Delayed increase of plasma selenoproteins and absence of side effect induced by infusion of pharmacological dose of sodium selenite in septic shock: Secondary analysis of a multicenter, randomized controlled trial.

Background: In sepsis, neutrophil respiratory bursts participate in endothelium damage, the first step to multiple organ failure. In plasma two antioxidant selenoenzymes, which protect the endothelium, decrease: selenoprotein-P, and to a lesser extent glutathione peroxidase (GPX3). Sodium selenite (NaSeO) is a Se donor, but also an oxidant chemotherapy drug depending on its concentration.

Selenocompounds and Sepsis-Redox Bypass Hypothesis: Part B-Selenocompounds in the Management of Early Sepsis.

Endothelial barrier damage, which is in part caused by excess production of reactive oxygen, halogen and nitrogen species (ROHNS), especially peroxynitrite (ONOO), is a major event in early sepsis and, with leukocyte hyperactivation, part of the generalized dysregulated immune response to infection, which may even become a complex maladaptive state. Selenoenzymes have major antioxidant functions. Their synthesis is related to the need to limit deleterious oxidant redox cycling by small selenocompounds, which may be of therapeutic cytotoxic interest.

The Prognostic Value of Brain Dysfunction in Critically Ill Patients with and without Sepsis: A Analysis of the ICON Audit.

Brain dysfunction is associated with poor outcome in critically ill patients. In a post hoc analysis of the Intensive Care over Nations (ICON) database, we investigated the effect of brain dysfunction on hospital mortality in critically ill patients. Brain failure was defined as a neurological sequential organ failure assessment (nSOFA) score of 3-4, based on the assumed Glasgow Coma Scale (GCS) score.

Selenocompounds and Sepsis: Redox Bypass Hypothesis for Early Diagnosis and Treatment: Part A-Early Acute Phase of Sepsis: An Extraordinary Redox Situation (Leukocyte/Endothelium Interaction Leading to Endothelial Damage).

Sepsis is a health disaster. In sepsis, an initial, beneficial local immune response against infection evolves rapidly into a generalized, dysregulated response or a state of chaos, leading to multiple organ failure. Use of life-sustaining supportive therapies creates an unnatural condition, enabling the complex cascades of the sepsis response to develop in patients who would otherwise die.

Effect of an ICU Diary on Posttraumatic Stress Disorder Symptoms Among Patients Receiving Mechanical Ventilation: A Randomized Clinical Trial.

Importance: Keeping a diary for patients while they are in the intensive care unit (ICU) might reduce their posttraumatic stress disorder (PTSD) symptoms.

Objectives: To assess the effect of an ICU diary on the psychological consequences of an ICU hospitalization.

Design, Setting, And Participants: Assessor-blinded, multicenter, randomized clinical trial in 35 French ICUs from October 2015 to January 2017, with follow-up until July 2017.

Hydrocortisone plus Fludrocortisone for Adults with Septic Shock.

Background: Septic shock is characterized by dysregulation of the host response to infection, with circulatory, cellular, and metabolic abnormalities. We hypothesized that therapy with hydrocortisone plus fludrocortisone or with drotrecogin alfa (activated), which can modulate the host response, would improve the clinical outcomes of patients with septic shock.

Methods: In this multicenter, double-blind, randomized trial with a 2-by-2 factorial design, we evaluated the effect of hydrocortisone-plus-fludrocortisone therapy, drotrecogin alfa (activated), the combination of the three drugs, or their respective placebos.

The ICU-Diary study: prospective, multicenter comparative study of the impact of an ICU diary on the wellbeing of patients and families in French ICUs.

Background: Post-intensive care syndrome includes the multiple consequences of an intensive care unit (ICU) stay for patients and families. It has become a new challenge for intensivists. Prevention programs have been disappointing, except for ICU diaries, which report the patient's story in the ICU.

Haemodynamic response to crystalloids or colloids in shock: an exploratory subgroup analysis of a randomised controlled trial.

Objective: To compare the haemodynamic effect of crystalloids and colloids during acute severe hypovolaemic shock.

Design: Exploratory subgroup analysis of a multicentre randomised controlled trial (Colloids Versus Crystalloids for the Resuscitation of the Critically Ill, CRISTAL, ClinicalTrials.gov NCT00318942).

Randomized intubation with polyurethane or conical cuffs to prevent pneumonia in ventilated patients.

Rationale: The occurrence of ventilator-associated pneumonia (VAP) is linked to the aspiration of contaminated pharyngeal secretions around the endotracheal tube. Tubes with cuffs made of polyurethane rather than polyvinyl chloride or with a conical rather than a cylindrical shape increase tracheal sealing.

Objectives: To test whether using polyurethane and/or conical cuffs reduces tracheal colonization and VAP in patients with acute respiratory failure.

Elements of margin of safety, toxicity and action of sodium selenite in a lipopolysaccharide rat model.

Project: Both septic shock and sodium selenite (Na2SeO3) lead to multiple organ failure through oxidation. Na2SeO3 has direct oxidant effects above the nutritional level and indirect anti-oxidant properties. In a lipopolysaccharide (LPS) rat model we assessed margin of safety, toxicity and beneficial effect of pentahydrate Na2SeO3 (5H2O·Na2SeO3) at oxidant doses.

Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock: the CRISTAL randomized trial.

Importance: Evidence supporting the choice of intravenous colloid vs crystalloid solutions for management of hypovolemic shock remains unclear.

Objective: To test whether use of colloids compared with crystalloids for fluid resuscitation alters mortality in patients admitted to the intensive care unit (ICU) with hypovolemic shock.

Design, Setting, And Participants: A multicenter, randomized clinical trial stratified by case mix (sepsis, trauma, or hypovolemic shock without sepsis or trauma).

Recombinant human activated protein C for adults with septic shock: a randomized controlled trial.

Rationale: A decade after drotrecogin alfa (activated) (DAA) was released on the market worldwide, its benefit-to-risk ratio remains a matter of debate.

Objectives: The current investigator-led trial was designed to evaluate the efficacy and safety of DAA, in combination with low-dose steroids, in adults with persistent septic shock.

Methods: This was a multicenter (24 intensive care units), placebo-controlled, double-blind, 2 × 2 factorial design trial in which adults with persistent septic shock and no contraindication to DAA were randomly assigned to DAA alone (24 μg/kg/h for 96 h), hydrocortisone and fludrocortisone alone, their respective combinations, or their respective placebos.

Assessment of hemodynamic efficacy and safety of 6% hydroxyethylstarch 130/0.4 vs. 0.9% NaCl fluid replacement in patients with severe sepsis: the CRYSTMAS study.

Introduction: Inadequate initial treatment and delayed hemodynamic stabilization (HDS) may be associated with increased risk of death in severe sepsis patients.

Methods: In order to compare the hemodynamic efficacy and safety of 6% HES 130/0.4 and NaCl 0.

A large-bolus injection, but not continuous infusion of sodium selenite improves outcome in peritonitis.

Administration of sodium selenite in septic shock has been associated with apparently conflicting results that may be related to different dosing schedules. Bolus administration, leading to a transient pro-oxidative effect, could limit the inflammatory reaction and improve outcomes. We studied 21 anesthetized, mechanically ventilated, invasively monitored, and fluid-resuscitated sheep.

Critically elucidating the role of selenium.

Purpose Of Review: To assess the current role of selenium supplementation in critically ill patients.

Recent Findings: Studies consistently demonstrate decreased selenium concentration in plasma and whole blood in some critically ill patients, especially those with septic shock, and have suggested that persistent low concentrations may be associated with worse outcomes. However, clinical trials of selenium administration have not consistently or convincingly demonstrated improved outcomes.

Effects of high doses of selenium, as sodium selenite, in septic shock patients a placebo-controlled, randomized, double-blind, multi-center phase II study--selenium and sepsis.

Selenium has a double action. (i) Seleno-compounds, among them sodium selenite have a direct pro-oxidant action leading to acute toxicity but may be also beneficial as drug. (ii) Selenium is an essential anti-oxidant required for anti-oxidant seleno-enzymes.

Effects of high doses of selenium, as sodium selenite, in septic shock: a placebo-controlled, randomized, double-blind, phase II study.

Introduction: Sepsis is associated with the generation of oxygen free radicals and (lacking) decreased selenium plasma concentrations. High doses of sodium selenite might reduce inflammation by a direct pro-oxidative effect and may increase antioxidant cell capacities by selenium incorporation into selenoenzymes. We investigated the effects of a continuous administration of high doses of selenium in septic shock patients.

Seleno-enzymes and seleno-compounds: the two faces of selenium.

Selenium protects cells and inhibits many inflammatory cell mechanisms through antioxidant seleno-enzymes. Immunity improvement is illustrated by the study of Berger and colleagues, with reduction of nosocomial pneumonia in burnt patients under multi-trace-element supplementation. As seleno-compounds (especially sodium selenite) are pro-oxidant, however, administration above 800 microg/day may be dangerous in septic shock.