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

Total stressed blood volume (SBVT\documentclass[12pt]and arterial elastance (Ea\documentclass[12pt]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, SBVT\documentclass[12pt] is a potential direct measurement of tissue perfusion, a critical component in treatment of sepsis. Ea\documentclass[12pt] is closely related to arterial tone thus provides insight into cardiac efficiency. However, it is not clinically feasible or ethical to measure SBVT\documentclass[12pt] 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 SBVT\documentclass[12pt] and Ea\documentclass[12pt]from clinical data. SBVT\documentclass[12pt] and Ea\documentclass[12pt]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 Ea\documentclass[12pt] and SBVT\documentclass[12pt] races. Results matched hypothesised increases in SBVT\documentclass[12pt]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%. Ea\documentclass[12pt]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 SBVT\documentclass[12pt] in tracking changes in hemodynamic state in septic shock and fluid therapy.