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The effect of early nasal CPAP on lung function and injury in a primate model of BPD

Presented at the Neonatal Society 2002 Summer Meeting (programme).

Thomson MA1, Yoder BA 2,3,4, Catland D2,4, Martin H3, Winter V2, Coalson JJ2

1 Imperial College of Science, Technology, and Medicine, London, UK
2 University of Texas Health Science Center, San Antonio, USA
3 Southwest Foundation for Biomedical Research, San Antonio, USA
4 Pediatrix Medical Group, San Antonio, Texas, USA

Background: No single treatment is likely to prevent Bronchopulmonary dysplasia (BPD). Minimizing volutrauma may reduce secondary lung injury and improve subsequent lung development. The study aim was to investigate the effect early nCPAP following prophylactic surfactant had on lung function and injury in the 125-day premature baboon model of BPD.
Methods: Following intramuscular betamethasone at 48 and 24 hours prior to birth, 125-day baboons (term, 185-days) were delivered by caesarean section. Surfactant (CurosurfTM 200mg/kg) was given before the first mechanical breath, and repeated (100mg/kg) at 6 hours. Caffeine citrate (20mg/kg) was given at 1 and 12 hours age followed by a daily maintenance dose (10mg/kg). Low tidal volume (4-6 ml/kg) positive pressure ventilation (PPV) was aggressively weaned over the first 24 hours. Extubation to nCPAP (Infant Flow DriverTM) was attempted at 24 hours age. Serial physiological parameters were recorded. Pulmonary function tests were obtained for the first 24 hours. Lung histology was examined following elective necropsy at 28 days. Data was compared to previously described controls (1).

Results: All 6 nCPAP animals were successfully extubated at a median 26.5 hours of life (range 24-29). Three required short periods of reventilation, median length of ventilation 47 hours (range 36-53). Five survived to 28 days, one died at 19 days from NEC and systemic sepsis.
Significant improvements in oxygenation index, a/A ratio, FiO2, mean airway pressure, PaO2, PaCO2, and mean arterial blood pressure were seen at multiple time points throughout the study in nCPAP animals compared to prior controls. Expiratory airway resistance and thoracic compliance were improved at 6, 12, and 24 hours of age (p< 0.05).

At necropsy, lungs of nCPAP animals were evenly expanded without gross evidence of atelectasis and infection, findings frequently present in PPV animals. Histopathologically, the evenly expanded nCPAP lungs showed remarkably thin saccular walls with minimal if any fibroproliferation. PPV lungs showed more unevenly expanded saccules with varying degrees of fibroproliferation. In spite of the more normal appearance of the lungs in the nCPAP animals, secondary crests and alveoli were rare, a finding previously documented in the PPV animals. Morphometric studies revealed no significant differences in mean linear intercept and volume to area ratio determinations, but internal surface area measurements were significantly higher in the nCPAP group when compared to the PPV animals (p <0.04).

Conclusion:  Early use of nasal CPAP, coupled with prophylactic surfactant can be used to successfully manage immature primates with RDS during the late canalicular stage of lung development. This approach results in dramatically improved lung histology at 28 days age, but still does not allow for normal alveolization.

1. Coalson JJ, Winter VT, Siler-Khodr T, Yoder BA: Neonatal chronic lung disease in extremely immature baboons. AM J Respir Crit Care Med 1999;160:1333-1346.

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