Abstract
Objective
To investigate whether the plasma disappearance rate of indocyanine green (ICG) assessed using a commercially available bedside monitor provides an accurate estimation of cumulative biliary ICG excretion in a clinically relevant model of long-term, hyperdynamic porcine endotoxemia.
Design and setting
Prospective experimental study in the animal laboratory in a university hospital.
Subjects
Fifteen domestic pigs.
Interventions
Pigs were anesthetized, mechanically ventilated, and instrumented. Intravenous endotoxin was continuously infused over 12 h concomitant with fluid resuscitation. Measurements were performed before and 12 h after the start of endotoxin infusion.
Measurements and results
All animals developed hyperdynamic circulation characterized by a sustained increase in cardiac output. Despite well maintained portal venous and consequently total liver blood flow endotoxemia decreased hepatic lactate uptake, which was accompanied by a significant fall in portal and hepatic venous pH. Both the cumulative bile flow and biliary ICG and bicarbonate excretion measured during 1 h after intravenous bolus of 25 mg ICG fell significantly. By contrast, neither the plasma disappearance rate of ICG nor the rate corrected for liver blood flow exhibited any changes over time.
Conclusions
In hyperdynamic porcine endotoxemia the plasma disappearance rate of ICG failed to accurately substitute for direct short-term measures of biliary ICG excretion. Hence normal values of plasma disappearance rate of ICG should be interpreted with caution in early, acute inflammatory conditions.
References
Hunton DB, Bollman JL, Hoffman HN (1960) Studies of hepatic function with indocyanine green. Gastroenterology 39:713–724
Uusaro A, Ruokonen E, Takala J (1995) Estimation of splanchnic blood flow by the Fick principle in man and problems in the use of indocyanine green. Cardiovasc Res 30:106–112
Kuntz HD, Schregel W (1990) Indocyanine green: evaluation of liver function—application in intensive care medicine. In: Lewis FR, Pfeiffer UJ (eds) Fiberoptics in critical care monitoring. Springer, Berlin Heidelberg New York, pp 57–62
Sakka SG, Reinhart K, Meier-Hellmann A (2000) Comparison of invasive and noninvasive measurements of indocyanine green plasma disappearance rate in critically ill patients with mechanical ventilation and stable hemodynamics. Intensive Care Med 26:1553–1556
Sakka SG, Reinhart K, Meier-Hellmann A (2002) Prognostic value of the indocyanine green plasma disappearance rate in critically ill patients. Chest 122:1715–1720
Ott P (1998) Hepatic elimination of indocyanine green with special reference to distribution kinetics and the influence of plasma protein binding. Pharmacol Toxicol 83 Suppl 2:1–48
Matejovic M, Radermacher P, Tugtekin I, Stehr A, Theisen M, Vogt J, Wachter U, Ploner F, Georgieff M, Träger K (2001) Effects of selective iNOS inhibition on gut and liver O2-exchange and energy metabolism during hyperdynamic porcine endotoxemia. Shock 16:203–210
Stehr A, Ploner F, Tugtekin I, Matejovic M, Theisen M, Zülke C, Georgieff M, Radermacher P, Jauch KW (2003) Effect of combining nicotinamide as a PARS-inhibitor with selective iNOS blockade during porcine endotoxemia. Intensive Care Med 29:995–1002
Theisen M, Träger K, Tugtekin I, Stehr A, Ploner F, Georgieff M, Radermacher P, Matejovic M (2001) Effects of nicotinamide, an inhibitor of PARS activity, on gut and liver O2 exchange and energy metabolism during hyperdynamic porcine endotoxemia. Intensive Care Med 27:586–592
Nickel N, Schummer A, Seifferle E (1967) Lehrbuch der Anatomie der Haustiere, vol II. Parey, Berlin
Bolder U, Ton-Nu HT, Schteingart CD, Frick E, Hofmann AF (1997) Hepatocyte transport of bile acids and organic anions in endotoxemic rats: impaired uptake and secretion. Gastroenterology 112:214–225
Chijiiwa K, Mizuta A, Ueda J, Takamatsu Y, Nakamura K, Watanabe M, Kuroki S, Tanaka M (2002) Relation of biliary bile acid output to hepatic adenosine triphosphate level and biliary indocyanine green excretion in humans. World J Surg 26:457–461
Ott P, Keiding S, Johnsen AH, Bass L (1994) Hepatic removal of two fractions of indocyanine green after bolus injection in anesthetized pigs. Am J Physiol 266:G1108–G1122
Kisor DF, Frye RF, Kudsk KA (1993) Estimation of the hepatic extraction ratio of indocyanine green in swine. Clin Sci (Lond) 84:681–685
Burns E, Ball CE, Christie JP, Broadhead GD, Tucker GT, Bax ND (1989) Direct, indirect measurement of the hepatic extraction ratio of indocyanine green in the rat (1989) Clin Sci (Lond) 76:503–508
Stoeckel K, McNamara PJ, McLean AJ, duSouich P, Lalka D, Gibaldi M (1980) Nonlinear pharmacokinetics of indocyanine green in the rabbit and rat. J Pharmacokinet Biopharm 8:483–496
Grainger SL, Keeling PW, Brown IM, Marigold JH, Thompson RP (1983) Clearance and non-invasive determination of the hepatic extraction of indocyanine green in baboons and man. Clin Sci (Lond) 64:207–212
Burns E, Triger DR, Tucker GT, Bax ND (1991) Indocyanine green elimination inpatients with liver disease and in normal subjects. Clin Sci (Lond) 80:155–160
Burczynski FJ, Pushka KL, Sitar DS, Greenway CV (1987) Hepatic plasma flow: accuracy of estimation from bolus injections of indocyanine green. Am J Physiol 252:H935–H962
Burczynski FJ, Greenway CV, Sitar DS (1987) Hepatic blood flow: accuracy of estimation from infusions of indocyanine green in anesthetized cats. Br J Pharmacol 91:651–659
Meijer DFK, Weert B, Vermeer (1988) Pharmacokinetics of biliary excretion in man. VI. Indocyanine green. Eur J Clin Pharmacol 35:295–303
Lund M, Kang L, Tygstrup N, Wolkoff AW, Ott P (1999) Effects of LPS on transport of indocyanine green and alanine uptake in perfused rat liver. Am J Physiol 277:G91–G100
Nakamura J, Nishida T, Hayashi K, Kawada N, Ueshima S, Sugiyama Y, Ito T, SobueK, Matsuda H (1999) Kupffer cell-mediated down-regulation of rat hepatic CMOAT/MRP2 gene expression. Biochem Biophys Res Commun 255:143–149
Author information
Authors and Affiliations
Corresponding author
Additional information
A. Stehr and F. Ploner contributed equally to this study
This research was supported by Deutsche Forschungsgemeinschaft (Ra 396/3-1) and a research fellowship from the Alexander von Humboldt Stiftung (M.M.)
Rights and permissions
About this article
Cite this article
Stehr, A., Ploner, F., Traeger, K. et al. Plasma disappearance of indocyanine green: a marker for excretory liver function?. Intensive Care Med 31, 1719–1722 (2005). https://doi.org/10.1007/s00134-005-2826-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00134-005-2826-7