Association of neurogranin with delirium among critically ill patients.

Background: Neurogranin (Ng) concentrates at dendritic spines. In patients with Alzheimer disease Ng levels are elevated. The role of Ng in delirium development has not been assessed, therefore we hypothesized that Ng levels are associated with delirium in critically ill patients. Materials & methods: From 94 critically ill patients, 47 developed delirium and 47 controls were included. Blood was collected during the first 24 h of intensive care unit (ICU) admission, and on the day of delirium diagnoses. Ng and IL-1ß were determined. Results: Ng and IL-1ß levels were higher in the delirium group at ICU admission and on the day of delirium diagnoses. IL-1ß and Ng were independently associated with delirium occurrence. Conclusion: Ng levels are associated with delirium development in ICU patients.

Identification of distinct clinical phenotypes in mechanically ventilated patients with acute brain dysfunction using cluster analysis.

Acute brain dysfunction (ABD) is a frequent and severe syndrome occurring in critically ill patients and early identification of high-risk patients is paramount. In the present analysis, we propose a clinically applicable model for early phenotype identification of ABD at the bedside in mechanically ventilated patients, improving the recognition of patients with prolonged ABD.Prospective cohort with 629 mechanically ventilated patients in two medical-surgical intensive care units at academic centers. We applied cluster analysis to identify phenotypes using clinical and biological data. We then tested the association of phenotypes and its respective clinical outcomes. We performed a validation on a new cohort of patients select on subsequent patients admitted to the participants intensive care units.A model with 3 phenotypes best described the study population. A 4-variable model including medical admission, sepsis diagnosis, simplified acute physiologic score II and basal serum C-reactive protein (CRP) accurately classified each phenotype (area under curve 0.82; 95% CI, 0.79-0.86). Phenotype A had the shorter duration of ABD (median, 1 day), while phenotypes B and C had progressively longer duration of ABD (median, 3 and 6 days, respectively; P < .0001). There was an association between the duration of ABD and the baseline CRP levels and simplified acute physiology score II score (sensitivity and specificity of 80%). To increase the sensitivity of the model, we added CRP kinetics. By day 1, a CRP < 1.0 times the initial level was associated with a shorter duration of ABD (specificity 0.98).A model based on widely available clinical variables could provide phenotypes associated with the duration of ABD. Phenotypes with longer duration of ABD (phenotypes B and C) are characterized by more severe inflammation and by significantly worse clinical outcomes.

Septic encephalopathy: does inflammation drive the brain crazy?

Sepsis and the multiorgan dysfunction syndrome are among the most common reasons for admission to an intensive care unit, and are a leading cause of death. During sepsis, the central nervous system (CNS) is one of the first organs affected, and this is clinically manifested as sepsis-associated encephalopathy (SAE). It is postulated that the common final pathway that leads to SAE symptoms is the deregulation of neurotransmitters, mainly acetylcholine. Thus, it is supposed that inflammation can affect neurotransmitters, which is associated with SAE development. In this review, we will cover the current evidence (or lack thereof) for the mechanisms by which systemic inflammation interferes with the metabolism of major CNS neurotransmitters, trying to explain how systemic inflammation drives the brain crazy.

Inflammation biomarkers and delirium in critically ill patients.

INTRODUCTION: Delirium is a common occurrence in critically ill patients and is associated with an increase in morbidity and mortality. Septic patients with delirium may differ from a general critically ill population. The aim of this investigation was to study the relationship between systemic inflammation and the development of delirium in septic and non-septic critically ill patients. METHODS: We performed a prospective cohort study in a 20-bed mixed intensive care unit (ICU) including 78 (delirium = 31; non-delirium = 47) consecutive patients admitted for more than 24 hours. At enrollment, patients were allocated to septic or non-septic groups according to internationally agreed criteria. Delirium was diagnosed using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) during the first 72 hours of ICU admission. Blood samples were collected within 12 hours of enrollment for determination of tumor necrosis factor (TNF)-α, soluble TNF Receptor (STNFR)-1 and -2, interleukin (IL)-1ß, IL-6, IL-10 and adiponectin. RESULTS: Out of all analyzed biomarkers, only STNFR1 (P = 0.003), STNFR2 (P = 0.005), adiponectin (P = 0.005) and IL-1ß (P < 0.001) levels were higher in delirium patients. Adjusting for sepsis and sedation, these biomarkers were also independently associated with delirium occurrence. However, none of them were significant influenced by sepsis. CONCLUSIONS: STNFR1, STNFR2, adiponectin and IL-1ß were associated with delirium. Sepsis did not modify the relationship between the biomarkers and delirium occurrence.

Septic encephalopathy: does inflammation drive the brain crazy?

Sepsis and the multiorgan dysfunction syndrome are among the most common reasons for admission to an intensive care unit, and are a leading cause of death. During sepsis, the central nervous system (CNS) is one of the first organs affected, and this is clinically manifested as sepsis-associated encephalopathy (SAE). It is postulated that the common final pathway that leads to SAE symptoms is the deregulation of neurotransmitters, mainly acetylcholine. Thus, it is supposed that inflammation can affect neurotransmitters, which is associated with SAE development. In this review, we will cover the current evidence (or lack thereof) for the mechanisms by which systemic inflammation interferes with the metabolism of major CNS neurotransmitters, trying to explain how systemic inflammation drives the brain crazy.

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.