Intensive Care Medicine

, Volume 31, Issue 12, pp 1719–1722 | Cite as

Plasma disappearance of indocyanine green: a marker for excretory liver function?

  • Alexander Stehr
  • Franz Ploner
  • Karl Traeger
  • Marc Theisen
  • Carl Zuelke
  • Peter Radermacher
  • Martin Matejovic
Brief Report

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.

Keywords

Endotoxin Sepsis Indocyanine green Liver function Liver blood flow Biliary excretion 

References

  1. 1.
    Hunton DB, Bollman JL, Hoffman HN (1960) Studies of hepatic function with indocyanine green. Gastroenterology 39:713–724PubMedGoogle Scholar
  2. 2.
    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 30:106–112CrossRefPubMedGoogle Scholar
  3. 3.
    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 57–62Google Scholar
  4. 4.
    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 26:1553–1556CrossRefPubMedGoogle Scholar
  5. 5.
    Sakka SG, Reinhart K, Meier-Hellmann A (2002) Prognostic value of the indocyanine green plasma disappearance rate in critically ill patients. Chest 122:1715–1720CrossRefPubMedGoogle Scholar
  6. 6.
    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 2:1–48Google Scholar
  7. 7.
    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 16:203–210PubMedGoogle Scholar
  8. 8.
    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 29:995–1002PubMedGoogle Scholar
  9. 9.
    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 27:586–592CrossRefPubMedGoogle Scholar
  10. 10.
    Nickel N, Schummer A, Seifferle E (1967) Lehrbuch der Anatomie der Haustiere, vol II. Parey, BerlinGoogle Scholar
  11. 11.
    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 112:214–225PubMedGoogle Scholar
  12. 12.
    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 26:457–461CrossRefPubMedGoogle Scholar
  13. 13.
    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–G1122PubMedGoogle Scholar
  14. 14.
    Kisor DF, Frye RF, Kudsk KA (1993) Estimation of the hepatic extraction ratio of indocyanine green in swine. Clin Sci (Lond) 84:681–685Google Scholar
  15. 15.
    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) 76:503–508Google Scholar
  16. 16.
    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 8:483–496CrossRefPubMedGoogle Scholar
  17. 17.
    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) 64:207–212Google Scholar
  18. 18.
    Burns E, Triger DR, Tucker GT, Bax ND (1991) Indocyanine green elimination inpatients with liver disease and in normal subjects. Clin Sci (Lond) 80:155–160Google Scholar
  19. 19.
    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–H962Google Scholar
  20. 20.
    Burczynski FJ, Greenway CV, Sitar DS (1987) Hepatic blood flow: accuracy of estimation from infusions of indocyanine green in anesthetized cats. Br J Pharmacol 91:651–659PubMedGoogle Scholar
  21. 21.
    Meijer DFK, Weert B, Vermeer (1988) Pharmacokinetics of biliary excretion in man. VI. Indocyanine green. Eur J Clin Pharmacol 35:295–303CrossRefPubMedGoogle Scholar
  22. 22.
    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–G100PubMedGoogle Scholar
  23. 23.
    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 255:143–149CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Alexander Stehr
    • 1
  • Franz Ploner
    • 2
  • Karl Traeger
    • 4
  • Marc Theisen
    • 5
  • Carl Zuelke
    • 1
  • Peter Radermacher
    • 4
  • Martin Matejovic
    • 3
    • 4
  1. 1.Klinik und Poliklinik für ChirurgieUniversitätsklinikumRegensburgGermany
  2. 2.Regional Hospital SterzingDepartment of Anesthesiology and Intensive CareSterzingItaly
  3. 3.JIP, 1. Interni Klinika, Lekarska Fakulta a Fakultni Nemocnice PlzenKarlova Univerzita PrahaPlzenCzech Republic
  4. 4.Sektion Anästhesiologische Pathophysiologie und VerfahrensentwicklungUniversitätsklinikumUlmGermany
  5. 5.Klinik und Poliklinik für Anästhesiologie und Operative IntensvimedizinWestfälische Wilhelms-UniversitätMünsterGermany

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