Skip to main content
Top
Published in: Intensive Care Medicine 7/2013

01-07-2013 | Original

Clinical impact of arterial ammonia levels in ICU patients with different liver diseases

Authors: Andreas Drolz, Bernhard Jäger, Marlene Wewalka, Reinhard Saxa, Thomas Horvatits, Kevin Roedl, Thomas Perkmann, Christian Zauner, Ludwig Kramer, Peter Ferenci, Valentin Fuhrmann

Published in: Intensive Care Medicine | Issue 7/2013

Login to get access

Abstract

Purpose

Increased arterial ammonia levels are associated with high mortality in patients with acute liver failure (ALF). Data on the prognostic impact of arterial ammonia is lacking in hypoxic hepatitis (HH) and scarce in critically ill patients with cirrhosis.

Methods

The patient cohort comprised 72 patients with HH, 43 patients with ALF, 100 patients with liver cirrhosis and 45 patients without evidence for liver disease. Arterial ammonia concentrations were assessed on a daily basis in all patients and the results were compared among these four patient groups and between 28-day survivors and 28-day non-survivors overall and in each group.

Results

Overall 28-day mortality rates in patients with HH, ALF and cirrhosis and in the control group were 54, 30, 49 and 27 %, respectively. Peak arterial ammonia levels differed significantly between transplant-free 28-day survivors and non-survivors in the HH and ALF groups (p < 0.01 for both). Multivariate regression identified peak arterial ammonia concentrations as an independent predictor of 28-day mortality or liver transplantation in patients with HH and ALF, respectively (p < 0.01). There was no association between mortality and arterial ammonia in patients with liver cirrhosis and in the control group. Admission arterial ammonia levels were independently linked to hepatic encephalopathy grades 3/4 in patients with HH (p < 0.01), ALF (p < 0.05) and cirrhosis (p < 0.05), respectively.

Conclusions

Elevated arterial ammonia levels indicate a poor prognosis in acute liver injury and are associated with advanced HE in HH, ALF and cirrhosis. Arterial ammonia levels provide additional information in the risk assessment of critically ill patients with liver disease.
Appendix
Available only for authorised users
Literature
1.
go back to reference Bernal W, Hall C, Karvellas CJ, Auzinger G, Sizer E, Wendon J (2007) Arterial ammonia and clinical risk factors for encephalopathy and intracranial hypertension in acute liver failure. Hepatology 46:1844–1852CrossRefPubMed Bernal W, Hall C, Karvellas CJ, Auzinger G, Sizer E, Wendon J (2007) Arterial ammonia and clinical risk factors for encephalopathy and intracranial hypertension in acute liver failure. Hepatology 46:1844–1852CrossRefPubMed
2.
go back to reference Bhatia V, Singh R, Acharya SK (2006) Predictive value of arterial ammonia for complications and outcome in acute liver failure. Gut 55:98–104CrossRefPubMed Bhatia V, Singh R, Acharya SK (2006) Predictive value of arterial ammonia for complications and outcome in acute liver failure. Gut 55:98–104CrossRefPubMed
3.
go back to reference Clemmesen JO, Larsen FS, Kondrup J, Hansen BA, Ott P (1999) Cerebral herniation in patients with acute liver failure is correlated with arterial ammonia concentration. Hepatology 29:648–653CrossRefPubMed Clemmesen JO, Larsen FS, Kondrup J, Hansen BA, Ott P (1999) Cerebral herniation in patients with acute liver failure is correlated with arterial ammonia concentration. Hepatology 29:648–653CrossRefPubMed
5.
go back to reference Haussinger D (1986) Regulation of hepatic ammonia metabolism: the intercellular glutamine cycle. Adv Enzyme Regul 25:159–180CrossRefPubMed Haussinger D (1986) Regulation of hepatic ammonia metabolism: the intercellular glutamine cycle. Adv Enzyme Regul 25:159–180CrossRefPubMed
6.
go back to reference Haussinger D (1990) Nitrogen metabolism in liver: structural and functional organization and physiological relevance. Biochem J 267:281–290PubMed Haussinger D (1990) Nitrogen metabolism in liver: structural and functional organization and physiological relevance. Biochem J 267:281–290PubMed
7.
go back to reference Haussinger D (2006) Low grade cerebral edema and the pathogenesis of hepatic encephalopathy in cirrhosis. Hepatology 43:1187–1190CrossRefPubMed Haussinger D (2006) Low grade cerebral edema and the pathogenesis of hepatic encephalopathy in cirrhosis. Hepatology 43:1187–1190CrossRefPubMed
8.
go back to reference Lockwood AH, McDonald JM, Reiman RE, Gelbard AS, Laughlin JS, Duffy TE, Plum F (1979) The dynamics of ammonia metabolism in man. Effects of liver disease and hyperammonemia. J Clin Invest 63:449–460CrossRefPubMed Lockwood AH, McDonald JM, Reiman RE, Gelbard AS, Laughlin JS, Duffy TE, Plum F (1979) The dynamics of ammonia metabolism in man. Effects of liver disease and hyperammonemia. J Clin Invest 63:449–460CrossRefPubMed
9.
go back to reference Walker CO, Schenker S (1970) Pathogenesis of hepatic encephalopathy–with special reference to the role of ammonia. Am J Clin Nutr 23:619–632PubMed Walker CO, Schenker S (1970) Pathogenesis of hepatic encephalopathy–with special reference to the role of ammonia. Am J Clin Nutr 23:619–632PubMed
10.
go back to reference Kundra A, Jain A, Banga A, Bajaj G, Kar P (2005) Evaluation of plasma ammonia levels in patients with acute liver failure and chronic liver disease and its correlation with the severity of hepatic encephalopathy and clinical features of raised intracranial tension. Clin Biochem 38:696–699CrossRefPubMed Kundra A, Jain A, Banga A, Bajaj G, Kar P (2005) Evaluation of plasma ammonia levels in patients with acute liver failure and chronic liver disease and its correlation with the severity of hepatic encephalopathy and clinical features of raised intracranial tension. Clin Biochem 38:696–699CrossRefPubMed
11.
go back to reference Jalan R, Olde Damink SW, Hayes PC, Deutz NE, Lee A (2004) Pathogenesis of intracranial hypertension in acute liver failure: inflammation, ammonia and cerebral blood flow. J Hepatol 41:613–620CrossRefPubMed Jalan R, Olde Damink SW, Hayes PC, Deutz NE, Lee A (2004) Pathogenesis of intracranial hypertension in acute liver failure: inflammation, ammonia and cerebral blood flow. J Hepatol 41:613–620CrossRefPubMed
12.
go back to reference Shawcross DL, Sharifi Y, Canavan JB, Yeoman AD, Abeles RD, Taylor NJ, Auzinger G, Bernal W, Wendon JA (2011) Infection and systemic inflammation, not ammonia, are associated with Grade 3/4 hepatic encephalopathy, but not mortality in cirrhosis. J Hepatol 54:640–649CrossRefPubMed Shawcross DL, Sharifi Y, Canavan JB, Yeoman AD, Abeles RD, Taylor NJ, Auzinger G, Bernal W, Wendon JA (2011) Infection and systemic inflammation, not ammonia, are associated with Grade 3/4 hepatic encephalopathy, but not mortality in cirrhosis. J Hepatol 54:640–649CrossRefPubMed
13.
go back to reference 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 21:696–703CrossRefPubMed 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 21:696–703CrossRefPubMed
14.
go back to reference 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 35:1397–1405CrossRefPubMed 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 35:1397–1405CrossRefPubMed
15.
go back to reference Fuhrmann V, Kneidinger N, Herkner H, Heinz G, Nikfardjam M, Bojic A, Schellongowski P, Angermayr B, Schoniger-Hekele M, Madl C, Schenk P (2011) Impact of hypoxic hepatitis on mortality in the intensive care unit. Intensive Care Med 37:1302–1310CrossRefPubMed Fuhrmann V, Kneidinger N, Herkner H, Heinz G, Nikfardjam M, Bojic A, Schellongowski P, Angermayr B, Schoniger-Hekele M, Madl C, Schenk P (2011) Impact of hypoxic hepatitis on mortality in the intensive care unit. Intensive Care Med 37:1302–1310CrossRefPubMed
17.
go back to reference Le Gall JR, Lemeshow S, Saulnier F (1993) A new simplified acute physiology score (SAPS II) based on a European/North American multicenter study. JAMA 270:2957–2963CrossRefPubMed Le Gall JR, Lemeshow S, Saulnier F (1993) A new simplified acute physiology score (SAPS II) based on a European/North American multicenter study. JAMA 270:2957–2963CrossRefPubMed
18.
go back to reference Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG (1996) The SOFA (sepsis-related organ failure assessment) score to describe organ dysfunction/failure. On behalf of the working group on sepsis-related problems of the European society of intensive care medicine. Intensive Care Med 22:707–710CrossRefPubMed Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG (1996) The SOFA (sepsis-related organ failure assessment) score to describe organ dysfunction/failure. On behalf of the working group on sepsis-related problems of the European society of intensive care medicine. Intensive Care Med 22:707–710CrossRefPubMed
19.
go back to reference Talmor M, Hydo L, Barie PS (1999) Relationship of systemic inflammatory response syndrome to organ dysfunction, length of stay, and mortality in critical surgical illness: effect of intensive care unit resuscitation. Arch Surg 134:81–87CrossRefPubMed Talmor M, Hydo L, Barie PS (1999) Relationship of systemic inflammatory response syndrome to organ dysfunction, length of stay, and mortality in critical surgical illness: effect of intensive care unit resuscitation. Arch Surg 134:81–87CrossRefPubMed
20.
go back to reference Kamath PS, Wiesner RH, Malinchoc M, Kremers W, Therneau TM, Kosberg CL, D’Amico G, Dickson ER, Kim WR (2001) A model to predict survival in patients with end-stage liver disease. Hepatology 33:464–470CrossRefPubMed Kamath PS, Wiesner RH, Malinchoc M, Kremers W, Therneau TM, Kosberg CL, D’Amico G, Dickson ER, Kim WR (2001) A model to predict survival in patients with end-stage liver disease. Hepatology 33:464–470CrossRefPubMed
21.
go back to reference Drolz AJB, Michl B, Furtmüller GJ, Wewalka M, Kitzberger R, Zauner C, Schenk P, Fuhrmann V (2010) Arterial ammonia in patients with hypoxic hepatitis. Intensive Care Med 36[Suppl 2]:380 Drolz AJB, Michl B, Furtmüller GJ, Wewalka M, Kitzberger R, Zauner C, Schenk P, Fuhrmann V (2010) Arterial ammonia in patients with hypoxic hepatitis. Intensive Care Med 36[Suppl 2]:380
22.
go back to reference Henrion J, Schapira M, Luwaert R, Colin L, Delannoy A, Heller FR (2003) Hypoxic hepatitis: clinical and hemodynamic study in 142 consecutive cases. Medicine (Baltimore) 82:392–406CrossRef Henrion J, Schapira M, Luwaert R, Colin L, Delannoy A, Heller FR (2003) Hypoxic hepatitis: clinical and hemodynamic study in 142 consecutive cases. Medicine (Baltimore) 82:392–406CrossRef
23.
go back to reference Polson J, Lee WM (2005) AASLD position paper: the management of acute liver failure. Hepatology 41:1179–1197CrossRefPubMed Polson J, Lee WM (2005) AASLD position paper: the management of acute liver failure. Hepatology 41:1179–1197CrossRefPubMed
25.
go back to reference Cash WJ, McConville P, McDermott E, McCormick PA, Callender ME, McDougall NI (2010) Current concepts in the assessment and treatment of hepatic encephalopathy. QJM 103:9–16CrossRefPubMed Cash WJ, McConville P, McDermott E, McCormick PA, Callender ME, McDougall NI (2010) Current concepts in the assessment and treatment of hepatic encephalopathy. QJM 103:9–16CrossRefPubMed
26.
go back to reference Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Blei AT (2002) Hepatic encephalopathy—definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology 35:716–721CrossRefPubMed Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Blei AT (2002) Hepatic encephalopathy—definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology 35:716–721CrossRefPubMed
27.
go back to reference Warren J, Fromm RE Jr, Orr RA, Rotello LC, Horst HM (2004) Guidelines for the inter- and intrahospital transport of critically ill patients. Crit Care Med 32:256–262CrossRefPubMed Warren J, Fromm RE Jr, Orr RA, Rotello LC, Horst HM (2004) Guidelines for the inter- and intrahospital transport of critically ill patients. Crit Care Med 32:256–262CrossRefPubMed
28.
go back to reference Wijdicks EF, Plevak DJ, Rakela J, Wiesner RH (1995) Clinical and radiologic features of cerebral edema in fulminant hepatic failure. Mayo Clin Proc 70:119–124CrossRefPubMed Wijdicks EF, Plevak DJ, Rakela J, Wiesner RH (1995) Clinical and radiologic features of cerebral edema in fulminant hepatic failure. Mayo Clin Proc 70:119–124CrossRefPubMed
29.
go back to reference Inamasu J, Miyatake S, Suzuki M, Nakatsukasa M, Tomioka H, Honda M, Kase K, Kobayashi K (2010) Early CT signs in out-of-hospital cardiac arrest survivors: temporal profile and prognostic significance. Resuscitation 81:534–538CrossRefPubMed Inamasu J, Miyatake S, Suzuki M, Nakatsukasa M, Tomioka H, Honda M, Kase K, Kobayashi K (2010) Early CT signs in out-of-hospital cardiac arrest survivors: temporal profile and prognostic significance. Resuscitation 81:534–538CrossRefPubMed
30.
go back to reference Naples R, Ellison E, Brady WJ (2009) Cranial computed tomography in the resuscitated patient with cardiac arrest. Am J Emerg Med 27:63–67CrossRefPubMed Naples R, Ellison E, Brady WJ (2009) Cranial computed tomography in the resuscitated patient with cardiac arrest. Am J Emerg Med 27:63–67CrossRefPubMed
31.
go back to reference Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL (2008) Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 36:296–327CrossRefPubMed Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL (2008) Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 36:296–327CrossRefPubMed
32.
go back to reference Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G (2003) 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 31:1250–1256CrossRefPubMed Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G (2003) 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 31:1250–1256CrossRefPubMed
33.
go back to reference Muckart DJ, Bhagwanjee S (1997) American college of chest physicians/society of critical care medicine consensus conference definitions of the systemic inflammatory response syndrome and allied disorders in relation to critically injured patients. Crit Care Med 25:1789–1795CrossRefPubMed Muckart DJ, Bhagwanjee S (1997) American college of chest physicians/society of critical care medicine consensus conference definitions of the systemic inflammatory response syndrome and allied disorders in relation to critically injured patients. Crit Care Med 25:1789–1795CrossRefPubMed
35.
go back to reference Goldberg RJ, Spencer FA, Gore JM, Lessard D, Yarzebski J (2009) Thirty-year trends (1975 to 2005) in the magnitude of, management of, and hospital death rates associated with cardiogenic shock in patients with acute myocardial infarction: a population-based perspective. Circulation 119:1211–1219CrossRefPubMed Goldberg RJ, Spencer FA, Gore JM, Lessard D, Yarzebski J (2009) Thirty-year trends (1975 to 2005) in the magnitude of, management of, and hospital death rates associated with cardiogenic shock in patients with acute myocardial infarction: a population-based perspective. Circulation 119:1211–1219CrossRefPubMed
36.
37.
go back to reference Shawcross DL, Davies NA, Williams R, Jalan R (2004) Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis. J Hepatol 40:247–254CrossRefPubMed Shawcross DL, Davies NA, Williams R, Jalan R (2004) Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis. J Hepatol 40:247–254CrossRefPubMed
38.
go back to reference Acharya SK, Bhatia V, Sreenivas V, Khanal S, Panda SK (2009) Efficacy of l-ornithine l-aspartate in acute liver failure: a double-blind, randomized, placebo-controlled study. Gastroenterology 136:2159–2168CrossRefPubMed Acharya SK, Bhatia V, Sreenivas V, Khanal S, Panda SK (2009) Efficacy of l-ornithine l-aspartate in acute liver failure: a double-blind, randomized, placebo-controlled study. Gastroenterology 136:2159–2168CrossRefPubMed
39.
go back to reference Vaid A, Chweich H, Balk EM, Jaber BL (2012) Molecular adsorbent recirculating system as artificial support therapy for liver failure: a meta-analysis. ASAIO J 58:51–59CrossRefPubMed Vaid A, Chweich H, Balk EM, Jaber BL (2012) Molecular adsorbent recirculating system as artificial support therapy for liver failure: a meta-analysis. ASAIO J 58:51–59CrossRefPubMed
Metadata
Title
Clinical impact of arterial ammonia levels in ICU patients with different liver diseases
Authors
Andreas Drolz
Bernhard Jäger
Marlene Wewalka
Reinhard Saxa
Thomas Horvatits
Kevin Roedl
Thomas Perkmann
Christian Zauner
Ludwig Kramer
Peter Ferenci
Valentin Fuhrmann
Publication date
01-07-2013
Publisher
Springer-Verlag
Published in
Intensive Care Medicine / Issue 7/2013
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-013-2926-8

Other articles of this Issue 7/2013

Intensive Care Medicine 7/2013 Go to the issue