The Science Journal of the American Association for Respiratory Care
Background: Nitric oxide (NO) has been the focus of intense clinical and laboratory studies for the treatment of persistent pulmonary hypertension of the newborn (PPHN). High frequency oscillatory ventilation (HFOV) is commonly used in conjunction with NO to treat PPHN. Since limited data is available concerning the use of NO with HFOV, this study was designed to determine the effects of clinically relevant ventilator parameters on the delivered nitric oxide concentration during HFOV. Methods & Materials: NO was injected by the INOvent delivery system (INO Therapeutics) into the inspiratory limb of a SensorMedics 3100A HFOV ventilator circuit. The ventilator was set at a constant I-time% of 0.33 and bias flow of 15 lpm. Independent variables were amplitude (0, 20, 25, and 30 cmH20), mean airway pressure (10, 15, and 20 cmH20), frequency (5, 10, and 15 Hz), FIO2 (.21, .50, and 1.0), humidity (dry gas vs. heated, humidified gas), and NO setting (10, 20 and 40 ppm). Variables were manipulated independently and sequentially. All ventilator parameter adjustments were made with a dry gas circuit in place and then repeated in the same sequence with heat and humidity applied to the circuit. Delivered [NO] was measured at the patient connection for each of 864 combinations of these variables. The study was replicated a total of three times.
Results: The response variable considered was the relative deviation between NO setting and delivered [NO]. The majority of the observations fell between ±2.5% of the target settings. Analysis of variance revealed a significant difference in group means, F(13, 2578)=45.50, p<.01. Multiple regression (R2 = 0.186, MSE = 0.053) was performed to eliminate the non-contributory variables which were found to be frequency and mean airway pressure.
Conclusions: Independent changes in FiO2, amplitude, NO setting, and humidity produce small, but statistically significant variations in the concentration of nitric oxide delivered with the INOvent system during HFOV. The majority of these deviations are small, however those greater than ± 5% can be attributed to specific combinations of variables. There were also significant correlations between the different levels within each of the four contributing variables. These variations become more clinically significant at lower nitric oxide settings.