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

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

ICU physician-based determinants of life-sustaining therapy during nights and weekends: French multicenter study from the Outcomerea Research Group.

OBJECTIVE: Patient- and organization-related factors are the most common influences affecting the ICU decision-making process. Few studies have investigated ICU physician-related factors and life-sustaining treatment use during nights and weekends, when staffing ratios are low. Here, we described patients admitted during nights/weekends and looked for physician-related determinants of life-sustaining treatment use in these patients after adjustment for patient- and center-related factors. DESIGN: Multicenter observational cohort study of admission procedures during nights/weekends shifts. SUBJECTS: ICU physicians working nights/weekends in 6 French ICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient characteristics and intensity of care were extracted from the prospective Outcomerea database. Physician characteristics were age, gender, religion and religiosity, ICU experience, specialty, being a permanent ICU staff member, degree in ethics, and degree in intensive care. We used hierarchical mixed models to adjust on center, physician random effects, and admission patient characteristics. Of 156 physicians contacted, 119 (77%) participated. Patients admitted during nights/weekends were younger and had fewer comorbidities and lower treatment intensity during the shift. ICU physicians who are younger than 35 years used more renal replacement therapy (odds ratio, 1.04; 95% CI, 1-1.07; p = 0.04), invasive mechanical ventilation (odds ratio, 1.09; 95% CI, 1.1-1.19; p = 0.04), and vasopressors (odds ratio, 1.16; 95% CI, 1.09-1.23; p < 0.0001). Internal or emergency medicine as the primary specialty was associated with invasive mechanical ventilation (odds ratio, 1.14; 95% CI, 1.04-1.24; p = 0.004) and vasopressor use (odds ratio, 1.09; 95% CI, 1.02-1.17; p = 0.01). Noninvasive ventilation was used less often by physicians with more than 10 years of night/weekend shifts and more often by those with religious beliefs (odds ratio, 1.05; 95% CI, 1.01-1.08; p = 0.008). CONCLUSIONS: Patients admitted during nights/weekends were younger and had fewer comorbidities. Age, specialty, ICU experience, and religious beliefs of the physicians were significantly associated life-sustaining treatments used.

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.

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.

Incidence and outcome of contrast-associated acute kidney injury in a mixed medical-surgical ICU population: a retrospective study.

BACKGROUND: Contrast-enhanced radiographic examinations carry the risk of contrast-associated acute kidney injury (CA-AKI). While CA-AKI is a well-known complication outside the intensive care unit (ICU) setting, data on CA-AKI in ICU patients are scarce. Our aim was to assess the incidence and short-term outcome of CA-AKI in a mixed medical-surgical ICU population. METHODS: We conducted a single-center retrospective analysis between September 2006 and December 2008 on adult patients who underwent a contrast-enhanced computed tomography for urgent diagnostic purposes. CA-AKI was defined as either a relative increment in serum creatinine of ≥ 25% or an absolute increment in serum creatinine of ≥ 0.3 mg/dL within 48 hrs after contrast administration. ICU mortality rates of patients with and without CA-AKI were compared in univariate and multivariate analyses. The need for renal replacement therapy (RRT) was also recorded. RESULTS: CA-AKI occurred in 24/143 (16.8%) patients. Coexisting risk factors for kidney injury, such as sepsis, nephrotoxic drugs and hemodynamic failure were commonly observed in patients who developed CA-AKI. ICU mortality was significantly higher in patients with than in those without CA-AKI (50% vs 21%, p = 0.004). In multivariate logistic regression, CA-AKI remained associated with ICU mortality (odds ratio: 3.48, 95% confidence interval: 1.10-11.46, p = 0.04). RRT was required in 7 (29.2%) patients with CA-AKI. CONCLUSIONS: In our cohort, CA-AKI was a frequent complication. It was associated with a poor short-term outcome and seemed to occur mainly when multiple risk factors for kidney injury were present. Administration of ICM should be considered as a potential high-risk procedure and not as a routine innocuous practice in ICU patients.

Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock: the CRISTAL randomized trial.

IMPORTANCE: Evidence supporting the choice of intravenous colloid vs crystalloid solutions for management of hypovolemic shock remains unclear. OBJECTIVE: To test whether use of colloids compared with crystalloids for fluid resuscitation alters mortality in patients admitted to the intensive care unit (ICU) with hypovolemic shock. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized clinical trial stratified by case mix (sepsis, trauma, or hypovolemic shock without sepsis or trauma). Therapy in the Colloids Versus Crystalloids for the Resuscitation of the Critically Ill (CRISTAL) trial was open label but outcome assessment was blinded to treatment assignment. Recruitment began in February 2003 and ended in August 2012 of 2857 sequential ICU patients treated at 57 ICUs in France, Belgium, North Africa, and Canada; follow-up ended in November 2012. INTERVENTIONS: Colloids (n = 1414; gelatins, dextrans, hydroxyethyl starches, or 4% or 20% of albumin) or crystalloids (n = 1443; isotonic or hypertonic saline or Ringer lactate solution) for all fluid interventions other than fluid maintenance throughout the ICU stay. MAIN OUTCOMES AND MEASURES: The primary outcome was death within 28 days. Secondary outcomes included 90-day mortality; and days alive and not receiving renal replacement therapy, mechanical ventilation, or vasopressor therapy. RESULTS: Within 28 days, there were 359 deaths (25.4%) in colloids group vs 390 deaths (27.0%) in crystalloids group (relative risk [RR], 0.96 [95% CI, 0.88 to 1.04]; P = .26). Within 90 days, there were 434 deaths (30.7%) in colloids group vs 493 deaths (34.2%) in crystalloids group (RR, 0.92 [95% CI, 0.86 to 0.99]; P = .03). Renal replacement therapy was used in 156 (11.0%) in colloids group vs 181 (12.5%) in crystalloids group (RR, 0.93 [95% CI, 0.83 to 1.03]; P = .19). There were more days alive without mechanical ventilation in the colloids group vs the crystalloids group by 7 days (mean: 2.1 vs 1.8 days, respectively; mean difference, 0.30 [95% CI, 0.09 to 0.48] days; P = .01) and by 28 days (mean: 14.6 vs 13.5 days; mean difference, 1.10 [95% CI, 0.14 to 2.06] days; P = .01) and alive without vasopressor therapy by 7 days (mean: 5.0 vs 4.7 days; mean difference, 0.30 [95% CI, -0.03 to 0.50] days; P = .04) and by 28 days (mean: 16.2 vs 15.2 days; mean difference, 1.04 [95% CI, -0.04 to 2.10] days; P = .03). CONCLUSIONS AND RELEVANCE: Among ICU patients with hypovolemia, the use of colloids vs crystalloids did not result in a significant difference in 28-day mortality. Although 90-day mortality was lower among patients receiving colloids, this finding should be considered exploratory and requires further study before reaching conclusions about efficacy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00318942.

Efficacy of renal replacement therapy in critically ill patients: a propensity analysis.

INTRODUCTION: Although renal replacement therapy (RRT) is a common procedure in critically ill patients with acute kidney injury (AKI), its efficacy remains uncertain. Patients who receive RRT usually have higher mortality rates than those who do not. However, many differences exist in severity patterns between patients with and those without RRT and available results are further confounded by treatment selection bias since no consensus on indications for RRT has been reached so far. Our aim was to account for these biases to accurately assess RRT efficacy, with special attention to RRT timing. METHODS: We performed a propensity analysis using data of the French longitudinal prospective multicenter Outcomerea database. Two propensity scores for RRT were built to match patients who received RRT to controls who did not despite having a close probability of receiving the procedure. AKI was defined according to RIFLE criteria. The association between RRT and hospital mortality was examined through multivariate conditional logistic regression analyses to control for residual confounding. Sensitivity analyses were conducted to examine the impact of RRT timing. RESULTS: Among the 2846 study patients, 545 (19%) received RRT. Crude mortality rates were higher in patients with than in those without RRT (38% vs 17.5%, P < 0.001). After matching and adjustment, RRT was not associated with a reduced hospital mortality. The two propensity models yielded concordant results. CONCLUSIONS: In our study population, RRT failed to reduce hospital mortality. This result emphasizes the need for randomized studies comparing RRT to conservative management in selected ICU patients, with special focus on RRT timing.

Postsurgical meningitis due to multiresistant Acinetobacter baumannii successfully treated with high doses of ampicillin/sulbactam combined with rifampicin and fosfomycin.

We report a case of postsurgical meningitis caused by multiresistant Acinetobacter baumannii successfully treated with high doses of ampicillin/sulbactam combined with rifampicin and fosfomycin.

Attributable mortality of ventilator-associated pneumonia: a reappraisal using causal analysis.

RATIONALE: Measuring the attributable mortality of ventilator-associated pneumonia (VAP) is challenging and prone to different forms of bias. Studies addressing this issue have produced variable and controversial results. OBJECTIVES: We estimate the attributable mortality of VAP in a large multicenter cohort using statistical methods from the field of causal inference. METHODS: Patients (n = 4,479) from the longitudinal prospective (1997-2008) French multicenter Outcomerea database were included if they stayed in the intensive care unit (ICU) for at least 2 days and received mechanical ventilation (MV) within 48 hours after ICU admission. A competing risk survival analysis, treating ICU discharge as a competing risk for ICU mortality, was conducted using a marginal structural modeling approach to adjust for time-varying confounding by disease severity. MEASUREMENTS AND MAIN RESULTS: Six hundred eighty-five (15.3%) patients acquired at least one episode of VAP. We estimated that 4.4% (95% confidence interval, 1.6-7.0%) of the deaths in the ICU on Day 30 and 5.9% (95% confidence interval, 2.5-9.1%) on Day 60 are attributable to VAP. With an observed ICU mortality of 23.3% on Day 30 and 25.6% on Day 60, this corresponds to an ICU mortality attributable to VAP of about 1% on Day 30 and 1.5% on Day 60. CONCLUSIONS: Our study on the attributable mortality of VAP is the first that simultaneously accounts for the time of acquiring VAP, informative loss to follow-up after ICU discharge, and the existence of complex feedback relations between VAP and the evolution of disease severity. In contrast to the majority of previous reports, we detected a relatively limited attributable ICU mortality of VAP.

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.

Early prediction of Candida glabrata fungemia in nonneutropenic critically ill patients.

OBJECTIVE: Candida species represent the fourth cause of nosocomial bloodstream infections worldwide. Because Candida glabrata has become the second most frequently identified yeast and because the rate of fluconazole-resistant C. glabrata strains reaches 10% to 15%, initial antifungal therapy based on fluconazole in nonneutropenic hemodynamically stable patients, as recommended by current guidelines, may be an ineffective option. Our aim was to determine easy-to-identify risk factors for C. glabrata fungemia likely to guide and improve initial antifungal therapy. DESIGN: Prospective multicenter cohort study. SETTING: Five French intensive care units. PATIENTS: Consecutive nonneutropenic patients without known Candida colonization who had blood culture-confirmed fungemia over a 4-yr period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 8206 patients were screened. One hundred fifty-four patients with blood culture-confirmed fungemia constituted the cohort, of whom 48 had C. glabrata fungemia and 106 had nonglabrata fungemia. Patients' baseline characteristics and in-intensive care unit events potentially related to C. glabrata fungemia were systematically recorded. Compared with patients with nonglabrata fungemia, patients with C. glabrata fungemia were older and more severely ill, had received more antibiotics, and were more likely to have undergone surgery. The stepwise logistic regression analysis identified six independent risk factors for C. glabrata fungemia: age >60 yrs, recent abdominal surgery, interval from intensive care unit admission to first positive blood culture

Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial.

CONTEXT: Corticosteroid therapy induces potentially detrimental hyperglycemia in septic shock. In addition, the benefit of adding fludrocortisone in this setting is unclear. OBJECTIVES: To test the efficacy of intensive insulin therapy in patients whose septic shock was treated with hydrocortisone and to assess, as a secondary objective, the benefit of fludrocortisone. DESIGN, SETTING, AND PATIENTS: A multicenter, 2 x 2 factorial, randomized trial, involving 509 adults with septic shock who presented with multiple organ dysfunction, as defined by a Sequential Organ Failure Assessment score of 8 or more, and who had received hydrocortisone treatment was conducted from January 2006 to January 2009 in 11 intensive care units in France. INTERVENTIONS: Patients were randomly assigned to 1 of 4 groups: continuous intravenous insulin infusion with hydrocortisone alone, continuous intravenous insulin infusion with hydrocortisone plus fludrocortisone, conventional insulin therapy with hydrocortisone alone, or conventional insulin therapy with intravenous hydrocortisone plus fludrocortisone. Hydrocortisone was administered in a 50-mg bolus every 6 hours, and fludrocortisone was administered orally in 50-microg tablets once a day, each for 7 days. MAIN OUTCOME MEASURE: In-hospital mortality. RESULTS: Of the 255 patients treated with intensive insulin, 117 (45.9%), and 109 of 254 (42.9%) treated with conventional insulin therapy died (relative risk [RR], 1.07; 95% confidence interval [CI], 0.88-1.30; P = .50). Patients treated with intensive insulin experienced significantly more episodes of severe hypoglycemia (<40 mg/dL) than those in the conventional-treatment group, with a difference in mean number of episodes per patient of 0.15 (95% CI, 0.02-0.28; P = .003). At hospital discharge, 105 of 245 patients treated with fludrocortisone (42.9%) died and 121 of 264 (45.8%) in the control group died (RR, 0.94; 95% CI, 0.77-1.14; P = .50). CONCLUSIONS: Compared with conventional insulin therapy, intensive insulin therapy did not improve in-hospital mortality among patients who were treated with hydrocortisone for septic shock. The addition of oral fludrocortisone did not result in a statistically significant improvement in in-hospital mortality. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00320099.

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.

Are daily routine chest radiographs useful in critically ill, mechanically ventilated patients? A randomized study.

OBJECTIVE: Whether chest radiographs (CXRs) in mechanically ventilated patients should be routinely obtained or only when an abnormality is anticipated remains debated. We aimed to compare the diagnostic, therapeutic and outcome efficacy of a restrictive prescription of CXRs with that of a routine prescription, focusing on delayed diagnoses and treatments potentially related to the restrictive prescription. DESIGN: Randomized controlled trial. SETTING: Intensive care unit of the Avicenne Teaching Hospital, Bobigny, France. PATIENTS AND PARTICIPANTS: All consecutive patients mechanically ventilated for > or = 48h between January and June 2006. INTERVENTIONS: Patients were randomly assigned to have daily routine CXRs (routine prescription group) or clinically indicated CXRs (restrictive prescription group). MEASUREMENTS AND RESULTS: For each CXR, a questionnaire was completed addressing the reason for the CXR, the new findings, and any subsequent therapeutic intervention. The endpoints were the rates of new findings, the rates of new findings that prompted therapeutic intervention, the rate of delayed diagnoses, and mortality. Eighty-four patients were included in the routine prescription group and 81 in the restrictive prescription group. The rates of new findings and the rates of new findings that prompted therapeutic intervention in the restrictive prescription group and in the routine prescription group were 66% vs. 7.2% (p < 0.0001), and 56.4% vs. 5.5% (p < 0.0001) respectively. The rate of delayed diagnoses in the restrictive prescription group was 0.7%. Mortality was similar. CONCLUSIONS: Restrictive use of CXRs in mechanically ventilated patients was associated with better diagnostic and therapeutic efficacies without impairing outcome.

Norepinephrine weaning in septic shock patients by closed loop control based on fuzzy logic.

INTRODUCTION: The rate of weaning of vasopressors drugs is usually an empirical choice made by the treating in critically ill patients. We applied fuzzy logic principles to modify intravenous norepinephrine (noradrenaline) infusion rates during norepinephrine infusion in septic patients in order to reduce the duration of shock. METHODS: Septic patients were randomly assigned to norepinephrine infused either at the clinician's discretion (control group) or under closed-loop control based on fuzzy logic (fuzzy group). The infusion rate changed automatically after analysis of mean arterial pressure in the fuzzy group. The primary end-point was time to cessation of norepinephrine. The secondary end-points were 28-day survival, total amount of norepinephine infused and duration of mechanical ventilation. RESULTS: Nineteen patients were randomly assigned to fuzzy group and 20 to control group. Weaning of norepinephrine was achieved in 18 of the 20 control patients and in all 19 fuzzy group patients. Median (interquartile range) duration of shock was significantly shorter in the fuzzy group than in the control group (28.5 [20.5 to 42] hours versus 57.5 [43.7 to 117.5] hours; P < 0.0001). There was no significant difference in duration of mechanical ventilation or survival at 28 days between the two groups. The median (interquartile range) total amount of norepinephrine infused during shock was significantly lower in the fuzzy group than in the control group (0.6 [0.2 to 1.0] microg/kg versus 1.4 [0.6 to 2.7] microg/kg; P < 0.01). CONCLUSIONS: Our study has shown a reduction in norepinephrine weaning duration in septic patients enrolled in the fuzzy group. We attribute this reduction to fuzzy control of norepinephrine infusion. TRIAL REGISTRATION: Trial registration: Clinicaltrials.gov NCT00763906.

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.

Attributable mortality of ICU-acquired bloodstream infections: Impact of the source, causative micro-organism, resistance profile and antimicrobial therapy.

OBJECTIVES: ICU-acquired bloodstream infection (ICUBSI) in Intensive Care unit (ICU) is still associated with a high mortality rate. The increase of antimicrobial drug resistance makes its treatment increasingly challenging. METHODS: We analyzed 571 ICU-BSI occurring amongst 10,734 patients who were prospectively included in the Outcomerea Database and who stayed at least 4 days in ICU. The hazard ratio of death associated with ICU-BSI was estimated using a multivariate Cox model adjusted on case mix, patient severity and daily SOFA. RESULTS: ICU-BSI was associated with increased mortality (HR, 1.40; 95% CI, 1.16-1.69; p = 0.0004). The relative increase in the risk of death was 130% (HR, 2.3; 95% CI, 1.8-3.0) when initial antimicrobial agents within a day of ICU-BSI onset were not adequate, versus only 20% (HR, 1.2; 95% CI, 0.9-1.5) when an adequate therapy was started within a day. The adjusted hazard ratio of death was significant overall, and even higher when the ICU-BSI source was pneumonia or unknown origin. When treated with appropriate antimicrobial agents, the death risk increase was similar for ICU-BSI due to multidrug resistant pathogens or susceptible ones. Interestingly, combination therapy with a fluoroquinolone was associated with more favorable outcome than monotherapy, whereas combination with aminoglycoside was associated with similar mortality than monotherapy. CONCLUSIONS: ICU-BSI was associated with a 40% increase in the risk of 30-day mortality, particularly if the early antimicrobial therapy was not adequate. Adequacy of antimicrobial therapy, but not pathogen resistance pattern, impacted attributable mortality.