NJCC_02 bwerk v4.indd

In contrast to pulmonary, cardiovascular, renal and neurological function, liver function is not easily monitored in the critically ill. Traditionally, the degree of liver dysfunction is assessed by using biochemical tests transaminases, bilirubin, albumin and prothrombin time. These are static tests, they only assess the presence of hepatobiliary injury and tend to respond late to damage. Moreover, they do not track organ perfusion, oxygenation or the functional capacity of the liver. Over the last decades, several dynamic tests have been developed that use hepatic clearance of tracer substances (indocyanine green) or metabolic capacity for certain drugs (lidocaine) as a measure of hepatic function. Recently, automatic non-invasive devices have become available which promise dynamic assessment of liver function based on indocyanine green plasma disappearance rate (ICG-PDR). This review focuses on the principles, limitations and clinical use of non-invasive liver monitoring with ICG-PDR in the critically ill. Although there is clinical evidence in favour of the prognostic use of ICG-PDR in critically ill patients, no interventions studies exist using ICG-PDR to titrate therapy. Finally, we also briefly describe some other non-invasive techniques in this context including the monoethylglycinexylidide (MEGX) test, Doppler ultrasound flowmetry and scintigraphy. Introduction Monitoring of organ function in the intensive care unit (ICU) is usually considered in terms of following moment-to-moment changes of relatively easily measurable parameters. Ideally, these parameters are able to detect organ dysfunction and help in guiding therapeutic interventions from the clinician, the aim being bedside titration of care. This concept is typically applied to pulmonary, cardiovascular, renal and neurological monitoring. Arterial oxygen saturation, pH, heart rate, cardiac output, blood pressure and urine output all represent critical aspects of function which are measurable and can be promptly addressed in the modern ICU. In contrast, the complexity of liver function, the inability to easily and inexpensively measure liver function and our limited ability to intervene, compromise the utility of liver monitoring. Liver function includes the removal of substances from blood passing through its sinusoids by uptake and metabolism, synthesis and storage of new products and secretion of manufactured substances into the blood and bile. These are determined not only by integrity of liver mass, but also by perfusion (hepatic artery, portal vein) and outflow pathways (hepatic vein, bile ducts). Traditionally, the degree of liver dysfunction is assessed by using tests which reflect cellular permeability (transaminases) and excretory (bilirubin) or synthetic capacity (albumin, bilirubin and prothrombin time). These are static tests and simply assess the presence or absence of hepatobiliary injury and thus tend to respond late to damage, although evidence exists that hepatic dysfunction arises soon after injury [1][2]. Moreover, they are not useful in tracking organ perfusion, oxygenation or functional capacity of the liver over short periods of time [3]. In addition, variables evaluating the excretory and synthetic capacity of the liver are influenced by the use of plasma products. In the vast majority of cases, these tests do not adequately monitor liver function or guide therapy in critically ill patients. Dynamic measurement of hepatic clearance of tracer substances like indocyanine green (ICG), seem to provide a more direct measure of the actual functional state of the liver. Other dynamic tests use the capacity of the liver to metabolize certain drugs (lidocaine or breath tests with antipyrine/aminopyrine) as a measure of hepatic function. These tests may provide more sensitive short-term indicators of disturbances in hepatic perfusion and function. Due to multiple interactions with inductors or inhibitors of the cytochrome oxidase system and due to a long half-life (15-35 hours), breath tests with antipyrine or aminopyrine are not suited as dynamic liver function tests in the ICU setting. Recently, automatic non-invasive devices have become available that promise assessment of liver function based on indocyanine green plasma disappearance rate (ICG-PDR) in contrast to previous more invasive liver monitoring tools requiring femoral artery or hepatic vein catheterization. The purpose of this review is to discuss the principles, limitations and clinical use of non-invasive liver monitoring with ICG-PDR in the critically ill. In addition, we will also put into context some other non-invasive techniques such as the monoethylglycinexylidide (MEGX) test, Doppler ultrasound flowmetry and scintigraphy. Indocyanine green plasma disappearance rate (ICG-PDR): underlying principles and limitations ICG is a water-soluble anionic dye which is highly protein-bound after injection into the circulation. ICG is taken up almost exclusively Correspondence: J Wauters E-mail: [email protected] Copyright ©2007, Nederlandse Vereniging voor Intensive Care. All Rights Reserved. Received: July 2006; Accepted: February 2007 NJCC_02 bwerk v4.indd 92 10-04-2007 17:35:47 netherlands journal of critical care 93 neth j crit care • volume 11 • no 2 • april 2007 by the hepatocytes and is excreted unchanged into the bile without enterohepatic recirculation (Figure 1). Elimination of ICG from the blood is determined by several factors: hepatic blood flow, ATP-independent hepato-cellular uptake over the sinusoidal membrane, passage through the hepatocytes and excretion into the bile via a highly ATP-demanding transporter in the canalicular membrane. ICG has no known side effects other than a quite rare allergic reaction with iodine with an incidence of 1:40 000 [4]. In 1945, Bradley et al. described the continuous dye infusion technique to measure total liver blood flow (TLBF) based on Fick’s principle [5]. Prerequisites for validity were the placement of a hepatic venous catheter and the presence of a steady-state arterial dye concentration within a 10% range. Bradley used bromsulphthalein (BSP), but subsequently indocyanine green (ICG) was used since it exhibits, unlike BSP, almost negligible extra-hepatic removal. Many authors have validated this continuous dye infusion technique for measurement of TLBF in a wide variety of intensive care patients