Methemoglobinemia occurs when oxidative injury to hemoglobin leads to conversion of the heme from the ferrous to the ferric
state. Methemoglobin is incapable of carrying oxygen. The blood of patients with methemoglobinemia is a characteristic chocolate-brown
color, and their mucous membranes may appear brown. Methemoglobinemia is reversible, and the body has enzyme systems that
reduce methemoglobin back to hemoglobin. Treatment is required when the body's enzyme systems become overloaded and clinical
signs of hypoxia develop. Patients become symptomatic when 20% to 30% of their hemoglobin has been converted to methemoglobin.12
Methemoglobinemia has been treated in dogs and cats with ascorbic acid (20 mg/kg orally, intramuscularly, or subcutaneously
up to every six hours10,13) or methylene blue (1.5 mg/kg slowly intravenously as a 1% solution10,14). Ascorbic acid is thought to reduce methemoglobin to hemoglobin by a nonenzymatic reserve mechanism that the body uses when
the enzyme systems normally responsible for the reduction are overloaded.13 This conversion is relatively slow,10 so ascorbic acid may not be useful for seriously affected patients unless it is used in conjunction with other treatments.
Methylene blue acts rapidly and works through its conversion to leucomethylene blue in the tissues. Leucomethylene blue acts
as a reducing agent in the conversion of methemoglobin to hemoglobin. Because methylene blue is an oxidizing agent, increased
methemoglobinemia is a possible adverse effect.11 Cats are reported to be at an increased risk for this adverse effect because of their unusual hemoglobin structure, so methylene
blue use in cats is considered controversial.11,12
N-Acetylcysteine may also be helpful in treating naphthalene- or paradichlorobenzene-induced methemoglobinemia, but it has
not been recommended in the literature for this purpose. Acetylcysteine is a precursor in the synthesis of glutathione, or
it can be oxidized to organic sulfate that is used in the sulfate conjugation pathway. Acetylcysteine is regularly administered
to patients with acetaminophen toxicosis to reduce methemoglobinemia by providing an alternative substrate for conjugation
with the metabolites of acetaminophen and maintaining glutathione concentrations.11,15 Based on its mechanism of action, acetylcysteine may also help maintain glutathione and sulfate concentrations during naphthalene
or paradichlorobenzene toxicosis. Acetylcysteine is available in 10% and 20% solutions; it should be diluted to a 5% solution,
using 5% dextrose solution or sterile water, before use. Administer an initial loading dose of 140 mg/kg, followed by 70 mg/kg
orally every six hours for seven treatments. When given orally, acetylcysteine may cause gastrointestinal upset.11 Proper dilution can decrease the chances of gastrointestinal upset developing. Acetylcysteine is not labeled for intravenous
use, but it can be given intravenously in severely affected patients or patients showing signs of gastrointestinal upset.
Administer intravenous acetylcysteine slowly over 15 to 20 minutes through a bacteriostatic (0.2-µ) filter.10
The prognosis for patients exposed to naphthalene- or paradichlorobenzene-containing moth repellents is favorable if the clinical
signs are treated and no underlying patient factors, such as liver disease or conditions causing anemia, are present. Therapy
and monitoring should continue until the clinical signs have resolved and complete blood count and serum chemistry profile
results have returned to normal.
1. U.S. Department of Health and Human Services, Agency for Toxic Substances and Disease Registry, Toxicological Profile for Naphthalene, 1-Methylnaphthalene, and 2-Methylnaphthalene. Research Triangle Institute, 1995.
2. Bischoff K. Naphthalene. In: Plumlee KH, ed. Clinical veterinary toxicology. St Louis, Mo: Mosby, 2004;163-164.
3. POISINDEX System Editorial Staff. Naphthalene (Management/Treatment Protocol). POISINDEX System. Greenwood Village, Colo:
MICROMEDEX, expires 3/04.
4. POISINDEX System Editorial Staff. Paradichlorobenzene (Management/Treatment Protocol). POISINDEX System. Greenwood Village,
Colo: MICROMEDEX, expires 3/04.
5. U.S. Department of Health and Human Services, Agency for Toxic Substances and Disease Registry, Toxicological Profile for 1,4-Dichlorobenzene. Research Triangle Institute, 1998.
6. Parkinson A. Biotransformation of xenobiotics. In: Klaassen CD, ed. Casarett and Doull's toxicology. 5th ed. New York, NY: McGraw-Hill, 1996;133-224.