The LIAISE study is a prospective observational study comparing the performance of load-incorporating echocardiographic parameters and conventional parameters in predicting adverse events among adult patients presenting to the ICU with sepsis. It will be conducted in hospitals in Australia, Hong Kong, South Africa, and Canada, with 199 patients recruited over 2 years. All included patients will receive an regular echocardiographic assessment and their haemodynamic parameters will be simultaneously recorded. Participants will be followed for up to 1 year after enrolment. Load incorporating parameters will be derived from regularly obtained echocardiography and haemodynamic data during offline analysis. The predictive value of cardiac parameters will be evaluated based on their statistical association with clinical outcomes.

Background Sepsis is a global killer, whereby an infection spreads throughout the body via the bloodstream. It often leads to lethal heart damage, "septic cardiomyopathy", with mortality rates for those affected soaring above 40%. To facilitate early and appropriate intervention for damaged hearts and improve their outcomes, accurate assessment of heart function, and proper prediction of their adverse events are crucial. However, conventional cardiac assessments cannot capture heart dysfunction accurately since they have a significant limitation called "load-dependency", which means these parameters' values are affected by loading conditions on the heart, such as blood pressure and circulating blood volume. In sepsis, as these loads on the heart dramatically change minute by minute, the values of cardiac assessment also fluctuate and frequently underestimates heart damage, failing to properly predict their adverse events. To address this, novel load-incorporating echocardiographic parameters can capture heart function more accurately regardless of these hemodynamic conditions, and previous data has demonstrated its better predictive value in cardiogenic shock cases where loading conditions similarly fluctuate. As a next step, this study seeks to elucidate their utility in patients with sepsis.

Aims

1. To investigate if novel load-incorporating echocardiography can predict adverse events more accurately than conventional parameters in adult patients with sepsis presenting to intensive care units (ICUs).
2. To identify the most sensitive cardiac parameter to predict adverse events in sepsis, from comprehensively collected cardiac parameters along with novel-incorporating echocardiography.

Hypothesis Load-incorporating echocardiographic parameters will be more accurate in predicting the incidence of adverse events within 30 days after ICU admission than conventional echocardiographic parameters.

Outcomes Primary outcome The incidence of all-cause death for 30 days after ICU admission

Secondary outcomes

• Incidence of and time to all-cause death or cardiovascular readmission for 1 year after ICU admission
• Incidence and duration of mechanical circulatory support, mechanical ventilation, renal replacement therapy, and vasoactive agent therapy during initial admission.
• Reversibility of cardiac function (LVEF increases ≥ 5% in echo 3-5 days after ICU admission)
• Sequential Organ Failure Assessment (SOFA) score at 3 days after ICU admission

Inclusion Criteria:

1. Adults ≥ 18 years old.
2. Clinically suspected of defined sepsis
3. Sepsis-induced hypotension or hypoperfusion (arterial or venous blood lactate ≥2.0 mmol/L OR mean artery pressure ≤65 mmHg over 30 mins OR at least one vasoactive or inotropic agent administered).
4. At least one dose of an IV antimicrobial has been commenced.

Exclusion Criteria:

1. Suspected or confirmed pregnancy.
2. Any severe concomitant diseases with limited life expectancy <30 days.

Patients with sepsis and hypotension / hypoperfusion signs, admitted for ICU

Study Protocol Statistical Analysis Plan Informed Consent Form

Start date: January 2025 End date: December 2027

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