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Neurocritical Care

, 9:97 | Cite as

Encephalopathy and Cerebral Edema in the Setting of Acute Liver Failure: Pathogenesis and Management

  • Julia Wendon
  • William Lee
Review Paper

Abstract

Cerebral edema is a potential life-threatening complication in patients with acute liver failure who progress to grade III/IV encephalopathy. The incidence is variably reported but appears to be most prevalent in those patients with hyperacute liver failure as opposed to subacute forms of liver failure. In those patients who are deemed at risk of cerebral edema and raised intracranial pressure, insertion of an intra-cranial pressure monitoring device may be considered to optimize treatment and interventions. The pathogenesis of cerebral edema in this setting remains controversial, although recent work suggests a pivotal role for arterial ammonia, whose effects appear to be potentiated by the presence of systemic inflammation. Recent work has also suggested the import of free radical formation occurring at a mitochondrial level as being the potential mediator of cellular dysfunction as opposed to ammonia per se. Treatment of such patients requires a multi-disciplinary approach incorporating both hepatology and critical care. In a significant proportion of such cases, consideration of liver transplantation may be required. Treatment should be focused at optimizing liver function and regenerative capacity and minimizing the inflammatory milieu. Controlled studies are lacking and much of the management has been extrapolated from neurocritical care. Sustained elevation of intracranial pressure may be responsive to mannitol or hypertonic saline bolus, and in those with hyperemia indomethacin has been reported as beneficial in case series. Recently, interest has developed into the use of cooling in the management of patients with acute liver failure and raised intracranial pressure. Animal studies support this treatment option as do case series, although randomized trials are still awaited.

Keywords

Cerebral edema Pathogenesis Acute liver failure 

References

  1. 1.
    O’Grady JG, Williams R. Classification of acute liver failure. Lancet. 1993;342:743.PubMedCrossRefGoogle Scholar
  2. 2.
    O’Grady JG, Schalm SW, Williams R. Acute liver failure: redefining the syndromes. Lancet. 1993;342:273–5.PubMedCrossRefGoogle Scholar
  3. 3.
    Bernal W, Hall C, Karvellas CJ, Auzinger G, Sizer E, Wendon J. Arterial ammonia and clinical risk factors for encephalopathy and intracranial hypertension in acute liver failure. Hepatology. 2007;46:1844–52.PubMedCrossRefGoogle Scholar
  4. 4.
    Bernuau J, Durand F. Intracranial pressure monitoring in patients with acute liver failure: a questionable invasive surveillance. Hepatology. 2006;44:502–4.PubMedCrossRefGoogle Scholar
  5. 5.
    Wendon JA, Larsen FS. Intracranial pressure monitoring in acute liver failure. A procedure with clear indications. Hepatology. 2006;44:504–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Vaquero J, Fontana RJ, Larson AM, et al. Complications and use of intracranial pressure monitoring in patients with acute liver failure and severe encephalopathy. Liver Transpl. 2005;11:1581–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Swain M, Butterworth RF, Blei AT. Ammonia and related amino acids in the pathogenesis of brain edema in acute ischemic liver failure in rats. Hepatology. 1992;15:449–53.PubMedCrossRefGoogle Scholar
  8. 8.
    Olde Damink SW, Jalan R, Deutz NE, et al. The kidney plays a major role in the hyperammonemia seen after simulated or actual GI bleeding in patients with cirrhosis. Hepatology. 2003;37:1277–85.PubMedCrossRefGoogle Scholar
  9. 9.
    Norenberg MD, Rao KV, Jayakumar AR. Mechanisms of ammonia-induced astrocyte swelling. Metab Brain Dis. 2005;20:303–18.PubMedCrossRefGoogle Scholar
  10. 10.
    Larsen FS, Wendon J. Brain edema in liver failure: basic physiologic principles and management. Liver Transpl. 2002;8:983–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Jalan R, Olde Damink SW, Hayes PC, Deutz NE, Lee A. Pathogenesis of intracranial hypertension in acute liver failure: inflammation, ammonia and cerebral blood flow. J Hepatol. 2004;41:613–20.PubMedCrossRefGoogle Scholar
  12. 12.
    Butterworth RF. Pathogenesis of hepatic encephalopathy: update on molecular mechanisms. Indian J Gastroenterol. 2003;22(Suppl 2):S11–6.PubMedGoogle Scholar
  13. 13.
    Antoniades CG, Berry PA, Davies ET, et al. Reduced monocyte HLA-DR expression: a novel biomarker of disease severity and outcome in acetaminophen-induced acute liver failure. Hepatology. 2006;44:34–43.PubMedCrossRefGoogle Scholar
  14. 14.
    Pedersen HR, Ring-Larsen H, Olsen NV, Larsen FS. Hyperammonemia acts synergistically with lipopolysaccharide in inducing changes in cerebral hemodynamics in rats anaesthetised with pentobarbital. J Hepatol. 2007;47:245–52.PubMedCrossRefGoogle Scholar
  15. 15.
    Wright G, Jalan R. Ammonia and inflammation in the pathogenesis of hepatic encephalopathy: Pandora’s box? Hepatology. 2007;46:291–4.PubMedCrossRefGoogle Scholar
  16. 16.
    Ware AJ, D’Agostino AN, Combes B. Cerebral edema: a major complication of massive hepatic necrosis. Gastroenterology. 1971;61:877–84.PubMedGoogle Scholar
  17. 17.
    Clemmesen JO, Larsen FS, Kondrup J, Hansen BA, Ott P. Cerebral herniation in patients with acute liver failure is correlated with arterial ammonia concentration. Hepatology. 1999;29:648–53.PubMedCrossRefGoogle Scholar
  18. 18.
    Bhatia V, Singh R, Acharya SK. Predictive value of arterial ammonia for complications and outcome in acute liver failure. Gut. 2006;55:98–104.PubMedCrossRefGoogle Scholar
  19. 19.
    Murphy N, Auzinger G, Bernel W, Wendon J. The effect of hypertonic sodium chloride on intracranial pressure in patients with acute liver failure. Hepatology. 2004;39:464–70.PubMedCrossRefGoogle Scholar
  20. 20.
    Cordoba J, Gottstein J, Blei AT. Chronic hyponatremia exacerbates ammonia-induced brain edema in rats after portacaval anastomosis. J Hepatol. 1998;29:589–94.PubMedCrossRefGoogle Scholar
  21. 21.
    Tofteng F, Hauerberg J, Hansen BA, Pedersen CB, Jorgensen L, Larsen FS. Persistent arterial hyperammonemia increases the concentration of glutamine and alanine in the brain and correlates with intracranial pressure in patients with fulminant hepatic failure. J Cereb Blood Flow Metab. 2006;26:21–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Jayakumar AR, Rao KV, Murthy ChR, Norenberg MD. Glutamine in the mechanism of ammonia-induced astrocyte swelling. Neurochem Int. 2006;48:623–8.PubMedGoogle Scholar
  23. 23.
    Jayakumar AR, Rama Rao KV, Schousboe A, Norenberg MD. Glutamine-induced free radical production in cultured astrocytes. Glia. 2004;46:296–301.PubMedCrossRefGoogle Scholar
  24. 24.
    Norenberg MD, Rama Rao KV, Jayakumar AR. Ammonia neurotoxicity and the mitochondrial permeability transition. J Bioenerg Biomembr. 2004;36:303–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Norenberg MD, Jayakumar AR, Rama Rao KV, Panickar KS. New concepts in the mechanism of ammonia-induced astrocyte swelling. Metab Brain Dis. 2007;22:219–34.PubMedCrossRefGoogle Scholar
  26. 26.
    Lichter-Konecki U, Mangin JM, Gordish-Dressman H, Hoffman EP, Gallo V. Gene expression profiling of astrocytes from hyperammonemic mice reveals altered pathways for water and potassium homeostasis in vivo. Glia. 2008;56:365–77.PubMedCrossRefGoogle Scholar
  27. 27.
    Desjardins P, Belanger M, Butterworth RF. Alterations in expression of genes coding for key astrocytic proteins in acute liver failure. J Neurosci Res. 2001;66:967–71.PubMedCrossRefGoogle Scholar
  28. 28.
    Wright G, Shawcross D, Olde Damink SW, Jalan R. Brain cytokine flux in acute liver failure and its relationship with intracranial hypertension. Metab Brain Dis. 2007;22:375–88.PubMedCrossRefGoogle Scholar
  29. 29.
    Strauss G, Hansen BA, Knudsen GM, Larsen FS. Hyperventilation restores cerebral blood flow autoregulation in patients with acute liver failure. J Hepatol. 1998;28:199–203.PubMedCrossRefGoogle Scholar
  30. 30.
    Rolando N, Wade J, Davalos M, Wendon J, Philpott-Howard J, Williams R. The systemic inflammatory response syndrome in acute liver failure. Hepatology. 2000;32:734–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Vaquero J, Polson J, Chung C, et al. Infection and the progression of hepatic encephalopathy in acute liver failure. Gastroenterology. 2003;125:755–64.PubMedCrossRefGoogle Scholar
  32. 32.
    Schmidt LE, Larsen FS. Prognostic implications of hyperlactatemia, multiple organ failure, and systemic inflammatory response syndrome in patients with acetaminophen-induced acute liver failure. Crit Care Med. 2006;34:337–43.PubMedCrossRefGoogle Scholar
  33. 33.
    Bernal W, Donaldson P, Underhill J, Wendon J, Williams R. Tumor necrosis factor genomic polymorphism and outcome of acetaminophen (paracetamol)-induced acute liver failure. J Hepatol. 1998;29:53–9.PubMedCrossRefGoogle Scholar
  34. 34.
    Clemmesen JO, Hansen BA, Larsen FS. Indomethacin normalizes intracranial pressure in acute liver failure: a twenty-three-year-old woman treated with indomethacin. Hepatology. 1997;26:1423–5.PubMedCrossRefGoogle Scholar
  35. 35.
    Stravitz RT, Kramer AH, Davern T, et al. Intensive care of patients with acute liver failure: recommendations of the U.S. Acute Liver Failure Study Group. Crit Care Med. 2007;35:2498–508.PubMedCrossRefGoogle Scholar
  36. 36.
    Rose C, Ytrebo LM, Davies NA, et al. Association of reduced extracellular brain ammonia, lactate, and intracranial pressure in pigs with acute liver failure. Hepatology. 2007;46:1883–92.PubMedCrossRefGoogle Scholar
  37. 37.
    Zwingmann C, Chatauret N, Rose C, Leibfritz D, Butterworth RF. Selective alterations of brain osmolytes in acute liver failure: protective effect of mild hypothermia. Brain Res. 2004;999:118–23.PubMedCrossRefGoogle Scholar
  38. 38.
    Chatauret N, Rose C, Therrien G, Butterworth RF. Mild hypothermia prevents cerebral edema and CSF lactate accumulation in acute liver failure. Metab Brain Dis. 2001;16:95–102.PubMedCrossRefGoogle Scholar
  39. 39.
    Belanger M, Desjardins P, Chatauret N, Rose C, Butterworth RF. Mild hypothermia prevents brain edema and attenuates up-regulation of the astrocytic benzodiazepine receptor in experimental acute liver failure. J Hepatol. 2005;42:694–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Jalan R, Olde Damink SW, Deutz NE, Lee A, Hayes PC. Moderate hypothermia for uncontrolled intracranial hypertension in acute liver failure. Lancet. 1999;354:1164–8.PubMedCrossRefGoogle Scholar
  41. 41.
    Jalan R, Olde Damink SW, Deutz NE, Hayes PC, Lee A. Moderate hypothermia in patients with acute liver failure and uncontrolled intracranial hypertension. Gastroenterology. 2004;127:1338–46.PubMedCrossRefGoogle Scholar
  42. 42.
    Jalan R, Olde Damink SW, Deutz NE, Hayes PC, Lee A. Restoration of cerebral blood flow autoregulation and reactivity to carbon dioxide in acute liver failure by moderate hypothermia. Hepatology. 2001;34:50–4.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2008

Authors and Affiliations

  1. 1.Liver Intensive Therapy Unit, Institute of Liver StudiesKings College HospitalLondonUK
  2. 2.South Western UniversityDallasUSA

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