Diabetes was the only comorbid condition associated with mortality of invasive pneumococcal infection in ICU patients: a multicenter observational study from the Outcomerea research group.

PURPOSES: Streptococcus 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. METHODS: Multicenter 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. RESULTS: Of 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). CONCLUSIONS: Diabetes 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.

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

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

Ventilator-Associated Events: Prevalence, Outcome, and Relationship With Ventilator-Associated Pneumonia.

OBJECTIVES: Centers for Disease Control and Prevention built up new surveillance paradigms for the patients on mechanical ventilation and the ventilator-associated events, comprising ventilator-associated conditions and infection-related ventilator-associated complications. We assess 1) the current epidemiology of ventilator-associated event, 2) the relationship between ventilator-associated event and ventilator-associated pneumonia, and 3) the impact of ventilator-associated event on antimicrobials consumption and mechanical ventilation duration. DESIGN: Inception cohort study from the longitudinal prospective French multicenter OUTCOMEREA database (1996-2012). PATIENTS: Patients on mechanical ventilation for greater than or equal to 5 consecutive days were classified as to the presence of a ventilator-associated event episode, using slightly modified Centers for Disease Control and Prevention definitions. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Among the 3,028 patients, 2,331 patients (77%) had at least one ventilator-associated condition, and 869 patients (29%) had one infection-related ventilator-associated complication episode. Multiple causes, or the lack of identified cause, were frequent. The leading causes associated with ventilator-associated condition and infection-related ventilator-associated complication were nosocomial infections (27.3% and 43.8%), including ventilator-associated pneumonia (14.5% and 27.6%). Sensitivity and specificity of diagnosing ventilator-associated pneumonia were 0.92 and 0.28 for ventilator-associated condition and 0.67 and 0.75 for infection-related ventilator-associated complication, respectively. A good correlation was observed between ventilator-associated condition and infection-related ventilator-associated complication episodes, and ventilator-associated pneumonia occurrence: R = 0.69 and 0.82 (p < 0.0001). The median number of days alive without antibiotics and mechanical ventilation at day 28 was significantly higher in patients without any ventilator-associated event (p < 0.05). Ventilator-associated condition and infection-related ventilator-associated complication rates were closely correlated with antibiotic use within each ICU: R = 0.987 and 0.99, respectively (p < 0.0001). CONCLUSIONS: Ventilator-associated event is very common in a population at risk and more importantly highly related to antimicrobial consumption and may serve as surrogate quality indicator for improvement programs.

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

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

Safety of intrahospital transport in ventilated critically ill patients: a multicenter cohort study*.

OBJECTIVES: To describe intrahospital transport complications in critically ill patients receiving invasive mechanical ventilation. DESIGN: Prospective multicenter cohort study. SETTING: Twelve French ICUs belonging to the OUTCOMEREA study group. PATIENTS: Patients older than or equal to 18 years old admitted in the ICU and requiring invasive mechanical ventilation between April 2000 and November 2010 were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Six thousand two hundred forty-two patients on invasive mechanical ventilation were identified in the OUTCOMEREA database. The statistical analysis included a description of demographic and clinical characteristics of the cohort, identification of risk factors for intrahospital transport and construction of an intrahospital transport propensity score, and an exposed/unexposed study to compare complication of intrahospital transport (excluding transport to the operating room) after adjustment on the propensity score, length of stay, and confounding factors on the day before intrahospital transport. Three thousand and six intrahospital transports occurred in 1,782 patients (28.6%) (1-17 intrahospital transports/patient). Transported patients had higher admission Simplified Acute Physiology Score II values (median [interquartile range], 51 [39-65] vs 46 [33-62], p < 10) and longer ICU stay lengths (12 [6-23] vs 5 [3-11] d, p < 10). Post-intrahospital transport complications were recorded in 621 patients (37.4%). We matched 1,659 intrahospital transport patients to 3,344 nonintrahospital transport patients according to the intrahospital transport propensity score and previous ICU stay length. After adjustment, intrahospital transport patients were at higher risk for various complications (odds ratio = 1.9; 95% CI, 1.7-2.2; p < 10), including pneumothorax, atelectasis, ventilator-associated pneumonia, hypoglycemia, hyperglycemia, and hypernatremia. Intrahospital transport was associated with a longer ICU length of stay but had no significant impact on mortality. CONCLUSIONS: Intrahospital transport increases the risk of complications in ventilated critically ill patients. Continuous quality improvement programs should include specific procedures to minimize intrahospital transport-related risks.

Initial use of one or two antibiotics for critically ill patients with community-acquired pneumonia: impact on survival and bacterial resistance.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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 (ß-lactam) and either of the two dual-therapy groups (ß-lactam plus macrolide or fluoroquinolone). The rates of nosocomial pneumonia and multidrug-resistant bacteria were not significantly different across these three groups. CONCLUSIONS: 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.

Prognostic consequences of borderline dysnatremia: pay attention to minimal serum sodium change.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Severe hypothermia increases the risk for intensive care unit-acquired infection.

BACKGROUND: Although hypothermia is widely accepted as a risk factor for subsequent infection in surgical patients, it has not been well defined in medical patients. We sought to assess the risk of acquiring intensive care unit (ICU)--acquired infection after hypothermia among medical ICU patients. METHODS: Adults (≥18 years) admitted to French ICUs for at least 2 days between April 2000 and November 2010 were included. Surgical patients were excluded. Patient were classified as having had mild hypothermia (35.0°C-35.9°C), moderate hypothermia (32°C-34.9°C), or severe hypothermia (<32°C), and were followed for the development of pneumonia or bloodstream infection until ICU discharge. RESULTS: A total of 6237 patients were included. Within the first day of admission, 648 (10%) patients had mild hypothermia, 288 (5%) patients had moderate hypothermia, and 45 (1%) patients had severe hypothermia. Among the 5256 patients who did not have any hypothermia at day 1, subsequent hypothermia developed in 868 (17%), of which 673 (13%), 176 (3%), and 19 (<1%) patients had lowest temperatures of 35.0°C-35.9°C, 32.0°C-34.9°C, and <32°C, respectively. During the course of ICU admission, 320 (5%) patients developed ICU-acquired bloodstream infection and 724 (12%) patients developed ICU-acquired pneumonia. After controlling for confounding variables in multivariable analyses, severe hypothermia was found to increase the risk for subsequent ICU-acquired infection, particularly in patients who did not present with severe sepsis or septic shock. CONCLUSIONS: The presence of severe hypothermia is a risk factor for development of ICU-acquired infection in medical patients.

Determinants of temperature abnormalities and influence on outcome of critical illness.

OBJECTIVE: To determine the occurrence and determinants of temperature abnormalities among patients presenting (<24 hrs) to an intensive care unit and assess their effect on mortality outcome. DESIGN: Inception cohort. SETTING: French intensive care units participating in the Outcomerea group. PATIENTS: Adults (≥ 18 yrs) admitted to an intensive care unit between April 2000 and November 2010. Patients undergoing therapeutic hypothermia were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 10,962 patients were included. The median age was 63 yrs (interquartile range, 49-76), 6639 (61%) admissions were in males, and the median admission Simplified Acute Physiology Score II and Sequential Organ Failure Assessment scores were 39 (interquartile range, 27-54) and 5 (interquartile range, 3-8), respectively. Patients were classified as medical in 8,237 (75%), nonscheduled surgical in 1,507 (14%), and scheduled surgical in 1,218 (11%). At presentation, 1,046 (10%) patients had mild hypothermia (35.0-35.9 °C), 541 (5%) had moderate hypothermia (32-35.9 °C), 72 (1%) had severe hypothermia (<32 °C), 2,264 (21%) patients had mild fever (38.3-39.4 °C), and 559 (5%) had high fever (>39.5 °C). Normothermia was present in 6,133 (55%) and mixed fever/hypothermia abnormalities occurred in 347 (3%) patients overall. Medical patients had the highest occurrence of any fever, whereas hypothermia was more common in surgical patients. The overall intensive care unit case-fatality was 1,944 of 10,962 (18%) and 828 of 6,133 (14%) for normothermia, 235 of 1,046 (22%) for mild hypothermia, 205 of 541 (38%) for moderate hypothermia, 43 of 72 (60%) for severe hypothermia, 412 of 2,264 (18%) for mild fever, 117 of 559 (21%) for high fever, and 104 of 347 (30%) for those with mixed temperature abnormalities. After controlling for confounding variables in logistic regression analyses, fever at presentation was not associated with any significantly increased risk for death. However, hypothermia was a significant independent predictor for death in medical patients. CONCLUSIONS: Temperature abnormalities are common among patients presenting to the intensive care unit. Hypothermia is a major, potentially modifiable factor associated with increased risk for death.

Multiple-center evaluation of mortality associated with acute kidney injury in critically ill patients: a competing risks analysis.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: By using a competing risks approach, we confirm in this study that AKI affecting critically ill patients is associated with increased in-hospital mortality.

Mortality associated with timing of admission to and discharge from ICU: a retrospective cohort study.

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.

Association between hypernatraemia acquired in the ICU and mortality: a cohort study.

BACKGROUND: The aim of this study is to describe the prevalence and outcomes of intensive care unit (ICU)-acquired hypernatraemia (IAH). METHODS: A retrospective analysis was performed on a prospectively collected database fed by 12 ICUs. Subjects are unselected patients with ICU stay >48 h. Mild and moderate to severe hypernatraemia were defined as serum sodium >145 and >150 mmol/L, respectively. IAH was hypernatraemia occurring >or=24 h after ICU admission in patients with normal serum sodium at ICU admission. RESULTS: Of the 8441 patients, 301 were excluded because they had hypernatraemia at ICU admission. Of the remaining 8140 patients, 901 (11.1%) experienced mild hypernatraemia, and 344 (4.2%) experienced moderate to severe hypernatraemia. Factors independently associated with IAH were male gender, severity at admission as assessed by the Simplified Acute Physiology Score version II (SAPS II), and organ failure or life-supporting treatment at ICU admission. Unadjusted hospital mortality was 15.2% in patients without hypernatraemia compared to 29.5% in patients with mild IAH and 46.2% in those with moderate to severe IAH (P < 0.0001). When any degree of IAH was handled as a time-dependent variable in a subdistribution hazard model, the subdistribution hazard ratio (SHR) for ICU mortality was 4.26 [95% confidence interval (CI), 3.74-4.84]. After stratification by centre and adjustment for confounders, both mild IAH and moderate to severe IAH were independently associated with mortality [SHR 2.03 (95% CI 1.73-2.39) and 2.67 (95% CI 2.19-3.26), respectively]. CONCLUSION: IAH is frequent and associated with mortality after adjustment on severity at ICU admission.

Predicting the risk of documented ventilator-associated pneumonia for benchmarking: construction and validation of a score.

OBJECTIVES: : To build and validate a ventilator-associated pneumonia risk score for benchmarking. The rate of ventilator-associated pneumonia varies widely with case-mix, a fact that has limited its use for measuring intensive care unit performance. METHODS: : We studied 1856 patients in the OUTCOMEREA database treated at intensive care unit admission by endotracheal intubation followed by mechanical ventilation for >48 hrs; they were allocated randomly to a training data set (n = 1233) or a validation data set (n = 623). Multivariate logistic regression was used. Calibration of the final model was assessed in both data sets, using the Hosmer-Lemeshow chi-square test and receiver operating characteristic curves. MEASUREMENTS AND MAIN RESULTS: : Independent risk factors for ventilator-associated pneumonia were male gender (odds ratio = 1.97, 95% confidence interval = 1.32-2.95); SOFA at intensive care unit admission (<3 [reference value], 3-4 [2.57, 1.39-4.77], 5-8 [7.37, 4.24-12.81], >8 [5.81 (3.2-10.52)], no use within 48 hrs after intensive care unit admission of parenteral nutrition (2.29, 1.52-3.45), no broad-spectrum antimicrobials (2.11, 1.46-3.06); and mechanical ventilation duration (<5 days (); 5-7 days (17.55, 4.01-76.85); 7-15 days (53.01, 12.74-220.56); >15 days (225.6, 54.3-936.7). Tests in the training set showed good calibration and good discrimination (area under the curve-receiver operating characteristic curve = 0.881), and both criteria remained good in the validation set (area under the curve-receiver operating characteristic curve = 0.848) and good calibration (Hosmer-Lemeshow chi-square = 9.98, p = .5). Observed ventilator-associated pneumonia rates varied across intensive care units from 9.7 to 26.1 of 1000 mechanical ventilation days but the ratio of observed over theoretical ventilator-associated pneumonia rates was >1 in only two intensive care units. CONCLUSIONS: : The ventilator-associated pneumonia rate may be useful for benchmarking provided the ratio of observed over theoretical rates is used. External validation of our prediction score is needed.

Model for predicting short-term mortality of severe sepsis.

INTRODUCTION: To establish a prognostic model for predicting 14-day mortality in ICU patients with severe sepsis overall and according to place of infection acquisition and to sepsis episode number. METHODS: In this prospective multicentre observational study on a multicentre database (OUTCOMEREA) including data from 12 ICUs, 2268 patients with 2737 episodes of severe sepsis were randomly divided into a training cohort (n = 1458) and a validation cohort (n = 810). Up to four consecutive severe sepsis episodes per patient occurring within the first 28 ICU days were included. We developed a prognostic model for predicting death within 14 days after each episode, based on patient data available at sepsis onset. RESULTS: Independent predictors of death were logistic organ dysfunction (odds ratio (OR), 1.22 per point, P < 10-4), septic shock (OR, 1.40; P = 0.01), rank of severe sepsis episode (1 reference, 2: OR, 1.26; P = 0.10 >or= 3: OR, 2.64; P < 10-3), multiple sources of infection (OR; 1.45, P = 0.03), simplified acute physiology score II (OR, 1.02 per point; P < 10-4), McCabe score ([greater than or equal to]2) (OR, 1.96; P < 10-4), and number of chronic co-morbidities (1: OR, 1.75; P < 10-3, >or= 2: OR, 2.24, P < 10-3). Validity of the model was good in whole cohorts (AUC-ROC, 0.76; 95%CI, 0.74 to 0.79; and HL Chi-square: 15.3 (P = 0.06) for all episodes pooled). CONCLUSIONS: In ICU patients, a prognostic model based on a few easily obtained variables is effective in predicting death within 14 days after the first to fourth episode of severe sepsis complicating community-, hospital-, or ICU-acquired infection.

Impact of adverse events on outcomes in intensive care unit patients.

OBJECTIVE: To examine the association between predefined adverse events (AE) (including nosocomial infections) and intensive care unit (ICU) mortality, controlling for multiple adverse events in the same patient and confounding variables. DESIGN: Prospective observational cohort study of the French OUTCOMEREA multicenter database. SETTING: Twelve medical or surgical ICUs. PATIENTS: Unselected patients hospitalized for > or = 48 hrs enrolled between 1997 and 2003. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 3,611 patients included, 1415 (39.2%) experienced one or more AEs and 821 (22.7%) had two or more AEs. Mean number of AEs per patient was 2.8 (range, 1-26). Six AEs were associated with death: primary or catheter-related bloodstream infection (BSI) (odds ratio [OR], 2.92; 95% confidence interval [CI], 1.6-5.32), BSI from other sources (OR, 5.7; 95% CI, 2.66-12.05), nonbacteremic pneumonia (OR, 1.69; 95% CI, 1.17-2.44), deep and organ/space surgical site infection without BSI (OR, 3; 95% CI, 1.3-6.8), pneumothorax (OR, 3.1; 95% CI, 1.5-6.3), and gastrointestinal bleeding (OR, 2.6; 95% CI, 1.4-4.9). The results were not changed when the analysis was confined to patients with mechanical ventilation on day 1, intermediate severity of illness (Simplified Acute Physiology Score II between 35 and 55), no treatment-limitation decisions, or no cardiac arrest in the ICU. CONCLUSIONS: AEs were common and often occurred in combination in individual patients. Several AEs independently contributed to death. Creating a safe ICU environment is a challenging task that deserves careful attention from ICU physicians.

Influence of gender on the outcome of severe sepsis: a reappraisal.

BACKGROUND: The influence of gender on survival of patients with severe sepsis is unclear. Earlier studies suggested better survival in women, possibly related to the sex-steroid profile. METHODS: To investigate whether mortality from severe sepsis was higher in men than in women and whether the difference varied with menopausal status, we studied 1,692 patients with severe sepsis included in the OutcomeRea database over an 8-year period. We conducted a nested case-control study, accurately matching men and women on three criteria: a death propensity score, age, and center. Subgroup analyses were performed on individuals 50 years old (men vs postmenopausal women). RESULTS: We matched 1,000 men to 608 women with severe sepsis before and after adjustment for confounding factors (ie, chronic respiratory failure; metastatic cancer; immunocompromised status; emergency surgery, acute respiratory failure, and shock at admission; urinary tract infection; and type of microorganism). Overall hospital mortality was significantly lower in women (adjusted odds ratio [OR], 0.75; 95% confidence interval [CI], 0.57 to 0.97; p = 0.02). In the group > 50 years old (481 women, 778 men), hospital mortality was significantly lower in women (OR, 0.69; 95% CI, 0.52 to 0.93; p = 0.014). Hospital mortality was not significantly different between men and women in the younger group (127 women, 222 men) [OR, 1.01; 95% CI, 0.52 to 1.97; p = 0.98]. Level of care, as assessed using the nine equivalents of nursing manpower use score, was identical in men and women. CONCLUSIONS: Among individuals > 50 years old with severe sepsis, women have a lower risk of hospital mortality than men.

Does catheter-associated urinary tract infection increase mortality in critically ill patients?

OBJECTIVE: To produce an accurate estimate of the association between catheter-associated urinary tract infection (UTI) and intensive care unit (ICU) and hospital mortality, controlling for major confounding factors. DESIGN: Nested case-control study in a multicenter cohort (the OutcomeRea database). SETTING: Twelve French medical or surgical ICUs. METHODS: All patients admitted between January 1997 and August 2005 who required the insertion of an indwelling urinary catheter. Patients who developed catheter-associated UTI (ie, case patients) were matched to control patients on the basis of the following criteria: sex, age (+/- 10 years), SAPS (Simplified Acute Physiology Score) II score (+/- 10 points), duration of urinary tract catheterization, and presence or absence of diabetes mellitus. The association of catheter-associated UTI with ICU and hospital mortality was assessed by use of conditional logistic regression. RESULTS: Of the 3,281 patients who had an indwelling urinary catheter, 298 (9%) developed at least 1 episode of catheter-associated UTI. The incidence density of catheter-associated UTI was 12.9 infections per 1,000 catheterization-days. Crude ICU mortality rates were higher among patients with catheter-associated UTI, compared with those without catheter-associated UTI (32% vs 25%, P=.02); the same was true for crude hospital mortality rates (43% vs 30%, P<.01). After matching and adjustment, catheter-associated UTI was no longer associated with increased mortality (ICU mortality: odds ratio [OR], 0.846 [95% confidence interval {CI}, 0.659-1.086]; P=.19 and hospital mortality: OR, 0.949 [95% CI, 0.763-1.181]; P=.64). CONCLUSION: After carefully controlling for confounding factors, catheter-associated UTI was not found to be associated with excess mortality among our population of critically ill patients in either the ICU or the hospital.

Potentially modifiable factors contributing to sepsis-associated encephalopathy.

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.

Respective impact of implementation of prevention strategies, colonization with multiresistant bacteria and antimicrobial use on the risk of early- and late-onset VAP: An analysis of the OUTCOMEREA network.

RATIONALE: The impact of prevention strategies and risk factors for early-onset (EOP) versus late-onset (LOP) ventilator-associated pneumonia (VAP) are still debated. OBJECTIVES: To evaluate, in a multicenter cohort, the risk factors for EOP and LOP, as the evolution of prevention strategies. METHODS: 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. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSION: VAP risk factors are mostly different according to the pneumonia time of onset, which should lead to differentiated prevention strategies.

Excess risk of death from intensive care unit-acquired nosocomial bloodstream infections: a reappraisal.

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 > or = 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.