Paraquat (PQ), also known as gramoxone, is a heterocyclic bipyridyl compound that functions as a highly effective, non-selective contact herbicide widely used worldwide. PQ acts rapidly after spraying and becomes inactive upon contact with soil. It exhibits strong toxicity to humans and animals. Acute paraquat poisoning refers to a condition primarily caused by PQ ingestion, characterized by progressive diffuse pulmonary fibrosis, leading to death from respiratory failure and/or multiple organ dysfunction syndrome (MODS). The mortality rate is as high as 90%–100%. PQ exists in the form of dichloride and dimethyl sulfate salts. Pure PQ appears as white crystals, is highly soluble in water, and remains stable in acidic or neutral solutions.
Etiology and Pathogenesis
Poisoning commonly occurs through intentional ingestion (suicide) or accidental ingestion. For adults, the lethal oral dose is 2–6 g. Poisoning can also occur through dermal absorption, inhalation, or intravenous injection. PQ ingestion results in corrosive damage to the contact site and rapid absorption into systemic tissues and organs, with peak blood concentrations achieved within 0.5–4 hours. PQ exhibits minimal binding to plasma proteins. The highest concentrations are found in lung tissues (10–100 times higher than in blood) and skeletal muscles. PQ undergoes limited metabolism in the human body and is eliminated primarily in its unchanged form: 50%–70% is excreted via the kidneys within 24 hours, approximately 30% through feces, and some traces via breast milk. Experiments show that 80%–90% of intravenously administered PQ is excreted within six hours through the kidneys, and nearly all is eliminated within 24 hours. PQ can also cross the blood-brain barrier and cause brain damage.
The mechanism of PQ poisoning remains incompletely understood. It is believed to involve redox reactions within cells, generating a large number of oxygen free radicals and peroxides. This leads to lipid peroxidation of cell membranes, resulting in MODS or death. Peroxide damage to type I and II alveolar epithelial cells reduces surfactant production. Due to the lungs' active uptake and accumulation of PQ, pulmonary damage is severe. Within 4–15 days after ingestion, irreversible pulmonary fibrosis and respiratory failure gradually develop, ultimately causing death from refractory hypoxemia. This condition is also referred to as “paraquat lung.”
Pathology
The primary pathological changes in paraquat lung include proliferative bronchiolitis and alveolitis. In individuals who die within one week, lung alveolar cells exhibit congestion, swelling, degeneration, and necrosis, along with alveolar septal rupture and fusion, pulmonary edema, hyaline membrane formation, and increased lung weight. For those who die beyond one week, there is interstitial cell proliferation, thickening of the pulmonary interstitium, and pulmonary fibrosis. Pulmonary fibrosis typically begins 5–9 days after poisoning and peaks within 2–3 weeks. Other pathological findings may include necrosis of renal tubules, centrilobular hepatic cells, myocardial inflammation, and adrenal cortex necrosis.
Clinical Manifestations
The clinical manifestations depend on the route, dose, and speed of toxin exposure, as well as the individual’s baseline health condition.
Local Damage
Delayed skin reactions may develop at contact sites, including redness, blisters, erosion, ulcers, and necrosis. In cases of oral intake, burns and ulcers of the oral cavity and esophageal mucosa may occur. Eye contamination with PQ can lead to burns of the conjunctiva or cornea. Inhalation exposure may result in epistaxis.
Systemic Damage
Respiratory System
The lungs are the primary target organ of PQ damage following ingestion. Gradual onset of symptoms, such as coughing and rapid breathing, may occur within 2–4 days, potentially due to metabolic acidosis, aspiration, or acute alveolitis. Pulmonary edema may also develop, and some cases may involve pneumomediastinum and pneumothorax. Most patients with lung injury die from respiratory failure caused by diffuse pulmonary fibrosis within 2–3 weeks. Those who ingest extremely high doses may develop pulmonary edema and hemorrhage within 24 hours and succumb to acute respiratory distress syndrome (ARDS) within days. Patients presenting with cyanosis and coma soon after poisoning often experience rapid fatality.
Digestive System
After PQ ingestion, symptoms such as retrosternal burning pain, nausea, vomiting, abdominal pain, diarrhea, gastrointestinal perforation, and bleeding occur. Hepatic injury and necrosis may develop within 1–3 days.
Other Systems
Cardiovascular manifestations may include palpitations, chest tightness, dyspnea, and toxic myocarditis. Neurological symptoms, such as dizziness, headache, seizures, or coma, have been documented. Renal damage typically develops within 24 hours of PQ absorption, presenting as hematuria, proteinuria, or acute renal failure. Additional findings may include hemolytic anemia, disseminated intravascular coagulation (DIC), and shock. Patients with MODS often die within days.
Clinical Classification
Clinical classification is typically based on the amount of paraquat (PQ) ingested:
- Mild Type: Ingestion of less than 20 mg/kg primarily results in gastrointestinal symptoms, with other symptoms being insignificant. Most patients fully recover.
- Moderate to Severe Type: Ingestion of 20–40 mg/kg may cause gastrointestinal symptoms along with manifestations of multi-system involvement. Within 1–4 days, renal and liver damage may appear, while pulmonary injury often develops within several days to 2 weeks. Death from respiratory failure typically occurs within 2–3 weeks.
- Fulminant Type: Ingestion of more than 40 mg/kg results in severe gastrointestinal symptoms, followed by death within 1–4 days from multi-organ failure (MOF).
Laboratory Tests
Toxin Detection
Testing for paraquat in the patient’s gastric fluid or blood samples assists in confirming the diagnosis. A blood paraquat concentration of ≥30 mg/L indicates a poor prognosis. Paraquat can also be detected in urine within six hours after ingestion.
Imaging Studies
Pulmonary X-ray or CT scans aid in diagnosis. Early findings include scattered fine spotted opacities in the lower lung fields, which can rapidly progress to pulmonary edema-like changes.
Diagnosis
Diagnosis is primarily based on the patient’s history of toxin exposure, prominent pulmonary symptoms, and positive toxicological testing for paraquat.
Treatment
There is currently no specific antidote available for paraquat poisoning.
Resuscitation
Maintaining Airway Patency
Continuous monitoring of blood oxygen saturation or arterial blood gas levels is necessary. Routine oxygen supplementation is not recommended for patients with mild to moderate hypoxemia, as it may accelerate the production of oxygen free radicals, exacerbate paraquat toxicity, and increase mortality. In cases of arterial oxygen partial pressure (PaO2) <40 mmHg or the development of ARDS, oxygen inhalation (with an oxygen concentration >21%) can be used to maintain PaO2 ≥70 mmHg. The outcomes of mechanical ventilation are generally suboptimal for patients with severe respiratory failure.
Managing Hypotension
Hypotension is often caused by insufficient blood volume and requires rapid intravenous fluid infusion to restore effective circulatory volume.
Organ Function Support
For upper gastrointestinal bleeding, proton pump inhibitors such as omeprazole, lansoprazole, or pantoprazole may be administered. In cases of symptomatic acute renal failure, hemodialysis may be considered.
Reducing Toxin Absorption
Decontamination of Toxic Exposure
Immediate removal of paraquat-contaminated clothing and washing of affected skin with soap and water are necessary. For oral ingestion, mouth rinsing with compound borax solution or chlorhexidine mouthwash is used. For eye contamination, washing with a 2%–4% sodium bicarbonate solution for 15 minutes followed by rinsing with physiological saline is performed.
Inducing Vomiting, Gastric Lavage, and Absorption
For oral poisoning, prompt throat stimulation to induce vomiting is necessary. Gastric lavage is performed using warm clear water or alkaline solutions (e.g., soapy water), less than 300 ml per flush under low pressure, repeatedly until the gastric washout is colorless and odorless. Gastric lavage is most beneficial within one hour of poisoning, but for cases with delayed gastric emptying or large ingested doses, it can still be performed beyond six hours. After gastric lavage, gastric motility agents like domperidone or mosapride can be administered to promote toxin excretion.
Absorption and Laxation
Following gastric lavage, timely oral administration of absorbents and laxatives is crucial. Common absorbents include 15% kaolin solution (1,000 ml for adults, 15 ml/kg for children) or activated charcoal (100 g for adults, 2 g/kg for children). Alternatively, montmorillonite powder (6 g mixed with 50 ml water) can be orally given every 2–3 hours. Sequentially, 20% mannitol (100–250 ml) is administered 30–60 minutes after montmorillonite use as a laxative, with repeated administration as needed. Other laxatives include magnesium sulfate, sodium sulfate, senna leaves (10–15 g soaked in 200 ml of boiled water, cooled before consumption), and rhubarb extract.
Enhancing Toxin Elimination
Forced Diuresis
After adequate intravenous fluid resuscitation, furosemide can be administered to maintain a urine output of at least 200 ml/hour.
Blood Purification
Early initiation of blood purification, preferably within 2–4 hours, is recommended. Hemoperfusion is prioritized, as its paraquat clearance is 5–7 times higher than that of hemodialysis.
Other Treatments
Immunosuppressive Drugs
High-dose intravenous methylprednisolone, dexamethasone, and/or cyclophosphamide are used in the early stages.
Antioxidants
Agents such as high-dose vitamin C or vitamin E, superoxide dismutase (SOD), acetylcysteine, reduced glutathione, ulinastatin, or edaravone may be administered. High-dose ambroxol is also effective in directly scavenging free radicals, mitigating acute lung injury caused by paraquat, and promoting the production of alveolar surfactants.
Anti-Fibrotic Drugs
Pirfenidone inhibits fibroblast activity and collagen synthesis, helping to prevent or reverse fibrosis and scar formation.
Paraquat Competitors
Propranolol (10–20 mg orally, three times daily) facilitates the release of paraquat bound to lung tissue. Low-dose levodopa competitively inhibits the transport of paraquat across the blood-brain barrier.
Prevention
Prevention is considered more effective than treatment. The use of paraquat should be centrally managed, with private storage strictly prohibited. Mixing paraquat into other herbicides is not allowed. Containers used for paraquat solutions should carry clear warning labels to prevent accidental ingestion. Safety education should be provided prior to use. When applying paraquat, wearing long-sleeved clothing, long pants, and protective goggles is advised. Avoid skin exposure and spraying against the wind.