Critical care : the official journal of the Critical Care Forum
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The development of disseminated intravascular coagulation (DIC) is associated with increased sepsis mortality. Antithrombin (AT) is one of several anticoagulants that have been studied in randomized trials of sepsis without benefit. In a recent study, Iba and colleagues reviewed data from patients who were treated for sepsis-related DIC with two lower doses of AT concentrate than studied in prior trials. ⋯ All patients had baseline antithrombin activity <40% and there was no placebo group. The AT 3,000 group had higher 28-day survival as well as a higher rate of DIC resolution than the AT 1,500 group. Though intriguing, the study findings are limited by the non-randomized retrospective nature of the findings, which resulted in baseline differences in multiple confounders that affect mortality, as well as the lack of a placebo group to compare outcomes.
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The RIFLE (Risk, Injury, Failure, Loss, and End-stage kidney disease) criteria were introduced in 2004, defining the clinical stage of acute kidney injury (AKI) and outcome measures based on serum creatinine, glomerular filtration rate, and urine output. However, a growing body of evidence suggests that these markers are insufficient in drawing an accurate illustration of kidney injury. Indeed, mortality and morbidity remain high in AKI, suggesting that accuracy and speed of patient evaluation are lacking. ⋯ Improvements in diagnosis, risk identification, stratification, prognosis, and therapeutic monitoring will benefit clinical decision-making in the individualized bundling of therapies and ongoing patient management. In particular, kidney protection and AKI prevention may become feasible if an earlier and more accurate diagnosis is made for AKI. Here, we discuss the opportunity to consider whether NGAL is ready for routine clinical use in a number of etiologies of AKI.
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Observational Study
Implementing evidence-based practice in the neuroscience intensive care unit.
Mechanical ventilation is associated with substantial morbidity in brain-injured patients. This study aimed to assess the effectiveness of an extubation readiness bundle to decrease duration of mechanical ventilation after brain injury. ⋯ Targeted education focused on an evidence-based extubation readiness bundle was associated with a reduction in the duration of ventilation in brain-injured patients.
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A major pathophysiologic mechanism in sepsis is impaired host immunity which results in failure to eradicate invading pathogens and increased susceptibility to secondary infections. Although many immunosuppressive mechanisms exist, increased expression of the inhibitory receptor programmed cell death 1 (PD-1) and its ligand (PD-L1) are thought to play key roles. The newly recognized phenomenon of T cell exhaustion is mediated in part by PD-1 effects on T cells. This study tested the ability of anti-PD-1 and anti-PD-L1 antibodies to prevent apoptosis and improve lymphocyte function in septic patients. ⋯ In vitro blockade of the PD-1:PD-L1 pathway decreases apoptosis and improves immune cell function in septic patients. The current results together with multiple positive studies of anti-PD-1 and anti-PD-L1 in animal models of bacterial and fungal infections and the relative safety profile of anti-PD-1/anti-PD-L1 in human oncology trials to date strongly support the initiation of clinical trials testing these antibodies in sepsis, a disorder with a high mortality.
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Multisystem organ failure remains a poorly understood complication of sepsis. During sepsis, reduced excitability contributes to organ failure of skeletal muscle, nerves and the spinal cord. The goal of this study was to determine whether reduced excitability might also contribute to cardiac failure during sepsis. ⋯ Our data suggest cardiac excitability is reduced during sepsis in rats. The reduction in excitability appears to be primarily due to reduction of sodium current. The reduction in sodium current may be sufficient to explain most of the reduction in cardiac contractility during sepsis.