Paraquat Poisoning

What Is Paraquat?

Epidemiology and Route of Exposure

• Ingestion is responsible for the vast majority of deaths, including both accidental and intentional (suicidal) ingestions.
• Skin absorption is minimal across intact skin; systemic toxicity via skin requires large surface area soaking or breached skin integrity.
• Inhalation of sprays causes upper respiratory irritation but is unlikely to produce systemic toxicity under usual conditions.
• Overall mortality from ingestion is 50-90%.

Pharmacokinetics

• Peak tissue distribution occurs in the 2-6 hours post-ingestion window.
• Highest concentrations accumulate in the kidneys and lungs.

Mechanism of Toxicity

• Severely corrosive to mucosal membranes, causing corrosion, ulceration, and potential esophageal perforation.

• Paraquat catalyzes formation of superoxide radicals (O2-) via redox cycling, sustained by the abundant electron supply and oxygen in the lungs.
• Superoxide radicals drive lipid peroxidation, causing degradation of cell membranes, cell dysfunction, and necrosis.
• Paraquat and oxygen enhance each other's toxicity (the reason supplemental O2 worsens outcome).
• Alveolar cells actively accumulate paraquat via an energy-dependent polyamine transporter, concentrating the toxin in lung tissue.

• Early destructive phase: Loss of type I and II alveolar epithelial cells, inflammatory cell infiltration, hemorrhage - potentially reversible.
• Later proliferative phase: Interstitial and alveolar fibrosis - irreversible.

Clinical Presentation

Tintinalli's Severity Classification

Timeline of Features

• Burning sensation of mouth and lips (within minutes to hours)
• Oral and oropharyngeal ulceration (1-2 days later)
• Nausea, vomiting, diarrhea, abdominal pain
• Buccopharyngeal and esophageal pain
• Hypovolemia from GI fluid losses

• Acute kidney injury (acute tubular necrosis) - may resolve if patient survives
• Hepatocellular necrosis
• Hypertension, then shock

• Progressive pulmonary fibrosis - the defining and lethal feature
• Refractory hypoxemia, restrictive ventilatory defect
• Decreased lung compliance and diffusing capacity
• Death from ventilatory failure

Diagnosis

Clinical Suspicion

• History of herbicide exposure (occupational or suicidal intent)
• Characteristic mucosal burns followed by multi-organ failure and delayed respiratory failure

Urine Dithionite Test (Qualitative - Rapid & Inexpensive)

• Add sodium dithionite to urine
• Blue color change = confirms paraquat in urine (more intense blue = higher exposure)
• A negative test at 12 hours makes significant toxicity unlikely

Serum Paraquat Level

• Quantitative serum paraquat concentration predicts mortality risk
• Validated nomograms correlate plasma levels with clinical outcome
• Unfortunately, few laboratories can perform quantitative paraquat assays

Prognostic Laboratory Markers

Radiologic Findings

• Diffuse pulmonary infiltrates (ARDS pattern)
• Progressive interstitial fibrosis on CT/CXR

Treatment

General Principles (Harrison's Poisoning Chapter)

1. Stabilize the patient (airway, breathing, circulation)
2. Volume resuscitation
3. Identify and treat complications

Specific Management

• Activated charcoal (1-2 g/kg) - preferred when available
• Fuller's earth (diatomaceous earth; 1-2 g/kg in 15% aqueous suspension)
• Bentonite (1-2 g/kg in 7% aqueous slurry)
• These agents bind paraquat and reduce absorption
• Note: Many commercial formulations already contain a pro-emetic and some contain alginate to reduce absorption

• Oxygen dramatically worsens paraquat toxicity by sustaining the redox cycle
• Restrict oxygen unless required for hypoxemia (SpO2 <90% or clinically necessary)
• If required for true hypoxemia, use the minimum amount necessary
• Patients requiring supplemental O2 have a very poor prognosis

• Because paraquat is a small molecule (~186 Da), minimally protein-bound (~5%), with Vd ~1 L/kg - it is removable by extracorporeal therapies
• Hemoperfusion (HP): Preferred; should be started as soon as possible, ideally within 4 hours of ingestion - limited evidence suggests possible survival benefit
• Intermittent hemodialysis (IHD): Can be used if hemoperfusion unavailable
• Continuous venovenous hemodialysis: Slower paraquat removal - not first-line, but useful for managing coexistent AKI
• Peritoneal dialysis: Of no benefit
• Key limitation: Paraquat rapidly distributes to lung tissue; once free-radical generation is established, elimination is unlikely to halt progression
• Rebound commonly occurs after ECTR

• Dexamethasone 8 mg IV every 8 hours for the first 72 hours - may be beneficial, relatively low toxicity; can be continued for weeks in severe poisoning
• Cyclophosphamide + corticosteroids (pulse doses): Small studies suggested benefit, but a large RCT showed no benefit
• High-dose corticosteroids are still recommended despite limited evidence

• N-acetylcysteine: May provide benefit; administer continuously while evidence of acute toxicity persists (low toxicity, reasonable to use)
• Vitamins C and E, superoxide dismutase, deferoxamine, selenium - none has proven to alter clinical outcome significantly
• Forced diuresis does not increase renal clearance of paraquat

• There is no known antidote for paraquat poisoning

• Serial monitoring: pulmonary function tests, chest radiographs, renal function, blood gases
• Integrate palliative care early given the dismal prognosis of severe cases

Disposition

• All patients: Observe for at least 12 hours
• Clinically well patients with a negative urine dithionite test at 12 hours: Unlikely to develop significant toxicity
• Clinical toxicity with unclear prognosis: Admit to critical care
• Evidence of severe toxicity with fatal prognostic markers: Supportive and palliative care

Key Differentiating Features vs. Diquat

Summary Points (Harrison's Framework)

1. Mechanism: Superoxide radical generation via redox cycling, sustained by lung O2 supply - leading to irreversible pulmonary fibrosis
2. Lung is the ultimate target organ in those surviving the first 24-48 hours
3. Oxygen worsens outcome - restrict aggressively
4. Decontamination is time-critical - within 1-2 hours
5. Early hemoperfusion (within 4 hours) is the best available elimination strategy
6. No antidote exists; treatment is supportive
7. Mortality is 50-90% with ingestion; prognosis is largely determined by the dose ingested

• Harrison's Principles of Internal Medicine 22E (2025) - Poisoning and Drug Overdose chapter (Chapter 470), pp. 3747-3749
• Tintinalli's Emergency Medicine - Bipyridyl Herbicides, Chapter 201
• Brenner and Rector's The Kidney - Paraquat section, p. 2869
• Murray & Nadel's Textbook of Respiratory Medicine - Paraquat, Chapter 24