Methods

Prematurely born infants remaining ventilated after the first week after birth were eligible for entry into this study if they were being supported by ACV. Infants were entered into the study if their parents gave informed written consent. The study was approved by the South East London Research Ethics Committee and King's College Hospital Research Ethics Committee.

Infants at King's College Hospital are routinely supported by the SLE 5000. For the purposes of this study, the infants were transferred from the SLE 5000 ventilator to ACV on the Stephanie ventilator using the same ventilator settings (baseline). All infants as per the unit's routine policy were ventilated via shouldered endotracheal tubes which have been shown to have minimal or no leaks.4 One hour was allowed for stabilisation of the infant on the Stephanie ventilator. A blood gas analysis was then performed and the baseline ventilator settings were noted. During the stabilisation period, compliance and resistance settings were noted every 10 min when the infant was not obviously fighting the ventilator and the six results meaned. The infant was then randomised to receive first either PAV or ACV mode each for 1 h and for the second hour the alternative mode. During ACV, the peak inspiratory pressure (PIP), positive end expiratory pressure (PEEP) and the inflation time were kept the same as at baseline. The backup rate was set at 40 breaths per minute. During PAV, the maximum PIP was set at 5 cm H₂O above the PIP on ACV, as recommended by Schulze et al.2 The PEEP level during PAV was the same as at baseline and the PEEP and the inflation time during back up ventilation was the same as at baseline. Whenever cessation of spontaneous breathing occurred for more than 5 s during PAV, mandatory backup inflations were automatically delivered by the ventilator until the infant made a spontaneous breath. Elastic unloading, which was used only during inspiration, was initially set at 75% of full unloading; full unloading was the level of unloading which increased the infant's compliance to the expected ‘normal’, that is, 2.0 mL/cm H₂O. If after 10 min the infant remained stable and no airway pressure waveform abnormalities were observed, the unloading was increased to 100%. If airway pressure waveform abnormalities were then noted,5 the unloading was reduced back to 75%. Although the infants currently studied were all ventilator dependent beyond 1 week after birth, their respiratory system resistances were not found, on average, to be very high; the median respiratory system resistance was 86.5 (range 85–174) cm H₂O/L/s. We have previously demonstrated that the likelihood of oscillations appearing in the airway pressure waveform was greater when elastic unloading was used in a low compared with a high resistance model.5 In addition, in the in vitro model,5 oscillations in the airway pressure waveform appeared when the resistive unloading was greater than 100 cm H₂O/L/s. Hence, in this study, we decided not to use resistive unloading.

During the last 5 min on each mode, the work of breathing, the level of asynchrony, respiratory muscle strength and blood gases were measured. The work of breathing was assessed by measurement of the transdiaphragmatic pressure time product (PTPdi). Transdiaphragmatic pressure (Pdi) was obtained from measurements of oesophageal (Poes) and gastric (Pgas) pressures, measured using a dual-pressure transducer tipped catheter and associated amplifier (Gaeltec, Dunvegan, UK). The two pressure transducers were 5 cm apart, with the lower transducer positioned 0.3 cm from the catheter tip. Correct positioning of the gastric transducer was confirmed by a positive pressure deflection during inspiration while the position of the oesophageal transducer was determined by comparing Poes and airway pressure during an occluded inspiratory effort. Agreement within 94% and 103% indicated that the catheter was correctly located in the lower third of the oesophagus, and intrathoracic pressure could be reliably estimated.6 ,7 Airflow was measured using a pneumotachograph (Mercury F10L; GM Instruments, Kilwinning, UK) connected to a differential pressure transducer (MP45; Validyne Corporation, Northridge, California, USA). The pneumotachograph was positioned between the endotracheal tube and the ventilator manifold. Airway pressure was measured from a side port on the pneumotachograph using a second differential pressure transducer (MP45; Validyne Corporation). The signals from the flow and airway pressure transducers were amplified using a carrier amplifier (CD280; Validyne Corporation). The pressure and flow signals were recorded and displayed in real time on a computer (Dell Optiplex 170L) running an application written with Labview software (National Instruments, Austin, Texas, USA) with 100 Hz analogue-to-digital sampling (PCI-MIO-16XE-50, National Instruments).

Transdiaphragmatic pressure was calculated by the digital subtraction of Poes from Pgas by the acquisition software. The PTPdi was obtained by integration of Pdi with time for each breath and expressed per minute. The beginning and the end of the inspiratory phase of each breath were determined from the phase transition of the flow signal. The mean PTPdi was calculated from the first set of 20 consecutive breaths without artefact during the last 5 min of each hour on ACV and PAV modes.

Respiratory muscle strength was assessed by performing airway occlusions to obtain the maximum inspiratory (Pimax), maximum expiratory (Pemax) and maximum transdiaphragmatic (Pdimax) pressures. Airway occlusions were maintained for five to seven breaths and three sets of occlusions were performed. Sufficient time was allowed between occlusions for the infant to settle to quiet tidal breathing. The airway occlusion was discontinued if a pronounced desaturation or bradycardia occurred. A two-way non-breathing valve attached to the distal end of the pneumotachograph was used during when performing the occlusion. To assess Pimax and Pdimax, the inspiratory limb of the two-way valve was occluded during the preceding expiratory phase; the valve allowed expiration, but not inspiration. To assess Pemax, the expiratory limb of the two-way valve was occluded during the preceding inspiratory phase; the valve allowed inspiration, but not expiration. The maximum pressures achieved from the series of occlusions were recorded.

TAA was assessed by respiratory inductance plethysmography (Ambulatory Monitoring Inc, Ardsley, New York, USA). The rib cage band was placed at the level of the nipples and the abdominal band was placed midway between the bottom of the rib cage and the iliac crest. The signals were recorded and displayed in real time on a computer (Dell Optiplex 170L) running Spectra software (3.0.1.4) (Grove Medical, London, UK). From the recorded traces of the rib cage and abdominal wall motion, 10 consecutive artefact free breaths were selected and a Lissajous figure constructed. The phase angle φ was calculated as an index of TAA.8 A 0° phase angle represents synchronous motion of the ribcage and abdomen while a 180° phase angle represents completely out-of-phase or paradoxical motion between rib cage and abdomen.9

The number of desaturations (desaturation defined as an oxygen saturation less than 88%) on each mode was noted. An arterial blood sample from an indwelling catheter was obtained at the end of each hour, the ventilatory settings were noted and the oxygenation index (OI) was calculated.