Active clinical trials for "Shock, Septic"

Septic shock is a life-threatening condition with mortality rate of up to -40%. Septic shock is catheterized by altered microcirculation that leads to tissue hypoperfusion and ultimately multi-organ dysfunction. Hence, maintenance of adequate tissue perfusion is the mainstay of resuscitation of patients with septic shock. Serum lactate is still considered the gold standard for evaluation of tissue perfusion. Thus, according to the latest definition, elevated serum lactate, as an indicator of tissue hypo-perfusion, is required for diagnosis of septic shock. However, lactate level change in response to resuscitation is slow even in survivors. Capillary refill time (CRT) is a simple method for assessing peripheral perfusion. Monitoring CRT was found to be a good tool for guiding resuscitation and delayed CRT showed good ability in predicting mortality in patients with septic shock. To the best of our knowledge, there is no previous report assessing the reliability of an index that include both serum lactate and CRT (lactate/CRT index) in predicting mortality in patients with septic shock. We hypothesize that the lactate/CRT index would have good accuracy in predicting mortality in patient with septic shock.

Biomarkers that provide an early indicator of kidney stress could be useful in clinical practice to detect silent episodes of acute kidney injury (AKI) or for early identification of subjects at risk of AKI. Two urinary biomarkers have been identified as early indicators of AKI. The NephroCheck® test is a commercially available test that uses these biomarkers, and this study assesses the use of these in reducing negative clinical outcomes for patients with sepsis-associated AKI. The study will enroll subjects diagnosed with sepsis, including septic shock, who will be randomly assigned to either receive NephroCheck®-guided kidney-sparing and fast-tracking interventions; or to receive current Standard of Care assessment and treatment. NOTE: Participants are no longer being recruited to this study.

The aim of the study is to assess carotid ultrasounds measurements, namely corrected flow time (FTc), velocity time integral (VTI) and respirophasic variation in carotid artery blood flow peak velocity (ΔVpeak), as a predictor of fluid responsiveness in septic shock patients.

The hallmarks of septic shock are hypovolemia and reduced pressor response to endogenous noradrenaline. The working hypothesis is that the higher the plasma concentration of endogenous noradrenaline will be, the lower the pressor response to exogenous noradrenaline will be. This will be tested in patients presenting with septic shock, following state of the art management (including repeated assessment of vena cava diameter and compliance, and response to dynamic indices of loading) following placebo vs clonidine administration (1 mcg.kg-1.h-1 over 24 h without bolus) and administration of increasing doses of noradrenaline (1 mcg, 2 mcg, etc. up to a delta systolic blood pressure circa 25-30 mm Hg).

Advanced stages of the response to life-threatening infection, severe trauma, or other physiological insults often lead to exhaustion of the homeostatic mechanisms that sustain normal blood pressure and oxygenation. These syndromic presentations often meet the diagnostic criteria of sepsis and/or the acute respiratory distress syndrome (ARDS), the two most common syndromes encountered in the intensive care unit (ICU). Although critical illness syndromes, such as sepsis and ARDS, have separate clinical definitions, they often overlap clinically and share several common injury mechanisms. Moreover, there are no specific therapies for critically ill patients, and as a consequence, approximately 1 in 4 patients admitted to the ICU will not survive. The purpose of this observational study is to identify early patient biologic factors that are present at the time of ICU admission that will help diagnose critical illness syndromes earlier, identify who could benefit most from specific therapies, and enable the discovery of new treatments for syndromes such as sepsis and ARDS.

Assesment of right ventricular dysfunction in septic shock patients in intensive care unit.

The aim of the study is to demonstrate that "frail" patients, defined as having a CFS score greater than or equal to 5, and "severely" frail patients, defined as having a CFS score between [6-7] as defined by Bagshaw et al (14), constitute an independent risk factor (RF) for mortality. In the same way, as an exploratory study, we will try to find out whether clinical frailty constitutes a risk factor for extending the length of hospital stay, the risk of short/medium-term readmission, as has already been demonstrated for patients admitted to intensive care from all causes (15), or for impaired quality of life. The objective is to have a better understanding of the implications and outcomes associated with pre-hospital frailty in young critically ill patients. This analysis will also help to clarify prognoses and contribute to better decision-making on the intensity and proportionality of care, as well as providing better information and helping to manage the expectations of patients and their families in terms of survival prognosis and subsequent quality of life.

Mortality rates associated septic shock remains unacceptably high, around 20-50%, with refractory hypotension in half of these patients. Widespread vasodilatation involves the activation of the soluble intracellular enzyme guanylate cyclase (GC) by nitric oxide (NO), resulting in the production of cyclic guanosine monophosphate (cGMP). Initially discovered as an endothelium-derived relaxing factor in blood vessels, NO is made by the enzyme nitric oxide synthase (NOS). It has been suggested that the inhibition of NO generation might be a treatment option for sepsis and septic shock. Methylene blue (MB) is a dye that easily crosses cell membranes, inhibits iNOS, and is capable of inhibiting the GC enzyme in vascular smooth muscle cells.Early use of MB can block the progressive decrease in systemic vascular resistance of patients unresponsive to noradrenaline and mitigate the need for prolonged vasoconstrictor use. The investigators propose to study the effect of methylene blue on cirrhotic adults with sepsis, with refractory vasoplegia unresponsive to maximum doses of noradrenaline and vasopressin.

Staphylococcus aureus and Streptococcus pyogenes produce many virulence factors. Some of them are responsible for severe infections in humans. Superantigen toxins synthesized by S. aureus or by S. pyogenes, are responsible for toxic shock syndromes (TSS) which lethality can attain 25% in children with validated criteria of septic shock. Previous studies, performed in vitro and in vivo in animals, have shown that Intravenous immunoglobulins [IVIG] contain antibodies [Ab] against these toxins and, when used at high concentration, IVIG are able to neutralize their toxicity. However, in all these studies, IVIG administration has been preventive and there is no reliable data demonstrating their therapeutic efficacy in vitro or in vivo in humans or in animals, once the disease is present. The efficacy of IVIG is established in other pathologies for which the role of the superantigens [superAg] is suspected, like Kawasaki disease in children. The mechanism of action, although not perfectly known, involves at the same time a direct effect on superAg (Ag-Ab complex) and indirect effects like the neutralisation of superAg within the network of anti-idiotype Ab or the neutralisation of the T-cells receptors. Staphylococcal and streptococcal toxic shocks imply bacterial exotoxins that are superAg. It seems thus consistent to imagine a same type of treatment with IVIG. However, there is currently no evidence of the efficacy of IVIG in this indication. One of the explanations relies on the lack of statistical power of previous adult studies, which principal objective was to show a reduction of the mortality. Taking into account the low prevalence of TSS, it has been hard to recruit enough patients to have the required statistical power. Moreover, some works have been extracted from larger studies on septic shock and the definitions of the TSS were nor always very reliable. Lastly, if the investigators consider the definition of the TSS as mentioned by the " Centre for Disease Control " [CDC], for which any hypotension, even a simple orthostatic hypotension, serves the diagnosis of TSS as long as the other symptoms are present, it is obvious that many patients are likely to be recruited in a study although it is highly probable that their health will get better with a " standard " treatment. The definition of a " real " TSS can be refined, keeping the CDC criteria, but changing the hypotension criterion in a more accurate criterion as described in the " surviving sepsis campaign ", internationally accepted and based on norms adapted to the age for paediatric forms. IVIG therapy is very expensive and TSS is not recognized as indication of IVIG according to their marketing authorization. The feasibility of a randomized controlled study with this treatment needs to be assessed as it would be hazardous to conduct a large prospective RCT without having first assessed this feasibility in terms of recruitment rates, consent rates or compliance rates. Inclusion, randomisation and collect of inform consent in the context of severe shock are challenging and require evaluation of feasibility. The sample size calculation of the large study on mortality required estimations of the event in the specific population of children with criteria of septic shock. Surrogates markers of outcome need to be better defined. For example it would be useful to determine the evolution of organ dysfunctions with and without IVIG treatment in this population. Various organ failure scores, used upon admission and later on, have been validated in adults and in children. The absence of improvement of the Paediatric logistic organ dysfunction (Pelod) score over time is a good indicator of mortality in Paediatric intensive care unit (PICU). It could be used as surrogate marker to evaluate the efficacy of IVIG.

Aim #1 To investigate the prevalence, risk and correlation of the level of sepsis with mitochondrial dysfunction in sepsis patients Aim 1.1 To investigate the prevalence of mitochondria dysfunction among sepsis patients Aim 1.2 To investigate the risk associated with mitochondrial dysfunction in sepsis patients. Aim 1.3 To investigate the association between sepsis severity (SOFA scoring system) and the degree of mitochondrial dysfunction Aim #2 To investigate the association of mitochondrial dysfunction in sepsis with ScvO2, lactate and ∆PCO2 Aim 3.1 To investigate the therapeutic efficacy of steroids on the improvement mitochondrial function in sepsis patients Aim 3.2. To investigate the efficacy of steroids on the reduction mortality rate in sepsis patients with norepinephrine-resistant hypotension