Kuuleialoha C. Finn

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.

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)

ALTERATION OF PHYSICAL, AND TRANSPORT PROPERTIES OF MECONIUM BY EXOSURF®† 1364

Meconium Aspiration Syndrome (MAS) is a serious disorder in the newborn which results from both alveolar and terminal airway disease. One of the reasons for symptoms in MAS could be related to poor clearance of the meconium(MEC) from the airway. We recently demonstrated that MEC has high surface tension, poor mucociliary transportability, and high tenacity. These properties are preserved even when MEC is diluted and/or reconstituted (Peds Res, in press). The objective of this study was to measure the physical and transport properties of MEC after the addition of the artificial surfactant Exosurf®. We hypothesized that surfactant would alter the physical properties of MEC and thus allow it to be more easily mobilized. Exosurf was added to a 44 gm% MEC mixture in concentrations of 1:3, 1:1, and 3:1 (v/v), and compared to the undiluted 44 gm% MEC. Linear displacement was measured using an artificial airway model and the SensorMedics oscillator (3100) at different amplitudes (range 10-60) and inspiratory times (30% and 70%). Linear displacement of the various surfactant-MEC mixtures all increased with amplitude (p<0.0001). Importantly, linear displacement was found to directly correlate as a function of surfactant content (p<0.0001). Moreover, surfactant decreased the wettability (contact angle θ) of the surfactant-MEC preparations in a dose dependent fashion, consistent with a decrease in surface tension and improvement in transport properties. We conclude that Exosurf alters the physical properties of MEC as demonstrated by improved linear displacement and decreased wettability. These properties may be desirable when designing treatment strategies to promote the clearance of MEC from the airway.