Trends in Antibiotic Consumption and Resistance in France Over 20 Years: Large and Continuous Efforts but Contrasting Results.

BACKGROUND: Antimicrobial resistance (AMR) is a serious threat to humanity. This paper describes the French efforts made since 2001 and presents data on antimicrobial consumption (AC) and AMR. METHODS: We gathered all data on AC and AMR recorded since 2001 from different national agencies, transferred on a regular basis to standardized European data on AC and resistance in both humans and animals. RESULTS: After a large information campaign implemented in France from 2001 to 2005 in humans, AC in the community decreased significantly (18% to 34% according to the calculation method used). It remained at the same level from 2005 to 2010 and increased again from 2010 to 2018 (8%). Contrasting results were observed for AMR. The resistance of Staphylococcus aureus decreased significantly. For gram-negative bacilli, the results were variable according to the microorganism. The resistance of Enterobacteriaceae to third-generation cephalosporins increased, remaining moderate for Escherichia coli (12% in 2017) but reaching 35% in the same year for Klebsiella pneumoniae. Resistance to carbapenems in those 2 microorganisms remained below 1%. Both global AC and resistance to most antibiotics decreased significantly in animals. CONCLUSIONS: Antibiotic consumption decreased significantly in France after a large public campaign from 2001 to 2005, but this positive effect was temporary. The effect on AMR varied according to the specific microorganism: The effect was very impressive for gram-positive cocci, variable for gram-negative bacilli, and moderate for E. coli, but that for K. pneumoniae was of concern. The consumption of and resistance to antibiotics decreased significantly in animals.

Epidemiology, clinical features, and management of severe hypercalcemia in critically ill patients.

BACKGROUND: Severe hypercalcemia (HCM) is a common reason for admission in intensive-care unit (ICU). This case series aims to describe the clinical and biological features, etiologies, treatments, and outcome associated with severe HCM. This study included all patients with a total calcemia above 12 mg/dL (3 mmol/L) admitted in two ICUs from January 2007 to February 2017. RESULTS: 131 patients with HCM were included. HCM was related to hematologic malignancy in 58 (44.3%), solid tumors in 29 (22.1%), endocrinopathies in 16 (12.2%), and other causes in 28 (21.3%) patients. 108 (82.4%) patients fulfilled acute kidney injury (AKI) criteria. Among them, 25 (19%) patients required renal replacement therapy (RRT). 51 (38.9%) patients presented with neurological symptoms, 73 (55.7%) patients had cardiovascular manifestations, and 50 (38.1%) patients had digestive manifestations. The use of bisphosphonates (HR, 0.42; 95% CI, 0.27-0.67; P < 0.001) was the only treatment significantly associated with a decrease of total calcemia below 12 mg/dL (3 mmol/L) at day 5. ICU and Hospital mortality rates were, respectively, 9.9% and 21.3%. Simplified Acute Physiologic Score (SAPS II) (OR, 1.05; 95% CI 1.01-1.1; P = 0.03) and an underlying solid tumor (OR, 13.83; 95% CI 2.24-141.25; P = 0.01) were two independent factors associated with hospital mortality in multivariate analysis. CONCLUSIONS: HCM is associated with high mortality rates, mainly due to underlying malignancies. The course of HCM may be complicated by organ failures which are most of the time reversible with early ICU management. Early ICU admission and prompt HCM management are crucial, especially in patients with an underlying solid tumor presenting with neurological symptoms.

Acute kidney injury in critically ill patients with solid tumours.

Background: Patients with solid tumours are at risk for acute kidney injury (AKI), however, epidemiological data are limited. Methods: We conducted a study that included patients with solid tumours admitted to a single-centre intensive care unit (ICU) from January 2011 to December 2015. We analysed factors associated with the occurence of AKI, ICU and Day-90 mortality. Results: Two-hundred and four patients were included. The incidence of AKI was 59%, chiefly related to sepsis (80%), hypovolaemia (40%) and outflow tract obstruction (17%). Renal replacement therapy was implemented in 12% of the patients, with a hospital mortality of 39%. Independent predictors of AKI were: Simplified Acute Physiological Score II (SAPS II) [odds ratio (OR) 1.05; 95% confidence interval (95% CI) 1.02-1.07; P < 0.001], abdominal or pelvic cancer (OR 2.84; 95% CI 1.35-5.97; P = 0.006), nephrotoxic chemotherapy within the previous 3 months (OR 3.84; 95% CI 1.67-8.84; P = 0.002) and sepsis (OR 2.74; 95% CI 1.30-5.77; P = 0.008). Renal recovery at Day 90 was inversely related to AKI severity. ICU, hospital and Day-90 mortality were 15, 29 and 37%, respectively. Factors independently associated with ICU mortality were: total serum protein (OR per 10 g/L, 0.44; 95% CI 0.23-0.86; P = 0.02) and SAPS II (OR 1.04; 95% CI 1.01-1.07; P = 0.02), while Day-90 mortality was associated with performance status 3-4 (OR 6.59; 95% CI 2.42-18; P < 0.001) and total serum protein (OR 0.60; 95% CI 0.38-0.94; P = 0.02). Conclusions: AKI in patients with solid tumours was frequent and renal recovery gradually decreased in proportion to AKI severity. However, AKI was not independently associated with a higher short-term mortality.

Management of superior vena cava syndrome in critically ill cancer patients.

PURPOSE: The purpose of this study is to describe the management and outcome of critically ill cancer patients with Superior Vena Cava Syndrome (SVCS). METHODS: All cancer patients admitted to the medical intensive care unit (ICU) of the Saint-Louis University Hospital for a SVCS between January 2004 and December 2016 were included. RESULTS: Of the 50 patients included in the study, obstruction of the superior vena cava was partial in two-thirds of the cases and complete in one-third. Pleural effusion was reported in two-thirds of the patients, pulmonary atelectasis in 16 (32%), and pulmonary embolism in five (10%). Computed tomography of the chest showed upper airway compression in 18 (36%) cases, while echocardiography revealed 22 (44%) pericardial effusions. The causes of SVCS were diagnosed one (0-3) day after ICU admission, using interventional radiology procedures in 70% of the cases. Thirty (60%) patients had hematological malignancies, and 20 (40%) had solid tumors. Fifteen (30%) patients required invasive mechanical ventilation, seven (14%) received vasopressors, and renal replacement therapy was implemented in three (6%). ICU, in-hospital, and 6-month mortality rates were 20, 26, and 48%, respectively. The cause of SVCS was the only factor independently associated with day 180 mortality by multivariate analysis. Patients with hematological malignancies had a lower mortality than those with solid tumors (27 versus 80%) (odds ratio 0.12, 95% confidence interval (0.02-0.60), p < 0.01). CONCLUSION: Airway obstruction and pleural and pericardial effusions contributed to the unstable condition of cancer patients with SVCS. The vital prognosis of SVCS was mainly related to the underlying diagnosis.

Plasma exchange in the intensive care unit: Technical aspects and complications.

BACKGROUND: Data on plasma exchange therapy in the intensive care unit (ICU) setting are scarce. We aimed to describe the technical aspects and the adverse events associated with the procedure in critically ill patients. METHODS: All adult patients treated by plasma exchange in the medical ICU of the Saint-Louis university hospital between January 1, 2013 and March 31, 2015 were prospectively included. RESULTS: We report on 260 plasma exchange procedures performed in 50 patients. The centrifugation technique was used for 159 (61%) procedures and the filtration technique for the other 101 (39%) procedures. Both techniques had similar efficacy to treat hyperviscosity syndrome (n = 18). Seventy (26.9%) of the 260 plasma exchange procedures were reported with at least one adverse reaction. Centrifugation and filtration techniques had similar rates of adverse reactions (23.9 vs. 31.7%, P = .19). Hypotension was the most reported (n = 21, 8%) and correlates with a low hematocrit before therapy. Most complications were related to allergic reactions to the replacement fluids. Coagulation disorders depended on the type of replacement fluid. The post-exchange fibrinogen level was decreased by 54% [48;66] with albumin 5%, and 4% [-5;17] with plasma frozen within 24 h. Twenty-three (22.8%) of the 101 filtration procedures experienced filter clotting. Filter clotting was associated with a higher volume exchange prescribed when compared to procedures without filter clotting (4600 [4000;5000] ml vs. 3900 [3600;4800] ml, P < .01). CONCLUSION: Plasma exchange is a relatively safe and generally well-tolerated procedure in the ICU setting. Most adverse events are unpredictable and related to minor allergic reactions.

Increased mortality in hematological malignancy patients with acute respiratory failure from undetermined etiology: a Groupe de Recherche en Réanimation Respiratoire en Onco-Hématologique (Grrr-OH) study.

BACKGROUND: Acute respiratory failure (ARF) is the most frequent complication in patients with hematological malignancies and is associated with high morbidity and mortality. ARF etiologies are numerous, and despite extensive diagnostic workflow, some patients remain with undetermined ARF etiology. METHODS: This is a post-hoc study of a prospective multicenter cohort performed on 1011 critically ill hematological patients. Relationship between ARF etiology and hospital mortality was assessed using a multivariable regression model adjusting for confounders. RESULTS: This study included 604 patients with ARF. All patients underwent noninvasive diagnostic tests, and a bronchoscopy and bronchoalveolar lavage (BAL) was performed in 155 (25.6%). Definite diagnoses were classified into four exclusive etiological categories: pneumonia (44.4%), non-infectious diagnoses (32.6%), opportunistic infection (10.1%) and undetermined (12.9%), with corresponding hospital mortality rates of 40, 35, 55 and 59%, respectively. Overall hospital mortality was 42%. By multivariable analysis, factors associated with hospital mortality were invasive pulmonary aspergillosis (OR 7.57 (95% CI 3.06-21.62); p < 0.005), use of invasive mechanical ventilation (OR 1.65 (95% CI 1.07-2.55); p = 0.02), a SOFA score >7 (OR 3.32 (95% CI 2.15-5.15); p < 0.005) and an undetermined ARF etiology (OR 2.92 (95% CI 1.71-5.07); p < 0.005). CONCLUSIONS: In patients with hematological malignancies and ARF, up to 13% remain with undetermined ARF etiology despite comprehensive diagnostic workup. Undetermined ARF etiology is independently associated with hospital mortality. Studies to guide second-line diagnostic strategies are warranted. ClinicalTrials.Gov NCT01172132.

Formal Academic Training on Ethics May Address Junior Physicians' Needs.

BACKGROUND: Surveys have highlighted perceived deficiencies among ICU residents in end-of-life care, symptom control, and confidence in dealing with dying patients. Lack of formal training may contribute to the failure to meet the needs of dying patients and their families. The objective of this study was to evaluate junior intensivists' perceptions of triage and of the quality of the dying process before and after formal academic training. METHODS: Formal training on ethics was implemented as a part of resident training between 2007 and 2012. A cross-sectional survey was performed before (2007) and after (2012) this implementation. This study included 430 junior intensivists who were interviewed during these periods. RESULTS: More responders attended a dedicated training course on ethics and palliative care during 2012 (38.5%) than during 2007 (17.4%; P < .0001). During 2012, respondents reported less discomfort and fewer uncertainties regarding decisions about limiting life-sustaining treatment (17.7% vs 39.1% in 2007; P < .0001) or the triage process (48.5% vs 69.4% in 2007; P < .0001). Factors independently associated with positive perceptions of the dying process were physician's age (OR, 1.19 per year; 95% CI, 1.09-1.25) and male sex (OR, 1.61; 95% CI, 1.05-2.47). Conversely, anxiety about family members' reactions (OR, 0.58; 95% CI, 0.0.37-0.87) and lack of training (OR, 0.29; 95% CI, 0.17-0.50) were associated with negative perceptions of this process. CONCLUSIONS: Formal training dedicated to ethics and palliative care was associated with a more comfortable perception of the dying process. This training may decrease the uncertainty and discomfort of junior intensivists in these situations.

Pre-treatment with oral hydroxyurea prior to intensive chemotherapy improves early survival of patients with high hyperleukocytosis in acute myeloid leukemia.

Acute myeloid leukemia with high white blood cell count (WBC) is a medical emergency. A reduction of tumor burden with hydroxyurea may prevent life-threatening complications induced by straight chemotherapy. To evaluate this strategy, we reviewed medical charts of adult patients admitted to our institution from 1997 to 2011 with non-promyelocytic AML and WBC over 50 G/L. One hundred and sixty patients were included with a median WBC of 120 G/L (range 50-450), 107 patients received hydroxyurea prior to chemotherapy, and 53 received emergency induction chemotherapy (CT). Hospital mortality was lower for patients treated with hydroxyurea (34% versus 19%, p = 0.047) even after adjusting for age (p < 0.01) and initial WBC count (p = 0.02). No evidence of any difference between treatment groups in terms of WBC decline kinetics and disease free survival (p = 0.87) was found. Oral hydroxyurea prior to chemotherapy seems a safe and efficient strategy to reduce early death of hyperleukocytic AML patients.

Acute kidney injury in critically ill patients with haematological malignancies: results of a multicentre cohort study from the Groupe de Recherche en Réanimation Respiratoire en Onco-Hématologie.

BACKGROUND: Cancer patients are at high risk for acute kidney injury (AKI), which is associated with high morbidity and mortality. We sought to appraise the incidence, risk factors, and outcome of AKI in a large multicentre cohort study of critically ill patients with haematological malignancies. METHODS: We used a retrospective analysis of a prospectively collected database. The study was carried out in 17 university or university-affiliated centres in France and Belgium between 2010 and 2012. AKI was defined according to the Acute Kidney Injury Network (AKIN) definition. RESULTS: Of the 1011 patients admitted into the intensive care unit (ICU) during the study period, 1009 were included in this study. According to the AKIN definition, 671 patients (66.5%) developed an AKI during their ICU stay, of which 258 patients (38.4%) were AKI stage 1, 75 patients (11.2%) AKI stage 2 and 338 patients (50.4%) AKI stage 3. After adjustment for confounders, main adverse risk factors of AKI were older age, severity [non-renal Sequential Organ Failure Assessment (SOFA)], history of hypertension, tumour lysis syndrome, exposure to nephrotoxic agents and myeloma. Hospital mortality was 44.3% in patients with AKI and 25.4% in patients without AKI (P < 0.0001). After adjustment for confounders, AKI was independently associated with hospital mortality [OR 1.65 (95% CI 1.19-2.29)]. Overall, 271 patients required renal replacement therapy (RRT), of whom 57.2% died during their hospital stay as compared with 31.2% (P < 0.0001) in those not requiring RRT. CONCLUSION: Two-thirds of critically ill patients with haematological malignancies developed AKI. Hospital mortality in this population of patients developing AKI or requiring RRT is close to that in general ICU population.

Complicated grief after death of a relative in the intensive care unit.

An increased proportion of deaths occur in the intensive care unit (ICU). We performed this prospective study in 41 ICUs to determine the prevalence and determinants of complicated grief after death of a loved one in the ICU. Relatives of 475 adult patients were followed up. Complicated grief was assessed at 6 and 12 months using the Inventory of Complicated Grief (cut-off score >25). Relatives also completed the Hospital Anxiety and Depression Scale at 3 months, and the Revised Impact of Event Scale for post-traumatic stress disorder symptoms at 3, 6 and 12 months. We used a mixed multivariate logistic regression model to identify determinants of complicated grief after 6 months. Among the 475 patients, 282 (59.4%) had a relative evaluated at 6 months. Complicated grief symptoms were identified in 147 (52%) relatives. Independent determinants of complicated grief symptoms were either not amenable to changes (relative of female sex, relative living alone and intensivist board certification before 2009) or potential targets for improvements (refusal of treatment by the patient, patient died while intubated, relatives present at the time of death, relatives did not say goodbye to the patient, and poor communication between physicians and relatives). End-of-life practices, communication and loneliness in bereaved relatives may be amenable to improvements.

Acute kidney injury in adults with hemophagocytic lymphohistiocytosis.

BACKGROUND: Acute kidney injury (AKI) in the setting of hemophagocytic lymphohistiocytosis (HLH) is poorly characterized. This study aims to describe the incidence, clinical and biological features, and outcome associated with AKI in this population. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: Patients with secondary HLH admitted to a single center from February 2007 through January 2013. 95 patients were included in the study. PREDICTOR: AKI. OUTCOMES: Recovery of kidney function, 6-month mortality, and complete remission of the underlying disease. MEASUREMENTS: AKI was defined according to the KDIGO 2012 guideline. Recovery of kidney function was defined as improvement in serum creatinine level, with return to baseline serum creatinine level ±26.5µmol/L. RESULTS: HLH was related to hematologic malignancy in 73 (77%), infectious disease in 21 (22%), and autoimmune disease in 9 (10%) patients and was multifactorial in 10 (11%) patients. The cause was undetermined in 2 (2%) patients. The incidence of AKI during HLH is high (62%), and 59% of the AKI population required renal replacement therapy. Main causes of AKI were acute tubular necrosis (49%), hypoperfusion (46%), tumor lysis syndrome (29%), or HLH-associated glomerulopathies (17%). At 6 months, 32% of the patients with AKI had chronic kidney disease. Two factors were associated independently with 6-month mortality by multivariable analysis: AKI stage ≥ 2 (OR, 2.61; 95% CI, 1.08-6.29; P=0.03) and an underlying hematologic malignancy (OR, 3.1; 95% CI, 1.05-9.14; P=0.04). In patients with hematologic malignancy, AKI was associated with lower 6-month complete remission (non-AKI, 25%; AKI patients, 5%; P=0.05). LIMITATIONS: Retrospective study, lack of histologic data. CONCLUSIONS: AKI in patients with HLH is frequent and adversely affects remission and survival. Early intensive management, including administration of etoposide, nephrotoxic drug withdrawal, prevention of tumor lysis syndrome, or aggressive supportive care, might improve kidney function and survival.

Metastatic cancer-related thrombotic microangiopathies: a cohort study.

Thrombotic microangiopathies (TMAs) in patients with metastatic cancer are poorly characterized. We recorded 17 patients who had TMAs associated with disseminated solid cancer in our intensive care unit over an 11-year period. We compared them with a group of 20 patients with proven idiopathic thrombotic thrombocytopenic purpura hospitalized during the same period. We aimed to specify the clinical and biological features of cancer-related TMAs (CR-TMAs). CR-TMAs can either be inaugural of the underlying cancer or reflect worsening course. Clues to the presence of CR-TMA include respiratory symptoms, bone pain, myelemia or higher platelet count than in thrombotic thrombocytopenic purpura. In this context, bone marrow aspiration is a fast and gainful investigation to avoid plasmatherapy and immunosuppressive drugs. Indeed, this severe and poor-prognosis disease requires prompt diagnosis and rapid initiation of specific chemotherapy.

Acute respiratory failure in critically ill patients with interstitial lung disease.

BACKGROUND: Patients with chronic known or unknown interstitial lung disease (ILD) may present with severe respiratory flares that require intensive management. Outcome data in these patients are scarce. PATIENTS AND METHODS: Clinical and radiological features were collected in 83 patients with ILD-associated acute respiratory failure (ARF). Determinants of hospital mortality and response to corticosteroid therapy were identified by logistic regression. RESULTS: Hospital and 1-year mortality rates were 41% and 54% respectively. Pulmonary hypertension, computed tomography (CT) fibrosis and acute kidney injury were independently associated with mortality (odds ratio (OR) 4.55; 95% confidence interval (95%CI) (1.20-17.33); OR, 7.68; (1.78-33.22) and OR 10.60; (2.25-49.97) respectively). Response to steroids was higher in patients with shorter time from hospital admission to corticosteroid therapy. Patients with fibrosis on CT had lower response to steroids (OR, 0.03; (0.005-0.21)). In mechanically ventilated patients, overdistension induced by high PEEP settings was associated with CT fibrosis and hospital mortality. CONCLUSION: Mortality is high in ILD-associated ARF. CT and echocardiography are valuable prognostic tools. Prompt corticosteroid therapy may improve survival.

Respiratory events at the earliest phase of acute myeloid leukemia.

Acute myeloid leukemia (AML) can result in acute respiratory failure (ARF) during the first days, requiring intensive care unit (ICU) admission in half the cases. We describe three leukemia-specific syndromes responsible for ARF: leukostasis, pulmonary leukemic infiltration (PLI) and acute lysis pneumopathy (ALP). We retrospectively analyzed clinical and laboratory data from 114 patients admitted to a medical ICU within 10 days after a diagnosis of AML. Respiratory events (REs) occurred in 95 patients and were leukemia-specific in 58 patients (61%). Day-28 mortality was 34.5% in patients with leukemia-specific REs (leukostasis, 41%; PLI, 23%; and ALP, 31%) and 48.6% in patients with other REs. By multivariate analysis, independent risk factors for death were age > 50 (odds ratio, 13; 95% confidence interval, 3-51), Eastern Cooperative Oncology Group (ECOG) status ≥ 2 (5.4; 1.8-17) and need for invasive mechanical ventilation (19; 5-75). Dexamethasone therapy was protective (0.26; 0.09-0.8), suggesting a role as a preventive treatment in patients with AML-related non-infectious pulmonary involvement.

Burden of respiratory viruses in patients with acute respiratory failure.

Respiratory viruses (RVs) are ubiquitous pathogens that represent a major cause of community-acquired pneumonia and chronic pulmonary diseases exacerbations. However, their contribution to acute respiratory failure events requiring intensive care unit admission in the era of rapid multiplex molecular assay deserves further evaluation. This study investigated the burden of viral infections in non immunocompromised patients admitted to the intensive care unit for acute respiratory failure using a multiplex molecular assay. Patients were investigated for RVs using immunofluoresence testing and a commercial multiplex molecular assay, and for bacteria using conventional culture. Half the patients (34/70, 49%) had a documented RVs infection. No other pathogen was found in 24 (71%) patients. Viral infection was detected more frequently in patients with obstructive respiratory diseases (64% vs. 29%; P = 0.0075). Multiplex molecular assay should be considered as an usefull diagnostic tool in patients admitted to the intensive care unit with acute respiratory failure, especially those with acute exacerbations of chronic obstructive pulmonary disease and asthma.

Plasma uric acid response to rasburicase: early marker for acute kidney injury in tumor lysis syndrome?

Acute kidney injury (AKI) is associated with high morbidity and mortality in tumor lysis syndrome (TLS). The goal of this study was to assess a practical approach involving a simple risk-prediction model for AKI in patients at high risk for clinical TLS treated according to standardized guidelines. We collected data on 62 patients at high risk for clinical TLS. We evaluated whether the magnitude of the plasma uric acid decrease in response to rasburicase predicted AKI. According to RIFLE criteria (Risk, Injury, Failure, sustained Loss, End-stage kidney disease), 41 (66.1%) patients had AKI. AKI was associated with higher hospital (26.8% vs. 0%, p = 0.01) and 6-month (41.4% vs. 9.5%, p = 0.04) mortality. The plasma uric acid decrease after rasburicase was significantly larger in patients who did not develop AKI than in those who did (95% vs. 84%; p < 0.01). By multivariate analysis, independent determinants of AKI were hypertension and a plasma uric acid decrease smaller than 92.9% 6 h after rasburicase.

The prognostic value of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) deficiency in septic shock patients involves interleukin-6 and is not dependent on disseminated intravascular coagulation.

INTRODUCTION: ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) deficiency has been reported in patients with sepsis but its clinical relevance and pathophysiology remain unclear. Our objectives were to assess the clinical significance, prognostic value and pathophysiology of ADAMTS13 deficiency in patients with septic shock with and without disseminated intravascular coagulation (DIC). METHODS: This was a prospective monocenter cohort study of patients with septic shock. Von Willebrand Factor, ADAMTS13-related parameters and plasma IL-6 concentration were measured at inclusion to the study. Patients were categorized into three groups according to the presence of ADAMT13 deficiency (<30%) or DIC. RESULTS: This study included 72 patients with a median age of 59 years (interquartile range (IQR) 50 to 71). Each of the included patients received vasopressors; 55 (76%) were under mechanical ventilation and 22 (33%) underwent renal replacement therapy. Overall, 19 patients (26%) had DIC, and 36 patients had ADMTS13 deficiency (50%). Patients with DIC, ADAMTS13 deficiency or both were more severe at ICU admission. Mortality was higher in septic shock patients from group one. By multivariate analysis, Simplified Acute Physiology Score 2 (SAPS2) score (odds ratio (OR) 1.11/point; 95% CI 1.01 to 1.24) and ADAMTS13 activity <30% (OR 11.86; 95% CI 1.36 to 103.52) were independently associated with hospital mortality. There was no correlation between ADAMTS13 activity and the International Society for Thrombosis and Haemostasis (ISTH) score (rs = -0.97, P = 0.41) suggesting that ADAMTS13 functional deficiency and DIC were independent parameters. IL-6 level was higher in patients with ADAMTS13 activity <30% [895 (IQR 330 to 1843) pg/mL versus 83 (IQR 43 to 118), P = 0.0003). CONCLUSIONS: Septic shock was associated with a functional deficiency of ADAMTS13, independently of DIC. ADAMTS13 functional deficiency is then a prognostic factor for mortality in septic shock patients, independently of DIC.

Outcomes of critically ill patients with hematologic malignancies: prospective multicenter data from France and Belgium--a groupe de recherche respiratoire en réanimation onco-hématologique study.

PURPOSE Patients with hematologic malignancies are increasingly admitted to the intensive care unit (ICU) when life-threatening events occur. We sought to report outcomes and prognostic factors in these patients. PATIENTS AND METHODS Ours was a prospective, multicenter cohort study of critically ill patients with hematologic malignancies. Health-related quality of life (HRQOL) and disease status were collected after 3 to 6 months. Results Of the 1,011 patients, 38.2% had newly diagnosed malignancies, 23.1% were in remission, and 24.9% had received hematopoietic stem-cell transplantations (HSCT, including 145 allogeneic). ICU admission was mostly required for acute respiratory failure (62.5%) and/or shock (42.3%). On day1, 733 patients (72.5%) received life-supporting interventions. Hospital, day-90, and 1-year survival rates were 60.7%, 52.5%, and 43.3%, respectively. By multivariate analysis, cancer remission and time to ICU admission less than 24 hours were associated with better hospital survival. Poor performance status, Charlson comorbidity index, allogeneic HSCT, organ dysfunction score, cardiac arrest, acute respiratory failure, malignant organ infiltration, and invasive aspergillosis were associated with higher hospital mortality. Mechanical ventilation (47.9% of patients), vasoactive drugs (51.2%), and dialysis (25.9%) were associated with mortality rates of 60.5%, 57.5%, and 59.2%, respectively. On day 90, 80% of survivors had no HRQOL alterations (physical and mental health similar to that of the overall cancer population). After 6 months, 80% of survivors had no change in treatment intensity compared with similar patients not admitted to the ICU, and 80% were in remission. CONCLUSION Critically ill patients with hematologic malignancies have good survival, disease control, and post-ICU HRQOL. Earlier ICU admission is associated with better survival.

Unresponsive thrombotic thrombocytopenic purpura in critically ill adults.

INTRODUCTION: The prognosis of thrombotic thrombocytopenic purpura (TTP) has considerably improved since the introduction of plasma exchange (PEX) therapy. However, unresponsive thrombotic thrombocytopenic purpura (Un-TTP) still carries high morbidity and mortality rates, indicating a need for early specific treatments. PATIENTS AND METHODS: In a retrospective study including consecutive adults with TTP admitted between January 1997 and January 2011 in a teaching hospital intensive care unit (ICU), our objective here is to identify early clinical and laboratory features predicting Un-TTP. Patients who responded to plasma exchange and steroids (N = 49) were compared with patients with unresponsive TTP defined as requirement for other treatments, protracted course, or death (N = 37, 43 %). RESULTS: Hospital mortality was 24.3 % in the Un-TTP group. Variables associated with Un-TTP on univariate logistic regression were older age, cardiac involvement, neurological involvement, higher anti-a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS13) immunoglobulin G (IgG) titer, lower platelet counts starting on day 2, higher Sequential Organ Failure Assessment (SOFA) scores starting on day 3, need for higher plasma volumes to obtain remission, and greater use of adjuvant treatments and life-sustaining interventions. Multivariate logistic regression identified four factors independently associated with Un-TTP: age over 60 years [odds ratio (OR) 7.90; 95 % confidence interval (95 % CI) 1.06-78.34], cardiac (OR 5.17; 95 % CI 1.63-16.39) or neurological (OR 8.04; 95 % CI 1.27-51.03) manifestations at diagnosis, and day 2 platelet count less than 15 G/l (OR 3.88; 95 % CI 1.30-11.62). CONCLUSION: Therapeutic intensification starting on day 3 or even earlier in patients with the independent risk factors for unresponsive TTP identified in our study deserves evaluation in a multicenter prospective study.