Methylene blue methemoglobinemia

Etteldorf, J.N. 1951. Methylene blue in the treatment of methemoglobinemia in premature infants caused by marking ink. J. Pediat. 38 24-27. 

It was shown that trivalent iron was able to provide the electronic linkage and to produce a 4-fold stimulation of MHbR activity in the absence of any dye (H23). Furthermore, it has been found that the addition of methylene blue to crude enzyme preparations was necessary for reducing MHb but not for using oxygen as a terminal electron acceptor (H23). The enhancement of MHb reduction in methemoglobinemia by ascorbic acid (e.g., B14) also indicates the implication of reduction-oxidation mechanisms in MHbR activity. 

Vitamin C in doses of at least 150 mg has been used to control idiopathic methemoglobinemia (less effective than methylene blue). 

Methemoglobinemia has occurred in premature and full-term neonates given metoclopramide orally, IV or IM, 1 to 4 mg/kg/day for 1 to at least 3 days this did not occur at 0.5 mg/kg/day. Reverse methemoglobinemia by IV administration of methylene blue. 

Smooth muscle relaxant activity. Tine-ture of the gland, administered to rabbits, was active on the bladder and intestine " . Toxic effect. Gum, administered orally to adults, was active. A case of methemoglobinemia occurred in a 5-week-old male infant, after administration of asafetida preparation to alleviate colic. Treatment was with intravenous methylene blue and the infant recovered . Tumor-promoting activity. Water extract of the dried oleoresin, administered externally to mice at a dose of 200 pL/animal, was active vs 7,12-dimethylbenz[a]anthra-cene and croton oil treatment ". ... 

Contraindications Hypersensitivity to methylene blue or any component of its formulation, glucose-6-phosphatedehydrogenase (G6PD) deficiency, intraspinal injection, severe renal insufficiency, treatment of methemoglobinemia in cyanide poisoning... 

Clinical use Due to the low lipophilicity and therefore the low ability to penetrate neuronal membranes, the clinical use of benzocaine is limited to topical anesthesia such as mucous membrane anesthesia prior to endoscopic examination or for temporary relief of oral or dental pain. With higher doses, oxidation of the ferric form of hemoglobin to the ferrous form can occur the resulting methemoglobinemia is usually benign and can be reversed with methylene blue. Benzocaine is more likely to cause contact sensitization than amide-type LAs. 

Rodents (mice, rats, rabbits) have a higher activity of this enzyme than do humans, so that extrapolation of rodent experiments with methemoglobinemia to humans is usually inappropriate. Methylene blue can also bring about the reduction of HbFe(III) to HbFe(II) and is used as an antidote for aniline poisoning. 

Dapsone Supportive treatment for the adverse effects of dapsone may be initiated with stomach wash and activated charcoal. Methylene blue could be given to treat methemoglobinemia, but this is not effective in patients with glucose-6-phosphate dehydrogenase deficiency. Infusion of human erythrocytes can be... 

Flutamide can cause methemoglobinemia (6-8) or sulfhemoglobinemia (5). The latter occurred in a 70-year-old man who had taken flutamide 150 mg tds for 1 month and developed cyanosis and anemia that was not responsive to methylthioninium chloride (methylene blue). 

Animals may manifest toxicity to salicylates with signs and symptoms similar to those seen in humans. These may include fever, hyperpnea, seizures, respiratory alkalosis, metabolic acidosis, gastric hemorrhage, and kidney damage. Methemoglobinemia has also been seen in animals following salicylate toxicity. Activated charcoal has been used in animals. Methylene blue or ascorbic acid may be utilized for the treatment of methemoglobinemia. 

Treatment is basically symptomatic and supportive no specific antidotes are available. Artificial ventilation with 100% humidified oxygen is necessary in cases of respiratory distress. If patient is cyanotic and cyanosis does not respond to oxygen administration, methemoglobin levels should be determined. Methemoglobinemia can be treated by intravenous administration of methylene blue. Support of cardiovascular function may also be required. Bladder damage can be determined by urinalysis. Hypotension may be treated with isotonic intravenous fluids. Dopamine or norepinephrine may be used if hypotension does not respond to infusion of fluids. Convulsions may be treated with intravenous benzodiazepines (diazepam or loraze-pam) phenobarbital may be used if the convulsions are recurrent. Because chlordimeform is a monoamine oxidase inhibitor, foods with large amounts of... 

Clinical management should be symptomatic and supportive. A benzodiazepine can be administered to control seizures. Methylene blue can be used to treat methemoglobinemia. 

There is no specific antidote for naphthalene toxicity. Treatment is symptomatic and supportive. Gastric decontamination should be considered with emesis or lavage, followed by activated charcoal. Hemolysis may require urinary alkalinization and transfusion. Methemoglobinemia may be treated with methylene blue. Emesis is more useful for mothballs because of size. Lavage may be useful for ingestion of flakes. Information on activated charcoal is scant, but adsorption is thought to occur. Mothballs dissolve slowly gastric decontamination should be performed... 

Significant levels of methemoglobinemia were produced when mice were exposed to butyl nitrites via inhalation. Pretreatment of the mice with methylene blue prevented the methemoglobin formation associated with the butyl nitrite exposure. A single intravenous dose of 30 mg kg of sodium nitrite caused methemoglobinemia in dogs. The minimum lethal dose of sodium nitrite is estimated to be 150-170 mg kg in cattle and 70-75 mg kg in pigs. 

Plasma nitrobenzene levels are not clinically useful. The metabolites in urine, p-nitro- and p-aminophe-nol, primarily in long-term exposure to nitrobenzene can be used as evidence of exposure. Methemoglobin levels should be determined in all cyanotic patients cyanosis that does not respond to oxygen therapy may appear when the plasma methemoglobin level is 15%. Symptomatic methemoglobinemia should be treated with methylene blue. For seizures, diazepam should be administered via an intravenous bolus. 

If dermal or eye contact with the liquid occurs, the affected areas should be flushed thoroughly with water for at least 15 min and the patient observed for resulting skin or eye irritation. In case of inhalation, the victim should be moved to fresh air and the patient should be monitored for respiratory irritation and pulmonary edema. If ingestion occurs, basic and advanced life-support measures should be utilized as necessary. Gastrointestinal decontamination procedures are unlikely to provide clinical benefit. The use of methylene blue should be considered in the treatment of nitroethane-induced methemoglobinemia. Repeat doses of methylene blue may be necessary for patients with profound methemoglobinemia. 

Methylene blue therapy (unlike with methemoglobinemia) does not help with the hematological effects. 

Symptomatic and supportive care is the mainstay of therapy. Adequate urine output should be assured. In acute overdose, charcoal may be considered. Methylene blue therapy may be considered for patients with methemoglobinemia. Dialysis has been used for phenazopyridine-induced renal dysfunction, but no studies have demonstrated an increased elimination of phenazopyridine with dialysis. In patients with hemolysis and marked anemia, transfusion may be necessary. 

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