The association of premorbid conditions with 6-month mortality in acutely admitted ICU patients over 80 years.

BACKGROUND: Premorbid conditions influence the outcome of acutely ill adult patients aged 80 years and over who are admitted to the ICU. The aim of this study was to determine the influence of such premorbid conditions on 6 month survival. METHODS: Prospective cohort study in 242 ICUs from 22 countries including patients 80 years or above, admitted over a 6 months period to an ICU between May 2018 and May 2019. Only emergency (acute) ICU admissions in adult patients ≥ 80 years of age were eligible. Patients who were admitted after planned/elective surgery were excluded. We measured the Clinical Frailty Scale (CFS), the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), disability with the Katz activities of daily living (ADL) score, comorbidities and a Polypharmacy Score (CPS). RESULTS: Overall, the VIP2 study included 3920 patients. During ICU stay 1191 patients died (30.9%), and another 436 patients (11.1%) died after ICU discharge but within the first 30 days of admission, and an additional 895 patients died hereafter but within the first 6 months after admission (22.8%). The 6 months mortality was 64%. The median CFS was 4 (IQR 3-6). Frailty (CFS ≥ 5) was present in 26.6%. Cognitive decline (IQCODE above 3.5) was found in 30.2%. The median IQCODE was 3.19. A Katz ADL of 4 or less was present in 27.7%. Patients who surviving > 6 months were slightly younger (median age survivors 84 with IQR 81-86) than patients dying within the first 6 months (median age 84, IQR 82-87, p = 0.013), were less frequently frail (CFS > 5 in 19% versus 34%, p < 0.01) and were less dependent based on their Katz activities of daily living measurement (median Katz score 6, IQR 5-6 versus 6 points, IQR 3-6, p < 0.01). CONCLUSIONS: We found that Clinical Frailty Scale, age, and SOFA at admission were independent prognostic factors for 6 month mortality after ICU admission in patients age 80 and above. Adding other geriatric syndromes and scores did not improve the model. This information can be used in shared-decision making. CLINICALTRIALS: gov: NCT03370692.

Albumin versus saline infusion for sepsis-related peripheral tissue hypoperfusion: a proof-of-concept prospective study.

BACKGROUND: Albumin has potential endothelial protective effects through antioxidant and anti-inflammatory properties. However, the effect of albumin on peripheral tissue perfusion in human sepsis remains poorly known. METHODS: Bi-centric prospective study included patients with sepsis with or without shock and prolonged CRT > 3 s despite initial resuscitation. Clinicians in charge of the patients were free to infuse either saline 500 mL or human serum albumin 20% 100 mL over 15 min. Global hemodynamic parameters as well as peripheral tissue perfusion were analyzed after 1 (H1) and 4 h (H4). The primary endpoint was CRT normalization (< 3 s) at H1. RESULTS: 62 patients were screened, and 50 patients (13 sepsis and 37 septic shock) were included, 21 in the saline group and 29 in the albumin group. SOFA score was 8 [5-11], and SAPS II was 53 [45-70]. Median age was 68 [60-76] years with a higher proportion of men (74%). The primary sources of infection were respiratory (54%) and abdominal (24%). At baseline, comorbidities, clinical and biological characteristics were similar between groups. At H1, CRT normalization (< 3 s) was more frequent in patients receiving albumin as compared to patients treated by saline (63 vs 29%, P = 0.02). The decrease in fingertip CRT was more important in the albumin group when compared to saline group (- 1.0 [- 0.3; - 1.5] vs - 0.2 [- 0.1; - 1.1] seconds, P = 0.04) as well as decrease in mottling score. At H4, beneficial effects of albumin on peripheral tissue perfusion were maintained and urinary output trended to be higher in the albumin group (1.1 [0.5-1.8] vs 0.7 [0.5-0.9] ml/kg/h, P = 0.08). Finally, arterial lactate level did not significantly change between H0 and H4 in the saline group but significantly decreased in the albumin group (P = 0.03). CONCLUSION: In patients with resuscitated sepsis, albumin infusion might lead to greater improvement of tissue hypoperfusion compared to saline. CLINICALTRIALS: gov Identifier: NCT05094856.

Corticosteroids induce an early but limited decrease in IL-6 dependent pro-inflammatory responses in critically ill COVID-19 patients.

BACKGROUND: Corticosteroids have become standard of care for COVID-19 but their effect on the systemic immune-inflammatory response has been little investigated. METHODS: Multicenter prospective cohort, including critically ill COVID-19 patients between March and November 2020. C-reactive protein (CRP), lymphocyte count and fibrinogen levels were collected upon hospital admission before initiation of steroid treatment and at ICU admission, three days and seven days later, along with interleukin (IL)-6, IL-10 and tumor necrosis factor-alpha (TNF-α) plasma levels. RESULTS: A hundred and fifty patients were included, 47 received corticosteroids, 103 did not. Median age was 62 [53-70], and 96 (65%) patients were mechanically ventilated. Propensity score matching rendered 45 well-balanced pairs of treated and non-treated patients, particularly on pre-treatment CRP levels. Using a mixed model, CRP (P=0.019), fibrinogen (P=0.003) and lymphocyte counts (P=0.006) remained lower in treated patients over ICU stay. Conversely, there was no significant difference over the ICU stay for Il-6 (P=0.146) and IL-10 (0.301), while TNF- α levels were higher in the treated group (P=0.013). Among corticosteroid-treated patients, CRP (P=0.012), fibrinogen (P=0.041) and lymphocyte count (P=0.004) over time were associated with outcome, whereas plasma cytokine levels were not. CONCLUSIONS: Steroid treatment was associated with an early and sustained decrease in the downstream IL-6-dependent inflammatory signature but an increase in TNF-α levels. In corticosteroid-treated patients, CRP and lymphocyte count were associated with outcome, conversely to plasma cytokine levels. Further research on using these biomarker's kinetics to individualize immunomodulatory treatments is warranted.

Epidemiology and Clinical Patterns of Lung Abscesses in ICU: A French Multicenter Retrospective Study.

BACKGROUND: Data are scarce regarding epidemiology and management of critically ill patients with lung abscesses. RESEARCH QUESTION: What are the clinical and microbiological characteristics of critically ill patients with lung abscesses, how are they managed in the ICU, and what are the risk factors of in-ICU mortality? STUDY DESIGN AND METHODS: This was a retrospective observational multicenter study, based on International Classification of Diseases, 10th Revision, codes, between 2015 and 2022 in France. In-ICU mortality-associated factors were determined by multivariate logistic regression. RESULTS: We analyzed 171 ICU patients with pulmonary abscesses. Seventy-eight percent were male, with a mean age of 56.5 ± 16.4 years; 20.4% misused alcohol, 25.2% had a chronic lung disease (14% COPD), and 20.5% had a history of cancer. Overall, 40.9% were immunocompromised and 38% qualified for nosocomial infection. Presenting symptoms included fatigue or weight loss in 62%, fever (50.3%), and dyspnea (47.4%). Hemoptysis was reported in 21.7%. A polymicrobial infection was present in 35.6%. The most frequent pathogens were Enterobacteriaceae in 31%, Staphylococcus aureus in 22%, and Pseudomonas aeruginosa in 19.3%. Fungal infections were found in 10.5%. Several clusters of clinicoradiologic patterns were associated with specific microbiological documentation and could guide empiric antibiotic regimen. Percutaneous abscess drainage was performed in 11.7%; surgery was performed in 12.7%, and 12% required bronchial artery embolization for hemoptysis. In-ICU mortality was 21.5%, and age (OR: 1.05 [1.02-1.91], P = .007], renal replacement therapy during ICU stay (OR, 3.56 [1.24-10.57], P = .019), and fungal infection (OR, 9.12 [2.69-34.5], P = .0006) were independent predictors of mortality after multivariate logistic regression, and drainage or surgery were not. INTERPRETATION: Pulmonary abscesses in the ICU are a rare but severe disease often resulting from a polymicrobial infection, with a high proportion of Enterobacteriaceae, S aureus, and P aeruginosa. Percutaneous drainage, surgery, or arterial embolization was required in more than one-third of cases. Further prospective studies focusing on first-line antimicrobial therapy and source control procedure are warranted to improve and standardize patient management.

Kinetics of capillary refill time after fluid challenge.

BACKGROUND: Capillary refill time (CRT) is a valuable tool for triage and to guide resuscitation. However, little is known about CRT kinetics after fluid infusion. METHODS: We conducted a prospective observational study in a tertiary teaching hospital. First, we analyzed the intra-observer variability of CRT. Next, we monitored fingertip CRT in sepsis patients during volume expansion within the first 24 h of ICU admission. Fingertip CRT was measured every 2 min during 30 min following crystalloid infusion (500 mL over 15 min). RESULTS: First, the accuracy of repetitive fingertip CRT measurements was evaluated on 40 critically ill patients. Reproducibility was excellent, with an intra-class correlation coefficient of 99.5% (CI 95% [99.3, 99.8]). A CRT variation larger than 0.2 s was considered as significant. Next, variations of CRT during volume expansion were evaluated on 29 septic patients; median SOFA score was 7 [5-9], median SAPS II was 57 [45-72], and ICU mortality rate was 24%. Twenty-three patients were responders as defined by a CRT decrease > 0.2 s at 30 min after volume expansion, and 6 were non-responders. Among responders, we observed that fingertip CRT quickly improved with a significant decrease at 6-8 min after start of crystalloid infusion, the maximal improvement being observed after 10-12 min (-0.7 [-0.3;-0.9] s) and maintained at 30 min. CRT variations significantly correlated with baseline CRT measurements (R = 0.39, P = 0.05). CONCLUSIONS: CRT quickly improved during volume expansion with a significant decrease 6-8 min after start of fluid infusion and a maximal drop at 10-12 min.

Impact on 6-month outcomes of hospital trajectory in critically ill older patients: analysis of the ICE-CUB2 clinical trial.

BACKGROUND: Little is known about the impact of hospital trajectory on survival and functional decline of older critically ill patients. We evaluate 6-month outcomes after admission to: intensive care units (ICU), intermediate care units (IMCU) or acute medical wards (AMW). METHODS: Data from the randomised prospective multicentre clinical trial ICE-CUB2 was secondarily analysed. Inclusion criteria were: presenting at emergency departments in critical condition; age ≥ 75 years; activity of daily living (ADL) ≥ 4; preserved nutritional status; and no active cancer. A Cox model was fitted to compare survival according to admission destination adjusting for patient characteristics. Sensitivity analysis using multiple imputation for missing data and propensity score matching were performed. RESULTS: Among 3036 patients, 1675 (55%) were women; median age was 85 [81-99] years; simplified acute physiology score (SAPS-3) 62 [55-69]; 1448 (47%) were hospitalised in an ICU, 504 in IMCU (17%), and 1084 (36%) in AMW. Six-month mortality was 629 (44%), 155 (31%) and 489 (45%) after admission in an ICU, IMCU and AMW (p < 0.001), respectively. In multivariate analysis, AMW admission was associated with worse 6-month survival (HR 1.31, 95% CI 1.04-1.63) in comparison with IMCU admission, after adjusting for age, gender, comorbidities, ADL, SAPS-3 and diagnosis. Survival was not significantly different between patients admitted in an ICU and an IMCU (HR 1.17, 95% CI 0.95-1.46). Sensitivity analysis using multiple imputation for missing data and propensity score matching found similar results. Hospital destination was not significantly associated with the composite criterion loss of 1-point ADL or mortality. Physical and mental components of the 12-Item Short-Form Health Survey were significantly lower in the acute medical ward group (34.3 [27.5-41.7], p = 0.037 and 44.3 [38.6-48.6], p = 0.028, respectively) than in the ICU group (34.7 [28.4-45.3] and 45.5 [40.0-50.0], respectively) and IMCU group (35.7 [29.7-43.8] and 44.5 [39.7-48.4], respectively). CONCLUSIONS: Admission in an AMW was associated with worse 6-month survival in older critically ill patients in comparison with IMCU admission, with no difference of survival between ICU and IMCU admission. There were no clinically relevant differences in quality of life in each group. These results should be confirmed in specific studies and raise the question of dedicated geriatric IMCUs.

Delayed inflammation decrease is associated with mortality in Tocilizumab-treated critically ill SARS-CoV-2 patients: A retrospective matched-cohort analysis.

Little is known about the immuno-inflammatory response to Tocilizumab and its association with outcome in critically-ill SARS-CoV2 pneumonia. In this multicenter retrospective cohort of SARS-CoV-2 patients admitted to three intensive care units between March and April 2020, we matched on gender and SAPS II 21 Tocilizumab-treated patients to 42 non-treated patients. Need for mechanical ventilation was 76% versus 79%. IL-6, C-reactive protein, and fibrinogen had been collected within the first days of admission (T1), 3 d (T2) and 7 d (T3) later. Tocilizumab-treated patients had persistently higher IL-6 plasma levels and persistently lower C-Reactive protein and fibrinogen levels. Among Tocilizumab-treated patients, baseline levels of inflammatory biomarkers were not different according to outcome. Conversely, C-reactive protein and fibrinogen decrease was delayed in non-survivors. C-Reactive protein decreased at T1 in survivors (45 [30-98] vs 170 [69-204] mg/l, P < 0.001) but only at T2 in non-survivors (37 [13-74] vs 277 [235-288], P = 0.03). Fibrinogen decreased at T2 in survivors (4.11 [3.58-4.69] vs 614 [5.61-7.85] g/l, P = 0.005) but not in non-survivors (4.79 [4.12-7.58] vs 7.24 [6.22-9.24] g/l, P = 0.125). Tocilizumab treatment was thus associated with a persistent both increase in plasma IL-6, and decrease in C-reactive protein and fibrinogen. Among Tocilizumab-treated patients, the decrease in inflammatory biomarkers was delayed in non-survivors.

Outcome of allogeneic hematopoietic stem cell transplant recipients admitted to the intensive care unit with a focus on haploidentical graft and sequential conditioning regimen: results of a retrospective study.

Haploidentical transplantation has extended the availability of allogeneic hematopoietic stem cell transplant (alloHCT) to almost all patients. Sequential conditioning regimens have been proposed for the treatment of hematological active disease. Whether these new transplantation procedures affect the prognosis of critically ill alloHCT recipients remains unknown. We evaluated this question in a retrospective study including consecutive alloHCT patients admitted to the intensive care unit of a tertiary academic center from 2010 to 2017. During the study period, 412 alloHCTs were performed and 110 (27%) patients-median age 55 (36-64) years-were admitted to ICU in a median time of 58.5 (14-245) days after alloHCT. Twenty-nine (26%) patients had received a haploidentical graft and 34 (31%) a sequential conditioning. Median SOFA score was 9 (6-11). Invasive mechanical ventilation (MV) was required in 61 (55%) patients. Fifty-six (51%) patients died in the hospital. Independent factors associated with in-hospital mortality were as follows: MV (OR=8.44 [95% CI 3.30-23.19], p<0.001), delta SOFA between day 3 and day 1 (OR=1.60 [95% CI 1.31-2.05], p<0.0001), and sequential conditioning (OR=3.7 [95% CI 1.14-12.92], p=0.033). Sequential conditioning was also independently associated with decreased overall survival (HR=1.86 [95% CI 1.05-3.31], p=0.03). Other independent factors associated with reduced overall survival were HCT-specific comorbidity index ≥2 (HR=1.76 [95% CI 1.10-2.84], p=0.02), acute GVHD grade ≥2 (HR=1.88 [95% CI 1.14-3.10], p=0.01), MV (HR=2.37 [95% CI 1.38-4.07, p=0.002), and vasopressors (HR=2.21 [95% CI 1.38-3.54], p=0.001). Haploidentical transplantation did not affect outcome. Larger multicenter studies are warranted to confirm these results.

Frailty is associated with long-term outcome in patients with sepsis who are over 80 years old: results from an observational study in 241 European ICUs.

BACKGROUND: Sepsis is one of the most frequent reasons for acute intensive care unit (ICU) admission of very old patients and mortality rates are high. However, the impact of pre-existing physical and cognitive function on long-term outcome of ICU patients ≥ 80 years old (very old intensive care patients (VIPs)) with sepsis is unclear. OBJECTIVE: To investigate both the short- and long-term mortality of VIPs admitted with sepsis and assess the relation of mortality with pre-existing physical and cognitive function. DESIGN: Prospective cohort study. SETTING: 241 ICUs from 22 European countries in a six-month period between May 2018 and May 2019. SUBJECTS: Acutely admitted ICU patients aged ≥80 years with sequential organ failure assessment (SOFA) score ≥ 2. METHODS: Sepsis was defined according to the sepsis 3.0 criteria. Patients with sepsis as an admission diagnosis were compared with other acutely admitted patients. In addition to patients' characteristics, disease severity, information about comorbidity and polypharmacy and pre-existing physical and cognitive function were collected. RESULTS: Out of 3,596 acutely admitted VIPs with SOFA score ≥ 2, a group of 532 patients with sepsis were compared to other admissions. Predictors for 6-month mortality were age (per 5 years): Hazard ratio (HR, 1.16 (95% confidence interval (CI), 1.09-1.25, P < 0.0001), SOFA (per one-point): HR, 1.16 (95% CI, 1.14-1.17, P < 0.0001) and frailty (CFS > 4): HR, 1.34 (95% CI, 1.18-1.51, P < 0.0001). CONCLUSIONS: There is substantial long-term mortality in VIPs admitted with sepsis. Frailty, age and disease severity were identified as predictors of long-term mortality in VIPs admitted with sepsis.

Acute cholangitis in intensive care units: clinical, biological, microbiological spectrum and risk factors for mortality: a multicenter study.

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 < 0.001), total serum bilirubin (OR 1.26 [95% CI 1.12-1.41], by 50 µmol/L, p < 0.001), obstruction non-related to gallstones (p < 0.05) and AC complications (OR 2.74 [95% CI 1.45-5.17], 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.

Economic model of albumin infusion in septic shock: The EMAISS study.

BACKGROUND: The cost-effectiveness of albumin-based fluid support in patients with septic shock is currently unknown. METHODS: In a simulation study, we compared standard medical practice and systematic 20% albumin infusion. The study population consisted of patients with septic shock admitted to one of the 28 ICUs belonging to the Cub-Réa regional database between 1 January 2014 and 31 December 2016. Cost estimates were based on French diagnosis-related groups and fixed daily prices. Estimation of mortality reduction relied on ALBIOS trial data documenting a Risk Ratio of 0.87 in a non-preplanned subgroup of patients with septic shock. Life expectancy was estimated with follow up data of 184 patients with septic shock admitted in the year 2000 in the same ICUs. Several sensitivity analyses were performed including a one-way Deterministic Sensitivity Analysis (DSA) and a Probabilistic multivariate Sensitivity Analysis (PSA). RESULTS: About 6406 patients were included. In the base-case scenario, the mean live years gained with albumin was 0.49. The mean extra cost of using albumin was €480 per year. The cost per year gained was €974. Sensitivity analyses confirmed the robustness of the results. The probability of albumin being cost-effective was 95% and 97% for a threshold fixed at €20 000 and €30 000 per life-year saved, respectively. CONCLUSION: Based on the risk reduction observed in the septic shock subgroup analysis of the ALBIOS dataset, the application of the ALBIOS trial results to Cub-Réa data may suggest that albumin infusion is likely cost-effective in septic shock.

The contribution of frailty, cognition, activity of daily life and comorbidities on outcome in acutely admitted patients over 80 years in European ICUs: the VIP2 study.

PURPOSE: Premorbid conditions affect prognosis of acutely-ill aged patients. Several lines of evidence suggest geriatric syndromes need to be assessed but little is known on their relative effect on the 30-day survival after ICU admission. The primary aim of this study was to describe the prevalence of frailty, cognition decline and activity of daily life in addition to the presence of comorbidity and polypharmacy and to assess their influence on 30-day survival. METHODS: Prospective cohort study with 242 ICUs from 22 countries. Patients 80 years or above acutely admitted over a six months period to an ICU between May 2018 and May 2019 were included. In addition to common patients' characteristics and disease severity, we collected information on specific geriatric syndromes as potential predictive factors for 30-day survival, frailty (Clinical Frailty scale) with a CFS > 4 defining frail patients, cognitive impairment (informant questionnaire on cognitive decline in the elderly (IQCODE) with IQCODE ≥ 3.5 defining cognitive decline, and disability (measured the activity of daily life with the Katz index) with ADL ≤ 4 defining disability. A Principal Component Analysis to identify co-linearity between geriatric syndromes was performed and from this a multivariable model was built with all geriatric information or only one: CFS, IQCODE or ADL. Akaike's information criterion across imputations was used to evaluate the goodness of fit of our models. RESULTS: We included 3920 patients with a median age of 84 years (IQR: 81-87), 53.3% males). 80% received at least one organ support. The median ICU length of stay was 3.88 days (IQR: 1.83-8). The ICU and 30-day survival were 72.5% and 61.2% respectively. The geriatric conditions were median (IQR): CFS: 4 (3-6); IQCODE: 3.19 (3-3.69); ADL: 6 (4-6); Comorbidity and Polypharmacy score (CPS): 10 (7-14). CFS, ADL and IQCODE were closely correlated. The multivariable analysis identified predictors of 1-month mortality (HR; 95% CI): Age (per 1 year increase): 1.02 (1.-1.03, p = 0.01), ICU admission diagnosis, sequential organ failure assessment score (SOFA) (per point): 1.15 (1.14-1.17, p < 0.0001) and CFS (per point): 1.1 (1.05-1.15, p < 0.001). CFS remained an independent factor after inclusion of life-sustaining treatment limitation in the model. CONCLUSION: We confirm that frailty assessment using the CFS is able to predict short-term mortality in elderly patients admitted to ICU. Other geriatric syndromes do not add improvement to the prediction model. Since CFS is easy to measure, it should be routinely collected for all elderly ICU patients in particular in connection to advance care plans, and should be used in decision making.

Transfusion-related acute lung injury (TRALI) after intravenous immunoglobulins: French multicentre study and literature review.

Transfusion-related acute lung injury (TRALI), defined as the onset of acute respiratory distress after blood transfusion, is a rare complication which is a leading cause of transfusion related-mortality. In this retrospective study, we report the French nationwide experience of intravenous immunoglobulin (IVIG)-related TRALI, with a literature review and analysis of management and outcome of this rare condition. With the pharmacovigilance services, we conducted a retrospective multicenter study in the French network of intensive care units with TRALI concomitant to IVIG use and pooled with data from a literature review. Overall, 17 cases have been included in this case-series, our case report, seven personal cases and nine cases from the literature review. The median age was 55 years [2-79] with 10/17 (59%) male subjects. The underlying diseases motivating IVIG infusion were neurologic diseases in 35% of cases (Guillain Barre syndrome = 2, peripheral neuropathy = 2, neurolupus = 1, myasthenia = 1), multiple myeloma with hypogammaglobulinemia (n = 2; 12%), primary hypogammaglobulinemia (n = 2; 12%), autoimmune cytopenias (n = 2; 12%), graft versus host cutaneous disease after allogeneic hematopoietic stem cell transplantation for acute myeloid leukaemia (n = 1), anti-HLA antibodies after lung transplant (n = 1), cancer-associated thrombotic thrombocytopenic purpura-haemolytic uremic syndrome (n = 1), Kawasaki disease (n = 1) and in experimental essay (n = 1). TRALI symptoms begin either after the start or during the infusion (n = 7; 41%), or after the infusion (n = 10; 59%, 10 min to 24 h). Besides respiratory distress, it was also noted shock (33%), fever (18 %), cough (18%), nausea/vomiting (18 %), chills (12%) and agitation (12%). The X-ray showed mainly bilateral alveolar opacities (n = 15; 88%). Mechanical ventilation was needed in nine cases (53%), with median 1-day duration [1-4]. Four patients (24%) died during hospitalisation in the intensive care unit. Given the increasing use of intravenous immunoglobulins, TRALI must now be discussed in cases of respiratory distress occurring during or immediately following the infusion even if this side effect remains rare.Key Points• TRALI must now be discussed in cases of respiratory distress occurring during or immediately following an infusion of intravenous immunoglobulins.

One-Year Prognosis of Kidney Injury at Discharge From the ICU: A Multicenter Observational Study.

OBJECTIVES: The association between outcome and kidney injury detected at discharge from the ICU using different biomarkers remains unknown. The objective was to evaluate the association between 1-year survival and kidney injury at ICU discharge. DESIGN: Ancillary investigation of a prospective observational study. SETTING: Twenty-one ICUs with 1-year follow-up. PATIENTS: Critically ill patients receiving mechanical ventilation and/or hemodynamic support for at least 24 hours were included. INTERVENTIONS: Serum creatinine, plasma Cystatin C, plasma neutrophil gelatinase-associated lipocalin, urinary neutrophil gelatinase-associated lipocalin, plasma Proenkephalin A 119-159, and estimated glomerular filtration rate (on serum creatinine and plasma Cystatin C) were measured at ICU discharge among ICU survivors. MEASUREMENTS AND MAIN RESULTS: The association between kidney biomarkers at discharge and mortality was estimated using logistic model with and without adjustment for prognostic factors previously identified in this cohort. Subgroup analyses were performed in patients with discharge serum creatinine less than 1.5-fold baseline at ICU discharge. Among 1,207 ICU survivors included, 231 died during the year following ICU discharge (19.2%). Estimated glomerular filtration rate was significantly lower and kidney injury biomarkers higher at discharge in nonsurvivors. The association between biomarker levels or estimated glomerular filtration rate and mortality remained after adjustment to potential cofounding factors influencing outcome. In patients with low serum creatinine at ICU discharge, 25-47% of patients were classified as subclinical kidney injury depending on the biomarker. The association between kidney biomarkers and mortality remained and mortality was higher than patients without subclinical kidney injury. The majority of patients who developed acute kidney injury during ICU stay had elevated biomarkers of kidney injury at discharge even with apparent recovery based on serum creatinine (i.e., subclinical acute kidney disease). CONCLUSIONS: Elevated kidney biomarkers measured at ICU discharge are associated with poor 1-year outcome, including in patients with low serum creatinine at ICU discharge.

A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention.

BACKGROUND: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (≥80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed. METHODS: In total, 5063 VIPs were included in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality. RESULTS: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 ±â€¯5 vs 7 ±â€¯7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02). CONCLUSIONS: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery. TRIAL REGISTRATION: NCT03134807. Registered 1st May 2017.

Epidemiology of infective endocarditis in French intensive care units over the 1997-2014 period-from CUB-Réa Network.

BACKGROUND: Few studies focus only on severe forms of infective endocarditis, for which organ failure requires admission to an intensive care unit (ICU). This study aimed to describe demographical, comorbidities, organ failure, and pathogen-related characteristics in a population of critically ill patients admitted to ICU for infective endocarditis and to identify risk factors of in-ICU mortality. METHODS: Retrospective observational multicenter (N = 34) study of the CUB-Rea register, based on ICD-10 coding rules, between 1997 and 2014 in France including ICU patients managed for infective endocarditis. In-ICU mortality associated factors were assessed by multivariate logistic regression including an interrupted time analysis of three periods (1997-2003, 2004-2009, and 2010-2014). RESULTS: Four thousand four hundred five patients admitted in ICU for infective endocarditis were included. We observed an increase in endocarditis prevalence, as well as an increase in organ failure severity over the three periods. In addition, valve surgery was more frequently performed (27%, 31%, and 42%, P < 0.0001) while in-ICU mortality significantly decreased (28%, 29%, and 23%, P < 0.001). Since 2010, a significant increase in the trends' slope of incidence for Streptococcus sp. and Staphylococcus sp. was observed with no change concerning intracellular bacteria, Enterococcus sp. or Candida sp. slope trends. In multivariate analysis, age, SAPS2, organ failure, stroke, and Staphylococcus sp. were associated with ICU mortality. Conversely, surgery, intracardiac devices, male gender, and Streptococcus sp.-related infective endocarditis were associated with a better outcome. CONCLUSIONS: Our study reveals a shifting landscape of infective endocarditis epidemiology in French ICUs, characterized by reduced in-ICU mortality despite higher severity, more surgery, and substantial changes in microbial epidemiology.

Effect of Systematic Intensive Care Unit Triage on Long-term Mortality Among Critically Ill Elderly Patients in France: A Randomized Clinical Trial.

Importance: The high mortality rate in critically ill elderly patients has led to questioning of the beneficial effect of intensive care unit (ICU) admission and to a variable ICU use among this population. Objective: To determine whether a recommendation for systematic ICU admission in critically ill elderly patients reduces 6-month mortality compared with usual practice. Design, Setting, and Participants: Multicenter, cluster-randomized clinical trial of 3037 critically ill patients aged 75 years or older, free of cancer, with preserved functional status (Index of Independence in Activities of Daily Living ≥4) and nutritional status (absence of cachexia) who arrived at the emergency department of one of 24 hospitals in France between January 2012 and April 2015 and were followed up until November 2015. Interventions: Centers were randomly assigned either to use a program to promote systematic ICU admission of patients (n=1519 participants) or to follow standard practice (n=1518 participants). Main Outcomes and Measures: The primary outcome was death at 6 months. Secondary outcomes included ICU admission rate, in-hospital death, functional status, and quality of life (12-Item Short Form Health Survey, ranging from 0 to 100, with higher score representing better self-reported health) at 6 months. Results: One patient withdrew consent, leaving 3036 patients included in the trial (median age, 85 [interquartile range, 81-89] years; 1361 [45%] men). Patients in the systematic strategy group had an increased risk of death at 6 months (45% vs 39%; relative risk [RR], 1.16; 95% CI, 1.07-1.26) despite an increased ICU admission rate (61% vs 34%; RR, 1.80; 95% CI, 1.66-1.95). After adjustments for baseline characteristics, patients in the systematic strategy group were more likely to be admitted to an ICU (RR, 1.68; 95% CI, 1.54-1.82) and had a higher risk of in-hospital death (RR, 1.18; 95% CI, 1.03-1.33) but had no significant increase in risk of death at 6 months (RR, 1.05; 95% CI, 0.96-1.14). Functional status and physical quality of life at 6 months were not significantly different between groups. Conclusions and Relevance: Among critically ill elderly patients in France, a program to promote systematic ICU admission increased ICU use but did not reduce 6-month mortality. Additional research is needed to understand the decision to admit elderly patients to the ICU. Trial Registration: clinicaltrials.gov Identifier: NCT01508819.

Designing and conducting a cluster-randomized trial of ICU admission for the elderly patients: the ICE-CUB 2 study.

BACKGROUND: The benefit of ICU admission for elderly patients remains controversial. This report highlights the methodology, the feasibility of and the ethical and logistical constraints in designing and conducting a cluster-randomized trial of intensive care unit (ICU) admission for critically ill elderly patients. METHODS: We designed an interventional open-label cluster-randomized controlled trial in 24 centres in France. Clusters were healthcare centres with at least one emergency department (ED) and one ICU. Healthcare centres were randomly assigned either to recommend a systematic ICU admission (intervention group) or to follow standard practices regarding ICU admission (control group). Clusters were stratified by the number of ED annual visits (<44,616 or >44,616 visits), the presence or absence of a geriatric ward and the geographical area (Paris area vs other regions in France). All elderly patients (≥75 years of age) who got to the ED were assessed for eligibility. Patients were included if they had one of the pre-established critical conditions, a preserved functional status as assessed by an ADL scale ≥4 (0 = very dependent, 6 = independent), a preserved nutritional status (subjectively assessed by physicians) and without active cancer. Exclusion criteria were an ED stay >24 h, a secondary referral to the ED and refusal to participate. The primary outcome was the mortality at 6 months calculated at the individual patient level. Secondary outcomes were ICU and hospital mortality, as well as ADL scale and quality of life (as assessed by the SF-12 Health Survey) at 6 months. RESULTS: Between January 2012 and April 2015, 3036 patients were included in the trial, 1518 patients in 11 clusters allocated to intervention group and 1518 patients in 13 clusters allocated to standard care. There were 51 protocol violations. CONCLUSIONS: The ICE-CUB 2 trial was deemed feasible and ethically acceptable. The ICE-CUB 2 trial will be the first cluster-randomized trial to assess the benefits of ICU admission for selected elderly patients on long-term mortality. Trial registration Clinical trials.gov identifier: NCT01508819.

A case of melphalan sustained accumulation in an 80-year old patient.

Case We report the case of melphalan accumulation in an 80-year old female with multiple myeloma. Her initial health status was good except for a moderate chronic renal failure (estimated glomerular filtration rate: 31 ml/min) and anemia. Among other drugs, her usual treatment included trimethoprim/sulfamethoxazole and the patient received melphalan from day 1 to day 4 for multiple myeloma. On day 13, she was admitted in intensive care unit for acute renal failure and severe sepsis with pancytopenia. Usual treatments were stopped. Melphalan blood concentrations were 123.6 ng/ml on day 16 and 87.5 ng/ml on day 17 while cerebrospinal fluid concentration was 173.8 ng/ml on day 25. Patient recovered on day 30. Melphalan accumulation may be explained by substrate competition between sulfamethoxazole and melphalan in metabolism pathway and chronic renal failure. Conclusion close clinical and renal monitoring should be performed in patient receiving melphalan and sulfamethoxazole.

Temporal trends in critical events complicating HIV infection: 1999-2010 multicentre cohort study in France.

PURPOSE: Multicentre data are limited to appraise the management and prognosis of critically ill human immunodeficiency virus (HIV)-infected patients. We sought to describe temporal trends in demographic and clinical characteristics, indications for intensive care and outcome in this patient population. METHODS: We conducted a cohort study of unselected HIV-infected patients admitted between 1999 and 2010 to 34 French ICUs contributing to the CUB-Réa prospective database. RESULTS: We included 6,373 consecutive patients. Over the 12-year period, increases occurred in median age (39 years in 1999-2001; 47 years in 2008-2010, p < 0.0001) and prevalence of comorbidities (notably malignancies, from 6.7 to 16.4%, p < 0.0001). Admissions for respiratory failure (39.8% overall), shock (8.1%) and coma (22.7%) decreased (p < 0.0001), while those for sepsis (19.3%) remained stable. The main final diagnoses were bacterial sepsis (24.6%) and non-bacterial acquired immune deficiency syndrome (AIDS)-defining diseases (steady decline from 26.0 to 17.5%, p < 0.0001). Patients increasingly received mechanical ventilation (from 42.9 to 54.0%) and renal replacement therapy (from 9.6 to 16.8%) (p < 0.0001), whereas vasopressor use remained stable (27.4%). ICU readmissions increased after 2004 (p < 0.0001). ICU and hospital mortality (17.6 and 26.9%, respectively) dropped markedly in the most severely ill patients requiring multiple life-sustaining therapies. Malignancies and chronic liver disease were heavily associated with hospital mortality by multivariate analysis, while the most common AIDS-defining complications (Pneumocystis jirovecii pneumonia, cerebral toxoplasmosis and tuberculosis) had no independent impact. CONCLUSIONS: Progressive ageing, increasing prevalence of comorbidities (mainly malignancies), a steady decline in AIDS-related illnesses and improved benefits from life-sustaining therapies were the main temporal trends in HIV-infected patients requiring ICU admission.