Paraquat Poisoning: Current Advances in Pathophysiology, Diagnostic Biomarkers, and Evidence-Based Management Protocols

Introduction: Paraquat (1,1′-dimethyl-4,4′-bipyridinium dichloride), a widely used herbicide with high human lethality due to its redox cycling, generating reactive oxygen species that induce irreversible multi-organ failure and pulmonary fibrosis. Despite known mechanisms, clinical management remains challenging and mortality exceeds 60%. This systematic review synthesizes global evidence on paraquat toxicity mechanisms, prognostic biomarkers, therapeutic interventions, and public health policies to guide clinical practice and regulatory decision-making. Methods: Following PRISMA guidelines, PubMed, MEDLINE, Embase, Scopus, Web of Science, and WHO IRIS were searched till January 2026. Studies on pathophysiology, diagnostics, treatments, and policy were narratively evaluated. Results: From 1,842 identified studies, 39 met inclusion criteria. Pathophysiologically, cellular uptake via polyamine transporters drives mitochondrial electron leakage, p38 MAPK/NF-κB inflammatory signaling, and TGF-β-mediated interstitial fibrosis. While plasma nomograms and lactate levels reliably predict mortality, targeted therapies show variable success. Randomized controlled trial evidence refutes high-dose immunosuppression benefits, whereas early hemoperfusion (under 4 hours) and restrictive oxygen therapy demonstrate clinical utility. Public health bans in Sri Lanka, South Korea, and Taiwan yielded a 40–50% reduction in pesticide suicides without harming agricultural yields. Conclusion: Prognostic biomarkers accurately identify severe exposures, yet proven clinical treatments remain limited beyond early extracorporeal clearance and restrictive oxygenation. National regulatory restriction stands as the single most effective, evidence-based intervention to prevent paraquat-related fatalities worldwide.