View clinical trials related to Shock, Septic.
Filter by:Prior work has shown that exogenous L-carnitine administration enhances glucose and lactate oxidation, attenuates fatty acid toxicity, and improves endothelial-smooth muscle coupling and cardiac mechanical efficiency. The overall goal of this proposal is to investigate L-carnitine as a novel adjunctive treatment of septic shock. In this study the investigators will test our primary hypothesis: Early adjunctive L-carnitine administration in vasopressor dependent septic shock will significantly reduce cumulative organ failure at 48 hours with an associated decrease in 28-day mortality suggesting the need for further phase III study. To accomplish this the investigators will conduct a phase II, double blinded, placebo controlled, adaptive randomized trial of 250 eligible patients with vasopressor-dependent septic shock. Study subjects will be assigned to one of four arms: low (6g), medium (12g) or high (18g) dose intravenous L-carnitine or placebo for 12 hours as a part of early resuscitative care.
The primary aim of this study is to assess the effects of adjunctive therapy with Interferon (IFN)-gamma on immune function in patients with septic shock in a placebo-controlled manner. Moreover, the investigators want to evaluate new markers that could be used to identify patients with immunoparalysis, and to monitor the patient's immunological response to IFN-γ. In addition, mechanistic studies will be performed to further elucidate mechanisms (such as epigenetic modifications) behind immunoparalysis and the effects of IFN-γ on these mechanisms. With use of the results the investigators will obtain in this pilot study, the investigators will conduct a large multicentre clinical trial with IFN-γ.
Life-threatening infections account for 10% of all intensive care unit admissions and constitute the second more frequent cause of death in the ICU after heart diseases. The most common cause of death in patients admitted with life-threatening infections is multi-organ failure that is mediated by severe inflammation. Given the relationship between inflammation and blood clotting, blood-thinners (also called anticoagulants) have been used to decrease inflammation and the formation of small clots. Several lines of evidence suggest that heparin, a proven and inexpensive blood-thinner, may reduce improve survival in patients diagnosed with life-threatening infection. The primary objective of this study is to demonstrate the feasibility of enrolling patients in a large randomized controlled trial investigating heparin in patients with severe infections. In this study, patients with life-threatening infections will have an equal chance of receiving an intravenous infusion of heparin, or a low dose of a similar drug to prevent of blood clots while patients are immobile. The primary purpose of the study is to demonstrate that an average of 2 patients per site, per month, can be enrolled. Other measures of feasibility include the consent rate, the number of protocol violations that occur during the trial, and the number of dose reductions needed due to excessive anticoagulation. To study the biologic effects of heparin in patients with severe infection, specific laboratory markers will be measured and analyzed. If the feasibility of the trial is confirmed, a large randomized trial designed to tell if heparin can safely improve survival will be conducted. Given its low cost and availability, if heparin is shown to improve survival in patients with severe infection, adoption of this therapy on a global scale is anticipated.
Examination of ADMA (Asymmetric-Dimethylarginine)-serum level and DDAH II (Dimethylarginine Dimethylaminohydrolase)- Polymorphism in patients with severe Sepsis and septic shock as prognostic value. This study looks into ADMA as a good prognostic factor for sepsis. Further more the dependency of the ADMA level to the DDAH II polymorphisms is reviewed this study.
The purpose of this trial is to investigate the potential of FE 202158 as a treatment which can stabilize blood pressure for treatment of patients in early septic shock.
The purpose of this study was to evaluate the immediate effects of red blood cells transfusion on central venous oxygen saturation and lactate levels in septic shock patients randomized to two different hemoglobin levels. The influence of red blood cell (RBC) transfusion on the adequacy of oxygen delivery (DO2) and supply (VO2) could be assessed by systemic oxygen variables such as central venous oxygen saturation (ScvO2) and lactate levels. Although it is not clear that alterations in these parameters actually represent an improvement in the DO2/VO2 ratio, they might represent a better transfusion trigger than the absolute hemoglobin value. Patients admitted with a diagnosis of septic shock and hemoglobin levels lower than 9.0 g/dL , less than 48 hours of shock diagnosis, were included, a central venous catheter in the superior vena cava and signed informed consent. The investigators randomized all patients into two groups. Patients in the liberal group received transfusions immediately, as the objective was to maintain hemoglobin levels above 9.0 g/dL. In the restrictive group, transfusion was withheld until their hemoglobin levels fell below 7.0 g/dL. Each time a patient received a transfusion, the investigators collected a set of laboratory tests, including hemoglobin levels, ScvO2 and lactate, at two time points, immediately before transfusion and one hour after its ending. The sample size was calculated by considering that in 80% of the transfusions in patients in the restrictive group ScvO2 would improve compared to only 45% of those in the liberal group, with an alpha error of 0.05 and 80% power. Improvement was defined as an increase of 5% over the pre-transfusion ScvO2. Twenty-eight transfusions in each group would be necessary, but to correct for potential non-parametric distribution of the main variables, the number was adjusted to 35 transfusions in each group. Trends in ScvO2 and lactate were categorized as worsening or improving. The investigators defined improvement when ScvO2 reached 70% in patients with baseline levels below this threshold or when there was an absolute increase of at least 5% after transfusion. Any increase in patients with previous ScvO2 ≥ 70% was considered to be "no change". Worsening was defined as a reduction of 5% in the previous levels or a decline to less than 70% in patients with pre-transfusion levels in the range of 70 to 75%. The investigators also carried out a ROC curve analysis to assess the accuracy of the pre-transfusion hemoglobin levels, pre-transfusion lactate and pre-transfusion ScvO2 in predicting the patients whose ScvO2 would increase more than 5% with transfusion. For this analysis, the investigators used a different approach because it would also be necessary to analyze patients with a lower chance of response to assess the prediction of response. Thus, this analysis included all patients with ScvO2 below 75%, rather than only those below 70%. As before, the investigators defined improvement as any increase ≥ 5%. The investigators did not consider patients with levels above 75% in this analysis, as the physiological interpretation of this situation is challenging. The investigators considered as altered any lactate levels above 1.5 times the reference level, and a change ≥ 10% was defined as improvement or worsening. In patients with baseline normal levels, the status was recorded as worsening if a 10% increase was detected. Afterwards, the investigators tested the association between these categorized variables and the baseline levels of hemoglobin. The impact on perfusion was also assessed by the determination of Δlactate (lactate post-transfusion x 100/lactate pre-transfusion) and ΔScvO2 (ScvO2 post-transfusion x 100/ScvO2 pre-transfusion), and their correlation with the baseline hemoglobin levels was analyzed using the Spearman correlation test. In all tests, the results were considered significant if the p level was lower than 0.05.
Microparticles (MPs) result from plasma cell membrane remodeling and shedding after cell stimulation or apoptosis. MPs are know recognized as a pool of bioactive messengers with emerging role in pathophysiology of immune and cardiovascular diseases. MPs have been characterized during septic shock and may contribute to dissemination of pro-inflammatory and procoagulant mediators. This is a prospective observational study of circulating MPs and blood coagulation in 100 septic shock patients admitted in 3 tertiary hospitals medical ICU at baseline (D1), D2, D3, D4 and D7.
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.
The purpose of this study is to evaluate the role of several enzymes of the gut mucosa in preventing invasion of gastrointestinal bacteria.
PiCCO has been widely used in critical care settings for several decades. Together with pulmonary artery catheter, it is regarded as the important tool for guiding fluid management in patients with shock or acute respiratory distress syndrome. However, its effects on patients' outcome remain untested. The investigators study is a pilot study that is designed to test whether the use of PiCCO will improve patients' outcome, as compared to those without PiCCO monitoring.