Efficacy of inhaled nitric oxide in a porcine model of adult respiratory distress syndrome.

OBJECTIVE: To assess the efficacy of inhaled nitric oxide (NO) in reducing pulmonary hypertension in a porcine model of adult respiratory distress syndrome. DESIGN: Nonrandomized, controlled experiment without blinding. SETTING: Surgical research laboratory. PARTICIPANTS: Twelve pigs, matched equally for body weight. INTERVENTION: Acute lung injury was induced by intravenous injection of oleic acid. Animals were then divided into either a control group, for monitoring without any further intervention, or a NO-treatment group, in which NO was administered at concentrations of 10 to 80 ppm, with each step separated by a NO-free interval to assess duration of effect. MAIN OUTCOME MEASURES: Pulmonary artery pressure, systemic blood pressure, PaO2, intrapulmonary shunt fraction, and extravascular lung water. Nitrosylated hemoglobin, arterial methemoglobin, and plasma nitrite and nitrate concentrations. RESULTS: All animals responded to oleic acid injection with rapid development of pulmonary hypertension and deterioration of PaO2 and intrapulmonary shunt fraction. Inhaled NO reversed these changes in a concentration-dependent manner. Cessation of NO administration led to a prompt return of pulmonary hypertension. A small but significant drop in systemic blood pressure was observed only at the highest concentration of NO administered (80 ppm). Extravascular lung water almost doubled following oleic acid injury. This increase was sustained in all animals for the remainder of the experiment. Significant increases in circulating methemoglobin and plasma nitrite and nitrate concentrations were measured during NO inhalation. CONCLUSION: Inhaled NO appears to be a selective pulmonary vasodilator and may prove to be useful in improving gas exchange in adult respiratory distress syndrome.

Cardiopulmonary bypass significantly reduces surfactant activity in children.

Lung injury remains an important problem after cardiopulmonary bypass. The contribution of altered surfactant concentration or activity to pulmonary dysfunction after cardiopulmonary bypass is unclear. Recent evidence indicates that alveolar surfactant exists in specific aggregate forms that differ with respect to density, phospholipid composition, and function. A transition from surface active, higher density, large aggregates of surfactant to lower density, small aggregates that possess reduced surface activity has been demonstrated after experimental lung injury. The purpose of the present study was to examine surfactant aggregate fractions before and after bypass in children. Twelve acyanotic patients, aged 2 to 12 years, underwent intraoperative pulmonary function testing followed by bronchoalveolar lavage before incision and approximately 1 hour after termination of cardiopulmonary bypass. Saturated phosphatidylcholine pool sizes and total protein content of the small- and large-aggregate fractions of bronchoalveolar lavage fluid were determined. One hour after termination of cardiopulmonary bypass, the ratio of saturated phosphatidylcholine in small-aggregate as compared with that in large-aggregate fractions increased (mean +/- standard error) from 0.19 +/- 0.03 to 0.37 +/- 0.07 (p < 0.02), as did the ratio of saturated phosphatidylcholine to protein in the small-aggregate fraction (from 0.04 +/- 0.01 to 0.08 +/- 0.02, p < 0.05). Reductions in forced vital capacity (-19% +/- 5%), inspiratory capacity (-15% +/- 3%), and small airway flow rates (-32% +/- 6%) were also observed after bypass. These changes were accompanied by a fivefold increase in alveolar polymorphonuclear leukocyte content. The present study suggests that cardiopulmonary bypass of moderate duration in relatively healthy children is associated with surfactant changes that are similar in type and magnitude to those observed in experimental lung injury.

Lung mechanics during and after extracorporeal membrane oxygenation for meconium aspiration syndrome.

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.

Pulmonary dysfunction in surgical conditions of the newborn infant.

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.

Effect of preoperative stabilization on respiratory system compliance and outcome in newborn infants with congenital diaphragmatic hernia.

To determine whether preoperative stabilization and delay of operative repair of congenital diaphragmatic hernia (CDH) may decrease operative risk, we performed serial pulmonary function tests on 22 newborn infants with CDH and on four infants without pulmonary hypoplasia (two with ileal atresia and two with tracheoesophageal anomalies) who served as control subjects. We used 2 passive respiratory mechanics technique to measure respiratory system compliance. All patients with CDH had respiratory distress immediately after birth, and required mechanical ventilation. Thirteen babies underwent emergency repair (six survived, seven died); nine of them received extracorporeal membrane oxygenation (ECMO) after the operation (two survived, seven died). Operative repair was delayed deliberately for 2 to 11 days in nine infants with severe hypoxemia. Six immediately received ECMO for 4 to 10 days; one died of intraventricular hemorrhage, and five survived and later underwent surgical repair. The seventh patient did not receive ECMO but appeared to have respiratory distress syndrome of infancy and improved after administration of synthetic surfactant. Improvement was seen in two additional infants who received conventional assisted ventilation during a 48-hour delay before surgery, and survived. In all, eight of nine infants who underwent preoperative stabilization survived (p less than 0.05 compared with survival after emergency surgery). Following surgical repair immediately after birth, respiratory system compliance improved only slightly during the first week of life, a time when control infants had a rapid increase in respiratory system compliance (p less than 0.001). In contrast, respiratory system compliance increased nearly twofold in the nine patients undergoing preoperative stabilization (p less than 0.02). Preoperative ECMO was associated with an increase in respiratory system compliance of more than 60% for 1 week, a significant difference from respiratory system compliance among patients undergoing emergency CDH repair (p less than 0.05). These observations provide physiologic evidence of possible benefits of preoperative stabilization before repair of CDH.

Determination of optimal continuous positive airway pressure for the treatment of IRDS by measurement of esophageal pressure.

We describe a simple and reliable method to determine optimal airway pressure in infants with idiopathic respiratory distress syndrome who require continuous positive airway pressure treatment. Esophageal pressure was monitored in ten infants with IRDS during initial application of CPAP. As the level of CPAP was increased in 2 cm H2O increments, changes in Pes were compared with changes in PaO2. Below optimal airway pressure, Pes as well as PaO2 increased insignificantly. When optimal airway pressure (8.1 +/- 0.8 cm H2O) was applied, there was a marked increase in Pes (3.6 +/- 0.8 cm H2O. p less than 0.001) and PaO2 (39.0 +/- 10.0 mm Hg, p less than 0.01). Further increase in CPAP did not result in any subsequent appreciable increase in Pes while PaO2 decreased slightly and PaCO2 increased. Less than optimal CPAP increases F102 requirements and may increase the associated risk of bronchopulmonary dysplasia, while excessive levels of CPAP may increase the risk of pneumothorax. We suggest that esophageal pressure be monitored routinely to determine the optimal level of CPAP for each infant during the initial application of therapy.

Lung elasticity and airway dynamics in Peruvian natives to high altitude.

To evaluate the role of genetic and environmental factors in the genesis of large lungs in high-altitude natives, we measured forced vital capacity (FVC), static lung pressure-volume characteristics and maximum expiratory flow-volume loops in 17- to 20-yr-old Peruvian natives to 3,850 m (highlanders) and 800 m (lowlanders). Forced vital capacity was 5.11 +/- 0.64 liters in highlanders, 116 +/- 11% of predicted; and 3.73 +/- 0.32 liters in lowlanders, 84 +/- 7% of predicted. Lung elastic recoil at functional residual capacity and at total lung capacity, and size-corrected pressure volume curves were similar in the two groups. Despite the larger volumes in highlanders, density-corrected maximum flow rates were similar in highlanders and lowlanders, and flow expressed in FVC'S-S-1 was less in highlanders. Upstream conductance at 50% FVC expressed in fvc's-s-1-cmH2O was 0.094 +/- 0.023 in highlanders vs. 0.147 +/- 0.050 in lowlanders. Flow rates did not change in sojourners to altitude, suggesting that the lower values of highlanders were due to anatomic factors. These findings suggest that airways, which form in fetal life, do not participate in adaptation to altitude, and that the large lungs of highlanders result from postnatal environmental hypoxic stimulation of lung growth. Our results illustrate the importance of "dysynaptic" lung growth in determining patterns of adult lung function.