Patient-Specific Monitoring and Trend Analysis of Model-Based Markers of Fluid Responsiveness in Sepsis: A Proof-of-Concept Animal Study

Abstract

Total stressed blood volume ($SBV_{\text{T}}$) and arterial elastance ($E_{\text{a}}$) are two potentially important, clinically applicable metrics for guiding treatment in patients with altered hemodynamic states. Defined as the total pressure generating blood in the circulation, $SBV_{\text{T}}$ is a potential direct measurement of tissue perfusion, a critical component in treatment of sepsis. $E_{\text{a}}$ is closely related to arterial tone thus provides insight into cardiac efficiency. However, it is not clinically feasible or ethical to measure $SBV_{\text{T}}$ in patients, so a three chambered cardiovascular system model using measured left ventricle pressure and volume, aortic pressure and central venous pressure is implemented to identify $SBV_{\text{T}}$ and $E_{\text{a}}$ from clinical data. $SBV_{\text{T}}$ and $E_{\text{a}}$ are identified from clinical data from six (6) pigs, who have undergone clinical procedures aimed at simulating septic shock and subsequent treatment, to identify clinically relevant changes. A novel, validated trend analysis method is used to adjudge clinically significant changes in state in the real-time $E_{\text{a}}$ and $SBV_{\text{T}}$ traces. Results matched hypothesised increases in $SBV_{\text{T}}$ during fluid therapy, with a mean change of + 21% during initial therapy, and hypothesised decreases during endotoxin induced sepsis, with a mean change of − 29%. $E_{\text{a}}$ displayed the hypothesised reciprocal behaviour with a mean changes of − 12 and + 30% during initial therapy and endotoxin induced sepsis, respectively. The overall results validate the efficacy of $SBV_{\text{T}}$ in tracking changes in hemodynamic state in septic shock and fluid therapy.