575 - A dose-ranging evaluation of inhaled atomized perfluorocarbon for partial liquid ventilation in spontaneously-breathing non-intubated preterm lambs with respiratory distress.
Professor of Pediatrics Childrens Hospital of Philadelphia narberth, Pennsylvania, United States
Background: Perfluorooctyl bromide (PFOB), a perfluorocarbon with antiinflammatory, inert, and surfactant-like properties, has been widely studied for its therapeutic potential in treating preterm infant respiratory distress syndrome (RDS). Many studies have evaluated the effects of partial filling of the alveoli with PFOB in intubated and mechanically ventilated preterm animal models or infants. However, the feasibility or safety of inhaled delivery of PFOB in non-intubated spontaneously-breathing infants is unknown. Objective: To evaluate the safety and efficacy of PFOB administered as an atomized spray of 0, 2.5, 5, or 10 ml/kg to spontaneously-breathing non-intubated preterm lambs with RDS. Design/Methods: Preterm lambs were delivered at 134 to 136 days gestation and mechanically ventilated for approximately 30 minutes to establish stable arterial blood gases. Following intravenous caffeine and doxapram, lambs were extubated and breathed spontaneously with CPAP and supportive breaths provided via binasal cannulae. PFOB was administered via an atomizer nozzle with a camera inserted orally and positioned to direct the atomized PFOB into the trachea in half-doses with the lamb in a prone and then supine position. Arterial blood gases, ventilatory support, blood pressure, and heart rate were recorded for 3h following PFOB administration. Chest radiographs were obtained to assess PFOB distribution. Lambs were re-intubated at 3h for a final measurement of pulmonary compliance. Results: PFOB administration had no effect on arterial blood pressure or heart rate. There was no difference between study groups with respect to arterial PO2, PCO2, or alveolar-arterial PO2 gradient. Final pulmonary compliance was higher in the 5 and 10 ml/kg groups (4.68 ± 0.52 and 5.60 ± 0.22 ml⋅cmH2O -1⋅kg-1, respectively) compared to the 0 and 2 ml/kg groups (2.65 ± 0.28 and 2.80 ± 0.47 ml⋅cmH2O -1⋅kg-1, respectively, n = 5 per group). However, the 10 ml/kg group required more ventilatory support due to central apnea. Chest radiographs showed a gravity-dependent deposition of PFOB, with expected evaporative loss after 3h. Significantly fewer animals in the control group survived to the end of the protocol (n = 3) compared to the other groups.
Conclusion(s): This study demonstrates safety and establishes a proposed neonatal dose of atomized PFOB for a clinical trial. At the doses used in this study, intratracheal PFOB administration via an atomized nozzle is well-tolerated by preterm lambs, with no significant hemodynamic effects, no adverse effects on pulmonary gas exchange, and improved pulmonary compliance at 5 and 10 ml/kg.
