Paraquat poisoning
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Paraquat Poisoning
Overview
Paraquat (1,1'-dimethyl-4,4'-bipyridinium) is a widely used contact herbicide notorious for causing severe, often fatal, multi-organ toxicity. It is one of the most lethal agricultural poisons — ingestion of as little as 10–20 mL of the 20% concentrate can be fatal. It remains a major cause of intentional self-poisoning in Asia (Sri Lanka, South Korea, Taiwan, Japan).
Pathophysiology
Paraquat undergoes redox cycling within cells:
- Paraquat (PQ²⁺) accepts an electron from NADPH via intracellular reductases → forms the paraquat radical (PQ•⁺)
- PQ•⁺ rapidly donates its electron to molecular O₂ → generates superoxide (O₂•⁻) and regenerates PQ²⁺
- O₂•⁻ → H₂O₂ → via Fenton reaction → hydroxyl radical (•OH)
- Massive oxidative stress → lipid peroxidation, DNA damage, cell death
Why the lung is the primary target:
- Type I and II pneumocytes actively concentrate paraquat via the polyamine transport system (putrescine/spermine uptake pathway)
- High O₂ tension in the lung amplifies radical generation
Pathological progression:
| Phase | Timing | Features |
|---|---|---|
| Destructive | Days 1–3 | Alveolar epithelial destruction, hemorrhage |
| Proliferative | Days 5–14 | Fibroblast proliferation |
| Fibrotic | Days 10–21+ | Irreversible pulmonary fibrosis, obliteration of alveolar spaces |
Clinical Presentation
Depends on Dose Ingested
| Severity | Dose (20% concentrate) | Features |
|---|---|---|
| Mild | < 20 mg/kg | GI symptoms, full recovery possible |
| Moderate–severe | 20–40 mg/kg | Pulmonary fibrosis, death in days–weeks |
| Fulminant | > 40 mg/kg | Multi-organ failure, death within 1–4 days |
Systemic Features by Organ
- Oropharynx/GI: Burning pain in mouth, throat, esophagus; ulceration; vomiting; diarrhea; dysphagia — begins within hours
- Lungs: Initially may appear well; progressive dyspnea, hypoxemia → respiratory failure (most common cause of death)
- Kidneys: Acute tubular necrosis → AKI (early, within 24–48 h); can partially recover
- Liver: Hepatocellular injury, elevated transaminases, jaundice
- Heart: Myocarditis, arrhythmias (in severe poisoning)
- Adrenals: Adrenal hemorrhage (rare)
- CNS: Cerebral edema, seizures (rare, usually reflects severe systemic toxicity)
Diagnosis
Clinical Suspicion
- History of ingestion (often deliberate self-harm)
- Oropharyngeal ulceration + GI symptoms + progressive respiratory failure
Tests
| Test | Significance |
|---|---|
| Urine dithionite test | Blue/green color confirms paraquat; rapid bedside test; negative result does not exclude poisoning |
| Plasma paraquat level | Quantitative; compared to severity nomogram (Hart & Lim/Proudfoot nomogram) for prognosis |
| ABG | Hypoxemia; initial PaO₂ may be normal or near-normal |
| Renal function (Cr, BUN) | AKI onset |
| LFTs | Hepatotoxicity |
| CBC | Leukocytosis common |
| Chest X-ray / CT | Early: normal or diffuse infiltrates; late: bilateral consolidation, fibrosis |
Proudfoot Nomogram
Plasma paraquat level plotted against time since ingestion — classifies into:
- Probably survive
- Probably die
- Helps guide intensity of treatment
Management
No proven antidote. Treatment is largely supportive and aimed at reducing absorption and oxidative injury.
1. Decontamination (Time-Critical)
- Skin/eyes: Remove clothing; copious water irrigation
- Ingestion: Gastric lavage if within 1–2 hours (use with caution due to oropharyngeal ulceration)
- Adsorbents: Fuller's earth (best) or activated charcoal — adsorb paraquat in the gut; give as soon as possible
- Fuller's earth: 1–2 g/kg PO in aqueous suspension + magnesium sulfate as cathartic
- Activated charcoal: 1 g/kg if Fuller's earth unavailable
2. Reduce Oxidative Damage
| Intervention | Evidence |
|---|---|
| Antioxidants (Vit C, Vit E, N-acetylcysteine) | Theoretically beneficial; clinical evidence weak |
| Immunosuppression (methylprednisolone + cyclophosphamide) | Some benefit in moderate poisoning; used empirically |
| Deferoxamine | Chelates iron → reduces Fenton reaction; limited human data |
| Salicylate (aspirin) | Experimental; not standard |
3. Oxygen — Use with Extreme Caution
- Supplemental O₂ accelerates radical generation and worsens lung injury
- Avoid O₂ unless PaO₂ < 50 mmHg (SaO₂ < 85%)
- Target SpO₂ ~85–90% — deliberate permissive hypoxemia is standard practice
- This is one of the most critical and counterintuitive aspects of management
4. Enhance Elimination
| Method | Details |
|---|---|
| Hemoperfusion (charcoal) | Most effective elimination method; must be initiated early (within 4–12 h); reduces plasma levels but clinical mortality benefit uncertain |
| Hemodialysis | Useful for AKI; paraquat not efficiently dialyzed |
| Forced diuresis | No benefit; may worsen renal injury |
5. Supportive Care
- IV fluids for AKI, but avoid fluid overload (worsens pulmonary edema)
- Renal replacement therapy for severe AKI
- Nutritional support (enteral preferred; oropharyngeal ulceration may require NGT)
- Analgesia and wound care for mucosal burns
- ICU monitoring
6. Lung Transplantation
- Has been attempted in selected cases of severe pulmonary fibrosis
- Very rarely successful — recurrence of injury in transplanted lung reported; not widely recommended
Prognosis
| Predictor | Significance |
|---|---|
| Dose ingested | Most important predictor |
| Plasma level + time (nomogram) | Stratifies survival probability |
| Early AKI | Associated with higher mortality |
| Plasma creatinine > 265 µmol/L within 24 h | Poor prognosis |
| Metabolic acidosis | Poor sign |
Overall mortality in moderate–severe poisoning: 50–90% despite treatment. Fulminant ingestions are almost universally fatal.
Key Points Summary
- Paraquat is highly toxic at small doses; no antidote exists
- Mechanism: redox cycling → free radical generation → lipid peroxidation
- Primary target: lungs (progressive fibrosis)
- Restrict oxygen — this is critical and counterintuitive
- Early decontamination with Fuller's earth and hemoperfusion may improve outcomes
- Plasma paraquat level + nomogram guides prognosis
- Supportive care including AKI management is essential
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