Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

ALF:

Acute liver failure

AUROC:

Area under receiver operating characteristic (ROC) curve

CPR:

Cardiopulmonary resuscitation

CT:

Computed tomography

HE:

Hepatic encephalopathy

HH:

Hypoxic hepatitis

ICU:

Intensive care unit

INR:

International normalized ratio

MELD:

Model of end stage liver disease

SIRS:

Systemic inflammatory response syndrome

SAPS II:

Simplified acute physiology score II

SOFA:

Sequential organ failure assessment score

References

  1. 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 46:1844–1852

    Article  CAS  PubMed  Google Scholar 

  2. Bhatia V, Singh R, Acharya SK (2006) Predictive value of arterial ammonia for complications and outcome in acute liver failure. Gut 55:98–104

    Article  CAS  PubMed  Google Scholar 

  3. 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 29:648–653

    Article  CAS  PubMed  Google Scholar 

  4. Bernal W, Auzinger G, Dhawan A, Wendon J (2010) Acute liver failure. Lancet 376:190–201

    Article  PubMed  Google Scholar 

  5. Haussinger D (1986) Regulation of hepatic ammonia metabolism: the intercellular glutamine cycle. Adv Enzyme Regul 25:159–180

    Article  CAS  PubMed  Google Scholar 

  6. Haussinger D (1990) Nitrogen metabolism in liver: structural and functional organization and physiological relevance. Biochem J 267:281–290

    CAS  PubMed  Google Scholar 

  7. Haussinger D (2006) Low grade cerebral edema and the pathogenesis of hepatic encephalopathy in cirrhosis. Hepatology 43:1187–1190

    Article  PubMed  Google Scholar 

  8. 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 63:449–460

    Article  CAS  PubMed  Google Scholar 

  9. Walker CO, Schenker S (1970) Pathogenesis of hepatic encephalopathy–with special reference to the role of ammonia. Am J Clin Nutr 23:619–632

    CAS  PubMed  Google Scholar 

  10. 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 38:696–699

    Article  CAS  PubMed  Google Scholar 

  11. 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 41:613–620

    Article  CAS  PubMed  Google Scholar 

  12. 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 54:640–649

    Article  CAS  PubMed  Google Scholar 

  13. 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 21:696–703

    Article  CAS  PubMed  Google Scholar 

  14. 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 35:1397–1405

    Article  PubMed  Google Scholar 

  15. 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 37:1302–1310

    Article  PubMed  Google Scholar 

  16. Henrion J (2012) Hypoxic hepatitis. Liver Int 32:1039–1052

    Article  CAS  PubMed  Google Scholar 

  17. 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 270:2957–2963

    Article  PubMed  Google Scholar 

  18. 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 22:707–710

    Article  CAS  PubMed  Google Scholar 

  19. 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 134:81–87

    Article  CAS  PubMed  Google Scholar 

  20. 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 33:464–470

    Article  CAS  PubMed  Google Scholar 

  21. 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

    Google Scholar 

  22. 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) 82:392–406

    Article  Google Scholar 

  23. Polson J, Lee WM (2005) AASLD position paper: the management of acute liver failure. Hepatology 41:1179–1197

    Article  PubMed  Google Scholar 

  24. O’Grady JG (2005) Acute liver failure. Postgrad Med J 81:148–154

    Article  PubMed  Google Scholar 

  25. Cash WJ, McConville P, McDermott E, McCormick PA, Callender ME, McDougall NI (2010) Current concepts in the assessment and treatment of hepatic encephalopathy. QJM 103:9–16

    Article  CAS  PubMed  Google Scholar 

  26. 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 35:716–721

    Article  PubMed  Google Scholar 

  27. 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 32:256–262

    Article  PubMed  Google Scholar 

  28. Wijdicks EF, Plevak DJ, Rakela J, Wiesner RH (1995) Clinical and radiologic features of cerebral edema in fulminant hepatic failure. Mayo Clin Proc 70:119–124

    Article  CAS  PubMed  Google Scholar 

  29. 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 81:534–538

    Article  PubMed  Google Scholar 

  30. Naples R, Ellison E, Brady WJ (2009) Cranial computed tomography in the resuscitated patient with cardiac arrest. Am J Emerg Med 27:63–67

    Article  PubMed  Google Scholar 

  31. 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 36:296–327

    Article  PubMed  Google Scholar 

  32. 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 31:1250–1256

    Article  PubMed  Google Scholar 

  33. 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 25:1789–1795

    Article  CAS  PubMed  Google Scholar 

  34. Califf RM, Bengtson JR (1994) Cardiogenic shock. N Engl J Med 330:1724–1730

    Article  CAS  PubMed  Google Scholar 

  35. 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 119:1211–1219

    Article  PubMed  Google Scholar 

  36. Heinz G (2006) Cardiogenic shock–an inflammatory disease. Wien Klin Wochenschr 118:382–388

    Article  PubMed  Google Scholar 

  37. Shawcross DL, Davies NA, Williams R, Jalan R (2004) Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis. J Hepatol 40:247–254

    Article  CAS  PubMed  Google Scholar 

  38. 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 136:2159–2168

    Article  CAS  PubMed  Google Scholar 

  39. 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 58:51–59

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

No financial support was received for this study.

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Intensive Care Unit 13H1, Division of Gastroenterology and Hepatology, Department of Internal Medicine III , Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria

    Andreas Drolz, Bernhard Jäger, Marlene Wewalka, Reinhard Saxa, Thomas Horvatits, Kevin Roedl, Christian Zauner, Peter Ferenci & Valentin Fuhrmann

  2. Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria

    Thomas Perkmann

  3. Division of Gastroenterology and Hepatology, Krankenhaus Hietzing, Vienna, Austria

    Ludwig Kramer

Authors
  1. Andreas Drolz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bernhard Jäger
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marlene Wewalka
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Reinhard Saxa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thomas Horvatits
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kevin Roedl
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Thomas Perkmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Christian Zauner
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ludwig Kramer
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Peter Ferenci
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Valentin Fuhrmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Andreas Drolz or Valentin Fuhrmann.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 48 kb)

Supplementary material 2 (TIFF 10541 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Drolz, A., Jäger, B., Wewalka, M. et al. Clinical impact of arterial ammonia levels in ICU patients with different liver diseases. Intensive Care Med 39, 1227–1237 (2013). https://doi.org/10.1007/s00134-013-2926-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00134-013-2926-8

Keywords

Search

Navigation