Cyclophosphamide Dosing for Paraquat Poisoning
For moderate to severe paraquat poisoning, administer intravenous cyclophosphamide 15 mg/kg daily for 2 consecutive days (maximum 1 gram per day) in combination with methylprednisolone 1 gram daily for 3 days, alongside standard care including hemoperfusion. 1, 2
Evidence-Based Dosing Protocol
The most robust evidence comes from clinical trials specifically evaluating paraquat poisoning, which demonstrated significant mortality reduction with this immunosuppressive regimen:
Cyclophosphamide Dosing
- Dose: 15 mg/kg intravenously daily for 2 consecutive days 2
- Alternative fixed dose: 1 gram daily for 2 days 1
- Maximum: Do not exceed 1 gram per infusion 1
Mandatory Combination Therapy
- Methylprednisolone: 1 gram intravenously daily for 3 days 1, 2
- Mesna: 15 mg/kg for 4 days to prevent hemorrhagic cystitis 2
- Standard care: Hemoperfusion/hemodialysis, gastric decontamination, and supportive measures 3, 4
Clinical Efficacy Data
The combination of cyclophosphamide with glucocorticoids reduces mortality in moderate to severe paraquat poisoning:
- Mortality reduction: From 70.6% with standard care alone to 25% with pulse immunosuppression (p = 0.01) 1
- Alternative study: Mortality reduced from 81.8% to 33.3% (p < 0.05) 2
- Meta-analysis: Risk ratio for death 0.72 (95% CI 0.59 to 0.89) across 164 patients 3, 4
All deaths in these studies resulted from progressive respiratory failure and acute respiratory distress syndrome, which the immunosuppressive regimen helps prevent by blocking inflammatory cell recruitment and subsequent pulmonary fibrosis 1, 2, 5.
Critical Timing Considerations
- Initiate immediately upon diagnosis of moderate to severe poisoning 2
- Treatment effectiveness depends on early administration before irreversible pulmonary fibrosis develops 5
- No significant differences in outcomes were observed based on time from ingestion to hospital presentation in the treatment groups, suggesting the regimen works across various presentation times 1, 2
Patient Selection Criteria
This regimen is specifically indicated for moderate to severe paraquat poisoning, defined by:
- Positive urine dithionite test indicating significant paraquat exposure 1
- Clinical evidence of systemic toxicity 3, 4
- Estimated ingestion >20-40 mg/kg of paraquat concentrate 5
Essential Protective Measures
- Mesna administration: 15 mg/kg for 4 days is mandatory to prevent cyclophosphamide-induced hemorrhagic cystitis 2
- Oxygen therapy: Use low-inspired oxygen concentrations until hypoxemia makes it impractical, as oxygen exacerbates paraquat-induced oxidative injury 5
- Hemoperfusion: Continue aggressive extracorporeal elimination alongside immunosuppression 3, 4, 5
Monitoring Requirements
- Respiratory function: Serial assessment for progressive respiratory failure 5
- Plasma/urinary paraquat levels: Intermittent monitoring to guide prognosis 5
- Complete blood counts: Monitor for leukopenia during and after treatment 6
- Adequate hydration: Maintain throughout cyclophosphamide administration 6
Mechanism of Action
Paraquat toxicity operates through oxidative radical formation (superoxide, singlet oxygen, hydroxyl, and peroxide radicals), followed by inflammatory cell recruitment leading to irreversible pulmonary fibrosis 5. The cyclophosphamide-glucocorticoid combination interrupts this inflammatory cascade before fibrosis becomes established 3, 4.
Important Caveats
- This regimen has been studied only in moderate to severe poisoning; mild cases may not require immunosuppression 3, 4
- The evidence base consists of three small RCTs with 164 total participants, though results are consistent across studies 3, 4
- All studies used historical controls or concurrent randomization with allocation concealment 3, 4, 1, 2
- Long-term toxicity concerns with cyclophosphamide (gonadal toxicity, secondary malignancies) are less relevant in this acute poisoning context where short-term survival is the primary concern 7