Impact of prone position on dead-space fraction in COVID-19 related acute respiratory distress syndrome.

INTRODUCTION: COVID-19 Related Acute Respiratory Syndrome (C-ARDS) is characterized by a mismatch between respiratory mechanics and hypoxemia, suggesting increased dead-space fraction (DSF). Prone position is a cornerstone treatment of ARDS under invasive mechanical ventilation reducing mortality. We sought to investigate the impact of prone position on DSF in C-ARDS in a cohort of patients receiving invasive mechanical ventilation. METHODS: we retrospectively analysed data from 85 invasively mechanically ventilated patients with C-ARDS in supine and in prone positions, hospitalized in Intensive Care Unit (Reims University Hospital), between November, 1st 2020 and November, 1st 2022. DSF was estimated via 3 formulas usable at patients' bedside, based on partial pressure of carbon dioxide (PaCO2) and end-tidal carbon dioxide (EtCO2). RESULTS: there was no difference of DSF between supine and prone position, using the 3 formulas. According to Enghoff, Frankenfield and Gattinoni equations, DSF in supine vs. prone position was in median respectively [IQR]: 0.29 [0.13-0.45] vs. 0.31 [0.19-0.51] (p = 0.37), 0.5 [0.48-0.52] vs. 0.51 [0.49-0.53] (p = 0.43), and 0.71 [0.55-0.87] vs. 0.69 [0.57-0.81], (p = 0.32). CONCLUSION: prone position did not change DSF in C-ARDS.

Brain abscesses in infective endocarditis: contemporary profile and neuroradiological findings.

BACKGROUND: Brain abscesses (BA) are severe lesions in the course of infective endocarditis (IE). We compare the bacteriological, clinical data, background, associated lesions, and outcome of IE patients with and without BAs, and assess the MRI characteristics of BAs. METHODS: Retrospective study of 351 consecutive patients with definite IE (2005-2020) and at least one brain MRI. Patients with and without BAs were compared. RESULTS: Twenty patients (5.7%) had BA (80% men; median age: 44.9 ± 11.5). They were younger (p = 0.035) and had a higher rate of predisposing factors (previous IE 20% vs 2.2%, p = 0.03), intravenous drug use [25% vs 2.2%; p < 0.0001]), underlying conditions (HIV infection, 20% vs 2.2%, p < 0.0001; alcohol abuse, 20% vs 2.2% p < 0.0001]; liver disease p = 0.04; hemodialysis, p = 0.001; type 2 diabetes, p = 0.001), bacterial meningitis (p = 0.0029), rare species involvement (35% vs 7%, p < 0.0006) and extra-cerebral abscesses (p = 0.0001) compared to patients without BA. Valve vegetations were larger in Group 1 (p = 0.046). Clinical presentation could suggest the diagnosis of BA in only 7/20 (35%) patients. MR identified 58 BAs (mean/patient 2.9; range 2-12): often multiple (80%), bilateral (55%) and ≤ 10 mm (72%). The presence of BA did not modify cardiac surgery indication and timing. Favorable outcome was observed in 85% of patients. CONCLUSION: Rates of predisposing, underlying conditions, rare IE agents, meningitis and metastatic abscesses are significantly higher in BA-IE patients. As BAs can develop in asymptomatic IE patients, the impact of brain MRI on their management needs thoroughly to be further investigated.

Outcomes in critically Ill HIV-infected patients between 1997 and 2020: analysis of the OUTCOMEREA multicenter cohort.

PURPOSE: Despite antiviral therapy (ART), 800,000 deaths still occur yearly and globally due to HIV infection. In parallel with the good virological control and the aging of this population, multiple comorbidities [HIV-associated-non-AIDS (HANA) conditions] may now be observed. METHODS: HIV adult patients hospitalized in intensive care unit (ICU) from all the French region from university and non-university hospital who participate to the OutcomeRea™ database on a voluntary basis over a 24-year period. RESULTS: Of the 24,298 stays registered, 630 (2.6%) were a first ICU stay for HIV patients. Over time, the mean age and number of comorbidities (diabetes, renal and respiratory history, solid neoplasia) of patients increased. The proportion of HIV diagnosed on ICU admission decreased significantly, while the median duration of HIV disease as well as the percentage of ART-treated patients increased. The distribution of main reasons for admission remained stable over time (acute respiratory distress > shock > coma). We observed a significant drop in the rate of active opportunistic infection on admission, while the rate of active hemopathy (newly diagnosed or relapsed within the last 6 months prior to admission to ICU) qualifying for AIDS increased-nonsignificantly-with a significant increase in the anticancer chemotherapy administration in ICU. Admissions for HANA or non-HIV reasons were stable over time. In multivariate analysis, predictors of 60-day mortality were advanced age, chronic liver disease, past chemotherapy, sepsis-related organ failure assessment score > 4 at admission, hospitalization duration before ICU admission > 24 h, AIDS status, but not the period of admission. CONCLUSION: Whereas the profile of ICU-admitted HIV patients has evolved over time (HIV better controlled but more associated comorbidities), mortality risk factors remain stable, including AIDS status.

Surfaces and Air Contamination by Severe Acute Respiratory Syndrome Coronavirus 2 Using High-Flow Nasal Oxygenation or Assisted Mechanical Ventilation in Intensive Care Unit Rooms of Patients With Coronavirus Disease 2019.

BACKGROUND: Understanding patterns of environmental contamination by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for infection prevention policies. METHODS: We screened surfaces and air samples from single-bed intensive-care unit rooms of adult patients with coronavirus disease 2019 (COVID-19) for SARS-CoV-2 RNA and viable viruses. RESULTS: We evidenced viral RNA environmental contamination in 76% of 100 surfaces samples and in 30% of 40 air samples without any viable virus detection by cell culture assays. No significant differences of viral RNA levels on surfaces and in ambient air were observed between rooms of patients with assisted mechanical ventilation and those of patients with a high-flow nasal cannula system. Using an original experimental SARS-CoV-2 infection model of surfaces, we determined that infectious viruses may have been present on benches within 15 hours before the time of sampling in patient rooms. CONCLUSIONS: We observed that SARS-CoV-2 environmental contamination around patients with COVID-19 hospitalized in single-bed ICU rooms was extensive and that a high-flow nasal cannula system did not generate more viral aerosolization than a mechanical ventilation system in patients with COVID-19. Despite an absence of SARS-CoV-2 viable particles in study samples, our experimental model confirmed the need to apply strict environmental disinfection procedures and classic standard and droplet precautions in ICU wards.

Cluster analysis unveils a severe persistent respiratory impairment phenotype 3-months after severe COVID-19.

BACKGROUND: The mid-term respiratory sequelae in survivors of severe COVID-19 appear highly heterogeneous. In addition, factors associated with respiratory sequelae are not known. In this monocentric prospective study, we performed a multidisciplinary assessment for respiratory and muscular impairment and psychological distress 3 months after severe COVID-19. We analysed factors associated with severe persistent respiratory impairment, amongst demographic, COVID-19 severity, and 3-month assessment. METHODS: Patients with severe SARS-CoV-2 pneumonia requiring ≥ 4L/min were included for a systematic 3-month visit, including respiratory assessment (symptoms, lung function, CT scan), muscular evaluation (body composition, physical function and activity, disability), psychopathological evaluation (anxiety, depression, post-traumatic stress disorder-PTSD) and quality of life. A cluster analysis was performed to identify subgroups of patients based on objective functional measurements: DLCO, total lung capacity and 6-min walking distance (6MWD). RESULTS: Sixty-two patients were analysed, 39% had dyspnea on exercise (mMRC ≥ 2), 72% had DLCO < 80%, 90% had CT-scan abnormalities; 40% had sarcopenia/pre-sarcopenia and 31% had symptoms of PTSD. Cluster analysis identified a group of patients (n = 18, 30.5%) with a severe persistent (SP) respiratory impairment (DLCO 48 ± 12%, 6MWD 299 ± 141 m). This SP cluster was characterized by older age, severe respiratory symptoms, but also sarcopenia/pre-sarcopenia, symptoms of PTSD and markedly impaired quality of life. It was not associated with initial COVID-19 severity or management. CONCLUSIONS AND CLINICAL IMPLICATION: We identified a phenotype of patients with severe persistent respiratory and muscular impairment and psychological distress 3 months after severe COVID-19. Our results highlight the need for multidisciplinary assessment and management after severe SARS-CoV-2 pneumonia. Trial registration The study was registered on ClinicalTrials.gov (May 6, 2020): NCT04376840.

Long-term neuro-functional disability in adult patients with community-acquired bacterial meningitis.

PURPOSE: To investigate the prevalence of neuro-functional disability and its determinants 12 months after community-acquired bacterial meningitis (CABM) in adult patients. METHODS: In a prospective multicenter cohort study (COMBAT), all consecutive cases of CABM were enrolled and followed up for 12 months. Neuro-functional disability at 12 months was evaluated using a combination of the Glasgow Outcome Scale (functional disability), and the modified Rankin Disability Scale (physical disability). Factors associated with neuro-functional disability were identified by multivariate logistic regression. RESULTS: Among 281 patients, 84 (29.9%) patients exhibited neuro-functional disability at 12 months: 79 (28.1%) with functional disability and 51 (18.1%) with physical disability. Overall, 6 patients (2.1%) died during the follow-up. The most common pathogen identified was Streptococcus pneumoniae (131/272, 48.2%); 77/268 patients (28.7%) had a physical disability at hospital discharge. Factors independently associated with 12-month neuro-functional disability were a pneumococcal meningitis (adjusted OR = 2.8; 95% confidence interval (CI) = [1.3; 6.7]), the presence of a physical disability at hospital discharge (aOR = 2.3; 95%CI = [1.2; 4.4]) and the presence of behavioral disorders at hospital-discharge (aOR = 5.9; 95%CI = [1.6; 28.4]). Dexamethasone use was not significantly associated with neuro-functional disability (OR = 0.2; 95%CI = [< 0.1;1.3]). CONCLUSION: Neuro-functional disability is frequently reported 12 months after CABM. Detailed neurological examination at discharge is needed to improve the follow-up. TRIAL REGISTRATION: NCT01730690.

Association of COVID-19 Acute Respiratory Distress Syndrome With Symptoms of Posttraumatic Stress Disorder in Family Members After ICU Discharge.

IMPORTANCE: Persistent physical and mental disorders are frequent in survivors of COVID-19-related acute respiratory distress syndrome (ARDS). However, data on these disorders among family members are scarce. OBJECTIVE: To determine the association between patient hospitalization for COVID-19 ARDS vs ARDS from other causes and the risk of posttraumatic stress disorder (PTSD)-related symptoms in family members. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study in 23 intensive care units (ICUs) in France (January 2020 to June 2020 with final follow-up ending in October 2020). ARDS survivors and family members (1 family member per patient) were enrolled. EXPOSURES: Family members of patients hospitalized for ARDS due to COVID-19 vs ARDS due to other causes. MAIN OUTCOMES AND MEASURES: The primary outcome was family member symptoms of PTSD at 90 days after ICU discharge, measured by the Impact of Events Scale-Revised (score range, 0 [best] to 88 [worst]; presence of PTSD symptoms defined by score >22). Secondary outcomes were family member symptoms of anxiety and depression at 90 days assessed by the Hospital Anxiety and Depression Scale (score range, 0 [best] to 42 [worst]; presence of anxiety or depression symptoms defined by subscale scores ≥7). Multivariable logistic regression models were used to determine the association between COVID-19 status and outcomes. RESULTS: Among 602 family members and 307 patients prospectively enrolled, 517 (86%) family members (median [IQR] age, 51 [40-63] years; 72% women; 48% spouses; 26% bereaved because of the study patient's death; 303 [50%] family members of COVID-19 patients) and 273 (89%) patients (median [IQR] age, 61 [50-69] years; 34% women; 181 [59%] with COVID-19) completed the day-90 assessment. Compared with non-COVID-19 ARDS, family members of patients with COVID-19 ARDS had a significantly higher prevalence of symptoms of PTSD (35% [103/293] vs 19% [40/211]; difference, 16% [95% CI, 8%-24%]; P < .001), symptoms of anxiety (41% [121/294] vs 34% [70/207]; difference, 8% [95% CI, 0%-16%]; P= .05), and symptoms of depression (31% [91/291] vs 18% [37/209]; difference, 13% [95% CI, 6%-21%]; P< .001). In multivariable models adjusting for age, sex, and level of social support, COVID-19 ARDS was significantly associated with increased risk of PTSD-related symptoms in family members (odds ratio, 2.05 [95% CI, 1.30 to 3.23]). CONCLUSIONS AND RELEVANCE: Among family members of patients hospitalized in the ICU with ARDS, COVID-19 disease, as compared with other causes of ARDS, was significantly associated with increased risk of symptoms of PTSD at 90 days after ICU discharge. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04341519.

Excess Soluble fms-like Tyrosine Kinase 1 Correlates With Endothelial Dysfunction and Organ Failure in Critically Ill Coronavirus Disease 2019 Patients.

Excess soluble fms-like tyrosine kinase 1 (sFlt-1), a soluble inhibitor of vascular endothelial growth factor pathway, has been demonstrated to promote endothelial dysfunction. Here, we demonstrate that sFlt-1 plasma levels correlate with respiratory symptom severity, expression of endothelial dysfunction biomarker, and incidence of organ failure in coronavirus disease 2019 patients. Clinical Trials Registration: NCT04394195.

Impact of Loading Dose of Caspofungin in Pharmacokinetic-Pharmacodynamic Target Attainment for Severe Candidiasis Infections in Patients in Intensive Care Units: the CASPOLOAD Study.

This study evaluated the impact of a high loading dose of caspofungin (CAS) on the pharmacokinetics of CAS and the pharmacokinetic-pharmacodynamic (PK-PD) target attainment in patients in intensive care units (ICU). ICU patients requiring CAS treatment were prospectively included to receive a 140-mg loading dose of CAS. Plasma CAS concentrations (0, 2, 3, 5, 7, and 24 h postinfusion) were determined to develop a two-compartmental population PK model. A Monte Carlo simulation was performed and the probabilities of target attainment (PTAs) were computed using previously published MICs. PK-PD targets were ratios of area under the concentration-time curve from 0 to 24 h (AUC0-24h) divided by the MIC (AUC0-24h/MIC) of 250, 450, and 865 and maximal concentration (Cmax) divided by the MIC (Cmax/MIC) of 5, 10, 15, and 20. Among 13 included patients, CAS clearance was 0.98 ± 0.13 liters/h and distribution volumes were V1 = 9.0 ± 1.2 liters and V2 = 11.9 ± 2.9 liters. Observed and simulated CAS AUC0-24h were 79.1 (IQR 55.2; 108.4) and 81.3 (IQR 63.8; 102.3) mg · h/liter during the first 24 h of therapy, which is comparable to values usually observed in ICU patients at day 3 or later. PTAs were >90% for MICs of 0.19 and 0.5 mg/liter, considering AUC/MIC = 250 and Cmax/MIC = 10 as PK-PD targets, respectively. Thus, a high loading dose of CAS (140 mg) increased CAS exposure in the first 24 h of therapy, allowing early achievement of PK-PD targets for most Candida strains. Such a strategy seems to improve treatment efficacy, though further studies are needed to assess the impact on clinical outcomes. (This study has been registered at ClinicalTrials.gov under identifier NCT02413892.).

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

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

Impact of species and antibiotic therapy of enterococcal peritonitis on 30-day mortality in critical care-an analysis of the OUTCOMEREA database.

INTRODUCTION: Enterococcus species are associated with an increased morbidity in intraabdominal infections (IAI). However, their impact on mortality remains uncertain. Moreover, the influence on outcome of the appropriate or inappropriate status of initial antimicrobial therapy (IAT) is subjected to debate, except in septic shock. The aim of our study was to evaluate whether an IAT that did not cover Enterococcus spp. was associated with 30-day mortality in ICU patients presenting with IAI growing with Enterococcus spp. MATERIAL AND METHODS: Retrospective analysis of French database OutcomeRea from 1997 to 2016. We included all patients with IAI with a peritoneal sample growing with Enterococcus. Primary endpoint was 30-day mortality. RESULTS: Of the 1017 patients with IAI, 76 (8%) patients were included. Thirty-day mortality in patients with inadequate IAT against Enterococcus was higher (7/18 (39%) vs 10/58 (17%), p = 0.05); however, the incidence of postoperative complications was similar. Presence of Enterococcus spp. other than E. faecalis alone was associated with a significantly higher mortality, even greater when IAT was inadequate. Main risk factors for having an Enterococcus other than E. faecalis alone were as follows: SAPS score on day 0, ICU-acquired IAI, and antimicrobial therapy within 3 months prior to IAI especially with third-generation cephalosporins. Univariate analysis found a higher hazard ratio of death with an Enterococcus other than E. faecalis alone that had an inadequate IAT (HR = 4.4 [1.3-15.3], p = 0.019) versus an adequate IAT (HR = 3.1 [1.0-10.0], p = 0.053). However, after adjusting for confounders (i.e., SAPS II and septic shock at IAI diagnosis, ICU-acquired peritonitis, and adequacy of IAT for other germs), the impact of the adequacy of IAT was no longer significant in multivariate analysis. Septic shock at diagnosis and ICU-acquired IAI were prognostic factors. CONCLUSION: An IAT which does not cover Enterococcus is associated with an increased 30-day mortality in ICU patients presenting with an IAI growing with Enterococcus, especially when it is not an E. faecalis alone. It seems reasonable to use an IAT active against Enterococcus in severe postoperative ICU-acquired IAI, especially when a third-generation cephalosporin has been used within 3 months.

Early Electroencephalography Findings in Cardiogenic Shock Patients Treated by Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: We aimed to assess early electroencephalography findings in patients treated by venoarterial extracorporeal membrane oxygenation and their association with neurologic outcome. DESIGN: Single-center observational study. SETTING: Medical ICU of a university hospital. PATIENTS: An early standardized electroencephalography assessment, that is, standard electroencephalography followed by continuous electroencephalography, was performed in consecutive cardiogenic shock patients requiring venoarterial extracorporeal membrane oxygenation. Associations between electroencephalography findings and outcome, defined as a composite of acute brain injury or death at 14 days, were investigated. MEASUREMENTS AND MAIN RESULTS: Twenty-two patients with a median Full Outline of Unresponsiveness score of 4 (interquartile range, 3-6) were studied. Pupillary light reflex, corneal reflex, and cough reflex were preserved in 20 (90%), 17 (77%), and 17 (77%) patients, respectively. Overall, standard electroencephalography findings consisted of diffuse slowing in 21 patients (95%) and severe background abnormalities in 13 patients (59%) (i.e., a discontinuous [n = 5; 23%] and/or an unreactive background [n = 9; 41%]). Severe background abnormalities on standard electroencephalography (poor outcome rate: 69% vs 22%; p = 0.03) and absence of sleep transients on continuous electroencephalography (poor outcome rate: 67% vs 14%; p = 0.02) were associated with a poor outcome, whereas neurologic findings and doses of sedation were not. Patients without sleep transients on continuous electroencephalography tended to have lower Full Outline of Unresponsiveness scores than patients with preserved sleep transients-appearing patterns. CONCLUSIONS: In patients treated by venoarterial extracorporeal membrane oxygenation, early severe background abnormalities on standard electroencephalography provide important information on neurologic outcome. The lack of sleep transients on continuous electroencephalography reflects the severity of brain dysfunction and might represent an additional prognostic marker.

Functional outcomes in adults with tuberculous meningitis admitted to the ICU: a multicenter cohort study.

BACKGROUND: Tuberculous meningitis (TBM) is a devastating infection in tuberculosis endemic areas with limited access to intensive care. Functional outcomes of severe adult TBM patients admitted to the ICU in nonendemic areas are not known. METHODS: We conducted a retrospective multicenter cohort study (2004-2016) of consecutive TBM patients admitted to 12 ICUs in the Paris area, France. Clinical, biological, and brain magnetic resonance imaging (MRI) findings at admission associated with a poor functional outcome (i.e., a score of 3-6 on the modified Rankin scale (mRS) at 90 days) were identified by logistic regression. Factors associated with 1-year mortality were investigated by Cox proportional hazards modeling. RESULTS: We studied 90 patients, of whom 61 (68%) had a score on the Glasgow Coma Scale ≤ 10 at presentation and 63 (70%) required invasive mechanical ventilation. Brain MRI revealed infarction and hydrocephalus in 38/75 (51%) and 25/75 (33%) cases, respectively. A poor functional outcome was observed in 55 (61%) patients and was independently associated with older age (adjusted odds ratio (aOR) 1.03, 95% CI 1.0-1.07), cerebrospinal fluid protein level ≥ 2 g/L (aOR 5.31, 95% CI 1.67-16.85), and hydrocephalus on brain MRI (aOR 17.2, 95% CI 2.57-115.14). By contrast, adjunctive steroids were protective (aOR 0.13, 95% CI 0.03-0.56). The multivariable adjusted hazard ratio of adjunctive steroids for 1-year mortality (47%, 95% CI 37%-59%) was 0.23 (95% CI 0.11-0.44). Among survivors at 1 year, functional independence (mRS of 0-2) was observed in 27/37 (73%, 95% CI 59%-87%) cases. CONCLUSIONS: A poor functional outcome in adult TBM patients admitted to the ICU in a nonendemic area is observed in 60% of cases and is independently associated with elevated cerebrospinal fluid protein level and hydrocephalus. Our data also suggest a protective effect of adjunctive steroids, with reduced disability and mortality, irrespective of immune status and severity of disease at presentation. One-year follow-up revealed functional independence in most survivors.

Initial nutritional management during noninvasive ventilation and outcomes: a retrospective cohort study.

BACKGROUND: Patients starting noninvasive ventilation (NIV) to treat acute respiratory failure are often unable to eat and therefore remain in the fasting state or receive nutritional support. Maintaining a good nutritional status has been reported to improve patient outcomes. In the present study, our primary objective was to describe the nutritional management of patients starting first-line NIV, and our secondary objectives were to assess potential associations between nutritional management and outcomes. METHODS: Observational retrospective cohort study of a prospective database fed by 20 French intensive care units. Adult medical patients receiving NIV for more than 2 consecutive days were included and divided into four groups on the basis of nutritional support received during the first 2 days of NIV: no nutrition, enteral nutrition, parenteral nutrition only, and oral nutrition only. RESULTS: Of the 16,594 patients admitted during the study period, 1075 met the inclusion criteria; of these, 622 (57.9%) received no nutrition, 28 (2.6%) received enteral nutrition, 74 (6.9%) received parenteral nutrition only, and 351 (32.7%) received oral nutrition only. After adjustment for confounders, enteral nutrition (vs. no nutrition) was associated with higher 28-day mortality (adjusted HR, 2.3; 95% CI, 1.2-4.4) and invasive mechanical ventilation needs (adjusted HR, 2.1; 95% CI, 1.1-4.2), as well as with fewer ventilator-free days by day 28 (adjusted relative risk, 0.7; 95% CI, 0.5-0.9). CONCLUSIONS: Nearly three-fifths of patients receiving NIV fasted for the first 2 days. Lack of feeding or underfeeding was not associated with mortality. The optimal route of nutrition for these patients needs to be investigated.

Colonization and infection with extended-spectrum ß-lactamase-producing Enterobacteriaceae in ICU patients: what impact on outcomes and carbapenem exposure?

OBJECTIVES: It remains uncertain whether colonization and infection with ESBL-producing Enterobacteriaceae (ESBL-PE) affect the outcomes for ICU patients. Our objectives were to measure the effects of ESBL-PE carriage and infection on mortality, ICU length of stay (LOS) and carbapenem exposure in this population. METHODS: A cause-specific hazard model based on prospectively collected data was built to assess the impact of ESBL-PE colonization and infection on competing risks of death and ICU discharge at day 28 in a multicentre cohort of ICU patients. Carbapenem exposure during the ICU stay was compared between infected carriers, uninfected carriers and non-carriers. RESULTS: Among the 16,734 included patients, 594 (3.5%) were ESBL-PE carriers, including 98 (16.4%) with one or more ESBL-PE infections during the ICU stay. After adjustment for baseline and time-dependent confounders, ESBL-PE infections increased the probability of death at day 28 [adjusted cause-specific hazard ratio (aCSHR), 1.825, 95% CI 1.235-2.699, P = 0.0026] and the ICU LOS (aCSHR for discharge alive at day 28, 0.563, 95% CI 0.432-0.733, P < 0.0001). ESBL-PE carriage without infection extended the LOS (aCSHR, 0.623, 95% CI, 0.553-0.702, P < 0.0001), without affecting mortality (aCSHR, 0.906, 95% CI, 0.722-1.136, P = 0.3916). Carbapenem exposure increased in both infected and uninfected carriers when compared with non-carriers (627, 241 and 69 carbapenem days per 1000 patient days, respectively, P < 0.001). CONCLUSIONS: ESBL-PE infections increased carbapenem consumption, LOS and day 28 mortality. ESBL-PE infections were rather infrequent in carriers; however, even ESBL-PE carriage without infection increased carbapenem exposure and delayed discharge, thereby amplifying the selective pressure and the colonization pressure in the ICU.

Viral-bacterial coinfection affects the presentation and alters the prognosis of severe community-acquired pneumonia.

BACKGROUND: Multiplex polymerase chain reaction (mPCR) enables recovery of viruses from airways of patients with community-acquired pneumonia (CAP), although their clinical impact remains uncertain. METHODS: Among consecutive adult patients who had undergone a mPCR within 72 hours following their admission to one intensive care unit (ICU), we retrospectively included those with a final diagnosis of CAP. Four etiology groups were clustered: bacterial, viral, mixed (viral-bacterial) and no etiology. A composite criterion of complicated course (hospital death or mechanical ventilation > 7 days) was used. A subgroup analysis compared patients with bacterial and viral-bacterial CAP matched on the bacterial pathogens. RESULTS: Among 174 patients (132 men [76 %], age 63 [53-75] years, SAPSII 38 [27;55], median PSI score 106 [78;130]), bacterial, viral, mixed and no etiology groups gathered 46 (26 %), 53 (31 %), 45 (26 %) and 30 (17 %) patients, respectively. Virus-infected patients displayed a high creatine kinase serum level, a low platelet count, and a trend toward more frequent alveolar-interstitial infiltrates. A complicated course was more frequent in the mixed group (31/45, 69 %), as compared to bacterial (18/46, 39 %), viral (15/53, 28 %) and no etiology (12/30, 40 %) groups (p < 0.01). In multivariate analysis, the mixed (viral-bacterial) infection was independently associated with complicated course (reference: bacterial pneumonia; OR, 3.58; CI 95 %, 1.16-11; p = 0.03). The subgroup analysis of bacteria-matched patients confirmed these findings. CONCLUSIONS: Viral-bacterial coinfection during severe CAP in adults is associated with an impaired presentation and a complicated course.

Treatment of bloodstream infections in ICUs.

Bloodstream infections (BSIs) are frequent in ICU and is a prognostic factor of severe sepsis. Community acquired BSIs usually due to susceptible bacteria should be clearly differentiated from healthcare associated BSIs frequently due to resistant hospital strains. Early adequate treatment is key and should use guidelines and direct examination of samples performed from the infectious source. Previous antibiotic therapy knowledge, history of multi-drug resistant organism (MDRO) carriage are other major determinants of first choice antimicrobials in heathcare-associated and nosocomial BSIs. Initial antimicrobial dose should be adapted to pharmacokinetic knowledge. In general, a high dose is recommended at the beginning of treatment. If MDRO is suspected combination antibiotic therapy is mandatory because it increase the spectrum of treatment. Most of time, combination should be pursued no more than 2 to 5 days.Given the negative impact of useless antimicrobials, maximal effort should be done to decrease the antibiotic selection pressure. De-escalation from a broad spectrum to a narrow spectrum antimicrobial decreases the antibiotic selection pressure without negative impact on mortality. Duration of therapy should be shortened as often as possible especially when organism is susceptible, when the infection source has been totally controlled.

Extracorporeal membrane oxygenation for pandemic influenza A(H1N1)-induced acute respiratory distress syndrome: a cohort study and propensity-matched analysis.

RATIONALE: Many patients with severe acute respiratory distress syndrome (ARDS) caused by influenza A(H1N1) infection receive extracorporeal membrane oxygenation (ECMO) as a rescue therapy. OBJECTIVES: To analyze factors associated with death in ECMO-treated patients and the influence of ECMO on intensive care unit (ICU) mortality. METHODS: Data from patients admitted for H1N1-associated ARDS to French ICUs were prospectively collected from 2009 to 2011 through the national REVA registry. We analyzed factors associated with in-ICU death in ECMO recipients, and the potential benefit of ECMO using a propensity score-matched (1:1) cohort analysis. MEASUREMENTS AND MAIN RESULTS: A total of 123 patients received ECMO. By multivariate analysis, increasing values of age, lactate, and plateau pressure under ECMO were associated with death. Of 103 patients receiving ECMO during the first week of mechanical ventilation, 52 could be matched to non-ECMO patients of comparable severity, using a one-to-one matching and using control subjects only once. Mortality did not differ between the two matched cohorts (odds ratio, 1.48; 95% confidence interval, 0.68-3.23; P = 0.32). Interestingly, the 51 ECMO patients who could not be matched were younger, had lower Pa(o(2))/Fi(o(2)) ratio, had higher plateau pressure, but also had a lower ICU mortality rate than the 52 matched ECMO patients (22% vs. 50%; P < 0.01). CONCLUSIONS: Under ECMO, an ultraprotective ventilation strategy minimizing plateau pressure may be required to improve outcome. When patients with severe influenza A(H1N1)-related ARDS treated with ECMO were compared with conventionally treated patients, no difference in mortality rates existed. The unmatched, severely hypoxemic, and younger ECMO-treated patients had, however, a lower mortality.

Pseudomonas aeruginosa ventilator-associated pneumonia. predictive factors of treatment failure.

RATIONALE: The predictive factors of treatment failure for ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa (PA) remain uncertain. OBJECTIVES: To describe PA-VAP recurrence prognosis and to identify associated risk factors in a large cohort of intensive care unit patients with PA-VAP. METHODS: From the multicenter OUTCOMEREA database (1997-2011), PA-VAP onset and recurrence were recorded. All suspected cases of VAP were confirmed by a positive quantitative culture of a respiratory sample. Multidrug-resistant PA strains were defined by the resistance to two antibiotics among piperacillin, ceftazidime, imipenem, colistine, and fluoroquinolones (FQ). An extensively resistant PA was defined by resistance to piperacillin, ceftazidime, imipenem, and FQ. A treatment failure was defined as a PA-VAP recurrence or by the death occurrence. MEASUREMENTS AND MAIN RESULTS: A total of 314 patients presented 393 PA-VAP. Failure occurred for 112 of them, including 79 recurrences. Susceptible, multidrug resistant, and extensively resistant PA represented 53.7%, 32%, and 14.3% of the samples, respectively. Factors associated with treatment failure were age (P = 0.02); presence of at least one chronic illness (P = 0.02); limitation of life support (P = 0.0004); a high Sepsis-Related Organ Failure Assessment score (P < 0.0001); PA bacteremia (P = 0.003); and previous use of FQ before the first PA-VAP (P = 0.0007). The failure risk was not influenced by the strain resistance profile or by the biantibiotic treatment, but decreased in case of VAP treatment that includes FQ (subdistribution hazard ratio, 0.5 [0.3-0.7]; P = 0.0006). However, the strain resistance profile slowed down the intensive care unit discharge hazard (subdistribution hazard ratio, 0.6 [0.4-1.0]; P = 0.048). CONCLUSIONS: Neither resistance profile nor biantibiotic therapy decreased the risk of PA-VAP treatment failure. However, the profile of PA resistance prolonged the length of stay. Better evaluation of the potential benefit of an initial treatment containing FQ requires further randomized trials.

Recombinant human activated protein C for adults with septic shock: a randomized controlled trial.

RATIONALE: A decade after drotrecogin alfa (activated) (DAA) was released on the market worldwide, its benefit-to-risk ratio remains a matter of debate. OBJECTIVES: The current investigator-led trial was designed to evaluate the efficacy and safety of DAA, in combination with low-dose steroids, in adults with persistent septic shock. METHODS: This was a multicenter (24 intensive care units), placebo-controlled, double-blind, 2 × 2 factorial design trial in which adults with persistent septic shock and no contraindication to DAA were randomly assigned to DAA alone (24 µg/kg/h for 96 h), hydrocortisone and fludrocortisone alone, their respective combinations, or their respective placebos. Primary outcome was mortality rate on Day 90. MEASUREMENTS AND MAIN RESULTS: On October 25, 2011, the trial was suspended after the withdrawal from the market of DAA. The Scientific Committee decided to continue the trial according to a two parallel group design comparing low-dose steroids with their placebos and to analyze the effects of DAA on patients included before trial suspension. At the time trial was suspended, 411 patients had been recruited, 208 had received DAA, and 203 had received its placebo. There was no significant interaction between DAA and low-dose steroids (P = 0.47). On Day 90, there were 99 deaths (47.6%) among the 208 patients receiving DAA and 94 deaths (46.3%) among the 203 patients receiving placebo (P = 0.79). There was no evidence of a difference between DAA and its placebo for any secondary outcomes or serious adverse events. CONCLUSIONS: In adults with established and severe septic shock, DAA showed no evidence of benefit or harm. Clinical trial registered with www.clinicaltrials.gov (NCT00625209).