Fulminant hepatic failure, metabolic

Haemofiltration This procedure turned out to be of more value than haemodialysis. No dialysate fluid is required. Instead, a solution containing buffered bicarbonate is used to replace the ultrafiltrate. In fulminant hepatic failure, continuous venovenous haemofiltration is recommended because of its advantages for the circulation and metabolism. Heparin or prostacyclin can be used as anticoagulants (C.A.E. Gimson et al., 1980). 

F. Cerebral metabolism of ammonia and amino acids in patients with fulminant hepatic failure. Gastroenterology 2001 121 1109-1119... 

Because the liver is a major processor of dietary and endogenous carbohydrates, liver disease affects carbohydrate metabolism in a variety of ways (see Chapter 25). However, none of the conventional modes of evaluating carbohydrate metabolism have value in the diagnosis of liver disease. Because the liver is the major site of both glycogen storage and gluconeogenesis, hypoglycemia is a common complication in certain liver diseases, particularly Reye s syndrome, fulminant hepatic failure, advanced cirrhosis, and hepatocellular carcinoma. 

Prompt referral for liver transplantation is the therapy of choice for most patients with fulminant hepatic failure. Transplantation should be considered in all cases in which the patient demonstrates progressive clinical deterioration (encephalopathy, hypoglycemia, metabolic acidosis, renal failure, and coagulation defects)." Patients should be transferred at the first sign of altered mental status, because these patients often worsen very rapidly. One-year smvival rates with liver transplantation for fulminant hepatitis are 50% to 80% (as compared to <20% with medical management alone)."... 

B. After 24-48 hours, when transaminase levels (AST and ALT) begin to rise, hepatic necrosis becomes evident. If acute fulminant hepatic failure occurs, death may ensue. Encephalopathy, metabolic acidosis, and a continuing rise in the prothrombin time (PT) indicate a poor prognosis. Acute renal failure occasionally occurs, with or without concomitant liver failure. 

Provide general supportive care for hepatic or renal failure if it occurs. Emergency liver transplant may be necessary for fulminant hepatic failure. Encephalopathy, metabolic acidosis, hypoglycemia, and progressive rise in the prothrombin time are indications of severe liver injury. 

B. Hepatic failure. Liver injury may be apparent within 24-36 hours, with rapidly rising transaminase levels. Fulminant hepatic failure may follow, with jaundice, encephalopathy, and death. Encephalopathy, metabolic acidosis, severe coagulopathy, and hypoglycemia are grave prognostic signs and usually predict a fatal outcome. 

However, encephalopathies with a metabohc basis tend to be the most problanatic for infants or children, with functional outcomes dependent upon timely and pradent interventions. Three varieties of metabolic encephalopathy in children are discussed here. The first two are closely related. Inborn (genetic) errors of metabolism can present in the newborn as severe encephalopathy from hyperammonemia alone. When a metabolic error presents months to years later, a degree of hepatic insufficiency may complicate the metabolic derangement. In acute or fulminant hepatic failure of any etiology (i.e., infections, drug-induced, toxin-related), the rise in serum ammonia may be only moderate but other factors contribute to the ensuing encephalopathy, which may be devastating within days. 

Schnittger, C., Weissenborn, K., Boker, K., Kolbe, H., Dengler, R., Manns, M.R 1997. Continuous noninvasive cerebral perfusion monitoring in fulminant hepatic failure and brain oedema. In Advances in Hepatic Encephalopathy Metabolism in Liver Disease, eds C. Record and H. A1 Mardini (eds.)., pp. 515-519. New Castle upon Tyne Medical Faculty of the University of Newcastle upon Tyne... 

Tofteng F, Larsen FS. The effect of indomethacin on intracranial pressure, cerebral perfusion and extracellular lactate and glutamate concentrations in patients with fulminant hepatic failure. Journal of cerebral blood flow and metabolism 2004 24(7) 798-804... 

Liver disease may decrease hepatic metabolism resulting in enhanced responses to parent chemicals however, for many compounds, metabolism is only slightly impaired in moderate to severe liver disease. Disease-induced alterations in clearance and volume of distribution often act in opposite directions with respect to their effect on half-life. Bioavailability may be markedly increased in liver disease with portal/systemic anastomosis (the connection of normally separate parts so they intercommunicate) so that orally administered chemicals bypass hepatic first-pass metabolism. Altered receptor sensitivity has been observed for some chemical substances in liver cirrhosis. When liver tissue repair is inhibited by chemical co-exposure, even an inconsequential level of liver injury may lead to fulminating liver failure from a nonlethal exposure of hepatotoxic-ants. (Several articles, as reviewed by Dybing and Spderlund 1999.)... 

Halothane reduces splanchnic and hepatic blood flow. Halothane can produce fulminant hepatic necrosis in a small number of patients, a syndrome characterized by fever, anorexia, nausea, and vomiting, developing several days after anesthesia and sometimes accompanied by a rash and peripheral eosinophilia. There is a rapid progression to hepatic failure, with a fatality rate of -50%. This syndrome occurs in about 1 in 10,000 patients receiving halothane and is referred to as halothane hepatitis. Halothane hepatitis may be the result of an immune response to hepatic proteins that become trifluoroacetylated as a consequence of halothane metabolism see Pharmacokinetics, above). 

C. Acute ingestion may cause gastrointestinal burns, severe vomiting and abdominal pain, and diarrhea with smoking stools. Systemic effects include headache, delirium, shock, seizures, coma, and arrhythmias (atrial fibrillation, QT prolongation, ventricular tachycardia, and fibrillation). Metabolic derangements, including hypocalcemia and hyperphosphatemia (or hypophosphatemia), may occur. Fulminant hepatic or renal failure may occur after 2-3 days. 

Wendon JA, Harrison PM, Keays R, Williams R. Cerebral blood flow and metabolism in fulminant liver failure. Hepatology, 19, 1407—1413, 1994 Yao H, Sadoshima S, Fujii K, Kusada K, Ishitsuka T, Tameiki K, Fujishima M. Cerebrospinal fluid lactate in patients with hepatic encephalopathy. Eur. Neurol, 27, 182-187, 1987 Young SN, Lai S. CNS tryptamine metabolism in hepatic coma. J. Neural. Transm., 47,153-161, 1980... 

Fulminant or protracted liver failure is caused by medicaments in 10-15% of cases. A reduction in the functional liver mass to < 20-35% is deemed to be a critical stage. However, the death of the patient may already occur due to secondary metabolic disorders (so-called exogenous hepatic coma) before the extent of the parenchymal loss has fallen below the critical threshold (so-called endogenous hepatocellular disintegration coma), (s. tab. 29.10)... 

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