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Describe the manifestations of methylene blue toxicity, with a review of the literature.

Patient 1:2400 g female infant, with trisomy 21 and biliary atresia, who underwent correction of duodenal atresia on day 1 and was given an undetermined amount of methylene blue via her jejunostomy and gastrostomy tubes. She voided blue-green urine within hours and experienced jaundice, fever, hypotension, respiratory and other organ failure over the next several days; on day 15 she died. She was determined to have developed Heinz body hemolytic anemia within hours of receiving the methylene blue.

Patient 2: 2580 g female infant transferred on day 2 with suspected metabolic disorder. Symptoms included coma, metabolic acidosis, seizures, renal failure. On day 4, she was given 50 mg (20 mg/kg) methylene blue for butyric aciduria type II. On day 10 Meinz body preparation revealed 95% of red cells with hemoglobin precipitates; she died on day 11.

• The recommended dose of methylene blue is 2 mg/kg. Some infants exposed to doses of 2-4 mg/kg develop hemolytic anemia and hyperbilirubinemia. Infant 2 received 10 times the recieved dose. Both infants had complex medical circumstances in which methylene blue toxicity was only partially responsible for the outcome.
• Recommend substitution of alternate formulas, such as nonredox dyes, when methylene blue is considered as the diagnostic marker
• Propose screening technique such as dye decolorization test when methylene blue is considered for infants or pregnant women

University/Hospital:

John Hopkins

Contains a brief review of studies of methylene blue toxicity in infants.