Determinants of protection against SARS-CoV-2 Omicron BA.1 and Delta infections in fully vaccinated outpatients.

We aimed to evaluate the association between the humoral and cellular immune responses and symptomatic SARS-CoV-2 infection with Delta or Omicron BA.1 variants in fully vaccinated outpatients. Anti-receptor binding domain (RBD) IgG levels and interferon-gamma (IFN-γ) release were evaluated at PCR-diagnosis of SARS-CoV-2 in 636 samples from negative and positive patients during Delta and Omicron BA.1 periods. Median levels of anti-RBD IgG in positive patients were significantly lower than in negative patients for both variants (p < 0.05). The frequency of Omicron BA.1 infection in patients with anti-RBD IgG concentrations ≥1000 binding antibody units (BAU)/mL was 51.0% and decreased to 34.4% in patients with concentrations ≥3000 BAU/mL. For Delta infection, the frequency of infection was significantly lower when applying the same anti-RBD IgG thresholds (13.3% and 5.3% respectively, p < 0.05). In addition, individuals in the hybrid immunity group had a 4.5 times lower risk of Delta infection compared to the homologous vaccination group (aOR = 0.22, 95% CI: [0.05-0.64]. No significant decrease in the risk of Omicron BA.1 infection was observed in the hybrid group compared to the homologous group, but the risk decreased within the hybrid group as anti-RBD IgG titers increased (aOR = 0.08, 95% CI: [0.01-0.41], p = 0.008). IFN-γ release post-SARS-CoV-2 peptide stimulation was not different between samples from patients infected (either with Delta or Omicron BA.1 variant) or not (p > 0.05). Our results show that high circulating levels of anti-RBD IgG and hybrid immunity were independently associated with a lower risk of symptomatic SARS-CoV-2 infection in outpatients with differences according to the infecting variant (www.clinicaltrials.gov; ID NCT05060939).

Timing of Renal-Replacement Therapy in Patients with Acute Kidney Injury and Sepsis.

BACKGROUND: Acute kidney injury is the most frequent complication in patients with septic shock and is an independent risk factor for death. Although renal-replacement therapy is the standard of care for severe acute kidney injury, the ideal time for initiation remains controversial. METHODS: In a multicenter, randomized, controlled trial, we assigned patients with early-stage septic shock who had severe acute kidney injury at the failure stage of the risk, injury, failure, loss, and end-stage kidney disease (RIFLE) classification system but without life-threatening complications related to acute kidney injury to receive renal-replacement therapy either within 12 hours after documentation of failure-stage acute kidney injury (early strategy) or after a delay of 48 hours if renal recovery had not occurred (delayed strategy). The failure stage of the RIFLE classification system is characterized by a serum creatinine level 3 times the baseline level (or ≥4 mg per deciliter with a rapid increase of ≥0.5 mg per deciliter), urine output less than 0.3 ml per kilogram of body weight per hour for 24 hours or longer, or anuria for at least 12 hours. The primary outcome was death at 90 days. RESULTS: The trial was stopped early for futility after the second planned interim analysis. A total of 488 patients underwent randomization; there were no significant between-group differences in the characteristics at baseline. Among the 477 patients for whom follow-up data at 90 days were available, 58% of the patients in the early-strategy group (138 of 239 patients) and 54% in the delayed-strategy group (128 of 238 patients) had died (P=0.38). In the delayed-strategy group, 38% (93 patients) did not receive renal-replacement therapy. Criteria for emergency renal-replacement therapy were met in 17% of the patients in the delayed-strategy group (41 patients). CONCLUSIONS: Among patients with septic shock who had severe acute kidney injury, there was no significant difference in overall mortality at 90 days between patients who were assigned to an early strategy for the initiation of renal-replacement therapy and those who were assigned to a delayed strategy. (Funded by the French Ministry of Health; IDEAL-ICU ClinicalTrials.gov number, NCT01682590 .).

Targeted screening for third-generation cephalosporin-resistant Enterobacteriaceae carriage among patients admitted to intensive care units: a quasi-experimental study.

INTRODUCTION: Identification of third-generation, cephalosporin-resistant Enterobacteriaceae (3GC-RE) carriers by rectal screening at admission seems to be an important step in the prevention of transmission and outbreaks; however, little is known about its effectiveness. The aim of this study was to evaluate the impact of 'targeted screening' at patient admission to intensive care units (ICUs) on the incidence of 3GC-RE hospital-acquired infections (HAIs) and compare it to 'universal screening'. METHODS: We undertook a quasi-experimental study of two ICUs (unit A: intervention group; unit B: control group) at a university-affiliated hospital between 1 January 2008 and 31 December 2011. In unit A, patients were screened universally for 3GC-RE at admission during period 1 (1 January 2008 through 30 September 2010). During period 2 (2011 calendar year), the intervention was implemented in unit A; patients transferred from another unit or hospital were screened selectively. In unit B, all patients were screened throughout periods 1 and 2. 3GC-RE-related HAI incidence rates were expressed per 1,000 patient-days. Incidence rate ratios (IRRs) were examined by multivariate Poisson regression modelling. RESULTS: In unit A, 3GC-RE-related HAI incidence rates decreased from 5.4 (95% confidence interval (CI), 4.1 to 7.0) during period 1 to 1.3 (95% CI, 0.5 to 2.9) during period 2 (P < 0.001). No changes were observed in unit B between periods 1 and 2 (P = 0.5). In unit A, the adjusted incidence of 3GC-RE-related HAIs decreased in period 2 compared with period 1 (adjusted IRR, 0.3; 95% CI, 0.1 to 0.9; P = 0.03) independently of temporal trend, trauma and age. No changes were seen in unit B (P = 0.4). The total number of rectal swabs taken showed an 85% decrease in unit A between period 1 and 2 (P < 0.001). CONCLUSIONS: Targeted screening of 3GC-RE carriers at ICU admission was not associated with an increase in 3GC-RE-related HAI incidence compared with universal screening. Total number of rectal swabs decreased significantly. These findings suggest that targeted screening may be worth assessing as an alternative to universal screening.

Factors associated with short- and long-term outcomes in lung cancer patients requiring unplanned invasive mechanical ventilation.

OBJECTIVE: Unplanned invasive mechanical ventilation (IMV) is associated with high mortality in lung cancer patients. We aimed to identify factors associated with weaning from IMV, intensive care unit (ICU) survival and 1-year survival in lung cancer patients requiring unplanned IMV. DESIGN: Retrospective observational study (2007-2017). SETTING: University-affiliated ICU. PATIENTS: Lung cancer patients requiring unplanned IMV. INTERVENTION: None. MAIN VARIABLES OF INTEREST: Weaning from IMV, ICU and 1-year survival. RESULTS: Of the 136 patients included in the analysis (age 64 (9) years, male 110 (81%), metastatic disease 97 (62%)), 52 (38%) were weaned from IMV, 51 (38%) were discharged from ICU and 22 (16%) were alive at 1year. The main indication for intubation was acute respiratory failure. In multivariate analysis, PaO2/FiO2 >175mmHg at ICU admission and intubation before ICU admission were associated with successful weaning from IMV while intubation for cardiac arrest was associated with weaning failure. Same factors were associated with ICU survival. Absence of metastasis at ICU admission and lung resection surgery were independently associated with 1-year survival. CONCLUSIONS: A significant proportion of patients with lung cancer treated with unplanned IMV could be weaned from IMV and survived to ICU discharge, especially in the absence of severe hypoxemia at ICU admission. The low one-year survival was mostly driven by metastatic status.

Fatal influenza A(H1N1)pdm09 encephalopathy in immunocompetent man.

We report an immunocompetent patient who had fatal encephalopathy after mild influenza. He rapidly died after unusual symptoms related to intracerebral thrombosis and hemorrhage. A brain biopsy specimen was positive for influenza A(H1N1)pdm09 virus RNA, but a lung biopsy specimen and cerebrospinal spinal fluid samples were negative.

Effect of statin therapy on mortality in patients with ventilator-associated pneumonia: a randomized clinical trial.

IMPORTANCE: Observational studies have reported that statin use may be associated with improved outcomes of various infections. Ventilator-associated pneumonia (VAP) is the most common infection in the intensive care unit (ICU) and is associated with substantial mortality. OBJECTIVE: To determine whether statin therapy can decrease day-28 mortality in patients with VAP. DESIGN, SETTING, AND PARTICIPANTS: Randomized, placebo-controlled, double-blind, parallel-group, multicenter trial performed in 26 intensive care units in France from January 2010 to March 2013. For power to detect an 8% absolute reduction in the day-28 mortality rate, we planned to enroll 1002 patients requiring invasive mechanical ventilation for more than 2 days and having suspected VAP, defined as a modified Clinical Pulmonary Infection Score of 5 or greater. The futility stopping rules were an absolute increase in day-28 mortality of at least 2.7% with simvastatin compared with placebo after enrollment of the first 251 patients. INTERVENTIONS: Participants were randomized to receive simvastatin (60 mg) or placebo, started on the same day as antibiotic therapy and given until ICU discharge, death, or day 28, whichever occurred first. MAIN OUTCOMES AND MEASURES: Primary outcome was day-28 mortality. Day-14, ICU, and hospital mortality rates were determined, as well as duration of mechanical ventilation and Sequential Organ Failure Assessment (SOFA) scores on days 3, 7, and 14. RESULTS: The study was stopped for futility at the first scheduled interim analysis after enrollment of 300 patients, of whom all but 7% in the simvastatin group and 11% in the placebo group were naive to statin therapy at ICU admission. Day-28 mortality was not lower in the simvastatin group (21.2% [95% CI, 15.4% to 28.6%) than in the placebo group (15.2% [95% CI, 10.2% to 22.1%]; P = .10; hazard ratio, 1.45 [95% CI, 0.83 to 2.51]); the between-group difference was 6.0% (95% CI, -3.0% to 14.9%). In statin-naive patients, day-28 mortality was 21.5% (95% CI, 15.4% to 29.1%) with simvastatin and 13.8% (95% CI, 8.8% to 21.0%) with placebo (P = .054) (between-group difference, 7.7% [95%CI, -1.8% to 16.8%). There were no significant differences regarding day-14, ICU, or hospital mortality rates; duration of mechanical ventilation; or changes in SOFA score. CONCLUSIONS AND RELEVANCE: In adults with suspected VAP, adjunctive simvastatin therapy compared with placebo did not improve day-28 survival. These findings do not support the use of statins with the goal of improving VAP outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01057758.

Performance of the Fresno-Quebec Rule in identifying patients with concomitant fractures not requiring a radiograph before shoulder dislocation reduction: a multicenter retrospective cohort study.

BACKGROUND AND IMPORTANCE: Although shoulder dislocation diagnosis is often solely based on clinical examination, physicians may order a radiograph to rule out a concomitant shoulder fracture before performing reduction. The Fresno-Québec decision rule aims to identify patients requiring a radiograph before reduction to avoid unnecessary systematic imaging. However, this novel approach needs further validation. OBJECTIVE: To evaluate the performance of the Fresno-Québec rule in identifying patients who do not require a prereduction radiograph and assess the variables associated with a clinically significant fracture. DESIGN, SETTINGS, AND PARTICIPANTS: A multicenter, retrospective cohort study from 2015 to 2021. Data were extracted from three ED university-affiliated tertiary-care centers. Patients aged ≥18 years with a final diagnosis of anterior glenohumeral dislocation were included. OUTCOMES MEASURE AND ANALYSIS: Accuracy metrics [sensitivity (Se), specificity (Sp), positive (PPV), negative predictive value (NPV), positive likelihood ratio (PLR) and negative likelihood ratio (NLR)] of the Fresno-Québec rule were measured. Multivariable logistic regression model was used to identify variables associated with the presence of a concomitant clinically significant fracture. MAIN RESULTS: A total of 2129 patients were included, among whom 9.7% had a concomitant fracture. The performance metrics of the Fresno-Québec rule were as follows: Se 0.96 95% confidence interval (0.92-0.98), Sp 0.36 (0.34-0.38), PPV 0.14 (0.12-0.16), NPV 0.99 (0.98-0.99), PLR 1.49 (1.42-1.55) and NLR 0.12 (0.06-0.23). A total of 678 radiographs could have been avoided, corresponding to a reduction of 35.2%. Age ≥40 years, first dislocation episode [odds ratio (OR) = 3.18 (1.95-5.38); P  < 0.001], the following mechanisms: road collision [OR = 6.26 (2.65-16.1)], low-level fall [OR = 3.49 (1.66-8.28)], high-level fall [OR = 3.95 (1.62-10.4)], and seizure/electric shock [OR = 10.6 (4.09-29.2)] were associated with the presence of a concomitant fracture. CONCLUSION: In this study, the Fresno-Québec rule has excellent Se in identifying concomitant clinically significant fractures in patients with an anterior glenohumeral dislocation. The use of this clinical decision rule may be associated with a reduction of approximately a third of unnecessary prereduction radiographs.

Changes over time in anxiety, depression, and stress symptoms among healthcare workers in French emergency departments during the first COVID-19 outbreak.

STUDY OBJECTIVE: Assess the changes in anxiety, depression, and stress levels over time and identify risk factors among healthcare workers in French emergency departments (EDs) during the first COVID-19 outbreak. METHOD: A prospective, multicenter study was conducted in 4 EDs and an emergency medical service (SAMU). During 3 months, participants completed fortnightly questionnaires to assess anxiety, depression, and stress using the Hospital Anxiety and Depression and the Chamoux-Simard scale. The changes in anxiety, depression, and stress levels over time were modelled by a linear mixed model including a period effect and a continuous time effect within periods. RESULTS: A total of 211 respondents (43.5 %) completed the survey at inclusion. There was a decrease in mean anxiety (from 7.33 to 5.05, p < 0.001), mean depression (from 4.16 to 3.05, p = 0.009), mean stress at work (from 41.2 to 30.2, p = 0.008), and mean stress at home (from 33.0 to 26.0, p = 0.031) at the beginning of each period. The mean anxiety level was higher for administrative staff (+0.53) and lower for paramedics (-0.61, p = 0.047) compared to physicians. The anxiety level increased with the number of day and night shifts (0.13/day, p < 0.001, 0.12/night, p = 0.025) as did stress at work (1.6/day, p < 0.001, 1.1/night, p = 0.007). Reassigned healthcare workers were at higher risk of stress particularly compared to SAMU workers (stress at work: p = 0.015, at home: p = 0.021, in life in general: p = 0.018). CONCLUSION: Although anxiety, depression, and stress decreased over time, anxiety was higher among physicians and administrative staff. Reassignment and working hours were identified as potential risk factors for mental health distress in EDs.

Burden of critically ill patients with influenza in a French catchment population.

Despite the particular focus given to influenza since the 2009 influenza A(H1N1) pandemic, true burden of influenza-associated critical illness remains poorly known. The aim of this study was to identify factors influencing influenza burden imposed on intensive care units (ICUs) in a catchment population during recent influenza seasons. From 2008 to 2013, all adult patients admitted with a laboratory-confirmed influenza infection to one of the ICUs in the catchment area were prospectively included. A total of 201 patients (mean age: 63 ± 16, sex-ratio: 1.1) were included. The influenza-related ICU-bed occupancy rate averaged 4.3% over the five influenza seasons, with the highest mean occupancy rate (16.9%) observed during the 2012 winter. In-hospital mortality for the whole cohort was 26%. Influenza A(H1N1)pdm infections (pdm in the mentioned nomenclature refers to Pandemic Disease Mexico 2009), encountered in 51% of cases, were significantly associated with neither longer length of stay nor higher mortality (ICU and hospital) when compared to infections with other virus subtypes. SOFA score (OR, 1.12; 95% CI, 1.04-1.29) was the only independent factor significantly associated with a prolonged hospitalization. These results highlight both the frequency and the severity of influenza-associated critical illness, leading to a sustained activity in ICUs. Severity of the disease, but not A(H1N1)pdm virus, appears to be a major determinant of ICU burden related to influenza.

Factors Associated with Clostridioides (Clostridium) Difficile Infection and Colonization: Ongoing Prospective Cohort Study in a French University Hospital.

INTRODUCTION: Clostridioides (Clostridium) difficile can be isolated from stool in 3% of healthy adults and in at least 10% of asymptomatic hospitalized patients. C. difficile, the most common cause of hospital-acquired infectious diarrhea in the developed world, has re-emerged in recent years with increasing incidence and severity. In an effort to reduce the spread of the pathogen, published recommendations suggest isolation and contact precautions for patients suffering from C. difficile infection (CDI). However, asymptomatic colonized patients are not targeted by infection control policies, and active surveillance for colonization is not routinely performed. Moreover, given the current changes in the epidemiology of CDI, particularly the emergence of new virulent strains either in the hospital or community settings, there is a need for identification of factors associated with colonization by C. difficile and CDI. Methods and analysis: We are carrying out a prospective, observational, cohort study in Edouard Herriot Hospital, Hospices Civils de Lyon, a 900-bed university hospital in Lyon, France. All consecutive adult patients admitted on selected units are eligible to participate in the study. Stool samples or rectal swabs for C. difficile testing are obtained on admission, every 3-5 days during hospitalization, at the onset of diarrhea (if applicable), and at discharge. Descriptive and logistic regression analyses will be completed to mainly estimate the proportion of asymptomatic colonization at admission, and to evaluate differences between factors associated with colonization and those related to CDI. Ethics: The study is conducted in accordance with the ethical principles of the Declaration of Helsinki, French law, and the Good Clinical Practice guidelines. The study protocol design was approved by the participating units, the ethics committee and the hospital institutional review board (Comité de protection des personnes et Comission Nationale de l'Informatique et des Libertés; N°: 00009118). Dissemination: The results of this study will be disseminated by presenting the findings locally at each participating ward, as well as national and international scientific meetings. Findings will be shared with interested national societies crafting guidelines in CDI.

Evaluation of first-line therapies for the treatment of candidemia in ICU patients: A propensity score analysis.

BACKGROUND: Candidemia is a major cause of mortality in the intensive care unit (ICU). According to the Infectious Diseases Society of America (IDSA), an echinocandin is recommended as initial therapy and fluconazole as an alternative. In a context of echinocandin resistance development, the question arising is whether azoles are a suitable alternative to echinocandins for the treatment of candidemia in critically ill patients. METHODS: A 3-year (2015-2017) retrospective multicentric cohort study was conducted. Adult patients with a diagnosis of candidemia during the ICU stay and treated with echinocandins or azoles were included. Demographic, clinical data, mycological data, and antifungal treatments were collected. Kaplan-Meier survival analysis, univariate analysis, and a multivariate logistic regression analysis using a propensity score with the inverse probability of treatment weighting method were performed. FINDINGS: Seventy-nine patients (n = 79) were analyzed. Treatment success, as well as survival on day 90 (Kaplan-Meier survival analysis, log rank test, p = 0.542), were comparable between patients who received echinocandins (caspofungin (n = 47)) or azoles (fluconazole (n = 29) or voriconazole (n = 3)). A multivariable analysis demonstrated that higher SOFA score on the day of candidemia diagnosis and absence of adequate Candida source control were independently associated with a greater risk of 90-day mortality, whereas azoles treatment was not associated with an excess 90-day mortality. INTERPRETATION: This study confirms that the use of azoles recommended for candidemia, mostly fluconazole, as a first-line therapy is a reasonable alternative to caspofungin for ICU patients in our institution. This needs to be included in local guidelines through antifungal stewardship programs.

Cirrhotic Patients Admitted to the ICU With Septic Shock: Factors Predicting Short and Long-Term Outcome.

Cirrhotic patients with septic shock have a poor prognosis in ICU compared to general population of critically ill patients. Little is known about long-term outcome in these patients. We performed a retrospective analysis of a prospective cohort of cirrhotic patients with septic shock. The aim of this study was to describe both short and long-term outcomes and to evaluate factors predicting mortality. Data from 149 patients were analyzed (mean age: 60 ±â€Š11 years, sex ratio: 2.4). Mortality rate in the ICU was 54% and at 1 year it was 73%. Among factors associated with adverse outcome, independent factors predicting ICU mortality were early need for renal replacement therapy (odds ratios, OR 13.95, 95% confidence interval, CI 3.30; 59.03) and arterial lactate >5 mmol.L (OR 7.27, 95% CI 2.92; 18.10), and early use of mechanical ventilation (OR 3.05, 95% CI 1.08; 8.58). For 1-year mortality, independent prognostic factors were the need for renal replacement therapy during ICU stay (OR 9.60, 95% CI 2.90; 31.82), prothrombin time ≤40% (OR 3.47, 95% CI 1.43; 8.43), and Charlson score (OR 1.36 per point, 95% CI 1.11; 1.67). The results emphasize the poor prognosis of cirrhotic patients with septic shock admitted to the ICU. The need for organ supports appears to be a better predictor of short-term outcome than the underlying hepatic disease. Renal replacement therapy is associated with both short and long-term outcomes.

Pupillary abnormalities in non-selected critically ill patients: an observational study.

BACKGROUND: Repeated pupillary examination is a key element of neurologic surveillance in intensive care units (ICU). However, in non-selected critically ill patients, the clinical interest of monitoring pupillary diameter and light reflex is poorly documented. We aimed to determine the prevalence and the etiologies of pupillary abnormalities (PAs) in this ICU patient population. METHODS: We performed a prospective, observational study in a medical university affiliated ICU over a 6-month period. All patients with at least one pupillary examination were included. PA was defined as areflexia and/or anisocoria present at the time of ICU admission or occurring during the ICU stay. RESULTS: During the study period, we included 297 patients who had 6±9 pupillary examinations per day (totaling 11,360 pupillary assessments). The majority of patients (n=161, 54%) were admitted to the ICU for acute respiratory or cardiovascular failure. A total of 128 PAs were recorded in 109 patients: 78 areflexia alone (61%), 33 anisocoria alone (26%) and 17 (13%) with associated anisocoria and areflexia. The main causes of PAs were related to acute brain ischemia (n=41, 32%) and sedation/analgesia (n=50, 39%). Among the PAs, 59 (46%) were present upon ICU admission. The etiologies of the PAs at admission did not differ from those occurring during ICU stay (P=NS). Interestingly, 9 (7%) PAs were attributed to ipratropium nebulization in patients with chronic obstructive pulmonary disease exacerbation. CONCLUSIONS: The high prevalence of PAs, frequently associated with both brain organic lesions and drug side effects, highlights the clinical interest of pupillary surveillance in non-selected critically ill patients.

SOFA score to assess the severity of the post-cardiac arrest syndrome.

AIM OF THE STUDY: The aim of the study was to assess the prognostic impact of organ failures at ICU admission after out-of-hospital cardiac arrest (CA) according to the SOFA score. METHODS: We performed a retrospective analysis of a prospective cohort of all adult patients admitted to a 15-bed medical ICU in a university-affiliated hospital after an out-of-hospital CA. In addition to demographic and clinical data, initial illness severity was measured using the SOFA score. Outcomes (mortality and neurological prognosis) were also collected at day 28 and one year. RESULTS: A total of 304 patients (age: 66±16 years, male: 55%) were admitted for post-CA management. An initial nonshockable cardiac rhythm was recorded in 274 (90%) cases. At admission, SOFA score averaged 9.8±3.1 for the entire cohort (8.1±3.3 for day 28 survivors versus 10.1±3.1 for non-survivors, p<0.001). At day 1, SOFA remained significantly (p<0.001) higher in nonsurvivors (9.8±3.8) when compared to survivors (6.5±4.1). Death occurred in 269 (88%) and 275 (90%) patients within the 28-day and one-year period, respectively. Neurological outcome at one year was favorable (CPC score 1-2) in 23patients (8%). Multivariate analysis identified the SOFA score at admission as independently associated with mortality at day28 (OR per point of SOFA score 1.17; 95% CI 1.01-1.35; p=0.03). CONCLUSIONS: In the present study, early organ failures, as assessed by the SOFA score at ICU admission, were independently associated with day 28 mortality. SOFA score may help clinicians objectively evaluate the severity of the post-CA syndrome.

Predictors of haemodynamic instability during the changeover of norepinephrine infusion pumps.

BACKGROUND: Changeovers of norepinephrine infusion pumps (CNIPs) frequently lead to haemodynamic instability. The aim of this study was to identify risk factors for haemodynamic instability associated with CNIP, independent of the method used to perform the relay. METHODS: We performed a prospective study, in a university-affiliated intensive care unit. Over a 1-year period, all adult patients who had at least one CNIP were included. CNIPs were automatically performed using smart pumps, in accordance with a standardised protocol. CNIP-induced haemodynamic instability was defined as a variation in mean arterial pressure (MAP) >25 %. A multivariate mixed effects logistic regression was fitted to assess the factors associated with CNIP-induced haemodynamic instability. RESULTS: From the 118 patients included in the study, 764 CNIPs were analysed. Most of the patients were treated with norepinephrine for septic shock of medical origin (n = 83, 70 %). Haemodynamic instability occurred 114 times (15 %) in 63 patients (53 %). Among the risk factors identified by the univariate analysis (age, heart rate, dose of norepinephrine infused, and change in the concentration of the vasoactive drug; p < 0.05), change in the norepinephrine concentration was the only independent risk factor for CNIP-induced haemodynamic instability identified in the multivariate analysis (adjusted OR 11.8, 95 % CI 7.2-19.5, p < 0.001). CONCLUSIONS: Changes in the norepinephrine concentration during CNIPs lead to a high risk of haemodynamic instability, while the clinical severity of patients, as well as the doses of norepinephrine, was not.

Short- and long-term outcomes in onco-hematological patients admitted to the intensive care unit with classic factors of poor prognosis.

Although the overall mortality of patients admitted to intensive care units (ICU) with hematological malignancy has decreased over the years, some groups of patients still have low survival rates. We performed a monocentric retrospective study including all patients with hematological malignancy in a ten-year period, to identify factors related to the outcome for the whole cohort and for patients with allogeneic hematopoietic stem cell transplantation (HSCT), neutropenia, or those requiring invasive mechanical ventilation (IMV). A total of 418 patients with acute leukemia (n=239; 57%), myeloma (n=69; 17%), and lymphoma (n=53; 13%) were studied. Day-28 and 1-year mortality were 49% and 72%, respectively. The type of disease was not associated with outcome. The disease status was independentlty associated with 1-year mortality only. Independent predictors of day-28 mortality were IMV, renal replacement therapy (RRT), and performance status. For allogeneic HSCT recipients (n=116), neutropenic patients (n=124) and patients requiring IMV (n=196), day-28 and 1-year mortality were 52%, 54%, 74% and 81%, 78%, 87%, respectively. Multivariate analysis showed that IMV and RRT for allogeneic HSCT recipients, performance status and IMV for neutropenic patients, and RRT for patients requiring IMV were independently associated with short-term mortality (p<0.05).These results suggest that IMV is the strongest predictor of mortality in hematological patients admitted to ICUs, whereas allogeneic HSCT and neutropenia do not worsen their short-term outcome.

Effect of Cyclosporine in Nonshockable Out-of-Hospital Cardiac Arrest: The CYRUS Randomized Clinical Trial.

IMPORTANCE: Experimental evidence suggests that cyclosporine prevents postcardiac arrest syndrome by attenuating the systemic ischemia reperfusion response. OBJECTIVE: To determine whether early administration of cyclosporine at the time of resuscitation in patients with out-of-hospital cardiac arrest (OHCA) would prevent multiple organ failure. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, single-blind, randomized clinical trial was conducted from June 22, 2010, to March 13, 2013 (Cyclosporine A in Out-of-Hospital Cardiac Arrest Resuscitation [CYRUS]). Sixteen intensive care units in 7 university-affiliated hospitals and 9 general hospitals in France participated. A total of 6758 patients who experienced nonshockable OHCA (ie, asystole or pulseless electrical activity) were assessed for eligibility. Analyses were performed according to the intention-to-treat analysis. INTERVENTIONS: Patients received an intravenous bolus injection of cyclosporine, 2.5 mg/kg, at the onset of advanced cardiovascular life support (cyclosporine group) or no additional intervention (control group). MAIN OUTCOMES AND MEASURES: The primary end point was the Sequential Organ Failure Assessment (SOFA) score, assessed 24 hours after hospital admission, which ranges from 0 to 24 (with higher scores indicating more severe organ failure). Secondary end points included survival at 24 hours, hospital discharge, and favorable neurologic outcome at discharge. RESULTS: Of the 6758 patients screened, 794 were included in intention-to-treat analysis (cyclosporine, 400; control, 394). The median (interquartile range [IQR]) ages were 63.0 (54.0-71.8) years for the cyclosporine group and 66.0 (57.0-74.0) years for the control group. The cohorts included 293 men (73.3%) in the treatment group and 288 men (73.1%) in the control group. At 24 hours after hospital admission, the SOFA score was not significantly different between the cyclosporine (median, 10.0; IQR, 7.0-13.0) and the control (median, 11.0; IQR, 7.0-15.0) groups. Survival was not significantly different between the 98 (24.5%) cyclosporine vs 101 (25.6%) control patients at hospital admission (adjusted odds ratio [aOR], 0.94; 95% CI, 0.66-1.34), at 24 hours for 67 (16.8%) vs 62 (15.7%) patients (aOR, 1.08; 95% CI, 0.71-1.63), and at hospital discharge for 10 (2.5%) vs 5 (1.3%) patients (aOR, 2.00; 95% CI, 0.61-6.52). Favorable neurologic outcome at discharge was comparable between the cyclosporine and control groups: 7 (1.8%) vs 5 (1.3%) patients (aOR, 1.39; 95% CI, 0.39-4.91). CONCLUSION AND RELEVANCE: In patients presenting with nonshockable cardiac rhythm after OHCA, cyclosporine does not prevent early multiple organ failure. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01595958; EudraCT Identifier: 2009-015725-37.

Cost awareness of physicians in intensive care units: a multicentric national study.

PURPOSE: Physicians play an important role in strategies to control health care spending. Being aware of the cost of prescriptions is surely the first step to incorporating cost-consciousness into medical practice. The aim of this study was to evaluate current intensivists' knowledge of the costs of common prescriptions and to identify factors influencing the accuracy of cost estimations. METHODS: Junior and senior physicians in 99 French intensive care units were asked, by questionnaire, to estimate the true hospital costs of 46 selected prescriptions commonly used in critical care practice. RESULTS: With an 83% response rate, 1092 questionnaires were examined, completed by 575 (53%) and 517 (47%) junior and senior intensivists, respectively. Only 315 (29%) of the overall estimates were within 50% of the true cost. Response errors included a 14,756 ± 301 € underestimation, i.e., -58 ± 1% of the total sum (25,595 €). High-cost drugs (>1000 €) were significantly (p < 0.001) the most underestimated prescriptions (-67 ± 1%). Junior grade physicians underestimated more costs than senior physicians (p < 0.001). Using multivariate analysis, junior physicians [odds ratio (OR), 2.1; 95% confidence interval (95% CI), 1.43-3.08; p = 0.0002] and female gender (OR, 1.4; 95% CI, 1.04-1.89; p = 0.02) were both independently associated with incorrect cost estimations. CONCLUSIONS: ICU physicians have a poor awareness of prescriptions costs, especially with regards to high-cost drugs. Considerable emphasis and effort are still required to integrate the cost-containment problem into the daily prescriptions in ICUs.

Long-term outcome of critically ill adult patients with acute epiglottitis.

BACKGROUND: Acute epiglottitis is a potentially life threatening disease, with a growing incidence in the adult population. Its long-term outcome after Intensive Care Unit (ICU) hospitalization has rarely been studied. METHODOLOGY AND PRINCIPAL FINDINGS: Thirty-four adult patients admitted for acute epiglottitis were included in this retrospective multicentric study. The mean age was 44 ± 12 years (sex ratio: 5.8). Sixteen patients (47%) had a history of smoking while 8 (24%) had no previous medical history. The average time of disease progression before ICU was 2.6 ± 3.6 days. The main reasons for hospitalization were continuous monitoring (17 cases, 50%) and acute respiratory distress (10 cases, 29%). Microbiological documentation could be made in 9 cases (26%), with Streptococcus spp. present in 7 cases (21%). Organ failure at ICU admission occurred in 8 cases (24%). Thirteen patients (38%) required respiratory assistance during ICU stay; 9 (26%) required surgery. Two patients (6%) died following hypoxemic cardiac arrest. Five patients (15%) had sequelae at 1 year. Patients requiring respiratory assistance had a longer duration of symptoms and more frequent anti inflammatory use before ICU admission and sequelae at 1 year (p < 0.05 versus non-ventilated patients). After logistic regression analysis, only exposure to anti-inflammatory drugs before admission was independently associated with airway intervention (OR, 4.96; 95% CI, 1.06-23.16). CONCLUSIONS AND SIGNIFICANCE: The profile of the cases consisted of young smoking men with little comorbidity. Streptococcus spp. infection represented the main etiology. Outcome was favorable if early respiratory tract protection could be performed in good conditions. Morbidity and sequelae were greater in patients requiring airway intervention.