACT: This review provides the readers with background information on the state of the art and science of inhaled nitric oxide (iNO) as therapy for prevention or amelioration of bronchopulmonary dysplasia (BPD) in preterm infants. The goal is to review and critique relevant published information. A total of six clinical trials, all placebo-controlled, four out of six blinded, four out of six multi-centered with a predetermined outcome of reduction in death or BPD, have been reported in full text. These definitive studies have included a total of > 2100 preterm, mostly very preterm, infants. Their designs were informed by results of earlier non-definitive studies which cumulatively enrolled > 350 preterm patients. This very substantial experience provides a firm framework for asserting that iNO will be useful in this population of patients. The use of iNO can reduce the occurrence of BPD and possibly the severity of the disorder. Optimal time of initiation, dosing (both initial dose, duration of treatment and possibly the route of administration) and most importantly, optimal patient subset selection, are not determined. Any clear adverse neurological finding in iNO-treated infants will of course limit or halt the use of this promising therapy.
    No preview · Article · Jul 2007 · Expert Opinion on Pharmacotherapy
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