Active clinical trials for "Shock, Septic"

The purpose of this study is to evaluate the efficacy of terlipressin for treating septic shock.

Beta adrenergic system, over-activated in septic shock patients, is a key modulator of the inflammatory response. Experimental works demonstrated that Esmolol, an highly selective beta-1 blocker, reduces heart rate and regulates the inflammatory response. A recent mono centric, double blind, randomized clinical work in septic shock patients has shown that Esmolol administration is safe and reduces effectively heart rate. However there are only sparse data on 1) regional and micro-circulation, 2) inflammation modulation in human resuscitated septic shock patients treated by esmolol.

Terlipressin becomes a vasopressin for septic shock. But some studies found it may lead to severe intesitnal complications such as intestinal ischemia. The investigators study was designed to find the effect of terlipressin on intestinal function in septic shock patients.

Early and adequate fluid resuscitation (< 6 hours) in patients with circulatory failure is essential but may exacerbate oedema, which may itself: 1) aggravate pulmonary lesions and prolong mechanical ventilation, 2) aggravate organ failure and 3) increase mortality notably in patients with acute renal failure. Improving fluid balance is considered crucial in the management of patients in septic shock, but the efficacy of the measures currently proposed (diuretics associated or not with albumin and/or dialysis) is controversial. The investigators hypothesize that a whole-body compression using a body bandage could reduce capillary leakage and thus lead to faster restoration of a normal transmural pressure gradient in postcapillary venules and improve venous return. This is the first study to evaluate mechanical compression using a body bandage to reduce oedema in septic shock. To do this, a whole-body compression will be set up within the 12 hours following admission. Water balance will be monitored daily throughout the duration of the compression and vital status of patients will be search at 7 days, 28 days and 90 days.

Septic shock is one of the major causes of death worldwide with in-hospital mortality rates varying between (11.9% to 47.2 %). Alterations in microcirculatory blood flow were associated with high risk of organ dysfunction and death. Experimental studies on septic rats revealed that dexmedetomidine treatment can effectively reduce the generation of inflammatory mediators and yields beneficial effects on endotoxemic animals' microcirculation.

De-escalation aims at reducing the use of broad-spectrum antibiotics and therefore the emergence of multidrug-resistant (MDR) pathogens. Observational studies suggested that this strategy seems to be safe. However, there is no adequate, direct evidence showing de-escalation of antimicrobial agents to be effective and safe for onco-hematology patients with sepsis or septic shock. Thus, randomized clinical trials are needed for testing the safety and efficiency of de-escalation of antimicrobial therapy. The investigator's hypothesis is that de-escalation of empirical antimicrobial therapy in onco-hematology patients with sepsis or septic shock is noninferior to the continuation of empirical antimicrobial therapy. The first aim of the study is to demonstrate that de-escalation is noninferior to the continuation of broad-spectrum antibiotics in terms of hospital mortality. The secondary aims are to compare the two strategies in terms of mortality, duration of antimicrobial therapy, durations of mechanical ventilation, vasopressor use, numbers of superinfections, organ failure. Antimicrobial de-escalation (ADE) of antimicrobial therapy is a strategy proposed to allow for the rational use of broad-spectrum antimicrobial therapy as the empiric treatment for infections and minimize the overall exposure to these broad-spectrum agents. The need for prompt, effective antimicrobial therapy for patients with known or suspected infections is widely accepted. This principle leads to the use of very broad-spectrum antimicrobial therapy to increase the odds that all suspected potential pathogens are adequately treated. However, the potential drawback is selection of multidrug-resistant (MDR) organisms. ADE is widely recommended in the management of antimicrobial therapy in intensive care unit (ICU) patients. The Surviving Sepsis Campaign guidelines describe and recommend the process for selecting antimicrobial therapy as commencement of antimicrobials within the first hour, antimicrobial therapy broad enough to cover all likely pathogens, and daily reassessment for potential ADE. To date, no randomized study assessing this strategy is available for this specific population of cancer critically ill patients. In a recent systematic review based on 13 observational studies and one randomized controlled trial, the authors conclude that the equipoise remains and a large randomized trial is required to assess the effect of the antibiotics de-escalation strategy on the bacterial ecosystem, on MDR carriage, and on patient outcomes.

Septic shock is a frequent complication associated with high mortality in patients with malignancies. The best transfusion strategy (restrictive or liberal) for the resuscitation of septic shock remains a controversial issue, in relation with potentially discrepant goals of tissue oxygenation and transfusion sparing. In this study, the investigators propose to address the efficacy of two RBC transfusion strategies (liberal or restrictive) in restoring appropriate tissue oxygenation as well as their tolerance. The investigators designed a prospective randomized multicenter trial aimed at comparing liberal and restrictive RBC transfusion strategies applied during the first 48 hours of resuscitation in cancer patients with septic shock and anemia.

In patients with septic shock, low levels of circulating immunoglobulins are common and they are kinetic, particularly of immunoglobulin M (IgM), seems to be related with clinical outcome. These observations, combined with the pivotal role of immunoglobulins on host immune response to infections, led to consider therapy with polyclonal intravenous immunoglobulins a promising option in patients with septic shock. IgM-enriched preparations have been used since now most of all at a standard dose recommended by the producer although a more tailored approach may improve patients' outcomes. This study hypothesizes that in patients with septic shock and low IgM immunoglobulins titers at shock onset, adjunctive treatment with a personalized dose of IgM-enriched immunoglobulins based on IgM serum titers of the patient may reduce mortality compared to a standard dose of IgM-enriched immunoglobulins. The study is designed as a multicentre, national, interventional, randomized, single-blinded, prospective, investigator-sponsored, two arms study. Patients will be randomly assigned to IgM titer-based treatment or flat treatment group in a 1:1 ratio. One group of patients will receive IgM-enriched immunoglobulins adjunctive treatment in a standard dose of 250mg/kg for 3 days. The other group will receive IgM-enriched immunoglobulins adjunctive treatment in a variable dose calculated taking note of the extent of IgM deficit, in order to achieve an IgM threshold value of 100 mg/dL or above. IgM preparation will be administered in this group up to the withdrawal of vasoactive drugs with a maximum allowed of 7 days. The confirmation of the efficacy of a tailored strategy for IgM-enriched immunoglobulin administration in reducing the mortality rate among patients with septic shock and low IgM titers will lead to a revision of the current clinical practice in the use of this adjunctive treatment.

In this prospective randomized controlled trial, investigators aim to study the effects and safety of bicarbonated Ringer's solution in patients with septic shock compared with lactated ringer's solution, and provide evidence for current fluid resuscitation strategies for septic shock.

The inflammatory response represents an important, central component of sepsis. Therefore, it is believed that blunting inflammation will decrease mortality. In vivo test series with mice that had undergone cecal ligation and puncture (recognized sepsis model), physostigmine salicylate significantly inhibited the release of various cytokines (tumor necrosis factor α, interleukin1β, and interleukin 6). These results were similar to those obtained by vagus nerve stimulation. In animal sepsis model using physostigmine not only decreased inflammation but also, diminished the decrease in blood pressure following infection. Animals treated with the peripheral choline esterase inhibitor neostigmine showed no difference compared with physostigmine-treated animals. Therefore, this study aims to investigate the efficacy of choline esterase inhibitors as adjuvant therapy in patients with sepsis or septic shock. Outcome measures include: percentage reduction in procalcitonin blood level, percentage of patients achieving significant reduction in procalcitonin levels, Mean Sequential Organ Failure Assessment score, percentage decrease in lactate dehydrogenase blood level, length of stay in hospital intensive care unit, and in hospital mortality.