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.

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.

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.

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.

Epidemiology and economic evaluation of severe sepsis in France: age, severity, infection site, and place of acquisition (community, hospital, or intensive care unit) as determinants of workload and cost.

PURPOSE: Severe sepsis is a leading cause of death in critically ill patients. We evaluated cost and workload according to infection site, place and time of acquisition, and severity. MATERIAL AND METHOD: We used a prospective 3-year database from 6 intensive care units (ICUs) including 1698 patients. RESULTS: Of the 1698 patients, 713 (42%) had severe sepsis at admission and 339 during the ICU stay (211 had both). Mortality was twice as high in patients with than those without ICU-acquired infection, independent of the presence of severe sepsis at admission. The mean (SD; median) cost of severe sepsis was 22 800 (21 400 ; 15 800 ). Among patients with severe sepsis at admission, workload and cost were higher for pneumonia, peritonitis, and multiple-site infections and for hospital-acquired (17,400 [14,700; 17,400]) vs community-acquired infection (12,600 [12,100 ; 8900 ]). Intensive care unit-acquired severe sepsis was associated with greater than 3-fold increases in workload and costs. By multiple linear regression, older age, emergency surgery, septic shock, Acute Physiological and Chronic Health Evaluation II score, and hospital or ICU-acquired severe sepsis were independently associated with higher costs. CONCLUSIONS: The wide variations in cost and workload invite efforts to identify patient subgroups most likely to benefit from high-cost treatments and from prevention, particularly targeting severe nosocomial infections.

Symptoms of anxiety and depression in family members of intensive care unit patients before discharge or death. A prospective multicenter study.

STUDY OBJECTIVES: More than two thirds of family members visiting intensive care unit (ICU) patients have symptoms of anxiety or depression during the first days of hospitalization. Identifying determinants of these symptoms would help caregivers support families at patient discharge or when death is imminent. DESIGN AND SETTING: Prospective multicenter study including 78 ICUs (1184 beds) in France. PARTICIPANTS: Family members completed the Hospital Anxiety and Depression Scale on the day of patient discharge or death to allow evaluation of the prevalence and potential factors associated with symptoms of anxiety and depression. RESULTS: Three hundred fifty-seven patients were included in the study, and 544 family members completed the Hospital Anxiety and Depression Scale. Symptoms of anxiety and depression were found in 73.4% and 35.3% of family members, respectively; 75.5% of family members and 82.7% of spouses had symptoms of anxiety or depression (P = .007). Symptoms of depression were more prevalent in family members of nonsurvivors (48.2%) than of survivors (32.7%) (P = .008). The multivariate model identified 3 groups of factors associated with symptoms: (1) patient-related: severity as assessed by the Simplified Acute Physiology Score II (odds ratio [OR] 1.017 per point) and patient age (OR 0.984 per year) predicted anxiety, and Simplified Acute Physiology Score II (OR, 1.015 per point), patient death (OR 2.092), and patient age (OR 0.981) predicted depression; (2) family-related: the spouse predicted anxiety (OR 2.085); and (3) ICU-related: a room with more than 1 bed (OR 1.539) predicted depression. CONCLUSION: The prevalence of symptoms of anxiety and depression remains high at the end of the ICU stay, whether the patient is well enough to be discharged or is near death.

Body mass index. An additional prognostic factor in ICU patients.

OBJECTIVE: To examine the association between body mass index (BMI) and mortality in adult intensive care unit (ICU) patients. DESIGN. A prospective multi-center study. INTERVENTIONS: None. METHODS: A cohort study (yielding the OUTCOMEREA database) was conducted over 2 years in 6 medical-surgical ICUs. In each participating ICU, the following were collected daily: demographic information, admission height and weight, comorbidities, severity scores (SAPS II, LOD, and SOFA), ICU and hospital lengths of stay, and ICU and hospital mortality rates. RESULTS: A total of 1,698 patients were examined and divided into 4 groups based on BMI: <18.5, 18.5-24.9, 25-29.9, and >30 kg/m(2). These groups differed significantly for age, gender, admission category (medical, scheduled surgery, unscheduled surgery), ICU and hospital lengths of stay, and comorbidities. Severity at admission and within the first 2 days was similar in the 4 groups, except for the SOFA score. Overall hospital mortality was 31.3% (532 out of 1,698 patients). By multivariate analysis, a BMI below 18.5 kg/m(2) was independently associated with increased mortality (odds ratio 1.63; 95% confidence intervals 1.11-2.39). None of the other BMI categories were associated with higher mortality and even a BMI>30 kg/m(2) was protective of mortality (odds ratio 0.60, 95% confidence intervals 0.40-0.88). CONCLUSIONS: A low BMI was independently associated with higher mortality and a high BMI with lower mortality in this large cohort of critically ill patients. Since BMI is absent from currently available scoring systems, further studies are needed to determine whether adding BMI would improve the effectiveness of scores in predicting mortality.

Determinants of postintensive care unit mortality: a prospective multicenter study.

OBJECTIVE: Six to 25 percent of patients discharged alive from the intensive care unit (ICU) die before hospital discharge. Although this post-ICU mortality may indicate premature discharge from a full ICU or suboptimal management in the ICU or ward, another factor may be discharge from the ICU as part of a decision to limit treatment of hopelessly ill patients. We investigated determinants of post-ICU mortality, with special attention to this factor. DESIGN: Prospective, multicenter, database study. SETTING: Seven ICUs in or near Paris, France. PATIENTS: A total of 1,385 patients who were discharged alive from an ICU after a stay of > or = 48 hrs; 150 (10.8%) died before hospital discharge. Decisions to withhold or withdraw life-sustaining treatments were implemented in the ICUs in 80 patients, including 47 (58.7%) who died before hospital discharge. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In the univariate analysis, post-ICU mortality was associated with advanced age, poor chronic health status, severe comorbidities, severity and organ failure scores (Simplified Acute Physiology Score II, sepsis-related organ failure assessment, and Logistic Organ Dysfunction at admission and at ICU discharge), decisions to withhold or withdraw life-sustaining treatments, and Omega score (reflecting ICU resource utilization and length of ICU stay). Multivariate stepwise logistic regression identified five independent determinants of post-ICU mortality: McCabe class 1 (odds ratio, 0.388 [95% confidence interval, 0.26-0.58]), transfer from a ward (odds ratio, 1.89 [95% confidence interval, 1.27-2.80]), Simplified Acute Physiology Score II score at admission >36 (odds ratio, 1.57 [95% confidence interval, 1.6-2.33]), decisions to withhold or withdraw life-sustaining treatments (odds ratio, 9.64 [95% confidence interval, 5.75-16.6]), and worse sepsis-related organ failure assessment score at discharge (odds ratio, 1.11 [95% confidence interval, 1.03-1.18] per point). CONCLUSIONS: More than 10% of ICU survivors died before hospital discharge. Determinants of post-ICU mortality included variables reflecting patient status before and during the ICU stay. However, the most powerful predictor of post-ICU mortality was the decision to withhold or withdraw life-sustaining treatments in the ICU, suggesting that the decision has been made not to use the unique services of the ICU for these patients.

Calibration and discrimination by daily Logistic Organ Dysfunction scoring comparatively with daily Sequential Organ Failure Assessment scoring for predicting hospital mortality in critically ill patients.

OBJECTIVE: The Logistic Organ Dysfunction (LOD) score has been proved effective in evaluating severity during the first day in an intensive care unit but has not been evaluated later. To evaluate attributable mortality related to nosocomial events, organ dysfunction scores that remain accurate throughout the intensive care unit stay are needed. The objective of this study was to evaluate how accurately daily LOD scoring predicts mortality comparatively with daily Sequential Organ Failure Assessment (SOFA) scoring. DESIGN: Prospective multicenter study. SETTING: Six intensive care units in France. PATIENTS: A total of 1685 patients with intensive care unit stays longer than 48 hrs were included in this study (511 hospital deaths). Median age was 66 yrs, and median Simplified Acute Physiology Score II at admission was 38. For each patient, a senior physician recorded the variables needed to compute organ dysfunction scores daily throughout the intensive care unit stay. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: SOFA and LOD scores were computed daily during the first 7 days. Calibration was evaluated based on goodness-of-fit by the Hosmer-Lemeshow chi-square statistic (lower chi-square values and higher values indicate better fit) and discrimination based on the receiver operating characteristics (ROC) area under the curve (AUC; a ROC-AUC of 1 indicates faultless discrimination and a ROC-AUC of 0.5 indicates the effects of chance alone). Because calibration of both scores was poor at all time points ( p<.001), customization was performed using the total score (model 1) or separate introduction of each dysfunction (model 2). The performance of customized LOD and SOFA scores on a given day in predicting mortality was assessed in those patients who spent at least one more calendar day in the intensive care unit. The original LOD and SOFA scores had satisfactory ROC-AUC values (0.720 to 0.766). Internal consistency of both scores was acceptable ( p< 10(-4) for each organ dysfunction). After customization, the original scores calibrated well between days 1 and 7. Discrimination by both scores was better with model 2 (AUC-ROC, 0.729-0.784). CONCLUSION: Daily LOD and SOFA scores showed good accuracy and internal consistency, and they could be used to adjust severity for events occurring in the intensive care unit.

Impact of unplanned extubation and reintubation after weaning on nosocomial pneumonia risk in the intensive care unit: a prospective multicenter study.

BACKGROUND: The authors prospectively evaluated the occurrence and outcomes of unplanned extubations (self-extubation and accidental extubation) and reintubation after weaning, and examined the hypothesis that these events may differ regarding their influence on the risk of nosocomial pneumonia. METHODS: Data were taken from a prospective, 2-yr database including 750 mechanically ventilated patients from six intensive care units. RESULTS: One hundred five patients (14%) experienced at least one episode of these 3 events; 51 self-extubations occurred in 38 patients, 24 accidental extubations in 22 patients, and 56 reintubations after weaning in 45 patients. The incidence density of these 3 events was 16.4 per 1,000 mechanical ventilation days. Reintubation within 48 h was needed consistently after accidental extubation but was unnecessary in 37% of self-extubated patients. Unplanned extubation and reintubation after weaning were associated with longer total mechanical ventilation (17 vs. 6 days; P < 0.0001), intensive care unit stay (22 vs. 9 days; P < 0.0001), and hospital stay (34 vs. 18 days; P < 0.0001) than in control group, but did not influence intensive care unit or hospital mortality. The incidence of nosocomial pneumonia was significantly higher in patients with unplanned extubation or reintubation after weaning (27.6% vs. 13.8%; P = 0.002). In a Cox model adjusting on severity at admission, unplanned extubation and reintubation after weaning increased the risk of nosocomial pneumonia (relative risk, 1.80; 95% confidence interval, 1.15-2.80; P = 0.009). This risk increase was entirely ascribable to accidental extubation (relative risk, 5.3; 95% confidence interval, 2.8-9.9; P < 0.001). CONCLUSION: Accidental extubation but not self-extubation or reintubation after weaning increased the risk of nosocomial pneumonia. These 3 events may deserve evaluation as an indicator for quality-of-care studies.