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

Abstract

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.

Interstitial washdown during crystalloid fluid loading in graded hypovolemia –A retrospective analysis in volunteers

“…A previous study using the same methodological approach as used in the present study showed negative covariance between the Hb–albumin dilution difference and the urinary excretion [ 3 ]. A similar dependence was close to reaching statistical significance in the present study.…”

“…At the nadir of the redistribution, at 60–70 min, the Hb–albumin difference began to increase. A previous study showed that the albumin concentration of recruited fluid decreases over time [ 3 ], and this probably contributes to the finding that the Hb–albumin dilution difference was not consistently positive during the post-infusion phase.…”

“…The influence of interstitial washdown on the turnover of infusion fluids is poorly understood, largely because of the lack of a suitable methodology for studying this phenomenon. However, a kinetic method to study interstitial washdown was recently suggested [ 3 ]. This method is based on the fact that the lymph has an albumin concentration that is approximately half that of the plasma [ 4, 5 ].…”

Pathophysiology of fluid administration in critically ill patients

“…Colloids are composed of large molecules designed to remain in the intravascular space for several hours, increasing plasma osmotic pressure and reducing the need for further fluids. Despite their theoretical advantages, patients with sepsis often have alterations in glycocalyx and increased endothelial permeability, which may lead to extravasation of colloids' large molecules [63,64], increases the risk of global increased permeability syndrome and abolishes the primary advantage [65]. Colloids are further divided into semisynthetic colloids and albumin.…”

Albumin Kinetics in Sepsis and COVID-19

“…Compared with survivors, age of the population (78 vs 64 yr), underlying severity of illness (Sequential Organ Failure Assessment score: 12 vs 9), comorbidities like active hematological cancer (17% vs 6.8%) and liver disease (29% vs 14%), prevalence of pneumonia (56% vs 38%), and intra-abdominal sepsis (25% vs 18%) were significantly higher in the nonsurvivors. Thus, plausible mechanisms behind the observed albumin trends in nonsurvivors could be high protein nutrition therapy, enhanced hepatic albumin synthesis (acute phase response), and resuscitative measures like hyperoncotic albumin infusions, blood products, or fluid resuscitation leading to PA enrichment by interstitial washdown and enhanced vascular refill of albumin by lymphatics (7). Additionally, host response in sepsis is heterogeneous involving a complex interplay between pro-and anti-inflammatory pathways and may not have a uniform albumin kinetics.…”