Revised Starling equation and the glycocalyx model of transvascular fluid exchange: an improved paradigm for prescribing intravenous fluid therapy

Abstract

I.V. fluid therapy does not result in the extracellular volume distribution expected from Starling's original model of semi-permeable capillaries subject to hydrostatic and oncotic pressure gradients within the extracellular fluid. Fluid therapy to support the circulation relies on applying a physiological paradigm that better explains clinical and research observations. The revised Starling equation based on recent research considers the contributions of the endothelial glycocalyx layer (EGL), the endothelial basement membrane, and the extracellular matrix. The characteristics of capillaries in various tissues are reviewed and some clinical corollaries considered. The oncotic pressure difference across the EGL opposes, but does not reverse, the filtration rate (the 'no absorption' rule) and is an important feature of the revised paradigm and highlights the limitations of attempting to prevent or treat oedema by transfusing colloids. Filtered fluid returns to the circulation as lymph. The EGL excludes larger molecules and occupies a substantial volume of the intravascular space and therefore requires a new interpretation of dilution studies of blood volume and the speculation that protection or restoration of the EGL might be an important therapeutic goal. An explanation for the phenomenon of context sensitivity of fluid volume kinetics is offered, and the proposal that crystalloid resuscitation from low capillary pressures is rational. Any potential advantage of plasma or plasma substitutes over crystalloids for volume expansion only manifests itself at higher capillary pressures.

A Practical Approach to the Difficult-to-Wean Patient

“…There is some suggestion that albumin may have a capillary sealing effect; however, supplementation to manipulate plasma oncotic pressure appears misguided. 29 We hypothesise that the commonly observed anecdotal benefit of infusing albumin, a weak acid, may in part be explained by its effect on weak acids as explained by Stewart' s method in those patients who are both alkalotic and hypoalbuminaemic. In our practice, we tend to avoid 'routine' albumin infusions, however, in patients that are difficult to wean and hypoalbuminaemic, we would give 100 mL 20% albumin twice daily for several days.…”

Must hypervolaemia be avoided? A critique of the evidence

“…Although the glycocalyx layer is damaged from inflammation and high ANP levels [17], it is less clear whether the doubled ANP level that develops in response to fluid infusions is sufficient to create an effect that warrants generally held warnings of hypervolaemia.…”

“…The most recent attempt claims that haemodilution is erroneous because the method does not take into account the changes in the fluid volume bound by the glycocalyx along the endothelial lining [17,22].…”

“…However, the magnitude of the washout is directly dependent on the same erroneous calculation of the post-infusion plasma volume with ICG as discussed previously. The 700 mL derived from these ICG measurements have even been further extrapolated to indicate that the glycocalyx layer has an average thickness of 2 µm in the human cardiovascular system [17].…”

Les mécanismes physiopathologiques du lymphœdème

“…Woodcock T. E. et Woodcock T. M. tiennent un raisonnement similaire en considérant que le retour du volume plasmatique filtré vers le secteur vasculaire, se fait principalement par la voie lymphatique. Si des arguments cliniques prouvent notamment que la perfusion de substituts du plasma ou d'albumine humaine, malgré leur fort pouvoir oncotique, ne font jamais régresser un oedème, il n'est pas démontré que le système lymphatique, soit capable de drainer l'intégralité du volume plasmatique filtré [8].…”