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 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the efficacy of low-dose nitric oxide inhalation in nine consecutive patients with severe persistent pulmonary hypertension of the newborn (PPHN) who were candidates for extracorporeal membrane oxygenation (ECMO). All patients had marked hypoxemia despite aggressive ventilator management and echocardiographic evidence of pulmonary hypertension. Associated diagnoses included meconium aspiration syndrome (3 patients), sepsis (3 patients), and congenital diaphragmatic hernia (2 patients). Infants were initially treated with inhaled nitric oxide at 20 ppm for 4 hours and then at 6 ppm for 20 hours. In all infants, oxygenation promptly improved (arterial/alveolar oxygen ratio, 0.077 +/- 0.016 at baseline vs 0.193 +/- 0.030 at 4 hours; p < 0.001) without a decrease in systemic blood pressure. Sustained improvement in oxygenation was achieved in eight patients treated with inhaled nitric oxide for 24 hours at 6 ppm (arterial/alveolar oxygen ratio, 0.270 +/- 0.053 at 24 hours; p < 0.001 vs baseline). One patient with overwhelming sepsis had an initial improvement of oxygenation with nitric oxide but required ECMO for multiorgan and cardiac dysfunction. We conclude that low doses of nitric oxide cause sustained clinical improvement in severe PPHN and may reduce the need for ECMO. However, immediate availability of ECMO is important in selected cases of PPHN complicated by severe systemic hemodynamic collapse.
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PMID:Clinical responses to prolonged treatment of persistent pulmonary hypertension of the newborn with low doses of inhaled nitric oxide. 832 Jun 29

To study the potential role of endothelin-1, a potent endothelium-derived vasoconstrictor peptide, in the pathophysiology of persistent pulmonary hypertension of the newborn (PPHN), we measured arterial concentrations of immunoreactive endothelin-1 (irET-1) in 24 neonates with PPHN. Secondary diagnoses included meconium aspiration syndrome (13 patients), sepsis (2), congenital diaphragmatic hernia (1), asphyxia (1), pulmonary hemorrhage (1), aspiration of blood (1), and respiratory distress syndrome (1). Compared with irET-1 levels in umbilical cord blood in normal infants (15.1 +/- 4.1 pg/ml; mean +/- SEM) and in newborn infants with hyaline membrane disease who were supported by mechanical ventilation (11.8 +/- 1.2 pg/ml), infants with PPHN had markedly elevated circulating irET-1 levels (27.6 +/- 3.6 pg/ml; p < 0.01 vs cord blood, hyaline membrane disease). Infants with severe PPHN requiring extracorporeal membrane oxygenation (ECMO) therapy had higher irET-1 levels than infants with milder disease (31.0 +/- 4.7 for ECMO-treated infants vs 21.2 +/- 2.0 for non-ECMO-treated infants; p < 0.05). In patients treated without ECMO, irET-1 progressively decreased during the following 3 to 5 days, paralleling clinical improvement. In contrast, irET-1 concentrations remained elevated in infants with severe PPHN during ECMO therapy. We conclude that circulating irET-1 levels are elevated in newborn infants with PPHN, are positively correlated with disease severity, and decline with resolution of disease in patients who do not require ECMO therapy. Whether endothelin-1 contributes directly to the pathophysiology of PPHN or is simply a marker of disease activity remains speculative.
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PMID:Elevated immunoreactive endothelin-1 levels in newborn infants with persistent pulmonary hypertension. 815 68

Despite an association with meconium and blood aspiration, pneumonia, sepsis, pneumothorax, prematurity, and congenital diaphragmatic hernia, no cause for persistent pulmonary hypertension of the newborn can be found in many cases. This article discusses the advances in current therapies including the promising new therapy of inhaled nitric oxide.
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PMID:Advances in the treatment of persistent pulmonary hypertension of the newborn. 841 18

Extracorporeal membrane oxygenation (ECMO) is an important means of supporting newborns with respiratory failure. While short- and long-term follow-up of ECMO survivors has been thoroughly addressed, there is no systematic study of nonsurvivors. Nineteen nonsurvivors of newborn ECMO with autopsy results are divided into two groups: group 1: 12 patients who had intracranial lesions as the primary cause of death (hemorrhage 8, encephalomalacia 2, infarct 2); and group 2: 7 patients with nonintracranial primary causes of death. Patients in group 1 were significantly more acidotic, hypotensive, and smaller in age and birth weight pre-ECMO. Among group 2 patients, two with diaphragmatic hernia died of primary pulmonary disease (diffuse alveolar damage, pulmonary hypoplasia and necrosis, bronchopneumonia). One of 2 patients with persistent fetal circulation (PFC) was treated with massive doses of tolazoline and suffered fatal gastrointestinal hemorrhage and ischemic necrosis of heart, spleen, testes, and adrenals. The other PFC patient had severe pulmonary interstitial fibrosis. Two patients with meconium aspiration and a patient with streptococcal sepsis had diffuse pulmonary damage and multiple organ failure (renal medullary necrosis, and infarcts of adrenal, spleen, liver). In this series, intracranial pathology was the most common cause of death in ECMO patients, related to gestational age, acidosis, hypoxia, and size, but probably unrelated to carotid ligation.
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PMID:A clinical-pathological study of nonsurvivors of newborn ECMO. 843 64

The incidence of neonatal extracorporeal membrane oxygenation (ECMO) is decreasing nationally. This decrease is presumed to be a result of the emergence of alternative technologies such as high-frequency oscillatory ventilation (HFOV), nitric oxide (NO), and surfactant therapy as well as others. The purposes of the present report were to determine just how rapidly the demographics of ECMO are changing and to determine the impact of competing technologies on ECMO use. The authors reviewed their entire ECMO experience of 455 cases (370 neonatal, 38 pediatric, and 47 cardiac). The neonatal cases also were separated into diagnostic groups: MAS (meconium aspiration syndrome), PPHN (persistent pulmonary hypertension of the newborn), RDS (respiratory distress syndrome), and sepsis. To allow statistical comparison, the patients were divided into four chronological groups, of equal 3-year duration, spanning the 12 years that ECMO has been available. The results of the analysis demonstrated four principle findings. (1) The total number of patients receiving ECMO per year was declining (P = .0001). This decline was attributable to a reduction in the total number of neonatal patients, with the exception of cases of congenital diaphragmatic hernia. (2) The complexity of each ECMO run was increasing, as evidenced by substantial increases in mean ECMO duration per patient and an increase in the incidence of patient complications on ECMO (P = .0001). (3) There has been a significant decrease in the overall survival rate for patients treated with ECMO (P = .0001). (4) The ECMO population mix has shifted away from straightforward neonatal cases and toward the more complex pediatric and cardiac cases. This demographic shift has occurred as a result of improvements in pre-ECMO management of neonatal patients, and is primarily responsible for the findings noted above. However, there also has been a worsening of condition severity within each diagnostic group, which also is partly responsible for the changes noted. If these trends continue, pediatric, cardiac, and CDH patients will likely account for the majority of ECMO patients. Consequently, existing ECMO centers must be prepared to adapt to the changing demographics by evolving programs that support pediatric, cardiac, and adult patients, in addition to neonates. Furthermore, the complexity associated with transporting these unstable older patients and the likelihood that the number of active ECMO centers will decline may require remaining ECMO centers to develop long-distance ECMO transport capabilities.
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PMID:ECMO in evolution: the impact of changing patient demographics and alternative therapies on ECMO. 886 46

Misalignment of pulmonary veins with alveolar capillary dysplasia (MPV) has been reported to be a rare cause of persistent pulmonary hypertension of the newborn (PPHN) and to be fatal despite extracorporeal membrane oxygenation (ECMO). A full-term female neonate with PPHN was brought to the hospital for ECMO therapy at 2 days of age. On the 14th day of life, she was extubated early after the second run of ECMO, and underwent nitric oxide (NO) inhalation therapy in the incubator. She died of catheter-related sepsis on the 61st day of life. After autopsy findings revealed MPV, the longest survival with this disease was documented. NO inhalation therapy in the incubator may provide time for lung transplantation.
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PMID:Nitric oxide inhalation therapy for an infant with persistent pulmonary hypertension caused by misalignment of pulmonary veins with alveolar capillary dysplasia. 902 81

Cardiopulmonary physiology was assessed by Doppler echocardiography in neonates undergoing pre-ECMO evaluation for meconium aspiration syndrome, congenital diaphragmatic hernia, persistent fetal circulation, and sepsis, from March 1987 through July 1992 (n = 136). Percent survival by diagnosis was: meconium aspiration syndrome, 86%; persistent fetal circulation, 68%; congenital diaphragmatic hernia, 63%; sepsis, 33%. Survival odds by diagnosis predicted a better outcome for meconium aspiration syndrome than for congenital diaphragmatic hernia and sepsis, and a better outcome for persistent fetal circulation than for sepsis. Percent survival for right-to-left patent ductus arteriosus flow (PDA) was 56%; other patent ductus arteriosus flow was 84%. In multivariate analysis, percent survival in congenital diaphragmatic hernia and persistent fetal circulation patients with right-to-left PDA flow suggested a worse outcome (% survival right-to-left vs other: congenital diaphragmatic hernia, 13% vs 70%; persistent fetal circulation, 25% vs 85%), whereas percent survival did not appear to suggest the same in meconium aspiration syndrome or sepsis patients. Similar analysis in non-ECMO patients suggested a worse outcome with right-to-left PDA flow in patients with meconium aspiration syndrome and congenital diaphragmatic hernia. Right-to-left PDA flow, sepsis, and congenital diaphragmatic hernia were associated with a poorer ECMO outcome. Initial assessment of PDA flow helps predict ECMO outcome.
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PMID:Echocardiographic prediction of neonatal ECMO outcome. 917 23

Using information from our database, a review of mortality for the Newborn Intensive Care Unit at Providence Alaska Medical Center was conducted for 1987-1996. There has been a significant decline in mortality over the last decade (p = 0.003). An analysis of mortality by birthweight and gestational age groups demonstrated a decline in mortality (p = 0.005) for infants with birthweight < 2 kg and infants < or = 34 weeks gestation, but no change for infants > or = 2 kg and > or = 35 weeks gestation. As a result, larger and more mature babies now account for an increasing proportion of NICU deaths. For 1995 and 1996 the major contributors to mortality for the smaller neonates were respiratory distress syndrome and congenital and nosocomial sepsis/pneumonia. The major contributors to mortality for larger neonates were persistent pulmonary hypertension of the newborn, congenital heart disease, congenital diaphragmatic hernia, and primary birth asphyxia. A majority of deaths in the larger neonates were due to non-lethal causes. We contend that improved survival in the larger neonate is an important and achievable goal. The introduction of ECMO (Extracorporeal Membrane Oxygenation) for the NICU and a focused review of the neonatal cardiac program offers the best possible potential for achieving this goal.
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PMID:The next challenge for newborn intensive care in Alaska: improving the survival of the larger neonate. 947 9

Nitric oxide (NO) is an important endogenous vasodilator. NO, produced in the endothelial cell, causes vasodilation by relaxation of the vascular smooth muscle cell. Inhalation of NO plays a role in the treatment of persistent pulmonary hypertension of the newborn, a syndrome with considerable morbidity and mortality. NO inhalation specifically leads to pulmonary vasodilation without systemic hypotension, since NO binds avidly to haemoglobin. Neonates with pulmonary hypertension associated with lung hypoplasia, meconium aspiration syndrome, infantile inspiratory distress syndrome due to surfactant deficiency, and sepsis have been treated with inhaled NO. Literature data on NO inhalation and experience in our units with NO inhalation show an improvement in arterial oxygen tension and a decreased need for extracorporeal membrane oxygenation, but no reduction in mortality. NO toxicity as a result of NO inhalation in the newborn has not been reported yet.
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PMID:[Nitric oxide inhalation in newborn infants with pulmonary hypertension]. 955 9

Inhaled nitric oxide (iNO) has been shown to improve oxygenation in severe persistent pulmonary hypertension of the newborn (PPHN). However, PPHN is often associated with various lung diseases. Thus, response to iNO may depend upon the aetiology of neonatal acute respiratory failure. A total of 150 (29 preterm and 121 term) newborns with PPHN were prospectively enrolled on the basis of oxygenation index (OI) higher than 30 and 40, respectively. NO dosage was stepwise increased (10-80 ppm) during conventional mechanical or high-frequency oscillatory ventilation while monitoring the oxygenation. Effective dosages ranged from 5 to 20 ppm in the responders, whereas iNO levels were unsuccessfully increased up to 80 ppm in the nonresponders. Within 30 min of iNO therapy, OI was significantly reduced in either preterm neonates (51+/-21 vs 23+/-17, P < .0001) or term infants with idiopathic or acute respiratory distress syndrome (45+/-20 vs 20+/-17, P < .0001), 'idiopathic' PPHN (39+/-14 vs 14+/-9, P < .0001), and sepsis (55+/-25 vs 26+/-20, P < .0001) provided there was no associated refractory shock. Improvement in oxygenation was less significant and sustained (OI=41+/-16 vs 28+/-18, P < .001) in term neonates with meconium aspiration syndrome and much less (OI=58+/-25 vs 46+/-32, P < .01) in those with congenital diaphragmatic hernia. Only 21 of the 129 term newborns (16%) required extracorporeal membrane oxygenation (57% survival). Survival was significantly associated with the magnitude in the reduction in OI at 30 min of iNO therapy, a gestational age > or =34 weeks, and associated diagnosis other than congenital diaphragmatic hernia. Conclusion, iNO improves the oxygenation in most newborns with severe hypoxaemic respiratory failure including preterm neonates. However, response to iNO is disease-specific. Furthermore, iNO when combined with adequate alveolar recruitment and limited barotrauma using exogenous surfactant and HFOV may obviate the need for extracorporeal membrane oxygenation in many term infants.
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PMID:Disease-related response to inhaled nitric oxide in newborns with severe hypoxaemic respiratory failure. French Paediatric Study Group of Inhaled NO. 977 35


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