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 or longer for observation 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 symptoms develop.
Administer oxygen 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. [29]
Transferring the patient to a tertiary care center for further diagnostic evaluation and ventilatory support may be necessary.
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 are anecdotal.
Monitor continuous pulse oximetry. Pulse oximetry results may be misleading in the presence of methemoglobinemia, however.
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. Few data suggest that prophylactic steroids will prevent development of bronchiolitis obliterans. As mentioned above, constrictive bronchiolitis is not as responsive to steroid therapy.
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. [30] 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. [31, 32] This remains an area in need of ongoing research.
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.
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. [33, 34, 35] 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.
-
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 Air Quality Analysis Group, US Environmental Protection Agency (EPA).
