In acute paraquat poisoning, should a 1 g pulse of methylprednisolone be given as a single daily intravenous infusion rather than divided doses?

Methylprednisolone 1g for Paraquat Poisoning: Single Daily Infusion

For paraquat poisoning, administer methylprednisolone 1 g as a single daily intravenous infusion over at least 30–60 minutes for 3 consecutive days, rather than dividing the dose. 1, 2

Rationale for Single Daily Dosing

The evidence from paraquat-specific studies consistently demonstrates that 1 g methylprednisolone is given as a single daily dose, not divided throughout the day:

• The landmark randomized controlled trial by Lin et al. used 1 g/day as a single infusion for 3 days in severe paraquat poisoning (>50% to <90% predicted mortality), achieving a dramatic mortality reduction from 85.7% to 31.3% (p = 0.0272). 3

• Multiple case series and controlled studies uniformly report 1 g daily as a single dose for 3 days, combined with cyclophosphamide, showing mortality reductions from 70.6% to 25% in moderate-to-severe poisoning. 4, 5

• General pulse methylprednisolone guidelines across all conditions specify 500–1000 mg IV once daily as the standard administration method, with infusion over at least 30 minutes to minimize acute adverse effects. 1, 2

Complete Treatment Protocol for Paraquat Poisoning

Initial Pulse Therapy (Days 1–3)

• Methylprednisolone 1 g IV daily as a single infusion over 60 minutes 3
• Cyclophosphamide 15 mg/kg IV daily for 2 days 5, 3
• Mesna 15 mg/kg for bladder protection during cyclophosphamide 5

Maintenance Phase (After Day 3)

• Dexamethasone 20 mg/day continued until PaO₂ >80 mm Hg (>11.5 kPa) 3
• Monitor arterial blood gases every 6–12 hours 6

Repeated Pulse Criteria

• Repeat methylprednisolone 1 g daily for 3 days plus cyclophosphamide 15 mg/kg for 1 day if PaO₂ drops below 60 mm Hg (<8.64 kPa) 3
• This repeated pulse approach was critical in the Lin et al. trial that achieved 68.7% survival in severe poisoning 3

Monitoring During Single-Dose Infusion

Immediate Monitoring (During and 24 Hours Post-Infusion)

• Blood glucose before infusion and every 4–6 hours for 24 hours, with peak hyperglycemia at 6–9 hours post-dose 1
• Blood pressure before, during, and after each infusion 1, 2
• Electrolytes (potassium, sodium) throughout therapy, especially with renal impairment 1

Respiratory Monitoring

• Arterial blood gases regularly to assess for progressive hypoxemia 6, 3
• Chest radiography weekly to monitor for pulmonary fibrosis 6

Why Single Daily Dosing Is Superior

Pharmacologic Rationale

• Peak anti-inflammatory effect is achieved with high-dose bolus administration, which is the mechanism by which pulse therapy suppresses the severe inflammatory cascade in paraquat-induced lung injury 6, 3
• Dividing the dose would reduce peak concentrations and potentially diminish the immunosuppressive efficacy needed to prevent progressive respiratory failure 3

Evidence-Based Practice

• All successful paraquat protocols in the literature use single daily dosing, not divided doses 4, 5, 3
• The dramatic survival benefit (mortality reduction from 85.7% to 31.3%) was achieved specifically with 1 g as a single daily infusion 3

Critical Pitfalls to Avoid

• Do not delay pulse therapy: Initiate within hours of presentation, as the window for preventing irreversible lung injury is narrow 4, 5
• Do not underdose: The 1 g dose is critical; lower doses have not shown comparable efficacy in severe poisoning 3
• Do not stop dexamethasone prematurely: Continue maintenance dexamethasone until PaO₂ is consistently >80 mm Hg, as inflammation persists for weeks 3
• Do not skip cyclophosphamide: The combination with cyclophosphamide is essential; methylprednisolone alone has shown mixed results 4, 5, 3
• Infuse slowly: Administer over 60 minutes to minimize cardiac arrhythmias and sudden hypertension, particularly critical in patients with paraquat-induced myocardial damage 1, 2

High-Risk Patient Considerations

• Elderly patients or those with cardiac disease have markedly increased mortality risk with high-dose methylprednisolone; however, in paraquat poisoning the untreated mortality approaches 100%, making the risk-benefit ratio still favor treatment 1
• Monitor for opportunistic infections given the profound immunosuppression from combined cyclophosphamide and steroids 1
• Consider antifungal prophylaxis during the prolonged dexamethasone maintenance phase 1