Brain-derived neurotrophic factor plasma levels are associated with mortality in critically ill patients even in the absence of brain injury.

INTRODUCTION: Because of its relevance to the functioning of the central nervous system, brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of different neuropsychiatric diseases. Whether the BDNF level can be a marker of brain dysfunction and thus predict mortality in critically ill patients is not known. Thus we aimed to determine whether the plasma levels of BDNF are associated with morbidity and mortality in critically ill patients. METHODS: Healthy volunteers (n = 40) and consecutive patients older than 18 years (n = 76) admitted for more than 24 hours in an Intensive Care Unit (ICU) in a University hospital between July and October 2010 were included in the present study. First blood samples were collected within 12 hours of enrollment (D0), and a second sample, 48 hours after (D2) for determination of plasma BDNF levels. The relation between BDNF levels and mortality was the primary outcome. The secondary outcomes were the relation between BDNF levels and delirium and coma-free days (DCFD) and ICU and hospital length of stay (LOS). RESULTS: Admission plasma levels of BDNF were higher in ICU patients when compared with healthy volunteers (1,536 (962) versus 6,565 (2,838) pg/ml). The mean BDNF D2 was significantly lower in nonsurvivor patients (5,865 (2,662) versus 6,741 (2,356) pg/ml). After adjusting for covariates, BDNF levels, the need for mechanical ventilation, and sepsis were associated with mortality. Even in patients without clinically detectable brain dysfunction, lower BDNF D2 levels were associated with mortality. BDNF D2 had a mild correlation to DCFD (r = 0.44), but not to ICU and hospital LOS. In addition, plasma BDNF did not correlate to different plasma cytokines and platelets levels. CONCLUSIONS: The plasma levels of BDNF were independently associated with mortality, even in the absence of clinically detectable brain dysfunction.

Regulation of lung oxidative damage by endogenous superoxide dismutase in sepsis.

BACKGROUND: The purpose of this research is to study the relationship between superoxide dismutase (SOD) and lung redox state in an animal model of sepsis. METHODS: Sepsis was induced in rats by the cecal ligation and perforation model (CLP). After 3, 6, and 12 h, CLP protein content and expression of SOD1, SOD2, and SOD3 were evaluated, and SOD activity was assessed. Oxidative damage was determined by quantifying nitrotyrosine content. Lung localization of SOD3 was performed by immunohistochemistry. The protective effect of a SOD mimetic on oxidative damage, inflammation, and lung permeability was assessed 12 and 24 h after sepsis induction. RESULTS: Lung levels of SOD1 decreased 3 and 12 h after sepsis, but SOD2 and SOD3 increased, as well as SOD activity. These alterations were not associated with changes in sod gene expression. Nitrotyrosine levels increased 3 and 12 h after sepsis. The administration of a SOD mimetic decreased nitrotyrosine and proinflammatory cytokine levels and improved lung permeability. CONCLUSIONS: SOD2 and SOD3 increased after sepsis induction, but this was insufficient to protect the lung. Treatments based on SOD mimetics could have a role in lung injury associated with sepsis.

Lack of association of S100ß and neuron-specific enolase with mortality in critically ill patients.

OBJECTIVE: To evaluate the relationship between brain damage biomarkers and mortality in the intensive care unit (ICU). METHODS: The sample comprised 70 patients admitted to an ICU. Blood samples were collected from all patients on ICU admission, and levels of S100ß and neuron-specific enolase (NSE) were determined by ELISA. RESULTS: Acute Physiologic and Chronic Health Evaluation (APACHE II) score was associated with mortality, but NSE and S100ß were not associated with this outcome. In contrast, S100ß levels were significantly higher in delirious and non-delirious patients who required mechanical ventilation during ICU stay. CONCLUSION: Levels of brain biomarkers at the time of ICU admission did not predict mortality in critically ill patients.

Comparison of CAM-ICU and ICDSC for the detection of delirium in critically ill patients focusing on relevant clinical outcomes.

PURPOSE: Delirium is a frequent and serious problem in the intensive care unit (ICU) that is associated with increased mortality, prolonged mechanical ventilation, and prolonged hospital length of stay (LOS). The main objective of the present study was to compare and assess the agreement between the diagnosis of delirium obtained by the Confusion Assessment Method for the ICU (CAM-ICU) and Intensive Care Delirium Screening Checklist (ICDSC) in patients admitted to the ICU and their association with outcomes. METHODS: Adult patients admitted to the ICU for more than 24 hours between May and November 2008 were included. Patients with a Richmond Agitation-Sedation Scale score of -4 to -5 for more than 3 days were excluded. Delirium was evaluated twice a day by the ICDSC and CAM-ICU. Patients were followed-up until ICU discharge or for a maximum of 28 days. RESULTS: During the study period, 383 patients were admitted to the ICU and 162 (42%) were evaluated; delirium was identified in 26.5% of patients by CAM-ICU and in 34.6% by ICDSC. There was agreement in diagnosing delirium diagnosis between the 2 methods in 42 (27.8%) patients and in excluding delirium in 105 (64.8%) patients. The ICDSC was positive in 14 (8.6%) patients in whom CAM-ICU was negative. Delirium, diagnosed either by ICDSC or CAM-ICU assessments, was associated with both significantly increased hospital LOS (14.8 ± 8.3 vs 9.8 ± 6.4, P < .001; 15.3 ± 8.7 vs 10.5 ± 7.1, P < .001, respectively), mortality in the ICU (11.1% vs 5.8%, P < .001; 12.5% vs 2.5%, P = .022), and in the hospital (10.7% vs 5.6%, P < .001; 23.2% vs 10.9%, P = .047). In addition, patients with positive ICDSC presenting with negative CAM-ICU had similar outcomes as compared with those without delirium. CONCLUSION: The findings of our study suggest that the CAM-ICU is better predictor of outcome when compared with ICDSC.

CAM-ICU and ICDSC agreement in medical and surgical ICU patients is influenced by disease severity.

INTRODUCTION: Delirium is a prevalent condition in patients admitted to intensive care units (ICU) associated with worse outcomes. The principal aim of the present study was compare the agreement between two tools for delirium assessment in medical and surgical patients admitted to the ICU. METHODS: Consecutive adult surgical and medical patients admitted to the ICU for more than 24 hours between March 2009 and September 2010 were included. Delirium was evaluated twice a day using the Intensive Care Delirium Screening Checklist (ICDSC) and Confusion Assessment Method adapted to the Intensive Care Unit (CAM-ICU). The kappa (k) and AC1 coefficients were calculated as a measure of agreement between the CAM-ICU and ICDSC. RESULTS: A total of 595 patients were enrolled in the study. There were 69 (12%) emergency surgical, 207 (35%) elective surgical and 319 (54%) medical patients. Delirium incidence evaluated by the ICDSC, but not by the CAM-ICU, was similar among the three groups. Overall agreement between CAM-ICU and ICDSC was moderate (k = 0.5) to substantial (AC1 = 0.71). In medical patients the agreement between the two instruments was moderate (k = 0.53) to substantial (AC1 = 0.76). The agreement between the two tools in emergency surgical patients was also moderate (k = 0.53) to substantial (AC1 = 0.68). In elective surgical patients the agreement between the two instruments was low (k = 0.42) to substantial (AC1 = 0.74).Agreement rates seemed to be influenced by disease severity. The agreement rate in the general ICU population with APACHE II = <14 was k = 0.57 and AC1 = 0.81, compared to k = 0.44 and AC1 = 0.59, in patients with more severe disease. This was even more different when the need for mechanical ventilation was used as a surrogate of disease severity. CONCLUSIONS: The agreement rates between CAM-ICU and ICDSC may vary between different groups of ICU patients and seems to be affected by disease severity.

Lack of association of S100 and neuron-specific enolase with mortality in critically ill patients

Objective: To evaluate the relationship between brain damage biomarkers and mortality in the intensive care unit (ICU). Methods: The sample comprised 70 patients admitted to an ICU. Blood samples were collected from all patients on ICU admission, and levels of S100β and neuron-specific enolase (NSE) were determined by ELISA. Results: Acute Physiologic and Chronic Health Evaluation (APACHE II) score was associated with mortality, but NSE and S100β were not associated with this outcome. In contrast, S100β levels were significantly higher in delirious and non-delirious patients who required mechanical ventilation during ICU stay. Conclusion: Levels of brain biomarkers at the time of ICU admission did not predict mortality in critically ill patients. .