The recent publication by Löffel et al1 concerning the Starling principle reveals some important misunderstandings common amongst clinicians about the science. The Authors confuse the Frank Starling Law (of the heart) with Starling’s principle of fluid exchange, often expressed as the Starling equation which I explain here.
Jv is the transendothelial solvent filtration rate, A is the surface area of fluid exchange, Lp is the hydraulic conductance of the exchange membrane. The hydrostatic pressure difference across the membrane is ΔP, and ΔΠ is the actual colloid osmotic pressure difference. Stavermann’s reflection coefficient σ modifies the latter to the effective colloid osmotic pressure difference σΔΠ.
Löffel et al falsely claim that “the Revised Starling mechanism” (sic) holds that interstitial fluid cannot be recruited by raising the plasma oncotic pressure and that capillary leakage of albumin increases from the inflammation induced by major surgery.” There being no such thing as the Revised Starling mechanism I can only guess they are referring to the Michel-Weinbaum model (also called the glycocalyx model) which explains the dependence of subglycocalyx colloid osmotic pressure on the filtration rate Jv. As they cite my work2 I have to state that I have never denied that the colloid osmotic pressure of plasma is an absorptive Starling force. What I actually wrote about this sort of protocol was “When albumin is used for normovolaemic haemodilution, keeping capillary pressure normal, the transendothelial solvent filtration rate is not increased and so most of the infused volume remains intravascular.” My Model for prescribers of fluid therapy is therefore affirmed by the findings reported, and certainly not disproven.
Starling believed, as is still incorrectly taught by some experts, that most microvessels are impermeable to plasma proteins and that the concentrations of proteins in the interstitial fluids are very low. He proposed that fluid movements between the plasma and the tissues are self-limiting and therefore could explain the regulation of plasma volume. In Starling’s 19th century view, filtration is followed by solvent reabsorption as blood passes along capillaries and uninvested venules. Michel, Curry and myself have recently explained the current status of the Starling principle. It has long been known that albumin is normally circulated from plasma to the interstitial fluid, returning to the blood stream in efferent lymph. The permeability of microvessels to proteins, expressed in the Starling equation as Stavermann’s reflection coefficient σ, makes a filtration/ reabsorption equilibrium physically impossible. At the arteriolar commencement of a capillary the dominant capillary pressure drives Jv which dilutes subglycocalyx proteins creating a local microdomain of the tissue fluid with very low colloid osmotic pressure. As blood flows towards the venule, capillary pressure declines and Jv is consequently reduced. With a reduced rate of dilution by protein-free filtrate the subglycocalyx protein concentration rises by diffusion from the interstitial fluid, increasing the subglycocalyx colloid osmotic pressure and reducing σΔΠ. At steady state filtration is thus preserved along the length of a continuous microvessel and reabsorption does not occur3.
Many researchers have documented the changing transcapillary escape rate of albumin (TCERA) in surgical patients since the landmark study of Adam Fleck and his team in Glasgow4. As the authors did not measure TCERA they have no grounds for denying that it may have changed.
- Löffel LM, Hahn RG, Engel D, Wuethrich PY. Intraoperative Intravascular Effect of Lactated Ringer’s Solution and Hyperoncotic Albumin During Hemorrhage in Cystectomy Patients. Anesthesia & Analgesia: August 2021 – Volume 133 – Issue 2 – p 413-422
- Woodcock TE, Woodcock TM. Revised Starling equation and the glycocalyx model of transvascular fluid exchange: an improved paradigm for prescribing intravenous fluid therapy. Br J Anaesth. 2012;108:384-394.
- Michel CC, Woodcock TE, Curry FE. Understanding and extending the Starling Principle. Acta Anaesthesiol Scand. 2020;64:1032-1037.
- Fleck A, Raines G, Hawker F et al. Increased vascular permeability: a major cause of hypoalbuminaemia in disease and injury. Lancet. 1985;1:781-784.