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.

The effects of normovolemic anemia and blood transfusion on cerebral microcirculation after severe head injury.

Background: Cerebral regional microcirculation is altered following severe head injury. In addition to tissue disruption, partial pressure of tissue oxygenation is impaired due to an increase in the oxygen tissue gradient. The heterogenic distribution of cerebral microcirculation is multifactorial, and acute anemia challenges further the delivery of oxygen to tissues.

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.

Cerebral Microcirculation and Histological Mapping After Severe Head Injury: A Contusion and Acceleration Experimental Model.

Background: Cerebral microcirculation after severe head injury is heterogeneous and temporally variable. Microcirculation is dependent upon the severity of injury, and it is unclear how histology relates to cerebral regional blood flow.

Objective: This study assesses the changes of cerebral microcirculation blood flow over time after an experimental brain injury model in sheep and contrasts these findings with the histological analysis of the same regions with the aim of mapping cerebral flow and tissue changes after injury.

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.

An Ovine Model of Hyperdynamic Endotoxemia and Vital Organ Metabolism.

Background: Animal models of endotoxemia are frequently used to understand the pathophysiology of sepsis and test new therapies. However, important differences exist between commonly used experimental models of endotoxemia and clinical sepsis. Animal models of endotoxemia frequently produce hypodynamic shock in contrast to clinical hyperdynamic shock.

Reliability of thermodilution derived cardiac output with different operator characteristics.

Cardiac output (CO) is commonly measured using the thermodilution technique at the time of right heart catheterisation (RHC). However inter-operator variability, and the operator characteristics which may influence that, has not been quantified. Therefore, this study aimed to assess inter-operator variability with the thermodilution technique using a mock circulation loop (MCL) with calibrated flow sensors.

Cerebral microcirculation during mild head injury after a contusion and acceleration experimental model in sheep.

Background: Cerebral microcirculation after head injury is heterogeneous and temporally variable. Regions at risk of infarction such as peri-contusional areas are vulnerable to anaemia. However, direct quantification of the cerebral microcirculation is clinically not feasible.

Activation of the protein C pathway and endothelial glycocalyx shedding is associated with coagulopathy in an ovine model of trauma and hemorrhage.

Introduction: Acute traumatic coagulopathy (ATC) is an endogenous coagulopathy that develops following tissue injury and shock. The pathogenesis of ATC remains poorly understood, with platelet dysfunction, activation of the protein C pathway, and endothelial glycocalyx shedding all hypothesized to contribute to onset. The primary aim of this study was to develop an ovine model of traumatic coagulopathy, with a secondary aim of assessing proposed pathophysiological mechanisms within this model.

Single-Lung Transplant Results in Position Dependent Changes in Regional Ventilation: An Observational Case Series Using Electrical Impedance Tomography.

Background. Lung transplantation is the optimal treatment for end stage lung disease. Donor shortage necessitates single-lung transplants (SLT), yet minimal data exists regarding regional ventilation in diseased versus transplanted lung measured by Electrical Impedance Tomography (EIT).

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.

Cerebral Microcirculation during Experimental Normovolaemic Anemia.

Anemia is accepted among critically ill patients as an alternative to elective blood transfusion. This practice has been extrapolated to head injury patients with only one study comparing the effects of mild anemia on neurological outcome. There are no studies quantifying microcirculation during anemia.

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.