Infamy, infamy, why have they got it in for me?

Debates in fluid therapy recommendations can get a bit hot; first it was Colloids versus Crystalloids, then it was Chloride Max versus Chloride Lite solutions. Now I enjoy a good civilised debate, even a Fluid Controversy if that’s what it takes to attract the attention of ticket-buying Conference Delegates, but what I want to talk about here are the people who don’t understand Starling physiology but cite my 2012 paper on rational prescribing then claim to have disproved the physiology without giving me the courtesy of a heads-up or right to reply. Let’s look at some of them.

“An alternative therapeutic option is the mobilisation of tissue fluid by infusing a small amount of hyperoncotic fluid. Per the Starling principle, raising the plasma albumin concentration would mobilise fluid from the interstitial fluid volume into the blood volume. Although hyperoncotic albumin has historically been used for this purpose, its effectiveness has recently been questioned in the so-called “revised Starling equation”. In this new theory, the plasma’s oncotic pressure is less important to the transcapillary distribution of fluid than previously believed. However, the impact of the revised Starling equation on fluid distribution in humans has not been elucidated.” (1)

“Hyperoncotic albumin has also been given to reduce peripheral edema in normovolemic patients during the de-escalation phase of fluid therapy, the reason being that because 20% albumin is believed to cause a fluid shift from the interstitial space to the plasma. However, this view has recently been called into question because of the Revised Starling Equation, which holds that there is no oncotic gradient between the plasma and the interstitial fluid. Moreover, the so-called nonabsorption rule means that fluid can only be recruited to the plasma via the lymph, the endothelial glycocalyx layer, and from glands. The intra-vascular persistence of infused albumin may also be shorter in inflammatory conditions, such as those associated with major surgery, due to breakdown of the endothelial glyco- calyx layer (shedding), which serves as the key barrier to capillary leakage of plasma proteins. These findings have been documented in microcirculatory research, but they need validation in large biological systems.” (2)

“One of the main implicit assumptions in the literature has been that the glycocalyx barrier is the key vascular component defining vascular barrier permeability (VBP) and that its disruption is the primary cause of vascular leakage causing tissue edema.” (3)

When Fluid Physiology: a Handbook for Anaesthesia and Critical Care Practice hits your local online bookseller I have to make sure the Editors of Anesth Analg and Acta Anaesth Scand get a copy! In the meantime, let’s see if we can explain the misunderstandings going on here.

  1. The updated form of the traditional Starling equation is the basis of all transient fluid movements and attaches at least as great an importance to the plasma colloid osmotic pressure as the traditional Starling Principle.
  2. The revised Starling principle recognizes that fluid uptake from the tissues can occur transiently in nearly all organs and tissues, liver and spleen being possible exceptions. In tissues where interstitial fluid is formed as an ultrafiltrate of plasma (and these tissues represent the bulk of the body mass) fluid uptake can only be transient. The duration of this absorptive period varies from tissue to tissue, being brief in the lung and the mesentery and 30 minutes or more in skeletal muscle.
  3. The variation in transience of fluid exchange in tissues reflects the volume of a microdomain of interstitial fluid in contact with tissue side of microvascular walls. It is the differences between the hydrostatic and colloid osmotic pressures of this microdomain and the hydrostatic and colloid osmotic pressures of the plasma that determine fluid exchange. The colloid osmotic pressure in the subglycocalyx microdomain is lower than the general interstitial colloid osmotic pressure at steady state.
  4. Where interstitial fluid is formed entirely as an ultrafiltrate of plasma, a steady state can only be achieved if there is at least a low level of filtration at a constant rate. This level of filtration depends upon the permeability coefficients of the microvascular walls, the transendothelial hydrostatic pressure difference ΔP and the plasma oncotic pressure ΠP. Steady state reabsorption in such tissues cannot and does not occur – the no-reabsorption rule.
  5. Filtration maintains a constant colloid osmotic pressure in the subglycocalyx microdomain, and hence a constant value of the effective colloid osmotic pressure difference σΔΠ. After transient adjustments, the mean steady state filtration rate Jv is about the same as the lymph drainage from any tissue.
  6. The revised Starling principle explains the steady uptake of fluid in the absorbing microvessels of tissues such as the intestinal mucosa and the post-glomerular vessels of the renal microcirculation, where a large fraction of the interstitial fluid arises from a protein-free secretion of nearby epithelia.

Now happily the studies I present here are all entirely compatible with the new physiology. They are the “validation in large biological systems” that the Karolinska Institute researchers call for. Have I somehow done a disservice to the physiologists who are still developing Starling physiology? Have I said something to offend Professor Hahn or Professor Ince? Describing concepts of blood-tissue fluid exchange developed over the past 40 years as a revised Starling Principle may be too grandiose and misleading. The ideas are so close to Starling’s own thinking that these concepts are really “The Extended Starling Principle”.

Ernest Starling
  1. Zdolsek M, Hahn RG, Zdolsek JH. Recruitment of extravascular fluid by hyperoncotic albumin. Acta Anaesthesiol Scand. 2018;62:1255-1260.
  2. Hasselgren E, Zdolsek M, Zdolsek JH et al. Long Intravascular Persistence of 20% Albumin in Postoperative Patients. Anesth Analg. 2019
  3. Guerci P, Ergin B, Uz Z et al. Glycocalyx Degradation Is Independent of Vascular Barrier Permeability Increase in Nontraumatic Hemorrhagic Shock in Rats. Anesth Analg. 2018

By admin

after more than a quarter of a century of intensive care medicine consultancy in one of the UK's largest teaching hospitals Dr Woodcock is on a mission to ensure the steady state Starling principle is known and understood by every student and every practitioner.

Leave a comment

Your email address will not be published. Required fields are marked *