Volume Kinetic Analysis in Living Humans: Background History and Answers to 15 Questions in Physiology and Medicine

Volume kinetics is a pharmacokinetic method for analysis of the distribution and elimination of infusion fluids. The approach has primarily been used to improve the planning of fluid therapy during surgery but is also useful for answering physiological questions. The kinetics is based on 15–35 serial measurements of the blood hemoglobin concentration during and after the fluid is administered intravenously. Crystalloid fluid, such as isotonic saline and Ringer’s lactate, distributes between three compartments that are filled in succession depending on how much fluid is administered. The equilibration of fluid between these three compartments is governed by five rate constants. The compartments are the plasma (Vc), and a fast-exchange (Vt1) and a slow-exchange interstitial compartment (Vt2). The last compartment operates like an overflow reservoir and, if filled, markedly, prolongs the half-life of the fluid. By contrast, the volume of a colloid fluid distributes in a single compartment (Vc) from where the expansion is reduced by capillary leakage and urinary excretion. This review gives 15 examples of physiological or medical questions where volume kinetics has provided answers. These include why urine flow is low during general anesthesia, the inhibitory effects of anesthetics on lymphatic pumping, the influence of dopamine and phenylephrine on urine output, fluid maldistribution in pre-eclampsia, plasma volume oscillations, and issues related to the endothelial glycocalyx layer.