Key points
- We recommend to consult your poison centre with the use of this antidote.
- Methylene blue may be less effective or ineffective in patients deficient in glucose - 6 - phosphate dehydrogenase (G6PD); it may even cause hemolysis. However, it is not contraindicated in the event of partial deficiency.
- If ineffective, consider hyperbaric oxygen therapy (children, adults) or whole blood exchange transfusion (newborns, infants)
- When correction of methemoglobinemia is slow, consider the possibility of a G6PD deficiency or the ongoing absorption of the toxic agent.
- In case of methemoglobinemia without access to IV methylene blue, consult your poison center. More invasive therapies such as exchange transfusion may be considered on a case by case basis.
- WARNING:Health Canada notice issued on February 16, 2011: Methylene blue injectable in combination with serotonin reuptake inhibitors - Association with serotonin toxicity
+ Synonyms and other terms
- Methylthioninium chloride
- Methylene blue chloride
- Tetramethylthionine chloride
+ Indications
- Methemoglobinemia (metHb) greater than 0.20 (20%)
- MetHb lower than 0.20 (20%) with symptomatic patient (angina, confusion, agitation, anemia).
- For treatment of resistant shock du to toxin exposure (ex: calcium channel blockers), contact your poison centre.
+ Dosage
+ Pediatric Dose
- 1 - 2 mg/kg by direct IV. Repeat 30 - 60 min. later if partial response.
- Maximum dose: 7 mg/kg of ideal body weight by 24 hours.
+ Adult Dose
- 1 - 2 mg/kg by direct IV Repeat 30 - 60 min later if partial response.
- Maximum dose: 7 mg/kg of ideal body weight by 24 hours.
+ Renal Impairment
- No data suggests that the dose should be modified for short-term use.
+ Hepatic Impairment
- No data suggests that the dose should be modified for short-term use.
+ Hemodialysis Patient
- No data suggests that the dose should be modified for short-term use.
+ Pregnancy
- Methylene blue is considered teratogenic (jejunal atresia) when administered by intra-amniotic route, but there is no available data on IV administration.
- Do not hesitate to use methylene blue during pregnancy if anticipated toxic effects pose a significant risk of morbidity or mortality.
- No data suggests that the dose should be modified for short-term use.
+ Obese or Overweight Patient
- No data suggests that the dose should be modified for short-term use.
+ Adverse effects
- Nausea, vomiting, headaches, abdominal pain, dizziness, dyspnea, hypotension, especially if rapid injection or significant dose
- Blue-green discolouration of mucous membranes, urine, stool, and skin
- Methemoglobinemia if dose of methylene blue is greater than 7 mg/kg
- Thrombophlebitis
+ Monitoring
- Vital signs
- Body temperature
- Colour of skin and mucous membranes
- Serum electrolytes, hematocrit, bilirubin
- Serum methemoglobin levels
- Do not rely on bedside pulse oxygen saturation before or after administration of methylene blue. Saturation will not be accurate.
- If the concentration of metHb is greater than 0.05 (5%), blood will take on a chocolate brown colour. Sulfhemoglobin will give blood the same colour, but will not respond to methylene blue.
- During administration of methylene blue, a temporary drop in saturation may be observed.
- Arterial blood gases
- Administration site: extravasation may result in tissue necrosis
+ End of treatment
- Absence of relapse.
- Total absence of effect after one dose, suggesting a significant deficiency in glucose-6-phosphate dehydrogenase (G6PD) or other diagnosis.
- Total dose of 7 mg/kg of ideal body weight has been reached.
+ Special Notes on Administration
Intravenous Route (IV)
- Direct IV :
- Administer 10 mg/ml of the solution for injection by direct IV over 5 min using a volumetric pump.
- For smaller doses, the antidote can be diluted in NS in order to facilitate its administration.
- Rinse the tubing before and after each injection using 2.5 to 30 ml of NS in order to reduce the risk of thrombophlebitis.
Subcutaneous Route (SC)
- Do not administer by this route.
Intramuscular Route (IM)
- Do not administer by this route.
Intraosseous Route (IO)
- Possible alternative to IV route.
Enteral Route (PO or NG-tube)
- Possible, absorption varies from 53 to 97%.
- Risk of blue-green staining of all mucous membranes of the gastrointestinal tract.
Compatibility
Partial list only. Consult the pharmacist on duty at your healthcare facility.
- Compatible solutions: NS, D5W, LR
- Y-site compatibility: No data available.
- Y-site incompatibility: No data available.
Stability
- No data available
+ Available products
- Methylene blue, 10 mg/ml, Inj. Sol., 1 ml and 5 ml per vial, Alveda , DIN02431548
- Methylene blue, 10 mg/ml, Inj. Sol., 1 ml and 5 ml per vial, Omega , DIN02230770
+ Amount required to treat a person weighting 70kg during 24 hours
- At least 500 mg.
+ References
“37th International Congress of the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) 16-19 May 2017, Basel, Switzerland.” 2017. Clinical Toxicology 55 (5):371–544.
Berlin, G., B. Brodin, J. O. Hilden, and J. Mårtensson. 1984. “Acute Dapsone Intoxication: A Case Treated with Continuous Infusion of Methylene Blue, Forced Diuresis and Plasma Exchange.” Journal of Toxicology. Clinical Toxicology 22 (6):537–48.
Canning, Joshua, and Michael Levine. 2011. “Case Files of the Medical Toxicology Fellowship at Banner Good Samaritan Medical Center in Phoenix, AZ: Methemoglobinemia Following Dapsone Exposure.” Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology 7 (2):139–46.
Clifton, Jack, and Jerrold B. Leikin. 2016. “Methylene Blue.” In Critical Care Toxicology, edited by Jeffrey Brent, Keith Burkhart, Paul Dargan, Benjamin Hatten, Bruno Megarbane, and Robert Palmer, 1–12. Cham: Springer International Publishing.
A.H Dawson and I.M Whyte. 1999. “Management of Dapsone Poisoning Complicated by Methaemoglobinaemia”, Med Toxicol. Adverse Drug Exp.4(5) 387-392
Fisher, J., G. Taori, G. Braitberg, and A. Graudins. 2014. “Methylene Blue Used in the Treatment of Refractory Shock Resulting from Drug Poisoning.” Clinical Toxicology 52 (1):63–65.
Kim, Youn-Jung, Chang Hwan Sohn, Seung Mok Ryoo, Shin Ahn, Dong Woo Seo, Yoon-Seon Lee, Jae Ho Lee, Bum Jin Oh, Kyoung Soo Lim, and Won Young Kim. 2016. “Difference of the Clinical Course and Outcome between Dapsone-Induced Methemoglobinemia and Other Toxic-Agent-Induced Methemoglobinemia.” Clinical Toxicology 54 (7):581–84.
Southgate H John, Masterson R, Lessons to be learned: a case study approach: Prolonged methaemolobinaemia due to inadvertent dapson poisoning; treatment with methylene blue and exchange transfusion, The Journal of The Royal Society for the Promotion of Health; 1999, 119(1) pp 52-55
Prasad, Rajniti, R. Singh, O. P. Mishra, and Madhukar Pandey. 2008. “Dapsone Induced Methemoglobinemia : Intermittent vs Continuous Intravenous Methylene Blue Therapy.” Indian Journal of Pediatrics 75 (3):245–47.
Skold, Anna, Dominique L. Cosco, and Robin Klein. 2011. “Methemoglobinemia: Pathogenesis, Diagnosis, and Management.” Southern Medical Journal 104 (11):757–61.
Warrick, Brandon J., Anita Paula Tataru, and Susan Smolinske. 2016. “A Systematic Analysis of Methylene Blue for Drug-Induced Shock.” Clinical Toxicology 54 (7):547–55.
Wright, R. O., W. J. Lewander, and A. D. Woolf. 1999. “Methemoglobinemia: Etiology, Pharmacology, and Clinical Management.” Annals of Emergency Medicine 34 (5):646–56.
Zuckerman, Matthew, Howard A. Greller, and Kavita M. Babu. 2015. “A Review of the Toxicologic Implications of Obesity.” Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology 11 (3):342–54.
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