Decreased Lung Injury after Surfactant in Piglets Treated with Continuous Positive Airway Pressure or Synchronized Intermittent Mandatory Ventilation

Abstract

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 H₂O₂. Results: No physiologic differences were noted. BAL fluid from CPAP–S animals contained more neutrophils and more neutrophil H₂O₂ 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.

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*

“…Indicators of lung injury have been shown to be measurable within 2 hrs of preterm birth (15). Similarly, in previous studies performed in our laboratory, we have been able to detect evidence of early lung inflammation within 4 hrs (16). In this study, we were unable to show differences using biochemical evidence of inflammatory changes, although we did see changes in lung pathology.…”

An Open Label, Pilot Study of Aerosurf®Combined with nCPAP to Prevent RDS in Preterm Neonates

“…(7,11) A recent study in newborn piglets with respiratory failure produced by lung saline lavage, however, found that nCPAP alone resulted in more lung injury, as determined by bronchoalveolar lavage neutrophil and neutrophil hydrogen peroxide levels, when compared with surfactant combined either with bubble CPAP or synchronized intermittent mandatory ventilation (SIMV). (12) Given the shift toward less invasive modes of treating infants at risk for RDS and the greater awareness of postintubation complications, a novel delivery system has been designed that delivers lucinactant for inhalation (Aerosurf Ò , Discovery Laboratories, Inc., Warrington, PA, USA) to infants receiving nCPAP. Lucinactant is a novel synthetic surfactant that contains KL 4 , a 21-amino acid peptide mimicking the function of surfactant protein B (SP-B).…”

Cerebral oxygenation associated with INSURE versus LISA procedures in surfactant‐deficient newborn piglet RDS model

“…The newborn piglet model was chosen because the brain maturation, lung volume, and birth weight resemble those of newborn infants. Moreover, the feasibility of using nCPAP and SF strategies in this model of SF‐deficient lung injury has been previously demonstrated . Nevertheless, 2‐ to 4‐day‐old piglets have a greater level of brain development than a 32‐week human fetus, The effects of INSURE and LISA procedures on the brain need to be interpreted with caution, as effects on the term piglet brain may not be the same as those on the vulnerable premature brain of newborn infants.…”

“…Limitations of this study include the use of newborn piglets (2‐4 days old), which require SF washout lavage to induce lung injury. The SF washout lavage model has been frequently used in adult and juvenile animals to implement successful animal models of acute pulmonary failure in the context of RDS . The newborn piglet model was chosen because the brain maturation, lung volume, and birth weight resemble those of newborn infants.…”