What is the recommended cyclophosphamide (CY) and methylprednisolone (MP) regimen for treating paraquat poisoning?

Cyclophosphamide and Methylprednisolone Regimen for Paraquat Poisoning

For moderate to severe paraquat poisoning, administer pulse therapy with intravenous cyclophosphamide 15 mg/kg/day for 2 days combined with intravenous methylprednisolone 1 gram/day for 3 days, followed by continuous dexamethasone 20 mg/day until PaO2 exceeds 80 mm Hg, with repeated pulse cycles if PaO2 falls below 60 mm Hg. 1

Initial Pulse Therapy Protocol

First 3 Days

• Methylprednisolone: 1 gram IV daily for 3 consecutive days 2, 1, 3
• Cyclophosphamide: 15 mg/kg IV daily for 2 days 2, 1, 3
• Mesna: 15 mg/kg for 4 days (mandatory for hemorrhagic cystitis prevention) 2

This initial pulse therapy targets the severe inflammatory response that drives lethal hypoxemia in paraquat poisoning, not the fibrotic changes that develop later 4. The evidence shows this approach reduces mortality from 70-86% to 25-33% in patients with moderate to severe poisoning 2, 3.

Continuous Maintenance Phase

After Initial Pulse

• Dexamethasone: 20 mg/day continuously until PaO2 consistently exceeds 80 mm Hg (11.5 kPa) 1
• Alternative regimen: Dexamethasone 5 mg every 8 hours 5

The prolonged dexamethasone maintains anti-inflammatory suppression during the critical subacute period when respiratory failure typically develops 4, 1.

Repeated Pulse Therapy Criteria

Indications for Additional Cycles

• Trigger: PaO2 falls below 60 mm Hg (8.64 kPa) 1
• Regimen: Methylprednisolone 1 gram/day for 3 days PLUS cyclophosphamide 15 mg/kg/day for 1 day 1
• Frequency: Repeat as needed based on oxygenation status 1

This repeated pulse approach addresses the fluctuating inflammatory burden and has demonstrated survival rates of approximately 69% in patients with predicted mortality >50% 1.

Patient Selection and Severity Assessment

Appropriate Candidates

• Moderate to severe paraquat poisoning with predicted mortality 50-90% based on plasma paraquat levels 1, 3
• Patients with severe hypoxemia (PaO2 <70 mm Hg) 4, 2
• Serum paraquat levels >0.13 μg/mL at 10-60 hours post-ingestion 4, 5

The strongest evidence comes from a randomized controlled trial showing mortality reduction from 85.7% to 31.3% with this protocol 1. This represents the highest quality evidence available for paraquat poisoning treatment.

Mandatory Supportive Measures

Concurrent Interventions

• Hemodialysis/hemoperfusion: Initiate early to remove circulating paraquat 2, 3
• Pneumocystis prophylaxis: Trimethoprim/sulfamethoxazole 800/160 mg on alternate days throughout cyclophosphamide treatment 6
• Hydration: Maintain 2-3 L/24 hours to prevent hemorrhagic cystitis 6

Monitoring Requirements

Essential Parameters

• Arterial blood gases: Monitor PaO2 regularly to guide repeated pulse therapy decisions 4, 1
• Chest radiography: Weekly to assess pulmonary inflammation progression 4
• Leukocyte count: Adjust cyclophosphamide if acute leukopenia develops 6
• Renal function: Monitor creatinine, as paraquat causes acute renal failure 4

Critical Pitfalls and Cautions

Common Errors to Avoid

• Delaying treatment: The protocol must begin immediately upon diagnosis; delayed initiation reduces efficacy 2, 3
• Premature discontinuation: Continue dexamethasone until sustained oxygenation improvement, not just initial response 1
• Ignoring repeated pulse criteria: Failure to re-pulse when PaO2 drops below 60 mm Hg increases mortality 1
• Inadequate mesna protection: Omitting mesna significantly increases hemorrhagic cystitis risk with cyclophosphamide 2

Gonadotoxicity Warning

• Cyclophosphamide causes amenorrhea in 20-85% of menstruating women and azoospermia in men 6
• However, in the context of paraquat poisoning with >50% mortality without treatment, this toxicity is acceptable given the life-threatening nature of the poisoning 1

Evidence Quality Assessment

The recommendation is based on one randomized controlled trial 1 and three prospective cohort studies 2, 3, 5, all showing consistent mortality reduction. The RCT demonstrated the strongest effect (mortality reduction from 85.7% to 31.3%, p=0.0272) and used the most refined protocol with repeated pulse therapy 1. Earlier studies using single-pulse therapy showed less dramatic but still significant benefits (mortality 25% vs 70.6%) 3.

The mechanism of benefit appears to be suppression of the severe inflammatory cascade rather than prevention of fibrosis, as evidenced by dramatic improvements in oxygenation (PaO2 rising from 66 to 97 mm Hg) and chest radiographs after pulse therapy 4.