Search

Abstract Background Non-ventilator-associated ICU-acquired pneumonia (NV-ICU-AP), a nosocomial pneumonia that is not related to invasive mechanical ventilation (IMV), has been less studied than ventilator-associated pneumonia, and never in the context of patients in an ICU for severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD), a common cause of ICU admission. This study aimed to determine the factors associated with NV-ICU-AP occurrence and assess the association between NV-ICU-AP and the outcomes of these patients. Methods Data were extracted from the French ICU database, OutcomeRea™. Using survival analyses with competing risk management, we sought the factors associated with the occurrence of NV-ICU-AP. Then we assessed the association between NV-ICU-AP and mortality, intubation rates, and length of stay in the ICU. Results Of the 844 COPD exacerbations managed in ICUs without immediate IMV, NV-ICU-AP occurred in 42 patients (5%) with an incidence density of 10.8 per 1,000 patient-days. In multivariate analysis, prescription of antibiotics at ICU admission (sHR, 0.45 [0.23; 0.86], p = 0.02) and no decrease in consciousness (sHR, 0.35 [0.16; 0.76]; p

Abstract Background Inhaled nitric oxide (iNO) has been widely used in patients with COVID-19-related acute respiratory distress syndrome (C-ARDS), though its physiological effects and outcome are debated in this setting. The objective of this cohort study was to describe the modalities of iNO use, clinical response, and outcomes in a large cohort of C-ARDS patients. Methods Multicentre, retrospective cohort study conducted in France. Results From end February to December 2020, 300 patients (22.3% female) were included, 84.5% were overweight and 69.0% had at least one comorbidity. At ICU admission, their median (IQR) age, SAPS II, and SOFA score were 66 (57–72) years, 37 (29–48), and 5 (3–8), respectively. Patients were all ventilated according to a protective ventilation strategy, and 68% were prone positioned before iNO initiation. At iNO initiation, 2%, 37%, and 61% of patients had mild, moderate, and severe ARDS, respectively. The median duration of iNO treatment was 2.8 (1.1–5.5) days with a median dosage of 10 (7–13) ppm at initiation. Responders (PaO2/FiO2 ratio improving by 20% or more) represented 45.7% of patients at 6 h from iNO initiation. The severity of ARDS was the only predictive factor associated with iNO response. Among all evaluable patients, the crude mortality was not significantly different between responders at 6 h and their counterparts. Of the 62 patients with refractory ARDS (who fulfilled extracorporeal membrane oxygenation criteria before iNO initiation), 32 (51.6%) no longer fulfilled these criteria after 6 h of iNO. The latter showed significantly lower mortality than the other half (who remained ECMO eligible), including after confounder adjustment (adjusted OR: 0.23, 95% CI 0.06, 0.89, p = 0.03). Conclusions Our study reports the benefits of iNO in improving arterial oxygenation in C-ARDS patients. This improvement seems more relevant in the most severe cases. In patients with ECMO criteria, an iNO-driven improvement in gas exchange was associated with better survival. These results must be confirmed in well-designed prospective studies.

Background: Cardiac injury caused by a sharp object is a medical and surgical therapeutic challenge. Mortality risk factors have been identified but there are major discrepancies in the literature. The aim of this study was to analyse the management of victims of penetrating cardiac injuries before and after admission to hospital and the anatomical characteristics of these injuries in order to facilitate diagnosis of the most critical patients. Methods: To carry out this study, we conducted a retrospective analytical study with epidemiological data on victims of penetrating cardiac injuries. We included two types of patients, with those who underwent autopsy in our institution after death from sharp injury to the heart or great vessels and those who survived with treatment in the emergency department or intensive care unit between January 2015 and February 2022. Results: We included 30 autopsied patients and 12 survivors aged between 18 and 73 years. Higher mortality was associated with prehospital or in-hospital cardiorespiratory arrest (OR = 4, CI [1.71–9.35]), preoperative mechanical ventilation (OR = 10, CI [1.53–65.41]), preoperative catecholamines (OR = 7, CI [1.12–6.29]), preoperative and perioperative adrenaline (OR = 13, CI [1.98–85.46] and [1.98–85.46]), penetrating cardiac injury (OR = 14, CI [2.10–93.22]), multiple cardiac injuries (OR = 1.5, CI [1.05–2.22]) and an Organ Injury Scaling of the American Association for the Surgery of Trauma (AAST-OIS) score of 5 (OR = 2.9, CI [1.04–8.54]; p = 0.0329) with an AUC-ROC curve value of 0.708 (CI [0.543–0.841]). Conclusions: This study identified risk mortality factors in penetrating cardiac injury patients. These findings can help improve the diagnosis and management of these patients. The AAST-OIS score may be a good tool to diagnose critical patients.

In the early months of the outbreak (2020–2022), COVID-19 was responsible for acute respiratory distress syndrome (ARDS) and an exceptional number of intensive care unit (ICU) admissions. Weaning difficulties from invasive mechanical ventilation (IMV) and many deaths related to COVID-19 were associated with persistent pulmonary hyperinflammation leading to pulmonary fibrosis and sometimes, in the first wave of the pandemic and before the use of dexamethasone was introduced, pulmonary cystic necrosis. A 72-year-old man hospitalized with severe COVID-19 required IMV and died on day 31 of refractory ARDS. Postmortem examination of the lungs found obliterative endotheliitis proximal to pulmonary cystic necrosis. The presence of SARS-CoV-2 envelope and complement/lectin (MASP-2) deposits near the endotheliitis lesions suggested that the virus acted directly on vascular involvement by a complement-mediated mechanism. Together with classic features of ARDS (epithelial lesions and diffuse alveolar damage), endothelial involvement with endotheliitis was the hallmark of severe COVID-19. Corticosteroids and complement blockade were sometimes beneficial for treating severe COVID-19, perhaps by preventing microvascular damage.

IntroductionAcute exacerbation of chronic obstructive pulmonary disease (COPD) is a frequent cause of intensive care unit (ICU) admission. However, data are scarce and conflicting regarding the impact of systemic corticosteroid treatment in critically ill patients with acute exacerbation of COPD. The aim of the study was to assess the impact of systemic corticosteroids on the occurrence of death or need for continuous invasive mechanical ventilation at day 28 after ICU admission.MethodsIn the OutcomeReaTM prospective French national ICU database, we assessed the impact of corticosteroids at admission (daily dose ≥ 0.5 mg/kg of prednisone or equivalent during the first 24 hours ICU stay) on a composite outcome (death or invasive mechanical ventilation) using an inverse probability treatment weighting.ResultsBetween January 1, 1997 and December 31, 2018, 391 out of 1,247 patients with acute exacerbations of COPDs received corticosteroids at ICU admission. Corticosteroids improved the main composite endpoint (OR = 0.70 [0.49; 0.99], p = 0.044. However, for the subgroup of most severe COPD patients, this did not occur (OR = 1.12 [0.53; 2.36], p = 0. 770). There was no significant impact of corticosteroids on rates of non-invasive ventilation failure, length of ICU or hospital stay, mortality or on the duration of mechanical ventilation. Patients on corticosteroids had the same prevalence of nosocomial infections as those without corticosteroids, but more glycaemic disorders.ConclusionUsing systemic corticosteroids for acute exacerbation of COPD at ICU admission had a positive effect on a composite outcome defined by death or need for invasive mechanical ventilation at day 28.

OBJECTIVES:. To determine the effect of the awake prone position (APP) on gas exchange and the work of breathing in spontaneously breathing patients with COVID-19–associated acute hypoxemic respiratory failure (AHRF) supported by high-flow nasal oxygen. DESIGN:. Prospective randomized physiologic crossover multicenter trial. SETTINGS:. Four ICUs in Marseille, France. PATIENTS:. Seventeen patients with laboratory-confirmed COVID-19 pneumonia and Pao2/Fio2 less than or equal to 300 mm Hg while treated with high-flow nasal cannula oxygen therapy. INTERVENTIONS:. Periods of APP and semirecumbent position (SRP) were randomly applied for 2 hours and separated by a 2-hour washout period. MEASUREMENTS AND MAIN RESULTS:. Arterial blood gases, end-tidal CO2. and esophageal pressure were recorded prior to and at the end of each period. Inspiratory muscle effort was assessed by measuring the esophageal pressure swing (∆PES) and the simplified esophageal pressure–time product (sPTPES). The other endpoints included physiologic dead space to tidal volume ratio (VD/VT) and the transpulmonary pressure swing. The APP increased the Pao2/Fio2 from 84 Torr (61–137 Torr) to 208 Torr (114–226 Torr) (p = 0.0007) and decreased both the VD/VT and the respiratory rate from 0.54 (0.47–0.57) to 0.49 (0.45–0.53) (p = 0.012) and from 26 breaths/min (21–30 breaths/min) to 21 breaths/min (19–22 breaths/min), respectively (p = 0.002). These variables remained unchanged during the SRP. The ∆PES and sPTPES per breath were unaffected by the position. However, the APP reduced the sPTPES per minute from 225 cm H2O.s.m–1 (176–332 cm H2O.s.m–1) to 174 cm H2O.s.m–1 (161–254 cm H2O.s.m–1) (p = 0.049). CONCLUSIONS:. In spontaneously breathing patients with COVID-19–associated AHRF supported by high-flow nasal oxygen, the APP improves oxygenation and reduces the physiologic dead space, respiratory rate, and work of breathing per minute.

BackgroundAspiration pneumonia is the most common respiratory complication following out-of-hospital cardiac arrests (OHCA). Alpha-amylase (α-amylase) in pulmonary secretions is a biomarker of interest in detecting inhalation. The main goal of this study is to evaluate the performance of bronchoalveolar levels of α-amylase in early diagnosis of aspiration pneumonia, in patients admitted to intensive care unit (ICU) after OHCA.MethodsThis is a prospective single-center trial, led during 5 years (July 2015 to September 2020). We included patients admitted to ICU after OHCA. A protected specimen bronchial brushing and a mini-bronchoalveolar lavage (mini-BAL) were collected during the first 6 h after admission. Dosage of bronchial α-amylase and standard bacterial analysis were performed. Investigators confirmed pneumonia diagnosis using clinical, radiological, and microbiological criteria. Every patient underwent targeted temperature management.Results88 patients were included. The 34% (30 patients) developed aspiration pneumonia within 5 days following admission. The 55% (17) of pneumonias occurred during the first 48 h. The 57% of the patients received a prophylactic antibiotic treatment on their admission day. ICU mortality was 50%. Median value of bronchial α-amylase did not differ whether patients had aspiration pneumonia (15 [0–94]) or not (3 [0–61], p = 0,157). Values were significantly different concerning early-onset pneumonia (within 48 h) [19 (7–297) vs. 3 (0–82), p = 0,047]. If one or more microorganisms were detected in the initial mini-BAL, median value of α-amylase was significantly higher [25 (2–230)] than in sterile cultures (2 [0–43], p = 0,007). With an 8.5 IU/L cut-point, sensitivity and specificity of α-amylase value for predicting aspiration pneumonia during the first 2 days were respectively 74 and 62%. True positive and negative rates were respectively 44 and 86%. The area under the ROC curve was 0,654 (CI 95%; 0,524–0,785). Mechanical ventilation duration, length of ICU stay, and mortality were similar in both groups.ConclusionIn our study, dosage of bronchial α-amylase was not useful in predicting aspiration pneumonia within the first 5 days after ICU admission for OHCA. Performance in predicting early-onset pneumonia was moderate.

Abstract Background Most prognostic studies in acute stroke patients requiring invasive mechanical ventilation are outdated and have limitations such as single-center retrospective designs. We aimed to study the association of ICU admission factors, including the reason for intubation, with 1-year survival of acute stroke patients requiring mechanical ventilation. Methods We conducted a secondary data use analysis of a prospective multicenter database (14 ICUs) between 1997 and 2016 on consecutive ICU stroke patients requiring mechanical ventilation at admission. We excluded patients with stroke of traumatic origin, subdural hematoma or cerebral venous thrombosis. The primary outcome was survival 1 year after ICU admission. Factors associated with the primary outcome were identified using a multivariable Cox model stratified on inclusion center. Results We identified 419 patients (age 68 [58–76] years, males 60%) with a Glasgow coma score (GCS) of 4 [3–8] at admission. Stroke subtypes were acute ischemic stroke (AIS, 46%), intracranial hemorrhage (ICH, 42%) and subarachnoid hemorrhage (SAH, 12%). At 1 year, 96 (23%) patients were alive. Factors independently associated with decreased 1-year survival were ICH and SAH stroke subtypes, a lower GCS score at admission, a higher non-neurological SOFA score. Conversely, patients receiving acute-phase therapy had improved 1-year survival. Intubation for acute respiratory failure or coma was associated with comparable survival hazard ratios, whereas intubation for seizure was not associated with a worse prognosis than for elective procedure. Survival did not improve over the study period, but patients included in the most recent period had more comorbidities and presented higher severity scores at admission. Conclusions In acute stroke patients requiring mechanical ventilation, the reason for intubation and the opportunity to receive acute-phase stroke therapy were independently associated with 1-year survival. These variables could assist in the decision process regarding the initiation of mechanical ventilation in acute stroke patients.

Objectives: In a conventional hospital ward, we used high-flow nasal oxygen (HFNO) to treat elderly COVID-19 patients noneligible for intensive care unit transfer. Methods: This study was conducted in the Institut Hospitalo-Universitaire Méditerranée Infection, Assistance Publique-Hôpitaux de Marseille (AP-HM), France. We used high-flow nasal oxygen (HFNO) in our conventional infectious disease ward from 15 September 2020 for elderly patients noneligible for intensive care unit transfer. Results: Of the 44 patients (median age 83 years (57–94), mean: 80.25), 61.4% (27/44) were men. The median Charlson score was 7 (1–15). The median of the NEWS-2 score upon admission was 8 (3–11) and was 10 at the time of initiation of HFNO. The median PaO2/FiO2 ratio was 103 (71–151) prior to HNFO initiation. Among the 44 patients, 16 patients (36.4%) had been weaned from HFNO, and 28 patients had died (63.6%). Conclusions: In this preliminary report, we observed that HFNO saved the lives of one-third of elderly COVID-19 patients who would have systematically died.

Venovenous extracorporeal membrane oxygenation (VV-ECMO) is an adjuvant treatment for severe acute respiratory distress syndrome (ARDS) with refractory hypoxemia. Contraindications to therapeutic anticoagulation must be ruled out prior to ECMO implementation. We report the case of a 17-year-old male admitted in intensive care unit (ICU) for penetrating chest trauma due to multiple gunshot wounds. The body computed tomography (body CT scan) documented right pulmonary contusions and a homolateral hemothorax. His condition rapidly deteriorated with refractory hypoxemia due to lung contusion requiring invasive mechanical ventilation (IMV) and polytransfused hemorrhagic shock. During his stay in ICU, venovenous ECMO (VV-ECMO) was implemented twice, firstly for trauma-induced ARDS and secondly after thoracic surgery. This case emphasizes the successful use of VV-ECMO in posttraumatic ARDS without increasing the risk of bleeding.

Objectives:. The determinants of decisions to limit life support (withholding or withdrawal) in ventilated stroke patients have been evaluated mainly for patients with intracranial hemorrhages. We aimed to evaluate the frequency of life support limitations in ventilated ischemic and hemorrhagic stroke patients compared with a nonbrain-injured population and to determine factors associated with such decisions. Design:. Multicenter prospective French observational study. Setting:. Fourteen ICUs of the French OutcomeRea network. PATIENTS:. From 2005 to 2016, we included stroke patients and nonbrain-injured patients requiring invasive ventilation within 24 hours of ICU admission. INTERVENTION:. None. MEASUREMENTS AND MAIN RESULTS:. We identified 373 stroke patients (ischemic, n = 167 [45%]; hemorrhagic, n = 206 [55%]) and 5,683 nonbrain-injured patients. Decisions to limit life support were taken in 41% of ischemic stroke cases (vs nonbrain-injured patients, subdistribution hazard ratio, 3.59 [95% CI, 2.78–4.65]) and in 33% of hemorrhagic stroke cases (vs nonbrain-injured patients, subdistribution hazard ratio, 3.9 [95% CI, 2.97–5.11]). Time from ICU admission to the first limitation was longer in ischemic than in hemorrhagic stroke (5 [3–9] vs 2 d [1–6] d; p < 0.01). Limitation of life support preceded ICU death in 70% of ischemic strokes and 45% of hemorrhagic strokes (p < 0.01). Life support limitations in ischemic stroke were increased by a vertebrobasilar location (vs anterior circulation, subdistribution hazard ratio, 1.61 [95% CI, 1.01–2.59]) and a prestroke modified Rankin score greater than 2 (2.38 [1.27–4.55]). In hemorrhagic stroke, an age greater than 70 years (2.29 [1.43–3.69]) and a Glasgow Coma Scale score less than 8 (2.15 [1.08–4.3]) were associated with an increased risk of limitation, whereas a higher nonneurologic admission Sequential Organ Failure Assessment score was associated with a reduced risk (per point, 0.89 [0.82–0.97]). Conclusions:. In ventilated stroke patients, decisions to limit life support are more than three times more frequent than in nonbrain-injured patients, with different timing and associated risk factors between ischemic and hemorrhagic strokes.

Background: Adult hemophagocytic lymphohistiocytosis (HLH) is highly lethal in the ICU. The diagnostic and therapeutic emergency that HLH represents is compounded by its unknown pathophysiological mechanisms. Here, we report on a large cohort of adult HLH in the ICU (ICU-HLH). We analyzed prognostic factors associated with mortality to define the diagnostic and therapeutic challenges in this specific population.Methods: This retrospective study included adult patients diagnosed with HLH in four ICUs in Marseille, France between 2010 and 2020. Patients who fulfilled the HLH-2004 criteria (≥ 4/8) and/or had an HScore ≥ 169 were diagnosed with HLH. HLH was categorized into four groups according to etiology: sepsis-associated HLH, intracellular infection-associated HLH, malignancy-associated HLH, and idiopathic HLH.Results: Two hundred and sixty patients were included: 121 sepsis-associated HLH (47%), 84 intracellular infection-associated HLH (32%), 28 malignancy-associated HLH (11%), and 27 idiopathic HLH (10%). The ICU mortality rate reached 57% (n = 147/260) without a statistical difference between etiological groups. Independent factors associated with mortality in multivariate analysis included age (OR (5 years) = 1.31 [1.16–1.48], p < 0.0001), SOFA score at ICU admission (OR = 1.37 [1.21–1.56], p < 0.0001), degradation of the SOFA score between ICU arrival and HLH diagnosis (Delta SOFA) (OR = 1.47 [1.28–1.70], p < 0.0001), the presence of bone-marrow hemophagocytosis (OR = 5.27 [1.11–24.97], p = 0.04), highly severe anemia (OR = 1.44 [1.09–1.91], p = 0.01), and hypofibrinogenemia (OR = 1.21 [1.04–1.41], p = 0.02).Conclusions: In this large retrospective cohort study of critically ill patients, ICU-HLH in adults was associated with a 57% mortality rate, regardless of HLH etiology or specific treatment. Factors independently associated with prognosis included age, presence of hemophagocytosis in bone-marrow aspirates, organ failure at admission, and worsening organ failure during the ICU stay. Whether a rapid diagnosis and the efficacy of specific therapy improve outcome is yet to be prospectively investigated.

Introduction At the time of the worrying emergence and spread of bacterial resistance, reducing the selection pressure by reducing the exposure to antibiotics in patients with community-acquired pneumonia (CAP) is a public health issue. In this context, the combined use of molecular tests and biomarkers for guiding antibiotics discontinuation is attractive. Therefore, we have designed a trial comparing an integrated approach of diagnosis and treatment of severe CAP to usual care.Methods and analysis The multiplex PCR and procalcitonin to reduce duration of antibiotics exposure in patients with severe-CAP (MULTI-CAP) trial is a multicentre (n=20), parallel-group, superiority, open-label, randomised trial. Patients are included if adult admitted to intensive care unit for a CAP. Diagnosis of pneumonia is based on clinical criteria and a newly appeared parenchymal infiltrate. Immunocompromised patients are excluded. Subjects are randomised (1:1 ratio) to either the intervention arm (experimental strategy) or the control arm (usual strategy). In the intervention arm, the microbiological diagnosis combines a respiratory multiplex PCR (mPCR) and conventional microbiological investigations. An algorithm of early antibiotic de-escalation or discontinuation is recommended, based on mPCR results and the procalcitonin value. In the control arm, only conventional microbiological investigations are performed and antibiotics de-escalation remains at the clinician’s discretion. The primary endpoint is the number of days alive without any antibiotic from the randomisation to day 28. Based on our hypothesis of 2 days gain in the intervention arm, we aim to enrol a total of 450 patients over a 30-month period.Ethics and dissemination The MULTI-CAP trial is conducted according to the principles of the Declaration of Helsinki, is registered in Clinical Trials and has been approved by the Committee for Protection of Persons and the National French Drug Safety Agency. Written informed consents are obtained from all the patients (or representatives). The results will be disseminated through educational institutions, submitted to peer-reviewed journals for publication and presented at medical congresses.Trial registration number NCT03452826; Pre-results.

Objectives:. About 5% of patients with coronavirus disease-2019 are admitted to the ICU for acute hypoxemic respiratory failure. Opinions differ on whether invasive mechanical ventilation should be used as first-line therapy over noninvasive oxygen support. The aim of the study was to assess the effect of early invasive mechanical ventilation in coronavirus disease-2019 with acute hypoxemic respiratory failure on day-60 mortality. Design:. Multicenter prospective French observational study. Setting:. Eleven ICUs of the French OutcomeRea network. Patients:. Coronavirus disease-2019 patients with acute hypoxemic respiratory failure (Pao2/Fio2 ≤ 300 mm Hg), without shock or neurologic failure on ICU admission, and not referred from another ICU or intermediate care unit were included. Intervention:. We compared day-60 mortality in patients who were on invasive mechanical ventilation within the first 2 calendar days of the ICU stay (early invasive mechanical ventilation group) and those who were not (nonearly invasive mechanical ventilation group). We used a Cox proportional-hazard model weighted by inverse probability of early invasive mechanical ventilation to determine the risk of death at day 60. Measurement and Main Results:. The 245 patients included had a median (interquartile range) age of 61 years (52–69 yr), a Simplified Acute Physiology Score II score of 34 mm Hg (26–44 mm Hg), and a Pao2/Fio2 of 121 mm Hg (90–174 mm Hg). The rates of ICU-acquired pneumonia, bacteremia, and the ICU length of stay were significantly higher in the early (n = 117 [48%]) than in the nonearly invasive mechanical ventilation group (n = 128 [52%]), p < 0.01. Day-60 mortality was 42.7% and 21.9% in the early and nonearly invasive mechanical ventilation groups, respectively. The weighted model showed that early invasive mechanical ventilation increased the risk for day-60 mortality (weighted hazard ratio =1.74; 95% CI, 1.07–2.83, p=0.03). Conclusions:. In ICU patients admitted with coronavirus disease-2019-induced acute hypoxemic respiratory failure, early invasive mechanical ventilation was associated with an increased risk of day-60 mortality. This result needs to be confirmed.

Objectives In severe COVID-19 pneumonia, the appropriate timing and dosing of corticosteroids (CS) is not known. Patient subgroups for which CS could be more beneficial also need appraisal. The aim of this study was to assess the effect of early CS in COVID-19 pneumonia patients admitted to the ICU on the occurrence of 60-day mortality, ICU-acquired-bloodstream infections(ICU-BSI), and hospital-acquired pneumonia and ventilator-associated pneumonia(HAP-VAP). Methods We included patients with COVID-19 pneumonia admitted to 11 ICUs belonging to the French OutcomeReaTM network from January to May 2020. We used survival models with ponderation with inverse probability of treatment weighting (IPTW). Results The study population comprised 303 patients having a median age of 61.6 (53–70) years of whom 78.8% were male and 58.6% had at least one comorbidity. The median SAPS II was 33 (25–44). Invasive mechanical ventilation was required in 34.8% of the patients. Sixty-six (21.8%) patients were in the Early-C subgroup. Overall, 60-day mortality was 29.4%. The risks of 60-day mortality (IPTWHR = 0.86;95% CI 0.54 to 1.35, p = 0.51), ICU-BSI and HAP-VAP were similar in the two groups. Importantly, early CS treatment was associated with a lower mortality rate in patients aged 60 years or more (IPTWHR, 0.53;95% CI, 0.3–0.93; p = 0.03). In contrast, CS was associated with an increased risk of death in patients younger than 60 years without inflammation on admission (IPTWHR = 5.01;95% CI, 1.05, 23.88; p = 0.04). Conclusion For patients with COVID-19 pneumonia, early CS treatment was not associated with patient survival. Interestingly, inflammation and age can significantly influence the effect of CS.

Background Heterogeneity in sepsis expression is multidimensional, including highly disparate data such as the underlying disorders, infection source, causative micro-organismsand organ failures. The aim of the study is to identify clusters of patients based on clinical and biological characteristic available at patients’ admission. Methods All patients included in a national prospective multicenter ICU cohort OUTCOMEREA and admitted for sepsis or septic shock (Sepsis 3.0 definition) were retrospectively analyzed. A hierarchical clustering was performed in a training set of patients to build clusters based on a comprehensive set of clinical and biological characteristics available at ICU admission. Clusters were described, and the 28-day, 90-day, and one-year mortality were compared with log-rank rates. Risks of mortality were also compared after adjustment on SOFA score and year of ICU admission. Results Of the 6,046 patients with sepsis in the cohort, 4,050 (67%) were randomly allocated to the training set. Six distinct clusters were identified: young patients without any comorbidities, admitted in ICU for community-acquired pneumonia (n = 1,603 (40%)); young patients without any comorbidities, admitted in ICU for meningitis or encephalitis (n = 149 (4%)); elderly patients with COPD, admitted in ICU for bronchial infection with few organ failures (n = 243 (6%)); elderly patients, with several comorbidities and organ failures (n = 1,094 (27%)); patients admitted after surgery, with a nosocomial infection (n = 623 (15%)); young patients with immunosuppressive conditions (e.g., AIDS, chronic steroid therapy or hematological malignancy) (n = 338 (8%)). Clusters differed significantly in early or late mortality (p < .001), even after adjustment on severity of organ dysfunctions (SOFA) and year of ICU admission. Conclusions Clinical and biological features commonly available at ICU admission of patients with sepsis or septic shock enabled to set up six clusters of patients, with very distinct outcomes. Considering these clusters may improve the care management and the homogeneity of patients in future studies.

Abstract 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 Background Neuromuscular blocking agents (NMBAs) have been shown to improve the outcome of the most severely hypoxemic, acute respiratory distress syndrome (ARDS) patients. However, the recommended dosage as well as the necessity of monitoring the neuromuscular block is unknown. We aimed to evaluate the efficiency of a nurse-directed protocol of NMBA administration based on a train-of-four (TOF) assessment to ensure a profound neuromuscular block and decrease cisatracurium consumption compared to an elevated and constant dose regimen. A prospective open labeled study was conducted in two medical intensive care units of two French university hospitals. Consecutive ARDS patients with a PaO2/FiO2 ratio less than 120 with a PEEP ≥5 cm H2O were included. Cisatracurium administration was driven by the nurses according to an algorithm based on TOF monitoring. The primary endpoint was cisatracurium consumption. The secondary endpoints included the quality of the neuromuscular block, the occurrence of adverse events, and the evolution of ventilatory and blood gas parameters. Results Thirty patients were included. NMBAs were used for 54 ± 30 h. According to this new algorithm, the initial dosage of cisatracurium was 11.8 ± 2 mg/h, and the final dosage was 14 ± 4 mg/h, which was significantly lower than in the ACURASYS study protocol (37.5 mg/h with a constant infusion rate (p

Background: Septic shock, a major cause of death in critical care, is the clinical translation of a cytokine storm in response to infection. It can be complicated by sepsis-induced immunosuppression, exemplified by blood lymphopenia, an excess of circulating Treg lymphocytes, and decreased HLA-DR expression on circulating monocytes. Such immunosuppression is associated with secondary infections, and higher mortality. The effect of these biological modifications on circulating innate lymphoid cells (ILCs) has been little studied.Methods: We prospectively enrolled patients with septic shock (Sepsis-3 definition) in the intensive care unit (ICU) of Timone CHU Hospital. ICU controls (trauma, cardiac arrest, neurological dysfunction) were recruited at the same time (NCT03297203). We performed immunophenotyping of adaptive lymphocytes (CD3+ T cells, CD19+ B cells, CD4+CD25+FoxP3+ Treg lymphocytes), ILCs (CD3−CD56+ NK cells and helper ILCs – ILC1, ILC2, and ILC3), and monocytes by flow cytometry on fresh blood samples collected between 24 and 72 h after admission.Results: We investigated adaptive and innate circulating lymphoid cells in the peripheral blood of 18 patients in septic shock, 15 ICU controls, and 30 healthy subjects. As expected, the peripheral blood lymphocytes of all ICU patients showed lymphopenia, which was not specific to sepsis, whereas those of the healthy volunteers did not. Circulating CD3+ T cells and CD3−CD56+ NK cells were mainly concerned. There was a tendency toward fewer Treg lymphocytes and lower HLA-DR expression on monocytes in ICU patients with sepsis. Although the ILC1 count was higher in septic patients than healthy subjects, ILC2, and ILC3 counts were lower in both ICU groups. However, ILC3s within the total ILCs were overrepresented in patients with septic shock. The depression of immune responses has been correlated with the occurrence of secondary infections. We did not find any differences in ILC distribution according to this criterion.Conclusion: All ICU patients exhibit lymphopenia, regardless of the nature (septic or sterile) of the initial medical condition. Specific distribution of circulating ILCs, with an excess of ILC1, and a lack of ILC3, may characterize septic shock during the first 3 days of the disease.

BACKGROUND:Fibroproliferative repair phase of the acute respiratory distress syndrome (ARDS) is followed by a restitutio ad integrum of lung parenchyma or by an irreversible lung fibrosis and patients' death. Transforming Growth Factor-β1 (TGF-β1) is involved in collagen production and lung repair. We investigated whether alveolar TGF-β1 was associated with the presence of fibroproliferation and the outcome of ARDS patients. METHODS:Sixty-two patients were included the first day of moderate-to-severe ARDS. Bronchoalveolar lavage fluid (BALF) was collected at day 3 (and day 7 when the patients were still receiving invasive mechanical ventilation) from the onset of ARDS. Survival was evaluated at day 60. TGF-β1 was measured by immunoassay. The patients were classified as having lung fibroproliferation when the alveolar N-terminal peptide for type III procollagen (NT-PCP-III) measured on day 3 was > 9 μg/L as recently reported. The main objective of this study was to compare the alveolar levels of total TGF-β1 according to the presence or not a lung fibroproliferation at day 3. RESULTS:Forty-three patients (30.6%) presented a fibroproliferation at day 3. BALF levels of total TGF-β1 were not statistically different at day 3 (and at day 7) according to the presence or not lung fibroproliferation. Mortality at day 60 was higher in the group of patients with fibroproliferation as compared with patients with no fibroproliferation (68.4% vs. 18.6% respectively; p < 0.001). Total TGF-β1 measured on BALF at day 3 was not associated with the outcome. Multiple logistic regression showed that the presence of lung fibroproliferation was associated with death. In contrast, TGF-β1 was not independently associated with death. CONCLUSIONS:Pulmonary levels of TGF-β1 during the first week of ARDS were not associated nor with the presence of fibroproliferation neither with death. TGF-β1 should not be used as a biomarker to direct anti-fibrotic therapies.

We report the case of a 36-year-old woman suffering from liver injury caused by the malfunction of a whipped cream siphon. When this patient handled the whipped cream siphon, the screwed metallic upper part of the siphon was suddenly dissociated from its base and came violently striking her right hypochondrium. At first, the severity of injury was underestimated. Subsequently, due to the persistence of pain experienced by the patient, an abdominal CT scan was performed. It highlighted a severe liver injury with rupture of a branch of the hepatic artery. The evolution was favorable after completion of an embolization and a secondary capsular rupture.