Published online November 1, 2006
PEDIATRICS Vol. 118 No. 5 November 2006, pp. 2038-2050 (doi:10.1542/10.1542/peds.2006-0622)
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ARTICLE

Delayed Extubation to Nasal Continuous Positive Airway Pressure in the Immature Baboon Model of Bronchopulmonary Dysplasia: Lung Clinical and Pathological Findings

Merran A. Thomson, MB, ChBa, Bradley A. Yoder, MDb, Vicki T. Winter, BSc, Luis Giavedoni, PhDd,e, Ling Yi Chang, PhDf and Jacqueline J. Coalson, PhDc,d

a Clinical Sciences Division, Imperial College, London, United Kingdom
b Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah
c Department of Pathology, University of Texas Health Science Center, San Antonio, Texas
d Southwest Foundation for Biomedical Research, San Antonio, Texas
e Southwest National Primate Center, San Antonio, Texas
f Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado

OBJECTIVE. Using the 125-day baboon model of bronchopulmonary dysplasia treated with prenatal steroid and exogenous surfactant, we hypothesized that a delay of extubation from low tidal volume positive pressure ventilation to nasal continuous positive airway pressure at 5 days (delayed nasal continuous positive airway pressure group) would not induce more lung injury when compared with baboons aggressively weaned to nasal continuous positive airway pressure at 24 hours (early nasal continuous positive airway pressure group), because both received positive pressure ventilation.

METHODS AND RESULTS. After delivery by cesarean section at 125 days (term: 185 days), infants received 2 doses of Curosurf (Chiesi Farmaceutica S.p.A., Parma, Italy) and daily caffeine citrate. The delay in extubation to 5 days resulted in baboons in the delayed nasal continuous positive airway pressure group having a lower arterial to alveolar oxygen ratio, high PaCO2, and worse respiratory function. The animals in the delayed nasal continuous positive airway pressure group exhibited a poor respiratory drive that contributed to more reintubations and time on mechanical ventilation. A few animals in both groups developed necrotizing enterocolitis and/or sepsis, but infectious pneumonias were not documented. Cellular bronchiolitis and peribronchiolar alveolar wall thickening were more frequently seen in the delayed nasal continuous positive airway pressure group. Bronchoalveolar lavage levels of interleukin-6, interleukin-8, monocyte chemotactic protein-1, macrophage inflammatory protein-1 {alpha}, and growth-regulated oncogene-{alpha} were significantly increased in the delayed nasal continuous positive airway pressure group. Standard and digital morphometric analyses showed no significant differences in internal surface area and nodal measurements between the groups. Platelet endothelial cell adhesion molecule vascular staining was not significantly different between the 2 nasal continuous positive airway pressure groups.

CONCLUSIONS. Volutrauma and/or low-grade colonization of airways secondary to increased reintubations and ventilation times are speculated to play causative roles in the delayed nasal continuous positive airway pressure group findings.

Key Words: nasal continuous positive airway pressure • bronchopulmonary dysplasia • bronchiolitis • alveolization • vasculogenesis • cytokines • chemokines • necrotizing enterocolitis • volutrauma • biotrauma • sepsis

Abbreviations: nCPAP—nasal continuous positive airway pressure • BPD—bronchopulmonary dysplasia • ISA—internal surface area • LV-PPV—low tidal volume positive pressure mechanical ventilation • EnCPAP—early nasal continuous positive airway pressure • DnCPAP—delayed nasal continuous positive airway pressure • PIP—peak inspiratory pressure • PEEP—positive end-expiratory pressure • FIO2—fraction of inspired oxygen • PDA—patent ductus arteriosus • NEC—necrotizing enterocolitis • PV curve—pressure–volume curve • PECAM—platelet endothelial cell adhesion molecule • BAL—bronchoalveolar lavage • BALF—bronchoalveolar lavage fluid • IFN—interferon • IL—interleukin • MCP—monocyte chemotactic protein • MIP—macrophage inflammatory protein • TNF—tumor necrosis factor • a/A ratio—arterial to alveolar oxygen ratio • IQR—interquartile range

Accepted Jul 10, 2006.


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