Outcomes
All outcome parameters were measures/recorded prior to administration and 30 minutes after completion of each dose of medication. The primary study outcome was the absolute difference in expiratory flow at 75% of exhalation (EF75), measured directly from the ventilator flow volume loops (Figure 1) 30 minutes post study medication administration compared to immediately prior to administration (post – pre treatment). Measurement of EF75 was accomplished by calculating the exhaled volume at 25% of the breath (tidal volume x 0.25) and then recording flow at this point on the expiratory side of the flow volume loop (Figure 1). Measurement of EF75 has not been used in prior studies with mechanically ventilated neonates and was chosen as a measurement that would not require specialized equipment or the need to alter the mechanical ventilator mode or settings to perform measurements. Although the measurement was not performed under conditions of forced exhalation, we reasoned that the measurement would be made over the effort-independent portion of the flow-volume curve, especially in a population of patients with obstructive lung disease. With the administration of a bronchodilator, we anticipated that the EF75 would become higher with small airway dilation.
Secondary outcomes were the proportional change in peak inspiratory pressure (PIP) required to deliver the participant’s set tidal volume, minute ventilation, total respiratory rate, blood oxygen saturation level (SpO2), heart rate (HR), and the occurrence of any abnormal heart rhythm pre- and post- treatment.