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Purpose Identifying modifiable factors for sepsis-associated encephalopathy may help improve patient care and outcomes. Methods We conducted a retrospective analysis of a prospective multicenter database. Sepsis-associated encephalopathy (SAE) was defined by a score on the Glasgow coma scale (GCS) <15 or when features of delirium were noted. Potentially modifiable risk factors for SAE at ICU admission and its impact on mortality were investigated using multivariate logistic regression analysis and Cox proportional hazard modeling, respectively. Results We included 2513 patients with sepsis at ICU admission, of whom 1341 (53%) had sepsis-associated encephalopathy. After adjusting for baseline characteristics, site of infection, and type of admission, the following factors remained independently associated with sepsis-associated encephalopathy: acute renal failure [adjusted odds ratio (aOR) = 1.41, 95% confidence interval (CI) 1.19–1.67], hypoglycemia <3 mmol/l (aOR = 2.66, 95% CI 1.27–5.59), hyperglycemia >10 mmol/l (aOR = 1.37, 95% CI 1.09–1.72), hypercapnia >45 mmHg (aOR = 1.91, 95% CI 1.53–2.38), hypernatremia >145 mmol/l (aOR = 2.30, 95% CI 1.48–3.57), and S. aureus (aOR = 1.54, 95% CI 1.05–2.25). Sepsis-associated encephalopathy was associated with higher mortality, higher use of ICU resources, and longer hospital stay. After adjusting for age, comorbidities, year of admission, and non-neurological SOFA score, even mild alteration of mental status (i.e., a score on the GCS of 13–14) remained independently associated with mortality (adjusted hazard ratio = 1.38, 95% CI 1.09–1.76). Conclusions Acute renal failure and common metabolic disturbances represent potentially modifiable factors contributing to sepsis-associated encephalopathy. However, a true causal relationship has yet to be demonstrated. Our study confirms the prognostic significance of mild alteration of mental status in patients with sepsis.

Purpose Noninvasive ventilation (NIV) had proven benefits in clinical trials that included selected patients admitted to highly skilled centers. Whether these benefits apply to every patient and in everyday practice deserves appraisal. The aim of the study was to assess the use and outcomes of NIV over the last 15 years. Methods Multicenter database study of critically ill patients who required ventilatory support for acute respiratory failure between 1997 and 2011. The impact of first-line NIV on 60-day mortality was evaluated using a marginal structural model. Follow-up was censored on day 60. Results Of 3,163 patients, 1,232 (39 %) received NIV. Over the study period, first-line NIV increased from 29 to 42 %, and NIV success rates increased from 69 to 84 %. NIV decreased 60-day mortality [adjusted hazard ratio (aHR), 0.75; 95 % confidence interval (95 % CI), 0.68–0.83; P  < 0.0001]. This protective effect was observed in patients with acute-on-chronic respiratory failure (aHR, 0.71; 95 % CI, 0.57–0.90; P  = 0.004), but not in patients with cardiogenic pulmonary edema (aHR, 0.85; 95 % CI, 0.70–1.03; P  = 0.10) or in patients with hypoxemic ARF, either immunocompetent (aHR, 1.18; 95 % CI, 0.87–1.59; P  = 0.30) or immunocompromised (aHR, 0.89; 95 % CI, 0.70–1.13; P  = 0.35). NIV failure was an independent time-dependent risk factor for mortality (aHR, 4.2; 95 % CI, 2.8–6.2; P  < 0.0001). Conclusions The use of NIV increased steadily over the study period. First-line NIV was associated with better 60-day survival and fewer ICU-acquired infections compared to first-line intubation. Survival benefits from NIV occurred only in patients with acute-on-chronic respiratory failure and immunocompromised patients.

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.

The impact of prevention strategies and risk factors for early-onset (EOP) versus late-onset (LOP) ventilator-associated pneumonia (VAP) are still debated. To evaluate, in a multicenter cohort, the risk factors for EOP and LOP, as the evolution of prevention strategies. 7,784 patients with mechanical ventilation (MV) for at least 48 hours were selected into the multicenter prospective OUTCOMEREA database (1997-2016). VAP occurring between the 3rd and 6th day of MV defined EOP, while those occurring after defined LOPs. We used a Fine and Gray subdistribution model to take the successful extubation into account as a competing event. Overall, 1,234 included patients developed VAP (EOP: 445 (36%); LOP: 789 (64%)). Male gender was a risk factor for both EOP and LOP. Factors specifically associated with EOP were admission for respiratory distress, previous colonization with multidrug-resistant Pseudomonas aeruginosa, chest tube and enteral feeding within the first 2 days of MV. Antimicrobials administrated within the first 2 days of MV were all protective of EOP. ICU admission for COPD exacerbation or pneumonia were early risk factors for LOP, while imidazole and vancomycin use within the first 2 days of MV were protective factors. Late risk factors (between the 3rd and the 6th day of MV) were the intra-hospital transport, PAO2-FIO2<200 mmHg, vasopressor use, and known colonization with methicillin-resistant Staphylococcus aureus. Among the antimicrobials administered between the 3rd and the 6th day, fluoroquinolones were the solely protective one.Contrarily to LOP, the risk of EOP decreased across the study time periods, concomitantly with an increase in the compliance with bundle of prevention measures. VAP risk factors are mostly different according to the pneumonia time of onset, which should lead to differentiated prevention strategies.

Background. Overall rates of bloodstream infection (BSI) are often used as quality indicators in intensive care units (ICUs). We investigated whether ICU-acquired BSI increased mortality (by ⩾10%) after adjustment for severity of infection at ICU admission and during the pre-BSI stay. Methods. We conducted a matched, risk-adjusted (1 : n), exposed-unexposed study of patients with stays longer than 72 h in 12 ICUs randomly selected from the Outcomerea database. Results. Patients with BSI after the third ICU day (exposed group) were matched on the basis of risk-exposure time and mortality predicted at admission using the Three-Day Recalibrated ICU Outcome (TRIO) score to patients without BSI (unexposed group). Severity was assessed daily using the Logistic Organ Dysfunction (LOD) score. of 3247 patients with ICU stays of >3 days, 232 experienced BSI by day 30 (incidence, 6.8 cases per 100 admissions); among them, 226 patients were matched to 1023 unexposed patients. Crude hospital mortality was 61.5% among exposed and 36.7% among unexposed patients (P < .0001). Attributable mortality was 24.8%. The only variable associated with both BSI and hospital mortality was the LOD score determined 4 days before onset of BSI (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.03–1.16; P = .0025). The adjusted OR for hospital mortality among exposed patients (OR, 3.20; 95% CI, 2.30–4.43) decreased when the LOD score determined 4 days before onset of BSI was taken into account (OR, 3.02; 95% CI, 2.17–4.22; P < .0001). The estimated risk of death from BSI varied considerably according to the source and resistance of organisms, time to onset, and appropriateness of treatment. Conclusions. When adjusted for risk-exposure time and severity at admission and during the ICU stay, BSI was associated with a 3-fold increase in mortality, but considerable variation occurred across BSI subgroups. Focusing on BSI subgroups may be valuable for assessing quality of care in ICUs.

Background.Excess mortality associated with methicillin resistance in patients with Staphylococcus aureus ventilator-associated pneumonia (SA-VAP), taking into account such confounders as treatment adequacy and time in the intensive care unit (ICU), have not been adequately estimated. Methods.One hundred thirty-four episodes of SA-VAP entered in the Outcomerea database were studied. Patients from whom methicillin-resistant S. aureus (MRSA) was recovered were compared with those from whom methicillin-susceptible S. aureus (MSSA) was recovered, stratified for duration of stay in the ICU at the time of VAP diagnosis and adjusted for confounders (severity at admission, characteristics at VAP diagnosis, and treatment adequacy). Results.Treatment was adequate within 24 h after VAP diagnosis for 86% of the 65 MSSA-infected patients and 77% of the 69 MRSA-infected patients (P = .2). Polymicrobial VAP was more commonly associated with MSSA than with MRSA (49.2% vs. 25.7%; P = .01). MRSA infection was associated with a lower prevalence of coma at hospital admission and a higher rate of use of central venous lines and fluoroquinolones during the first 48 h of the ICU stay. The rates of shock, recurrence, and superinfection were similar in both groups. The crude hospital mortality rate was higher for MRSA-infected patients than for MSSA-infected patients (59.4% vs. 40%; P = .024). This difference disappeared after controlling for time in the ICU before VAP and parameters imbalanced at ICU admission (odds ratio [OR], 1.23; 95% confidence interval [CI], 0.49–3.12; P = .7) and remained unchanged after further adjustments for initial treatment adequacy and polymicrobial VAP (OR, 0.98; 95% CI, 0.36–2.66). Conclusions.Differences in patient characteristics, initial ICU treatment, and time in the ICU confounded estimates of excess death due to MRSA VAP. After careful adjustment, methicillin resistance did not affect ICU or hospital mortality rates.

Background 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. Methods Adults (≥18 years) admitted to French ICUs participating in Outcomerea between January 2006 and November 2010 were included. Results 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. Conclusions 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.

Purpose Methods for estimating the excess mortality attributable to ventilator-associated pneumonia (VAP) should handle VAP as a time-dependent covariate, since the probability of experiencing VAP increases with the time on mechanical ventilation. VAP-attributable mortality (VAP-AM) varies with definitions, case-mix, causative microorganisms, and treatment adequacy. Our objectives here were to compare VAP-AM estimates obtained using a traditional cohort analysis, a multistate progressive disability model, and a matched-cohort analysis; and to compare VAP-AM estimates according to VAP characteristics. Methods We used data from 2,873 mechanically ventilated patients in the Outcomerea ® database. Among these patients from 12 intensive care units, 434 (15.1%) experienced VAP; of the remaining patients, 1,969 (68.5%) were discharged alive and 470 (16.4%) died. With the multistate model, VAP-AM was 8.1% (95% confidence interval [95%CI], 3.1–13.1%) for 120 days’ complete observation, compared to 10.4% (5.6–24.5%) using a matched-cohort approach (2,769 patients) with matching on mechanical ventilation duration followed by conditional logistic regression. VAP-AM was higher in surgical patients and patients with intermediate (but not high) Simplified Acute Physiologic Score II values at ICU admission. VAP-AM was significantly influenced by time to VAP but not by resistance of causative microorganisms. Higher Logistic Organ Dysfunction score at VAP onset dramatically increased VAP-AM (to 31.9% in patients with scores above 7). Conclusion A multistate model that appropriately handled VAP as a time-dependent event produced lower VAP-AM values than conditional logistic regression. VAP-AM varied widely with case-mix. Disease severity at VAP onset markedly influenced VAP-AM; this may contribute to the variability of previous estimates.

Purpose To assess the prevalence of decisions to forgo life-sustaining treatment (DFLST), the patients characteristics, and to estimate the impact of DFLST stages on mortality. Methods Observational study of a prospective database between 2005 and 2012 from 13 ICUs. DFLST were defined as follows: no escalation of treatment (stage 1), not to start or escalate treatment even if such treatment is considered in the future; withholding (stage 2), not to start or escalate necessary treatment; withdrawal (stage 3), to stop necessary treatment. The impact of daily DFLST stage on day-30 hospital mortality was tested with a discrete-time Cox’s model and adjusted for admission severity and daily SOFA score. Results Of 10,080 patients, 1290 (13 %) made DFLST. The highest DFLST stage during the ICU stay was no escalation of treatment in 339 (26 %) patients, withholding in 502 (39 %) patients, and withdrawal in 449 (35 %) patients. Older patients, patients with at least one chronic disease, and patients with greater ICU severity were significantly more numerous in the DFLST group. Day-30 mortality was 13 % for non-DFLST patients, 35 % for no escalation of treatment, 75 % for withholding, 93 % for withdrawal. After adjustment, an increase in day-30 mortality was associated with withholding and withdrawal (hazard ratio 95 % CI 5.93 [4.95–7.12] and 20.05 [15.58–25.79], P  < 0.0001), but not with no escalation of treatment (HR 1.14 [0.91–1.44], P  = 0.25). Conclusions DFLST were made in 13 % of ICU patients. Withholding, withdrawal, older age, more comorbidities, and higher severity of illness were associated with higher mortality. No escalation of treatment was not associated with increased mortality.

PurposesStreptococcus pneumoniae is a leading pathogen of severe community, hospital or nursing facility infections. We sought to describe characteristics of invasive pneumococcal infection (IPI) and pneumonia (due to the high mortality of intensive care-associated pneumonia) and to report outcomes according to various types of comorbidity.MethodsMulticenter observational cohort study on the prospective Outcomerea database, including adult patients, with a hospital stay < 48 h before ICU admission and a documented IPI within the first 72 h of ICU admission. Comorbid conditions were defined according to the Knaus and Charlson classification.ResultsOf the 20,235 patients, 5310 (26.4%) had an invasive infection, including 560/5,310 (10.6%) who had an IPI. The ICU 28-day mortality was 109/560 (19.8%). Four factors were independently associated with mortality: SOFA day 1–2: [hazard ratio (HR) 1.21; 95% confidence interval (95% CI) 1.15–1.27, p < 0.001]; maximum lactate level day 1–2: (HR 1.07, 95% CI 1.02–1.12, p = 0.006); diabetes mellitus: (HR 1.91, 95% CI 1.23–3.03, p = 0.006) and appropriate antibiotics (HR 0.28, 95% CI 0.15–0.50, p < 0.001). Comparable results were obtained when other comorbid conditions were forced into the model. Diabetes impact was more pronounced in case of micro- or macro-angiopathy (HR 4.17, 95%CI 1.68–10.54, p = 0.003), in patients ≥ 65 years old (HR 2.59, 95% CI 1.56–4.28, < 0.001) and in those with body mass index (BMI) < 25 kg/m2 (HR 2.11, 95% CI 1.10–4.06, p = 0.025).ConclusionsDiabetes mellitus was the only comorbid condition which independently influenced mortality in patients with IPI. Its impact was more pronounced in patients with complications, aged ≥ 65 years and with BMI < 25 kg/m2.