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1/27. 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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2/27. 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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3/27. 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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4/27. Use of extracorporeal membrane oxygenation to rescue a newborn with early-onset group B streptococcal sepsis and cardiopulmonary failure.

    Group B streptococcal (GBS) infection is an important cause of perinatal morbidity and mortality. We report the use of extracorporeal membrane oxygenation (ECMO) to rescue a newborn with refractory GBS sepsis and meningitis who developed cardiopulmonary failure. This 2-day-old infant weighed 2640 g and was born to a healthy mother at full term. Respiratory distress, hypotension, and persistent pulmonary hypertension developed on the second day of life. The clinical condition deteriorated rapidly despite conventional treatment, and venoarterial ECMO was established to rescue this moribund newborn. During ECMO, the patient regained stable hemodynamics and good oxygenation, and infection was controlled. ECMO was used for 90 hours and the baby was weaned smoothly. Neurologic assessment after ECMO revealed hydrocephalus, abnormal electroencephalogram, and increased brain auditory evoked potential threshold. This report emphasizes that ECMO may be considered to rescue neonatal patients with cardiopulmonary failure due to GBS sepsis. Possible neurologic complications after ECMO should be carefully monitored.
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5/27. Persistent pulmonary hypertension complicating cystic adenomatoid malformation in neonates.

    Neonates with congenital diaphragmatic hernia (CDH) are known to be susceptible to stress-induced persistent pulmonary hypertension (PPHN). Congenital cystic adenomatoid malformations (CCAMs) may also present as respiratory distress in the newborn. intubation and mechanical ventilation cause clinical deterioration because of air trapping within cystic spaces; these patients require prompt lobectomy. PPHN has not been commonly associated with CCAM. Three patients with CCAM were encountered who developed PPHN postlobectomy. Three newborns, 36 to 38 weeks' gestation, presented with respiratory distress. Two had diagnosis of thoracic tumors on fetal ultrasound (22 and 33 weeks). Chest x-ray at birth confirmed cystic intrathoracic tumors in all and they underwent immediate thoracotomy and lobectomy (1 right upper, 1 left lower, 1 left upper). The patients were stable for 4 hours to 5 days postoperatively and then developed findings consistent with PPHN by cardiac echocardiography and required extracorporeal membrane oxygen (ECMO) support. ECMO was required for 66.5 to 120 hours. Each patient was successfully weaned to conventional ventilatory support. The clinical course of these patients was similar to those with CDH who undergo immediate surgery. The stress of surgical intervention combined with hypoxia and hypercarbia stimulates a hyperactive pulmonary vasculature and the development of PPHN. ECMO provides an effective adjunct to support patients with PPHN on the basis of congenital cystic adenomatoid malformations.
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keywords = hypoxia, oxygen
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6/27. Neonatal thyrotoxicosis and persistent pulmonary hypertension necessitating extracorporeal life support.

    We report a case of neonatal Graves' disease involving an infant with severe persistent pulmonary hypertension (PPHN) associated with neonatal thyrotoxicosis that necessitated extracorporeal membrane oxygenation. hyperthyroidism, although uncommon in the newborn period, has been associated with pulmonary hypertension among adults. The exact mechanisms responsible for this effect on pulmonary vascular pressure are not well understood. Recent studies have provided evidence that thyrotoxicosis has direct and indirect effects on pulmonary vascular maturation, metabolism of endogenous pulmonary vasodilators, oxygen economy, vascular smooth muscle reactivity, and surfactant production, all of which may contribute to the pathophysiologic development of PPHN. Therefore, because PPHN is a significant clinical entity among term newborns and the symptoms of hyperthyroidism may be confused initially with those of other underlying disorders associated with PPHN (eg, sepsis), it would be prudent to perform screening for hyperthyroidism among affected newborns.
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7/27. Neonatal persistent pulmonary hypertension treated with milrinone: four case reports.

    Current standard therapy for persistent pulmonary hypertension of the newborn (PPHN) consists of optimal lung inflation, hemodynamic support and selective vasodilation with inhaled nitric oxide (iNO). However, not all infants will respond. milrinone, a phosphodiesterase (PDE) III inhibitor, is routinely used in pediatric cardiac intensive care units to improve inotropy and reduce afterload. Although its use in post-operative cardiac failure has been proven in a randomized trial, it has not been reported to be beneficial in PPHN. We report four cases with severe PPHN treated with a combination of iNO and milrinone. All four cases were unresponsive to therapy including iNO, with a mean oxygenation index (OI) of 40 (standard deviation (SD) 12)) before milrinone. Substantial improvement in OI (mean of 28; SD 16) was followed by extubation and survival. However, of 4 patients, 2 developed serious intraventricular hemorrhages (IVHs), and 1 had a small IVH. To clarify the risk benefit ratio, of death versus survival with impairment, a randomized controlled trial is needed.
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ranking = 1
keywords = oxygen
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8/27. nitric oxide in neonatal transposition of the great arteries.

    Three newborn infants with transposition of the great arteries (TGA) and intact ventricular septum (IVS) developed postnatal persistent pulmonary hypertension of the newborn (PPHN) and were successfully treated with inhaled nitric oxide (iNO). Intervention with balloon atrial septostomy (BAS) was performed in two of the infants before the iNO treatment, but they continued to be severely hypoxic with metabolic acidosis. However, the iNO immediately improved oxygenation and the clinical condition. The third neonate had a moderately large atrial communication and echocardiographic signs of PPHN. He received iNO before BAS with dramatic clinical improvement, which therefore postponed BAS. CONCLUSION: early diagnosis of PPHN and treatment with iNO may improve final outcome in neonates with TGA and IVS. In the presence of moderately large atrial communication and PPHN, treatment with iNO might be considered before BAS.
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9/27. 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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ranking = 3
keywords = oxygen
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10/27. 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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ranking = 1
keywords = oxygen
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