Jeremy Road

It is established that mechanical ventilation (MV), depending on mode and length of ventilation, influences diaphragm structure and function, and by extension, may influence outcomes. Patient–ventilator asynchrony imposes an additional burden on the respiratory system and may increase the morbidity of critically ill patients. The asynchrony index (AI) is used to quantify patient-ventilator asynchrony. An AI > 10% is associated with higher intensive care unit (ICU) and hospital mortality and longer duration of MV when compared to patients with an AI ≤ 10%, suggesting that this phenomenon plays an important role in clinical outcomes and potentially ICU mortality. We proposed to investigate the impact of patient-ventilator asynchrony on diaphragm structure and function, and determine how this may influence outcomes in critically ill patients.Methodology: Patients were eligible for inclusion as soon as they were admitted to the ICU and intubated with an expectation of invasive MV for more than 48 hours. On inclusion, a waveform analysis software tethered to the MV continuously recorded airflow, airway pressure and tidal volume from admission until liberation from the ventilator, transfer out of the ICU or death, whichever occurred first. Data acquisition commenced immediately and surrogate decision makers were contacted as soon as was feasible to obtain ongoing consent for participation. The software calculated AI for each patient. We calculated diaphragm thickening fraction (DTF) using measurements from ultrasound images of the right hemidiaphragm. DTF was used as a surrogate for diaphragm strength of contraction. We correlated AI with DTF, change in diaphragm thickness and ventilator days to investigate how AI influenced patient outcomes. Conclusion: Low level of diaphragm activity in deeply sedated MV patients is associated with high incidence of asynchrony, longer ICU stay and increased mortality. Ineffective effort (IE) is the most frequently occurring asynchronous event in all modes of MV, and is associated with higher incidence of asynchrony, mortality, greater number of ventilator days and longer ICU stay. A DTF of ≥ 11% allows for preservation of diaphragm thickness in CMV. Titrating sedation and ventilator settings to achieve greater diaphragm activity may reduce AI and improve patient outcomes.

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Since the discovery in the late 1980’s that the endothelium relaxing factor is nitric oxide (NO) there has been intensive scientific pursuit to understand the many roles of NO in biological systems. NO is a messenger molecule with both paracrine and autocrine functions. NO is produced by phagocytes as part of the immune system as a non-specific antimicrobial which may be effective against Influenza. Influenza is a virus that infects millions of people each year resulting in hundreds of thousands of deaths. While vaccination and antivirals have helped reduce the death toll, their effectiveness is limited because of the rapidly evolving nature of the influenza virus and the development of resistance. The recent 2009 influenza pandemic has highlighted the need for new and novel antivirals. We hypothesize that the direct exposure of influenza viruses to gaseous nitric oxide (gNO) will have an antiviral effect. We also show that it is feasible and safe to deliver inhaled gNO to humans at antiviral concentrations using an intermittent high dose regimen.

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