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

Abstract

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. 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 > or = 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. 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. 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.