Background
During synchronised mechanical ventilation, positive airway pressure and spontaneous inspiration coincide. If synchronous ventilation is provoked, adequate gas exchange should be achieved at lower peak airway pressures, potentially reducing baro/volutrauma, air leak and bronchopulmonary dysplasia. Synchronous ventilation can potentially be achieved by manipulation of rate and inspiratory time during conventional ventilation and employment of patient-triggered ventilation.

Objectives
To compare the efficacy of:

(i) synchronised mechanical ventilation, delivered as high-frequency positive pressure ventilation (HFPPV) or patient-triggered ventilation (assist control ventilation (ACV) and synchronous intermittent mandatory ventilation (SIMV)), with conventional ventilation or high-frequency oscillation (HFO);

(ii) different types of triggered ventilation (ACV, SIMV, pressure-regulated volume control ventilation (PRVCV), SIMV with pressure support (PS) and pressure support ventilation (PSV)).

Search methods
We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 5), MEDLINE via PubMed (1966 to June 5 2016), EMBASE (1980 to June 5 2016), and CINAHL (1982 to June 5 2016). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.

Selection criteria
Randomised or quasi-randomised clinical trials comparing synchronised ventilation delivered as HFPPV to CMV, or ACV/SIMV to CMV or HFO in neonates. Randomised trials comparing different triggered ventilation modes (ACV, SIMV, SIMV plus PS, PRVCV and PSV) in neonates.

Data collection and analysis
Data were collected regarding clinical outcomes including mortality, air leaks (pneumothorax or pulmonary interstitial emphysema (PIE)), severe intraventricular haemorrhage (grades 3 and 4), bronchopulmonary dysplasia (BPD) (oxygen dependency beyond 28 days), moderate/severe BPD (oxygen/respiratory support dependency beyond 36 weeks' postmenstrual age (PMA) and duration of weaning/ventilation.

Eight comparisons were made: (i) HFPPV versus CMV; (ii) ACV/SIMV versus CMV; (iii) SIMV or SIMV + PS versus HFO; iv) ACV versus SIMV; (v) SIMV plus PS versus SIMV; vi) SIMV versus PRVCV; vii) SIMV vs PSV; viii) ACV versus PSV. Data analysis was conducted using relative risk for categorical outcomes, mean difference for outcomes measured on a continuous scale.

Main results
Twenty-two studies are included in this review. The meta-analysis demonstrates that HFPPV compared to CMV was associated with a reduction in the risk of air leak (typical relative risk (RR) for pneumothorax was 0.69, 95% confidence interval (CI) 0.51 to 0.93). ACV/SIMV compared to CMV was associated with a shorter duration of ventilation (mean difference (MD) −38.3 hours, 95% CI −53.90 to −22.69). SIMV or SIMV + PS was associated with a greater risk of moderate/severe BPD compared to HFO (RR 1.33, 95% CI 1.07 to 1.65) and a longer duration of mechanical ventilation compared to HFO (MD 1.89 days, 95% CI 1.04 to 2.74).

ACV compared to SIMV was associated with a trend to a shorter duration of weaning (MD −42.38 hours, 95% CI −94.35 to 9.60). Neither HFPPV nor triggered ventilation was associated with a significant reduction in the incidence of BPD. There was a non-significant trend towards a lower mortality rate using HFPPV versus CMV and a non-significant trend towards a higher mortality rate using triggered ventilation versus CMV. No disadvantage of HFPPV or triggered ventilation was noted regarding other outcomes.

Authors' conclusions
Compared to conventional ventilation, benefit is demonstrated for both HFPPV and triggered ventilation with regard to a reduction in air leak and a shorter duration of ventilation, respectively. In none of the trials was complex respiratory monitoring undertaken and thus it is not possible to conclude that the mechanism of producing those benefits is by provocation of synchronised ventilation. Triggered ventilation in the form of SIMV ± PS resulted in a greater risk of BPD and duration of ventilation compared to HFO. Optimisation of trigger and ventilator design with respect to respiratory diagnosis is encouraged before embarking on further trials. It is essential that newer forms of triggered ventilation are tested in randomised trials that are adequately powered to assess long-term outcomes before they are incorporated into routine clinical practice.

Synchronized mechanical ventilation for respiratory support in newborn infants

Background and Aim. Volume guarantee (VG) is a new composite mode of pressure-limited ventilation, available on the Drager Babylog 8000 ventilator, which allows the clinician to set a target mean tidal volume to be delivered while still maintaining control over peak airway pressures. This study aimed to investigate the feasibility and efficacy of this mode of ventilation in premature newborn infants with respiratory distress syndrome (RDS). Methods. Two groups of infants were studied: those receiving synchronized intermittent positive pressure ventilation (SIPPV) in early phase of RDS (group 1) and those in recovery phase of RDS being weaned from artificial ventilation through synchronized intermittent mandatory ventilation (SIMV; group 2). Both groups of infants were studied over a 4-hour period. Before the start of the study, the infants were either receiving SIPPV (group 1) or SIMV (group 2). Infants in group 1 were randomized to either continue on SIPPV for the first hour of the study or to receive SIPPV plus VG for the first hour. Subsequently, the 2 modes were used alternately for the remaining three 1-hour periods. Similarly, infants in group 2 were randomized to either continue on SIMV for the first hour of the study or to receive SIMV plus VG for the first hour. Data on ventilation parameters and transcutaneous carbon dioxide and oxygen were collected continuously. Results. Forty infants were studied, 20 in each group. The mean (standard error) gestational age was 27.9 (0.3) weeks; birth weight was 1064 (60) g. No adverse events were observed during the study. Fractional inspired oxygen during SIMV plus VG was 0.31 (0.3); during SIMV, 0.31 (0.3); during SIPPV plus VG, 0.41 (0.4); and during SIPPV, 0.40 (0.4). Transcutaneous carbon dioxide pressure during SIMV plus VG was 6.0 (2.2) kPa; during SIMV, 5.9 (2.2) kPa; during SIPPV plus VG, 6.4 (2.9) kPa; and during SIPPV, 6.4 (2.8) kPa. Transcutaneous partial pressure of oxygen during SIMV plus VG was 8.4 (8.7) kPa; during SIMV, 8.6 (8.8) kPa; during SIPPV plus VG, 7.6 (4.0) kPa; and during SIPPV, 7.7 (4.2) kPa. None of these differences was statistically significant. The mean (standard error) peak inspiratory pressure used during SIMV was 17.1 (3.4) cm of water; during SIMV plus VG, 15.0 (7.5) cm of water; during SIPPV plus VG, 17.1 (9.3) cm of water; and during SIPPV, 18.7 (8.3) cm of water. The mean airway pressure during SIMV plus VG was 6.5 (3.1) cm of water; during SIMV, 6.9 (2.8) cm of water; during SIPPV plus VG, 9.6 (4.5) cm of water; and during SIPPV, 9.8 (4.6) cm of water. Conclusion. VG seems to be a stable and feasible ventilation mode for neonatal patients and can achieve equivalent gas exchange using statistically significant lower peak airway pressures both during early and recovery stages of RDS. ventilation, airway pressure, volume guarantee, tidal volume.

Feasibility of tidal volume-guided ventilation in newborn infants: a randomized, crossover trial using the volume guarantee modality.

Randomized controlled trials (RCTs) investigating various lung-protective ventilation modes or strategies in newborn infants have failed to show clear differences in mortality or bronchopulmonary dysplasia. This review tries to identify possible reasons for this observation, applying modern concepts on ventilator-induced lung injury and lung-protective ventilation.

Lung-protective ventilation strategies in neonatology: what do we know--what do we need to know?

Background: Ventilation with higher PaCO2 goals may reduce lung injury and bronchopulmonary dysplasia (BPD). The effect may be enhanced by using a higher PaCO2 goal than in previous trials. Objective: To determine the clinical benefits and safety of higher PaCO2 goals for ventilated preterm infants. Study Design: Preterm infants with a gestational age between 23 and 28 completed weeks receiving mechanical ventilation within 6 h of birth were randomized to be managed with either a PaCO2 target between 55 and 65 mm Hg (7.3– 8.7 kPa, minimal ventilation) or 35 and 45 mm Hg (4.7– 6.0 kPa, routine ventilation) for the first 7 days of life. The primary outcome measure was BPD, defined as need for mechanical ventilation or supplemental oxygen at 36 weeks postmenstrual age, or death. The neurodevelopmental status was assessed at 18–22 months corrected age. Results: The trial was stopped early after enrolling 31% of the projected sample size. Enrolled infants had a median birth weight of 640 g. BPD or death occurred in 21/33 (64%) infants after minimal ventilation and 19/32 (59%) infants after routine ventilation. Minimal ventilation was associated with trends towards higher mortality and higher incidence of neurodevelopmental impairment, and a significantly increased combined outcome of mental impairment or death (p Conclusion: Minimal ventilation as performed in this study did not improve clinical outcome, and may have been associated with a worse neurodevelopmental outcome.

Outcome of extremely preterm infants randomized at birth to different PaCO2 targets during the first seven days of life.

Objective: Randomised controlled trials comparing elective use of high frequency ventilation (HFV) with conventional mechanical ventilation (CMV) in preterm infants have yielded conflicting results. We hypothesised that the variability of results may be explained by differences in study design, ventilation strategies, delay in initiation of HFV, and use of permissive hypercapnia. 

Methods: Randomised controlled trials comparing the elective use of HFV with any form of CMV were identified. Trials were classified according to the ventilation strategies used for HFV and CMV and oscillator device employed. For cumulative meta-analyses, trials were arranged by the following covariables: mean duration until randomisation, Paco2 limits, publication date, and sample size. Odds ratios (OR) and 95% confidence intervals were calculated using fixed and random effects models. 

Results: Seventeen randomised trials enrolling 3776 patients were included. Unlike previous meta-analyses, there was no significant difference in the incidence of bronchopulmonary dysplasia or death (OR 0.87, 0.75–1.00) and severe intraventricular haemorrhage grade 3–4 (1.14, 0.96–1.37). The incidence of air leaks (OR 1.23, 1.06–1.44) was significantly increased with HFV. Subgroup analyses and cumulative meta-analyses demonstrated that trial results were related to the ventilation strategies used for HFV and CMV. No influence was found for mean time to randomisation, degree of permissive hypercapnia, or sample size. 

Conclusions: Heterogeneity among trials of elective HFV compared to CMV in preterm infants is mainly due to differences in ventilatory strategies. Optimising CMV strategy appeared to be as effective as using HFV in improving pulmonary outcome in preterm infants.

https://fn.bmj.com/content/fetalneonatal/90/6/F466.full.pdf

Ventilation strategies and outcome in randomised trials of high frequency ventilation.

AIM To compare patient triggered, with conventional fast rate, ventilation in a randomised controlled trial using the incidence of chronic lung disease as the primary outcome measure. METHODS Three hundred and eighty six preterm infants with birthweights from 1000 to 2000 g, and requiring ventilation for respiratory distress syndrome within 24 hours of birth, were randomised to receive either conventional or trigger ventilation with the SLE 2000 ventilator. RESULTS There were no significant differences in the incidence of chronic lung disease (28 day and 36 week definitions), death, pneumothorax, intraventricular haemorrhage, number of ventilator days, or length of oxygen dependency between groups. CONCLUSIONS Patient triggered ventilation in preterm infants with respiratory distress syndrome is feasible. No significant differences, when compared with conventional fast rate ventilation in important medium and longer term outcome measures, were evident.

https://fn.bmj.com/content/fetalneonatal/82/1/F14.full.pdf

Randomised controlled trial of patient triggered and conventional fast rate ventilation in neonatal respiratory distress syndrome

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Randomised controlled trial of patient triggered and conventional fast rate ventilation in neonatal respiratory distress syndrome