Evaluation of GSK2789917-induced TRPV4 inhibition in animal models of fluid induced lung injury.

Administration of bolus intravenous fluids, common in pre-hospital and hospitalised patients, is associated with increased lung vascular permeability and mortality outside underlying disease states. In our laboratory, the induction of lung injury and oedema through rapid administration of intravenous fluid in rats was reduced by a non-specific antagonist of transient receptor potential vanilloid 4 (TRPV4) channels. The aims of this study were to determine the effect of selective TRPV4 inhibition on fluid-induced lung injury (FILI) and compare the potency of FILI inhibition to that of an established model of TRPV4 agonist-induced lung oedema.

A New Global Definition of Acute Respiratory Distress Syndrome.

Since publication of the 2012 Berlin definition of acute respiratory distress syndrome (ARDS), several developments have supported the need for an expansion of the definition, including the use of high-flow nasal oxygen, the expansion of the use of pulse oximetry in place of arterial blood gases, the use of ultrasound for chest imaging, and the need for applicability in resource-limited settings. A consensus conference of 32 critical care ARDS experts was convened, had six virtual meetings (June 2021 to March 2022), and subsequently obtained input from members of several critical care societies. The goal was to develop a definition that would ) identify patients with the currently accepted conceptual framework for ARDS, ) facilitate rapid ARDS diagnosis for clinical care and research, ) be applicable in resource-limited settings, ) be useful for testing specific therapies, and ) be practical for communication to patients and caregivers.

Monocyte chemotactic protein (MCP)-1 (CCL2) and its receptor (CCR2) are elevated in chronic heart failure facilitating lung monocyte infiltration and differentiation which may contribute to lung fibrosis.

Background: Dyspnea, the cardinal manifestation of chronic heart failure (CHF), may reflect both pulmonary oedema and pulmonary remodeling resulting in tissue stiffening. Emerging evidence suggests that predominance of distinct phenotypes of alveolar and recruited macrophages, designated M1 and M2, may regulate the course of inflammatory tissue repair and remodeling in the lung.

Methods: In a CHF rat model, we found fibrotic reinforcement of the extracellular matrix with an increase in monocyte chemotactic protein (MCP)-1/CCL2 in bronchoalveolar lavage (BAL), corresponding to a 3-fold increase in recruited macrophages.

ADMA and homoarginine independently predict mortality in critically ill patients.

Background: Arginine metabolites are associated with cardiovascular and all-cause mortality in several patient groups. We investigated whether arginine metabolites are associated with mortality in patients with critical illness and whether associations are independent of other factors affecting prognosis in an Intensive Care Unit (ICU).

Methods: 1155 acutely unwell adult patients admitted to a mixed medical-surgical ICU were studied.

Hospital-acquired complications: the relative importance of hospital- and patient-related factors.

Objective: To quantify the prevalence of hospital-acquired complications; to determine the relative influence of patient- and hospital-related factors on complication rates.

Design, Participants: Retrospective analysis of administrative data (Integrated South Australian Activity Collection; Victorian Admitted Episodes Dataset) for multiple-day acute care episodes for adults in public hospitals.

Setting: Thirty-eight major public hospitals in South Australia and Victoria, 2015-2018.

Induced hypernatremia in patients with moderate-to-severe ARDS: a randomized controlled study.

Background: Induced hypernatremia and hyperosmolarity is protective in animal models of lung injury. We hypothesized that increasing and maintaining plasma sodium between 145 and 150 mmol/l in patients with moderate-to-severe ARDS would be safe and will reduce lung injury. This was a prospective randomized feasibility study in moderate-to-severe ARDS, comparing standard care with intravenous hypertonic saline to achieve and maintain plasma sodium between 145 and 150 mmol/l for 7 days (HTS group).

Potential for bacteriophage therapy for pneumonia with influenza A coinfection.

The ability of influenza A virus to evolve, coupled with increasing antimicrobial resistance, could trigger an influenza pandemic with great morbidity and mortality. Much of the 1918 influenza pandemic mortality was likely due to bacterial coinfection, including pneumonia. resists many antibiotics.

Understanding Restrictive Versus Liberal Fluid Therapy for Major Abdominal Surgery Trial Results: Did Liberal Fluids Associate With Increased Endothelial Injury Markers?

Unlabelled: Liberal fluid strategies in critically ill patients are associated with harm, thought to be due to endothelial and glycocalyx injury. As the restrictive versus liberal fluid therapy for major abdominal surgery trial not only failed to report survival benefit with restrictive fluids but was associated with a higher rate of acute kidney injury, we hypothesized that factors other than endothelial and glycocalyx injury were likely to account for these findings. Consequently, we measured injury biomarkers in a cohort of the restrictive versus liberal fluid therapy for major abdominal surgery trial.

Systemic Markers of Monocyte Activation in Acute Pulmonary Oedema.

Background: Hydrostatic lung injury followed by pulmonary remodelling variably complicates cardiogenic acute pulmonary oedema (APO). Pulmonary remodelling may be regulated by the balance between distinct phenotypes of pulmonary macrophages; activated/inflammatory (M1), and reparative/anti-inflammatory (M2), derived from circulating monocyte populations. The aim of this study was to identify biomarkers in peripheral blood that are consistent with hydrostatic lung injury and pulmonary remodelling in APO and which follow the variable clinical course.

Reduced Surfactant Contributes to Increased Lung Stiffness Induced by Rapid Inspiratory Flow.

Introduction: The mechanism of fast inspiratory flow rate (V') induced lung injury is unclear. As fast V' increases hysteresis, a measure of surface tension at the air-liquid interface, surfactant release or function may be important. This experimental study examines the contribution of impaired surfactant release or function to dynamic-VILI.

Prevention and Amelioration of Rodent Ventilation-Induced Lung Injury with Either Prophylactic or Therapeutic feG Administration.

Purpose: Mechanical ventilation is a well-established therapy for patients with acute respiratory failure. However, up to 35% of mortality in acute respiratory distress syndrome may be attributed to ventilation-induced lung injury (VILI). We previously demonstrated the efficacy of the synthetic tripeptide feG for preventing and ameliorating acute pancreatitis-associated lung injury.

Efficacy and safety of 20% albumin fluid loading in healthy subjects: a comparison of four resuscitation fluids.

Recently, buffered salt solutions and 20% albumin (small volume resuscitation) have been advocated as an alternative fluid for intravenous resuscitation. The relative comparative efficacy and potential adverse effects of these solutions have not been evaluated. In a randomized, double blind, cross-over study of six healthy male subjects we compared the pulmonary and hemodynamic effects of intravenous administration of 30 ml/kg of 0.

Healthcare costs and outcomes for patients undergoing tracheostomy in an Australian tertiary level referral hospital.

Objective: Patients undergoing tracheostomy represent a unique cohort, as often they have prolonged hospital stay, require multi-disciplinary, resource-intensive care, and may have poor outcomes. Currently, there is a lack of data around overall healthcare cost for these patients and their outcomes in terms of morbidity and mortality. The objective of the study was to estimate healthcare costs and outcomes associated in tracheostomy patients at a tertiary level hospital in South Australia.

Addressing the inadvertent sodium and chloride burden in critically ill patients: a prospective before-and-after study in a tertiary mixed intensive care unit population.

Background: Inadvertent fluid loading - and resultant sodium and chloride - is common in critically ill patients. Sources such as fluid used as vehicles for drug infusions and boluses (fluid creep) and maintenance fluid are a common cause. We hypothesised that total sodium and chloride loading can be safely reduced in critically ill patients both by the use of 5% glucose as a diluent for infusions and boluses, when possible, and by its use as a maintenance fluid.

Small volume resuscitation with 20% albumin in intensive care: physiological effects : The SWIPE randomised clinical trial.

Purpose: We set out to assess the resuscitation fluid requirements and physiological and clinical responses of intensive care unit (ICU) patients resuscitated with 20% albumin versus 4-5% albumin.

Methods: We performed a randomised controlled trial in 321 adult patients requiring fluid resuscitation within 48 h of admission to three ICUs in Australia and the UK.

Results: The cumulative volume of resuscitation fluid at 48 h (primary outcome) was lower in the 20% albumin group than in the 4-5% albumin group [median difference - 600 ml, 95% confidence interval (CI) - 800 to - 400; P < 0.

Fluid resuscitation associated with elevated angiopoietin-2 and length of mechanical ventilation after cardiac surgery.

Background: Fluid restriction in patients with acute respiratory distress syndrome increases ventilator-free days while lowering plasma angiopoietin-2 (Ang-2), a marker of pulmonary endothelial injury. We hypothesised that fluid resuscitation may lead to endothelial injury after cardiac surgery and analysed Ang-2, angiopoietin-1 (Ang-1) and phospholipase A (PLA) levels and the impact of fluid management on ventilation time.

Methods: Patients enrolled in a single-centre, prospectively randomised interventional study of liberal or conservative fluid resuscitation strategy had plasma Ang-2, Ang-1 and PLA levels measured at baseline (pre-operative), 6 and 24 hours after commencement of cardiopulmonary bypass, and analysed by linear mixed models as liberal conservative (intention to treat) or high low fluid group (actual treatment, ≥ 3250 mL of fluid administered), and further subclassified as EuroSCORE (European System for Cardiac Operative Risk Evaluation) II ≥ 0.

Concordance between point-of-care blood gas analysis and laboratory autoanalyzer in measurement of hemoglobin and electrolytes in critically ill patients.

Background: We tested the hypothesis that the results of the same test performed on point-of-care blood gas analysis (BGA) machine and automatic analyzer (AA) machine in central laboratory have high degree of concordance in critical care patients and that the two test methods could be used interchangeably.

Methods: We analyzed 9398 matched pairs of BGA and AA results, obtained from 1765 patients. Concentration pairs of the following analytes were assessed: hemoglobin, glucose, sodium, potassium, chloride, and bicarbonate.

Lung fluid clearance in chronic heart failure patients.

Chronic elevation of pulmonary microvascular pressure (Pmv) consistently leads to alveolocapillary barrier thickening and reduction in the filtration coefficient. In animal models of chronic heart failure (CHF) the lung remains dry despite hydrostatic forces. As fluid flux is bi-directional, it has been postulated that an increase in alveolar fluid clearance may facilitate the dry lung when Pmv is chronically elevated.