Exogenous surfactant decreases oxygenation in Escherichia coli endotoxin-treated neonatal piglets.

Abnormalities of pulmonary surfactant function have been described in association with the acute respiratory distress syndrome (ARDS). Because gram-negative sepsis is a common cause of ARDS, we treated neonatal piglets with Escherichia coli endotoxin to create a neonatal ARDS model. We hypothesized that under these conditions administration of exogenous surfactant would improve pulmonary function. Study groups included: control (n-8), Exosurf (5 mL/kg, 13.5 mg phospholipid/mL, n-7), Survanta (4 mL/kg, 25 mg phospholipid/mL, n-6), and saline (5 mL/kg, n = 6). E. coli endotoxin 12 micrograms/kg was infused over 30 min and resulted in significant pulmonary and hemodynamic abnormalities, histopathologic evidence of nonhomogeneous lung injury, and elevated protein levels in bronchoalveolar lavage washings. Neither Exosurf nor Survanta ameliorated the pulmonary effects of endotoxin. Instead, there was a prolonged decrease in arterial oxygen tension (PaO2) and dynamic lung compliance after administration of surfactant and saline. Distribution of a bolus of Exosurf was uneven throughout the lung. We conclude that in this neonatal piglet model of ARDS, bolus surfactant administration had a detrimental effect on oxygenation and pulmonary function.

Giardia duodenalis: exposure to metronidazole inhibits competitive interactions between isolates of the parasite in vitro.

The competitive interactions of genetically distinct isolates of Giardia duodenalis with different growth rates were studied in vitro. Electrophoretic analysis of mixed cultures showed that competition between 2 cloned isolates occurs under normal in vitro culture conditions, with faster-growing isolates outcompeting those with slower growth rates. The addition of sublethal concentrations of metronidazole to clonal mixtures in vitro prevented the competitive exclusion, which was seen in normal culture. This apparently occurred because the drug reduced the growth rate of the faster-growing but not the slower-growing clone.

Physiologic response and lung distribution of lavage versus bolus Exosurf in piglets with acute lung injury.

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.

Exogenous surfactants in a piglet model of acute respiratory distress syndrome.

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.

Preservation of pulmonary function in the ventilated neonatal piglet with normal lungs.

Little attention has been focused on the progressive pulmonary deterioration which occurs in mechanically ventilated infants with normal or mildly abnormal lungs. We hypothesized that lung function would deteriorate over a 24-hr period in anesthetized neonatal piglets with normal lungs mechanically ventilated at 2 cm H2O PEEP (2PEEP group). We further hypothesized that an intermittent lung inflation procedure consisting of 15 out of 60 min of increasing lung distention (4, 8, 12 cm H2O PEEP), with the remaining 45 min at 2 cm H2O PEEP (Inflation group) would prevent this deterioration in lung function, similar to piglets mechanically ventilated continuously at 6 cm H2O PEEP (6PEEP). Results indicate that 2PEEP piglets experienced progressive deterioration in lung function, including dynamic lung compliance (-42%) and lung resistance (+55%). In contrast, inflation piglets and 6PEEP piglets had no deterioration in lung function. Hemodynamics were similar between groups, although they were the most stable in the 6PEEP group. Histopathological changes were not significantly different. We conclude that (1) prolonged mechanical ventilation at 2 cm H2O PEEP in neonatal piglets resulted in progressive deterioration in pulmonary function, (2) intermittent lung inflation or continuous 6 cm H2O PEEP prevented deterioration, and (3) functional changes occurred without changes in histopathology. Lung inflation strategies other than PEEP can be used to prevent deterioration in lung function which accompanies prolonged mechanical ventilation in anesthetized nonspontaneously breathing piglets with normal lungs.

Effect of baseline lung compliance on the subsequent response to positive end-expiratory pressure in ventilated piglets with normal lungs.

OBJECTIVE: To determine the pulmonary function and hemodynamic effects of incremental positive end-expiratory pressure in two groups of normal ventilated newborn piglets with different baseline dynamic lung compliance. DESIGN: Prospective, controlled, intervention study. SETTING: Animal laboratory. INTERVENTIONS: One group of piglets (inflation group) was prepared with 3 cm H2O (0.29 kPa) positive end-expiratory pressure and a maximal lung inflation to increase baseline lung compliance as compared with the other group (no-inflation group), prepared by 3 hrs of ventilation at zero end-expiratory pressure. Both groups were then subjected to a sequence of incremental positive end-expiratory pressures from 0 to 12 cm H2O (0 to 1.18 kPa) in 2-cm increments for 15-min periods at each level followed by a 60-min recovery period at zero end-expiratory pressure. MEASUREMENTS AND MAIN RESULTS: Pulmonary function, hemodynamic and blood gas data were collected at each positive end-expiratory pressure value and at 15-min intervals during recovery. Baseline dynamic lung compliance was 5.2 +/- 0.3 mL/cm H2O (53.04 +/- 3.06 mL/kPa) in the inflation group and 2.5 +/- 0.1 mL/cm H2O (25.5 +/- 1.02 mL/kPa) in the no-inflation group. No differences were found in any other pulmonary function, hemodynamic or blood gas value at baseline. Incremental positive end-expiratory pressure resulted in a decrease in dynamic lung compliance and an increase in end-expiratory lung volume in both groups of piglets; dynamic lung compliance was greater in the inflation group at all times. No differences were found in end-expiratory lung volume between groups. Hemodynamic changes in both groups of piglets included: decreased cardiac output and increased pulmonary vascular resistance and systemic vascular resistance. The changes in cardiac output (-23% vs. -32%), pulmonary vascular resistance (+53% vs. +95%), and systemic vascular resistance (17% vs. 51%) were less in the inflation group as compared with the no-inflation group. CONCLUSIONS: Baseline dynamic lung compliance is an important determinant of the subsequent effect of positive end-expiratory pressure on pulmonary function and hemodynamics in the ventilated piglet with normal lungs.

Continuous negative extrathoracic pressure versus positive end-expiratory pressure in piglets after saline lung lavage.

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.

The effects of reversing distending pressure sequences in the neonatal piglet.

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.

Pancuronium does not alter the hemodynamic status of piglets after normoxia or hypoxia.

Pancuronium is a neuromuscular blocking agent commonly used to eliminate agitation in sick newborn infants requiring mechanical ventilation. Experimental data supporting this method of intervention are controversial, and hemodynamic studies in newborn infants report conflicting results. This study was designed to determine the hemodynamic effects of pancuronium administered under conditions of normoxia, hypoxia, and preexposure to hypoxia in neonatal piglets with normal lungs. After baseline hemodynamic and blood gas measurements were obtained, pancuronium was administered in two i.v. bolus injections of 0.1 mg/kg. Tidal volume and minute ventilation were maintained constant during the experimental procedure by adjusting ventilator settings. Twenty min after pancuronium, no changes from baseline values were found in arterial blood gases, heart rate, cardiac output, mean arterial pressure, systemic vascular resistance, pulmonary artery pressure, pulmonary vascular resistance, central venous pressure, or pulmonary capillary wedge pressure in any of the three conditions studied. In conclusion, pancuronium administered during normoxia, hypoxia, or after preexposure to hypoxia while controlled ventilation is maintained does not alter systemic or pulmonary hemodynamic status of the newborn piglet.