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Hemophagocytic lymphohistiocytosis (HLH) may be secondary to cancer or other conditions in adults. We aimed to compare characteristics and outcomes of secondary HLH depending on cancer status among adults. Weight loss over 10 %, headache and enlarged lymph nodes were more frequent in malignant- HLH (M-HLH). Higher phosphatase alkaline level and CRP level were present in M-HLH. Mortality rate tended to be higher in M-HLH group in the first month and during the two years follow-up. Some clinical features and biological abnormalities are associated with an increased probability of malignancy in secondary HLH among adults.

Purpose We hypothesized that a protocol of standardized fixed dose using prolonged infusion during the early phase of sepsis may avoid insufficient β-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 β-lactam concentrations. Conclusion Despite a fixed dose antibiotic administration protocol with prolonged infusion insufficient β-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

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.

Background The prevalence of pressure injuries (PIs) in critically ill patients has been extensively studied, but there is uncertainty regarding the risk factors. The main objective of this study was to describe the prevalence of PIs in critically ill patients. Secondary objectives were to describe PI, use of preventive measures for PI, and factors associated with occurrence of PI in the intensive care unit (ICU). Material and methods This was a 1-day point-prevalence study performed on a weekday in June 2017 in ICUs in France. On the same day, we noted the presence or absence of PI in all hospitalised patients of the participating ICUs, data on the ICUs, and the characteristics of patients and of PI. Results Eighty-six participating ICUs allowed the inclusion of 1228 patients. The prevalence of PI on the study day was 18.7% (95% confidence interval: 16.6–21.0). PIs acquired in the ICU were observed in 12.5% (95% confidence interval: 10.6–14.3) of critically ill patients on the study day. The most frequent locations of PI were the sacrum (57.4%), heel (35.2%), and face (8.7%). Severe forms of PI accounted for 40.8% of all PIs. Antiulcer mattresses were used in 91.5% of the patients, and active and/or passive mobilisation was performed for all the patients. Multiple logistic regression analysis identified longer length of stay in the ICU, a higher Simplified Acute Physiology Score, higher body weight, motor neurological disorder, high-dose steroids, and absence of oral nutrition on the study day as factors independently associated with occurrence of PI in the ICU. Conclusion This large point-prevalence study shows that PIs are found in about one of five critically ill patients despite extensive use of devices for preventing PI. Acquisition of PI in the ICU is strongly related to the patient's severity of illness on admission to the ICU and length of stay in the ICU.

Background Patients with obesity are at higher risk for community-acquired and nosocomial infections. However, no study has specifically evaluated the relationship between obesity and ventilator-associated pneumonia (VAP). Research Question Is obesity associated with an increased incidence of VAP? Study Design and Methods This study was a post hoc analysis of the Impact of Early Enteral vs Parenteral Nutrition on Mortality in Patients Requiring Mechanical Ventilation and Catecholamines (NUTRIREA2) open-label, randomized controlled trial performed in 44 French ICUs. Adults receiving invasive mechanical ventilation and vasopressor support for shock and parenteral nutrition or enteral nutrition were included. Obesity was defined as BMI ≥ 30 kg/m2 at ICU admission. VAP diagnosis was adjudicated by an independent blinded committee, based on all available clinical, radiologic, and microbiologic data. Only first VAP episodes were taken into account. Incidence of VAP was analyzed by using the Fine and Gray model, with extubation and death as competing risks. Results A total of 699 (30%) of the 2,325 included patients had obesity; 224 first VAP episodes were diagnosed (60 and 164 in obese and nonobese groups, respectively). The incidence of VAP at day 28 was 8.6% vs 10.1% in the two groups (hazard ratio, 0.85; 95% CI 0.63-1.14; P = .26). After adjustment on sex, McCabe score, age, antiulcer treatment, and Sequential Organ Failure Assessment at randomization, the incidence of VAP remained nonsignificant between obese and nonobese patients (hazard ratio, 0.893; 95% CI, 0.66-1.2; P = .46). Although no significant difference was found in duration of mechanical ventilation and ICU length of stay, 90-day mortality was significantly lower in obese than in nonobese patients (272 of 692 [39.3%] patients vs 718 of 1,605 [44.7%]; P = .02). In a subgroup of patients (n = 123) with available pepsin and alpha-amylase measurements, no significant difference was found in rate of abundant microaspiration of gastric contents, or oropharyngeal secretions between obese and nonobese patients. Interpretation Our results suggest that obesity has no significant impact on the incidence of VAP.

Background and Aims Routine laboratory tests can be useful predictors in the early assessment of the severity and mortality of acute pancreatitis (AP). The aim of this study was to evaluate the accuracy of clinical and laboratory parameters for the prediction of mortality among patients admitted to the intensive care unit (ICU) for AP. Methods We conducted a retrospective analysis of prospectively collected data from Beth Israel Deaconess Hospital made publicly available to examine the relationship between routine clinical and laboratory parameters with respect to mortality for AP. Cox proportional hazard ratio was used to evaluate the impact of several routine laboratory markers on mortality. Receiver operation characteristic (ROC) curve was performed to determine the accuracy of diagnosis of laboratory tests by using area under curve (AUC) for the respective analysis. Results In total, 499 patients were admitted to the ICU for AP. Several factors for predicting mortality in AP at admission were identified in the multivariate analysis: alkaline phosphatase hazard ratio (HR) = 1.00 (1.00–1.00, p = 0.024), anion gap HR = 1.09 (1.00–1.20, p = 0.047), bilirubin total HR = 1.11 (1.06–1.17, p, Key Points This is the first study that evaluates the role of serum phosphate at baseline for predicting the mortality of acute pancreatitis (AP) in intensive care unit (ICU).This study found that serum phosphate is a useful laboratory marker for predicting the mortality of AP independently of other known factors.This study found that serum phosphate value greater than 3.78 mg/dl within the first 24 h after admission in the ICU could predict mortality (area under curve = 0.7, p

INTRODUCTION To identify factors associated with irreversible transmural necrosis (ITN) among critically ill patients experiencing nonocclusive mesenteric ischemia (NOMI) and to compare the predictive value regarding ITN risk stratification with that of the previously described Clichy score. METHODS All consecutive patients admitted to the intensive care unit between 2009 and 2019 who underwent exploratory laparotomy for NOMI and who had an available contrast-enhanced computed tomography with at least 1 portal venous phase were evaluated for inclusion. Clinical, laboratory, and radiological variables were collected. ITN was assessed on pathological reports of surgical specimens and/or on laparotomy findings in cases of open-close surgery. Factors associated with ITN were identified by univariate and multivariate analysis to derive a NOMI-ITN score. This score was further compared with the Clichy score. RESULTS We identified 4 factors associated with ITN in the context of NOMI: absence of bowel enhancement, bowel thinning, plasma bicarbonate concentration ≤15 mmol/L, and prothrombin rate

To evaluate the diagnostic performance of CT for transmural necrosis (TN) in non-occlusive mesenteric ischemia (NOMI) according to the bowel segment involved. From January 2009 to December 2019, all patients admitted to the intensive care unit (ICU) and requiring laparotomy for NOMI were retrospectively studied. CT had to have been performed within 24 h prior to laparotomy and were reviewed by two abdominal radiologists, with a consensus reading in case of disagreement. A set of CT features of mesenteric ischemia were assessed, separating the stomach, jejunum, ileum, and right (RC) and left colon (LC). Univariate and multivariate analyses were performed to identify features associated with TN. Its influence on overall survival (OS) was assessed. Among 145 patients, 95 (66%) had ≥ 1 bowel segment with TN, including 7 (5%), 31 (21%), 43 (29%), 45 (31%), and 52 (35%) in the stomach, jejunum, ileum, RC, and LC, respectively. Overall inter-reader agreement of CT features was significantly lower in the colon than in the small bowel (0.59 [0.52–0.65] vs 0.74 [0.70–0.77] respectively). The absence of bowel wall enhancement was the only CT feature associated with TN by multivariate analysis, whatever the bowel segment involved. Proximal TN was associated with poorer OS (p < 0.001). The absence of bowel wall enhancement remains the most consistent CT feature of transmural necrosis, whatever the bowel segment involved in NOMI. Inter-reader agreement of CT features is lower in the colon than in the small bowel. Proximal TN seems to be associated with poorer OS. • The absence of bowel wall enhancement is the most consistent CT feature associated with transmural necrosis in NOMI, whatever is the bowel segment involved. • Inter-reader agreement is lower in the colon than in the small bowel in NOMI. • In NOMI, the more proximal the bowel necrosis, the worse the prognosis.

Background The aim of this study is to determine whether severe COVID-19 patients harbour a higher risk of ICU-acquired pneumonia. Methods This retrospective multicentre cohort study comprised all consecutive patients admitted to seven ICUs for severe COVID-19 pneumonia during the first COVID-19 surge in France. Inclusion criteria were laboratory-confirmed SARS-CoV-2 infection and requirement for invasive mechanical ventilation for 48 h or more. Control groups were two historical cohorts of mechanically ventilated patients admitted to the ICU for bacterial or non-SARS-CoV-2 viral pneumonia. The outcome of interest was the development of ICU-acquired pneumonia. The determinants of ICU-acquired pneumonia were investigated in a multivariate competing risk analysis. Result One hundred and seventy-six patients with severe SARS-CoV-2 pneumonia admitted to the ICU between March 1st and 30th June of 2020 were included into the study. Historical control groups comprised 435 patients with bacterial pneumonia and 48 ones with viral pneumonia. ICU-acquired pneumonia occurred in 52% of COVID-19 patients, whereas in 26% and 23% of patients with bacterial or viral pneumonia, respectively (p p = 0.011). Conclusion COVID-19 appears an independent risk factor of ICU-acquired pneumonia in mechanically ventilated patients with pneumonia. Whether this is driven by immunomodulatory properties by the SARS-CoV-2 or this is related to particular processes of care remains to be investigated.

Objectives Standard nursing interventions, especially bed-baths, in ICUs can lead to complications or adverse events defined as a physiologic change that can be life-threatening or that prolongs hospitalization. However, the frequency and type of these adverse events are rarely reported in the literature. The primary objective of our study was to describe the proportion of patients experiencing at least one serious adverse event during bed-bath. The secondary objectives were to determine the incidence of each type of serious adverse event and identify risk factors for these serious adverse events. Design Prospective multicenter observational study. Setting Twenty-four ICUs in France, Belgium, and Luxembourg. Patients The patients included in this study had been admitted to an ICU for less than 72 hours and required at least one of the following treatments: invasive ventilation, vasopressors, noninvasive ventilation, high-flow oxygen therapy. Serious adverse events were defined as cardiac arrest, accidental extubation, desaturation and/or mucus plugging/inhalation, hypotension and/or arrhythmia and/or agitation requiring therapeutic intervention, acute pain, accidental disconnection or dysfunction of equipment, and patient fall requiring additional assistance. Interventions None. Measurements and main results The study included 253 patients from May 1, 2018, to July 31, 2018 in 24 ICUs, representing 1,529 nursing procedures. The mean Simplified Acute Physiology Score II was 54 ± 19. Nursing care was administered by an average of 2 ± 1 caregivers and lasted between 11 and 20 minutes. Of the 253 patients included, 142 (56%) experienced at least one serious adverse event. Of the 1,529 nursing procedures, 295 (19%) were complicated by at least one serious adverse event. In multivariate analysis, the factors associated with serious adverse event were as follows: presence of a specific protocol (p = 0.011); tracheostomy (p = 0.032); administration of opioids (p = 0.007); presence of a physician (p = 0.0004); duration of nursing care between 6 and 10 minutes (p = 0.003), duration of nursing care between 11 and 20 minutes (p = 0.005), duration of nursing care greater than 40 minutes (p = 0.04) with a reference duration of nursing care between 20 and 40 minutes. Conclusions Serious adverse events were observed in one-half of patients and concerned one-fifth of nurses, confirming the need for caution. Further studies are needed to test systematic serious adverse event prevention strategies.

OBJECTIVE. The purpose of this study was to assess whether transmural bowel necrosis has distinct CT features based on the three main causes: occlusive acute mesenteric ischemia (AMI), nonocclusive AMI, and strangulated small-bowel obstruction (SBO). MATERIALS AND METHODS. From January 2010 to December 2017, the records of all patients with a pathologic diagnosis of transmural bowel necrosis were extracted from the pathology department database of a university hospital. The inclusion criteria for the study were presence of transmural bowel necrosis at pathologic examination and available contrast-enhanced CT images obtained within the 24 hours before surgery. Seventy-seven patients were finally included. The CT scans were retrospectively independently reviewed by two abdominal radiologists to identify the classic CT findings of transmural bowel necrosis. Statistical analyses were performed. RESULTS. Pneumatosis intestinalis was statistically more frequent in nonocclusive AMI (59%) than in occlusive AMI (29%) and strangulated SBO (7%) (p < 0.01), as were superior mesenteric venous gas (55%, 29%, and 0%; p < 0.01) and portal venous gas (48%, 10%, and 0%; p < 0.01). Decreased or absent bowel wall enhancement was more frequent in AMI than in SBO (nonocclusive AMI, 83%; occlusive AMI, 81%; SBO, 56%; p = 0.02), as was thinned bowel wall (nonocclusive AMI, 52%; occlusive AMI, 48%; SBO, 18%; p = 0.02). Spontaneous hyperattenuation of the bowel wall was more frequent in strangulated SBO (41%) than in nonocclusive AMI (10%) and occlusive AMI (14%) (p < 0.01). CONCLUSION. Transmural bowel necrosis has distinct CT findings according to its three main causes. Occlusive AMI is characterized by an absence of bowel wall enhancement and less mesenteric fat stranding, nonocclusive AMI by a high prevalence of pneumatosis intestinalis and portal venous gas, and strangulated SBO by spontaneous hyperattenuation of the bowel wall and an absence of pneumatosis intestinalis and portal venous gas.

The effects of the route of nutrition on the gut mucosa of patients with shock are unclear. Plasma citrulline concentration is a marker of enterocyte mass, and plasma intestinal fatty acid binding protein (I-FABP) concentration is a marker of enterocyte damage. We aimed to study the effect of the route of nutrition on plasma citrulline concentration measured at day 3 of nutrition. Ancillary study of the NUTRIREA-2 trial. Ventilated adults with shock were randomly assigned to receive enteral or parenteral nutrition. Enterocyte biomarkers were measured at baseline, day 3, and day 8 of nutrition. A total of 165 patients from 13 French ICUs were included in the study: 85 patients in the enteral group and 80 patients in the parenteral group. At baseline, plasma citrulline was low without difference between groups (12.2 µmol L−1 vs 13.3 µmol L−1). At day 3, plasma citrulline concentration was higher in the enteral group than in the parenteral group (18.7 µmol L−1 vs 15.3 µmol L−1, p = 0.01). Plasma I-FABP concentration was increased at baseline, without difference between groups (245 pg mL−1 vs 244 pg mL−1). Plasma I-FABP concentration was higher in the enteral group than in the parenteral group at day 3 and day 8 (158 pg mL−1 vs 50 pg mL−1, p = 0.005 and 225 pg mL−1 vs 50 pg mL−1, p = 0.03). Plasma citrulline concentration was higher after 3 days of enteral nutrition than after 3 days of parenteral nutrition. This result raises the question of the possibility that enteral nutrition is associated with a more rapid restoration of enterocyte mass than parenteral nutrition.

Background The death rate in intensive care units (ICUs) can reach 20%. More than half occurs after a decision of care withholding/withdrawal. We aimed at describing and evaluating the experience of ICU physicians and nurses involved in the end-of-life (EOL) procedure. Primary objective was the evaluation of the experience of EOL assessed by the CAESAR questionnaire. Secondary objectives were to describe factors associated with a low or high score and to examine the association between Numeric Analogic Scale and quality of EOL. Methods Consecutive adult patients deceased in 52 ICUs were included between April and June 2018. Characteristics of patients and caregivers, therapeutics and care involved after withdrawal were recorded. CAESAR score included 15 items, rated from 1 (traumatic experience) to 5 (comforting experience). The sum was rated from 15 to 75 (the highest, the best experience). Numeric Analogic Scale was rated from 0 (worst EOL) to 10 (optimal EOL). Results Five hundred and ten patients were included, 403 underwent decision of care withholding/withdrawal, and among them 362 underwent effective care withdrawal. Among the 510 patients, mean CAESAR score was 55/75 (± 6) for nurses and 62/75 (± 5) for physicians (P P = 0.06). CAESAR score and Numeric Analogic Scale were significantly but weakly correlated. They were significantly higher for both nurses and physicians if the patient died after a decision of withholding/withdrawal. In multivariable analysis, among the 362 patients with effective care withdrawal, disagreement on the intensity of life support between caregivers, non-invasive ventilation and monitoring and blood tests the day of death were associated with lower score for nurses. For physicians, cardiopulmonary resuscitation the day of death was associated with lower score in multivariable analysis. Conclusion Experience of EOL was better in patients with withholding/withdrawal decision as compared to those without. Our results suggest that improvement of nurses’ participation in the end-of-life process, as well as less invasive care, would probably improve the experience of EOL for both nurses and physicians. Registration: ClinicalTrial.gov: NCT03392857.

IntroductionInternational guidelines include early nutritional support (≤48 hour after admission), 20–25 kcal/kg/day, and 1.2–2 g/kg/day protein at the acute phase of critical illness. Recent data challenge the appropriateness of providing standard amounts of calories and protein during acute critical illness. Restricting calorie and protein intakes seemed beneficial, suggesting a role for metabolic pathways such as autophagy, a potential key mechanism in safeguarding cellular integrity, notably in the muscle, during critical illness. However, the optimal calorie and protein supply at the acute phase of severe critical illness remains unknown. NUTRIREA-3 will be the first trial to compare standard calorie and protein feeding complying with guidelines to low-calorie low-protein feeding. We hypothesised that nutritional support with calorie and protein restriction during acute critical illness decreased day 90 mortality and/or dependency on intensive care unit (ICU) management in mechanically ventilated patients receiving vasoactive amine therapy for shock, compared with standard calorie and protein targets.Methods and analysisNUTRIREA-3 is a randomised, controlled, multicentre, open-label trial comparing two parallel groups of patients receiving invasive mechanical ventilation and vasoactive amine therapy for shock and given early nutritional support according to one of two strategies: early calorie-protein restriction (6 kcal/kg/day-0.2–0.4 g/kg/day) or standard calorie-protein targets (25 kcal/kg/day, 1.0–1.3 g/kg/day) at the acute phase defined as the first 7 days in the ICU. We will include 3044 patients in 61 French ICUs. Two primary end-points will be evaluated: day 90 mortality and time to ICU discharge readiness. The trial will be considered positive if significant between-group differences are found for one or both alternative primary endpoints. Secondary outcomes include hospital-acquired infections and nutritional, clinical and functional outcomes.Ethics and disseminationThe NUTRIREA-3 study has been approved by the appropriate ethics committee. Patients are included after informed consent. Results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT03573739.

Background The prognosis of critical ill patients with non-occlusive mesenteric ischemia (NOMI) is poor and not fully understood. Preoperative prognostic factors are needed. The aim of this study was to determine preoperative factors associated with 28-day mortality in a cohort of ICU patients requiring laparotomy for NOMI. The secondary objective was to determine general prognostic factors associated with NOMI. Methods This retrospective observational study was performed in a University Hospital among critically ill patients 18 years old or older who underwent a laparotomy for NOMI from January 1, 2009 to December 31, 2019, and who had an available contrast enhanced CT with at least one portal venous phase. Variables were collected at the time of the CT. All variables associated with 28-day mortality were entered into a multivariate cox regression model and were used to compute a NOMI mortality score. Results During the study period, 154 patients underwent laparotomy for NOMI after having benefited from an abdominal enhanced CT. The 28-day mortality rate was 56%. Variable at the time of ICU admission and at the time of the CT were collected. Surgical and histopathologic findings were recorded. Multivariable analyses on 28-day mortality including variables at the time of the CT identified three independent variables (i.e. lactates > 7mmol/l, prothrombin rate

Background The classification of invasive pulmonary aspergillosis (IPA) issued by the European Organization for the Research and Treatment of Cancer/Mycoses Study Group Education and Research Consortium (EORTC/MSGERC) is used for immunocompromised patients. An alternative algorithm adapted to the intensive care unit (ICU) population has been proposed (AspICU), but this algorithm did not include microbial biomarkers such as the galactomannan antigen and the Aspergillus quantitative PCR. The objective of the present pilot study was to evaluate a new algorithm that includes fungal biomarkers (BM-AspICU) for the diagnosis of probable IPA in an ICU population. Patients and methods Data from 35 patients with pathology-proven IPA according to European Organization for the Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSGERC)-2008 criteria were extracted from the French multicenter database of the Invasive Fungal Infections Surveillance Network (RESSIF). The patients were investigated according to the AspICU algorithm, and the BM-AspICU algorithm in analyzing the clinical, imaging, and biomarker data available in the records, without taking into account the pathology findings. Results Eight patients had to be excluded because no imaging data were recorded in the database. Among the 27 proven IPAs with complete data, 16 would have been considered as putative IPA with the AspICU algorithm and 24 would have been considered as probable IPA using the new algorithm BM-AspICU. Seven out of the 8 patients with probable BM-AspICU IPA (and not classified with the AspICU algorithm) had no host factors and no Aspergillus-positive broncho-alveolar lavage fluid (BALF) culture. Three patients were non-classifiable with any of the two algorithms, because they did not have any microbial criteria during the course of the infection, and diagnosis of proven aspergillosis was done using autopsy samples. Conclusion Inclusion of biomarkers could be effective to identify probable IPA in the ICU population. A prospective study is needed to validate the routine application of the BM-AspICU algorithm in the ICU population.

Background Little is known on the outcome and risk factors for mortality of patients admitted in Intensive Care units (ICUs) for Acute cholangitis (AC). Methods Retrospective multicenter study included adults admitted in eleven intensive care units for a proven AC from 2005 to 2018. Risk factors for in-hospital mortality were identified using multivariate analysis. Results Overall, 382 patients were included, in-hospital mortality was 29%. SOFA score at admission was 8 [5–11]. Biliary obstruction was mainly related to gallstone (53%) and cancer (22%). Median total bilirubin and PCT were respectively 83 µmol/L [50–147] and 19.1 µg/L [5.3–54.8]. Sixty-three percent of patients (n = 252) had positive blood culture, mainly Gram-negative bacilli (86%) and 14% produced extended spectrum beta lactamase bacteria. At ICU admission, persisting obstruction was frequent (79%) and biliary decompression was performed using therapeutic endoscopic retrograde cholangiopancreatography (76%) and percutaneous transhepatic biliary drainage (21%). Adjusted mortality significantly decreased overtime, adjusted OR for mortality per year was 0.72 [0.54–0.96] (p = 0.02). In a multivariate analysis, factors at admission associated with in-hospital mortality were: SOFA score (OR 1.14 [95% CI 1.05–1.24] by point, p = 0.001), lactate (OR 1.21 [95% CI 1.08–1.36], by 1 mmol/L, p p p p = 0.002). Time between ICU admission and biliary decompression > 48 h was associated with in-hospital mortality (adjusted OR 2.73 [95% CI 1.30–6.22], p = 0.02). Conclusions In this large retrospective multicenter study, we found that AC-associated mortality significantly decreased overtime. Severity of organ failure, cause of obstruction and local complications of AC are risk factors for mortality, as well as delayed biliary drainage > 48 h.

Background Previous studies reporting the causes of death in patients with severe COVID-19 have provided conflicting results. The objective of this study was to describe the causes and timing of death in patients with severe COVID-19 admitted to the intensive care unit (ICU). Methods We performed a retrospective study in eight ICUs across seven French hospitals. All consecutive adult patients (aged ≥ 18 years) admitted to the ICU with PCR-confirmed SARS-CoV-2 infection and acute respiratory failure were included in the analysis. The causes and timing of ICU deaths were reported based on medical records. Results From March 1, 2020, to April 28, 287 patients were admitted to the ICU for SARS-CoV-2 related acute respiratory failure. Among them, 93 patients died in the ICU (32%). COVID-19-related multiple organ dysfunction syndrome (MODS) was the leading cause of death (37%). Secondary infection-related MODS accounted for 26% of ICU deaths, with a majority of ventilator-associated pneumonia. Refractory hypoxemia/pulmonary fibrosis was responsible for death in 19% of the cases. Fatal ischemic events (venous or arterial) occurred in 13% of the cases. The median time from ICU admission to death was 15 days (25th–75th IQR, 7–27 days). COVID-19-related MODS had a median time from ICU admission to death of 14 days (25th–75th IQR: 7–19 days), while only one death had occurred during the first 3 days since ICU admission. Conclusions In our multicenter observational study, COVID-19-related MODS and secondary infections were the two leading causes of death, among severe COVID-19 patients admitted to the ICU.

Purpose To evaluate whether abdominal atherosclerosis was associated with poorer outcome in a single-centre cohort of patients suffering from nonocclusive mesenteric ischemia (NOMI). Methods From January 2009 to December 2019, 121 consecutive patients from the critical care unit who underwent laparotomy for suspected NOMI and with available unenhanced and contrast-enhanced CT were included. Clinical and biological data at the time of the CT scan were retrospectively extracted from medical charts and reviewed by a single radiologist. Unenhanced CT acquisitions were used to calculate calcium scores of the abdominal aorta, celiac trunk, superior mesenteric artery (SMA) and common iliac arteries according to the Agatston method. Univariate and multivariate analysis were performed. Results Among the 121 patients with NOMI and calcium score calculation, only 4 patients had no aortic calcifications (3 %) and 32 had no superior mesenteric artery calcification (26 %). 35 patients (29 %) died within 24 h after the abdominal CT scan. Univariate analysis showed that a total abdominal calcium score greater than 15 000 (last quartile) was significantly associated with death within 24 h (14 (40 %) vs 17 (20 %) patients, p = 0.035). By multivariate analysis, a total abdominal calcium score greater than 15 000 was an independent risk factor for death (HR = 1.94, 95 %CI [1.02–3.73], p = 0.044). Regarding separate calcium scores, only a SMA calcium score greater than 50 was a risk factor for death (HR 2.46, 95 %CI [1.14–3.93], p = 0.019). Conclusion Our results show that abdominal atherosclerosis, especially in the SMA, is associated with poorer outcome in NOMI.

Background The properties of semi-elemental enteral nutrition might theoretically improve gastrointestinal tolerance in brain-injured patients, known to suffer gastroparesis. The purpose of this study was to compare the efficacy and tolerance of a semi-elemental versus a polymeric formula for enteral nutrition (EN) in brain-injured critically ill patients. Methods Prospective, randomized study including brain-injured adult patients [Glasgow Coma Scale (GCS) ≤ 8] with an expected duration of mechanical ventilation > 48 h. Intervention: an enteral semi-elemental (SE group) or polymeric (P group) formula. EN was started within 36 h after admission to the intensive care unit and was delivered according to a standardized nurse-driven protocol. The primary endpoint was the percentage of patients who received both 60% of the daily energy goal at 3 days and 100% of the daily energy goal at 5 days after inclusion. Tolerance of EN was assessed by the rate of gastroparesis, vomiting and diarrhea. Results Respectively, 100 and 95 patients were analyzed in the SE and P groups: Age (57[44–65] versus 55[40–65] years) and GCS (6[3–7] versus 5[3–7]) did not differ between groups. The percentage of patients achieving the primary endpoint was similar (46% and 48%, respectively; relative risk (RR) [95% confidence interval (CI)] = 1.05 (0.78–1.42); p = 0.73). The mean daily energy intake was, respectively, 20.2 ± 6.3 versus 21.0 ± 6.5 kcal/kg/day (p = 0.42). Protein intakes were 1.3 ± 0.4 versus 1.1 ± 0.3 g/kg/day (p p = 0.21), and 16% versus 8% patients suffered from diarrhea (p = 0.11). No patient presented vomiting in either group. Conclusion Semi-elemental compared to polymeric formula did not improve daily energy intake or gastrointestinal tolerance of enteral nutrition. Trial registration EudraCT/ID-RCB 2012-A00078-35 (registered January 17, 2012).

IntroductionA palliative approach to intensive care unit (ICU) patients with acute respiratory failure and a do-not-intubate order corresponds to a poorly evaluated target for non-invasive oxygenation treatments. Survival alone should not be the only target; it also matters to avoid discomfort and to restore the patient’s quality of life. We aim to conduct a prospective multicentre observational study to analyse clinical practices and their impact on outcomes of palliative high-flow nasal oxygen therapy (HFOT) and non-invasive ventilation (NIV) in ICU patients with do-not-intubate orders.Methods and analysisThis is an investigator-initiated, multicentre prospective observational cohort study comparing the three following strategies of oxygenation: HFOT alone, NIV alternating with HFOT and NIV alternating with standard oxygen in patients admitted in the ICU for acute respiratory failure with a do-not-intubate order. The primary outcome is the hospital survival within 14 days after ICU admission in patients weaned from NIV and HFOT. The sample size was estimated at a minimum of 330 patients divided into three groups according to the oxygenation strategy applied. The analysis takes into account confounding factors by modelling a propensity score.Ethics and disseminationThe 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 numberNCT03673631

Background Hospital death rates following ICU admission of cirrhotic patients remain high. Identifying patients at high risk of mortality after few days of aggressive management is imperative for providing adequate interventions. Herein, we aimed to evaluate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) combined with usual organ failure scores in the outcome prediction of cirrhotic patients hospitalized more than 3 days in ICU. Methods We conducted a retrospective bicentric study in two cohorts of cirrhotic patients hospitalized more than 3 days in French university hospital ICUs. At admission and day 3, we calculated several clinico-biological scores grading liver disease and organ failure severity and calculated the NLR. The primary outcome was 28-day mortality. Results The test cohort included 116 patients. At day 28, 43 (37.1%) patients had died. Variations of MELD score (ΔMELD), SOFA score (ΔSOFA), CLIF-SOFA score (ΔCLIF-SOFA) and NLR (ΔNRL) between admission and day 3 were significantly associated with 28-day mortality in univariate analysis. When included in bivariate analysis ΔNLR remained a significant predictor of 28-day mortality independently of these severity scores. Kaplan-Meier curves and statistics using reclassification methods showed a better 28-day mortality risk prediction using ΔNRL in association with ΔSOFA in comparison to ΔSOFA alone. These results were confirmed in an external validation cohort, including 101 critically ill cirrhotic patients. Conclusions ΔNLR is an independent predictor of mortality in the critically ill cirrhotic patients' population who requires intensive care supportive treatment and should be used in association with ΔSOFA as a prognostic biomarker.

Background There is now substantial evidence to support venovenous extracorporeal membrane oxygenation efficacy and safety for patients with severe acute respiratory distress syndrome. However, recent guidelines recommend against the initiation of extracorporeal membrane oxygenation in patients with mechanical ventilation for coronavirus disease 2019 severe acute respiratory distress syndrome for greater than 7-10 days. Case summary We report the case of a patient with coronavirus disease 2019 severe acute respiratory distress syndrome with successful late venovenous extracorporeal membrane oxygenation initiation after 20 days of mechanical ventilation. Respiratory compliance, arterial blood gases, and radiological lesions improved progressively under venovenous extracorporeal membrane oxygenation and ultraprotective ventilation. The patient was discharged from ICU. Conclusions As coronavirus disease 2019 is a new and incompletely understood entity, we believe that late extracorporeal membrane oxygenation may be considered in selected patients as a bridge to recovery. Further prospective studies are, however, needed.

Patients with obesity are at higher risk for community-acquired and nosocomial infections. However, no study has specifically evaluated the relationship between obesity and ventilator-associated pneumonia (VAP).Is obesity associated with an increased incidence of VAP?This study was a post hoc analysis of the Impact of Early Enteral vs Parenteral Nutrition on Mortality in Patients Requiring Mechanical Ventilation and Catecholamines (NUTRIREA2) open-label, randomized controlled trial performed in 44 French ICUs. Adults receiving invasive mechanical ventilation and vasopressor support for shock and parenteral nutrition or enteral nutrition were included. Obesity was defined as BMI ≥ 30 kg/mA total of 699 (30%) of the 2,325 included patients had obesity; 224 first VAP episodes were diagnosed (60 and 164 in obese and nonobese groups, respectively). The incidence of VAP at day 28 was 8.6% vs 10.1% in the two groups (hazard ratio, 0.85; 95% CI 0.63-1.14; P = .26). After adjustment on sex, McCabe score, age, antiulcer treatment, and Sequential Organ Failure Assessment at randomization, the incidence of VAP remained nonsignificant between obese and nonobese patients (hazard ratio, 0.893; 95% CI, 0.66-1.2; P = .46). Although no significant difference was found in duration of mechanical ventilation and ICU length of stay, 90-day mortality was significantly lower in obese than in nonobese patients (272 of 692 [39.3%] patients vs 718 of 1,605 [44.7%]; P = .02). In a subgroup of patients (n = 123) with available pepsin and alpha-amylase measurements, no significant difference was found in rate of abundant microaspiration of gastric contents, or oropharyngeal secretions between obese and nonobese patients.Our results suggest that obesity has no significant impact on the incidence of VAP.

L’ischémie mésentérique aiguë est définie par l’association d’une insuffisance vasculaire mésentérique aiguë à une ischémie intestinale. L’insuffisance vasculaire peut être occlusive (occlusion artérielle ou veineuse) ou non-occlusive (bas débit, hypotension, ou hypoxémie dans les vaisseaux à destination de l’intestin). L’ischémie intestinale est définie comme précoce (en général réversible) ou tardive (possiblement irréversible). La mortalité reste très élevée, entre 65 % et 80 %. La démarche diagnostique repose sur un haut degré de suspicion du diagnostic. La confirmation du diagnostic repose sur la réalisation en urgence, dès la suspicion, d’un scanner AP sans puis avec injection. Celui-ci identifie le mécanisme de l’insuffisance mésentérique, et recherche des signes d’ischémie intestinale. Les résultats du scanner déterminent directement la prise en charge thérapeutique. Le traitement repose sur une triade : revascularisation en urgence ; résection de l’intestin non viable ; mesures générales de réanimation. La prise en charge multidisciplinaire, en centre expert, est primordiale.

A 22-year-old man with no relevant medical history except hashish use (10 joints a day) was admitted to the intensive care unit in December 2018 for refractory acute respiratory distress syndrome (ARDS). He presented dry cough and dyspnoea for 1 week. After intubation, veno-venous extracorporeal membrane oxygenation (VV-ECMO) was required because of severe hypoxemia and very low respiratory compliance (15 mL/cmH2O). Given the possibility of severe community-acquired pneumonia and influenza, urgent antibiotic therapy associating cephalosporin plus macrolid and …

Objectifs : Bien que quotidiennement géré par les infirmier(ière)s diplômé(e)s d’État (IDE) de réanimation, le sevrage des catécholamines a rarement été étudié. L’hypothèse de notre étude était que l’augmentation du nombre d’interventions menées sur la vitesse de perfusion des catécholamines permettait de raccourcir la durée d’administration de celles-ci. Patients et méthodes : Il s’agissait d’une étude prospective observationnelle dans 21 réanimations. Tous les patients traités par vasopresseurs pendant la période d’étude ont été inclus. Le nombre d’interventions effectuées par l’IDE en charge du patient sur la vitesse d’administration des catécholamines était noté toutes les quatre heures. La posologie de catécholamines en cours ainsi que la pression artérielle moyenne (PAM) du patient étaient également relevées. Les facteurs influençant la rapidité du sevrage des catécholamines étaient également analysés. Résultats : Nous avons inclus 226 patients dont l’âge moyen était de 65 ± 14 ans. La durée moyenne du traitement par catécholamines était de 71,6 (±81) heures. Le nombre d’interventions IDE par quatre heures était de 1,9 (±2,8) intervention. La durée du traitement par catécholamines était significativement moindre lorsque le nombre d’interventions augmentait (p = 0,04). L’existence d’un protocole spécifique à la gestion des catécholamines raccourcissait leur durée de sevrage. Un IGS2 élevé, une PAM élevée ainsi que la période diurne étaient associés à une augmentation du nombre des interventions IDE. Conclusion : Le nombre d’interventions par les IDEs menées sur la perfusion de catécholamines était inversement lié à la durée du traitement par catécholamines. Des études complémentaires permettront d’évaluer l’impact de ces interventions sur le pronostic des patients.

Risk factors associated with pulmonary embolism in coronavirus disease 2019 acute respiratory distress syndrome patients deserve to be better known. We therefore performed a post hoc analysis from the COronaVirus-Associated DIsease Study (COVADIS) project, a multicenter observational study gathering 21 ICUs from France (n = 12) and Belgium (n = 9). Three-hundred seventy-five consecutive patients with moderate-to-severe acute respiratory distress syndrome and positive coronavirus disease 2019 were included in the study. At day 28, 15% were diagnosed with pulmonary embolism. Known risk factors for pulmonary embolism including cancer, obesity, diabetes, hypertension, and coronary artery disease were not associated with pulmonary embolism. In the multivariate analysis, younger age (< 65 yr) (odds ratio, 2.14; 1.17-4.03), time between onset of symptoms and antiviral administration greater than or equal to 7 days (odds ratio, 2.39; 1.27-4.73), and use of neuromuscular blockers greater than or equal to 7 days (odds ratio, 1.89; 1.05-3.43) were independently associated with pulmonary embolism. These new findings reinforce the need for prospective studies that will determine the predictors of pulmonary embolism among patients with severe coronavirus disease 2019.

Summary Background Altered body composition may impact on the clinical course of Crohn's disease (CD) but is not detected by the simple body mass index (BMI) assessment. Aim To assess the prevalence of sarcopenia and visceral obesity by a single computed tomography (CT) slice, and its association with adverse events in an adult hospitalized CD cohort. Methods 88 CD patients who had abdominal CT scans during hospitalization were retrospectively enrolled. The skeletal muscle index (SMI) at the third lumbar vertebra level was used to assess sarcopenia. Sarcopenia was defined as a SMI Results The prevalence of sarcopenia was 58%, malnutrition 21.6%, and visceral obesity 19.3%. Among sarcopenic patients, 49% had a normal BMI, 13.7% were overweight, and 1(2%) was obese. Sarcopenic CD patients had significantly more abscesses (51% vs 16.7%, p = 0.001), hospitalizations (61.2% vs 36.1%, p = 0.022) and digestive surgery (63.3% vs 27.8%, p = 0.001) than non-sarcopenic patients during the follow-up, whereas usual malnutrition assessment was not correlated with disease outcomes. In multivariate analysis, both sarcopenia and visceral obesity were associated with further occurrence of digestive surgery. Conclusion Both sarcopenia and visceral obesity were associated with adverse outcomes in severe CD patients whereas usual nutritional assessment was not.

International audience; Purpose: To report the incidence, risk factors, clinical presentation, and outcome predictors of severe leptospirosis requiring intensive care unit (ICU) admission in a temperate zone.Methods: LEPTOREA was a retrospective multicentre study conducted in 79 ICUs in metropolitan France. Consecutive adults admitted to the ICU for proven severe leptospirosis from January 2012 to September 2016 were included. Multiple correspondence analysis (MCA) and hierarchical classification on principal components (HCPC) were performed to distinguish different clinical phenotypes.Results: The 160 included patients (0.04% of all ICU admissions) had median values of 54 years [38-65] for age, 40 [28-58] for the SAPSII, and 11 [8-14] for the SOFA score. Hospital mortality was 9% and was associated with older age; worse SOFA score and early need for endotracheal ventilation and/or renal replacement therapy; chronic alcohol abuse and worse hepatic dysfunction; confusion; and higher leucocyte count. Four phenotypes were identified: moderately severe leptospirosis (n = 34, 21%) with less organ failure and better outcomes; hepato-renal leptospirosis (n = 101, 63%) with prominent liver and kidney dysfunction; neurological leptospirosis (n = 8, 5%) with the most severe organ failures and highest mortality; and respiratory leptospirosis (n = 17, 11%) with pulmonary haemorrhage. The main risk factors for leptospirosis contamination were contact with animals, contact with river or lake water, and specific occupations.Conclusions: Severe leptospirosis was an uncommon reason for ICU admission in metropolitan France and carried a lower mortality rate than expected based on the high severity and organ-failure scores. The identification in our population of several clinical presentations may help clinicians establish an appropriate index of suspicion for severe leptospirosis.

Background Microaspiration of gastric and oropharyngeal secretions is the main mechanism of entry of bacteria into the lower respiratory tract in intubated critically ill patients. The aim of this study is to determine the impact of enteral nutrition, as compared with parenteral nutrition, on abundant microaspiration of gastric contents and oropharyngeal secretions. Methods Planned ancillary study of the randomized controlled multicenter NUTRIREA2 trial. Patients with shock receiving invasive mechanical ventilation were randomized to receive early enteral or parenteral nutrition. All tracheal aspirates were collected during the 48 h following randomization. Abundant microaspiration of gastric contents and oropharyngeal secretions was defined as the presence of significant levels of pepsin (> 200 ng/ml) and salivary amylase (> 1685 UI/ml) in > 30% of tracheal aspirates. Results A total of 151 patients were included (78 and 73 patients in enteral and parenteral nutrition groups, respectively), and 1074 tracheal aspirates were quantitatively analyzed for pepsin and amylase. Although vomiting rate was significantly higher (31% vs 15%, p = 0.016), constipation rate was significantly lower (6% vs 21%, p = 0.010) in patients with enteral than in patients with parenteral nutrition. No significant difference was found regarding other patient characteristics. The percentage of patients with abundant microaspiration of gastric contents was significantly lower in enteral than in parenteral nutrition groups (14% vs 36%, p = 0.004; unadjusted OR 0.80 (95% CI 0.69, 0.93), adjusted OR 0.79 (0.76, 0.94)). The percentage of patients with abundant microaspiration of oropharyngeal secretions was significantly higher in enteral than in parenteral nutrition groups (74% vs 54%, p = 0.026; unadjusted OR 1.21 (95% CI 1.03, 1.44), adjusted OR 1.23 (1.01, 1.48)). No significant difference was found in percentage of patients with ventilator-associated pneumonia between enteral (8%) and parenteral (10%) nutrition groups (HR 0.78 (0.26, 2.28)). Conclusions Our results suggest that enteral and parenteral nutrition are associated with high rates of microaspiration, although oropharyngeal microaspiration was more common with enteral nutrition and gastric microaspiration was more common with parenteral nutrition. Trial registration ClinicalTrials.gov, NCT03411447. Registered 18 July 2017. Retrospectively registered.