Survival in Immunocompromised Patients Ultimately Requiring Invasive Mechanical Ventilation: A Pooled Individual Patient Data Analysis.

Rationale: Acute respiratory failure (ARF) is associated with high mortality in immunocompromised patients, particularly when invasive mechanical ventilation is needed. Therefore, noninvasive oxygenation/ventilation strategies have been developed to avoid intubation, with uncertain impact on mortality, especially when intubation is delayed. Objectives: We sought to report trends of survival over time in immunocompromised patients receiving invasive mechanical ventilation. The impact of delayed intubation after failure of noninvasive strategies was also assessed. Methods: Systematic review and meta-analysis using individual patient data of studies that focused on immunocompromised adult patients with ARF requiring invasive mechanical ventilation. Studies published in English were identified through PubMed, Web of Science, and Cochrane Central (2008-2018). Individual patient data were requested from corresponding authors for all identified studies. We used mixed-effect models to estimate the effect of delayed intubation on hospital mortality and described mortality rates over time. Measurements and Main Results: A total of 11,087 patients were included (24 studies, three controlled trials, and 21 cohorts), of whom 7,736 (74%) were intubated within 24 hours of ICU admission (early intubation). The crude mortality rate was 53.2%. Adjusted survivals improved over time (from 1995 to 2017, odds ratio [OR] for hospital mortality per year, 0.96 [0.95-0.97]). For each elapsed day between ICU admission and intubation, mortality was higher (OR, 1.38 [1.26-1.52]; P < 0.001). Early intubation was significantly associated with lower mortality (OR, 0.83 [0.72-0.96]), regardless of initial oxygenation strategy. These results persisted after propensity score analysis (matched OR associated with delayed intubation, 1.56 [1.44-1.70]). Conclusions: In immunocompromised intubated patients, survival has improved over time. Time between ICU admission and intubation is a strong predictor of mortality, suggesting a detrimental effect of late initial oxygenation failure.

Non-invasive ventilation for SARS-CoV-2 acute respiratory failure: a subanalysis from the HOPE COVID-19 registry.

BACKGROUND: The COVID-19 pandemic has seriously challenged worldwide healthcare systems and limited intensive care facilities, leading to physicians considering the use of non-invasive ventilation (NIV) for managing SARS-CoV-2-related acute respiratory failure (ARF). METHODS: We conducted an interim analysis of the international, multicentre HOPE COVID-19 registry including patients admitted for a confirmed or highly suspected SARS-CoV-2 infection until 18 April 2020. Those treated with NIV were considered. The primary endpoint was a composite of death or need for intubation. The components of the composite endpoint were the secondary outcomes. Unadjusted and adjusted predictors of the primary endpoint within those initially treated with NIV were investigated. RESULTS: 1933 patients who were included in the registry during the study period had data on oxygen support type. Among them, 390 patients (20%) were treated with NIV. Compared with those receiving other non-invasive oxygen strategy, patients receiving NIV showed significantly worse clinical and laboratory signs of ARF at presentation. Of the 390 patients treated with NIV, 173 patients (44.4%) met the composite endpoint. In-hospital death was the main determinant (147, 37.7%), while 62 patients (15.9%) needed invasive ventilation. Those requiring invasive ventilation had the lowest survival rate (41.9%). After adjustment, age (adjusted OR (adj(OR)) for 5-year increase: 1.37, 95% CI 1.15 to 1.63, p<0.001), hypertension (adj(OR) 2.95, 95% CI 1.14 to 7.61, p=0.03), room air O2 saturation <92% at presentation (adj(OR) 3.05, 95% CI 1.28 to 7.28, p=0.01), lymphocytopenia (adj(OR) 3.55, 95% CI 1.16 to 10.85, p=0.03) and in-hospital use of antibiotic therapy (adj(OR) 4.91, 95% CI 1.69 to 14.26, p=0.003) were independently associated with the composite endpoint. CONCLUSION: NIV was used in a significant proportion of patients within our cohort, and more than half of these patients survived without the need for intubation. NIV may represent a viable strategy particularly in case of overcrowded and limited intensive care resources, but prompt identification of failure is mandatory to avoid harm. Further studies are required to better clarify our hypothesis. TRIAL REGISTRATION NUMBERS: NCT04334291/EUPAS34399.

Long-term clinical effectiveness of continuous positive airway pressure therapy versus non-invasive ventilation therapy in patients with obesity hypoventilation syndrome: a multicentre, open-label, randomised controlled trial.

BACKGROUND: Obesity hypoventilation syndrome is commonly treated with continuous positive airway pressure or non-invasive ventilation during sleep. Non-invasive ventilation is more complex and costly than continuous positive airway pressure but might be advantageous because it provides ventilatory support. To date there have been no long-term trials comparing these treatment modalities. We therefore aimed to determine the long-term comparative effectiveness of both treatment modalities. METHODS: We did a multicentre, open-label, randomised controlled trial at 16 clinical sites in Spain. We included patients aged 15-80 years with untreated obesity hypoventilation syndrome and an apnoea-hypopnoea index of 30 or more events per h. We randomly assigned patients, using simple randomisation through an electronic database, to receive treatment with either non-invasive ventilation or continuous positive airway pressure. Both investigators and patients were aware of the treatment allocation. The research team was not involved in deciding hospital treatment, duration of treatment in the hospital, and adjustment of medications, as well as adjudicating cardiovascular events or cause of mortality. Treating clinicians from the routine care team were not aware of the treatment allocation. The primary outcome was the number of hospitalisation days per year. The analysis was done according to the intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT01405976. FINDINGS: From May 4, 2009, to March 25, 2013, 100 patients were randomly assigned to the non-invasive ventilation group and 115 to the continuous positive airway pressure group, of which 97 patients in the non-invasive ventilation group and 107 in the continuous positive airway pressure group were included in the analysis. The median follow-up was 5·44 years (IQR 4·45-6·37) for all patients, 5·37 years (4·36-6·32) in the continuous positive airway pressure group, and 5·55 years (4·53-6·50) in the non-invasive ventilation group. The mean hospitalisation days per patient-year were 1·63 (SD 3·74) in the continuous positive airway pressure group and 1·44 (3·07) in the non-invasive ventilation group (adjusted rate ratio 0·78, 95% CI 0·34-1·77; p=0·561). Adverse events were similar between both groups. INTERPRETATION: In stable patients with obesity hypoventilation syndrome and severe obstructive sleep apnoea, non-invasive ventilation and continuous positive airway pressure have similar long-term effectiveness. Given that continuous positive airway pressure has lower complexity and cost, continuous positive airway pressure might be the preferred first-line positive airway pressure treatment modality until more studies become available. FUNDING: Instituto de Salud Carlos III, Spanish Respiratory Foundation, and Air Liquide Spain.

Intubation rate, duration of noninvasive ventilation and mortality after noninvasive neurally adjusted ventilatory assist (NIV-NAVA).

BACKGROUND: Asynchrony is a common problem in patients treated with noninvasive ventilation (NIV). Neurally adjusted ventilatory assist (NAVA) has shown to improve patient-ventilator interaction. However, it is unknown whether NIV-NAVA improves outcomes compared to noninvasive pressure support (NIV-PS). METHODS: This observational cohort study included patients 18 years or older receiving noninvasive ventilation using an oro-nasal face mask for more than 2 hours in a Danish ICU. The study included a NIV-NAVA cohort (year 2013-2015) and two comparison cohorts: (a) a historical NIV-PS cohort (year 2011-2012) before the implementation of NIV-NAVA at the ICU in 2013, and (b) a concurrent NIV-PS cohort (year 2013-2015). Outcomes of NIV-NAVA (intubation rate, duration of NIV and 90-day mortality) were assessed and compared using multivariable linear and logistic regression adjusted for relevant confounders. RESULTS: The study included 427 patients (91 in the NIV-NAVA, 134 in the historic NIV-PS and 202 in the concurrent NIV-PS cohort). Patients treated with NIV-NAVA did not have improved outcome after adjustment for measured confounders. Actually, there were statistically imprecise higher odds for intubation in NIV-NAVA patients compared with both the historical [OR 1.48, CI (0.74-2.97)] and the concurrent NIV-PS cohort [OR 1.67, CI (0.87-3.19)]. NIV-NAVA might also have a longer length of NIV [63%, CI (19%-125%)] and [139%, CI (80%-213%)], and might have a higher 90-day mortality [OR 1.24, CI (0.69-2.25)] and [OR 1.39, CI (0.81-2.39)]. Residual confounding cannot be excluded. CONCLUSION: This present study found no improved clinical outcomes in patients treated with NIV-NAVA compared to NIV-PS.

Association of Noninvasive Oxygenation Strategies With All-Cause Mortality in Adults With Acute Hypoxemic Respiratory Failure: A Systematic Review and Meta-analysis.

Importance: Treatment with noninvasive oxygenation strategies such as noninvasive ventilation and high-flow nasal oxygen may be more effective than standard oxygen therapy alone in patients with acute hypoxemic respiratory failure. Objective: To compare the association of noninvasive oxygenation strategies with mortality and endotracheal intubation in adults with acute hypoxemic respiratory failure. Data Sources: The following bibliographic databases were searched from inception until April 2020: MEDLINE, Embase, PubMed, Cochrane Central Register of Controlled Trials, CINAHL, Web of Science, and LILACS. No limits were applied to language, publication year, sex, or race. Study Selection: Randomized clinical trials enrolling adult participants with acute hypoxemic respiratory failure comparing high-flow nasal oxygen, face mask noninvasive ventilation, helmet noninvasive ventilation, or standard oxygen therapy. Data Extraction and Synthesis: Two reviewers independently extracted individual study data and evaluated studies for risk of bias using the Cochrane Risk of Bias tool. Network meta-analyses using a bayesian framework to derive risk ratios (RRs) and risk differences along with 95% credible intervals (CrIs) were conducted. GRADE methodology was used to rate the certainty in findings. Main Outcomes and Measures: The primary outcome was all-cause mortality up to 90 days. A secondary outcome was endotracheal intubation up to 30 days. Results: Twenty-five randomized clinical trials (3804 participants) were included. Compared with standard oxygen, treatment with helmet noninvasive ventilation (RR, 0.40 [95% CrI, 0.24-0.63]; absolute risk difference, -0.19 [95% CrI, -0.37 to -0.09]; low certainty) and face mask noninvasive ventilation (RR, 0.83 [95% CrI, 0.68-0.99]; absolute risk difference, -0.06 [95% CrI, -0.15 to -0.01]; moderate certainty) were associated with a lower risk of mortality (21 studies [3370 patients]). Helmet noninvasive ventilation (RR, 0.26 [95% CrI, 0.14-0.46]; absolute risk difference, -0.32 [95% CrI, -0.60 to -0.16]; low certainty), face mask noninvasive ventilation (RR, 0.76 [95% CrI, 0.62-0.90]; absolute risk difference, -0.12 [95% CrI, -0.25 to -0.05]; moderate certainty) and high-flow nasal oxygen (RR, 0.76 [95% CrI, 0.55-0.99]; absolute risk difference, -0.11 [95% CrI, -0.27 to -0.01]; moderate certainty) were associated with lower risk of endotracheal intubation (25 studies [3804 patients]). The risk of bias due to lack of blinding for intubation was deemed high. Conclusions and Relevance: In this network meta-analysis of trials of adult patients with acute hypoxemic respiratory failure, treatment with noninvasive oxygenation strategies compared with standard oxygen therapy was associated with lower risk of death. Further research is needed to better understand the relative benefits of each strategy.

An observational study on the practice of noninvasive ventilation at a tertiary level Australian intensive care unit.

BACKGROUND: Failure of Non-Invasive Ventilation (NIV) is associated with increased morbidity and mortality among critically ill patients. Although there is evidence of association between disease related factors and NIV failure, it is unclear whether factors related to NIV application contribute to NIV failure. OBJECTIVES: To evaluate NIV failure rate and factors associated with NIV failure. DESIGN, SETTINGS AND OUTCOMES: Prospective, observational, pilot study conducted in a 23-bed, tertiary care Intensive Care Unit (ICU). NIV failure was defined as application of NIV resulting in intubation or death in ICU. RESULTS: Amongst 238 patients admitted with respiratory failure, NIV was administered to 60 patients (34 males, 26 females) for a total of 70 application episodes. The etiology of respiratory failure included acute pulmonary edema (28.6%), acute lung injury (22.9%) and pneumonia (15.7%). The mean (SD) age was 62 (17.6) years, BMI 32.0 (8.5) kg/m2 and median APACHE-II score 17.5 (14.0-23.8). NIV failure occurred in 22 out of 70 applications (31.4% [95%CI 20.0-43.0]). NIV failure assessed by simple logistic regression analysis, was associated with admission diagnosis (OR 6.0, 95%CI: 1.3-28.7, p = 0.03), use of bi-level NIV-PS (OR 5.00, 95%CI: 1.04-24.1, p = 0.04), presence of nasogastric tube (OR 6.20, 95%CI: 1.9-19.8, p < 0.01) and with short NIV breaks in the 2nd 24-hours (OR 0.96, 95%CI: 0.91-0.99, p = 0.04). CONCLUSION: NIV failure was observed in 31.4%. Factors associated with NIV failure were etiology of respiratory illness, type of NIV support and short NIV breaks, presumably reflecting illness severity or progress of disease. The presence of a nasogastric tube during application of NIV may adversely impact NIV application.

Non-invasive positive pressure ventilation for prevention of complications after pulmonary resection in lung cancer patients.

BACKGROUND: Pulmonary complications are often seen during the postoperative period following lung resection for patients with lung cancer. Some situations such as intubation, a long stay in the intensive care unit, the high cost of antibiotics and mortality may be avoided with the prevention of postoperative pulmonary complications. Non-invasive positive pressure ventilation (NIPPV) is widely used in hospitals, and is thought to reduce the number of pulmonary complications and mortality after this type of surgery. Therefore, a systematic review is needed to critically assess the benefits and harms of NIPPV for patients undergoing lung resection. This is an update of a Cochrane review first published in 2015. OBJECTIVES: To assess the effectiveness and safety of NIPPV for preventing complications in patients following pulmonary resection for lung cancer. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS and PEDro until 21 December 2018, to identify potentially eligible trials. We did not use any date or language restrictions in the electronic searches. We searched the reference lists of relevant papers and contacted experts in the field for information about additional published and unpublished studies. We also searched the Register of Controlled Trials (www.controlled-trials.com) and ClinicalTrials.gov (clinicaltrials.gov) to identify ongoing studies. SELECTION CRITERIA: We considered randomised or quasi-randomised clinical trials that compared NIPPV in the immediate postoperative period after pulmonary resection with no intervention or conventional respiratory therapy. DATA COLLECTION AND ANALYSIS: Two authors collected data and assessed trial risk of bias. Where possible, we pooled data from the individual studies using a fixed-effect model (quantitative synthesis), but where this was not possible we tabulated or presented the data in the main text (qualitative synthesis). Where substantial heterogeneity existed, we applied a random-effects model. MAIN RESULTS: Of the 190 references retrieved from the searches, 7 randomised clinical trials (RCTs) (1 identified with the new search) and 1 quasi-randomised trial fulfilled the eligibility criteria for this review, including a total of 486 patients. Five studies described quantitative measures of pulmonary complications, with pooled data showing no difference between NIPPV compared with no intervention (RR 1.03; 95% CI 0.72 to 1.47). Three studies reported intubation rates and there was no significant difference between the intervention and control groups (RR 0.55; 95% CI 0.25 to 1.20). Five studies reported measures of mortality on completion of the intervention period. There was no statistical difference between the groups for this outcome (RR 0.60; 95% CI 0.24 to 1.53). Similar results were observed in the subgroup analysis considering ventilatory mode (bi-level versus continuous positive airway pressure (CPAP). No study evaluated the postoperative use of antibiotics. Two studies reported the length of intensive care unit stay and there was no significant difference between the intervention and control groups (MD -0.75; 95% CI -3.93 to 2.43). Four studies reported the length of hospital stay and there was no significant difference between the intervention and control groups (MD -0.12; 95% CI -6.15 to 5.90). None of the studies described any complications related to NIPPV. Of the seven included studies, four studies were considered as 'low risk of bias' in all domains, two studies were considered 'high risk of bias' for the allocation concealment domain, and one of these was also considered 'high risk of bias' for random sequence generation. One other study was considered 'high risk of bias' for including participants with more severe disease. The new study identified could not be included in the meta-analysis as its intervention differed from the other studies (use of pre and postoperative NIPPV in the same population). AUTHORS' CONCLUSIONS: This review demonstrated that there was no additional benefit of using NIPPV in the postoperative period after pulmonary resection for all outcomes analysed (pulmonary complications, rate of intubation, mortality, postoperative consumption of antibiotics, length of intensive care unit stay, length of hospital stay and adverse effects related to NIPPV). However, the quality of evidence is 'very low', 'low' and 'moderate' since there were few studies, with small sample size and low frequency of outcomes. New well-designed and well-conducted randomised trials are needed to answer the questions of this review with greater certainty.

Effect of Postextubation High-Flow Nasal Oxygen With Noninvasive Ventilation vs High-Flow Nasal Oxygen Alone on Reintubation Among Patients at High Risk of Extubation Failure: A Randomized Clinical Trial.

Importance: High-flow nasal oxygen may prevent postextubation respiratory failure in the intensive care unit (ICU). The combination of high-flow nasal oxygen with noninvasive ventilation (NIV) may be an optimal strategy of ventilation to avoid reintubation. Objective: To determine whether high-flow nasal oxygen with prophylactic NIV applied immediately after extubation could reduce the rate of reintubation, compared with high-flow nasal oxygen alone, in patients at high risk of extubation failure in the ICU. Design, Setting, and Participants: Multicenter randomized clinical trial conducted from April 2017 to January 2018 among 641 patients at high risk of extubation failure (ie, older than 65 years or with an underlying cardiac or respiratory disease) at 30 ICUs in France; follow-up was until April 2018. Interventions: Patients were randomly assigned to high-flow nasal oxygen alone (n = 306) or high-flow nasal oxygen alternating with NIV (n = 342) immediately after extubation. Main Outcomes and Measures: The primary outcome was the proportion of patients reintubated at day 7; secondary outcomes included postextubation respiratory failure at day 7, reintubation rates up until ICU discharge, and ICU mortality. Results: Among 648 patients who were randomized (mean [SD] age, 70 [10] years; 219 women [34%]), 641 patients completed the trial. The reintubation rate at day 7 was 11.8% (95% CI, 8.4%-15.2%) (40/339) with high-flow nasal oxygen and NIV and 18.2% (95% CI, 13.9%-22.6%) (55/302) with high-flow nasal oxygen alone (difference, -6.4% [95% CI, -12.0% to -0.9%]; P = .02). Among the 11 prespecified secondary outcomes, 6 showed no significant difference. The proportion of patients with postextubation respiratory failure at day 7 (21% vs 29%; difference, -8.7% [95% CI, -15.2% to -1.8%]; P = .01) and reintubation rates up until ICU discharge (12% vs 20%, difference -7.4% [95% CI, -13.2% to -1.8%]; P = .009) were significantly lower with high-flow nasal oxygen and NIV than with high-flow nasal oxygen alone. ICU mortality rates were not significantly different: 6% with high-flow nasal oxygen and NIV and 9% with high-flow nasal oxygen alone (difference, -2.4% [95% CI, -6.7% to 1.7%]; P = .25). Conclusions and Relevance: In mechanically ventilated patients at high risk of extubation failure, the use of high-flow nasal oxygen with NIV immediately after extubation significantly decreased the risk of reintubation compared with high-flow nasal oxygen alone. Trial Registration: ClinicalTrials.gov Identifier: NCT03121482.

Noninvasive Ventilation of Patients with Acute Respiratory Distress Syndrome. Insights from the LUNG SAFE Study.

RATIONALE: 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. OBJECTIVES: To determine whether, during NIV, the categorization of ARDS severity based on the PaO2/FiO2 Berlin criteria is useful. METHODS: 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 PaO2/FiO2 ratio in classifying patients receiving NIV, and the impact of NIV on outcome. MEASUREMENTS AND MAIN RESULTS: 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 PaO2/FiO2 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 PaO2/FiO2 lower than 150 mm Hg. CONCLUSIONS: 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 PaO2/FiO2 lower than 150 mm Hg. Clinical trial registered with www.clinicaltrials.gov (NCT 02010073).

Hospital outcomes and long-term survival after referral to a specialized weaning unit.

BACKGROUND.: Prolonged invasive mechanical ventilation (IMV) is a frequent challenge, and an increasing number of patients are transferred from intensive care units to long-term acute care hospitals or specialized weaning units. There are few published data for discharge home rates, use of noninvasive ventilation (NIV), or long-term survival. METHODS.: A case-note and database review was conducted of patients admitted to a UK national specialized weaning unit for weaning from IMV between 1992 and 2012. Patients were grouped into diagnostic categories according to the predominant cause of weaning failure. Weaning outcomes and long-term survival were assessed according to diagnostic group and mode of ventilation on discharge. RESULTS.: Four hundred and fifty-eight patients were transferred for weaning from IMV. Four hundred and seventeen (91%) survived to hospital discharge, of whom at least 343 (82%) were ultimately discharged to their own home. Three hundred and thirty (72%) weaned from IMV, of whom 142 weaned from all ventilation and 188 weaned to nocturnal NIV. Weaning success was highest for patients with chronic obstructive pulmonary disease and chest wall disorders. Median survival from unit discharge was 25 months (interquartile range 5-74), with the longest survival seen for patients discharged with nocturnal NIV [37 (12-81) months]. CONCLUSIONS.: These results confirm successful weaning outcomes for patients transferred to a specialized weaning and long-term ventilation service. In contrast to other service models, most patients achieved discharge to their own home.

Mortality in acute non-invasive ventilation.

A prospective study of non-invasive ventilation at The Prince Charles Hospital outside of the intensive care unit from March 2015 to March 2016 was performed. Overall 69 patients were included. Acute hypercapnic respiratory failure was the most common indication (n = 59; 85%). 49 (71%) had multifactorial respiratory failure. 15 (22%) patients died. Premorbid inability to perform self-care (P = 0.001) and the combination of mean pH < 7.25 and mean PaCO2 ≥ 75 mmHg within 2 h of NIV initiation (P = 0.037) were significantly associated with mortality. There was a non-significant association between older age and mortality.

Long-Term Survival Rate in Patients With Acute Respiratory Failure Treated With Noninvasive Ventilation in Ordinary Wards.

OBJECTIVE: Noninvasive ventilation is a life-saving technique increasingly used to treat acute respiratory failure. Noninvasive ventilation has been applied mostly in ICUs, but several reasons brought to an increasing application of noninvasive ventilation in ordinary wards. Few articles evaluated the outcomes of patients receiving noninvasive ventilation including long-term follow-up. The aim of the present study was to assess 1-year survival rate of patients treated with noninvasive ventilation outside the ICU for acute respiratory failure of heterogeneous causes and to identify the predictors of long-term mortality. DESIGN: Prospective, observational, pragmatic study. SETTING: Ordinary wards of a teaching hospital. PATIENTS: Consecutive patients treated with noninvasive ventilation for acute respiratory failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two-hundred and twenty-patients were enrolled. Mortality rates at 30-day, 90-days, and 1-year follow-up were 20%, 26%, and 34%. When excluding patients with "do-not-resuscitate" status, mortality rates were 13%, 19%, and 28%. The multivariate analyses identified solid cancer, pneumonia in hematologic patients, and do-not-resuscitate status as independent predictors of mortality with postoperative acute respiratory failure associated with improved survival. The same predictors were confirmed when excluding do-not-resuscitate patients from the analyses. CONCLUSIONS: Noninvasive ventilation applied in ordinary wards was effective, with long-term outcomes not different from those reported for ICU settings. Solid cancer, pneumonia in hematologic malignancies, and do-not-resuscitate status predicted mortality, whereas patients with postoperative acute respiratory failure had the best survival rate. Additional studies are required to evaluate noninvasive ventilation efficacy in the wards compared with ICU.

Effect of Noninvasive Ventilation on Tracheal Reintubation Among Patients With Hypoxemic Respiratory Failure Following Abdominal Surgery: A Randomized Clinical Trial.

IMPORTANCE: It has not been established whether noninvasive ventilation (NIV) reduces the need for invasive mechanical ventilation in patients who develop hypoxemic acute respiratory failure after abdominal surgery. OBJECTIVE: To evaluate whether noninvasive ventilation improves outcomes among patients developing hypoxemic acute respiratory failure after abdominal surgery. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized, parallel-group clinical trial conducted between May 2013 and September 2014 in 20 French intensive care units among 293 patients who had undergone abdominal surgery and developed hypoxemic respiratory failure (partial oxygen pressure <60 mm Hg or oxygen saturation [SpO2] ≤90% when breathing room air or <80 mm Hg when breathing 15 L/min of oxygen, plus either [1] a respiratory rate above 30/min or [2] clinical signs suggestive of intense respiratory muscle work and/or labored breathing) if it occurred within 7 days after surgical procedure. INTERVENTIONS: Patients were randomly assigned to receive standard oxygen therapy (up to 15 L/min to maintain SpO2 of 94% or higher) (n = 145) or NIV delivered via facial mask (inspiratory pressure support level, 5-15 cm H2O; positive end-expiratory pressure, 5-10 cm H2O; fraction of inspired oxygen titrated to maintain SpO2 ≥94%) (n = 148). MAIN OUTCOMES AND MEASURES: The primary outcome was tracheal reintubation for any cause within 7 days of randomization. Secondary outcomes were gas exchange, invasive ventilation-free days at day 30, health care-associated infections, and 90-day mortality. RESULTS: Among the 293 patients (mean age, 63.4 [SD, 13.8] years; n=224 men) included in the intention-to-treat analysis, reintubation occurred in 49 of 148 (33.1%) in the NIV group and in 66 of 145 (45.5%) in the standard oxygen therapy group within+ 7 days after randomization (absolute difference, -12.4%; 95% CI, -23.5% to -1.3%; P = .03). Noninvasive ventilation was associated with significantly more invasive ventilation-free days compared with standard oxygen therapy (25.4 vs 23.2 days; absolute difference, -2.2 days; 95% CI, -0.1 to 4.6 days; P = .04), while fewer patients developed health care-associated infections (43/137 [31.4%] vs 63/128 [49.2%]; absolute difference, -17.8%; 95% CI, -30.2% to -5.4%; P = .003). At 90 days, 22 of 148 patients (14.9%) in the NIV group and 31 of 144 (21.5%) in the standard oxygen therapy group had died (absolute difference, -6.5%; 95% CI, -16.0% to 3.0%; P = .15). There were no significant differences in gas exchange. CONCLUSIONS AND RELEVANCE: Among patients with hypoxemic respiratory failure following abdominal surgery, use of NIV compared with standard oxygen therapy reduced the risk of tracheal reintubation within 7 days. These findings support use of NIV in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01971892.

Is non-invasive ventilation safe in acute severe asthma?

BACKGROUND AND OBJECTIVE: The effect of non-invasive ventilation (NIV) in acute severe asthma is unclear and there are concerns regarding its safety. METHODS: We undertook a 5-year case-control review of mortality and morbidity associated with NIV use in acute severe asthma and compared this with asthma requiring invasive mechanical ventilation (IMV) and a control group with less severe asthma without ventilatory support. RESULTS: Eight hundred seventy-three patients had acute severe asthma of whom 30 were treated with NIV, 17 with IMV and 90 served as controls. The mean duration of NIV was 9.5 ± 7.3 h with inspiratory positive airway pressure and expiratory positive airway pressure of 11.9 ± 1.4 and 5.8 ± 1.2 cmH2 O respectively. Mortality was zero in the NIV and control groups, compared with 41% in the IMV group. None of the NIV or control groups required escalation to invasive ventilation. There were no instances of haemodynamic compromise in the NIV or control groups. Length of hospital stay was 121 ± 96 h in the NIV group and similar to the severe IMV group (136 ± 99 h, P > 0.05) and significantly longer than the control group (42 ± 40 h, P < 0.05). CONCLUSIONS: NIV can be safely used in acute severe asthma although further work is needed to delineate the precise patient selection process.

Effect of Noninvasive Ventilation vs Oxygen Therapy on Mortality Among Immunocompromised Patients With Acute Respiratory Failure: A Randomized Clinical Trial.

IMPORTANCE: Noninvasive ventilation has been recommended to decrease mortality among immunocompromised patients with hypoxemic acute respiratory failure. However, its effectiveness for this indication remains unclear. OBJECTIVE: To determine whether early noninvasive ventilation improved survival in immunocompromised patients with nonhypercapnic acute hypoxemic respiratory failure. DESIGN, SETTING, AND PARTICIPANTS: Multicenter randomized trial conducted among 374 critically ill immunocompromised patients, of whom 317 (84.7%) were receiving treatment for hematologic malignancies or solid tumors, at 28 intensive care units (ICUs) in France and Belgium between August 12, 2013, and January 2, 2015. INTERVENTIONS: Patients were randomly assigned to early noninvasive ventilation (n = 191) or oxygen therapy alone (n = 183). MAIN OUTCOMES AND MEASURES: The primary outcome was day-28 mortality. Secondary outcomes were intubation, Sequential Organ Failure Assessment score on day 3, ICU-acquired infections, duration of mechanical ventilation, and ICU length of stay. RESULTS: At randomization, median oxygen flow was 9 L/min (interquartile range, 5-15) in the noninvasive ventilation group and 9 L/min (interquartile range, 6-15) in the oxygen group. All patients in the noninvasive ventilation group received the first noninvasive ventilation session immediately after randomization. On day 28 after randomization, 46 deaths (24.1%) had occurred in the noninvasive ventilation group vs 50 (27.3%) in the oxygen group (absolute difference, -3.2 [95% CI, -12.1 to 5.6]; P = .47). Oxygenation failure occurred in 155 patients overall (41.4%), 73 (38.2%) in the noninvasive ventilation group and 82 (44.8%) in the oxygen group (absolute difference, -6.6 [95% CI, -16.6 to 3.4]; P = .20). There were no significant differences in ICU-acquired infections, duration of mechanical ventilation, or lengths of ICU or hospital stays. CONCLUSIONS AND RELEVANCE: Among immunocompromised patients admitted to the ICU with hypoxemic acute respiratory failure, early noninvasive ventilation compared with oxygen therapy alone did not reduce 28-day mortality. However, study power was limited. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01915719.

The use of non-invasive ventilation in very old patients with hypercapnic acute respiratory failure because of COPD exacerbation.

AIMS: We prospectively enrolled 207 patients (121 were 75 or older and 86 younger than 75) who were admitted to three Respiratory Monitoring Units. The primary outcomes were intubation and mortality rates; the secondary outcomes were changes in arterial blood gases analysis, non-invasive ventilation (NIV) duration and length of hospital stay. RESULTS: Hospital mortality was similar in the two groups, as were intubation rates. The proportion who died in the very old patient group was 19.8% (24/121) vs. 10.4% (9/86) in the younger group. Intubation rate was 10.7% (13/121) in the very old patient group and 11.6% (10/86) in the younger group. The presence of comorbidities, the severity of illness (SAPS II), the level of consciousness, NIV failure (intubation), absolute value of pH prior to NIV, as well as the changes in pH and paCO2 and PaO2 /FiO2 after 2 h of NIV, were the variables associated with higher mortality. Very old patients had significantly higher NIV duration than younger patients (69.0 ± 47.0 vs. 57.0 ± 27.0 h) (p ≤ 0.03) and hospital stays (11.6 ± 3.8 vs. 8.4 ± 1.4) (p ≤ 0.02). CONCLUSIONS: The use of NIV in very old patients was effective in many cases. Endotracheal intubation after NIV failure was not efficacious in either group.

[Current concepts of augmented spontaneous breathing: new modes of effort-adapted weaning]. / Aktuelle Konzepte der unterstützten Spontanatmung: Neue Wege zum differenzierten Weaning.

The use of augmented spontaneous breathing is an important component in a bundle concept of weaning from mechanical ventilation as it was demonstrated that controlled ventilation with diaphragmatic underuse induces rapid muscle atrophy and impairs successful weaning. On the other hand spontaneous breathing is often associated with disturbed patient-ventilator interaction resulting in asynchrony (e.g. ineffective triggering, early termination of inspiration and overflow or underflow). It was shown that asynchrony can impair gas exchange, increase work of breathing and enhance deleterious aspects of mechanical ventilation. Concepts of assisted breathing, such as proportional assist ventilation (PAV), adaptive support ventilation (ASV) and neurally adjusted ventilatory support (NAVA), which are intended to increase effort-adapted spontaneous breathing by an electronic or physiological closed loop feedback system with the patient's work of breathing were developed more than 20 years ago and are currently experiencing a renaissance. It was shown in some smaller clinical investigations that these newer modes are able to improve patient-ventilator interaction, to reduce the burden on respiratory muscles and to increase ventilation comfort. Although large randomized controlled studies are lacking, effort-adapted modes of augmented breathing will become a routine part in the management of weaning from mechanical ventilation.

Clinical outcomes of patients requiring ventilatory support in Brazilian intensive care units: a multicenter, prospective, cohort study.

INTRODUCTION: Contemporary information on mechanical ventilation (MV) use in emerging countries is limited. Moreover, most epidemiological studies on ventilatory support were carried out before significant developments, such as lung protective ventilation or broader application of non-invasive ventilation (NIV). We aimed to evaluate the clinical characteristics, outcomes and risk factors for hospital mortality and failure of NIV in patients requiring ventilatory support in Brazilian intensive care units (ICU). METHODS: In a multicenter, prospective, cohort study, a total of 773 adult patients admitted to 45 ICUs over a two-month period requiring invasive ventilation or NIV for more than 24 hours were evaluated. Causes of ventilatory support, prior chronic health status and physiological data were assessed. Multivariate analysis was used to identifiy variables associated with hospital mortality and NIV failure. RESULTS: Invasive MV and NIV were used as initial ventilatory support in 622 (80%) and 151 (20%) patients. Failure with subsequent intubation occurred in 54% of NIV patients. The main reasons for ventilatory support were pneumonia (27%), neurologic disorders (19%) and non-pulmonary sepsis (12%). ICU and hospital mortality rates were 34% and 42%. Using the Berlin definition, acute respiratory distress syndrome (ARDS) was diagnosed in 31% of the patients with a hospital mortality of 52%. In the multivariate analysis, age (odds ratio (OR), 1.03; 95% confidence interval (CI), 1.01 to 1.03), comorbidities (OR, 2.30; 95% CI, 1.28 to 3.17), associated organ failures (OR, 1.12; 95% CI, 1.05 to 1.20), moderate (OR, 1.92; 95% CI, 1.10 to 3.35) to severe ARDS (OR, 2.12; 95% CI, 1.01 to 4.41), cumulative fluid balance over the first 72 h of ICU (OR, 2.44; 95% CI, 1.39 to 4.28), higher lactate (OR, 1.78; 95% CI, 1.27 to 2.50), invasive MV (OR, 2.67; 95% CI, 1.32 to 5.39) and NIV failure (OR, 3.95; 95% CI, 1.74 to 8.99) were independently associated with hospital mortality. The predictors of NIV failure were the severity of associated organ dysfunctions (OR, 1.20; 95% CI, 1.05 to 1.34), ARDS (OR, 2.31; 95% CI, 1.10 to 4.82) and positive fluid balance (OR, 2.09; 95% CI, 1.02 to 4.30). CONCLUSIONS: Current mortality of ventilated patients in Brazil is elevated. Implementation of judicious fluid therapy and a watchful use and monitoring of NIV patients are potential targets to improve outcomes in this setting. TRIAL REGISTRATION: ClinicalTrials.gov NCT01268410.