Spontaneous-Breathing Trials with Pressure-Support Ventilation or a T-Piece.

BACKGROUND: Spontaneous-breathing trials can be performed with the use of either pressure-support ventilation (PSV) or a T-piece. Whether PSV trials may result in a shorter time to tracheal extubation than T-piece trials, without resulting in a higher risk of reintubation, among patients who have a high risk of extubation failure is unknown. METHODS: In this multicenter, open-label trial, we randomly assigned patients who had a high risk of extubation failure (i.e., were >65 years of age or had an underlying chronic cardiac or respiratory disease) to undergo spontaneous-breathing trials performed with the use of either PSV (with a pressure-support level of 8 cm of water and no positive end-expiratory pressure) or a T-piece. The primary outcome was the total time without exposure to invasive ventilation (reported as the number of ventilator-free days) at day 28 after the initial spontaneous-breathing trial. Secondary outcomes included extubation within 24 hours and extubation within 7 days after the initial spontaneous-breathing trial, as well as reintubation within 7 days after extubation. RESULTS: A total of 969 patients (484 in the PSV group and 485 in the T-piece group) were included in the analysis. At day 28, the median number of ventilator-free days was 27 (interquartile range, 24 to 27) in the PSV group and 27 (interquartile range, 23 to 27) in the T-piece group (difference, 0 days; 95% confidence interval [CI], -0.5 to 1; P = 0.31). Extubation was performed within 24 hours in 376 patients (77.7%) in the PSV group and in 350 patients (72.2%) in the T-piece group (difference, 5.5 percentage points; 95% CI, 0.01 to 10.9), and extubation was performed within 7 days in 473 patients (97.7%) and 458 patients (94.4%), respectively (difference, 3.3 percentage points; 95% CI, 0.8 to 5.9). Reintubation was performed in 72 of 481 patients (14.9%) in the PSV group and in 65 of 477 patients (13.6%) in the T-piece group (difference, 1.3 percentage points; 95% CI, -3.1 to 5.8). Cardiac or respiratory arrest was a reason for reintubation in 9 patients (3 in the PSV group and 6 in the T-piece group). CONCLUSIONS: Among patients who had a high risk of extubation failure, spontaneous-breathing trials performed with PSV did not result in significantly more ventilator-free days at day 28 than spontaneous-breathing trials performed with a T-piece. (Supported by the French Ministry of Health; TIP-EX ClinicalTrials.gov number, NCT04227639.).

Pattern of Brain Injury in Patients With Thrombotic Thrombocytopenic Purpura in the Precaplacizumab Era.

OBJECTIVES: To describe short- and long-term neurologic prognosis of patients with thrombotic thrombocytopenic purpura and to identify clusters associated with evolution. DESIGN: Prospective French cohort. SETTING: ICU in a reference center. PATIENTS: All consecutive patients with newly diagnosed thrombocytopenic purpura. INTERVENTION: Comprehensive clinical, biological, and radiological evaluation at admission. Neurocognitive recovery was assessed using Glasgow Outcome Scale (range 1-5, with 1 representing death and 5 representing no or minimal neurologic deficit). MEASUREMENTS AND MAIN RESULTS: Among the 130 newly diagnosed patients with thrombocytopenic purpura, 108 (83%; age 43 [30-52]; 73% women) presented with neurologic signs, including headaches (51%), limb weakness, paresthesia, and/or aphasia (49%), pyramidal syndrome (30%), decreased consciousness (20%), seizure (19%), cognitive impairment (34%), cerebellar syndrome (18%), and visual symptoms (20%). A hierarchical cluster analysis identified three distinct groups of patients. Cluster 1 included younger patients (37 [27-48], 41 [32-52], and 48 [35-54], in clusters 1, 2 and 3, respectively; p = 0.045), with a predominance of headaches (75%, 27%, and 36%; p < 0.0001). Cluster 2 patients had ataxic gait and cerebellar syndrome (77%, 0%, and 0%; p < 0.0001) and dizziness (50%, 0%, and 0%; p < 0.0001). Cluster 3 included patients with delirium (36%, 0%, and 9%; p < 0.0001), obtundation (58%, 0%, and 24%; p < 0.0001), and seizure (36%, 0%, and 14%; p < 0.0001). Acute kidney injury was 32%, 68%, and 77%, in clusters 1, 2, and 3, respectively (p < 0.0001). The three clusters did not differ for other biological or brain imaging. After a median follow-up of 34 months (12-71 mo), 100 patients (93%) were alive with full neurocognitive recovery (i.e., Glasgow Outcome Scale score 5) in 89 patients (89%). Patients from cluster 1 more frequently exhibited full recovery (Glasgow Outcome Scale score of 5) compared with clusters 2 and 3, (44 [98%], 13 [65%], and 21 [60%] at 3 mo; p < 0.0001), (44 [100%], 15 [68%], and 23 [69%] at 6 mo; p < 0.0001), and (40 [100%], 15 [79%], and 20 [57%] at 1 yr; p < 0.0001). CONCLUSIONS: Initial clinical neurologic evaluation in thrombocytopenic purpura patients distinguishes three groups of patients with different clinical and functional outcomes.

Barriers to research findings utilization amongst critical care nurses and allied health professionals: An international survey.

OBJECTIVES: To determine the perceived barriers to the implementation of research findings in clinical practice among critical care nurses and allied health professionals. METHODS: A cross-sectional study was conducted using an online questionnaire sent to critical care nurses and allied health professionals in French-speaking countries. The primary objective was the identification and grading of perceived barriers to implementation of research findings into clinical practice, using a previously validated tool (French version of the BARRIERS scale). The scale is divided into 4 dimensions, each containing 6 to 7 questions to be answered using a 4-point Likert scale (1: no barrier, 4: great barrier). Descriptive statistics were performed and weighted score per dimensions were compared. Univariate and multivariate linear regressions were performed to identify factors associated with the total score by dimension. RESULTS: A total of 994 nurses and allied health professionals (85.1 % of ICU nurses) from 5 countries (71.8 % from France) responded to the survey. Main reported barriers to research findings utilization were "Statistical analyses are not understandable" (54.5 %), "Research articles are not readily available" (54.3 %), and "Implications for practice are not made clear" (54.2 %). Weighted scores differed between dimensions, with the "communication" and "organization" dimensions being the greatest barriers (median [IQR]: 2.3 [1.8-2.7] and 2.0 [1.6-2.4], while the "adopter" and "innovation" dimensions having lower scores (1.5 [1.2-1.8] and 1.5 [1.0-1.8] (all pairwise comparisons p-value < 0.0001, except for the adopter vs. innovation comparison, p > 0.05). CONCLUSIONS: Accessibility and understanding of research results seem to be the main barriers to research utilization in practice by respondents. A large number of the reported barriers could be overcome through education and organizational change. IMPLICATIONS FOR PRACTICE: Promoting a research culture among nurses and allied health professionals is an issue that needs investment. This should include training in critical reading of scientific articles and statistics.

Oxygen therapy in acute hypoxemic respiratory failure: guidelines from the SRLF-SFMU consensus conference.

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.

ß-lactam dosing at the early phase of sepsis: Performance of a pragmatic protocol for target concentration achievement in a prospective cohort study.

PURPOSE: We hypothesized that a protocol of standardized fixed dose using prolonged infusion during the early phase of sepsis may avoid insufficient ß-lactam concentrations. METHODS: In this single center prospective study, patients with sepsis and vasopressors were enrolled if they were treated by either piperacillin-tazobactam, meropenem or cefepime. Βeta-lactams were administered at fixed dose by prolonged infusion. Targeted plasma concentrations for piperacillin, meropenem and cefepime were above 80 mg/L, 8 mg/L and 38 mg/L respectively. Three blood samples were collected per patient over the first 48 h of treatment. Primary endpoint was target concentration achievement during the 48 first hours, defined as all plasma concentrations above the targeted threshold. RESULTS: Among the 89 patients completing the three samples, target concentrations were achieved for 61 (69%). Target concentrations were achieved in 20 (53%), 32 (89%), and 9 (60%) of the patients treated with piperacillin, meropenem and cefepime, respectively. By multivariate analysis, lower APACHE 2 score, higher baseline MDRD creatinine clearance, and piperacillin use were independently associated with insufficient ß-lactam concentrations. CONCLUSION: Despite a fixed dose antibiotic administration protocol with prolonged infusion insufficient ß-lactam concentration was frequent at the early phase of sepsis, especially in less severe patients, without renal failure, and treated with piperacillin. In septic patients with vasopressors, piperacillin dosing higher than 16 g may be needed to achieve the recommended target concentration. TRIAL REGISTRATION: NCT02820987.

Nicotine patches in patients on mechanical ventilation for severe COVID-19: a randomized, double-blind, placebo-controlled, multicentre trial.

PURPOSE: Epidemiologic studies have documented lower rates of active smokers compared to former or non-smokers in symptomatic patients affected by coronavirus disease 2019 (COVID-19). We assessed the efficacy and safety of nicotine administered by a transdermal patch in critically ill patients with COVID-19 pneumonia. METHODS: In this multicentre, double-blind, placebo-controlled trial conducted in 18 intensive care units in France, we randomly assigned adult patients (non-smokers, non-vapers or who had quit smoking/vaping for at least 12 months) with proven COVID-19 pneumonia receiving invasive mechanical ventilation for up to 72 h to receive transdermal patches containing either nicotine at a daily dose of 14 mg or placebo until 48 h following successful weaning from mechanical ventilation or for a maximum of 30 days, followed by 3-week dose tapering by 3.5 mg per week. Randomization was stratified by centre, non- or former smoker status and Sequential Organ Function Assessment score (< or ≥ 7). The primary outcome was day-28 mortality. Main prespecified secondary outcomes included 60-day mortality, time to successful extubation, days alive and free from mechanical ventilation, renal replacement therapy, vasopressor support or organ failure at day 28. RESULTS: Between November 6th 2020, and April 2nd 2021, 220 patients were randomized from 18 active recruiting centers. After excluding 2 patients who withdrew consent, 218 patients (152 [70%] men) were included in the analysis: 106 patients to the nicotine group and 112 to the placebo group. Day-28 mortality did not differ between the two groups (30 [28%] of 106 patients in the nicotine group vs 31 [28%] of 112 patients in the placebo group; odds ratio 1.03 [95% confidence interval, CI 0.57-1.87]; p = 0.46). The median number of day-28 ventilator-free days was 0 (IQR 0-14) in the nicotine group and 0 (0-13) in the placebo group (with a difference estimate between the medians of 0 [95% CI -3-7]). Adverse events likely related to nicotine were rare (3%) and similar between the two groups. CONCLUSION: In patients having developed severe COVID-19 pneumonia requiring invasive mechanical ventilation, transdermal nicotine did not significantly reduce day-28 mortality. There is no indication to use nicotine in this situation.

High-flow nasal oxygen alone or alternating with non-invasive ventilation in critically ill immunocompromised patients with acute respiratory failure: a randomised controlled trial.

BACKGROUND: Although non-invasive ventilation (NIV) is recommended for immunocompromised patients with acute respiratory failure in the intensive care unit (ICU), it might have deleterious effects in the most severe patients. High-flow nasal oxygen (HFNO) alone might be an alternative method to reduce mortality. We aimed to determine whether HFNO alone could reduce the rate of mortality at day 28 compared with HFNO alternated with NIV. METHODS: FLORALI-IM is a multicentre, open-label, randomised clinical trial conducted in 29 ICUs (28 in France and one in Italy). Adult immunocompromised patients with acute respiratory failure, defined as respiratory rate of 25 breaths per min or more and a partial pressure of arterial oxygen to inspired fraction of oxygen ratio of 300 mm Hg or lower, were randomly assigned (1:1) to HFNO alone (HFNO alone group) or NIV alternating with HFNO (NIV group). Key exclusion criteria were severe hypercapnia above 50 mm Hg, patients who could strongly benefit from NIV (ie, those with underlying chronic lung disease, with cardiogenic pulmonary oedema, or who were postoperative), severe shock, impaired consciousness defined as Glasgow coma score ≤12, urgent need for intubation, do not intubate order, and contraindication to NIV. Patients were assigned using computer-generated permuted blocks and were stratified according to centre and to the type of immunosuppression using a centralised web-based management system. In the HFNO alone group, patients were continuously treated by HFNO with a gas flow rate of 60 L/min or the highest tolerated. In the NIV group, patients were treated with NIV with a first session of at least 4 h, and then by sessions for a minimal duration of 12 h a day, with a dedicated ventilator, targeting a tidal volume below 8 mL/kg of predicted bodyweight, and with a positive end-expiratory level of at least 8 cm H2O. NIV sessions were interspaced with HFNO delivered as in the HFNO alone group. The primary outcome was mortality at day 28 and was assessed in the intention-to-treat population. Secondary outcomes were mortality in the ICU, in hospital, at day 90 and at day 180, intubation at day 28, length of stay in the ICU and in hospital, number of ventilator-free days at day 28, number of oxygenation technique-free days at day 28, and efficacy and tolerance of oxygenation techniques. The trial is registered with ClinicalTrials.gov, NCT02978300, and is complete. FINDINGS: Between Jan 21, 2017 to March 4, 2019, of 497 eligible patients, 300 were randomly assigned but one patient withdrew consent, leaving 299 patients included in the intention-to-treat analysis (154 assigned to the HFNO alone group and 145 assigned to NIV group). Mortality rate at day 28 was 36% (95% CI 29·2 to 44·2; 56 of 154 patients) in the HFNO alone group and 35% (27·9 to 43·2; 51 of 145 patients) in the NIV group (absolute difference 1·2% [95% CI -9·6 to 11·9]; p=0·83). None of the other prespecified secondary outcomes were different between groups except for greater decreased discomfort after initiation of HFNO than with NIV (-4 mm on visual analogic scale [IQR -18 to 4] vs 0 mm [-16 to 17]; p=0·040). INTERPRETATION: In critically ill immunocompromised patients with acute respiratory failure, the mortality rate did not differ between HFNO alone and NIV alternating with HFNO. However, study power was limited, so results should be interpreted with caution. FUNDING: French Ministry of Health.

Characterization of pulmonary impairment associated with COVID-19 in patients requiring mechanical ventilation. / Caracterização do comprometimento pulmonar associado à COVID-19 em pacientes com necessidade de ventilação mecânica.

OBJECTIVE: To detect early respiratory and hemodynamic instability to characterize pulmonary impairment in patients with severe COVID-19. METHODS: We retrospectively analyzed data collected from COVID-19 patients suffering from acute respiratory failure requiring intubation and mechanical ventilation. We used transpulmonary thermodilution assessment with a PiCCO™ device. We collected demographic, respiratory, hemodynamic and echocardiographic data within the first 48 hours after admission. Descriptive statistics were used to summarize the data. RESULTS: Fifty-three patients with severe COVID-19 were admitted between March 22nd and April 7th. Twelve of them (22.6%) were monitored with a PiCCO™ device. Upon admission, the global-end diastolic volume indexed was normal (mean 738.8mL ± 209.2) and moderately increased at H48 (879mL ± 179), and the cardiac index was subnormal (2.84 ± 0.65). All patients showed extravascular lung water over 8mL/kg on admission (17.9 ± 8.9). We did not identify any argument for cardiogenic failure. CONCLUSION: In the case of severe COVID-19 pneumonia, hemodynamic and respiratory presentation is consistent with pulmonary edema without evidence of cardiogenic origin, favoring the diagnosis of acute respiratory distress syndrome.

OBJETIVO: Detectar precocemente a instabilidade respiratória e hemodinâmica para caracterizar o comprometimento pulmonar em pacientes com COVID-19 grave. MÉTODOS: Analisamos retrospectivamente os dados colhidos de pacientes com COVID-19 que apresentaram insuficiência respiratória aguda com necessidade de intubação e ventilação mecânica. Utilizamos a avaliação da termodiluição transpulmonar por meio do dispositivo PiCCO™. Foram coletados os dados demográficos, respiratórios, hemodinâmicos e ecocardiográficos dentro das primeiras 48 horas após a admissão. Para resumir os dados, utilizamos estatística descritiva. RESULTADOS: Entre 22 de março e 7 de abril de 2020, foram admitidos 23 pacientes com COVID-19 grave. Foram monitorados com o dispositivo PiCCO™ 12 (22,6%) deles. Quando da admissão, o volume diastólico final global indexado era normal (média de 738,8mL ± 209,2) e, na hora 48, encontrava-se moderadamente aumentado (879mL ± 179), enquanto o índice cardíaco se achava abaixo do normal (2,84 ± 0,65). Todos os pacientes revelaram a presença de água extravascular pulmonar acima de 8mL/kg na admissão (17,9 ± 8,9). Não identificamos qualquer evidência de origem cardiogênica. CONCLUSÃO: No caso de pneumonia grave por COVID-19, o quadro hemodinâmico e respiratório é compatível com edema pulmonar sem evidência de origem cardiogênica, o que favorece o diagnóstico de síndrome do desconforto respiratório agudo.

Impact on antimicrobial consumption of procalcitonin-guided antibiotic therapy for pneumonia/pneumonitis associated with aspiration in comatose mechanically ventilated patients: a multicenter, randomized controlled study.

BACKGROUND: In comatose patients receiving oro-tracheal intubation for mechanical ventilation (MV), the risk of aspiration is increased. Aspiration can lead to chemical pneumonitis (inflammatory reaction to the gastric contents), or aspiration pneumonia (infection caused by inhalation of microorganisms). Distinguishing between the two types is challenging. We tested the interest of using a decisional algorithm based on procalcitonin (PCT) values to guide initiation and discontinuation of antibiotic therapies in intubated patients. METHODS: The PROPASPI (PROcalcitonin Pneumonia/pneumonitis Associated with ASPIration) trial is a multicenter, prospective, randomized, controlled, single-blind, superiority study comparing two strategies: (1) an intervention group where threshold PCT values were used to guide initiation and discontinuation of antibiotics (PCT group); and (2) a control group, where antibiotic therapy was managed at the physician's discretion. Patients aged 18 years or over, intubated for coma (Glasgow score ≤ 8), with MV initiated within 48 h after admission, were eligible. The primary endpoint was the duration of antibiotic treatment during the first 15 days after admission to the ICU. RESULTS: From 24/2/2015 to 28/8/2019, 1712 patients were intubated for coma in the 5 participating centers, of whom 166 were included in the study. Data from 159 were available for intention-to-treat analysis: 81 in the PCT group, and 78 in the control group. Overall, 67 patients (43%) received antibiotics in the intensive care unit (ICU); there was no significant difference between groups (37 (46%) vs 30 (40%) for PCT vs control, p = 0.432). The mean duration of antibiotic treatment during the first 15 days in the ICU was 2.7 ± 3.8 days; there was no significant difference between groups (3.0 ± 4.1 days vs 2.3 ± 3.4 days for PCT vs control, p = 0.311). The mean number of days under MV was significantly higher in the PCT group (3.7 ± 3.6 days) than in controls (2.7 ± 2.5 days, p = 0.033). The duration of ICU stay was also significantly longer in the PCT group: 6.4 ± 6.5 days vs 4.6 ± 3.5 days in the control group (p = 0.043). After adjustment for SAPS II score, the difference in length of stay and duration of mechanical ventilation between groups was no longer significant. CONCLUSION: The use of PCT values to guide therapy, in comparison to the use of clinical, biological (apart from PCT) and radiological criteria, does not modify exposure to antibiotics in patients intubated for coma. Trial registration Clinicaltrials.gov Identifier NCT02862314.

Comparison of a preventive or curative strategy of fluid removal on the weaning of mechanical ventilation: a study protocol for a multicentre randomised open-label parallel-group trial.

INTRODUCTION: Fluid overload is associated with a poor prognosis in the critically ill patients, especially at the time of weaning from mechanical ventilation as it may promote weaning failure from cardiac origin. Some data suggest that early administration of diuretics would shorten the duration of mechanical ventilation. However, this strategy may expose patients to a higher risk of haemodynamic and metabolic complications. Currently, there is no recommendation for the use of diuretics during weaning and there is an equipoise on the timing of their initiation in this context. METHODS AND ANALYSIS: This study is a multicentre randomised controlled trial comparing two strategies of fluid removal during weaning in 13 French intensive care units (ICU). The preventive strategy is initiated systematically when the fluid balance or weight change is positive and the patients have criteria for clinical stability; the curative strategy is initiated only in case of weaning failure documented as of cardiac origin. Four hundred and ten patients will be randomised with a 1:1 ratio. The primary outcome is the duration of weaning from mechanical ventilation, defined as the number of days between randomisation and successful extubation (alive without reintubation nor tracheostomy within the 7 days after extubation) at day 28. Secondary outcomes include daily and cumulated fluid balance, metabolic and haemodynamic complications, ventilator-associated pneumonia, weaning complications, number of ventilator-free days, total duration of mechanical ventilation, the length of stay in ICU and mortality in ICU, in hospital and, at day 28. A subgroup analysis for the primary outcome is planned in patients with kidney injury (Kidney Disease: Improving Global Outcomes class 2 or more) at the time of randomisation. ETHICS AND DISSEMINATION: The study has been approved by the ethics committee (Comité de Protection des Personnes Paris 1) and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04050007. PROTOCOL VERSION: V.1; 12 March 2019.

Macrophage Activation in COVID-19 Patients in Intensive Care Unit.

We report six cases of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, admitted to intensive care unit (ICU), for whom bone marrow aspirate revealed hemophagocytosis. We compared their clinical presentation and laboratory findings to those that can be encountered during a hemophagocytic lymphohistiocytosis. These observations might evoke a macrophage activation mechanism different from the one encountered in the hemophagocytic lymphohistiocytosis (HLH).

Influence of deprivation on initial severity and prognosis of patients admitted to the ICU: the prospective, multicentre, observational IVOIRE cohort study.

BACKGROUND: The influence of socioeconomic status on patient outcomes is unclear. We assessed the impact of socioeconomic deprivation on severity of illness at intensive care unit (ICU) admission, and on the risk of death at 3 months after ICU admission. METHODS: The IVOIRE study was a prospective, observational, multicentre cohort study in the ICU of 8 participating hospitals in France, including patients aged ≥ 18 years admitted to the ICU and receiving at least one life support therapy for organ failure. The primary outcomes were severity at admission (assessed by SAPSII score), and mortality at 3 months. Socioeconomic data were obtained from interviews with patients or family. Deprivation was assessed using the EPICES score. RESULTS: Among 1294 patents included between 2013 and 2016, 629 (48.6%) were classed as deprived and differed significantly from non-deprived subjects in terms of sociodemographic characteristics and pre-existing conditions. The mean SAPS II score at admission was 50.1 ± 19.4 in deprived patients and 52.3 ± 17.3 in non-deprived patients, with no significant difference by multivariable analysis (ß = - 1.85 [95% CI - 3.86; + 0.16, p = 0.072]). The proportion of death was 31.1% at 3 months, without significant differences between deprived and non-deprived patients, even after adjustment for confounders. CONCLUSIONS: Deprivation is frequent in patients admitted to the ICU and is not associated with disease severity at admission, or with mortality at 3 months between deprived and non-deprived patients. Trial registration The IVOIRE cohort is registered with ClinicalTrials.gov under the identifier NCT01907581, registration date 17/7/2013.

T-piece versus pressure-support ventilation for spontaneous breathing trials before extubation in patients at high risk of reintubation: protocol for a multicentre, randomised controlled trial (TIP-EX).

INTRODUCTION: In intensive care unit (ICU), the decision of extubation is a critical time because mortality is particularly high in case of reintubation. To reduce that risk, guidelines recommend to systematically perform a spontaneous breathing trial (SBT) before extubation in order to mimic the postextubation physiological conditions. SBT is usually performed with a T-piece disconnecting the patient from the ventilator or with low levels of pressure-support ventilation (PSV). However, work of breathing is lower during PSV than during T-piece. Consequently, while PSV trial may hasten extubation, it may also increase the risk of reintubation. We hypothesise that, compared with T-piece, SBT performed using PSV may hasten extubation without increasing the risk of reintubation. METHODS AND ANALYSIS: This study is an investigator-initiated, multicentre randomised controlled trial comparing T-piece vs PSV for SBTs in patients at high risk of reintubation in ICUs. Nine hundred patients will be randomised with a 1:1 ratio in two groups according to the type of SBT. The primary outcome is the number of ventilator-free days at day 28, defined as the number of days alive and without invasive mechanical ventilation between the initial SBT (day 1) and day 28. Secondary outcomes include the number of days between the initial SBT and the first extubation attempt, weaning difficulty, the number of patients extubated after the initial SBT and not reintubated within the following 72 hours, the number of patients extubated within the 7 days following the initial SBT, the number of patients reintubated within the 7 days following extubation, in-ICU length of stay and mortality in ICU, at day 28 and at day 90. ETHICS AND DISSEMINATION: The study has been approved by the central ethics committee 'Ile de France V' (2019-A02151-56) and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04227639.

High-flow nasal oxygen therapy alone or with non-invasive ventilation in immunocompromised patients admitted to ICU for acute hypoxemic respiratory failure: the randomised multicentre controlled FLORALI-IM protocol.

INTRODUCTION: Non-invasive ventilation (NIV) is recommended as first-line therapy in respiratory failure of critically ill immunocompromised patients as it can decrease intubation and mortality rates as compared with standard oxygen. However, its recommendation is only conditional. Indeed, the use of NIV in this setting has been challenged recently based on results of trials finding similar outcomes with or without NIV or even deleterious effects of NIV. To date, NIV has been compared with standard oxygen but not to high-flow nasal oxygen therapy (HFOT) in immunocompromised patients. Several studies have found lower mortality rates using HFOT alone than when using HFOT with NIV sessions in patients with de novo respiratory failure, and even in immunocompromised patients. We are hypothesising that HFOT alone is more effective than HFOT with NIV sessions and reduces mortality of immunocompromised patients with acute hypoxemic respiratory failure. METHODS AND ANALYSIS: This study is an investigator-initiated, multicentre randomised controlled trial comparing HFOT alone or with NIV in immunocompromised patients admitted to intensive care unit (ICU) for severe acute hypoxemic respiratory failure. Around 280 patients will be randomised with a 1:1 ratio in two groups. The primary outcome is the mortality rate at day 28 after inclusion. Secondary outcomes include the rate of intubation in each group, length of ICU and hospital stay and mortality up to day 180. ETHICS AND DISSEMINATION: The study has been approved by the ethics committee and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02978300.

Daily use of extracorporeal CO2 removal in a critical care unit: indications and results.

BACKGROUND: While outcome improvement with extracorporeal CO2 removal (ECCO2R) is not demonstrated, a strong pathophysiological rational supports its use in the setting of acute respiratory distress syndrome (ARDS) and COPD exacerbation. We aimed to describe our single-center experience of ECCO2R indications and outcome. METHODS: Patients treated with ECCO2R in our medial ICU, from March 2014 to November 2017, were retrospectively enrolled. Primary end point was evolution of ventilator settings during the two first days following ECCO2R start. RESULTS: Thirty-three patients received ECCO2R. Seventeen were managed with Hemolung®, 10 with Prismalung®, 4 with ILA®, and 2 with Cardiohelp®. Indications for ECCO2R were mild or moderate ARDS (n = 16), COPD exacerbation (n = 11), or uncontrolled hypercapnia due to other causes (n = 6). Four patients were not intubated at the time of ECCO2R start. Median duration of ECCO2R treatment was 7 days [5-10]. In ARDS patients, between baseline and day 2, median tidal volume and driving pressure decreased from 5.3 [4.4-5.9] mL/kg and 10 [8-15] to 3.8 [3.3-4.1] mL/kg and 9 [8-11], respectively. Prone positioning was performed in 10 of the 16 patients, without serious adverse event. In COPD patients, between baseline and day 2, median ventilation minute and PaCO2 decreased significantly from respectively 7.6 [6.6-8.7] L/min and 9.4 [8.4-10.1] kPa to 5.8 [4.9-6.2] L/min and 6 [5.3-6.8] kPa. Four out of 11 COPD patients were extubated while on ECCO2R. Device thrombosis occurred in 5 patients (15%). Hemolysis was documented in 16 patients (48%). One patient died of intracranial hemorrhage, while on ECCO2R. Twenty-four patients were discharged from ICU alive. Twenty-eight day mortality was 31% in ARDS, 9% in COPD patients, and 50% in other causes of refractory hypercapnic respiratory failure. CONCLUSION: ECCO2R was useful to apply ultra-protective ventilation among ARDS patients and improved PaCO2, pH, and minute ventilation in COPD patients.

Prevalence and outcome of heparin-induced thrombocytopenia diagnosed under veno-arterial extracorporeal membrane oxygenation: a retrospective nationwide study.

PURPOSE: Thrombocytopenia is a frequent and serious adverse event in patients treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for refractory cardiogenic shock. Similarly to postcardiac surgery patients, heparin-induced thrombocytopenia (HIT) could represent the causative underlying mechanism. However, the epidemiology as well as related mortality regarding HIT and VA-ECMO remains largely unknown. We aimed to define the prevalence and associated 90-day mortality of HIT diagnosed under VA-ECMO. METHODS: This retrospective study included patients under VA-ECMO from 20 French centers between 2012 and 2016. Selected patients were hospitalized for more than 3 days with high clinical suspicion of HIT and positive anti-PF4/heparin antibodies. Patients were classified according to results of functional tests as having either Confirmed or Excluded HIT. RESULTS: A total of 5797 patients under VA-ECMO were screened; 39/5797 met the inclusion criteria, with HIT confirmed in 21/5797 patients (0.36% [95% CI] [0.21-0.52]). Fourteen of 39 patients (35.9% [20.8-50.9]) with suspected HIT were ultimately excluded because of negative functional assays. Drug-induced thrombocytopenia tended to be more frequent in Excluded HIT at the time of HIT suspicion (p = 0.073). The platelet course was similar between Confirmed and Excluded HIT (p = 0.65). Mortality rate was 33.3% [13.2-53.5] in Confirmed and 50% [23.8-76.2] in Excluded HIT (p = 0.48). CONCLUSIONS: Prevalence of HIT among patients under VA-ECMO is extremely low at 0.36% with an associated mortality rate of 33.3%, which appears to be in the same range as that observed in patients treated with VA-ECMO without HIT. In addition, HIT was ultimately ruled out in one-third of patients with clinical suspicion of HIT and positive anti-PF4/heparin antibodies.

Estimation of critically ill patients' complaints by the nurse, the physician and the patient's family: A prospective comparative study.

OBJECTIVES: To evaluate the ability of the families of critically ill patients and of the intensive care team caring for the patient to communicate and accurately identify patients' complaints. DESIGN: The complaints of critically ill patients were evaluated by a psychologist using a list of 12 items. The same day as the patient interview, the psychologist collected an estimation of the patient's complaints from the family, the nurse and the physician. SETTING: 20-bed Intensive Care Unit in a large University Hospital. MAIN OUTCOME MEASURES: Patients' complaints. RESULTS: 51 patients were included. The most frequently reported complaints were insomnia, the inability to talk and presence of a tracheal tube. Patients reported a significantly higher prevalence of "misunderstanding" than that estimated by the nurses (55% vs 33%, p=0.045). The reported prevalence of "inability to talk" as the main complaint was significantly higher among patients than estimated by nurses and physicians (16% vs 2%, p=0.03 and 16% vs 2%, p=0.03 respectively). For the analysis of the individual complaints, there was a poor agreement between the patients and the other respondents. CONCLUSION: This study found that the estimation of critically ill patients' complaints by their families, nurses and physicians was largely suboptimal.

Clinical spectrum and therapeutic management of systemic lupus erythematosus-associated macrophage activation syndrome: A study of 103 episodes in 89 adult patients.

OBJECTIVES: Macrophage activation syndrome (MAS) is a life-threatening hyperinflammatory syndrome that can occur during systemic lupus erythematosus (SLE). Data on MAS in adult SLE patients are very limited. The aim of this study is to describe the clinical characteristics, laboratory findings, treatments, and outcomes of a large series of SLE-associated MAS. METHODS: We conducted a retrospective study that included 103 episodes of MAS in 89 adult patients with SLE. RESULTS: 103 episodes in 89 adult patients were analyzed. Median age at first MAS episode was 32 (18-80) years. MAS was inaugural in 41 patients (46%).Thirteen patients relapsed. Patients had the following features: fever (100% episodes), increased serum levels of AST (94.7%), LDH (92.3%), CRP (84.5%), ferritin (96%), procalcitonin (41/49 cases). Complications included myocarditis (n=22), acute lung injury (n=15) and seizures (n=11). In 33 episodes, patients required hospitalization in an ICU and 5 died. Thrombocytopenia and high CRP levels were associated independently with an increased risk for ICU admission. High dose steroids alone as first line therapy induced remission in 37/57 cases (65%). Additional medications as first or second line therapies included IV immunoglobulins (n=22), cyclophosphamide (n=23), etoposide (n=11), rituximab (n=3). Etoposide and cyclophosphamide-based regimens had the best efficacy. CONCLUSION: MAS is a severe complication and is often inaugural. High fever and high levels of AST, LDH, CRP, ferritin and PCT should be considered as red flags for early diagnosis. High dose steroids lead to remission in two third of cases. Cyclophosphamide or etoposide should be considered for uncontrolled/severe forms.