Nitrous Dioxide Toxicity Clinical Presentation

  • Author: Jeffrey S Peterson, MD; Chief Editor: Asim Tarabar, MD   more...
 
Updated: Mar 15, 2012
 

History

The diagnosis of nitrogen dioxide (NO2) toxicity largely depends on the history of exposure. Query patients on this history if possible.

Inquire about exposure and occupation. Welders, firefighters, military and aerospace personnel, individuals working with explosives, and farmers generally have higher risk of exposure than those in other occupations.

Try to establish duration of exposure. Short term and low-dose NO2 exposures have little, if any, adverse effects in humans.[6]

In acute exposure, symptoms may range from mild cough to mucous membrane irritation to sudden fatality. Suspect methemoglobinemia in patients exposed to NO2 who exhibit cyanosis or dyspnea. The initial absence of significant symptoms does not exclude a subsequent development of serious disease.

Following a delay of 2-48 hours, patients exposed to NO2 may develop the following symptoms:

  • Dyspnea
  • Cough
  • Chest pain
  • Clinical manifestations of noncardiogenic pulmonary edema

The following may develop 2-6 weeks after initial exposure:

  • Bronchiolitis obliterans, manifested as fever, cough, and dyspnea
  • Diffuse reticulonodular or miliary pattern on chest radiography
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Physical

Initial physical findings are sometimes mild but may progress over the following 72 hours to life-threatening respiratory distress.

Pulmonary symptoms are the most common manifestation of NO2 toxicity. These include the following:

  • Cough
  • Dyspnea
  • Chest tightness
  • Choking
  • Wheezing
  • Chest pain
  • Rales
  • Rhonchi
  • Decreased breath sounds
  • Stridor

Other acute symptoms include the following:

  • Light-headedness
  • Loss of consciousness
  • Restlessness
  • Agitation
  • Confusion
  • Irritation of mucous membranes, including the eyes
  • Conjunctival infection
  • Weakness
  • Fatigue
  • Nausea
  • Abdominal pain
  • Skin burns, in cases of liquid N2 O4 exposure

Delayed symptoms include the following:

  • Tachypnea
  • Headache
  • Fever, chills
  • Insomnia
  • Myalgias
  • Hemoptysis
  • Palpitations
  • Cyanosis
  • Coma
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Causes

  • Occupational risk factors for NO2 exposure are high among farmers, particularly those who work near silos, firefighters, arc welders, military personnel, and aerospace workers (missile fuel). Any occupation that involves the production, transportation, or use of nitric acid is at risk.
  • Other significant sources of risk include ice arenas with ice resurfacing (Zamboni) machines. Gas-fired and kerosene-fired household appliances and motor vehicle exhaust all pose significant risk of exposure.
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Contributor Information and Disclosures
Author

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.

Coauthor(s)

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.

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.

Specialty Editor Board

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.

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.

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

Disclosure: Nothing to disclose.

John D Halamka, MD, MS  Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center

John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Chief Editor

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.

References

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  5. van Strien RT, Gent JF, Belanger K, et al. Exposure to NO2 and nitrous acid and respiratory symptoms in the first year of life. Epidemiology. Jul 2004;15(4):471-8. [Medline].

  6. Hesterberg TW, Bunn WB, McClellan RO, et al. Critical review of the human data on short-term nitrogen dioxide (NO2) exposures: evidence for NO2 no-effect levels. Crit Rev Toxicol. 2009;39(9):743-81. [Medline].

  7. US Food and Drug Administration. FDA Drug Safety Communication: Serious CNS reactions possible when methylene blue is given to patients taking certain psychiatric medications. Available at http://www.fda.gov/Drugs/DrugSafety/ucm263190.htm. Accessed July 27, 2011.

  8. Becker S, Soukup JM. Effect of nitrogen dioxide on respiratory viral infection in airway epithelial cells. Envir Res. 1999;81(2):159-66. [Medline].

  9. Douglas WW, Hepper NG, Colby TV. Silo-filler's disease. Mayo Clin Proc. Mar 1989;64(3):291-304. [Medline].

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  17. Prutz WA, Monig H, Butler J, Land EJ. Reactions of nitrogen dioxide in aqueous model systems: oxidation of tyrosine units in peptides and proteins. Arch Biochem Biophys. Nov 15 1985;243(1):125-34. [Medline].

  18. Sagai M, Ichinose T. Lipid peroxidation and antioxidative protection mechanism in rat lungs upon acute and chronic exposure to nitrogen dioxide. Environ Health Perspect. Aug 1987;73:179-89. [Medline].

  19. van Bree L, Rietjens I, Alink GM, et al. Biochemical and morphological changes in lung tissue and isolated lung cells of rats induced by short-term nitrogen dioxide exposure. Hum Exp Toxicol. Jul 2000;19(7):392-401. [Medline].

  20. Veeramachaneni NK, Harken AH, Cairns CB. Clinical implications of hemoglobin as a nitric oxide carrier. Arch Surg. Apr 1999;134(4):434-7. [Medline].

  21. Weller BL, Witschi H, Pinkerton KE. Quantitation and localization of pulmonary manganese superoxide dismutase and tumor necrosis factor alpha following exposure to ozone and nitrogen dioxide. Toxicol Sci. Apr 2000;54(2):452-61. [Medline].

  22. World Health Organization. Nitrogen oxides. In: Recommended Health-Based Occupation Exposure Limits for Respiratory Irritants. 1984:73-114.

 
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Bronchiolitis obliterans following exposure to nitrogen dioxide. (Radiograph courtesy of Dr Ann Leung, Stanford University Hospital, Department of Radiology, Palo Alto, CA)
Noncardiogenic pulmonary edema following exposure to nitrogen dioxide. (Radiograph courtesy of Dr Ann Leung, Stanford University Hospital, Department of Radiology, Palo Alto, CA)
 
 
 
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