Paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride) is one of the most lethal herbicides worldwide, with a case fatality rate of 60–90% following oral ingestion. [1-2] There is no specific antidote. [1] Toxicity is driven by redox cycling and generation of reactive oxygen species, causing lipid peroxidation, mitochondrial damage, and severe inflammation, with the lungs as the primary target organ due to active uptake against a concentration gradient. [1-2] Death typically results from progressive, irreversible pulmonary fibrosis or multi-organ failure. [1][3]
1. History
- Route of exposure: Oral ingestion (most common, most lethal), dermal, or inhalational
- Intent: Intentional self-harm accounts for the vast majority of cases; accidental ingestion (especially pediatric) and occupational dermal exposure also occur [3-4]
- Amount ingested: Critical prognostic factor — even 10–15 mL of 20% concentrate can be fatal [5]
- Time since ingestion: Drives urgency of decontamination; paraquat is rapidly absorbed and largely eliminated in urine within 12–24 hours [2]
- Formulation and concentration: Commercial concentrates (e.g., Gramoxone, 20–24%) vs. dilute solutions
- Symptoms: Nausea, vomiting (93%), throat/mouth pain (85%), dysphagia, odynophagia, abdominal pain, diarrhea [5]
- Important negatives: Absence of dyspnea at presentation does not exclude significant poisoning — patients may appear asymptomatic while lung fibrosis is developing [1]
2. Alarm Features
- Dyspnea or respiratory distress at presentation — strongly predicts mortality (adjusted OR 16.18 for death when present) [6]
- Large volume ingested (>40 mg/kg paraquat ion → fulminant poisoning with death in 24–48 hours from multi-organ failure) [1]
- Oropharyngeal/esophageal ulceration or perforation — indicates significant caustic injury
- Oliguria or anuria — suggests acute kidney injury
- Metabolic acidosis (80% of patients in one series had mixed metabolic/respiratory acidosis) [3]
- Hemodynamic instability, altered mental status, seizures, cardiac arrhythmias — signs of fulminant poisoning [1]
3. Medications
- No specific antidote exists [1]
- Activated charcoal (1 g/kg): First-line GI decontamination; an additional dose is appropriate for paraquat given prolonged GI transit. Activated charcoal with magnesium citrate showed superior survival in animal models [7-9]
- Fuller's earth: Alternative adsorbent with comparable efficacy to activated charcoal; less widely available [2][10]
- Immunosuppressive pulse therapy: Methylprednisolone + cyclophosphamide ± dexamethasone — the most widely used pharmacologic regimen; meta-analyses suggest reduced mortality (60.4% vs. 85.3% in controls), though evidence quality is low. A large Taiwanese cohort (n=1811) found the combination of methylprednisolone, cyclophosphamide, and daily dexamethasone associated with the highest survival rate (48%) [1][11-13]
- N-acetylcysteine (NAC): Antioxidant with theoretical benefit via free radical scavenging and NF-κB inhibition; used in case reports with favorable outcomes but no RCT data [2][14-15]
- Pirfenidone: Anti-fibrotic agent used in a pediatric case to prevent pulmonary fibrosis with good outcome at 6-month follow-up [15]
- Deferoxamine: Iron chelator with antioxidant properties; used in a case of massive ingestion with survival [14]
- Contraindicated: Supplemental oxygen should be avoided or minimized unless the patient is severely hypoxic — oxygen potentiates paraquat-induced oxidative lung injury [2]
- Gastric lavage is NOT recommended — contraindicated due to caustic injury risk and unlikely to add benefit beyond spontaneous vomiting [2][16]
4. Diet
- NPO initially if significant oropharyngeal/esophageal injury is present
- Assess for caustic GI injury before initiating oral feeds; endoscopy may be needed
- Parenteral nutrition may be required in severe cases with extensive mucosal damage
- Hydration: Aggressive IV fluid resuscitation to support renal perfusion and paraquat excretion
- No specific long-term dietary modifications are established
5. Review of Systems
- GI: Nausea, vomiting, diarrhea, dysphagia, odynophagia, hematemesis, abdominal pain
- Respiratory: Dyspnea, cough, chest tightness (may be delayed days to weeks)
- Renal: Decreased urine output, hematuria
- Hepatic: Jaundice, right upper quadrant pain
- Cardiac: Palpitations, chest pain
- Neurologic: Headache, confusion, seizures (fulminant cases)
- Dermatologic: Skin burns, nail damage, contact dermatitis (dermal exposure) [4]
- Oral: Mouth/tongue ulceration, mucosal sloughing [1][15]
6. Collateral History and Family History
- Collateral: Confirm substance identity (product label, container), amount ingested, time of ingestion, co-ingestants, intent (suicidal vs. accidental)
- Psychiatric history: Most cases are intentional self-harm — assess for prior suicide attempts, psychiatric comorbidities, access to lethal means [3]
- Occupational context: Agricultural workers, farmers, gardeners — assess for chronic low-level exposure [3-4]
- Family history: Not directly relevant to acute management, but family dynamics may influence disposition decisions (in some settings, families request discharge against medical advice) [3]
7. Risk Factors
- Agricultural occupation — farmers and gardeners with access to paraquat [3]
- Psychiatric illness / suicidal ideation — intentional self-poisoning is the predominant mechanism [3][5]
- Geographic: Highest incidence in South/Southeast Asia, Pacific Islands, and parts of Latin America where paraquat is readily available [2]
- Young males: Mean age ~30 years, ~70% male in large series [5]
- Lack of regulatory restrictions: Countries without paraquat bans have higher poisoning rates
- Dermal exposure risk factors: Prolonged skin contact, broken skin, inadequate PPE [4]
8. Differential Diagnosis
- Other herbicide/pesticide poisoning: Glyphosate, diquat, organophosphates — distinguish by history and specific toxidromes
- Caustic ingestion (acids/alkalis): Similar oropharyngeal burns but different systemic toxicity pattern
- Other causes of ARDS: Sepsis, aspiration pneumonitis, inhalational injury
- Mushroom poisoning (e.g., Amanita): Delayed hepatorenal failure
- Iron poisoning: GI hemorrhage, metabolic acidosis, hepatic failure
- Methanol/ethylene glycol: Metabolic acidosis with anion gap, but different clinical trajectory
- Diquat poisoning: Closely related bipyridyl herbicide; causes renal failure and GI injury but less pulmonary fibrosis
9. Past Medical History
- Pre-existing lung disease: May accelerate respiratory failure
- Chronic kidney disease: Impairs paraquat excretion, worsens prognosis
- Liver disease: Reduces detoxification capacity
- Prior self-harm attempts: Informs psychiatric risk assessment
- Immunosuppression: Relevant when considering cyclophosphamide/steroid therapy
10. Physical Exam
- Vital signs: Tachycardia, tachypnea, hypotension (late/fulminant); SpO₂ may be initially normal
- Oropharynx: Mucosal erythema, ulceration, white pseudomembranes, tongue swelling — hallmark of significant ingestion [1][15]
- Skin: Chemical burns, erythema, blistering (dermal exposure); nail discoloration/dystrophy [4]
- Lungs: May be initially clear; crackles and decreased breath sounds develop as pulmonary injury progresses
- Abdomen: Tenderness, guarding (if esophageal/gastric perforation)
- Renal: Assess urine output
- Neurologic: Mental status changes in fulminant cases
11. Lab Studies
A composite prognostic index using amount ingested, absolute neutrophil count, urine protein, serum bicarbonate, creatinine, and blood glucose demonstrated an AUC of 0.921 for predicting death; a score ≥5 predicted mortality with 94% probability. [18]
12. Imaging
- Chest X-ray: Initial CXR may be normal; patchy infiltrates and ground-glass opacities develop within days; progressive consolidation and fibrosis over 1–3 weeks. Presence of infiltrates on admission CXR is an independent predictor of mortality (OR 0.003) [5][19]
- CT chest: More sensitive than CXR; shows ground-glass opacities, consolidation, interstitial changes, and eventually honeycombing and fibrosis. Serial CT can track progression — the ratio of injured lung volume fraction between sequential CTs has strong prognostic value (ratio <0.3 = universally fatal; >0.8 = all survived) [19-21]
- Abdominal imaging: Consider if esophageal/gastric perforation suspected (CT with water-soluble contrast)
The following figure demonstrates the prognostic value of serial CT-based injured lung volume fraction ratios in paraquat poisoning:
13. Special Tests
- Urine dithionite test: Bedside qualitative test — add sodium dithionite + NaOH to urine; blue-green color indicates paraquat [2]
- Plasma dithionite test: Similar principle applied to plasma
- Plasma paraquat concentration with Proudfoot-Dougall nomogram: Time-adjusted plasma level plotted against hours post-ingestion to predict survival [2]
- APACHE II score: Higher scores in non-survivors (median 15.5 vs. 7) [5]
- IPCS Poisoning Severity Score: Increasing grade correlates with increasing mortality [5]
- Spirometry / DLCO: For survivors — may show obstructive ventilatory dysfunction, reduced CO diffusion capacity long-term [14][20]
14. ECG
- Indications: All patients with significant paraquat ingestion
- Findings: Sinus tachycardia is common; cardiac arrhythmias may occur in fulminant poisoning [1]
- Monitor for: QT prolongation, ventricular arrhythmias, signs of hyperkalemia (if renal failure develops)
- Continuous cardiac monitoring recommended for all admitted patients
15. Assessment
Severity stratification by dose: [1]
- Low-dose (<20 mg/kg paraquat ion): Mild GI symptoms; good prognosis
- Moderate-dose (20–40 mg/kg): Renal/hepatic dysfunction, oral mucosal damage; progressive pulmonary fibrosis developing over 10–14 days; death at 2–4 weeks if untreated
- Fulminant/high-dose (>40 mg/kg): Multi-organ failure, death within 24–48 hours from cardiovascular collapse, renal failure, seizures, esophageal perforation
Key clinical pearl: Patients may appear deceptively well in the first 24–48 hours despite having ingested a lethal dose. Oral mucosal burns and rising creatinine are early warning signs. Progressive dyspnea developing days later signals irreversible pulmonary fibrosis. [1]
16. Treatment Plan
Initial stabilization
- ABCs with minimal supplemental O₂ — oxygen worsens oxidative lung injury; use only if SpO₂ <85–90% [2]
- IV access, continuous monitoring, aggressive IV fluid resuscitation
GI decontamination (within 1–2 hours, but consider beyond if ongoing absorption suspected):
- Activated charcoal 1 g/kg PO/NG; consider a second dose [7-8]
- Fuller's earth 15% suspension (150 g in 1L water) if available [2]
- Do NOT perform gastric lavage [2]
Immunosuppressive pulse therapy
- Methylprednisolone 1 g IV daily × 3 days, then taper with dexamethasone
- Cyclophosphamide 15 mg/kg IV daily × 2 days [11-13]
- This combination demonstrated the highest survival rate (48%) in a large nationwide cohort [13]
Extracorporeal therapies
- Hemoperfusion (HP): Most promising modality; early initiation (within 4–6 hours) improves survival [3][22]
- HP + CRRT combination: Synergistic effects for toxin removal and renal support [22]
- Hemodialysis alone: Ineffective for paraquat removal but useful for AKI management; early initiation (Day 1) still associated with improved survival (30% vs. 12%) [6]
Antioxidant therapy (adjunctive, limited evidence)
- N-acetylcysteine 300 mg/kg/day continuous infusion [14-15]
- Deferoxamine 100 mg/kg over 24 hours [14]
Anti-fibrotic therapy
17. Disposition
- All confirmed paraquat ingestions require hospital admission, regardless of initial appearance [1]
- ICU admission: Any patient with respiratory distress, hemodynamic instability, significant ingestion volume (>10–15 mL of concentrate), renal impairment, metabolic acidosis, or altered mental status
- Hemoperfusion/CRRT capability: Transfer to a center with extracorporeal therapy if not available locally [15]
- Toxicology/Poison Control consultation: Mandatory for all cases
- Psychiatry consultation: For all intentional ingestions
- Burn center referral: If significant dermal chemical burns [4]
- Discharge: Only after confirmed low-dose exposure with negative or very low plasma paraquat levels, normal renal function, normal CXR, and adequate observation period (minimum 24–48 hours)
18. Follow Up / Return Precautions
- Survivors require long-term pulmonary follow-up: Serial spirometry and DLCO; CT chest to monitor for fibrosis [20]
- Long-term survivors of moderate-severe poisoning may develop obstructive ventilatory dysfunction, bronchiectasis, and airway hyperresponsiveness [20]
- DLCO impairment may persist >14 months even in patients with otherwise good recovery [14]
- Renal and hepatic function typically normalize within 1 month in survivors [14]
- Psychiatric follow-up is essential for all intentional self-poisoning cases
- Return precautions: Worsening dyspnea, cough, decreased exercise tolerance, decreased urine output, jaundice, fever
- Expected course: If the patient survives the first 2–4 weeks without developing severe pulmonary fibrosis, long-term survival is likely, though residual pulmonary impairment is common [1][20]
References
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2. Medical Management of Paraquat Ingestion. — Gawarammana IB, Buckley NA. British Journal of Clinical Pharmacology. 2011.
3. Epidemiological Profile of Paraquat Poisoning in Tertiary Care Center of Eastern Nepal: A Retrospective Observational Study. — Chaudhary RK, Rajbanshi LK, Aryal D, Singh A. Medicine. 2026.
4. Single-Center Experience With Paraquat Exposure in Nine Patients. — McKinzie BP, Powell BD, Sljivic S, et al. Journal of Burn Care & Research : Official Publication of the American Burn Association. 2022.
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18. Combined Routine Blood and Urine Laboratory Indicators Are Efficient Predictors of Prognosis in Patients With Acute Paraquat Poisoning: A Retrospective Study. — Su Y, Li G, Fang W, et al. Clinical Toxicology. 2025.
19. Radiological Features of Paraquat-Induced Pulmonary Fibrosis. — Wang M, Jiao J, Liu J, Zhao J, Gong B. Clinical Toxicology. 2025.
20. Follow-Up of Patients With a 5-Year Survival After Paraquat Poisoning Using Computed Tomography Images and Spirometry. — Fan L, Wang X, Lv T, et al. Human & Experimental Toxicology. 2023.
21. Ratio of Injured Lung Volume Fraction in Prognosis Evaluation of Acute PQ Poisoning. — Liu J, Xiong Y, Jiang M. BioMed Research International. 2017.
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