Michelle Chew

Myocardial dysfunction is one of the most severe manifestations of critically ill patients with sepsis, affecting 20-70% of this population. The absence of consensus criteria for the diagnosis of sepsis-induced myocardial dysfunction (SIMD), coupled with no defining pathophysiological process hampers diagnosis and prognosis of SIMD. Current prognostic indicators, including echocardiographic parameters and biomarkers, exhibit significant variability in their predictive accuracy, often failing to account for the complex interplay of chronic comorbidities and therapeutic interventions such as mechanical ventilation, vasopressors/inotropes, and fluid therapy.We hypothesize that a comprehensive integration of echocardiographic, biomarker, haemodynamic, and clinical data holds the key to accurate prognostication in SIMD. To elucidate this, our proposed clinical study aims to uncover nuanced prognostic patterns, leveraging a multidimensional approach using traditional statistical inference and machine learning approaches. Concurrently, findings from the clinical study will be mechanistically explored in animal models to better understand underlying pathophysiological mechanisms, offering invaluable insights into potential therapeutic avenues. Furthermore, we hope to establish a foundation for the development of consensus guidelines for the identification and management of SIMD, ultimately facilitating more precise and effective patient care strategies.

Observational studies have shown an association between a positive fluid balance and poor outcome in septic shock. By reducing fluid administration outcome could be improved. The REDUSE trial is a multicentre, investigator initiated, randomized clinical superiority trial comparing a protocolized restrictive strategy for administration of non-resuscitation fluids with usual care in participants with septic shock. Adult patients with septic shock (P) will be eligible for inclusion. Participants will be randomized within 12 hours of admission. In the intervention arm (I), intravenous drugs and nutrition will be concentrated and administered with the objective to reduce fluid volume, and participants will not receive maintenance fluids unless total fluid volume of is not enough to provide hydration. Resuscitation fluids will be administered according to local routines. The intervention will last for the duration of the ICU stay. Participants in the control arm (C) will receive usual care. The primary outcome (O) will be mortality at 90 days and the trial will be powered to detect a of 7.5% absolute risk reduction (n=1850). Secondary outcomes will be complications, need for mechanical ventilation, health-related quality of life (HRQoL), and cognitive function. Healthcare staff involved in the care of the participant will not be blinded to the intervention but participants, outcome assessors, statisticians, and authors will be blinded to treatment allocation.