Improved gas exchange and survival after KL-4 surfactant in newborn pigs with severe acute lung injury.

OBJECTIVE: To determine the effectiveness of artificial surfactant therapy using KL-4 surfactant in newborn pigs with hydrochloric acid (HCl)-induced acute lung injury (ALI). DESIGN: After induction of ALI via intratracheal HCl instillation, pigs were randomized to receive 5.8 ml/kg KL-4 surfactant or no surfactant prior to extubation to bubble CPAP. SETTING: Clinical laboratory. SUBJECTS: Spontaneously breathing newborn pigs (<1 week of age). INTERVENTIONS: Treatment with KL-4 surfactant on bubble CPAP with PEEP of 6 cmH(2)O for 3.5 hr after extubation compared with controls. MEASUREMENTS: Physiologic parameters and arterial blood gases were measured every 15 min. At the conclusion of the study, the lungs were excised for the analysis of histopathology and morphometric data. MAIN RESULTS: Pigs treated with KL-4 surfactant had arterial blood gases with less acidosis (P < 0.001), higher P(a)O(2) levels (P < 0.001), and lower P(a)CO(2) levels (P < 0.001). Pigs treated with KL-4 surfactant had improved survival compared with controls (6/12 KL-4, 2/12 control, P < 0.05). Postmortem morphometric data demonstrated that pigs treated with KL-4 surfactant had larger (P < 0.05) exchange units in the caudal-dorsal lung as compared to relatively atelectatic region in the control animals. CONCLUSIONS: In newborn pigs with severe HCl-induced ALI, treatment with KL-4 surfactant resulted in improved respiratory parameters, less dependent atelectasis, and improved short-term survival.

Laryngeal mask airway for surfactant administration in a newborn animal model.

Premature infants are subjected to adverse effects of intubation to benefit from surfactant. We hypothesized that administration of surfactant through a laryngeal mask airway (LMA) is as effective as administration through an endotracheal tube (ETT) and that time and physiologic changes during instrumentation will be less in the LMA group. This study is a randomized, controlled trial using newborn pigs. Lung injury was induced via surfactant washout. Animals were randomized into groups: 1) LMA placed, no surfactant administered (control; n = 8); 2) surfactant via an LMA (LMA group; n = 8); and 3) surfactant via an ETT (ETT group; n = 8). We demonstrated that partial pressure of oxygen in arterial blood (Pao2) levels of the LMA and ETT groups were not statistically different. Time for successful placement of LMA was 19 ± 1 s versus ETT 123 ± 35 s (mean ± SEM); number of attempts for successful LMA placement was 1.1 (1-2) versus ETT 1.9 (1-7) [mean (range)]. Administration of surfactant via an LMA compared with an ETT resulted in similar improvements in oxygenation. Placement of the device required less time and fewer attempts. These data suggest that further study in human neonates is justified. If proven effective, some infants with respiratory distress may be able to receive surfactant while avoiding intubation.

Observational study of humidified high-flow nasal cannula compared with nasal continuous positive airway pressure.

OBJECTIVES: To conduct an in vitro evaluation of a humidified high-flow nasal cannula (HFNC) system at different flows, cannula sizes, and air leaks and also an in vivo analysis of mean end-expiratory esophageal pressure (EEEP) from nasal continuous positive airway pressure at 6 cm H(2)O (NCPAP+6) versus HFNC. STUDY DESIGN: In the in vitro study, we measured HFNC system pressure and flow, with varying degrees of leak and with and without the use of a pressure-limiting valve. In the in vivo study, we measured EEEP in 15 newborns on NCPAP+6 and then on HFNC at 6 L/minute, with flow decreased by 1 L/minute every 30 minutes. Heart rate, respiratory rate, fraction of inspired oxygen, arterial oxygen saturation, respiratory distress syndrome score, and EEEP were recorded for each intervention. Data analysis was done using repeated-measures analysis of variance and linear regression. RESULTS: In the in vitro study, in the absence of leaks, the pressures were limited by the pressure-limiting valve only at flows > or = 2 L/minute. With leaks of 30% and 50%, delivered pressures were always < 3 cm H(2)O. In the in vivo study, respiratory rate increased from baseline (NCPAP+6) as flow decreased (P < .02). Intrapatient and interpatient coefficients of variation were always high. CONCLUSIONS: A pressure-limiting valve is necessary in a HFNC system. Although mean EEEP levels were similar in NCPAP+6 and HFNC, tachypnea developed as flow diminished. This system apparently cannot predict EEEP, because of interpatient and intrapatient variation.

Gas exchange and lung inflammation using nasal intermittent positive-pressure ventilation versus synchronized intermittent mandatory ventilation in piglets with saline lavage-induced lung injury: an observational study.

OBJECTIVE: Physiologic and pathologic comparison of two modes of assisted ventilation, nasal intermittent positive-pressure ventilation (NIPPV) and synchronized intermittent mandatory ventilation (SIMV), in spontaneously breathing term newborn piglets with saline lavage-induced lung injury. DESIGN: After inducing acute lung injury via repetitive saline lavage, piglets were randomized to NIPPV (n = 12) or SIMV (n = 11) and treated for 6 hrs. SETTING: Clinical laboratory. SUBJECTS: Spontaneously breathing term newborn piglets. INTERVENTIONS: Invasive (SIMV) or noninvasive (NIPPV) assisted ventilation for 6 hrs. MEASUREMENTS: Physiologic parameters and arterial blood gases were continuously monitored. At the conclusion of the study, lung tissue was obtained to analyze for evidence of inflammation, including myeloperoxidase, interleukin-8, and hydrogen peroxide levels, as well as for evidence of pathologic injury. MAIN RESULTS: Piglets treated with NIPPV demonstrated higher arterial blood gas pH (p < .001), lower PaCO2 (p < .05), and a lower set respiratory rate (p < .0001) as compared with the SIMV-treated piglets. The piglets in the SIMV group had higher PaO2/PaO2 ratio than those in the NIPPV group (p = .001). There was significantly more interstitial inflammation (p = .04) in the SIMV-treated piglets compared with the NIPPV-treated piglets. Total respiratory rate, heart rate, blood pressure, oxygen saturation, and biochemical markers of lung inflammation were not different between the groups. CONCLUSION: In surfactant-deficient term newborn piglets, NIPPV offers an effective and noninvasive ventilatory strategy with the potential for less pathologic lung inflammation.

Decreased lung injury after surfactant in piglets treated with continuous positive airway pressure or synchronized intermittent mandatory ventilation.

BACKGROUND: Treatment with surfactant (S) decreases lung injury in paralyzed, mechanically ventilated animals. The use of nasal continuous positive airway pressure (CPAP) as an alternative to mechanical ventilation may further improve acute pulmonary outcomes. OBJECTIVES: To evaluate the effect of surfactant (+S, -S) and synchronized intermittent mandatory ventilation (SIMV) on lung morphology and inflammatory markers in 24 spontaneously breathing piglets treated with CPAP or SIMV after saline lavage-induced lung injury. METHODS: After induction of lung injury, animals were randomized to CPAP-S, CPAP+S or SIMV+S and treated for 4 h. Physiologic parameters were continuously monitored. After treatment, animals were euthanized and lungs fixed. Bronchoalveolar lavage (BAL) samples were collected for neutrophil count and H(2)O(2). RESULTS: No physiologic differences were noted. BAL fluid from CPAP-S animals contained more neutrophils and more neutrophil H(2)O(2) than fluid from the SIMV+S or CPAP+S groups (p < 0.05 or greater). Pathologic injury scores were higher in dependent lung regions from CPAP groups (p < 0.05). Injury pattern scores showed greater dependent alveolar inflammation in all (p < 0.02), with more dependent atelectasis in the CPAP groups (p < 0.01). Morphometrics showed less total open alveolar air space in nondependent regions of the SIMV+S group compared to CPAP groups (p < 0.001). Dependent regions showed less total open alveolar air space compared to nondependent regions in the CPAP groups (p < 0.001). CONCLUSIONS: Animals treated with surfactant prior to CPAP or SIMV had less acute lung injury. SIMV+S animals had less open air space in nondependent regions. This suggests, during early ventilatory support, surfactant administration may modulate pulmonary inflammation. CPAP alone without surfactant may not provide optimal pulmonary protection. The addition of mechanical breaths may alter and add to injury.

Altered pathways for auditory discrimination and recognition memory in preterm infants.

Preterm infants are at increased risk for cognitive disorders, including impairments in recognition memory. This study evaluated the effects of extreme prematurity on the neural pathway for auditory recognition memory using event-related potentials (ERPs), a neurophysiological technique widely used in cognitive neuroscience. ERPs were recorded at term postmenstrual age in 35 preterm infants born at less than 32 weeks' gestation (22 males, 13 females; mean birthweight ([BW] 1154g, SD 374g) with normal brain ultrasounds, compared with 40 healthy, term newborns (1 to 3 days of age; 20 males, 20 females; BW 3672g, SD 420g). Because infants must be able to detect and discriminate sounds before recognizing them, two paradigms were used to assess these functions. The first evaluated the detection and discrimination of speech sounds. The second tested recognition of the mother's voice compared with a stranger's. Results showed significantly different patterns of speech sound discrimination in preterm infants compared with term infants. No evidence of maternal voice recognition was elicited from the preterm infants. No specific patterns of auditory detection or discrimination were associated with patterns of recognition memory, suggesting that the function of multiple neural pathways may have been altered in this group of preterm infants. These results provide a functional corroboration of magnetic resonance imaging studies showing effects of prematurity on early brain development, even among preterm infants with normal cranial ultrasonography.