Combined gas ventilation and perfluorochemical tracheal instillation as an alternative treatment for lethal congenital diaphragmatic hernia in lambs

Abstract

Tracheal instillation of perfluorochemical liquid (PFC) lowers surface tension in the lung and thus might reduce barotrauma commonly associated with conventional gas ventilation (GV) in highly immature and hypoplastic lungs. It could be a promising alternative treatment for congenital diaphragmatic hernia (CDH) when GV alone is proving inefficient. The authors compared data for eight newborn lambs with surgically induced CDH. The animals had GV and were studied (in 2 groups) for up to 3.5 hours. Group 1 (GV, n = 4) had gas ventilation only. In group 2 (PFC, n = 4), after 30 minutes of GV, 10 to 12 mL/kg of warmed, oxygenated PFC liquid (LiquiVent) was instilled into the lung via the trachea under pressure-volume curve monitoring. Arterial pressure, blood chemistry, and pulmonary mechanics were evaluated serially; histological analysis was performed. One preassigned animal in group 1 died after 15 minutes. After 30 minutes of life, the cardiopulmonary profile of survivors was indicative of severe respiratory distress (Pa o 2 < 72 mm Hg with F io 2 at 1.0, Pa co 2 > 90 mm Hg, compliance < 0.10 mL/cm H 2O/kg) and not different between groups; the severity of pulmonary hypoplasia was further confirmed postmortem; the ratio of lung weight to body weight was 41% of that observed in control lambs, in both gas-only and combined gas/PFC-ventilated animals, compared with their respective controls. After instillation of PFC, there were dramatic improvements in acid-base status and pulmonary compliance in group 2. Survival at 3.5 hours also was markedly different (4 of 4 PFC animals and 1 of 3 GV animals). Perivascular emphysema was present on morphometric analysis in all animals, and the mean perivascular compression index (PCI = % perivascular emphysema/% vessels × 100) was not different between the groups at this point. Conventional GV for the first 30 minutes in all lambs may be the cause of a preexisting barotrauma. The average period of ventilation was longer in the PFC group, and cure with long-term ventilation appears to be possible because the lower pressures required would imply less risk of increasing PCI. Based on physiological and clinical responses, this technique of ventilation appears promising, but further experiments are needed to define the optimal ventilatory strategy to avoid pulmonary trauma.