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Query: UMLS:C0019270 (hernia)
 15,856 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The vasodilator molecule nitric oxide is critically involved in the successful cardiopulmonary transition from fetal to postnatal life. It is produced in the pulmonary endothelium by the endothelial isoform of the enzyme nitric oxide synthase. The expression of endothelial nitric oxide synthase in the lung increases dramatically during late gestation, optimizing the capacity for nitric oxide production at the time of birth. Studies in cultured cell models indicate that the developmental upregulation may be mediated by estrogen, and that the expression of the enzyme is also upregulated by oxygen. Pulmonary endothelial nitric oxide synthase expression is diminished in models of congenital diaphragmatic hernia and neonatal pulmonary hypertension induced by fetal ductal ligation. Thus, there is normally a marked developmental upregulation in endothelial nitric oxide synthase expression in the lung during late fetal life, and attenuated expression of the enzyme may contribute to the pathophysiology of a variety of forms of neonatal pulmonary vascular disease.
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PMID:Ontogeny of nitric oxide in the pulmonary vasculature. 935 11

Nitric oxide given as an inhalation (INO) is a novel selective pulmonary vasodilator without effects on the systemic circulation. Preliminary observations indicated that INO treatment was associated with improvements in oxygenation in near-term newborn infants with hypoxic respiratory failure and persistent pulmonary hypertension of the newborn (PPHN). Subsequently, at least eight prospective randomized controlled trials evaluating the use of INO in the near-term neonate with hypoxic respiratory failure have been presented or published. A meta-analysis of these trials has provided evidence that INO improves the PaO2 in the INO-treated infants by 52.8 mm Hg (weighted mean difference) compared with controls (95% CI, 38.2, 67.4), and significantly decreases the oxygenation index by 16.9 compared with controls (95% CI, -22.2, -11.6). The incidence of death or need for ECMO is significantly reduced by treatment with INO, relative risk 0.71 compared to control (95% CI, 0.57, 0.87), with the majority of the improvement observed in the reduction in the need for ECMO. A single study of infants with congenital diaphragmatic hernia (CDH) did not show a benefit for early INO therapy, with treated infants having a greater requirement for ECMO (P = .043). At present, there are no long-term evaluations of infants who have received INO as part of these prospective trials. INO improves oxygenation and reduces the need for ECMO in the near-term hypoxic neonate, but further research is required to evaluate the ultimate safety and benefit of this therapy.
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PMID:Nitric oxide in respiratory failure in the newborn infant. 935 15

Liquid-assisted ventilation, as an alternative ventilation strategy for respiratory distress, is progressing from theory and basic science research to clinical application. Biochemically inert perfluorochemical liquids have low surface tension and high solubility for respiratory gases. From early immersion experiments, two primary techniques for liquid-assisted ventilation have emerged: total liquid ventilation and partial liquid ventilation. While computer-controlled, time-cycled, pressure/volume-limited total liquid ventilators can take maximum advantage of these liquids by completely eliminating the gas phase in the distressed lung, partial liquid ventilation takes advantage of having these liquids in the lung while maintaining gas ventilation. The benefits of both partial and total techniques have been demonstrated in animal models of neonatal and adult respiratory distress syndrome, aspiration syndromes and congenital diaphragmatic hernia and also in combination with other therapeutic modalities including extracorporeal membrane oxygenation, high-frequency ventilation and nitric oxide. Additionally, nonrespiratory applications have expanding potential including pulmonary drug delivery and radiographic imaging. Since its use in neonates in 1989, liquid-assisted ventilation in humans has progressed to a variety of clinical experiences with different aetiologies of respiratory distress. The future holds the opportunity to clarify and optimize the potential of multiple clinical applications for liquid-assisted ventilation.
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PMID:Liquid-assisted ventilation: physiology and clinical application. 956 17

Severe respiratory failure of the newborn often results in persistent pulmonary hypertension, which is characterized by increased pulmonary vascular resistance, decreased pulmonary blood flow and severe hypoxaemia. Since 3 years inhaled nitric oxide (iNO) has been used as a selective pulmonary vasodilator with variable success in the treatment of persistent pulmonary hypertension. In the present clinical pilot study 10 patients (4 newborns and 6 preterm infants) suffering from severe respiratory failure were treated with iNO. The aim of this study was to evaluate the effectiveness of inhaled NO and to discuss whether or not extracorporeal membrane oxygenation (ECMO) could be delayed or avoided. In all patients oxygenation improved without a decrease in systemic blood pressure. The median OI decreased from 41 to 16.5 during the first 4 hours of treatment and to 12 during the first 12 hours. One patient with congenital diaphragmatic hernia required ECMO therapy and died post operative. One preterm infant with primary pulmonary hypertension died during prolongated hypotension and hypoxemia. iNO may have reduced the need for ECMO which however should be available as an ultimate therapeutic option.
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PMID:[Persistent pulmonary hypertension in premature and newborn infants: selective pulmonary vasodilation with inhaled nitric oxide (iNO)]. 957 19

Congenital diaphragmatic hernia (CDH) is still an unsolved problem. A disease which was, for a long time, thought to be merely a hole in the diaphragm appears today to be an intriguing malformation with a poorly understood pathogenesis and a complex pathophysiology. CDH results in various degrees of pulmonary hypoplasia and severe persistent pulmonary hypertension of the newborn. Despite antenatal ultrasound diagnosis and continuous improvement in neonatal intensive care, these features could not be overcome, and the overall mortality rate in CDH is still reaching 50%. Experimental works during the past 20 years suggest that CDH is a disease of impaired lung development associated with, but not caused by, a structural defect of the diaphragm. Furthermore, there is increasing evidence that the lung in CDH is not only small but that there are numerous disorders (e.g. surfactant deficiency, decreased anti-oxidant activity, increased vascular reactivity with decreased nitric oxide and increased endothelin 1 activity, and left heart hypoplasia) which may be associated with impaired lung development. Although antenatal diagnosis of CDH is feasible by ultrasound, there is no reliable predictor of pulmonary hypoplasia, the main prognostic factor in CDH. Whilst modern therapeutic strategies such as high-frequency oscillatory ventilation, exogenous surfactant or inhaled nitric oxide may be beneficial in selected subjects, most newborns with hypoplastic lungs will not survive despite these postnatal therapies. Perhaps these newborns would benefit from antenatal treatment directed at altering lung growth early in utero to minimize pulmonary hypoplasia. Therefore, research is needed to elucidate the aetiology and pathogenesis of CDH. Knowledge about the cellular control of proliferation, differentiation and programmed cell death (apoptosis) in the organogenesis should clarify our understanding of these processes and allow us to develop drugs that stimulate lung growth or even correct the anatomical defect. Furthermore, early and reliable assessment of prognosis for fetuses with CDH at risk of death will become increasingly important in the identification of fetuses most likely to benefit from antenatal therapies and may eventually lead to decreased mortality.
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PMID:Congenital diaphragmatic hernia. A cause of persistent pulmonary hypertension of the newborn which lacks an effective therapy. 974 61

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

Despite many advances in the management of congenital diaphragmatic hernia (CDH), the condition carries a mortality rate of 40-50% usually consequent to pulmonary hypoplasia and/or persistent pulmonary hypertension. Several centers have reported improved survival with preoperative stabilization and delayed surgery, which is now an accepted method of management. This is a retrospective analysis of all neonates with respiratory distress at birth due to CDH who were treated at our institution with neither extracorporeal membrane oxygenation nor nitric oxide being used. The medical records of all neonates with CDH and respiratory distress at birth who were treated at this institution from August 1, 1992 through March 1, 1997 were reviewed. There were 21 patients, 11 male and 10 female. There were 17 full-term and 4 premature infants; two premature infants at 30 and 34 weeks' gestation were not resuscitated because of severe associated congenital anomalies. Surgery was performed from 5 to 144 hr (mean 45 hr) in 18 infants. One infant died during preoperative stabilization from severe pulmonary hypoplasia and pulmonary hypertension and one infant died postoperatively from the same conditions. Seventeen of 19 infants (89.5%) survived and were discharged home. Three infants (17.6%) who failed to thrive due to severe gastroesophageal reflux (GER) required fundoplication. Eleven infants (64.7%) who had sepsis proven by blood culture responded satisfactorily to appropriate antibiotics. Preoperative stabilization and delayed surgery has been a satisfactory form of management in our series. The significant complication was sepsis, which must be addressed.
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PMID:Congenital diaphragmatic hernia: experience with preoperative stabilization and delayed surgery without ECMO and inhaled nitric oxide. 978 47

We observed clinical response to inhaled nitric oxide (iNO) in 12 neonates with persistent pulmonary hypertension of the newborn (PPHN). Clinical response was defined as a decrease in oxygenation index (OI) by 40%. Ten of 12 neonates had response to iNO showing decrease OI from 46.1+/-7.6 to 14.4+/-6.8 at 1 hour after inhalation. Sustained improvement of OI was achieved in 8 neonates and two neonates were relapsed. In the group of neonates who had OI above 40 (n=7), 6 of them showed the decrease of OI from 66.1+/-4.8 to 18.3+/-8.0 at 1 hour. In two groups, one had OI of 40 or greater, and the other OI of 40 or less, there were no differences in pattern of response and early death rate. The response rates according to underlying diseases were as follows; idiopathic PPHN 100%, respiratory distress syndrome 100%, and diaphragmatic hernia 66.7%. Relapse was observed in one neonate with sepsis caused by pneumonia and in one infant with meconium aspiration syndrome. Two infants showed no response to iNO (one diaphragmatic hernia and one suspected pulmonary hypoplasia). We conclude that iNO therapy could improve oxygenation in high percentage of newborn infants with severe PPHN of various underlying conditions except pulmonary hypoplasia.
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PMID:Clinical response to inhaled nitric oxide in persistent pulmonary hypertension of the newborn. 981 Nov 79

Inhaled nitric oxide (INO) is a novel selective pulmonary vasodilator without significant effects on the systemic circulation. Initial case studies of near-term newborn infants with hypoxic respiratory failure and persistent pulmonary hypertension of the newborn showed that INO was associated with improvements in oxygenation. There have now been at least 11 prospective randomized controlled trials evaluating the use of INO in the near-term neonate with hypoxic respiratory failure, 10 of which have been published. A meta-analysis of these trials provides evidence that INO improved the PaO2 in the INO treated infants by 46.4 torr (weighted mean difference) compared with controls (95% CI, 34.2, 58.5) and significantly decreased the oxygenation index by 10.7 compared with controls (95% CI, -14.1, -7.4). The incidence of death or need for extracorporeal membrane oxygenation (ECMO) was significantly reduced by treatment with INO, relative risk (RR) 0.72 compared to control (95% CI, 0.6, 0.87) with the majority of the improvement seen in the reduction in the need for ECMO. Infants with congenital diaphragmatic hernia do not appear to benefit from early INO therapy. The only prospective trials evaluating INO in premature infants to date have not found that this therapy is associated with significant clinical benefit. The long-term evaluations of near-term and full-term infants who have received INO suggest that this therapy does not increase the incidence of adverse neurodevelopmental sequelae in these high-risk infants. INO is an effective therapy for the hypoxic term neonate and will reduce the occurrence of death or the need for ECMO in this population. Further research is required to evaluate the benefit of this therapy in the hypoxic preterm infant.
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PMID:Nitric oxide therapy for the newborn infant. 1070 62

The objective of the investigation was to evaluate the success of a new therapeutic protocol in patients with congenital diaphragmatic hernia (CDH). During the period from 1/1994 till 12/1998 41 patients with CDH were admitted. In 36 patients (88%) left-sided CDH was diagnosed, in 4 patients (10%) right-sided CDH and one neonate (2%) bilateral CDH. Fifteen cases (37%) of CDH were assessed prenatally. Twenty-two children (54%) were treated by inhalation of nitric oxide (INO) and 4 patients (10%) by extracorporeal membrane oxygenation. The total incidence of associated developmental defects was 20% and the total mortality 34%. On comparison of the surviving (group S, n = 27) and the non-surviving NS, n = 14) patients statistically significant differences were found in the Apgar score during the first minute (S: 5.9 +/- 0.5 vs. NS: 3.4 +/- 0.7, p < 0.008), in the oxygenation index (OI) two hours after admission (S: 11.9 +/- 2.9 vs. NS: 27.7 +/- 8.3, p < 0.03), in the alveolo-arterial oxygen difference (AaDO2) 2 hours and 12 hours after admission (S: 369 +/- 47 torr and 237 +/- 47 torr resp. vs. NS: 552 +/- 29 torr and 557 +/- 26 torr resp., p < 0.02) and in the need to start extracorporeal membrane oxygenation (S: 3.7% vs. NS: 21.4%, p < 0.009). The investigation confirmed a reduced mortality of neonates with CDH by introducing new therapeutic methods. Risk factors are early prenatal diagnosis, the presence of associated developmental defects, high values of oxygenation and ventilation with the necessity to start nitric oxide inhalation.
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PMID:[Delayed surgery in congenital diaphragmatic hernia without drainage of the ipsilateral hemithorax]. 1074 84


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