Low interleukin-10 release after ex vivo stimulation of whole blood is associated with persistent organ dysfunction in sepsis: A prospective observational study.

BACKGROUND: Sepsis profoundly alters immune homeostasis. Cytokine release after whole blood lipopolysaccharide (LPS)-stimulation reflects cell function across multiple immune cell classes and represents the immune response to LPS. The main goal of this study was to evaluate the prognostic value of ex vivo stimulation of whole blood with LPS in sepsis. METHODS: Blood was drawn on day 1 and day 7 after admission, and stimulated ex vivo with LPS. Tumour necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and IL-10 were measured with and without stimulation. Our primary outcome measure was the persistence of at least one organ dysfunction at day 7. Organ dysfunction was defined according to the SOFA components by a score ≥ 2. RESULTS: Forty-nine patients with sepsis from a 21-bed intensive care unit, and 23 healthy volunteers were enrolled. The blood of septic patients was less responsive to ex vivo stimulation with LPS than that of healthy controls at day 1 and 7, as demonstrated by lower TNF-α, IL-1ß, IL-6 and IL-10 release. Persistent organ dysfunction was more frequent in patients with lower IL-10 release at day 1 but such an association was not found for pro-inflammatory cytokines. A persistent low IL-10 release at day 7 was also associated with persistent organ dysfunction. CONCLUSION: These data suggest that the capacity to produce IL-10 in response to whole blood ex vivo stimulation early in sepsis, as well as persistent low IL-10 response over time, may help in prognostication and patient stratification. These results will need to be confirmed in future studies.

Patient factors and outcomes associated with the withdrawal or withholding of life-sustaining therapies in mechanically ventilated brain-injured patients: An observational multicentre study.

BACKGROUND: Knowledge of the factors associated with the decision to withdraw or withhold life support (WWLS) in brain-injured patients is limited. However, most deaths in these patients may involve such a decision. OBJECTIVES: To identify factors associated with the decision to WWLS in brain-injured patients requiring mechanical ventilation who survive the first 24 h in the ICU, and to analyse the outcomes and time to death. DESIGN: A retrospective observational multicentre study. SETTINGS: Twenty French ICUs in 18 university hospitals. PATIENTS: A total of 793 mechanically ventilated brain-injured adult patients. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Decision to WWLS within 3 months of ICU admission, and death or Glasgow Outcome Scale (GOS) score at day 90. RESULTS: A decision to WWLS was made in 171 patients (22%), of whom 89% were dead at day 90. Out of the 247 deaths recorded at day 90, 153 (62%) were observed after a decision to WWLS. The median time between admission and death when a decision to WWLS was made was 10 (5 to 20) days vs. 10 (5 to 26) days when no end-of-life decision was made (P < 0.924). Among the 18 patients with a decision to WWLS who were still alive at day 90, three patients (2%) had a GOS score of 2, nine patients (5%) had a GOS score of 3 and five patients (3%) a GOS score of 4. Older age, presence of one nonreactive and dilated pupil, Glasgow Coma Scale less than 7, barbiturate use, acute respiratory distress syndrome and worsening lesions on computed tomography scans were each independently associated with decisions to WWLS. CONCLUSION: Using a nationwide cohort of brain-injured patients, we observed a high proportion of deaths associated with an end-of-life decision. Older age and several disease severity factors were associated with the decision to WWLS.

Constipation in long-term ventilated patients: associated factors and impact on intensive care unit outcomes.

OBJECTIVES: To characterize the factors associated with delayed defecation in long-term ventilated patients and to examine the relationship between delayed defecation and logistic organ dysfunction scores, acquired bacterial infections, and mortality in the intensive care unit. DESIGN: Prospective observational cohort study. SETTING: A 21-bed polyvalent intensive care unit in a university hospital. PATIENTS: A total of 609 adult patients admitted over a 41-month period who underwent mechanical ventilation for ≥ 6 days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three hundred fifty-three patients (58%) passed stools ≥ 6 days after they were admitted to the intensive care unit ("late" defecation). Patients with early and late defecation had similar general characteristics when admitted to the intensive care unit and had similar logistic organ dysfunction scores on the first day of mechanical ventilation. Several variables were independently associated with a delay in defecation: a Pao2/Fio2 ratio of less than 150 mm Hg (adjusted hazard ratio 1.40; 95% confidence interval: 1.06-1.60; p = .0073), a systolic blood pressure between 70 and 89 mm Hg (adjusted hazard ratio 1.48; 95% confidence interval: 1.17-1.79; p = .002), and systolic blood pressure < 68 mm Hg (adjusted hazard ratio 1.29; 95% confidence interval: 1.01-1.60; p = .03). Logistic organ dysfunction scores were significantly higher on the fourth and ninth days of mechanical ventilation in patients with late defecation than in those with early defecation. The crude intensive care unit mortality rate was 18% in patients with early defecation and 30% in patients with late defecation (p < .001). Acquired bacterial infections at any site occurred in 34% of patients with early defecation and 66% of patients with late defecation (p < .001). CONCLUSION: A Pao2/Fio2 ratio of < 150 mm Hg and systolic blood pressure of < 90 mm Hg during the first 5 days of mechanical ventilation were independently associated with a delay in defecation. Our results suggest that constipation is associated with adverse outcomes in long-term ventilated patients.

Effectiveness of simple daily sensitization of physicians to the duration of central venous and urinary tract catheterization.

PURPOSE: To evaluate the effectiveness of simple daily sensitization of physicians to the duration of central venous and urinary tract catheterization, and impact on infection rates. METHODS: A prospective, before-after study in a surgical intensive care unit. All consecutive patients who had a central venous catheter (CVC) and/or urinary tract catheter (UTC) were included during two consecutive periods. Period 1 (August 2005 to May 2006) served as the control period. During Period 2 (July 2006 to April 2007), a red square, added to the patient's daily care sheet, questioned the physician about the utility of the CVC and/or UTC. If the response was "No", the CVC and/or the UTC were removed by a nurse. RESULTS: A total of 1,271 patients were analyzed (Period 1, n = 676; Period 2, n = 595). The duration of catheterization (median [interquartile range]) was significantly reduced in Period 2 compared to Period 1 (from (5 [3-9] to 4 [3-7] days, p < 0.001, for CVC, and from 5 [3-11] to 4 [3-8] days, p < 0.001, for UTC). The incidence and density incidence of CVC infection decreased in Period 2 compared to Period 1 (from 1.8% to 0.3%, p = 0.010, and from 2.8 to 0.7/1,000 CVC-days, p = 0.051) whereas UTC infections were not significantly different (4.3 to 3.0%, p = 0.230, and 5.0 to 4.9/1,000 UTC-days, p = 0.938, respectively). CONCLUSIONS: A simple daily reminder to physicians on the patients' care sheets decreased the duration of central venous and urinary tract catheterization, and tended to decrease CVC infection rate without affecting UTC infection.

Late-onset ventilator-associated pneumonia in nontrauma intensive care unit patients.

BACKGROUND: Most studies designed to determine the factors associated with the acquisition of late-onset ventilator-associated pneumonia (VAP) were performed in critically ill trauma patients. The impact of enteral nutrition (EN) on the risk of acquiring VAP has been discussed. In this study, we assessed factors associated with late-onset VAP in nontrauma patients and determined whether nutrition provided early was associated with development of late-onset VAP in this population. METHODS: We performed a prospective observational cohort study in a 21-bed polyvalent intensive care unit in a university hospital. RESULTS: Three hundred sixty-one intubated adult patients with a duration of mechanical ventilation (MV) of 6 days or more were admitted over a 28-mo period. Late-onset VAP was confirmed in 76 patients (21%) by the presence of at least one microorganism at a concentration >or=10(4) colony-forming units/mL on the bronchoalveolar lavage. Gram-negative bacilli represented 75% and Staphylococcus aureus 21% of recovered organisms. Factors independently associated with late-onset VAP by multivariate analysis included a high simplified acute physiology score II score (odds ratio: 1.021; 95% confidence interval [CI]: 1.005-1.038; P = 0.01), development of acute respiratory distress syndrome during the first 5 days of MV (odds ratio: 1.98; 95% CI: 1.05-3.67; P = 0.04), and size of the endotracheal tube >or=7.5 (odds ratio: 2.06; 95% CI: 1.88-3.90; P = 0.03). EN started within 48 h of MV onset was not associated with a higher risk for late-onset VAP. CONCLUSION: In our nontrauma patient population, early EN was not associated with development of late-onset VAP. In this population, severity of the disease during the first 5 days of MV seemed to be associated with late-onset VAP. In addition, our results suggest that the risk of late-onset VAP is higher in patients with a tube size >or=7.5 than in patients with a tube size <7.5.