Intensive Care Medicine

, Volume 37, Issue 8, pp 1302–1310 | Cite as

Impact of hypoxic hepatitis on mortality in the intensive care unit

  • Valentin FuhrmannEmail author
  • Nikolaus Kneidinger
  • Harald Herkner
  • Gottfried Heinz
  • Mariam Nikfardjam
  • Anja Bojic
  • Peter Schellongowski
  • Bernhard Angermayr
  • Maximilian Schöniger-Hekele
  • Christian Madl
  • Peter Schenk



Hypoxic hepatitis (HH) is a form of hepatic injury following arterial hypoxemia, ischemia, and passive congestion of the liver. We investigated the incidence and the prognostic implications of HH in the medical intensive care unit (ICU).


A total of 1,066 consecutive ICU admissions at three medical ICUs of a university hospital were included in this prospective cohort study. All patients were screened prospectively for the presence of HH according to established criteria. Independent risk factors of mortality in this cohort of critically ill patients were identified by a multivariate Poisson regression model.


A total of 118 admissions (11%) had HH during their ICU stay. These patients had different baseline characteristics, longer median ICU stay (8 vs. 6 days, p < 0.001), and decreased ICU survival (43 vs. 83%, p < 0.001). The crude mortality rate ratio of admissions with HH was 4.62 (95% CI 3.63–5.86, p < 0.001). Regression analysis demonstrated strong mortality risk for admissions with HH requiring vasopressor therapy (adjusted rate ratio 4.91; 95% CI 2.51–9.60, p < 0.001), whereas HH was not significantly associated with mortality in admissions without vasopressor therapy (adjusted rate ratio 1.79, 95% CI 0.52–6.23, p = 0.359).


Hypoxic hepatitis (HH) occurs frequently in the medical ICU. The presence of HH is a strong risk factor for mortality in the ICU in patients requiring vasopressor therapy.


Hypoxic liver injury Ischemic hepatitis Shock liver Mortality Vasopressors Epidemiology Outcome 



Serum alanine transaminase


Serum aspartate transaminase


Confidence interval


Intensive care unit


Interquartile range


Hypoxic hepatitis


Rate ratio


Simplified acute physiology score


Conflict of interest

The authors of have nothing to disclose.


  1. 1.
    Fuchs S, Bogomolski-Yahalom V, Paltiel O, Ackerman Z (1998) Ischemic hepatitis. Clinical and laboratory observations of 34 patients. J Clin Gastroenterol 26:183–186PubMedCrossRefGoogle Scholar
  2. 2.
    Henrion J, Schapira M, Luwart L, Colin L, Delannoy A, Heller FR (2003) Hypoxic hepatitis: clinical and hemodynamic study in 142 consecutive cases. Medicine 82:392–406PubMedCrossRefGoogle Scholar
  3. 3.
    Fuhrmann V, Kneidinger N, Herkner H, Heinz G, Nikfardjam M, Bojic A, Schellongowski P, Angermayr B, Kitzberger R, Warszawska J, Holzinger U, Schenk P, Madl C (2009) Hypoxic hepatitis: underlying conditions and risk factors for mortality in critically ill patients. Intensive Care Med 35:1397–1405PubMedCrossRefGoogle Scholar
  4. 4.
    Thomson SJ, Cowan ML, Johnston I, Musa S, Grounds M, Rahman TM (2009) “Liver function tests” on the intensive care unit: a prospective, observational study. Intensive Care Med 35:1406–1411PubMedCrossRefGoogle Scholar
  5. 5.
    Kramer L, Jordan B, Druml W, Bauer P, Metnitz PG, Austrian Epidemiologic Study on Intensive Care, ASDI Study Group (2007) Incidence and prognosis of early hepatic funciton in critically ill patients—a prospective multicenter study. Crit Care Med 35:1099–1104PubMedCrossRefGoogle Scholar
  6. 6.
    Birrer R, Takuda Y, Takara T (2007) Hypoxic hepatopathy: pathophysiology and prognosis. Intern Med 46:1063–1070PubMedCrossRefGoogle Scholar
  7. 7.
    Ebert E (2006) Hypoxic liver injury. Mayo Clin Proc 81:1232–1236PubMedCrossRefGoogle Scholar
  8. 8.
    Richardson P, McKenna W, Bristow M, Maisch B, Mautner B, O’Connell J, Olsen E, Thiene G, Goodwin J, Gyarfas I, Martin I, Nordet P (1996) Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of Cardiomyopathies. Circulation 93:841–842PubMedCrossRefGoogle Scholar
  9. 9.
    Gibson PR, Dudely F (1984) Ischemic hepatitis: clinical features, diagnosis and prognosis. Aust N Z J Med 14:825–922Google Scholar
  10. 10.
    Gitlin N, Serio K (1992) Ischemic hepatitis: widening horizons. Am J Gastroenterol 87:831–836PubMedGoogle Scholar
  11. 11.
    Hickman PE, Potter J (1990) Mortality associated with ischemic hepatitis. Aust N Z J Med 20:32–34PubMedGoogle Scholar
  12. 12.
    Rawson JS, Achord J (1985) Shock liver. South Med J 78:1421–1425PubMedCrossRefGoogle Scholar
  13. 13.
    Seeto RK, Fenn B, Rockey DC (2000) Ischemic hepatitis: clinical presentation and pathogenesis. Am J Med 109:109–113PubMedCrossRefGoogle Scholar
  14. 14.
    Whitehead MW, Hawkes ND, Hainsworth I, Kingham JG (1999) A prospective study of the causes of notably raised aspartate aminotransferases of liver origin. Gut 45:129–133PubMedCrossRefGoogle Scholar
  15. 15.
    Gillum BS, Graves E, Kozak LJ (1989) Vital and health statistics. Trends in hospital utilization: United States 1965–86. Vital Health Stat 13:1–57Google Scholar
  16. 16.
    Martin GS, Mannino D, Eaton S, Moss M (2003) The epidemiology of sepsis in the United States from 1979 to 2000. N Engl J Med 348:1546–1554PubMedCrossRefGoogle Scholar
  17. 17.
    Waikar SS, Curhan G, Wald R, McCarthy EP, Chertow GM (2006) Declining mortality in patients with acute renal failure, 1988 to 2002. J Am Soc Nephrol 17:1143–1150PubMedCrossRefGoogle Scholar
  18. 18.
    Annane D, Aegerter P, Jars-Guincestre MC, B Guidet for the CUB-Rea Network (2003) Current epidemiology of septic shock. Am J Respir Crit Care Med 168:165–172PubMedCrossRefGoogle Scholar
  19. 19.
    Johnson RD, O′Connor C, Kerr M (1995) Extreme serum elevations of aspirate aminotransferase. Am J Gastroenterol 90:1244–1245PubMedGoogle Scholar
  20. 20.
    Fuhrmann V, Madl C, Mueller C, Holzinger U, Kitzberger R, Funk GC, Schenk P (2006) Hepatopulmonary syndrome in patients wit hypoxic hepatitis. Gastroenterology 131:69–75PubMedCrossRefGoogle Scholar
  21. 21.
    Hirsch LJ, Ayabe T, Glick G (1976) Direct effects of various catecholamines on liver circulation in dogs. Am J Physiol 230:1394–1399PubMedGoogle Scholar
  22. 22.
    Reilly FD, McCuseky R, Cilento EV (1981) Hepatic microvascular regulatory mechanism. I. Adrenergic mechanis. Microvasc Res 21:103–116PubMedCrossRefGoogle Scholar
  23. 23.
    Krejci V, Hiltebrand L, Sigurdson GH (2006) Effect of epinephrine, norepinephrine, and phenylepinephrine on microvascular blood flow in the gastrointestinal tract in sepsis. Crit Care Med 34:1456–1463PubMedCrossRefGoogle Scholar
  24. 24.
    Mehrabi A, Golling M, Kashfi A, Boucsein T, Schemmer P, Gutt CN, Schmidt J, Büchler MW, Kraus TW (2005) Negative impact of systemic catecholamine administration on hepatic blood perfusion after porcine liver transplantation. Liver Transpl 11:174–187PubMedCrossRefGoogle Scholar
  25. 25.
    Aninat C, Seguin P, Descheemaeker PN, Morel F, Malledant Y, Guillouzo A (2008) Catecholamines induce an inflammatory response in human hepatocytes. Crit Care Med 36:848–854PubMedCrossRefGoogle Scholar
  26. 26.
    Fuhrmann V, Jäger B, Zubkova A, Drolz A (2010) Hypoxic hepatitis-epidemiology, pathophysiology and clinical management. Wien Klin Wochenschr 122:129–139PubMedCrossRefGoogle Scholar
  27. 27.
    Nielsen VG, Tan S, Baird MS, Samuelson PN, McCammon AT, Parks DA (1997) Xanthine oxidase mediates myocardial injury after hepatoenteric ischemia–reperfusion. Crit Care Med 25:1044–1050PubMedCrossRefGoogle Scholar
  28. 28.
    Peralta C, Perales JC, Bartrons R, Mitchell C, Gilgenkrantz H, Xaus C, Prats N, Fernández L, Gelpí E, Panés J, Roselló-Catafau J (2002) The combination of ischemic preconditioning and liver Bcl-2 over expression is a suitable strategy to prevent liver and lung damage after hepatic ischemia–reperfusion. Am J Pathol 160:2111–2122PubMedCrossRefGoogle Scholar
  29. 29.
    Jiang H, Meng F, Li W, Tong L, Qiao H, Sun X (2007) Splenectomy ameliorates acute multiple organ damage induced by warm ischemia reperfusion in rats. Surgery 141:32–40PubMedCrossRefGoogle Scholar
  30. 30.
    Szabo G, Romics L, Frendl G (2002) Liver in sepsis and systemic inflammatory response syndrome. Clin Liver Dis 6:1045–1066PubMedCrossRefGoogle Scholar
  31. 31.
    Antoniades CG, Berry PA, Wendon JA, Vergani D (2008) The importance of immune dysfunction in determining outcome in acute liver failure. J Hepatol 49:845–861PubMedCrossRefGoogle Scholar
  32. 32.
    Sakka S, von Hout N (2006) Relation between indocyanine green clearance (ICG) plasma disappearance rate and ICG blood clearance in critically ill patients. Intensive Care Med 32:766–769PubMedCrossRefGoogle Scholar
  33. 33.
    Sakka S, Reinhart K, Meier-Hellmann A (2002) Prognostic value of the indocyanine green plasma disappearance rate in critically ill patients. Chest 122:1715–1720PubMedCrossRefGoogle Scholar
  34. 34.
    Dresing K, Armstrong VW, Leip CL, Streit F, Burchardi H, Stürmer KM, Oellerich M (2007) Real-time assessment of hepatic function is related to clinical outcome in critically ill patients after polytrauma. Clin Biochem 40:1194–2000PubMedCrossRefGoogle Scholar
  35. 35.
    Henrion J, Descamps O, Luwaert R, Schapira M, Parfonry A, Heller F (1994) Hypoxic hepatitis in patients with cardiac failure: incidence in a coronary care unit and measurement of hepatic blood flow. J Hepatol 21:696–703PubMedCrossRefGoogle Scholar
  36. 36.
    Naschitz JE, Yeshurun D (1987) Compensated cardiogenic shock: a subset with damage limited to liver and kidneys. The possible salutary effect of low-dose dopamine. Cardiology 74:212–218PubMedCrossRefGoogle Scholar
  37. 37.
    Guo L, Richardson KS, Tucker LM, Doll MA, Hein DW, Arteel GE (2004) Role of the renin-angiotensin system in hepatic ischemia reperfusion injury in rats. Hepatology 40:583–589PubMedCrossRefGoogle Scholar
  38. 38.
    Casillas-Ramirez A, Amine-Zaouali M, Massip-Salcedo M, Padrissa-Altés S, Bintanel-Morcillo M, Ramalho F, Serafín A, Rimola A, Arroyo V, Rodés J, Roselló-Catafau J, Peralta C (2008) Inhibition of angiotenin II action protects steatotic liver against ischemia–reperfusion injury. Crit Care Med 36:1256–1266PubMedCrossRefGoogle Scholar
  39. 39.
    Dezfulian C, Raat N, Shiva S, Gladwin MT (2007) Role of anion nitrite in ischemia–reperfusion cytoprotection and therapeutics. Cardiovasc Res 75:327–388PubMedCrossRefGoogle Scholar
  40. 40.
    Lang JD Jr, Teng X, Chumley P, Crawford JH, Isbell TS, Chacko BK, Liu Y, Jhala N, Crowe DR, Smith AB, Cross RC, Frenette L, Kelley EE, Wilhite DW, Hall CR, Page GP, Fallon MB, Bynon JS, Eckhoff DE, Patel RP (2007) Inhaled NO accelerates restoration of liver function in adults following orthotopic liver transplantation. J Clin Invest 117:2583–2591PubMedCrossRefGoogle Scholar

Copyright information

© Copyright jointly held by Springer and ESICM 2011

Authors and Affiliations

  • Valentin Fuhrmann
    • 1
    Email author
  • Nikolaus Kneidinger
    • 1
  • Harald Herkner
    • 2
  • Gottfried Heinz
    • 3
  • Mariam Nikfardjam
    • 3
  • Anja Bojic
    • 4
  • Peter Schellongowski
    • 4
  • Bernhard Angermayr
    • 5
  • Maximilian Schöniger-Hekele
    • 5
  • Christian Madl
    • 1
  • Peter Schenk
    • 1
  1. 1.Intensive Care Unit 13H1, Department of Gastroenterology and Hepatology, Internal Medicine 3Medical University of ViennaViennaAustria
  2. 2.Department of Emergency MedicineMedical University of ViennaViennaAustria
  3. 3.Intensive Care Unit 13H3, Department of Cardiology, Internal Medicine 2Medical University of ViennaViennaAustria
  4. 4.Intensive Care Unit 13I2, Internal Medicine 1Medical University of ViennaViennaAustria
  5. 5.Department of Gastroenterology and Hepatology, Internal Medicine 3Medical University of ViennaViennaAustria

Personalised recommendations