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1/19. 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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2/19. 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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3/19. 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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4/19. 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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5/19. 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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6/19. 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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7/19. 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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8/19. Fatal ureaplasmal pneumonia and sepsis in a newborn infant.

    ureaplasma urealyticum was isolated in pure culture from blood tracheal aspirate and lung tissue in a newborn infant, who died of a severe pneumonia within 48 h after birth. The clinical course was characterized by persistent pulmonary hypertension of the newborn (PPHN). Post-mortem examination revealed extensive hyaline membrane formation combined with signs of inflammation in both lungs. The clinical and histopathological picture resembled that of early onset group B haemolytic streptococcal pneumonia/sepsis.
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9/19. Pulmonary hypertension in neonatal cystic lung disease: survival following lobectomy and ECMO in two cases.

    extracorporeal membrane oxygenation (ECMO) is an accepted form of therapy in the treatment of neonates with otherwise lethal persistent pulmonary hypertension related to meconium aspiration, congenital diaphragmatic hernia, and sepsis. This report concerns two neonates with congenital cystic lesions of the lung who developed severe pulmonary hypertension and were salvaged with lobectomy and ECMO. These cases present an additional group of patients in whom ECMO may be a life-saving measure.
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10/19. Historical controls for extracorporeal membrane oxygenation in neonates.

    A retrospective review of all patients cared for who met Loe's criteria for extracorporeal membrane oxygenation (ECMO) was conducted covering the 3-yr period 1983 through 1985. There were five out of 3,726 admissions who met criteria for ECMO (three of 127 outborn admissions). All infants were greater than 2 kg birth weight and met criteria based on alveolar-arterial oxygen pressure difference (P[A-a]O2), barotrauma criteria, or both P(A-a)O2 and barotrauma criteria. All infants had persistent pulmonary hypertension. Two patients also had hyaline membrane disease and one also had asphyxia and meconium aspiration. All patients were treated with conventional therapy and all survived. There were no patients who met criteria for ECMO and died and there were no patients referred for ECMO during this period. Published criteria for ECMO estimate a control group mortality rate of 80% to 94%. mortality for this series was 0%. (Ninety-five percent confidence interval for mortality in a group of five survivors is 0% to 45%.) Controlled trials of ECMO were not done initially because it was considered unethical. This series shows that historical mortality rates are no longer valid and that controlled trials must be done.
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