Comparison of Pressure Reactivity Index and Mean Velocity Index to Evaluate Cerebrovascular Reactivity During Induced Arterial Blood Pressure Variations in Severe Brain Injury.

OBJECTIVES: To compare the assessment of cerebral autoregulation by cerebrovascular reactivity indices based on intracranial pressure (Pressure Reactivity Index, PRx) and on transcranial Doppler (Mean Velocity Index, Mx) during controlled variations of arterial blood pressure in severe brain injury. Primary outcome was the agreement between both cerebrovascular reactivity indices measured by the Bland-and-Altman method. Secondary outcomes were the association of cerebrovascular reactivity indices with arterial blood pressure variation, and the comparison of optimal cerebral perfusion pressures determined by both indices. METHODS: All consecutive comatose (Glasgow Coma Scale < 8) patients from the surgical intensive care unit of Bicetre Hospital who had an acute brain injury on computerized tomography and needed vasopressor support were prospectively included. Step-by-step arterial pressure variations using vasopressors were performed to compare PRx and Mx and to calculate optimal cerebral perfusion pressure (CPPopt). MEASUREMENTS AND MAIN RESULTS: 15 patients were included. Mean difference between both indices measured by Bland-and-Altman plot was - 0.07 (IC 95% [- 1.02 to 0.87]). Mx was significantly associated with arterial pressure variation (one-way ANOVA test, p = 0.007), whereas PRx was not (p = 0.44). Optimal cerebral perfusion pressure calculated with PRx and Mx was respectively 11 and 15mmHg higher than the mean perfusion pressure prescribed. Optimal cerebral perfusion pressure calculation was possible in all cases. CONCLUSIONS: Cerebral vasoreactivity indices calculated with intracranial pressure or transcranial Doppler show only moderate agreement. Both indices nonetheless suggest substantially higher optimal cerebral perfusion pressure than those currently provided by international guidelines.

Sepsis severe or septic shock: outcome according to immune status and immunodeficiency profile.

OBJECTIVES: This study evaluated the influence of the immune profile on the outcome at day 28 (D28) of patients admitted to the ICU for septic shock or severe sepsis. METHODS: We conducted an observational study using a prospective multicenter database and included all patients admitted to 11 ICUs for severe sepsis or septic shock from January 1997 to August 2011. Seven profiles of immunodeficiency were defined. The prognostic analysis used a competitive risk model (Fine and Gray), in which being alive at ICU or hospital discharge before D28 competed with death. RESULTS: Among the 1,981 included patients, 607 (31%) were immunocompromised (including nonneutropenic solid tumor [19.6%], nonneutropenic hematologic malignancies [26.3%], and all-cause neutropenia [28%]). Compared with immunocompetent patients, immunocompromised patients were younger, with less comorbidity, were more often admitted for medical reasons, and presented less often with septic shock. The D28 crude mortality was 31.3% in immunocompromised patients and 28.8% in immunocompetent patients (P = .26). However, after adjustment for other prognostic factors, immunodeficiency was an independent risk factor for death at D28 (subdistribution hazard ratio [sHR], 1.37; 95% CI, 1.12-1.67). The immunodeficiency profiles independently associated with death were AIDS (sHR = 1.9), non-neutropenic solid tumor (sHR = 1.8), nonneutropenic hematologic malignancies (sHR = 1.4), and all-cause neutropenia (sHR = 1.7). CONCLUSIONS: Immunodeficiency is common in patients with severe sepsis or septic shock. Despite a similar crude mortality, immunodeficiency was associated with an increased risk of short-term mortality after multivariate analysis. Neutropenia and specific, but not all, profiles of immunodeficiency were independently associated with an increased risk of 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.

Outcomes in severe sepsis and patients with septic shock: pathogen species and infection sites are not associated with mortality.

OBJECTIVES: We evaluated the respective influence of the causative pathogen and infection site on hospital mortality from severe sepsis related to community-, hospital-, and intensive care unit-acquired infections. DESIGN: We used a prospective observational cohort 10-yr database. We built a subdistribution hazards model with corrections for competing risks and adjustment for potential confounders including early appropriate antimicrobial therapy. SETTING: Twelve intensive care units. PATIENTS: We included 4,006 first episodes of acquisition-site-specific severe sepsis in 3,588 patients. INTEVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 1562 community-acquired, 1432 hospital-acquired, and 1012 intensive care unit-acquired episodes of severe sepsis. After adjustment, we found no independent associations of the causative organism, multidrug resistance of the causative organism, infection site, or presence of bacteremia with mortality. Early appropriate antimicrobial therapy was consistently associated with better survival in the community-acquired (0.64 [0.51-0.8], p = .0001), hospital-acquired (0.72 [0.58-0.88], p = .0011), and intensive care unit-acquired (0.79 [0.64-0.97], p = .0272) groups. CONCLUSION: The infectious process may not exert as strong a prognostic effect when severity, organ dysfunction and, above all, appropriateness of early antimicrobials are taken into account. Our findings emphasize the importance of developing valid recommendations for early antimicrobial therapy.

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.

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.

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.

Is methicillin resistance associated with a worse prognosis in Staphylococcus aureus ventilator-associated pneumonia?

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.