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Methemoglobinemia: Treatment & Medication
Updated: Jul 15, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Prehospital Care
- Administration of supplemental oxygen
- Removal of the offending oxidizing agent
Emergency Department Care
- Clinical recognition is paramount, as patients may have only vague complaints.
- Treatment is determined by symptomatology.
- Healthy asymptomatic patients without evidence of end-organ damage may require only observation.
- Patients with coronary artery disease or anemia may require therapeutic intervention at lower methemoglobin levels (eg, 10%) than a typical patient would, especially if end-organ dysfunction (eg, cardiac ischemia) is present.
- Supplemental oxygen
- Methylene blue is the first-line antidotal agent. Hyperbaric oxygen therapy or packed RBC exchange transfusions are alternative therapies for patients who are not candidates for methylene blue.
- Dermal decontamination (eg, water rinse, soap scrub, water rinse again)
- GI decontamination (eg, gastric lavage, activated charcoal administration)
- Investigational agents and therapies have no proven benefitsin the treatment of methemoglobinemia (eg, vitamin C, an antioxidant, and N- acetylcysteine, a cellular antioxidant)
Consultations
An American Association of Poison Control Centers (AAPCC)-certified regional poison control center or a medical toxicologist should be consulted in life-threatening cases.
Medication
Methylene blue is the first-line antidotal therapy.
Methylene blue accelerates the enzymatic reduction of methemoglobin by NADPH-methemoglobin reductase and also reduces to leucomethylene blue that, in turn, reduces methemoglobin. The initial dose is 1-2 mg/kg IV over 5 min. Its effects should be seen in approximately 20 min to 1 h. Patients who are exposed may require repeated dosing, but high doses of methylene blue may actually induce a paradoxical methemoglobinemia.
Treatment failure may occur in patients with ongoing exposure, patients exposed to sulfhemoglobinemia, and patients who have deficient NADPH-methemoglobin reductase enzymatic pathways. Methylene blue should be avoided in patients with G-6-PD deficiency, if possible, because case reports and in vitro models suggest that this antidote may induce hemolysis in this patient population. G-6-PD deficiency should be considered in patients who fail to respond to methylene blue.
Cimetidine can be used in dapsone-induced methemoglobinemia to prevent further formation of its metabolite who is also responsive as an oxidizing agent.
Hyperbaric oxygen and exchange transfusion should be considered for patients who are not candidates for methylene blue treatment or when methylene blue is ineffective.
Pharmacologic antidotes
Are used to pharmacologically counteract the condition. Cimetidine may be used in dapsone-induced methemoglobinemia.
Methylene blue (Urolene blue)
Effective treatment for methemoglobinemia. Most patients require only 1 dose. Resolution of toxicity should be seen within 1 h, often within 20 min.
Available as 1% solution (10 mg/mL).
Adult
1-2 mg/kg (0.1-0.2 mL/kg) IV over 3-5 min; repeat dose in 1 h if continued symptomatology or significant methemoglobinemia
Total dose not to exceed 7 mg/kg
Pediatric
<6 years: Not recommended (although there are reports of successful use in neonates and infants)
>6 years: Dosage is individualized; most cases reported in medical literature have utilized starting doses of 1 mg/kg IV/IM/IO over 5 min
Successful intraosseous administration in a 6-wk-old infant has been reported
None reported
Methylene blue is available as 1% solution (10 mg/mL)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus
Precautions
In G-6-PD deficiency can cause profound anemia; do not inject into CNS
Cytochrome P-450 inhibitors
Recommended only for patients with methemoglobinemia secondary to dapsone.
Cimetidine (Tagamet)
Inhibits conversion of dapsone to its oxidizing metabolite, dapsone hydroxylamine, by the P-450 system. Thus, cimetidine prevents further development of methemoglobinemia in this select patient population.
Adult
300 mg PO/IV q6-8h
Pediatric
Not established; doses of 20-40 mg/kg/d PO/IV may be given; given q6-8h
Can increase blood levels of theophylline, warfarin, tricyclic antidepressants, triamterene, phenytoin, quinidine, propranolol, metronidazole, procainamide, and lidocaine
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Elderly persons may experience confusional states; may cause impotence and gynecomastia in young males; may increase levels of many drugs; adjust dose or discontinue treatment if changes in renal function occur
More on Methemoglobinemia |
| Overview: Methemoglobinemia |
| Differential Diagnoses & Workup: Methemoglobinemia |
 Treatment & Medication: Methemoglobinemia |
| Follow-up: Methemoglobinemia |
| Multimedia: Methemoglobinemia |
| References |
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References
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Ash-Bernal R, Wise R, Wright SM. Acquired methemoglobinemia: a retrospective series of 138 cases at 2 teaching hospitals. Medicine (Baltimore). Sep 2004;83(5):265-73. [Medline].
Conkling PR. Brown blood: understanding methemoglobinemia. N C Med J. Mar 1986;47(3):109-11. [Medline].
Ellenhorn MJ, Barceloux DG. Nitrates, nitrites, and methemoglobinemia. In: Medical Toxicology, Diagnosis and Treatment of Human Poisonings. 1988:844-851.
Fitzsimons MG, Gaudette RR, Hurford WE. Critical rebound methemoglobinemia after methylene blue treatment: case report. Pharmacotherapy. Apr 2004;24(4):538-40. [Medline].
Henretig FM, Gribetz B, Kearney T, Lacouture P, Lovejoy FH. Interpretation of color change in blood with varying degree of methemoglobinemia. J Toxicol Clin Toxicol. 1988;26(5-6):293-301. [Medline].
Herman MI, Chyka PA, Butler AY, Rieger SE. Methylene blue by intraosseous infusion for methemoglobinemia. Ann Emerg Med. Jan 1999;33(1):111-3. [Medline].
Howland MA. Methylene blue. In: Goldfrank's Toxicologic Emergencies. 8th ed. 2006:1746-1748.
Price D. Methemoglobin inducers. In: Goldfrank's Toxicologic Emergencies. 8th ed. 2006:1734-1745.
Umbreit J. Methemoglobin--it's not just blue: a concise review. Am J Hematol. Feb 2007;82(2):134-44. [Medline].
Further Reading
Keywords
methemoglobinemia, red blood cells, hemoglobin, methemoglobin levels, methemoglobin, hexose-monophosphate shunt pathway, diaphorase I, diaphorase II, heme group, iron, oxidation of iron, nicotinamide adenine dinucleotide, NADH, nicotinamide adenine dinucleotide phosphate, NADPH, methylene blue, cellular hypoxia, cyanosis, discoloration of skin, acidosis
