Effects of IV fluid restriction according to site-specific intensity of standard fluid treatment-protocol.

Background: Variation in usual practice in fluid trials assessing lower versus higher volumes may affect overall comparisons. To address this, we will evaluate the effects of heterogeneity in treatment intensity in the Conservative versus Liberal Approach to Fluid Therapy of Septic Shock in Intensive Care trial. This will reflect the effects of differences in site-specific intensities of standard fluid treatment due to local practice preferences while considering participant characteristics.

Albumin use in patients with septic shock-Post-hoc analyses of an international randomised fluid trial.

Background: Albumin administration is suggested in patients with sepsis and septic shock who have received large volumes of crystalloids. Given lack of firm evidence, clinical practice variation may exist. To address this, we investigated if patient characteristics or trial site were associated with albumin use in septic shock.

Restrictive versus standard IV fluid therapy in adult ICU patients with septic shock-Bayesian analyses of the CLASSIC trial.

Background: The CLASSIC trial assessed the effects of restrictive versus standard intravenous (IV) fluid therapy in adult intensive care unit (ICU) patients with septic shock. This pre-planned study provides a probabilistic interpretation and evaluates heterogeneity in treatment effects (HTE).

Methods: We analysed mortality, serious adverse events (SAEs), serious adverse reactions (SARs) and days alive without life-support within 90 days using Bayesian models with weakly informative priors.

Long-term effects of restriction of intravenous fluid in adult ICU patients with septic shock.

Purpose: To assess long-term outcomes of restrictive versus standard intravenous (IV) fluid therapy in adult intensive care unit (ICU) patients with septic shock included in the European Conservative versus Liberal Approach to Fluid Therapy in Septic Shock in Intensive Care (CLASSIC) trial.

Methods: We conducted the pre-planned analyses of mortality, health-related quality of life (HRQoL) using EuroQol (EQ)-5D-5L index values and EQ visual analogue scale (VAS), and cognitive function using Mini Montreal Cognitive Assessment (Mini MoCA) test at 1 year. Deceased patients were assigned numerical zero for HRQoL as a state equal to death and zero for cognitive function outcomes as worst possible score, and we used multiple imputation for missing data on HRQoL and cognitive function.

Albumin administration in septic shock-Protocol for post-hoc analyses of data from a multicentre RCT.

Background: Intravenous (IV) albumin is suggested for patients with septic shock who have received large amounts of IV crystalloids; a conditional recommendation based on moderate certainty of evidence. Clinical variation in the administration of IV albumin in septic shock may exist according to patient characteristics and location.

Methods: This is a protocol and statistical analysis plan for a post-hoc secondary study of the Conservative versus Liberal Approach to Fluid Therapy of Septic Shock in Intensive Care (CLASSIC) RCT of 1554 adult ICU patients with septic shock.

Lower vs Higher Fluid Volumes in Adult Patients With Sepsis: An Updated Systematic Review With Meta-Analysis and Trial Sequential Analysis.

Background: IV fluids are recommended for adults with sepsis. However, the optimal strategy for IV fluid management in sepsis is unknown, and clinical equipoise exists.

Research Question: Do lower vs higher fluid volumes improve patient-important outcomes in adult patients with sepsis?

Study Design And Methods: We updated a systematic review with meta-analysis and trial sequential analysis of randomized clinical trials assessing lower vs higher IV fluid volumes in adult patients with sepsis.

Restriction of Intravenous Fluid in ICU Patients with Septic Shock.

Background: Intravenous fluids are recommended for the treatment of patients who are in septic shock, but higher fluid volumes have been associated with harm in patients who are in the intensive care unit (ICU).

Methods: In this international, randomized trial, we assigned patients with septic shock in the ICU who had received at least 1 liter of intravenous fluid to receive restricted intravenous fluid or standard intravenous fluid therapy; patients were included if the onset of shock had been within 12 hours before screening. The primary outcome was death from any cause within 90 days after randomization.

Conservative vs. liberal fluid therapy in septic shock - Protocol for secondary Bayesian analyses of the CLASSIC trial.

Background: Clinical equipoise exists regarding intravenous (IV) fluid volumes in sepsis. The Conservative vs. Liberal Approach to fluid therapy of Septic Shock in Intensive Care (CLASSIC) trial investigates the effect of restricted vs.

Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia: The COVID STEROID randomised, placebo-controlled trial.

Background: In the early phase of the pandemic, some guidelines recommended the use of corticosteroids for critically ill patients with COVID-19, whereas others recommended against the use despite lack of firm evidence of either benefit or harm. In the COVID STEROID trial, we aimed to assess the effects of low-dose hydrocortisone on patient-centred outcomes in adults with COVID-19 and severe hypoxia.

Methods: In this multicentre, parallel-group, placebo-controlled, blinded, centrally randomised, stratified clinical trial, we randomly assigned adults with confirmed COVID-19 and severe hypoxia (use of mechanical ventilation or supplementary oxygen with a flow of at least 10 L/min) to either hydrocortisone (200 mg/d) vs a matching placebo for 7 days or until hospital discharge.

An international comparison of the cost of fluid resuscitation therapies.

Objective: Fluid resuscitation is a ubiquitous intervention in the management of patients treated in the intensive care unit, which has implications for intensive care unit resourcing and budgets. Our objective was to calculate the relative cost of resuscitation fluids in several countries to inform future economic evaluations.

Methods: We collected site-level data regarding the availability and cost of fluids as part of an international survey.

Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia (COVID STEROID) trial-Protocol and statistical analysis plan.

Introduction: Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance.

Neutrophil Gelatinase-Associated Lipocalin Measured on Clinical Laboratory Platforms for the Prediction of Acute Kidney Injury and the Associated Need for Dialysis Therapy: A Systematic Review and Meta-analysis.

Rationale & Objective: The usefulness of measures of neutrophil gelatinase-associated lipocalin (NGAL) in urine or plasma obtained on clinical laboratory platforms for predicting acute kidney injury (AKI) and AKI requiring dialysis (AKI-D) has not been fully evaluated. We sought to quantitatively summarize published data to evaluate the value of urinary and plasma NGAL for kidney risk prediction.

Study Design: Literature-based meta-analysis and individual-study-data meta-analysis of diagnostic studies following PRISMA-IPD guidelines.

Lower vs Higher Fluid Volumes During Initial Management of Sepsis: A Systematic Review With Meta-Analysis and Trial Sequential Analysis.

Objective: IV fluids are recommended during the initial management of sepsis, but the quality of evidence is low, and clinical equipoise exists. We aimed to assess patient-important benefits and harms of lower vs higher fluid volumes in adult patients with sepsis.

Methods: We conducted a systematic review with meta-analysis and trial sequential analysis (TSA) of randomized clinical trials of IV fluid volume separation in adult patients with sepsis.

Long-term patient-important outcomes after septic shock: A protocol for 1-year follow-up of the CLASSIC trial.

Background: In patients with septic shock, mortality is high, and survivors experience long-term physical, mental and social impairments. The ongoing Conservative vs Liberal Approach to fluid therapy of Septic Shock in Intensive Care (CLASSIC) trial assesses the benefits and harms of a restrictive vs standard-care intravenous (IV) fluid therapy. The hypothesis is that IV fluid restriction improves patient-important long-term outcomes.

Conservative vs liberal fluid therapy in septic shock (CLASSIC) trial-Protocol and statistical analysis plan.

Introduction: Intravenous (IV) fluid is a key intervention in the management of septic shock. The benefits and harms of lower versus higher fluid volumes are unknown and thus clinical equipoise exists. We describe the protocol and detailed statistical analysis plan for the conservative versus liberal approach to fluid therapy of septic shock in the Intensive Care (CLASSIC) trial.