Combined effects of high-frequency ventilation and surfactant treatment in experimental meconium aspiration syndrome.

Background: Deterioration of lung function in meconium aspiration syndrome may in part be due to inactivation of endogenous surfactant. We evaluated the efficacy of high-frequency ventilation (HFV) and the combination of HFV and surfactant therapy in the management of respiratory failure induced by experimental meconium aspiration in adult rats. Methods: Animals were anesthetized and tracheotomized, and received via the tracheal cannula a suspension of human meconium (25 mg/ml, dose 4 or 5 ml/kg). After 30 min of conventional ventilation (CV) with 100% oxygen, animals were in respiratory failure as indicated by a decrease in lung-thorax compliance of ≥30% and PaO2 <10 kPa. They were then ventilated for an additional 3 h with either CV (frequency 40/min, inspiration time 50%) or HFV (frequency 15 Hz, inspiration time 50%) using comparable mean airway pressures (about 20 cmH2O) and variable FiO2. Subgroups of animals were treated with Curosurf (80 mg/ml, dose 200 mg/kg) 30 min after meconium aspiration; no additional material was instilled in controls. Results: From 30 min onwards, values for PaO2/FiO2 were significantly higher in animals ventilated with HFV without receiving surfactant than in control animals subjected to CV alone (at 120 min: 18±7.3 vs. 7.4±0.8 kPa, P<0.05). Additional improvement in oxygenation was seen in HFV-treated animals receiving Curosurf (at 120 min: 39±16 kPa: P vs. HFV alone <0.01). Relative lung volumes at a deflation pressure of 10 cmH2O, expressed as percent of maximum volume, were larger in animals ventilated with HFV than in those undergoing CV (41±12 vs. 33±10%; P<0.05), and were further increased in the groups of animals treated with surfactant and ventilated with HFV (55±9.9%; P vs. animals ventilated with HFV not receiving surfactant <0.01) or CV (49±9.6%; P vs. animals ventilated with CV without receiving surfactant <0.05). Hyaline membranes, granulocytes in cytospin preparations from lung lavage fluid, and vascular-to-alveolar leak of albumin were less prominent in the HFV than in the CV group, particularly in animals treated with surfactant. Conclusion: Our data indicate that HFV, especially in combination with surfactant therapy, may be superior to CV for treatment of respiratory failure in this animal model of meconium aspiration syndrome.