title: Continuous positive airway pressure causes lung injury in a model of sepsis.
abstract: Continuous positive airway pressure, aimed at preventing pulmonary atelectasis, has been used for decades to reduce lung injury in critically ill patients. In neonatal practice, it is increasingly used worldwide as a primary form of respiratory support due to its low cost and because it reduces the need for endotracheal intubation and conventional mechanical ventilation. We studied the anesthetized in vivo rat and determined the optimal circuit design for delivery of continuous positive airway pressure. We investigated the effects of continuous positive airway pressure following lipopolysaccharide administration in the anesthetized rat. Whereas neither continuous positive airway pressure nor lipopolysaccharide alone caused lung injury, continuous positive airway pressure applied following intravenous lipopolysaccharide resulted in increased microvascular permeability, elevated cytokine protein and mRNA production, and impaired static compliance. A dose-response relationship was demonstrated whereby higher levels of continuous positive airway pressure (up to 6 cmH(2)O) caused greater lung injury. Lung injury was attenuated by pretreatment with dexamethasone. These data demonstrate that despite optimal circuit design, continuous positive airway pressure causes significant lung injury (proportional to the airway pressure) in the setting of circulating lipopolysaccharide. Although we would currently avoid direct extrapolation of these findings to clinical practice, we believe that in the context of increasing clinical use, these data are grounds for concern and warrant further investigation.
authors.affiliation: Lung Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.
authors.forename: Shinya
authors.initials: S
authors.lastname: Tsuchida
authors.forename: Doreen
authors.initials: D
authors.lastname: Engelberts
authors.forename: Matthias
authors.initials: M
authors.lastname: Roth
authors.forename: Colin
authors.initials: C
authors.lastname: McKerlie
authors.forename: Martin
authors.initials: M
authors.lastname: Post
authors.forename: Brian P
authors.initials: BP
authors.lastname: Kavanagh
mesh_terms: D000818:Animals; D045422:Continuous Positive Airway Pressure / Q000009:adverse effects* / Q000379:methods; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D001261:Pulmonary Atelectasis / Q000628:therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012131:Respiratory Insufficiency / Q000188:drug therapy / Q000209:etiology*; D018805:Sepsis / Q000150:complications*
chemical_list: D005938:Glucocorticoids; D008070:Lipopolysaccharides; D003907:Dexamethasone