Active clinical trials for "Shock, Septic"

The overall hypotheses of this project is that severe sepsis is associated with endothelial dysfunction; that endothelial dysfunction, in turn, is predictive of subsequent organ failure and death; and that protocolized resuscitation attenuates endothelial cell (EC) dysfunction and improves patient survival.

Sepsis is a significant cause health care expenditure and carries an extremely high rate of morbidity and mortality if not treated appropriately. From 1979 to 2000, sepsis resulted in over 10 million admissions to hospital in the United States with a mortality rate of 17.9 to 27.8 percent. In Canada, it is estimated that the incidence of sepsis from 2008-2009 was 103.3 per 100,000 per year. Advances in the multifaceted management of sepsis in recent years have resulted in improved clinical outcomes. However, the cornerstone of sepsis management relies on the prompt administration of appropriate antibiotics. Current clinical practice suggests that antibiotic administration can be delayed up to 45 minutes in order to obtain blood cultures, whose results have a profound impact on the type and duration of antimicrobial therapy. Unfortunately, this recommendation is based on very little evidence and the investigators have found that potential life-saving treatment is often delayed in order to abide by it. Furthermore, recent data suggest that mortality could be increased by approximately 5% by delaying antibiotic administration for that time period. The investigators therefore wish to organize a prospective, multi-centre trial in order to identify the effect of antibiotic administration on blood culture positivity in patients presenting with severe sepsis or septic shock. Other objectives will be to elucidate which patient factors, including age, co-morbid conditions and clinical presentation, as well as antibiotic choice will affect blood culture results. This study will be conducted in the emergency departments at St. Paul's Hospital (SPH), Vancouver General Hospital (VGH), Lion's Gate Hospital (LGH), Surrey Memorial Hospital, Montreal General Hospital (MGH), Royal Victoria Hospital (RVH) and Maricopa Integrated Health System. Patients identified for the aforementioned conditions will be treated as per routine hospital protocol. If the patient is deemed eligible for the study, a second set of blood of blood cultures will subsequently be drawn ideally between 30 and 60 minutes after the administration of antibiotic therapy. Subject demographic data will be collected pertaining to age, comorbid immunocompromised conditions, vital signs, laboratory tests pertaining to end organ dysfunction, suspected source of sepsis, the type antibiotics administered and the timing of antimicrobial administration with respect to the second set of blood cultures taken. Our hypothesis is that blood culture positivity in patients presenting with severe sepsis and septic shock will not be altered significantly by antibiotic therapy. If so, our study would strongly argue against delaying life-saving therapy and would thus greatly improve patient care in our local emergency rooms. If incorrect, our study would be the first to demonstrate the benefit of obtaining blood cultures before antibiotic therapy and would strengthen current recommendations.

Antibiotic dosing in septic shock patients poses a challenge for clinicians due to the pharmacokinetic changes seen in this population. Piperacillin/tazobactam is often used for empirical treatment, and initial appropriate dosing is crucial for reducing mortality. We determined the pharmacokinetic profile of piperacillin 4g every 8 hour in 15 patients treated empirically for septic shock. A PK population model was established with the dual purpose to assess current standard treatment and to simulate alternative dosing regimens and modes of administration. Time above the minimal inhibitory concentration (T>MIC) predicted for each patient were evaluated against clinical breakpoint MIC for Pseudomonas aeruginosa (16 mg/L). Pharmacokinetic-pharmacodynamic (PK-PD) targets evaluated were 100% f T>MIC and 50% fT>4xMIC.

Some studies have shown that antiplatelets agents could reduce organ dysfunction in septic shock in mice and human models. Platelets are actors in immunity and their activation can be complicated by tissue damage with vascular occlusions which can lead to organ dysfunction. Investigators can hypothesize an increase in platelet activation and in leukocyte-platelet aggregates in septic shock.

The aim of this study is to evaluate the effect of Acetaminophen on the main parameters of microcirculation, on the plasmatic levels of free hemoglobin/oxidative stress markers and on the expression of PD1/Pd-L1, in pyrexial septic patient.

Introduction: Evidence suggests that sepsis and septic shock severely impair mitochondria and that the resulting mitochondrial dysfunction is related to the severity and outcome of the resulting organ dysfunction. In sepsis mitochondrial abnormalities - biochemical and ultrastructural - have been recognized in multiple organs, including liver, kidney, skeletal and heart muscle tissue and blood cells. Circulating immune cells play an important role in the pathophysiology of sepsis. Stimulation of the immune system alters the energy requirements of immune cells; down-regulation of immune-cell activity has been associated with prolonged sepsis and unfavourable outcome. The aim of the project is to comprehensively investigate changes in mitochondrial function of immune cells in patients with severe sepsis and septic shock. The following main hypotheses will be evaluated: Severe sepsis and septic shock leads to increased energy requirements of immune cells and to an increase in mitochondrial enzyme activities and energy production. Changes of mitochondrial function in human immune cells are associated with alterations in clinical and laboratory markers of severity of sepsis. Prolonged sepsis and unfavourable outcome is associated with down regulation of mitochondrial function. Methods: A total of 30 adult patients admitted to the intensive care unit (ICU) due to severe sepsis or septic shock will be included in the study; 30 healthy volunteers serve as controls. Patients with any type of chronic infectious, inflammatory or autoimmune diseases, after transplantations or receiving immunosuppressive agents are excluded. Collected baseline characteristics include patient demographics, diagnosis and severity of illness scores at the time of admission. Daily collected follow up data include clinical and laboratory parameters of organ dysfunction, use of vasopressors/inotropes, use of antibiotics, use of steroids and results of microbiological cultures/stains. Negative identification and isolation of monocytes, B cells and CD4 T cells will be performed daily from ICU admission to discharge using an antibody-antigen mediated immunomagnetic cell isolation procedure that depletes all blood cells except the specific target cells. Mitochondrial function of immune cells will be assessed by measurement of mitochondrial complex activity for complexes I to IV by a standard titration protocol. Additionally, the levels of pro- and anti-inflammatory cytokines (Interleukin (IL)-1, IL-6, IL-10, TNF-α) will be assessed throughout the stay in the ICU. For comparison mitochondrial function of of monocytes, B cells and CD4 T cells and cytokine levels will be measured in a group of 10 healthy volunteers. Analysis plan: Changes in mitochondrial function of immune cells over time compared to a healthy control group and during the course of severe sepsis and septic shock is the main outcome parameter of this study. Assessed predictors are determined by the severity of the underlying septic condition and include clinical and laboratory evidence for dysfunction of vital organ systems and changes in levels of inflammatory and anti-inflammatory cytokines.

To validate the use of the Heparin Binding Protein (HBP) concentration to assist in the evaluation of patients admitting to the emergency department with suspected infection.

The aim of this project is to constitute a prospective cohort of all the patients presenting to the adult emergencies of the University Hospital Centre (CHU) of Rennes for a septic syndrome of community origin.

Endotoxin is the major mediator of gram-negative bacteria which cause the systemic inflammation and result in microcirculatory dysfunction, and it leads to multiple organ dysfunction and death in patients with severe sepsis and septic shock. The goal of this study is to measure the endotoxin activity of patients with severe sepsis and septic shock at certain time points, and furthermore, to compare the difference of endotoxin activity among different pathogens, infection source, and antibiotics. The study will enroll severe sepsis and septic shock patients. The endotoxin activity will be measured at certain time points according to the protocol.

The purpose of this study is to reveal if higher doses of vasopressors in septic shock patients correlates with cerebral vasoconstriction and lower cerebral oximetry.