Marlies Ostermann

• PhD and MD
• Professor at King's College London Guy's and St Thomas' NHS Foundation Trust

Objectives In the Conservative vs. Liberal Approach to Fluid Therapy of Septic Shock in Intensive Care (CLASSIC) trial, restriction of IV fluid volumes led to similar overall mortality in ICU patients with septic shock. We assessed if variation in standard IV fluid treatment intensity across sites impacted the effects of fluid restriction. Design...

Introduction Feeding intolerance complicates enteral nutrition in intensive care unit (ICU) patients but is poorly defined. Prokinetic agents are administered to facilitate the uptake of enteral nutrition, but preferences for their use among clinicians in ICUs are unknown. Methods We conducted an international electronic survey targeting ICU docto...

Rationale: Early detection, standardized therapy, adequate infrastructure, and strategies for quality improvement should constitute essential components of every hospital's sepsis plan. Objectives: To investigate the extent to which recommendations from the sepsis guidelines are implemented and the availability of infrastructure for the care of pat...

Shock is a life-threatening condition marked by inadequate tissue perfusion and organ dysfunction with high morbidity and mortality. Activation of the sympatho-adrenergic system is pivotal in response to all four major categories (i.e., hypovolemic, distributive, cardiogenic, and obstructive). In addition, exogenous vasopressors are often used to m...

Background Artificial Intelligence (AI) through machine learning (ML) models appears to provide accurate and precise acute kidney injury (AKI) risk classification in some clinical settings, but their performance and implementation in real-world settings has not been established. Methods PubMed, EMBASE, Web of Science, and Scopus were searched unti...

Objectives Among critically ill patients with severe acute kidney injury (AKI) who lack emergent indications for renal replacement therapy (RRT), a strategy of preemptive RRT initiation does not lead to improved outcomes. However, for patients with persistent AKI and without urgent indications for RRT, the safety of prolonged delays in RRT initiati...

This systematic review and meta-analysis updates a previous evaluation of the performance of risk-prediction models for contrast-associated acute kidney injury.

Background Venous thromboembolism (VTE) is a frequent complication in critically ill patients, who often have multiple risk factors. Pharmacological thromboprophylaxis is widely applied to lower this risk, but guidelines lack dosing recommendations. Objective This survey aims to assess current thromboprophylaxis preferences and willingness to part...

Purpose: Intensive care unit (ICU) strain is associated with increased mortality. Most strain metrics focus on simple measures such as bed occupancy or admissions. There is limited data mitigation strategies, such as procedure teams or staff well-being services on strain, or the impact of increased patient-to-nurse ratios and non-ICU trained nurses...

Background No standardized index exists to assess cardiovascular responsiveness to angiotensin-II. We hypothesized that a standardized index of initial blood pressure response to angiotensin-II treatment would be associated with clinical outcomes. Methods Using data from the Angiotensin Therapy for High Output Shock (ATHOS-3) trial, we developed a...

Rationale: Early detection, standardized therapy, adequate infrastructure, and strategies for quality improvement should constitute essential components of every hospital's sepsis plan. Objectives: To investigate the extent to which recommendations from the sepsis guidelines are implemented and the availability of infrastructure for the care of pat...

Objectives Randomized clinical trials informing clinical practice (e.g., like large, pragmatic, and late-phase trials) should ideally mostly use harmonized outcomes that are important to patients, family members, clinicians, and researchers. Core outcome sets for specific subsets of ICU patients exist, for example, respiratory failure, delirium, an...

To generate consensus and provide expert clinical practice statements for the management of adult sepsis in resource-limited settings. An international multidisciplinary Steering Committee with expertise in sepsis management and including a Delphi methodologist was convened by the Asia Pacific Sepsis Alliance (APSA). The committee selected an inter...

Background Clinical practice guidelines recommend use of buffered crystalloid solutions in critically ill patients but do not distinguish between solutions based on different buffering anions, that is, acetate‐ versus lactate‐buffered solutions. We therefore surveyed relevant physicians about their preferences and attitudes toward each solution. M...

Dysregulation of the renin–angiotensin–aldosterone-system (RAAS) in sepsis is a complex and early phenomenon with a likely significant contribution to organ failure and patient outcomes. A better understanding of the pathophysiology and intricacies of the RAAS in septic shock has led to the use of exogenous angiotensin II as a new therapeutic agent...

The European Society of Intensive Care Medicine (ESICM) Green Paper aims to address the challenge of environmental sustainability in intensive care and proposes actionable strategies for integrating sustainability into intensive care unit (ICU) stakeholder actions. The ESICM Executive Committee appointed a task force of topic experts and ESICM comm...

Background Feeding intolerance is common in critically ill patients and can lead to malnutrition. Prokinetic agents may be used to enhance the uptake of nutrition. However, the evidence on the effectiveness and safety of prokinetic agents is sparse, and there is a lack of data on their use in intensive care units (ICU). Methods We will conduct an...

Acute kidney injury (AKI) is a multifactorial syndrome with a high risk of short- and long-term complications as well as increased health care costs. The traditional biomarkers of AKI, serum creatinine and urine output, have important limitations. The discovery of new functional and damage/stress biomarkers has enabled a more precise delineation of...

Background Post‐lung transplantation (LTx) fluid accumulation can lead to dilution of serum creatinine (SCr). We hypothesized that fluid accumulation might impact the diagnosis, staging, and outcome of posttransplant acute kidney injury (AKI). Methods In this retrospective study, we analyzed data from 131 adult LTx patients at a single German lung...

Acute kidney injury (AKI) is associated with an increased risk of morbidity, mortality, and healthcare expenditure, posing a major challenge in clinical practice, and affecting about 50% of patients in the intensive care unit (ICU), particularly the elderly and those with pre-existing chronic comorbidities. In health, intra-renal blood flow is main...

Novel interventions for the prevention or treatment of acute kidney injury (AKI) are currently lacking. To facilitate the evaluation and adoption of new treatments, the use of the most appropriate design and endpoints for clinical trials in AKI is critical and yet there is little consensus regarding these issues. We aimed to develop recommendations...

Background Rhabdomyolysis describes a syndrome characterized by muscle necrosis and the subsequent release of creatine kinase and myoglobin into the circulation. Myoglobin elimination with extracorporeal hemoadsorption has been shown to effectively remove myoglobin from the circulation. Our aim was to provide best practice consensus statements deve...

Purpose To generate consensus and provide expert clinical practice statements for the management of adult sepsis in resource-limited settings. Methods An international multidisciplinary Steering Committee with expertise in sepsis management and including a Delphi methodologist was convened by the Asia Pacific Sepsis Alliance (APSA). The committee...

Introduction Use of albumin is suggested for some patients with shock, but preferences for its use may vary among intensive care unit (ICU) physicians. Methods We conducted an international online survey of ICU physicians with 20 questions about their use of albumin and their opinion towards a randomised trial among adults with shock comparing the...

Background: Whether proton-pump inhibitors are beneficial or harmful for stress ulcer prophylaxis in critically ill patients undergoing invasive ventilation is unclear. Methods: In this international, randomized trial, we assigned critically ill adults who were undergoing invasive ventilation to receive intravenous pantoprazole (at a dose of 40...

Introduction Acute kidney injury (AKI) is a common complication of septic shock and together these conditions carry a high mortality risk. In septic patients who develop severe AKI, renal cortical perfusion is deficient despite normal macrovascular organ blood flow. This intra-renal perfusion abnormality may be amenable to pharmacological manipulat...

OBJECTIVES Acute kidney injury (AKI) is a common form of organ dysfunction in the ICU. AKI is associated with adverse short- and long-term outcomes, including high mortality rates, which have not measurably improved over the past decade. This review summarizes the available literature examining the evidence of the need for precision medicine in AKI...

Objective This article describes the statistical analysis plan for the Biomarker-guided intervention to prevent AKI after major surgery (BigpAK-2) trial. Design Adaptive trial design with an interim analysis after enrolment of 618 evaluable patients. Setting The BigpAK.-2 trial is an international, prospective, randomised controlled multicentre s...

Purpose Randomised clinical trials should ideally use harmonised outcomes that are important to patients and to facilitate meta-analyses and ensuring generalisability. Core outcome sets for specific subsets of ICU patients exist, e.g., respiratory failure, delirium, and COVID-19, but not for ICU patients in general. Accordingly, we aimed to develop...

Background During the COVID-19 pandemic, many intensive care units (ICUs) halted research to focus on COVID-19-specific studies. Objective To describe the conduct of an international randomized trial of stress ulcer prophylaxis (Re-Evaluating the Inhibition of Stress Erosions in the ICU [REVISE]) during the pandemic, addressing enrolment patterns,...

Background Urinary Chemokine (C–C motif) ligand 14 (CCL14) is a biomarker associated with persistent severe acute kidney injury (AKI). There is limited data to support the implementation of this AKI biomarker to guide therapeutic actions. Methods Sixteen AKI experts with clinical CCL14 experience participated in a Delphi-based method to reach cons...

Background Angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blockers (ARB) medications are widely prescribed. We sought to assess how pre-admission use of these medications might impact the response to angiotensin-II treatment during vasodilatory shock. Methods In a post-hoc subgroup analysis of the randomized, placebo-contr...

Adsorption-based extracorporeal therapies have been subject to technical developments and clinical application for close to five decades. More recently, new technological developments in membrane and sorbent manipulation have made it possible to deliver more biocompatible extracorporeal adsorption therapies to patients with a variety of conditions....

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 diff...

Background Vitamin D deficiency in critically ill patients is associated with poor outcomes, and vitamin D supplementation is recommended for patients with chronic kidney disease. Whether acute kidney injury (AKI) is associated with altered Vitamin D metabolism is unknown. We aimed to compare the longitudinal profiles of serum 25(OH)D and 1,25(OH)...

Acute kidney injury (AKI) often complicates sepsis and is associated with high morbidity and mortality. In recent years, several important clinical trials have improved our understanding of sepsis-associated AKI (SA-AKI) and impacted clinical care. Advances in sub-phenotyping of sepsis and AKI and clinical trial design offer unprecedented opportuni...

Background Ascertainment of the severity of the primary outcome of upper gastrointestinal (GI) bleeding is integral to stress ulcer prophylaxis trials. This protocol outlines the adjudication process for GI bleeding events in an international trial comparing pantoprazole to placebo in critically ill patients (REVISE: Re-Evaluating the Inhibition of...

OBJECTIVES Among patients with severe acute kidney injury (AKI) admitted to the ICU in high-income countries, regional practice variations for fluid balance (FB) management, timing, and choice of renal replacement therapy (RRT) modality may be significant. DESIGN Secondary post hoc analysis of the STandard vs. Accelerated initiation of Renal Repla...

OBJECTIVES To identify research priorities in the management, epidemiology, outcome, and pathophysiology of sepsis and septic shock. DESIGN Shortly after publication of the most recent Surviving Sepsis Campaign Guidelines, the Surviving Sepsis Research Committee, a multiprofessional group of 16 international experts representing the European Socie...

Ilofotase alfa is a human recombinant alkaline phosphatase with reno-protective effects that showed improved survival and reduced Major Adverse Kidney Events by 90 days (MAKE90) in sepsis-associated acute kidney injury (SA-AKI) patients. REVIVAL, was a phase-3 trial conducted to confirm its efficacy and safety. In this international double-blinded...

Background The physiological effects of renin-angiotensin system modulation in acute respiratory distress syndrome (ARDS) remain controversial and have not been investigated in randomized trials. We sought to determine whether angiotensin-II treatment is associated with improved oxygenation in shock-associated ARDS. Methods Post-hoc subgroup analy...

Background The REVISE (Re-Evaluating the Inhibition of Stress Erosions in the ICU) trial will evaluate the impact of the proton pump inhibitor pantoprazole compared to placebo in invasively ventilated critically ill patients. Objective To outline the statistical analysis plan for the REVISE trial. Methods REVISE is a randomized clinical trial ong...

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. Methods We conducted...

Introduction The R e- Ev aluating the I nhibition of S tress E rosions (REVISE) Trial aims to determine the impact of the proton pump inhibitor pantoprazole compared with placebo on clinically important upper gastrointestinal (GI) bleeding in the intensive care unit (ICU), 90-day mortality and other endpoints in critically ill adults. The objective...

Background Early mobilisation (EM) is an intervention that may improve the outcome of critically ill patients. There is limited data on EM in COVID-19 patients and its use during the first pandemic wave. Methods This is a pre-planned subanalysis of the ESICM UNITE-COVID, an international multicenter observational study involving critically ill COV...

Drug-induced kidney disease (DIKD) accounts for about one-fourth of all cases of acute kidney injury (AKI) in hospitalized patients, especially in critically ill setting. There is no standard definition or classification system of DIKD. To address this, a phenotype definition of DIKD using expert consensus was introduced in 2015. Recently, a novel...

Background Acute kidney injury (AKI) is independently associated with increased morbidity and mortality across the life course, yet care for AKI remains mostly supportive. Raising awareness of this life-threatening clinical syndrome through education and advocacy efforts is the key to improving patient outcomes. Here, we describe the unique roles e...

The development of new extracorporeal blood purification (EBP) techniques has led to increased application in clinical practice but also inconsistencies in nomenclature and misunderstanding. In November 2022, an international consensus conference was held to establish consensus on the terminology of EBP therapies. It was agreed to define EBP therap...

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 (...

There is controversy regarding the optimal renal-replacement therapy (RRT) modality for critically ill patients with acute kidney injury (AKI). We conducted a secondary analysis of the STandard versus Accelerated Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial to compare outcomes among patients who initiated RRT with either cont...

Background: Fluid overload is associated with increased mortality in intensive care unit (ICU) patients. The GODIF trial aims to assess the benefits and harms of fluid removal with furosemide versus placebo in stable adult patients with moderate to severe fluid overload in the ICU. This article describes the detailed statistical analysis plan for t...

Despite significant advancements in critical care medicine, limited attention has been given to sex and gender disparities in management and outcomes of patients admitted to the intensive care unit (ICU). While "sex" pertains to biological and physiological characteristics, such as reproductive organs, chromosomes and sex hormones, "gender" refers...

Acute kidney injury (AKI) in children is associated with increased morbidity, reduced health-related quality of life, greater resource utilization, and higher mortality. Improvements in the timeliness and precision of AKI diagnosis in children are needed. In this report, we highlight existing, novel, and on-the-horizon diagnostic and risk-stratific...

Acute kidney injury (AKI) is a common clinical condition with various causes and is associated with increased mortality. Despite advances in supportive care, AKI increases not only the risk of premature death compared with the general population but also the risk of developing chronic kidney disease and progressing towards kidney failure. Currently...

Background: Critically ill patients commonly receive proton pump inhibitors (PPIs) to prevent gastrointestinal (GI) bleeding from stress-induced ulceration. Despite widespread use in the intensive care unit (ICU), observational data suggest that PPIs may be associated with adverse outcomes in patients with COVID-19 infection. This preplanned study...

Acute kidney injury impacts the micronutrient status by various mechanisms including decreased enteral absorption, changes in redistribution, altered metabolism, and increased consumption. When renal replacement therapy (RRT) is applied, there are additional losses of vitamins, trace elements, and amino acids, and their derivatives due to diffusion...

Acute kidney injury (AKI), which is a common complication of acute illnesses, affects the health of individuals in community, acute care and post-acute care settings. Although the recognition, prevention and management of AKI has advanced over the past decades, its incidence and related morbidity, mortality and health care burden remain overwhelmin...

Introduction Drug-induced acute kidney injury (DI-AKI) is a frequent adverse event. The identification of DI-AKI is challenged by competing etiologies, clinical heterogeneity among patients, and a lack of accurate diagnostic tools. Our research aims to describe the clinical characteristics and predictive variables of DI-AKI. Methods We analyzed da...

Background: This Rapid Practice Guideline provides an evidence-based recommendation to address the question: in adults with sepsis or septic shock, should we recommend using or not using intravenous vitamin C therapy? Methods: The panel included 21 experts from 16 countries and used a strict policy for potential financial and intellectual confli...

Purpose: Ilofotase alfa is a human recombinant alkaline phosphatase with reno-protective effects that showed improved survival and reduced MAKE90 in sepsis-associated acute kidney injury (SA-AKI) patients. ‘REVIVAL’, was aphase 3 trial, conducted to confirm its efficacy and safety. Methods: In this international double-blinded randomized-controlled...

Background: Immune checkpoint inhibitors (ICPi) can cause immune-related adverse events (irAEs) including acute kidney injury (AKI). We investigated the incidence of ICPi-associated AKI (ICPi-AKI) and AKI from other causes (non-ICPi-AKI) in cancer patients treated with ICPi. Methods: This was a single-centre retrospective cohort study of patient...

PurposeTo 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, h...

Purpose: Venous thromboembolism (VTE) is a common complication of critical illness. Sex- or gender-based analyses are rarely conducted and their effect on outcomes is unknown. We assessed for an effect modification of thromboprophylaxis (dalteparin or unfractionated heparin [UFH]) by sex on thrombotic (deep venous thrombosis [DVT], pulmonary embol...

The Surviving Sepsis Campaign (SSC) International Guidelines for the Management of Sepsis and Septic Shock provide recommendations on the care of hospitalized adult patients with (or at risk for) sepsis. This review discusses what is new or different in the 2021 SSC adult sepsis guidelines compared to 2016. The guidelines include new weak recommend...

OBJECTIVES:. Acute kidney injury (AKI) and fluid overload (FO) are among the top reasons to initiate intermittent hemodialysis (IHD) or continuous renal replacement therapy (CRRT). Prior research suggests CRRT provides more precise volume control, but whether CRRT is cost-effective remains unclear. We assessed the cost-effectiveness of CRRT for vol...

Individuals with kidney failure undergoing maintenance dialysis frequently report a high symptom burden that can interfere with functioning and diminish life satisfaction. Until recently, the focus of nephrology care for dialysis patients has primarily related to numerical targets for laboratory measures and outcomes such as cardiovascular disease...

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: Thi...

Critical illness is a continuum, but patient care is often fragmented. Value-based critical care focuses on the overall health of the patient, not on an episode of care. The “ICU without borders” model incorporates a concept where members of the critical care team are involved in the management of patients from the onset of critical illness until r...

Therapeutic plasma exchange (TPE) is a therapeutic intervention that separates plasma from blood cells to remove pathological factors or to replenish deficient factors. The use of TPE is increasing over the last decades. However, despite a good theoretical rationale and biological plausibility for TPE as a therapy for numerous diseases or syndromes...

Background High dose vasopressors portend poor outcome in vasodilatory shock. We aimed to evaluate the impact of baseline vasopressor dose on outcomes in patients treated with angiotensin II (AT II). Methods Exploratory post-hoc analysis of the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) trial data. The ATHOS-3 trial randomized...

Anemia is common in patients with chronic kidney disease (CKD) and is associated with a high burden of morbidity and adverse clinical outcomes. In 2012, Kidney Disease: Improving Global Outcomes (KDIGO) published a guideline for the diagnosis and management of anemia in CKD. Since then, new data from studies assessing established and emerging thera...

Background: Despite its diagnostic and prognostic importance, physiologic dead space fraction is not included in the current ARDS definition or severity classification. ARDS caused by COVID-19 (C-ARDS) is characterized by increased physiologic dead space fraction and hypoxemia. Our aim was to investigate the relationship between dead space indices...