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Introduction: Although largely used, the place of oxygen therapy and its devices in patients with acute hypoxemic respiratory failure (ARF) deserves to be clarified. The French Intensive Care Society (Société de Réanimation de Langue Française, SRLF) and the French Emergency Medicine Society (Société Française de Médecine d'Urgence, SFMU) organized a consensus conference on oxygen therapy in ARF (excluding acute cardiogenic pulmonary oedema and hypercapnic exacerbation of chronic obstructive diseases) in December 2023. Methods: A committee without any conflict of interest (CoI) with the subject defined 7 generic questions and drew up a list of sub questions according to the population, intervention, comparison and outcomes (PICO) model. An independent work group reviewed the literature using predefined keywords. The quality of the data was assessed using the GRADE methodology. Fifteen experts in the field from both societies proposed their own answers in a public session and answered questions from the jury (a panel of 16 critical-care and emergency medicine physicians, nurses and physiotherapists without any CoI) and the public. The jury then met alone for 48 h to write its recommendations. Results: The jury provided 22 statements answering 11 questions: in patients with ARF (1) What are the criteria for initiating oxygen therapy? (2) What are the targets of oxygen saturation? (3) What is the role of blood gas analysis? (4) When should an arterial catheter be inserted? (5) Should standard oxygen therapy, high-flow nasal cannula oxygen therapy (HFNC) or continuous positive airway pressure (CPAP) be preferred? (6) What are the indications for non-invasive ventilation (NIV)? (7) What are the indications for invasive mechanical ventilation? (8) Should awake prone position be used? (9) What is the role of physiotherapy? (10) Which criteria necessarily lead to ICU admission? (11) Which oxygenation device should be preferred for patients for whom a do-not-intubate decision has been made? Conclusion: These recommendations should optimize the use of oxygen during ARF. [ABSTRACT FROM AUTHOR]

Background: Evidence for the management of pregnant women with acute hypoxaemic respiratory failure (AHRF) is currently lacking. The likelihood of avoiding intubation and the risks of continuing the pregnancy under invasive ventilation remain undetermined. We report the management and outcome of pregnant women with pneumonia related to SARS-CoV-2 admitted to the ICU of tertiary maternity hospitals of the Paris area. Methods: We studied a retrospective cohort of pregnant women admitted to 15 ICUs with AHRF related to SARS-CoV-2 defined by the need for O2 ≥ 6 L/min, high-flow nasal oxygen (HFNO), non-invasive or invasive ventilation. Trajectories were assessed to determine the need for intubation and the possibility of continuing the pregnancy on invasive ventilation. Results: One hundred and seven pregnant women, 34 (IQR: 30–38) years old, at a gestational age of 27 (IQR: 25–30) weeks were included. Obesity was present in 37/107. Intubation was required in 47/107 (44%). Intubation rate according to respiratory support was 14/19 (74%) for standard O2, 17/36 (47%) for non-invasive ventilation and 16/52 (31%) for HFNO. Factors significantly associated with intubation were pulmonary co-infection: adjusted OR: 3.38 (95% CI 1.31–9.21), HFNO: 0.11 (0.02–0.41) and non-invasive ventilation: 0.20 (0.04–0.80). Forty-six (43%) women were delivered during ICU stay, 39/46 (85%) for maternal pulmonary worsening, 41/46 (89%) at a preterm stage. Fourteen non-intubated women were delivered under regional anaesthesia; 9/14 ultimately required emergency intubation. Four different trajectories were identified: 19 women were delivered within 2 days after ICU admission while not intubated (12 required prolonged intubation), 23 women were delivered within 2 days after intubation, in 11 intubated women pregnancy was continued allowing delivery after ICU discharge in 8/11, 54 women were never intubated (53 were delivered after discharge). Timing of delivery after intubation was mainly dictated by gestational age. One maternal death and one foetal death were recorded. Conclusion: In pregnant women with AHRF related to SARS-CoV-2, HFNO and non-invasive mechanical ventilation were associated with a reduced rate of intubation, while pulmonary co-infection was associated with an increased rate. Pregnancy was continued on invasive mechanical ventilation in one-third of intubated women. Study registration retrospectively registered in ClinicalTrials (NCT05193526). [ABSTRACT FROM AUTHOR]

Background: In the last decade, Ibrutinib has become the standard of care in the treatment of several lymphoproliferative diseases such as chronic lymphocytic leukemia (CLL) and several non-Hodgkin lymphoma. Beyond Bruton tyrosine kinase inhibition, Ibrutinib shows broad immunomodulatory effects that may promote the occurrence of infectious complications, including opportunistic infections. The infectious burden has been shown to vary by disease status, neutropenia, and prior therapy but data focusing on severe infections requiring intensive care unit (ICU) admission remain scarce. We sought to investigate features and outcomes of severe infections in a multicenter cohort of 69 patients receiving ibrutinib admitted to 10 French intensive care units (ICU) from 1 January 2015 to 31 December 2020. Results: Median time from ibrutinib initiation was 6.6 [3–18] months. Invasive fungal infections (IFI) accounted for 19% (n = 13/69) of severe infections, including 9 (69%; n = 9/13) invasive aspergillosis, 3 (23%; n = 3/13) Pneumocystis pneumonia, and 1 (8%; n = 1/13) cryptococcosis. Most common organ injury was acute respiratory failure (ARF) (71%; n = 49/69) and 41% (n = 28/69) of patients required mechanical ventilation. Twenty (29%; n = 20/69) patients died in the ICU while day-90 mortality reached 55% (n = 35/64). In comparison with survivors, decedents displayed more severe organ dysfunctions (SOFA 7 [5–11] vs. 4 [3–7], p = 0.004) and were more likely to undergo mechanical ventilation (68% vs. 31%, p = 0.010). Sixty-three ibrutinib-treated patients were matched based on age and underlying malignancy with 63 controls receiving conventional chemotherapy from an historic cohort. Despite a higher median number of prior chemotherapy lines (2 [1–2] vs. 0 [0–2]; p < 0.001) and higher rates of fungal [21% vs. 8%, p = 0.001] and viral [17% vs. 5%, p = 0.027] infections in patients receiving ibrutinib, ICU (27% vs. 38%, p = 0.254) and day-90 mortality (52% vs. 48%, p = 0.785) were similar between the two groups. Conclusion: In ibrutinib-treated patients, severe infections requiring ICU admission were associated with a dismal prognosis, mostly impacted by initial organ failures. Opportunistic agents should be systematically screened by ICU clinicians in this immunocompromised population. [ABSTRACT FROM AUTHOR]

Background We evaluated the safety and efficacy of XAV-19, an antispike glyco-humanized swine polyclonal neutralizing antibody in patients hospitalized with severe coronavirus disease 2019 (COVID-19). Methods This phase 2b clinical trial enrolled adult patients from 34 hospitals in France. Eligible patients had a confirmed diagnosis of severe acute respiratory syndrome coronavirus 2 within 14 days of onset of symptoms that required hospitalization for low-flow oxygen therapy (<6 L/min of oxygen). Patients were randomly assigned to receive a single intravenous infusion of 2 mg/kg of XAV-19 or placebo. The primary end point was the occurrence of death or severe respiratory failure between baseline and day 15. Results Between January 12, 2021, and April 16, 2021, 398 patients were enrolled in the study and randomly assigned to XAV-19 or placebo. The modified intention-to-treat population comprised 388 participants who received full perfusion of XAV-19 (199 patients) or placebo (189 patients). The mean (SD) age was 59.8 (12.4) years, 249 (64.2%) individuals were men, and the median time (interquartile range) from symptom onset to enrollment was 9 (7–10) days. There was no statistically significant decrease in the cumulative incidence of death or severe respiratory failure through day 15 in the XAV-19 group vs the placebo group (53/199 [26.6%] vs 48/189 [25.4%]; adjusted risk difference, 0.6%; 95% CI, −6% to 7%; hazard ratio, 1.03; 95% CI, 0.64–1.66; P =.90). In the safety population, adverse events were reported in 75.4% of 199 patients in the XAV-19 group and in 76.3% of 190 patients in the placebo group through D29. Conclusions Among patients hospitalized with COVID-19 requiring low-flow oxygen therapy, treatment with a single intravenous dose of XAV-19, compared with placebo, did not show a significant difference in terms of disease progression at day 15. [ABSTRACT FROM AUTHOR]

Introduction: Monitoring changes in symptoms over time during long-term nocturnal home non-invasive ventilation (NIV) using patient-reported outcome measures is crucial. This study aimed to identify factors associated with changes in the S3-NIV total score, its two domains ("respiratory symptoms" and "sleep and NIV-related side effects") and individual item responses., Methods: We conducted a retrospective, longitudinal data analysis of a cohort of adults with chronic respiratory failure treated with NIV. Data were obtained from a French homecare provider. Multivariate linear and multinomial ordinal mixed effect models were used to identify factors associated with changes in S3-NIV scores over time., Results: Median follow-up was 2 years for 2135 participants. Each participant completed a median of five S3-NIV questionnaires; totaling 11,359 analyzed questionnaires. Type of respiratory condition, sex, age and time since NIV initiation were associated with change in S3-NIV score over time. NIV adherence was not associated with total S3-NIV score but high adherence was associated with more severe respiratory symptoms and an improvement in sleep and NIV-related side effects during the follow-up. Intensity of pressure support was associated with a lower total S3-NIV score and more side effects. Face masks and supplemental oxygen were associated with a lower S3-NIV total score., Conclusion: Changes in S3-NIV scores over time are associated with the individual's characteristics and NIV settings. Analysis of the two domains and individual items of the S3-NIV could increase understanding of the difficulties experienced by people on NIV., (Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Data regarding immediate-release (IR)-tramadol exposures in children remain sparse. We aimed to investigate the incidence of IR-tramadol exposures in ≤6-year-old children, to describe the characteristics and resulting outcome of ingestions involving IR-tramadol alone, and to estimate a clinically relevant toxic dose in this population. Retrospective analysis of IR-tramadol exposures in ≤6-year-old children, collected by the French Poison Control Centers (PCCs) in 2003–2019. The incidence was estimated using IR-tramadol prescription data from the Health Improvement Network database (the French version of THIN). The Poison severity score (PSS) was used to grade severity. We found 1260 IR-tramadol exposures in ≤6-year-old children. The number of cases per 100,000 IR-tramadol-treated patients increased over time (p <.0001). One hundred forty-five cases involving IR-tramadol alone were analyzed. The median age was 3.0 years (IQR: 1.9, 4.0), the M/F ratio was 1.5 and the median dose was 5.0 mg/kg (IQR 3.3–11.1). Half of the children (49.7%) remained asymptomatic (PSS0) while 29.6% and 14.5% developed minor (PSS1) or moderate-to-severe (PSS2–PSS3) neurological symptoms, respectively. Twelve children developed respiratory depression. No seizures and no fatality were reported. All symptomatic children recovered within 24 h. The ingested IR-tramadol dose was positively correlated with the PSS (p <.0001). Using a receiver operating characteristic (ROC) curve approach (area under the curve, 0.92; p <.001), ingestion of ≥7.4 mg/kg IR-tramadol was appropriate to recommend hospital referral (sensitivity, 100% [95% confidence interval (CI), 85–100]; specificity, 73% [95% CI, 64–80]; predictive positive value, 39% [95% CI, 35–57]; negative predictive value, 100% [95% CI, 96–100]). Children who ingested <7.4 mg/kg IR-tramadol developed no (n = 68) or minor (n = 22) neurological symptoms. Despite increasing tramadol prescriptions in adults during the study period in France, oral exposure to IR-tramadol in ≤6-year-old children was rare but possibly responsible for severe toxicity. Children with no underlying disease and concomitant medication ingesting <7.4 mg/kg IR-tramadol alone could be observed at home. However, given the observed variability in the onset of seizures after tramadol ingestion, which can occur at ingested tramadol doses below 7.4 mg and even at therapeutic doses, parents or guardians should be specifically warned about the risk of seizures. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is a rare genetic multisystemic disease, the manifestations of which are due to mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein and can lead to respiratory insufficiency and premature death. CFTR modulators, which were developed in the past decade, partially restore CFTR protein function. Their clinical efficacy has been demonstrated in phase 3 clinical trials, particularly in terms of lung function and pulmonary exacerbations, nutritional status, and quality of life in people with gating mutations (ivacaftor), homozygous for the F508del mutation (lumacaftor/ivacaftor and tezacaftor/ivacaftor), and in those with at least one F508del mutation (elexacaftor/tezacaftor/ivacaftor). However, many questions remain regarding their long-term safety and effectiveness, particularly in patients with advanced lung disease, liver disease, renal insufficiency, or problematic bacterial colonization. The impact of CFTR modulators on other important outcomes such as concurrent treatments, lung transplantation, chest imaging, or pregnancies also warrants further investigation. The French CF Reference Network includes 47 CF centers that contribute patient data to the comprehensive French CF Registry and have conducted nationwide real-world studies on CFTR modulators. This review seeks to summarize the results of these real-world studies and examine their findings against those of randomized control trials. [ABSTRACT FROM AUTHOR]

Copyright of Annales Françaises de Médecine d'Urgence is the property of John Libbey Eurotext Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BACKGROUND: High-flow nasal cannula (HFNC) is increasingly used for the management of respiratory failure. Settings include FIO2, total gas flow, and temperature target. Resulting absolute humidity (AH) at the nasal cannula may affect clinical tolerance, and optimal settings with respect to hygrometry remain poorly documented. METHODS: A bench study was designed to assess AH delivered by 4 HFNC devices (Optiflow, Airvo 2, Precision Flow, and Hydrate) according to flow, ambient temperature, and other available settings. Clinical tolerance of different levels of hygrometry (20, 30, and 40 mg H2O/L) was evaluated in 15 healthy volunteers. RESULTS: With FIO2 set at 1.0, normal ambient temperature, and settings made accordingly to the manufacturers' recommendations, mean ± SD AH was 42.2 ± 3.1, 39.5 ± 1.8, 35.7 ± 2.0, and 32.9 ± 2.7 mg H2O/L for the Airvo 2, Optiflow, Hydrate, and Precision Flow, respectively, (P < .001). AH dropped from -3.5 to -10.7 mg H2O/L (P <. 001) with high ambient temperature, except for the Precision Flow. Increasing flow did not significantly affect AH except for the Precision Flow (from 36.4 ± 1.6 to 29.8 ± 0.2 mg H2O/L at 10 and 40 L/min, respectively, [P < .001]). The lowest AH was encountered with the Optiflow set with noninvasive ventilation (NIV) mode, without compensation algorithm, and at high ambient temperature (14.2 ± 1.5 mg H2O/L). In studied subjects, AH significantly affected breathing comfort, reduced from 7.0 ± 1.0 to 3.0 ± 2.0 at 40 and 20 mg H2O/L, respectively, (P < .001). Comfort was similar at 30 and 40 mg H2O/L. CONCLUSIONS: When used according to manufacturer's recommendations and at normal ambient temperature, all the HFNC devices evaluated achieved satisfactory hygrometric output with respect to breathing comfort evaluated in healthy subjects (≥ 30 mg H2O/L). Substantial differences exist between devices, and optimal knowledge of their working principles is required as inappropriate usage may dramatically alter efficacy and clinical tolerance. [ABSTRACT FROM AUTHOR]

Background: Sleep had never been assessed immediately after extubation in patients still in the ICU. However, sleep deprivation may alter respiratory function and may promote respiratory failure. We hypothesized that sleep alterations after extubation could be associated with an increased risk of post-extubation respiratory failure and reintubation. We conducted a prospective observational cohort study performed at the medical ICU of the university hospital of Poitiers in France. Patients at high-risk of extubation failure (> 65 years, with any underlying cardiac or lung disease, or intubated > 7 days) were included. Patients intubated less than 24 h, with central nervous or psychiatric disorders, continuous sedation, neuroleptic medication, or uncooperative were excluded. Sleep was assessed by complete polysomnography just following extubation including the night. The main objective was to compare sleep between patients who developed post-extubation respiratory failure or required reintubation and the others. Results: Over a 3-year period, 52 patients had complete polysomnography among whom 12 (23%) developed post-extubation respiratory failure and 8 (15%) required reintubation. Among them, 10 (19%) had atypical sleep, 15 (29%) had no deep sleep, and 33 (63%) had no rapid eye movement (REM) sleep. Total sleep time was 3.2 h in median [interquartile range, 2.0–4.4] in patients who developed post-extubation respiratory failure vs. 2.0 [1.1–3.8] in those who were successfully extubated (p = 0.34). Total sleep time, and durations of deep and REM sleep stages did not differ between patients who required reintubation and the others. Reintubation rates were 21% (7/33) in patients with no REM sleep and 5% (1/19) in patients with REM sleep (difference, − 16% [95% CI − 33% to 6%]; p = 0.23). Conclusions: Sleep assessment by polysomnography after extubation showed a dramatically low total, deep and REM sleep time. Sleep did not differ between patients who were successfully extubated and those who developed post-extubation respiratory failure or required reintubation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Patients with neuromuscular disorders (NMD) share the risk of acute respiratory failure (ARF) leading to ICU admissions. Noninvasive ventilation (NIV) is often proposed as an alternative to invasive ventilation. This study describes clinical features, ventilation management, and outcomes of subjects with NMD admitted to ICU and managed for ARF. METHODS: We performed a multicenter retrospective study in 7 adult ICUs in the Auvergne-Rhone-Alpes area in France involving subjects with NMD admitted to the ICU for ARF. The primary end point was ICU mortality. Secondary end points were NIV failure, weaning from invasive ventilation, and long-term mortality. We hypothesized a poorer outcome in the case of bulbar musculature involvement. RESULTS: A total of 242 subjects were included; 142 subjects had nonhereditary NMD (58.7%), and 100 had hereditary NMD (41.3%). Eleven subjects had home ventilation through a tracheostomy. While 112 were intubated at admission, 119 initially underwent NIV. NIV was successful in avoiding orotracheal intubation in 78 subjects (65.5%). ICU mortality was 13.6%. Factors associated with ICU mortality were nonhereditary NMD and requirement for invasive ventilation. The involvement of bulbar musculature in ARF and hereditary NMD were associated with NIV failure. After a median follow-up of 1.2 y, 53 of 209 subjects had died. CONCLUSIONS: The ICU mortality of NMD subjects with ARF was low, with no impact of bulbar muscles involvement. NIV was proposed for approximately half of the subjects, and it was more effective when ARF was not attributed to bulbar musculature involvement. The long-term outcome was good. [ABSTRACT FROM AUTHOR]

Copyright of Population & Sociétés is the property of Institut National d'Etudes Demographiques and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background In patients with severe coronavirus disease 2019 (COVID-19), data are scarce and conflicting regarding whether chronic use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) influences disease outcomes. In patients with severe COVID-19, we assessed the association between chronic ACEI/ARB use and the occurrence of kidney, lung, heart, and liver dysfunctions and the severity of the inflammatory reaction as evaluated by biomarkers kinetics, and their association with disease outcomes. Methods We performed a retrospective longitudinal cohort study on consecutive patients with newly diagnosed severe COVID-19. Independent predictors were assessed through receiver operating characteristic analysis, time-series analysis, logistic regression analysis, and multilevel modeling for repeated measures. Results On the 149 patients included in the study 30% (44/149) were treated with ACEI/ARB. ACEI/ARB use was independently associated with the following biochemical variations: phosphorus >40 mg/L (odds ratio [OR], 3.35, 95% confidence interval [CI], 1.83–6.14), creatinine >10.1 mg/L (OR, 3.22, 2.28–4.54), and urea nitrogen (UN) >0.52 g/L (OR, 2.65, 95% CI, 1.89–3.73). ACEI/ARB use was independently associated with acute kidney injury stage ≥1 (OR, 3.28, 95% CI, 2.17–4.94). The daily dose of ACEI/ARB was independently associated with altered kidney markers with an increased risk of +25 to +31% per each 10 mg increment of lisinopril-dose equivalent. In multivariable multilevel modeling, UN >0.52 g/L was independently associated with the risk of acute respiratory failure (OR, 3.54, 95% CI, 1.05–11.96). Conclusions Patients chronically treated with ACEI/ARB who have severe COVID-19 are at increased risk of acute kidney injury. In these patients, the increase in UN associated with ACEI/ARB use could predict the development of acute respiratory failure. [ABSTRACT FROM AUTHOR]

Introduction: Although home non-invasive ventilation (NIV) is increasingly used to manage patients with chronic ventilatory failure, there are limited data on the long-term outcome of these patients. Our aim was to report on home NIV populations and the long-term outcome from two European centres.Methods: Cohort analysis including all patients established on home NIV from two European centres between 2008 and 2014.Results: Home NIV was initiated in 1746 patients to treat chronic ventilatory failure caused by (1) obesity hypoventilation syndrome±obstructive sleep apnoea (OHS±OSA) (29.5%); (2) neuromuscular disease (NMD) (22.7%); and (3) obstructive airway diseases (OAD) (19.1%). Overall cohort median survival following NIV initiation was 6.6 years. Median survival varied by underlying aetiology of respiratory failure: rapidly progressive NMD 1.1 years, OAD 2.7 years, OHS±OSA >7 years and slowly progressive NMD >7 years. Multivariate analysis demonstrated higher mortality in patients with rapidly progressive NMD (HR 4.78, 95% CI 3.38 to 6.75), COPD (HR 2.25, 95% CI 1.64 to 3.10), age >60 years at initiation of home NIV (HR 2.41, 95% CI 1.92 to 3.02) and NIV initiation following an acute admission (HR 1.38, 95% CI 1.13 to 1.68). Factors associated with lower mortality were NIV adherence >4 hours per day (HR 0.64, 95% CI 0.51 to 0.79), OSA (HR 0.51, 95% CI 0.31 to 0.84) and female gender (HR 0.79, 95% CI 0.65 to 0.96).Conclusion: The mortality rate following initiation of home NIV is high but varies significantly according to underlying aetiology of respiratory failure. In patients with chronic respiratory failure, initiation of home NIV following an acute admission and low levels of NIV adherence are poor prognostic features and may be amenable to intervention. [ABSTRACT FROM AUTHOR]

BACKGROUND: Noninvasive ventilation (NIV) is the recommended ventilatory support for acute cardiogenic pulmonary edema (CPE) associated with acute respiratory failure or hypercapnia. High-flow nasal cannula (HFNC) has emerged as an alternative to NIV in acute hypoxemic respiratory failure. We aimed to assess the efficacy of HFNC on early changes in P... and respiratory parameters in patients in the emergency department with acute hypercapnic CPE and to compare it to NIV. METHODS: We conducted a prospective observational study in consecutive emergency department patients with acute hypercapnic CPE. Subjects received either HFNC or NIV, according to the attending emergency physician's expertise in HFNC. The primary outcome was change in P... after treatment for 1 h. Secondary outcomes were change in pH, breathing frequency, signs of work of breathing, and comparisons to NIV. RESULTS: Twenty-seven subjects with a discharge diagnosis of hypercapnic CPE were analyzed. Subjects had a median age of 87 y (interquartile range [IQR] 78-93); 37% were male. Twelve (44%) received HFNC, and 15 (56%) received NIV. Median of changes in P... from baseline to after 1 h of treatment were 7 mm Hg (IQR 4-11, P = .002) for HFNC and 3 mm Hg (IQR 1-8, P = .02) for NIV, with no between-group difference. pH, breathing frequency and signs of work of breathing also improved after both HFNC and NIV. CONCLUSION: This preliminary study suggests that HFNC treatment for 1 h improves P... and respiratory parameters in subjects with hypercapnic acute CPE in a manner that is comparable to NIV. Further studies are needed to assess HFNC as a possible alternative to NIV in early management of acute hypercapnic respiratory failure of cardiogenic origin. (ClinicalTrials.gov registration NCT03883555.). [ABSTRACT FROM AUTHOR]

BACKGROUND: The use of noninvasive ventilation (NIV) in the emergency setting to reverse hypercapnic coma in frail patients with end-stage chronic respiratory failure and do-not-intubate orders remains a questionable issue given the poor outcome of this vulnerable population. We aimed to answer this issue by assessing not only subjects' outcome with NIV but also subjects' point of view regarding NIV for this indication. METHODS: A prospective observational case-control study was conducted in 3 French tertiary care hospitals during a 2-y period. Forty-three individuals who were comatose (with pH < 7.25 and PaCO2 > 100 mm Hg at admission) were compared with 43 subjects who were not comatose and who were treated with NIV for acute hypercapnic respiratory failure. NIV was applied by using the same protocol in both groups. They all had a do-notintubate order and were considered vulnerable individuals with end-stage chronic respiratory failure according to well-validated scores. RESULTS: NIV yielded similar outcomes in the 2 groups regarding in-hospital mortality (n = 12 [28%] vs n = 12 [28%] in the noncomatose controls, P > .99) and 6-month survival (n = 28 [65%] vs n = 22 [51%] in the noncomatose controls, P = .31). Despite poor quality of life scores (21.5 ± 10 vs 31 ± 6 in the awakened controls, P = .056) as assessed by using the VQ11 questionnaire 6 months to 1 y after hospital discharge, a large majority of the survivors (n = 23 [85%]) would be willing to receive NIV again if a new episode of acute hypercapnic respiratory failure occurs. CONCLUSIONS: In the frailest subjects with supposed end-stage chronic respiratory failure that justifies treatment limitation decisions, it is worth trying NIV when acute hypercapnic respiratory failure occurs, even in the case of extreme respiratory acidosis with hypercapnic coma at admission. [ABSTRACT FROM AUTHOR]

Few studies have assessed the impact of home ventilation in patients with myotonic dystrophy type 1 (DM1) and no specific recommendations are available. We assessed the survival associated with category of home ventilation adherence of patients with DM1 followed up at a home ventilation unit using a Cox proportional hazards model. 218 patients were included; those who refused or delayed their acceptance of non-invasive ventilation were at higher risk for severe events (invasive ventilation or death) (P=0.03). Risk of death was associated with orthopnoea (HR 2.37; 95% CI 1.17 to 4.80; P<0.02) and adherence category (100 to 90% vs >75%: HR 3.26; 95% CI 1.32 to 8.04; P<0.03). Failure to use home ventilation as prescribed may be associated with increased mortality in patients with DM1. [ABSTRACT FROM AUTHOR]

Around the tenth day after diagnosis,∼20% of patients with coronavirus disease 2019 (COVID-19)−associated pneumonia evolve to-ward severe oxygen dependence (stage 2b) and acute respiratory distress syndrome (stage 3) associated with systemic inflammation often termed a “cytokine storm.” Because interleukin-1 (IL-1) blocks the production of IL-6 and other proinflammatory cytokines, we treated COVID-19 patients early in the disease with the IL-1 receptor antagonist, anakinra. We retrospectively compared 22 patients from three different centers in France with stages 2b and 3 COVID-19−associated pneumonia presenting with acute severe respiratory failure and systemic inflammation who received either standard-of-care treatment alone (10 patients) or combined with intravenous anakinra (12 patients). Treatment started at 300 mg·d−1for 5 d, then tapered with lower dosing over 3 d. Both populations were comparable for age, comorbidities, clinical stage, and elevated biomarkers of systemic inflammation. All of the patients treated with anakinra improved clinically (P<0.01), with no deaths, significant decreases in oxygen requirements (P<0.05), and more days without invasive mechanical ventilation (P<0.06), compared with the control group. The effect of anakinra was rapid, as judged by significant decrease of fever and C-reactive protein at day 3. A mean total dose of1,950 mg was infused with no adverse side effects or bacterial infection. We conclude that early blockade of the IL-1 receptor is therapeutic in acute hyper inflammatory respiratory failure in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Background: Patients starting noninvasive ventilation (NIV) to treat acute respiratory failure are often unable to eat and therefore remain in the fasting state or receive nutritional support. Maintaining a good nutritional status has been reported to improve patient outcomes. In the present study, our primary objective was to describe the nutritional management of patients starting first-line NIV, and our secondary objectives were to assess potential associations between nutritional management and outcomes.Methods: Observational retrospective cohort study of a prospective database fed by 20 French intensive care units. Adult medical patients receiving NIV for more than 2 consecutive days were included and divided into four groups on the basis of nutritional support received during the first 2 days of NIV: no nutrition, enteral nutrition, parenteral nutrition only, and oral nutrition only.Results: Of the 16,594 patients admitted during the study period, 1075 met the inclusion criteria; of these, 622 (57.9%) received no nutrition, 28 (2.6%) received enteral nutrition, 74 (6.9%) received parenteral nutrition only, and 351 (32.7%) received oral nutrition only. After adjustment for confounders, enteral nutrition (vs. no nutrition) was associated with higher 28-day mortality (adjusted HR, 2.3; 95% CI, 1.2-4.4) and invasive mechanical ventilation needs (adjusted HR, 2.1; 95% CI, 1.1-4.2), as well as with fewer ventilator-free days by day 28 (adjusted relative risk, 0.7; 95% CI, 0.5-0.9).Conclusions: Nearly three-fifths of patients receiving NIV fasted for the first 2 days. Lack of feeding or underfeeding was not associated with mortality. The optimal route of nutrition for these patients needs to be investigated. [ABSTRACT FROM AUTHOR]

Background: Respective proportions of final etiologies are disparate in cohorts of cardiac arrest patients, depending on examined population and diagnostic algorithms. In particular, prevalence and characteristics of sudden unexplained death syndrome (SUDS) are debated. We aimed at describing etiologies in a large cohort of aborted out-of-hospital cardiac arrest (OHCA) patients, in order to assess prevalence and outcome of SUDS.Patients and Methods: We analyzed data from our prospective registry of successfully resuscitated OHCA patients admitted to a cardiac arrest centre between January 2002 and December 2014. The in-ICU diagnostic strategy included early coronary angiogram, brain and chest CT scan. This was completed by an extensive diagnostic strategy, encompassing biological and toxicological tests, repeated electrocardiograms and echocardiography, MRI and pharmacologic tests. Two independent investigators reviewed each final diagnosis. Baseline characteristics were compared between subgroups of patients. Three-month mortality was compared between subgroups using univariate Kaplan-Meier curves.Results: Over the study period, 1657 patients were admitted to our unit after an aborted OHCA. The event was attributed to a non-cardiac and a cardiac cause in 478 (32.0%) and 978 (65.5%) patients, respectively. The main cause of cardiac related OHCA was ischemic heart disease (76.7%) while primary electrical diseases accounted for only 2.5%. Sudden unexplained deaths (SUDS) were observed in 37 (2.5%) patients.Conclusion: We observed that ischemic heart disease was by far the most common cause of cardiac arrest, while primary electrical diseases were much less frequent. SUDS accounted for a very small proportion of patients who suffered an aborted OHCA. [ABSTRACT FROM AUTHOR]

BACKGROUND: Duchenne muscular dystrophy (DMD) is a sex-linked genetic disorder in which progressive impairment of skeletal muscle function eventually leads to severe respiratory failure requiring continuous noninvasive ventilation (NIV) at home. A current focus of debate is whether NIV may slow the decline in respiratory function or, on the contrary, worsen respiratory function when started early. Our objective here was to describe the effects of NIV on vital capacity (VC) and maximum respiratory pressures in DMD. METHODS: We analyzed retrospective data from 71 subjects with DMD, including VC, maximum static respiratory pressures, and sniff nasal inspiratory pressure before and after NIV initiation. The declines in these variables from the highest value to the most recent value were computed. RESULTS: Although respiratory function continued to deteriorate over time, NIV introduction was followed by significant slowing in the annual rates of decline in VC (from 4.28 to 1.36 percent predicted), maximum inspiratory pressure (from 2.77 to 1.48 cm H2O), and maximum expiratory pressure (from 2.00 to 1.00 cm H2O). NIV had no effect on sniff nasal inspiratory pressure. CONCLUSIONS: Introducing NIV in subjects with DMD was followed by slowing of the declines in VC and in maximum static inspiratory and expiratory pressures. [ABSTRACT FROM AUTHOR]

Background: Acquired hemophagocytic lymphohistiocytosis (HLH) is a life-threatening event that usually occurs as a complication of immunodeficiency. Lung involvement in HLH has received little attention. This article describes lung involvement in HLH and assesses whether it affects the prognosis.Methods: We retrospectively studied 219 patients with HLH admitted to a national reference center over a 14-year period, including 118 (54%) with lung involvement.Results: Dyspnea and cough were the most common onset symptoms. Radiographs revealed interstitial infiltrates with centrilobular nodules, ill-defined consolidation, or localized ground-glass opacities. Pleural effusions and mediastinal lymphadenopathies were found in approximately one-half of the patients. One or more causes of lung involvement were documented in 91 of 118 patients (77.1%) and included infection (n = 52), pulmonary edema (n = 34), and malignancies (n = 22 [mostly lymphoma]). HLH-specific treatment combined with treatment of the cause of lung involvement improved respiratory function in only 67 of the 188 patients (56.7%). Hospital mortality was higher in patients with lung involvement (52.5% vs 20%). Infection as the cause of lung involvement was the only determinant of death (56% vs 30%; P = .004).Conclusions: Lung involvement is common and of poor prognosis in patients with HLH. Studies should assess whether specific diagnostic and therapeutic strategies are warranted in patients with HLH and lung involvement. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BACKGROUND: The aim of this study was to evaluate the clinical efficacy of humidified oxygen via high-flow nasal cannula (HFNC) alternating with noninvasive ventilation (NIV) in acute hypoxemic respiratory failure (AHRF). METHODS: We performed a prospective observational study in a 12-bed ICU of a university hospital. All subjects with a PaO2 /FIO2 of ≤ 300 mm Hg with standard mask oxygen and a breathing frequency of > 30 breaths/min or signs of respiratory distress were included and treated with HFNC first and then NIV. Ventilatory parameters, blood gases, and tolerance were recorded during 2 consecutive sessions of NIV and HFNC. Outcome was assessed after continuation of this noninvasive strategy. RESULTS: Twenty-eight subjects with AHRF were studied, including 23 (82%) with ARDS. Compared with standard oxygen therapy, PaO2- significantly increased from 83 (68-97) mm Hg to 108 (83-140) mm Hg using HFNC and to 125 (97-200) mm Hg using NIV (P < .01), whereas breathing frequency significantly decreased. HFNC was significantly better tolerated than NIV, with a lower score on the visual analog scale. The non-intubated subjects received HFNC for 75 (27-127) h and NIV for 23 (8-31) h. Intubation was required in 10 of 28 subjects (36%), including 8 of 23 subjects with ARDS (35%). After HFNC initiation, a breathing frequency of ≥ 30 breaths/min was an early factor associated with intubation. CONCLUSIONS: HFNC was better tolerated than NIV and allowed for significant improvement in oxygenation and tachypnea compared with standard oxygen therapy in subjects with AHRF, a large majority of whom had ARDS. Thus, HFNC may be used between NIV sessions to avoid marked impairment of oxygenation. [ABSTRACT FROM AUTHOR]

BACKGROUND: We sought to identify risk factors for mechanical ventilation in patients with malignancies and acute respiratory failure (ARF). METHODS: We analyzed data from a previous randomized controlled trial in which nonintubated oncology and hematology subjects with ARF were randomized to early bronchoalveolar lavage or routine care in 16 ICUs in France. Consecutive patients with malignancies were admitted to the ICU for ARF in 2005 and 2006 with no intervention. RESULTS: During the study period, 219 patients were admitted to the ICU for ARF, and 8 patients were not included due to a nonintubation order. Data on the underlying disease, pulmonary involvement, and extrapulmonary organ dysfunctions were recorded at admission in the 211 remaining subjects. Ventilatory support included oxygen only (49 subjects), noninvasive ventilation (NIV) only (81 subjects), NIV followed by invasive mechanical ventilation (49 subjects), and first-line invasive mechanical ventilation (32 subjects). The 81 subjects who required invasive mechanical ventilation were compared with the 130 subjects who remained on oxygen or NIV. Factors associated with invasive mechanical ventilation by multivariate analysis were the oxygen flow required at ICU admission, the number of quadrants involved on chest x-ray, and hemodynamic dysfunction. Mortality rates for subjects who had NIV failure were 65.3% compared with 50% for subjects who were First-line intubated (P = .34). CONCLUSIONS: In cancer patients with ARF, hypoxemia, extent of pulmonary infiltration on chest x-ray, or hemodynamic dysfunction are risk factors for invasive mechanical ventilation. Mortality was not significantly different between NIV failure and first-line intubation. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine whether optoelectronic plethysmography accurately evaluated vital capacity (VC) in patients with respiratory muscle dysfunction of variable severity, including those with paradoxical abdominal movements. METHODS: In 20 subjects, VC was measured in the supine position using both spirometry and optoelectronic plethysmography (6 optoelectronic cameras and 52 reflective markers on the anterior chest wall). RESULTS: Spirometry VC (VC-Spiro) correlated positively with optoelectronic VC (VC-Opto) (r2 0.99, P < .001), and the regression line was very close to the identity line (VC-Opto [mL] -1.202 1.007 VC-Spiro [mL]). A Bland-Altman plot showed that the mean difference was 20 mL (95% CI -63 mL to 24 mL) and the limits of agreement were 163 mL (95% CI 106 mL to 231 mL) and -203 mL (95% CI -271 mL to -146 mL). The difference between the 2 values expressed as the percentage of the mean value was < 15% in all 20 subjects, < 10% in 17 (85%) subjects, and < 5% in 11 (55%) subjects. The difference, expressed as the percentage of the mean value, was unrelated to the contribution of abdominal motion to VC (r 0.02 and P .94), but was significantly related to body mass index (r 0.53, P .02). CONCLUSIONS: Optoelectronic plethysmography is accurate and suitable for VC measurement in patients with various degrees of respiratory failure, including those with paradoxical abdominal movements. This noninvasive method may be an attractive alternative for accurately measuring VC in the event of air leakage (through the mouth or tracheostomy) or when patients are unable to breathe with the dead space added by the spirometer. [ABSTRACT FROM AUTHOR]

Background: Acute exacerbation is a substantial cause of death in patients with idiopathic pulmonary fibrosis with poorly described prognostic factors. Objectives: To review the features associated with acute exacerbation of idiopathic pulmonary fibrosis and assess its prognostic factors. Methods: Thirty-seven occurrences of acute exacerbation of idiopathic pulmonary fibrosis were retrospectively reviewed in the medical records of 27 patients. Clinical presentation, radiographic studies, pulmonary function tests, laboratory data, treatment, and outcome were analyzed. Results: Acute exacerbation of idiopathic pulmonary fibrosis occurred more frequently between December and May (75.7%) than between June and November (24.3%) (p = 0.01). In-hospital mortality was 27% and median survival was 4.2 months (range 0.2-36.6). Significant differences between nonsurvivors and survivors included the time elapsed between their admission and the initiation of treatment for acute exacerbation (6 vs. 3.1 days, p = 0.04), lactate dehydrogenase levels at admission (801 vs. 544.6 IU/l, p = 0.002), impairment of the prior forced vital capacity (51.2 vs. 65%, p = 0.01) and diffusing capacity for carbon monoxide (21.7 vs. 34%, p = 0.01). Furthermore, the evolution of gas exchange in the first 10 days after the initiation of treatment was associated with in-hospital and long-term mortality. Conclusions: Acute exacerbations of idiopathic pulmonary fibrosis are more frequent during winter and spring. The time between admission and initiation of treatment is a new reported prognostic factor that should be investigated further. This finding highlights the need for a fast diagnostic approach that should probably be standardized. Early gas exchange modifications reflect the response to treatment and predict the prognosis. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: Human herpesvirus 6 (HHV6) is an emerging cause of interstitial pneumonia in immunocompromised hosts. However, the clinical significance of a positive PCR test for HHV6 in respiratory samples from patients with hematological malignancies remains unclear. Methods: We retrospectively studied the features and outcomes of 29 critically ill hematology patients with acute respiratory failure and lung pulmonary infiltrates visible on a chest radiograph, who tested positive for a qualitative PCR for HHV6 in bronchoalveolar lavage fluid. Results: Of the 29 patients, 18 (62%) were stem cell transplant recipients and 11 (38%) had received chemotherapy. All patients had a fever. Clinical manifestations consistent with extra-pulmonary HHV6 disease were noted in 17 (59%) patients. One or more co-pathogens were found in 25 (86%) patients. The four remaining patients diagnosed with HHV6 pneumonia and subsequently recovered with foscarnet therapy. Antiviral therapy was also given to seven patients with co-infections, of whom two ultimately died. Conclusions: In most cases, HHV6 recovered from BAL fluid is a co-pathogen whose clinical relevance remains undetermined. However, in some cases, HHV6 is the only pathogen, along with disseminated systemic viral disease, and the patient is likely to benefit from foscarnet therapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: The Stewart approach theorizes that plasma pH depends on PaCO2, the strong ion difference, and the plasma total concentration of non-volatile weak acids (Atot). The conventional approach measures standardized base excess, bicarbonate (HCO3‾), and the anion gap. OBJECTIVE: To describe acid-base disorders with the Stewart approach and the conventional approach in patients with chronic respiratory failure. METHODS: This was an observational prospective study in a medical intensive care unit and a pneumology ward of a university hospital. There were 128 patients included in the study, of which 14 had more than one admission, resulting in 145 admissions. These were allocated to 4 groups: stable respiratory condition and elevated HCO3‾ (Group 1, n = 23), stable respiratory condition and non-elevated HCO3‾ (Group 2, n = 41), unstable respiratory condition and elevated HCO3‾ (Group 3, n = 44), and unstable respiratory condition and non-elevated HCO3‾ (Group 4, n = 37). Elevated HCO3‾ was defined as ≥ 3 standard deviations higher than the mean value we found in 8 healthy volunteers. Measurements were taken on admission. RESULTS: In groups 1, 2, 3, and 4, the respective mean ± SD values were: HCO3‾ 33 ± 3 mM, 26 ± 3 mM, 37 ± 4 mM, and 27 ± 3 mM (P < .001); strong ion difference 45 ± 3 mM, 38 ± 4 mM, 46 ± 4 mM, and 36 ± 4 mM (P < .001); and Atot 12 ± 1 mM, 12 ± 1 mM, 10 ± 1 mM, 10 ± 2 mM (P < .001). Non-respiratory disorders related to high strong ion difference were observed in 12% of patients with elevated HCO3‾, and in none of those with non-elevated HCO3‾ (P = .003). Non-respiratory disorders related to low strong ion difference were observed in 9% of patients with non-elevated HCO3‾, and in none of those with elevated HCO3‾ (P = .02). Hypoalbuminemia was common, especially in unstable patients (group 3, 66%; group 4, 65%). Normal standardized base excess (16%), HCO3‾ (28%), and anion gap (30%) values were common. The Stewart approach detected high effective strong ion difference in 13% of normal standardized base excess, and in 20% of normal anion gap corrected for albuminemia, and low effective strong ion difference in 22% of non-elevated HCO3‾. CONCLUSIONS: In patients with chronic respiratory failure the acid-base pattern is complex, metabolic alkalosis is present in some patients with elevated HCO3‾, and metabolic acidosis is present in some with non-elevated HCO3‾. The diagnostic performance of the Stewart approach was better than that of the conventional approach, even when corrected anion gap was taken into account. [ABSTRACT FROM AUTHOR]

PURPOSE: The aim of this study was to confirm the ability of the airway occlusion pressure after 0.1 second (P0.1) recorded after extubation to define chronic obstructive pulmonary disease (COPD) patients with a high risk of postextubation respiratory failure and to evaluate the role of the expiratory flow limitation (EFL) in these patients. MATERIALS AND METHODS: Thirty 5 COPD patients who had been weaned from mechanical ventilation and extubated were included in the study. Expiratory flow limitation by the negative expiratory pressure method and P0.1 were recorded at the first hour of postextubation. We determined whether those patients who developed postextubation respiratory failure (failed extubation group) differed from those who did not (successful extubation group). RESULTS: Fourteen patients presented a postextubation respiratory failure. Expiratory flow limitation and P0.1 values in the failed extubation group, respectively (61.6% +/- 34.0%; 4.3 +/- 1.7 cm H(2)0) were significantly different (P < .05) from those observed in the successful extubation group, respectively (20.3% +/- 24.6%; 1.8 +/- 0.8 cm H(2)0). P0.1 and EFL would seem to be of use in predicting extubation outcome, respectively (OR 3.66, 95% confidence interval 1.68-7.94; OR 1.04, 95% confidence interval 1.01-1.07). The area under the receiver operating characteristic curve for diagnosing postextubation respiratory failure was 0.84 for EFL and 0.87 for P0.1. CONCLUSION: Bedside evaluation of EFL and P0.1 helps to define COPD patients at high risk for postextubation respiratory failure. Extubation failure in COPD was associated with higher EFL. © 2008 Elsevier Inc. All rights reserved. [ABSTRACT FROM AUTHOR]

BACKGROUND: No guidelines are available for noninvasive ventilation (NIV) for cystic fibrosis (CF). OBJECTIVE: To survey and evaluate the use of NIV for CF in France. METHODS: We surveyed the coordinator physicians of every accredited CF center in France. RESULTS: The respondents represented 36 centers (15 pediatric centers, 13 adult centers, and 8 centers that see both pediatric and adult patients), which had a total of 4,416 patients with CF at the time of the study, 168 (3.8%) of whom were using NIV. NIV was being used more often in the adults centers (7.6% of these patients) than in the pediatric centers (1.2% of these patients) or adult-and-pediatric centers (4.1% of these patients) (P = .01). All the respondent centers use NIV as first-line treatment for severe hypercapnic respiratory exacerbation and for stable diurnal hypercapnia, especially when associated with sleep disturbance. Bi-level pressure-targeted ventilation is the preferred ventilation mode. Settings are adjusted based on arterial blood gas values, noninvasive evaluation of patient-ventilator synchrony, patient comfort, and sometimes a sleep study. The surveyed centers reported a number of expected benefits from NIV, but few of those benefits have been proven. Problems with NIV are common and limit its use. CONCLUSIONS: We found a relative homogeneity in these French centers' stated indications for and use of NIV, which highlights their numerous expectations about the benefits of NIV, which contrasts with the few validated benefits. Studies of the benefits of NIV are needed. [ABSTRACT FROM AUTHOR]

Background: The benefits of long-termnoninvasive positive pressure ventilation (NPPV) have not yet been evaluated in patients with cystic fibrosis (CF). Objectives: To evaluate the effect of 1 year of NPPV on lung function in patients with advanced CF. Methods: Data were obtained from the French CF Registry. Patients who started NPPV (ventilated group, n = 41) were compared to matched controls (control group, n = 41). Each ventilated patient was matched to a control 1 year before the start of NPPV (year –1) for gender, CFTR genotype, age ± 5 years and forced expiratory volume in 1 s (FEV1) ± 10%. The ventilated group was compared to the control group at year –1, during the year of NPPV initiation (year 0) and 1 year after NPPV (year +1). Results: At year –1, the two groups were comparable with regard to forced vital capacity (FVC; 43.7 vs. 49.1% in the ventilated group and the control group, respectively) and FEV1 (28.2 vs. 28.5%). At year 0, the ventilated group had significantly greater declines in FVC (–3.6 ± 9.2 vs. +0.8 ± 8.9%, p = 0.03) and in FEV1 (–3.0 ± 6.7 vs. +2.6 ± 4.4, p < 0.0001). At year +1, the decreases in FVC (–2.1 ± 10.0 vs. –2.2 ± 9.9%) and in FEV1 (–2.2 ± 6.7 vs. –2.3 ± 6.2%) were similar in both groups. Conclusions: These data show that NPPV is associated with stabilization of the decrease in lung function in patients with advanced CF. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The measurement of respiratory system resistance during mechanical ventilation is important to ascertain the causes of increase in airway pressure during volume-controlled ventilation, which may include airways resistance and decreased respiratory system compliance.Discussion: Separation of total resistance from compliance of the respiratory system can be assessed by the end-inspiratory hold maneuver that separates peak pressure from plateau pressure.Conclusions: Although this method assumes a homogeneous respiratory system, it has proven useful clinically to separate flow-dependence issues such as bronchospasm or endotracheal tube obstruction from stiff lungs (acute lung injury) or decrease chest wall (abdominal distension) compliance. [ABSTRACT FROM AUTHOR]

Objectives: A prospective survey of French intensive care units (ICUs) in 1997 showed moderate and variable use of noninvasive ventilation (NIV). This study examined changes in NIV use in French ICUs after the intervening 5years.Settings: Patients were enrolled in a prospective survey in 70 French ICUs.Methods: Three-week survey, with prospective inclusion of all patients requiring ventilatory support.Measurements and Results: Overall 1,076 patients received ventilatory support (55% of admissions). First-line NIV was significantly more common than 5years earlier, overall (23% vs. 16%) and especially in patients not intubated before ICU admission (52% vs. 35%). Reasons for respiratory failure were coma (33%), cardiogenic pulmonary edema (8%), acute-on-chronic respiratory failure (17%), and de novo respiratory failure (41%). Significant increases in NIV use were noted for acute-on-chronic respiratory failure (64% vs. 50%) and de novo respiratory failure (22% vs. 14%). Among patients given NIV, 38% subsequently required endotracheal intubation (not significantly different). Independent risk factors for NIV failure were high SAPS II and de novo respiratory failure, whereas factors associated with success were good NIV tolerance and high body mass index.Conclusions: NIV use has significantly increased in French ICUs during the past 5years, and the success rate has remained unchanged. In patients not previously intubated, NIV is the leading first-line ventilation modality. The proportion of patients successfully treated with NIV increased significantly over the 5-year period (13% vs. 9% of all patients receiving ventilatory support). [ABSTRACT FROM AUTHOR]

Context A recent trial showed that placing patients with acute lung injury in the prone position did not increase survival; however, whether those results hold true for patients with hypoxemic acute respiratory failure (ARF) is unclear. Objective To determine whether prone positioning improves mortality in ARF patients. Design, Setting, and Patients Prospective, unblinded, multicenter controlled trial of 791 ARF patients in 21 general intensive care units in France using concealed randomization conducted from December 14, 1998, through December 31, 2002. To be included, patients had to be at least 18 years, hemodynamically stable, receiving mechanical ventilation, and intubated and had to have a partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FIO2) ratio of 300 or less and no contraindications to lying prone. Interventions Patients were randomly assigned to prone position placement (n = 413), applied as early as possible for at least 8 hours per day on standard beds, or to supine position placement (n = 378). Main Outcome Measures The primary end point was 28-day mortality; secondary end points were 90-day mortality, duration of mechanical ventilation, incidence of ventilator-associated pneumonia (VAP), and oxygenation. Results The 2 groups were comparable at randomization. The 28-day mortality rate was 32.4% for the prone group and 31.5% for the supine group (relative risk [RR], 0.97; 95% confidence interval [CI], 0.79-1.19; P = .77). Ninety-day mortality for the prone group was 43.3% vs 42.2% for the supine group (RR, 0.98; 95% CI, 0.84-1.13; P = .74). The mean (SD) duration of mechanical ventilation was 13.7 (7.8) days for the prone group vs 14.1 (8.6) days for the supine group (P = .93) and the VAP incidence was 1.66 vs 2.14 episodes per 100-patients days of intubation, respectively (P = .045). The PaO2/FIO2 ratio was significantl... [ABSTRACT FROM AUTHOR]

Points out that lessons from France can inform the development of cost-effective chronic care models in the U.S. Review of the French experience in the context of the U.S. Supreme Court's Olmstead decision, mandating the people in more restrictive settings such as nursing homes be offered community-based supports; Suggestion that regional demonstration projects for patients with chronic respiratory failure on insufficiency can provide an important step in the development of effective chronic care systems in the U.S.

France is the country with the highest prevalence of cannabis use in Europe, despite the fact that cannabis has not been legalized. This prevalence is still increasing along with THC content in cannabis products. In the meantime, unintentional cannabis poisoning by ingestion in toddlers is constantly rising. The aim of this study was to document children's cannabis poisoning biologically and clinically. Plasma and urine samples were extracted by solid phase extraction and analyzed by liquid chromatography coupled to tandem mass spectrometry. Children under 4 years old admitted in pediatric emergency departments for cannabis intoxication between February 1st 2019 and January 31st 2020 were included in this study. Twenty-six children were included (14 female and 12 male), the mean age was 17 months (10-41 months). THC, 11-OH-THC and THC-COOH plasma concentrations ranged from 2.9 to 93 ng/mL, 2.6-65 ng/mL and 29-914 ng/mL, respectively. The most frequent symptoms were drowsiness and hypotonia. Six critical cases were observed: 5 coma and 1 respiratory depression. All children having THC plasma concentrations over 60 ng/mL were in coma. Cannabis poisoning in toddlers become more frequent, 9 cases/year were reported in Marseille in 2007 and 26 cases/year in this study. There is a rising in severe clinical cases, particularly coma. These observations could be explained by an increase in THC content in cannabis products, and a trivialization of cannabis consumption. The unintentional ingestion of cannabis by children is a serious public health concern, and cannabis legalization could worsen this problem. [ABSTRACT FROM AUTHOR]

Objective: To explore translation, conversion and definition ambiguities, when using severity scoring systems in patients admitted to intensive care units (ICUs).Design: A prospective study of the prognosis of acute renal failure in ICUs.Setting: The study was conducted in 20 French ICUs.Patients: 360 patients presenting with severe acute renal failure were studied during their ICU stay.Measurements and Results: The inter-observer variability of Apache II (acute physiology and chronic health evaluation), SAPS (simplified acute physiology score), and OSF (organ-system failure) was considered. For Apache II, we explored the uncertainty of measurements arising from conversion into SI units, the rounding procedures used for the non-inclusive intervals defined for quantitative parameters such as age, mean arterial pressure (MAP) or serum creatinine, the absence of definition of acute renal failure (ARF) and its consequence on doubling serum creatinine values, and the absence of guidelines in the case of spontaneous ventilation when arterial blood gases (ABG) and forced inspiratory oxygen (FIO2) were not measured. The resulting variability was evaluated, calculating the lowest and the highest value of the scoring system for each patient. The mean difference by patient was greater than 1.5 (p < 0.0001). Other examples were presented and discussed for SAPS and OSF.Conclusions: Translation, conversion and definition ambiguities are a source of inter-observer variability and increase the risk of classification and/or selection biases. This gives rise to particular concern in the design and analysis of multicenter trials of meta-analysis, and improvement of these scoring systems should be envisaged in the future. [ABSTRACT FROM AUTHOR]

Objective: We assessed the performance of the ratio of peripheral arterial oxygen saturation to the inspired fraction of oxygen (SpO 2 /FiO 2 ) to predict the ratio of partial pressure arterial oxygen to the fraction of inspired oxygen (PaO 2 /FiO 2 ) among patients admitted to our emergency department (ED) during the SARS-CoV-2 outbreak., Methods: We retrospectively studied patients admitted to an academic-level ED in France who were undergoing a joint measurement of SpO 2 and arterial blood gas. We compared SpO 2 with SaO 2 and evaluated performance of the SpO 2 /FiO 2 ratio for the prediction of 300 and 400 mmHg PaO 2 /FiO 2 cut-off values in COVID-19 positive and negative subgroups using receiver-operating characteristic (ROC) curves., Results: During the study period from February to April 2020, a total of 430 arterial samples were analyzed and collected from 395 patients. The area under the ROC curves of the SpO 2 /FiO 2 ratio was 0.918 (CI 95% 0.885-0.950) and 0.901 (CI 95% 0.872-0.930) for PaO 2 /FiO 2 thresholds of 300 and 400 mmHg, respectively. The positive predictive value (PPV) of an SpO 2 /FiO 2 threshold of 350 for PaO 2 /FiO 2 inferior to 300 mmHg was 0.88 (CI95% 0.84-0.91), whereas the negative predictive value (NPV) of the SpO 2 /FiO 2 threshold of 470 for PaO 2 /FiO 2 inferior to 400 mmHg was 0.89 (CI95% 0.75-0.96). No significant differences were found between the subgroups., Conclusions: The SpO 2 /FiO 2 ratio may be a reliable tool for hypoxemia screening among patients admitted to the ED, particularly during the SARS-CoV-2 outbreak., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2021. Published by Elsevier Inc.)

Background: Acute respiratory failure related to diffuse alveolar hemorrhage (DAH) is a typical presentation of small-vessel vasculitis that requires prompt multidisciplinary management. The primary treatment is based on immunosuppressive drugs, whereas urgent plasma exchange has been proposed in case of life-threatening complications. We addressed the course of respiratory failure in 12 patients with ANCA-associated vasculitis-related DAH.Patients and Methods: Observational retrospective case series performed in the medical ICU of a tertiary hospital in Paris, France. Consecutive patients with ANCA-associated DAH admitted to our ICU for acute respiratory failure and treated by plasmapheresis were included in the analysis. We evaluated the SpO2/FiO2 ratio and assessed the mechanical ventilation mode hourly for 7 days.Results: Twelve patients were included. Five of them required invasive mechanical ventilation. All patients were treated by plasma exchange in addition to a combination of glucocorticoids and immunosuppressive agents. Oxygenation improved over the first 7 days following initiation of plasma exchange, as shown by a dramatic increase in the median SpO2/FiO2 ratio from 183 [interquartile 137-321] to 353 [239-432] (p = 0.003), along with a decrease in the level of ventilatory support. All but one patient survived.Conclusions: A multimodal induction regimen combining immunosuppressants and plasma exchange may rapidly reverse the respiratory dysfunction in ANCA-associated vasculitis-related DAH. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory failure (ARF) is the leading reason for intensive care unit (ICU) admission in immunocompromised patients. High-flow nasal oxygen (HFNO) therapy is an alternative to standard oxygen. By providing warmed and humidified gas, HFNO allows the delivery of higher flow rates via nasal cannula devices, with FiO2 values of nearly 100%. Benefits include alleviation of dyspnea and discomfort, decreased respiratory distress and decreased mortality in unselected patients with acute hypoxemic respiratory failure. However, in preliminary reports, HFNO benefits are controversial in immunocompromised patients in whom it has never been properly evaluated.Methods/design: This is a multicenter, open-label, randomized controlled superiority trial in 30 intensive care units, part of the Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique (GRRR-OH). Inclusion criteria will be: (1) adults, (2) known immunosuppression, (3) ARF, (4) oxygen therapy ≥ 6 L/min, (5) written informed consent from patient or proxy. Exclusion criteria will be: (1) imminent death (moribund patient), (2) no informed consent, (3) hypercapnia (PaCO2 ≥ 50 mmHg), (4) isolated cardiogenic pulmonary edema, (5) pregnancy or breastfeeding, (6) anatomical factors precluding insertion of a nasal cannula, (7) no coverage by the French statutory healthcare insurance system, and (8) post-surgical setting from day 1 to day 6 (patients with ARF occurring after day 6 of surgery can be included). The primary outcome measure is day-28 mortality. Secondary outcomes are intubation rate, comfort, dyspnea, respiratory rate, oxygenation, ICU length of stay, and ICU-acquired infections. Based on an expected 30% mortality rate in the standard oxygen group, and 20% in the HFNO group, error rate set at 5%, and a statistical power at 90%, 389 patients are required in each treatment group (778 patients overall). Recruitment period is estimated at 30 months, with 28 days of additional follow-up for the last included patient.Discussion: The HIGH study will be the largest multicenter, randomized controlled trial seeking to demonstrate that survival benefits from HFNO reported in unselected patients also apply to a large immunocompromised population.Trial Registration: ClinicalTrials.gov, ID: NCT02739451 . Registered on 15 April 2016. [ABSTRACT FROM AUTHOR]

Background: Generalized tonic-clonic seizures (GTCSs) are the main risk factor for sudden unexpected death in epilepsy (SUDEP). Experimental and clinical data strongly suggest that the majority of SUDEP results from a postictal respiratory dysfunction progressing to terminal apnea. Postictal apnea could partly derive from a seizure-induced massive release of endogenous opioids. The main objective of this study is to evaluate the efficacy of an opioid antagonist, naloxone, administered in the immediate aftermath of a GTCS, in reducing the severity of the postictal central respiratory dysfunction.Methods/design: The Efficacy of Naloxone in Reducing Postictal Central Respiratory Dysfunction in Patients with Epilepsy (ENALEPSY) study is a multicenter, double-blind, randomized, placebo-controlled trial conducted in patients with drug-resistant focal epilepsy who are undergoing long-term video-electroencephalogram (EEG) monitoring (LTM) in an epilepsy monitoring unit (EMU). We plan to randomize 166 patients (1:1) to receive intravenous naloxone (0.4 mg) or placebo in the immediate aftermath of a GTCS. Because inclusion in the study needs to take place prior to the occurrence of the GTCS, and because such occurrence is observed in about one-fourth of patients undergoing LTM, we plan to include a maximum of 700 patients upon admission in the EMU. The primary endpoint will be the proportion of patients whose oxygen saturation is <90 % between 1 and 3 min after the end of a GTCS. Secondary outcomes will include the following: the proportion of patients who show postictal apnea, the occurrence and duration of postictal generalized EEG suppression, the total duration of the postictal coma, postictal pain, and the number of patients who have a second GTCS within 120 min after the intravenous injection.Discussion: The demonstration of naloxone's efficacy on the severity of postictal hypoxemia will have two primary consequences. First, naloxone would be the first and only therapeutic approach that could be delivered immediately to reverse postictal apnea. Second, demonstration that an opioid antagonist can effectively reduce postictal apnea would pave the way for an assessment of a preventive therapy for SUDEP targeting the same pathophysiological pathway using oral administration of naltrexone.Trial Registration: ClinicalTrials.gov identifier: NCT02332447 . Registered on 5 January 2015. [ABSTRACT FROM AUTHOR]

Background: Characteristics and outcomes of adult patients with disseminated toxoplasmosis admitted to the intensive care unit (ICU) have rarely been described., Methods: We performed a retrospective study on consecutive adult patients with disseminated toxoplasmosis who were admitted from January 2002 through December 2012 to the ICUs of 14 university-affiliated hospitals in France. Disseminated toxoplasmosis was defined as microbiological or histological evidence of disease affecting >1 organ in immunosuppressed patients. Isolated cases of cerebral toxoplasmosis were excluded. Clinical data on admission and risk factors for 60-day mortality were collected., Results: Thirty-eight patients were identified during the study period. Twenty-two (58%) had received an allogeneic hematopoietic stem cell transplant (median, 61 [interquartile range {IQR}, 43-175] days before ICU admission), 4 (10%) were solid organ transplant recipients, and 10 (27%) were infected with human immunodeficiency virus (median CD4 cell count, 14 [IQR, 6-33] cells/µL). The main indications for ICU admission were acute respiratory failure (89%) and shock (53%). The 60-day mortality rate was 82%. Allogeneic hematopoietic stem cell transplant (hazard ratio [HR] = 2.28; 95% confidence interval [CI], 1.05-5.35; P = .04) and systolic cardiac dysfunction (HR = 3.54; 95% CI, 1.60-8.10; P < .01) within 48 hours of ICU admission were associated with mortality., Conclusions: Severe disseminated toxoplasmosis leading to ICU admission has a poor prognosis. Recipients of allogeneic hematopoietic stem cell transplant appear to have the highest risk of mortality. We identified systolic cardiac dysfunction as a major determinant of outcome. Strategies aimed at preventing this fatal opportunistic infection may improve outcomes.

Unlabelled: INTRODUCTION, AIMS: The authors present the Cotard's syndrome, a rare psychiatric condition, pointing out the latest results in terms of etiology and psychoneurology. The central feature of the syndrome is a nihilistic delusion, in which the patient denies his or her own existence and that of the external world., Method: We searched electronic databases using the appropriate search terms, relevant articles were carefully reviewed. We present three cases from our clinical practice., Results: After the overview of the latest biological and neuropsychological findings, the historical aspects of the condition, the terminology, the nosology, the classification, the differential diagnostics and the etiology are discussed. The psychopathology and the phenomenology of Cotard's syndrome are also presented, shedding light on existential aspects as well. To sum up with useful information for the clinical practice, the possible treatment strategies, the course and the prognosis of the disease are also discussed., Conclusions: The presented theoretical and practical aspects give a lead on deeper understanding, easier recognition and more adequate therapy of the Cotard's syndrome.