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7 "Methemoglobinemia"
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A Case of a Herbicide Poisoning Induced Methemoglobinemia Patient Treated with High-dose Vitamin C
Kyung Hoon Sun, Jun Kew Kim, Chang Yeon Ryu, Seo Jin Kim, Hyeon Kyu Jo, Tae Ho Yoo, Yong Jin Park, Sun pyo Kim
J Korean Soc Clin Toxicol. 2017;15(2):148-151.   Published online December 31, 2017
DOI: https://doi.org/10.22537/jksct.2017.15.2.148
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Methemoglobinemia is a condition in which the iron portion of hemoglobin, which binds to oxygen, is oxidized to produce methemoglobin, which increases blood concentration. There are many causes of methemoglobinemia, the most common being food, drugs, and chemicals. A 75-year-old male patient who had taken an herbicide did not notice any nonspecific symptoms. However, after 4 hours, his methemoglobin levels increased to 17.1%, while after 7 hours it increased to 26.5%, at which time intravenous administration of methylene blue 1 mg/kg (an antidote) was started. After a total of five doses of methylene blue at 1 mg/kg due to reactive methemoglobinemia for about 36 hours, the methemoglobin levels increased to 23.7%. Because no more methylene blue could be administered, 10 g of ascorbic acid (vitamin C) was administered intravenously. After 82 hours, ascorbic acid 10 g was administered six times for repeated reactive methemoglobinemia. No additional reactive methemoglobinemia was observed. The ventilator and endotracheal tube were successfully removed on day 5 after admission.
Methylene Blue
Ji-Young You
J Korean Soc Clin Toxicol. 2010;8(1):1-6.   Published online June 30, 2010
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Methylene blue is a very effective reducer of drug-induced methemoglobinemia. It has dose-dependent oxidation or reduction properties. In most cases, a dose of 1 to 2 mg/kg IV given over 5 minutes and immediately followed by a 15- to 30-mL fluid flush to minimize the local pain is both effective and relatively safe. The onset of action is quite rapid, and the effects are usually seen within 30 minutes. The dose may be repeated after 30 to 60 minutes and then every 2 to 4 hours as needed. The total dose should not exceed 7 mg/kg as a single dose or 15 mg/kg within 24 hours. Repeated treatment may be needed for treating compounds that have prolonged elimination or those compounds that undergo enterohepatic recirculation (e.g., dapsone). Methylene blue can cause dose-related toxicity. At high doses, methylene blue can also induce an acute hemolytic anemia and rebound methemoglobinemia. The reasons for treatment failure with methylene blue include ineffective GI decontamination, the existence of other forms of hemoglobin (e.g., sulfhemoglobin), a low or high dose of methylene blue and the toxicokinetics of some agents, such as aniline, benzocaine or dapsone.
A Patient with Methemoglobinemia after Herbicide Intoxication has Hemolytic Anemia Induced by Methylene Blue
Sun-Pyo Kim, Dong-Hwan Kim, Kyung-Hoon Sun, Dae-Heung Yoon, Seong-Jung Kim, Soo-Hyeong Cho, Nam-Soo Cho
J Korean Soc Clin Toxicol. 2008;6(2):134-137.   Published online December 31, 2008
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Methylene blue is the first choice for treating methemoglobinemia, any increase in normal methemoglobin levels. Methemoglobin is an abnormal hemoglobin in which the iron has been oxidized to the ferric(+3) state, making it incapable of oxygen transport. Methemoglobinemia most commonly results from exposure to oxidizing chemicals, but may also arise form genetic, dietary, or even idiopathic etiologies. Patients with low methemoglobin levels are asymptomatic, but high methemoglobin levels can lead to headaches or even death. Methylene blue, the first-line treatment for methemoglobinemia, can also produce hemolytic anemia. Jaundice or dark urine during methylene blue treatment may indicate hemolytic anemia. A 47-year-old female patient with a history of depressive mood disorder developed significant methemoglobinemia after ingesting a Propanil overdose. Twenty-two hours after ingestion, methemoglobin levels in the blood were 73.2%. She was treated with intravenous methylene blue in the therapeutic range (1 mg/kg every 4 h for 3days). The 2nd day after methylene blue use, methemoglobin levels in the blood were 33%, and the 5th day decreased to 10% with better general condition. The patient had hyperbilirubinemia after hemolytic anemia, but she recovered completely.
Exchange Transfusion Treatment for Dapsone-induced Methemoglobinemia
Hwa-Yoen Yi, Jang-Young Lee
J Korean Soc Clin Toxicol. 2008;6(1):37-41.   Published online June 30, 2008
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Methemoglobinemia can be caused by dapsone toxicity. We report a case dapsone induced methemoglobinemia unresponsive to methylene blue successfully treated by exchange transfusion. A 52-year-old male ingested a handful of dapsone. He presented with severe peripheral cyanosis in lips and fingertips and his methemoglobin level was found to be 21.9%. After admission, methylene blue (1%) at 1 mg/kg was injected each time peripheral cyanosis and rising serum methemoglobin occurred. Despite methylene blue therapy, the patient‘s methemoglobin level continued to fluctuate. Five days after the injections of methylene blue, many Heinz bodies were visualized in the peripheral blood, suggestive of hemolytic anemia occurrence. By hospital day 6, serum methemoglobine levels were elevated and not measurable (> 50%) and the patient was constantly in a semi-comatose mental state. An exchange transfusion carried out by utilizing 6 units of packed red blood cells and 4 units of fresh frozen plasma was performed. The patient's methemoglobin levels were subsequently kept up below 20% and his peripheral cyanosis receded. Physicians should recognize the important role of exchange transfusion in refractory dapsoneinduced methemoglobinemia.
A Fatal Case of Methylene Blue Threatment Failure in Methemoglobinemia
Ji-Yae Shim, Yun-Seok Seo, Jong-Oh Yang, Eun-Young Lee, Sae-Yong Hong, Hyo-Wook Gil
J Korean Soc Clin Toxicol. 2006;4(2):151-154.   Published online December 31, 2006
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Acute toxic methemoglobinemia is an infrequent complication of the use of various drugs. Severe methemoglobinemia is very often fatal. Methylene blue is an effective drug in the treatment of methemoglobinemia patients. However, failure to respond to methylene blue has been described in patients with sulfhemoglobinemia, chlorate poisoning, and glucose-6-phosphate dehydrogenase deficiency. It is even possible that hemolysis may occur due to methylene blue treatment itself. We encountered a case of a 71-year-old woman who developed methemoglobinemia caused by alprazolam intoxication. She presented with hemolytic anemia and did not respond to methylene blue. In spite of concerted N-acetylcysteine therapy, the hemolytic anemia became aggravated and the patient died eleven days after intoxication.
Indoxacarb Pesticide Poisoning with Methemoglobinemia
Jae-Hoon Shin, Jae-Kwang Lee, Seong-Soo Park, Sang-Jun Na, Joon-Seok Park
J Korean Soc Clin Toxicol. 2006;4(2):158-160.   Published online December 31, 2006
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Acute methemoglobinemia is induced by various causes, especially ingestion of oxidizing agents such as phenazopyridine, dapsone, and nitrite. Indoxacarb is an oxadiazine insecticide with high insecticidal activity and low mammalian toxicity. It is known to block voltage-gated Na+ channels in insects and mammals, but the mechanism is not yet well understood. We describe a case of a 41-year-old woman with methemoglobinemia that developed following Indoxacarb ingestion, which improved after intravenous injection of methylene blue. This is the first known such case. If signs and symptoms of methemoglobinemia occur after Indoxacarb ingestion, antidotal therapy with methylene blue should be considered as a necessary treatment.
A Case of Acute Dapsone Poisoning Complicated with Methylene Blue-induced Hemolytic Anemia
Mi-Jin Lee, Kyu-Nam Park
J Korean Soc Clin Toxicol. 2006;4(2):170-174.   Published online December 31, 2006
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Methylene blue is a basic thiazine dye frequently used for histologic staining. In clinical toxicology settings, it is also used to treat clinically significant methemoglobinemia. It has dose-dependent oxidation or reduction properties, acting as a reducing agent at lower doses and as an oxidizing agent at higher doses. Hemolytic anemia and hyperbilirubinemia are known toxic effects of methylene blue treatment that have been reported clinically. A 42-year-old woman developed significant methemoglobinemia after acute dapsone overdose; she was treated appropriately with intravenous methylene blue in the therapeutic range. The patient's methemoglobin levels returned to normal. However, 2-4 days later she was noted to have rebound methemoglobinemia, hemolytic anemia, and hyperbilirubinemia. A repeat of Coomb's test and other anemia workups were negative. For management of methylene blue-induced hemolytic anemia, she was administered steroid therapy, N-acetylcysteine, and a blood transfusion. She ultimately recovered, and there were no long-term sequelae from the methylene blue poisoning.

JKSCT : Journal of The Korean Society of Clinical Toxicology