Sorbitol as a test substance for measurement of liver plasma flow in humans

The objective of this study was to evaluate whole-body removal kinetics of sorbitol, the use of extrarenal sorbitol clearance to estimate hepatic plasma flow in humans, and to compare measurements of liver flow by Fick's principle using either indocyanine green (ICG) or sorbitol. A sorbitol bolus (5 mmol/kg) was given intravenously to 6 controls for determination of sorbitol elimination capacity (SEC) and distribution volume, V(sorb)d. Sorbitol infusion (287 micromol/ min) was given to 17 liver patients and 11 controls. Extrarenal sorbitol clearance (V(sorb)x was calculated as infusion rate (corrected for renal excretion and accumulation in V(sorb)d) divided by arterial concentration. Liver flow (Q(ICG)) was calculated from the ICG infusion and arterial and hepatic venous ICG concentrations by Fick's principle. Average SEC was 73 micromol/min/kg, V(sorb)d was 0.16 L plasma per kilogram, and in vivo V(sorb)d was 3 mmol/L. Renal sorbitol excretion rate was 0.03 to 0.31 of infusion rate. Extrahepatic extrarenal removal was not significantly different from zero but varied considerably. Hepatic extraction fraction of sorbitol, (E(sorb)), measured by liver vein catheterization, was 0.35 to 1.04 (median, 0.86) in cirrhotic patients and 0.90 to 0.98 (0.86) in controls. The requirements for using Cl(sorb)x as an estimate of Q(ICG) was not violated by the data in controls, Cl(sorb)x/Q(ICG) 0.70 to 1.55 [median, 1.08]), whereas there was a systematic underestimation in cirrhotic patients (0.72-1.08 [0.85]). Liver flow calculated by Fick's principle using either sorbitol or ICG agreed well. E(sorb) > E(ICG) in each individual except one. Curvilinear relationship between E(sorb) and E(ICG) was in agreement with different kinetic parameters for sorbitol and ICG, and did not require additional assumption of intrahepatic shunts.