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Paraquat poisoning

Paraquat poisoning. Dr. Wong Oi Fung TMH. History (case 1). 76/M Hx of knee pain otherwise good past health Attended A&E on 5/12/2004 Quarreled with his neighbor; sprayed paraquat over his eyes Vital signs: Bp117/79; Pulse 85/min; SpO2 99% RA; GCS 15/15 Cat. 3. Progress.

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Paraquat poisoning

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  1. Paraquat poisoning Dr. Wong Oi Fung TMH

  2. History (case 1) • 76/M • Hx of knee pain otherwise good past health • Attended A&E on 5/12/2004 • Quarreled with his neighbor; sprayed paraquat over his eyes • Vital signs: Bp117/79; Pulse 85/min; SpO2 99% RA; GCS 15/15 • Cat. 3

  3. Progress • NS irrigation to both eyes • RFT and ABG normal • Close monitoring in medical ward • Observed for 1 week; RFT all along normal; no respiratory distress • Seen by eye doctor • Discharged after 1 week of observation • Referred to eye clinic for follow-up

  4. History (case 2 ) • 70/M • History of HT and gout • Attended on 13/2/2005 for paraquat ingestion • Committed suicide because of chronic joint pain • Drank ~ 100 ml paraquat ( 24% paraquat dichloride)

  5. History (case 2) • Vital signs: BP 159/70; pulse 77bpm; afebrile; SpO2 100% on RA; GCS 15/15 • Cat. 2 • CXR clear lung field • ECG SR • Poor prognosis explained to relatives • Admitted to medical ward

  6. Progress • Hemoperfusion tried but developed high fever and confusion with tachycardia and stopped • Rapidly deteriorated with confusion, oral ulceration and dyspnoea • ↓Renal function: Cr 122  337 • Succumbed on 15/2/2005

  7. Discussion • Paraquat • 1,1’ –dimethyl-4,4’-dipyridylium • Bipyridyl herbicides • Exposure: • Toxic ingestion intentional • Dermal exposure occupational • Other e.g. eye • Fetal dose 20 to 40mg/kg H3C +N N+ CH3 2Cl-

  8. Paraquat as herbicide • As contact herbicide with low environmental toxicity due to rapid deactivation upon soil contact • In plants • disrupts photosynthesis by inhibiting the electron transport chain • In humans • Poorly absorbed (1-5% of oral dose absorbed in gut ) • Vol. of distribution 2 to 8 Liters/kg • Cause multiple organ damage

  9. Type 1 and type 2 pulmonary epithelial cells O2 NADPH Oxidising cytochrome P-450 reductase PQ+ Reduced cytochrome P-450 reductase NADP PQ2+ O2 PQ in blood Redox cycling of paraquat O2 + O2 + 2H+ H2O2 + O2 GSH GSSG H2O O2 Fe3+ OH + OH- Lipid peroxidation O2 Fe2+ H2O2

  10. Clinical features • Resp. system • Delayed (3 to 14 days) progressive pulmonary fibrosis • Renal system • Acute renal failure (within 24 to 96 hours) • GI system • N, V & D • Burning in oral mucosa and hemorrhagic ulceration • CVS • Cerebral edema and brain damage • CNS • Ventricular arrhythmias, hypotension and cardiorespiratory arrest • Eye • Protracted opacification of the cornea • Skin • Dermatitis • Well adsorbed in injured skin  severe system toxicity • Other • Methemoglobinemia, transient reversible liver injury

  11. Management • Airway management and adequate ventilation • High O2 CONTRAINDICATED • Use the lowest O2 levels possible to limit pulmonary complication • Decontamination (Fuller’s earth/ activated charcoal) • IVF to maintain adequate urine output • Hemodialysis or hemoperfusion • Administration of “antidotes” • Antioxidants NAC or deferoxamine • Immunosuppressive therapy • Explain the poor prognosis to patient’s relative

  12. Investigation • Blood test • RFT, LFT, ABG • CXR and ECG • ?? Paraquat level Paraquat nomogram 5 4 Plasma paraquat ug/ml 3 10% 2 50% 90% 1 0 4 8 12 16 20 24 28 Hours post ingestion

  13. Investigation • Urine dithionite test • Paraquat stable blue radical ion • Colourless or light blue mild poisoning • Navy or dark blue  moderate to sever poisoning • ??validity • Urine paraquat concentration depend on renal function • Urine production as poisoning progress since paraquat caused renal failure Sodium thionite under alkaline condition

  14. Type 1 and type 2 pulmonary epithelial cells O2 NADPH Oxidised cytochrome P-450 reductase PQ+ ??hypoxic atomospheres HP/Fuller’s Earth Reduced cytochrome P-450 reductase NADP PQ2+ O2 PQ in blood NAC O2 + O2 + 2H+ H2O2 + O2 DFO GSH GSSG H2O O2 Fe3+ OH + OH Lipid peroxidation Methylprednisolone &cyclophosphamide O2 Fe2+ H2O2

  15. Gut Decontamination Fuller’s Earth Vs Activated charcoal Animal study showed: No significant difference found in the effectiveness of either adsorbent Administration of an adsorbent as early as possible will reduce paraquat absorption from the GI tract Activated charcoal is still effective in lowering serum paraquat concentration when given >1hour after ingestion of paraquat Idid SZ. Lee CY.: Effect of Fuller’s Earth and activated charocal on oral absorption of paraquat in rabbits.Clinical & Experimental pharmacology & Physiology. 23(8):679-81, 1996 Aug

  16. Extracorporeal Elimination Techniques • Hemodialysis/hemoperfusion • Do they increased the survival rate?? • Probably not. • When these techniques are initiated, potential lethal concentration of paraquat have already been attained in the highly vascular tissue of vital organs and in the pneumocytes • Bismuth C. Scherrmann Jm. Garnier R. Baud FJ. Pontal PG.: Elimination of paraquat. Human Toxicology. 6(1):63-7, 1987 Jan. • Hemodialysis • Paraquat NOT dialyze effectively • Supportive treatment for renal failure

  17. Immunosuppressive therapy • RCT of pulse methylprednisolone & cyclophosphamide in paraquat poisoning showed survival: 43% to 72/% (p=0.008) • Lin in 1999 • Really benefit?? • Exclude “fulminant” poisoning (died within 7 days); 50% was excluded • Reanalysis on an intention-to-treat basis showed an improvement NOT significant at the 0.05 statistical level :18% to 32% (p=0.095 )

  18. Treatment • Deferoxamine and NAC • rat mortality and morbidity • Lung transplantation • Successful outcome after single lung transplantation in paraquat poisoning has been reported • Licker, Marc: Single lung transplantation for adult respiratory distress syndrome after paraquat poisoning. Thorax 1998;53:620-621

  19. Thank you

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