Acute nitrite poisoning refers to an acute toxic condition characterized primarily by tissue hypoxia caused by the ingestion of nitrites or nitrite/nitrate-containing food, as well as drinking water contaminated with high nitrite concentrations (e.g., well water or steamed water). Nitrites have high toxicity; ingestion of 0.2–0.5 g by an adult can cause poisoning, with a lethal dose of 1–3 g. For children, ingestion of 0.1 g may result in acute poisoning or even death.
Nitrites are white powders or crystals with a similar appearance to table salt. They have a slightly bitter or mildly salty taste and are commonly found in the forms of sodium nitrite or potassium nitrite, both of which dissolve easily in water. Nitrites can bind with myoglobin in meat products, serving as preservatives, coloring agents, and color stabilizers, and are often used in the food processing industry for these purposes. Nitrites also inhibit the growth of Clostridium botulinum, enhancing the safety of edible meat products. As a permissible food additive in the production of meat products, nitrites pose a risk of poisoning if their use exceeds the maximum doses established by national health standards. Furthermore, nitrites can combine with amine compounds in food proteins to form nitrosamines and nitrosamides. Under acidic gastrointestinal conditions, these compounds are converted into nitrosamines, which have strong carcinogenic effects. Prolonged and excessive consumption of nitrite-containing foods carries the potential for long-term cancer risks. Moreover, nitrosamines can cross the placental barrier, posing teratogenic effects on fetuses.
Etiology
Poisoning often results from mistakenly ingesting nitrites, such as confusing them with table salt, sugar, or baking soda. Consumption of food containing excessive nitrites—due to overuse of nitrite as a food additive—is also a frequent cause. Certain fresh vegetables, including cabbage, celery, spinach, chives, lettuce, and radishes, naturally contain relatively high amounts of nitrates or nitrites. If these vegetables decay, spoil, or are inadequately pickled (the nitrite content increases between the second and fourth days of pickling, peaking within 1–2 weeks) or are left unrefrigerated for extended periods after cooking, nitrites can form through the action of nitrate-reducing bacteria. Excessive intake can then result in poisoning. Long-term consumption of well water contaminated with nitrites may also lead to poisoning.
Pathogenesis
Nitrites, as strong oxidizing agents, convert normal hemoglobin (Fe2+) into methemoglobin (Fe3+), which loses its oxygen-carrying and transport capacity. Methemoglobinemia is defined as methemoglobin levels exceeding 1% of total hemoglobin. When methemoglobin levels reach 10% of total hemoglobin, cyanosis of the skin and mucous membranes occurs, causing systemic tissue and organ hypoxia. Levels of 20%–30% lead to hypoxic symptoms such as headache, fatigue, and weakness. Levels of 50%–60% result in tachycardia, shallow rapid respiration, and mild dyspnea. Levels exceeding 60% cause delayed reactions, altered consciousness, respiratory and circulatory failure, and may lead to death. Brain cells are especially sensitive to hypoxia, making the central nervous system the first to be affected. Protective inhibition of the cerebral cortex occurs, manifesting as headache, dizziness, delayed responses, drowsiness, or even coma. Prolonged hypoxia can cause severe damage to the central nervous system, circulatory failure, and respiratory failure. Additionally, nitrites relax vascular smooth muscle, resulting in decreased blood pressure.
Clinical Manifestations
When foods rich in nitrates are consumed, extensive proliferation of nitrate-reducing bacteria (primarily Salmonella and Escherichia coli) in the gastrointestinal tract causes nitrates to be converted into nitrites through reductive pathways. If the body is unable to break down the resulting large amounts of nitrites into ammonia for excretion, the nitrites enter the bloodstream and cause poisoning, a condition referred to as enterogenous cyanosis. Children are particularly susceptible to this condition due to gastrointestinal dysfunction or weakened immunity, and cases are typically sporadic. Cyanosis of the skin and mucous membranes is the most prominent presentation, with the lips and extremities being most notably affected.
Mild cases present with symptoms such as headache, palpitations, nausea, vomiting, abdominal pain, and bloating. Severe cases exhibit cyanosis of the lips, ashen-blue skin tone, dyspnea, arrhythmia, hypotension, and signs of shock. Extremely severe cases involve complications such as seizures, heart failure, respiratory failure, pulmonary edema, cerebral edema, coma, and manifestations of multiple organ failure.
Laboratory Tests
Methemoglobin content is significantly elevated compared to normal levels. Qualitative testing for nitrites in urine yields positive results. Electrocardiograms may show sinus tachycardia. Increased levels of cardiac enzymes may indicate myocardial damage.
Diagnosis
Diagnosis involves a detailed medical history review and the integration of clinical symptoms with relevant laboratory findings. A high suspicion of nitrite poisoning arises in cases of cyanosis of the skin and mucous membranes that cannot be explained by underlying conditions or hypoxia. Diagnostic confirmation of methemoglobinemia can be performed using the following method: 5 mL of venous blood is agitated vigorously in air for 15 minutes. If the blood remains a deep brown color without turning bright red (as normal hemoglobin binds oxygen to form oxyhemoglobin), hypoxia due to respiratory or circulatory failure is ruled out, and methemoglobinemia is considered likely.
Additional evidence supporting the diagnosis includes positive results for toxicological analysis of residual food, vomitus, blood, or urine (particularly qualitative detection of nitrites), along with exclusion of urinary system infections.
Differential Diagnosis
In addition to differentiating nitrite poisoning from acute gastroenteritis, intestinal obstruction, coronary atherosclerotic heart disease, pulmonary embolism, and carbon monoxide (CO) poisoning, distinction needs to be made from the following conditions:
Propanil Poisoning
Propanil, an organic nitrogen-based agricultural insecticide, can cause methemoglobinemia when ingested. Propanil poisoning is often accompanied by other characteristic symptoms such as hemorrhagic cystitis (frequent urination, urgent urination, hematuria) and dilated pupils. The condition is typically severe, with a high case fatality rate. Patients often have a clear history of ingestion or exposure to propanil.
Sulfhemoglobinemia
Sulfhemoglobinemia is absent in normal individuals. When sulfhemoglobin levels exceed 4% or surpass 5 g/L, cyanosis may occur. Some individuals may develop sulfhemoglobinemia with concurrent hemolysis after ingesting drugs such as phenacetin or sulfonamides. Sulfhemoglobin, once formed, cannot revert to normal hemoglobin, either in vivo or in vitro. No effective treatment currently exists for this condition. If methylene blue therapy is ineffective, sulfhemoglobinemia should be considered.
Treatment
The treatment principles include high-flow oxygen inhalation, establishing intravenous access, gastric lavage, emesis induction, catharsis, administration of antidotes, sputum aspiration, volume expansion, symptomatic and supportive measures, maintaining warmth, and closely monitoring changes in vital signs.
Oxygen Inhalation
The oxygen flow rate should range from 4 to 6 L/min. Hyperbaric oxygen therapy may be necessary in severe cases. This approach is particularly useful for patients with severe hypoxia combined with complications such as acute pulmonary edema, cerebral edema, or coma. High-concentration oxygen enhances blood oxygen partial pressure, increases oxygen diffusion speed, improves blood flow to ischemic areas, and optimizes microcirculatory hemodynamics. Consequently, it alleviates organ hypoxia, reduces intracranial pressure, mitigates pulmonary and cerebral edema, disrupts the hypoxia-edema vicious cycle, and promotes the establishment of collateral circulation. Additionally, increased oxygen partial pressure expedites the displacement of nitrites from methemoglobin and restores the oxygen-carrying capacity of ferrous hemoglobin.
Use of Antidotes
Methylene blue is an effective antidote for nitrite poisoning. A dose of 1–2 mg/kg is diluted in 40 mL of 25% glucose solution and administered via slow intravenous injection. If symptoms persist after 30–60 minutes, a second dose may be given. Vitamin C, known for its strong reducing properties, can inhibit nitrite synthesis in the body and complements methylene blue as a first-line treatment for nitrite poisoning. Dosages of 1–5 g are added to 500 mL of 5% glucose solution and administered via continuous intravenous infusion. In mild cases, vitamin C can also be taken orally. Hypertonic glucose, by increasing plasma osmolality, boosts detoxification, provides energy, strengthens the efficacy of methylene blue, and induces temporary diuresis. For severe cases, 50 U of coenzyme A may be administered intramuscularly 1–2 times daily to enhance the reductive effects of methylene blue.
Methylene blue exhibits both oxidative and reductive properties depending on its concentration. At low concentrations (1–2 mg/kg), under the influence of reduced nicotinamide adenine dinucleotide phosphate (NADPH), methylene blue converts methemoglobin back to ferrous hemoglobin, restoring its oxygen-carrying capacity. At high concentrations (5–10 mg/kg), however, it paradoxically oxidizes ferrous hemoglobin into methemoglobin. During the first 10–20 minutes of methylene blue administration, SpO2 may transiently decrease, but it usually returns to normal within 1–2 hours. This might occur because the initial influx of methylene blue temporarily exceeds the available NADPH, increasing the proportion of oxidized methylene blue, which in turn oxidizes hemoglobin into methemoglobin. To mitigate this risk, small dosages of methylene blue should be administered slowly to avoid aggravating hypoxia.
Additionally, patients undergoing methylene blue treatment require close observation for changes in the color of the conjunctiva, skin, lips, extremities, and urine. If a bluish discoloration occurs, methylene blue should be immediately discontinued. Methylene blue is a blue, clear liquid and is fully metabolized and excreted through the kidneys over 3–5 days. Repeated high-dose administration may lead to cumulative toxicity, manifesting as serious adverse effects such as blue discoloration of skin and mucosa, urinary irritation, delirium, agitation, seizures, hemolysis, jaundice, and even shock. Methylene blue should be used cautiously in patients with hemolytic anemia or glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and must not be used in those with severe renal insufficiency. Furthermore, methylene blue is highly irritating to blood vessels, and extravasation during infusion should be avoided to prevent tissue necrosis.
Prevention
Awareness campaigns should be strengthened to increase public knowledge of nitrite-related risks. Efforts should focus on promoting healthier lifestyle habits while enhancing regulatory oversight of nitrite production and sales processes.