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Nitrogen Dioxide Toxicity Treatment & Management

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

Approach Considerations

If no initial symptoms are present, observe the patient for at least 12 hours for hypoxemia. Hospitalize the patient for 12-24 hours for observation or longer if gas exchange is compromised. Noncardiogenic pulmonary edema can take up to 48 hours to develop. Educate the patient on the possible symptoms and instruct the patient to return if the symptoms develop.

Administer oxygen to the patient for hypoxemia. Intubation and mechanical ventilation may be necessary if gas exchange is severely impaired. Treat secondary infection, if present.

Administer volume expanders cautiously. The patient may require invasive monitoring because excessive administration of volume expanders can cause hydrostatic pulmonary edema. Nitrogen dioxide (NO2) forms nitric oxide, causing vasodilation and an apparent volume depletion.[22]

Transferring the patient to a tertiary care center for further diagnostic evaluation and ventilatory support may be necessary.

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Prehospital and Emergency Department Care

Rescuers must remove the patient from the source of exposure without endangering themselves. Wearing a self-contained breathing apparatus (SCBA) may be indicated. The patient should then receive supplemental oxygen, and, if needed, airway management and ventilatory support.

The primary emergency department (ED) treatment of NO2 -induced respiratory illness is supportive therapy directed at correction of hypoxemia, ventilatory failure, and secondary infection. Endotracheal intubation and mechanical ventilation may be required, depending on the degree of respiratory distress and hypoxemia. High-dose corticosteroids are suggested in the treatment of pulmonary manifestations, but data on their prophylactic use after nitrogen dioxide (NO2) exposure is anecdotal.

Monitor continuous pulse oximetry. Pulse oximetry monitoring may be misleading in the presence of methemoglobinemia, however.

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Inpatient Care

Patients who have been exposed to nitrogen dioxide (NO2) should be admitted for at least 24 hours if they have any of the following:

  • Dyspnea
  • Altered mental status
  • Hypoxemia
  • A widened alveolar-arterial oxygen gradient

In patients who are critically ill, placement of a pulmonary artery catheter for monitoring of mixed venous oxygenation and pulmonary vascular resistance may assist in the management of oxygenation requirements, fluids, acute respiratory distress syndrome (ARDS), and physiologic variables.

Evidence of significant methemoglobinemia should prompt treatment with methylene blue (see Medication). Clinical improvement and resolution of hypoxemia and methemoglobinemia are helpful endpoints for discharge. Advise the patient to avoid exercise for 1-2 days after exposure.

In prolonged cases of toxicity with evidence of proliferative bronchiolitis obliterans, patients may be responsive to steroid therapy. Resolution of symptoms generally occurs slowly over a period of several months. There is little data to suggest that prophylactic steroids will prevent development of bronchiolitis obliterans. As mentioned above, constrictive bronchiolitis is not as responsive to steroid therapy.

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Deterrence/Prevention

Working environments should be evaluated for elevated nitrogen dioxide (NO2) levels and proper ventilation and protective gear, such as SCBA, should be used. American Conference of Governmental Industrial Hygienists threshold limit values (ACGIH-TLV) for NO2 are as follows:

  • Time weighted average (TWA): 3 ppm
  • Short-term exposure limit (STEL): 5 ppm

National Institute of Occupational Safety and Health (NIOSH) values are as follows:

  • Recommended exposure limit (REL): 1 ppm
  • STEL (immediately dangerous to life or health): 20 ppm

National Fire Protection Association (NFPA) hazard ratings are as follows:

  • Health (Blue) - 3
  • Flammability (Red) - 0
  • Reactivity (Yellow) - 0

Other workplace safety measures are as follows:

  • Labels required: Poison gas, oxidizer, corrosive
  • Respiratory equipment recommendations: Positive-pressure SCBA (according to North American Emergency Response Guide [NAERG] 124)
  • Protective clothing: Chemically protective clothing, as recommended by the manufacturer (according to NAERG 124)

Exposure to air pollution and nitrogen dioxide in particular is increasingly recognized as a significant factor in the development of asthma, COPD and pulmonary disease.[23] Some studies suggest the potential for antibiotics or anti-oxidants such as vitamin C or vitamin E to prevent or mitigate the progression of disease.[24, 25] This remains an area in need of ongoing research.

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Consultations

Consult a pulmonary medicine or critical care specialist if the patient requires endotracheal intubation or hemodynamic monitoring. Consult with a regional poison control center or a local medical toxicologist (certified through the American Board of Medical Toxicology and/or the American Board of Emergency Medicine) to obtain additional information and patient care recommendations.

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Long-Term Monitoring

When a patient who has been placed on corticosteroid therapy acutely is discharged, prescribe corticosteroid taper for at least 8 weeks. Most authors agree that patients with bronchiolitis obliterans should be maintained on corticosteroids until their symptoms have resolved. A longer duration of therapy (ie, 6-12 months) may be indicated if symptoms of bronchiolitis obliterans persist or recur after initial steroid taper.

Inhaled sympathomimetics (eg, albuterol), anticholinergics (eg, ipratropium bromide), and steroids (eg, fluticasone propionate) may also be indicated if the patient develops symptoms of reactive airway disease. A typical asthma disease management plan can be used for these patients.

Conduct follow-up examinations at 1 week, 1 month, and 3 months after exposure, with serial pulmonary function testing and radiographs.

Multiple studies have shown an increased association between bacterial pneumonia, increased mortality, and inhalational exposures.[26, 27, 28] At this time, however, the use of prophylactic antibiotics has not shown any long-term benefits in randomized controlled trials. Given the propensity for development of antibiotic resistance, long-term prophylactic antibiotics are not recommended.

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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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