Medication Summary
Methylene blue is indicated for significant methemoglobinemia. However, note that methylene blue can cause serious central nervous system reactions in patients taking serotonergic psychiatric medications, which include numerous antidepressants and antipsychotic agents. [36]
Other possible treatments may include antibiotics if infection becomes evident, and vasopressor drugs are required to correct normovolemic shock. High-dose corticosteroids are suggested in the treatment of pulmonary manifestations, but data on their use for prevention of bronchiolitis obliterans after nitrogen dioxide (NO2) exposure are anecdotal.
Antidotes, Other
Class Summary
Methylene blue (ie, tetramethyl thionine chloride) is the recommended antidote for methemoglobinemia. It is reduced to leukomethylene blue, which is then available to reduce methemoglobin to hemoglobin.
Methylene blue
Methylene blue is the drug of choice for patients who are cyanotic from methemoglobinemia and symptomatic or whose methemoglobin level exceeds 30%. It is administered intravenously. It is available as 1% solution (10 mg/mL) in 10 mL ampules.
The US Food and Drug Administration (FDA) warns against the concurrent use of methylene blue with serotonergic psychiatric drugs, unless indicated for life-threatening or urgent conditions. Methylene blue may increase serotonin levels in the central nervous system as a result of monoamine oxidase–A (MAO-A) inhibition, increasing the risk of serotonin syndrome.
Corticosteroids
Class Summary
These agents reduce the inflammatory response. Whether early administration can prevent development of noncardiogenic pulmonary edema is unknown. The decision to administer corticosteroids must be made on clinical grounds.
Corticosteroids are effective in treating bronchiolitis obliterans. Because not all patients with acute lung injury develop this condition, judge the risk factors and choose between prescribing the patient corticosteroids for prevention and monitoring the patient for clinical or radiographic evidence of bronchiolitis obliterans.
Methylprednisolone (Solu-Medrol, Depo-Medrol, A-Methapred)
Methylprednisolone decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability, thus reducing the inflammatory response of bronchiolitis obliterans. Consider tapering if prolonged dosing (>14 d) is required. The dose can be tapered over 8 weeks, on the basis of clinical symptoms, radiographic findings, and spirometry results.
Vasodilators
Class Summary
One case report described a patient with ARDS secondary to silo filler’s disease who required nitric oxide (NO) therapy because of worsening oxygenation. Use of NO therapy requires great care because of the possibility of worsening pulmonary damage and methemoglobinemia, which are already present in patients with NO2 toxicity.
Nitric oxide (INOmax)
NO is produced endogenously from the action of the enzyme NO synthetase on arginine. It relaxes vascular smooth muscle by binding to the heme moiety of cytosolic guanylate cyclase, activating guanylate cyclase and increasing intracellular levels of cyclic guanosine monophosphate (cGMP), which then leads to vasodilation. When inhaled, NO decreases pulmonary vascular resistance and improves lung blood flow.
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Bronchiolitis obliterans following exposure to nitrogen dioxide. Courtesy of Dr. Ann Leung, Department of Radiology, Stanford University Hospital.
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Noncardiogenic pulmonary edema following exposure to nitrogen dioxide. Courtesy of Dr. Ann Leung, Department of Radiology, Stanford University Hospital.
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Nitrogen dioxide air quality from 1980 to 2012. Courtesy of the Air Quality Analysis Group, US Environmental Protection Agency (EPA).
