QUIVER · Elucidating the Impact of Mechanical Ventilation and Sepsis on Diaphragm blood flow: Insights from Contrast-Enhanced Ultrasound

Diaphragm dysfunction is highly prevalent in mechanically ventilated patients on the intensive care unit (ICU) and is strongly associated with weaning failure, prolonged ICU stay, and increased mortality. Remarkably, diaphragm dysfunction can develop within 24 hours of ICU admission, suggesting mechanisms beyond muscle disuse atrophy. Based on preclinical evidence, I hypothesize that diaphragm blood flow impairment is a key contributor to early diaphragm dysfunction mediated by two mechanisms: (1) reduced diaphragm blood flow from mechanical compression of the diaphragmatic vasculature from increasing levels of positive end-expiratory pressure (PEEP) during mechanical ventilation, and (2) sepsis-induced impairment of diaphragm blood flow. However, no human data currently exist on diaphragm blood flow during mechanical ventilation or sepsis in the ICU, due to the lack of available techniques to measure it. In the QUIVER project, I will address this critical gap by utilizing contrast-enhanced ultrasound, a novel bedside imaging technique, to quantify diaphragm blood flow. QUIVER has two objectives: (1) to determine PEEP-induced changes in diaphragm blood flow in healthy volunteers during non-invasive ventilation and in invasively ventilated ICU patients, and (2) to unravel the effects of sepsis on diaphragm blood flow, first in healthy volunteers using an established human endotoxemia model and subsequently in septic ICU patients during and after the acute septic phase. By integrating my expertise with my supervisor’s in intensive care medicine, advanced ultrasound imaging and respiratory (muscle) physiology, QUIVER will elucidate the impact of mechanical ventilation and sepsis on diaphragm blood flow in ICU patients. This approach has the potential to mitigate early diaphragm dysfunction in ICU patients by introducing real-time assessment of diaphragm blood flow into clinical practice, enabling personalized ventilator settings and hemodynamic management strategies.