Hypovolemia with peripheral edema: What is wrong?

Abstract

Fluid normally exchanges freely between the plasma and interstitial space and is returned primarily via the lymphatic system. This balance can be disturbed by diseases and medications. In inflammatory disease states, such as sepsis, the return flow of fluid from the interstitial space to the plasma seems to be very slow, which promotes the well-known triad of hypovolemia, hypoalbuminemia, and peripheral edema. Similarly, general anesthesia, for example, even without mechanical ventilation, increases accumulation of infused crystalloid fluid in a slowly equilibrating fraction of the extravascular compartment. Herein, we have combined data from fluid kinetic trials with previously unconnected mechanisms of inflammation, interstitial fluid physiology and lymphatic pathology to synthesize a novel explanation for common and clinically relevant examples of circulatory dysregulation. Experimental studies suggest that two key mechanisms contribute to the combination of hypovolemia, hypoalbuminemia and edema; (1) acute lowering of the interstitial pressure by inflammatory mediators such as TNFα, IL-1β, and IL-6 and, (2) nitric oxide-induced inhibition of intrinsic lymphatic pumping.

Capillary leak and endothelial permeability in critically ill patients: a current overview

“…Fluids in the intercellular space can be categorized into two types: unbound fluid and fluid that is part of the gel phase. The gel phase consists of a lattice-like structure made up of collagen and various other fibrous matrix proteins [ 151 ]. Fluids are typically free to move between the interstitial space and plasma.…”

“…Post-filtration, these fluids are channeled back into the circulatory system through the lymphatic network. However, pathological states and certain drugs can disrupt this equilibrium [ 151 ]. In inflammatory conditions like sepsis, the fluid's return from the interstitial space towards the plasma may be significantly hindered, leading to the characteristic triad of low blood volume, low albumin levels, and peripheral edema [ 151 , 152 ].…”

“…However, pathological states and certain drugs can disrupt this equilibrium [ 151 ]. In inflammatory conditions like sepsis, the fluid's return from the interstitial space towards the plasma may be significantly hindered, leading to the characteristic triad of low blood volume, low albumin levels, and peripheral edema [ 151 , 152 ]. Even general anesthesia, without the use of mechanical ventilation, has been observed to cause an accumulation of crystalloid fluid, that was previously infused, in a slowly equalizing segment of extravascular spaces [ 151 , 153 ].…”

Un-supervised classification of ICU patients according to congestion endotypes identifies clinical profiles associated with distinct outcomes: theCodOrea study.

“…The "volume overload congestion" endotype exhibits uid overload with hypervolemia. In the ICU, positive uid balance may not necessarily lead to venous congestion due to alterations in the endothelium and uid distribution [25]. Due to preserved cardiac function the ventricular lling pressures remain within the normal range despite a high portal pulsatility index.…”

Blood volume and hemodynamics during treatment of major hemorrhage with Ringer solution, 5% albumin, and 20% albumin: a single-center randomized controlled trial

“…Intravenous fluid administration during surgery should still be planned to maintain normovolemia and adequate hemodynamics. However, fluid management is more challenging than in the awake state, as general anesthesia obtunds the body´s ability to correct both fluid overload and hypovolemia; the diuretic response to infused fluid is only 10–15% of normal and the depressive effect of intravenous and volatile anesthetics on lymphatic pumping promotes hypovolemia and decreases the ability to compensate hypovolemia by capillary refill [ 1 – 5 ].…”