Clinical Significance of Upper Airway Virus Detection in Critically Ill Hematology Patients.

RATIONALE: Noninvasive diagnostic multiplex molecular tests may enable the early identification and treatment of viral infections in critically ill immunocompromised patients. OBJECTIVES: To assess the association between viral detection in nasopharyngeal swabs and ICU mortality in critically ill hematology patients. METHODS: This was a post hoc analysis of a prospective cohort of critically ill hematology patients admitted to 17 ICUs. Nasal swabs sampled and frozen at ICU admission were tested using a multiplex PCR assay. Predictors of ICU mortality and assay positivity were identified. MEASUREMENTS AND MAIN RESULTS: Of the 747 patients (447 with acute respiratory failure [ARF]), 21.3% had a virus detected (56.4% rhinovirus/enterovirus and 30.7% influenza/parainfluenza/respiratory syncytial viruses). Overall ICU and hospital mortality rates were 26% and 37%, respectively. Assay positivity was associated with lymphoproliferative disorders, hematopoietic stem cell transplantation, treatment with steroids or other immunosuppressants, ARF (25.5% vs. 16.3%; P = 0.004), and death in the ICU (28.9% vs. 19.3%; P = 0.008). The association with ICU mortality was significant for all viruses and was strongest for influenza/parainfluenza/respiratory syncytial viruses. In patients with ARF, detection of any respiratory virus was independently associated with ICU mortality (odds ratio, 2.07; 95% confidence interval, 1.22-3.50). CONCLUSIONS: Respiratory virus detection in the upper airway by multiplex PCR assay is common in critically ill hematology patients. In patients with ARF, respiratory virus detection was independently associated with ICU mortality. Multiplex PCR assay may prove helpful for the risk stratification of hematology patients with ARF. Studies to understand whether respiratory tract viruses play a causal role in outcomes are warranted.

A Multivariable Prediction Model for Pneumocystis jirovecii Pneumonia in Hematology Patients with Acute Respiratory Failure.

RATIONALE: The incidence of Pneumocystis jirovecii pneumonia (PjP) is rising. Longer time to treatment is associated with higher mortality. OBJECTIVES: To develop a multivariable risk prediction model for PjP diagnosis. METHODS: In a prospective multicenter cohort of ICU patients with hematological malignancies and acute respiratory failure, factors associated with documented PjP were identified. The risk prediction model was tested in an independent prospective multicenter cohort. We assessed discrimination (by areas under the receiver operating characteristic curves [AUCs]) and goodness of fit (by Hosmer-Lemeshow statistics). Model performance was assessed using 30 sets of imputed data sets. MEASUREMENTS AND MAIN RESULTS: Among the 1,330 patients, 134 of 1,092 (12.3%; 95% confidence interval [CI], 10.4-14.4%) had proven PjP in the derivation cohort, as did 15 of 238 (6.3%, 95% CI, 3.6-10.2%) in the validation cohort. The model included age, lymphoproliferative disease, anti-Pneumocystis prophylaxis, the number of days between respiratory symptom onset and ICU admission, shock, chest radiograph pattern, and pleural effusion. The median (interquartile range) score was 3.5 (1.5-5.0) (range, -3.5 to 8.5) in the derivation cohort and 1.0 (0-2.0) (range, -3.5 to 6.0) in the validation cohort. The best threshold was defined on the validation sample as 3, allowing us to reach 86.7% sensitivity and 67.7% specificity for PjP, with a negative predictive value of 97.9% in the case of 10% prevalence. The score had good calibration (goodness of fit, -0.75) and discrimination in the derivation cohort (mean AUC, 0.80; 95% CI, 0.76-0.84) and validation cohort (mean AUC, 0.83; 95% CI, 0.72-0.93). CONCLUSIONS: The PjP score for hematology patients with acute respiratory failure can be computed at admission, based on readily available variables. Potential clinical benefits of using this score deserve assessment.

Endothelial Cell-Specific Molecule-1 in Critically Ill Patients With Hematologic Malignancy.

OBJECTIVES: To assess whether serum concentration of endothelial cell-specific molecule-1 (Endocan) at ICU admission is associated with the use of ICU resources and outcomes in critically ill hematology patients. DESIGN: Prospective multicenter cohort study. SETTING: Seventeen ICUs in France and Belgium. PATIENTS: Seven hundred forty-four consecutive critically ill hematology patients; 72 critically ill septic patients without hematologic malignancy; 276 healthy subjects. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Median total endocan concentrations were 4.46 (2.7-7.8) ng/mL. Endocan concentrations were higher in patients who had received chemotherapy before ICU admission (4.7 [2.8-8.1] ng/mL vs. 3.7 [2.5-6.3] ng/mL [p = 0.002]). In patients with acute respiratory failure, endocan levels were increased in patients with drug-induced pulmonary toxicity compared with other etiologies (p = 0.038). Total endocan levels higher than 4.46 ng/mL were associated with a higher cumulative probability of renal replacement therapy requirement (p = 0.006), a higher requirement of mechanical ventilation (p = 0.01) and a higher requirement of vasopressors throughout ICU stay (p < 0.0001). By multivariate analysis, total endocan levels at admission were independently associated with ICU mortality (odds ratios, 1.39; 95% CI, 1.06-1.83; p = 0.018). The predictive value of endocan peptide fragments of 14 kDa in terms of mortality and life-sustaining therapies requirement was inferior to that of total endocan. Endocan levels were higher in critically ill hematology patients compared with healthy subjects (p < 0.0001) but lower than endocan values in critically ill septic patients without hematologic malignancy (p = 0.005) CONCLUSIONS:: Serum concentrations of endocan at admission are associated with the use of ICU resources and mortality in critically ill hematology patients. Studies to risk-stratify patients in the emergency department or in the hematology wards based on endocan concentrations to identify those likely to benefit from early ICU management are warranted.

Postoperative outcomes of frequent exacerbator patients with Chronic Obstructive Pulmonary Disease after resection of Non-Small Cells Lung Cancer.

Chronic obstructive pulmonary disease (COPD) is a risk factor of post-operative complications after lung cancer resection. The influence of the "frequent exacerbator (FE)" phenotype (at least three exacerbations per year) is unknown. Postoperative outcomes of frequent exacerbators (POFE) was a prospective observational study of patients with COPD undergoing lung resection for cancer. The inclusion criteria were: age >40 years, FEV1/FVC <70%, non-urgent surgery for lung cancer, filled out self-questionnaires. The primary outcome was assessment of postoperative pulmonary complications (purulent tracheobronchitis, atelectasis, pneumonia, acute respiratory failure, need of mechanical ventilation). Secondary outcomes encompassed the prevalence of the FE phenotype and its impact on postoperative complications. A total of 682 patients were screened from June 2014 to October 2015. 93 patients with COPD were included, 21 (23%) were FE. Postoperative tracheobronchitis, atelectasis pneumonia or respiratory failure (isolated or associated) occurred in 47%, 48%, 26%, and 38% of patients, respectively. Non-invasive and invasive mechanical ventilation were necessary in 4 (4%) and 22 (23%) patients. Purulent tracheobronchitis, pneumonia and hypercapnia (this last requiring noninvasive mechanical ventilation) were more frequent in FE (p = 0.043, 0.042, 0.015); however the number of patients wth at least one respiratory complication was not different (76% vs. 52%, p = 0.056). In all patients, multivariate logistic regression identified two independent factors of postoperative respiratory complications: male sex (OR 10.6 [95% CI 1.97-57.6], p = 0.006) and the FE phenotype (OR 6.33 [1.04-38.39], p = 0.045). Occurrence of postoperative complications in patients with COPD is high. FE phenotype is an independent risk factor.

Urgent Chemotherapy for Life-Threatening Complications Related to Solid Neoplasms.

OBJECTIVES: Solid neoplasms can be directly responsible for organ failures at the time of diagnosis or relapse. The management of such specific complications relies on urgent chemotherapy and eventual instrumental or surgical procedures, combined with advanced life support. We conducted a multicenter study to address the prognosis of this condition. DESIGN: A multicenter retrospective (2001-2015) chart review. SETTING: Medical and respiratory ICUs. PATIENTS: Adult patients who received urgent chemotherapy in the ICU for organ failure related to solid neoplasms were included. The modalities of chemotherapy, requirements of adjuvant instrumental or surgical procedures, and organ supports were collected. Endpoints were short- and long-term survival rates. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred thirty-six patients were included. Lung cancer was the most common malignancy distributed into small cell lung cancer (n = 57) and non-small cell lung cancer (n = 33). The main reason for ICU admission was acute respiratory failure in 111 patients (81.6%), of whom 89 required invasive mechanical ventilation. Compression and tissue infiltration by tumor cells were the leading mechanisms resulting in organ involvement in 78 (57.4%) and 47 (34.6%) patients. The overall in-ICU, in-hospital, 6-month, and 1-year mortality rates were 37%, 58%, 74%, and 88%, respectively. Small cell lung cancer was identified as an independent predictor of hospital survival. However, this gain in survival was not sustained since the 1-year survival rates of small cell lung cancer, non-small cell lung cancer, and non-lung cancer patients all dropped below 20%. CONCLUSIONS: Urgent chemotherapy along with aggressive management of organ failures in the ICU can be lifesaving in very selected cancer patients, most especially with small cell lung cancer, although the long-term survival is hardly sustainable.

High-Flow Nasal Cannula Oxygenation in Immunocompromised Patients With Acute Hypoxemic Respiratory Failure: A Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique Study.

OBJECTIVE: In immunocompromised patients with acute respiratory failure, invasive mechanical ventilation remains associated with high mortality. Choosing the adequate oxygenation strategy is of the utmost importance in that setting. High-flow nasal oxygen has recently shown survival benefits in unselected patients with acute respiratory failure. The objective was to assess outcomes of immunocompromised patients with hypoxemic acute respiratory failure treated with high-flow nasal oxygen. DESIGN: We performed a post hoc analysis of a randomized controlled trial of noninvasive ventilation in critically ill immunocompromised patients with hypoxemic acute respiratory failure. SETTING: Twenty-nine ICUs in France and Belgium. PATIENTS: Critically ill immunocompromised patients with hypoxemic acute respiratory failure. INTERVENTION: A propensity score-based approach was used to assess the impact of high-flow nasal oxygen compared with standard oxygen on day 28 mortality. MEASUREMENTS AND MAIN RESULTS: Among 374 patients included in the study, 353 met inclusion criteria. Underlying disease included mostly malignancies (n = 296; 84%). Acute respiratory failure etiologies were mostly pneumonia (n = 157; 44.4%) or opportunistic infection (n = 76; 21.5%). Noninvasive ventilation was administered to 180 patients (51%). Invasive mechanical ventilation was ultimately needed in 142 patients (40.2%). Day 28 mortality was 22.6% (80 deaths). Throughout the ICU stay, 127 patients (36%) received high-flow nasal oxygen whereas 226 patients received standard oxygen. Ninety patients in each group (high-flow nasal oxygen or standard oxygen) were matched according to the propensity score, including 91 of 180 (51%) who received noninvasive ventilation. High-flow nasal oxygen was neither associated with a lower intubation rate (hazard ratio, 0.42; 95% CI, 0.11-1.61; p = 0.2) nor day 28 mortality (hazard ratio, 0.80; 95% CI, 0.45-1.42; p = 0.45). CONCLUSIONS: In immunocompromised patients with hypoxemic acute respiratory failure, high-flow nasal oxygen when compared with standard oxygen did not reduce intubation or survival rates. However, these results could be due to low statistical power or unknown confounders associated with the subgroup analysis. A randomized trial is needed.

Severe varicella-zoster virus pneumonia: a multicenter cohort study.

BACKGROUND: Pneumonia is a dreaded complication of varicella-zoster virus (VZV) infection in adults; however, the data are limited. Our objective was to investigate the clinical features, management, and outcomes of critically ill patients with VZV-related community-acquired pneumonia (VZV-CAP). METHODS: This was an observational study of patients with VZV-CAP admitted to 29 intensive care units (ICUs) from January 1996 to January 2015. RESULTS: One hundred and two patients with VZV-CAP were included. Patients were young (age 39 years (interquartile range 32-51)) and 53 (52%) were immunocompromised. Time since respiratory symptom onset was 2 (1-3) days. There was a seasonal distribution of the disease, with more cases during spring and winter time. All but four patients presented with typical skin rash on ICU admission. Half the patients received mechanical ventilation within 1 (1-2) day following ICU admission (the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) = 150 (80-284), 80% with acute respiratory distress syndrome (ARDS)). Sequential Organ Failure Assessment (SOFA) score on day 1 (odds ratio (OR) 1.90 (1.33-2.70); p < 0.001), oxygen flow at ICU admission (OR 1.25 (1.08-1.45); p = 0.004), and early bacterial co-infection (OR 14.94 (2.00-111.8); p = 0.009) were independently associated with the need for mechanical ventilation. Duration of mechanical ventilation was 14 (7-21) days. ICU and hospital mortality rates were 17% and 24%, respectively. All patients were treated with aciclovir and 10 received adjunctive therapy with steroids. Compared to 60 matched steroid-free controls, patients treated with steroids had a longer mechanical ventilation duration, ICU length of stay, and a similar hospital mortality, but experienced more ICU-acquired infections. CONCLUSIONS: Severe VZV-CAP is responsible for an acute pulmonary involvement associated with a significant morbidity and mortality. Steroid therapy did not influence mortality, but increased the risk of superinfection.

Effect of Acetazolamide vs Placebo on Duration of Invasive Mechanical Ventilation Among Patients With Chronic Obstructive Pulmonary Disease: A Randomized Clinical Trial.

IMPORTANCE: Acetazolamide has been used for decades as a respiratory stimulant for patients with chronic obstructive pulmonary disease (COPD) and metabolic alkalosis, but no large randomized placebo-controlled trial is available to confirm this approach. OBJECTIVE: To determine whether acetazolamide reduces mechanical ventilation duration in critically ill patients with COPD and metabolic alkalosis. DESIGN, SETTING, AND PARTICIPANTS: The DIABOLO study, a randomized, double-blind, multicenter trial, was conducted from October 2011 through July 2014 in 15 intensive care units (ICUs) in France. A total of 382 patients with COPD who were expected to receive mechanical ventilation for more 24 hours were randomized to the acetazolamide or placebo group and 380 were included in an intention-to treat analysis. INTERVENTIONS: Acetazolamide (500-1000 mg, twice daily) vs placebo administered intravenously in cases of pure or mixed metabolic alkalosis, initiated within 48 hours of ICU admission and continued during the ICU stay for a maximum of 28 days. MAIN OUTCOMES AND MEASURES: The primary outcome was the duration of invasive mechanical ventilation via endotracheal intubation or tracheotomy. Secondary outcomes included changes in arterial blood gas and respiratory parameters, weaning duration, adverse events, use of noninvasive ventilation after extubation, successful weaning, the duration of ICU stay, and in-ICU mortality. RESULTS: Among 382 randomized patients, 380 (mean age, 69 years; 272 men [71.6%]; 379 [99.7%] with endotracheal intubation) completed the study. For the acetazolamide group (n = 187), compared with the placebo group (n = 193), no significant between-group differences were found for median duration of mechanical ventilation (-16.0 hours; 95% CI, -36.5 to 4.0 hours; P = .17), duration of weaning off mechanical ventilation (-0.9 hours; 95% CI, -4.3 to 1.3 hours; P = .36), daily changes of minute-ventilation (-0.0 L/min; 95% CI, -0.2 to 0.2 L/min; P = .72), or partial carbon-dioxide pressure in arterial blood (-0.3 mm Hg; 95% CI, -0.8 to 0.2 mm Hg; P = .25), although daily changes of serum bicarbonate (between-group difference, -0.8 mEq/L; 95% CI, -1.2 to -0.5 mEq/L; P < .001) and number of days with metabolic alkalosis (between-group difference, -1; 95% CI, -2 to -1 days; P < .001) decreased significantly more in the acetazolamide group. Other secondary outcomes also did not differ significantly between groups. CONCLUSIONS AND RELEVANCE: Among patients with COPD receiving invasive mechanical ventilation, the use of acetazolamide, compared with placebo, did not result in a statistically significant reduction in the duration of invasive mechanical ventilation. However, the magnitude of the difference was clinically important, and it is possible that the study was underpowered to establish statistical significance. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01627639.

Epidemiology of spontaneous pneumothorax: gender-related differences.

BACKGROUND: Epidemiology of spontaneous pneumothorax has been scantily studied. We aimed to assess the incidence of spontaneous pneumothorax and describe patients' characteristics with respect to age, sex, seasonal occurrence, primary or secondary character, surgical management and rehospitalisations on a large-scale database. METHODS: Data from all patients aged ≥14 years and hospitalised with a diagnosis of non-traumatic pneumothorax in France from 2008 to 2011 were retrieved from the National Hospitalisation Database. RESULTS: There were 59 637 hospital stays corresponding to 42 595 patients. Twenty-eight per cent of patients were rehospitalised at least once during the 4-year period. Annual rate of pneumothorax could be estimated at 22.7 (95% CI 22.4 to 23.0) cases for 100 000 habitants. The women to men ratio was 1:3.3. Mean age was significantly higher in women than in men (41±19 vs 37±19 years, p<0.0001). No seasonal variation was observed. A surgical procedure was performed in 14 352 hospital stays (24%). In the group of patients aged <30 years, there was no statistical difference between men and women with regard to type of pneumothorax (primary or secondary), type of hospitalisation unit (surgery vs medicine), treatment modality (surgery or not), intensive care unit (ICU) admission and hospital stay duration. Rehospitalisation was more frequent in women than in men (56% vs 52%, p<0.0001). In the 30-49 years age group, surgery and rehospitalisation were more frequent in women than in men (each, p<0.001). In the 50-64 years age group, surgical procedures and rehospitalisations were more frequent in men than in women (p=0.002 and p<0.0001, respectively). CONCLUSIONS: Sex and age are determinant factors in the course of spontaneous pneumothorax.

Acute kidney injury in critically ill patients with haematological malignancies: results of a multicentre cohort study from the Groupe de Recherche en Réanimation Respiratoire en Onco-Hématologie.

BACKGROUND: Cancer patients are at high risk for acute kidney injury (AKI), which is associated with high morbidity and mortality. We sought to appraise the incidence, risk factors, and outcome of AKI in a large multicentre cohort study of critically ill patients with haematological malignancies. METHODS: We used a retrospective analysis of a prospectively collected database. The study was carried out in 17 university or university-affiliated centres in France and Belgium between 2010 and 2012. AKI was defined according to the Acute Kidney Injury Network (AKIN) definition. RESULTS: Of the 1011 patients admitted into the intensive care unit (ICU) during the study period, 1009 were included in this study. According to the AKIN definition, 671 patients (66.5%) developed an AKI during their ICU stay, of which 258 patients (38.4%) were AKI stage 1, 75 patients (11.2%) AKI stage 2 and 338 patients (50.4%) AKI stage 3. After adjustment for confounders, main adverse risk factors of AKI were older age, severity [non-renal Sequential Organ Failure Assessment (SOFA)], history of hypertension, tumour lysis syndrome, exposure to nephrotoxic agents and myeloma. Hospital mortality was 44.3% in patients with AKI and 25.4% in patients without AKI (P < 0.0001). After adjustment for confounders, AKI was independently associated with hospital mortality [OR 1.65 (95% CI 1.19-2.29)]. Overall, 271 patients required renal replacement therapy (RRT), of whom 57.2% died during their hospital stay as compared with 31.2% (P < 0.0001) in those not requiring RRT. CONCLUSION: Two-thirds of critically ill patients with haematological malignancies developed AKI. Hospital mortality in this population of patients developing AKI or requiring RRT is close to that in general ICU population.

Strongyloides stercoralis hyperinfection syndrome: a case series and a review of the literature.

BACKGROUND: Strongyloides stercoralis may lead to overwhelming infestation [Strongyloides hyperinfection syndrome (SHS)]. We aimed at describing a case series of patients admitted in intensive care unit (ICU) with SHS and report a literature review of such cases. PATIENTS AND METHODS: Retrospective multicenter study of 11 patients admitted to the ICU of tertiary hospitals with SHS between 2000 and 2013. Literature review with Pubmed retrieved 122 cases. Logistic regression analysis was performed to identify predictive factors of ICU mortality and shock occurrence. RESULTS: 133 patients [median age 53 (39, 64), 72.2 % males] were included. Underlying immunosuppression was present in 127 patients, mostly long-term corticosteroid treatment in 111 (83.5 %) patients. Fever (80.8 %), respiratory (88.6 %), and gastrointestinal (71.2 %) symptoms were common clinical manifestations. Shock occurred in 75 (57.3 %) patients and mechanical ventilation was required in 89 (67.9 %) patients. Hypereosinophilia and a concomitant bacterial infection were observed in 34 (34.3 %) and 51 (38.4 %) patients, respectively. The in-ICU mortality rate was 60.3 %. Predictive factors of ICU mortality were shock occurrence [Odds ratio (OR) 18.1, 95 % confidence interval (95 % CI) 3.03-107.6, p < 0.01] and mechanical ventilation (OR 28.1, 95 % CI 3.6-217, p < 0.01). Hypereosinophilia (OR 0.21, 95 % CI 0.06-0.7, p = 0.01) and a concomitant bacterial infection (OR 4.68, 95 % CI 1.3-16.8, p = 0.02) were independent predictors of shock occurrence. CONCLUSION: SHS remains associated with a poor outcome, especially when associated with shock and mechanical ventilation. Deterioration to shock is often related to concomitant bacterial infection. The poor outcome of established SHS pleads for a large application of antiparasitic primary prophylaxis in at-risk patients.

The effects of a 2-h trial of high-flow oxygen by nasal cannula versus Venturi mask in immunocompromised patients with hypoxemic acute respiratory failure: a multicenter randomized trial.

INTRODUCTION: In immunocompromised patients, acute respiratory failure (ARF) is associated with high mortality, particularly when invasive mechanical ventilation (IMV) is required. In patients with severe hypoxemia, high-flow nasal oxygen (HFNO) therapy has been used as an alternative to delivery of oxygen via a Venturi mask. Our objective in the present study was to compare HFNO and Venturi mask oxygen in immunocompromised patients with ARF. METHODS: We conducted a multicenter, parallel-group randomized controlled trial in four intensive care units. Inclusion criteria were hypoxemic ARF and immunosuppression, defined as at least one of the following: solid or hematological malignancy, steroid or other immunosuppressant drug therapy, and HIV infection. Exclusion criteria were hypercapnia, previous IMV, and immediate need for IMV or noninvasive ventilation (NIV). Patients were randomized to 2 h of HFNO or Venturi mask oxygen. RESULTS: The primary endpoint was a need for IMV or NIV during the 2-h oxygen therapy period. Secondary endpoints were comfort, dyspnea, and thirst, as assessed hourly using a 0-10 visual analogue scale. We randomized 100 consecutive patients, including 84 with malignancies, to HFNO (n = 52) or Venturi mask oxygen (n = 48). During the 2-h study treatment period, 12 patients required IMV or NIV, and we found no significant difference between the two groups (15 % with HFNO and 8 % with the Venturi mask, P = 0.36). None of the secondary endpoints differed significantly between the two groups. CONCLUSIONS: In immunocompromised patients with hypoxemic ARF, a 2-h trial with HFNO improved neither mechanical ventilatory assistance nor patient comfort compared with oxygen delivered via a Venturi mask. However, the study was underpowered because of the low event rate and the one-sided hypothesis. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02424773 . Registered 20 April 2015.

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.

Influence of ICU case-volume on the management and hospital outcomes of acute exacerbations of chronic obstructive pulmonary disease*.

OBJECTIVES: To study the relationship between case-volume and the use of noninvasive ventilation during acute exacerbations of chronic obstructive pulmonary disease in ICUs. DESIGN: A 13-year multicenter retrospective cohort study of prospectively collected data. SETTING: Medical ICUs. PATIENTS: From 1998 to 2010, patients with acute exacerbations of chronic obstructive pulmonary disease were identified through a regional database. INTERVENTIONS: The characteristics of hospitalization (including the type of mechanical ventilation) and demographic data of the patients were analyzed. ICUs were categorized into tertiles of the running mean annual volume of admissions. A logistic model performed a conditional multivariate analysis of prognostic factors after matching on a propensity score of being admitted to a high-volume unit and on the year of admission. MEASUREMENTS AND MAIN RESULTS: Fourteen thousand four hundred forty acute exacerbations of chronic obstructive pulmonary disease were identified. The Simplified Acute Physiology Score II and ICU mortality increased during the study period (36 to 41 and 12% to 14%, respectively). The proportion of patients receiving any mechanical ventilation support also increased during the study period (from 64% to 86%), with a marked increase in the use of noninvasive ventilation (from 18% to 49%) and a decrease in the use of invasive ventilation (from 34% to 19%). Participating units were distributed into low-volume (< 25 patients per year), medium-volume (26-47 patients per year), and high-volume (> 47 patients per year) tertiles. There was a significant association between case-volume and 1) the proportion of patients receiving noninvasive ventilation (highest vs lowest case-volume tertiles: odds ratio, 1.43 [95% CI, 1.23-1.66]) and 2) lower mortality. CONCLUSIONS: Between 1998 and 2010, severity and mortality of acute exacerbations of chronic obstructive pulmonary disease admitted to Collège des Utilisateurs de Données en Réanimation ICUs increased. There was an increasing use of noninvasive ventilation and a decreasing use of invasive ventilation. Use of noninvasive ventilation was related to case-volume, suggesting that increasing experience favors the use of noninvasive ventilation and was associated with a strong trend toward decreased mortality.

Noninvasive ventilation and weaning in patients with chronic hypercapnic respiratory failure: a randomized multicenter trial.

RATIONALE: The use of noninvasive ventilation (NIV) as an early weaning/extubation technique from mechanical ventilation remains controversial. OBJECTIVES: To investigate NIV effectiveness as an early weaning/extubation technique in difficult-to-wean patients with chronic hypercapnic respiratory failure (CHRF). METHODS: In 13 intensive care units, 208 patients with CHRF intubated for acute respiratory failure (ARF) who failed a first spontaneous breathing trial were randomly assigned to three groups: conventional invasive weaning group (n = 69), extubation followed by standard oxygen therapy (n = 70), or NIV (n = 69). NIV was permitted as rescue therapy for both non-NIV groups if postextubation ARF occurred. Primary endpoint was reintubation within 7 days after extubation. Secondary endpoints were: occurrence of postextubation ARF or death within 7 days after extubation, use of rescue postextubation NIV, weaning time, and patient outcomes. MEASUREMENTS AND MAIN RESULTS: Reintubation rates were 30, 37, and 32% for invasive weaning, oxygen-therapy, and NIV groups, respectively (P = 0.654). Weaning failure rates, including postextubation ARF, were 54, 71, and 33%, respectively (P < 0.001). Rescue NIV success rates for invasive and oxygen-therapy groups were 45 and 58%, respectively (P = 0.386). By design, intubation duration was 1.5 days longer for the invasive group than in the two others. Apart from a longer weaning time in NIV than in invasive group (2.5 vs. 1.5 d; P = 0.033), no significant outcome difference was observed between groups. CONCLUSIONS: No difference was found in the reintubation rate between the three weaning strategies. NIV decreases the intubation duration and may improve the weaning results in difficult-to-wean patients with CHRF by reducing the risk of postextubation ARF. The benefit of rescue NIV in these patients deserves confirmation.

Diagnostic strategy for hematology and oncology patients with acute respiratory failure: randomized controlled trial.

RATIONALE: Respiratory events are common in hematology and oncology patients and manifest as hypoxemic acute respiratory failure (ARF) in up to half the cases. Identifying the cause of ARF is crucial. Fiberoptic bronchoscopy with bronchoalveolar lavage (FO-BAL) is an invasive test that may cause respiratory deterioration. Recent noninvasive diagnostic tests may have modified the risk/benefit ratio of FO-BAL. OBJECTIVES: To determine whether FO-BAL in cancer patients with ARF increased the need for intubation and whether noninvasive testing alone was not inferior to noninvasive testing plus FO-BAL. METHODS: We performed a multicenter randomized controlled trial with sample size calculations for both end points. Patients with cancer and ARF of unknown cause who were not receiving ventilatory support at intensive care unit admission were randomized to early FO-BAL plus noninvasive tests (n = 113) or noninvasive tests only (n = 106). The primary end point was the number of patients needing intubation and mechanical ventilation. The major secondary end point was the number of patients with no identified cause of ARF. MEASUREMENTS AND MAIN RESULTS: The need for mechanical ventilation was not significantly greater in the FO-BAL group than in the noninvasive group (35.4 vs. 38.7%; P = 0.62). The proportion of patients with no diagnosis was not smaller in the noninvasive group (21.7 vs. 20.4%; difference, -1.3% [-10.4 to 7.7]). CONCLUSIONS: FO-BAL performed in the intensive care unit did not significantly increase intubation requirements in critically ill cancer patients with ARF. Noninvasive testing alone was not inferior to noninvasive testing plus FO-BAL for identifying the cause of ARF. Clinical trial registered with www.clinicaltrials.gov (NCT00248443).

[Acute exacerbation of chronic obstructive pulmonary disease]. / Exacerbations aiguës de BPCO.

Exacerbation of COPD is a common problem, which causes a considerable burden to the patient and the healthcare system. Management of exacerbations is broadly based on clinical features and severity. Initial clinical evaluation is crucial to define the patients requiring hospital admissions and those that could be managed as outpatients. Medical treatment should follow updated recommendations including rest, inhaled or nebulized short-acting bronchodilators (B2-agonists and anticholinergic agents), and in most severe patients steroids unless there are contraindications and antibiotics. Hospitalized patients should receive titrated oxygen therapy, and DVT prevention. Unless contra indicated, noninvasive ventilation should be the first line ventilatory support for COPD with acute hypercapnic respiratory failure. Future exacerbations should be avoided by respiratory specialists' management.

Chronic obstructive pulmonary disease exacerbations in emergency departments: predictors of outcome.

PURPOSE OF REVIEW: Exacerbations have a major short-term and long-term impact on patients with chronic obstructive pulmonary disease (COPD). Risk stratification of patients presenting to the emergency department for an exacerbation of COPD is of utmost importance to help in deciding patients' orientation and treatment and in improving outcomes. RECENT FINDINGS: Studies on predictors of outcomes of COPD exacerbations are markedly heterogeneous in terms of assessed variables, outcomes of interest and timeframe (short-term vs. long-term outcomes). Age, severity of underlying disease, clinical signs of immediate severity, and comorbidities are among the most frequently identified prognostic factors of in-hospital outcome. In the most severe patients, ICU scores such as the Acute Physiology and Chronic Health Evaluation II (APACHE II) also have a prognostic value. Several biomarkers have also been studied, but their additional value for risk stratification is not clarified. SUMMARY: Scores predicting the risk of poor outcome could prove useful in the management of COPD exacerbations. Some have been suggested but remain to be further validated before their use can be generalized.

Clinical features of H1N1 2009 infection in critically ill immunocompromised patients.

Seasonal influenza virus has been described as an emerging and severe pathogen in immunocompromised hosts. Since the beginning of the 2009 influenza A novel H1N1 pandemic, several series have described the clinical course of the disease in various populations. We report the clinical course of H1N1 2009 infection in 10 immunocompromised patients. Half of the patients received long-term steroid therapy. Disease was characterized by a clinical picture similar to that of non-immunocompromised patients but with prolonged course and higher mortality.