Rapid determination of functional liver plasma flow in ICU patients by a modified hepatic D-sorbitol plasma clearance method

Abstract

Changes in liver perfusion may have a substantial influence on the pharmacokinetics of drugs with flow-controlled metabolism. This may have important implications for drug dosage in patients in an intensive care unit (ICU). The hepatic D-sorbitol plasma clearance has been suggested as a non-invasive test for evaluating functional liver plasma flow, which is in reasonable agreement with the direct blood measurement. However, its determination requires D-sorbitol infusion for 3 h or administration of a D-sorbitol bolus and withdrawal of blood specimens every 3-5 min. Since both variants are impractical in the ICU setting, a bolus/infusion technique was tested. A combined technique applying a bolus (0.85 mg/kg) and steady-state infusion (0.0014 mg/kg/min) of D-sorbitol was tested in 10 ICU patients without hepatic disease (group 1) and in 10 ICU patients with liver disease (group 2). Steady-state plasma levels (+/- 9%, P < 0.05) could be achieved within 60 min in all patients. The modified D-sorbitol clearance method requires a bolus and an infusion of D-sorbitol and withdrawal of a single blood specimen after 60 min. The lowest values of functional liver plasma flow were determined in patients with decompensated liver cirrhosis, acute fatty degeneration of the liver or Budd-Chiari syndrome. The method for routine determination of functional hepatic plasma perfusion proved to be rapid, safe and non-invasive in ICU patients. Hepatic D-sorbitol clearance may be especially useful for assessing the functional aspect of liver perfusion.

Hepatic plasma flow estimated according to fick's principle in patients with hepatic encephalopathy: Evaluation of indocyanine green and d-sorbitol as test substances

“…[2][3][4]7,9,10 One earlier study of patients with severe ALF (information about presence of HE was not given), where flow was estimated by use of systemic sorbitol clearance, it was concluded that hepatic plasma flow was low; around 450 mL/min. 1 As seen from Table 2, a clearance method will grossly underestimate hepatic plasma flow because it requires that E equals 1. When the methodology with liver vein catheterization was applied, we found that hepatic plasma flow was clearly elevated.…”

“…A single study indicated that estimated hepatic plasma flow (EHPF) was low, i.e., 450 mL/min in patients with ALF. 1 Studies in patients with CLF without HE have reported either normal or decreased EHPF in this condition. [2][3][4] The lack of solid data in this field is primarily a method problem.…”

Location and function of intrahepatic shunts in anaesthetised rats

“…14 15 However, the shunt fraction measured by radiolabelled microspheres is limited by the 15 µm diameter of microspheres used, and by definition, blood flow through small shunts (<15 µm) is excluded. Most clearance methods currently available for human studies, including sorbitol clearance, require long infusion times, numerous large volumes of blood, [16][17][18][19][20] and are thus unsuitable for use in small animals such as the rat.…”

“…Sorbitol was selected because it is safe, easy to measure, and has a high extraction ratio in the normal liver without interference from glucose. [16][17][18][19] Thus the aims of the present study were to determine: (i) the proportion (shunt fraction) of intrahepatic shunt flow in the normal rat liver following intrahepatic portal occlusion by microspheres; (ii) the anatomical origin of these shunts in the normal liver; and (iii) the site of confluence between the hepatic artery and portal vein.…”