To ventilate, oscillate, or cannulate?

Ventilatory management of acute respiratory distress syndrome has evolved significantly in the last few decades. The aims have shifted from optimal gas transfer without concern for iatrogenic risks to adequate gas transfer while minimizing lung injury. This change in focus, along with improved ventilator and multiorgan system management, has resulted in a significant improvement in patient outcomes.

The ECMO PK Project: an incremental research approach to advance understanding of the pharmacokinetic alterations and improve patient outcomes during extracorporeal membrane oxygenation.

Background: Extracorporeal membrane oxygenation (ECMO) is a supportive therapy and its success depends on optimal drug therapy along with other supportive care. Emerging evidence suggests significant interactions between the drug and the device resulting in altered pharmacokinetics (PK) of vital drugs which may be further complicated by the PK changes that occur in the context of critical illness. Such PK alterations are complex and challenging to investigate in critically ill patients on ECMO and necessitate mechanistic research.

Stored blood transfusion induces transient pulmonary arterial hypertension without impairing coagulation in an ovine model of nontraumatic haemorrhage.

Background And Objectives: Transfusion of blood products in particular older products is associated with patient morbidity. Previously, we demonstrated a higher incidence of acute lung injury in lipopolysaccharide-treated sheep transfused with stored blood products. As transfusion following haemorrhage is more common, we aimed to determine whether a 'first hit' of isolated haemorrhage would precipitate similar detrimental effects following transfusion and also disrupt haemostasis.

Assessment of cardiac proteome dynamics with heavy water: slower protein synthesis rates in interfibrillar than subsarcolemmal mitochondria.

Traditional proteomics provides static assessment of protein content, but not synthetic rates. Recently, proteome dynamics with heavy water ((2)H2O) was introduced, where (2)H labels amino acids that are incorporated into proteins, and the synthesis rate of individual proteins is calculated using mass isotopomer distribution analysis. We refine this approach with a novel algorithm and rigorous selection criteria that improve the accuracy and precision of the calculation of synthesis rates and use it to measure protein kinetics in spatially distinct cardiac mitochondrial subpopulations.

Is hyperoxaemia helping or hurting patients during extracorporeal membrane oxygenation? Review of a complex problem.

Extracorporeal membrane oxygenation (ECMO) facilitates organ support in patients with refractory cardiorespiratory failure whilst disease-modifying treatments can be administered. Improvements to the ECMO process have resulted in its increased utilisation. However, iatrogenic injuries remain, with bleeding and thrombosis the most significant concerns.

Enhanced resistance to permeability transition in interfibrillar cardiac mitochondria in dogs: effects of aging and long-term aldosterone infusion.

Functional differences between subsarcolemmal and interfibrillar cardiac mitochondria (SSM and IFM) have been observed with aging and pathological conditions in rodents. Results are contradictory, and there is little information from large animal models. We assessed the respiratory function and resistance to mitochondrial permeability transition (MPT) in SSM and IFM from healthy young (1 yr) and old (8 yr) female beagles and in old beagles with hypertension and left ventricular (LV) wall thickening induced by 16 wk of aldosterone infusion.

Remarkable photocytotoxicity of a novel triazole-linked cationic porphyrin-β-carboline conjugate.

Employing a click chemistry approach we have synthesized a novel triazole-linked cationic porphyrin-β-carboline conjugate which exhibited remarkable photocytotoxicity against the A549 cancer cell line (IC(50) = 60 nM).

ASAP ECMO: Antibiotic, Sedative and Analgesic Pharmacokinetics during Extracorporeal Membrane Oxygenation: a multi-centre study to optimise drug therapy during ECMO.

Background: Given the expanding scope of extracorporeal membrane oxygenation (ECMO) and its variable impact on drug pharmacokinetics as observed in neonatal studies, it is imperative that the effects of the device on the drugs commonly prescribed in the intensive care unit (ICU) are further investigated. Currently, there are no data to confirm the appropriateness of standard drug dosing in adult patients on ECMO. Ineffective drug regimens in these critically ill patients can seriously worsen patient outcomes.

Glucose 6-phosphate dehydrogenase deficiency increases redox stress and moderately accelerates the development of heart failure.

Background: Glucose 6-phosphate dehydrogenase (G6PD) is the most common deficient enzyme in the world. In failing hearts, G6PD is upregulated and generates reduced nicotinamide adenine dinucleotide phosphate (NADPH) that is used by the glutathione pathway to remove reactive oxygen species but also as a substrate by reactive oxygen species-generating enzymes. Therefore, G6PD deficiency might prevent heart failure by decreasing NADPH and reactive oxygen species production.

Sequestration of drugs in the circuit may lead to therapeutic failure during extracorporeal membrane oxygenation.

Introduction: Extracorporeal membrane oxygenation (ECMO) is a supportive therapy, with its success dependent on effective drug therapy that reverses the pathology and/or normalizes physiology. However, the circuit that sustains life can also sequester life-saving drugs, thereby compromising the role of ECMO as a temporary support device. This ex vivo study was designed to determine the degree of sequestration of commonly used antibiotics, sedatives and analgesics in ECMO circuits.

High-throughput assay for simultaneous quantification of the plasma concentrations of morphine, fentanyl, midazolam and their major metabolites using automated SPE coupled to LC-MS/MS.

A rapid LC-MS/MS assay method for simultaneous quantification of morphine, fentanyl, midazolam and their major metabolites: morphine-3-β-D-glucuronide (M3G), morphine-6-β-D-glucuronide (M6G), norfentanyl, 1'-hydroxymidazolam (1-OH-MDZ) and 4-hydroxymidazolam (4-OH-MDZ) in samples of human plasma has been developed and validated. Robotic on-line solid phase extraction (SPE) instrumentation was used to elute the eight analytes of interest from polymeric SPE cartridges to which had been added aliquots (150 μL) of human plasma and aliquots (150 μL) of a mixture of two internal standards, viz. morphine-d3 (200 ng/mL) and 1'-hydroxymidazolam-d5 (50 ng/mL) in 50 mM ammonium acetate buffer (pH 9.

Effects of glucose-6-phosphate dehydrogenase deficiency on the metabolic and cardiac responses to obesogenic or high-fructose diets.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common human enzymopathy that affects cellular redox status and may lower flux into nonoxidative pathways of glucose metabolism. Oxidative stress may worsen systemic glucose tolerance and cardiometabolic syndrome. We hypothesized that G6PD deficiency exacerbates diet-induced systemic metabolic dysfunction by increasing oxidative stress but in myocardium prevents diet-induced oxidative stress and pathology.

Increased sedation requirements in patients receiving extracorporeal membrane oxygenation for respiratory and cardiorespiratory failure.

Critically ill patients receiving extracorporeal membrane oxygenation (ECMO) are often noted to have increased sedation requirements. However, data related to sedation in this complex group of patients is limited. The aim of our study was to characterise the sedation requirements in adult patients receiving ECMO for cardiorespiratory failure.

Outcomes of the first 30 cases of an adult extracorporeal membrane oxygenation program: strategies to manage the "learning curve" and implications for intensive care unit risk adjustment models.

Background: We established an adult extracorporeal membrane oxygenation (ECMO) service for cardiorespiratory support in April 2009. Complex therapies may show a learning curve and volume-outcome relationship.

Objectives: To describe our model of care, casemix and outcomes for the first 30 cases together with unique features of this service and potential strategies to manage the learning curve.

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.

Transnasal K-wire to stabilise a complex zygomatic fracture: a forgotten method of fixation.

Zygomatic complex fractures make up approximately 60% of facial fractures. The vast majority treated surgically use titanium miniplates. These require longer operating times and facial incisions to access the fracture.

Donation after cardiac death in Queensland: review of the pilot project.

Organ transplantation is a viable therapeutic option for patients with endstage organ failure when other therapies have been exhausted. Donation after cardiac death (DCD) is re-emerging as a potential option to expand the donor pool to meet an increasing demand for organ transplantation. In this review, we evaluate the evolution of the Queensland DCD pilot project since its inception in August 2008.

Pharmacokinetic changes in patients receiving extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) is a form of prolonged cardiopulmonary bypass used to temporarily sustain cardiac and/or respiratory function in critically ill patients. Extracorporeal membrane oxygenation further complicates the management of critically ill patients who already have profound physiologic derangements with consequent altered pharmacokinetics. The purpose of this study is to identify and critically review the published literature describing pharmacokinetics in the presence of ECMO.

Post-operative deep sternal wound infections: making an early microbiological diagnosis.

Objectives: Early microbiological diagnosis of deep sternal wound infections (DSWI) could improve outcomes by allowing targeted antibiotic treatment. This study aims to analyse the utility of superficial sternal wound swabs and blood cultures.

Methods: From January 2005 to June 2011, 70 patients were prospectively identified with DSWI.