Interstitial washdown and vascular albumin refill during fluid infusion: novel kinetic analysis from three clinical trials

Robert G Hahn,Randal O Dull

doi:10.1186/s40635-021-00407-6

Abstract

Background and aimsIncreased capillary filtration may paradoxically accelerate vascular refill of both fluid and albumin from the interstitial space, which is claimed to be edema-preventing. We characterized this proposed mechanism, called “interstitial washdown”, by kinetic analyses of the hemodilution induced by intravenous infusion of crystalloid fluid during 3 distinct physiological states.MethodsGreater plasma dilution of hemoglobin as compared to albumin during fluid therapy indicated recruitment of albumin, which was compared to the flow of interstitial fluid to the plasma as indicated by population volume kinetic analysis. Data for the comparison were derived from 24 infusions of crystalloid fluid in conscious volunteers, 30 in anesthetized patients, and 31 in patients with ketoacidosis from hyperglycemia.Results“Interstitial washdown” increased the plasma albumin concentration by between 0.3 and 1.0 g/L in the three series of infusions. The initial albumin concentration in the interstitial fluid returning to the plasma was estimated to between 22 g/L and 29 g/L, which decreased to an average of 50–75% lower during the subsequent 2–3 h. Kinetic simulations show that pronounced washdown was associated with increased capillary filtration (high k12) and, in conscious subjects, with greater plasma and interstitial volume expansion and restricted urine flow. During anesthesia, the main effect was an increase in the non-exchangeable fluid volume (“third-spacing”).ConclusionsCrystalloid fluid accelerates lymphatic flow that moderately increases plasma albumin, but more clearly helps to maintain the intravascular volume. This “interstitial washdown” mechanism becomes exhausted after a few hours.

Highlights

Current evidence suggests that distribution and kinetics of crystalloid fluid differ greatly between the awake state, general anesthesia, and in pathological metabolic syndromes
The present study explores this “interstitial washdown”, which implies that interstitial albumin is transferred to the plasma either by acceleration of the lymphatic flow or by some other mechanism that recruits albumin
Evaluated trials This retrospective study of interstitial washdown was based on the difference in plasma dilution when calculated from the blood hemoglobin (Hb) and plasma albumin concentrations during and after infusion of Ringer’s acetate in three populations

Summary

Introduction

Current evidence suggests that distribution and kinetics of crystalloid fluid differ greatly between the awake state, general anesthesia, and in pathological metabolic syndromes [1].Hahn and Dull ICMx (2021)9:44Unresolved issues remain with regard to the turnover of crystalloid fluid in the human body that may serve to explain such differences. Second is the poorly studied mechanism of “interstitial washdown” originally suggested by the eminent physiologist Arthur Guyton to counteract peripheral edema when capillary filtration is increased [3]. Lymphatic flow increases promptly in response to intravenous volume loading in the dog [6], but whether the induced flow is sufficient to prevent edema during crystalloid fluid therapy in humans is unknown. Increased capillary filtration may paradoxically accelerate vascular refill of both fluid and albumin from the interstitial space, which is claimed to be edema-preventing. We characterized this proposed mechanism, called “interstitial washdown”, by kinetic analyses of the hemodilution induced by intravenous infusion of crystalloid fluid during 3 distinct physiological states

Objectives

Methods

Results

Conclusion