O1087: Acute Effects of Partial Liquid Ventilation as an Adjunct to Pumpless Extracorporeal Membrane Oxygenation (P-ECMO) in the Lamb Model of CDH

Background: Partial liquid ventilation (PLV) involves the endotracheal instillation of perfluorocarbon (PFC) liquids combined with conventional gas ventilation. PLV has been shown to enhance gas exchange and pulmonary compliance in several models of neonatal respiratory disease, but has not yet been studied in combination with Pumpless Extracorporeal Membrane Oxygenation (P-ECMO). This study aims to determine the acute respiratory and hemodynamic effects of perfluorocarbon PLV as an adjunct to P-ECMO in a lamb model of congenital diaphragmatic hernia (CDH).

Methods: Lambs underwent diaphragm defect creation at 65-80 days gestation, then were delivered at term (130-145 days gestation) onto the P-ECMO circuit with endotracheal intubation. After 24h of stabilization on conventional mechanical ventilation, PLV was initiated with repeated 2 mL/kg doses of PFCs instilled endotracheally every 6 hours for up to 20 days. Ventilator settings were maintained constant for all observed doses in a pressure-regulated mode. Pulmonary compliance, pulmonary resistance, tidal volume, mean arterial blood pressure, heart rate, pre-oxygenator (arterial) oxygen saturation and P-ECMO circuit flows were captured continuously, then averaged over 5-minute intervals pre-PFC delivery and at 15, 30, 45 and 60 minutes post-PFC delivery. Results were compared by RM one-way ANOVA with Dunnett multiple comparisons testing and a significance threshold of p< 0.05.

Results: A total of 356 PFC doses were observed among 8 lambs. Following PFC administration, we observed significant and sustained increases in pre-oxygenator (arterial) oxygen saturation (mean increase 2.12%, 95%CI 1.46–2.85%, p< 0.0001), dynamic pulmonary compliance (mean increase 0.026 mL/cmH2O/kg, 95%CI 0.010–0.041 mL/cmH2O/kg, p=0.0002), tidal volume (mean increase 0.237 mL/kg, 95%CI 0.054–0.421 mL/kg, p< 0.006) and minute ventilation (mean increase 0.014 L/min, 95%CI 0.004–0.023 L/min, p< 0.002) between 15 and 60 minutes post-PFC delivery as compared to pre-treatment levels. Conversely, decreases were observed in pulmonary resistance (mean decrease 22.63 cmH2O/L/s, 95%CI 6.96-38.3 cmH2O/L/s, p=0.0017). Hemodynamics across the P-ECMO circuit were unchanged by administration of PFC over the observed time intervals, specifically heart rate, circuit flow and circuit blood pressures (p=0.405, p=0.643 and p=0.695 respectively).

Acute changes in pulmonary compliance were significantly more pronounced following PFC doses delivered in the first 10 days of treatment as compared to the following 10 days (p < 0.0001). By contrast, acute improvements in pre-oxygenator (arterial) oxygen saturation and pulmonary resistance were more pronounced in the second half of treatment (p=0.036, p=0.080). PFC-associated changes in other outcomes were not significantly altered by treatment duration. In addition, PFC-associated acute effects did not significantly vary by ventilator settings.

Conclusion: Perfluorocarbon delivery in the CDH lamb model was associated with acute, sustained and time-dependent improvements in pulmonary mechanics and oxygen saturation without changes in P-ECMO circuit hemodynamics. These results provide insight into the safety, therapeutic timing and effectiveness of this lung-protective therapy.