Clinical Research Directory

Diaphragm Hibernation and Its Driving Factors in Mechanically Ventilated ICU Patients

Rationale: Patients with invasive mechanical ventilation (IMV) frequently develop diaphragm dysfunction and experience difficult weaning. Recent ex vivo work suggests that a subset of mechanically ventilated ICU patients may exhibit diaphragm hibernation, an energy conserving myosin state that reduces force generation and may lead to a reversible increase in diaphragm strength over time. However, it is unknown whether diaphragm hibernation can be demonstrated in vivo during IMV and which clinical and biological factors are associated with this phenotype. Objective: Primary objective is to determine the driving factors (biomarkers) of diaphragm hibernation during IMV. Secondary objectives are to determine the proportion of ventilated critically ill patients who exhibit diaphragm hibernation during IMV, to investigate inflammatory and metabolic factors and other clinical exposures associated with diaphragm hibernation, and to explore associations between diaphragm hibernation and weaning related and survival outcomes. Study design: Prospective, observational, longitudinal cohort study. Study population: Adult ICU patients receiving IMV, expected to remain mechanically ventilated for at least 72 hours. Intervention (if applicable): Not applicable. This is an observational study. Study specific procedures consist of repeated phrenic nerve magnetic stimulation and additional blood sampling. Main study parameters/endpoints: The primary study parameter is the proportion of participants exhibiting diaphragm hibernation during IMV. Diaphragm hibernation is defined as an increase in stimulated twitch tracheal pressure (Ptr,stim), a measure of diaphragm strength, of at least 10% relative to baseline (Day 0-1) at any follow up assessment (Day 2, 3, 5, or 7) obtained before extubation or death. Ptr,stim will be assessed repeatedly on Day 0-1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participant burden is limited and mainly consists of repeated phrenic nerve magnetic stimulation during a ventilator delivered end expiratory occlusion and additional blood sampling of 9.5 mL per time point, up to a total of 47.5 mL across the study period. Magnetic stimulation is non-invasive and expected discomfort is transient. Rare transient physiological changes may occur and measurements are performed under continuous ICU monitoring and will be postponed or omitted if considered unsafe or interfering with clinical care. Direct benefit for participants is limited, but the study may provide clinically relevant knowledge on diaphragm hibernation and its driving factors. The research questions are specific to diaphragm physiology during IMV in critically ill patients, therefore the study is group related and cannot be performed in a different population.

Personalized Ventilator Settings for Patients on ECMO

While mechanical ventilation can be used to sustain life in those with lung injury, it, can further worsen lung injury or prevent lung healing resulting in high morbidity and mortality as seen in Acute Respiratory Distress Syndrome (ARDS). Using extracorporeal membrane oxygenation (ECMO), the highest level of life support also known as the heart-lung machine, investigators may minimize injury from mechanical ventilation to allow the lungs to heal; however, the optimal ventilator strategies while on ECMO are unknown. This study will evaluate personalized ventilator strategy compared to standard of care ventilation.

Weaning From High Flow Nasal Oxygen in Acute Respiratory Failure : a Target Trial Emulation

Acute respiratory failure is a frequent reason for admission to the intensive care unit (ICU). It is associated with high healthcare consumption and mortality. High-flow nasal oxygen (HFNO) improves comfort, reduces the risk of intubation and may reduce the risk of mortality in the most severe patients with acute hypoxemic respiratory failure compared with other oxygenation strategies. Therefore, HFNO is recommended as a first-line non-invasive oxygenation strategy in acute hypoxemic respiratory failure. The timing of weaning patients from HFNO is complex. On the one hand, failure to wean from HFNO is associated with prolonged duration of HFNO and prolonged ICU stay. On the other hand, continued HFNO in patients ready to be weaned may unnecessarily prolong ICU stay and contribute to overwhelming of ICU capacities. The overarching goal of this study is to identify the characteristics of patients in whom weaning from HFNO is not beneficial.