Despite evidence of surfactant dysfunction in the acute respiratory distress syndrome (ARDS), treatment with exogenous surfactant remains experimental. Uneven pulmonary distribution is one factor that may limit response. We investigated whether exogenous surfactant administered by lavage, consisting of a 35 ml/kg volume instilled by gravity and followed immediately by passive drainage (LAVAGE), would result in better lung distribution and physiologic response than with surfactant administered as a 5 ml/kg bolus (BOLUS). Exosurf, an artificial surfactant, was administered after acute lung injury induced by saline lung lavage in neonatal piglets. In the LAVAGE group (n= 9), 10.1 +/- 0.4 ml/kg of surfactant was retained, corresponding to a phospholipid dose of 136 +/- 5 mg/kg. In the BOLUS group (n = 9), the dose administered was 203 mg/kg phospholipid. Piglets in the LAVAGE group demonstrated greater improvement in pulmonary function, including PaO2, PaCO2, ventilation efficiency index, functional residual capacity (FRC), and pressure-volume curves than piglets in the BOLUS group. Some differences were found in lung distribution of surfactant. We conclude that Exosurf is more effective when administered by lavage in this lung injury model. We speculate that the lavage method of administration holds promise as an alternative method of surfactant administration in patients with ARDS.

Evidence for surfactant dysfunction in acute respiratory distress syndrome (ARDS) suggests a role for exogenous surfactant which contains apoprotein for resistance to protein inhibition. We compared the effects of KL-4-Surfactant, an artificial preparation containing a synthetic 21 amino acid peptide with SP-B-like activity, with Exosurf, an artificial protein-free surfactant, and Survanta, a bovine protein-containing surfactant, in a saline lung lavage model of ARDS in neonatal piglets. Two sequential series of lung lavages were performed to lower PaO2 < 100 mm Hg, each followed by administration of surfactant or air and a 90-min observation period. Progressive lung injury was demonstrated by deterioration in pulmonary function, increasing bronchoalveolar lavage protein, and changes in histopathology. All surfactants improved oxygenation, although oxygenation was generally better with Survanta and KL-4-Surfactant. Further, Survanta and KL-4-Surfactant groups showed improvement in ventilation, with decreases in PaCO2 and increases in FRC. Only KL-4-Surfactant demonstrated greater pressure-volume characteristics and lower bronchoalveolar protein than those of Controls. We conclude that the physiologic effects of KL-4-Surfactant are more like Survanta in this model. We speculate that KL-4-Surfactant may improve pulmonary function, reduce alveolar protein leak, and thus be efficacious in the treatment of ARDS.

Recent reports have suggested that substituting continuous negative extrathoracic pressure (CNEP) for positive end-expiratory pressure (PEEP) may result in clinical benefits to infants with pulmonary disease. Other studies have suggested potential hemodynamic advantages. We compared the effects of CNEP and PEEP in 13 mechanically ventilated newborn piglets after acute lung injury induced by saline lavage. The piglets were instrumented, saline-lavaged, and exposed to 15 minute periods of incremental CNEP (-3, -6, -9, -12 cmH2O) (n = 7) or PEEP (3, 6, 9, 12 cmH2O) (n = 6). We measured and/or calculated dynamic lung compliance (CLdyn), lung resistance (RL), end-expiratory lung volume (EELV), blood gases, cardiac output (CO), heart rate (HR), transmural vascular pressures, and pulmonary and systemic vascular resistance. Pulmonary function abnormalities after saline lavage included decreased PaO2, CLdyn, EELV, and increased PaCO2 and RL (P < 0.05). Except for decreased CO, lung inflation with both CNEP and PEEP resulted in large increases in PaO2 without major pulmonary or hemodynamic effects. Other than differences in EELV at 3, 6, and 9 cmH2O distending pressure, there were no differences in pulmonary function or hemodynamics between sequences of incremental CNEP and PEEP. We conclude that CNEP and PEEP are physiologically equivalent in this model of acute lung injury.

No abstract

We studied different sequences of lung inflation in ventilated newborn piglets with normal lungs in order to determine the effects of sequence, magnitude and duration of distending pressure on pulmonary function, and/or hemodynamics. End-expiratory pressure was varied using a continuous negative extrathoracic pressure (CNEP) device. Three groups of ventilated piglets with normal lungs were exposed to 2 cmH2O increments of CNEP from -2 to -12 cmH2O, and to decrements from -12 to -2 cmH2O, or to only -6 cmH2O. Lung inflation sequence, magnitude of inflation pressure, and duration of inflation had significant effects on end-expiratory lung volume and lung compliance at numerically equivalent pressure levels. End-expiratory lung volume and lung compliance varied (at four and five of six inflation pressures studied) by as much as 68% and 104%, respectively. Hemodynamic effects of the lung inflation sequence were more variable; those found to be different at numerically equivalent pressure levels were associated with changes in lung compliance and ventilation. Differences in pulmonary mechanics can best be explained by the effects of lung inflation on alveolar recruitment versus overinflation.