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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).

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.

PurposeNoninvasive 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.MethodsHighly 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.ResultsWe 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.ConclusionsIn highly selected hypoxemic patients, early extubation followed by immediate NIV application reduced the days spent on invasive ventilation without affecting ICU LOS.

Purpose Over the last two decades, noninvasive ventilation (NIV) has been proposed in various causes of acute respiratory failure (ARF) but some indications are debated. Current trends in NIV use are unknown. Methods Comparison of three multicenter prospective audits including all patients receiving mechanical ventilation and conducted in 1997, 2002, and 2011 in francophone countries. Results Among the 4132 patients enrolled, 2094 (51 %) required ventilatory support for ARF and 2038 (49 %) for non-respiratory conditions. Overall NIV use was markedly increased in 2010/11 compared to 1997 and 2002 (37 % of mechanically ventilated patients vs. 16 % and 28 %, P  < 0.05). In 2010/11, the use of first-line NIV for ARF had reached a plateau (24 % vs. 16 % and 23 %, P  < 0.05) whereas pre-ICU and post-extubation NIV had substantially increased (11 % vs. 4 % and 11 % vs. 7 %, respectively, P  < 0.05). First-line NIV remained stable in acute-on-chronic RF, continued to increase in cardiogenic pulmonary edema, but decreased in de novo ARF (16 % in 2010/11 vs. 23 % in 2002, P  < 0.05). The NIV success rate increased from 56 % in 2002 to 70 % in 2010/11 and remained the lowest in de novo ARF. NIV failure in de novo ARF was associated with increased mortality in 2002 but not in 2010/11. Mortality decreased over time, and overall, NIV use was associated with a lower mortality. Conclusion Increases in NIV use and success rate, an overall decrease in mortality, and a decrease of the adverse impact NIV failure has in de novo ARF suggest better patient selection and greater proficiency of staff in administering NIV. Trial registration Clinicaltrials.gov Identifier NCT01449331.

The role of non-invasive respiratory support (high-flow nasal oxygen and noninvasive ventilation) in the management of acute hypoxemic respiratory failure and acute respiratory distress syndrome is debated. The oxygenation improvement coupled with lung and diaphragm protection produced by non-invasive support may help to avoid endotracheal intubation, which prevents the complications of sedation and invasive mechanical ventilation. However, spontaneous breathing in patients with lung injury carries the risk that vigorous inspiratory effort, combined or not with mechanical increases in inspiratory airway pressure, produces high transpulmonary pressure swings and local lung overstretch. This ultimately results in additional lung damage (patient self-inflicted lung injury), so that patients intubated after a trial of noninvasive support are burdened by increased mortality. Reducing inspiratory effort by high-flow nasal oxygen or delivery of sustained positive end-expiratory pressure through the helmet interface may reduce these risks. In this physiology-to-bedside review, we provide an updated overview about the role of noninvasive respiratory support strategies as early treatment of hypoxemic respiratory failure in the intensive care unit. Noninvasive strategies appear safe and effective in mild-to-moderate hypoxemia (PaO2/FiO2 > 150 mmHg), while they can yield delayed intubation with increased mortality in a significant proportion of moderate-to-severe (PaO2/FiO2 ≤ 150 mmHg) cases. High-flow nasal oxygen and helmet noninvasive ventilation represent the most promising techniques for first-line treatment of severe patients. However, no conclusive evidence allows to recommend a single approach over the others in case of moderate-to-severe hypoxemia. During any treatment, strict physiological monitoring remains of paramount importance to promptly detect the need for endotracheal intubation and not delay protective ventilation.

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.

One important concern during high-flow nasal cannula (HFNC) therapy in patients with acute hypoxemic respiratory failure is to not delay intubation. To validate the diagnostic accuracy of an index (termed ROX and defined as the ratio of oxygen saturation as measured by pulse oximetry/Fi to respiratory rate) for determining HFNC outcome (need or not for intubation). This was a 2-year multicenter prospective observational cohort study including patients with pneumonia treated with HFNC. Identification was through Cox proportional hazards modeling of ROX association with HFNC outcome. The most specific cutoff of the ROX index to predict HFNC failure and success was assessed. Among the 191 patients treated with HFNC in the validation cohort, 68 (35.6%) required intubation. The prediction accuracy of the ROX index increased over time (area under the receiver operating characteristic curve: 2 h, 0.679; 6 h, 0.703; 12 h, 0.759). ROX greater than or equal to 4.88 measured at 2 (hazard ratio, 0.434; 95% confidence interval, 0.264-0.715;  = 0.001), 6 (hazard ratio, 0.304; 95% confidence interval, 0.182-0.509;  < 0.001), or 12 hours (hazard ratio, 0.291; 95% confidence interval, 0.161-0.524;  < 0.001) after HFNC initiation was consistently associated with a lower risk for intubation. A ROX less than 2.85, less than 3.47, and less than 3.85 at 2, 6, and 12 hours of HFNC initiation, respectively, were predictors of HFNC failure. Patients who failed presented a lower increase in the values of the ROX index over the 12 hours. Among components of the index, oxygen saturation as measured by pulse oximetry/Fi had a greater weight than respiratory rate. In patients with pneumonia with acute respiratory failure treated with HFNC, ROX is an index that can help identify those patients with low and those with high risk for intubation. Clinical trial registered with www.clinicaltrials.gov (NCT02845128).

Background Robust evidence supports the use of preemptive non-invasive ventilation (NIV) after extubation in selected high-risk patient cohorts. In contrast, current guidelines discourage the use of NIV as a rescue therapy for respiratory failure that develops later after extubation, based on earlier studies indicating a potential increase in hospital mortality due to delayed reintubation. Nonetheless, NIV continues to be employed in this setting. We conducted a post-hoc analysis of a randomized trial to assess the clinical outcomes of rescue NIV for post-extubation respiratory failure. Methods In this post-hoc analysis of a randomized trial comparing high-flow with Venturi mask oxygen in hypoxemic patients after extubation, we included those who developed post-extubation respiratory failure according to prespecified criteria; patients who received rescue NIV per physician’s decision were compared to those who received direct re-intubation. Criteria for re-intubation during NIV were prespecified. Odds ratio after inverse probability of treatment weighting and posterior probabilities by Bayesian regression are reported. Results Among 494 extubated patients, 147 developed respiratory failure while receiving oxygen therapy, occurring at a median of 37 h [IQR 13–85] after extubation: 83 (57%) were treated with rescue NIV and 64 (43%) received immediate re-intubation. The rate of NIV failure was 58%, without differences between patients with hypoxemic respiratory failure and those with hypercapnia and/or respiratory distress (60% vs. 56%, p = 0.82). In the weighted cohort, the use of rescue NIV, compared to direct re-intubation, was associated with lower intensive care unit mortality (adjusted odds ratio = 0.31 [95%CI: 0.12–0.82], p = 0.019) and similar hospital mortality (adjusted odds ratio = 1.01 [95%CI: 0.43–2.33], p = 0.99). The posterior probability that NIV reduced intensive care unit mortality was > 90% across all priors. The posterior probability that NIV did not increase hospital mortality was 44% under a noninformative prior, 47% under a skeptical prior, and 39% under a pessimistic prior. Conclusion Rescue NIV for post-extubation respiratory failure is associated with high failure rates; however, when applied with well-defined criteria for reintubation, it does not appear to be clearly associated with increases in hospital mortality. A randomized trial to re-evaluate the efficacy of rescue NIV for post-extubation respiratory failure is warranted. Clinical trial registration Registered at clinicaltrials.gov (NCT02107183) on April 8th, 2014.

Background Non-invasive ventilation (NIV) is widely used in emergency settings for acute respiratory failure, with NIV failure, usually defined by the need for tracheal intubation, as its primary complication. In emergency settings where patients may not be intubated or or where NIV represents the ceiling of care, a pragmatic understanding of NIV failure requires a broader definition that incorporates early clinical deterioration, including presumptive intubation criteria. This study assessed the prevalence of early clinical deterioration under NIV initiated in emergency settings (emergency department [ED] or mobile emergency medical services [EMS]) and its associated variables. Methods A prospective multicentre study was conducted in 68 French EDs and EMS in the Initiative Recherche Urgences (IRU) network. Adult patients (≥ 18 years) requiring NIV in emergency settings were included, excluding those with a known do-not-resuscitate order or low autonomy. The primary endpoint was early clinical deterioration under NIV at 1 h. Early clinical deterioration under NIV was defined as either (1) the need for tracheal intubation or; (2) the presence of presumptive criteria for intubation. Secondary endpoints were baseline factors associated with failure, the need for tracheal intubation or death within 7 days among patients surviving without tracheal intubation at 1 h, and 7-day mortality. Results A total of 198 patients were included over 5 days. Early clinical deterioration at 1 h was reported in 41% of the patients. Early clinical deterioration under NIV was associated with a Glasgow Coma Scale score < 14 (adjusted odds ratio [aOR] = 5.5, 95% confidence interval [CI] [1.8 –19.4]), heart rate > 115 beats per minute (aOR = 2.5, 95%CI [1.3–5.2]), and signs of increased work of breathing (aOR = 2.8, 95%CI [1.2–7.1]). Among the surviving patients not intubated at 1 h, 12% required intubation within 7 days in the Early Clinical Deterioration group and 3% in the No Early Clinical Deterioration group (p < 0.001). Within 7 days, 28% died in the Early Clinical Deterioration group and 10% in the No Early Clinical Deterioration group (p = 0.001). NIV failure was associated with increased 7-day mortality (aHR = 4.1, 95%CI [1.8–9.1]). Conclusions Early clinical deterioration under NIV is common in EDs, affecting nearly one out of two patients, and is associated with higher 7-day mortality. Clinical trial registration Registered 2024 january, 23th. NCT06213623. Prior to the first inclusion.