Skip to main content
SpringerLink
Log in

Unmeasured anions are associated with short-term mortality in patients with hypoxic hepatitis

Ungemessene Anionen sind bei Patienten mit hypoxischer Hepatitis mit erhöhter Kurzzeitmortalität assoziiert

  • original article
  • Published:
Wiener klinische Wochenschrift Aims and scope Submit manuscript

Summary

Objective

Hypoxic hepatitis is a common cause of hepatic impairment in critically ill patients and is an independent risk factor for mortality. An elevated level of unmeasured anions is another unfavourable prognostic marker in many disease entities. While the biochemical nature of unmeasured anions is unknown, data suggest that they may be released from the liver. Therefore, the purpose of this study was to determine whether the strong ion gap—the gold standard for estimation of unmeasured anions—is elevated and associated with outcome in patients with hypoxic hepatitis.

Methods

One hundred and five consecutive patients with hypoxic hepatitis admitted to the (intensive care unit) ICU of a university hospital were prospectively included in the study and compared with 15 healthy controls.

Results

Compared with the controls, patients with hypoxic hepatitis had an elevated strong ion gap (4.0 ± 2.6 vs. 7.8 ± 4.0 mmol/L; p = 0.0002) that contributed to metabolic acidosis. Patients dying within 5 days had a larger strong ion gap upon admission than did patients surviving beyond 5 days. The mean strong ion gap (SIG) over the course of the first 5 days after admission to the ICU was 1.3 mmol/L (0.3–2.3 mmol/L) larger in patients who died compared with patients who survived, p = 0.008. In multivariate Cox-regression, larger strong ion gaps were associated with shorter survival time. The SIG correlated positively with both AST and ALT.

Conclusions

Unmeasured anions are elevated in patients with hypoxic hepatitis, contribute to metabolic acidosis and are associated with mortality. The liver is a possible source of the unmeasured anions, which may represent markers of tissue damage in hypoxic hepatitis.

Zusammenfassung

Ziel der Studie

Die hypoxische Hepatitis ist bei kritisch kranken Patienten eine häufige Ursache einer Leberschädigung und geht mit einer erhöhten Mortalität einher. Hohe Plasmaspiegel ungemessener Anionen sind ein ungünstiger Prognosefaktor bei verschiedenen Erkrankungen. Obgleich die (biochemische) Identität dieser Anionen nicht bekannt ist, wird die Leber als Ursprungsort vermutet. Das Ziel dieser Studie war es, zu untersuchen, ob bei Patienten mit hypoxischer Hepatits die „Starke Ionen Lücke“ (SIG) – der Goldstandard zur Bestimmung ungemessener Anionen – erhöht ist und mit dem Ausgang der Erkrankung korreliert.

Methodik

Einhundertfünf konsekutive auf die Intensivstation eines Universitätskrankenhauses aufgenommene Patienten mit hypoxischer Hepatitis wurden prospektiv in die Studie eingeschlossen und mit 15 gesunden Kontrollen verglichen.

Ergebnisse

Im Vergleich zu den Kontrollen hatten Patienten mit hypoxischer Hepatitis eine erhöhte SIG (4,0 ± 2,6 vs. 7,8 ± 4,0 mmol/L; p = 0,0002), welche zur metabolischen Azidose beitrug. Patienten, die innerhalb der ersten fünf Tage verstarben, hatten bei Aufnahme eine höhere SIG als Patienten, die diesen Zeitraum überlebten. Bei Patienten, die verstarben, war die mittlere SIG über den Zeitraum der ersten fünf Tage nach Aufnahme war um 1,3 mmol/L (0,3–2,3 mmol/L) höher als bei Patienten, die überlebten (p = 0,008). In der multivariaten Cox-Regression, war eine erhöhte SIG mit einer kürzeren Überlebenszeit assoziiert. Die SIG korrelierte positiv mit AST und ALT.

Schlussfolgerungen

Ungemessene Anionen sind bei Patienten mit hypoxischer Hepatitis erhöht, tragen zur metabolischen Azidose bei, und sind mit einer erhöhten Mortalität assoziiert. Die Leber ist ein möglicher Ursprung ungemessener Anionen, welche in Patienten mit hypoxischer Hepatitis als Marker des Gewebeuntergangs betrachtet werden können.

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

Similar content being viewed by others

References

  1. Fuhrmann V, Kneidinger N, Herkner H, Heinz G, Nikfardjam M, Bojic A, et al. Impact of hypoxic hepatitis on mortality in the intensive care unit. Intensive Care Med. 2011;37:1302–10.

    Google Scholar 

  2. Fuhrmann V, Kneidinger N, Herkner H, Heinz G, Nikfardjam M, Bojic A, et al. Hypoxic hepatitis: underlying conditions and risk factors for mortality in critically ill patients. Intensive Care Med. 2009;35:1397–405.

    Article  PubMed  Google Scholar 

  3. Henrion J, Minette P, Colin L, Schapira M, Delannoy A, Heller FR. Hypoxic hepatitis caused by acute exacerbation of chronic respiratory failure: a case-controlled, hemodynamic study of 17 consecutive cases. Hepatology. 1999;29:427–33.

    Article  PubMed  CAS  Google Scholar 

  4. Henrion J, Schapira M, Luwaert R, Colin L, Delannoy A, Heller FR. Hypoxic hepatitis: clinical and hemodynamic study in 142 consecutive cases. Medicine. (Baltimore) 2003;82:392–406.

    Google Scholar 

  5. Seeto RK, Fenn B, Rockey DC. Ischemic hepatitis: clinical presentation and pathogenesis. Am J Med. 2000;109:109–13.

    Article  PubMed  CAS  Google Scholar 

  6. Funk GC, Doberer D, Kneidinger N, Lindner G, Holzinger U, Schneeweiss B. Acid–base disturbances in critically ill patients with cirrhosis. Liver Int. 2007;27:901–9.

    Article  PubMed  CAS  Google Scholar 

  7. Naka T, Bellomo R, Morimatsu H, Rocktaschel J, Wan L, Gow P, et al. Acid–base balance in combined severe hepatic and renal failure: a quantitative analysis. Int J Artif Organs. 2008;31:288–94.

    PubMed  CAS  Google Scholar 

  8. Funk GC, Doberer D, Fuhrmann V, Holzinger U, Kitzberger R, Kneidinger N, et al. The acidifying effect of lactate is neutralized by the alkalinizing effect of hypoalbuminemia in non-paracetamol-induced acute liver failure. J Hepatol. 2006;45:387–92.

    Article  PubMed  CAS  Google Scholar 

  9. Kaplan LJ, Kellum JA. Initial pH, base deficit, lactate, anion gap, strong ion difference, and strong ion gap predict outcome from major vascular injury. Crit Care Med. 2004;32:1120–4.

    Article  PubMed  CAS  Google Scholar 

  10. Dondorp AM, Chau TT, Phu NH, Mai NT, Loc PP, Chuong LV, et al. Unidentified acids of strong prognostic significance in severe malaria. Crit Care Med. 2004;32:1683–8.

    Article  PubMed  CAS  Google Scholar 

  11. Funk GC, Doberer D, Sterz F, Richling N, Kneidinger N, Lindner G, et al. The strong ion gap and outcome after cardiac arrest in patients treated with therapeutic hypothermia: a retrospective study. Intensive Care Med. 2009;35:232–9.

    Article  PubMed  Google Scholar 

  12. Kellum JA, Bellomo R, Kramer DJ, Pinsky MR. Hepatic anion flux during acute endotoxemia. J Appl Physiol. 1995;78:2212–7.

    PubMed  CAS  Google Scholar 

  13. Fuhrmann V, Madl C, Mueller C, Holzinger U, Kitzberger R, Funk GC, et al. Hepatopulmonary syndrome in patients with hypoxic hepatitis. Gastroenterology. 2006;131:69–75.

    Article  PubMed  Google Scholar 

  14. Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA. 1993;270:2957–63.

    Article  PubMed  CAS  Google Scholar 

  15. Gibson PR, Dudley FJ. Ischemic hepatitis: clinical features, diagnosis and prognosis. Aust N Z J Med. 1984;14:822–5.

    Article  PubMed  CAS  Google Scholar 

  16. Hickman PE, Potter JM. Mortality associated with ischaemic hepatitis. Aust N Z J Med. 1990;20:32–4.

    Article  PubMed  CAS  Google Scholar 

  17. Siggaard-Andersen O, Wimberley PD, Fogh-Andersen N, Gothgen IH. Measured and derived quantities with modern pH and blood gas equipment: calculation algorithms with 54 equations. Scand J Clin Lab Invest. 1988;48(Suppl. 189):7–15.

    Google Scholar 

  18. Stewart PA. Modern quantitative acid–base chemistry. Can J Physiol Pharmacol. 1983;61:1444–61.

    Article  PubMed  CAS  Google Scholar 

  19. Figge J, Mydosh T, Fencl V. Serum proteins and acid–base equilibria: a follow-up. J Lab Clin Med. 1992;120:713–19.

    PubMed  CAS  Google Scholar 

  20. Kellum JA. Closing the gap on unmeasured anions. Crit Care. 2003;7:219–20.

    Article  PubMed  Google Scholar 

  21. Gilfix BM, Bique M, Magder S. A physical chemical approach to the analysis of acid–base balance in the clinical setting. J Crit Care. 1993;8:187–97.

    Article  PubMed  CAS  Google Scholar 

  22. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986;1:307–10.

    Article  PubMed  CAS  Google Scholar 

  23. Forni LG, McKinnon W, Lord GA, Treacher DF, Peron JM, Hilton PJ. Circulating anions usually associated with the Krebs cycle in patients with metabolic acidosis. Crit Care. 2005;9:591–5.

    Article  Google Scholar 

  24. Kneidinger N, Lindner G, Fuhrmann V, Doberer D, Dunkler D, Schneeweiss B, et al. Acute phase proteins do not account for unmeasured anions in critical illness. Eur J Clin Invest. 2007;37:820–5.

    Article  PubMed  CAS  Google Scholar 

  25. Bruegger D, Kemming GI, Jacob M, Meisner FG, Wojtczyk CJ, Packert KB, et al. Causes of metabolic acidosis in canine hemorrhagic shock: role of unmeasured ions. Crit Care. 2007;11:R130.

    Article  PubMed  Google Scholar 

  26. Moviat M, Terpstra AM, Ruitenbeek W, Kluijtmans LA, Pickkers P, van der Hoeven JG. Contribution of various metabolites to the “unmeasured” anions in critically ill patients with metabolic acidosis. Crit Care Med. 2008;36:752–8.

    Article  PubMed  CAS  Google Scholar 

  27. Murray D, Grant D, Murali N, Butt W. Unmeasured anions in children after cardiac surgery. J Thorac Cardiovasc Surg. 2007;133:235–40.

    Article  PubMed  Google Scholar 

  28. Kellum JA, Bellomo R, Kramer DJ, Pinsky MR. Splanchnic buffering of metabolic acid during early endotoxemia. J Crit Care. 1997;12:7–12.

    Article  PubMed  CAS  Google Scholar 

  29. Henrion J, Descamps O, Luwaert R, Schapira M, Parfonry A, Heller F. Hypoxic hepatitis in patients with cardiac failure: incidence in a coronary care unit and measurement of hepatic blood flow. J Hepatol. 1994;21:696–703.

    Article  PubMed  CAS  Google Scholar 

  30. Kneidinger N, Fuhrmann V, Kitzberger R, Wraszawska J, Holzinger U, Lindner G, et al. Assessment of liver function in patients with hypoxic hepatitis by indocyanine green clearance. Intensive Care Med. 2007;33(Suppl. 2)52.

    Google Scholar 

  31. Khosravani H, Shahpori R, Stelfox HT, Kirkpatrick AW, Laupland KB. Occurrence and adverse effect on outcome of hyperlactatemia in the critically ill. Crit Care. 2009;13:R90.

    Article  PubMed  Google Scholar 

  32. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368–77.

    Article  PubMed  CAS  Google Scholar 

  33. Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006;34:1589–96.

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

Author information

Authors and Affiliations

  1. Department of Medicine V, Ludwig-Maximilians-University, Klinikum Grosshadern, Munich, Germany

    Nikolaus Kneidinger MD, PhD

  2. Department of Respiratory and Critical Care Medicine, Otto Wagner Spital, Sanatoriumstrasse 2, 1140, Vienna, Austria

    Georg-Christian Funk MD

  3. Department for Anaesthesia, General Intensive Care Medicine and Pain Management, Medical University of Vienna, Vienna, Austria

    Gregor Lindner MD

  4. Intensive Care Unit 13H1, Department of Gastroenterology and Hepatology, Internal Medicine 3, Medical University of Vienna, Vienna, Austria

    Andreas Drolz MD & Valentin Fuhrmann MD

  5. Department for Pneumology, Landesklinikum Thermenregion Hochegg, Grimmenstein, Austria

    Peter Schenk MD

Authors
  1. Nikolaus Kneidinger MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Georg-Christian Funk MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gregor Lindner MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andreas Drolz MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Peter Schenk MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Valentin Fuhrmann MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Georg-Christian Funk MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kneidinger, N., Funk, GC., Lindner, G. et al. Unmeasured anions are associated with short-term mortality in patients with hypoxic hepatitis. Wien Klin Wochenschr 125, 474–480 (2013). https://doi.org/10.1007/s00508-013-0400-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00508-013-0400-9

Schlüsselwörter

Keywords

Search

Navigation