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

Background and aims: 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. Methods: Greater 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”). Conclusions: Crystalloid 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.