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Objective: To assess the efficacy of inhaled nitric oxide in improving pulmonary hypertension and gas exchange following oleic acid-induced acute lung injury., Design: Prospective, pharmacologic study., Setting: Surgical research laboratory at the University of Pittsburgh, Pittsburgh, PA., Subjects: Instrumented, intubated pigs weighing 16 to 27 kg., Interventions: Intravenous oleic acid and inhaled nitric oxide., Measurements and Main Results: All pigs treated with intravenous oleic acid (0.11 mL/kg) developed a severe lung injury with pulmonary hypertension, accompanied by impaired oxygenation, intrapulmonary shunting, and increased extravascular lung water (p < .05 compared with baseline). Following nitric oxide inhalation, although pulmonary hypertension decreased in a dose-dependent fashion, no amelioration in pulmonary gas exchange was observed, as reflected by PaO2 and intrapulmonary shunt. Plasma nitrite and nitrate concentrations, the stable end products of nitric oxide metabolism, did not increase following nitric oxide exposure in this model of severe lung injury., Conclusions: The effect of inhaled nitric oxide, restricted to relieving pulmonary vasoconstriction in this model of lung injury, may have limited benefit in improving pulmonary gas exchange when diffusion is impaired by severe lung injury and inflammatory thickening of the alveolar-capillary barrier. Nitric oxide inhalation may have better results when used at an earlier, less severe stage of acute lung injury.

Objective: To determine whether airway hyperresponsiveness contributes to the development of lower airway obstruction in infants recovering from severe meconium aspiration syndrome treated with extracorporeal membrane oxygenation (ECMO)., Design: Prospective comparison study of the response to bronchodilator during the acute and convalescent phase of severe meconium aspiration., Setting: Pediatric/neonatal intensive care unit in a tertiary care hospital., Patients: Seven neonates with severe meconium aspiration syndrome that was refractory to conventional mechanical ventilation, requiring ECMO treatment., Interventions: Evaluation of the effect of bronchodilator treatment on the airway function at a postnatal age of 14 +/- 2.7 (SEM) days, after the patients had been off ECMO for 4.6 +/- 1.4 days, and comparison with the response the same patients had shown at a postnatal age of 2.7 +/- 0.6 days, when they had been on ECMO for 1.3 +/- 0.6 days. Lung mechanics and lower airway function were measured and compared before and after administration of aerosolized isoetharine early in the course of ECMO and again several days after ECMO. Maximum expiratory flow-volume curves produced by the deflation flow-volume curve technique were used for evaluating the lower airway function, and partial passive flow-volume curves were used for measuring respiratory system compliance and resistance., Measurements and Main Results: During the first test, isoetharine produced a mild increase in maximum expiratory flows at 25% (MEF25) of forced vital capacity (FVC) (48 +/- 27% compared with baseline values), without significant change in the MEF25 to FVC ratio. During the second test approximately 2 wks later (post-ECMO), isoetharine increased MEF25 by 123 +/- 29% and increased the MEF25/FVC by 40 +/- 13% compared with baseline values. The percent change in both indices was significantly higher during the second test (p < .05) than in the first test., Conclusions: Airway obstruction in infants recovering from severe meconium aspiration syndrome is partially reversible with aerosolized isoetharine, indicating that airway hyperresponsiveness contributes to the pathogenesis of airway obstruction.

Objective: To determine whether abnormalities in lung mechanics detected in infants during the acute phase of meconium aspiration syndrome persist after treatment with extracorporeal membrane oxygenation (EMCO)., Design: Prospective, descriptive study. Prospective evaluation of airway function and lung mechanics during and after ECMO by pulmonary function testing at 1.8 +/- 0.5 days of EMCO (period 1), follow-up at 1.4 +/- 0.2 days (period 2), and 7.0 +/- 0.9 days (period 3) after decannulation from ECMO., Setting: Tertiary care neonatal/pediatric ICU., Patients: Twelve neonates undergoing ECMO treatment for severe meconium aspiration syndrome that was refractory to conventional mechanical ventilation., Interventions: Maximum expiratory flow-volume curves were studied with the deflation flow-volume curve technique, and compliance and resistance of the respiratory system were studied with partial passive flow-volume curves., Measurements and Main Results: Respiratory system compliance was the only index of respiratory mechanics that was significantly (p less than .05) improved (0.96 +/- 0.1 vs. 0.61 +/- 0.1 mL/cm H2O/kg) immediately after decannulation from ECMO compared with period 1. Clinically important (p less than .05) improvement in forced vital capacity (28.0 +/- 5.5 vs. 16.1 +/- 1.9 mL/kg), respiratory system compliance (1.01 +/- 0.2 vs. 0.61 +/- 0.1 mL/cm H2O/kg), and maximum expiratory flow at 25%/forced vital capacity (1.0 +/- 0.3 vs. 2.2 +/- 0.3) was evident only during period 3 compared with period 1., Conclusions: We conclude that improvements in the clinical condition and oxygenation, permitting successful decannulation from ECMO, are achieved before clinically important improvements in lung mechanics.

Objective: To describe the pathophysiology of surgical conditions that are associated with respiratory insufficiency in the newborn infant., Design: Survey., Setting: Newborn ICU in a children's hospital., Patients: Twenty-four newborn infants (1 to 28 days old) who required endotracheal intubation and mechanical ventilation for operative procedures or postoperative ventilatory support., Interventions: Flow-volume curves obtained by manual inflation of the lungs, followed by forced deflation by negative pressure, and by passive expiration, under sedation and pharmacologic paralysis., Measurements: Deflation flow-volume curves and passive expiratory curves were measured. Pulmonary function testing before and after bronchodilator administration (n = 11) began midway during the study period. Term and preterm groups served as controls., Main Results: Forced vital capacity (FVC) was decreased in all groups with surgical disease as follows: abdominal wall defects and necrotizing enterocolitis groups to 48.3% and 62.1% that of preterm, respectively; pulmonary hypoplasia group to 55.5% that of term (p less than .05). Maximal expiratory flow at 25% of FVC decreased in all groups: abdominal wall defects and necrotizing enterocolitis group, to 36.8% and 37.9% that of preterm, respectively (p less than .05); pulmonary hypoplasia group, 20.0% that of term (p less than .05). The ratio of maximal expiratory flow at 25% of FVC divided by FVC was significantly decreased in necrotizing enterocolitis and pulmonary hypoplasia groups compared with that of preterm and term groups, respectively, but not in the abdominal wall defects group. Maximal expiratory flow at 25% of FVC, but not FVC, increased significantly (36%, p less than .05) after bronchodilator nebulization, indicating the presence of airway reactivity. Respiratory system compliance was decreased significantly (p less than .05) in all surgical disease groups compared with the term group., Conclusions: Bronchial reactivity contributes to decreased maximal expiratory flow at 25% of FVC, a feature also seen in premature infants with respiratory distress syndrome who later develop bronchopulmonary dysplasia. Babies who require chronic ventilatory support after operation and who have developed reactive airways may benefit from the administration of bronchodilators during postoperative ventilatory management.

Background and Methods: Liquid ventilation using perfluorocarbons is a new technique for ventilation of infants with restrictive lung disease. However, this method of ventilation has been shown to impair cardiac output (Qt) in several animal species, casting doubt as to its feasibility. This study tested whether Qt could be maintained during liquid breathing by intravascular volume expansion. Seven piglets were carefully hydrated, instrumented for continuous Qt measurement, and subjected to 2 hr of liquid breathing. PaCO2 was maintained at 40 to 50 torr (5.3 to 6.7 kPa), and PaO2 greater than 80 torr (greater than 10.7 kPa). Additional colloid was given during liquid breathing if Qt decreased to less than 90% of preliquid breathing values., Results: Four piglets maintained Qt throughout the liquid breathing trial with maintenance fluids only. Three piglets each required one 10 mL/kg fluid bolus for Qt 82% to 89% of the baseline value, after which Qt rapidly increased to greater than 90% of baseline. Oxygen consumption and serum lactate levels remained normal throughout liquid breathing., Conclusion: Qt is readily maintained during liquid breathing in properly hydrated animals.