The Extended Starling principle needs clinical validation.

The Revised(or "Extended") Starling principle is based on highly controlled laboratory-basedfrog and rodent experiments and remains a hypothesis awaiting clinical validation. A key point is that the endothelial glycocalyx layer moves the oncotic gradient from being between the plasma and the interstitium to between the plasma and a virtually protein-free space between the glycocalyx and the endothelial cell membrane, which dramatically changes the prerequisites for fluid absorption from tissue to plasma. However, many experimental and clinical observations in humans agree poorly with the new microcirculatory proposals. The most troubling aspect of the explanation regarding the role of the glycocalyx in the Revised Starling principle is the effective reabsorption of fluid by skeletal muscle when the capillary filtration pressure is acutely reduced. Other issues include the plasma volume effects of hypertonic saline, iso-oncotic and hyper-oncotic albumin, fluid distribution during cardio-pulmonary bypass, and the virtually identical capillary leakage of plasma and albumin despite marked inflammation found in our fluid therapy studies. The RevisedStarling principle deals mainly with steady-state conditions, but the circulatory system is highly dynamic. Second to second vasomotion is always operational and must be considered to understand what we observe in humans. EDITORIAL COMMENT: In this special article, which is one of a pair of invited narrative reviews, the author group focuses on clinical validation of intravascular fluid kinetics, particularly related to developing thought concerning the theoretical framework for trans-capillary fluid filtration.