K I Wheeler

Volume-Targeted versus Pressure-Limited Ventilation for Preterm Infants: A Systematic Review and Meta-Analysis

Background: The causes of bronchopulmonary dysplasia (BPD) are multifactorial. Overdistension of the lung (volutrauma) is considered an important contribution. As an alternative to traditional pressure-limited ventilation (PLV), modern neonatal ventilators offer modes which can target a set tidal volume. Objectives: To determine whether volume-targeted neonatal ventilation, compared with PLV, reduces death or BPD. Methods: We performed a systematic review and meta-analysis using the methodology of the Neonatal Review Group of the Cochrane Collaboration. A comprehensive literature search was undertaken, and data for prespecified outcomes were combined where appropriate using the fixed effects model. Results: Nine trials were eligible. Volume-targeted ventilation resulted in a reduction in: the combined outcome of death or BPD [typical relative risk, RR, 0.73 (95% confidence interval, 0.57–0.93), numbers needed to treat, NNT, 8 (95% CI 5–33)], the incidence of pneumothorax [typical RR 0.46 (95% CI 0.25–0.84), NNT 17 (95% CI 10–100)], days of ventilation [weighted mean difference 0.8 days (log-transformed data, p = 0.05)], hypocarbia (pCO2 <35 mm Hg/4.7 kPa); [typical RR 0.56 (95% CI 0.33–0.96), NNT 4 (95% CI 2–25)], and the combined outcome of periventricular leukomalacia or grade 3–4 intraventricular hemorrhage [typical RR 0.48 (95% CI 0.28–0.84), NNT 11 (95% CI 7–50)]. Conclusions: Compared with PLV, infants ventilated using volume-targeted ventilation had reduced death/BPD, duration of ventilation, pneumothoraces, hypocarbia and periventricular leukomalacia/severe intraventricular hemorrhage. Further studies are needed to assess neurodevelopmental outcomes.

A practical guide to neonatal volume guarantee ventilation

A recent systematic review and meta-analysis shows that volume-targeted ventilation (VTV) compared with pressure-limited ventilation (PLV) reduce death and bronchopulmonary dysplasia, pneumothorax, hypocarbia and severe cranial ultrasound abnormalities. In this paper, we present published research and our experience with volume guarantee (VG) ventilation, a VTV mode available on the Dräger Babylog 8000plus and VN500 ventilators. The VG algorithm measures the expired tidal volume (VT) for each inflation and adjusts the peak inflating pressure for the next inflation to deliver a VT set by the clinician. The advantage of controlling expired VT is that this is less influenced by endotracheal tube leak than inspired VT. VG ventilation can be used with an endotracheal tube leak up to ∼50%. Initial set VT for infants with respiratory distress syndrome should be 4.0 to 5.0 ml kg−1. The set VT should be adjusted to maintain normocapnoea. Setting the peak inflating pressure limit well above the working pressure is important to enable the ventilator to deliver the set VT, and to avoid frequent alarms. This paper provides a practical guide on how to use VG ventilation.

Ventilation/perfusion mismatch during lung aeration at birth.

At birth, the transition to newborn life is triggered by lung aeration, which stimulates a large increase in pulmonary blood flow (PBF). Current theories predict that the increase in PBF is spatially related to ventilated lung regions as they aerate after birth. Using simultaneous phase-contrast X-ray imaging and angiography we investigated the spatial relationships between lung aeration and the increase in PBF after birth. Six near-term (30-day gestation) rabbits were delivered by caesarean section, intubated and an intravenous catheter inserted, before they were positioned for X-ray imaging. During imaging, iodine was injected before ventilation onset, after ventilation of the right lung only, and after ventilation of both lungs. Unilateral ventilation increased iodine levels entering both left and right pulmonary arteries (PAs) and significantly increased heart rate, iodine ejection per beat, diameters of both left and right PAs, and number of visible vessels in both lungs. Within the 6th intercostal space, the mean gray level (relative measure of iodine level) increased from 68.3 ± 11.6 and 70.3 ± 7.5%·s to 136.3 ± 22.6 and 136.3 ± 23.7%·s in the left and right PAs, respectively. No differences were observed between vessels in the left and right lungs, despite the left lung not initially being ventilated. The increase in PBF at birth is not spatially related to lung aeration allowing a large ventilation/perfusion mismatch, or pulmonary shunting, to occur in the partially aerated lung at birth.

An international survey of volume-targeted neonatal ventilation

Objective To evaluate clinical practice of volume-targeted ventilation (VTV). Design Internet-based survey of all 50 tertiary neonatal units in Australia, New Zealand, Sweden, Denmark, Finland and Norway. Results Response rate was 100%. VTV was routinely used in 25 (50%) units; 15/25 (60%) in Australasia and 10/25 (40%) in the Nordic countries. The most common reason given for using VTV was that it reduces bronchopulmonary dysplasia (13/25; 52%). The median (IQR) of upper limits of target tidal volume were (1) for initial ventilation of preterm infants with respiratory distress syndrome 5.0 (4.6–6.0) ml/kg and (2) for infants with ventilator-dependent bronchopulmonary dysplasia 6.0 (5.0–8.0) ml/kg. The median (IQR) maximum peak inspiratory pressure limit units were prepared to use in VTV-mode was 35 (30–42.5) cm H2O. Conclusion Half of the units used VTV routinely, but with a considerable variation in VTV practice. More studies are required to establish best VTV practice.

Assist control volume guarantee ventilation during surfactant administration

Objective: To measure changes in ventilator parameters in preterm infants receiving surfactant during assist control volume guarantee (AC/VG) ventilation. Methods: 22 preterm infants (up to 32 weeks’ gestation) receiving surfactant for respiratory distress syndrome were enrolled in a prospective study of ventilator parameters during AC/VG ventilation at a tertiary neonatal intensive care unit. Ventilator pressures, flow and tidal volume waveforms were recorded from the Dräger Babylog 8000 plus in real time, and compared to pre-surfactant measurements. Results: Following surfactant administration, 21 of 22 babies experienced completely obstructed endotracheal gas flow. Peak inflation pressure (PIP) increased by a median (IQR) of 8 (4–10) cm H2O, and took 30–60 min to return to baseline. Inspired oxygen concentration was reduced from a median (IQR) of 39% (26%–44%) to 26% (21%–30%) in the first 5 min. The set maximum PIP (Pmax) limited the delivered PIP such that most babies received tidal volumes less than the target value (VTtarget) immediately following surfactant delivery. Four infants, in a subgroup of 11 infants where Pmax was set to less than 10 cm H2O above baseline PIP, were still receiving <90% of VTtarget 20 min post surfactant. Conclusions: When giving surfactant during AC/VG ventilation, complete obstruction is common. PIPs increased and remain elevated for 30–60 min. The Pmax setting may restrict tidal volume delivery.

Frequency of respiratory deterioration after immunisation in preterm infants

Aim:  To determine the relationship between the initiation of respiratory support and the first routine immunisation of neonates at 2 months of age during primary hospitalisation.

Clinical evaluation of a novel adaptive algorithm for automated control of oxygen therapy in preterm infants on non-invasive respiratory support

Objective To evaluate the performance of a novel rapidly responsive proportional-integral-derivative (PID) algorithm for automated oxygen control in preterm infants with respiratory insufficiency. Design Interventional study of a 4-hour period of automated oxygen control compared with combined data from two flanking periods of manual control (4 hours each). Setting Neonatal intensive care unit. Participants Preterm infants (n=20) on non-invasive respiratory support and supplemental oxygen, with oxygen saturation (SpO2) target range 90%–94% (manual control) and 91%–95% (automated control). Median gestation at birth 27.5 weeks (IQR 26–30 weeks), postnatal age 8.0 (1.8–34) days. Intervention Automated oxygen control using a standalone device, receiving SpO2 input from a standard oximeter and computing alterations to oxygen concentration that were actuated with a modified blender. The PID algorithm was enhanced to avoid iatrogenic hyperoxaemia and adapt to the severity of lung dysfunction. Main outcome measure Proportion of time in the SpO2 target range, or above target range when in air. Results Automated oxygen control resulted in more time in the target range or above in air (manual 56 (48–63)% vs automated 81 (76–90)%, p<0.001) and less time at both extremes of oxygenation. Prolonged episodes of hypoxaemia and hyperoxaemia were virtually eliminated. The control algorithm showed benefit in every infant. Manual changes to oxygen therapy were infrequent during automated control (0.24/hour vs 2.3/hour during manual control), and oxygen requirements were unchanged (automated control period 27%, manual 27% and 26%, p>0.05). Conclusions The novel PID algorithm was very effective for automated oxygen control in preterm infants, and deserves further investigation.

Establishing lung gas volumes at birth: interaction between positive end-expiratory pressures and tidal volumes in preterm rabbits.

Background:We investigated the effects of positive end-expiratory pressure (PEEP) and tidal volume (VT) on lung aeration, pulmonary mechanics, and the distribution of ventilation immediately after birth using a preterm rabbit model.Methods:Sixty preterm rabbits (27 d) received volume-targeted positive pressure ventilation from birth, with one of the 12 combinations of PEEP (0, 5, 8, or 10 cmH2O) and VT (4, 8, or 12 ml/kg). Outcomes included functional residual capacity (FRC), peak inflating pressure (PIP), dynamic compliance (Cd), and distribution of ventilation.Results:Increasing PEEP from 0 to 10 cmH2O increased FRC by 4 ml/kg, increased Cd by 0.2 ml/kg/cmH2O, and reduced PIP by 5 cmH2O. Increasing VT from 4 to 12 ml/kg increased FRC by 2 ml/kg, increased Cd by 0.3 ml/kg/cmH2O, and increased PIP by 4 cmH2O. No effect of VT on FRC occurred at 0 or 5 PEEP, and no effect of PEEP occurred at VT = 4 ml/kg. At 0 PEEP, increasing VT increased the proportion of gas entering the smaller apical regions, whereas at 10 PEEP, increasing VT increased the proportion of gas entering basal regions, from 47% to 63%.Conclusion:Both PEEP and VT have independent, additive effects on FRC, lung mechanics, and the distribution of ventilation during the immediate newborn period.

Assessment of validity and predictability of the FiO2–SpO2 transfer-function in preterm infants

In this paper an investigation of the gain, delay, and time-constant parameters of the transfer function describing the relation between fraction of inspired oxygen (FiO2) and oxygen saturation in the blood (SpO2) in preterm infants is presented. The parameters were estimated following FiO2 adjustments and goodness of fit was used to assess the validity of the model when using an assumed first-order transfer function. For responses identified to be first-order, the estimated parameters were then clustered to identify areas where they tended to be concentrated. Each group described an operating region of the transfer function; thus, predicting the right operating region could potentially assist a range-based robust inspired oxygen controller to provide more optimal control by adapting itself to different clusters. Accordingly, the samples were assigned labels based on their cluster associations and 14 features available at the time of each adjustment were used as inputs to an artificial neural network to classify the clustered samples. The validity study suggested that 37% of the adjustments were followed by first-order responses. Prediction studies on the first-order responses indicated that the clusters could be predicted with an average accuracy of 64% when the parameters were divided into two groups.

Lower back-up rates improve ventilator triggering during assist-control ventilation: a randomized crossover trial.

Objective:The objective of this study is to compare the effects of back-up ventilation rates (BURs) on triggered inflations and patient cardiorespiratory stability during assist-control/volume guarantee ventilation (AC/VG).Study Design:This study is a randomized crossover trial conducted in a neonatal unit in an Australian tertiary NICU. In all, 26 stable preterm infants on AC/VG ventilation were studied at BUR settings of 30, 40 and 50 min−1. Inflation rate, triggering and cardiorespiratory measures of patient stability were compared during 20 min epochs with 10 min washout periods.Result:The 26 infants studied were median (inter-quartile range) gestational age 27 (26, 30) weeks, birth weight 0.84 (0.75, 1.14) kg and FiO2 0.24 (0.21, 0.31) and age 6 (4, 19) days. At BURs of 30, 40 and 50, the proportions of inflations, which were triggered, were mean (s.d.) 85% (11), 75% (19) and 61% (25); P<0.01 for all comparisons. Total delivered inflation rates were 56 (8), 58 (9) and 62 (8) min−1, respectively. Cardiorespiratory parameters did not vary between the settings.Conclusion:Using a lower BUR allows greater triggering of ventilator inflations. Cardiorespiratory parameters including CO2 levels were stable at all rates.