Isoniazid Toxicity Workup

Updated: Jul 14, 2016
  • Author: Joseph L D'Orazio, MD, FAAEM; Chief Editor: BS Anand, MD  more...
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Workup

Approach Considerations

Serum isoniazid (INH) levels are not readily available and do not help in the initial management of INH toxicity.

Laboratory studies generally are not helpful in the diagnosis of acute INH toxicity but may identify complications. Laboratory abnormalities observed with acute INH toxicity complications may include the following:

  • Metabolic acidosis
  • Rhabdomyolysis
  • Renal failure

Laboratory abnormalities seen with hepatotoxicity from INH therapy includes the following:

  • Elevated liver enzyme levels
  • Granulocytopenia or agranulocytosis
  • Eosinophilia
  • Thrombocytopenia
  • Anemia
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Laboratory Studies

Serum transaminases

Levels of serum transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) should be determined. Patients with pretreatment AST levels above the upper limit of normal are predisposed to hepatotoxicity.

If transaminase values are elevated less than 3-fold in a patient who is asymptomatic, cautious continued administration of isoniazid (INH) is permissible. However, additional testing to exclude other causes of hepatitis is usually indicated. If transaminase levels are elevated more than 3-fold, discontinue INH and other hepatotoxic drugs.

Viral serologies

Hepatitis A may be excluded by a negative test result for anti-HAV (hepatitis A virus) immunoglobulin M (IgM). Hepatitis C is excluded by a negative result for anti-HCV (hepatitis C virus) antibody; however, this test occasionally may remain negative for several weeks after the onset of hepatitis C. Hepatitis B may be excluded by a negative result for either hepatitis B surface antigen (HBsAg) or antibody to hepatitis B core antigen (anti-HBc). Testing for viral DNA or RNA also may be used, but it is more expensive.

Toxicology

Potential hepatotoxins other than INH should be considered. In patients with a compatible history, blood acetaminophen and ethanol levels may be useful.

Prothrombin time/international normalized ratio

The international normalized ratio (INR) usually is normal in early and mild cases of INH overdose. Significant elevation of the INR that does not respond to parenteral vitamin K is a grave sign that should prompt evaluation for liver transplantation.

Serum iron

High transferrin saturations associated with high ferritin levels suggest hemochromatosis, which often presents with transaminase abnormalities. However, ferritin is an acute-phase reactant that often is elevated in other types of hepatitis. Thus, the presence of high ferritin levels does not suggest hemochromatosis unless the iron saturation also is high. Genetic testing for hemochromatosis may be useful in these patients.

Serum ceruloplasmin

In younger persons, efforts must be made exclude Wilson disease, especially if any neuropsychiatric component exist.

Additional tests

Additional laboratory studies may be performed to assess for the following:

  • Acetaminophen level in patients with intentional exposure
  • Urine screen for drugs of abuse
  • Urine pregnancy test
  • Leukocytosis (complete blood cell [CBC] count)
  • Lactic acidosis
  • Hyperglycemia
  • Ketonuria
  • Glycosuria
  • Ketonemia
  • Hypokalemia
  • Transient elevation of liver enzymes
  • Myoglobinuria
  • Cerebrospinal fluid (CSF) pleocytosis
  • Ketonemia
  • Positive disseminated intravascular coagulation (DIC) panel
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Other Studies

Electrocardiography (ECG) may be useful if seizure is precipitated by cardiac dysrhythmia. ECG may identify a multitude of cardiac abnormalities including prolonged QTc, widened QRS, prominent R in aVR, and heart block.

Electroencephalography (EEG) is not routinely available in the emergency department (ED). EEG should be part of the full neurodiagnostic workup, as it has substantial yield and ability to predict risk of seizure recurrence.

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Histologic Findings

Liver biopsy is rarely indicated for evaluation of acute hepatitis, because the histologic features typically are nonspecific. Liver histology findings closely resemble that of acute viral hepatitis and includes ballooning degeneration, sinusoidal acidophilic bodies, and focal necrosis occasionally accompanied by slight cholestasis. Necrosis is more extensive in cases that are more severe. Inflammatory infiltrates with lymphocytes and plasma cells are common, whereas eosinophilic infiltrates are rarely seen.

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Imaging Studies

For patients with new-onset seizures, unexplained seizures, or status epilepticus, noncontrast computed tomography (CT) scanning of the head is the imaging procedure of choice because of its ready availability and its ability to identify potential catastrophic pathologies.

Abdominal imaging is not normally required and should only be considered in patients with symptoms suggesting biliary disease or to exclude biliary obstruction if the alkaline phosphatase level is elevated more than the transaminase levels are. Abdominal imaging may show hepatomegaly, but splenomegaly and ascites typically are absent

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