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Purpose Noninvasive ventilation (NIV) may facilitate withdrawal of invasive mechanical ventilation (i-MV) and shorten intensive care unit (ICU) length of stay (LOS) in hypercapnic patients, while data are lacking on hypoxemic patients. We aim to determine whether NIV after early extubation reduces the duration of i-MV and ICU LOS in patients recovering from hypoxemic acute respiratory failure. Methods Highly selected non-hypercapnic hypoxemic patients were randomly assigned to receive NIV after early or standard extubation. Co-primary end points were duration of i-MV and ICU LOS. Secondary end points were treatment failure, severe events (hemorrhagic, septic, cardiac, renal or neurologic episodes, pneumothorax or pulmonary embolism), ventilator-associated pneumonia (VAP) or tracheobronchitis (VAT), tracheotomy, percent of patients receiving sedation after study enrollment, hospital LOS, and ICU and hospital mortality. Results We enrolled 130 consecutive patients, 65 treatments and 65 controls. Duration of i-MV was shorter in the treatment group than for controls [4.0 (3.0–7.0) vs. 5.5 (4.0–9.0) days, respectively, p  = 0.004], while ICU LOS was not significantly different [8.0 (6.0–12.0) vs. 9.0 (6.5–12.5) days, respectively ( p  = 0.259)]. Incidence of VAT or VAP (9% vs. 25%, p  = 0.019), rate of patients requiring infusion of sedatives after enrollment (57% vs. 85%, p  = 0.001), and hospital LOS, 20 (13–32) vs. 27(18–39) days ( p  = 0.043) were all significantly reduced in the treatment group compared with controls. There were no significant differences in ICU and hospital mortality or in the number of treatment failures, severe events, and tracheostomies. Conclusions In highly selected hypoxemic patients, early extubation followed by immediate NIV application reduced the days spent on invasive ventilation without affecting ICU LOS.

Background Extubation failure leading to reintubation is associated with high mortality. In patients at high-risk of extubation failure, clinical practice guidelines recommend prophylactic non-invasive ventilation (NIV) over high-flow nasal oxygen (HFNO) immediately after extubation. However, the physiological effects supporting the beneficial effect of NIV have been poorly explored. We hypothesized that NIV may reduce patient inspiratory efforts to a greater extent than HFNO after extubation. Methods In a prospective physiological study, patients at high-risk of extubation failure (> 65 years old or underlying cardiac or respiratory disease) were included to receive after planned extubation prophylactic NIV and HFNO in a randomized crossover order, followed by standard oxygen. Inspiratory efforts were assessed by calculation of the simplified esophageal pressure–time-product per minute (sPTP es in cmH 2 O s/min). Tidal volumes, distribution and homogeneity of ventilation were estimated using electrical impedance tomography. Results Twenty patients were retained in the analysis. Inspiratory efforts were lower with NIV than with HFNO (sPTP es 196 cm H 2 O s/min [116–234] vs. 220 [178–327], p  < 0.001) whereas tidal volumes were larger with NIV than with HFNO (8.4 mL/kg of predicted body weight [6.7–9.9] vs. 6.9 [5.3–8.6], p  = 0.005). There was a non-significant increase in dorsal region ventilation under NIV compared to HFNO. Conclusions In patients at high-risk of extubation failure, prophylactic NIV significantly decreased inspiratory efforts with increased tidal volumes compared to HFNO. The clinical benefits of NIV to prevent reintubation in patients at high-risk may be mediated by these physiological effects. Trial registration Clinicaltrials.gov: ID NCT04036175), retrospectively registered 17 June 2019.

Rationale Our pilot study suggested that noninvasive ventilation (NIV) reduced the need for intubation compared with conventional administration of oxygen on patients with “early” stage of mild acute respiratory distress syndrome (ARDS, PaO 2 /FIO 2 between 200 and 300). Objectives To evaluate whether early NIV can reduce the need for invasive ventilation in patients with pneumonia-induced early mild ARDS. Methods Prospective, multicenter, randomized controlled trial (RCT) of NIV compared with conventional administration of oxygen through a Venturi mask. Primary outcome included the numbers of patients who met the intubation criteria. Results Two hundred subjects were randomized to NIV ( n  = 102) or control ( n  = 98) groups from 21 centers. Baseline characteristics were similar in the two groups. In the NIV group, PaO 2 /FIO 2 became significantly higher than in the control group at 2 h after randomization and remained stable for the first 72 h. NIV did not decrease the proportion of patients requiring intubation than in the control group (11/102 vs. 9/98, 10.8% vs. 9.2%, p  = 0.706). The ICU mortality was similar in the two groups (7/102 vs. 7/98, 4.9% vs. 3.1%, p  = 0.721). Multivariate analysis showed minute ventilation greater than 11 L/min at 48 h was the independent risk factor for NIV failure (OR, 1.176 [95% CI, 1.005–1.379], p  = 0.043). Conclusions Treatment with NIV did not reduce the need for intubation among patients with pneumonia-induced early mild ARDS, despite the improved PaO 2 /FIO 2 observed with NIV compared with standard oxygen therapy. High minute ventilation may predict NIV failure. Trial registration NCT01581229 . Registered 19 April 2012

Nasal highflow (NHF) provides a warmed and humidified air stream up to 60 L/min. Recent data demonstrated a positive effect in patients with acute hypoxemic respiratory failure, especially when caused by pneumonia. Preliminary data show a decrease in hypercapnia in patients with COPD. Therefore, NHF should be evaluated as a new ventilatory support device. This study was conducted to assess the impact of different flow rates on ventilatory parameters in patients with COPD. This interventional clinical study was performed with patients suffering from severe COPD. The aim was to characterize flow-dependent changes in mean airway pressure, breathing volumes, breathing frequency, and decrease in partial pressure of CO2 (pCO2). Mean airway pressure was measured in the nasopharyngeal space (19 patients). To evaluate breathing volumes, we used a polysomnographic device (18 patients). All patients received 20 L/min, 30 L/min, 40 L/min, and 50 L/min and - to illustrate the effects - nasal continuous positive airway pressure and nasal bilevel positive airway pressure. Capillary blood gas analyses were performed in 54 patients with hypercapnic COPD before and two hours after the use of NHF. We compared the extent of decrease in pCO2 when using 20 L/min and 30 L/min. Additionally, comfort and dyspnea during the use of NHF were surveyed. NHF resulted in a minor flow dependent increase in mean airway pressure. Tidal volume increased, and breathing rate decreased. The calculated minute volume decreased under NHF breathing. In spite of this fact, hypercapnia decreased with increasing flow (20 L/min vs 30 L/min). Additionally, an improvement in dyspnea was observed. The rapid shallow breathing index shows a decrease when using NHF. NHF leads to a flow-dependent reduction in pCO2. This is most likely achieved by a washout of the respiratory tract and a functional reduction in dead space. In summary, NHF enhances effectiveness of breathing in patients with COPD, reduces pCO2, the work of breathing, and rapid shallow breathing index as an indicator of respiratory work load.

Background Noninvasive neurally adjusted ventilator assist (NIV-NAVA) was introduced to our clinical practice via a pilot and a randomized observational study to assess its safety, feasibility, and short-term physiological effects. Methods The pilot protocol applied NIV-NAVA to 11 infants on nasal CPAP, high-flow nasal cannula, or nasal intermittent mandatory ventilation (NIMV), in multiple 2- to 4-h periods of NIV-NAVA for comparison. This provided the necessary data to design a randomized, controlled observational crossover study in eight additional infants to compare the physiological effects of NIV-NAVA with NIMV during 2-h steady-state conditions. We recorded the peak inspiratory pressure (PIP), FiO 2 , Edi, oxygen saturations (histogram analysis), transcutaneous PCO 2 , and movement with an Acoustic Respiratory Movement Sensor. Results The NAVA catheter was used for 81 patient days without complications. NIV-NAVA produced significant reductions (as a percentage of measurements on NIMV) in the following: PIP, 13%; FiO 2 , 13%; frequency of desaturations, 42%; length of desaturations, 32%; and phasic Edi, 19%. Infant movement and caretaker movement were reduced by 42% and 27%, respectively. Neural inspiratory time was increased by 39 ms on NIV-NAVA, possibly due to Head’s paradoxical reflex. Conclusion NIV-NAVA was a safe, alternative mode of noninvasive support that produced beneficial short-term physiological effects, especially compared with NIMV.

Background Although cumulative studies have demonstrated a beneficial effect of high-flow nasal cannula oxygen (HFNC) in acute hypercapnic respiratory failure, randomized trials to compare HFNC with non-invasive ventilation (NIV) as initial treatment in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients with acute-moderate hypercapnic respiratory failure are limited. The aim of this randomized, open label, non-inferiority trial was to compare treatment failure rates between HFNC and NIV in such patients. Methods Patients diagnosed with AECOPD with a baseline arterial blood gas pH between 7.25 and 7.35 and PaCO 2  ≥ 50 mmHg admitted to two intensive care units (ICUs) at a large tertiary academic teaching hospital between March 2018 and December 2022 were randomly assigned to HFNC or NIV. The primary endpoint was the rate of treatment failure, defined as endotracheal intubation or a switch to the other study treatment modality. Secondary endpoints were rates of intubation or treatment change, blood gas values, vital signs at one, 12, and 48 h, 28-day mortality, as well as ICU and hospital lengths of stay. Results 225 total patients (113 in the HFNC group and 112 in the NIV group) were included in the intention-to-treat analysis. The failure rate of the HFNC group was 25.7%, while the NIV group was 14.3%. The failure rate risk difference between the two groups was 11.38% (95% CI 0.25–21.20, P  = 0.033), which was higher than the non-inferiority cut-off of 9%. In the per-protocol analysis, treatment failure occurred in 28 of 110 patients (25.5%) in the HFNC group and 15 of 109 patients (13.8%) in the NIV group (risk difference, 11.69%; 95% CI 0.48–22.60). The intubation rate in the HFNC group was higher than in the NIV group (14.2% vs 5.4%, P  = 0.026). The treatment switch rate, ICU and hospital length of stay or 28-day mortality in the HFNC group were not statistically different from the NIV group (all P  > 0.05). Conclusion HFNC was not shown to be non-inferior to NIV and resulted in a higher incidence of treatment failure than NIV when used as the initial respiratory support for AECOPD patients with acute-moderate hypercapnic respiratory failure. Trial registration : chictr.org (ChiCTR1800014553). Registered 21 January 2018, http://www.chictr.org.cn

Background High flow nasal cannula therapy (HFNC) and continuous positive airway pressure (CPAP) are two widely used modes of non-invasive respiratory support in paediatric critical care units. The FIRST-ABC randomised controlled trials (RCTs) evaluated the clinical and cost-effectiveness of HFNC compared with CPAP in two distinct critical care populations: acutely ill children (‘step-up’ RCT) and extubated children (‘step-down’ RCT). Clinical effectiveness findings (time to liberation from all forms of respiratory support) showed that HFNC was non-inferior to CPAP in the step-up RCT, but failed to meet non-inferiority criteria in the step-down RCT. This study evaluates the cost-effectiveness of HFNC versus CPAP. Methods All-cause mortality, health-related Quality of Life (HrQoL), and costs up to six months were reported using FIRST-ABC RCTs data. HrQoL was measured with the age-appropriate Paediatric Quality of Life Generic Core Scales questionnaire and mapped onto the Child Health Utility 9D index score at six months. Quality-Adjusted Life Years (QALYs) were estimated by combining HrQoL with mortality. Costs at six months were calculated by measuring and valuing healthcare resources used in paediatric critical care units, general medical wards and wider health service. The cost-effectiveness analysis used regression methods to report the cost-effectiveness of HFNC versus CPAP at six months and summarised the uncertainties around the incremental cost-effectiveness results. Results In both RCTs, the incremental QALYs at six months were similar between the randomised groups. The estimated incremental cost at six months was − £4565 (95% CI − £11,499 to £2368) and − £5702 (95% CI − £11,328 to − £75) for step-down and step-up RCT, respectively. The incremental net benefits of HFNC versus CPAP in step-down RCT and step-up RCT were £4388 (95% CI − £2551 to £11,327) and £5628 (95% CI − £8 to £11,264) respectively. The cost-effectiveness results were surrounded by considerable uncertainties. The results were similar across most pre-specified subgroups, and the base case results were robust to alternative assumptions. Conclusions HFNC compared to CPAP as non-invasive respiratory support for critically-ill children in paediatric critical care units reduces mean costs and is relatively cost-effective overall and for key subgroups, although there is considerable statistical uncertainty surrounding this result.

Abstract Discoveries have emerged highlighting the complex nature of the interorgan cross-talk between the kidney and the lung. Vascular rigidity, neurohormonal activation, tissue hypoxia, and abnormal immune cell signaling have been identified as common pathways leading to the development and progression of chronic kidney disease. However, our understanding of the causal relationships between lung injury and kidney injury is not precise. This review discusses a number of features and mechanisms of renal dysfunction in pulmonary disorders in relation to respiratory acidosis, impaired gas exchange, systemic congestion, respiratory support/replacement therapies, and other issues relevant to the clinical care of these patients. Biotrauma due to injurious ventilatory strategies can lead to the release of mediators into the lung, which may then translocate into the systemic circulation and cause end-organ dysfunction, including renal dysfunction. Right ventricular dysfunction and congestive states may contribute to alterations of renal perfusion and oxygenation, leading to diuretic resistance and recurrent hospitalization. In patients with concomitant respiratory failure, noninvasive ventilation represents a promising treatment option for the correction of impaired renal microcirculation and endothelial dysfunction. In patients requiring extracorporeal membrane oxygenation, short- and long-term monitoring of kidney function is warranted, as they are at highest risk of developing acute kidney injury and fluid overload.

Noninvasive ventilation (NIV) is increasingly used in patients with acute respiratory distress syndrome (ARDS). The evidence supporting NIV use in patients with ARDS remains relatively sparse. To determine whether, during NIV, the categorization of ARDS severity based on the Pa /Fi Berlin criteria is useful. The LUNG SAFE (Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure) study described the management of patients with ARDS. This substudy examines the current practice of NIV use in ARDS, the utility of the Pa /Fi ratio in classifying patients receiving NIV, and the impact of NIV on outcome. Of 2,813 patients with ARDS, 436 (15.5%) were managed with NIV on Days 1 and 2 following fulfillment of diagnostic criteria. Classification of ARDS severity based on Pa /Fi ratio was associated with an increase in intensity of ventilatory support, NIV failure, and intensive care unit (ICU) mortality. NIV failure occurred in 22.2% of mild, 42.3% of moderate, and 47.1% of patients with severe ARDS. Hospital mortality in patients with NIV success and failure was 16.1% and 45.4%, respectively. NIV use was independently associated with increased ICU (hazard ratio, 1.446 [95% confidence interval, 1.159-1.805]), but not hospital, mortality. In a propensity matched analysis, ICU mortality was higher in NIV than invasively ventilated patients with a Pa /Fi lower than 150 mm Hg. NIV was used in 15% of patients with ARDS, irrespective of severity category. NIV seems to be associated with higher ICU mortality in patients with a Pa /Fi lower than 150 mm Hg. Clinical trial registered with www.clinicaltrials.gov (NCT 02010073).

PurposeAlthough noninvasive ventilation (NIV) may reduce reintubation in patients with acute hypoxemic respiratory failure following abdominal surgery, this strategy has not been specifically assessed in patients with obesity.MethodsWe conducted a post hoc analysis of a multicenter randomized controlled trial comparing NIV delivered via facial mask to standard oxygen therapy among patients with obesity and acute hypoxemic respiratory failure within 7 days after abdominal surgery. The primary outcome was reintubation within 7 days. Secondary outcomes were invasive ventilation-free days at day 30, intensive care unit (ICU)-acquired pneumonia and 30-day survival.ResultsAmong 293 patients with hypoxemic respiratory failure following abdominal surgery, 76 (26%) patients had obesity and were included in the intention-to-treat analysis. Reintubation rate was significantly lower with NIV (13/42, 31%) than with standard oxygen therapy (19/34, 56%) within 7 days (absolute difference: − 25%, 95% confidence interval (CI) − 49 to − 1%, p = 0.03). NIV was associated with significantly more invasive ventilation-free days compared with standard oxygen therapy (27.1 ± 8.6 vs 22.7 ± 11.1 days; p = 0.02), while fewer patients developed ICU-acquired pneumonia (1/42, 2% vs 6/34, 18%; p = 0.04). The 30-day survival was 98% in the NIV group (41/42) versus 85% in the standard oxygen therapy (p = 0.08). In patients with body mass index (BMI) < 30 kg/m2, no significant difference was observed between NIV (36/105, 34%) and standard oxygen therapy (47/109, 43%, p = 0.03). An interaction test showed no statistically significant difference between the two subsets (BMI ≥ 30 kg/m2 and BMI < 30 kg/m2).ConclusionsAmong patients with obesity and hypoxemic respiratory failure following abdominal surgery, use of NIV compared with standard oxygen therapy reduced the risk of reintubation within 7 days, contrary to patients without obesity. However, no interaction was found according to the presence of obesity or not, suggesting either a lack of power to conclude in the non-obese subgroup despite existing differences, or that the statistical difference found in the overall sample was driven by a large effect in the obese subsets.