eMedicine Specialties > Pediatrics: General Medicine > Gastroenterology
Fulminant Hepatic Failure: Treatment & Medication
Updated: Nov 12, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Reaching a diagnosis of fulminant hepatic failure (FHF) is of vital importance so that appropriate and early treatment can be initiated. Unfortunately, in most patients, no definitive therapy that can result in regeneration of hepatocytes or reversal of injury is available. Increasing public awareness of potential hepatotoxins, including over the counter medications such as acetaminophen (ie, paracetamol) and ibuprofen, is essential.
- General concerns include the following:
- An ICU and pediatric hepatology setting with facilities for liver transplantation should be available for proper diagnosis and management.
- Maintain urine output and correct hypoglycemia and any associated electrolyte disturbances.
- Patients may require intravenous administration of calcium, phosphorous, magnesium, factor concentrate, and platelets.
- An infusion of 10-20% of glucose is usually required.
- Avoid fluid overload (restrict hydration up to 2 mL/kg/h). Hemodynamic monitoring of central pressures is advised to assess volume depletion and overload.
- Parenteral vitamin K and plasmapheresis are needed to correct coagulopathy and prevent its serious sequelae. However, unless acute hemorrhage is present or an invasive procedure is performed, empiric transfusion with fresh frozen plasma (FFP) is not warranted. It can present a significant volume challenge to the kidneys. It also normalizes prothrombin time (PT), reducing the prognostic importance of this variable in respect to prognosis.
- Platelet transfusion may be indicated in severe cases of FHF with coagulopathy and thrombocytopenia. It occasionally is required to maintain a platelet count of greater than 50,000.
- A parenteral H2-receptor blocker is administered prophylactically to prevent potential GI bleeding.
- Avoid nephrotoxic agents, benzodiazepines, and other sedative medications.
- Despite an effective antidote, acetaminophen overdose remains a frequent cause of acute liver failure in children.
- Direct treatment toward the specific cause of FHF when an identifiable etiology is found. Provide symptomatic treatment and life support. Use appropriate antibiotics to treat serious infections, septicemia, peritonitis, and pneumonia.
- Focus on management of renal impairment due to hepatorenal syndrome (HRS) or acute renal tubular necrosis.
- Pay special attention to management of cerebral edema. Proper positioning and avoidance of manipulations that increase intracranial pressure (ICP) can help prevent cerebral edema. Continuously monitoring ICP in severe illness is of vital importance, especially in stage 3 or 4 of hepatic encephalopathy. Mannitol is used in patients with documented ICP greater than 30 mm Hg and is considered in patients with progressive edema.
- Restrict protein intake to 0.5 g/kg/d or less.
- Use lactulose enemas to evacuate the bowel.
- Oral neomycin is indicated to decrease enteric bacteria that produce ammonia.
- Monitor blood glucose regularly for possible complicating hypoglycemia, and treat with intravenous glucose administration.
- Specific treatment is as follows
- Hepatitis is treated with acyclovir for herpesvirus hepatitis and with prednisone and azathioprine for autoimmune hepatitis.
- Acetaminophen overdose is treated with an antidote for hepatotoxicity (ie, N -acetylcysteine).
- Galactosemia and fructosemia are treated with dietary elimination. Hereditary tyrosinemia type I is treated with dietary elimination and 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC).
Surgical Care
Orthotopic liver transplantation remains the only effective mode of treatment of FHF. Consider this in any patient presenting with FHF, regardless of the etiology. FHF is the indication for 11-13% of liver transplantations and carries an important prognostic implication.
- Consider urgent transplant when international normalized ratio (INR) reaches 4, especially in very young children.
- A more recent approach is to try using liver-assist devices, such as matrices of cultured hepatocytes, to support the patient's liver until hepatic regeneration occurs or a suitable donor is made available for liver transplant.
- In acute emergency, segment liver transplant or living related donor transplant is performed to spare the child with FHF the potentially fatal outcome of rapidly progressive liver necrosis.
- Innovative approaches, such as auxiliary hepatic transplantation, xenograft, extracorporeal human liver, and artificial liver support devices, also are considered in emergency situations. Their role holds promise but requires further investigation.
- Despite technical difficulties and a donor organ shortage, the results of liver transplantation in the pediatric age group with end-stage liver disease have demonstrated promising results. Therefore, early referral to a specialized center for liver transplantation is vital.
Consultations
- Gastroenterologist
- Neurosurgeon
- Hematologist
- Infectious disease specialist
- Transplantation surgeon
Diet
Special attention to diet is indicated. Patients require high calories, high carbohydrates, and moderate fat. Total parenteral nutrition (TPN) may be needed to ensure adequate nutrition, especially when enteral feeding is not possible.
- Monitor glucose carefully, and avoid volume overload.
- Special formulas are available that are high in branched-chain amino acids and low in aromatic amino acids and electrolytes.
Medication
No definite treatment is available for fulminant hepatic failure (FHF). Medical treatment is usually directed at causative agents or at minimizing morbidity or mortality caused by serious complications (see Treatment).
Vitamins
Organic substances required by the body in small amounts for various metabolic processes. Vitamins may be synthesized in small or insufficient amounts in the body or not synthesized at all, thus requiring supplementation.
Phytonadione (AquaMEPHYTON, Mephyton)
Vitamin K, a fat-soluble vitamin absorbed by the gut and stored in the liver.
Necessary for function of clotting factors in the coagulation cascade and, thus, is used in coagulopathy resulting from liver failure.
Adult
10 mg/d IM; may repeat in 8-12 h
Pediatric
2.5-5 mg/d PO; 1-2 mg IM/SC
Effects of warfarin and dicumarol are antagonized
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Rapid IV infusion may result in flushing and a feeling of constriction in the chest; relatively nontoxic, even in massive doses
Ammonia inhibitors
These agents are used to prevent and treat portal systemic encephalopathy. Lactulose may be used to inhibit diffusion of ammonia into the blood and enhance diffusion from the blood into the gut. Neomycin is used to decrease ammonia-producing bacteria in the gut. The subsequent reduction in blood ammonia has resulted in neurologic improvement.
Lactulose (Cephulac)
Inhibits diffusion of NH3 into blood by producing an acidic pH that causes conversion of NH3 to NH4, a nondiffusable form of ammonia. Also used to evacuate the bowel and reduce intestinal stasis.
Adult
20-30 g (30-45 mL) PO q1-2h; slowly adjust to produce 2-3 soft stools
Alternatively, 200 g diluted with 700 mL of water or 0.9% NaCl PR via rectal balloon catheter; retain 30-60 min q4-6h
Pediatric
2.5-10 mL/d PO divided tid/qid; adjust dose to produce 2-3 stools per d
Decreases effects of neomycin, laxatives, and antacids
Documented hypersensitivity; patients who require a galactose diet
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in diabetes; monitor for electrolyte imbalance
Neomycin (Mycifradin)
Interferes with bacterial protein synthesis by binding to 30S ribosomal subunits, thus reducing the number of ammonia-producing bacteria in the intestine.
Adult
500-2000 mg PO q6-8h
Hepatic coma: 4-12 g/d PO divided q4-6h
Pediatric
50-100 mg/kg/d PO divided q6-8h
2.5-7 g/m2/d divided q4-6h for 5 d; not to exceed 12 g/d in hepatic coma
May potentiate effects of PO anticoagulants; may decrease GI absorption of digoxin and methotrexate; synergistic effects observed with penicillins; increased adverse effects observed with other neurotoxic, ototoxic, or nephrotoxic drugs
Documented hypersensitivity; patients with intestinal obstruction
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Use with caution in patients with renal impairment, preexisting hearing impairment, or neuromuscular disorders
Osmotic diuretics
These agents may reduce subarachnoid space pressure by creating osmotic gradient between cerebrospinal fluid in arachnoid space and plasma. They are not for long-term use.
Mannitol (Osmitrol, Resectisol)
Used to decrease ICP.
Adult
1.5-2 g/kg IV as 20% solution (7.5-10 mL/kg) or as 15% solution (10-13 mL/kg) over a period as short as 30 min
Initially assess for adequate renal function by administering a test dose of 200 mg/kg, given IV over 3-5 min; should produce a urine flow of at least 30-50 mL/h over 2-3 h
Pediatric
Initial: 0.5-1 g/kg IV
Maintenance dose: 0.25-0.5 g/kg IV q4-6h
Assess for adequate renal function by administering a test dose of 200 mg/kg, given IV over 3-5 min; should produce a urine flow of at least 1 mL/h over 1-3 h
None reported
Documented hypersensitivity; anuria; severe pulmonary congestion; progressive renal damage; severe dehydration; active intracranial bleeding; progressive heart failure
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Carefully evaluate cardiovascular status before rapid administration of mannitol because a sudden increase in extracellular fluid may lead to fulminating CHF; avoid pseudoagglutination; when blood is given simultaneously, add at least 20 mEq of sodium chloride to each liter of mannitol solution; do not give electrolyte-free mannitol solutions with blood
Antiviral agents
These agents inhibit activity of herpesvirus types 1 and 2. They have affinity for viral thymidine kinase and, once phosphorylated, cause DNA chain termination when acted on by DNA polymerase.
Acyclovir (Zovirax)
Indicated in viral hepatitis.
Adult
5 mg/kg/dose IV q8h or 750 mg/m2/d divided q8h
Pediatric
Administer as in adults
Concomitant use of probenecid or zidovudine prolongs half-life and increases CNS toxicity of acyclovir
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in renal failure or when using nephrotoxic drugs
Antidotes
These agents are used in the management of poisoning and overdose, for prevention of toxic effects, or for metabolic disorders when toxic substances accrue.
N-acetylcysteine (Mucomyst)
Indicated in acetaminophen toxicity. May provide substrate for conjugation with toxic metabolite of acetaminophen. All doses should be administered, even if acetaminophen level has dropped below toxic range.
Adult
140 mg/kg PO, followed by 17 doses of 70 mg/kg PO q4h; repeat dose if emesis occurs within 1 h of administration
Pediatric
Administer as in adults
None reported
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
GI distress may occur
Immunosuppressive agents
These agents are used in autoimmune hepatitis for immunosuppression effect.
Prednisone (Deltasone, Orasone)
Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and suppresses lymphocytes and antibody production.
Adult
5-60 mg/d PO qd or divided bid/qid; taper over 2 wk as symptoms resolve
Pediatric
4-5 mg/m2/d PO; alternatively, 0.05-2 mg/kg PO divided bid/qid; taper over 2 wk as symptoms resolve
Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI bleeding or ulceration
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use
Azathioprine (Imuran)
Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity.
Adult
1 mg/kg/d PO for 6-8 wk; increase by 0.5 mg/kg q4wk until response or dose reaches 2.5 mg/kg/d
Pediatric
Initial dose: 2-5 mg/kg/d PO/IV
Maintenance dose: 1-2 mg/kg/d PO/IV
Toxicity increases with allopurinol; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine
Documented hypersensitivity; low levels of serum thiopurine methyl transferase (TPMT)
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Increases risk of neoplasia; caution with liver disease and renal impairment; hematologic toxicities may occur; check TPMT level before therapy, and monitor liver, renal, and hematologic function; pancreatitis rarely associated
Histamine H2 antagonists
These agents inhibit histamine stimulation of the H2 receptor in gastric parietal cells, which, in turn, reduces gastric acid secretion, gastric volume, and reduced hydrogen concentrations. These agents are used to prevent stress ulcer development and potential GI bleeding.
Ranitidine (Zantac)
Indicated in peptic ulcer disease and upper GI bleeding for both treatment and prophylaxis.
Adult
150 mg PO bid; not to exceed 600 mg/d
Alternatively, 50 mg/dose IV/IM q6-8h
Pediatric
1 month-16 years: 2-4 mg/kg/d PO divided bid; alternatively, 2-4 mg/kg/d IV divided q6-8h
>16 years: Administer as in adults
May decrease effects of ketoconazole and itraconazole; may alter serum levels of ferrous sulfate, diazepam, nondepolarizing muscle relaxants, and oxaprozin
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
If changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment
More on Fulminant Hepatic Failure |
| Overview: Fulminant Hepatic Failure |
| Differential Diagnoses & Workup: Fulminant Hepatic Failure |
 Treatment & Medication: Fulminant Hepatic Failure |
| Follow-up: Fulminant Hepatic Failure |
| References |
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References
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Cochran JB, Losek JD. Acute liver failure in children. Pediatr Emerg Care. Feb 2007;23(2):129-35. [Medline].
Lee WS, McKiernan P, Kelly DA. Etiology, outcome and prognostic indicators of childhood fulminant hepatic failure in the United kingdom. J Pediatr Gastroenterol Nutr. May 2005;40(5):575-81. [Medline].
Baccarani U, Adani GL, Sainz M, et al. Human hepatocyte transplantation for acute liver failure: state of the art and analysis of cell sources. Transplant Proc. Jul-Aug 2005;37(6):2702-4. [Medline].
Caraceni P, Van Thiel DH. Acute liver failure. Lancet. Jan 21 1995;345(8943):163-9. [Medline].
Dhawan A, Cheeseman P, Mieli-Vergani G. Approaches to acute liver failure in children. Pediatr Transplant. Dec 2004;8(6):584-8. [Medline].
Goss JA, Shackleton CR, Maggard M, et al. Liver transplantation for fulminant hepatic failure in the pediatric patient. Arch Surg. Aug 1998;133(8):839-46. [Medline].
Hattori H, Higuchi Y, Tsuji M, et al. Living-related liver transplantation and neurological outcome in children with fulminant hepatic failure. Transplantation. Mar 15 1998;65(5):686-92. [Medline].
Lee WM. Acute liver failure. N Engl J Med. Dec 16 1993;329(25):1862-72. [Medline].
Suchy FJ. Fulminant hepatic failure in children. Saudi J Gastro. 1996;2(1):34-43.
Treem WR. Fulminant hepatic failure in children. J Pediatr Gastroenterol Nutr. 2002;35 Suppl 1:S33-8. [Medline].
Whittington PF. Fulminant hepatic failure in children. In: FJ Suchy, ed. Liver Disease in Children. Philadelphia, PA: Mosby; 1994:180-213.
Further Reading
Keywords
fulminant hepatic failure, FHF, hepatic failure, acute hepatic failure, liver failure, sudden-onset liver failure, hepatic encephalopathy, sepsis, disseminated intravascular coagulation, hyperacute liver failure, liver dysfunction, acetaminophen toxicity, jaundice, subacute liver failure, Wilson disease, autoimmune liver disease, liver transplantation, fetor hepaticus, ascites, cerebral edema, viral hepatitis, Epstein-Barr virus, cytomegalovirus, CMV, paramyxovirus, varicella-zoster virus, parvovirus, adenovirus, hepatitis A virus, HAV, hepatitis C virus, HCV, hepatocellular necrosis, tyrosinemia, hereditary fructose intolerance, galactosemia, neonatal hemochromatosis, congestive heart failure, Hodgkin disease, leukemia
