Cyclophosphamide Combined with Glucocorticoids Reduces Mortality in Moderate to Severe Paraquat Poisoning
For patients with moderate to severe paraquat poisoning, cyclophosphamide combined with glucocorticoids in addition to standard care (hemoperfusion/hemodialysis) should be administered, as this regimen reduces mortality by approximately 28% compared to standard care alone. 1, 2
Evidence Supporting Immunosuppressive Therapy
The rationale for cyclophosphamide use in paraquat poisoning centers on the immune system's role in exacerbating paraquat-induced lung fibrosis, which is the primary cause of death in these patients 1, 2. Three randomized controlled trials involving 164 patients with moderate to severe paraquat poisoning demonstrated that patients receiving glucocorticoid with cyclophosphamide had a significantly lower risk of death (RR 0.72; 95% CI 0.59 to 0.89) 1, 2.
A nationwide population-based study of 1,811 paraquat-poisoned patients who received hemoperfusion found that adding immunosuppressive treatment increased survival from 24.3% to 29.3% (p<0.001) 3. The combination of methylprednisolone, cyclophosphamide, and dexamethasone was associated with the highest survival rate at 48% 3.
Recommended Treatment Protocol
Initial Pulse Therapy
- Methylprednisolone 1 g/day IV for 3 consecutive days 4, 3
- Cyclophosphamide 15 mg/kg/day IV for 2 days initially 4
- Followed by dexamethasone 20 mg/day continuously until PaO₂ exceeds 80 mm Hg (11.5 kPa) 4
Repeated Pulse Therapy
- If PaO₂ falls below 60 mm Hg (8.64 kPa), repeat pulse therapy with:
This repeated pulse approach with long-term steroid therapy reduced mortality from 85.7% to 31.3% (p=0.0272) in patients with 50-90% predicted mortality based on plasma paraquat levels 4.
Patient Selection Criteria
This treatment is specifically indicated for patients with moderate to severe paraquat poisoning, defined as those with 50-90% predicted mortality based on plasma paraquat levels 1, 2, 4. Younger patients (under 45 years) derive the greatest benefit, with survival rates of 41.0% versus 33.7% in older patients (p<0.001) 3.
Essential Supportive Measures
Standard Care Must Continue
- Hemoperfusion or hemodialysis to reduce paraquat load remains the foundation of treatment 1, 2, 3
- Prevention of further absorption through gastric decontamination 1, 2
- The average frequency of hemoperfusion in survivors is approximately twice 3
Critical Monitoring
- Respiratory parameters, particularly PaO₂/FiO₂ ratio, should guide repeated pulse therapy decisions 5, 4
- Complete blood counts must be monitored regularly for leucopenia during and after cyclophosphamide treatment 5
- Adequate hydration is essential to prevent hemorrhagic cystitis 5
Infection Prophylaxis
- Pneumocystis jirovecii prophylaxis with trimethoprim/sulfamethoxazole (800/160 mg on alternate days or 400/80 mg daily) is strongly recommended for all patients receiving cyclophosphamide 6, 7
Clinical Pitfalls and Caveats
The window for intervention is narrow—paraquat causes rapid, progressive lung fibrosis, and treatment must be initiated as soon as possible after exposure 4, 8. Immediate decontamination followed by prompt initiation of immunosuppressive therapy may be life-saving 8.
Do not withhold treatment based on concerns about immunosuppression toxicity in this population—the mortality from untreated moderate to severe paraquat poisoning approaches 75-85%, far exceeding the risks of short-term cyclophosphamide and glucocorticoid therapy 1, 2, 4.
Cutaneous exposure alone may not require the full immunosuppressive protocol—in one case series, 78% of patients had cutaneous injury but only one required surgical intervention, and all survived with appropriate decontamination 8. However, any evidence of systemic absorption (respiratory symptoms, elevated plasma levels) warrants aggressive immunosuppressive treatment 4, 3.
The combination of methylprednisolone, cyclophosphamide, and continuous dexamethasone represents the most effective immunosuppressive regimen based on the largest available evidence 3, and should be considered the preferred approach over glucocorticoids alone or other immunosuppressive combinations 1, 2.