Inhaled nitric oxide for oligohydramnios-induced pulmonary hypoplasia: a report of two cases and review of the literature.
ABSTRACT We describe the clinical courses of two premature infants, a male born at 29(4/7) weeks' gestational age after an 8-week period of rupture of membranes (ROM) and severe oligohydramnios, and a female infant born at 31 weeks' gestational age after an 18-week period of ROM and severe oligohydramnios. Within hours after birth, despite intubation and aggressive ventilation, both infants developed fulminant hypoxic respiratory failure. Their clinical courses were consistent with pulmonary hypertension and both infants were transferred for trials of inhaled nitric oxide (iNO). Both infants had dramatic responses to iNO, suggesting that the pulmonary disease seen after prolonged oligohydramnios may have a component of nitric oxide-sensitive pulmonary hypertension. The goals of this article are to (1) review oligohydramnios-induced pulmonary hypoplasia, (2) discuss patients at highest mortality risk, and (3) describe the effects of iNO on pulmonary hypertension in infants with hypoxemia following prolonged ROM and severe oligohydramnios.
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ABSTRACT: We evaluated the use of inhaled nitric oxide in eight premature infants (520 to 1440 gm, 24 to 31 weeks of gestation) who failed to respond to conventional management and who had prolonged rupture of the membranes and oligohydramnios. All infants had a significant improvement in oxygenation and a fall in mean airway pressure with inhaled nitric oxide. Further studies are required to determine the safety and efficacy of this form of therapy.Journal of Pediatrics 04/1995; 126(3):450-3. · 4.04 Impact Factor
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ABSTRACT: Although inhaled nitric oxide (iNO) causes selective pulmonary vasodilation and improves oxygenation in newborn infants with persistent pulmonary hypertension, its effects are variable. We hypothesized (1) that the response to iNO therapy is dependent on the primary disease associated with persistent pulmonary hypertension of the newborn (PPHN) and (2) that the combination of high-frequency oscillatory ventilation (HFOV) with iNO would be efficacious in patients for whom either therapy alone had failed. To determine the relative roles of iNO and HFOV in the treatment of severe PPHN, we enrolled 205 neonates in a randomized, multicenter clinical trial. Patients were stratified by predominant disease category: respiratory distress syndrome (n = 70), meconium aspiration syndrome (n = 58), idiopathic PPHN or pulmonary hypoplasia (excluding congenital diaphragmatic hernia) ("other": n = 43), and congenital diaphragmatic hernia (n = 34); they were then randomly assigned to treatment with iNO and conventional ventilation or to HFOV without iNO. Treatment failure (partial pressure of arterial oxygen [PaO2] < 60 mm Hg) resulted in crossover to the alternative treatment; treatment failure after crossover led to combination treatment with HFOV plus iNO. Treatment response with the assigned therapy was defined as sustained PaO2 of 60 mm Hg or greater. Baseline oxygenation index and PaO2 were 48 +/- 2 and 41 +/- 1 mm Hg, respectively, during treatment with conventional ventilation. Ninety-eight patients were randomly assigned to initial treatment with HFOV, and 107 patients to iNO. Fifty-three patients (26%) recovered with the initially assigned therapy without crossover (30 with iNO [28%] and 23 with HFOV [23%]; p = 0.33). Within this group, survival was 100% and there were no differences in days of mechanical ventilation, air leak, or supplemental oxygen requirement at 28 days. Of patients whose initial treatment failed, crossover treatment with the alternate therapy was successful in 21% and 14% for iNO and HFOV, respectively (p = not significant). Of 125 patients in whom both treatment strategies failed, 32% responded to combination treatment with HFOV plus iNO. Overall, 123 patients (60%) responded to either treatment alone or combination therapy. By disease category, response rates for HFOV plus iNO in the group with respiratory syndrome and the group with meconium aspiration syndrome were better than for HFOV alone or iNO with conventional ventilation (p < 0.05). Marked differences in outcomes were noted among centers (percent death or treatment with extracorporeal membrane oxygenation = 29% to 75%). We conclude that treatment with HFOV plus iNO is often more successful than treatment with HFOV or iNO alone in severe PPHN. Differences in responses are partly related to the specific disease associated with PPHN.Journal of Pediatrics 07/1997; 131(1 Pt 1):55-62. · 4.04 Impact Factor
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ABSTRACT: The authors' have shown pulmonary alveolarization (capillary and alveolar growth) both after fetal tracheal occlusion and postnatal pulmonary distension. The trophic and developmental mechanisms responsible for this growth remain largely unknown; however, experimental systems have defined an enhanced expression of angiogenic proteins in response to tissue stretch. The authors hypothesize that the stimulation of pulmonary alveolarization after stretch is secondary to upregulation of the potent endothelial cell mitogen vascular endothelial growth factor (VEGF) and that the endothelial cell represents the central stimulus of parenchymal growth. A mixed primary pulmonary cell culture obtained by enzymatic digestion of fetal, neonatal, and adult mouse lung was plated on Bioflex elastomer bottom plates, grown to confluence, rendered quiescent, and subjected to continuous cycles of stretch-relaxation with nonstretched cells as controls. Cells were harvested at time-points 0, 30 minutes, 2 hours, 4 hours, 8 hours, and 24 hours. RNA was extracted and VEGF gene expression analyzed by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). Similar cell groups were harvested, processed, and analyzed utilizing Western Blot techniques. VEGF PCR of mRNA isolated from fetal sheep subjected to surgical creation of diaphragmatic hernia both with (DH-TL) and without (DH) tracheal ligation also was analyzed. VEGF mRNA isoforms 120, 164, and 188 showed increased expression in all stretched groups, which was noted by 30 minutes with maximal expression seen at 2 to 4 hours and a return to baseline expression by 24 hours. VEGF protein was similarly elevated in all stretched cell groups. In preliminary studies, DH/TL sheep showed upregulation of VEGF compared with DH sheep alone. These data show in an in vitro system that "pulmonary stretch" upregulates VEGF mRNA and protein expression supporting the role of angiogenesis in the stretch-induced pulmonary alveolarization. The authors speculate that such angiogenic activity is a rate-limiting factor in stimulating alveolar epithelial development, and as a treatment modality, therapeutic angiogenesis may provide a noninvasive method with which to treat pulmonary hypoplasia.Journal of Pediatric Surgery 07/2000; 35(6):906-12; discussion 912-3. · 1.38 Impact Factor