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Purpose Neurally adjusted ventilatory assist (NAVA) is a ventilatory mode that tailors the level of assistance delivered by the ventilator to the electromyographic activity of the diaphragm. The objective of this study was to compare NAVA and pressure support ventilation (PSV) in the early phase of weaning from mechanical ventilation. Methods A multicentre randomized controlled trial of 128 intubated adults recovering from acute respiratory failure was conducted in 11 intensive care units. Patients were randomly assigned to NAVA or PSV. The primary outcome was the probability of remaining in a partial ventilatory mode (either NAVA or PSV) throughout the first 48 h without any return to assist-control ventilation. Secondary outcomes included asynchrony index, ventilator-free days and mortality. Results In the NAVA and PSV groups respectively, the proportion of patients remaining in partial ventilatory mode throughout the first 48 h was 67.2 vs. 63.3 % ( P  = 0.66), the asynchrony index was 14.7 vs. 26.7 % ( P  < 0.001), the ventilator-free days at day 7 were 1.0 day [1.0–4.0] vs. 0.0 days [0.0–1.0] ( P  < 0.01), the ventilator-free days at day 28 were 21 days [4–25] vs. 17 days [0–23] ( P  = 0.12), the day-28 mortality rate was 15.0 vs. 22.7 % ( P  = 0.21) and the rate of use of post-extubation noninvasive mechanical ventilation was 43.5 vs. 66.6 % ( P  < 0.01). Conclusions NAVA is safe and feasible over a prolonged period of time but does not increase the probability of remaining in a partial ventilatory mode. However, NAVA decreases patient–ventilator asynchrony and is associated with less frequent application of post-extubation noninvasive mechanical ventilation. Trial Registration. clinicaltrials.gov Identifier: NCT02018666.

Background High-frequency oscillatory ventilation (HFOV) use was associated with greater mortality in adult acute respiratory distress syndrome (ARDS). Nevertheless, HFOV is still frequently used as rescue therapy in paediatric acute respiratory distress syndrome (PARDS). In view of the limited evidence for HFOV in PARDS and evidence demonstrating harm in adult patients with ARDS, we hypothesized that HFOV use compared to other modes of mechanical ventilation is associated with increased mortality in PARDS. Methods Patients with PARDS from 10 paediatric intensive care units across Asia from 2009 to 2015 were identified. Data on epidemiology and clinical outcomes were collected. Patients on HFOV were compared to patients on other modes of ventilation. The primary outcome was 28-day mortality and secondary outcomes were 28-day ventilator- (VFD) and intensive care unit- (IFD) free days. Genetic matching (GM) method was used to analyse the association between HFOV treatment with the primary outcome. Additionally, we performed a sensitivity analysis, including propensity score (PS) matching, inverse probability of treatment weighting (IPTW) and marginal structural modelling (MSM) to estimate the treatment effect. Results A total of 328 patients were included. In the first 7 days of PARDS, 122/328 (37.2%) patients were supported with HFOV. There were significant differences in baseline oxygenation index (OI) between the HFOV and non-HFOV groups (18.8 [12.0, 30.2] vs. 7.7 [5.1, 13.1] respectively; p  < 0.001). A total of 118 pairs were matched in the GM method which found a significant association between HFOV with 28-day mortality in PARDS [odds ratio 2.3, 95% confidence interval (CI) 1.3, 4.4, p value 0.01]. VFD was indifferent between the HFOV and non-HFOV group [mean difference − 1.3 (95%CI − 3.4, 0.9); p  = 0.29] but IFD was significantly lower in the HFOV group [− 2.5 (95%CI − 4.9, − 0.5); p  = 0.03]. From the sensitivity analysis, PS matching, IPTW and MSM all showed consistent direction of HFOV treatment effect in PARDS. Conclusion The use of HFOV was associated with increased 28-day mortality in PARDS. This study suggests caution but does not eliminate equivocality and a randomized controlled trial is justified to examine the true association.

To achieve gas exchange goals and mitigate lung injury, infants who fail with conventional ventilation (CV) are generally switched to high-frequency oscillatory ventilation (HFOV). Although preferred in many neonatal intensive care units (NICUs), research on this type of rescue HFOV has not been reported recently. An online registry database for a multicenter, prospective study was set to evaluate factors affecting the response of newborn infants to rescue HFOV treatment. The study population consisted of 372 infants with CV failure after at least 4 hours of treatment in 23 participating NICUs. Patients were grouped according to their final outcome as survived (Group S) or as died or received extracorporeal membrane oxygenation (ECMO) (Group D/E). Patients' demographic characteristics and underlying diseases in addition to their ventilator settings, arterial blood gas (ABG) analysis results at 0, 1, 4, and 24 hours, type of device, ventilation duration, and complications were compared between groups. HFOV as rescue treatment was successful in 58.1% of patients. Demographic and treatment parameters were not different between groups, except that infants in Group D/E had lower birthweight (BW) (1655 ± 1091 vs. 1858 ± 1027 g, p = 0.006), a higher initial FiO2 setting (83% vs. 72%, p < 0.001), and a higher rate of nitric oxide exposure (21.8% vs. 11.1%, p = 0.004) in comparison to infants who survived (Group S). The initial cut-offs for a successful response on ABG were defined as pH >7.065 (OR: 19.74, 95% CI 4.83-80.6, p < 0.001), HCO3 >16.35 mmol/L (OR: 1.06, 95% CI 1.01-1.1, p = 0.006), and lactate level <3.75 mmol/L (OR: 1.09%95 CI 1.01-1.16, p = 0.006). Rescue HFOV duration was associated with retinopathy of prematurity (p = 0.005) and moderate or severe chronic lung disease (p < 0.001), but not with patent ductus arteriosus or intraventricular hemorrhage, in survivors (p > 0.05). Rescue HFOV as defined for this population was successful in more than half of the patients with CV failure. Although the response was not associated with gestational age, underlying disease, device used, or initial MV settings, it seemed to be more effective in patients with higher BW and those not requiring nitric oxide. Initial pH, HCO3, and lactate levels on ABG may be used as predictors of a response to rescue HFOV.

Objective To determine clinical and physiological effects of high frequency oscillation compared with conventional ventilation in patients with acute lung injury/acute respiratory distress syndrome (ARDS).Design Systematic review and meta-analysis.Data sources Electronic databases to March 2010, conference proceedings, bibliographies, and primary investigators.Study selection Randomised controlled trials of high frequency oscillation compared with conventional ventilation in adults or children with acute lung injury/ARDS.Data selection Three authors independently extracted data on clinical, physiological, and safety outcomes according to a predefined protocol. We contacted investigators of all included studies to clarify methods and obtain additional data. Analyses used random effects models.Results Eight randomised controlled trials (n=419 patients) were included; almost all patients had ARDS. Methodological quality was good. The ratio of partial pressure of oxygen to inspired fraction of oxygen at 24, 48, and 72 hours was 16-24% higher in patients receiving high frequency oscillation. There were no significant differences in oxygenation index because mean airway pressure rose by 22-33% in patients receiving high frequency oscillation (P≤0.01). In patients randomised to high frequency oscillation, mortality was significantly reduced (risk ratio 0.77, 95% confidence interval 0.61 to 0.98, P=0.03; six trials, 365 patients, 160 deaths), and treatment failure (refractory hypoxaemia, hypercapnoea, hypotension, or barotrauma) resulting in discontinuation of assigned therapy was less likely (0.67, 0.46 to 0.99, P=0.04; five trials, 337 patients, 73 events). Other risks were similar. There was substantial heterogeneity between trials for physiological (I2=21-95%) but not clinical (I2=0%) outcomes. Pooled results were based on few events for most clinical outcomes.Conclusion High frequency oscillation might improve survival and is unlikely to cause harm. As ongoing large multicentre trials will not be completed for several years, these data help clinicians who currently use or are considering this technique for patients with ARDS.

In this trial, high-frequency oscillatory ventilation was compared with conventional ventilation with a lung-protective protocol. When the study was stopped early, hospital mortality was 47% with HFOV versus 35% with the control ventilation strategy. The acute respiratory distress syndrome (ARDS) is a common complication of critical illness. 1 , 2 Mortality is high, and survivors often have long-term complications. 3 , 4 Although mechanical ventilation is life-sustaining for patients with ARDS, it can perpetuate lung injury. Basic research suggests that repetitive overstretching or collapse of lung units with each respiratory cycle can generate local and systemic inflammation, contributing to multiorgan failure and death. 5 Consistent with these findings are data from clinical trials that support the use of smaller tidal volumes (6 vs. 12 ml per kilogram of predicted body weight) 6 and higher levels of positive end-expiratory pressure (PEEP). . . .

High-frequency oscillatory ventilation (HFOV) is theoretically beneficial for lung protection, but the results of clinical trials are inconsistent, with study-level meta-analyses suggesting no significant effect on mortality. The aim of this individual patient data meta-analysis was to identify acute respiratory distress syndrome (ARDS) patient subgroups with differential outcomes from HFOV. After a comprehensive search for trials, two reviewers independently identified randomized trials comparing HFOV with conventional ventilation for adults with ARDS. Prespecified effect modifiers were tested using multivariable hierarchical logistic regression models, adjusting for important prognostic factors and clustering effects. Data from 1,552 patients in four trials were analyzed, applying uniform definitions for study variables and outcomes. Patients had a mean baseline Pa /Fi of 114 ± 39 mm Hg; 40% had severe ARDS (Pa /Fi <100 mm Hg). Mortality at 30 days was 321 of 785 (40.9%) for HFOV patients versus 288 of 767 (37.6%) for control subjects (adjusted odds ratio, 1.17; 95% confidence interval, 0.94-1.46; P = 0.16). This treatment effect varied, however, depending on baseline severity of hypoxemia (P = 0.0003), with harm increasing with Pa /Fi among patients with mild-moderate ARDS, and the possibility of decreased mortality in patients with very severe ARDS. Compliance and body mass index did not modify the treatment effect. HFOV increased barotrauma risk compared with conventional ventilation (adjusted odds ratio, 1.75; 95% confidence interval, 1.04-2.96; P = 0.04). HFOV increases mortality for most patients with ARDS but may improve survival among patients with severe hypoxemia on conventional mechanical ventilation.

High-frequency oscillatory ventilation has been advocated for hypoxemia accompanying the acute respiratory distress syndrome. In this trial comparing HFOV with conventional ventilation, HFOV had no significant effect on 30-day mortality. The acute respiratory distress syndrome (ARDS) is a severe, diffuse inflammatory lung condition caused by a range of acute illnesses. Mortality in affected patients is high, 1 and survivors may have functional limitations for years. 2 , 3 Although mechanical ventilation can initially be lifesaving in patients with ARDS, it can also further injure the patients' lungs and contribute to death. 4 High-frequency oscillatory ventilation (HFOV) was first used experimentally in the 1970s to minimize the hemodynamic effects of mechanical ventilation. 5 Patients' lungs are held inflated to maintain oxygenation, and carbon dioxide is cleared by small volumes of gas moved in and out of . . .

This systematic review aimed to analyze, in neonates, the effects of high-frequency oscillatory ventilation (HFOV) with volume-targeted (VT) compared with conventional HFOV. The authors searched PubMed, EMBASE, Cochrane, and ClinicalTrials.gov from inception until August 4th, 2024, to identify studies comparing HFOV with and without VT in neonates under 44 weeks corrected age. Outcomes analyzed were VThf, amplitude and carbon dioxide partial pressure (PCO2) variability, episodes of hypoxemia, hypocarbia or hypercarbia, duration of mechanical ventilation, rates of bronchopulmonary dysplasia (BPD) or intraventricular hemorrhage (IVH), and mortality. ROB-2 and ROBINS were used for risk of bias assessment. This systematic review included 260 preterm infants from two crossover and four cohort studies. Five studies were considered as having a relevant risk of bias. Meta-analysis could not be performed, due to the differences in study design and incomplete reporting. The report of included studies indicates that HFOV with VT, compared with HFOV, may reduce VThf variability, hypocarbia and hypercarbia incidence. Findings on hypoxemia incidence and mechanical ventilation duration are mixed. Two studies found no difference in BPD rates, while one noted higher survival without BPD grades 2–3 under HFOV with VT. IVH, leukomalacia, and mortality outcomes were similar. Inclusion of VT during HFOV may reduce VThf variability, hypocarbia and hypercarbia incidence. However, there is a need for randomized trials to compare clinical outcomes from both ventilatory strategies.

Non-invasive high-frequency oscillatory ventilation (NHFOV) consists of the application of a bias flow generating a continuous distending positive pressure with superimposed oscillations, which have constant frequency and active expiratory phase. NHFOV matches together the advantages of high-frequency ventilation (no need for synchronisation, high efficacy in removing CO2) and nasal continuous positive airway pressure (CPAP) (non-invasive interface, increase in functional residual capacity allowing oxygenation to improve). There is enough clinical expertise demonstrating that NHFOV may be tried in some selected cases, in whom CPAP or conventional non-invasive ventilation have failed. Nonetheless, there are no clear data about its clinical usefulness and there is a need for randomised controlled studies. Our purpose is to review the physiology and biological effects of NHFOV, to present the current clinical evidence on its use, to provide some guiding principles to clinicians and suggest directions for further research.