Convalescent Plasma for Covid-19-Induced ARDS in Mechanically Ventilated Patients.

BACKGROUND: Passive immunization with plasma collected from convalescent patients has been regularly used to treat coronavirus disease 2019 (Covid-19). Minimal data are available regarding the use of convalescent plasma in patients with Covid-19-induced acute respiratory distress syndrome (ARDS). METHODS: In this open-label trial, we randomly assigned adult patients with Covid-19-induced ARDS who had been receiving invasive mechanical ventilation for less than 5 days in a 1:1 ratio to receive either convalescent plasma with a neutralizing antibody titer of at least 1:320 or standard care alone. Randomization was stratified according to the time from tracheal intubation to inclusion. The primary outcome was death by day 28. RESULTS: A total of 475 patients underwent randomization from September 2020 through March 2022. Overall, 237 patients were assigned to receive convalescent plasma and 238 to receive standard care. Owing to a shortage of convalescent plasma, a neutralizing antibody titer of 1:160 was administered to 17.7% of the patients in the convalescent-plasma group. Glucocorticoids were administered to 466 patients (98.1%). At day 28, mortality was 35.4% in the convalescent-plasma group and 45.0% in the standard-care group (P = 0.03). In a prespecified analysis, this effect was observed mainly in patients who underwent randomization 48 hours or less after the initiation of invasive mechanical ventilation. Serious adverse events did not differ substantially between the two groups. CONCLUSIONS: The administration of plasma collected from convalescent donors with a neutralizing antibody titer of at least 1:160 to patients with Covid-19-induced ARDS within 5 days after the initiation of invasive mechanical ventilation significantly reduced mortality at day 28. This effect was mainly observed in patients who underwent randomization 48 hours or less after ventilation initiation. (Funded by the Belgian Health Care Knowledge Center; ClinicalTrials.gov number, NCT04558476.).

Perceived Quality of Life in Intensive Care Medicine Physicians: A French National Survey.

Purpose: There is a growing interest in the quality of work life (QWL) of healthcare professionals and staff well-being. We decided to measure the perceived QWL of ICU physicians and the factors that could influence their perception. Methods: We performed a survey coordinated and executed by the French Trade Union of Intensive Care Physicians (SMR). QWL was assessed using the French version of the Work-Related Quality of Life (WRQoL) scale, perceived stress using the French version of 10 item-Perceived Stress Scale (PSS-10) and group functioning using the French version of the Reflexivity Scale, the Social Support at Work Questionnaire (QSSP-P). Results: 308 French-speaking ICU physicians participated. 40% perceived low WRQoL, mainly due to low general well-being, low satisfaction with working conditions and low possibility of managing the articulation between their private and professional lives. Decreased QWL was associated with being a woman (p = .002), having children (p = .022) and enduring many monthly shifts (p = .022). Conclusions: This work highlights the fact that ICU physicians feel a significant imbalance between the demands of their profession and the resources at their disposal. Communication and exchanges within a team and quality of social support appear to be positive elements to maintain and/or develop within our structures.

Incidence of near-death experiences in patients surviving a prolonged critical illness and their long-term impact: a prospective observational study.

BACKGROUND: So far, the few prospective studies on near-death experience (NDE) were carried out only in intensive care unit (ICU) patients with homogeneous aetiologies, such as cardiac arrest or trauma survivors. The aims of this 1-year prospective and monocentric study were to investigate the incidence of NDE in ICU survivors (all aetiologies) as well as factors that may affect its frequency, and to assess quality of life up to 1 year after enrolment. METHODS: We enrolled adults with a prolonged ICU stay (> 7 days). During the first 7 days after discharge, all eligible patients were assessed in a face-to-face interview for NDE using the Greyson NDE scale, dissociative experiences using the Dissociative Experience Scale, and spirituality beliefs using the WHOQOL-SRPB. Medical parameters were prospectively collected. At 1-year after inclusion, patients were contacted by phone to measure quality of life using the EuroQol five-dimensional questionnaire. RESULTS: Out of the 126 included patients, 19 patients (15%) reported having experienced a NDE as identified by the Greyson NDE scale (i.e. cut-off score ≥ 7/32). In univariate analyses, mechanical ventilation, sedation, analgesia, reason for admission, primary organ dysfunction, dissociative and spiritual propensities were associated with the emergence of NDE. In multivariate logistic regression analysis, only the dissociative and spiritual propensity strongly predicted the emergence of NDE. One year later (n = 61), the NDE was not significantly associated with quality of life. CONCLUSIONS: The recall of NDE is not so rare in the ICU. In our cohort, cognitive and spiritual factors outweighed medical parameters as predictors of the emergence of NDE. Trial registration This trial was registered in Clinicaltrials.gov in February 2020 ( NCT04279171 ).

What is the nutritional status of patients with prolonged disorders of consciousness? A retrospective cross-sectional study.

BACKGROUND: Nutritional status of patients with disorders of consciousness (DoC) is poorly studied. OBJECTIVES: To evaluate the relationship between nutritional status (body mass index, daily calories intake) and clinical variables (level of consciousness, time since injury, diagnosis, etiology and spastic muscle overactivity; SMO,) in patients with prolonged DoCor emerging. Our main hypotheses are i) patients with lower level of consciousness (UWS) have worse nutritional status compared to patients in minimally conscious state (MCS) and ii) SMO could influence nutritional status. METHODS AND RESULTS: Among the 80 patients included in the study (19 UWS, 47 MCS, 14 emerging MCS; 43 ± 15 yo; 3 ± 4 years post-injury, 35 traumatic etiology, 34 females), 9% were at risk to be undernourished, with no differences between UWS and MCS. Patients without SMO had a higher BMI compared to patients with severe SMO. Compared to the recommended daily calories intake, patients with the highest BMI received less calories and patients with the lowest BMI received more calories. We observed a negative correlation between SMO (in lower limbs) and BMI. CONCLUSION: Our study shows that most patients are well nourished, independently from the level of consciousness. SMO may require additional calories in patients' daily needs; however, longitudinal studies are needed to explore the causal relationship between these variables.

Diaphragm function in patients with sepsis and septic shock: A longitudinal ultrasound study.

BACKGROUND: Previous literature on the determinants of diaphragm dysfunction in septic patients is limited. The goal of this study is to assess diaphragm dysfunction in terms of its prevalence and its potential associated factors in septic intensive care unit (ICU) patients. METHODS: This prospective and observational study was conducted between June 2015 and July 2019. Ultrasound measures of diaphragm thickness were performed daily on septic patients. The primary outcome was the prevalence of diaphragm dysfunction at baseline and during the ICU stay. The secondary outcome was the diaphragm thickness. Possible associated factors were prospectively recorded. RESULTS: Fifty patients were enrolled in the study. The prevalence of diaphragm dysfunction was 58%. No diaphragm atrophy was found during the ICU stay. Diaphragm dysfunction was associated with the alteration of consciousness, intra-abdominal sepsis, hypnotics and opioids, and mechanical ventilation. Administration of hypnotics, opioids, and steroids was associated with a decreased diaphragm thickening fraction. Diaphragm dysfunction had no impact on patient outcomes. CONCLUSIONS: Our data reveal a high prevalence of diaphragm dysfunction in septic patients at the onset of sepsis. Administration of hypnotics, opioids, and steroids was associated with the alteration of diaphragm function as well as intra-abdominal sepsis.

Post-intensive care screening: French translation and validation of the Healthy Aging Brain Care-Monitor, hybrid version.

BACKGROUND: The Healthy Aging Brain Care-Monitor (HABC-M) questionnaires (self-reported version and caregiver version) have been validated for post-intensive care syndrome (PICS) detection in patients surviving a stay in the intensive care unit (ICU). Their authors have also developed a hybrid version (HABC-M-HV) suited to the daily needs of their post-ICU follow-up clinic. The objectives of the present cross-sectional observational study were to translate the HABC-M-HV questionnaire into French (HABC-M-HV-F) according to international guidelines and to test its measurement properties. METHODS: The HABC-M-HV was translated according to international guidelines. The measurement performances of the questionnaire were tested using internal consistency, test-retest reliability, Standard Error of Measurement (SEM) and Smallest Detectable Change (SDC) calculation, floor and ceiling effect measurement and construct validity. RESULTS: The validation study included 51 ICU survivors (27.5% women, 63 [55-71] years old). The questionnaire was administered by phone. The internal consistency was very good (Cronbach's alpha coefficient 0.79). The intra- and inter-examinator reliabilities were excellent (Intraclass Coefficient Correlation = 0.99 and 0.97, respectively). The SEM was 0.62 and the SDC was 1.72. No floor or ceiling effects were observed. The convergent validity was almost entirely confirmed with 71.4% of our hypothesis confirmed. CONCLUSION: The HABC-M-HV-F has been shown to be a valid and reliable tool for PICS screening and follow-up in French-speaking ICU survivors. A remote administration by phone was feasible. TRIAL REGISTRATION: Not applicable.

Physical capacities assessment in critically ill patients: An exploratory study.

BACKGROUND: The severity of muscle weakness after critical illness is very heterogeneous. To identify those patients who may maximally benefit from early exercises would be highly valuable. This implies an assessment of physical capacities, comprised at least of strength measurement and functional tests. OBJECTIVES: The objective of this study was to investigate the relationship between muscle strength and functional tests in an intensive care unit (ICU) setting. METHODS: Adults with ICU length of stay ≥2 days were included. Handgrip strength (HG) and maximal isometric quadriceps strength (QS) were assessed using standardised protocols as soon as patients were alert and able to obey commands. At the same time, their maximal level of mobilisation capabilities and their autonomy were assessed using ICU Mobility Scale (ICU-MS) and Barthel Index, respectively. RESULTS: Ninety-three patients with a median age of 64 [57-71.5] years, body mass index of 26.4 [23.4-29.6] kg/m2, and Simplified Acute Physiology Score II of 33 [27.7-41] were included. Absolute and relative QS were, respectively, 146.7 [108.5-196.6] N and 1.87 [1.43-2.51] N/kg. HG was 22 [16-31] kg. The ICU-MS score was 4 [1-5]. A significant positive correlation was observed between HG and absolute QS (rs = 0.695, p < 0.001) and between HG and relative QS (rs = 0.428, p < 0.001). The ICU-MS score correlated with HG, with a weak positive relationship (rs = 0.215, p = 0.039), but not with QS. The ICU-MS score did not statistically differ between the weakest and strongest patients for absolute or relative QS, but was lower in patients with the lowest HG values (p = 0.01). A weak positive correlation was observed between the Barthel Index and muscle strengths (maximum rs = 0.414, p < 0.001). CONCLUSIONS: The present results suggest that, during ICU stay, there is no strong association between muscle strength and functional test such as the ICU-MS or Barthel Index. Muscle dynamometry and functional tests are probably complementary tools for physical capacities quantification.

Hydrocortisone plus Fludrocortisone for Adults with Septic Shock.

BACKGROUND: Septic shock is characterized by dysregulation of the host response to infection, with circulatory, cellular, and metabolic abnormalities. We hypothesized that therapy with hydrocortisone plus fludrocortisone or with drotrecogin alfa (activated), which can modulate the host response, would improve the clinical outcomes of patients with septic shock. METHODS: In this multicenter, double-blind, randomized trial with a 2-by-2 factorial design, we evaluated the effect of hydrocortisone-plus-fludrocortisone therapy, drotrecogin alfa (activated), the combination of the three drugs, or their respective placebos. The primary outcome was 90-day all-cause mortality. Secondary outcomes included mortality at intensive care unit (ICU) discharge and hospital discharge and at day 28 and day 180 and the number of days alive and free of vasopressors, mechanical ventilation, or organ failure. After drotrecogin alfa (activated) was withdrawn from the market, the trial continued with a two-group parallel design. The analysis compared patients who received hydrocortisone plus fludrocortisone with those who did not (placebo group). RESULTS: Among the 1241 patients included in the trial, the 90-day mortality was 43.0% (264 of 614 patients) in the hydrocortisone-plus-fludrocortisone group and 49.1% (308 of 627 patients) in the placebo group (P=0.03). The relative risk of death in the hydrocortisone-plus-fludrocortisone group was 0.88 (95% confidence interval, 0.78 to 0.99). Mortality was significantly lower in the hydrocortisone-plus-fludrocortisone group than in the placebo group at ICU discharge (35.4% vs. 41.0%, P=0.04), hospital discharge (39.0% vs. 45.3%, P=0.02), and day 180 (46.6% vs. 52.5%, P=0.04) but not at day 28 (33.7% and 38.9%, respectively; P=0.06). The number of vasopressor-free days to day 28 was significantly higher in the hydrocortisone-plus-fludrocortisone group than in the placebo group (17 vs. 15 days, P<0.001), as was the number of organ-failure-free days (14 vs. 12 days, P=0.003). The number of ventilator-free days was similar in the two groups (11 days in the hydrocortisone-plus-fludrocortisone group and 10 in the placebo group, P=0.07). The rate of serious adverse events did not differ significantly between the two groups, but hyperglycemia was more common in hydrocortisone-plus-fludrocortisone group. CONCLUSIONS: In this trial involving patients with septic shock, 90-day all-cause mortality was lower among those who received hydrocortisone plus fludrocortisone than among those who received placebo. (Funded by Programme Hospitalier de Recherche Clinique 2007 of the French Ministry of Social Affairs and Health; APROCCHSS ClinicalTrials.gov number, NCT00625209 .).

Quadriceps strength in intensive care unit survivors: Variability and influence of preadmission physical activity.

BACKGROUND: Muscle weakness is common in patients who survive a stay in the intensive care unit (ICU). Quadriceps strength (QS) measurement allows evaluation of lower limb performances that are associated with mobility outcomes. OBJECTIVES: The objective of the study was to characterise the range of QS in ICU survivors (ICUS) during their short-term evolution, by comparing them with surgical patients without critical illness and with healthy participants. The secondary aim was to explore whether physical activity before ICU admission influenced QS during that trajectory. METHODS: Patients with length of ICU stay ≥2 days, adults scheduled for elective colorectal surgery, and young healthy volunteers were included. Maximal isometric QS was assessed using a handheld dynamometer and a previously validated standardised protocol. The dominant leg was tested in the supine position. ICUSs were tested in the ICU and 1 month after ICU discharge, while surgical patients were tested before and on the day after surgery, as well as 1 month after discharge. Healthy patients were tested once only. Patients were classified as physically inactive or active before admission from the self-report. RESULTS: Thirty-eight, 32, and 34 participants were included in the ICU, surgical, and healthy groups, respectively. Demographic data were similar in the ICUS and surgical groups. In the ICU, QS was lower in the ICU group than in the surgical and healthy groups (3.01 [1.88-3.48], 3.38 [2.84-4.37], and 5.5 [4.75-6.05] N/kg, respectively). QS did not significantly improve 1 month after ICU discharge, excepted in survivors who were previously physically active (22/38, 56%): the difference between the two time points was -6.6 [-27.1 to -1.7]% vs 20.4 [-3.4 to 43.3]%, respectively, in physically inactive and active patients (p = 0.002). CONCLUSIONS: Patients who survived an ICU stay were weaker than surgical patients. However, a huge QS heterogeneity was observed among them. Their QS did not improve during the month after ICU discharge. Physically inactive patients should be early identified as at risk of poorer recovery.

A multicenter randomized trial to assess the efficacy of CONvalescent plasma therapy in patients with Invasive COVID-19 and acute respiratory failure treated with mechanical ventilation: the CONFIDENT trial protocol.

BACKGROUND: The COVID-19 pandemic reached Europe in early 2020. Convalescent plasma is used without a consistent evidence of efficacy. Our hypothesis is that passive immunization with plasma collected from patients having contracted COVID-19 and developed specific neutralizing antibodies may alleviate symptoms and reduce mortality in patients treated with mechanical ventilation for severe respiratory failure during the evolution of SARS-CoV-2 pneumonia. METHODS: We plan to include 500 adult patients, hospitalized in 16 Belgian intensive care units between September 2020 and 2022, diagnosed with SARS-CoV-2 pneumonia, under mechanical ventilation for less than 5 days and a clinical frailty scale less than 6. The study treatment will be compared to standard of care and allocated by randomization in a 1 to 1 ratio without blinding. The main endpoint will be mortality at day 28. We will perform an intention to treat analysis. The number of patients to include is based on an expected mortality rate at day 28 of 40 percent and an expected relative reduction with study intervention of 30 percent with α risk of 5 percent and ß risk of 20 percent. DISCUSSION: This study will assess the efficacy of plasma in the population of mechanically ventilated patients. A stratification on the delay from mechanical ventilation and inclusion will allow to approach the optimal time use. Selecting convalescent plasmas with a high titer of neutralizing antibodies against SARS-CoV-2 will allow a homogeneous study treatment. The inclusion in the study is based on the consent of the patient or his/her legal representative, and the approval of the Investigational Review Board of the University hospital of Liège, Belgium. A data safety monitoring board (DSMB) has been implemented. Interim analyses have been planned at 100, 2002, 300 and 400 inclusions in order to decide whether the trail should be discontinued prematurely for ethical issues. We plan to publish our results in a peer-reviewed journal and to present them at national and international conferences. FUNDING AND REGISTRATION: The trial is funded by the Belgian Health Care Knowledge Center KCE # COV201004 TRIAL REGISTRATION: Clinicaltrials.gov registration number NCT04558476. Registered 14 September 2020-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04558476.

Effect of an ICU Diary on Posttraumatic Stress Disorder Symptoms Among Patients Receiving Mechanical Ventilation: A Randomized Clinical Trial.

Importance: Keeping a diary for patients while they are in the intensive care unit (ICU) might reduce their posttraumatic stress disorder (PTSD) symptoms. Objectives: To assess the effect of an ICU diary on the psychological consequences of an ICU hospitalization. Design, Setting, and Participants: Assessor-blinded, multicenter, randomized clinical trial in 35 French ICUs from October 2015 to January 2017, with follow-up until July 2017. Among 2631 approached patients, 709 adult patients (with 1 family member each) who received mechanical ventilation within 48 hours after ICU admission for at least 2 days were eligible, 657 were randomized, and 339 were assessed 3 months after ICU discharge. Interventions: Patients in the intervention group (n = 355) had an ICU diary filled in by clinicians and family members. Patients in the control group (n = 354) had usual ICU care without an ICU diary. Main Outcomes and Measures: The primary outcome was significant PTSD symptoms, defined as an Impact Event Scale-Revised (IES-R) score greater than 22 (range, 0-88; a higher score indicates more severe symptoms), measured in patients 3 months after ICU discharge. Secondary outcomes, also measured at 3 months and compared between groups, included significant PTSD symptoms in family members; significant anxiety and depression symptoms in patients and family members, based on a Hospital Anxiety and Depression Scale score greater than 8 for each subscale (range, 0-42; higher scores indicate more severe symptoms; minimal clinically important difference, 2.5); and patient memories of the ICU stay, reported with the ICU memory tool. Results: Among 657 patients who were randomized (median [interquartile range] age, 62 [51-70] years; 126 women [37.2%]), 339 (51.6%) completed the trial. At 3 months, significant PTSD symptoms were reported by 49 of 164 patients (29.9%) in the intervention group vs 60 of 175 (34.3%) in the control group (risk difference, -4% [95% CI, -15% to 6%]; P = .39). The median (interquartile range) IES-R score was 12 (5-25) in the intervention group vs 13 (6-27) in the control group (difference, -1.47 [95% CI, -1.93 to 4.87]; P = .38). There were no significant differences in any of the 6 prespecified comparative secondary outcomes. Conclusions and Relevance: Among patients who received mechanical ventilation in the ICU, the use of an ICU diary filled in by clinicians and family members did not significantly reduce the number of patients who reported significant PTSD symptoms at 3 months. These findings do not support the use of ICU diaries for preventing PTSD symptoms. Trial Registration: ClinicalTrials.gov Identifier: NCT02519725.

Urgent Chemotherapy for Life-Threatening Complications Related to Solid Neoplasms.

OBJECTIVES: Solid neoplasms can be directly responsible for organ failures at the time of diagnosis or relapse. The management of such specific complications relies on urgent chemotherapy and eventual instrumental or surgical procedures, combined with advanced life support. We conducted a multicenter study to address the prognosis of this condition. DESIGN: A multicenter retrospective (2001-2015) chart review. SETTING: Medical and respiratory ICUs. PATIENTS: Adult patients who received urgent chemotherapy in the ICU for organ failure related to solid neoplasms were included. The modalities of chemotherapy, requirements of adjuvant instrumental or surgical procedures, and organ supports were collected. Endpoints were short- and long-term survival rates. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred thirty-six patients were included. Lung cancer was the most common malignancy distributed into small cell lung cancer (n = 57) and non-small cell lung cancer (n = 33). The main reason for ICU admission was acute respiratory failure in 111 patients (81.6%), of whom 89 required invasive mechanical ventilation. Compression and tissue infiltration by tumor cells were the leading mechanisms resulting in organ involvement in 78 (57.4%) and 47 (34.6%) patients. The overall in-ICU, in-hospital, 6-month, and 1-year mortality rates were 37%, 58%, 74%, and 88%, respectively. Small cell lung cancer was identified as an independent predictor of hospital survival. However, this gain in survival was not sustained since the 1-year survival rates of small cell lung cancer, non-small cell lung cancer, and non-lung cancer patients all dropped below 20%. CONCLUSIONS: Urgent chemotherapy along with aggressive management of organ failures in the ICU can be lifesaving in very selected cancer patients, most especially with small cell lung cancer, although the long-term survival is hardly sustainable.

Impact of Proactive Nurse Participation in ICU Family Conferences: A Mixed-Method Study.

OBJECTIVES: To investigate family perceptions of having a nurse participating in family conferences and to assess the psychologic well being of the same families after ICU discharge. DESIGN: Mixed-method design with a qualitative study embedded in a single-center randomized study. SETTING: Twelve-bed medical-surgical ICU in a 460-bed tertiary hospital. SUBJECTS: One family member for each consecutive patient who received more than 48 hours of mechanical ventilation in the ICU. INTERVENTION: Planned proactive participation of a nurse in family conferences led by a physician. In the control group, conferences were led by a physician without a nurse. MEASUREMENTS AND MAIN RESULTS: Of the 172 eligible family members, 100 (60.2%) were randomized; among them, 88 underwent semistructured interviews at ICU discharge and 86 completed the Peritraumatic Dissociative Experiences Questionnaire at ICU discharge and then the Hospital Anxiety Depression Questionnaire and the Impact of Event Scale (for posttraumatic stress-related symptoms) 3 months later. The intervention and control groups were not significantly different regarding the prevalence of posttraumatic stress-related symptoms (52.3 vs 50%, respectively; p = 0.83). Anxiety and depression subscale scores were significantly lower in the intervention group. The qualitative data indicated that the families valued the principle of the conference itself. Perceptions of nurse participation clustered into four main themes: trust that ICU teamwork was effective (50/88; 56.8%), trust that care was centered on the patient (33/88; 37.5%), trust in effective dissemination of information (15/88; 17%), and trust that every effort was made to relieve anxiety in family members (12/88; 13.6%). CONCLUSIONS: Families valued the conferences themselves and valued the proactive participation of a nurse. These positive perceptions were associated with significant anxiety or depression subscale scores but not with changes in posttraumatic stress-related symptoms.

CD24-triggered caspase-dependent apoptosis via mitochondrial membrane depolarization and reactive oxygen species production of human neutrophils is impaired in sepsis.

Apoptosis is the most common pathway of neutrophil death under both physiological and inflammatory conditions. In this study, we describe an apoptotic pathway in human neutrophils that is triggered via the surface molecule CD24. In normal neutrophils, CD24 ligation induces death through depolarization of the mitochondrial membrane in a manner dependent on caspase-3 and caspase-9 and reactive oxygen species. Proinflammatory cytokines such as TNF-α, IFN-γ, and GM-CSF upregulated the expression of CD24 in vitro, favoring the emergence of a new CD16(high)/CD24(high) subset of cultured neutrophils. We observed that CD24 expression (at both mRNA and protein levels) was significantly downregulated in neutrophils from sepsis patients but not from patients with systemic inflammatory response syndrome. This downregulation was reproduced by incubation of neutrophils from healthy controls with corticosteroids or with plasma collected from sepsis patients, but not with IL-10 or TGF-ß. Decreased CD24 expression observed on sepsis neutrophils was associated with lack of functionality of the molecule, because cross-ligation of CD24 failed to trigger apoptosis in neutrophils from sepsis patients. Our results suggest a novel aspect of CD24-mediated immunoregulation and represent, to our knowledge, the first report showing the role of CD24 in the delayed/defective cell death in sepsis.

Characteristics and risk factors for 28-day mortality of hospital acquired fungemias in ICUs: data from the EUROBACT study.

BACKGROUND: To characterize and identify prognostic factors for 28-day mortality among patients with hospital-acquired fungemia (HAF) in the Intensive Care Unit (ICU). METHODS: A sub-analysis of a prospective, multicenter non-representative cohort study conducted in 162 ICUs in 24 countries. RESULTS: Of the 1156 patients with hospital-acquired bloodstream infections (HA-BSI) included in the EUROBACT study, 96 patients had a HAF. Median time to its diagnosis was 20 days (IQR 10.5-30.5) and 9 days (IQR 3-15.5) after hospital and ICU admission, respectively. Median time to positivity of blood culture was longer in fungemia than in bacteremia (48.7 h vs. 38.1 h; p = 0.0004). Candida albicans was the most frequent fungus isolated (57.1%), followed by Candida glabrata (15.3%) and Candida parapsilosis (10.2%). No clear source of HAF was detected in 33.3% of the episodes and it was catheter-related in 21.9% of them. Compared to patients with bacteremia, HAF patients had a higher rate of septic shock (39.6% vs. 21.6%; p = 0.0003) and renal dysfunction (25% vs. 12.4%; p = 0.0023) on admission and a higher rate of renal failure (26% vs. 16.2%; p = 0.0273) at diagnosis. Adequate treatment started within 24 h after blood culture collection was less frequent in HAF patients (22.9% vs. 55.3%; p < 0.001). The 28-day all cause fatality was 40.6%. According to multivariate analysis, only liver failure (OR 14.35; 95% CI 1.17-175.6; p = 0.037), need for mechanical ventilation (OR 8.86; 95% CI 1.2-65.24; p = 0.032) and ICU admission for medical reason (OR 3.87; 95% CI 1.25-11.99; p = 0.020) were independent predictors of 28-day mortality in HAF patients. CONCLUSIONS: Fungi are an important cause of hospital-acquired BSI in the ICU. Patients with HAF present more frequently with septic shock and renal dysfunction on ICU admission and have a higher rate of renal failure at diagnosis. HAF are associated with a significant 28-day mortality rate (40%), but delayed adequate antifungal therapy was not an independent risk factor for death. Liver failure, need for mechanical ventilation and ICU admission for medical reason were the only independent predictors of 28-day mortality.

Randomized intubation with polyurethane or conical cuffs to prevent pneumonia in ventilated patients.

RATIONALE: The occurrence of ventilator-associated pneumonia (VAP) is linked to the aspiration of contaminated pharyngeal secretions around the endotracheal tube. Tubes with cuffs made of polyurethane rather than polyvinyl chloride or with a conical rather than a cylindrical shape increase tracheal sealing. OBJECTIVES: To test whether using polyurethane and/or conical cuffs reduces tracheal colonization and VAP in patients with acute respiratory failure. METHODS: We conducted a multicenter, prospective, open-label, randomized study in four parallel groups in four intensive care units between 2010 and 2012. A cohort of 621 patients with expected ventilation longer than 2 days was included at intubation with a cuff composed of cylindrical polyvinyl chloride (n = 148), cylindrical polyurethane (n = 143), conical polyvinyl chloride (n = 150), or conical polyurethane (n = 162). We used Kaplan-Meier estimates and log-rank tests to compare times to events. MEASUREMENTS AND MAIN RESULTS: After excluding 17 patients who secondarily refused participation or had met an exclusion criterion, 604 were included in the intention-to-treat analysis. Cumulative tracheal colonization greater than 10(3) cfu/ml at Day 2 was as follows (median [interquartile range]): cylindrical polyvinyl chloride, 0.66 (0.58-0.74); cylindrical polyurethane, 0.61 (0.53-0.70); conical polyvinyl chloride, 0.67 (0.60-0.76); and conical polyurethane, 0.62 (0.55-0.70) (P = 0.55). VAP developed in 77 patients (14.4%), and postextubational stridor developed in 28 patients (6.4%) (P = 0.20 and 0.28 between groups, respectively). CONCLUSIONS: Among patients requiring mechanical ventilation, polyurethane and/or conically shaped cuffs were not superior to conventional cuffs in preventing tracheal colonization and VAP. Clinical trial registered with clinicaltrials.gov (NCT01114022).

Epidemiology of invasive aspergillosis in critically ill patients: clinical presentation, underlying conditions, and outcomes.

INTRODUCTION: Invasive aspergillosis (IA) is a fungal infection that particularly affects immunocompromised hosts. Recently, several studies have indicated a high incidence of IA in intensive care unit (ICU) patients. However, few data are available on the epidemiology and outcome of patients with IA in this setting. METHODS: An observational study including all patients with a positive Aspergillus culture during ICU stay was performed in 30 ICUs in 8 countries. Cases were classified as proven IA, putative IA or Aspergillus colonization according to recently validated criteria. Demographic, microbiologic and diagnostic data were collected. Outcome was recorded 12 weeks after Aspergillus isolation. RESULTS: A total of 563 patients were included, of whom 266 were colonized (47%), 203 had putative IA (36%) and 94 had proven IA (17%). The lung was the most frequent site of infection (94%), and Aspergillus fumigatus the most commonly isolated species (92%). Patients with IA had higher incidences of cancer and organ transplantation than those with colonization. Compared with other patients, they were more frequently diagnosed with sepsis on ICU admission and more frequently received vasopressors and renal replacement therapy (RRT) during the ICU stay. Mortality was 38% among colonized patients, 67% in those with putative IA and 79% in those with proven IA (P < 0.001). Independent risk factors for death among patients with IA included older age, history of bone marrow transplantation, and mechanical ventilation, RRT and higher Sequential Organ Failure Assessment score at diagnosis. CONCLUSIONS: IA among critically ill patients is associated with high mortality. Patients diagnosed with proven or putative IA had greater severity of illness and more frequently needed organ support than those with Aspergillus spp colonization.

ICU physician-based determinants of life-sustaining therapy during nights and weekends: French multicenter study from the Outcomerea Research Group.

OBJECTIVE: Patient- and organization-related factors are the most common influences affecting the ICU decision-making process. Few studies have investigated ICU physician-related factors and life-sustaining treatment use during nights and weekends, when staffing ratios are low. Here, we described patients admitted during nights/weekends and looked for physician-related determinants of life-sustaining treatment use in these patients after adjustment for patient- and center-related factors. DESIGN: Multicenter observational cohort study of admission procedures during nights/weekends shifts. SUBJECTS: ICU physicians working nights/weekends in 6 French ICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient characteristics and intensity of care were extracted from the prospective Outcomerea database. Physician characteristics were age, gender, religion and religiosity, ICU experience, specialty, being a permanent ICU staff member, degree in ethics, and degree in intensive care. We used hierarchical mixed models to adjust on center, physician random effects, and admission patient characteristics. Of 156 physicians contacted, 119 (77%) participated. Patients admitted during nights/weekends were younger and had fewer comorbidities and lower treatment intensity during the shift. ICU physicians who are younger than 35 years used more renal replacement therapy (odds ratio, 1.04; 95% CI, 1-1.07; p = 0.04), invasive mechanical ventilation (odds ratio, 1.09; 95% CI, 1.1-1.19; p = 0.04), and vasopressors (odds ratio, 1.16; 95% CI, 1.09-1.23; p < 0.0001). Internal or emergency medicine as the primary specialty was associated with invasive mechanical ventilation (odds ratio, 1.14; 95% CI, 1.04-1.24; p = 0.004) and vasopressor use (odds ratio, 1.09; 95% CI, 1.02-1.17; p = 0.01). Noninvasive ventilation was used less often by physicians with more than 10 years of night/weekend shifts and more often by those with religious beliefs (odds ratio, 1.05; 95% CI, 1.01-1.08; p = 0.008). CONCLUSIONS: Patients admitted during nights/weekends were younger and had fewer comorbidities. Age, specialty, ICU experience, and religious beliefs of the physicians were significantly associated life-sustaining treatments used.