Nitrogen Dioxide Toxicity: Health Hazards and Mitigation Approaches

Introduction:

When nitric oxide reacts with oxygen, it forms nitrogen dioxide. Nitric oxides and nitrogen dioxides are forms of nitrogen oxide gasses released from various processes such as, the reaction of nitric acid with organic materials, as a byproduct of burning nitrocellulose, during the breakdown of rocket fuel, during electroplating, engraving, and electric welding and a byproduct of the combustion of fuels.

Nitrogen dioxide gasses can also form from non-combustion sources. Sometimes, the farm silos are filled with fresh organic material, which leads to the fermentation of crops resulting in the production of nitrogen dioxide gasses.

What Are the Signs and Symptoms of Nitrogen Dioxide Toxicity?

The common signs and symptoms of nitrogen dioxide toxicity include:

• Light-headedness.

• Cough.

• Wheezing.

• Irritation in eyes, nose, or throat.

• Choking.

• Chest pain.

• Diaphoresis (sweating).

• Dyspnea (shortness of breath).

• Chest tightness.

Severe symptoms of nitrogen dioxide toxicity may indicate a severe worsening of the disease, and these include:

• Rapid heart rate.

• Severe shortness of breath.

• Discoloration of lips, fingers, or toes.

• Rapid breathing rate.

• Fever.

• Frequent use of inhalers.

What Are the Various Investigations of Nitrogen Dioxide Toxicity?

There are no specific laboratory studies for diagnosing nitrogen dioxide toxicity. However, specific blood tests are recommended based on the history, which is helpful in easy diagnosis, excluding other causes of illness. The subsequent investigations help to evaluate the severity of the disease. These include:

• Lactate level.

• Arterial blood gas (ABG) or venous blood gas levels (VBG).

• Methemoglobin (MHb) level.

Specific tests are taken to rule out the underlying causes, and these include:

• Gram stain and sputum culture.

• Urine Legionella.

• Respiratory virus polymerase chain reaction (PCR) panel.

• Histoplasma enzyme immunoassay.

• Cryptococcal antigen.

• Coccidioides immunoglobulin M and immunoglobulin G.

• Complete blood count (CBC) and glucose levels are monitored.

• Chest Radiography:

• The chest radiography findings may or may not be normal.

• In the case of acute injury, the radiographic findings reveal ill-defined alveolar opacities, which are also typical findings of pulmonary edema or acute respiratory distress syndrome (ARDS).

• In the case of subacute injury, the findings reveal patchy, bilateral confluent wooly air-opacities. The small opacities are misdiagnosed as miliary tuberculosis.

• Computed Tomography (CT) Scan: The presentations from this test may represent patchy subpleural ground-glass opacities and diffuse hyper-lucency.

• Pulmonary Function Testing: The pulmonary function test performed early helps determine the disease's extent. If delayed, bronchiolitis obliterans develops, presenting prolonged forced expiratory volume at one second. Therefore, these tests are performed at intervals to monitor the progress and the recovery rate.

What Are the Treatment Approaches for Nitrogen Dioxide Toxicity?

• If there are no associated symptoms, the patient is observed for 12 hours of hypoxemia.

• In the case of gas exchange abnormalities, the patient should be hospitalized for about 12 to 24 hours or longer.

• The symptoms of noncardiogenic pulmonary edema may develop in 48 hours.

• The patient should be educated about the symptoms, and instructions should be given to return if symptoms develop.

• Oxygen therapy is administered immediately in the case of hypoxemia.

• In the case of severe gas exchange abnormalities, intubation, and mechanical ventilation are essential.

• Volume expanders are administered carefully. Because excessive administration of volume expanders can cause hydrostatic pulmonary edema.

• The primary goal of treating nitrogen dioxide-induced respiratory illness is supportive therapy for ventilatory failure, hypoxemia, and secondary infection.

• Depending on hypoxia and respiratory distress syndrome, endotracheal intubation and mechanical ventilation may be required.

• High doses of corticosteroids are suggested to treat pulmonary manifestations, but anecdotal data on their prophylactic use after exposure to nitrogen dioxide (NO2). Monitor continuous pulse oximetry.

• Pulse oximetry results may be misleading in the presence of methemoglobinemia.

• Patients who are exposed to nitrogen dioxide should be admitted for at least 24 hours if they have dyspnea, altered mental status, hypoxemia, or widened alveolar-arterial oxygen gradient.

• If patients are critically ill, placing a pulmonary artery catheter for monitoring mixed venous oxygenation levels and pulmonary vascular resistance may assist in managing oxygenation requirements, fluids, and acute respiratory distress syndrome (ARDS).

• In the cases of proliferative bronchiolitis obliterans, the patient may respond to steroid therapy.

• But the resolution of symptoms generally occurs, and recovery takes several months.

• Few reports suggest that steroids can prevent the development of obstructive bronchiolitis obliterans. However, constrictive bronchiolitis does not respond to steroid therapy.

• Exposure to nitrogen dioxide is considered a significant factor in developing chronic obstructive pulmonary disease, asthma, and pulmonary disease.

• The potential for antibiotics or anti-oxidants, namely vitamin E or vitamin C, prevents disease progression.

• When a patient is on corticosteroid therapy and is discharged, the corticosteroid should be gradually tapered in due course within a period of eight weeks.

• The bronchiolitis obliterans should be maintained on corticosteroids until their symptoms have resolved.

• Inhaled sympathomimetics and anticholinergics (Fluticasone propionate) are indicated if they develop airway disease symptoms.

• A typical asthma management procedure with bronchodilators is recommended.

• Review follow-up examination at one week, one month, and three months after exposure with serial pulmonary function testing and radiographs.

Drug Therapy:

• Methylene blue is indicated in the case of methemoglobinemia.

• It can cause severe central nervous system reactions in patients with serotonergic psychiatric medications, including antidepressants and antipsychotic agents.

• Other treatments include antibiotics if the infection is present. In addition, vasopressor drugs are used to correct normovolemic shock.

• Larger doses of corticosteroids are prescribed for the treatment of pulmonary manifestations. In addition, it also prevents the development of bronchiolitis obliterans.

Corticosteroids:

• The corticosteroids are effective in reducing inflammatory responses. It is effective in treating the pulmonary manifestations of bronchiolitis obliterans. Methylprednisolone acts by decreasing inflammation, in which the migration of leukocytes is suppressed and reverses increased capillary permeability.

• The dose of corticosteroids is reduced over eight weeks based on the clinical symptoms and radiographic findings.

Conclusion:

Nitrogen dioxide toxicity is one of the common occupational exposures which may result in life-threatening complications. Therefore, an interprofessional approach team is required to manage the patient's condition effectively. Early diagnosis and timely management can help in positive outcomes for the patient. In addition, avoidance of further exposure before the treatment procedure can help in faster recovery.