Patient-Level Meta-Analysis of Low-Dose Hydrocortisone in Adults with Septic Shock.

BACKGROUND: Trials and study-level meta-analyses have failed to resolve the role of corticosteroids in the management of patients with septic shock. Patient-level meta-analyses may provide more precise estimates of treatment effects, particularly subgroup effects. METHODS: We pooled individual patient data from septic shock trials investigating the adjunctive use of intravenous hydrocortisone.

The prevalence of sepsis-induced coagulopathy in patients with sepsis - a secondary analysis of two German multicenter randomized controlled trials.

Background: Sepsis and septic shock are frequently accompanied by coagulopathy. Since the sepsis-induced coagulopathy (SIC) score was first described, subsequent studies from Asia revealed a SIC prevalence of 40-60%. In Europe, however, SIC prevalence in patients fulfilling sepsis criteria according to the third international consensus definition (SEPSIS-3) has not yet been evaluated.

Corticotropin-stimulated steroid profiles to predict shock development and mortality in sepsis: From the HYPRESS study.

Rationale: Steroid profiles in combination with a corticotropin stimulation test provide information about steroidogenesis and its functional reserves in critically ill patients.

Objectives: We investigated whether steroid profiles before and after corticotropin stimulation can predict the risk of in-hospital death in sepsis.

Methods: An exploratory data analysis of a double blind, randomized trial in sepsis (HYPRESS [HYdrocortisone for PRevention of Septic Shock]) was performed.

Use of IFNγ/IL10 Ratio for Stratification of Hydrocortisone Therapy in Patients With Septic Shock.

Large clinical trials testing hydrocortisone therapy in septic shock have produced conflicting results. Subgroups may benefit of hydrocortisone treatment depending on their individual immune response. We performed an exploratory analysis of the database from the international randomized controlled clinical trial Corticosteroid Therapy of Septic Shock (CORTICUS) employing machine learning to a panel of 137 variables collected from the Berlin subcohort comprising 83 patients including demographic and clinical measures, organ failure scores, leukocyte counts and levels of circulating cytokines.

Treatment and Mortality of Hemophagocytic Lymphohistiocytosis in Adult Critically Ill Patients: A Systematic Review With Pooled Analysis.

Objectives: Hemophagocytic lymphohistiocytosis is a cytokine release syndrome caused by uncontrolled immune activation resulting in multiple organ failure and death. In this systematic review, we aimed to analyze triggers, various treatment modalities, and mortality in critically ill adult hemophagocytic lymphohistiocytosis patients.

Data Sources: MEDLINE database (PubMed) at October 20, 2019.

Hemophagocytic lymphohistiocytosis in critically ill patients: diagnostic reliability of HLH-2004 criteria and HScore.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare though often fatal hyperinflammatory syndrome mimicking sepsis in the critically ill. Diagnosis relies on the HLH-2004 criteria and HScore, both of which have been developed in pediatric or adult non-critically ill patients, respectively. Therefore, we aimed to determine the sensitivity and specificity of HLH-2004 criteria and HScore in a cohort of adult critically ill patients.

Hyperferritinemia in Critically Ill Patients.

Objective: Hyperferritinemia is frequently seen in critically ill patients. A rather rare though life-threatening condition related to severely elevated ferritin is hemophagocytic lymphohistiocytosis. We analyze ferritin levels to differentiate hemophagocytic lymphohistiocytosis from other causes of hyperferritinemia in a mixed cohort of critically ill patients.

Corticosteroids for treating sepsis in children and adults.

Background: Sepsis occurs when an infection is complicated by organ failure. Sepsis may be complicated by impaired corticosteroid metabolism. Thus, providing corticosteroids may benefit patients.

Hemophagocytic Lymphohistiocytosis in Critically Ill Patients.

Background: Hemophagocytic lymphohistiocytosis (HLH), an uncontrolled overactivation of the immune system, is well characterized in pediatric patients, yet, much less is known about this life-threatening condition in adult patients. As HLH is often complicated by organ failure, patients will require admission to the intensive care unit for organ support therapy. However, recognition of HLH patients in the intensive care unit (ICU) is challenged by the clinical overlap with sepsis.

Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis: The HYPRESS Randomized Clinical Trial.

Importance: Adjunctive hydrocortisone therapy is suggested by the Surviving Sepsis Campaign in refractory septic shock only. The efficacy of hydrocortisone in patients with severe sepsis without shock remains controversial.

Objective: To determine whether hydrocortisone therapy in patients with severe sepsis prevents the development of septic shock.

Corticosteroids for treating sepsis.

Background: Sepsis occurs when an infection is complicated by organ failures as defined by a sequential organ failure assessment (SOFA) score of two or higher. Sepsis may be complicated by impaired corticosteroid metabolism. Giving corticosteroids may benefit patients.

High-protein enteral nutrition enriched with immune-modulating nutrients vs standard high-protein enteral nutrition and nosocomial infections in the ICU: a randomized clinical trial.

Importance: Enteral administration of immune-modulating nutrients (eg, glutamine, omega-3 fatty acids, selenium, and antioxidants) has been suggested to reduce infections and improve recovery from critical illness. However, controversy exists on the use of immune-modulating enteral nutrition, reflected by lack of consensus in guidelines.

Objective: To determine whether high-protein enteral nutrition enriched with immune-modulating nutrients (IMHP) reduces the incidence of infections compared with standard high-protein enteral nutrition (HP) in mechanically ventilated critically ill patients.

Impact of compliance with infection management guidelines on outcome in patients with severe sepsis: a prospective observational multi-center study.

Introduction: Current sepsis guidelines recommend antimicrobial treatment (AT) within one hour after onset of sepsis-related organ dysfunction (OD) and surgical source control within 12 hours. The objective of this study was to explore the association between initial infection management according to sepsis treatment recommendations and patient outcome.

Methods: In a prospective observational multi-center cohort study in 44 German ICUs, we studied 1,011 patients with severe sepsis or septic shock regarding times to AT, source control, and adequacy of AT.

Risk factors in critical illness myopathy during the early course of critical illness: a prospective observational study.

Introduction: Non-excitable muscle membrane indicates critical illness myopathy (CIM) during early critical illness. We investigated predisposing risk factors for non-excitable muscle membrane at onset of critical illness.

Methods: We performed sequential measurements of muscle membrane excitability after direct muscle stimulation (dmCMAP) in 40 intensive care unit (ICU) patients selected upon a simplified acute physiology (SAPS-II) score >OR= 20 on 3 successive days within 1 week after ICU admission.

Perioperative gene expression analysis for prediction of postoperative sepsis.

Background: Postoperative sepsis is one of the main causes of death after major abdominal surgery; however, the immunologic factors contributing to the development of sepsis are not completely understood. In this study, we evaluated gene expression in patients who developed postoperative sepsis and in patients with an uncomplicated postoperative course.

Methods: We enrolled 220 patients in a retrospective matched-pair, case-control pilot study to investigate the perioperative expression of 23 inflammation-related genes regarding their properties for predicting postoperative sepsis.

Multicenter comparison of cortisol as measured by different methods in samples of patients with septic shock.

Purpose: To compare inter-laboratory and inter-assay measurements of total cortisol in patients with septic shock and to evaluate current recommendations for diagnosis of corticosteroid insufficiency in septic shock.

Methods: In the multinational CORTICUS study duplicate serum samples were taken before and after corticotropin stimulation tests in patients with septic shock. Serum cortisol was measured in paired samples, one being measured by the chemical laboratory of each participating site and the other by a central laboratory using an electrochemiluminescence immunoassay.

Granulocyte-macrophage colony-stimulating factor to reverse sepsis-associated immunosuppression: a double-blind, randomized, placebo-controlled multicenter trial.

Rationale: Sustained sepsis-associated immunosuppression is associated with uncontrolled infection, multiple organ dysfunction, and death.

Objectives: In the first controlled biomarker-guided immunostimulatory trial in sepsis, we tested whether granulocyte-macrophage colony-stimulating factor (GM-CSF) reverses monocyte deactivation, a hallmark of sepsis-associated immunosuppression (primary endpoint), and improves the immunological and clinical course of patients with sepsis.

Methods: In a prospective, randomized, double-blind, placebo-controlled, multicenter trial, 38 patients (19/group) with severe sepsis or septic shock and sepsis-associated immunosuppression (monocytic HLA-DR [mHLA-DR] <8,000 monoclonal antibodies (mAb) per cell for 2 d) were treated with GM-CSF (4 microg/kg/d) or placebo for 8 days.

Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review.

Context: The benefit of corticosteroids in severe sepsis and septic shock remains controversial.

Objective: We examined the benefits and risks of corticosteroid treatment in severe sepsis and septic shock and the influence of dose and duration.

Data Sources: We searched the CENTRAL, MEDLINE, EMBASE, and LILACS (through March 2009) databases as well as reference lists of articles and proceedings of major meetings, and we contacted trial authors.

Adjunctive therapies in severe sepsis and septic shock: current place of steroids.

For more than five decades, the use of corticosteroids as an adjunctive therapy to treat severe sepsis and septic shock has incited consistent debate. Negative results of the Corticosteroid Therapy of Septic Shock (CORTICUS) study evoked a revision of Surviving Sepsis Campaign guidelines suggesting a more restricted use of low-dose hydrocortisone only in patients with severe septic shock. Hemodynamic improvement by low-dose steroids was evident and independent from adrenal insufficiency, but did not improve survival.

Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine.

Objective: To develop consensus statements for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients.

Participants: A multidisciplinary, multispecialty task force of experts in critical care medicine was convened from the membership of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. In addition, international experts in endocrinology were invited to participate.

Hydrocortisone therapy for patients with septic shock.

Background: Hydrocortisone is widely used in patients with septic shock even though a survival benefit has been reported only in patients who remained hypotensive after fluid and vasopressor resuscitation and whose plasma cortisol levels did not rise appropriately after the administration of corticotropin.

Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, we assigned 251 patients to receive 50 mg of intravenous hydrocortisone and 248 patients to receive placebo every 6 hours for 5 days; the dose was then tapered during a 6-day period. At 28 days, the primary outcome was death among patients who did not have a response to a corticotropin test.

Bispectral index monitoring does not improve anesthesia performance in patients with movement disorders undergoing deep brain stimulating electrode implantation.

Background: Deep brain stimulation (DBS) has emerged as a promising therapy for movement disorders. During the implantation procedure for the electrodes, the patient emerges from anesthesia repeatedly to facilitate neurological testing. We investigated whether Bispectral Index (BIS) monitoring would be beneficial in patients receiving "sleep-awake-sleep" anesthesia with respect to time of arousal, consumption of propofol, and cardiopulmonary stability (i.