Mean systemic filling pressure - from Guyton to the ICU, and back again

Introduction: Mean systemic filling pressure (MSFP) is the equilibrated vascular pressure at zero flow. Venous return (VR) driving pressure (VRdP) is the difference between MSFP and right atrial pressure (RAP). In clinical research, MSFP can be estimated: MSFPinsp_hold is the zero-flow extrapolation of RAP-cardiac output data-pairs from inspiratory hold maneuvers; MSFPa is a dynamic analogue computed from clinically available hemodynamics. However, results are controversial and fundamental concepts of VR physiology are questioned. We aimed to test experimentally the concept of VRdP in dynamic conditions and validate estimates of MSFP against zero-flow measurements. Methods: We compared estimates of MSFP against zero-flow measurements from right atrial balloon occlusion (MSFPRAO), or from intermittently paused venoarterial extracorporeal membrane oxygenation (ECMO), in three porcine models exposed to changing blood volumes and vasoconstriction. Results: Changes in RAP resulted in immediate and directionally opposite changes in VR. Temporary VR and ECMO flow imbalance resulted in dynamically changing VRdP and RAP. In euvolemia, MSFP was increased by increased airway pressure. A moderate increase in positive end-expiratory pressure increased RAP, MSFPRAO and VRdP. Resistance to VR did not change. Changing blood volume led to concordant changes in RAP, MSFPRAO, VRdP and flow. Vasoconstriction and volume expansion increased MSFP and maximum achievable ECMO flow with similar effects on oxygen delivery. MSFPinsp_hold overestimated MSFPRAO in euvolemia due to flow restoration predominantly occurring in the inferior vena cava. Methods for MSFP estimation had an accuracy that was dependent on volume status. All methods tracked changes in the reference method concordantly. However, with the possible exception of MSFPa, the bias was clinically unacceptable. Conclusion: If pressure effects from volume shifts are accounted for, the concept of VRdP is valid also during dynamic conditions. VR physiology can explain the responses of volume expansion and vasoconstriction on venoarterial ECMO flow. Inspiratory hold maneuvers are unsuitable for the estimation of MSFP due to clinically significant bias