Nitrous Oxide Toxicity - Cause, Symptoms, and Treatment

Introduction:

Nitric oxide is produced by every cell in the body. It relaxes the inner blood vessel, promoting blood flow and lowering blood pressure. The gas slows down the body’s reaction time and results in euphoria. Nitric oxide in the body relaxes the blood vessels and stimulates the release of growth hormones and insulin. Nitric oxide supplements include L-citrulline and L-arginine. Nitric oxide reduces blood vessel wall stiffness, enhances muscle oxygen delivery, and reduces soreness after a workout. It enhances the tolerance to exercise. It reduces high blood pressure by relaxing the blood vessel wall (arterial dilation). It is a vasodilating agent. It is an important signaling molecule in animals and humans, transmitting signals to the nervous, cardiovascular, and immune systems. It is colorless toxic gas formed by the oxidation of nitrogen. The nitric oxide molecule possesses a free radical, making it more reactive than other signaling molecules. The body produces nitric oxide from the amino acid L-arginine through nitric oxide synthase. The nitric oxide from the blood vessel wall diffuses into the muscle and relaxes them. It is a potent regulator of blood pressure as it relaxes the smooth muscles of blood vessels.

Why Is Nitrous Oxide Toxic?

The main route of exposure is inhalation. The exposure causes systemic effects. Nitrogen oxides irritate mucous membranes, skin, and eyes. In addition, nitrogen oxides such as N2O3, N2O, and NO irritate the lungs at lower concentrations. It causes eye irritation and inflammation. If ingested, it leads to gastrointestinal burns or irritation. The gas is used as anesthesia for pain relief. It gives a calm and euphoric feeling and it works fast as a sedative. The potential side effects of nitrous oxide are wheezing, chills, fever, and breathlessness.

What Is the Pathophysiology of Nitrogen Dioxide?

The pathophysiology involves:

• The nitrogen dioxide is converted into nitric and nitrous acids in the distal airways.

• Initiates free radical generation that results in lipid peroxidation and cell membrane damage.

• Decreases the immunity of the body to fight against infections.

• The primary site of toxic effects happens in the lower respiratory tract. It causes burns, tissue swelling, spasms, and upper airway obstruction at very high concentrations.

• Exposure to high levels of nitrous oxide causes megaloblastic bone marrow depression. It interacts with vitamin B12 resulting in the inhibition of methionine synthase. Methionine synthase is a key enzyme in folate and methionine metabolism.

• Nitric oxide causes the formation of methemoglobin by oxidizing heme iron into a ferric state.

• It oxidizes hemoglobin into methemoglobin which reduces the oxygen supply to the tissues.

• Inhalation of this gas causes breathlessness and cough.

What Is the Mechanism of Nitrous Oxide Toxicity?

The mechanism of nitrous oxide toxicity is:

• Inhaling nitric oxide can cause targeted pulmonary vasodilation (relaxation of the blood vessels of the lungs), which is essential in treating acute respiratory distress and lung disease patients. It plays a vital role in the regulation of physiological processes. The nitric oxide causes increased cellular cyclic GMP (cyclic guanosine monophosphate). The increased cGMP disturbs normal cellular proliferation. It breaks the mutagenic DNA strand.

• Nitric oxide reacts with oxygen in the lungs to form nitrogen dioxide. Nitrogen dioxide is a potential irritant to the lungs. Nitric oxide has been shown to cause breaks in the DNA strands and mutagenic alterations. It is also misused for recreational purposes.

• Nitrogen oxides are irritant gases with lower water solubility, and high water-soluble gases generally deposit in the upper airways causing relatively quick onset upper airway and mucous membrane irritation. After receiving a larger cumulative inhaled nitrogen dioxide dose, the gas travels deeper into the respiratory tract.

• Nitrogen dioxide and other oxides of nitrogen damage the lung tissue by generating reactive nitrogen-derived free radicals.

• Further, the oxides of nitrogen that come into contact with water damage the lung. Since nitrogen dioxide is low water-soluble gas, it can penetrate the alveoli and bronchioles of the lung. It causes direct injury to the alveolar cells of the lungs by generating free radicals that ultimately lead to diffuse alveolar damage.

• At 25 to 100 ppm nitrogen levels, there is an increased risk of pulmonary edema (too much fluid in the lungs), bronchiolitis (inflammatory bronchial reaction), and toxic pneumonitis (inflammation of the lung).

Who Are at Risk for Nitrous Oxide Toxicity?

The risk factors include:

• People with cobalamin deficiency (vitamin B12).

• History of substance use disorders.

• People that have methylenetetrahydrofolate reductase deficiency.

How Does Nitric Oxide Cause Pollution?

It is an important component of air pollution. Nitric oxide is generated from automobile engines; a mixture of air and hydrocarbon fuel is burned in an internal combustion engine that inserts nitrogen in the air and, at high temperatures, combines with oxygen to form nitric oxide. High levels of nitric oxide in the atmosphere due to industrial activities are one of the reasons for ozone layer depletion. The inhaled nitric oxide in the lungs reacts with oxygen to form nitrogen dioxide. Since nitric oxide is an unstable molecule in the air, it undergoes oxidation to form nitrogen dioxide. Nitrogen dioxide is directly toxic to the respiratory tract. Patients who are exposed to nitrogen dioxide are at risk of respiratory illness. The gas has significant potential to cause mortality and morbidity.

What Are the Signs and Symptoms of Nitrogen Dioxide Toxicity?

The early symptoms after exposure to nitrogen dioxide include sore throat, nausea, and cough. Chemical pneumonitis develops one day after exposure that manifests as pulmonary edema. Patients continuously exposed to nitrogen dioxide are at risk for acute heart failure, acute respiratory distress, and sepsis. The initial presentation of nitrogen dioxide toxicity is wheezing, cough, chest pain in the center, sweating, fever, and weakness. At later stages, the patient develops bronchiolitis obliterans; the patient may experience wheezing, cough, and chest pain.

How the Nitric Oxide Toxicity Managed?

The patients should be monitored regularly for vital signs and mental status. The respiratory status is monitored by continuously monitoring the oxygen saturation. The arterial blood gas testing is done to determine whether the patient is hypoxemic or has a low partial pressure of oxygen. Pulmonary function tests are done to check for a restrictive lung pattern, such as bronchiolitis obliterans.

What Is the Treatment for Nitrogen Oxide Toxicity?

The individuals exposed to nitrogen oxide have progressive lung inflammation several hours or days after exposure. It also leads to methemoglobinemia depending on the gas mixture's nitric oxide concentration. Patients with bronchospasm are given bronchodilators. Advanced life support protocols are carried out for patients with seizures and cardiac arrhythmias. If there is shock, then fluid should be administered. For adults, 1000mL per hour intravenous saline or lactated Ringers solution is given if the blood pressure is very high.

Conclusion:

Though nitric oxide is a safe sedation method, side effects can occur afterward. Most of the side effects are reversible and don't cause much damage. But if misused, nitric oxide can be dangerous.