Study protocol
Neonates were enrolled after informed consent was obtained from 			 parents. At enrollment, postductal arterial blood samples were drawn for 			 determination of pH, blood gas tensions, and methemoglobin saturation (270 			 Cooxime, Ciba-Corning, Diagnostics, Medfield, Massachusetts, USA) 10 min prior 			 to the treatment with INO and every 2–4 h thereafter. The mean oxygenation index 			 of all neonates [OI = mean airway pressure × fractional inspired 			 concentration of oxygen (FiO2)/post-ductal partial pressure of 			 arterial oxygen (PaO2)] during high-frequency ventilation and before 			 starting INO was 46.3 ± 5 (mean ± SEM). The NO gas (AHG, Jeddah, Saudi 			 Arabia) used in this study was certified at a concentration of 800 ppm NO with 			 < 1% contamination by other oxides of nitrogen. NO gas was introduced into 			 the ventilator circuit via an adaptor positioned on the inspiratory port of the 			 Fisher and Paykel humidification chamber. Thus, NO was mixed with the bias flow 			 gas of the oscillator and subsequently delivered to the neonate via the 			 inspiratory limb of the ventilator circuit. The resulting concentration of the 			 inhaled NO and NO2 was verified in-line by using an electrochemical 			 sensor (Pulmonox, Tofield, Alberta, Canada). Exhaled gas was scavenged; the 			 oxygen concentration was analyzed continuously before it reached the 			 neonate's endotracheal tube. Nitric oxide was initially administered at 			 20 ppm for at least 2 h. If there was no response while the neonate was on high 			 ventilatory support and FIO2 of 1.0, INO was increased gradually by 			 2 ppm to a maximum of 80 ppm. If there was a response, INO was maintained at 			 20 ppm and FIO2 was gradually decreased to 0.6, provided the 			 PaO2 was 80–120 mmHg. Nitric oxide then was weaned to 			 discontinuation. Ventilatory parameters thereafter were weaned and HFOV was 			 replaced by a conventional ventilator. An arterial/alveolar oxygen (a/A) ratio 			 less than 0.22 was used to define failure of HFOV and INO therapy, if INO 			 reached 80ppm on high ventilatory support.