Pre-clinical study protocol: Blood transfusion in endotoxaemic shock.

The Surviving Sepsis Campaign (SCC) and the American College of Critical Care Medicine (ACCM) guidelines recommend blood transfusion in sepsis when the haemoglobin concentration drops below 7.0 g/dL and 10.0 g/dL respectively, while the World Health Organisation (WHO) guideline recommends transfusion in septic shock 'if intravenous (IV) fluids do not maintain adequate circulation', as a supportive measure of last resort.

Fluid resuscitation with 0.9% saline alters haemostasis in an ovine model of endotoxemic shock.

Introduction: Fluid resuscitation is a cornerstone of severe sepsis management, however there are many uncertainties surrounding the type and volume of fluid that is administered. The entire spectrum of coagulopathies can be seen in sepsis, from asymptomatic aberrations to fulminant disseminated intravascular coagulation (DIC). The aim of this study was to determine if fluid resuscitation with saline contributes to the haemostatic derangements in an ovine model of endotoxemic shock.

Inflammation and lung injury in an ovine model of fluid resuscitated endotoxemic shock.

Background: Sepsis is a multi-system syndrome that remains the leading cause of mortality and critical illness worldwide, with hemodynamic support being one of the cornerstones of the acute management of sepsis. We used an ovine model of endotoxemic shock to determine if 0.9% saline resuscitation contributes to lung inflammation and injury in acute respiratory distress syndrome, which is a common complication of sepsis, and investigated the potential role of matrix metalloproteinases in this process.

Unintended Consequences: Fluid Resuscitation Worsens Shock in an Ovine Model of Endotoxemia.

Rationale: Fluid resuscitation is widely considered a life-saving intervention in septic shock; however, recent evidence has brought both its safety and efficacy in sepsis into question.

Objectives: In this study, we sought to compare fluid resuscitation with vasopressors with the use of vasopressors alone in a hyperdynamic model of ovine endotoxemia.

Methods: Endotoxemic shock was induced in 16 sheep, after which they received fluid resuscitation with 40 ml/kg of 0.

Extracorporeal membrane oxygenation line-associated complications: in vitro testing of cyanoacrylate tissue adhesive and securement devices to prevent infection and dislodgement.

Background: Extracorporeal membrane oxygenation (ECMO) delivers cardiac and/or respiratory support to critically ill patients who have failed conventional medical therapies. If the large-bore cannulas used to deliver ECMO become infected or dislodged, the patient consequences can be catastrophic. ECMO cannula-related infection has been reported to be double the rate of other vascular devices (7.

Speaking valves in tracheostomised ICU patients weaning off mechanical ventilation--do they facilitate lung recruitment?

Background: Patients who require positive pressure ventilation through a tracheostomy are unable to phonate due to the inflated tracheostomy cuff. Whilst a speaking valve (SV) can be used on a tracheostomy tube, its use in ventilated ICU patients has been inhibited by concerns regarding potential deleterious effects to recovering lungs. The objective of this study was to assess end expiratory lung impedance (EELI) and standard bedside respiratory parameters before, during and after SV use in tracheostomised patients weaning from mechanical ventilation.

Nasal high flow oxygen therapy in patients with COPD reduces respiratory rate and tissue carbon dioxide while increasing tidal and end-expiratory lung volumes: a randomised crossover trial.

Unlabelled: Patients with COPD using long-term oxygen therapy (LTOT) over 15 h per day have improved outcomes. As inhalation of dry cold gas is detrimental to mucociliary clearance, humidified nasal high flow (NHF) oxygen may reduce frequency of exacerbations, while improving lung function and quality of life in this cohort. In this randomised crossover study, we assessed short-term physiological responses to NHF therapy in 30 males chronically treated with LTOT.

Novel 24-h ovine model of brain death to study the profile of the endothelin axis during cardiopulmonary injury.

Background: Upregulation of the endothelin axis has been observed in pulmonary tissue after brain death, contributing to primary graft dysfunction and ischaemia reperfusion injury. The current study aimed to develop a novel, 24-h, clinically relevant, ovine model of brain death to investigate the profile of the endothelin axis during brain death-associated cardiopulmonary injury. We hypothesised that brain death in sheep would also result in demonstrable injury to other transplantable organs.

Securing All intraVenous devices Effectively in hospitalised patients--the SAVE trial: study protocol for a multicentre randomised controlled trial.

Introduction: Over 70% of all hospital admissions have a peripheral intravenous device (PIV) inserted; however, the failure rate of PIVs is unacceptably high, with up to 69% of these devices failing before treatment is complete. Failure can be due to dislodgement, phlebitis, occlusion/infiltration and/or infection. This results in interrupted medical therapy; painful phlebitis and reinsertions; increased hospital length of stay, morbidity and mortality from infections; and wasted medical/nursing time.

A novel echocardiographic imaging technique, intracatheter echocardiography, to guide veno-venous extracorporeal membrane oxygenation cannulae placement in a validated ovine model.

Background: Echocardiography plays a fundamental role in cannulae insertion and positioning for extracorporeal membrane oxygenation (ECMO). Optimal access and return cannulae orientation is required to prevent recirculation. The aim of this study was to compare a novel imaging technique, intracatheter echocardiography (iCATHe), with conventional intracardiac echocardiography (ICE) to guide placement of ECMO access and return venous cannulae.

An improved mounting device for attaching intracranial probes in large animal models.

Background: The rigid support of intracranial probes can be difficult when using animal models, as mounting devices suitable for the probes are either not available, or designed for human use and not suitable in animal skulls. A cheap and reliable mounting device for securing intracranial probes in large animal models is described.

Methods: Using commonly available clinical consumables, a universal mounting device for securing intracranial probes to the skull of large animals was developed and tested.

Ovine platelet function is unaffected by extracorporeal membrane oxygenation within the first 24 h.

This study investigated platelet dysfunction during short-term extracorporeal membrane oxygenation (ECMO) and secondarily to determine if hyperoxaemia contributes to this dysfunction. Healthy sheep were anaesthetized and maintained on ECMO for either 2 or 24 h, with or without induction of smoke inhalation acute lung injury. A specialized animal-operating theatre was used to conduct the experimentation.

The impact of acute lung injury, ECMO and transfusion on oxidative stress and plasma selenium levels in an ovine model.

The purpose of this study was to determine the effects of smoke induced acute lung injury (S-ALI), extracorporeal membrane oxygenation (ECMO) and transfusion on oxidative stress and plasma selenium levels. Forty ewes were divided into (i) healthy control (n=4), (ii) S-ALI control (n=7), (iii) ECMO control (n=7), (iv) S-ALI+ECMO (n=8) and (v) S-ALI+ECMO+packed red blood cell (PRBC) transfusion (n=14). Plasma thiobarbituric acid reactive substances (TBARS), selenium and glutathione peroxidase (GPx) activity were analysed at baseline, after smoke injury (or sham) and 0.

Feasibility of perflutren microsphere contrast transthoracic echocardiography in the visualization of ventricular endocardium during venovenous extracorporeal membrane oxygenation in a validated ovine model.

Background: Transthoracic echocardiography (TTE) during extra corporeal membrane oxygenation (ECMO) is important but can be technically challenging. Contrast-specific TTE can improve imaging in suboptimal studies. These contrast microspheres are hydrodynamically labile structures.

Optimal management of the critically ill: anaesthesia, monitoring, data capture, and point-of-care technological practices in ovine models of critical care.

Animal models of critical illness are vital in biomedical research. They provide possibilities for the investigation of pathophysiological processes that may not otherwise be possible in humans. In order to be clinically applicable, the model should simulate the critical care situation realistically, including anaesthesia, monitoring, sampling, utilising appropriate personnel skill mix, and therapeutic interventions.

Intracardiac echocardiography guided transeptal catheter injection of microspheres for assessment of cerebral microcirculation in experimental models.

The use of microspheres for the determination of regional microvascular blood flow (RMBF) has previously used different approaches. This study presents for the first time the intracardiac injection of microspheres using transeptal puncture under intracardiac echocardiography guidance. Five Merino sheep were instrumented and cardiovascularly supported according to local guidelines.

Cerebral blood flow is not affected during perfluorocarbon dosing with volume-controlled ventilation.

Aims: Perfluorocarbon administration increases cerebral blood flow. This can be mitigated by preventing a rise in carbon dioxide by adjusting pressure-controlled ventilation. Volume-controlled ventilation should prevent increases in arterial carbon dioxide and cerebral blood flow.

Ventilation distribution in rats: Part 2--A comparison of electrical impedance tomography and hyperpolarised helium magnetic resonance imaging.

Background: Hyperpolarised helium MRI (He3 MRI) is a new technique that enables imaging of the air distribution within the lungs. This allows accurate determination of the ventilation distribution in vivo. The technique has the disadvantages of requiring an expensive helium isotope, complex apparatus and moving the patient to a compatible MRI scanner.

Ventilation distribution in rats: Part I--The effect of gas composition as measured with electrical impedance tomography.

Unlabelled: The measurement of ventilation distribution is currently performed using inhaled tracer gases for multiple breath inhalation studies or imaging techniques to quantify spatial gas distribution. Most tracer gases used for these studies have properties different from that of air. The effect of gas density on regional ventilation distribution has not been studied.

Development of simulated and ovine models of extracorporeal life support to improve understanding of circuit-host interactions.

Background: Extracorporeal life support (ECLS) is a lifesaving technology that is being increasingly used in patients with severe cardiorespiratory failure. However, ECLS is not without risks. The biosynthetic interface between the patient and the circuit can significantly alter inflammation, coagulation, pharmacokinetics and disposition of trace elements.

Heating of gases during neonatal resuscitation: a bench study.

Aim: Standard practice within the neonatal unit is to use heated humidified gas as it decreases respiratory complications in neonates requiring respiratory support. Using cold unhumidified gases during resuscitation could potentially cool the baby as well as exacerbate potential lung injury. We aimed to study the temperature and humidity aspects of using heated, humidified gas for neonatal resuscitation.