Predictive value of arterial ammonia for complications and outcome in acute liver failure

V Bhatia, R Singh, S K Acharya, V Bhatia, R Singh, S K Acharya

Abstract

Background and aims: In acute liver failure (ALF), the brain is exposed to high levels of ammonia. Human studies defining the clinical significance of ammonia in ALF are lacking. This prospective study evaluated the relationship of arterial ammonia levels at admission to complications and survival among patients with ALF.

Methods: Eighty consecutive ALF patients admitted from March 2001 to December 2003 were followed up until death or complete recovery. All had arterial ammonia estimation at admission (enzymatic method). Logistic regression analysis was performed to identify independent predictors of mortality.

Results: Forty two (52.5%) patients died. Non-survivors had significantly higher median ammonia levels than survivors (174.7 v 105.0 micromol/l; p<0.001). An arterial ammonia level of > or = 124 micromol/l was found to predict mortality with 78.6% sensitivity and 76.3% specificity, and had 77.5% diagnostic accuracy. Patients with higher ammonia levels also developed more complications, including deeper encephalopathy (p = 0.055), cerebral oedema (p = 0.020), need for ventilation (p<0.001), and seizures (p = 0.006). Logistic regression analysis showed that pH, presence of cerebral oedema, and arterial ammonia at admission were independent predictors of mortality (odds ratios 6.6, 12.6, and 10.9, respectively). Incorporating these variables, a score predicting mortality risk at admission was derived: 2.53 + 2.91 ammonia + 2.41 oedema + 1.40 pH, where ammonia is scored as 0 (if <124 micromol/l) or 1 (if > or =124 micromol/l); oedema is scored as 0 (absent) or 1(present); and pH is scored as 1 (if < or =7.40) or 0 (if >7.40). Levels of partial pressure of ammonia were equally correlated with outcome.

Conclusion: Arterial ammonia at presentation is predictive of outcome and can be used for risk stratification. Ammonia lowering therapies in patients with ALF should be evaluated.

Conflict of interest statement

Conflict of interest: None declared.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/1856380/bin/gt61754.f1.jpg
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/1856380/bin/gt61754.f2.jpg
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/1856380/bin/gt61754.f3.jpg
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/1856380/bin/gt61754.f4.jpg

References

    1. Jalan R, Olde Damink S W M, Deutz N E al Moderate hypothermia for uncontrolled intracranial hypertension in acute liver failure. Lancet 19993541164–1168.
    1. Strauss G I, Knudson G M, Kondrup al Cerebral metabolism of ammonia and amino acids in patients with fulminant hepatic failure. Gastroenterology 20011211109–1119.
    1. Hazell A S, Butterworth R F. Hepatic encephalopathy: An update of pathophysiologic mechanisms. Proc Soc Exp Biol Med 199922299–112.
    1. Felipo V, Butterworth R F. Neurobiology of ammonia. Prog Neurobiol 200267259–279.
    1. Clemmesen J O, Larsen F S, Kondrup al Cerebral herniation in patients with acute liver failure is correlated with arterial ammonia concentration. Hepatology 199929648–653.
    1. Warren K, Nathan D G. Passage of ammonia across blood‐brain barrier and its relation to blood pH. J Clin Invest 1958371724–1728.
    1. Tandon B N, Bernauau J, O Grady al Recommendations of the International Association for the Study of the Liver Subcommittee on nomenclature of acute and sub acute liver failure. J Gastroenterol Hepatol 199914403–404.
    1. Acharya S K, Dasarathy S, Kumer T al Fulminant hepatitis in a tropical population: clinical course, cause and early predictors of outcome. Hepatology 1996231448–1455.
    1. Bhatia V, Batra Y, Acharya S K. Prophylactic phenytoin does not improve cerebral edema or survival in ALF—a controlled clinical trial. J Hepatol 20044189–96.
    1. Riegler J L, Lake J R. Fulminant hepatic failure. Med Clin North Am 1993771057–1083.
    1. Nanda S K, Yalchinkaya K, Panigrahi A al Etiological role of hepatitis ‘E' virus in sporadic fulminant hepatitis. J Med Virol 199442133–137.
    1. Jameel S, Durgapal H, Habibullah C al Enteric non A, non B hepatitis: epidemics, animal transmission, and hepatitis E virus detection by the polymerase chain reaction. J Med Virol 199237263–270.
    1. Manning R T. A nomogram for estimation of pNH3. J Lab Clin Med 196463297–298.
    1. Altmann D G.Practical statistics for medical research. London: Chapman and Hall, 1991
    1. Kleinbaum D G, Klein M. Logistic regression. In: Dietz K, Gail M, Krickeberg K, et al. A self learning text, 2nd edn. New York: Springer Verlag, 200218
    1. Acharya S K, Panda S K, Saxena al Acute liver failure in India: a perspective from the East. J Gastroenterol Hepatol 200015473–479.
    1. Ostapowicz G, Lee W M. Acute hepatic failure: A western perspective. J Gastroenterol Hepatol 200015480–488.
    1. Hoofnagle J H, Carithers R L, Shapiro al Fulminant hepatic failure: summary of a workshop. Hepatology 199521240–252.
    1. Bernal W, Wendon J. Acute liver failure; clinical features and management. Eur J Gastroenterol Hepatol 19991977–984.
    1. Bernau J, Rueff B, Benhamou J P. Fulminant and subfulminant liver failure: Definitions and causes. Semin Liver Dis 1986697–106.
    1. O'Grady J G, Alexander G J, Hayllar K al Early indicators of prognosis in fulminant hepatic failure. Gastroenterology 198997439–445.
    1. Batra Y, Acharya S K. Acute liver failure: prognostic markers. Indian J Gastroenterol 200322(suppl 2)S66–S68.
    1. Pauwals A, Mostifa N, Florent al Emergency liver transplantation for acute liver failure: evaluation of London and Clichy criteria. J Hepatol 199417124–127.
    1. Sanyal A J, Stravitz R T. Acute liver failure. In: Zakim D, Boyer TD, eds. Hepatology: a textbook of liver disease. Philadelphia: Saunders, 2003445–496.
    1. Bernau J, Benhamou J P. Fulminant and subfulminant liver failure. In: Bircher J, Benhamou JP, McIntyre N, et al, eds. Oxford textbook of clinical hepatology. New York: Oxford Medical Publications, 19991341–1371.
    1. Williams R, Riordan Fulminant hepatic failure. In: Schiff ER, Sorrel MF, Maddrey WC, eds. Diseases of the liver. Philadelphia: Lippincott Williams and Wilkins, 2003941–970.
    1. Yee H F, Lidofsky S D. Acute liver failure. In: Feldman M, Friedman LS, Sleisenger MH, eds. Gastrointestinal and liver disease. Philadelphia: Saunders, 20021567–1576.
    1. Rose C, Michalak A, Rama Rao K al L‐ornithine‐L‐aspartate lowers plasma and cerebrospinal fluid ammonia and prevents brain edema in rats with acute liver failure. Hepatology 199930636–640.
    1. Butterworth R F. Pathophysiology of hepatic encephalopathy: a new look at ammonia. Metab Brain Dis 200217221–227.
    1. Rose C, Michalak A, Pannunzio al Mild hypothermia delays the onset of coma and prevents brain edema and extracellular brain glutamate accumulation in rats with acute liver failure. Hepatology 200031872–877.
    1. Flannery D B, Hsia Y E, Wsolf B. Current status of hyperammonemia syndromes. Hepatology 19822495–506.
    1. Blei A T. Medical therapy of brain edema in fulminant hepatic failure. Hepatology 200032666–669.
    1. Blei A T. Cerebral edema and intracranial hypertension in acute liver failure: distinct aspects of the same problem. Hepatology 199113376–379.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren