Active clinical trials for "Shock"

Circulatory shock occurs when the supply of oxygen in the tissues decreases, which leads to cell damage and affects about one third of patients admitted to Intensive Care Units (ICU). Cardiac Output (CO) can be defined as the volume of blood ejected by the left ventricle per minute and is a very useful hemodynamic parameter in the monitoring of patients with signs of circulatory shock, since it can help define the etiology and management of such patients. Nevertheless, this parameter is underused in patients treated in Emergency Units, as its measurement usually involves invasive methods and few are available in this scenario. The pulmonary artery catheter is considered the gold standard method for determining the cardiac output, however, since it is an invasive method, in recent decades other devices capable of providing this hemodynamic variable in a less invasive way have been developed. Any method capable of providing CO without the need for pulmonary artery catheter insertion is called minimally invasive CO monitoring. The potential advantages of using these methods include the simplicity of measurements, faster acquisition of hemodynamic parameters and the possibility of implementing a monitoring strategy in places such as emergencies and emergency rooms. The evaluation of these parameters allows a faster determination of the etiology of circulatory shock, which enables the early initiation of goal-guided therapy. It is known that the use of goal-guided therapy proved to be effective in reducing peri- and postoperative morbidity and mortality in patients with high surgical risk; this strategy is also associated with reduced mortality, length of stay in the ICU and on mechanical ventilation in patients admitted to the ICU who are fluid responsive. To date, there is no data regarding the impact of a hemodynamic optimization strategy on patients in the first hours of shock. The investigators aim to assess whether goal-based hemodynamic therapy, through non-invasive hemodynamic monitoring, reduces the incidence of acute renal failure in patients with circulatory shock. A multicenter, randomized, open-label study will be carried out. The study will include patients over 18 years of age with signs of shock (systolic blood pressure less than 90 mmHg and/or mean arterial pressure less than 70 mmHg plus at least one of the following changes: lactate greater than 15 mg/dL, oliguria, neurological changes, and capillary refill time greater than 3 seconds) and who have signed an informed consent form (ICF). Included patients will be randomized in a 1:1 ratio into two groups. The Goal-Directed Therapy Group will be the one in which patients will be monitored by the ClearSight™ System (Edwards Life Sciences, Irvine, CA, USA) in the first 24 hours after randomization, where the parameters cardiac index (CI), systolic volume (SV), systolic blood pressure (SBP) and mean arterial pressure (MAP) will be used to determine medical management; if the CI is less than 2.2 L/min/m² and the SV less than 35 mL/beat, an aliquot of 500 mL of crystalloid solution will be administered; if the patient presents with CI less than 2.2 L/min/m², associated with SV greater than 35 mL/beat, dobutamine will be initiated; in patients with SBP less than 90 mmHg and/or MAP less than 70 mmHg, associated with SV greater than or equal to 35 mL/beat, norepinephrine will be initiated. In the Conventional Therapy group, the allocated patients will be treated according to the assistant team, where the following parameters will be evaluated: blood pressure, peripheral oximetry, heart rate, respiratory rate, and urine output; patients showing signs of hypovolemia will receive crystalloid solution; those who remain with hypotension refractory to volume replacement will be given vasoactive drugs; those with suggestive of cardiogenic shock will be given inotropic drugs; these procedures will be determined according to the clinical judgment of the assistant team.

Sepsis is a systemic inflammatory response that has deleterious effects and considered the leading cause of death in critically ill patients 1 . One of the hallmarks of severe sepsis is the progressive, injurious inflammatory response to infection, mediated by the excessive release of inflammatory mediators and consequently, associated with multiple organs damage 2 . Various studies have demonstrated that adverse outcomes in sepsis patients are closely related to the development of myocardial dysfunction 3 . The mortality of sepsis combined with cardiac functional insufficiency has increased significantly to 70%-90% 4 . Therefore, targeting cardiac insufficiency and heart injury may represent a novel treatment strategy. Several reports documented critical involvement of serotonin 5-hydroxytryptamine in the pathogenesis of sepsis. The aim of the current study is to evaluate the efficacy of ondansetron adjuvant use in patients with sepsis and septic shock.

The purpose of this study is to determine the most suitable dose of Fludrocortisone in reversal of sepsis and shock associated with sepsis in patients who are admitted to the ICU. The investigators will be looking to see whether patients receiving Fludrocortisone at different doses recover quicker and spend less time in hospital and in ICU, and to understand the reasons why this happens at certain doses. Sepsis is caused by toxic substances (toxins) from bacteria and other organism entering the bloodstream from a site of infection. In some people, the infection can progress to sepsis and septic shock where the functions of organs in the body are affected. Patients suffering from sepsis and septic shock are commonly managed in the intensive care unit (ICU) where they are prescribed antibiotics as standard therapy, as well as other therapies to support the functions of the body. Fludrocortisone is a steroid that has previously shown to be beneficial to help in shock in patients in ICU, but more information is required about the exact dose that is required to achieve this. This has been shown by previous research. However, the exact role of Fludrocortisone and the best dose has not been studied adequately to date as well as the ways in how it works within the body. The study aims to look tat the dose and the way it works.

Septic shock remains a major cause of death in critically ill patients. Alterations in microcirculation have long been proposed as a key pathophysiological factor of organ dysfunction and death in septic shock patients. Persistence of mottling, prolonged skin recoloration time and cyanosis of the extremities are the easily and frequently observed manifestations of these microcirculatory disorders. Ilomedin is a prostaglandin analog with a potent vasodilatory effect together with anti-thrombotic properties (inhibition of platelet aggregation) preferentially at the microcirculatory level. An increase in cardiac output with increased arterial oxygen delivery has been observed in clinical and preclinical studies with no episodes of hypotension. Improvement in mesenteric perfusion has moreover been observed in experimental sepsis using Ilomedin. Our group has furthermore reported that administration of Ilomedin in patients with refractory septic shock (peripheral hypoperfusion) resulted in a rapid and sustained improvement in peripheral perfusion. Altogether, Ilomedin may prevent or improve recovery of organ dysfunction in septic shock patients through recruitment of the microcirculation and, thereby, ultimately improve outcome.

Study purpose is to compare the outcome after proximal row carpectomy (PRC) vs four-corner fusion (FCA) for SLAC/SNAC II-III type osteoarthritis (OA) in a double-blinded randomized controlled study setting. Patients with radiologically and clinically confirmed OA are randomized (1:1 computer generated sequence with random block size) to two parallel groups and will undergo either PRC or FCA. The study will be patient and assessor blinded. Baseline data is collected preoperatively and is followed by a follow-up visits at 2 and 6 weeks, 3, 6, 12 months, and 5, 10 years after the intervention. Unveiling of the allocation is at 12 months post-intervention.

ULIS-1 is an open-label pilot study concerning utility of molar sodium lactate in fluid balance in septic shock patients

Several data emphasize the relation between tachycardia (>90/min) and high mortality during septic shock. The investigators previously demonstrated the high mortality associated with hypercontractility, tachycardia and the presence of a left ventricular obstruction. A severe hypovolemia, a hyper adrenergic stimulation or a severe vasoplegia can all explain this relation between tachycardia, hypercontractility and the mortality during septic shock. Landiolol is another short-term acting beta-blocker with a half-life of 4 minutes without any beta 2 activity or membrane stabilizing effect. The landiolol has been used in critically ill patients to control supraventricular tachycardia but not in this context of tachycardia and septic shock. The investigators hypothesize that landiolol by reducing the heart rate may improve the survival of patients treated for a septic shock and presenting with an hypercontractility state.

To date, the end-expiratory occlusion test in infants or children has never been evaluated as a marker of preload dependence. It therefore appears clinically relevant to evaluate this new indicator to predict fluid responsiveness in all infants hospitalized in pediatric and neonatal intensive care. The main objective of this study is to determine whether the hemodynamic effects of a 15-second end-expiratory occlusion were able to predict fluid responsiveness in the mechanically ventilated infant or newborn in pediatric intensive care.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Intensive care unit (ICU) mortality in patients with septic shock and acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) remains high and approximates 50-60%. Sepsis is the leading etiology for AKI and CRRT requirement in ICU patients. In septic shock, the dysregulated host response to infectious pathogens leads to a cytokine storm with uncontrolled production and release of humoral pro-inflammatory mediators. These pro-inflammatory mediators and cytokines exert cellular toxicity and promote the development of organ dysfunction and increased mortality. In addition to treating AKI, CRRT techniques can be employed for adsorption of inflammatory mediators extracorporally using specially developed adsorption membranes, hemoperfusion sorbent cartridges or columns. Several methods and devices, such as Oxiris®-AN69 membrane, CytoSorb® cytokine hemoadsorption and polymyxin B (Toraymyxin) endotoxin adsorption and plasmapheresis have been evaluated in small study series but to date the data on outcome benefits remains controversial. HA380 (Jafron Biomedical Co , Ltd, Zhuhai, China) is a CE-labeled hemoadsorption cartridge developed to treat patients with septic shock. It contains hemo-compatible, porous polymeric beads that adsorp cytokines and mid-molecular weight toxins on their surface. The cytokines absorved using this cartridge are IL-1, IL-6, IL-8, IL-10 in addition to TNF-α8. Therefore, this study aims to examine the potential effects of cytokine adsorption using HA380 in addition to hemodiafiltration with the Oxiris®-AN69 membrane on ICU- and 90-day mortality in patients with septic shock and AKI.

Immunonutrition in intensive care has not yet demonstrated a beneficial effect on organ failure, the acquisition of nosocomial infections, or mortality. It did not correct for acquired immunosuppression in intensive care patients. Despite numerous methodological problems (use of several pharmaconutrients, very heterogeneous set of patients) and the absence of clinical data, deleterious effects have been attributed to immunonutrition in intensive care, in particular in septic patients and patients in intensive care . Arginine (ARG) is a semi-essential amino acid involved in many immunological mechanisms. It is synthesized in sufficient quantity under normal conditions but quickly becomes insufficient under catabolic conditions such as in severe sepsis. Arginine is not only the precursor of nitrogen monoxide (NO) but also an essential substrate for numerous enzymatic reactions which participate in the maintenance of immune homeostasis, in particular T lymphocyte function. Depletion of the cellular medium in arginine will induce an abnormality in the metabolism of immune cells responsible for a dysfunction of these cells (lymphopenia linked to early apoptosis) and thus expose patients to organ failure and nosocomial infections. It has been found that hypoargininemia in intensive care patients is associated with the persistence of organ dysfunction (SOFA score), the occurrence of nosocomial infections and mortality. Also, it has been demonstrated that in these patients, enteral administration of ARG was not deleterious and increased ornithine synthesis, suggesting a preferential use of ARG via the arginases route, without significant increase in argininaemia or effect on immune functions. L-citrulline (CIT), an endogenous precursor of ARG, constitutes an interesting alternative for increasing the availability of ARG. Sponsor recent data demonstrate that the administration of CIT in intensive care is not deleterious and that it very significantly reduces mortality in an animal model of sepsis, corrects hypoargininemia, with convincing data on immunological parameters such as lymphopenia, which is associated with mortality, organ dysfunction and the occurrence of nosocomial infections. The availability of ARG directly impacts the mitochondrial metabolism of T lymphocytes and their function. Our hypothesis is therefore that CIT supplementation is more effective than administration of ARG in correcting hypoargininemia, reducing lymphocyte dysfunction, correcting immunosuppression and organ dysfunction in septic patients admitted to intensive care.