To the Editor, Most patients requiring intensive care unit (ICU) admission for Coronavirus disease 2019 (COVID-19) presented acute respiratory distress syndrome (ARDS) [1]. However, a significant proportion of critically ill COVID-19 patients developed an acute COVID-19 cardiovascular syndrome (ACovCS) characterized by acute myocardial injury, evidenced by an increase in circulating biomarkers including

Mechanical ventilation can induce or even worsen lung injury, at least in part via overdistension caused by too large volumes or too high pressures. The complement system has been suggested to play a causative role in ventilator-induced lung injury. This was a single-center prospective study investigating associations between pulmonary levels of complement activation products and two ventilator settings

Accumulated airway secretions in the endotracheal tube increase work of breathing and may favor airway colonization eventually leading to pneumonia. The aim of this preplanned substudy of the ‘Preventive Nebulization of Mucolytic Agents and Bronchodilating Drugs in Intubated and Ventilated Intensive Care Unit Patients trial’ (NEBULAE) was to compare the effect of routine vs on-demand nebulization of

The animal experimental counterpart of human acute respiratory distress syndrome (ARDS) is acute lung injury (ALI). Most models of ALI involve reproducing the clinical risk factors associated with human ARDS, such as sepsis or acid aspiration; however, none of these models fully replicates human ARDS. To compare different experimental animal models of ALI, based on direct or indirect mechanisms of

Outcome prediction in critically ill patients under invasive ventilation remains extremely challenging. The driving pressure (ΔP) and the mechanical power of ventilation (MP) are associated with patient-centered outcomes like mortality and duration of ventilation. The objective of this study was to assess the predictive validity for mortality of the ΔP and the MP at 24 h after start of invasive ventilation

Continuous external negative pressure (CENP) during positive pressure ventilation can recruit dependent lung regions. We hypothesised that CENP applied regionally to the thorax or the abdomen only, increases the caudal end-expiratory transpulmonary pressure depending on positive end-expiratory pressure (PEEP) in lung-injured pigs. Eight pigs were anesthetised and mechanically ventilated in the supine

Patients with liver diseases are at high risk for the development of acute respiratory distress syndrome (ARDS). The liver is an important organ that regulates a complex network of mediators and modulates organ interactions during inflammatory disorders. Liver function is increasingly recognized as a critical determinant of the pathogenesis and resolution of ARDS, significantly influencing the prognosis

Alkaline phosphatase (AP), a dephosphorylating enzyme, is involved in various physiological processes and has been shown to have anti-inflammatory effects. To determine the correlation between pulmonary AP activity and markers of inflammation in invasively ventilated critically ill patients with or without acute respiratory distress syndrome (ARDS), and to investigate the effect of administration of

Outcome prediction in patients with acute respiratory distress syndrome (ARDS) greatly improves when patients are reclassified based on predefined arterial oxygen partial pressure to fractional inspired oxygen ratios (PaO2/FiO2) and positive end–expiratory pressure (PEEP) cutoffs 24 h after the initial ARDS diagnosis. The aim of this study was to test whether outcome prediction improves when patients

In hemorrhaging trauma patients, the endothelium is activated, resulting in excessive endothelial synthesis of von Willebrand Factor (vWF), which may enhance micro-thrombi formation, resulting in obstruction of the microcirculation and endothelial injury, aggravating bleeding, as well as contributing to organ failure. Under normal conditions, vWF is cleaved by the metalloprotease ADAMTS-13. After trauma

In patients with acute respiratory distress syndrome (ARDS), lung recruitment could be maximised with the use of recruitment manoeuvres (RM) or applying a positive end-expiratory pressure (PEEP) higher than what is necessary to maintain minimal adequate oxygenation. We aimed to determine whether ventilation strategies using higher PEEP and/or RMs could decrease mortality in patients with ARDS. We searched

Glucocorticoids (GCs) are stress hormones that regulate developmental and physiological processes and are among the most potent anti-inflammatory drugs to suppress chronic and acute inflammation. GCs act through the glucocorticoid receptor (GR), a ubiquitously expressed ligand-activated transcription factor, which translocates into the nucleus and can act via two different modes, as a GR monomer or

This review addresses the plausibility of hydrogen sulfide (H2S) therapy for acute lung injury (ALI) and circulatory shock, by contrasting the promising preclinical results to the present clinical reality. The review discusses how the narrow therapeutic window and width, and potentially toxic effects, the route, dosing, and timing of administration all have to be balanced out very carefully. The development

In acute respiratory distress syndrome (ARDS), increased pulmonary vascular permeability makes the lung vulnerable to edema. The use of conservative as compared to liberal fluid strategies may increase the number of ventilator-free days and survival, as well as reduce organ dysfunction. Monitoring the effects of fluid administration is of the utmost importance; dynamic indexes, such as stroke volume

Immune cell activation leads to the acquisition of new functions, such as proliferation, chemotaxis, and cytokine production. These functional changes require continuous metabolic adaption in order to sustain ATP homeostasis for sufficient host defense. The bioenergetic demands are usually met by the interconnected metabolic pathways glycolysis, TCA cycle, and oxidative phosphorylation. Apart from

Flow-controlled ventilation (FCV) allows expiratory flow control, reducing the collapse of the airways during expiration. The performance of FCV during one-lung ventilation (OLV) under intravascular normo- and hypovolaemia is currently unknown. In this explorative study, we hypothesised that OLV with FCV improves PaO2 and reduces mechanical power compared to volume-controlled ventilation (VCV). Sixteen

Acute ischaemic stroke is associated with a high risk of non-neurological complications, which include respiratory failure, cardiovascular dysfunction, kidney and liver injury, and altered immune and endocrine function. The aim of this manuscript is to provide an overview of the main forms of stroke-induced distal organ damage, providing new pathophysiological insights and recommendations for clinical

Extracellular vesicles (EVs) are small, lipid bilayer-delimited particles of cellular origin that recently gained increasing attention for their potential use as diagnostic biomarkers, and beyond that for their role in intercellular communication and as regulators of homeostatic and disease processes. In acute kidney injury (AKI) and chronic kidney disease (CKD), the potential use of EVs as diagnostic

Sepsis is a syndrome of shock and dysfunction of multiple vital organs that is caused by an uncontrolled immune response to infection and has a high mortality rate. There are no therapies for sepsis, and it has become a global cause for concern. Advances in patient care and management now mean that most patients survive the initial hyper-inflammatory phase of sepsis but progress to a later immunosuppressed

Post cardiac arrest syndrome is associated with high morbidity and mortality, which is related not only to a poor neurological outcome but also to respiratory and cardiovascular dysfunctions. The control of gas exchange, and in particular oxygenation and carbon dioxide levels, is fundamental in mechanically ventilated patients after resuscitation, as arterial blood gases derangement might have important

Targeted hypothermia, as used after cardiac arrest, increases electrical and mechanical systolic duration. Differences in duration of electrical and mechanical systole are correlated to ventricular arrhythmias. The electromechanical window (EMW) becomes negative when the electrical systole outlasts the mechanical systole. Prolonged electrical systole corresponds to prolonged QT interval, and is associated

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COVID19 is caused by the SARS-CoV-2 virus and has been associated with severe inflammation leading to organ dysfunction and mortality. Our aim was to profile the transcriptome in leukocytes from critically ill patients positive for COVID19 compared to those negative for COVID19 to better understand the COVID19-associated host response. For these studies, all patients admitted to our tertiary care intensive

When severe, COVID-19 shares many clinical features with bacterial sepsis. Yet, secondary bacterial infection is uncommon. However, as epithelium is injured and barrier function is lost, bacterial products entering the circulation might contribute to the pathophysiology of COVID-19. We studied 19 adults, severely ill patients with COVID-19 infection, who were admitted to King Chulalongkorn Memorial

Ex vivo lung perfusion (EVLP) is a widespread accepted platform for preservation and evaluation of donor lungs prior to lung transplantation (LTx). Standard lungs are ventilated using volume-controlled ventilation (VCV). We investigated the effects of flow-controlled ventilation (FCV) in a large animal EVLP model. Fourteen porcine lungs were mounted on EVLP after a warm ischemic interval of 2 h and

Nosocomial infection contributes to adverse outcome after brain injury. This study investigates whether autonomic nervous system activity is associated with a decreased host immune response in patients following stroke or traumatic brain injury (TBI). A prospective study was performed in adult patients with TBI or stroke who were admitted to the Intensive Care Unit of our tertiary university hospital

Intensive care unit workers are at high risk of acquiring COVID-19 infection, especially when performing invasive techniques and certain procedures that generate aerosols (< 5 μm). Therefore, one of the objectives of the health systems should implement safety practices to minimize the risk of contagion among these health professionals. Monitoring environmental contamination of SARS-CoV-2 may help to

Lethal B. anthracis infection produces high proinflammatory peptidoglycan (PGN) burdens in hosts. We investigated whether the lethality and inflammation anthrax PGN can produce are related. At 6 h before and the start of 24 h anthrax PGN infusions, rats (n = 198) were treated with diluent (controls) or one of three IV-doses of either hydrocortisone (125, 12.5 or 1.25 mg/kg) or TNF-soluble receptor

Traumatic brain injury (TBI) is one of the most frequent and severe neurological diseases. In the last few decades, significant advances have been made in TBI pathophysiology and monitoring, however new treatments have not emerged. Although the central nervous system (CNS) has been historically defined as an immunologically privileged organ, recent studies show the increasingly predominant role of

Intensive Care Medicine Experimental (ICMx) was founded as an official journal of the European Society of Intensive Care Medicine (ESICM) community, in recognition that an improved understanding of the underlying pathophysiology of critical care syndromes is essential to advance clinical care for our patients. As a sister journal to Intensive Care Medicine (ICM), that focusses on publishing clinical

Venous–arterial carbon dioxide (CO2) to arterial–venous oxygen (O2) content difference ratio (Cv-aCO2/Ca-vO2) > 1 is supposed to be both sensitive and specific for anaerobic metabolism. What regional hemodynamic and metabolic parameters determine the ratio has not been clarified. To address determinants of systemic and renal, spleen, gut and liver Cv-aCO2/Ca-vO2. Post hoc analysis of original data

There are limited therapeutic options directed at the underlying pathological processes in acute respiratory distress syndrome (ARDS). Experimental therapeutic strategies have targeted the protective systems that become deranged in ARDS such as surfactant. Although results of surfactant replacement therapy (SRT) in ARDS have been mixed, questions remain incompletely answered regarding timing and dosing

Existing clinical practice guidelines support the use of neuromuscular blocking agents (NMBA) in acute respiratory distress syndrome (ARDS); however, a recent large randomized clinical trial (RCT) has questioned this practice. Therefore, we updated a previous systematic review to determine the efficacy and safety of NMBAs in ARDS. We searched MEDLINE, EMBASE (October 2012 to July 2019), the Cochrane

Early treatment of severe hyperglycemia involves large shifts of body fluids that entail a risk of hemodynamic instability. We studied the feasibility of applying a new electrolyte equation that estimates the degree of volume depletion and the distribution of infused 0.9% saline in this setting. The new equation was applied to plasma and urinary concentrations of sodium and chloride measured before

Stroke volume measurement should provide estimates of acute treatment responses. The current pulse contour method estimates left ventricle stroke volume. Heart-lung interactions change right ventricular stroke volume acutely. We investigated the accuracy, precision, and trending abilities of four calibrated stroke volume estimates based on pulmonary artery pulse contour analysis. Stroke volume was

To the Editor, We thank Peyton and Fletcher for their interest in our paper, where we devised a method to infer shunt fraction from a single arterial blood gas sample, with the intention to allow clinical research and prediction without the need for additional invasive measurements, as stated both in the abstract and the main text of our report. Peyton and Fletcher have usefully emphasised this point

The ex vivo human perfused lung model has enabled optimizing donor lungs for transplantation and delineating mechanisms of lung injury. Perfusate and airspace biomarkers are a proxy of the lung response to experimental conditions. However, there is a lack of studies evaluating biomarker kinetics during perfusion and after exposure to stimuli. In this study, we analyzed the ex vivo-perfused lung response

Change of the corrected flow time (Ftc) is a surrogate for tracking stroke volume (SV) in the intensive care unit. Multiple Ftc equations have been proposed; many have not had their diagnostic characteristics for detecting SV change reported. Further, little is known about the inherent Ftc variability induced by the respiratory cycle. Using a wearable Doppler ultrasound patch, we studied the clinical

Immunological dysfunction is common in critically ill patients but its clinical significance and the optimal method to measure it are unknown. The level of tumor necrosis factor alpha (TNF-α) after ex-vivo whole blood stimulation with lipopolysaccharide (LPS) has been proposed as a possible method to quantify immunological function. We hypothesized that in a cohort of critically ill patients, those

In the current pandemic of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), the therapeutic administration of oxygen is a common procedure in order to mitigate patient’s hypoxia in the course of severe corona virus disease 2019 (COVID-19) pneumonia. However, additional oxygen causes a variety of well-known side-effects, impacting a number of systems regulating cardiovascular and respiratory

Extracorporeal carbon dioxide removal (ECCO2R) is a promising yet limited researched therapy for hypercapnic respiratory failure in acute respiratory distress syndrome and exacerbated chronic obstructive pulmonary disease. Herein, we describe a new mock circuit that enables experimental ECCO2R research without animal models. In a second step, we use this model to investigate three experimental scenarios

Heparin-binding protein (HBP) is a neutrophil-derived pro-inflammatory protein, an inducer of endothelial dysfunction and vascular permeability and a promising prognostic biomarker in sepsis. This exploratory study aims to describe the kinetics of plasma HBP during septic shock and investigate an association between repeated measures of HBP concentration and cardiovascular organ dysfunction severity

Pseudo-pulseless electrical activity (pseudo-PEA) is a lifeless form of profound cardiac shock characterized by measurable cardiac mechanical activity without clinically detectable pulses. Pseudo-PEA may constitute up to 40% of reported cases of cardiac arrest. Resuscitation from pseudo-PEA is often associated with hypotension refractory to catecholamine pressors. We hypothesized that this post-resuscitation

The microbiome has emerged as an important player in the pathophysiology of a whole spectrum of diseases that affect the critically ill. We hypothesized that differences in microbiota composition across vendors can influence murine models of pulmonary lipopolysaccharide (LPS) inflammation and Gram-negative pneumonia. A multi-vendor approach was used with genetically similar mice derived from three

Non-invasive and lung-protective ventilation techniques may improve outcomes for patients with an acute exacerbation of chronic obstructive pulmonary disease or moderate acute respiratory distress syndrome by reducing airway pressures. These less invasive techniques can fail due to hypercapnia and require transitioning patients to invasive mechanical ventilation. Extracorporeal CO2 removal devices

Alteration of the mechanisms of cerebral blood flow (CBF) regulation might contribute to the pathophysiology of sepsis-associated encephalopathy (SAE). However, previous clinical studies on dynamic cerebral autoregulation (dCA) in sepsis had several cofounders. Furthermore, little is known on the potential impairment of neurovascular coupling (NVC) in sepsis. The aim of our study was to determine the

This study aimed to assess right ventricular (RV) function during cardiogenic shock due to acute left ventricular (LV) failure, including during LV unloading with Impella CP and an added moderate dose of norepinephrine. Cardiogenic shock was induced by injecting microspheres in the left main coronary artery in 18 adult Danish Landrace pigs. Conductance catheters were placed in both ventricles and pressure-volume

Acute bacterial meningitis is a disease with a high mortality and a high incidence of neurological sequelae in survivors. There is an acute need to develop new adjuvant therapies. To ensure that new therapies evaluated in animal models are translatable to humans, studies must evaluate clinically relevant and patient-important outcomes, including neurological symptoms and sequelae. We developed and

3,4-Methylenedioxymethamphetamine intoxication can result in potentially lethal multi-organ failure, for which the current treatment is largely supportive. Recently, a report of the use of the CytoSorb device as a part of the successful treatment of a patient with 3,4-methylenedioxymethamphetamine intoxication and multi-organ failure has been described. While 3,4-methylenedioxymethamphetamine was very

Positive end-expiratory pressure (PEEP) is used to optimize oxygenation by preventing alveolar collapse. However, PEEP can potentially decrease cardiac output through cardiopulmonary interactions. The effect of PEEP on cardiac output during cardiopulmonary resuscitation (CPR) is not known. This was a preclinical randomized, controlled, animal study conducted in an animal research facility on 25 Landrace-Yorkshire

To the Editor, In a recent review published in Intensive Care Medicine, Abrams et al. listed the research agenda of extracorporeal membrane oxygenation (ECMO)-associated infections. One of the questions was “how should cannula-associated infection be defined?” [1]. Literature on ECMO cannula-associated infections is very scarce [2, 3], and no clear definition is available. Then, diagnostic workup of

Noise levels on intensive care units (ICUs) are typically elevated. While many studies reported negative effects of ICU ambient sounds on patients, only few investigated noise as a factor to influence well-being or performance in healthcare professionals. An online survey in the German-speaking part of Switzerland was conducted to assess how ICU soundscapes are subjectively perceived by healthcare

Expound upon priorities for basic/translational science identified in a recent paper by a group of experts assigned by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Original paper, search of the literature. This study is selected by several members of the original task force with specific expertise in basic/translational science. Data extraction and data

An amendment to this paper has been published and can be accessed via the original article.

The water volume of the endothelial glycocalyx layer has been estimated at 0.7 to 1.7 L using tracer methods of unclear value. The present study attempts to measure this fluid volume by analyzing the kinetics of a crystalloid fluid load. An intravenous infusion of approximately 1 L of Ringer’s acetate was administered to 35 healthy volunteers, and the central volume of distribution of the water volume

We read with interest the recent paper on “a novel non-invasive estimation of effective shunt fraction” (Chang et al. Intensive Care Medicine Experimental (2019) 7:49) [1]. The study retrospectively investigated the validity of various oxygenation indices in predicting the change in PaO2 in response to a change in FIO2 in critically ill patients. In particular, they investigated a method to estimate

Primary blast lung injury (PBLI) presents as a syndrome of respiratory distress and haemoptysis resulting from explosive shock wave exposure and is a frequent cause of mortality and morbidity in both military conflicts and terrorist attacks. The optimal mode of mechanical ventilation for managing PBLI is not currently known, and clinical trials in humans are impossible due to the sporadic and violent

Plasma-Lyte is a balanced, crystalloid intravenous fluid which has been shown to avoid the hyperchloremic metabolic acidosis associated with 0.9% sodium chloride. Data on physical, pH and chemical compatibility with other medicines are essential. The compatibility of adrenaline, dobutamine, dopamine, furosemide, midazolam, morphine and milrinone with Plasma-Lyte 148 (PLA) and Plasma-Lyte 148 with 5%

3,4-Methylenedioxymethamphetamine (MDMA, “ecstasy”) abuse is frequent, and overdosing might cause severe and eventually lethal multi-organ failure. To date, there is no causal therapy of MDMA intoxication and removal of MDMA from the circulation might be a reasonable measure to prevent adverse courses after overdosing. We present here first-in-man experience and in vitro data supporting a potential

To the Editor, Sepsis shows a high incidence and is associated with a high mortality [1, 2], and experimental studies are useful for a better understanding of sepsis and for identifying new therapies [3]. The cecal ligation and puncture (CLP) model is considered as the gold standard experiment for studying sepsis