Methods

The clinical trial was performed in the neonatal intensive care unit at South Cleveland Hospital after approval by the district ethics committee. Infants were deemed eligible for participation if they weighed 1200 g or more at birth and had RDS severe enough to warrant assisted mechanical ventilation and exogenous surfactant replacement. The diagnosis of RDS was based on a composite of clinical and radiological criteria along with evidence of pulmonary insufficiency according to arterial blood gas analysis. Babies with confirmed or suspected sepsis/pneumonia, congenital malformation, or lack of arterial access were excluded.

Success outcome criteria for this trial were determined a priori, and consisted of either AaDO₂ <13 Kpa (100 torr), or a mean airway pressure <8.0 cm H₂O maintained for at least 12 hours. If successful (>12 hours) extubation occurred, either inadvertently or as a part of clinical management before reaching success criteria; this was also regarded as an end point. The period of mechanical ventilation from the time of entry into the study until achievement of success criteria, as well as the total duration of mechanical ventilation was calculated for each baby. Secondary outcome measures were also noted and included complications frequently associated with mechanical ventilation, such as intraventricular haemorrhage (IVH), periventricular leucomalacia (PVL), patent ductus arteriosus (PDA), and chronic lung disease or bronchopulmonary dysplasia (BPD), defined as oxygen dependency beyond the 36th postconceptional week with suggestive radiological changes.

Informed parental consent was obtained for each patient before enrolment in the study. Assignment of ventilatory mode was done by block randomisation using sealed envelopes. Once randomised, the mode of ventilation was not allowed to cross over. If deemed necessary, on the basis of severe respiratory failure characterised by AaDO₂ >80 Kpa (600 torr), oxygenation index >25, or intractable air leak, high frequency oscillatory ventilation (HFOV) was an option. However, analysis of data was done on an intention to treat basis, based on the originally assigned mode. We hypothesised that infants assigned to VC would require 33% less time to achieve the success end points and determined that 50 patients would be required to demonstrate significance (<0.05) with a power of 0.8.

Fifty consecutive patients were assigned to either VC or TCPL ventilation. Both groups were ventilated with the VIP bird Infant/Paediatric Ventilator (Bird Products Corp., Palm Springs, California, USA). This permitted monitoring of proximal airway inspiratory and expiratory tidal volumes, breathing rate, and minute ventilation. All babies in the study were initially placed in the PTV (assist/control) setting to assure adequate minute ventilation and the lowest possible work of breathing. The triggering mechanism for each mode is slightly different: VC is pressure triggered, requiring a 1.0 cm H₂O deflection below baseline, whereas TCPL is flow triggered, requiring a 0.2 LPM change in airway flow.

Infants were managed with a standardised unit clinical protocol (table1). In both groups we deliberately controlled the tidal volume delivery at 5–8 ml/kg.3 By matching tidal volume, the only difference between the two groups was the ventilatory modality, or in other words, the manner in which flow was delivered. Infants in the TCPL group received fully synchronised ventilation by using termination sensitivity, which is an expiratory trigger.1 Babies in the VC group were weaned using pressure support ventilation because of its striking similarity to flow synchronised assist/control: it is flow cycled, pressure limited, and patient triggered.4 Weaning in the two modes was thus very similar. All remaining clinical care was provided according to routine ward practices and included intravenous caffeine administration during the process of weaning, routine cranial ultrasound scans, and colour Doppler echocardiography. Clinical information relevant to the study was recorded prospectively for each infant. The timing of chest radiographs on babies in the study was governed by clinical practice. However, the final radiological assessment of the severity of the lung disease and complications was done by the study radiologist (MM) who was unaware of the mode of ventilation at the discharge of each patient. A modified scoring system was used for each lung, with special reference to parenchymal opacities, pulmonary interstitial emphysema, and gross air leaks requiring pleurocentesis.5 6 The final grade was that assigned to the worst radiographic appearance.