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2.  Involvement of ICU families in decisions: fine-tuning the partnership 
Families of patients are not simple visitors to the ICU. They have just been separated from a loved one, often someone they live with, either abruptly or, in nearly half the cases, because a chronic condition has suddenly worsened. They must cope with a serious illness of a loved one, while having to adapt to the unfamiliar and intimidating ICU environment. In many cases, the outcome of the critical illness is uncertain, a situation that causes considerable distress to the relatives. As shown by our research group and others, families exhibit symptoms of anxiety (70%) and depression (35%) in the first few days after admission, as well as symptoms of stress (33%) and difficulty understanding the information delivered by the healthcare staff (50%). Furthermore, relatives of patients who die in the ICU are at risk for psychiatric syndromes such as generalized anxiety, panic attacks, depression, and posttraumatic stress syndrome. In this setting of psychological distress, families are asked to consider sharing in healthcare decisions about their loved one in the ICU. This article aims to foster the debate about the shared decision-making process. We have three objectives: to transcend the overly simplistic position that opposes paternalism and autonomy, to build a view founded only on an evaluation of actual practice and experience in the field, and to keep the focus squarely on the patient. Families want information and communication time from the staff. Nurses and physicians need to understand that families can share in decisions only if the entire ICU staff actively promotes family involvement and, of course, if the family wants to participate in all or part of the decision-making process.
PMCID: PMC4273688  PMID: 25593753
Information; Communication; End of life; Bereavement; Randomized controlled trials
3.  How to treat severe infections in critically ill neutropenic patients? 
BMC Infectious Diseases  2014;14(1):512.
Severe infections in neutropenic patient often progress rapidly leading to life-threatening organ dysfunction requiring admission to the Intensive Care Unit. Management strategies include early adequate appropriate empirical antimicrobial, early admission to ICU to avoid any delay in the diagnostic and therapeutic management of organ dysfunction. This review discusses the main clinical situations encountered in critically ill neutropenic patients. Specific diagnostic and therapeutic approaches have been proposed for acute respiratory failure, shock, neutropenic enterocolitis, catheter-related infections, cellulitis and primary bacteriemia. Non anti-infectious agents and recent advances will also be discussed. At present, most of large-scale studies and recommendations in neutropenic patients stem from hematological patients and will need further validation in ICU patients.
PMCID: PMC4289060  PMID: 25431154
4.  Sleepless nights in the ICU: the awaken family 
Critical Care  2013;17(5):1003.
Having a loved-one in the ICU is a traumatic experience for family members that can lead to a cluster of psychological complications, recently defined as post-intensive care family syndrome. In a previous issue of Critical Care, Day and colleagues stressed the severe sleep disturbance and fatigue experienced by a majority of ICU patient family members. However, despite this burden being well characterised, the best preventive coping strategy remains undetermined.
PMCID: PMC4056364  PMID: 24099493
5.  Early non-invasive ventilation for acute respiratory failure in immunocompromised patients (IVNIctus): study protocol for a multicenter randomized controlled trial 
Trials  2014;15(1):372.
Acute respiratory failure (ARF) remains the leading reason for intensive care unit (ICU) admission of immunocompromised patients. In the most severe cases, high-flow oxygen therapy may fail to ensure adequate gas exchange, and mechanical ventilation (MV) must be used. This scenario is associated with high mortality rates of 40 to 60%, depending on the cause of ARF and type of immune deficiency. The use of non-invasive ventilation (NIV) in this situation has been criticized as potentially delaying the initiation of optimal treatment. In contrast, early NIV used prophylactically in patients with ARF who do not meet the criteria for invasive MV (IMV) may obviate the need for IMV, thereby decreasing the morbidity and mortality rates. We aim to demonstrate that a management strategy including early NIV decreases 28-day mortality rates compared to oxygen therapy alone in immunocompromised patients with ARF.
This is a multicenter parallel-group randomized controlled trial comparing early NIV to oxygen therapy alone in immunocompromised patients with ARF. All immunocompromised adult patients admitted to admission for ARF are eligible for randomization. Patient with ARF onset more than 72 hours earlier or ARF related to cardiogenic pulmonary edema or hypercapnia, or with a need for immediate endotracheal intubation or other organ failure are not eligible.
After inclusion patient are allocated to receive early NIV (intervention arm) or oxygen therapy only (control arm).
We plan to enroll 374 patients in 29 ICUs. An interim analysis is planned after the inclusion of 187 patients. The main objective is to demonstrate early NIV increases survival as compared to oxygen therapy alone. Other outcomes include the need of IMV, organ failure evolution, nosocomial infections rate, 6 months survival.
This study is expected to demonstrate an improved 28-day survival in immunocompromised patients managed with early NIV.
Trial registration
Registration number: NCT01915719. Registered on 26 July 2013.
Electronic supplementary material
The online version of this article (doi:10.1186/1745-6215-15-372) contains supplementary material, which is available to authorized users.
PMCID: PMC4190291  PMID: 25257210
Non-invasive ventilation; Immunocompromised patient; Acute respiratory failure
6.  Acute Respiratory Failure in Critically Ill Patients with Interstitial Lung Disease 
PLoS ONE  2014;9(8):e104897.
Patients with chronic known or unknown interstitial lung disease (ILD) may present with severe respiratory flares that require intensive management. Outcome data in these patients are scarce.
Patients and Methods
Clinical and radiological features were collected in 83 patients with ILD-associated acute respiratory failure (ARF). Determinants of hospital mortality and response to corticosteroid therapy were identified by logistic regression.
Hospital and 1-year mortality rates were 41% and 54% respectively. Pulmonary hypertension, computed tomography (CT) fibrosis and acute kidney injury were independently associated with mortality (odds ratio (OR) 4.55; 95% confidence interval (95%CI) (1.20–17.33); OR, 7.68; (1.78–33.22) and OR 10.60; (2.25–49.97) respectively). Response to steroids was higher in patients with shorter time from hospital admission to corticosteroid therapy. Patients with fibrosis on CT had lower response to steroids (OR, 0.03; (0.005–0.21)). In mechanically ventilated patients, overdistension induced by high PEEP settings was associated with CT fibrosis and hospital mortality.
Mortality is high in ILD-associated ARF. CT and echocardiography are valuable prognostic tools. Prompt corticosteroid therapy may improve survival.
PMCID: PMC4130629  PMID: 25115557
7.  Intensive care unit admission in chronic obstructive pulmonary disease: patient information and the physician’s decision-making process 
Critical Care  2014;18(3):R115.
ICU admission is required in more than 25% of patients with chronic obstructive pulmonary disease (COPD) at some time during the course of the disease. However, only limited information is available on how physicians communicate with COPD patients about ICU admission.
COPD patients and relatives from 19 French ICUs were interviewed at ICU discharge about their knowledge of COPD. French pulmonologists self-reported their practices for informing and discussing intensive care treatment preferences with COPD patients. Finally, pulmonologists and ICU physicians reported barriers and facilitators for transfer of COPD patients to the ICU and to propose invasive mechanical ventilation.
Self-report questionnaires were filled in by 126 COPD patients and 102 relatives, and 173 pulmonologists and 135 ICU physicians were interviewed. For 41% (n = 39) of patients and 54% (n = 51) of relatives, ICU admission had never been expected prior to admission. One half of patients were not routinely informed by their pulmonologist about possible ICU admission at some time during the course of COPD. Moreover, treatment options (that is, non-invasive ventilation, intubation and mechanical ventilation or tracheotomy) were not explained to COPD patients during regular pulmonologist visits. Pulmonologists and ICU physician have different perceptions of the decision-making process pertaining to ICU admission and intubation.
The information provided by pulmonologists to patients and families concerning the prognosis of COPD, the risks of ICU admission and specific care could be improved in order to deliver ICU care in accordance with the patient’s personal values and preferences. Given the discrepancies in the decision-making process between pulmonologists and intensivists, a more collaborative approach should probably be discussed.
PMCID: PMC4229873  PMID: 24898342
8.  Safety of performing fiberoptic bronchoscopy in critically ill hypoxemic patients with acute respiratory failure 
Intensive Care Medicine  2012;39(1):45-52.
Safety of fibreoptic bronchoscopy (FOB) in nonintubated critically ill patients with acute respiratory failure have not been extensively evaluated. We aimed to measure the incidence of intubation and need to increase ventilatory support following FOB and to identify predictive factors of this event.
A prospective multicenter observational study was carried out in 8 French adult intensive care units. 169 FOB performed in patients with a PaO2/FiO2 ratio equal or less than 300 were analyzed. Our main end point was intubation rate. The secondary end point was rate of increased ventilatory support defined as greater than a 50% increase in oxygen requirement, the need to start non invasive-positive pressure ventilation (NI-PPV) or increase NI-PPV support.
Within 24 hours, an increase in ventilatory support was required following 59 (35%) bronchoscopies, of which 25 (15%) led to endotracheal intubation. The existence of chronic obstructive pulmonary disease (COPD) (OR:5.2 [1.6–17.8], p=0.007) or immunosuppression (OR : 5.4 [1.7–17.2], p=0.004) were significantly associated with the need for intubation in multivariable analysis. None of the baseline physiological parameters including the PaO2/FiO2 ratio was associated with intubation.
Bronchoscopy is often followed by an increase in ventilatory support in hypoxemic critically ill patients, but less frequently by the need for intubation. COPD, immunosuppression are associated with a need for invasive ventilation in the following 24 hours.
PMCID: PMC3939027  PMID: 23070123
Acute Disease; Adult; Aged; Aged, 80 and over; Anoxia; therapy; Bronchoscopy; Critical Illness; Female; Humans; Male; Middle Aged; Positive-Pressure Respiration; Prospective Studies; Respiration, Artificial; Respiratory Insufficiency; therapy
9.  EMPIRICUS micafungin versus placebo during nosocomial sepsis in Candida multi-colonized ICU patients with multiple organ failures: study protocol for a randomized controlled trial 
Trials  2013;14:399.
The potential interest of antifungal treatment of non-immunocompromized patients with sepsis, extra-digestive Candida colonization and multiple organ failure is unknown. It represents three-quarters of antifungals prescribed in Intensive Care Units. It may allow early treatment of invasive fungal infection in the incubation phase but expose patients to unnecessary antifungal treatments with subsequent cost and fungal selection pressure. As early diagnostic tests for invasive candidiasis are still considered to be insufficient, the potential interest in this strategy needs to be demonstrated.
This prospective multicenter, double blind, randomized-controlled trial is conducted in 23 French Intensive Care Units. All adult patients, mechanically ventilated for more than four days with sepsis of unknown origin and with at least one extradigestive fungal colonization site and multiple organ failure are eligible for randomization. Patients with proven invasive candidiasis are not included. After a complete mycological screening, patients are allocated to receive micafungin 100 mg intravenously once a day or placebo for 14 days. We plan to enroll 260 patients. The main objective is to demonstrate that micafungin increases survival of patients without invasive candidiasis at day 28 as compared to placebo. Other outcomes include day 28 and 90 survival and organ failure evolution. Additionally, pharmacokinetics of micafungin in enrolled patients will be measured and evolution of fungal biomarkers and susceptibility profiles of infecting fungi will also be followed.
This study will help to provide guidelines for treating non-immunocompromized patients with fungal colonization multiple organ failure and sepsis of unknown origin.
Trial registration number NCT01773876
PMCID: PMC4222830  PMID: 24261608
Colonization; Nosocomial sepsis; Candidemia; Invasive candidiasis; Micafungin
10.  The prognostic value of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) deficiency in septic shock patients involves interleukin-6 and is not dependent on disseminated intravascular coagulation 
Critical Care  2013;17(6):R273.
ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) deficiency has been reported in patients with sepsis but its clinical relevance and pathophysiology remain unclear. Our objectives were to assess the clinical significance, prognostic value and pathophysiology of ADAMTS13 deficiency in patients with septic shock with and without disseminated intravascular coagulation (DIC).
This was a prospective monocenter cohort study of patients with septic shock. Von Willebrand Factor, ADAMTS13-related parameters and plasma IL-6 concentration were measured at inclusion to the study. Patients were categorized into three groups according to the presence of ADAMT13 deficiency (<30%) or DIC.
This study included 72 patients with a median age of 59 years (interquartile range (IQR) 50 to 71). Each of the included patients received vasopressors; 55 (76%) were under mechanical ventilation and 22 (33%) underwent renal replacement therapy. Overall, 19 patients (26%) had DIC, and 36 patients had ADMTS13 deficiency (50%). Patients with DIC, ADAMTS13 deficiency or both were more severe at ICU admission. Mortality was higher in septic shock patients from group one. By multivariate analysis, Simplified Acute Physiology Score 2 (SAPS2) score (odds ratio (OR) 1.11/point; 95% CI 1.01 to 1.24) and ADAMTS13 activity <30% (OR 11.86; 95% CI 1.36 to 103.52) were independently associated with hospital mortality. There was no correlation between ADAMTS13 activity and the International Society for Thrombosis and Haemostasis (ISTH) score (rs = -0.97, P = 0.41) suggesting that ADAMTS13 functional deficiency and DIC were independent parameters. IL-6 level was higher in patients with ADAMTS13 activity <30% [895 (IQR 330 to 1843) pg/mL versus 83 (IQR 43 to 118), P = 0.0003).
Septic shock was associated with a functional deficiency of ADAMTS13, independently of DIC. ADAMTS13 functional deficiency is then a prognostic factor for mortality in septic shock patients, independently of DIC.
PMCID: PMC4056532  PMID: 24238574
11.  Initial use of one or two antibiotics for critically ill patients with community-acquired pneumonia: impact on survival and bacterial resistance 
Critical Care  2013;17(6):R265.
Several guidelines recommend initial empirical treatment with two antibiotics instead of one to decrease mortality in community-acquired pneumonia (CAP) requiring intensive-care-unit (ICU) admission. We compared the impact on 60-day mortality of using one or two antibiotics. We also compared the rates of nosocomial pneumonia and multidrug-resistant bacteria.
This is an observational cohort study of 956 immunocompetent patients with CAP admitted to ICUs in France and entered into a prospective database between 1997 and 2010.
Patients with chronic obstructive pulmonary disease were excluded. Multivariate analysis adjusted for disease severity, gender, and co-morbidities was used to compare the impact on 60-day mortality of receiving adequate initial antibiotics and of receiving one versus two initial antibiotics.
Initial adequate antibiotic therapy was significantly associated with better survival (subdistribution hazard ratio (sHR), 0.63; 95% confidence interval (95% CI), 0.42 to 0.94; P = 0.02); this effect was strongest in patients with Streptococcus pneumonia CAP (sHR, 0.05; 95% CI, 0.005 to 0.46; p = 0.001) or septic shock (sHR: 0.62; 95% CI 0.38 to 1.00; p = 0.05). Dual therapy was associated with a higher frequency of initial adequate antibiotic therapy. However, no difference in 60-day mortality was found between monotherapy (β-lactam) and either of the two dual-therapy groups (β-lactam plus macrolide or fluoroquinolone). The rates of nosocomial pneumonia and multidrug-resistant bacteria were not significantly different across these three groups.
Initial adequate antibiotic therapy markedly decreased 60-day mortality. Dual therapy improved the likelihood of initial adequate therapy but did not predict decreased 60-day mortality. Dual therapy did not increase the risk of nosocomial pneumonia or multidrug-resistant bacteria.
PMCID: PMC4056004  PMID: 24200097
13.  Adjunctive steroid in HIV-negative patients with severe Pneumocystis pneumonia 
Respiratory Research  2013;14(1):87.
High-dose steroid therapy has been proven effective in AIDS-related Pneumocystis pneumonia (PCP) but not in non-AIDS-related cases. We evaluated the effects on survival of steroids in HIV-negative patients with PCP.
Retrospective study patients admitted to the ICU with hypoxemic PCP. We compared patients receiving HDS (≥1 mg/Kg/day prednisone equivalent), low-dose steroids (LDS group, <1 mg/Kg/day prednisone equivalent), and no steroids (NS group). Variables independently associated with ICU mortality were identified.
139 HIV-negative patients with PCP were included. Median age was 48 [40–60] years. The main underlying conditions were hematological malignancies (n=55, 39.6%), cancer (n=11, 7.9%), and solid organ transplantation (n=73, 52.2%). ICU mortality was 26% (36 deaths). The HDS group had 72 (51.8%) patients, the LDS group 35 (25%) patients, and the NS group 32 (23%) patients. Independent predictors of ICU mortality were SAPS II at ICU admission (odds ratio [OR], 1.04/point; [95%CI], 1.01-1.08, P=0.01), non-hematological disease (OR, 4.06; [95%CI], 1.19-13.09, P=0.03), vasopressor use (OR, 20.31; 95%CI, 6.45-63.9, P<0.001), and HDS (OR, 9.33; 95%CI, 1.97-44.3, P=0.02). HDS was not associated with the rate of ICU-acquired infections.
HDS were associated with increased mortality in HIV-negative patients with PCP via a mechanism independent from an increased risk of infection.
PMCID: PMC3765749  PMID: 23981859
Pneumocystis jiroveci infection; Immunocompromised host; Mortality
15.  Acute Kidney Injury in Patients with Newly Diagnosed High-Grade Hematological Malignancies: Impact on Remission and Survival 
PLoS ONE  2013;8(2):e55870.
Optimal chemotherapy with minimal toxicity is the main determinant of complete remission in patients with newly diagnosed hematological malignancies. Acute organ dysfunctions may impair the patient’s ability to receive optimal chemotherapy.
Design and Methods
To compare 6-month complete remission rates in patients with and without acute kidney injury (AKI), we collected prospective data on 200 patients with newly diagnosed high-grade malignancies (non-Hodgkin lymphoma, 53.5%; acute myeloid leukemia, 29%; acute lymphoblastic leukemia, 11.5%; and Hodgkin disease, 6%).
According to RIFLE criteria, 137 (68.5%) patients had AKI. Five causes of AKI accounted for 91.4% of cases: hypoperfusion, tumor lysis syndrome, tubular necrosis, nephrotoxic agents, and hemophagocytic lymphohistiocytosis. Half of the AKI patients received renal replacement therapy and 14.6% received suboptimal chemotherapy. AKI was associated with a lower 6-month complete remission rate (39.4% vs. 68.3%, P<0.01) and a higher mortality rate (47.4% vs. 30.2%, P<0.01) than patients without AKI. By multivariate analysis, independent determinants of 6-month complete remission were older age, poor performance status, number of organ dysfunctions, and AKI.
AKI is common in patients with newly diagnosed high-grade malignancies and is associated with lower complete remission rates and higher mortality.
PMCID: PMC3573047  PMID: 23457485
16.  Prognostic consequences of borderline dysnatremia: pay attention to minimal serum sodium change 
Critical Care  2013;17(1):R12.
To assess the prevalence of dysnatremia, including borderline changes in serum sodium concentration, and to estimate the impact of these dysnatremia on mortality after adjustment for confounders.
Observational study on a prospective database fed by 13 intensive care units (ICUs). Unselected patients with ICU stay longer than 48 h were enrolled over a 14-year period were included in this study. Mild to severe hyponatremia were defined as serum sodium concentration < 135, < 130, and < 125 mmol/L respectively. Mild to severe hypernatremia were defined as serum sodium concentration > 145, > 150, and > 155 mmol/L respectively. Borderline hyponatremia and hypernatremia were defined as serum sodium concentration between 135 and 137 mmol/L or 143 and 145 respectively.
A total of 11,125 patients were included in this study. Among these patients, 3,047 (27.4%) had mild to severe hyponatremia at ICU admission, 2,258 (20.3%) had borderline hyponatremia at ICU admission, 1,078 (9.7%) had borderline hypernatremia and 877 (7.9%) had mild to severe hypernatremia. After adjustment for confounder, both moderate and severe hyponatremia (subdistribution hazard ratio (sHR) 1.82, 95% CI 1.002 to 1.395 and 1.27, 95% CI 1.01 to 1.60 respectively) were associated with day-30 mortality. Similarly, mild, moderate and severe hypernatremia (sHR 1.34, 95% CI 1.14 to 1.57; 1.51, 95% CI 1.15 to 1.99; and 2.64, 95% CI 2.00 to 3.81 respectively) were independently associated with day-30 mortality.
One-third of critically ill patients had a mild to moderate dysnatremia at ICU admission. Dysnatremia, including mild changes in serum sodium concentration, is an independent risk factor for hospital mortality and should not be neglected.
PMCID: PMC4056804  PMID: 23336363
17.  Efficacy of renal replacement therapy in critically ill patients: a propensity analysis 
Critical Care  2012;16(6):R236.
Although renal replacement therapy (RRT) is a common procedure in critically ill patients with acute kidney injury (AKI), its efficacy remains uncertain. Patients who receive RRT usually have higher mortality rates than those who do not. However, many differences exist in severity patterns between patients with and those without RRT and available results are further confounded by treatment selection bias since no consensus on indications for RRT has been reached so far. Our aim was to account for these biases to accurately assess RRT efficacy, with special attention to RRT timing.
We performed a propensity analysis using data of the French longitudinal prospective multicenter Outcomerea database. Two propensity scores for RRT were built to match patients who received RRT to controls who did not despite having a close probability of receiving the procedure. AKI was defined according to RIFLE criteria. The association between RRT and hospital mortality was examined through multivariate conditional logistic regression analyses to control for residual confounding. Sensitivity analyses were conducted to examine the impact of RRT timing.
Among the 2846 study patients, 545 (19%) received RRT. Crude mortality rates were higher in patients with than in those without RRT (38% vs 17.5%, P < 0.001). After matching and adjustment, RRT was not associated with a reduced hospital mortality. The two propensity models yielded concordant results.
In our study population, RRT failed to reduce hospital mortality. This result emphasizes the need for randomized studies comparing RRT to conservative management in selected ICU patients, with special focus on RRT timing.
PMCID: PMC3672625  PMID: 23254304
18.  Determinants of Recovery from Severe Posterior Reversible Encephalopathy Syndrome 
PLoS ONE  2012;7(9):e44534.
Few outcome data are available about posterior reversible encephalopathy syndrome (PRES). We studied 90-day functional outcomes and their determinants in patients with severe PRES.
70 patients with severe PRES admitted to 24 ICUs in 2001–2010 were included in a retrospective cohort study. The main outcome measure was a Glasgow Outcome Scale (GOS) of 5 (good recovery) on day 90.
Main Results
Consciousness impairment was the most common clinical sign, occurring in 66 (94%) patients. Clinical seizures occurred in 57 (81%) patients. Median mean arterial pressure was 122 (105–143) mmHg on scene. Cerebral imaging abnormalities were bilateral (93%) and predominated in the parietal (93%) and occipital (86%) white matter. Median number of brain areas involved was 4 (3–5). Imaging abnormalities resolved in 43 (88%) patients. Ischaemic and/or haemorrhagic complications occurred in 7 (14%) patients. The most common causes were drug toxicity (44%) and hypertensive encephalopathy (41%). On day 90, 11 (16%) patients had died, 26 (37%) had marked functional impairments (GOS, 2 to 4), and 33 (56%) had a good recovery (GOS, 5). Factors independently associated with GOS<5 were highest glycaemia on day 1 (OR, 1.22; 95%CI, 1.02–1.45, p = 0.03) and time to causative-factor control (OR, 3.3; 95%CI, 1.04–10.46, p = 0.04), whereas GOS = 5 was associated with toxaemia of pregnancy (preeclampsia/eclampsia) (OR, 0.06; 95%CI, 0.01–0.38, p = 0.003).
By day 90 after admission for severe PRES, 44% of survivors had severe functional impairments. Highest glycaemia on day 1 and time to causative-factor control were strong early predictors of outcomes, suggesting areas for improvement.
PMCID: PMC3443081  PMID: 23024751
19.  Symptoms of depression in ICU physicians 
Work and family are the two domains from which most adults develop satisfaction in life. They also are responsible for stressful experiences. There is a perception in the community that work is increasingly the source of much of our stress and distress. Depressive symptoms may be related to repeated stressful experiences. Intensive care unit (ICU) physicians are exposed to major stressors. However, the existence of depressive symptoms in these doctors has been poorly studied. This study was designed to evaluate the prevalence and associated risk factors of depressive symptoms in junior and senior ICU physicians.
A one-day national survey was conducted in adult intensive care units (ICU) in French public hospitals. Symptoms of depression were assessed using the Centers of Epidemiologic Studies Depression Scale (CES-D).
A total of 189 ICUs participated, and 901 surveys were returned (75.8% response rate). Symptoms of depression were found in 23.8% of the respondents using the CES-D scale. Fifty-eight percent of these intensivists presenting symptoms of depression wished to leave their job compared with only 33% of those who did not exhibit signs of depression as assessed by the CES-D scale (p < 0.0001). Multiple logistic regression showed that organizational factors were associated with the presence of depressive symptoms. Workload (long interval since the last nonworking weekend, absence of relief of service until the next working day after a night shift) and impaired relationships with other intensivists were independently associated with the presence of depressive symptoms. A high level of burnout also was related to the presence of depressive symptoms. In contrast, no demographic factors regarding ICU physicians and no factor related to the severity of illness of patients were retained by the model. The quality of relationships with other physicians (from other departments) was associated with the absence of depressive symptoms (protective effect).
Approximately one of four intensivists presented symptoms of depression. The next step could be to test whether organization modification is associated with less depressive symptoms and less desire to leave the job.
PMCID: PMC3543176  PMID: 22839744
Intensive care unit; Organizational management; Conflict; Burnout; Depression; Physicians
20.  A Multicentre Study of Acute Kidney Injury in Severe Sepsis and Septic Shock: Association with Inflammatory Phenotype and HLA Genotype 
PLoS ONE  2012;7(6):e35838.
To investigate the association between severity of acute kidney injury (AKI) and outcome, systemic inflammatory phenotype and HLA genotype in severe sepsis.
Methodology/Principal Findings
Prospective multicenter observational study done in 4 intensive care units in two university hospitals. Severe sepsis and septic shock patients with at least 2 organ failures based on the SOFA score were classified: 1) "no AKI", 2) "mild AKI" (grouping stage 1 and 2 of AKIN score) and 3) "severe AKI" (stage 3 of AKIN score). Sequential measurements: The vasopressor dependency index (VDI; dose and types of drugs) to evaluate the association between hemodynamic status and the development of early AKI; plasma levels of IL-10, macrophage migration inhibitory factor (MIF), IL-6 and HLA-DR monocyte expression. Genotyping of the 13 HLA-DRB1 alleles with deduction of presence of HLA-DRB3, -DRB4 and -DRB5 genes. We used multivariate analysis with competitive risk model to study associations. Overall, 176 study patients (146 with septic shock) were classified from AKIN score as "no AKI" (n = 43), "mild AKI" (n = 74) or "severe AKI" (n = 59). The VDI did not differ between groups of AKI. After adjustment, "mild and severe AKI" were an independent risk factor for mortality (HR 2.42 95%CI[1.01-5.83], p = 0.048 and HR 1.99 95%CI[1.30-3.03], p = 0.001 respectively). "Severe AKI" had higher levels of plasma IL-10, MIF and IL-6 compared to “no AKI” and mild AKI (p<0.05 for each), with no difference in mHLA-DR at day 0. HLA-DRB genotyping showed a significantly lower proportion of 4 HLA-DRB alleles among patients requiring renal replacement therapy (RRT) (58%) than in patients with severe AKI who did not receive RRT (84%) (p = 0.004).
AKI severity is independently associated with mortality and plasma IL-10, MIF or IL-6 levels. Presence of 4 alleles of HLA-DRB in severe AKI patients seems associated with a lower need of RRT.
PMCID: PMC3368929  PMID: 22701553
21.  Ventilator-associated pneumonia and ICU mortality in severe ARDS patients ventilated according to a lung-protective strategy 
Critical Care  2012;16(2):R65.
Ventilator-associated pneumonia (VAP) may contribute to the mortality associated with acute respiratory distress syndrome (ARDS). We aimed to determine the incidence, outcome, and risk factors of bacterial VAP complicating severe ARDS in patients ventilated by using a strictly standardized lung-protective strategy.
This prospective epidemiologic study was done in all the 339 patients with severe ARDS included in a multicenter randomized, placebo-controlled double-blind trial of cisatracurium besylate in severe ARDS patients. Patients with suspected VAP underwent bronchoalveolar lavage to confirm the diagnosis.
Ninety-eight (28.9%) patients had at least one episode of microbiologically documented bacterial VAP, including 41 (41.8%) who died in the ICU, compared with 74 (30.7%) of the 241 patients without VAP (P = 0.05). After adjustment, age and severity at baseline, but not VAP, were associated with ICU death. Cisatracurium besylate therapy within 2 days of ARDS onset decreased the risk of ICU death. Factors independently associated with an increased risk to develop a VAP were male sex and worse admission Glasgow Coma Scale score. Tracheostomy, enteral nutrition, and the use of a subglottic secretion-drainage device were protective.
In patients with severe ARDS receiving lung-protective ventilation, VAP was associated with an increased crude ICU mortality which did not remain significant after adjustment.
PMCID: PMC3681394  PMID: 22524447
22.  Mortality associated with timing of admission to and discharge from ICU: a retrospective cohort study 
Although the association between mortality and admission to intensive care units (ICU) in the "after hours" (weekends and nights) has been the topic of extensive investigation, the timing of discharge from ICU and outcome has been less well investigated. The objective of this study was to assess effect of timing of admission to and discharge from ICUs and subsequent risk for death.
Adults (≥18 years) admitted to French ICUs participating in Outcomerea between January 2006 and November 2010 were included.
Among the 7,380 patients included, 61% (4,481) were male, the median age was 62 (IQR, 49-75) years, and the median SAPS II score was 40 (IQR, 28-56). Admissions to ICU occurred during weekends (Saturday and Sunday) in 1,708 (23%) cases, during the night (18:00-07:59) in 3,855 (52%), and on nights and/or weekends in 4,659 (63%) cases. Among 5,992 survivors to ICU discharge, 903 (15%) were discharged on weekends, 659 (11%) at night, and 1,434 (24%) on nights and/or weekends. After controlling for a number of co-variates using logistic regression analysis, admission during the after hours was not associated with an increased risk for death. However, patients discharged from ICU on nights were at higher adjusted risk (odds ratio, 1.54; 95% confidence interval, 1.12-2.11) for death.
In this study, ICU discharge at night but not admission was associated with a significant increased risk for death. Further studies are needed to examine whether minimizing night time discharges from ICU may improve outcome.
PMCID: PMC3269385  PMID: 22115194
23.  The strategy of antibiotic use in critically ill neutropenic patients 
Suspicion of sepsis in neutropenic patients requires immediate antimicrobial treatment. The initial regimen in critically ill patients should cover both Gram-positive and Gram-negative pathogens, including Pseudomonas aeruginosa. However, the risk of selecting multidrug-resistant pathogens should be considered when using broad-spectrum antibiotics for a prolonged period of time. The choice of the first-line empirical drugs should take into account the underlying malignancy, local bacterial ecology, clinical presentation and severity of acute illness. This review provides an up-to-date guide that will assist physicians in choosing the best strategy regarding the use of antibiotics in neutropenic patients, with a special focus on critically ill patients, based on the above-mentioned considerations and on the most recent international guidelines and literature.
PMCID: PMC3224396  PMID: 21906359
24.  Multiple-center evaluation of mortality associated with acute kidney injury in critically ill patients: a competing risks analysis 
Critical Care  2011;15(3):R128.
In this study, we aimed to assess the association between acute kidney injury (AKI) and mortality in critically ill patients using an original competing risks approach.
Unselected patients admitted between 1997 and 2009 to 13 French medical or surgical intensive care units were included in this observational cohort study. AKI was defined according to the RIFLE criteria. The following data were recorded: baseline characteristics, daily serum creatinine level, daily Sequential Organ Failure Assessment (SOFA) score, vital status at hospital discharge and length of hospital stay. Patients were classified according to the maximum RIFLE class reached during their ICU stay. The association of AKI with hospital mortality with "discharge alive" considered as a competing event was assessed according to the Fine and Gray model.
Of the 8,639 study patients, 32.9% had AKI, of whom 19.1% received renal replacement therapy. Patients with AKI had higher crude mortality rates and longer lengths of hospital stay than patients without AKI. In the Fine and Gray model, independent risk factors for hospital mortality were the RIFLE classes Risk (sub-hazard ratio (SHR) 1.58 and 95% confidence interval (95% CI) 1.32 to 1.88; P < 0.0001), Injury (SHR 3.99 and 95% CI 3.43 to 4.65; P < 0.0001) and Failure (SHR 4.12 and 95% CI 3.55 to 4.79; P < 0.0001); nonrenal SOFA score (SHR 1.19 per point and 95% CI 1.18 to 1.21; P < 0.0001); McCabe class 3 (SHR 2.71 and 95% CI 2.34 to 3.15; P < 0.0001); and respiratory failure (SHR 3.08 and 95% CI 1.36 to 7.01; P < 0.01).
By using a competing risks approach, we confirm in this study that AKI affecting critically ill patients is associated with increased in-hospital mortality.
PMCID: PMC3218994  PMID: 21586153
25.  Impact of ureido/carboxypenicillin resistance on the prognosis of ventilator-associated pneumonia due to Pseudomonas aeruginosa 
Critical Care  2011;15(2):R112.
Although Pseudomonas aeruginosa is a leading pathogen responsible for ventilator-associated pneumonia (VAP), the excess in mortality associated with multi-resistance in patients with P. aeruginosa VAP (PA-VAP), taking into account confounders such as treatment adequacy and prior length of stay in the ICU, has not yet been adequately estimated.
A total of 223 episodes of PA-VAP recorded into the Outcomerea database were evaluated. Patients with ureido/carboxy-resistant P. aeruginosa (PRPA) were compared with those with ureido/carboxy-sensitive P. aeruginosa (PSPA) after matching on duration of ICU stay at VAP onset and adjustment for confounders.
Factors associated with onset of PRPA-VAP were as follows: admission to the ICU with septic shock, broad-spectrum antimicrobials at admission, prior use of ureido/carboxypenicillin, and colonization with PRPA before infection. Adequate antimicrobial therapy was more often delayed in the PRPA group. The crude ICU mortality rate and the hospital mortality rate were not different between the PRPA and the PSPA groups. In multivariate analysis, after controlling for time in the ICU before VAP diagnosis, neither ICU death (odds ratio (OR) = 0.73; 95% confidence interval (CI): 0.32 to 1.69; P = 0.46) nor hospital death (OR = 0.87; 95% CI: 0.38 to 1.99; P = 0.74) were increased in the presence of PRPA infection. This result remained unchanged in the subgroup of 87 patients who received adequate antimicrobial treatment on the day of VAP diagnosis.
After adjustment, and despite the more frequent delay in the initiation of an adequate antimicrobial therapy in these patients, resistance to ureido/carboxypenicillin was not associated with ICU or hospital death in patients with PA-VAP.
PMCID: PMC3219393  PMID: 21481266

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