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

29 Feb 2016


wenty-five years ago, Twigley and Hillman announced ‘the end of the crystalloid era’. Using a simplified diagram of plasma, interstitial and intracellular fluid compartments, and their anatomic volumes, they argued that colloids could be used to selectively maintain the plasma volume. Plasma volume being about 20% of the extracellular fluid (ECF), it was presumed that the volume equivalence for resuscitation from intravascular hypovolaemia would be of the order of 20 ml colloid to 100 ml isotonic salt solution (ISS). Moreover, it was presumed from Starling’s principle that transfusion of hyperoncotic colloid solutions would absorb fluid from the interstitial fluid (ISF) to the intravascular volume. This simple concept of colloid for plasma volume and ISS for ECF replacement has been continued and developed. Two trials in critically ill patients have found that over the first 4 days of fluid resuscitation, 100 ml ISS is as effective as 62–76 ml human albumin solution5 or 63–69 ml hyperoncotic plasma substitute.6 In blunt trauma patients during the first day of resuscitation, 100 ml ISS was as effective as 97 ml isosmotic plasma substitute, while in gunshot or stabbing victims, 100 ml was as effective as 67 ml. A trial of paediatric resuscitation practices in resource-poor facilities in Africa demonstrated no advantages of bolus therapy with albumin compared with ISS, and a survival advantage for slow ISS resuscitation without bolus therapy.A series of volume kinetics experiments have demonstrated that the central volume of distribution of ISS is much smaller than the anatomic ECF volume, and an editorial had to conclude that ‘Fluid therapy might be more difficult than you think’. This review attempts to reconcile clinical trial data and bedside experience of fluid therapy with recent advances in microvascular physiology to improve our working paradigm for rational prescribing.

T. E. Woodcock1* and T. M. Woodcock2
1 Critical Care Service, Southampton University Hospitals NHS Trust, Tremona Road, Southampton SO16 6YD, UK
2 The Australian School of Advanced Medicine, Macquarie University, NSW 2109, Australia
* Corresponding author. E-mail: tom.woodcock@me.com
Revised Starling equation and the glycocalyx model of transvascular fluid exchange: an improved paradigm for prescribing intravenous fluid therapy

Summary. 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.

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