Efficacy and Safety of Early Administration of 4-Factor Prothrombin Complex Concentrate in Patients With Trauma at Risk of Massive Transfusion: The PROCOAG Randomized Clinical Trial.

Importance: Optimal transfusion strategies in traumatic hemorrhage are unknown. Reports suggest a beneficial effect of 4-factor prothrombin complex concentrate (4F-PCC) on blood product consumption. Objective: To investigate the efficacy and safety of 4F-PCC administration in patients at risk of massive transfusion. Design, Setting, and Participants: Double-blind, randomized, placebo-controlled superiority trial in 12 French designated level I trauma centers from December 29, 2017, to August 31, 2021, involving consecutive patients with trauma at risk of massive transfusion. Follow-up was completed on August 31, 2021. Interventions: Intravenous administration of 1 mL/kg of 4F-PCC (25 IU of factor IX/kg) vs 1 mL/kg of saline solution (placebo). Patients, investigators, and data analysts were blinded to treatment assignment. All patients received early ratio-based transfusion (packed red blood cells:fresh frozen plasma ratio of 1:1 to 2:1) and were treated according to European traumatic hemorrhage guidelines. Main Outcomes and Measures: The primary outcome was 24-hour all blood product consumption (efficacy); arterial or venous thromboembolic events were a secondary outcome (safety). Results: Of 4313 patients with the highest trauma level activation, 350 were eligible for emergency inclusion, 327 were randomized, and 324 were analyzed (164 in the 4F-PCC group and 160 in the placebo group). The median (IQR) age of participants was 39 (27-56) years, Injury Severity Score was 36 (26-50 [major trauma]), and admission blood lactate level was 4.6 (2.8-7.4) mmol/L; prehospital arterial systolic blood pressure was less than 90 mm Hg in 179 of 324 patients (59%), 233 patients (73%) were men, and 226 (69%) required expedient hemorrhage control. There was no statistically or clinically significant between-group difference in median (IQR) total 24-hour blood product consumption (12 [5-19] U in the 4F-PCC group vs 11 [6-19] U in the placebo group; absolute difference, 0.2 U [95% CI, -2.99 to 3.33]; P = .72). In the 4F-PCC group, 56 patients (35%) presented with at least 1 thromboembolic event vs 37 patients (24%) in the placebo group (absolute difference, 11% [95% CI, 1%-21%]; relative risk, 1.48 [95% CI, 1.04-2.10]; P = .03). Conclusions and Relevance: Among patients with trauma at risk of massive transfusion, there was no significant reduction of 24-hour blood product consumption after administration of 4F-PCC, but thromboembolic events were more common. These findings do not support systematic use of 4F-PCC in patients at risk of massive transfusion. Trial Registration: ClinicalTrials.gov Identifier: NCT03218722.

Oil droplet formation and vertical transport in the upper ocean.

The dispersion of oil droplets near ocean surface is important for evaluating the impact to the environment. Under breaking wave conditions, the surface oil experiences mainly two processes: the generation of oil droplets at/near the water surface, and the transport of oil droplets due to ocean dynamics. We investigated the vertical behavior by incorporating the transport equation and the VDROP model. The transport equation adopted the ocean dynamics by K-profile parameterization (KPP) and the impact of additional turbulence by imposing the energy dissipation rate on the ocean surface. The oil droplet distribution was obtained, and the entrained distribution and entrainment rate was computed. The results shows that although the entrained distribution and the entrainment rate shares certain consistency with previous studies, divergences are also noticed. Accordingly, the model that describes the physics should be adopted to avoid incorrect qualification of the oil concentration dispersed in the ocean.

Ultrasound guidance for urgent arterial and venous catheterisation: randomised controlled study.

BACKGROUND: Haemodynamically unstable patients often require arterial and venous catheter insertion urgently. We hypothesised that ultrasound-guided arterial and venous catheterisation would reduce mechanical complications. METHODS: We performed a prospective RCT, where patients requiring both urgent arterial and venous femoral catheterisation were randomised to either ultrasound-guided or landmark-guided catheterisation. Complications and characteristics of catheter insertion (procedure duration, number of punctures, and procedure success) were recorded at the time of insertion (immediate complications). Late complications were investigated by ultrasound examination performed between the third and seventh days after randomisation. Primary outcome was the proportion of patients with at least one mechanical complication (immediate or late), by intention-to-treat analysis. Secondary outcomes included success rate, procedure time, and number of punctures. RESULTS: We analysed 136 subjects (102 [75%] male; age range: 27-62 yr) by intention to treat. The proportion of subjects with one or more complications was lower in 22/67 (33%) subjects undergoing ultrasound-guided catheterisation compared with landmark-guided catheterisation (40/69 [58%]; odds ratio: 0.35 [95% confidence interval: 0.18-0.71]; P=0.003). Ultrasound-guided catheterisation reduced both immediate (27%, compared with 51% in the landmark approach group; P=0.004) and late (10%, compared with 23% in the landmark approach group; P=0.047) complications. Ultrasound guidance also reduced the proportion of patients who developed deep vein thrombosis (4%, compared with 22% following landmark approach; P=0.012), and achieved a higher procedural success rate (96% vs 78%; P=0.004). CONCLUSIONS: An ultrasound-guided approach reduced mechanical complications after urgent femoral arterial and venous catheterisation, while increasing procedural success. CLINICAL TRIAL REGISTRATION: NCT02820909.

Clinical and biological clusters of sepsis patients using hierarchical clustering.

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.

Factors Associated with Clostridioides (Clostridium) Difficile Infection and Colonization: Ongoing Prospective Cohort Study in a French University Hospital.

INTRODUCTION: Clostridioides (Clostridium) difficile can be isolated from stool in 3% of healthy adults and in at least 10% of asymptomatic hospitalized patients. C. difficile, the most common cause of hospital-acquired infectious diarrhea in the developed world, has re-emerged in recent years with increasing incidence and severity. In an effort to reduce the spread of the pathogen, published recommendations suggest isolation and contact precautions for patients suffering from C. difficile infection (CDI). However, asymptomatic colonized patients are not targeted by infection control policies, and active surveillance for colonization is not routinely performed. Moreover, given the current changes in the epidemiology of CDI, particularly the emergence of new virulent strains either in the hospital or community settings, there is a need for identification of factors associated with colonization by C. difficile and CDI. Methods and analysis: We are carrying out a prospective, observational, cohort study in Edouard Herriot Hospital, Hospices Civils de Lyon, a 900-bed university hospital in Lyon, France. All consecutive adult patients admitted on selected units are eligible to participate in the study. Stool samples or rectal swabs for C. difficile testing are obtained on admission, every 3-5 days during hospitalization, at the onset of diarrhea (if applicable), and at discharge. Descriptive and logistic regression analyses will be completed to mainly estimate the proportion of asymptomatic colonization at admission, and to evaluate differences between factors associated with colonization and those related to CDI. Ethics: The study is conducted in accordance with the ethical principles of the Declaration of Helsinki, French law, and the Good Clinical Practice guidelines. The study protocol design was approved by the participating units, the ethics committee and the hospital institutional review board (Comité de protection des personnes et Comission Nationale de l'Informatique et des Libertés; N°: 00009118). Dissemination: The results of this study will be disseminated by presenting the findings locally at each participating ward, as well as national and international scientific meetings. Findings will be shared with interested national societies crafting guidelines in CDI.

Life Support Limitations in Mechanically Ventilated Stroke Patients.

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.

Evolution of Practices in a French Trauma Centre: Decrease in Blood Transfusions and Fresh Frozen Plasma to Red Blood Cell Ratios.

OBJECTIVE: The aim of this study was to describe the evolution of transfusion practices following the introduction of tranexamic acid (TXA) and ROTEMVR in a trauma resuscitation unit (TRU) from a French teaching hospital (FTH). METHODS: This is a single-centre, retrospective study at a TRU from a FTH. All trauma patients aged 18 years or more and transfused with at least 4 red blood cells (RBCs) within 24 hours after trauma, from 2011 to 2016, were included. The primary objective was to analyse transfusion practices over this time period. The secondary objectives aimed at assessing differences between populations according to the fresh frozen plasma (FFP):RBC ratio applied. RESULTS: A total of 122 patients were included. There was a significant decrease in the proportion of patients requiring at least 4 RBCs 24 hours after trauma (9% vs. 3%, P trend < .0001) as well as a decrease in the proportion of patients with a high FFP:RBC ratio (86% vs. 62% at 6 hours, P trend » .0056 and 86% vs. 56% at 24 hours, P trend » .0047). After 2013, fibrinogen was administered to more than 70% of patients and TXA to 100% of them. The observed mortality was lower than the predicted one, irrespective of FFP:RBC ratio. CONCLUSION: An important evolution of practices occurred including a decrease in the proportion of transfusions and use of high FFP:RBC ratios. The origin of these changes is multifactorial, likely including the systematic use of TXA and optimisation of the ROTEM protocol for fibrinogen administration.

Hypofibrinolytic state and high thrombin generation may play a major role in SARS-COV2 associated thrombosis.

BACKGROUND: Thirty percent of Covid-19 patients admitted to intensive care units present with thrombotic complications despite thromboprophylaxis. Bed rest, obesity, hypoxia, coagulopathy, and acute excessive inflammation are potential mechanisms reported by previous studies. Better understanding of the underlying mechanisms leading to thrombosis is crucial for developing more appropriate prophylaxis and treatment strategies. OBJECTIVE: We aimed to assess fibrinolytic activity and thrombin generation in 78 Covid-19 patients. PATIENTS AND METHODS: Forty-eight patients admitted to the intensive care unit and 30 patients admitted to the internal medicine department were included in the study. All patients received thromboprophylaxis. We measured fibrinolytic parameters (tissue plasminogen activator, PAI-1, thrombin activatable fibrinolysis inhibitor, alpha2 anti-plasmin, and tissue plasminogen activator-modified ROTEM device), thrombin generation, and other coagulation tests (D-dimer, fibrinogen, factor VIII, antithrombin). RESULTS AND CONCLUSIONS: We observed two key findings: a high thrombin generation capacity that remained within normal values despite heparin therapy and a hypofibrinolysis mainly associated with increased PAI-1 levels. A modified ROTEM is able to detect both hypercoagulability and hypofibrinolysis simultaneously in Covid-19 patients with thrombosis.

One-year survival in acute stroke patients requiring mechanical ventilation: a multicenter cohort study.

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.

Ventilator-associated pneumonia due to Stenotrophomonas maltophilia: Risk factors and outcome.

BACKGROUND: Stenotrophomonas maltophilia (SM) is increasingly identified in intensive care unit (ICU). This study aim to identify risk factors for SM ventilator-associated pneumonia (VAP) and whether it affects ICU mortality METHODS: Two nested matched case-control studies were performed based in OUTCOMEREA database. The first episodes of SM-VAP patients were matched with two different control groups: VAP due to other micro-organisms (VAP-other) and Pseudomonas aeruginosa VAP (Pyo-VAP). Matching criteria were the hospital, the SAPS II, and the previous duration of mechanical ventilation (MV). RESULTS: Of the 102 SM-VAP patients (6.2% of all VAP patients), 92 were matched with 375 controls for the SM-VAP/other-VAP matching and 84 with 237 controls for the SM-VAP/Pyo-VAP matching. SM-VAP risk factors were an exposition to ureido/carboxypenicillin or carbapenem during the week before VAP, and respiratory and coagulation components of SOFA score upper to 2 before VAP. SM-VAP received early adequate therapy in 70 cases (68.6%). Risk factors for Day-30 were age (OR = 1.03; p < 0.01) and Chronic heart failure (OR = 3.15; p < 0.01). Adequate treatment, either monotherapy or combination of antimicrobials, did not modify mortality. There was no difference in 30-day mortality, but 60-day mortality was higher in patients with SM-VAP compared to Other-VAP (P = 0.056). CONCLUSIONS: In a large series, independent risk factors for the SM-VAP were ureido/carboxypenicillin or carbapenem exposure the week before VAP, and respiratory and coagulation components of the SOFA score > 2 before VAP. Mortality risk factors of SM-VAP were age and chronic heart failure. Adequate treatment did not improve SM-VAP prognosis.

Influence of dyskalemia at admission and early dyskalemia correction on survival and cardiac events of critically ill patients.

OBJECTIVES: Our objectives were (1) to characterize the distribution of serum potassium levels at ICU admission, (2) to examine the relationship between dyskalemia at ICU admission and occurrence of cardiac events, and (3) to study both the association between dyskalemia at ICU admission and dyskalemia correction by day 2 on 28-day mortality. DESIGN: Inception cohort study from the longitudinal prospective French multicenter OUTCOMEREA database (1999-2014) SETTING: 22 French OUTCOMEREA network ICUs PATIENTS: Patients were classified into six groups according to their serum potassium level at admission: three groups of hypokalemia and three groups of hyperkalemia defined as serious hypokalemia [K+] < 2.5 and serious hyperkalemia [K+] > 7 mmol/L, moderate hypokalemia 2.5 ≤ [K+] < 3 mmol/L and moderate hyperkalemia 6 < [K+] ≤ 7 mmol/L, and mild hypokalemia 3 ≤ [K+] < 3.5 mmol/L and mild hyperkalemia 5 < [K+] ≤ 6 mmol/L. We sorted evolution at day 2 of dyskalemia into three categories: balanced, not-balanced, and overbalanced. INTERVENTION: None MEASUREMENTS AND MAIN RESULTS: Of 12,090 patients, 2108 (17.4%) had hypokalemia and 1445 (12%) had hyperkalemia. Prognostic impact of dyskalemia and its correction was assessed using multivariate Cox models. After adjustment, hypokalemia and hyperkalemia were independently associated with a greater risk of 28-day mortality. Mild hyperkalemic patients had the highest mortality (hazard ratio (HR) 1.29, 95% confidence interval (CI) [1.13-1.47], p < 0.001). Adjusted 28-day mortality was higher if serum potassium level was not-balanced at day 2 (aHR = 1.51, 95% CI [1.30-1.76], p < 0.0001) and numerically higher but not significantly different if serum potassium level was overbalanced at day 2 (aHR = 1.157, 95% CI [0.84-1.60], p = 0.38). Occurrence of cardiac events was evaluated by logistic regression. Except for patients with serious hypokalemia at admission, the depth of dyskalemia was associated with increased risk of cardiac events. CONCLUSIONS: Dyskalemia is common at ICU admission and associated with increased mortality. Occurrence of cardiac events increased with dyskalemia depth. A correction of serum potassium level by day 2 was associated with improved prognosis.

Pneumonia in acute ischemic stroke patients requiring invasive ventilation: Impact on short and long-term outcomes.

OBJECTIVES: To describe the epidemiology and prognostic impact of pneumonia in acute ischemic stroke patients requiring invasive mechanical ventilation. METHODS: Retrospective analysis from a prospective multicenter cohort study of critically ill patients with acute ischemic stroke requiring invasive mechanical ventilation at admission. Impact of pneumonia was investigated using Cox regression for 1-year mortality, and competing risk survival models for ICU mortality censored at 30-days. RESULTS: We included 195 patients. Stroke was supratentorial in 62% and 64% of patients had a Glasgow coma scale score <8 on admission. Mortality at day-30 and 1 year were 56%, and 70%, respectively. Post-stroke pneumonia was identified in 78 (40%) patients, of which 46/78 (59%) episodes were present at ICU admission. Post-stroke pneumonia was associated with an increase in 1-year mortality (adjusted HR 1.49, 95%CI [1.01-2.20]). Post-stroke pneumonia was not associated with ICU mortality but was associated with a 1.6-fold increase in ICU length of stay (CSHR 0.62 [0.39-0.99], p = 0.06). CONCLUSIONS: In ischemic stroke patients requiring invasive ventilation, pneumonia occurred in 40% of cases and was associated with a 49% increase in 1-year mortality. Post-stroke pneumonia did not impact day-30 mortality but increased ICU length of stay.

A Comparison of the Mortality Risk Associated With Ventilator-Acquired Bacterial Pneumonia and Nonventilator ICU-Acquired Bacterial Pneumonia.

OBJECTIVES: To investigate the respective impact of ventilator-associated pneumonia and ICU-hospital-acquired pneumonia on the 30-day mortality of ICU patients. DESIGN: Longitudinal prospective studies. SETTING: French ICUs. PATIENTS: Patients at risk of ventilator-associated pneumonia and ICU-hospital-acquired pneumonia. INTERVENTIONS: The first three episodes of ventilator-associated pneumonia or ICU-hospital-acquired pneumonia were handled as time-dependent covariates in Cox models. We adjusted using the case-mix, illness severity, Simplified Acute Physiology Score II score at admission, and procedures and therapeutics used during the first 48 hours before the risk period. Baseline characteristics of patients with regard to the adequacy of antibiotic treatment were analyzed, as well as the Sequential Organ Failure Assessment score variation in the 2 days before the occurrence of ventilator-associated pneumonia or ICU-hospital-acquired pneumonia. Mortality was also analyzed for Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species(ESKAPE) and P. aeruginosa pathogens. MEASUREMENTS AND MAIN RESULTS: Of 14,212 patients who were admitted to the ICUs and who stayed for more than 48 hours, 7,735 were at risk of ventilator-associated pneumonia and 9,747 were at risk of ICU-hospital-acquired pneumonia. Ventilator-associated pneumonia and ICU-hospital-acquired pneumonia occurred in 1,161 at-risk patients (15%) and 176 at-risk patients (2%), respectively. When adjusted on prognostic variables, ventilator-associated pneumonia (hazard ratio, 1.38 (1.24-1.52); p < 0.0001) and even more ICU-hospital-acquired pneumonia (hazard ratio, 1.82 [1.35-2.45]; p < 0.0001) were associated with increased 30-day mortality. The early antibiotic therapy adequacy was not associated with an improved prognosis, particularly for ICU-hospital-acquired pneumonia. The impact was similar for ventilator-associated pneumonia and ICU-hospital-acquired pneumonia mortality due to P. aeruginosa and the ESKAPE group. CONCLUSIONS: In a large cohort of patients, we found that both ICU-hospital-acquired pneumonia and ventilator-associated pneumonia were associated with an 82% and a 38% increase in the risk of 30-day mortality, respectively. This study emphasized the importance of preventing ICU-hospital-acquired pneumonia in nonventilated patients.

Modelling the association between fibrinogen concentration on admission and mortality in patients with massive transfusion after severe trauma: an analysis of a large regional database.

BACKGROUND: The relationship between fibrinogen concentration and traumatic death has been poorly explored after severe trauma. Existing studies analysed this relationship in unselected trauma population, often considering fibrinogen concentration as a categorical variable. The aim of our study was to model the relationship between fibrinogen concentration and in-hospital mortality in severe trauma patients requiring massive transfusion using fibrinogen on admission as a continuous variable. METHODS: We designed a retrospective observational study based on prospectively collected data from 2009 to 2015 in seven French level-I trauma centres. All consecutive patients requiring a transfusion of at least 10 packed red blood cells (RBC) within 24 h were included. To assess the relationship between in-hospital death and fibrinogen concentration on admission, we performed generalized linear and additive models with death as a dependent variable. We also assessed the relationship between fibrinogen concentration below 1.5 g.L- 1 and potential predictors. RESULTS: Within the study period, 366 patients were included. A non-linear relationship was found between fibrinogen concentration and death. Graphical modelling of this relationship depicted a negative association between fibrinogen levels and death below a fibrinogen concentration of 1.5 g.L- 1. Predictors of low fibrinogen concentration (< 1.5 g.L- 1) were systolic blood pressure, Glasgow coma scale and haemoglobin concentration on admission. CONCLUSIONS: A complex and robust approach for modelling the relationship between fibrinogen and mortality revealed a critical fibrinogen threshold of 1.5 g.L- 1 for severe trauma patients requiring massive transfusion. This trigger may guide the administration of procoagulant therapies in this context.

Diabetes was the only comorbid condition associated with mortality of invasive pneumococcal infection in ICU patients: a multicenter observational study from the Outcomerea research group.

PURPOSES: Streptococcus pneumoniae is a leading pathogen of severe community, hospital or nursing facility infections. We sought to describe characteristics of invasive pneumococcal infection (IPI) and pneumonia (due to the high mortality of intensive care-associated pneumonia) and to report outcomes according to various types of comorbidity. METHODS: Multicenter observational cohort study on the prospective Outcomerea database, including adult patients, with a hospital stay < 48 h before ICU admission and a documented IPI within the first 72 h of ICU admission. Comorbid conditions were defined according to the Knaus and Charlson classification. RESULTS: Of the 20,235 patients, 5310 (26.4%) had an invasive infection, including 560/5,310 (10.6%) who had an IPI. The ICU 28-day mortality was 109/560 (19.8%). Four factors were independently associated with mortality: SOFA day 1-2: [hazard ratio (HR) 1.21; 95% confidence interval (95% CI) 1.15-1.27, p < 0.001]; maximum lactate level day 1-2: (HR 1.07, 95% CI 1.02-1.12, p = 0.006); diabetes mellitus: (HR 1.91, 95% CI 1.23-3.03, p = 0.006) and appropriate antibiotics (HR 0.28, 95% CI 0.15-0.50, p < 0.001). Comparable results were obtained when other comorbid conditions were forced into the model. Diabetes impact was more pronounced in case of micro- or macro-angiopathy (HR 4.17, 95%CI 1.68-10.54, p = 0.003), in patients ≥ 65 years old (HR 2.59, 95% CI 1.56-4.28, < 0.001) and in those with body mass index (BMI) < 25 kg/m2 (HR 2.11, 95% CI 1.10-4.06, p = 0.025). CONCLUSIONS: Diabetes mellitus was the only comorbid condition which independently influenced mortality in patients with IPI. Its impact was more pronounced in patients with complications, aged ≥ 65 years and with BMI < 25 kg/m2.

Association Between Body Weight Variation and Survival and Other Adverse Events in Critically Ill Patients With Shock: A Multicenter Cohort Study of the OUTCOMEREA Network.

OBJECTIVES: This study in critically ill patients with shock assessed the prognostic value of body weight variations occurring each day from day 3 to day 7 on the 30-day outcome in terms of mortality, occurrence of ventilator-associated pneumonia and of bedsore, and occurrence of length of stay. DESIGN: Retrospective analysis of data. Multivariate subdistribution survival models were used at each day, from day 3 to day 7. The impact of body weight variations on length of stay was estimated through a multivariate negative binomial regression model. SETTING: Prospective multicenter cohort study. PATIENTS: Critically ill patients admitted in ICU with shock and requiring mechanical ventilation within 48 hours. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Two-thousand three-hundred seventy-four patients were included. Their median body weight variations increased from 0.4 kg (interquartile range, 0-4.8 kg) on day 3 to 3 kg (interquartile range, -0.4 to 8.2 kg) on day 7. Categories of body weight variations were defined depending on body weight variations interquartiles: weight loss, no weight gain, moderate and severe weight gain. A severe weight gain tended to be associated with death at days 5 and 6 (day 5: subdistribution hazard ratio, 1.27; 95% CI, 0.99-1.63; p = 0.06 and day 6: subdistribution hazard ratio, 1.43; 95% CI, 1.08-1.89; p = 0.01), a weight loss tended to be associated with bedsore, and a severe gain between at days 5 and 6 was associated with ventilator-associated pneumonia. Any body weight variations were associated with an increased length of stay. CONCLUSIONS: In survivors at day 3, body weight variations during the first days of ICU stay might be a clinically relevant tool to prevent weight gain but also for prognostication of 30-day mortality, occurrence of ventilator-associated pneumonia, and occurrence of prolonged ICU stay.

Management and outcomes of acute respiratory distress syndrome patients with and without comorbid conditions.

RATIONALE: The standard of care for patients with acute respiratory distress syndrome (ARDS) has been developed based on studies that usually excluded patients with major comorbidities. OBJECTIVES: To describe treatments and outcomes according to comorbidities in patients with ARDS admitted to 19 ICUs (1997-2014). METHODS: Patients were grouped based on comorbidities. Determinants of day-28 mortality were identified by multivariable Cox analysis stratified on center. MEASUREMENTS AND MAIN RESULTS: Among 4953 ARDS patients, 2545 (51.4%) had major comorbidities; the proportion with major comorbidities increased after 2008. Hematological malignancy was associated with severe ARDS and rescue therapies for refractory hypoxemia. COPD, HIV infection, and hematological malignancy were associated with a lower likelihood of invasive mechanical ventilation on the admission day. Admission-day SOFA score was higher in patients with major comorbidities, who more often received vasopressors, dialysis, or treatment-limitation decisions. Day-28 mortality was 33.7% overall, 27.2% in patients without major comorbidities, and 31.1% (COPD) to 56% (hematological malignancy) in patients with major comorbidities. By multivariable analysis, mortality was lower in patients with COPD and higher in those with chronic heart failure, solid tumors, or hematological malignancies. Mortality was independently associated with PaO2/FiO2 and PaCO2 on day 1, ARDS of pulmonary origin, worse SOFA score, and ICU-acquired events. CONCLUSIONS: Half the patients with ARDS had major comorbidities, which were associated with severe ARDS, multiple organ dysfunction, and day-28 mortality. These findings do not support the exclusion of ARDS patients with severe comorbidities from randomized clinical trials. Trials in ARDS patients with whatever comorbidities are warranted.

Correction to: Infection-related ventilator-associated complications in ICU patients colonised with extended-spectrum ß-lactamase-producing Enterobacteriaceae.

The members of the OUTCOMEREA Study Group were provided in such a way that they could not be indexed as collaborators on PubMed. The publisher apologizes for this error and is pleased to list the members of the group here.

Infection-related ventilator-associated complications in ICU patients colonised with extended-spectrum ß-lactamase-producing Enterobacteriaceae.

PURPOSE: To investigate the clinical significance of infection-related ventilator-associated complications (IVAC) and their impact on carbapenem consumption in mechanically ventilated (MV) patients colonised with extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBLE). METHODS: Inception cohort study from the French prospective multicenter OUTCOMEREA database (17 ICUs, 1997-2015) including all ESBLE carriers (systematic rectal swabbing at admission then weekly and/or urinary or superficial surgical site colonisation) with MV duration > 48 h and ≥ 1 episode of IVAC after carriage documentation. All ICU-acquired infections were microbiologically documented. RESULTS: The 318 enrolled ESBLE carriers (median age 68 years; males 67%; medical admission 68%; imported carriage 53%) experienced a total of 576 IVAC comprising 361 episodes (63%) without documented infection, 124 (21%) related to infections other than ventilator-associated pneumonia (VAP), 73 (13%) related to non-ESBLE VAP and 18 (3%) related to ESBLE VAP. Overall, ESBLE infections accounted for only 43 episodes (7%). Carbapenem exposure within the preceding 3 days was the sole independent predictor of ESBLE infection as the causative event of IVAC, with a protective effect (adjusted odds ratio 0.2, 95% confidence interval 0.05-0.6; P < 0.01). Carbapenems were initiated in 9% of IVAC without infection, 15% of IVAC related to non-VAP infections, 42% of IVAC related to non-ESBLE VAP, and 56% of IVAC related to ESBLE VAP (ESBLE VAP versus non-ESBLE VAP: P = 0.43). CONCLUSIONS: IVAC in ESBLE carriers mostly reflect noninfectious events but act as a strong driver of empirical carbapenem consumption. ESBLE infections are scarce yet hard to predict, strengthening the need for novel diagnostic approaches and carbapenem-sparing alternatives.

Uncontrolled donation after circulatory death: comparison of two kidney preservation protocols on graft outcomes.

BACKGROUND: Kidney transplantation following uncontrolled donation after circulatory death (uDCD) presents a high risk of delayed graft function due to prolonged warm ischemia time. In order to minimise the effects of ischemia/reperfusion injury during warm ischemia, normothermic recirculation recently replaced in situ perfusion prior to implantation in several institutions. The aim of this study was to compare these preservation methods on kidney graft outcomes. METHODS: The primary endpoint was the one-year measured graft filtration rate (mGFR). We collected retrospective data from 64 consecutive uDCD recipients transplanted over a seven-year period in a single centre. RESULTS: Thirty-two grafts were preserved by in situ perfusion and 32 by normothermic recirculation. The mean ± SD mGFR at 1 year post-transplantation was 43.0 ± 12.8 mL/min/1.73 m2 in the in situ perfusion group and 53.2 ± 12.8 mL/min/1.73 m2 in the normothermic recirculation group (p = 0.01). Estimated GFR levels were significantly higher in the normothermic recirculation group at 12 months (p = 0.01) and 24 months (p = 0.03) of follow-up. We did not find any difference between groups regarding patient and graft survival, delayed graft function, graft rejection, or interstitial fibrosis. CONCLUSIONS: Function of grafts preserved by normothermic recirculation was better at 1 year and the results suggest that this persists at 2 years, although no difference was found in short-term outcomes. Despite the retrospective design, this study provides an additional argument in favour of normothermic recirculation.