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Nitrogen Dioxide Toxicity Medication

  • Author: Nader Kamangar, MD, FACP, FCCP, FCCM; Chief Editor: Ryland P Byrd, Jr, MD  more...
 
Updated: Apr 28, 2014
 

Medication Summary

Methylene blue is indicated for significant methemoglobinemia. Other possible treatments may include antibiotics if infection becomes evident, and vasopressor drugs are required to correct the 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.

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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.

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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.

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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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Contributor Information and Disclosures
Author

Nader Kamangar, MD, FACP, FCCP, FCCM Professor of Clinical Medicine, University of California, Los Angeles, David Geffen School of Medicine; Chief, Division of Pulmonary and Critical Care Medicine, Vice-Chair, Department of Medicine, Olive View-UCLA Medical Center

Nader Kamangar, MD, FACP, FCCP, FCCM is a member of the following medical societies: Academy of Persian Physicians, American Academy of Sleep Medicine, American Association for Bronchology and Interventional Pulmonology, American College of Chest Physicians, American College of Critical Care Medicine, American College of Physicians, American Lung Association, American Medical Association, American Thoracic Society, Association of Pulmonary and Critical Care Medicine Program Directors, Association of Specialty Professors, California Sleep Society, California Thoracic Society, Clerkship Directors in Internal Medicine, Society of Critical Care Medicine, Trudeau Society of Los Angeles, World Association for Bronchology and Interventional Pulmonology

Disclosure: Nothing to disclose.

Coauthor(s)

Caleb Hsieh, MD, MS Department of Internal Medicine, Olive View-UCLA Medical Center

Caleb Hsieh, MD, MS is a member of the following medical societies: American College of Physicians, American Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Ryland P Byrd, Jr, MD Professor of Medicine, Division of Pulmonary Disease and Critical Care Medicine, James H Quillen College of Medicine, East Tennessee State University

Ryland P Byrd, Jr, MD is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

Acknowledgements

Rebecca Bascom, MD, MPH Professor of Medicine, Pennsylvania State College of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Milton S Hershey Medical Center

Disclosure: Nothing to disclose.

Charles B Cairns, MD Professor and Chair, Department of Emergency Medicine, University of North Carolina School of Medicine; Consulting Faculty, Department of Emergency Medicine, Duke University Medical School and Duke Clinical Research Institute

Charles B Cairns, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Emergency Physicians, American Heart Association, American Thoracic Society, American Trauma Society, European Respiratory Society, New York Academy of Sciences, Sigma Xi, Society for Academic Emergency Medicine, and Society for Experimental Biology and Medicine

Disclosure: Nothing to disclose.

Lex Chen, MD Resident Physician, Department of Internal Medicine, University of California Los Angeles, Olive View Medical Center

Lex Chen, MD is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Miguel C Fernandez, MD, FAAEM, FACEP, FACMT, FACCT Associate Clinical Professor, Department of Surgery/Emergency Medicine and Toxicology, University of Texas School of Medicine at San Antonio; Medical and Managing Director, South Texas Poison Center

Miguel C Fernandez, MD, FAAEM, FACEP, FACMT, FACCT is a member of the following medical societies: American Academy of Emergency Medicine, American College of Clinical Toxicologists, American College of Emergency Physicians, American College of Medical Toxicology, American College of Occupational and Environmental Medicine, Society for Academic Emergency Medicine, and Texas Medical Association

Disclosure: Nothing to disclose.

Fred Harchelroad, MD, FACMT, FAAEM, FACEP Director of Medical Toxicology, Allegheny General Hospital

Disclosure: Nothing to disclose.

Suzanne M Miller, MD Clinical Instructor, Emergency Medicine, George Washington University School of Medicine and Health Sciences; Attending Physician, Department of Emergency Medicine, INOVA Fairfax Hospital; Chief Executive Officer, MDadmit

Suzanne M Miller, MD is a member of the following medical societies: American Academy of Emergency Medicine and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Jeffrey S Peterson, MD Clinical Assistant Professor of Surgery/Emergency Medicine, Stanford University School of Medicine, Stanford University Hospital; Founder and Sports Medicine Physician, Innovative Sports Medicine

Jeffrey S Peterson, MD, is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Sports Medicine, Massachusetts Medical Society, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Mark D Rasmussen, MD Staff Physician, Department of Anesthesia, Naval Medical Center San Diego

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Asim Tarabar, MD Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

Gregory Tino, MD Director of Pulmonary Outpatient Practices, Associate Professor, Department of Medicine, Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania Medical Center and Hospital

Gregory Tino, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and American Thoracic Society

Disclosure: Nothing to disclose.

John T VanDeVoort, PharmD Regional Director of Pharmacy, Sacred Heart and St Joseph's Hospitals

John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists

Disclosure: Nothing to disclose.

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Bronchiolitis obliterans following exposure to nitrogen dioxide. Courtesy of Dr. Ann Leung, Department of Radiology, Stanford University Hospital.
Noncardiogenic pulmonary edema following exposure to nitrogen dioxide. Courtesy of Dr. Ann Leung, Department of Radiology, Stanford University Hospital.
Nitrogen dioxide air quality from 1980 to 2012. Courtesy of the US Environmental Protection Agency.
 
 
 
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