Inhaled Nitric Oxide: Evaluation of a Continuous Titration Delivery Technique for Infant Mechanical and Manual Ventilation

Abstract

BACKGROUND: The application of inhaled NO for the treatment of pulmonary hypertension and respiratory failure is an important development. We evaluated NO delivery by an infant ventilator (time-cycled, IMV mode) connected to a test lung, with NO titrated into the circuit upstream from the humidifier. METHODS: V_T, airway pressures, and F_DO2 were measured and NO and NO₂ analyzed at baseline and at various NO flows, at 3 F_DO2 levels and at a ventilator flow of 8 L/min. NO₂ conversion with 80 ppm NO and F_DO2 setting 1.0 was assessed at 3 ventilator flows. The effect of a scavenging device, the sensitivity of the low-airway-pressure alarm (LAP), and a manual ventilation system were also evaluated. RESULTS: Measured NO levels (NO_meas) were compared to calculated values (NO_calc) in 126 samples ranging from 2.5 to 80.9 ppm. Correlations of NO_meas and NO_cale were strong at F_DO2 0.3, r = 0.993, p < 0.001; at 0.6, r = 0.995, p < 0.001; and at 1.0, r = 0.993, p < 0.001. NO_cale underestimated NO_meas with a bias of 4.86 ± 3.77 ppm (13.5%) and precision of 3.91 and 5.81 ppm. NO₂ did not significantly decrease when flow was increased. Airway pressures and V_T remained stable; F_DO2 fell 0.01-0.08 over the range of NO flows. Scavenging did not alter baseline pressure. The LAP did not signal when 3-mm ID tubing was disconnected but did with disconnection of 5-mm tubing. Exhaled NO and NO₂ were effectively eliminated with the manual system (NO = 0.015 ± 0.05 ppm; NO₂ = 0.553 ± 0.31 ppm). CONCLUSIONS: Accurate NO doses can be delivered by this method. NO_cale does not replace NO analysis. Production of NO₂ is unchanged when ventilator flow is increased from 8 to 12 L/min. NO doses ≤ 40 ppm ensure that NO₂ remains < 2.1 ppm. If a dose > 40 ppm is needed and F_DO2 > 0.95 required, then a higher NO_source is required, and toxic levels of NO₂ may result. It is feasible to deliver and scavenge NO and NO₂ during manual ventilation. These systems may permit the precise and safe delivery of inhaled NO.