Venkataraman Balaraman

Congenital chylothorax and mediastinal neuroblastoma

This is the first reported association of congenital chylothorax and mediastinal neuroblastoma in a newborn infant. The infant exhibited features of both congenital and acquired chylothorax. Resolution of the chylothorax occurred following ligation of thoracic duct after failure of conservative management with multiple thoracentesis and chest tube drainage.

Lavage administration of dilute recombinant surfactant in acute lung injury in piglets.

In an acute lung injury model, we previously observed reversal of pulmonary dysfunction with natural surfactant administered by lavage (dose = 18 mg/kg phospholipid). The present study questioned whether a lower dose of phospholipid would be effective if a recombinant preparation rather than natural surfactant were used. Acute lung injury was induced by repeated saline lung lavage in ventilated, sedated, and paralyzed piglets. Three concentrations of recombinant surfactant were studied (low phospholipid, 1 mg/mL; medium phospholipid, 4 mg/mL; high phospholipid, 13.5 mg/mL). Control piglets received no surfactant. Thirty-five milliliters per kilogram of surfactant was administered by gravity, followed by passive drainage of excess fluid. All treatment groups retained similar volumes (4.7 ± 0.3 mL/kg), corresponding to phospholipid doses of 4 ± 0.4, 22 ± 3, and 67 ± 4 mg/kg in low, medium, and high-dose groups, respectively. Treatment groups showed significant improvement in PaO2 compared with controls. Other parameters different from controls were found in only the medium and high-dose groups. All surfactant-treated groups showed improvement over time in PaO2, PaCO2, lung resistance, mean airway pressure, functional residual capacity, and dynamic compliance. These data support the statement that whereas there is a dose response to exogenous surfactant, the effective dose of recombinant surfactant in acute lung injury may be as low as 4 mg/kg phospholipid when administered by lavage.

Lavage administration of dilute surfactant in a piglet model of meconium aspiration.

Maldistribution of exogenous surfactant may preclude any clinical response in acute lung injury associated with surfactant dysfunction. Our previous studies have shown the effectiveness of surfactant lavage after homogenous lung injury. The present study utilizes a histologically confirmed non-homogeneous lung injury model induced by saline lung-lavage followed by meconium injected into a mainstem bronchus. Piglets were then treated with Infasurf® or Exosurf® by lavage (I-LAVAGE, n = 7; E-LAVAGE, n = 5) or bolus (I-BOLUS, n = 8; E-BOLUS, n = 5), or went untreated (CONTROL, n = 4). Lavage administration utilized a dilute surfactant (35 ml/kg; 4 mg phospholipid/ml) instilled into the lung, followed by gravity drainage. The retained doses of the respective surfactant in the lavage and bolus groups were similar. Results showed that the surfactant distribution was more uniform in the lavage groups compared to the bolus groups. Significant and consistent increases in PaO2 were observed in the lavage groups compared to the bolus groups and the controls. PaO2 (mmHg) at 240 min posttreatment: I-LAVAGE = 297 ± 54, E-LAVAGE = 280 ± 57; I-BOLUS = 139 ± 31; E-BOLUS = 152 ± 29; C = 119 ± 73 (mean ± SEM). Other improved pulmonary function parameters favored lavage administration. We conclude that better surfactant distribution achieved by lavage administration can be more effective than bolus administration in this type of non-homogeneous lung injury.

End-Tidal Carbon Monoxide in Newborn Infants: Observations during the 1st Week of Life

Serial end-tidal carbon monoxide corrected for ambient CO (ETCOc) levels were measured in an ethnically diverse population of 87 normal newborn infants during the first 5 days of life. The results demonstrate a progressive reduction in ETCOc from 1.6 +/- 0.4 to 0.8 +/- 0.2 ppm. These levels were unrelated to ethnicity, but were inversely related to serum bilirubin levels. We conclude that ETCOc is not a useful indicator for predicting the course of transitional hyperbilirubinemia in the normal newborn infant.

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

ABSTRACT: 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.

Promoting Meconium Clearance from the Lungs of the Neonatal Piglet with Asymmetric High Frequency Oscillation

To investigate the role of high frequency oscillation (HFO) in promoting meconium clearance from the airway, we used a commercially available ventilator configured with maximal expiratory flow exceeding inspiratory flow(asymmetric HFO or AHFO). We hypothesized that AHFO would move meconium in an expiratory direction (toward the ventilator). We first tested our hypothesis in vitro and, later, in vivo using the neonatal piglet .In vitro experiments using a Plexiglas airway confirmed meconium movement in an expiratory direction when bias ratio was ≥2. For in vivo experiments, each piglet received a 3 mL/kg intratracheal bolus of a 44 g/100 mL meconium mixture followed by 45 min of mechanical ventilation. Then, in part 1, the piglet was placed in a 15 ° head down tilt position and randomized to either AHFO [ratio of inspiratory time/expiratory time (I:E) of 70:30] or HFO (I:E ratio of 30:70). After 30 min of either AHFO or HFO, the piglet was crossed over to the alternate strategy for an additional 30 min. For part 2, we maintained the piglet on either AHFO or HFO continuously for 4 h. Results demonstrate that, although there was a tendency for larger volumes of meconium to be aspirated from the airway during AHFO in part 1 experiments, there was no difference found in part 2. We also found no significant differences in blood gases or hemodynamic measurements between AHFO and HFO during the prolonged observation period in part 2 of our study. We conclude that AHFO is of no benefit in the treatment of meconium aspiration syndrome.

Developmental Changes in Sodium Nitroprusside and Atrial Natriuretic Factor Mediated Relaxation in the Guinea Pig Aorta

ABSTRACT: Sodium nitroprusside (SNP), a nonreceptor mediated stimulant of soluble guanylate cyclase, and atrial natriuretic factor, a receptor-dependent stimulator of particulate guanylate cyclase, mediate relaxation responses by increasing intracellular cGMP. This in vitro study was designed to compare the ontogeny of relaxation responses to SNP and atrial natriuretic factor in the guinea pig thoracic aorta. Aortic rings from fetuses at 55-60 d gestation (term = 68 d), 1- to 3-d-old newborn, and 12-wk-old adult Hartley guinea pigs were mounted in an organ bath, bathed in Krebs solution, and connected to a force-displacement transducer to measure isometric tension. Relaxation responses to SNP and atriopeptin III were studied with the vessels at optimal resting tension and after preconstriction with an EC85 concentration of norepinephrine. SNP-mediated relaxation showed a significant increase in sensitivity with development among the three age groups (p < 0.05). Methylene blue, an inhibitor of soluble guanylate cyclase, produced no inhibition of relaxation to SNP in fetal aortae, significantly decreased responses along the straight portion of the concentration-response curve in newborn aortae (p < 0.05), and significantly shifted the concentration-response curve to the right (p < 0.05) in adult aortae; but did not prevent vessels from relaxing almost 100% in any age group. However, atriopeptin III-mediated responses were similar in the three age groups and were unaffected by methylene blue. These results suggest that 1) sensitivity to SNP increases with age from fetal through adult life; 2) relaxation mediated by atriopeptin III is similar during development; 3) methylene blue does not affect SNP mediated relaxation in fetuses but progressively decreases sensitivity to SNP in newborns and adults; and4) methylene blue does not affect atriopeptin III-mediated relaxation in any age group.

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), Exosurfk (5 mL/kg. 13.5 mg phospholipid/mL, n = 7), Survantak (4 mL/kg. 25 mg phospholipid/mL, n = 6), and saline (5 mL/kg, n = 6). E. coli endotoxin 12 μg/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 Exosurfk nor Survantak 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 Exosurfk 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. Pediatr Pulmonol. 1996; 22:376–386.

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 (noinflation 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 noinflation 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. (Crit Care Med 1994; 22:1631–1638)

LAVAGE ADMINISTRATION OF EXOGENOUS SURFACTANT IS SUPERIOR TO BOLUS IN MECONIUM INDUCED NONHOMOGENEOUS ACUTE LUNG INJURY IN PIGLETS. † 1813

LAVAGE ADMINISTRATION OF EXOGENOUS SURFACTANT IS SUPERIOR TO BOLUS IN MECONIUM INDUCED NONHOMOGENEOUS ACUTE LUNG INJURY IN PIGLETS. † 1813