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1/12. Secondary infection presenting as recurrent pulmonary hypertension.

    Primary infection in the neonate, especially group B streptococcal infection, has long been recognized as a cause of persistent pulmonary hypertension of the newborn (PPHN), sometimes requiring treatment with inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO). However, secondary nosocomial infections in the neonatal period have not been widely reported as a cause of severe recurrent pulmonary hypertension (PHTN). We now present two cases of secondary infection in the neonate leading to significant PHTN. In both cases, the infants presented with PPHN soon after birth, requiring transfer to a level 3 neonatal intensive care unit and treatment with high-frequency oscillatory ventilation and iNO. After successful resolution of the initial PPHN, including extubation to nasal cannula, both infants developed signs of severe recurrent PHTN, leading to reintubation, high-frequency oscillatory ventilation and iNO therapy, and consideration of ECMO. In both cases, blood cultures taken at the time of recurrence of PHTN returned positive, one for staphylococcus epidermidis, the other for methicillin-resistant staphylococcus aureus. These unusual cases present the possibility of severe recurrent PHTN requiring iNO or ECMO in the setting of secondary infection. We speculate that these infants, although extubated after their first episodes of PHTN, were at risk for recurrence of PHTN due to continued pulmonary vascular reactivity.
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2/12. The use of L-arginine [correction of F-arginine] and phosphodiesterase inhibitor (dipyridamole) to wean from inhaled nitric oxide.

    A full-term, female neonate developed acute hypoxemic respiratory failure complicated by persistent pulmonary hypertension of the newborn (PPHN), and responded to high-frequency oscillatory ventilation (HFOV) and inhaled nitric oxide (iNO). Discontinuation of iNO was attempted three times and was followed by severe desaturation due to right-to-left shunt through the patent ductus arteriosus and patent foramen ovale. As a result of iNO dependency state and rebound pulmonary hypertension, the neonate was maintained on iNO therapy for dipyridamole alone was unsuccessful. However, successful discontinuation of iNO therapy was achieved by combination of L-arginine and dipyridamole. Exogeous NO may lead to down regulation of endogenous NO production, and further lead to rapid hydrolization of cyclic guanosine 3', 5' monophosphate (cGMP), the smooth muscle relaxant, by the enzyme phosphodiesterase. Moreover L-arginine, the precursor for the formation of endogenous NO, has been found to be deficient in neonates with PPHN, so we speculated that by inhibiting phosphodiesterase and administrating L-arginine smooth muscle relaxation occurred, and consequent weaning from iNO was achieved.
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3/12. Alveolar capillary dysplasia: a cause of persistent pulmonary hypertension of the newborn.

    The term alveolar capillary dysplasia refers to complex vascular abnormalities which have recently been identified in some infants with persistent pulmonary hypertension. We report four cases admitted to our institution for severe pulmonary hypertension unresponsive to maximal cardiorespiratory support, including high-frequency ventilation, inhaled nitric oxide and extracorporeal membrane oxygenation. The four infants died of refractory hypoxaemia. The diagnosis of alveolar capillary dysplasia was established by necropsy. We have used these cases as an opportunity for a thorough review of the literature containing comments regarding aetiology, pathophysiology, clinical presentation, associated malformations and treatment trials. CONCLUSION: alveolar capillary dysplasia should be ruled out in all newborn infants presenting severe idiopathic pulmonary hypertension associated with malformations. Open lung biopsy may prevent from using costly, invasive and probably ineffective procedures such as extracorporeal membrane oxygenation.
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4/12. iloprost in persistent pulmonary hypertension of the newborn.

    Aerosolized iloprost is now used as a therapeutic option in the treatment of pulmonary hypertension. We report on the administration of this derivative of prostacycline in treating severe pulmonary hypertension of the newborn. The combination of iloprost instilled endotracheally and inhaled was chosen as a last attempt at treatment in a critically ill patient who did not respond to advanced conventional treatments, including high frequency oscillation and inhalation of nitric oxide. The use of iloprost converted permanently the right-to-left shunting, leading to a substantial improvement in oxygenation.
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5/12. Pulmonary hypoplasia and persistent pulmonary hypertension: favorable clinical response to high-frequency jet ventilation.

    Pulmonary hypoplasia in the neonate is frequently fatal. This article reports two neonates with a clinical diagnosis of pulmonary hypoplasia complicated by persistent pulmonary hypertension (PPHN). Though both infants were progressively worsening while receiving conventional mechanical ventilatory support, they survived when treated with high-frequency jet ventilation.
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6/12. Inhaled nitric oxide in the treatment of persistent pulmonary hypertension/ hypoxic respiratory failure in neonates: an update.

    Persistent pulmonary hypertension (PPHN) and subsequent hypoxic respiratory failure is seen in association with numerous diseases and conditions in the neonate. This includes infections such as group B streptococcus, meconium aspiration syndrome, perinatal asphyxia, congenital diaphragmatic hernia, congenital heart disease, and as an idiopathic phenomenon. Conventional therapy of persistent pulmonary hypertension is discussed, as well as integrated with current treatment modalities such as surfactant replacement therapy and high frequency ventilation. The molecular action of nitric oxide including its relationship to neonatal cardiopulmonary transition at birth and the human neonatal clinical experience with term infants from 1992 to the present is explored. Also, the current use of inhaled nitric oxide in preterm infants is reviewed. Additionally, the follow-up of infants treated with inhaled nitric oxide is summarized, and novel therapies including inhaled prostacyclin and other pulmonary vasodilators such as sildenafil are introduced.
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7/12. Intravenous adenosine for refractory pulmonary hypertension in a low-weight premature newborn: a potential new drug for rescue therapy.

    OBJECTIVES: To use intravenous adenosine as a rescue therapy for neonatal refractory pulmonary hypertension in a low-weight premature infant. STUDY LINE: We report the successful use of a continuous intravenous adenosine infusion in a 1150-g premature baby with severe persistent pulmonary hypertension, refractory to classic management with high-frequency oscillatory ventilation, oxygen therapy and inhaled nitric oxide. RESULTS: adenosine infusion had a dramatic effect allowing for a rapid weaning of oxygen, ventilatory variables, and nitric oxide. CONCLUSIONS: Although experience with continuous adenosine infusion is still at an early stage, it might be worth considering its administration as a rescue therapy or even as an alternative to extracorporeal membrane oxygenation.
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8/12. Congenital diaphragmatic hernia: two case studies with atypical presentations.

    Congenital diaphragmatic hernia (CDH) affects 1 in every 2,000 to 4,000 live births. Many infants with this condition are diagnosed antenatally through routine ultrasound screening. Nearly 90 percent present at delivery with severe respiratory distress requiring intubation. Many of these infants develop persistent pulmonary hypertension of the newborn due to hypoplasia of the affected lung. The survival of infants with CDH is limited by the degree of pulmonary hypoplasia and requires sophisticated medical technology such as high-frequency ventilation and inhaled nitric oxide. Some infants also require treatment with extracoporeal membrane oxygenation. This article gives details of two cases of CDH in which the presentation was atypical. The more subtle presentation is discussed, as well as the embryology and pathophysiology of CDH and the possibility of associated anomalies. Clinical management and impact on the family are outlined.
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9/12. High-frequency oscillation for persistent fetal circulation after repair of congenital diaphragmatic hernia.

    A female neonate who had been diagnosed as having congenital diaphragmatic hernia by ultrasonography was delivered by cesarean section. After the hernia was repaired, she developed hypoxemia and hypercapnia, probably due to persistent fetal circulation (PFC). Neither conventional mechanical ventilation (CMV) nor manual ventilation improved the respiratory status. High-frequency oscillation (HFO) successfully improved pulmonary gas exchange, but we failed to wean the patient from HFO by using intermittent HFO. The patient was again placed on CMV for weaning and was extubated on the 12th ICU day. We conclude that HFO can be an alternative respiratory modality in patients with respiratory failure due to PFC after the repair of congenital diaphragmatic hernia.
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10/12. Piston-pump-type high frequency oscillatory ventilation for neonates with congenital diaphragmatic hernia: a new protocol.

    High frequency ventilation and extracorporeal membrane oxygenation (ECMO) are devices that are expected to save the lives of newborn infants whose pulmonary conditions have deteriorated. A piston-pump-type high-frequency oscillator (HFO), developed by Bryan and Miyasaka called "Hummingbird," is considered to be superior to high frequency "jet" ventilators or those of the flow-interrupter type, and was used successfully in two neonates with congenital diaphragmatic hernia (CDH) in a high-risk group. The first baby was on a conventional ventilator with pharmacologic support for the first 54 hours and then operated on. Postoperative deterioration necessitated the use of HFO for the next eight days. The infant then recovered uneventfully. For the second baby, HFO was necessary both preoperatively and postoperatively. This baby had a major diaphragmatic defect and her case was complicated with pneumothorax. There was a long stormy course on HFO (total, 70 days), but the patient was successfully extubated on the 75th day postoperatively and is now doing well. We believe active long preoperative stabilization with pharmacologic support and preoperative and postoperative hyperventilation with a piston-pump-type HFO may be a new innovative strategy for the management of severe CDH patients.
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keywords = high frequency, frequency
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