Partial liquid ventilation with and without inhaled nitric oxide in a newborn piglet model of meconium aspiration

Abstract

The object of this study was to determine the effects of partial liquid ventilation (PLV) with and without inhaled nitric oxide (NO) over a 4-h period on lung mechanics, gas exchange, and hemodynamics in an animal model of meconium aspiration syndrome (MAS). Twenty-four fentanyl-anesthetized piglets were instrumented and administered a slurry of human meconium to create a model with hypoxia, hypercarbia, acidosis, and pulmonary hypertension. They were then randomly assigned to conventional ventilation, conventional ventilation plus inhaled NO at 40 ppm, PLV using perfluorodecalin, or PLV plus inhaled NO. The perfluorocarbon was added until a meniscus was visible in the endotracheal tube during expiration. Hemodynamics, lung mechanics, and gas exchange were monitored for 4 h, and then the animals were killed. The conventionally ventilated animals continued to deteriorate, and three of the six died prior to 4 h. All the animals in the remaining groups survived. Oxygenation improved significantly immediately with the start of inhaled NO (from 43.8 SD 10.3 to 62.6 SD 11.7 mm Hg after 30 min) and stayed elevated compared with the control group for the remainder of the study (62.4 SD 21.8 mm Hg at 4 h compared with 44.9 SD 1.6 mm Hg for the control group, p < 0.05). Oxygenation improved more slowly in the PLV alone group, being slightly less than control at 30 min (p = NS) but increasing to 104 SD 34.9 after 4 h (p < 0.01 compared with the control group), at which time it was also greater than inhaled NO alone (p < 0.05). The combined group had an acute increase in oxygenation indistinguishable from the NO alone group and maintained this until the end of the study. Lung compliance was unaffected in the inhaled NO group. In both the liquid ventilation groups the lung compliance improved with the instillation of perfluorodecalin (from 0.46 SD 0.18 to 0.62 SD 0.09 ml/cm H2O/kg in the PLV alone group at 1 h, p < 0.05 compared with the control group) and remained stable for the remainder of the study. Cardiac output and pulmonary vascular resistance were not significantly affected by any of the treatments. It was concluded that in this animal model of MAS, inhaled NO led to an acute improvement in gas exchange and prolonged survival compared with conventional therapy. PLV improved lung mechanics, which was maintained over the course of the study. The combination of PLV and inhaled NO produced both effects, acutely improving both gas exchange and lung mechanics. Combined therapy with PLV and inhaled NO may have benefits in the MAS.